Parametric statistical tests used to assess body weight changes in rodent experiments assume a normal distribution, and the actual distribution of the rodent body weights is often assumed to be approximately normal. In order for statistical tests to be deemed appropriate without routinely confirming the normal distribution for rodent body weight data, the tests must be powerful enough to detect meaningful changes even when a population deviates from a normal distribution. Here, we present a novel analysis to assess the normality of rodent body weight data for control animals in 1,386 National Toxicology Program (NTP) studies and determined how robust a set of procedures are to detect departures from normality. The distributions of terminal body weight measurements from 90 day and chronic NTP studies were evaluated for normality using graphical and statistical testing methods. The percent of studies with terminal body weights that were not normally distributed in normality tests was typically higher in 90-day studies for Fischer 344/N (F344/N) rats and B6C3F1/N (B6C3F1) mice than Harlan Sprague-Dawley (HSD) rats across all routes of administration evaluated (feed, drinking water, gavage or inhalation). Through simulation studies, the t-test indicated adequate power to detect a difference in body weights in male B6C3F1 mice and F344/N rats in 90-day studies, even under a skew normal distribution. According to these results, common parametric tests display enough power to accurately detect body weight differences from populations not following a normal distribution, confirming the general notion that the study designs are appropriately powered. In addition to providing adequate power, the False Positive Rate (FPR) was controlled around 5% in all simulations. These results suggest that parametric tests are robust enough to give reliable results of body weight analysis in NTP studies where this is an important endpoint. Therefore, parametric testing approaches are appropriate to detect body weight changes in NTP studies when body weight distributions do not deviate too far from normality. Future steps will look at the distributions of non-terminal body weights in chronic studies, organ weights, and other species and strains of rodents.
In the current COVID-19 pandemic, various Automated Exposure Notification (AEN) systems have been proposed to help quickly identify potential contacts of infected individuals. All these systems try to leverage the current understanding of the following factors: transmission risk, technology to address risk modeling, system policies and privacy considerations. While AEN holds promise for mitigating the spread of COVID-19, using short-range communication channels (Bluetooth) in smartphones to detect close individual contacts may be inaccurate for modeling and informing transmission risk. This work finds that the current close contact definitions may be inadequate to reduce viral spread using AEN technology. Consequently, relying on distance measurements from Bluetooth Low-Energy may not be optimal for determining risks of exposure and protecting privacy. This paper's literature analysis suggests that AEN may perform better by using broadly accessible technologies to sense the respiratory activity, mask status, or environment of participants. Moreover, the paper remains cognizant that smartphone sensors can leak private information and thus recommends additional objectives for maintaining user privacy without compromising utility for population health. This literature review and analysis will simultaneously interest (i) health professionals who desire a fundamental understanding of the design and utility of AEN systems and (ii) technologists interested in understanding their epidemiological basis in the light of recent research. Ultimately, the two disparate communities need to understand each other to assess the value of AEN systems in mitigating viral spread, whether for the COVID-19 pandemic or for future ones.
Designer drugs, like Spice, are synthetic psychoactive analogs of illegal substances with understudied health effects since they have traditionally been sold in packages labeled "not for human consumption" and the molecular structures can be specifically altered to circumvent legislation. Recent legislation has focused on regulating packaging and has reduced, but not eliminated, the distribution of Spice in Alaska. Legally obtained Spice samples from three geographic regions in Alaska were analyzed using liquid injection gas chromatography-mass spectrometry (GC-MS). Most (70%) of the samples contained illegal cannabinoids that have been regulated by the Drug Enforcement Agency and 47% contained multiple active ingredients. We hypothesized that the heterogeneity of the active ingredients between brands and across regions could be used to indicate small- or larger-scale manufacturing, and the results indicate multiple manufacturing scales. Evidence for small-scale manufacturing included inconsistent packaging, several of which contained similar active ingredient profiles in different brands purchased from a single store. Evidence for large-scale production was also found with some brands having consistent active ingredient profiles across regions. This study provides preliminary data for the geographic variability of active ingredients in Spice as an indicator of mechanisms of manufacture and distribution to inform legislators and law enforcement and help prioritizing resource allocation in an effort to quell Spice use in Alaska.
Etheostoma is a genus of North American darter fish whose species have similar habitats and breeding seasons, yet hybridization is rare. Behavioral barriers have been demonstrated to play a key role in maintaining species boundaries. Further, conspecific (same species) sperm precedence has also been observed when the gametes of two different species come into contact. In this study, we investigated if physical characteristics of sperm could be a mechanism for the lower fertilization success of heterospecific (different species) males when eggs are simultaneously exposed to conspecific and heterospecific sperm. We chose to examine the sperm of two closely related species, E. zonale and E. barrenense. Using toluidine blue and immunofluorescent labeling methods, we compared head diameter and tail length of sperm cells between the two species. We found that head diameter was significantly larger for E. barrenense sperm compared to E. zonale. This difference in cell morphology may point to a physical mechanism underlying conspecific sperm precedence in Etheostoma. Our results are the first to describe a morphological difference in sperm between species in this genus and provide initial evidence for the role of sperm morphology in prezygotic reproductive isolation.
Recent studies highlight the health risks associated with toxic metal(loid)s [e.g., arsenic (As), zinc (Zn), and lead (Pb)] in dust from mining operations, urban settings, and rural roads. To have a deleterious health effect, inhaled or ingested metal(loid)s must dissolve under conditions in the lung or gastrointestinal tract. In this study, we determined total and physiologically-soluble fractions of metal(loid)s in road dust from four sites in east-central interior Alaska. Total As and antimony (Sb) were enriched up to 26.2 and 53.7, respectively in dusts relative to average crustal abundance. Several elements such as nickel (Ni), As, and Sb were highly to moderately soluble in simulated lung fluids (7-80%, 15-51%, and 5-42%, respectively). Nickel and As exceeded the EPA inhalation risk unit, which is an exposure level of minimal risk. Despite several elements being highly soluble in simulated gastric fluids, including Ni, Cu, As, and Pb, only As samples exceeded the oral reference dose for children (based on total elemental concentrations) in some samples. The highest exposure risks identified in this study are inhalation of As and Ni present in road dust and ingestion of As-containing dust, especially by children. Additional studies would be needed to further quantify the health risk posed by road dust in this region.
It has been shown that inhaled particulate matter such as air pollution and asbestos are linked to a number of immune diseases such as asthma, and Systemic Lupus Erythematosus (SLE), respectively. This research may contribute to understanding the mechanisms of how asbestos and air pollution particulate (PM10) produce oxidative stress on macrophages, as well as how the macrophages will respond to the oxidative stressors. Using Flow Cytometry, DCFDA Fluorescence, Glutamate Transport, and Cytokine Bead Array assays, we have shown that exposure to asbestos and PM10 up-regulates system x(c)- in macrophages, which reduces oxidative stress for the macrophage by providing substrates for antioxidants. The results demonstrate that asbestos, but not PM10, induces both expression and activity of system x(c)-. This led to differential cytokine production with a significantly increased expression of TNF alpha and MCP-1 for PM10 treatment but not for asbestos treatment. Inhibition of system x(c)- affected cytokine production only following asbestos exposure, further demonstrating a role for this antioxidant system in regulating immune outcomes for asbestos but not PM10. Understanding the mechanisms in which oxidative stress helps regulate macrophage responses may contribute to a better understanding of why certain diseases are brought on by asbestos and air pollution exposure.
The Deepwater Horizon spill was one of the largest oil spills in recorded history, depositing more than 2.6 million gallons of oil a day over the course of 84 days into the Gulf of Mexico, and with it considerable unprecedented problems and concerns. With an eventual total of 172 million gallons leaked into the Gulf, the Deepwater Horizon spill disrupted the ecology and deeply affected wildlife populations along 690 miles of U.S. coastline. The Exxon Valdez oil spill of 1989 resulted in the release of 10.8 million gallons of oil in Alaska. Comparatively speaking, however, the quantity of oil released from Deepwater Horizon was the equivalent of an Exxon Valdez spill happening every four days for three straight months. Although the volume of oil spilled from the Exxon Valdez tanker represents only a small fraction of that from Deepwater Horizon, Exxon Valdez cleanup efforts took decades and the effects of the spill on wildlife are still being observed today. While both disasters involved crude unprocessed oil, there are many factors that distinguish these two events. Oil spills, though generally involving similar compounds, often have unique characteristics and consequences, each depending on its environment, the nature of the spill, and many other natural factors. This review surveys the general environmental and toxicological effects and implications of oil spills, with particular emphasis on the unique aspects of the Deepwater Horizon spill.
Sensorimortor gating and locomotion are behaviors that reflect pre-attentive sensory filtering and higher order, top-down, sensory processing, respectively. These processes are thought to affect either the perception of novelty in an environment (filtering) or cognition (higher order processing), salient features of models of altered states of consciousness (ASC). Drugs with highly selective receptor affinities that produce ASC can help to establish neural correlates, pathways, and mechanisms underlying ASC. Furthermore, screening for substances that selectively reverse drug-induced sensory processing departures is valuable for development of experimental antipsychotics. This study investigated the anomalous opioid sub-type, the kappa opioid (KA) system, within the two ASC models. Significant interaction and reversal effects between KA and the serotonin/2A (5-HT2A) system - the serotonin sub-type associated with classical psychedelics - were observed in three BPM measures. These measures showed that KA activation-induced effects could be reversed by 5-HT2A deactivation. These results suggest that KA could function as an atypical antipsychotic medications and/or as a screening tool for new antipsychotic medicines. The experimental work for this study comprised dose-response and reversal experiments with drugs that activate and deactivate kappa opioid and serotonin systems in the two behavioral models for the first time in mice.
Acoustic sensors are commonly used today to detect and convert sounds, including those at frequencies outside the range detectable by humans, to quantifiable signals. They have been used extensively in various fields, such as medicine, law enforcement, robotics, and agriculture, just to name a few. For example, acoustic biosensors have certainly improved medical diagnostic tests for cancer by enabling the detection of characteristic protein markers. An important aspect of testing the functionality of these sensors involves tracking the resonance frequency of the devices, that is, the acoustic device’s natural frequency of vibration, which has traditionally been accomplished through the use of equipment known as oscillator circuits.
Aims:Urinary tract obstruction is a common clinical problem involving narrowing anywhere along the ureters or urethra. Current diagnostic methods are invasive and costly, and urologists are constantly seeking new, inexpensive, non-invasive measures to diagnose obstruction. The present study investigates diagnostic applications of computational fluid dynamics (CFD) to urinary tract obstruction for the first time.Methods:Various hypothetical models were initially created in Gambit 2.1.6, in which the physics of flow was evaluated based on varying geometries and conditions. These models presented short segments of the tract and possible effects of obstruction. Flow analysis was conducted in Fluent 6.1.22 by comparing contours of velocity, static pressure, dynamic pressure, total pressure, and wall shear stress to results predicted by flow theory. Realistic models of both healthy and obstructed urethras and ureters were then similarly created and simulated.Results:CFD equations accurately predicted the expected flow characteristics through both hypothetical and realistic models. Comparison of modeled urethral outlet velocity to human uroflowmetry data shows that the simulated conditions are almost identical to realistic human flow.Conclusions:The accuracy of the models suggests clinical potential of using CFD with current techniques in human tract analysis, secondary flow effects, disease prevention, and non-invasive diagnosis.
