Pharmacology, Toxicology and Environmental Health Commons^™

Targeting Squalene Epoxidase Interrupts Homologous Recombination Via The Er Stress Response And Promotes Radiotherapy Efficacy, Zhipeng Hong, Tao Liu, Lingfeng Wan, Pengyan Fa, Pankaj Kumar, Yanan Cao, Chandra Bhushan Prasad, Zhaojun Qiu, Joseph Liu, Hongbing Wang, Zaibo Li, Qi-En Wang, Peixuan Guo, Deliang Guo, Ayse S. Yilmaz, Lanchun Lu, Ioanna Papandreou, Naduparambil K. Jacob, Chunhong Yan, Qing-Bai She

Pharmacology and Nutritional Sciences Faculty Publications

Over 50% of all patients with cancer are treated with radiotherapy. However, radiotherapy is often insufficient as a monotherapy and requires a nontoxic radiosensitizer. Squalene epoxidase (SQLE) controls cholesterol biosynthesis by converting squalene to 2,3-oxidosqualene. Given that SQLE is frequently overexpressed in human cancer, this study investigated the importance of SQLE in breast cancer and non–small cell lung cancer (NSCLC), two cancers often treated with radiotherapy. SQLE-positive IHC staining was observed in 68% of breast cancer and 56% of NSCLC specimens versus 15% and 25% in normal breast and lung tissue, respectively. Importantly, SQLE expression was an independent predictor of …

Superfund And Society Benumbed: An In-Depth Look At Environmental Justice In South Carolina, Sydney A. Hampton

Senior Theses

This thesis investigates the relationship between superfund sites in minority communities and their public health through the lens of social vulnerability. Various demographic parameters were used to assess the risk associated with minority communities and exposure to hazardous waste. After investigating the history of the Environmental Justice movement, three superfund sites of interest in South Carolina, and demographic and public health data; each community was analyzed to determine association between exposure to hazardous waste and minority status. Each examined community exhibited characteristics contributing to heightened social vulnerability, potentially causing increased susceptibility to negative health outcomes from exposure to hazardous waste.

The Efficacy And Safety Of Roxadustat For The Treatment Of Anemia In Non-Dialysis Dependent Chronic Kidney Disease Patients: An Updated Systematic Review And Meta-Analysis Of Randomized Clinical Trials, Basel Abdelazeem, Joseph Shehata, Kirellos Said Abbas, Nahla Ahmed El-Shahat, Bilal Malik, Pramod Savarapu, Mostafa Eltobgy, Arvind Kunadi

School of Medicine Faculty Publications

Background Roxadustat (ROX) is a new medication for anemia as a complication of chronic kidney disease (CKD). Our meta-analysis aims to evaluate the efficacy and safety of ROX, especially on the cardiovascular risks, for anemia in NDD-CKD patients. Methods Electronic databases were searched systematically from inception to July 2021 to look for randomized control trials (RCTs) that evaluated ROX NDD-CKD patients. Hemoglobin level and iron utilization parameters, including ferritin, serum iron, transferrin saturation (TSAT), total iron-binding capacity (TIBC), transferrin, and hepcidin were analyzed for efficacy. Pooled risk ratios (RRs) and standardized mean differences (SMDs) were calculated and presented with their …

Investigation Of Oncogenic Ras And Endoplasmic Reticulum-Mitochondria Calcium Flux And Their Relationship In The Context Of Tumorigenesis, Emma Anderson

Senior Honors Theses

Intracellular calcium as a signaling molecule is a pervasive feature of cellular pathways, especially those that manage internal homeostasis and transitions through the cell cycle, so much so that regulated, responsive calcium flux between the endoplasmic reticulum (ER) and the mitochondria has been suggested to play a major role in cancer development. Another factor commonly implicated in tumorigenesis is RAS, an oncogene that controls signaling for many pathways that are also regulated by calcium. While both calcium and oncogenic RAS signaling are implicated in cancer development, possible links between them have yet to be determined. The identification of these links …

Evaluation Of Protective Efficacy Of Viral Vector Based Swine Influenza Vaccine And A Method For B Cell Culture For Monoclonal Antibody Generation, Sushmita Kumari

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

Influenza A virus of the swine (IAV-S) is an economically important swine pathogen that has the potential to spread to humans, thus posing an ongoing public health concern due to its zoonotic potential. Hemagglutinin (HA), the most abundant viral envelope protein, is known to be the key protective antigen. Anti-HA antibodies alone, have been shown to prevent IAV infection. In this study we evaluated the feasibility of a recombinant tri segmented Pichinde virus (PICV) as a viral vector to deliver IAV-S hemagglutinin antigen in pigs. Four groups of weaned pigs (T01-04) were immunized twice with PBS, rPICV-GFP as a vector …

Targeting Delivery Of Bcl-2 Family Protein Inhibitor Has The Potential To Treat Cancer And Fibrosis, Mohammad Nurul Huda

Open Access Theses & Dissertations

Apoptosis is a naturally occurring cell death mechanism to remove the selective cell population. B-cell leukemia/lymphoma-2 (BCL-2) family protein plays a critical role in activating the upstream apoptosis signaling pathway, primarily the intrinsic apoptosis pathway. The BCL-2 family consists of both pro-and anti-apoptotic proteins, which are structurally and functionally similar, containing up to four BCL-2 homologies (BH) motifs (BH1-4). Defecting apoptosis along this signaling pathway can lead to various events, including malignant cell transformation, tumor metastasis, tissue fibrosis, and drug resistance. In fibrosis, the aberrant apoptosis signaling also activates multiple effector proteins and growth factors, such as TGF-β, CTGF, and …

Efforts To Increase The Ketamine-Like Activity Of The Rapid-Acting Antidepressant Ro-25-6981 (Mi-4) By Increasing Ampa Potentiation, Nathan Heger

Annual Research Symposium

The small molecule ketamine has generated much interest due to its rapid antidepressant effects. Despite having a rapid onset, ketamine has poor bioavailability, short duration of action, toxicities with long-term use, and a high potential for abuse. The molecule MI-4 (RO 25-6981) has also been shown to have both a rapid and sustained antidepressant effect. Most of the research into the mechanism of the rapid onset of MI-4 and ketamine has focused on their interaction with the NMDA receptor in addition to some monoamine transporters. Some recent publications have shown a significant role of AMPA receptors in the ketamine antidepressant …

Lipid Based Nanoparticles As A Novel Treatment Modality For Hepatocellular Carcinoma: A Comprehensive Review On Targeting And Recent Advances, Khaled Mahmoud, Shady Swidan, Mohamed A. El-Nabarawi, Mahmoud H. Teaima

Pharmacy

Liver cancer is considered one of the deadliest diseases with one of the highest disease burdens worldwide. Among the different types of liver cancer, hepatocellular carcinoma is considered to be the most common type. Multiple conventional approaches are being used in treating hepatocellular carcinoma. Focusing on drug treatment, regular agents in conventional forms fail to achieve the intended clinical outcomes. In order to improve the treatment outcomes, utilizing nanoparticles—specifically lipid based nanoparticles—are considered to be one of the most promising approaches being set in motion. Multiple forms of lipid based nanoparticles exist including liposomes, solid lipid nanoparticles, nanostructured lipid carriers, …

Enhancing The Capabilities Of Fluid Bed Granulation Through Process Automation And Digitalisation, Marcus O'Mahony, Caroline Mccormack, Chris O'Callaghan, Ian Jones, Gavin Walker, Patrick Cronin

Level 3

This paper describes a PAT-enabled, digitalised, and automated fluid bed granulation system. A multichannel Near-Infrared (NIR) spectrophotometer and a direct imaging particle size and shape analyser in constant dialogue with the SmartX no-code/low-code platform provide a ground-breaking process automation toolset now located at the Bernal Institute in the University of Limerick. Two sets of results are presented for this study, from two iterations of the Advance Dynamic Process Control (ADPC) controller application. The results demonstrate the direct measurement and control of the product’s critical quality attributes through digitality enabled feedback control of processing setpoints and parameters. The platform controlled the …

Effect Of Rehmannia Glutinosa Libosch Extract On Proliferation And Cardiogenic Pre-Differentiation Of Human Mesenchymal Stem Cells, Huu Dat Nguyen, Len Ho Thi, Xuan Bach Ho, Van Anh Cao, Duy Minh Le Hoang

BioMedicine

Background: Vietnamese medicine tried and tested certain bioactive compounds from plants to increase the rate of tissue immunomodulation, regeneration, and differentiation. Although there are many research papers discovered about phytochemicals of Rehmannia glutinosa Libosch and differentiation induction potential of some substances purified from this herbal, it finds difficult to seek research that investigated the effect of Rehmannia glutinosa Libosch extract on proliferation and cardiogenic differentiation of mesenchymal stem cells, even though it has commonly been used for a long time because of its function as a restorative and as a critical role in cardiovascular treatment in traditional.

Results: Our …

Implementation Of A Drive-Through Covid-19 Mass Vaccination Site: Experiences From Louvax–Broadbent In Louisville, Kentucky, Ruth Carrico, Sarah Beth Hartlage, Valenchia Brown Msn, Aprn, Fnp-C, Sarah M. Bishop, Luanne Didelot, William Hayden, Beverly Williams Coleman, Sarah Tan, Delanor Manson, Kellie Kane, Dawn Balcom, Paul Kern

The University of Louisville Journal of Respiratory Infections

Background: Response to the COVID-19 pandemic has required innovative approaches to vaccination, including methods to rapidly and safely immunize communities. A major challenge to such a response involved access to untapped healthcare worker resources. The Louisville, Kentucky, response involved the use of a large volunteer workforce to supplement local public health employees in planning and implementing a large-scale drive-through vaccination event. The objective of this manuscript was to outline processes involved in training a mass immunization workforce and implementating a large-scale COVID-19 community vaccination.

Approach: Competency-based and standardized training was provided for every volunteer before working their shift. Volunteers worked …

Mise En Visibilité Des Situations D’Exposition Cutanée Aux Pesticides Et Des Pratiques De Prévention : Développement Méthodologique Réalisé En Collaboration Avec Des Producteurs De Pommes Québécois (2e Édition), Caroline Jolly, Sylvie Beaugrand, Ludovic Tuduri, Élise Ledoux, Alain Garrigou

Rapports de recherche scientifique

Dans une optique de rentabilité visant la survie de l’entreprise, et pour répondre aux attentes de qualité du marché, les agriculteurs utilisent des pesticides. La littérature scientifique documente largement les effets à la santé susceptibles d’être liés à l’utilisation des pesticides. Plusieurs auteurs mentionnent l’importance de la voie cutanée comme voie d’exposition aux pesticides. Ce rapport présente le développement d’une méthodologie mixte alliant ergonomie et expologie visant à documenter l’exposition cutanée, les situations d’exposition et les pratiques de prévention associées.

Il s’appuie sur un devis de recherche par étude de cas qui se décline en quatre étapes : une étude …

Body Mass Index (Bmi): A Screening Tool Analysis, Deepesh Khanna, Cadynce Peltzer, Payal Kahar, Mayur S. Parmar

HPD Articles

Body mass index (BMI), a measurement based on a person's height and weight, allows the classification of individuals into categories such as obese or overweight. With these classifications, we can assess risk for hypertension, diabetes, cancer, hypercholesterolemia, and other chronic diseases. Furthermore, childhood BMI serves as a prediction method for health and disease later in life. Along with BMI, researchers also study waist circumference and waist-to-hip ratio in correlation with the above-mentioned chronic illnesses. This brief review explores the associations between body mass index, waist circumference, and the waist-hip ratio as measurements and their capability as predictors for persistent conditions …

The Environment Under The Knife: A Review Of Current Eco-Surgical Strategies And Recommendations For Pakistan, Russell Seth Martins, Edward Anthony Joseph, Javeria Tariq, Namrah Aziz, Saulat H. Fatimi

Medical College Documents

The healthcare sector at its core is based on the fundamentals belief to do no harm and bring about betterment in the lives of the people. Paradoxically, hospitals are one of the leading contributors to pollution, greenhouse gas (GHG) emissions and toxic waste material worldwide. Surgical care delivery is quite resource intensive, consuming significant amount of energy and equipment as well as producing large quantities of waste. With climate change being a global priority, it is crucial that hospitals re-evaluate the environmental impact of such practices. The current review was planned to identify areas of improvement in surgical care in …

Repurposing Metformin And Antifolates For The Treatment Of Hepatocellular Carcinoma, Sherouk Mohamed Tawfik

Theses and Dissertations

Hepatocellular carcinoma (HCC), one of the most prevalent types of cancers worldwide, continues to maintain high levels of resistance to standard therapy. As clinical data revealed poor response rates, the need for developing new methods has increased to improve the overall wellbeing of patients with HCC. Due to its safety, wide availability and previously reported anti-cancer effects, metformin (MET) serves to be a possible therapeutic agent when combined with other well-known anti-cancer agents. The aim of this study was to investigate the potential anti-cancer effects of MET, an anti-diabetic agent, when combined with two antifolate drugs: trimethoprim (TMP) or methotrexate …

Selective Gsk3Β Inhibition Mediates An Nrf2-Independent Anti-Inflammatory Microglial Response, Mohamed H. Yousef

Theses and Dissertations

Glycogen Synthase Kinase 3 (GSK3) is associated with the proinflammatory phenotype of microglia and has been shown to act in concert with Nuclear factor kappa B (NF-κB). . GSK3 is also a suppressor of Nuclear factor erythroid 2-related factor 2 (Nrf2), the principal regulator of redox homeostasis. Agreeing with the oxidative paradigm of aging, Nrf2 is often deregulated in parainflammatory and neurodegenerative diseases. In this study, we aimed to explore a multimodal disease-modifying utility of GSK3 inhibition, beyond neuronal proteopathologies, Furthermore, we aimed to underscore the difference in therapeutic value between the two GSK3 paralogs by isoform-selective chemical inhibition.

The …

Results Of A Phase 1, Randomized, Placebocontrolled First-In-Human Trial Of Griffithsin Formulated In A Carrageenan Vaginal Gel, Natalia Teleshova, Maria J. Keller, José A. Fernández Romero, Barbara A. Friedland, George W. Creasy, Marlena G. Plagianos, Laurie Ray, Patrick Barnable, Larisa Kizima, Aixa Rodriguez, Nadjet Cornejal, Claudia Melo, Gearoff Cruz Rodriguez, Sampurna Mukhopadhyay, Giulia Calenda, Shweta U. Sinkar, Thierry Bonnaire, Asa Wesenberg, Shimin Zhang, Kyle Kleinbeck, Kenneth Palmer, Mohcine Alami, Barry R. O'Keefe, Patrick Gillevet, Hong Hur, Yupu Liang, Gabriela Santone, Raina N. Fichorova, Tamara Kalir, Thomas M. Zydowsky

Publications and Research

HIV pre-exposure prophylaxis (PrEP) is dominated by clinical therapeutic antiretroviral (ARV) drugs. Griffithsin (GRFT) is a non-ARV lectin with potent anti-HIV activity. GRFT’s preclinical safety, lack of systemic absorption after vaginal administration in animal studies, and lack of cross-resistance with existing ARV drugs prompted its development for topical HIV PrEP. We investigated safety, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of PC-6500 (0.1% GRFT in a carrageenan (CG) gel) in healthy women after vaginal administration. This randomized, placebo-controlled, parallel group, double-blind first-in-human phase 1 study enrolled healthy, HIV-negative, non-pregnant women aged 24–45 years. In the open label period, all participants (n …

Breadth Of Vaccinated Cancer Patient Humoral Response To Sars-Cov-2 Spike Protein And Rbd Variants, Julia Corman, Joey Breckenridge Jr., Adrienne M. Bushau-Sprinkle, Krystal T. Hamorsky, Joshua L. Fuqua

Posters-at-the-Capitol

SARS-CoV-2, the virus responsible for the COVID-19 of which several variants have emerged, such as the B.1.351 SARS-CoV-2 variant. The Receptor Binding Domain (RBD), located within the Spike protein is an immunogenic epitope for potent neutralizing antibodies. Current mRNA vaccines encode for the Spike protein, allowing the body to build antigen-specific antibodies. Assays measuring protective antibodies are essential to manage the COVID-19 pandemic and can be used as a platform for variant screening. RBD-foldon 2.2 is a novel antigen produced by fusing RBD with the trimerization domain Fibritin from Bacteriophage T4. Its amino acid sequence is based on the original …

The Effect Of A Vegetation Buffer On Sound Levels, Madison Cicha

Posters-at-the-Capitol

Noise pollution is a growing concern in the environmental health community. Unlike other common exposures, such as air and water pollution, noise is uniquely difficult for an individual to protect themselves from. Studies have shown multiple adverse health outcomes resulting from exposure to noise pollution, including hearing impairment, negative social behavior and annoyance, sleep disturbance, along with a strong association between noise pollution and high cardiovascular risk. It is important, then, to look for solutions to this exposure. This study is designed to assess the effects of a tree barrier in reducing traffic noise. Noise monitoring was conducted at Saint …

Investigation Of The Effects Of Prenatal Drug Exposure On Astrocyte-Mediated Synaptogenic Signaling, Taylor Christian Boggess

Theses, Dissertations and Capstones

One of the most significant outcomes of the rise in rates of opioid abuse in the United States has been a dramatic increase in the incidence of neonatal abstinence syndrome (NAS), the clinical diagnosis for the collection of withdrawal-like signs and symptoms commonly observed in the newborns of mothers who abused certain drugs, such as opioids, during pregnancy. While a great deal of research has investigated the short-term symptoms and potential treatments for NAS, including my own studies to identify emerging trends among a local population of NAS patients, there remains a critical need to investigate the long-term effects of …

Golimumab, Inderbir S. Padda, Rajat Bhatt, Mayur S. Parmar

HPD Articles

No abstract provided.

Provoking The Desire, Taking Away The Performance: Toxic Effects From An Erectile Dysfunction Supplement, Jenna Betz, Md, Anjali Das, Md Ms

Poster Presentations

No abstract provided.

Small Interfering Rna (Sirna)-Based Therapy, Inderbir S. Padda, Arun U. Mahtani, Mayur S. Parmar

HPD Articles

No abstract provided.

Sodium-Glucose Transport Protein 2 (Sglt2) Inhibitors, Inderbir S. Padda, Arun U. Mahtani, Mayur S. Parmar

HPD Articles

No abstract provided.

Poststroke Seizure And Epilepsy: A Review Of Incidence, Risk Factors, Diagnosis, Pathophysiology, And Pharmacological Therapies, Joseph Phan, Mario Ramos, Theodore Soares, Mayur S. Parmar

HPD Articles

Stroke is the most common cause of epilepsy and ultimately leads to a decrease in the quality of life of those affected. Ischemic and hemorrhagic strokes can both lead to poststroke epilepsy (PSE). Significant risk factors for PSE include age < 65age less than 65 years, stroke severity measured by the National Institutes of Health Stroke Scale (NIHSS), cortical involvement, and genetic factors such as TRPM6 polymorphism. The diagnosis of PSE is made by using imaging modalities, blood biomarkers, and prognostic criteria. Electroencephalography (EEG) is currently the gold standard to diagnose PSE, while new combinations of modalities are being tested to increase diagnostic specificity. This literature review uncovers a newly found mechanism for the pathology of poststroke epilepsy. The pathogenesis of early-onset and late-onset is characterized by sequelae of neuronal cellular hypoxia and disruption of the blood-brain barrier, respectively. Interleukin-6 is responsible for increasing the activity of glial cells, causing gliosis and hyperexcitability of neurons. Epinephrine, high-mobility group protein B1, downregulation of CD32, and upregulation of HLA-DR impact the pathology of poststroke epilepsy by inhibiting the normal neuronal immune response. Decreased levels of neuropeptide Y, a neurotransmitter, act through multiple unique mechanisms, such as inhibiting intracellular Ca accumulation and acting as an anti-inflammatory, also implemented in the worsening progression of poststroke epilepsy. Additionally, CA1 hippocampal resonant neurons that increase theta oscillation are associated with poststroke epilepsy. Hypertensive small vessel disease may also have an implication in the temporal lobe epilepsy by causing occult microinfarctions. Furthermore, this review highlights the potential use of statins as primary prophylaxis against PSE, with multiple studies demonstrating a reduction in incidence using statins alone, statins in combination with antiepileptic drugs (AEDs), and statins with aspirin. The evidence strongly suggests that the second generation AEDs are a superior treatment method for PSE. Data from numerous studies demonstrate their relative lack of significant drug interactions, increased tolerability, and potential superiority in maintaining seizure-free status.

Pfas Environmental Contamination In Central Maine, Megan H. Andersen

Honors Theses

PFAS (per- and polyfluoroalkyl substances) are toxic, persistent, and bioaccumulative chemicals that are used in a variety of consumer products and industrial applications. Paper mills across the state of Maine have used PFAS in their industrial paper making processes, and their wastes often flow for treatment into municipal sewage treatment facilities. PFAS contaminated municipal wastewater from the general use of PFAS consumer products are also processed by these plants. Liquid waste is condensed into solid waste septage and sludge, and in what was thought to be an environmentally friendly repurposing practice, municipal sludge and septage has been spread on plots …

Recyclage Primaire Des Matières Résiduelles Électroniques Au Québec : Portrait De La Santé Et De La Sécurité Du Travail Et Appréciation Du Risque Sanitaire, Sabrina Gravel, Bouchra Bakhiyi, Joseph Zayed, Sylvie Gravel, Daniel Côté, Brigitte Roberge, Jacques Lavoie, Loïc Wingert, France Labrèche

Rapports de recherche scientifique

En raison de l’utilisation croissante de composants et d’appareils électriques et électroniques, de même que de leur durée de vie relativement courte, la quantité de matières résiduelles électroniques ne cesse d’augmenter. Conséquemment, le nombre d’entreprises spécialisées dans le recyclage électronique (e-recyclage) est en nette croissance au Québec, comme ailleurs dans le monde. Ces entreprises emploient des travailleurs qui ont pour tâche de démonter les appareils afin d’en trier les composants qui seront subséquemment valorisés ou éliminés de manière sécuritaire. Ces tâches peuvent cependant entraîner l’exposition des travailleurs à un mélange de substances potentiellement toxiques, comprenant entre autres des poussières, des …

Review Of Evidence For Environmental Causes Of Uveal Coloboma, Evan B Selzer, Delphine Blain, Robert B Hufnagel, Philip J Lupo, Laura E Mitchell, Brian P Brooks

Faculty, Staff and Student Publications

Uveal coloboma is a condition defined by missing ocular tissues and is a significant cause of childhood blindness. It occurs from a failure of the optic fissure to close during embryonic development and may lead to missing parts of the iris, ciliary body, retina, choroid, and optic nerve. Because there is no treatment for coloboma, efforts have focused on prevention. While several genetic causes of coloboma have been identified, little definitive research exists regarding the environmental causes of this condition. We review the current literature on environmental factors associated with coloboma in an effort to guide future research and preventative …

Disability In An American Indian Community : Prevalence, Distribution, And The Role Of Polychlorinated Biphenyls, Thoin Farzana Begum

Legacy Theses & Dissertations (2009 - 2024)

The Akwesasne reservation along the St. Lawrence River has experienced significant exposure to several persistent organic pollutants due to rapid industrialization. The Aluminum Company of America, General Motors, and Reynolds Metals operated aluminum foundries that used polychlorinated biphenyls (PCBs) as hydraulic fluids, which contaminated the community environment, the soil, air and water, and community food sources with PCBs. We administered the World Health Organization Disability Assessment Schedule II (WHODAS II) to 119 Akwesasne Mohawk adults residing along the St. Lawrence River in New York. We used exploratory factor analysis to summarize the 36- items comprising the WHODAS II. The 7 …

Trace Elements In Nails And Anemia In Children Living Along The Interoceanic Highway, Madre De Dios, Peru / Narrative Competence And Cognitive Mapping As A Culturally Sustaining Pedagogy In The Education Of Emergent Bilinguals, Tia Marks

Legacy Theses & Dissertations (2009 - 2024)

Anthropogenic changes in the Peruvian Amazon, including deforestation, highway development, agriculture, and artisanal and small-scale gold mining (ASGM), have increased community concern about potential exposures toxic trace elements (TTE) including arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb). Such exposures can lead to detrimental health effects in children, such as developmental delays and anemia. The overarching goal of my dissertation was to understand exposure to both toxic and essential (manganese (Mn), selenium (Se), and zinc (Zn)) trace elements, anemia prevalence, and the associations between hemoglobin (Hb) levels and trace elements. To do this, I leveraged existing data from a …