Medical Sciences Commons^™

Unlocking Hope: Mirtazapine's Promise In Obsessive-Compulsive Disorder Treatment, Rebecca K. Hicks, Iram Kingson, Jordan Gaal, Suzanne Holroyd

Marshall Journal of Medicine

Obsessive-compulsive disorder (OCD) is a chronic and debilitating psychiatric condition characterized by intrusive thoughts (obsessions) and repetitive behaviors (compulsions). While selective serotonin reuptake inhibitors (SSRIs) and cognitive-behavioral therapy (CBT) are first-line treatments for OCD, a significant proportion of patients remain refractory to these interventions. Mirtazapine, an atypical antidepressant with unique pharmacological properties, has emerged as a potential adjunctive therapy for treatment-resistant OCD. This review synthesizes existing evidence regarding the efficacy and safety profile of mirtazapine in OCD management. We analyze clinical trials, observational studies, and case reports, distinguishing high- vs. low-quality evidence, and discuss mechanisms underlying mirtazapine's therapeutic effects. Additionally, …

In Vitro Dihalobenzene Nephrotoxicity In Isolated Kidney Cells, Jana Ahmed Sherif

Theses, Dissertations and Capstones

Brominated and chlorinated benzenes are common industrial chemicals linked to kidney injury. This study evaluated the nephrotoxicity of several mono- and dihalogenated derivatives using isolated kidney cells from male Fischer 344 rats. LDH release and trypan blue exclusion were measured after 30- and 60-minute exposures to 0.25–1.0 mM to test compounds. Toxicity increased with increased concentration and longer times. Mixed-halogen bromobenzenes, particularly 1-bromo-4-chlorobenzene, showed one of the highest toxicity levels, while 1,4dichlorobenzene was the most toxic chlorobenzene. Antioxidants (glutathione, ascorbate, and αtocopherol) markedly reduced injury, indicating oxidative mechanisms play a role in toxicity. cytochromes P450 (CYP) inhibitors (piperonyl butoxide and …

Hepatocyte Peroxisome Biogenesis And Phytol-Induced Metabolic Stress In Liver Disease, William Galloway

Theses, Dissertations and Capstones

Hepatocyte peroxisomes are required for metabolism of phytol-derived branched-chain fatty acids through the ACOX2-SCPx beta-oxidation pathway. This study tests whether hepatocyte-specific deletion of PEX16 (Pex16^Alb-Cre), which eliminates peroxisome biogenesis, sensitizes the liver to phytol-induced injury. The Pex16^Alb-Cre mice and their normal control Pex16^fl/fl mice were fed the Lieber-DeCarli liquid with or without 0.1 percent phytol for eight weeks. Serum alanine aminotransferase (ALT) and liver index were measured. Liver sections were stained with hematoxylin and eosin and Masson’s trichrome. Immunoblot analysis of peroxisomal enzyme expression was also performed. Phytol had no effect in Pex16^fl/fl mice as …

Silver Nanoparticle-Induced Disruption Of Astrocytic Morphology And Synaptic Microarchitecture In Rat Brain, Elli Williams

Theses, Dissertations and Capstones

Silver nanoparticles (AgNPs) are widely incorporated into consumer and medical products due to their antibacterial properties, increasing the potential for chronic exposure. AgNPs can be released into the environment, enter the body through ingestion or inhalation, cross the blood-brain barrier (BBB), and bioaccumulate in brain tissue. Previous in vitro studies demonstrate that AgNP exposure disrupts cytoskeletal organization and induces neurite collapse in neural cells, suggesting vulnerability of cytoskeleton-dependent structures in vivo. Astrocytes, through their perisynaptic astrocytic processes (PAPs) and perivascular endfeet, play critical roles in maintaining synaptic and neurovascular architecture, both of which rely heavily on cytoskeletal integrity. This …

Using Genetically Diverse Mice To Examine The Effects Of Environmental Enrichment Of The Transcriptome, Michael Richard Leonardo

Theses, Dissertations and Capstones

Environmental impoverishment is a model of early life stress with direct consequences across a wide range of neurological and physiological conditions. Neuron morphology and density as well as anxiety disorders and addiction have shown to have significant relationships with environmental impoverishment models. Conversely, environmental enrichment confers therapeutic benefits that are protective across these conditions. There is an observed spectrum of resistance or vulnerability to the effects of housing conditions across populations, indicating genetics as an influential factor. Understanding this interaction is critical for deepening our knowledge of how genes and environment interact in ways that confer resistance or vulnerability, and …

Nicotine Self-Administration And The Impacts On Medial Habenula And Interpeduncular Nucleus Neurophysiology, Nathan Alexander Olszewski

Theses, Dissertations and Capstones

Nicotine use is a tremendous public health issue in the United States, with over 23 million people being dependent on the substance. Low cessation rates associated with nicotine use are largely attributed to the withdrawal and craving symptoms that occur after abstinence of use from nicotine. The medial habenula (MHb) and interpeduncular nucleus (IPN) are two brain regions heavily associated and linked with nicotine withdrawal. Here, I sought to understand how these brain regions are altered in their physiology during nicotine intake. Utilizing E-Vape self-administration, mice were first taught to selfadminister nicotine of various, clinically relevant, dosages which correlate to …

Disruption Of The Placenta–Brain Axis In Transgenic Mice Lacking Serotonin Transporter (Sert) In Trophoblast Cells, David T. Ellenberger, Zhen Lyu, Rosalind T. B. Herrington, Jessica A. Kinkade, Gustavo W. Leone, Ji Ying Sze, Nathan J. Bivens, R. Frank Baker, R. Michael Roberts, Trupti Joshi, Cheryl S. Rosenfeld

Biomedical Sciences

Serotonin reuptake inhibitors (SSRIs) are commonly prescribed to pregnant women experiencing depression. Such drugs, however, might adversely affect placenta and fetal brain development. Parietal trophoblast giant cells (pTGCs) in the mouse placenta are postulated to internalize maternal serotonin (5-HT) via transport through SERT, encoded by Slc6a4, and to provide the initial source of 5-HT to the emerging brain via the placental–brain axis. Genetic deletion of Slc6a4 in pTGCs has been hypothesized to impact placental and fetal brain development. A transgenic mouse line with high-affinity SERT, encoded by Slc6a4, was selectively deleted by pairing mice with Cre recombinase linked …

G2pdeep-V2: A Web-Based Deep-Learning Framework For Phenotype Prediction And Biomarker Discovery For All Organisms Using Multi-Omics Data, Shuai Zeng, Trinath Adusumilli, Sania Zafar Awan, Manish Sridhar Immadi, Dong Xu, Trupti Joshi

Biomedical Sciences

Multi-omics data offers rich insights into complex traits across organisms, yet integrating and analyzing these datasets for phenotype prediction and marker discovery remains challenging. Researchers need accessible tools that combine deep learning, hyperparameter optimization, visualization, and downstream analysis in a unified web platform. To address this, we developed G2PDeep-v2, a web-based platform powered by deep learning for phenotype prediction and marker discovery from multi-omics data across a wide range of organisms, including humans and plants. The server provides multiple services for researchers to create deep-learning models through an interactive interface and train these models using an automated hyperparameter tuning algorithm …

The Glymphatic System And Sleep: Functional Relevance For Brain Homeostasis And Beyond, David Gozal

Marshall Journal of Medicine

It has been less than 15 years since the glymphatic system was identified. The discovery has revolutionized the understanding of the unique functions of cerebrospinal fluid (CSF) and the extracellular fluid within the central nervous system (CNS) and their unique connectivity to the rest of the body. The role of sleep in regulating glymphatic clearance from the brain and the potential reciprocal role of the glymphatic system in modulating regional neuronal activities, including sleep states, is rapidly emerging. It is shedding light on the role of sleep and the glymphatic system as toxic waste clearance facilitators for the brain, revealing …

Ruptured Internal Mammary Artery Perforator After Reduction Mammoplasty: A Case Report, Carol Wright Becker, Abigail Roop, Daniel Sutphin, Roger Tillotson

Marshall Journal of Medicine

A 60-year-old female who was 10 days post-reduction mammoplasty presented to the emergency department due to the sudden onset of swelling and pain in her left breast. A contrast-enhanced CT scan of the chest revealed active arterial bleeding. The patient was emergently taken to the operating room, where she underwent evacuation of a large hematoma as well as ligation of a left internal mammary perforator artery. This case represents a rare occurrence of life-threatening postoperative bleeding into the chest wall/breast after reduction mammoplasty, which developed 10 days postoperatively. The successful outcome and complete recovery were attributed to the timely recognition …

Irnet: Immunotherapy Response Prediction Using Pathway Knowledge-Informed Graph Neural Network, Yuexu Jiang, Manish Sridhar Immadia, Duolin Wang, Shuai Zeng, Yen On Chan, Jing Zhou, Dong Xu, Trupti Joshi

Biomedical Sciences

Introduction: Immune checkpoint inhibitors (ICIs) are potent and precise therapies for various cancer types, significantly improving survival rates in patients who respond positively to them. However, only a minority of patients benefit from ICI treatments.

Objectives: Identifying ICI responders before treatment could greatly conserve medical resources, minimize potential drug side effects, and expedite the search for alternative therapies. Our goal is to introduce a novel deep-learning method to predict ICI treatment responses in cancer patients.

Methods: The proposed deep-learning framework leverages graph neural network and biological pathway knowledge. We trained and tested our method using ICI-treated patients’ data from several …

Successful Flexible Bronchoscopic Extraction Of A Dental Foreign Body Aspirated Into The Left Mainstem Bronchus, Alexys Bolden, Hayden Cooper, Lynnetta Payne, Mark Coomes, Mark Cooper

Marshall Journal of Medicine

Foreign body aspiration (FBA) is a potentially life-threatening emergency that commonly occurs in children but varies widely in clinical presentation. Rapid diagnosis and intervention are of the utmost importance to prevent complications such as airway obstruction, infection, and lung injury. While uncommon in adults, most encountered causes occur in the setting of intoxication, neuromuscular weakness, or iatrogenic dental work. Those with dental prostheses are especially susceptible due to the partially attached nature, rendering the risk of accidental dislodgement. This report discusses an uncommon case wherein an 82-year-old male aspirated a dental bridge into his left mainstem bronchus during routine dental …

Forearm Muscle Alterations During Maximal Voluntary Isometric Contraction, Jacob Hutchison, Mark Timmons, Brandon Jones

Appalachian Student Healthcare Research Review

Background: This study evaluated the relationship between grip strength and forearm skeletal muscle architecture during maximal grip contractions. Grip strength is a gauge for many different health related attributes, yet research on muscle architecture has been primarily completed in lower limb studies. This study aims to develop a better understanding of how biomechanical architecture of muscle operates to produce force during maximal isometric contractions of the forearms.

Methods: Sixteen individuals participated in this investigation (12 males, 4 females, mean age: 20.6 ± 2.5 years, mean height: 177.8 ± 8.3cm, mean weight: 79.2 ± 17.6Kg). Participants tested grip strength by performing …

Frontotemporal Dementia And Amyotrophic Lateral Sclerosis: A Case Report And Clinical Insights, Audrey Grigore, Lynne J. Goebel

Internal Medicine

Primary care providers are often the first contact for patients with neurodegenerative illnesses, however, they may not be aware of the relationship of certain diseases that may have an impact on their patients' longevity. This case report reminds clinicians of the association between frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Physicians should be aware of the association, because FTD commonly occurs first and may prepare clinicians to be alert to the signs of ALS in these patients, leading to earlier detection of ALS and the prescription of disease-modifying medication that may extend the lifespan of people with these diseases. …

In Vivo Evaluation Of Novel Nanoparticles And Repurposed Pharmaceuticals To Combat Antimicrobial Resistance, Sarah E. Evans

Theses, Dissertations and Capstones

In a 2019 report by the Centers for Disease Control and Prevention (CDC), infections resistant to antibiotic treatment amount to about three million infections and 48,000 deaths. Antimicrobial resistance is an escalating global threat as existing antibiotics lose efficacy over time. The project described is focused on partnering with pharmaceutical researchers and producers to test new nanoparticle-based or repurposed compounds. The central hypothesis of this thesis is that pharmaceutical formulations such as nanoparticles may provide a cost-effective means of combating the emerging antimicrobial resistance. The nanoparticle compounds allowed for a wide range of customization for the pharmaceutical design, since the …

Utilizing Probiotics To Reduce Diet Induced Dysbiosis And Inflammation In Myelodysplastic Syndromes Susceptible Mice, Tejaswee Bolloju

Theses, Dissertations and Capstones

Human gut microbiota is helpful in digestion by helping in breaking complex carbohydrates, proteins, fats and fibers and many other physiological functions. The Western diet which is high in fat and carbo hydrate percentage alters gut microbiota and leads to growth of pathogenic bacteria and altered gut flora referred to as dysbiosis, which in turn cause gut inflammation and increased permeability of gut and it causes translocation of Lipopolysaccharides (LPS) which causes low grade systemic inflammation. Disturbance in gut microbiota correlated with metabolic conditions like obesity and leads to progression of hematologic diseases like Myelodysplastic Syndromes (MDS). Myelodysplastic syndromes are …

Anti-Egfr Aptamer Exhibits Direct Anti-Cancer Effects In Nsclc Cells Harboring Egfr L858r Mutations, Brian J. Thomas, Sania Z. Awan, Trupti Joshi, Mark A. Daniels, David Porciani, Donald H. Burke

Biomedical Sciences

Non-small cell lung cancer (NSCLC) adenocarcinoma (LUAD) is a leading cause of death worldwide. Activating mutations in the tyrosine kinase domain of the oncogene epidermal growth factor receptor (EGFR) are responsible for ~10–50% of all LUAD cases. Although tyrosine kinase inhibitors (TKIs) have been effective in prolonging patient survival and quality of life, acquired resistance and disease progression are inevitable, presenting a clear unmet need for alternative or adjuvant therapeutics. Here we show that an anti-EGFR aptamer (EGFRapt) decreases viability and tumor growth of LUAD cell lines harboring the L858R ± T790M mutation in EGFR. Additionally, we elucidate …

Small And Long Non-Coding Rna Analysis For Humantrophoblast-Derived Extracellular Vesicles And Their Effect On The Transcriptome Profile Of Human Neural Progenitor Cells, Jessica A. Kinkade, Pallav Singh, Mohit Verma, Teka Khan, Toshihoko Ezashi, Nathan J. Bivens, R. Michael Roberts, Trupti Joshi, Cheryl S. Rosenfeld

Biomedical Sciences

In mice, the fetal brain is dependent upon the placenta for factors that guide its early development. This linkage between the two organs has given rise to the term, the placenta–brain axis. A similar interrelationship between the two organs may exist in humans. We hypothesize that extracellular vesicles (EVs) released from placental trophoblast (TB) cells transport small RNA and other informational biomolecules from the placenta to the brain where their contents have pleiotropic effects. Here, EVs were isolated from the medium in which human trophoblasts (TBs) had been differentiated in vitro from induced pluripotent stem cells (iPSC) and from cultured …

Industrial Explosion Survival After Presenting To A Rural Hospital: A Case Report, Carol L. Wright Becker, Roger Tillotson, William Krantz, Brad End, Stephanie Rellick, Emily Nutter

Marshall Journal of Medicine

Explosions can lead to numerous injuries.¹ Studies show that trauma mortality increases by 14% when patients are treated at rural hospitals compared to non-rural facilities.² A 43-year-old male arrived at a rural hospital with injuries from an explosion, where only a single board-certified emergency physician was on duty. The patient's polytrauma was severe, resulting in bilateral orbital compartment syndrome and Cushing's triad. Remarkably, he survived these extensive injuries. Despite the limitations of rural healthcare, such as restricted equipment, medications, and longer transfer times, rural emergency physicians should remain optimistic and help guide future management. This high-acuity, low-frequency trauma …

Enabling Cross-Modality Translation Between Single-Cell Rna-Seq And Single-Cell Atac-Seq Through Web-Based Portal, Zhen Lyu, Sabin Dahal, Shuai Zeng, Juexin Wang, Dong Xu, Trupti Joshi

Biomedical Sciences

In recent years, there has been a growing interest in profiling multiomic modalities within individual cells simultaneously. One such example is integrating combined single-cell RNA sequencing (scRNA-seq) data and single-cell transposase-accessible chromatin sequencing (scATAC-seq) data. Integrated analysis of diverse modalities has helped researchers make more accurate predictions and gain a more comprehensive understanding than with single-modality analysis. However, generating such multimodal data is technically challenging and expensive, leading to limited availability of single-cell co-assay data. Here, we propose a model for cross-modal prediction between the transcriptome and chromatin profiles in single cells. Our model is based on a deep neural …

Abnormal Morphology And Synaptogenic Signaling In Astrocytes Following Prenatal Opioid Exposure, Ethan B. Niebergall, Daron Weekley, Anna Mazur, Nathan A. Olszewski, Kayla M. Deschepper, N. Radant, Aishwarya S. Vijay

Biomedical Sciences

In recent decades, there has been a dramatic rise in the rates of children being born after in utero exposure to drugs of abuse, particularly opioids. Opioids have been shown to have detrimental effects on neurons and glia in the central nervous system (CNS), but the impact of prenatal opioid exposure (POE) on still-developing synaptic circuitry is largely unknown. Astrocytes exert a powerful influence on synaptic development, secreting factors to either promote or inhibit synapse formation and neuronal maturation in the developing CNS. Here, we investigated the effects of the partial µ-opioid receptor agonist buprenorphine on astrocyte synaptogenic signaling and …

Ogilvie's Syndrome: Acute Colonic Pseudoobstruction. A Review For Residents., Tyler Bayliss, Caleb Clark, Errington C. Thompson

Marshall Journal of Medicine

Ogilvie's syndrome (acute colonic pseudoobstruction) was first described in 1948. Acute colonic pseudoobstruction can occur in a variety of clinical settings, including postsurgical, obstetrics, pelvic surgery, critical care and sepsis. Clinicians need to recognize the syndrome early. Colonic distention without evidence of obstruction can be seen on plain films of the abdomen or CT scan. Successful therapies, including bowel rest, neostigmine and colonoscopic decompression, have been used. Avoiding respiratory compromise from abdominal distention and colonic perforation of the primary goals of treatment. Surgical intervention should be reserved for patients who are refractory to medical treatment or develops signs and symptoms …

Modulation Of Diet-Induced Gut Inflammation In Slowing Initiation Of Hematologic Malignancies, Esther Nyarkoa Mensah

Theses, Dissertations and Capstones

The intestinal tract serves as a host to an extremely complex microbial system. Microbes in the gut regulate their metabolism in response to chemicals generated by other microorganisms as well as nutrition supply from dietary intake. Alterations in gut bacteria have been implicated in the development of metabolic disorders such as obesity and the progression of diseases such as Myelodysplastic syndromes (MDS). Although the cause of obesity is multifactorial, the consumption of high-fat or sugar-rich diets (Western diets) has been proposed as a significant contributor to this global epidemic. Obesity is a major public health concern that has been extensively …

The E-Liquid Flavorings Cinnamaldehyde, Vanillin, And Ethyl Vanillin Induce Cellular Stress Responses In Human Proximal Tubule (Hk-2) Epithelial Cells, Ashley J. Cox

Theses, Dissertations and Capstones

The use of electronic nicotine delivery systems (ENDS) has become popular in recent years as an alternative to traditional cigarettes. These devices heat and subsequently vaporize e-liquids for inhalation by the user, which allows for the delivery of ingredients such as flavorings, nicotine, and solvents through the vapor. Flavorings used in e-liquids are “generally recognized as safe” (GRAS) for consumption by the Food and Drug Administration (FDA), however there are currently no recommendations on safety regarding the inhalation of flavoring agents. While research characterizing effects of e-liquids and their flavorings is abundant in lung and respiratory tract models, few studies …

Examining The Impact Of Firearm Recoil During A Round Of Trap Shooting On Neurometabolic Changes Associated With Traumatic Brain Injury, Lakota Jones

Theses, Dissertations and Capstones

The CDC identifies concussion as a blunt, blow, or jolt to the head resulting in brain injury. Shooting sports do not impose a direct blow to the head but instead inflict rapid acceleration to the brain via recoil transfer. Exposure to rapid, repetitive recoil may cause physiological disturbances in the brain, therefore resulting in mild traumatic brain injury (TBI). Chronic recoil transfer and overpressure exposure influencing neurometabolic changes of TBI have yet to be measured. The objective of this study was to examine kinetic energy experienced in trap and skeet shooters following one round of shooting in comparison to neurometabolic …

Role Of Insulin-Like Growth Factor-1 Signaling In Diet-Enhanced Bone Elongation, Cassaundra A. White

Theses, Dissertations and Capstones

Childhood obesity has increased precipitously to the point that almost 20% of children between the ages of 2 and 19 have been diagnosed with obesity. While obesity is a complex metabolic disorder, one contributing factor is diet, particularly a diet high in fat. Among many problems associated with diet-induced obesity, the impact on skeletal health is often overlooked. In addition to increased stress on the skeleton due to excess weight, obesity also disrupts the endocrine and immune systems that, in turn, can secondarily alter skeletal growth. Obesity during the early years of childhood is particularly detrimental because the skeleton is …

Inflammatory Protein Elicitation In Response To Whole-Body Vibration Exposure, Nicholas Miller

Theses, Dissertations and Capstones

This study aimed to assess the effects of whole-body vibration (WBV) on the brain through changes in blood protein concentrations, seat and head accelerations, and symptomatology over time. Subjects were assigned to control, 1-hour, or 8-hour vibration exposure groups. Glial fibrillary acidic protein (GFAP) and S100B concentrations were measured. Root mean square average weighted vibration (A_ws), vibration dose value (VDV), and seat-to-head transmissibility (STHT) were calculated. There were no differences in GFAP (p = 0.79) or S100B (p = 0.97) concentrations between 1-hour and 8-hour subjects (p = 0.79). Average weighted head acceleration (p …

A Novel Role Of Tgfbi In Macrophage Polarization And Macrophage-Induced Pancreatic Cancer Growth And Therapeutic Resistance, Jing Zhou, Nan Lyu, Qiongling Wanga, Ming Yang, Eric T. Kimchi, Kun Chenge, Trupti Joshi, Adama R. Tukulif, Kevin F. Staveley-O’Carroll, Guangfu Li

Biomedical Sciences

Tumor-associated macrophages (TAMs), as a major and essential component of tumor microenvironment (TME), play a critical role in orchestrating pancreatic cancer (PaC) tumorigenesis from initiation to angiogenesis, growth, and systemic dissemination, as well as immunosuppression and resistance to chemotherapy and immunotherapy; however, the critical intrinsic factors responsible for TAMs reprograming and function remain to be identified. By performing single-cell RNA sequencing, transforming growth factor-beta-induced protein (TGFBI) was identified as TAM-producing factor in murine PaC tumors. TAMs express TGFBI in human PaC and TGFBI expression is positively related with human PaC growth. By inducing TGFBI loss-of-function in macrophage (MΦs) in vitro …

Sprouty4 Is Epigenetically Upregulated In Human Colorectal Cancer, Alexei J. Stuckel, Shuai Zeng, Zhen Lyu, Wei Zhang, Xu Zhang, Urszula Dougherty, Reba Mustafi, Tripti Khare, Qiong Zhang, Trupti Joshi, Marc Bissonnette, Sharad Khare

Biomedical Sciences

Sprouty4 (SPRY4) has been frequently reported as a tumor suppressor and is therefore downregulated in various cancers. For the first time, we report that SPRY4 is epigenetically upregulated in colorectal cancer (CRC). In this study, we explored DNA methylation and hydroxymethylation levels of SPRY4 in CRC cells and patient samples and correlated these findings with mRNA and protein expression levels. Three loci within the promoter region of SPRY4 were evaluated for 5mC levels in CRC using the combined bisulfite restriction analysis. In addition, hydroxymethylation levels within SPRY4 were measured in CRC patients. Lastly, DNA methylation and mRNA expression data were …

Multi-Omics Analysis Of Circulating Exosomes In Adherent Long-Term Treated Osa Patients, Abdelnaby Khalyfa, Jose M. Marin, David Sanz-Rubio, Zhen Lyu, Trupti Joshi, David Gozal

Biomedical Sciences

Obstructive sleep apnea (OSA) is a highly prevalent chronic disease affecting nearly a billion people globally and increasing the risk of multi-organ morbidity and overall mortality. However, the mechanisms underlying such adverse outcomes remain incompletely delineated. Extracellular vesicles (exosomes) are secreted by most cells, are involved in both proximal and long-distance intercellular communication, and contribute toward homeostasis under physiological conditions. A multi-omics integrative assessment of plasma-derived exosomes from adult OSA patients prior to and after 1-year adherent CPAP treatment is lacking. We conducted multi-omic integrative assessments of plasma-derived exosomes from adult OSA patients prior to and following 1-year adherent CPAP …