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Characterization Of Staphylococcal Nuclease And Tudor Domain Containing Protein 1 (Snd1) As A Molecular Target In Hepatocellular Carcinoma And Non-Alcoholic Steatohepatitis, Nidhi H. Jariwala

Theses and Dissertations

CHARACTERIZATION OF STAPHYLOCOCCAL NUCLEASE AND TUDOR DOMAIN CONTAINING PROTEIN 1 (SND1) AS A MOLECULAR TARGET IN HEPATOCELLULAR CARCINOMA AND NON-ALCOHOLIC STEATOHEPATITIS

Nidhi Jariwala, PhD

A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Integrative Life Sciences

Virginia Commonwealth University, 2017

Devanand Sarkar, M.B.B.S., PhD.

Associate Professor, Department of Human and Molecular Genetics

Virginia Commonwealth University

Richmond, Virginia

SND1, a subunit of the miRNA regulatory complex RISC, has been implicated as an oncogene in hepatocellular carcinoma (HCC). Oncoprotein SND1 regulates gene expression at a post-transcriptional level in multiple cancers including hepatocellular carcinoma (HCC). …

The Impact Of Chemotherapy And Radiotherapy For Breast Cancer On Cognition And Functional Performance: A Comparative Analysis Of Survey Data Taken At Three Time Points Post-Treatment, Ann Marie Potter

Theses and Dissertations

Cognitive impairment related to treatment for breast cancer, affects as many as 75% of patients in study samples (Jansen, Cooper, Dodd & Miaskowski, 2011). Deficits in the cognitive domains of short-term memory, attention, speed of information processing, judgment, reasoning, spatial attention, and verbal memory have been documented. The extent to which these deficits impact functional performance within this population has not yet been quantified. The purpose of this study was to investigate the impact of breast cancer on self-reported cognition and functional performance in the six months post-completion in two groups of breast cancer survivors, a chemotherapy group and chemotherapy …

Discovering A Novel Antifungal Target In Downstream Sterol Biosynthesis Using A Squalene Synthase Functional Motif, Kristin Brooke Linscott

Theses and Dissertations--Molecular and Cellular Biochemistry

The sterol biosynthetic pathway is essential for growth of all eukaryotic cells and the main target of antifungal agents. The emergence of resistance to these antifungals in an already ill patient population indicates a need to develop drugs that have a broad spectrum of activity among pathogenic fungi and have minimal patient toxicity. Squalene synthase is the first committed step in the sterol pathway and has been studied intensively for development of antifungal agents. While the overall architecture of this enzyme is identical throughout eukaryotes, it was shown that plant and animal genes cannot complement a squalene synthase knockout mutation …

Epidemiological Investigation Of Candida Species Causing Bloodstream Infection In Pediatric Small Bowel Transplant Recipients, Mallory J. Suhr, João Carlos Gomes-Neto, Nabaraj Banjara, Diana F. Florescu, David F. Mercer, Peter C. Iwen, Heather E. Hallen-Adams

Department of Food Science and Technology: Faculty Publications

Small bowel transplantation (SBT) can be a life-saving medical procedure. However, these recipients experience high risk of bloodstream infections caused by Candida. This research aims to characterize the SBT recipient gut microbiota over time following transplantation and investigate the epidemiology of candidemia in seven pediatric patients. Candida species from the recipients’ ileum and bloodstream were identified by internal transcribed spacer sequence and distinguished to strain by multilocus sequence typing and randomly amplified polymorphic DNA. Antifungal susceptibility of bloodstream isolates was determined against nine antifungals. Twenty-two ileostomy samples harbored at least one Candida species. Fungemia were caused by Candida parapsilosis …

Peanut Allergen Threshold Study (Pats): Novel Single-Dose Oral Food Challenge Study To Validate Eliciting Doses In Children With Peanut Allergy, Jonathan O'B. Hourihane, Katrina J. Allen, Wayne G. Shreffler, Gillian Dunngalvin, Julie A. Nordlee, Giovanni A. Zurzolo, Audrey Dunngalvin, Lyle C. Gurrin, Joseph L. Baumert, Steve L. Taylor

Department of Food Science and Technology: Faculty Publications

Background: Eliciting doses (EDs) of allergenic foods can be defined by the distribution of threshold doses for subjects within a specific population. The ED₀₅ is the dose that elicits a reaction in 5% of allergic subjects. The predicted ED₀₅ for peanut is 1.5 mg of peanut protein (6 mg of whole peanut).

Objective: We sought to validate the predicted peanut ED05 (1.5 mg) with a novel single-dose challenge.

Methods: Consecutive eligible children with peanut allergy in 3 centers were prospectively invited to participate, irrespective of previous reaction severity. Predetermined criteria for objective reactions were used …

Impact Of Disease On The Survival Of Three Commercially Fished Species, John M. Hoenig, Maya L. Groner, Matthew W. Smith, Wolfgang K. Vogelbein, David M. Taylor, Donald F. Landers Jr., John T. Swenarton, David T. Gauthier

Biological Sciences Faculty Publications

Recent increases in emergent infectious diseases have raised concerns about the sustainability of some marine species. The complexity and expense of studying diseases in marine systems often dictate that conservation and management decisions are made without quantitative data on population-level impacts of disease. Mark-recapture is a powerful, underutilized, tool for calculating impacts of disease on population size and structure, even in the absence of etiological information. We applied logistic regression models to mark-recapture data to obtain estimates of disease-associated mortality rates in three commercially important marine species: snow crab (Chionoecetes opilio) in Newfoundland, Canada, that experience sporadic epizootics …

Evaluation Of A Primary Care Based Diabetes Education Program, Claire Pfister

DNP Projects

The improved management of diabetes is a critical clinical and economic challenge facing our healthcare system. Educating patients with diabetes to self-manage their disease is a vital component of diabetes care. The purpose of this DNP practice improvement project was to evaluate an innovative health care delivery method of individualized diabetes self-management education (DSME) in primary care. The approach combined individual DSME with a registered dietician and routine diabetes care with the primary care provider into one patient appointment. System data was reviewed to compare referral and attendance patterns of group and individual methods. Changes in clinical indicators of A1C, …

Deletion Of Cardiac Mir-17-92 Cluster Increases Ischemia/ Reperfusion Injury Via Pten Upregulation, Meeta B. Prakash

Theses and Dissertations

The miR-17- 92 cluster is necessary for cell proliferation and development of the cardiovascular system. Deletion of this cluster leads to death in neonatal mice. The role of this cluster still needs to be defined following ischemia and reperfusion. Methods and Results: Adult male mice were injected with Tamoxifen- was to induce inducible cardiac-specific miR-17- 92-deficient (miR-17- 92-def: MCM:TG:miR-17- 92 flox/flox ) and wild type (WT: MCM:NTG:miR-17-92 flox/flox ) mice were subjected to 30 minutes of myocardial ischemia via left anterior descending coronary artery ligation followed by reperfusion for 24 hours. Post I/R survival (48%) and ejection fraction were reduced, …

Oxidative Stress And Proteomic Studies Of Mammalian Models Of Age-Related Metabolic Dysfunction In Neurodegenerative Disorders, Aaron M. Swomley

Theses and Dissertations--Chemistry

Expression proteomics is the field of science wherein proteins that make up the cellular proteome are identified both by name and by fold-change. Depending on the application of proteomics, this change in level could be due to internal cellular stressors or introduction of xenobiotics. Global oxidative stress measures use immunohistochemistry to determine the relative level of oxidative stress of macromolecules within the cell. In this dissertation, both global oxidative stress measures and expression proteomics were used in a variety of mammalian models in order to determine the effects of protein upregulation, intranasal insulin administration, and resveratrol supplementation on the cellular …

Aedes Aegypti And Dengue In The Philippines: Centering History And Critiquing Ecological And Public Health Approaches To Mosquito-Borne Disease In The Greater Asian Pacific, Maria R. Pettis

Pomona Senior Theses

The global incidence of dengue has increase 30-fold over the past 50 years in the western or Asian Pacific, this region is also a contemporary epicenter for resource extraction and ecological destabilization. Dengue is addition to yellow fever, chikungunya and most recently zika virus, are transmitted by the mosquito vector Aedes aegypti- a domesticated mosquito adept at breeding in artificial household containers and within homes. The history of the domestication and global distribution of Aedes aegypti is intrinsically linked to European expansion into and among tropical worlds. Contemporary population genetics research suggest the westward expansion of the mosquito vector …

Mast Cell Activation By Diverse Stimuli Can Be Suppressed By Steroid Therapy And Targeting The Fyn-Stat5b Cascade, Anuya Paranjape

Theses and Dissertations

Mast cells are critical effectors of allergic disease that can be activated by numerous stimuli. We have examined mast cell control by the inflammatory cytokine, IL-33, as well as IgG. In the first study reported here, we found that the synthetic glucocorticoid, dexamethasone, potently and rapidly suppressed IL-33-induced cytokine production from murine bone marrow–derived and peritoneal mast cells, as well as human mast cells. Dexamethasone also antagonized IL-33-mediated enhancement of IgE-induced cytokine production and migration. Although dexamethasone had no effect on IL-33-induced phosphorylation of MAP kinases or NFκB p65 subunit, it antagonized AP-1 and NFκB-mediated transcriptional activity. Finally, intraperitoneal administration …

Contribution Of Asc-Inflammasome To Vascular Endothelial Dysfunction: Role Of Rna Receptor Rig-I, Ashley Pitzer

Theses and Dissertations

Retinoic acid-inducible gene-I (RIG-I) is a putative RNA helicase and recently identified as a cytosolic RNA receptor in mammalian cells. The role of RIG-I in the regulation of vascular function under physiological and pathological conditions is unknown. Recent studies have shown that the inflammasome serves as a crucial initiator of cytokine-mediated inflammation mediating the pathogenesis of cardiovascular disease. The present study tested whether RIG-I activation triggers inflammasome formation and subsequent cytokine-mediated inflammation in the endothelium of mice coronary arteries. Using both genetic and pharmacological interventions of the RIG-I inflammasome, we first characterized whether specific activation of RIG-I via 3pRNA transfection …

Design, Synthesis, And Biological Screening Of Selective Mu Opioid Receptor Ligands As Potential Treatments For Opioid Addiction, Samuel Obeng

Theses and Dissertations

Today, more Americans die each year because of drug overdoses than are killed in motor vehicle accidents. In fact, in 2015, more than 33,000 individuals died due to an overdose of heroin or prescription opioids. Sadly, 40-60 % of patients on current opioid addiction treatment medications relapse. Studies have shown that the addiction/abuse liability of opioids are abolished in mu opioid receptor (MOR) knock-out mice; this indicates that the addiction and abuse liability of opioids are mainly mediated through MOR. Utilizing the “message-address concept”, the our laboratory reported a novel non-peptide, reversible MOR selective ligand 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α (isoquinoline-3-carboxamido)morphinan (NAQ). Molecular modeling …

Short And Long Chain Free Fatty Acids Differentially Regulate Glucagon-Like Peptide-1 And Peptide Yy Transcript Levels In Enteroendocrine Cells (Stc-1), Colin M. Catherman

Theses and Dissertations

The regulation of glucagon-like peptide-1 and peptide YY hormone levels are regulated based on different influential factors, but primarily levels are dependent upon ingested food content. As meals today become more fat-enriched, there is greater requirement for evaluation of these hormones that regulate insulin and satiety levels within the body. We have shown that the gene expression transcript production of glucagon-like peptide-1 and peptide YY are modulated by different concentrations, and times of short-chain fatty acids and long-chain fatty acids. Although the peptide hormone levels have the influential physiological role on effector tissue, the regulation of these hormones begins at …

Treatment Options For Hidradenitis Suppurativa: Efficacy, Risks, Benefits, Katherine A. Hennager

Physician Assistant Scholarly Project Papers

Hidradenitis suppurativa is a chronic, recurrent follicular occlusion disease with painful, sometimes debilitating, cutaneous draining lesions and subcutaneous abscesses (DynaMed Plus, 2016). Hidradenitis suppurativa is understood to be a multifactorial disease that is hard to treat in some patients, especially those with a severe form of the disease. For this project, the efficacy of adalimumab for hidradenitis suppurativa was assessed and whether it is more beneficial than traditional treatments used. Adalimumab is a TNF-alpha inhibitor which belongs to the biologic DMARDs drug class. Kimball et al. (2012) found that at week 16 of their trial 3.9% of the placebo patients, …

The Effect Of Twist On The Mechanical Properties Of The Intervertebral Disc, Maxine Harvey-Burgess

Theses and Dissertations (Comprehensive)

Introduction: Intervertebral disc (IVD) herniation is a common injury to the IVD and a frequent source of low back pain. IVD herniation occurs when the nucleus pulposus migrates through both the inter- and intralamellar matrices of the annulus fibrosus (AF). There are a number of mechanical risk factors associated with herniation, including repetitive flexion and twist. In vivo, twist combined with repetitive flexion has been associated with increased experience of low back pain and herniation. Additionally, in vitro, when repetitive flexion is combined with twist, IVD herniation occurs more easily than repetitive flexion alone. However, the mechanisms behind …

Using Risk-Tracing Snowball Approach To Increase Hiv Case Detection Among High-Risk Populations In Cambodia: An Intervention Study, Srean Chhim, John Macom, Chettana Pav, Nirada Nim, Phearun Yun, Sopheap Seng, Siyan Yi

Background: Early HIV diagnosis and initiation onto antiretroviral therapy may prevent ongoing spread of HIV. Risk Tracing Snowball Approach (RTSA) has been shown to be effective in detecting new HIV cases in other settings. The main objective of this study is to evaluate the effectiveness of RTSA in increasing the rate of newly identified HIV cases among high-risk populations. Our second objective was to evaluate the effectiveness of RTSA, as compared to the walk-in group, in increasing the number of HIV tests and early case detection.

Methods: This study was conducted from April 1 to September 30, 2016 at two …

Quality Of Life And Depression Among Patients With Type I Diabetes: A Study Of Gender Differences, Eisha Gohil, Ruby Charak, Haroon Rashid, Priyanka Sharma

Psychological Science Faculty Publications

Diabetes is a progressive chronic condition which places a significant burden of self management on the individual, such as daily monitoring and medications management, worry about the future and distress about the impact of diabetes on various aspects of life. It is a group of metabolic diseases characterized by elevated blood glucose levels (hyperglycemia) resulting from defects in insulin secretion, insulin action or both. The present study aimed to assess gender differences in quality of life and depression in patients suffering from type I diabetes. A sample of 70 participants (44 male and 26 female) in the age range of …

Macular Pigment Is Associated With Glare-Affected Visual Function And Central Visual Field Loss In Glaucoma, James Loughman, We Fong Siah, Colm O’Brien

Articles

Aim

To evaluate the relationship between macular pigment optical density (MPOD) and glare disability in open-angle glaucoma.

Methods A cross-sectional analysis of baseline data (88 subjects; median age, 67 (range 36–84) years) collected during the Macular Pigment and Glaucoma Trial (ISRCTN registry number: 56985060). MPOD at 0.25°, 0.5° and 1° of retinal eccentricity was measured using customised heterochromatic flicker photometry. Mesopic contrast sensitivity with glare (mCSg), photostress recovery time (PRT) and self-reported glare symptoms were evaluated. Fourier-domain optical coherence tomography was used to analyse ganglion cell complex (GCC) and identify foveal involvement.

Results Low spatial frequency (f) mCSg was significantly …

Vitamin D Receptor Gene Bsm1 Polymorphism And Risk Of Breast Cancer, Sana Raza, Roshan Jahan, Anupam Dhasmana, Madan Lal Brahma Bhatt, Mohtashim Lohani, Jamal M. Arif

School of Medicine Publications

Breast cancer is a leading cause of death among women, around the world. It is a multifactorial disease involving genetic and environmental factors. Vitamin D is known to modulate biological processes like immune response, bone metabolism, cell growth regulation. The protective actions of vitamin D in cancer development are only sparsely understood, however, evidence shows that vitamin D participates in cell growth regulation, apoptosis and cell differentiation. It has also been implicated in the suppression of cancer cell invasion, angiogenesis and metastasis. The cellular effects of Vitamin D are mediated via Vitamin D receptor (VDR), which is a member of …

A Novel Approach To The Safe And Effective Mobilization Of A Super-Obese Patient: A Case Report, Jessica Anaf, Amy Wigmore, Kathy Stiller

Internet Journal of Allied Health Sciences and Practice

Purpose: The incidence of obesity is rising worldwide, as is the presentation of these patients to the acute hospital setting. As a result of their complex nature, including medical co-morbidities, psychosocial issues, and healthcare resource limitations, management of these patients requires a coordinated and intensive multi-disciplinary approach. Although there are considerable data reporting the surgical management of obese patients, there is very limited literature regarding non-surgical interventions, including approaches to safe and effective mobilization. Methods: A case report is presented of a 55-year-old super-obese male transferred to a major tertiary referral healthcare centre for management of his overall medical condition …

The Impact Of Drug And Gene Interaction On The Antipsychotic Medication For Schizophrenia, Michelle Cho, Adriana Contreras, Ashley Garza, Samantha Olvera, David Castillo, Gabriel A. De Erausquin, Chun Xu

Health & Biomedical Sciences Faculty Publications

Objective: Schizophrenia, a neuropsychiatric disorder, is known to be neurodevelopmentally progressive. Due to the extensive interindividual variability found in the responses of patients, management of schizophrenia has proven to be challenging. This interindividual variability to treatment could be justified by the variation of the enzymes in charge of metabolizing medications, especially those associated with cytochrome P450. Since genetic factors influence the phenotypic responses to drugs, researchers are involved in identifying schizophrenic genetic factors, which could impact responses and severe effects for commonly known neuroleptic drugs known as pharmacogenetics. In order to predict drug response at the personal level, genetic variants …

Racial And Ethnic Differences In Receipt Of Immediate Breast Reconstruction Surgery: Do Hospital Characteristics Matter?, Jaya Shankar Khushalani

Theses and Dissertations

Immediate Breast Reconstruction Surgery (IBRS) is associated with better quality of life among women who undergo a mastectomy. Despite insurance coverage for IBRS, utilization of IBRS remains low. Data from publicly available sources for 2010-2012 are used to examine the association between hospital characteristics receipt of IBRS by patients. Minority-serving status, low bed size, for-profit ownership, non-teaching status, high competition, low density of plastic surgeons in the market and non-metropolitan location are associated with lower likelihood of receipt of IBRS.

Racial and ethnic minorities are less likely to receive IBRS. A mixed effects logistic regression model with interactions between Black/Hispanic …

Contribution Of A Class Ii Ribonucleotide Reductase To The Manganese Dependence Of Streptococcus Sanguinis, John L. Smith

Theses and Dissertations

Manganese-deficient Streptococcus sanguinis mutants exhibit a dramatic decrease in virulence for infective endocarditis and in aerobic growth in manganese-limited media. Loss of activity of a manganese-dependent, oxygen-dependent ribonucleotide reductase (RNR) could explain the decrease in virulence. When the genes encoding this RNR are deleted, there is no growth of the mutant in aerobic broth culture or in an animal model. Testing the contribution of the aerobic RNR to the phenotype of a manganese transporter mutant, a heterologous class II RNR from Lactobacillus leichmannii called NrdJ that requires B₁₂ rather than manganese as a cofactor was previously introduced into an …

Unintended Pregnancies Among Married Women In Sindh Pakistan: Role Of Lady Health Workers, Sumera Aziz Ali, Unaib Rabbani

Community Health Sciences

Background: Unintended pregnancies, which pose substantial risks to both mothers and children, account for 24% of all pregnancies in Pakistan. Door to door visits and service provision by lady health workers (LHWs) may be related to the reduction of such pregnancies, particularly in rural areas. This study aimed to determine the association of knowledge about Lady Health Visitors (LHWs) and door to door visits by LHWs with unintended pregnancies among rural women.
Methods: We conducted a community-based, nested case-control study of 800 pregnant women, identified from the database of an active surveillance mechanism, which registers and follows all pregnant women …

Exercise Preserves Physical Function In Prostate Cancer Patients With Bone Metastases, Daniel A. Galvao, Dennis R. Taaffe, Nigel Spry, Prue Cormie, David Joseph, Suzanne K. Chambers, Raphael Chee, Carolyn J. Peddle-Mcintyre, Nicolas H. Hart, Freerk T. Baumann, James Denham, Michael Baker, Robert U. Newton

Research outputs 2014 to 2021

The presence of bone metastases has excluded participation of cancer patients in exercise interventions and is a relative contraindication to supervised exercise in the community setting due to concerns of fragility fracture. We examined the efficacy and safety of a modular multi-modal exercise program in prostate cancer patients with bone metastases.Between 2012 and 2015, 57 prostate cancer patients (70.0 ± 8.4 years; BMI 28.7 ± 4.0 kg/m) with bone metastases (pelvis 75.4%, femur 40.4%, rib/thoracic spine 66.7%, lumbar spine 43.9%, humerus 24.6%, other sites 70.2%) were randomised to multi-modal supervised aerobic, resistance and flexibility exercises undertaken thrice weekly (EX, n …

Plain Language Review Of Diabetes Among Aboriginal And Torres Strait Islander People, Kathy Ride

Research outputs 2014 to 2021

This review provides an overview of key information on diabetes among Aboriginal and Torres Strait Islander people in Australia. The review focuses mostly on type 2 diabetes among Aboriginal and Torres Strait Islander people because type 2 diabetes is responsible for the majority of cases of diabetes in this population. However, the review also refers to type 1 diabetes and gestational diabetes where information is available. It provides a historical, social and cultural background to the development of diabetes, and the behavioural and medical factors that contribute to diabetes among Aboriginal and Torres Strait Islander people.

It provides information on …

Caffeine Consumption With Relevance To Type 3 Diabetes And Accelerated Brain Aging, I. J. Martins

Research outputs 2014 to 2021

Major interests in caffeine consumption has increased with the alarming increase in the global NAFLD epidemic relevant to increased transport of caffeine to the brain with the induction of Type 3 diabetes. Specific nutritional diets are essential to maintain hepatic caffeine metabolism to facilitate rapid Aβ clearance in the periphery and to maintain the effects of drugs such as statins to reduce toxic Aβ formation not only in Type 3 diabetes but to various neurological diseases. Anti-aging gene Sirt 1 is responsible for brain Aβ and caffeine metabolism and inactivation of Sirt 1 by unhealthy diets is now relevant to …

Population-Based Cohort Study In Outcome Of Phased Progression Of Atherosclerosis In China (Persuade): Objective, Rationale And Design, Dong-Kai Shan, Yong Zhou, You-Xin Wang, Xiang Gao, Wei Wang, Jun-Jie Yang, Yun-Dai Chen

Research outputs 2014 to 2021

The coronary artery calcification score and pericardial fat volume have recently been reported to be strongly associated with the severity and presence of coronary atherosclerosis. However, no studies have explored the outcome of phased progression of atherosclerosis by non-contrast computed tomography in asymptomatic people in China. The population-based cohort study in outcome of phased progression of atherosclerosis in China (PERSUADE), an observational, longitudinal and prospective cohort study in a target population of healthy subjects based in Jidong Oilfield (China), prospectively analyzes the outcome of phased progression of atherosclerosis by non-contrast computed tomography in healthy population. The results of this study …

A Nested Environmental Approach To Typhoid Epidemiology In Central Division, Fiji, Aaron Jenkins

Theses: Doctorates and Masters

Many current disease threats involve interactions within and between nested subsystems of biological organisation. Typhoid fever is a serious disease threat in the South Pacific region, with Fiji reporting the highest annual number of cases, yet risk factors in this setting have been poorly studied. While localised behaviours have dominated perspectives on typhoid transmission, interactions between distal ecological conditions, conditions of the residential environment and localised behaviour deserve greater attention for their potential to influence transmission. This thesis demonstrates a nested approach to typhoid epidemiology using a fivefold methodology to explore how regional, river basin, residential, socio-cultural and behavioural subsystems …