Pharmacology, Toxicology and Environmental Health Commons^™

An Observational Study Of The Effect Of Concomitant Levetiracetam On Apixaban Concentrations In A Hospital Cohort, Chazmyn Riley, Kevin Lam, Cristina Micale, Lynda Thomson, Douglas F. Stickle, Walter K. Kraft

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Despite the lack of evidence of a mechanism-based drug interaction, some professional organizations have advised caution coadministering apixaban and levetiracetam. Eligible patients taking apixaban with or without levetiracetam for any indication for at least 72 h were screened from the electronic medical records. Plasma samples from 77 patients were retrieved from salvaged clinical blood collections. Apixaban minimum and maximum concentrations (Cmin and Cmax) were compared using descriptive statistics in R. While the median Cmin and Cmax appear to be marginally elevated, there were no apparent differences relative to apixaban alone. These findings suggest no apparent interaction of levetiracetam and support …

P300/Cbp Inhibition With Inobrodib In Combination With Gilteritinib And Venetoclax Targets Leukemia Stem Cells In Epigenetic Mutant Aml, Melanie L. Goetz, Jennifer S. Romer-Seibert, Amanda M. Versace, Scott Kogan, Chetan Jeurkar, Robert L. Bowman, Nigel Brooks, Kris Frese, Sara E. Meyer

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Acute myeloid leukemia (AML) is a fatal blood cancer with cytotoxic chemotherapy offering at best 25% 5-year survival. While targeted BCL2 and FLT3 inhibitors venetoclax and gilteritinib are used upfront in the treatment of a subset of adult patients with AML and help to extend the survival of some patients, a curative treatment combination with minimal side effects has yet to be discovered. We find that use of the dual histone acetyltransferase p300/CBP bromodomain inhibitor CCS1477 (inobrodib), together with venetoclax and gilteritinib, virtually eliminates leukemia stem cells in an aggressive preclinical model of DNMT3A/FLT3-mutant AML by impairing pro-oncogenic survival and …

Considerations For The Analysis Of Urinary Environmental Chemical Concentrations During Pregnancy, Danielle R. Stevens, Kaleigh Hinton, Katie M. O'Brien, Jessie P. Buckley, Barrett M. Welch, Jason A. Watts, Antonia M. Calafat, Julianne C. Botelho, Elena Sinkovskaya, Ann Przybylska, George Saade, Alfred Abuhamad, Kelly K. Ferguson

Department of Obstetrics & Gynecology Faculty Publications

Background:

Pregnancy physiology may impact indicators of hydration, affecting exposure assessment in gestational studies with urinary chemical biomarkers.

Methods:

We aimed to characterize hydration and demonstrate the impact of different methods for standardizing urinary chemical biomarker concentrations on exposure descriptives in the Human Placenta and Phthalates Study (n = 303, 2017-2020), a prospective pregnancy cohort with eight study visits between 12 and 38 weeks of gestation. We assessed trajectories and predictors of hydration using urine flow rate (UFR) and specific gravity (SG). Likewise, we examined trajectories and predictors of mono-n-butyl phthalate (MBP), for which concentrations were unstandardized or standardized via …

Pharmacogenetic Hslco1b1*14-Guided Dosing Of Methotrexate In Transgenic Arthritic Mice Normalizes Exposure And Response., Felicia Gooden, Brennan D. Meier, Griffin D. Shaffer, Kim Gibson, Paul Toren, Nieko C. Punt, Sandhya Subash, Dilip K. Singh, Bhagwat Prasad, Laura Ramsey, Zachary L. Taylor

Manuscripts, Articles, Book Chapters and Other Papers

Juvenile idiopathic arthritis (JIA) is a chronic autoimmune disease that negatively affects ~100,000 children under the age of 16 in the United States. About ~30% of these patients fail first-line drug therapy with low-dose methotrexate (MTX) due to poor tolerability or lack of efficacy. The SLCO1B1*14 allele is associated with increased MTX clearance and has been linked to reduced overall drug exposure and nonresponse to MTX in JIA patients. Herein, we describe transgenic hSLCO1B1*14 and hSLCO1B1*1 DBA1/J mSlco1b2 knock-out mice, which we used to assess arthritic response to MTX using the collagen-induced arthritis model. Mass spectrometry-based proteomics analysis revealed that …

The Clinical Pharmacogenetics Implementation Consortium's Consensus-Based Framework For Assigning Allele Function., Bailey M. Tibben, Andrea Gaedigk, Li Gong, Katrin Sangkuhl, Michelle Whirl-Carrillo, Mary V. Relling, Roseann S. Donnelly, Teri E. Klein, Kelly E. Caudle

Manuscripts, Articles, Book Chapters and Other Papers

The Clinical Pharmacogenetics Implementation Consortium (CPIC) is dedicated to integrating pharmacogenetic testing into clinical practice by developing and disseminating peer-reviewed, evidence-based gene-drug clinical practice guidelines. A critical component of this effort is the assignment of clinical function to pharmacogene alleles, which informs the translation of genetic test results into actionable prescribing decisions. This technology review outlines the standardized procedures and framework used by CPIC to assign allele clinical functional status through the work of Pharmacogene Curation Expert Panels (PCEPs). These panels, comprising multidisciplinary experts, systematically review and evaluate evidence to assign functional status to pharmacogenetic haplotypes. The process includes rigorous …

Pharmacodynamics Of Aspirin Through Gestation: Predictors Of Aspirin Response And Association With Pregnancy Outcome, A Prospective Cohort Study, Rupsa C. Boelig, Emily Foecke Munden, Tingting Zhan, Steven E. Mckenzie, Walter K. Kraft

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Low-dose aspirin is recommended for prevention of hypertensive disorders of pregnancy (HDP) and preterm birth (PTB) in high-risk pregnancies. There is limited data on factors impacting aspirin response in pregnancy. We aimed to evaluate predictors of aspirin response and association with pregnancy outcome with a prospective study of high-risk pregnancies taking 81 mg aspirin daily. Aspirin response was evaluated with Platelet Function Assay-100 (PFA-100) epinephrine closure time at baseline (< 16 weeks' gestation), follow-up 1 (2-4 weeks after aspirin initiation), and follow-up 2 (28-32 weeks gestation). Multivariable regression was used to identify factors associated with PFA-100 at each visit, and results presented with beta coefficient (B) and confidence interval. The median difference (MD) in PFA-100 in those with and without HDP or PTB was compared. Results included 108 who completed follow-up 1 and 96 who completed both visits with > 75% adherence. PFA-100 was increased from baseline at follow-ups 1 and 2 (MD 37 (27-49); MD 26 (15.5-38.5) respectively). At follow-up 1, obesity (B = -30 (-53 to -7) seconds), …

Pulmonopoly: A Game-Based Approach To Teach And Reinforce Basic Concepts Of Pulmonary Medicine To Medical Students, Michael Dong, James Uricheck, Urvashi Vaid

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

INTRODUCTION: Pulmonopoly is an innovative active-learning medical board game addressses core pulmonary concepts in an engaging, competitive style. The strength of Pulmonopoly lies in its ability to combine ease of setup and play with comprehensive content coverage that comprises a significant proportion of national board examinations, offering a gamification experience that can be readily applied in different settings and modified for learner levels.

METHODS: We created an instructional game, Pulmonopoly, based on pulmonary content delivered to preclinical medical students and required for national board examinations. We invited first-year medical students to participate in 60-minute small-group sessions. Content addressed pulmonary subject …

Bayesian Population Pharmacokinetic Modeling Of Ondansetron For Neonatal Opioid Withdrawal Syndrome, Kevin Lam, John Mondick, Gary Peltz, Manhong Wu, Walter Kraft

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Ondansetron is an anti-emetic 5-HT3 receptor antagonist being investigated for treating neonatal opioid withdrawal syndrome (NOWS). Sparse PK data were analyzed from a multicenter, double-blind clinical trial with 98 mother/neonate dyads. Pregnant women with opioid use disorder were randomized to receive either placebo or ondansetron 8 mg intravenously within 4 h of delivery. Neonates born to mothers who were randomized to ondansetron received 0.07 mg/kg orally once every 24 h for up to five doses. Using current PK data, model parameters from a two-compartmental structural model from the literature (i.e., a priori model) were updated with the Metropolis-Hastings Markov-chain Monte …

Visualizing Parcel-Level Lead Risk Using An Exterior Housing-Based Index., Neal J. Wilson, Ryan Allenbrand, Elizabeth Friedman, Kevin Kennedy, Amy Roberts, Stephen Simon

Manuscripts, Articles, Book Chapters and Other Papers

Pediatric lead poisoning remains a persistent public health problem. Children in the US spend the preponderance of their time at home; thus, housing is an important social determinant of health. Improving health outcomes derived from housing-based sources involves differentiating the risks posed by the existing housing stock. In this paper, we developed a parcel-level lead risk index (LRI) based on external housing conditions and the year of home construction. The purpose of this study was to introduce a housing-based lead risk index (LRI), developed using retrospective data, to estimate parcel-by-parcel variation in housing-based lead risk. We described how the LRI …

Adhesion G Protein-Coupled Receptor Latrophilin 1 (Adgrl1): A Novel Regulator Of Glucose And Energy Homeostasis., Kavaljit H Chhabra

Pharmacology and Nutritional Sciences Faculty Publications

No abstract provided.

An Approach To Identify Gene-Environment Interactions And Reveal New Biological Insight In Complex Traits, Xiaofeng Zhu, Yihe Yang, Noah Lorincz-Comi, Gen Li, Amy R Bentley, Paul S De Vries, Michael Brown, Alanna C Morrison, Charles N Rotimi, W James Gauderman, Dabeeru C Rao, Hugues Aschard

Faculty, Staff and Student Publications

There is a long-standing debate about the magnitude of the contribution of gene-environment interactions to phenotypic variations of complex traits owing to the low statistical power and few reported interactions to date. to address this issue, the Gene-Lifestyle Interactions Working Group within the Cohorts for Heart and Aging Research in Genetic Epidemiology Consortium has been spearheading efforts to investigate G × E in large and diverse samples through meta-analysis. Here, we present a powerful new approach to screen for interactions across the genome, an approach that shares substantial similarity to the Mendelian randomization framework. We identify and confirm 5 loci …

Adsorbents From Rice Husk And Shrimp Shell For Effective Removal Of Heavy Metals And Reactive Dyes In Water, Md Ibrahim H Mondal, Shovra Chandra Chakraborty, Md Saifur Rahman, Shaik Merkatur Hakim Marjuban, Firoz Ahmed, John L Zhou, Mohammad Boshir Ahmed, Masoumeh Zargar

Faculty, Staff and Student Publications

Widespread contamination by heavy metals (HMs) and dyes poses a major health risk to people and ecosystems requiring effective treatment. In this work, rice husk (RH) and shrimp shells were extracted to obtain amorphous silica and chitosan, respectively, which were utilized to produce nano-chitosan-coated silica (NCCS). To ensure the stability of the nanoparticles, silica was freeze-dried after being coated with nano-chitosan. Functional groups (-NH

Pediatric Beta Blocker Therapy: A Comprehensive Review Of Development And Genetic Variation To Guide Precision-Based Therapy In Children, Adolescents, And Young Adults., Mollie Walton, Jonathan B. Wagner

Manuscripts, Articles, Book Chapters and Other Papers

Beta adrenergic receptor antagonists, known as beta blockers, are one of the most prescribed medications in both pediatric and adult cardiology. Unfortunately, most of these agents utilized in the pediatric clinical setting are prescribed off-label. Despite regulatory efforts aimed at increasing pediatric drug labeling, a majority of pediatric cardiovascular drug agents continue to lack pediatric-specific data to inform precision dosing for children, adolescents, and young adults. Adding to this complexity is the contribution of development (ontogeny) and genetic variation towards the variability in drug disposition and response. In the absence of current prospective trials, the purpose of this comprehensive review …

Human Mitragynine And 7-Hydroxymitragynine Pharmacokinetics After Single And Multiple Daily Doses Of Oral Encapsulated Dried Kratom Leaf Powder, Marilyn A. Huestis, Martin A. Brett, John Bothmer, Ramsey Atallah

Institute of Emerging Health Professions Faculty Papers

Kratom leaves, consumed by millions worldwide as tea or ground leaf powder, contain multiple alkaloids, with mitragynine being the most abundant and responsible for most effects. Mitragynine is a partial µ-opioid receptor agonist and competitive antagonist at κ- and δ-opioid receptors; however, unlike morphine, it does not activate the β-arrestin-2 respiratory depression pathway. Due to few human mitragynine data, the largest randomized, between-subject, double-blind, placebo-controlled, dose-escalation study of 500–4000 mg dried kratom leaf powder (6.65–53.2 mg mitragynine) was conducted. LC-MS/MS mitragynine and 7-hydroxymitragynine plasma concentrations were obtained after single and 15 daily doses. Mitragynine and 7-hydroxymitragynine C_max increased dose …

Protecting Human And Animal Health: The Road From Animal Models To New Approach Methods, Barbara L F Kaplan, Alan M Hoberman, William Slikker, Mary Alice Smith, Emanuela Corsini, Thomas B Knudsen, M Sue Marty, Sonya K Sobrian, Suzanne C Fitzpatrick, Marcia H Ratner, Donna L Mendrick

Faculty, Staff and Student Publications

Animals and animal models have been invaluable for our current understanding of human and animal biology, including physiology, pharmacology, biochemistry, and disease pathology. However, there are increasing concerns with continued use of animals in basic biomedical, pharmacological, and regulatory research to provide safety assessments for drugs and chemicals. There are concerns that animals do not provide sufficient information on toxicity and/or efficacy to protect the target population, so scientists are utilizing the principles of replacement, reduction, and refinement (the 3Rs) and increasing the development and application of new approach methods (NAMs). NAMs are any technology, methodology, approach, or assay used …

Adgrl1 Is A Glucose Receptor Involved In Mediating Energy And Glucose Homeostasis, Kavaljit H Chhabra, Siresha Bathina, Tumininu S Faniyan, Dennis J Samuel, Muhammad Ummear Raza, Leticia Maria De Souza Cordeiro, Gonzalo Viana Di Prisco, Brady K Atwood, Jorge Robles, Lauren Bainbridge, Autumn Davis

Pharmacology and Nutritional Sciences Faculty Publications

AIMS/HYPOTHESIS: The brain is a major consumer of glucose as an energy source and regulates systemic glucose as well as energy balance. Although glucose transporters such as GLUT2 and sodium-glucose cotransporter 2 (SGLT2) are known to regulate glucose homeostasis and metabolism, the identity of a receptor that binds glucose to activate glucose signalling pathways in the brain is unknown. In this study, we aimed to discover a glucose receptor in the mouse hypothalamus.

METHODS: Here we used a high molecular mass glucose-biotin polymer to enrich glucose-bound mouse hypothalamic neurons through cell-based affinity chromatography. We then subjected the enriched neurons to …

Joint Problem-Solving Orientation, Mutual Value Recognition, And Performance In Fluid Teamwork Environments, Michaela Kerrissey, Zhanna Novikov

Faculty, Staff and Student Publications

INTRODUCTION: Joint problem-solving orientation (JPS) has been identified as a factor that promotes performance in fluid teamwork, but research on this factor remains nascent. This study pushes the frontier of understanding about JPS in fluid teamwork environments by applying the concept to within-organization work and exploring its relationships with performance, mutual value recognition (MVR), and expertise variety (EV).

METHODS: This is a longitudinal, survey-based field study within a large United States healthcare organization

RESULTS: Our results affirm a moderated mediation model wherein JPS enhances performance, both directly and through MVR; EV serves as a moderator in the JPS-MVR relationship. JPS …

Kinome Profiling Identifies Mark3 And Stk10 As Potential Therapeutic Targets In Uveal Melanoma, Usman Baqai, Alison M. Kurimchak, Isabella Trachtenberg, Timothy J. Purwin, Jelan I. Haj, Anna Han, Kristine Luo, Nikole Fandino Pachon, Angela Jeon, Vivian Chua, Michael A. Davies, J Silvio Gutkind, Jeffrey L. Benovic, James S. Duncan, Andrew E. Aplin

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Most uveal melanoma cases harbor activating mutations in either GNAQ or GNA11. Despite activation of the mitogen-activated protein kinase (MAPK) signaling pathway downstream of Gαq/11, there are no effective targeted kinase therapies for metastatic uveal melanoma. The human genome encodes numerous understudied kinases, also called the "dark kinome". Identifying additional kinases regulated by Gαq/11 may uncover novel therapeutic targets for uveal melanoma. In this study, we treated GNAQ-mutant uveal melanoma cell lines with a Gαq/11 inhibitor, YM-254890, and conducted a kinase signaling proteomic screen using multiplexed-kinase inhibitors followed by mass spectrometry. We observed downregulated expression and/or activity of 22 kinases. …

Artificial Light At Night And Social Vulnerability: An Environmental Justice Analysis In The Us 2012-2019, Qian Xiao, Yue Lyu, Meng Zhou, Jiachen Lu, Kehe Zhang, Jun Wang, Cici Bauer

Faculty, Staff and Student Publications

BACKGROUND: Artificial Light at Night (ALAN) is an emerging health risk factor that has been linked to a wide range of adverse health effects. Recent study suggested that disadvantaged neighborhoods may be exposed to higher levels of ALAN. Understanding how social disadvantage correlates with ALAN levels is essential for identifying the vulnerable populations and for informing lighting policy.

METHODS: We used satellite data from the National Aeronautics and Space Administration's (NASA) Black Marble data product to quantify annual ALAN levels (2012-2019), and the Center for Disease Control and Prevention's (CDC) Social Vulnerability Index (SVI) to quantify social disadvantage, both at …

Developing A National-Scale Exposure Index For Combined Environmental Hazards And Social Stressors And Applications To The Environmental Influences On Child Health Outcomes (Echo) Cohort., Sheena E. Martenies, Mingyu Zhang, Anne E. Corrigan, Anton Kvit, Timothy Shields, William Wheaton, Deana Around Him, Judy Aschner, Maria M. Talavera-Barber, Emily S. Barrett, Theresa M. Bastain, Casper Bendixsen, Carrie V. Breton, Nicole R. Bush, Ferdinand Cacho, Carlos A. Camargo, Kecia N. Carroll, Brian S. Carter, Andrea E. Cassidy-Bushrow, Whitney Cowell, Lisa A. Croen, Dana Dabelea, Cristiane S. Duarte, Anne L. Dunlop, Todd M. Everson, Rima Habre, Tina V. Hartert, Jennifer B. Helderman, Alison E. Hipwell, Margaret R. Karagas, Barry M. Lester, Kaja Z. Lewinn, Sheryl Magzamen, Rachel Morello-Frosch, Thomas G. O'Connor, Amy M. Padula, Michael Petriello, Sheela Sathyanarayana, Joseph B. Stanford, Tracey J. Woodruff, Rosalind J. Wright, Amii M. Kress, Program Collaborators For Environmental Influences On Child Health Outcomes

Manuscripts, Articles, Book Chapters and Other Papers

Tools for assessing multiple exposures across several domains (e.g., physical, chemical, and social) are of growing importance in social and environmental epidemiology because of their value in uncovering disparities and their impact on health outcomes. Here we describe work done within the Environmental influences on Child Health Outcomes (ECHO)-wide Cohort Study to build a combined exposure index. Our index considered both environmental hazards and social stressors simultaneously with national coverage for a 10-year period. Our goal was to build this index and demonstrate its utility for assessing differences in exposure for pregnancies enrolled in the ECHO-wide Cohort Study. Our unitless …

Self-Administered Intranasal Etripamil Using A Symptom-Prompted, Repeat-Dose Regimen For Atrioventricular-Nodal-Dependent Supraventricular Tachycardia (Rapid): A Multicentre, Randomised Trial, Bruce S Stambler, A John Camm, Marco Alings, Paul Dorian, Hein Heidbuchel, Jaco Houtgraaf, Peter R. Kowey, Jose L Merino, Blandine Mondésert, Jonathan P Piccini, Sean D Pokorney, Philip T Sager, Atul Verma, J Marcus Wharton, David B Bharucha, Francis Plat, Silvia Shardonofsky, Michael Chen, James E Ip

Department of Medicine Faculty Papers

BACKGROUND: Etripamil is a fast-acting, intranasally administered calcium-channel blocker in development for on-demand therapy outside a health-care setting for paroxysmal supraventricular tachycardia. We aimed to evaluate the efficacy and safety of etripamil 70 mg nasal spray using a symptom-prompted, repeat-dose regimen for acute conversion of atrioventricular-nodal-dependent paroxysmal supraventricular tachycardia to sinus rhythm within 30 min.

METHODS: RAPID was a multicentre, randomised, placebo-controlled, event-driven trial, conducted at 160 sites in North America and Europe as part 2 of the NODE-301 study. Eligible patients were aged at least 18 years and had a history of paroxysmal supraventricular tachycardia with sustained, symptomatic episodes …

Climate Change Imperils Pediatric Health: Child Advocacy Through Fossil Fuel Divestment., Sandra H. Jee, Elizabeth Friedman, Ruth A. Etzel, Vi T. Nguyen, Todd L. Sack, Kathi J. Kemper

Manuscripts, Articles, Book Chapters and Other Papers

Climate change poses an existential threat to children's health. Divestment of ownership stakes in fossil fuel companies is one tool available to pediatricians to address climate change. Pediatricians are trusted messengers regarding children's health and therefore bear a unique responsibility to advocate for climate and health policies that affect children. Among the impacts of climate change on pediatric patients are allergic rhinitis and asthma; heat-related illnesses; premature birth; injuries from severe storms and fires; vector-borne diseases; and mental illnesses. Children are disproportionately affected as well by climate-related displacement of populations, drought, water shortages, and famine. The human-generated burning of fossil …

Linking Social And Built Environmental Factors To Leisure-Time Physical Activity In Rural Cancer Survivors, Courtney J Stevens, Yue Liao, Minxing Chen, Natalia I Heredia, Hannah Arem, Jasmine Sukumar, Lenat Joffe, Kathryn H Schmitz, Scherezade K Mama

Faculty, Staff and Student Publications

BACKGROUND: This study explored associations between social and built environmental factors and leisure-time physical activity (LTPA) in rural cancer survivors (RCS) and whether these associations differed by exercise stage of change (SOC).

METHOD: RCS (n = 219) completed questionnaires assessing LTPA, SOC, and social (social status, connectedness, support) and environmental (home environment, neighborhood environment) factors. Linear regression models examined associations between social and built environmental factors and LTPA and tested for moderation by SOC.

RESULTS: Half (50.7%) of RCS were physically active, and 49.3% were not active. Social factors positively associated with LTPA included subjective social status in the community …

Fruit And Vegetable Intake And Home Nutrition Environment Among Low-Income Minority Households With Elementary-Aged Children, Brittni Naylor Metoyer, Ru-Jye Chuang, Minjae Lee, Christine Markham, Eric L Brown, Maha Almohamad, Jayna M Dave, Shreela V Sharma

Faculty, Staff and Student Publications

Racial/ethnic and socioeconomic differences were shown to have an influence on child fruit and vegetable intake. This study examined the associations between parent and child fruit and vegetable intake and the home nutrition environment among Hispanic/Latino and African American families. Through a cross-sectional study design, self-reported surveys (

Exposure To Pcb126 During The Nursing Period Reversibly Impacts Early-Life Glucose Tolerance, Brittany B. Rice, Keegan W. Sammons, Sara Y. Ngo Tenlep, Madeline T. Weltzer, Leryn J. Reynolds, Cetewayo S. Rashid, Hollie I. Swanson, Kevin J. Pearson

Human Movement Studies & Special Education Faculty Publications

Polychlorinated biphenyls (PCBs) are persistent environmental organic pollutants known to have detrimental health effects. Using a mouse model, we previously demonstrated that PCB126 exposure before and during pregnancy and throughout the perinatal period adversely affected offspring glucose tolerance and/or body composition profiles. The purpose of this study was to investigate the glucose tolerance and body composition of offspring born to dams exposed to PCB126 during the nursing period only. Female ICR mice were bred, and half of the dams were exposed to either vehicle (safflower oil) or 1 µmole PCB126 per kg of body weight via oral gavage on postnatal …

Wastewater Pandemic Preparedness: Toward An End-To-End Pathogen Monitoring Program, Justin R Clark, Austen Terwilliger, Vasanthi Avadhanula, Michael Tisza, Juwan Cormier, Sara Javornik-Cregeen, Matthew Clayton Ross, Kristi Louise Hoffman, Catherine Troisi, Blake Hanson, Joseph Petrosino, John Balliew, Pedro A Piedra, Janelle Rios, Jennifer Deegan, Cici Bauer, Fuqing Wu, Kristina D Mena, Eric Boerwinkle, Anthony W Maresso

Faculty, Staff and Student Publications

Molecular analysis of public wastewater has great potential as a harbinger for community health and health threats. Long-used to monitor the presence of enteric viruses, in particular polio, recent successes of wastewater as a reliable lead indicator for trends in SARS-CoV-2 levels and hospital admissions has generated optimism and emerging evidence that similar science can be applied to other pathogens of pandemic potential (PPPs), especially respiratory viruses and their variants of concern (VOC). However, there are substantial challenges associated with implementation of this ideal, namely that multiple and distinct fields of inquiry must be bridged and coordinated. These include engineering, …

Developmental Pharmacokinetics Of Indomethacin In Preterm Neonates: Severely Decreased Drug Clearance In The First Week Of Life., Wojciech Krzyzanski, Bradley Stockard, Andrea Gaedigk, Allison Scott, Whitney M. Nolte, Kim T. Gibson, J Steven Leeder, Tamorah Lewis

Manuscripts, Articles, Book Chapters and Other Papers

Indomethacin is used commonly in preterm neonates for the prevention of intracranial hemorrhage and closure of an abnormally open cardiac vessel. Due to biomedical advances, the infants who receive this drug in the neonatal intensive care unit setting have become younger, smaller, and less mature (more preterm) at the time of treatment. To develop a pharmacokinetics (PK) model to aid future dosing, we designed a prospective cohort study to characterize indomethacin PK in a dynamically changing patient population. A population PK base model was created using NONMEM, and a covariate model was developed in a primary development cohort and subsequently …

Chemical Explosion, Covid-19, And Environmental Justice: Insights From Low-Cost Air Quality Sensors, Guning Liu, Katie Moore, Wei-Chung Su, George L Delclos, David Gimeno Ruiz De Porras, Bing Yu, Hezhong Tian, Bin Luo, Shao Lin, Grace Tee Lewis, Elena Craft, Kai Zhang

Faculty, Staff and Student Publications

OBJECTIVES: to examine the impact of the Intercontinental Terminals Company (ITC) fire and COVID-19 on airborne particulate matter (PM) concentrations and the PM disproportionally affecting communities in Houston using low-cost sensors.

METHODS: We compared measurements from a network of low-cost sensors with a separate network of monitors from the Environmental Protection Agency (EPA) in the Houston metropolitan area from Mar 18, 2019, to Dec 31, 2020. Further, we examined the associations between neighborhood-level sociodemographic status and air pollution patterns by linking the low-cost sensor data to EPA environmental justice screening and mapping systems.

FINDINGS: We found increased PM levels during …

Discovering New Potential Inhibitors To Sars-Cov-2 Rna Dependent Rna Polymerase (Rdrp) Using High Throughput Virtual Screening And Molecular Dynamics Simulations., Dylan Brunt, Phillip M Lakernick, Chun Wu

College of Science & Mathematics Departmental Research

RNA dependent RNA polymerase (RdRp), is an essential in the RNA replication within the life cycle of the severely acute respiratory coronavirus-2 (SARS-CoV-2), causing the deadly respiratory induced sickness COVID-19. Remdesivir is a prodrug that has seen some success in inhibiting this enzyme, however there is still the pressing need for effective alternatives. In this study, we present the discovery of four non-nucleoside small molecules that bind favorably to SARS-CoV-2 RdRp over the active form of the popular drug remdesivir (RTP) and adenosine triphosphate (ATP) by utilizing high-throughput virtual screening (HTVS) against the vast ZINC compound database coupled with extensive …

Additive And Interactive Associations Of Environmental And Sociodemographic Factors With The Genotypes Of Three Glutathione S-Transferase Genes In Relation To The Blood Arsenic Concentrations Of Children In Jamaica, Mohammad H Rahbar, Maureen Samms-Vaughan, Yuansong Zhao, Sepideh Saroukhani, Sheikh F Zaman, Jan Bressler, Manouchehr Hessabi, Megan L Grove, Sydonnie Shakspeare-Pellington, Katherine A Loveland

Faculty, Staff and Student Publications

Arsenic (As) is a metalloid that has been classified as a xenobiotic with toxic effects on human beings, especially on children. Since the soil in Jamaica contains As, dietary intake is considered the main source of As exposure in Jamaicans. In addition, glutathione S-transferase (GST) genes, including