Pharmacology, Toxicology and Environmental Health Commons^™

Childhood Exposure To Per- And Polyfluoroalkyl Substances (Pfas) And Neurobehavioral Domains In Children At Age 8 Years, Ann M. Vuong, Kimberly Yolton, Changchun Xie, Kim N. Dietrich, Joseph M. Braun, Glenys M. Webster, Antonia M. Calafat, Bruce P. Lanphear, Aimin Chen

Environmental & Global Health Faculty Research

Background: Toxicological studies have raised concerns regarding the neurotoxic effects of per- and polyfluoroalkyl substances (PFAS). However, observational evidence from human studies investigating the association between childhood PFAS and neurobehavior is limited and remains unclear. Objectives: To examine whether childhood PFAS concentrations are associated with neurobehavior in children at age 8 years and whether child sex modifies this relationship. Methods: We used data from 208 mother-child dyads in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort (Cincinnati, OH, USA). We quantified PFAS in child serum at 3 and 8 years. We assessed …

Cocaine, Cocaethylene And Ethanol In Postmortem Blood Submitted To The New York City Office Of Chief Medical Examiner, Jada T. Alexis

Student Theses

Cocaine overdose deaths are on the rise in the United States. This increase may be due to the co-consumption of cocaine with other drugs. When cocaine is ingested in conjunction with alcohol, a specific metabolite called cocaethylene forms. Information regarding cocaethylene, specifically its interpretive value in post-mortem cases, has not been widely studied. Data from the Office of the Chief Medical Examiner in New York City revealed that there were 195 cases in 2017 positive for cocaethylene. These cases were most likely to involve black (42.1%) males (79.5%) in Manhattan (28.2%) aged 50 - 59 (34.4%). Most of the cases …

Innate Immune Activation By Checkpoint Inhibition In Human Patient-Derived Lung Cancer Tissues, Teresa W. M. Fan, Richard M. Higashi, Huan Song, Saeed Daneshmandi, Angela L. Mahan, Matthew S. Purdom, Therese J. Bocklage, Thomas A. Pittman, Daheng He, Chi Wang, Andrew N. Lane

Center for Environmental and Systems Biochemistry Faculty Publications

Although Pembrolizumab-based immunotherapy has significantly improved lung cancer patient survival, many patients show variable efficacy and resistance development. A better understanding of the drug’s action is needed to improve patient outcomes. Functional heterogeneity of the tumor microenvironment (TME) is crucial to modulating drug resistance; understanding of individual patients’ TME that impacts drug response is hampered by lack of appropriate models. Lung organotypic tissue slice cultures (OTC) with patients’ native TME procured from primary and brain-metastasized (BM) non-small cell lung cancer (NSCLC) patients were treated with Pembrolizumab and/or beta-glucan (WGP, an innate immune activator). Metabolic tracing with ¹³C₆-Glc/ …

Utilizing Proteolysis-Targeting Chimeras To Target The Transcriptional Cyclin-Dependent Kinases 9 And 12, Hannah King

Theses & Dissertations

Cyclin-dependent kinases (CDKs) are a family of serine-threonine kinases involved in various cellular functions, such as regulating the cell cycle and gene transcription. CDK9, a transcriptional CDK, regulates highly expressed enhancer-associated oncogenic transcription factors, including the oncogene Myc. CDK9 is responsible for the transcription and stabilization of Myc; consequently, it was a validated target for pancreatic cancer treatment.

As such, we developed a panel of aminopyrazole based proteolysis targeting chimera where we identified PROTAC 2 as a selective degrader of CDK9 (DC₅₀ = 158 ± 6 nM). PROTAC 2 was capable of cereblon mediated proteasomal degradation of CDK9 while …

Neonicotinoids Can Cause Arrested Pupal Ecdysis In Lepidoptera, Niranjana Krishnan, Russell A. Jurenka, Steven P. Bradbury

Biological Sciences Faculty Research & Creative Works

Recently, we reported a novel mode of action in monarch butterfly (Danaus plexippus) larvae exposed to neonicotinoid insecticides: arrest in pupal ecdysis following successful larval ecdysis. In this paper, we explore arrested pupal ecdysis in greater detail and propose adverse outcome pathways to explain how neonicotinoids cause this effect. Using imidacloprid as a model compound, we determined that final-instar monarchs, corn earworms (Helicoverpa zea), and wax moths (Galleria mellonella) showed high susceptibility to arrested pupal ecdysis while painted ladies (Vanessa cardui) and red admirals (Vanessa atalanta) showed low susceptibility. Fall …

Rsv-Induced Guillain–Barré Syndrome, Priyanga Jayakumar, Christe Shen, Dylan Goldsmith, Steven Lippmann

The University of Louisville Journal of Respiratory Infections

A patient with respiratory syncytial virus-induced Guillain–Barré Syndrome and acute disseminated encephalomyelitis is presented. This virus is the most common cause of upper respiratory infections, and it can become an etiology for extra-pulmonary pathology with serious complications. Such a case is rare, but the possibility of adverse comorbidities makes early diagnosis and treatment important.

Bacteria Assessment Of Soil Samples In Houston Watersheilds; Impact Of Heavy Metal, And Stress Responses In An Eukaryotic Co-Culture System., Folasade Adedoyin

Dissertations (2016-Present)

Houston has a complex watershed in which bayous intersect one another making the city prone to flooding, as evidenced by the 2017 Hurricane Harvey flood. We sought to evaluate bacterial population dynamics in Houston watershed soils pre- and post-Hurricane Harvey; additionally, we evaluated population dynamics in neighboring, downstream bayous ~ 1 year later in the summer and winter of 2018. This study quantified bacterial loads for pre-Hurricane Harvey (June 2017) and post-hurricane Harvey (November 2017) soil samples, as well as competitive samples from one year later [summer (June 2018) and winter (November) 2018]. Unexpectedly, bayous closer to Houston’s densely populated …

Investigating The Effects Of Perfluorooctanoic Sulfonate (Pfos) And Ethanol On Fatty Liver Disease Using A Modified Niaaa Model., Tyler Charles Gripshover

Electronic Theses and Dissertations

Perfluoroalkyl Substances (PFAS) are a family of man-made, surfactant-like compounds that are a major environmental contaminant. A multitude of studies have indicated that PFAS are able to induce fatty liver disease and modulate lipid metabolism. However, the distinct mechanism of PFAS influence on the liver and metabolism disruption remains to be elucidated. On the other hand, it is well documented that alcohol consumption has various adverse health impacts including fatty liver disease and subsequent progression to more adverse liver states. To date, there are no published studies on whether PFAS and alcohol can jointly exacerbate fatty liver progression or interact …

Toxicology Of Chemical Stress To Monarch Butterflies (Danaus Plexippus L.), Annie Krueger

Department of Entomology: Dissertations, Theses, and Student Research

Monarch butterfly (Danaus plexippus L.) population declines have caught the attention of the country and prompted nationwide conservation initiatives. The United States Fish and Wildlife Service has identified insecticide exposure and loss of milkweed (Asclepias spp.) reproductive habitat as primary threats to the monarch. In the Midwestern US, milkweed largely occurs around cropland borders where there may be a spatial and temporal overlap of monarch larvae, insecticide usage, and fertilizer applications. In this study, the acute toxicity and sub-lethal effects on growth and diet consumption of two commonly used pyrethroid insecticides, bifenthrin and beta-cyfluthrin, were characterized …

Geographic And Occupational Mobility Of Small-Scale Fishers Of Lake Malawi: An Exploratory Study Of Water, Sanitation, And Hygiene Access, Malawi., Rochelle H. Holm, Tikhala Chakalamba, Bwighane Ngasama, Fanuel Kapute

Faculty and Staff Scholarship

The livelihood of small-scale fishers on the world’s freshwater lakes cuts across the Sustainable Development Goal (SDG) 6, which covers water and sanitation, and SDG 8 on economic growth. The aim of this study was to examine the nature and extent of fishers’ mobility patterns and access to improved sanitation facilities, safe drinking water, and handwashing practices while at work and home for two fishing camps in Malawi. The study used key informant interviews, questionnaires, water quality testing, and an observational checklist, followed by interviews on fishers’ occupational migration. Many fishers (85%; 51/60) live and work in fishing camps with …

Biochar Applications To The Remediation Of Lead And Polychlorinated Biphenyl Contaminated Water, Victory Itua Igberase

Theses and Dissertations

This study investigated the performance of biochar materials as adsorbents to remove Pb and polychlorinated biphenyl (PCB) in aqueous solutions. Batch adsorption and column experiment packed with biochar and geomaterials (pumice) in 1:1 volume ratio was evaluated to address the efficacy of biochar in removing Pb while only batch adsorption was employed for PCB removal with biochar materials. Overall, PT biochars performed the best (42–53 mg g−1) followed by BE biochars (10–32 mg g−1) and AB biochars (17–27 mg g−1) while high temperature biochars were favored in terms of maximum Pb adsorption capacity. Column Pb breakthrough showed similar results, with …

Associations Between Physiological Biomarkers And Psychosocial Measures Of Pregnancy-Specific Anxiety And Depression With Support Intervention, Karen L Weis, Tony T Yuan, Katherine C Walker, Thomas F Gibbons, Wenyaw Chan

Faculty, Staff and Student Publications

Stress and anxiety significantly impact the hypothalamic-pituitary axis, and in pregnancy, the subsequent maternal-fetal response can lead to poor outcomes. The objective of this study was to assess the association between psychosocial measures of pregnancy-specific anxiety and physiologic inflammatory responses. Specifically, to determine the effectiveness of the Mentors Offering Maternal Support (M-O-M-S

The Disproportionate Impact Of Toxins In Consumer Products, Meredith Bollheimer, Elissa Reitz

The Seneca Falls Dialogues Journal

The number of chemicals used in everyday products has grown exponentially over the last century. Many of these chemicals are known endocrine disrupting compounds (EDC’s) and they have not been proven to be safe for humans or for the environment. Rather, many of these chemicals have been linked to negative human health outcomes and damage to the environment. Corporate America is responsible for the production and liberal use of these chemicals in consumer and personal care products. The federal government has failed to provide effective or meaningful standards or regulations for the myriad chemicals of concern that make their way …

Environmental Justice Analysis Of Drinking Water Policies In Michigan Cities, Annika Paldan

Honors Theses

This thesis examined environmental justice aspects of drinking water policies in four cities across Michigan: Flint, Birmingham, St. Joseph, and Benton Harbor. An overview of the history of the environmental justice movement, environmental racism, and drinking water policies provided the basis for a four-part evaluative criterion to assess environmental justice components at the municipal level. These criteria include (1) housing tenure, (2) age, size, and service line composition of the infrastructure, (3) public participation in the policy process, and (4) emergency management of the city. Findings indicate that environmental justice has come a long way, with cities now incorporating components …

Andrographolide Attenuates Gut-Brain-Axis Associated Pathology In Gulf War Illness By Modulating Bacteriome-Virome Associated Inflammation And Microglia-Neuron Proinflammatory Crosstalk, Punnag Saha, Peter T. Skidmore, Larinda A. Holland, Ayan Mondal, Dipro Bose, Ratanesh K. Seth, Kimberly Sullivan, Patricia A. Janulewicz, Ronnie Horner, Nancy Klimas, Mitzi Nagarkatti, Prakash Nagarkatti, Efrem S. Lim, Saurabh Chatterjee

Faculty Publications

Gulf War Illness (GWI) is a chronic multi-symptomatic illness that is associated with fatigue, pain, cognitive deficits, and gastrointestinal disturbances and presents a significant challenge to treat in clinics. Our previous studies show a role of an altered Gut-Brain axis pathology in disease development and symptom persistence in GWI. The present study utilizes a mouse model of GWI to study the role of a labdane diterpenoid andrographolide (AG) to attenuate the Gut-Brain axis-linked pathology. Results showed that AG treatment in mice (100 mg/kg) via oral gavage restored bacteriome alterations, significantly increased probiotic bacteria , , and , the genera that …

Afterschool Sustainability Club, Ethan Halman Gonzalez

Honors Program: Expanded Learning Clubs

In-depth lesson plans used at Riley Elementary to educate students about the environment around them and how to preserve it.

Cellular Toxicity Of Malonato (Ethylenediamine) Platinum (Ii) In Models Of Cancer, Sidikat Olanrewaju Olajuwon

Masters Theses & Specialist Projects

Platinum(II) compounds including the three FDA approved drugs, cisplatin, carboplatin, and oxaliplatin, are composed of two structural components, a leaving ligand, and a non-leaving ligand, each attached to a central platinum(II) atom. All bifunctional platinum compounds studied have similar mechanisms of initiating cell death. However, their efficacy as chemotherapeutics depends on the tissues in which the cancer originates. No model has explained these tissue-specific efficacies. We hypothesized that the efficacies of these platinum compounds vary due to structural differences in the leaving ligands. To test the influence of the leaving ligand on cellular survival, novel platinum compounds were synthesized, and …

Epidemiology, Pathogenesis, And Clinical Manifestations Of Acute Esophageal Necrosis In Adults, Obaid Rehman, Urooj Jaferi, Inderbir Padda, Nimrat Khehra, Harshan Atwal, Mayur Parmar

HPD Articles

Acute esophageal necrosis (AEN), also termed "black esophagus," is a unique and uncommon occurrence observed in severely sick patients. Other terminologies include acute necrotizing esophagitis and Gurvits syndrome. This condition is described as a darkened distal third of the esophagus observed on endoscopy and presents as an upper gastrointestinal (GI) bleed, difficulty swallowing, abdominal pain, fever, syncope, nausea, and vomiting. The etiology of AEN has been linked to several possibilities, such as excessive gastric acid reflux, hypoperfusion, and ischemia due to impaired vascular supply and hemodynamic instability. Risk factors include increased age, sex (male), heart disease, hemodynamic insufficiency, alcohol use, …

Development Of Vaccines And Antivirals Against Zika Virus, Aryamav Pattnaik

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

The re-emergence of Zika virus (ZIKV), an arbovirus, poses a major global human health concern because of its ability to cause congenital abnormalities and neurological diseases. While many candidate vaccines and antiviral drugs are in the developmental pipeline, none have been approved for use against ZIKV infection. This dissertation describes the characterization of one vaccine and two antiviral drug candidates against ZIKV infection. A bacterial ferritin-based nanoparticle vaccine, termed zDIII-F, is designed to display multiple copies of ZIKV E protein domain III on its surface. These stable nanoparticles are shown to induce robust antibody-mediated protection against lethal ZIKV infection in …

Computational Analysis Of Type 3 Iodothyronine Deiodinase: Potential Inhibitors, Substrate Binding, And Dimer Structure, Eric Scott Marsan

Chemistry & Biochemistry Theses & Dissertations

Thyroid hormones (THs) in mammalian tissues are crucial for development and maintaining metabolic homeostasis. Iodothyronine deiodinases (Dios) remove iodines from THs by a selenocysteine (Sec) residue, which either activates or inactivates them. Halogen bonding (XB) has been proposed to describe the interaction between the Se and I atoms of the T4-Dio complex. Disruption of TH homeostasis by xenobiotics, such as polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) can cause deleterious effects on the endocrine system. Experimental studies have indicated that PBDEs and PCBs could disrupt TH homeostasis by inhibiting Dio through XB formation. However, no current quantitative study exists …

Uptake, Acuumulation, And Toixicity Of Silver Nanoparticles To Juvenile Bivalve Mollusc’S Hard Clam Mercenaria Mercenaria, Hanaa Radhi Jolan Al Hameed

Theses and Dissertations

Nanoscience and nanotechnology have gained attention in the last 20 - 30 years. Manufactured nanoparticles (NPs), which are defined as having at least one dimension between 1 and 100 nm, are the main products of nanotechnology. Nanoscale materials often have novel properties due to their size and this has made them so attractive for a range of processes and sectors. These attractive properties have enhanced their use in a wide range of consumer products and applications including electronic, biomedical, and pharmaceutical. The overall objective of this dissertation was: 1) to investigate the transformation of well-characterized AgNPs, at environmentally relevant concentrations …

Partitioning Of Volatile Organic Compounds Into The Multiple Environmental Compartments, Jeonghyeon Ahn

Theses and Dissertations

Volatile organic compounds (VOCs) dominate the class of pollutants that accumulate in the atmosphere and indoors. Partitioning coefficient is a measure of a compound’s ability to distribute between two phases. Assessing the partitioning of VOCs is essential to determine their transport, fate, behavior, and adverse environmental and health impacts across multiple environmental compartments. Studies on VOC partitioning have been limited because discriminating the small mass fraction of VOCs in aerosol particles is difficult to quantify. The partitioning of VOCs into soil, air, and aerosol particle phases was investigated under dynamic laboratory conditions. A bench-scale system that precisely controlled the relative …

Wastewater Sample Site Selection To Estimate Geographically Resolved Community Prevalence Of Covid-19: A Sampling Protocol Perspective., R. Yeager, R. H. Holm, K. Saurabh, J. L. Fuqua, D. Talley, A. Bhatnagar, T. Smith

Faculty and Staff Scholarship

Wastewater monitoring for virus infections within communities can complement conventional clinical surveillance. Currently, most SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) clinical testing is voluntary and inconsistently available, except for a few occupational and educational settings, and therefore likely underrepresents actual population prevalence. Randomized testing on a regular basis to estimate accurate population-level infection rates is prohibitively costly and is hampered by a range of limitations and barriers associated with participation in clinical research. In comparison, community-level fecal monitoring can be performed through wastewater surveillance to effectively surveil communities. However, epidemiologically defined protocols for wastewater sample site selection are lacking. …

Isolation And Characterization Of Ethyl Acetate Fraction From Abroma Augusta L As An Anti-Inflammatory Agent, Madyawati Latief, Indra Lasmana Tarigan, Muhaimin Muhaimin, Hilda Amanda, Nike Desvi Yulianti

Makara Journal of Science

Abroma augusta is a bush plant that lives on the edge of the river. This plant is commonly used as an anti-inflammatory drug for joints and broken bones. It contains several secondary metabolites, such as alkaloids, triterpenoids, steroids, and flavonoids, which exhibit anti-inflammatory activity. UV-visible (UV-Vis) spectrophotometry of isolate 1.3 indicated absorption at a maximum wavelength of 282 nm. The wavelength suggested that the electron transition π–π* is the absorption of UV spectra typical for triterpenoid compounds that have chromophores in the form of non-conjugated double bonds. FT-IR spectrophotometer characterization data from isolate 1.3 revealed the presence of triterpenoid compounds …

Genetic Testing For Antipsychotic Pharmacotherapy: Bench To Bedside, Mujeeb U. Shad

Psychiatry & Behavioral Health Faculty Research

There is growing research interest in learning the genetic basis of response and adverse effects with psychotropic medications, including antipsychotic drugs. However, the clinical utility of information from genetic studies is compromised by their controversial results, primarily due to relatively small effect and sample sizes. Clinical, demographic, and environmental differences in patient cohorts further explain the lack of consistent results from these genetic studies. Furthermore, the availability of psychopharmacological expertise in interpreting clinically meaningful results from genetic assays has been a challenge, one that often results in suboptimal use of genetic testing in clinical practice. These limitations explain the difficulties …

The Effects Of Agrochemical Pesticide Applications On Target And Off-Target Species In Aquatic Ecosystems, Bryan K. Delius

USF Tampa Graduate Theses and Dissertations

The increase in the global human population is driving agricultural expansion, which increases the likelihood and degree by which agrochemicals impact aquatic systems. It is projected that by 2100 the global human population will exceed 11 billion, and to feed the increased human population, the necessary increase in agricultural infrastructure is estimated to double irrigation, nearly triple fertilizer applications, and increase pesticide applications by tenfold. It stands to reason that wetlands impacts from agriculture are also likely to increase as the industry expands its operation to meet the globally growing demand for food.

Wetlands are highly productive habitats that not …

Profiling Pretomanid As A Therapeutic Option For Tb Infection: Evidence To Date., Stephani L. Stancil, Fuad Mirzayev, Susan M. Abdel-Rahman

Manuscripts, Articles, Book Chapters and Other Papers

Tuberculosis (TB) is the most deadly infectious disease globally. Although most individuals achieve a cure, a substantial portion develop multi-drug resistant TB which is exceedingly difficult to treat, and the number of effective agents is dwindling. Development of new anti-tubercular medications is imperative to combat existing drug resistance and accelerate global eradication of TB. Pretomanid (PA-824) represents one of the newest drug classes (ie, nitroimidazooxazines) approved in 2019 by the United States Food and Drug Administration as part of a multi-drug regimen (with bedaquiline and linezolid, BPaL) and recommended by the World Health Organization (WHO) to treat extensively-resistant (XR-TB) and …

A Study Of Trpa1 Activation Via Covalent Electrophilic Modification Of Cysteines, Thomas A. Parks

USF Tampa Graduate Theses and Dissertations

A subset of sensory nerves called nociceptors are stimulated by noxious stimuli and evoke nocifensive responses in different organ systems. Transient Receptor Potential Ankyrin 1 (TRPA1) is a tetrameric, nonselective, cation channel that initiates the generator potential that evokes afferent signaling in nociceptive nerves. TRPA1 is activated many harmful irritants, such as food chemicals, environmental pollutants, reactive oxygen species and other endogenous mediators. Most TRPA1 agonists have electrophilic properties, which covalently modify cysteine residues on the cytosolic side of the channel. Biochemical studies in our lab have identified four cysteines (C273, C621, C665, C1085) that rapidly bound iodoacetamide (irreversible electrophile); …

Corrigendum To “Novel Uplc-Ms/Ms Method For Standardization Of Niazimicin Content In Edible Seeds And Leaves Of Moringa Oleifera Lam” [J Food Drug Anal 29 (2021) 128-143]

Journal of Food and Drug Analysis

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Corrigendum To “Determination Of Glycidyl Esters And 3-Mcpd Esters In Edible Oils By Sample Pretreatment With The Combination Of Lipase Hydrolysis And Modified Quechers For Gc-Ms Analysis” [J Food Drug Anal 29 (2021) 153-167]

Journal of Food and Drug Analysis

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