Digital Commons Network^™

Clinical Trial Protocol For Beach: A Phase 2a Study Of Mw189 In Patients With Acute Nontraumatic Intracerebral Hemorrhage, Radhika Avadhani, Wendy C. Ziai, Richard E. Thompson, W. Andrew Mould, Karen Lane, Angeline Nanni, Michael Lacobelli, Matthew F. Sharrock, Lauren H. Sansing, Linda J. Van Eldik, Daniel F. Hanley

Neurology Faculty Publications

Patients with acute spontaneous intracerebral hemorrhage (ICH) develop secondary neuroinflammation and cerebral edema that can further damage the brain and lead to increased risk of neurologic complications. Preclinical studies in animal models of acute brain injury have shown that a novel small-molecule drug candidate, MW01-6-189WH (MW189), decreases neuroinflammation and cerebral edema and improves functional outcomes. MW189 was also safe and well tolerated in phase 1 studies in healthy adults. The proof-of-concept phase 2a Biomarker and Edema Attenuation in IntraCerebral Hemorrhage (BEACH) clinical trial is a first-in-patient, multicenter, randomized, double-blind, placebo-controlled trial. It is designed to determine the safety and tolerability …

Nalfurafine Promotes Myelination In Vitro And Facilitates Recovery From Cuprizone + Rapamycin-Induced Demyelination In Mice, Ross Van De Wetering, Rabia Bibi, Andy Biggerstaff, Sheein Hong, Bria Pengelly, Thomas E. Prisinzano, Anne C. La Flamme, Bronwyn M. Kivell

Markey Cancer Center Faculty Publications

The kappa opioid receptor has been identified as a promising therapeutic target for promoting remyelination. In the current study, we evaluated the ability of nalfurafine to promote oligodendrocyte progenitor cell (OPC) differentiation and myelination in vitro, and its efficacy in an extended, cuprizone-induced demyelination model. Primary mouse (C57BL/6J) OPC-containing cultures were treated with nalfurafine (0.6–200 nM), clemastine (0.01–100 μM), T3 (30 ng/mL), or vehicle for 5 days. Using immunocytochemistry and confocal microscopy, we found that nalfurafine treatment increased OPC differentiation, oligodendrocyte (OL) morphological complexity, and myelination of nanofibers in vitro. Adult male mice (C57BL/6J) were given a diet con- taining …

Ezh2 Inhibition Promotes Tumor Immunogenicity In Lung Squamous Cell Carcinomas, Tanner Ducote, Xiulong Song, Kassandra J. Naughton, Fan Chen, Daniel Plaugher, Avery R. Childress, Abigail R. Gellert, Erika M. Skaggs, Xufeng Qu, Jinze Liu, Jinpeng Liu, Fei Li, Kwok-Kin Wong, Christine F. Brainson

Markey Cancer Center Faculty Publications

Two important factors that contribute to resistance to immune checkpoint inhibitors (ICI) are an immune-suppressive microenvironment and limited antigen presentation by tumor cells. In this study, we examine whether in- hibition of the methyltransferase enhancer of zeste homolog 2 (EZH2) can increase ICI response in lung squamous cell carcinomas (LSCC). Our in vitro experiments using two-dimensional human cancer cell lines as well as three-dimensional murine and patient-derived organoids treated with two inhibitors of the EZH2 plus IFNγ showed that EZH2 inhibition leads to expression of both MHC class I and II (MHCI/II) expression at both the mRNA and protein levels. …

Taste And Learning In The Gustatory Cortex, Martin Raymond

Alternative Theses and Dissertations (AETDs)

This research investigates the organization of taste representations in the gustatory cortex (GC) through two experiments utilizing miniscope imaging in mice. The first experiment focuses on conditioned taste aversion (CTA) and reveals that taste representations in GC are heavily dominated by palatability, with shifts in representational space occurring as a function of learning and extinction. The second experiment explores the interrelation of aversive stimuli, the impact of novelty on taste representations, and the role of somatosensory feedback. Findings suggest that familiarity and palatability emerge as positive signals with experience, shaping taste representations in GC. The study contributes to a nuanced …

Early Life Exposure To Deltamethrin Impairs Synaptic Function By Altering The Brain-Derived Extracellular Vesicle Proteome, Leandra Koff, Jessica Di Re, Subhash Chand, Yosef Avchalumov, Nghi M. Nguyen, Timothy J. Baumgartner, Aditya K. Singh, Nana A. Goode, Mate Marosi, Lance M. Hallberg, Bill T. Ameredes, Thomas A. Green, Sowmya V. Yelamanchili, Gurudutt Pendyala, Fernanda Laezza

Journal Articles: Anesthesiology

Pyrethroid pesticides have been associated with neurodevelopmental disorders including attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). While behavioral effects of pyrethroid exposure have been previously reported, the underlying mechanisms remain unclear. Here, we hypothesized that exposure to deltamethrin (DM), a widely used pyrethroid pesticide known for its neurotoxicity during early developmental stages, induces brain dysfunction through alterations in brain-derived extracellular vesicle (BDEV) signaling. Using a well-established rodent model of early life DM exposure within the recommended no observable effect level, we isolated BDEVs from postnatal 30-day-old vehicle-exposed (control) and DM-exposed mice using a differential sucrose density gradient. Following …

Association Between Gallstone Disease And Kidney Stone Disease: A Systematic Review And Meta-Analysis, Faramarz Beigi, Alizamen Salehifard Jouneghani, Sae Heari-Soureshjani, Catherine M.T. Sherwin, Ghorbanali Rahimian

Pediatrics Faculty Publications

Background and aims: Gallstone disease (GSD) and kidney stone disease (KSD) have increased due to lifestyle in recent decades. This systematic review and meta-analysis aimed to investigate the association between these two diseases. Methods: A comprehensive electronic database search was conducted before August 25, 2024. This systematic review and meta-analysis included observational studies. The meta-analysis employed a random-effects model to compute the overall summary estimates of the association between GSD and KSD using risk ratios with 95% confidence intervals (CIs) as the primary measure of the effect size. Heterogeneity was evaluated using chi-square tests, the I² statistic, and forest plots. …

Non-Coding Rnas Involved In The Molecular Pathology Of Alzheimer’S Disease: A Systematic Review, Reynand Jay Canoy, Jenica Clarisse Sy, Christian Deo Deguit, Caitlin Bridgette Castro, Lyoneil James Dimaapi, Beatrice Gabrielle Panlaqui, Wenzel Perian, Justine Yu, John Mark Velasco, Jesus Emmanuel Sevilleja, Anna Gibson

Ateneo School of Medicine and Public Health Publications

Alzheimer’s disease (AD) is the leading cause of dementia globally, having a pathophysiology that is complex and multifactorial. Recent findings highlight the significant role of non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and piwi-interacting RNAs (piRNAs) in the molecular mechanisms underlying AD. These ncRNAs are involved in critical biological processes such as cell proliferation, apoptosis, oxidative stress, amyloid-beta aggregation, tau phosphorylation, neuroinflammation, and autophagy, which are pivotal in AD development and progression. This systematic review aims to consolidate current scientific knowledge on the role of ncRNAs in AD, making it the first to encompass …

Projecting Temperature-Related Dengue Burden In The Philippines Under Various Socioeconomic Pathway Scenarios, Xerxes Seposo, Sary Valenzuela, Geminn Louis C. Apostol, Keith Alexius Wangkay, Percival Ethan Lao, Anna Beatrice Enriquez

Ateneo School of Medicine and Public Health Publications

Introduction

As climate change advances, the looming threat of dengue fever, intricately tied to rising temperatures, intensifies, posing a substantial and enduring public health challenge in the Philippines. This study aims to investigate the historical and projected excess dengue disease burden attributable to temperature to help inform climate change policies, and guide resource allocation for strategic climate change and dengue disease interventions.

Methods

The study utilized established temperature-dengue risk functions to estimate the historical dengue burden attributable to increased temperatures. Future projections were derived using Coupled Model Intercomparison Project Phase 6 (CMIP6) Shared Socioeconomic Pathway (SSP) scenarios to estimate the …

Impacts Of Climate Change On Vector-Borne Disease Burden In The United States: Exploring The Epidemiological Evidence, Leah V. Loetman

Honors Theses

Climate change models predict shifts in vector-borne diseases (VBDs) around the world, including in the United States. However, to my knowledge there has yet to be a comprehensive descriptive epidemiological study examining prevalence, geographic distribution, and trends for all tick- and mosquito-borne diseases in the United States. I compiled data from the U.S. Centers for Disease Control (CDC), which publishes yearly case numbers for 17 vector-borne diseases. However, these publications depend on a scattered framework of state regulations regarding disease reporting. I compiled data from the CDC to determine the current geographic distribution, prevalence, and trends of tick- and mosquito-borne …

Unveiling The Complex World Of Extracellular Vesicles: Novel Characterization Techniques And Manufacturing Considerations, James J Lai, John J Hill, Casey Y Huang, Gino C Lee, Karol W Mai, Maggie Y Shen, Simon K Wang

Faculty, Staff and Student Publications

Extracellular vesicles (EVs) function as potent mediators of intercellular communication for many in vivo processes, contributing to both health and disease related conditions. Given their biological origins and diverse functionality from correspondingly unique "cargo" compositions, both endogenous and modified EVs are garnering attention as promising therapeutic modalities and vehicles for targeted therapeutic delivery applications. Their diversity in composition, however, has revealed a significant need for more comprehensive analytical-based characterization methods, and manufacturing processes that are consistent and scalable. In this review, we explore the dynamic landscape of EV research and development efforts, ranging from novel isolation approaches, to their analytical …

Cyanide Toxicity Induced By Apricot Kernel Consumption: A Case Report, Jatin Sadarangani, Vaishnavi Singh, Benjamin K. Kingsly

North Texas GME Research Forum 2024

Functional foods are food items that should be consumed as part of a regular diet in order to provide advantages beyond what are typically referred to as traditional nutritional benefits. Furthermore, in order to support the better function claim or the decreased illness risk claim, these positive outcomes must be scientifically proven. Foods with particular health benefits have been referred to as "superfoods" more recently. Superfoods are conceptually defined as foods with high biological value because of their high concentration of bioactive components and high concentration of nutrients, as well as their high bioavailability and bioactivity in the body. As …

Angioedema Linked To Combination Pill Trandolapril/Verapamil, Aadil Bhutta, Sana Khan, Monica Dhiman, Udit Bhatt, Akinjide Onifade

North Texas GME Research Forum 2024

Angioedema is the swelling of deeper layers of skin caused by a build-up fluid, oftentimes due to the culmination of immune system activation against allergens. There are several causes of angioedema, including animal dander, exposure to various foods, insect bites, and medications such as Angiotensin-converting enzyme (ACE) inhibitors and Angiotensin II receptor blockers (ARBs). This swelling primarily presents periorbital and periorally, however can also less-commonly affect the airway. Angioedema can be life-threatening if involving the throat and larynx given the potential of respiratory airway compromise. This case presents a patient who had been on an ACE-ARB for almost 2 decades, …

Post Operative Atrial Fibrillation After Coronary Artery Bypass Grafting In Octogenarians: A Systematic Review, M Eliann Reinhardt, Manuel Jimenez, Priya Mohan, Bernardo Reyes

East Florida Division GME Research Day 2024

No abstract provided.

Informing A Care Plan For Hepatitis C Treatment On The Street, Claire Campbell

Scripps Senior Theses

This thesis aims to use community knowledge to inform clinical street treatment of Hepatitis C and to unpack the intersections of social systems within the realms of Street Medicine and healthcare for the unsheltered unhoused population. During the summer of 2023, 15 qualitative interviews were conducted with patients of the USC Keck School of Medicine Department of Street Medicine who received treatment for Hepatitis C infections. Using grounded theory analysis, participant responses were analyzed to identify key concepts and ideas from interview transcripts. Core themes fell into the following categories: how treatment affected patients’ lives, facilitators and barriers to treatment, …

Elucidating The Role Of Fatty Acid Synthase In Apc-Driven Colorectal Cancer, Courtney O. Kelson

Theses and Dissertations--Toxicology and Cancer Biology

Globally, colorectal cancer (CRC) is the second leading cause of cancer related deaths. Currently, there is a growing incidence rate for individuals aged 20-49 years. Genetic and environmental factors contribute to the risk of this cancer. Early detection of CRC allows for the most effective treatment option in which surgical resection of the primary tumor occurs along with adjuvant chemotherapy. This therapeutic approach contributes to 5-year survival rate of 91%. However, surgical procedures and chemotherapy struggles against metastatic and relapsed CRC resulting in 5-year survival rate of 14%. Inefficacious treatments for relapsed and metastatic diseases emphasizes the need for more …

Unleashing Wellness: Exploring The Impact Of Pet Therapy On Anxiety Reduction, Quality Of Life, And Treatment Adherence In Pediatric Oncology Patients, Karina Brouwer

Nursing | Senior Theses

Pet therapy is a complementary intervention that involves the interaction between a person and animal, with the focus of improving psychological well-being within diverse populations. In particular, children with oncological disorders have increases in anxiety and stress levels, therefore it is imperative to study the impact of animal interventions within this population. This literature critique explores the impact of pet therapy interventions on anxiety, stress, and quality of life perceptions in pediatric oncology patients. This research proposal will investigate how animal therapy interactions within pediatric oncology patients influence their anxiety levels and perceptions of quality of life and how these …

Zebrafish Drug Screening Identifies Erlotinib As An Inhibitor Of Wnt/ Β-Catenin Signaling And Self-Renewal In T-Cell Acute Lymphoblastic Leukemia, Majd A. Al-Hamaly, Anna H. Cox, Meghan G. Haney, Wen Zhang, Emma C. Arvin, Shilpa Sampathi, Mary Wimsett, Chunming Liu, Jessica S. Blackburn

Markey Cancer Center Faculty Publications

The Wnt/β-catenin pathway’s significance in cancer initiation, progression, and stem cell biology underscores its therapeutic potential. However, the clinical application of Wnt inhibitors remains limited due to challenges posed by off-target effects and complex cross-talk of Wnt signaling with other pathways. In this study, we leveraged a zebrafish model to perform a robust and rapid drug screening of 773 FDA-approved compounds to identify Wnt/β-catenin inhibitors with minimal toxicity. Utilizing zebrafish expressing a Wnt reporter, we identified several drugs that suppressed Wnt signaling without compromising zebrafish development. The effi- cacy of the top hit, Erlotinib, extended to human cells, where it …

Traditional Chinese Medicine: Employing Integrative Medicine As An Approach To Treat Cancer, Jade Hudson

CMC Senior Theses

This thesis explores the history of Traditional Chinese Medicine (TCM) through its depiction in the four classics of TCM and examines the evolution of the field to date. The five categories of TCM treatments analyzed in this paper include acupuncture, dietary therapy, herbal medicine, moxibustion, and physical exercise. Research highlights significant positive outcomes in cancer patients who incorporate TCM alongside modern cancer treatments, such as reduced nausea, vomiting, fatigue, anorexia, pain, and improvements in quality of life and overall well-being. However, notable risks associated with TCM herbal medicine and moxibustion underscore the need for further research into these practices before …

Food Allergies, The Immune Response, And Preventative Treatments: Milk, Egg, And Shellfish Allergies, Marissa Dimatteo

Undergraduate Honors Theses

Food allergies have been an increasing concern worldwide with very little information on preventative measures and treatment. They can have long lasting and life-threatening consequences with a wide range of symptoms from hives to anaphylactic shock. Long recommended feeding guidelines, vitamin and mineral deficiencies, and gastrointestinal alterations are thought to play a role in the increase in food allergies in infants. Early introduction of food, immunotherapy, and a properly supported gut microbiome have been recommended to decrease the likelihood of developing a food allergy and desensitizing the immune system.

Abnormalities In Pharyngeal Arch-Derived Structures In Satb2-Associated Syndrome, Yuri A. Zarate, Katherine Bosanko, Nada Derar, Jennifer L. Fish

Pediatrics Faculty Publications

SATB2-associated syndrome (SAS, glass syndrome, OMIM#612313) is a neurodevelopmental autosomal dominant disorder with frequent craniofacial abnormalities including palatal and dental anomalies. To assess the role of Satb2 in craniofacial development, we analyzed mutant mice at different stages of development. Here, we show that Satb2 is broadly expressed in early embryonic mouse development including the mesenchyme of the second and third arches. Satb2-/- mutant mice exhibit microglossia, a shortened lower jaw, smaller trigeminal ganglia, and larger thyroids. We correlate these findings with the detailed clinical phenotype of four individuals with SAS and remarkable craniofacial phenotypes with one requiring mandibular distraction in …

Importance Of Tropical Medicine, Chia-Chi Angela Fu, A Clinton White, Miguel Cabada, Ryan Northup

Posters

Overviews the importance of tropical medicine to society and global health.

Astrocytic Mitochondrial Transfer To Brain Endothelial Cells And Pericytes In Vivo Increases With Aging, Gopal V. Velmurugan, Hemendra J. Vekaria, Samir P. Patel, Patrick G. Sullivan, W. Brad Hubbard

Neurology Faculty Publications

Intercellular mitochondrial transfer (IMT) is an intriguing biological phenomenon where mitochondria are transferred between different cells and notably, cell types. IMT is physiological, occurring in normal conditions, but also is utilized to deliver healthy mitochondria to cells in distress. Transferred mitochondria can be integrated to improve cellular metabolism, and mitochondrial function. Research on the mitochondrial transfer axis between astrocytes and brain capillaries in vivo is limited by the cellular heterogeneity of the neurovascular unit. To this end, we developed an inducible mouse model that expresses mitochondrial Dendra2 only in astrocytes and then isolated brain capillaries to remove all intact astrocytes. …

Using Digital Pathology To Analyze The Murine Cerebrovasculature, Dana M. Niedowicz, Jenna L. Gollihue, Erica M. Weekman, Panhavuth Phe, Donna M. Wilcock, Christopher M. Norris, Peter T. Nelson

Neurology Faculty Publications

Research on the cerebrovasculature may provide insights into brain health and disease. Immunohistochemical staining is one way to visualize blood vessels, and digital pathology has the potential to revolutionize the measurement of blood vessel parameters. These tools provide opportunities for translational mouse model research. However, mouse brain tissue presents a formidable set of technical challenges, including potentially high background staining and crossreactivity of endogenous IgG. Formalin-fixed paraffin-embedded (FFPE) and fixed frozen sections, both of which are widely used, may require different methods. In this study, we optimized blood vessel staining in mouse brain tissue, testing both FFPE and frozen fixed …

Xuebijing Improves Intestinal Microcirculation Dysfunction In Septic Rats By Regulating The Vegf-A/Pi3k/Akt Signaling Pathway, A-Ling Tang, Yan Li, Li-Chao Sun, Xiao-Yu Liu, Nan Gao, Sheng-Tao Yan, Guo-Qiang Zhang

Faculty, Staff and Student Publications

BACKGROUND: This study aims to explore whether Xuebijing (XBJ) can improve intestinal microcirculation dysfunction in sepsis and its mechanism.

METHODS: A rat model of sepsis was established by cecal ligation and puncture (CLP). A total of 30 male SD rats were divided into four groups: sham group, CLP group, XBJ + axitinib group, and XBJ group. XBJ was intraperitoneally injected 2 h before CLP. Hemodynamic data (blood pressure and heart rate) were recorded. The intestinal microcirculation data of the rats were analyzed via microcirculation imaging. Enzyme-linked immunosorbent assay (ELISA) kits were used to detect the serum levels of interleukin-6 (IL-6), …

The Unequal Distribution Of Social Risk For Black Men Across The Life-Span. A Novel Framework., Waleed Y. Sami

Adultspan Journal

This conceptual overview offers a comprehensive overview of systemic pathways that negatively impact the mental health of Black Men throughout their lives. Our argument highlights the importance for counselors and mental health professionals to utilize a thorough social risk assessment that considers these pathways in order to effectively address the mental health needs of Black Men while fostering positive working relationships. This overview strongly advocates for the use of context and structural determinants when evaluating mental health symptoms. Without an appropriate understanding of social risk and determinants, counselors may inadvertently perpetuate disparities by decontextualizing symptomology, and reproducing racist discourse.

A Novel Non-Rodent Animal Model Of Hydrochloric Acid-Induced Acute And Chronic Lung Injury, Pavel A. Solopov, Ruben Manuel Luciano Biancatelli, Tierney Day, Christiana Dimitropoulou, John D. Catravas

Bioelectrics Publications

Hydrochloric acid is one of the most prevalent and hazardous chemicals. Accidental spills occur in industrial plants or during transportation. Exposure to HCl can induce severe health impairment, including acute and chronic pulmonary diseases. We have previously described the molecular, structural, and functional aspects of the development of chronic lung injury and pulmonary fibrosis caused by intratracheal instillation of HCl in mice. Although mouse models of human disease have many advantages, rodents are evolutionary far from human and exhibit significant anatomical and physiological differences. Genetic and anatomic similarities between rabbits and humans are significantly higher. Rabbit models of HCl-induced lung …

Extending The Gift—Utilizing Residual Human Anatomical Materials For Training Pathologists' Assistants In Surgical Pathology Techniques, Kerwin M. Kolheffer, Lauren Yoho, Matthew Myers, Ismail El Moudden

Department of Pathology & Anatomy Faculty Publications

This study investigates the effectiveness of using residual human anatomical materials, obtained from a gross anatomy course, for training Pathologists' Assistant (PathA) students in surgical pathology techniques. We utilized two surveys to assess the perceived efficacy of this approach: one survey targeted PathA students to evaluate their training experiences with both human and animal tissues, while the other assessed the impact of specimen collection on the educational experiences of gross anatomy course students.

Evaluating The Influence Of Trypanosomiasis On Murine Model Using Corchorus Olitorius Leaf Extract As A Trypanocidal Agent, Fatima M. Madaki, Adamu Y. Kabiru, Ogunrombi D. Clinton, Sakariyau A. Waheed, Yunusa O. Ibrahim

Chemistry & Biochemistry Faculty Publications

Trypanosomiasis, a parasitic disease caused by trypanosomes, which are flagellate protozoa transmitted through the bite of the tsetse fly, manifests with symptoms including substantial weight loss, anemia, fever, edema, adenitis, dermatitis, and nervous disorders. This research investigated the impact of trypanosomiasis on a murine model while utilizing Corchorus olitorius leaf extract as a potential trypanocidal agent. An acute toxicity analysis was conducted following Lorke's method, and the antitrypanosomal efficacy was assessed in rats at doses of 100, 200, and 400 mg/kg over three weeks, monitoring changes in parasitemia count, body weight, and hematological parameters. Additionally, lipid profile, electrolyte concentration, and …

Unleashing Wellness: Exploring The Impact Of Pet Therapy On Anxiety Reduction, Quality Of Life, And Treatment Adherence In Pediatric Oncology Patients, Karina Brouwer

Nursing | Student Research Posters

Pet therapy is a complementary type of therapeutics in which a person and animal have a guided interaction with the purpose of helping someone cope with physical and/or mental illness. Animal-assisted therapy is used in numerous settings and has been shown to reduce stress, lower blood pressure and heart rate, and decrease anxiety and depression (Husson University, 2022). In particular, pediatric oncology patients have enormous amounts of stress in their lives, which leads to increased anxiety and decreased quality of life (Children's Cancer Cause, 2023). While evidence shows that integrating pet therapy in pediatric oncology patients produces significant benefits on …

Intravenous Contrast Extravasations Of Ct Contrast Media Prevention Bundle, Shakerra T. Brown

Doctor of Nursing Practice (DNP) Scholarly Projects - Archive

Contrast extravasations pose significant risks during intravenous contrast media imaging procedures, with potential adverse outcomes ranging from minor skin irritation to severe tissue necrosis. Despite technological advancements and procedural safeguards, contrast extravasations remain a concern in healthcare settings. A comprehensive needs assessment at our institution revealed a notable incidence of contrast extravasations, highlighting the need for targeted interventions to mitigate risk and enhance patient safety. This project aims to explore the complexities of contrast extravasations, examining contributing factors, associated complications, and current prevention and management strategies to inform evidence-based practices and improve patient outcomes. This Doctor of Nursing Practice (DNP) …