Medical Sciences Commons^™

The Effects Of Vitamin B1 Analog, Benfotiamine, On The Prevention Of Non-Small Cell Lung Cancer, Emely Fernandez, Hannah Christensen, Kota A. Ramana

Annual Research Symposium

No abstract provided.

H2s, Sg-1002, Protects Against Myocardial Oxidative Damage And Hypertrophy In Vitro Via Induction Of Cystathionine Β-Synthase And Antioxidant Proteins, Rahib K. Islam, Erinn Donnelly, Erminia Donnarumma, Fokhrul Hossain, Jason D. Gardner, Kazi N. Islam

School of Medicine Faculty Publications

Endogenously produced hydrogen sulfide (H2S) is critical for cardiovascular homeostasis. Therapeutic strategies aimed at increasing H2S levels have proven cardioprotective in models of acute myocardial infarction (MI) and heart failure (HF). The present study was undertaken to investigate the effects of a novel H2S prodrug, SG-1002, on stress induced hypertrophic signaling in murine HL-1 cardiac muscle cells. Treatment of HL-1 cells with SG-1002 under serum starvation without or with H2O2 increased the levels of H2S, H2S producing enzyme, and cystathionine β-synthase (CBS), as well as antioxidant protein levels, such as super oxide dismutase1 (SOD1) and catalase, and additionally decreased oxidative …

Conditioned Place Avoidance Is Associated With A Distinct Hippocampal Phenotype, Partly Preserved Pattern Separation, And Reduced Reactive Oxygen Species Production After Stress, D. Parker Kelley, Lucas Albrechet-Souza, Shealan Cruise, Rajani Maiya, Aspasia Destouni, Siva S.V.P. Sakamuri, Alexander Duplooy, Meghan Hibicke, Charles Nichols, Prasad V.G. Katakam, Nicholas W. Gilpin, Joseph Francis

School of Medicine Faculty Publications

Stress is associated with contextual memory deficits, which may mediate avoidance of trauma-associated contexts in posttraumatic stress disorder. These deficits may emerge from impaired pattern separation, the independent representation of similar experiences by the dentate gyrus-Cornu Ammonis 3 (DG-CA3) circuit of the dorsal hippocampus, which allows for appropriate behavioral responses to specific environmental stimuli. Neurogenesis in the DG is controlled by mitochondrial reactive oxygen species (ROS) production, and may contribute to pattern separation. In Experiment 1, we performed RNA sequencing of the dorsal hippocampus 16 days after stress in rats that either develop conditioned place avoidance to a predator urine-associated …

Endogenous Mirna-Based Innate-Immunity Against Sars-Cov-2 Invasion Of The Brain, Walter J. Lukiw, Aileen I. Pogue

School of Medicine Faculty Publications

The severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19, possesses an unusually large positive-sense, single-stranded viral RNA (ssvRNA) genome of about ~29,903 nucleotides (nt). In many respects, this ssvRNA resembles a very large, polycistronic messenger RNA (mRNA) possessing a 5′-methyl cap (m7GpppN), a 3′- and 5′-untranslated region (3′-UTR, 5′-UTR), and a poly-adenylated (poly-A+) tail. As such, the SARS-CoV-2 ssvRNA is susceptible to targeting by small non-coding RNA (sncRNA) and/or microRNA (miRNA), as well as neutralization and/or inhibition of its infectivity via the human body’s natural complement of about ~2650 miRNA species. Depending on host cell and tissue …

Molecular Characteristics Of Periodontal Health: Collagens: Defining The Healthy Human Gingival Collagen Transcriptome, Christina Zachariadou, Thomas Hart, Deborah Hooper, Angelo Mariotti

School of Dentistry Faculty Publications

Background: Defining periodontal health has been an ambitious and complex goal. The numerous and varied definitions of what constitutes periodontal health have resulted in a collection of subjective and unreliable clinical findings to diagnose and classify periodontal health and disease. The aim of this study was to fundamentally delineate the molecular characteristics of healthy periodontal tissues in men and women as they age, using the most abundant connective tissue component: Collagens. Methods: Healthy gingival biopsies were separated into “young” (aged 18–35 years, five men/five women) and “old” (≥60 years, five men/four women) age groups depending on biological sex. RNA was …

Inhibition Of Ribosome Assembly Factor Pno1 By Crispr/Cas9 Technique Suppresses Lung Adenocarcinoma And Notch Pathway: Clinical Application, Sanjit K. Roy, Shivam Srivastava, Andrew Hancock, Anju Shrivastava, Jason Morvant, Sharmila Shankar, Rakesh K. Srivastava

School of Medicine Faculty Publications

Growth is crucially controlled by the functional ribosomes available in cells. To meet the enhanced energy demand, cancer cells re-wire and increase their ribosome biogenesis. The RNA-binding protein PNO1, a ribosome assembly factor, plays an essential role in ribosome biogenesis. The purpose of this study was to examine whether PNO1 can be used as a biomarker for lung adenocarcinoma and also examine the molecular mechanisms by which PNO1 knockdown by CRISPR/Cas9 inhibited growth and epithelial–mesenchymal transition (EMT). The expression of PNO1 was significantly higher in lung adenocarcinoma compared to normal lung tissues. PNO1 expression in lung adenocarcinoma patients increased with …

Mitochondria As Causes Of And Therapeutic Targets In Chronic Post-Sepsis Skeletal Muscle Weakness, Meagan Scott Kingren

Theses and Dissertations--Pharmacology and Nutritional Sciences

Sepsis, or the organ damage that ensues after the body fails to properly contain a local infection, is the leading cause of in-patient hospitalization in the United States. Advances in critical care medicine over the last 20 years have enabled most sepsis patients to survive the life-threatening dysregulated immune response. However, a majority of survivors report chronic weakness and fatigue years after sepsis, and the cause of this weakness remains largely unknown. This dissertation work focused first on elucidating the major causes of post-sepsis muscle weakness (Aim 1). This aim involved a time-course study to determine when muscle weakness was …

Parental Instincts: The Neurological And Biological Factors Associated With Parenthood, Jared Reeder

Undergraduate Honors Theses

The following project involves a systematic review of the scientific literature on neural and biological changes of mothers and fathers in parenthood. Until very recently, little scientific research was devoted to studying how bearing children affects a man or woman’s long-term biology. Over the last twenty years, studies of neuroplastic changes in new mothers show specific neural mechanisms responsible for altering the behaviors of mothers during and after pregnancy. These changes in neuroplasticity alter behavior in such a way that led to mothers requiring less sleep and being more prone to hearing the cries of their children. In addition to …

Multi-Ancestry Genome-Wide Association Analyses Improve Resolution Of Genes And Pathways Influencing Lung Function And Chronic Obstructive Pulmonary Disease Risk, Nick Shrine, Abril G. Izquierdo, Jing Chen, Richard Packer, Robert J. Hall, Anna L. Guyatt, Chiara Batini, Rebecca J. Thompson, Chandan Puvuluri, Vidhi Malik, Brian D. Hobbs, Matthew Moll, Wonji Kim, Ruth Tal-Singer, Per Bakke, Katherine A. Fawcett, Catherine John, Kayesha Coley, Noemi Nicole Piga, Sinjini Sikdar, Martin D. Tobin, Et Al.

Mathematics & Statistics Faculty Publications

Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of …

High Energy Blue Light Induces Oxidative Stress And Retinal Cell Apoptosis, Jessica Malinsky

Capstone Showcase

Blue light (BL) is a high energy, short wavelength spanning 400 to 500 nm. Found in technological and environmental forms, BL has been shown to induce photochemical damage of the retina by reactive oxygen species (ROS) production. Excess ROS leads to oxidative stress, which disrupts retinal mitochondrial structure and function. As mitochondria amply occupy photoreceptors, they also contribute to oxidative stress due to their selectively significant absorption of BL at 400 to 500 nm. ROS generation that induces oxidative stress subsequently promotes retinal mitochondrial apoptosis. BL filtering and preventative mechanisms have been suggested to improve or repair BL-induced retinal damage, …

Proposing An Rna Interference (Rnai)-Based Treatment For Human Immunodeficiency Virus (Hiv) By Analyzing The Post-Transcriptional Gene Targeting Of Sars-Cov-2, Hepatitis C Virus, And A549 Lung Cancer Cells, Arjun Jagdeesh

Undergraduate Research Posters

Human Immunodeficiency Virus (HIV) is a retrovirus that infects CD4+ T cell lymphocytes in humans, leading to the development of Acquired Immunodeficiency Syndrome (AIDS) if left untreated. While current treatment methods, including antiretroviral combination treatments, effectively limit HIV replication, HIV can evade these treatments due to its high mutation rate. Long-term antiretroviral treatment can also be toxic to patients, meaning patients would benefit from a new mechanism of HIV treatment. RNA interference (RNAi) is an antiviral pathway found in mammals, plants, and insects that involves a small-interfering RNA that is incorporated into a protein complex called the RNA-induced Silencing Complex …

Exploring The Efficacy Of Mir-33 Antagonism In Promoting Regression Of Intracranial Atherosclerosis In A Nonhuman Primate Model, Peter Hecker

Theses and Dissertations--Pharmacology and Nutritional Sciences

Atherosclerosis, characterized by lipid accumulation and arterial inflammation, is a major contributor to global morbidity and mortality. Despite significant progress in understanding atherosclerosis in extracranial arteries, the study of intracranial atherosclerosis (ICAS) has been relatively neglected, despite its crucial role in stroke and vascular cognitive impairment. Challenges related to ICAS, including its location within the cranium and limited availability of suitable animal models, have hindered research progress in this area. Although nonhuman primates (NHPs) are commonly used for studying extracranial atherosclerosis, a comprehensive understanding of ICAS pathophysiology in these animals is lacking. By subjecting NHPs to a high-fat/cholesterol diet, we …

Medical Professionals’ Perspective On Safety And Efficacy Of Early Mobilization In Acute Heart Failure Patients, Kevin Triangto, Febrian M. Santausa, Basuni Radi, Bambang Budi Siswanto

Journal of the Hong Kong College of Cardiology

Acute heart failure (HF) patients most of the time presents with hemodynamic instability, which often leads to prolonged bedrest. Newer studies had shown that early mobilization for HF patients would lead to better outcomes. However, the early mobilization practice has not always been done due to several barriers in the medical professionals’ perspective, especially regarding safety and efficacy. Prior studies had shown that medical professionals’ views would greatly affect patients’ perspectives, especially in HF rehabilitation. This study is aimed to describe medical professionals’ views on the safety of early mobilization for HF. It was then revealed that General Practitioners’ (GP) …

Role Of Adenylyl Cyclase Type 7 In Functions Of Bv-2 Microglia, Yawen Hu, Rebecca A. Hill, Masami Yoshimura

School of Medicine Faculty Publications

To assess the role of adenylyl cyclase type 7 (AC7) in microglia’s immune function, we generated AC7 gene knockout (AC7 KO) clones from a mouse microglial cell line, BV-2, using the CRISPR-Cas9 gene editing system. The ability of BV-2 cells to generate cAMP and their innate immune functions were examined in the presence or absence of ethanol. The parental BV-2 cells showed robust cAMP production when stimulated with prostaglandin-E1 (PGE1) and ethanol increased cAMP production in a dose-dependent manner. AC7 KO clones of BV-2 cells showed diminished and ethanol-insensitive cAMP production. The phagocytic activity of the parental BV-2 cells was …

Therapies For Mitochondrial Disorders, Kayli Sousa Smyth, Anne Mulvihill

SURE Journal: Science Undergraduate Research Experience Journal

Mitochondria are cytoplasmic, double-membrane organelles that synthesise adenosine triphosphate (ATP). Mitochondria contain their own genome, mitochondrial DNA (mtDNA), which is maternally inherited from the oocyte. Mitochondrial proteins are encoded by either nuclear DNA (nDNA) or mtDNA, and both code for proteins forming the mitochondrial oxidative phosphorylation (OXPHOS) complexes of the respiratory chain. These complexes form a chain that allows the passage of electrons down the electron transport chain (ETC) through a proton motive force, creating ATP from adenosine diphosphate (ADP). This study aims to explore current and prospective therapies for mitochondrial disorders (MTDS). MTDS are clinical syndromes coupled with abnormalities …

Preventing Clabsi In Bedside Nursing, Ashlyn Winegarner

Symposium of Student Scholars

Abstract

Central line associated blood stream infections, better known as CLASBIs, are a prominent problem in the hospital setting. Due to the direct connection between the blood stream and the outside world, these catheters are at great risk for growing infections that can spread to the bloodstream within hours. Research has been done on how compliant registered nurses are in regards to keeping these catheters sterile. A survey was conducted on one hundred and seventy-one nurses that concluded only seventy percent of the nurses were compliant in following the proper central line protocol. Another study was performed that introduced five …

Autopsy V. Virtopsy: A New Approach For Postmortem Forensic Examination, Nicole Elaine Lawson

Honors Projects

Virtopsy as a potential new standard in forensic science investigation in the place of a conventional autopsy. In recent years there have been new advancements across the forensic field and in the scientific world as a whole. These advancements have changed many approaches bringing new capabilities and new challenges and pushback. This report takes a specific interest in the evolution of forensic autopsy. With improvements such as magnetic resonance imaging (MRI), computed tomography scan (CT), X-Rays, and other approaches a new term and technique have been coined Virtopsy. As this new potential approach has come to light the resistance against …

Examining The Effects Of Npra Antagonist Anantin On Sci-Induced Ployuria., Lindsey Zipperer

Electronic Theses and Dissertations

Polyuria, or the over production of urine, is a prevalent condition that significantly impacts the quality of life in individuals suffering from a spinal cord injury (SCI). Post-SCI induced polyuria is thought to have been associated with altered levels of vasopressin (AVP), atrial natriuretic peptide (ANP), and natriuretic peptide receptor A (NPRA). In the present study, the function of NPRA was analyzed in the rat contusion model using anantin, an NPRA antagonist. A daily dose of either 100 µg of anantin or vehicle was administered intraperitoneally immediately following the SCI surgery and continued until termination, 4 weeks post injury (wpi). …

Impact Of Alcohol On Bone Health In People Living With Hiv: Integrating Clinical Data From Serum Bone Markers With Morphometric Analysis In A Non-Human Primate Model, Alexandra Denys, Allison Norman, Daniel S. Perrien, Larry J. Suva, Liz Simon, Lee S. Mcdaniel, Tekeda Ferguson, Kim Pedersen, David Welsh, Patricia E. Molina, Martin J.J. Ronis

School of Medicine Faculty Publications

People living with HIV (PLWH) represent a vulnerable population to adverse musculoskeletal outcomes due to HIV infection, antiretroviral therapy (ART), and at-risk alcohol use. Developing measures to prevent skeletal degeneration in this group requires a grasp of the relationship between alcohol use and low bone mass in both the PLWH population and its constituents as defined by sex, age, and race. We examined the association of alcohol use with serum biochemical markers of bone health in a diverse cohort of PLWH enrolled in the New Orleans Alcohol Use in HIV (NOAH) study. To explore the effects of alcohol on bone …

Detailing The Effects Of Cbd On Parp And Survivin Expression In Ewing Sarcoma, Tyler Carter

Theses

Ewing sarcoma (ES) is an aggressive pediatric bone cancer with low five-year survival rates, particularly with recurrent disease because ES often becomes resistant to chemotherapy in these recurrences. Cannabidiol (CBD) has been identified as a potentially promising therapeutic for patients with ES. In other cancer types, CBD has demonstrated effects on two major proteins that contribute to chemotherapy resistance. The first, Poly (ADP-ribose) Polymerase I (PARP1), is a DNA damage repair enzyme that is overexpressed in recurrent ES. Though chemotherapy induces DNA damage in these cancer cells, the high levels of PARP1 facilitate repair of the DNA, allowing the mutated …

Role Of Decorin At The Fetal-Maternal Interface, Chidambra D. Halari

Electronic Thesis and Dissertation Repository

The human placenta is an invasive tumor-like structure, this invasion being physiological. A subset of placental trophoblast called extra-villous trophoblast invades the uterine decidua and remodels uterine arteries into low-resistance, high-flow tubes to permit adequate flow of maternal blood to nourish the fetus. A poor extra-villous trophoblast invasion and uterine arterial remodeling can lead to fetal growth restriction and a serious pregnancy-associated maternal disease preeclampsia. Decorin, a leucine-rich proteoglycan produced by uterine decidual cells restrains multiple trophoblast functions: self-renewal and differentiation of trophoblast stem cells, migration, invasion, proliferation and endovascular differentiation. Additionally, decidual overproduction of decorin was associated with preeclampsia, …

Rapid Changes In Vascular Compliance Contribute To Cerebrovascular ​Adjustments During Vasovagal Syncope (Vvs), Aleena Sajid

Undergraduate Student Research Internships Conference

Background: The rapid reduction in arterial pressure (AP) during VVS is associated with a decline in diastolic cerebral blood velocity (CBV) and maintained systolic CBV. We tested the hypothesis that this response may represent increased cerebrovascular compliance (Ci) in the presence of rapid hypotension.

Methods: AP and CBV were recorded from 14 otherwise healthy patients (34 ± 11 years) at rest and during head-up tilt (80°, 5-28 min). Baseline, mid-tilt, and VVS were analyzed. Individual AP and CBV waveforms were input into a modified Windkessel model to calculate Ci.

Results: Upright posture resulted in a decrease in CBV (-9 ± …

Rna Isolation In Duchenne Muscular Dystrophy (Dmd) Mice Models, Salem Abu Al-Burak

Undergraduate Student Research Internships Conference

Fibrosis is a progressive and typically irreversible disease process characterized by the excessive deposition of collagen in organs and in tissues of the musculoskeletal (MSK) system^1,2. This process, which causes loss of organ and tissue function, can be initiated by micro-traumas³, an excessive and/or prolonged immune response¹, the activation and proliferation of fibrosis-inducing progenitor cells⁴, and a pro-fibrotic extra-cellular microenvironment⁵. In parallel with the events that initiate fibrosis, genetic or environmental influences may cause cells and tissues to become predisposed to fibrosis development prior to initiation. This suggests that these …

The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia

Dissertations & Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with dismal prognosis. The only curative option for patients is surgery, but over 80% of patients are not surgical candidates. Unfortunately, PDAC is resistant to the three remaining options. PDAC is characterized by a profoundly hypoxic and immunosuppressive stroma, which contributes to its therapeutic recalcitrance. Alpha-smooth muscle actin+ (αSMA+) cancer-associated fibroblasts (CAFs) are the most abundant stromal component, as well as mediators of stromal deposition. The hypoxia-inducible factors (HIF1 and HIF2) coordinate responses to hypoxia, yet, despite their known association to poor patient outcomes, their functions within the PDAC tumor microenvironment (TME) …

Real-World Third Covid-19 Vaccine Dosing And Antibody Response In Patients With Hematologic Malignancies, Michael A. Thompson, Sigrun Hallmeyer, Veronica E. Fitzpatrick, Yunqi Liao, Michael P. Mullane, Stephen C. Medlin, Kenneth Copeland, James L. Weese

Journal of Patient-Centered Research and Reviews

Purpose: This study sought to describe the changes in immune response to a third dose of either Pfizer’s or Moderna’s COVID-19 mRNA vaccine (3V) among patients with hematologic malignancies, as well as associated characteristics

Methods: This retrospective cohort study analyzed pre-3V and post-3V data on 493 patients diagnosed with hematologic malignancies across a large Midwestern health system between August 28, 2021, and November 1, 2021. For antibody testing, S1 spike antigen of the SARS-CoV-2 virus titer was used to determine serostatus.

Results: Among 493 participants, 274 (55.6%) were seropositive both pre- and post-3V (+/+) while 115 (23.3%) seroconverted to positive …

Heart To Heart, Mom To Mom, Karis L. Tekwani

Journal of Patient-Centered Research and Reviews

This essay describes the human connection forged between two young moms, one the physician and one the patient, when their paths collided one night in the emergency department of a busy hospital. It describes a challenging and most memorable care experience in the career of a young emergency physician, the clinical outcome, and the patient’s appreciative follow-up message years later.

Evaluation Of Neonatal Ankyloglossia, Ellen M. Ray

Dissertations

Problem Ankyloglossia occurs when the tongue cannot extend past the gums or lips due to frenulum restriction. In breast feeding, proper movement of the tongue around the nipple is hindered causing difficulty for the infant to obtain a proper latch. This may result in slow weight gain (SWG), failure to thrive (FTT), and dehydration due to poor milk production. Evaluating for ankyloglossia is difficult, however, the Hazelbaker Ankyloglossia Tool for Lingual Frenulum Function (HATLFF) may be of benefit.

Method Observational descriptive design utilizing a retrospective medical record review. The HATLFF was utilized in full term neonates suspected of ankyloglossia in …

Pathophysiology Of Aortic Stenosis, Melissa Lee

Nursing Student Class Projects (Formerly MSN)

Pathophysiology of Aortic Stenosis

Melissa J. Lee

Department of Nursing, Otterbein University

NURS 6810: Advanced Pathophysiology for the Advanced Practice Nurse

Dr. Deana Batross & Dr. Shivani Bhatnagar

July 29, 2022

Pathophysiology of Aortic Stenosis

Proper evaluation of co-morbidities is imperative for patient safety and successful outcomes for patients undergoing anesthesia. Aortic stenosis (AS) is one of the most complex diseases encountered in anesthesia, affecting five percent of older adults and ten percent of the 80-89-year-old-cohort (Joseph et al., 2017). The pathophysiological development of AS is the end result of an inflammatory process caused by endothelial damage from mechanical stress, …

Perioperative Risks Of The Patient With Heart Failure, Gabrielle Metoyer

Nursing Student Class Projects (Formerly MSN)

Perioperative Risks of the Patient with Heart Failure

Gabrielle Metoyer

Department of Nursing, Otterbein University

NURS 6810 – Advanced Pathophysiology

Dr. Deanna Batross and Dr. Shivani Bhatnagar

August 5, 2022

Abstract

According to the CDC (2020), heart failure occurs when the heart cannot pump enough blood and oxygen to support other organs in your body. Heart failure is an epidemic disease affecting 1-2% of the population worldwide (Schwinger, 2020). It is one of the leading causes of morbidity and mortality worldwide with an estimated 6.5 million adults with heart failure in the United States (Lo et al., 2021). Medical advances …

Primary Cilia Of The Cardiac Neural Crest & Hedgehog-Mediated Mechanisms Of Congenital Heart Disease, Lindsey A. Fitzsimons

Electronic Theses and Dissertations

Elimination of primary cilia in cardiac neural crest cell (CNCC) progenitors is hypothesized to cause a variety of congenital heart defects (CHDs), including atrioventricular septal defects, and malformations of the developing cardiac outflow tract. We present an in vivo model of CHD resulting from the conditional elimination of primary cilia from CNCC using multiple, Wnt1:Cre-loxP, neural crest-specific systems, targeting two distinctive, but critical, primary cilia structural genes: Intraflagellar transport protein 88 (Ift88) or kinesin family member 3A (Kif3a). CNCC loss of primary cilia leads to widespread CHD, where homozygous mutant embryos (MUT) display a variety of outflow tract malformations, septation …