Pharmacology, Toxicology and Environmental Health Commons^™

Seeing The Invisible: Revealing Atrial Ablation Lesions Using Hyperspectral Imaging Approach, Narine Muselimyan, Luther Swift, Huda Asfour, Tigran Chahbazian, Ramesh Mazhari, Marco Mercader, Narine Sarvazyan

Pharmacology and Physiology Faculty Publications

Background

Currently, there are limited means for high-resolution monitoring of tissue injury during radiofrequency ablation procedures.

Objective

To develop the next generation of visualization catheters that can reveal irreversible atrial muscle damage caused by ablation and identify viability gaps between the lesions.

Methods

Radiofrequency lesions were placed on the endocardial surfaces of excised human and bovine atria and left ventricles of blood perfused rat hearts. Tissue was illuminated with 365nm light and a series of images were acquired from individual spectral bands within 420-720nm range. By extracting spectral profiles of individual pixels and spectral unmixing, the relative contribution of ablated …

Development Of Activity In The Mouse Visual Cortex., Jing Shen, Matthew T Colonnese

Pharmacology and Physiology Faculty Publications

No abstract provided.

Intranasal Oxytocin Enhances Connectivity In The Neural Circuitry Supporting Social Motivation And Social Perception In Children With Autism., Ilanit Gordon, Allison Jack, Charlotte M Pretzsch, Brent Vander Wyk, James F Leckman, Ruth Feldman, Kevin A. Pelphrey

Pharmacology and Physiology Faculty Publications

Oxytocin (OT) has become a focus in investigations of autism spectrum disorder (ASD). The social deficits that characterize ASD may relate to reduced connectivity between brain sites on the mesolimbic reward pathway (nucleus accumbens; amygdala) that receive OT projections and contribute to social motivation, and cortical sites involved in social perception. Using functional magnetic resonance imaging and a randomized, double blind, placebo-controlled crossover design, we show that OT administration in ASD increases activity in brain regions important for perceiving social-emotional information. Further, OT enhances connectivity between nodes of the brain's reward and socioemotional processing systems, and does so preferentially for …

Use Of A Modified Greenscreen Tool To Conduct A Screening-Level Comparative Hazard Assessment Of Conventional Silver And Two Forms Of Nanosilver., Jennifer Sass, Lauren Heine, Nina Hwang

Environmental and Occupational Health Faculty Publications

BACKGROUND: Increased concern for potential health and environmental impacts of chemicals, including nanomaterials, in consumer products is driving demand for greater transparency regarding potential risks. Chemical hazard assessment is a powerful tool to inform product design, development and procurement and has been integrated into alternative assessment frameworks. The extent to which assessment methods originally designed for conventionally-sized materials can be used for nanomaterials, which have size-dependent physical and chemical properties, have not been well established. We contracted with a certified GreenScreen profiler to conduct three GreenScreen hazard assessments, for conventional silver and two forms of nanosilver. The contractor summarized publicly …

Aneuploidy: A Common And Early Evidence-Based Biomarker For Carcinogens And Reproductive Toxicants., Daniele Mandrioli, Fiorella Belpoggi, Ellen K Silbergeld, Melissa J. Perry

Environmental and Occupational Health Faculty Publications

Aneuploidy, defined as structural and numerical aberrations of chromosomes, continues to draw attention as an informative effect biomarker for carcinogens and male reproductive toxicants. It has been well documented that aneuploidy is a hallmark of cancer. Aneuploidies in oocytes and spermatozoa contribute to infertility, pregnancy loss and a number of congenital abnormalities, and sperm aneuploidy is associated with testicular cancer. It is striking that several carcinogens induce aneuploidy in somatic cells, and also adversely affect the chromosome compliment of germ cells. In this paper we review 1) the contributions of aneuploidy to cancer, infertility, and developmental abnormalities; 2) techniques for …

Consumer Product Chemicals In Indoor Dust: A Quantitative Meta-Analysis Of U.S. Studies, Susanna D. Mitro, Robin Dodson, Veena Singla, Gary Adamkiewicz, Angelo F. Elmi, Monica Tilly, Ami R. Zota

Environmental and Occupational Health Faculty Publications

Indoor dust is a reservoir for commercial consumer product chemicals, including many compounds with known or suspected health effects. However, most dust exposure studies measure few chemicals in small samples. We systematically searched the U.S. indoor dust literature on phthalates, replacement flame retardants (RFRs), perfluoroalkyl substances (PFASs), synthetic fragrances, and environmental phenols and estimated pooled geometric means (GMs) and 95% confidence intervals for 45 chemicals measured in ≥3 data sets. In order to rank and contextualize these results, we used the pooled GMs to calculate residential intake from dust ingestion, inhalation, and dermal uptake from air, and then identified hazard …

An Excitatory Cortical Feedback Loop Gates Retinal Wave Transmission In Rodent Thalamus, Yasunobu Murata, Matthew T. Colonnese

Pharmacology and Physiology Faculty Publications

Spontaneous retinal waves are critical for the development of receptive fields in visual thalamus (LGN) and cortex (VC). Despite a detailed understanding of the circuit specializations in retina that generate waves, whether central circuit specializations also exist to control their propagation through visual pathways of the brain is unknown. Here we identify a developmentally transient, corticothalamic amplification of retinal drive to thalamus as a mechanism for retinal wave transmission in the infant rat brain. During the period of retinal waves, corticothalamic connections excite LGN, rather than driving feedforward inhibition as observed in the adult. This creates an excitatory feedback loop …

School Siting Near Industrial Chemical Facilities: Findings From The U.S. Chemical Safety Board's Investigation Of The West Fertilizer Explosion., Veronica A Tinney, Jerad M Denton, Lucy Sciallo-Tyler, Jerome A. Paulson

Environmental and Occupational Health Faculty Publications

BACKGROUND: The U.S. Chemical Safety and Hazard Investigation Board (CSB) investigated the April 17, 2013 explosion at the West Fertilizer Company (WFC) that resulted in 15 fatalities, more than 260 injuries and damage to more than 150 buildings. Among these structures were four nearby school buildings cumulatively housing children in grades K-12, a nursing care facility and an apartment complex. The incident occurred during the evening when school was not in session, which reduced the number of injuries.

OBJECTIVES: The goal of this paper is to illustrate the consequences of siting schools near facilities that store or use hazardous chemicals, …

Effects Of Neonicotinoid Pesticide Exposure On Human Health: A Systematic Review., Andria M Cimino, Abee L Boyles, Kristina A Thayer, Melissa J. Perry

Environmental and Occupational Health Faculty Publications

BACKGROUND: Numerous studies have identified detectable levels of neonicotinoids (neonics) in the environment, adverse effects of neonics in many species including mammals, and pathways through which human exposure to neonics could occur, yet little is known about the human health effects of neonic exposure.

OBJECTIVE: This systematic review sought to identify human population studies on the health effects of neonics.

METHODS: Studies published in English between 2005 and 2015 were searched using PubMed, Scopus, and Web of Science databases. No restrictions were placed on the type of health outcome assessed. Risk of bias was assessed using guidance developed by the …

Estimating Indoor Pm2.5 And Co Concentrations In Households In Southern Nepal: The Nepal Cookstove Intervention Trials, C. Chen, S. Zeger, P. Breysse, J. Katz, W. Checkley, F. Curriero, James Tielsch

Global Health Faculty Publications

High concentrations of household air pollution (HAP) due to biomass fuel usage with unvented, insufficient combustion devices are thought to be an important health risk factor in South Asia population. To better characterize the indoor concentrations of particulate matter (PM2.5) and carbon monoxide (CO), and to understand their impact on health in rural southern Nepal, this study analyzed daily monitoring data collected with DataRAM pDR-1000 and LASCAR CO data logger in 2980 households using traditional biomass cookstove indoor through the Nepal Cookstove Intervention Trial–Phase I between March 2010 and October 2011. Daily average PM2.5 and CO concentrations collected in area …

Nitrate From Drinking Water And Diet And Bladder Cancer Among Postmenopausal Women In Iowa., Rena R Jones, Peter J Weyer, Curt T Dellavalle, Maki Inoue-Choi, Kristin E Anderson, Kenneth P Cantor, Stuart Krasner, Kim Robien, Laura E Beane Freeman, Debra T Silverman, Mary H Ward

Exercise and Nutrition Sciences Faculty Publications

BACKGROUND: Nitrate is a drinking water contaminant arising from agricultural sources and a precursor in the endogenous formation of N-nitroso compounds (NOC), which are possible bladder carcinogens.

OBJECTIVES: To investigate the ingestion of nitrate and nitrite from drinking water and diet and bladder cancer risk in women.

METHODS: We identified incident bladder cancers among a cohort of 34,708 postmenopausal women in Iowa (1986-2010). Dietary nitrate and nitrite intakes were estimated from a baseline food frequency questionnaire. Drinking water source and duration were assessed in a 1989 follow-up. For women using public water supplies (PWS) >10 years (N=15,577), we estimated average …

The Emergence Of Systematic Review In Toxicology, Martin L. Stephens, Kellyn Betts, Nancy Beck, Vincent Cogliano, Kay Dickersin, George Gray, +8 Additional Authors

Environmental and Occupational Health Faculty Publications

The Evidence-based Toxicology Collaboration hosted a workshop on “The Emergence of Systematic Review and Related Evidence-based Approaches in Toxicology,” on November 21, 2014 in Baltimore, Maryland. The workshop featured speakers from agencies and organizations applying systematic review approaches to questions in toxicology, speakers with experience in conducting systematic reviews in medicine and healthcare, and stakeholders in industry, government, academia, and non-governmental organizations. Based on the workshop presentations and discussion, here we address the state of systematic review methods in toxicology, historical antecedents in both medicine and toxicology, challenges to the translation of systematic review from medicine to toxicology, and thoughts …

Effect Of An Improved Biomass Stove On Acute Lower Respiratory Infections In Young Children In Rural Nepal: A Cluster-Randomised, Step-Wedge Trial, James M. Tielsch, Joanne Katz, Subarna K. Khatry, Laxman Shrestha, Patrick N. Breysse, Scott L. Zeger, +5 Additional Authors

Global Health Faculty Publications

Background

Acute lower respiratory infections (ALRI) are an important cause of death in young children in low income countries. High concentrations of fine particulate matter (PM2.5) indoors caused by open burning of biomass are associated with risk of ALRI. However, improved biomass stoves reduce emissions and might reduce the incidence of lower respiratory illness. A cluster-randomised, step-wedge, community-based trial was conducted to estimate the eff ect that a change from open burning of biomass to improved biomass stoves could have on rates of ALRI in children younger than 36 months in a rural area of southern Nepal.

Methods

Households were …

Treatment Of Men For “Low Testosterone”: A Systematic Review, Samantha Huo, Anthony R. Scialli, Sean Mcgarvey, Elizabeth Hill, Buğra Tügertimur, Alycia Hogenmiller, Alessandra I. Hirsch, Adriane Fugh-Berman

Pharmacology and Physiology Faculty Publications

Testosterone products are recommended by some prescribers in response to a diagnosis or presumption of “low testosterone” (low-T) for cardiovascular health, sexual function, muscle weakness or wasting, mood and behavior, and cognition. We performed a systematic review of 156 eligible randomized controlled trials in which testosterone was compared to placebo for one or more of these conditions. We included studies in bibliographic databases between January 1, 1950 and April 9, 2016, and excluded studies involving bodybuilding, contraceptive effectiveness, or treatment of any condition in women or children. Studies with multiple relevant endpoints were included in all relevant tables. Testosterone supplementation …

Brain Responses To Biological Motion Predict Treatment Outcome In Young Children With Autism, D. Yang, Kevin Pelphrey, D. Sukholdolsky, M. Crowley, E. Dayan, +6 Additional Authors

Pharmacology and Physiology Faculty Publications

Autism spectrum disorders (ASDs) are common yet complex neurodevelopmental disorders, characterized by social, communication and behavioral deficits. Behavioral interventions have shown favorable results—however, the promise of precision medicine in ASD is hampered by a lack of sensitive, objective neurobiological markers (neurobiomarkers) to identify subgroups of young children likely to respond to specific treatments. Such neurobiomarkers are essential because early childhood provides a sensitive window of opportunity for intervention, while unsuccessful intervention is costly to children, families and society. In young children with ASD, we show that functional magnetic resonance imaging-based stratification neurobiomarkers accurately predict responses to an evidence-based behavioral treatment—pivotal …

Sensory Hypo-Excitability In A Rat Model Of Fetal Development In Fragile X Syndrome, Julia Berzhanskaya, Marnie Phillips, Jing Shen, Matthew Colonnese

Pharmacology and Physiology Faculty Publications

Fragile X syndrome (FXS) is characterized by sensory hyper-sensitivity, and animal models suggest that neuronal hyper-excitability contributes to this phenotype. To understand how sensory dysfunction develops in FXS, we used the rat model (FMR-KO) to quantify the maturation of cortical visual responses from the onset of responsiveness prior to eye-opening, through age equivalents of human juveniles. Rather than hyper-excitability, visual responses before eye-opening had reduced spike rates and an absence of early gamma oscillations, a marker for normal thalamic function at this age. Despite early hypo-excitability, the developmental trajectory of visual responses in FMR-KO rats was normal, and showed the …

Enhancing Access To Alcohol Use Disorder Pharmacotherapy And Treatment In Primary Care Settings: Adapt-Pc., Hildi J Hagedorn, Randall Brown, Michael Dawes, Eric Dieperink, Donald Hugh Myrick, Elizabeth M Oliva, Todd H Wagner, Jennifer P. Wisdom, Alex H S Harris

Health Policy and Management Faculty Publications

BACKGROUND: Only 7.8 % of individuals meeting diagnostic criteria for alcohol use disorder (AUD) receive treatment in a given year. Most individuals with AUDs are identified in primary care (PC) settings and referred to substance use disorders (SUD) clinics; however, only a minority of those referred attend treatment services. Safe and effective pharmacological treatments for AUD exist, but they are rarely prescribed by PC providers. The objective of this study is to refine, implement, and evaluate an intervention to integrate pharmacological AUD treatment options into PC settings. This paper provides a detailed description of the intervention design and the evaluation …