Laboratory and Basic Science Research Commons^™

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

Dissertations and 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) …

Interlaboratory Comparison Of Metabolomics Analyses Of Human And Rodent Blood Using Biocrates Mxp Quant 500 Kit, Nadia Ashrafi, Ali Yilmaz, Stewart F. Graham, Thomas O'Connell, Sumeyya Akyol

Conference Presentation Abstracts

No abstract provided.

The Competitive Edge: Improving Absite Scores Through A Team-Based Approach, Sean Masters, Kathryn Howard, Darci Foote, Diane Studzinski, Rose E. Callahan, Felicia Ivascu, Begum Akay

Conference Presentation Abstracts

Introduction: A competitive team-based approach to encourage self-studying and didactic participation is a novel method of American Board of Surgery In-Training Examination (ABSITE) preparation. We aimed to determine if this method significantly improves residents’ percentile performances on the ABSITE. Methods: We reviewed ABSITE performance and preparation from general surgery residents for the last ten years. Percentile scores were compared before and after implementation of a purchased online question bank (TrueLearn LLC, Mooresville, NC), a team-based competition, and a virtual format of the team-based competition. Statistical analysis was performed with ANOVA Kruskal-Wallis and Mann Whitney tests where appropriate. Results: 378 ABSITE …

Impact Forces And Patterns Of Axonal Injury Differ Between Two Models Of Tbi, Edward Lai, David M Devilbiss

Rowan-Virtua Research Day

Traumatic brain injury (TBI) affects approximately 3.8 million Americans a year and results in complex neuropathological and neurocognitive sequelae. Animal models of TBI attempt to replicate the impact forces and pathology of injury in humans. However, in these models, the forces generated at the time of impact are poorly understood. Nonetheless, a variety of shear and strain forces generated at the time of impact can produce diffuse axonal injury. Injury to axons and neurons across a variety of brain regions resulting from axonal injury underlies the cognitive and behavioral impairments observed after TBI. Three critical brain regions, the corpus callosum …

Spontaneous Pneumomediastinum In Children Is Not Associated With Esophageal Perforation, Kevin Roby, Catherine Barkach, Diane Studzinsk, Nathan M. Novotny, Begum Akay, Pavan Brahmamdam

Conference Presentation Abstracts

Purpose: We hypothesized that esophageal perforation is not a common etiology for spontaneous pneumomediastinum (SPM), and that SPM is a self-limited disease not requiring routine admission. Methods: We performed a retrospective review of patients, ages 0 to 21 years, diagnosed with SPM in one hospital system (five hospitals) from 2009 – 2019. Cases were identified using ICD9 and 10 codes and confirmed through chart review. Cases were excluded for trauma, severe infections, or subsequent development of SPM after admission for a separate diagnosis. Data regarding patient characteristics, diagnostic tests, and outcomes were collected, and summary statistics were performed. Results: We …

Characterisation Of Drug-Resistant Mycobacterium Tuberculosis Mutations And Transmission In Pakistan, Gary Napier, Anwar Sheed Khan, Abdul Jabbar, Muhammad Tahir Khan, Sajid Ali, Muhammad Qasim, Noor Mohammad, Rumina Hasan, Zahra Hasan, Susana Campino

Department of Pathology and Laboratory Medicine

Tuberculosis, caused by Mycobacterium tuberculosis, is a high-burden disease in Pakistan, with multi-drug (MDR) and extensive-drug (XDR) resistance, complicating infection control. Whole genome sequencing (WGS) of M. tuberculosis is being used to infer lineages (strain-types), drug resistance mutations, and transmission patterns-all informing infection control and clinical decision making. Here we analyse WGS data on 535 M. tuberculosis isolates sourced across Pakistan between years 2003 and 2020, to understand the circulating strain-types and mutations related to 12 anti-TB drugs, as well as identify transmission clusters. Most isolates belonged to lineage 3 (n = 397; 74.2%) strain-types, and were MDR (n = …

The Correlation Of D-Dimer To Stroke Diagnosis Within 24 Hours: A Meta-Analysis, Adeel Ahmad, Zara Islam, Saad Manzoor Ahmad, Zouina Sarfraz, Azza Sarfraz, Miguel Felix, Ivan Cherrez-Ojeda

Department of Paediatrics and Child Health

Background: Diagnosing D-Dimer early is essential to optimize clinical treatment and quality of life and reduce mortality. This study aims to identify the difference of D-Dimer levels (ng/ml) in patients with stroke within the 6- and 24-h period compared to patients that mimic stroke.
Methods: An electronic database search across PubMed/MEDLINE, Cochrane, Web of Science, CINAHL, EMBASE, and Scopus was conducted until December 10, 2021. Studies were eligible if they included adult patients with stroke compared to stroke mimics or controls reporting D-Dimer values. Quality assessment was conducted using GRADE. The standardized mean difference and 95% confidence intervals were calculated …

A Review Of Coronaviruses Associated With Kawasaki Disease: Possible Implications For Pathogenesis Of The Multisystem Inflammatory Syndrome Associated With Covid-19, Fatima Farrukh Shahbaz, Russell Seth Martins, Abdullah Umair, Ronika Devi Ukrani, Kauser Jabeen, M Rizwan Sohail, Erum Khan

Medical College Documents

Multisystem Inflammatory Syndrome in Children (MIS-C), representing a new entity in the spectrum of manifestations of COVID-19, bears symptomatic resemblance with Kawasaki Disease (KD). This review explores the possible associations between KD and the human coronaviruses and discusses the pathophysiological similarities between KD and MIS-C and proposes implications for the pathogenesis of MIS-C in COVID-19. Since 2005, when a case-control study demonstrated the association of a strain of human coronavirus with KD, several studies have provided evidence regarding the association of different strains of the human coronaviruses with KD. Thus, the emergence of the KD-like disease MIS-C in COVID-19 may …

Lymphoma With Tuberculous Granulomas, Jyoti Mohan Lal, Anila Rashid

Department of Pathology and Laboratory Medicine

Chronic granulomatous inflammation is a common finding in lymphoproliferative disorders (LPDs), but it is important to exclude coexisting mycobacterium tuberculosis (MTB) especially in patients from areas of high endemicity. This case emphasizes the relevance of performing MTB culture on bone marrow exhibiting LPD and concomitant granulomas

Distribution Of Serotypes And Antibiotic Resistance Of Invasive Pseudomonas Aeruginosa In A Multi-Country Collection, Shamima Nasrin, Nicolas Hegerle, Shaichi Sen, Joseph Nkeze, Sunil Sen, Jasnehta Permala-Booth, Myeongjin Choi, James Sinclair, Milagritos D. Tapia, Sadia Shakoor

Department of Pathology and Laboratory Medicine

Background: Pseudomonas aeruginosa is an opportunistic pathogen that causes a wide range of acute and chronic infections and is frequently associated with healthcare-associated infections. Because of its ability to rapidly acquire resistance to antibiotics, P. aeruginosa infections are difficult to treat. Alternative strategies, such as a vaccine, are needed to prevent infections. We collected a total of 413 P. aeruginosa isolates from the blood and cerebrospinal fluid of patients from 10 countries located on 4 continents during 2005-2017 and characterized these isolates to inform vaccine development efforts. We determined the diversity and distribution of O antigen and flagellin types and …

Novel Mechanism Of Endogenous Pancreatic Cancer Cell Expression Of Immune Checkpoint Programmed Cell-Death 1 Protein (Pd-1) Inducing Epithelial-To-Mesenchymal Transition (Emt) Through The Met Pathway And Promoting Cancer Progression In An Immune-Independent Process, Megan M. Harper

Theses and Dissertations--Clinical and Translational Science

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers with few treatment options, necessitating an urgent need for novel therapeutics. Immuno-oncologic (IO) therapies have revolutionized anti-cancer regimens in the past decade but typically involve reactivation of adaptive immune responses. In particular, immune checkpoint PD-1 is traditionally expressed only on immune cells while PD-L1 (PD-1 ligand) is overexpressed on cancer cells. When tumor-endogenous PD-L1 binds the PD-1 receptor on T-cells, the immune cells undergo anergy resulting in self-tolerance and cancer cell immune evasion. However, contrary to standard dogma, we previously demonstrated tumor-endogenous PD-1 expression in PDAC. Our data indicated that …

D-Dimer Testing In Covid-19: From Basics To Clinical Application, Bushra Moiz

Department of Pathology and Laboratory Medicine

No abstract provided.

The Rotator Cuff Tendon-To-Bone Interface: Maturation, Aging, And 3d Bioprinting For Regeneration, Xiping Jiang

Theses & Dissertations

Rotator cuff tendon injuries often occur at the tendon-to-bone interface (i.e., enthesis) area with a high prevalence for the elderly population. In addition, regeneration of the gradient structure of the enthesis is still a significant clinical challenge. Our studies aim to identify the histological, molecular, and biomechanical alterations of the rotator cuff enthesis with maturation and aging, and develop a novel therapeutic method using three-dimensional (3D) bioprinting technique to regenerate a functional enthesis. Striking variations of the entheses were observed both histologically and biomechanically during the maturation process. The histological features did not show many differences at the insertion site …

The Role Of The Erbb Signaling Pathway In Cardiovascular Progenitor Cell-Based Repair, Christopher Ramos

Electronic Theses, Projects, and Dissertations

Adult mammalian hearts lack self-renewal and proliferative capabilities necessary for cardiovascular regeneration. Current treatments using cardiac progenitor cells (CPCs) for cell-based repair do not restore cardiac function in patients who experience a myocardial infarction (MI). Our laboratory has been studying Islet-1+ neonatal CPCs as a promising candidate for cell-based repair due to their ability to significantly improve cardiac function after MI in sheep. The current study addresses the hypothesis that the ERBB pathway is linked to the Hippo-pathway to activate YAP1 by the involvement of an autocrine loop that upregulates neuregulin (NRG). In our sheep model of MI and cardiovascular …

Biomedical Porcine Models For The Study Of Surgical Hemostasis, Hindlimb Ischemia, And Pancreatic Cancer, Shruthishree Aravind

Theses & Dissertations

Murine models have dominated the world of biomedical research and comparative medicine since their development in the early 1900s. [1] While they may be suitable models to study proteomics and genomics, they may not serve as effective translational models. [2-4] Murine models do not accurately model the pathophysiology of human disease and are limited by their size, application of medical imaging and intervention, which reduces their overall preclinical predictive value. [2-4]

Porcine models on the other hand, are slowly and steadily bridging the gap between murine models and human patients. [5] Pigs …

Perivascular Adipose Tissue In Relation To Diet, Thermogenesis And Cardiovascular Health, Ginger Paquette, Caitlin Stieber, Ashely Soucy, Benjamin Tero, Lucy Liaw

Thinking Matters Symposium

Adipose tissue is a diverse and crucial component to vascular health due to its role in energy storage and heat production. The primary function of white adipose tissue (WAT) is energy storage while the function of mitochondria-rich brown adipose tissue (BAT) is heat production. Perivascular adipose tissue (PVAT), which surrounds blood vessels, contains both WAT and BAT adipocytes. Dietary calorie restriction is associated with increased lifespan with decreased adiposity. Increased prevalence of WAT-like PVAT, due to high-fat diets and obesity, leads to increased metabolic disfunction and cardiovascular-disease. We used a calorie-restriction model in C57BL6/J mice to test the hypothesis that …

Importance Of Understanding Genetic Predisposition, Andrew Carter

Thinking Matters Symposium

Hypersensitivity reactions can be sudden and are often fatal. Many of these reactions occur as a result of allergies to prescribed medication. Adverse drug reactions or (ADR’s) were show in a recent study to affect over 6% of hospitalized patients and resulted in over 100,000 deaths a year in the US alone. This poster will review the importance of understanding genetic predisposition, through articles about possible genetic causes of allergies to penicillin and other beta-lactams. Changes in a specific HLA gene located on chromosome 6 showed a correlation to penicillin reactions in over 600,000 participants. Another study found a conclusive …

The Current Neuroscientific Understanding Of Alzheimer's Disease, Rachel A. Brandes

Pursuit - The Journal of Undergraduate Research at The University of Tennessee

Alzheimer’s disease is a degenerative neurological illness characterized by the deterioration of brain regions implicated in memory and cognitive function. While researchers have yet to find a cure or effective treatment, they have gained a better understanding of its pathology and development. Through years of neuroscience research, scientists have discovered much of what happens in the brain during Alzheimer’s disease onset and how this causes its symptoms; many hypotheses regarding this aspect of the illness involve temporal lobe atrophy, neurofibrillary tangles, and amyloid plaques. Although Alzheimer’s disease affects millions of people every day, it seems that most are unaware of …

Tick-Borne Infections In New Hampshire: An Evaluation Of The Diagnostic Process In A Local Patient Population, Katherine Anderson

Honors Theses and Capstones

Overall, approximately 95 percent of reported cases of vector-borne disease were associated with ticks, making these the most medically important group of arthropods in the United States.¹ Despite the prevalence of tick-borne infections, the process for the diagnosis of this condition is not well studied. This study aims to analyze data from a pool of 100 patients who underwent testing for tick-borne disease in the same institution in Dover, New Hampshire during the most recent peak tick season of 2019. Information utilized in this study included: patient age, sex, location of testing (inpatient versus outpatient), diagnostic testing methods used …

Kidney Stone Analysis And Spiritual Guides (Pir Faqir): The Known-Unknowns, Lena Jafri, Aysha Habib Khan, Humaira Asif

Department of Pathology and Laboratory Medicine

No abstract provided.

Glycogen Storage Diseases-Time To Flip The Outdated Diagnostic Approach Centered On Liver Biopsy With The Molecular Testing, Sibtain Ahmed, Bushra Afroze

Department of Pathology and Laboratory Medicine

The glycogen storage diseases (GSDs) are a group of inherited metabolic disorders that result from a defect in any one of several enzymes required for either glycogen synthesis or glycogen degradation. The traditional diagnostic approach is based on the invasive hepatic or muscle biopsies, which are neither cost effective nor convenient. Molecular (gene testing) has emerged over the course of past few years as a robust alternative diagnostic tool, which not only confirms the diagnosis of GSDs but also clearly differentiates the types of GSDs allowing the initiation of the type-specific appropriate treatment for the particular type of GSDs. The …

Role Of Nurd In Acute Leukemia Cell Survival, Javeria Aijaz

Theses and Dissertations

Depletion of the ATPase component of the Nucleosome Remodeling and Deacetylase (NuRD) complex, CHD4, reduces acute myeloid leukemia (AML) cell survival. This study identified other NuRD components, as potential therapeutic targets for disrupting protein-protein interactions within NuRD. In addition to AML, we established that T-cell Acute Lymphoblastic Leukemia (T-ALL) cell lines responded similarly to CHD4 depletion.

Greater than 90% depletion of either MBD2 or MBD3 (the mutually exclusive two DNA binding NuRD paralogues) – was unremarkable, but complete depletion of MBD3 increased apoptosis and genotoxic sensitivity. Combined depletion of MBD-NuRD proteins augmented apoptosis observed with complete MBD3 depletion - indicating …

Prevalence Of Malaria Reported During Summer And Winter At A Tertiary Care Hospital In Karachi, Pakistan, Fazal M. Arain, Aisha Memon, Roohi Jamal, Ahmed Raheem Buksh, Mohammad Asim Beg

Department of Biological & Biomedical Sciences

This study was designed to determine the prevalence and type of malaria cases that presented throughout the year 2014 in a tertiary care hospital in Karachi, Pakistan. A total of 1099 cases, (377 females, 722 males) were reported. Plasmodium vivax (P. vivax) was discovered in 93.7% cases compared to 6.3% Plasmodium falciparum (P. falciparum). Based on the highest and lowest weather temperatures, in summer (June, July and August) and in winter (December, January and February) were differentiated. The number of cases were greater during summer months compared to winter. Interestingly, the ratio of P. falciparum to P. vivax during winter …

A Comparison Of Lung Function Values Among A Scuba Diver Population And In Comparison To A Non-Diver Population, Gabriel C. Hutson, Jeremy D. Rentsch, Erin M. Eaton

Journal of the South Carolina Academy of Science

The purpose of this study was to investigate possible correlations between lung function values (PEF, IRV, ERV, and FVC) among a diver population, as well as in comparison to a non-diver population. Independent variables for both populations were biological sex, age, and weekly physical activity. Independent variables for the diver population were dive tenure, number of logged dives, certification level, and gas mixture used. A spirometry test was conducted to collect lung function values of both populations. Data from this study suggest a statistically significant relationship between diver and non-diver sex and FVC, diver age and ERV, diver sex and …

A Discrepancy Between The Human Reference Genome (Grch37) And Transcriptome (Refseq) Results In The Incorrect Annotation Of A Clinically-Relevant Sequence Variant In Recql4, Lisa A. Lansdon

Research Days

No abstract provided.

Different Methodologies To Characterize And Diagnose Sickle Cell Disease In Both Developed And Developing Nations, Mohammed Alharbi

Dissertations, Masters Theses, Capstones, and Culminating Projects

Sickle cell disease (SCD) is a genetic blood disorder that causes the RBC to become sickle shaped due to a mutation in the β-globin gene encoding the protein hemoglobin. This disease causes reduced oxygen carrying capacity of RBC resulting in painful crisis, hemolytic anemia, and infection susceptibility. SCD affects around 100,000 individuals in USA alone and 14 million people globally. SCD affected individuals have high mortality rates. Early detection and constant monitoring of this disease is essential. The following review focuses on various methodologies that have emerged in the diagnosis of SCD. Also, low cost methods that can be easily …

A Cytotoxic Evaluation Of A Chalcone Derivative Library On A549 Cells, Mary Elaine Kuo

Undergraduate Theses

Chalcones, a precursor to flavonoids, are chemical compounds found naturally in plants. The chalcones’ structure consists of a ketone bridge attached to two aromatic rings. Varying substituents on the aromatic rings allow for different affects, including anti-cancer properties. As a Michael acceptor, chalcones interact with pathways that cause inhibition of the initiation, promotion, and progression of cancer tumors. We have screened 32 compounds for growth inhibition in lung cells that vary the flexibility and confirmation of the 3 carbon bridge between the two aromatic rings as well as the effects of electronic modifications to the aromatic ring. We have found …

Mechanisms And Potential Therapy On Disrupted Blood Pressure Circadian Rhythm In Diabetes, Tianfei Hou

Theses and Dissertations--Pharmacology and Nutritional Sciences

Arterial blood pressure (BP) undergoes a 24-hour oscillation that peaks in the active day and reaches a nadir at night during sleep in humans. Reduced nocturnal BP fall (also known as non-dipper) is the most common disruption of BP circadian rhythm and is associated with increased risk of untoward cardiovascular events and target organ injury. Up to 75% of diabetic patients are non-dippers. However, the mechanisms underlying diabetes associated non-dipping BP are largely unknown. To address this important question, we generated a novel diabetic db/db-mPer2^Luc mouse model (db/db-mPer2^Luc) that allows quantitatively measuring of mPER2 protein oscillation …

Aging, Inflammation, And Gut Microbiota In Mice, Jody Demeo

Honors Projects

Inflammation and gut microbiota are two areas of study that can be linked to aging in the body. As a person ages, systemic inflammation tends to increase, and changes in microbiota in the gastrointestinal system occur as well.

Dopamine Levels In The Brain Of Rat Models Of Human Rheumatoid Arthritis, Amelia Stinson

Theses & Dissertations

Research Focus. Rheumatoid arthritis (RA) is a chronic, debilitating, autoimmune disease that causes the destruction of bone tissue and the articular structures of joints. At least 30% of RA patient populations have cognitive impairment. Acidic dopamine (DA) is the principal neuroimmunotransmitter that links the central nervous system and peripheral nervous system together. The aim of the present study was to determine the levels of DA and its two acidic metabolites: 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in arthritic induced rats, and whether their levels vary across four different parts of the brain: amygdala (AMG), front cerebral cortex (CX), hippocampus …