Medicine and Health Sciences Commons^™

Using S. Pombe To Study The Biological Roles Of The Histone Deacetylases Sir2 And Clr3 And The Dead-Box Rna Helicase Ded1, Brandon Ray Lowe

Theses and Dissertations (ETD)

The fission yeast Schizosaccharomyces pombe provides a good model system to quickly study basic mechanisms underlying biological pathways conserved in higher eukaryotes. Here we utilized fission yeast to study the roles of the histone deacetylases (HDACs) Sir2 and Clr3 in heterochromatin formation and cancer associated mutations of the DEAD-box RNA helicase DDX3X, homolog of fission yeast Ded1, in translational control. Heterochromatin in fission yeast is characterized by hypoacetylation as well as methylation of histone H3 on lysine 9 (H3K9me). Heterochromatin assembly can now be separated into three distinct steps: heterochromatin establishment, spreading, and maintenance. These steps involve the actions of …

A Novel Role For Osteopontin In Facilitating West Nile Virus Neuroinvasion, Amber M. Paul

Dissertations

West Nile virus (WNV) is a positive-sensed, single-stranded RNA flavivirus that can cause human neuroinvasive diseases, including encephalitis, meningitis, and flaccid paralysis. The mechanisms by which WNV enters the central nervous system and the host-factors that are involved in WNV-neuroinvasiveness are not completely understood. Osteopontin (OPN), a multifunctional glycoprotein, has been implicated as a bio-marker for a number of neuroinflammatory diseases. In particular, secreted (s)OPN has been implicated to participate in recruitment of polymorphonuclear neutrophils (PMN) to sites of its expression, while PMNs have been suggested to act as WNV reservoirs. Therefore, sOPN recruitment of PMNs may contribute to neuroinvasive …

An Exploratory Study Of The Utilization Of Evidence-Based Pharmacological Treatment On Heart Failure Patients In Mississippi And Its Impact On Readmission, Keri A. Barron

Dissertations

The purpose of this study was to explore the relationship of adherence to evidence-based guidelines for pharmacologic management by select Mississippi hospitals and their hospital readmission rates. This was an exploratory study with a retrospective design. This design offered insight into the relationship between readmissions of heart failure patients and adherence to the national guidelines for the pharmacologic treatment of heart failure. The study took place in a hospital in the southeastern section of the United States. Data were collected from a database of patients with heart failure seen between January 2011 and June 2014.

The unit of analysis for …

Study Of Rickettsia Parkeri Colonization And Proliferation In The Tick Host Amblyomma Maculatum (Acari: Ixodidae), Khemraj Budachetri

Dissertations

Amblyomma maculatum (Gulf coast tick) ticks are prevalent across the Atlantic to Gulf Coast region of United States. These ticks are recognized vectors of Rickettsia parkeri, a spotted fever group of Rickettsia (SFGR) known to cause American boutonneuse fever associated with fever and eschar rashes localized to the site of bites. We hypothesized that Rickettsia parkeri colonization and proliferation in the tick vector involve pathogen-symbiont dynamics and tick-pathogen interactions, which influence rickettsial transmission to the victims after tick bites. The rickettsial infection is maintained across the tick life cycle for many generations due to transovarial and transstadial transmission of …

Therapeutic Effects Of Ormeloxifene In Cervical Cancer Carcinogenesis, Neeraj Chauhan

Theses and Dissertations (ETD)

Cervical cancer (CxCa) remains the fourth leading cause of cancer related deaths among women worldwide. Cervical cancer is mainly (~ 99.7%) derived from high risk Human papillomavirus (HR HPV). HPV E6/E7 are the two main oncoproteins that interfere with p53 and pRb (retinoblastoma) cell cycle regulatory proteins and hinder their efficacy of controlling cell growth. Additionally, PI3K-Akt is a cell survival pathway that is aberrantly expressed in cervical cancer cells. This pathway has a profound role in inhibiting mitochondrial intrinsic apoptotic signaling pathway. Advanced stage cervical cancer is difficult to treat and patients diagnosed with metastatic disease have a poor …

Role Of Dendritic Cells In Pathology Of Respiratory Syncytial Virus Infection In Neonates, Bishwas Shrestha

Theses and Dissertations (ETD)

Respiratory syncytial virus (RSV) is one of the leading causes of bronchiolitis in children. We have shown that neonatal mice respond to primary RSV infection with T helper type 2 (Th2) biased immune responses, which are enhanced following reinfection. Dendritic cells (DCs) including myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) play important roles in driving host responses to RSV infection. mDCs present antigens to help Th cells differentiate, and pDCs protect against viral infection through type I interferons (IFNs). Despite data demonstrating importance of mDCs and pDCs in protection against RSV, it has not been studied in an age appropriate …

A Variant Pfcrt Isoform Can Contribute To Plasmodium Falciparum Resistance To The First-Line Partner Drug Piperaquine, Satish K. Dhingra, Devasha Redhi, Jill M. Combrinck, Tomas Yeo, John Okombo, Philipp P. Henrich, Annie N. Cowell, Purva Gupta, Matthew L. Stegman, Jonathan M. Hoke, Roland A. Cooper, Elizabeth Winzeler, Sachel Mok, Timothy J. Egan, David A. Fidock

Biological Sciences Faculty Publications

Current efforts to reduce the global burden of malaria are threatened by the rapid spread throughout Asia of Plasmodium falciparum resistance to artemisinin-based combination therapies, which includes increasing rates of clinical failure with dihydroartemisinin plus piperaquine (PPQ) in Cambodia. Using zinc finger nuclease-based gene editing, we report that addition of the C101F mutation to the chloroquine (CQ) resistance-conferring PfCRT Dd2 isoform common to Asia can confer PPQ resistance to cultured parasites. Resistance was demonstrated as significantly higher PPQ concentrations causing 90% inhibition of parasite growth (IC₉₀) or 50% parasite killing (50% lethal dose [LD₅₀]). This mutation …

A Quality Improvement Project To Improve Blood Specimen Acceptance Rates In An Emergency Department, Christian Hankins

DNP Projects

Purpose: The purpose of this project was to implement a quality improvement project to improve blood specimen acceptance rates at a specific Emergency Department (ED) using strategies to enhance knowledge, improve motivation, and reinforce skill. Background: Specimen acceptance rates continue to fall outside of the recommended target rate of 98% or higher at a specific ED. In this particular ED, the responsibility for specimen collection has shifted away from phlebotomists and towards nurses, many of whom have received little to no phlebotomy training. Without proper blood collection techniques, specimens are more likely to be rejected, and re-collection of rejected blood …

Parp Inhibitor Upregulates Pd-L1 Expression And Enhances Cancer-Associated Immunosuppression, Shiping Jiao

Dissertations and Theses (Open Access)

With recent approvals for therapeutic antibodies that block CTLA4, PD-1 and PD-L1, immune checkpoints have emerged as new targets in cancer therapy. In addition, there is accumulating evidence highlighting the role of cancer-associated immunity in patient response to cytotoxic anticancer agents. Inhibitors of poly (ADP-ribose) polymerase (PARP) have shown substantial cytotoxic effects against tumors with defects in DNA damage responses. However, whether a crosstalk between PARP inhibition and immune checkpoints exists remains unclear. Here, it has been shown that PARP inhibitors (PARPis) upregulate PD-L1 expression in multiple cancer cell lines, human xenograft tumors, and syngeneic mouse tumors. Mechanistically, PARPi inactivates …

Integrative Analysis Of Omics Data In Adult Glioma And Other Tcga Cancers To Guide Precision Medicine, Xin Hu, Xin Hu

Dissertations and Theses (Open Access)

Transcriptomic profiling and gene expression signatures have been widely applied as effective approaches for enhancing the molecular classification, diagnosis, prognosis or prediction of therapeutic response towards personalized therapy for cancer patients. Thanks to modern genome-wide profiling technology, scientists are able to build engines leveraging massive genomic variations and integrating with clinical data to identify “at risk” individuals for the sake of prevention, diagnosis and therapeutic interventions. In my graduate work for my Ph.D. thesis, I have investigated genomic sequencing data mining to comprehensively characterise molecular classifications and aberrant genomic events associated with clinical prognosis and treatment response, through applying high-dimensional …

Androgen Receptor And Prostate Cancer Cell Heterogeneity, Qu Deng

Dissertations and Theses (Open Access)

Androgen receptor (AR) plays an important role in prostate cancer (PCa) development and has been the main therapeutic target in advanced PCa. AR expression is heterogeneous in both primary PCa and castration resistant prostate cancer (CRPC). However, the functional significance of AR heterogeneity in regulating PCa biology and response to androgen/AR-targeted therapies remains unclear. The overarching hypothesis for my Ph.D is that AR heterogeneity contributes to PCa development, progression, and therapy resistance. A more specific postulate is that PCa cells expressing AR (i.e, AR⁺) and PCa cells expressing little AR (i.e, AR^-/lo) possess intrinsically distinct …

Economic Assessment Of A Highly Pathogenic Avian Influenza Outbreak In Washington And Benton Counties In Arkansas, Antonio Beitia

Graduate Theses and Dissertations

Highly Pathogenic Avian Influenza (HPAI) presents a substantial economic risk to the poultry industry. Domesticated fowl contract HPAI initially through exposure, direct or indirect with migratory waterfowl and outbreaks can result in significant economic losses to growers and the poultry industry at large. A HPAI outbreak occurred in Minnesota and Iowa and spread across over 13 other states in 2014 and 2015. This caused an estimated $1.6 billion in losses (CDC, 2016) and led to shortages of eggs and turkeys together with elevated prices (Anni et al. 2005). Even small outbreaks of HPAI inflict substantial damages as USDA-APHIS guidelines necessitate …

Effect Of Cannabinoids On Osteogenic Differentiation Of Cultured Vascular Smooth Muscle Cells, Bree A. Eccles

Undergraduate Honors Theses

Vascular calcification is strongly correlated with the clinical manifestations of atherosclerosis, heart attacks and strokes. The calcification process resembles bone formation and involves the osteogenic trans-differentiation of smooth muscles cells within the arterial wall. Cannabinoid receptors are known to modulate bone formation and are present in atherosclerotic vessels, suggesting they may also play a role in modulating calcification. Therefore, we evaluated the effects of cannabinoids on the expression of osteogenic proteins by vascular smooth muscle cells undergoing calcification.

Knowledge And Awareness Regarding Cervical Cancer And Uptake Of Pap Smear Among Women In Karachi, Pakistan, Shama Razzaq, Sayeeda Amber Sayed Amber Sayeeda Amber Sayed, Sumera Aziz Ali

Community Health Sciences

Objective: To determine the knowledge regarding cervical cancer, its symptoms and risk factors among women of 18 years and above attending the gynecology OPD in two public hospitals Karachi, Pakistan.
Methodology: A cross-sectional survey was held from February to June 2013 in Karachi, Pakistan. 384 females aged 18 years and above attending gynecology clinics in two public sector hospitals were taken through non-probability sampling method. The knowledge was assessed using a point scale method which had binary response i.e. correct and incorrect. A score of 50% (≥ 11 correct responses) was considered as optimum knowledge.
Results: Overall knowledge of cervical …

Dox Inducible Idh2 R140q Expression In Stem Cells Results In Cell Death, Opposite Of Cancerous Overgrowth, Reuben Hogan

Undergraduate Research Symposium Posters

Mutations in isocitrate dehydrogenase (IDH) 1 or 2 are found in about 23% of acute myeloid leukemia (AML) samples and about 90% of gliomas. Mutations result in neomorphic function of the IDH enzyme that yields the novel molecule 2-hydroxyglutarate (2HG) instead of alpha-ketoglutarate (aKG). 2HG is known to be associated with hypermethylation of DNA and histones, a phenotype seen in AML. Our lab intends to study the mechanism by which hypermethylation is achieved and how this mechanism relates to the onset of cancer. In this experiment, we utilized a line of H9 stem cells which we had developed. These cells …

Annual Wormwood Leaf Inhibits The Adipogenesis Of 3t3-L1 And Obesity In High-Fat Diet-Induced Obese Rats, Y Song, S Lee, S Jang, T Kim, Hong-Duck Kim, S Kim, C Won, J Cho

NYMC Faculty Publications

Annual wormwood (AW) (Artemisia annua L.) has anti-malarial, anti-bacterial, anti-oxidant, anti-tumour, and anti-inflammatory activities. In the present study, we evaluated the effects of annual wormwood leaves (AWL) on adipocyte differentiation in 3T3-L1 cells and high-fat diet (HFD)-induced obese rats. 3T3-L1 adipocytes and HFD-induced obese rats were treated with AWL, and its effect on gene expression was analyzed using RT-PCR and Western blotting experiments. Treatment with AWL effectively prevented triglyceride accumulation during adipogenesis in a dose-dependent manner. Consistently, AWL suppressed the differentiation of 3T3-L1 preadipocytes into adipocytes through the downregulation of dexamethasone, 3-isobutyl-1- methylxanthine, and insulin (DMI)-induced serine/threonine kinase protein kinase …

The Msaabcr Operon Mutant Staphylococcus Aureus Is Deficient In Persister Cells, Aaliyah D. Cole

Honors Theses

Persister cells comprise a phenotypic variant that shows extreme antibiotic tolerance resulting in chronic infections. While this phenomenon has posed a great threat in public health, mechanism underlying their formation in Staphylococcus aureus remains largely unknown. Increasing evidence of the presence of persister cells in recalcitrant infections underscores the great urgency to unravel the mechanism by which these cells are developed. The Elasri Research group characterized msaABCR operon that plays roles in regulation of virulence, biofilm development and antibiotic resistance. It was hypothesized that the operon also plays a role in persister cell formation. In this study, the persister cell …

Ophthalmic Manifestations Of Congenital Zika Syndrome In Colombia And Venezuela, Juan B. Yepez, Felipe A. Murati, Michele Petitto, Carlos F. Peñaranda, J. Fernando Arevalo, Gladys E. Maestre

School of Medicine Publications

IMPORTANCE The ocular manifestations and sequelae of Zika virus infection are not well known. Recently, the World Health Organization changed the declaration of Zika as a public health emergency and designated the viral outbreak and related microcephaly clusters as a long-term program of work. This change indicates the urgent need to evaluate and document ophthalmic manifestations in patients for timely management of this disease. In addition, confirmation whether the public health problem in Brazil extends to other regions in South America is needed.

OBJECTIVE To report the ocular manifestations of congenital Zika syndrome with microcephaly in Colombia and Venezuela.

DESIGN, …

Determining The Protective Effects Of Quercetin Against Cadmium Toxicity In Human Embryonic Kidney Cells, Caroline N. Smith

Undergraduate Theses

Cadmium is a toxic industrial and environmental pollutant found in groundwater, air, soils, food and cigarettes. Chronic intake of low levels of cadmium has been shown to result in renal dysfunction due to cell death which can occur via apoptosis as well as necrosis. Previous studies have shown that plant extracts containing quercetin, a flavonoid found in many fruits and vegetables, protect against cadmium toxicity in rat liver hepatocytes. To determine if quercetin may have a protective effect in a cadmium-treated human embryonic kidney cell line, HEK-293 cells were treated using concentrations of cadmium chloride from 10 to 50 μM …

A Comparative Analysis Of The West African Hemorrhagic Fevers Caused By The Lassa And Ebola Viruses, Emiene E. Amali-Adekwu

Selected Honors Theses

Lassa fever (LF) and Ebola Hemorrhagic Fever (EHF) are viral diseases endemic to West Africa.The etiological agent of Lassa fever is an enveloped virus from the Arenaviridae family and was first discovered in 1969 when two missionary nurses died of a mysterious illness in the town of Lassa in Borno state, Nigeria.1 This virus is animal-borne (zoonotic) and is carried by the animal vector Mastomys natalensis (multimammate rat). The Ebola virus is also zoonotic originating from fruit bats belonging to the Pteropodidae family.2 The first reported case of Ebola Virus Disease (EVD) was a principal who was believed to have …

Systematic Analysis Of Whole Exome Sequencing Determines Ret G691s Polymorphism As Germline Variant In Melanoma, Brent J. Smith Jr, Jennifer D. Hintzsche, Carol M. Amato, Aik-Choon Tan, Keith R. Wells, Allison J. Applegate, Rita T. Gonzalez, Jodie R. Barr, William A. Robinson

Marshall Journal of Medicine

Abstract

The RET proto-oncogene encodes a receptor tyrosine kinase that is activated by glial cell derived neutrotrophic factor (GDNF). Previous studies have found that a single nucleotide polymorphism (SNP), RETp (G691S), in the juxtamembrane domain enhances the signaling pathway and promotes tumor growth by GDNF in pancreatic and thyroid cancer in addition to melanoma. It is uncertain however whether this SNP is a germline variant or somatic mutation. A prior study reported that the RETp variant was a germline SNP in desmoplastic and non-desmoplastic melanomas. In the present study, we examined both melanoma tissue samples and matching peripheral blood DNA …

Mallampati Scoring And Its Relation To Obstructive Sleep Apnea, Austin Korczak

Honors Capstones

According to the American Sleep Apnea Association potentially 80% of moderate to severe cases of Obstructive Sleep Apnea (OSA) go undiagnosed with even optimistic estimates stating that at least 22 million Americans are afflicted by the disorder. These numbers are expected to continue to increase due to the rising rates of obesity in America. As a result, reliable criteria that can help physicians accurately predict the presence of an underlying sleep disorder, whose symptoms are masked during the day, is highly sought after. The objective of this research is to begin defining these criteria via a literature review of articles …

Colorectal Cancer Screenings In The United States, Charles Buhrman

Honors Capstones

Colorectal cancer is the second leading cancer killer in the United States behind lung cancer, so research is needed about this particular cancer (American Cancer Society, 2016). With medical advancements over the past decade, doctors are able to detect cancer symptoms earlier and treat cancers more readily. By compiling the medical record data for the Midwest and the Northeast, a picture can be painted that shows the prevalence of screenings in each region, and the mortality rates of those regions based on the amount of screenings done. The aim of this study is to examine the current colorectal cancer (CRC) …

The Malaria Testing And Treatment Landscape In Benin., Kathryn A. O'Connell, Vamsi Vasireddy, Megan Littrell, Andria Rusk, Actwatch Group, Cyprien Zinsou, Adjibabi Bello Cherifath

Collected Faculty Scholarship

BACKGROUND: Since 2004, artemisinin-based combination therapy (ACT) has been the first-line treatment for uncomplicated malaria in Benin. In 2016, a medicine outlet survey was implemented to investigate the availability, price, and market share of anti-malarial treatment and malaria diagnostics. Results provide a timely and important benchmark to measure future interventions aimed at increasing access to quality malaria case management services.

METHODS: Between July 5th to August 6th 2016, a cross sectional, nationally-representative malaria outlet survey was conducted in Benin. A census of all public and private outlets with potential to distribute malaria testing and/or treatment was implemented among 30 clusters …

Qt Prolongation Is Associated With Increased Mortality In End Stage Liver Disease, Sun Moon Kim, Bennet George, Diego Alcivar-Franco, Charles L. Campbell, Richard Charnigo, Brian P. Delisle, Jonathan Hundley, Yousef Darrat, Gustavo Morales, Samy-Claude Elayi, Alison L. Bailey

Internal Medicine Faculty Publications

AIM

To determine the prevalence of QT prolongation in a large series of end stage liver disease (ESLD) patients and its association to clinical variables and mortality.

METHODS

The QT interval was measured and corrected for heart rate for each patient, with a prolonged QT cutoff defined as QT > 450 ms for males and QT > 470 ms for females. Multiple clinical variables were evaluated including sex, age, serum sodium, international normalized ratio, creatinine, total bilirubin, beta-blocker use, Model for End-Stage Liver Disease (MELD), MELD-Na, and etiology of liver disease.

RESULTS

Among 406 ESLD patients analyzed, 207 (51.0%) had QT prolongation. …

A Mixed-Methods Study: Self-Efficacy And Barriers To Participation In Workplace Wellness Programs, Massiel Perez-Calhoon

Dissertations

America needs a healthy workforce to sustain the country. The scourge of obesity continues to plague Americans despite government initiatives such as the Affordable Care Act and wellness programs in the workplace to combat this epidemic. However, despite initiatives to make America healthy, barriers continued to impede the nation’s health. Lack of awareness and sensitivity to what motivates individual participants versus group participants built formidable barriers to accessing all workplace employees equitably. The purpose of this study was twofold. First, the intent of this study was to explore the relationship between self-efficacy and the impact on participation and engagement when …

Anti-Malarial Landscape In Myanmar: Results From A Nationally Representative Survey Among Community Health Workers And The Private Sector Outlets In 2015/2016., Kathryn A. O'Connell, Vamsi Vasireddy, Megan Littrell, Andria Rusk, Actwatch Group, Si Thu Thein, Hnin Su Su Khin, Aung Thi

Collected Faculty Scholarship

BACKGROUND: In 2015/2016, an ACTwatch outlet survey was implemented to assess the anti-malarial and malaria testing landscape in Myanmar across four domains (Eastern, Central, Coastal, Western regions). Indicators provide an important benchmark to guide Myanmar's new National Strategic Plan to eliminate malaria by 2030.

METHODS: This was a cross-sectional survey, which employed stratified cluster-random sampling across four regions in Myanmar. A census of community health workers (CHWs) and private outlets with potential to distribute malaria testing and/or treatment was conducted. An audit was completed for all anti-malarials, malaria rapid diagnostic tests.

RESULTS: A total of 28,664 outlets were approached and …

Insights Into The Availability And Distribution Of Oral Artemisinin Monotherapy In Myanmar: Evidence From A Nationally Representative Outlet Survey., Kathryn A. O'Connell, Vamsi Vasireddy, Megan Littrell, Andria Rusk, Actwatch Group, Si Thu Thein, Hnin Su Su Khin, Aung Thi

Collected Faculty Scholarship

BACKGROUND: The containment of artemisinin resistance in Myanmar, historically an important probable origin and route of anti-malarial resistance to the India sub-continent and beyond, is crucial to global malaria control and elimination. This paper describes what is currently known about the sale and distribution of oral artemisinin monotherapy (AMT) across Myanmar, where this medicine is commonly found.

METHODS: A nationally representative 2015 outlet survey was conducted in the private sector, and among community health workers across four geographical domains. A national sample of outlets was screened for availability of malaria testing and treatment, and an audit was completed for all …

What Happened To Anti-Malarial Markets After The Affordable Medicines Facility-Malaria Pilot? Trends In Act Availability, Price And Market Share From Five African Countries Under Continuation Of The Private Sector Co-Payment Mechanism., Kathryn A. O'Connell, Vamsi Vasireddy, Megan Littrell, Andria Rusk, Actwatch Group, Sarah Tougher, Kara Hanson, Catherine Goodman

Collected Faculty Scholarship

BACKGROUND: The private sector supplies anti-malarial treatment for large proportions of patients in sub-Saharan Africa. Following the large-scale piloting of the Affordable Medicines Facility-malaria (AMFm) from 2010 to 2011, a private sector co-payment mechanism (CPM) provided continuation of private sector subsidies for quality-assured artemisinin combination therapies (QAACT). This article analyses for the first time the extent to which improvements in private sector QAACT supply and distribution observed during the AMFm were maintained or intensified during continuation of the CPM through 2015 in Kenya, Madagascar, Nigeria, Tanzania and Uganda using repeat cross-sectional outlet survey data.

RESULTS: QAACT market share in all …

Evidence On Anti-Malarial And Diagnostic Markets In Cambodia To Guide Malaria Elimination Strategies And Policies, Kathryn A. O'Connell, Vamsi Vasireddy, Megan Littrell, Andria Rusk, Actwatch Group, Sochea Phok, Dysoley Lek

Collected Faculty Scholarship

BACKGROUND: Understanding Cambodia's anti-malarial and diagnostic landscape in 2015 is critical for informing and monitoring strategies and policies as Cambodia moves forward with national efforts to eliminate malaria. The aim of this paper is to present timely and key findings on the public and private sector anti-malarial and diagnostic landscape in Cambodia. This evidence can serve as a baseline benchmark for guiding implementation of national strategies as well as other regional initiatives to address malaria elimination activities.

METHODS: From August 17th to October 1st, 2015, a cross sectional, nationally-representative malaria outlet survey was conducted in Cambodia. A census of all …