Medical Sciences Commons^™

Quaternized Chitosan Derivatives Inhibit Growth And Affect Biofilm Formation Of Staphylococcus Aureus, Alex Miranda, Nichole D. Brandquist, Kristen Johnson, Elena Muldiiarova, Aleksandr Fadeev, Mahboubeh Ghanbari, Jennifer L. Endres, Kenneth W. Bayles, Jason N. Mactaggart, Denis Svechkarev, Marat Sadykov, Yury Salkovskiy

Journal Articles: Pathology and Microbiology

Antimicrobial resistance (AMR) poses a global health threat, severely impeding the effective treatment of bacterial infections and jeopardizing the safety of routine medical procedures. Methicillin-resistant Staphylococcus aureus (MRSA) is particularly problematic because of its resistance to beta-lactams and the ability to form resilient biofilms. Conventional antibiotics, including last-resort options, have serious side effects and may contribute to further resistance. Chitosan, a natural biopolymer, offers a promising alternative due to its biocompatibility and antimicrobial properties, though its effectiveness against biofilms is limited. Recent studies suggest that increasing the positive charge density and adding hydrophobic moieties to chitosan, can enhance its antimicrobial …

Interferon-Gamma Receptor Signaling Regulates Innate Immunity During Staphylococcus Aureus Craniotomy Infection, Zachary Van Roy, Gunjan Kak, Rachel W. Fallet, Tammy Kielian

Journal Articles: Pathology and Microbiology

A craniotomy is a neurosurgical procedure performed to access the intracranial space. In 3-5% of cases, infections can develop, most caused by Staphylococcus aureus biofilm formation on the skull surface. Medical management of this infection is difficult, as biofilm properties confer immune and antimicrobial recalcitrance to the infection and necessitate additional surgical procedures. Furthermore, treatment failure rates can be appreciably high. These factors, compounded with rapidly expanding rates of antimicrobial resistance, highlight the need to develop alternative treatment strategies to target and reverse the immune dysfunction that occurs during biofilm infection. Our recent work has identified CD4+ Th1 and Th17 …

Cd4+ T Cell-Innate Immune Crosstalk Is Critical During Staphylococcus Aureus Craniotomy Infection, Gunjan Kak, Zachary A. Van Roy, Rachel W. Fallet, Lee E. Korshoj, Tammy Kielian

Journal Articles: Pathology and Microbiology

Access to the brain for treating neurological sequalae requires a craniotomy, which can be complicated by infection. Staphylococcus aureus accounts for half of craniotomy infections, increasing morbidity in a medically fragile patient population. T cells preferentially traffic to the brain during craniotomy infection; however, their functional importance is unknown. Using a mouse model of S. aureus craniotomy infection, CD4+ T cells were critical for bacterial containment, as treatment of WT animals with anti-CD4 exacerbated infection that was similar to phenotypes in Rag1-/- mice. Single-cell RNA-Seq (scRNA-Seq) revealed transcriptional heterogeneity in brain CD3+ infiltrates, with CD4+ cells most prominent that displayed …

Pgc-1Α Activation To Enhance Macrophage Immune Function In Mycobacterial Infections, Joel R. Frandsen, Zhihong Yuan, Brahmchetna Bedi, Zohra Prasla, Seoung-Ryoung Choi, Prabagaran Narayanasamy, Ruxana Sadikot

Journal Articles: Pathology and Microbiology

Nontuberculous Mycobacteria (NTM) are a heterogeneous group of environmental microorganisms with distinct human pathogenesis. Their incidence and prevalence are rising worldwide, due in part to elevated antimicrobial resistance which complicates treatment and potential successful outcomes. Although information exists on the clinical significance of NTMs, little is known about host immune response to infection. NTM infections alter macrophage mitochondrial capacity and decrease ATP production, efficient immune response, and bacterial clearance. Transcription factor peroxisome proliferator activated receptor (PPAR) γ coactivator-1α (PGC-1α) is a master regulator of mitochondrial biogenesis, influencing metabolism, mitochondrial pathways, and antioxidant response. Mitochondrial transcription factor A (TFAM) is a …

Extracellular Adherence Proteins Reduce Matrix Porosity And Enhance Staphylococcus Aureus Biofilm Survival During Prosthetic Joint Infection, Mohini Bhattacharya, Tyler D. Scherr, Jessica Lister, Tammy Kielian, Alexander R. Horswill

Journal Articles: Pathology and Microbiology

Biofilms are a cause of chronic, non-healing infections. Staphylococcus aureus is a proficient biofilm-forming pathogen commonly isolated from prosthetic joint infections that develop following primary arthroplasty. Extracellular adherence protein (Eap), previously characterized in planktonic or non-biofilm populations as being an adhesin and immune evasion factor, was recently identified in the exoproteome of S. aureus biofilms. This work demonstrates that Eap and its two functionally orphaned homologs EapH1 and EapH2 contribute to biofilm structure and prevent macrophage invasion and phagocytosis in these communities. Biofilms unable to express Eap proteins demonstrated increased porosity and reduced biomass. We describe the role of Eap …

Diastolic Dysfunction With Vascular Deficits In Hiv-1-Infected Female Humanized Mice Treated With Antiretroviral Drugs, Fadhel A. Alomar, Prasanta K. Dash, Mahendran Ramasamy, Zachary L. Venn, Sean R. Bidasee, Chen Zhang, Bryan T. Hackfort, Santhi Gorantla, Keshore R. Bidasee

Journal Articles: Cellular & Integrative Physiology

Early-onset heart failure is a major treat to healthy aging individuals with HIV-1 infection. Women with HIV-1 infection (WLWH) are especially vulnerable and develop heart failure with preserved ejection fraction (HFpEF), of which left ventricular diastolic dysfunction, vascular deficits, myocardial infarction, and fibrosis are major components. HIV-infected rodent models that exhibit these pathophysiological features remain under-reported, and this has left a void in our understanding of their molecular causes and therapeutic strategies to blunt its development. Here, we show that female NOD.Cg-Prkdc^scidIl2rgt^m1Wjl/SzJ humanized mice (Hu-mice) infected with HIV-1_ADA and treated for 13 weeks with dolutegravir …

Development Of The Mechanoresponsive Pericellular Matrix Of Chondrons, Donghee Lee, Sydney E. Greer, Andrew T. Dudley

Journal Articles: Genetics, Cell Biology & Anatomy

Physical properties of cartilage are conferred by the composition and ultrastructure of the extracellular matrix. This study focuses on the development of the pericellular matrix (PCM), a domain that directly contacts the chondrocyte and is a key regulator of biomechanical and biochemical signaling. Using three-dimensional cell culture, microfluidic cell compression platforms, and genetic mouse models, we demonstrated that collagen VI is initially assembled at the cell surface and then displaced to form a shell at the PCM-territorial matrix boundary. Cell surface-bound hyaluronan is crucial for the assembly process, and hyaluronan-aggrecan complexes drive displacement. Integrin adhesion is not required early but …

Species-Specific Discrimination Of Bacterial Biofilms Using A Ratiometric Fluorescence Sensor Array And Machine Learning, Ritika Gupta, Aayushi Laliwala, Elena Muldiiarova, Kenneth W. Bayles, Denis Svechkarev, Marat Sadykov, Aaron M. Mohs

Journal Articles: Pathology and Microbiology

Biofilms are intricate bacterial communities encased in a self-produced extracellular matrix (ECM) of DNA, lipids, proteins, and polysaccharides. The diverse ECM composition across bacterial species significantly influences the progression of biofilm-associated infections, making precise identification crucial for effective treatment. Traditional methods such as biochemical assays, MALDI-TOF mass spectrometry, DNA sequencing and culturing provide valuable insights but have notable drawbacks, including time-consuming procedures, high costs, and the need for specialized equipment and trained personnel. These limitations hinder the rapid and widespread adoption of biofilm identification in clinical settings, underscoring the need for more streamlined, accurate, and accessible methods. In this study, …

Contract To Kill: Gnas Mutation, Pratima Raut, Poompozhil Mathivanan, Surinder K. Batra, Moorthy P. Ponnusamy

Journal Articles: Biochemistry & Molecular Biology

The mutation in Gsα-coding GNAS exons, popular as gsp oncogene, is the most frequent mutation across all heterotrimeric G proteins involved in oncogenesis. GNAS R201, the most frequently mutated, followed by Q227, are found predominantly across various neoplasms and cancers such as IPMN, pituitary, thyroid, appendiceal, colorectal, etc. This review emphasizes the pivotal significance of the gsp oncogene and its ramifications underpinning the sustained addiction to GNAS mutation. Recent studies delineating the mechanistic intricacies that provide solid evidence of the profound impact of oncogenic GNAS on tumor formation, progression, and maintenance are highlighted. We have leveraged the discoveries of Gsα …

Staphylococcus Aureus Encodes Four Differentially Regulated Pyruvate Transporters, Jennifer L. Endres, Cleofes Sarmiento, William Xiao, Marat R. Sadykov, Kenneth W. Bayles, Mckenzie K. Lehman

Journal Articles: Pathology and Microbiology

The success of Staphylococcus aureus as a pathogen is attributable, in part, to its ability to exploit the diverse nutrient sources available during infection. Critical to this success are the pathways involving pyruvate that serve as a nexus for energy production, oxidative metabolism, and biosynthetic processes. When available, bacteria acquire pyruvate from the environment to fuel growth. Recently, LrgAB was identified as a pyruvate transporter under microaerobic conditions, leading us to speculate that S. aureus encodes other pyruvate transporters that are active during aerobic growth. In this study, we used the toxic pyruvate analog, 3-fluoropyruvic acid (3-FP), to isolate mutants …

Targeting Cancer-Associated Fibroblast-Driven Lif/Lifr Axis Improves The Therapeutic Efficacy Of Gemcitabine And Nab-Paclitaxel In Pancreatic Cancer, Rakesh Bhatia, Imran Khan, Xiaoqi Li, Shailendra Gautam, Parthasarathy Seshacharyulu, Zahraa Wajih Alsafwani, Namita Bhyravbhatla, Moorthy P. Ponnusamy, Maneesh Jain, Mokenge Malafa, Santhamma Bindu, Ahmed Gulzar, Hareesh Nair, Surinder K. Batra, Sushil Kumar

Journal Articles: Biochemistry & Molecular Biology

Pancreatic ductal adenocarcinoma (PDAC) is inherently therapy resistant due to cancer cell-stroma crosstalk across several signaling pathways. Among these, the LIF/LIFR axis has been implicated in cancer cell and cancer-associated fibroblast (CAF) crosstalk. We evaluated the efficacy of EC359, a competitive inhibitor of LIFR, in combination with gemcitabine. EC359 reduced tumor burden by 90% compared to controls and by 55% compared to gemcitabine alone in cancer cell and CAFs co-implannation model. The RNA-seq analysis revealed a significant alteration in extracellular matrix components, stemness, microtubule assembly, and immune response, suggesting simultaneous targeting of cancer cell-intrinsic and stroma-mediated mechanisms by EC359. In …

Identification Of Potential Prophylactic Medical Countermeasures Against Acute Radiation Syndrome (Ars), Kia T. Liermann-Wooldrik, Arpita Chatterjee, Elizabeth A. Kosmacek, Molly Myers, Oluwaseun Adebisi, Louise Monga-Wells, Liu Mei, Michelle P. Takacs, Patrick H. Dussault, Daniel R. Draney, Robert Powers, James W. Checco, Chittibabu Guda, Tomáš Helikar, David B. Berkowitz, Kenneth W. Bayles, Alan H. Epstein, Lynnette Cary, Daryl J. Murry, Rebecca E. Oberley-Deegan

Journal Articles: Pathology and Microbiology

Acute radiation syndrome (ARS) occurs when hematopoietic or gastrointestinal cells are damaged by radiation exposure causing DNA damage to the bone marrow and gastrointestinal epithelial stem cell populations. In these highly proliferative cell types, DNA damage inhibits stem cell repopulation. In humans and animals, this inability to regenerate stem cells is lethal. Within this manuscript, several compounds, Amifostine, Captopril, Ciprofloxacin, PrC-210, 5-AED (5-androstene-3β,17β-diol), and 5-AET (5-androstene-3β,7β,17B-triol), are assessed for their ability to protect against ARS in an in vitro and/or in vivo setting. ARS was accomplished by irradiating mouse bone marrow cells or rat intestinal epithelial (IEC-6) cells in vitro …

Niclosamide-Loaded Polyanhydride Nanoparticles To Combat Gemcitabine Resistance In Pancreatic Cancer, Brianna M. White, Venugopal Gunda, Susheel Kumar Nethi, Nagabhishek Sirpu Natesh, Adam S. Mullis, Mariaelena Roman Sotelo, Jeffrey North, Chris Destache, Balaji Narasimhan, Surinder K. Batra, Surya K. Mallapragada, Satyanarayan Rachagani

Journal Articles: Biochemistry & Molecular Biology

Purpose

Pancreatic cancer (PC) is a highly lethal malignancy and lacks effective treatments. Current chemotherapies, including gemcitabine (Gem) in combination treatment regimens, produce dose-limiting toxicity, drug resistance, and ultimately limited improvement in the overall survival of PC patients. Niclosamide (Nic), a clinically safe FDA-approved anthelmintic drug has been shown to have anti-cancer properties; however, its limited bioavailability makes Nic largely ineffective as a therapeutic agent. To address this challenge, we have developed a novel combination therapy of Gem with the repurposed drug, Nic, loaded in biodegradable polyanhydride nanoparticles (NicNp), as an effective treatment option for PC.

Methods

We synthesized and …

Proteomics Profiling Of Research Models For Studying Pancreatic Ductal Adenocarcinoma, Mathilde Resell, Hanne-Line Rabben, Animesh Sharma, Lars Hagen, Linh Hoang, Nan T. Skogaker, Anne Aarvik, Eirik Knudsen Bjåstad, Magnus K. Svensson, Manoj Amrutkar, Caroline S. Verbeke, Surinder K. Batra, Gunnar Qvigstad, Timothy C. Wang, Anil Rustgi, Duan Chen, Chun-Mei Zhao

Journal Articles: Biochemistry & Molecular Biology

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with a five-year survival rate of 10-15% due to late-stage diagnosis and limited efficacy of existing treatments. This study utilized proteomics-based systems modelling to generate multimodal datasets from various research models, including PDAC cells, spheroids, organoids, and tissues derived from murine and human samples. Identical mass spectrometry-based proteomics was applied across the different models. The preparation and validation of the research models and the proteomics were described in detail. The assembly datasets we present here contribute to the data collection on PDAC, which will be useful for systems modelling, …

Metabolic And Proteomic Signatures Differentiate Inflammatory Phenotypes From Cancer And Predict Treatment Response In Patient Sera, Gabriel Cutshaw, Elena V. Demidova, Philip Czyzewicz, Elizabeth Quam, Nicole Lorang, Al Warith Al Siyabi, Surinder K. Batra, Sanjeevani Arora, Rizia Bardhan

Journal Articles: Biochemistry & Molecular Biology

Tumors shift their metabolic needs to enable uncontrolled proliferation. Therefore, metabolic assessment of cancer patient sera provides a significant opportunity to noninvasively monitor disease progression and enable mechanistic understanding of the pathways that lead to response. Here, we show Raman spectroscopy (RS), a highly sensitive and label-free analytical tool, is effective in metabolic profiling across diverse cancer types in patient sera from both pancreatic ductal adenocarcinoma (PDAC) and locally advanced rectal cancer (LARC). We also combine metabolic data with proteomic signatures to predict treatment response. Our data show RS peaks successfully differentiate PDAC patients from healthy controls. Peaks associated with …

Brightly Visualizing Pancreatic Cancer Margins In Orthotopic Mouse Models With An Anti-Ca19-9 Antibody Conjugated To A Near-Infrared Fluorophore, Kristin E. Cox, Javier Bravo, Sunidhi Jaiswal, Siamak Amirfakhri, Thinzar M. Lwin, Abhijit Aithal, Sumbal Talib, Lily J. Jih, Aylin Din Parast Saleh, Keita Kobayashi, Kavita Mallya, Maneesh Jain, Robert M. Hoffman, Aaron M. Mohs, Surinder K. Batra, Michael Bouvet

Journal Articles: Biochemistry & Molecular Biology

Background/Purpose: The only potentially curative procedure for pancreatic cancer is R0 resection, which is difficult to achieve due to poorly defined tumor margins. In the present study, we used an anti-CA19-9 antibody conjugated to a near-infrared fluorophore in orthotopic mouse models to target and visualize pancreatic cancer. Methods: Orthotopic models of the human pancreatic cancer cell lines SW1990 and BxPC3 were established by implanting tumor fragments into the pancreas of athymic nude mice. Anti-CA19-9 and control IgG were conjugated with IRDye800CW. Mice received 50 µg of CA19-9-IRDye800CW or IgG-IRDye800CW via tail-vein injection and were imaged after 72 h. MIA PaCa-2, …

Niclosamide Nanoparticles Enhance Pancreatic Cancer Sensitivity To Gemcitabine Via Hif-1Α Inhibition, Susheel Kumar Nethi, Venugopal Gunda, Nagabhishek Sirpu Natesh, Brianna M. White, Adam S. Mullis, Balaji Narasimhan, Surinder K. Batra, Surya K. Mallapragada, Satyanarayana Rachagani

Journal Articles: Biochemistry & Molecular Biology

Pancreatic cancer (PC) exhibits profound metabolic adaptations that support tumor progression, survival, and therapy resistance. Hypoxia-inducible factor-1α (HIF-1α) is a key regulator of these processes, promoting metabolic reprogramming and chemoresistance. Given that mitochondrial metabolites modulate HIF-1α stability, targeting mitochondrial metabolism offers a promising therapeutic strategy. Niclosamide (Nic), a clinically approved anthelmintic, disrupts mitochondrial function but is limited by poor bioavailability. To overcome this, we developed polyanhydride-based Nic nanoparticles (NicNps) to enhance bioavailability and efficacy. NicNps impaired mitochondrial function, suppressed metabolism, downregulated HIF-1α, and inhibited growth of PC cells and orthotopic gemcitabine (Gem)-resistant mouse tumor models. Notably, NicNps combined with Gem …

Design And Investigation Of Small Molecule Drugs For Potential Treatment Of Cns Disorders, Flaviviral Infections, And Cancers, Viktoriya Mashinson

Theses & Dissertations

Chapter 1 discusses the development of antagonists against the dopamine 4 receptor (D4R) that is expressed in the motor, associative, and limbic subdivisions of the basal ganglia network and is involved in Parkinson’s disease (PD). Levodopa is the firstline drug for the management of PD symptoms but its long-term use often leads to development of levodopa-induced dyskinesia (LID). D4R antagonists have been shown to decrease the abnormal involuntary movement scores in mouse models of LID. Chapter 1 outlines the development and optimization of selective D4R antagonists for potential treatment of LID. During the investigation of our D4R antagonists we discovered …

Sparkled: Social Programming In Kids Affects Risk Of Latent Endothelial Disease, Rebecca Drakowski

Theses & Dissertations

Background: Social Health Programming (SHP) is a holistic intervention that can empower communities to address modifiable risk factors for poor cardiovascular health, including suboptimal nutrition or psychosocial stressors. SHP participation has been shown to increase dietary intake of fruits and vegetables, decrease perceived stress, and improve cardiovascular endurance. However, it is unknown how SHP participation during adolescence affects carotenoid serum levels, hair cortisol concentrations (biological marker of chronic stress), or vascular reactivity index (VRI; measure of subclinical cardiovascular health).

Methods: Adolescent girls and young adult women (12–29-year-old) were enrolled in this observational cohort study. Serum, hair, and saliva samples were …

Understanding The Role Of Malondialdehyde-Acetaldehyde Adducts (Maa) In Inflammatory Bowel Disease, Megan L. Otte

Theses & Dissertations

Inflammatory Bowel Disease (IBD) comprises autoimmune diseases of the gastrointestinal tract that greatly reduce the quality of life of patients and currently afflict up to 200 individuals per 100,000 Americans. Ulcerative colitis (UC) and Crohn’s Disease (CD), the two principal diseases comprising IBD, share symptoms and risk factors, however, precise etiology remains unclear. The diagnostics and clinical management of IBD have progressed greatly in recent years especially due to immune modulating therapies and biologics, however, IBD and its specific forms are still difficult to diagnose and cannot be cured with current treatments. The overarching mechanisms of IBD pathogenesis are known …

Understanding The Role Of Mastl In Colon Homeostasis And Colitis-Associated Cancer Development, Kristina Pravoverov

Theses & Dissertations

Colitis-associated cancer (CAC) is the most devastating complication of longstanding inflammatory bowel disease (IBD). Understanding the mechanisms underlying the switch from damage-repair to dysplasia in IBD is critical for identifying novel therapies to facilitate mucosal healing while mitigating CAC risk. Microtubule-associated serine-threonine kinase-like (MASTL), though crucial in cell growth and repair, is upregulated in sporadic colorectal cancer and CAC. This study sought to delineate the role of MASTL in colitis and CAC development.

First, we examined whether MASTL is associated with colitis and recovery. Review of publicly available data found significant elevation of MASTL and interleukin (IL)-22 in biopsies from …

Novel Mechanisms For The Neural Control Of Breathing In Acute Lung Injury, Kajal Kamra

Theses & Dissertations

Acute lung injury (ALI) triggers inflammation that disrupts the normal alveolar-capillary endothelial barrier, impairing gas exchange and causing hypoxemia, which reflexively increases respiration. An elevated respiratory rate (fR) usually develops within hours to days following ALI. This acute respiratory failure disorder affects approximately 200,000 new cases annually in the US and accounts for 10% of ICU admissions, with high morbidity and mortality. The neural mechanisms underlying respiratory dysfunction post-ALI are not fully understood. My doctoral dissertation aimed to investigate the mediators of abnormal ventilation during ALI. Systemic hypoxia stimulates the carotid body (CB) chemoreflex, a crucial protective reflex that maintains …

Development, Validation, And Diagnostic Performance Of A Novel Radiomic Model For Predicting Prostate Cancer Recurrence, Linda M. Huynh

Theses & Dissertations

Multi-parametric magnetic resonance imaging (MP-MRI)-derived radiomics have been shown to capture sub-visual patterns for the quantitative characterization of prostate cancer (PC) phenotypes. The present dissertation seeks to develop, evaluate, and compare the performance of an MRI-derived radiomic model for the prediction of PC recurrence following definitive treatment with radical prostatectomy (RP).

MP-MRI was obtained from 339 patients who had a minimum of 2 years follow-up following RP at three institutions. The prostate was manually delineated as the region of interest and 924 radiomic features were extracted. All features were evaluated for stability via intraclass correlation coefficient (ICC) and image normalization …

Healthy Aging Modulates The Neural Oscillatory Activity Underlying Basic Visual Processing And Verbal Working Memory, Seth D. Springer

Theses & Dissertations

Worldwide economic and medical improvements have led to profound demographic shifts towards an older overall population. Unfortunately, with older age comes a variety of neurological changes which act to decrease individual quality of life and independence. Since the advent of functional neuroimaging, investigation of age-related changes in neural activity has been of particular interest. However, changes in population-level neural dynamics with age remain poorly characterized. Herein, we utilized magnetoencephalography (MEG), comprehensive neuropsychological assessments, and advanced analytical techniques to investigate spectrally-specific changes in neural oscillatory activity in a healthy aging population. First, we examined age-related deficiencies in visual processing using a …

Cognitive Control In Health And Disease: A Dynamic Approach To Mapping Oscillatory Activity Across The Lifespan, Mikki Schantell

Theses & Dissertations

Cognitive control is critical for flexibly adapting goal-directed behaviors to meet the demands of dynamically changing environments. The neural oscillatory dynamics serving cognitive control undergo changes across the lifespan, both in health and disease, with impairments in cognitive control functions being broadly implicated across a multitude of psychiatric disorders. Despite this, the trajectory of the population-level neural oscillatory dynamics supporting cognitive control across the lifespan remain poorly characterized, presenting challenges in fully understanding perturbations to these systems relative to one’s stage in neuronal maturation. Herein, we used the Eriksen flanker task during magnetoencephalographic (MEG) recording to map the neural oscillatory …

Impact Of Nutritional Status And Placental Malaria Infection On Pregnancy Outcome In A Population Of Nigerian Maternal-Infant Dyads, Shirley F. Delair

Theses & Dissertations

Nigeria is the most populous country in Africa and accounts for one-quarter of the newborn mortality on the continent. Most newborn deaths are from prematurity (33%), infections (33%), and intrapartum complications (31%). Using an adapted analytical framework for the study of child survival in developing countries, this dissertation aimed to look at the pregnancy outcome of a population of Nigerian women and their offspring by looking at proximate determinants of health from nutritional status and environmental conditions. In Chapter 1, we characterized the micronutrients of the mother-infant dyads, looking specifically at concentrations of vitamin D and its metabolites. In Chapter …

The Effect Of Repetitive Transcranial Magnetic Stimulation On Brain And Cognitive Variables In Patients With Amnestic Mild Cognitive Impairment, Connor J. Phipps

Theses & Dissertations

Healthy and pathological aging processes can impact human memory. Current interventions for clinical memory impairment offer little opportunity for restoration of memory ability. Fortunately, a novel therapy in the form of repetitive transcranial magnetic stimulation (rTMS) has exhibited promise in this regard. In healthy adults, rTMS of the angular gyrus (AG) has been reported to improve memory. The current study sought to determine the generalizability of these findings to individuals with clinical memory impairment by administering a clinical trial replicating an rTMS protocol reported to improve hippocampal-dependent memory in healthy individuals to individuals with amnestic mild cognitive impairment (aMCI). Individuals …

Unraveling The Role Of Gjb3 In Lung Adenocarcinoma, Swathi M. Priyanka

Theses & Dissertations

Lung cancer stands as a leading cause of cancer-related mortality worldwide, with small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) comprising its primary categories. NSCLC, representing nearly 85% of cases, exhibits a 5-year survival rate of less than 21%. Among NSCLC subtypes, lung adenocarcinoma (LUAD) prevails as the most common, followed by squamous cell carcinoma and large cell carcinoma. Gap junctions are crucial for intercellular communication and cellular homeostasis maintenance, demonstrate altered expression patterns in various diseases, including cancer. Gap junction beta 3 (GJB3 or Connexin31) exhibits significant expression in both preclinical and clinical LUAD samples, prompting investigation into …

Examining Patient Preferences And Perceptions Of Provider Communication Strategies For Variant Reclassification In Hereditary Cancer Genetic Testing, Mitchell Mcelfresh, Katie Hutto, Gwen Reiser, Bronson Riley, Charlie King

Capstones: Genetic Counseling

Genetic testing plays a role in oncology care by providing insight into patient’s cancer risk and guiding medical management. Variants in genes are classified by their potential to cause disease according to the five-tier system recommended by the American College of Medical Genetics (ACMG). Reclassification of variants is fluid and can lead to both changes in medical management and challenging discussions. Previous research has described methods genetic counselors use for recontacting patients about reclassification, but not whether these methods align with patient preferences. This study employed a mixed methods survey for patients in Nebraska (recruited via flyer and mail) and …

Evaluating The Association Of Influenza Vaccination On Long-Term Covid-19 Symptoms In U.S. Adults, Ratnakar Pingili

Capstone Experience: Master of Public Health

Objective. To evaluate the association of influenza vaccination in the past 12 months with Long COVID effects and clinical and sociodemographic factors.

Methods. Cross-sectional study with data from the 2022 Behavioral Risk Factor Surveillance System (BRFSS), covering 415,132 non-institutionalized U.S. adults with a confirmed COVID-19 diagnosis and influenza vaccination reported within the last 12 months. Logistic regression was conducted between influenza vaccination (exposure) and Long COVID (outcome), controlling for demographic variables, pre-existing health conditions, and socioeconomic status.

Results. Of 120,603 participants, 21.89% reported Long COVID symptoms and 42.04% had received an influenza vaccine. Findings indicate a statistically significant 13% reduction …