Search

Some industrial crane control panels were historically equipped with chrysotile-containing arc chutes. Because of the paucity of data regarding potential exposure from such equipment, we used a simulation approach to quantify the release of chrysotile from arc chutes in two functional 1970s-era industrial crane control panels during operation and maintenance. Two experienced operators separately simulated operation of crane controls under load; one of these operators then simulated two arc chute maintenance protocols: sanding (protocol 1) and scraping, sanding, and blowing (protocol 2). The original arc chutes contained approximately 36% chrysotile. Personal breathing zone (PBZ) (n = 8) and area samples (n = 8) were collected and analyzed using phase contrast microscopy (PCM) and transmission electron microscopy. PCM-equivalent (PCME) concentrations were derived, from which 8-h time-weighted averages (TWA) were calculated. During operation, chrysotile was identified in one of the four PBZ samples, equivalent to a PCME concentration of 0.012 f/cm3 (8-h TWA: 0.011 f/cm3). During protocols 1 and 2, chrysotile was identified in all PBZ samples (n = 4); PCME concentrations (and corresponding 8-h TWA) were <0.013 and 0.021 f/cm3 (0.001 and 0.004 f/cm3) and 0.013 and 0.017 f/cm3 (0.003 f/cm3), respectively. Many of the airborne chrysotile fibers had matrix attached, supporting the low exposure potential during this work. These data indicate very low, if any, exposures to chrysotile asbestos during the simulated scenarios. In addition, these data could assist with refining assumptions in exposure reconstruction and inform the state-of-the science on low-level chrysotile exposure. [ABSTRACT FROM AUTHOR]

Widespread adoption of evidence-based new healthcare practice guidelines can take years to occur. Policy leaders frequently make decisions based on incomplete and often incorrect information. These policy decisions can result in wasteful healthcare spending and poor health outcomes. Proponents of a medicolegal policy, Communication-and-Resolution Program (CRP), were successful in their endeavor to get hospitals to implement CRP, state legislators to pass state laws to encourage CRP adoption by hospitals, and national medical societies to endorse CRP to their members. The purpose of this paper is to explain the methods used by nine teams in their efforts to accomplish these goals. We identify reasons for the successes, failures, and obstacles faced by the teams in their effort to advance CRP. Our hope is to educate groups on a potentially more expeditious method to advance evidence-based policy than other methods. We propose that advocates of an innovation determine the concerns and goals of all stakeholder groups impacted by the policy. The specific concerns of each group should be the focus of the message to that group. Teams should identify the opinion leaders of each stakeholder group who can champion the new policy to their peers. Teams can aid the opinion leaders in their communication efforts to their peer group. National groups should be organized to help teams in their endeavor to advance evidence-based policies. [ABSTRACT FROM AUTHOR]

There is a vital safety requirement to appropriately warn users of chemical products that have acute hazards. As there is a very large amount and wide variety of chemical products, there is also a need to generalize acute hazards of chemicals so they can be reduced to a standardized, simple warning that can be found on a safety datasheet or product label. Acute lethality provides one simple, generalized indicator of the toxicity of a chemical product. The acute lethality hazard is typically determined using the LD50 which is defined as the median dose predicted to kill 50% of a given test population. The purpose of this paper is to provide a review of the LD50, including its history, the current studies used to develop it, and its integrated role in hazard communication. Continual improvement in animal welfare and reduction in animal costs has been one of the primary drivers of change for the LD50 and its regulatory integration. There are currently several well-established animal testing protocols designed to minimize the number of animals needed to produce an LD50 estimate that is sufficient for acute toxicity hazard communication. The utility of these animal testing protocols is further enhanced by ongoing regulatory adoption of The Globally Harmonized System of Classification and Labeling of Chemicals (GHS) that integrates LD50 data into a common hazard communication language. GHS can allow for multiple regulatory agencies to enforce a single and consistent hazard communication for a chemical or mixture without requiring new animal testing. This paper reviews the current progress and limitations of LD50 integration with GHS as well as approaches that can be taken to better streamline integration. [ABSTRACT FROM AUTHOR]

A shared Toll for innate immunity: Toll-like receptor 2 (TLR2) is found in various tissues but is best known for its role in the innate immune system of activating sentinel immune cells in response to infection. Using conditional knockout mice, McCoy et al. found that TLR2 also mediated innate immune signaling within the endothelium. TLR2 in endothelial cells activated proinflammatory signaling that promoted angiogenesis and immune cell recruitment in response to various "danger" signals, such as those produced during infection or tissue damage. Endothelial TLR2 also supported tumor growth in a mouse model of prostate cancer. These findings show that the endothelium contributes to innate immune responses and that TLR2 may be a therapeutic target in cancer (see also the Focus by Mahfoud and Petrova). Toll-like receptor 2 (TLR2) is implicated in various pathologies, mainly in terms of its function within innate immune cells. However, TLR2 is also present in endothelial cells. Here, we explored the physiological and pathophysiological roles of endothelial TLR2 signaling. We found that TLR2 was highly abundant in the endothelium within various tissues using TLR2-IRES-EGFP reporter mice and was required for proinflammatory endothelial cell function. Endothelial cells lacking TLR2 exhibited reduced proinflammatory potential at the protein, cell, and tissue levels. Loss of endothelial TLR2 blunted the inflammatory response to both exogenous and endogenous danger signals in endothelial cells in culture and in vivo. Endothelial TLR2 promoted tumor growth, angiogenesis, and protumorigenic immune cell recruitment in a mouse model of prostate cancer. Furthermore, the cell surface localization of P-selectin and the subsequent production of other critical cell adhesion molecules (such as E-selectin, ICAM-1, and VCAM-1) that recruit immune cells required endothelial TLR2. Our findings demonstrate that endothelial cells actively contribute to innate immune pathways and propose that endothelial TLR2 has a pathological role in proinflammatory conditions. [ABSTRACT FROM AUTHOR]

Fertilization studies have elucidated basic principles of the role of nutrients in shaping plant communities and demonstrated the potential effects of anthropogenic nutrient deposition. Yet less is known about how these effects are mediated by interacting ecological factors, particularly in nutrient‐poor wetland habitats. In a long‐term experiment in a coastal plain wetland, we examined how fertilization and mowing affected the diversity and composition of a plant community as it reestablished after major disturbance. A drainage ditch in proximity to the experimental plots allowed us also to consider the influence of hydrology and its interactions with nutrient addition. Fertilization decreased species richness, with wetland specialist species showing especially great losses, and several lines of evidence suggest that the effect was mediated by competition for light. Altered hydrology via ditch drainage had effects that were similar to fertilization, with more rapidly draining plots showing lower diversity and decreased abundance of wetland species. Plant community diversity and dynamics were influenced by complex interactions between fertilization, disturbance, and hydrology. The negative effect of fertilization on species richness was initially mitigated by mowing, but in later years was more evident in mowed than in unmowed plots. In the absence of disturbance, nutrient addition increased the rate of transition to primarily woody communities. Similarly, drained plots experienced increased rates of succession compared to wetter plots. Our results suggest that these interactions need to be considered to understand the potential effects of anthropogenic nutrient addition and hydrologic alterations to wetland ecosystems. [ABSTRACT FROM AUTHOR]

Environmental change and habitat fragmentation will affect population densities for many species. For those species that have locally adapted to persist in changed or stressful habitats, it is uncertain how density dependence will affect adaptive responses. Anurans (frogs and toads) are typically freshwater organisms, but some coastal populations of green treefrogs (Hyla cinerea) have adapted to brackish, coastal wetlands. Tadpoles from coastal populations metamorphose sooner and demonstrate faster growth rates than inland populations when reared solitarily. Although saltwater exposure has adaptively reduced the duration of the larval period for coastal populations, increases in densities during larval development typically increase time to metamorphosis and reduce rates of growth and survival. We test how combined stressors of density and salinity affect larval development between salt‐adapted ("coastal") and nonsalt‐adapted ("inland") populations by measuring various developmental and metamorphic phenotypes. We found that increased tadpole density strongly affected coastal and inland tadpole populations similarly. In high‐density treatments, both coastal and inland populations had reduced growth rates, greater exponential decay of growth, a smaller size at metamorphosis, took longer to reach metamorphosis, and had lower survivorship at metamorphosis. Salinity only exaggerated the effects of density on the time to reach metamorphosis and exponential decay of growth. Location of origin affected length at metamorphosis, with coastal tadpoles metamorphosing slightly longer than inland tadpoles across densities and salinities. These findings confirm that density has a strong and central influence on larval development even across divergent populations and habitat types and may mitigate the expression (and therefore detection) of locally adapted phenotypes. [ABSTRACT FROM AUTHOR]

Sea level rise is mixing formerly isolated freshwater communities with saltwater communities. The structure of these new aquatic communities is jointly controlled by pre- and post-colonization processes. Similarly, since salinity is a strong abiotic determinant of post-colonization survival in coastal systems, changes in salinity will likely impact community composition. In this study, we examine how a strong abiotic gradient affects the diversity and structure of bacterial and zooplankton communities and associated ecosystem functions (decomposition and carbon mineralization). We ran a six week dispersal experiment using mesocosm ponds with four distinct salinity profiles (0, 5, 9, and 13 psu). We find that salinity is the primary driver of both bacterial and zooplankton community composition. We find evidence that as bacterial richness increases so does the amount of decomposition. A phenomenological model suggests carbon mineralization may decrease at mid-salinities; this warrants future work into possible mechanisms for this apparent loss of function. Understanding how salinization changes community structure and ecosystem function may be paramount for managing and conserving coastal plain ecosystems where salinity is increasing due to sea level rise, saltwater intrusion, storm surges, and drought. [ABSTRACT FROM AUTHOR]

Opioid use disorder (OUD) is characterized by compulsive drug taking despite adverse life consequences. Here, we sought to identify neurobiological consequences associated with the behavioral effects of contingent footshocks administered after escalation of oxycodone self-administration. To reach these goals, Sprague-Dawley rats were trained to self-administer oxycodone for 4 weeks and were then exposed to contingent electric footshocks. This paradigm helped to dichotomize rats into two distinct behavioral phenotypes: (1) those that reduce lever pressing (shock-sensitive) and (2) others that continue lever pressing (shock-resistant) for oxycodone during contingent punishment. The rats were euthanized at 2-h after the last oxycodone plus footshock session. The dorsal striata and prefrontal cortices were dissected for use in western blot and RT-qPCR analyses. All oxycodone self-administration rats showed significant decreased expression of Mu and Kappa opioid receptor proteins only in the dorsal striatum. However, expression of Delta opioid receptor protein was decreased in both brain regions. RT-qPCR analyses documented significant decreases in the expression of c-fos , fosB , fra2 , junB , egr1 , and egr2 mRNAs in the dorsal striatum (but not in PFC) of the shock-sensitive rats. In the PFC, junD expression was reduced in both phenotypes. However, egr3 mRNA expression was increased in the PFC of only shock-resistant rats. These results reveal that, similar to psychostimulants and alcohol, footshocks can dichotomize rats that escalated their intake of oxycodone into two distinct behavioral phenotypes. These animals also show significant differences in the mRNA expression of immediate early genes, mainly, in the dorsal striatum. The increases in PFC egr3 expression in the shock-resistant rats suggest that Egr3 might be involved in the persistence of oxycodone-associated memory under aversive conditions. This punishment-driven model may help to identify neurobiological substrates of persistent oxycodone taking and abstinence in the presence of adverse consequences. [ABSTRACT FROM AUTHOR]

Background Methamphetamine (METH) use disorder is prevalent worldwide. There are reports of sex differences in quantities of drug used and relapses to drug use among individuals with METH use disorder. However, the molecular neurobiology of these potential sex differences remains unknown. Methods We trained rats to self-administer METH (0. 1 mg/kg/infusion, i.v.) on an fixed-ratio-1 schedule for 20 days using two 3-hour daily METH sessions separated by 30-minute breaks. At the end of self-administration training, rats underwent tests of cue-induced METH seeking on withdrawal days 3 and 30. Twenty-four hours later, nucleus accumbens was dissected and then used to measure neuropeptide mRNA levels. Results Behavioral results show that male rats increased the number of METH infusions earlier during self-administration training and took more METH than females. Both male and female rats could be further divided into 2 phenotypes labeled high and low takers based on the degree of escalation that they exhibited during the course of the METH self-administration experiment. Both males and females exhibited incubation of METH seeking after 30 days of forced withdrawal. Females had higher basal mRNA levels of dynorphin and hypocretin/orexin receptors than males, whereas males expressed higher vasopressin mRNA levels than females under saline and METH conditions. Unexpectedly, only males showed increased expression of nucleus accumbens dynorphin after METH self-administration. Moreover, there were significant correlations between nucleus accumbens Hcrtr1 , Hcrtr2 , Crhr2 , and Avpr1b mRNA levels and cue-induced METH seeking only in female rats. Conclusion Our results identify some behavioral and molecular differences between male and female rats that had self-administered METH. Sexual dimorphism in responses to METH exposure should be considered when developing potential therapeutic agents against METH use disorder. [ABSTRACT FROM AUTHOR]