Comparison of How Ambient PM\u3csub\u3ec\u3c/sub\u3e and PM\u3csub\u3e2.5\u3c/sub\u3e Influence the Inflammatory Potential

Airborne particulate matter (PM) is one of six criteria air pollutants currently regulated by the U.S. Environmental Protection Agency (EPA), with existing ambient standards for PM2.5 and PM10. Currently there are no health-based regulations for the size fraction between 2.5 and 10 μm, commonly known as the coarse fraction (PMc). The present study investigates current gaps in knowledge for PMc including exposure toxicity and PM ratios (PMc:PM2.5) in PM10. Throughout the world, all three PM size fractions have been shown to be associated with adverse impacts. Recent studies have shown that PMc can be more detrimental to susceptible populations when directly compared to PM2.5, and that the PMc fraction in PM10 can account for the majority of the inflammatory response from PM10 exposure. In our studies we utilized a bone marrow-derived mouse macrophage in vitro system to compare the inflammatory potential of PMc, PM2.5, and mixtures of the two. The result was a linear increase in interleukin(IL) −1β with increasing levels of exposure to winter and summer PMc, as compared to PM2.5, which exhibited logarithmic growth. Also, exposure to PM10 as a function of PM2.5 and PMc mass ratios showed that IL-1β and TNF-α levels increased synergistically with a greater burden of PMc. Endotoxin content in the PM did not correlate with these results, suggesting that other activators in PMc are likely responsible for activating the NF-κB pathway and the inflammasome

Macrophage Fusion into Multinucleated Giant Cells In Vitro

Multinucleated giant cells (MGC) have been observed in a variety of granulomatous conditions, including microbial infections (e.g., tuberculosis), foreign body reactions to implants (e.g., medical devices), foreign body reactions to inhaled particles (e.g., engineered nanomaterials), and disorders of unknown etiology (e.g., sarcoidosis). Generally, MGC are morphologically classified based on the number and arrangement of nuclei. The two major types of MGC are foreign body giant cells and Langhans giant cells. These MGC are formed by the fusion of macrophages, often in response to persistent, foreign microorganisms or materials. Although MGC are known to be associated with granulomas, their involvement in the development of these conditions has not been well described. This is in part due to a lack of well-characterized models of MGC populations. The objective of this study is to develop an in vitro model of macrophage fusion in order to study MGC function. Previous reports have shown that MGC formation is induced by interleukin-4 (IL-4). Therefore, we investigated a model of IL-4-induced fusion in murine bone marrow-derived macrophages (BMdM). As expected, IL-4 treatment resulted in increased percent fusion of BMdM. The formation of MGC was optimized by modification of culture conditions, including alteration of the growth surface and treatment with either macrophage colony-stimulating factor (M-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF). Ongoing studies involve identification of molecules that regulate MGC formation. An increased understanding of this mechanism will provide additional targets to control fusion. Further development of this controlled in vitro model will facilitate future investigation of MGC inflammatory activity and contribution to pathogenesis of granulomas

Implementation of a Dose Response to Wood Smoke PM: A Potential Method to Further Explain CVD in Wildland Firefighters.

The presentation of cardiovascular disease (CVD) and comorbidities in aging and retired wildland firefighters (WLFF) continues to be one of the top health priorities to address by The United States Forest Service. In the past 20 years, experts at multiple meetings and conferences have confronted this growing concern as a formal call to action to investigation the individual components related to working in the wildland fire setting. The inhalation of wood smoke particulate matter (PM) shows evidence of altering homeostasis in WLLF’s in the areas of oxidative stress, inflammation, and arterial stiffness, all of which contribute to the development of (CVD). To date, comprehensive investigation into the dose response of wood smoke PM and subsequent cardiovascular outcomes remains under studied. Emphasis on a wood smoke PM dose response is based on the inclusion of key variables measuring the size, concentration, sources, and inhalation rate of PM. The literature investigating wood smoke PM induced phycological changes is significantly lack in comparison to the reach studying anthropogenic PM and pollution. Recently, published studies in both field experiments and laboratory simulations provide new insight on how the PM dose of acute exposures alters normative cardiovascular function. There is a growing consensus within the scientific community of wood smoke PM inducing oxidative stress, upregulating inflammatory markers, and elevating pulmonary and systemic inflammation. At this time, fluctuations in autonomic nervous system control of heart rate and vascular tone do not warrant the same strength of confidence as the direct influence of wood smoke PM inhalation. Furthermore, the concentrations, volumes, PM size, and ventilation rates are contextual to each individual dose. What is true in one scenario cannot be extrapolated all wood smoke PM exposures and settings. Based on the findings of this academic exercise, we recommend that future scientific investigations in this area implement directed dose-response methodology, in combination with clinically relevant outcome measures, in order to determine the effects from multiple PM smoke exposures on the development of CVD aging and pathology

Sensitivity analysis and parameter estimation for an approximate analytical model of canal-aquifer interaction applied in the C-111 basin

The goal of this study was to better characterize parameters influencing the exchange of surface water in south Florida’s C-111 canal and Biscayne aquifer using the analytical model STWT1. A three-step model evaluation framework was implemented as follows: (1) qualitative parameter ranking by comparing two Morris method sampling strategies, (2) quantitative variance-based sensitivity analysis using Sobol’s method, and (3) estimation of parameter posterior probability distributions and statistics using the Generalized Likelihood Uncertainty Estimator (GLUE) methodology. Results indicated that the original Morris random sampling method underestimated total parameter effects compared to the improved global Morris sampling strategy. However, parameter rankings from the two sampling methods were similar. For the STWT1 model, only four out of the six parameters analyzed were important for predicting water table response to canal stage and recharge fluctuations. Morris ranking in order of decreasing importance resulted in specific yield (ASY), aquifer saturated thickness (AB), horizontal hydraulic conductivity (AKX), canal leakance (XAA), vertical hydraulic conductivity (AKZ), and half-width of canal (XZERO). Sobol’s sensitivity indices for the four most critical parameters revealed that summation of first-order parameter effects was 1.0, indicating that STWT1 behaved as an additive model or negligible parameter interactions. We estimated parameter values of 0.07 to 0.14 for ASY, 11,000 to 14,300 m d-1 for AKX, 13.4 to 18.3 m for AB, and 99.8 to 279 m for XAA. The estimated values were within the range of values estimated using more complex methods at nearby sites. The Nash-Sutcliffe coefficient of efficiency and root mean square error for estimated parameters ranged from 0.66 to 0.95 and from 4 to 7 cm, respectively. This study demonstrates a simple and inexpensive way to characterize hydrogeological parameters controlling groundwater-surface interactions in any region with aquifers that are highly permeable without using standard pumping tests or canal drawdown experiments. Hydrogeological parameters estimated using this approach could be used as starting values in large-scale numerical simulations

Fetal-Perinatal Exposure to Bisphenol-A Affects Quality of Spermatozoa in Adulthood Mouse

Bisphenol-A (BPA) is considered an endocrine disruptor with estrogenic activity. It is described as an environment-polluting industrial chemical whose adverse effects on the male reproductive system depend on the period of exposure (i.e., fetal, prepubertal, or adult life). We exposed male mice to BPA during the fetal-perinatal period (from 10 days post coitum to 31 days post partum) and investigated the impact of this early-life exposure on gamete health in adulthood animals at 78 days of age. Both in control and BPA-exposed mice, viability and motility of spermatozoa, as well as sperm motility acquisition and chromatin condensation of spermatozoa, have been evaluated. Results reveal harmful effect of BPA on viability and motility of sperm cells as well as on chromatin condensation status during epididymal maturation of spermatozoa. In particular, BPA exposure interferes with biochemical mechanism useful to stabilize sperm chromatin condensation, as it interferes with oxidation of thiol groups associated to chromatin

Tissue and circulating microRNAs as biomarkers of response to obesity treatment strategies

Background: Obesity, characterized by an increased amount of adipose tissue, is a metabolic chronic alteration which has reached pandemic proportion. Lifestyle changes are the first line therapy for obesity and a large variety of dietary approaches have demonstrated efficacy in promoting weight loss and improving obesity-related metabolic alterations. Besides diet and physical activity, bariatric surgery might be an effective therapeutic strategy for morbid obese patients. Response to weight-loss interventions is characterised by high inter-individual variability, which might involve epigenetic factors. microRNAs have critical roles in metabolic processes and their dysregulated expression has been reported in obesity. Aim: The aim of this review is to provide a comprehensive overview of current studies evaluating changes in microRNA expression in obese patients undergoing lifestyle interventions or bariatric surgery. Results: A considerable number of studies have reported a differential expression of circulating microRNAs before and after various dietary and bariatric surgery approaches, identifying several candidate biomarkers of response to weight loss. Significant changes in microRNA expression have been observed at a tissue level as well, with entirely different patterns between visceral and subcutaneous adipose tissue. Interestingly, relevant differences in microRNA expression have emerged between responders and non-responders to dietary or surgical interventions. A wide variety of dysregulated microRNA target pathways have also been identified, helping to understand the pathophysiological mechanisms underlying obesity and obesity-related metabolic diseases. Conclusions: Although further research is needed to draw firm conclusions, there is increasing evidence about microRNAs as potential biomarkers for weight loss and response to intervention strategies in obesity

Simulating water table response to proposed changes in surface water management in the C-111 agricultural basin of south Florida

As part of an effort to restore the hydrology of Everglades National Park (ENP), incremental raises in canal stage are proposed along a major canal draining south Florida called C-111, which separates ENP from agricultural lands. The study purpose was to use monitoring and modeling to investigate the effect of the proposed incremental raises in canal stage on water table elevation in agricultural lands. The objectives were to: (1) develop a MODFLOW based model for simulating groundwater flow within the study area, (2) apply the developed model to determine if the proposed changes in canal stage result in significant changes in water table elevation, root zone saturation or groundwater flooding and (3) assess aquifer response to large rainfall events. Results indicate the developed model was able to reproduce measured water table elevation with an average Nash-Sutcliffe > 0.9 and Root Mean Square Error 2 year return period storm), reduced water table intrusion into the root zone. We conclude that the impact of operational changes in canal stage management on root zone saturation and groundwater flooding depended on micro-topography within the field and depth of storm events. The findings of this study can be used in fine tuning canal stage operations to minimize root zone saturation and groundwater flooding of agricultural fields while maximizing environmental benefits through increased water flow in the natural wetland areas. This study also highlights the benefit of detailed field scale simulations

Characterization of estrogenic activity and site‐specific accumulation of bisphenol‐a in epididymal fat pad: Interfering effects on the endocannabinoid system and temporal progression of germ cells

The objective of this work has been to characterize the estrogenic activity of bisphenol‐A (BPA) and the adverse effects on the endocannabinoid system (ECS) in modulating germ cell progression. Male offspring exposed to BPA during the foetal‐perinatal period at doses below the no‐observed‐adverse‐effect‐level were used to investigate the exposure effects in adulthood. Results showed that BPA accumulates specifically in epididymal fat rather than in abdominal fat and targets testicular expression of 3β‐hydroxysteroid dehydrogenase and cytochrome P450 aromatase, thus promoting sustained increase of estrogens and a decrease of testosterone. The exposure to BPA affects the expression levels of some ECS components, namely type‐1 (CB1) and type‐2 cannabinoid (CB2) receptor and monoacylglycerol‐lipase (MAGL). Furthermore, it affects the temporal progression of germ cells reported to be responsive to ECS and promotes epithelial germ cell exfoliation. In particular, it increases the germ cell content (i.e., spermatogonia while reducing spermatocytes and spermatids), accelerates progression of spermatocytes and spermatids, promotes epithelial detachment of round and condensed spermatids and interferes with expression of cell–cell junction genes (i.e., zonula occcludens protein‐1, vimentin and β‐catenin). Altogether, our study provides evidence that early exposure to BPA produces in adulthood sustained and site‐specific BPA accumulation in epididymal fat, becoming a risk factor for the reproductive endocrine pathways associated to ECS

MicroRNA modulation by dietary supplements in obesity

The prevalence of obesity has dramatically increased over the last decades. Weight loss obtained through diet and exercise leads to a significant decrease in morbidity and mortality. Recently, there has been growing interest in the possible beneficial effects of dietary supplements (DSs), including polyphenols, fatty acids, and other plant-derived substances, as adjuvants in the management of obesity and metabolic diseases. Specifically, polyphenols, widely spread in vegetables and fruits, significantly modulate adipose tissue activities, contrasting inflammation and improving insulin sensitivity in preclinical and clinical studies. Remarkably, polyphenols are involved in complex microRNA networks, which play crucial roles in metabolic processes. The administration of different polyphenols and other plant-derived compounds led to significant changes in the microRNA expression profile in peripheral tissues in a growing number of preclinical studies. In particular, these compounds were able to revert obesity-induced microRNA dysregulation, leading to the inhibition of adipogenesis and the induction of weight loss. Furthermore, through microRNA modulation, they attenuated key metabolic alterations, including insulin resistance and lipid anomalies, in animal models of obesity. Some of them were also able to reduce proinflammatory cytokines in adipose tissue. The aim of this review is to summarize current evidence about the effect of plant-derived DSs on microRNA expression in obesity

Cosmology with the submillimetre galaxies magnification bias: Tomographic analysis

Context. High-z submillimetre galaxies can be used as a background sample for gravitational lensing studies thanks to their magnification bias. In particular, the magnification bias can be exploited in order to constrain the free parameters of a halo occupation distribution (HOD) model and some of the main cosmological parameters. A pseudo-tomographic analysis shows that the tomographic approach should improve the parameter estimation. Aims. In this work the magnification bias has been evaluated as cosmological tool in a tomographic set-up. The cross-correlation function (CCF) data have been used to jointly constrain the astrophysical parameters Mmin, M1, and α in each of the selected redshift bins as well as the cosmological parameters ωM, σ8, and H0 for the lambda cold dark matter (ΛCDM) model. Moreover, we explore the possible time evolution of the dark energy density by also introducing the ω0, ωa parameters in the joint analysis (ω0CDM and ω0ωaCDM). Methods. The CCF was measured between a foreground spectroscopic sample of Galaxy And Mass Assembly galaxies and a background sample of Herschel Astrophysical Terahertz Large Area Survey (H-ATLAS) galaxies. The foreground sample was divided into four redshift bins (0.1-0.2, 0.2-0.3, 0.3-0.5, and 0.5-0.8) and the sample of H-ATLAS galaxies has photometric redshifts > 1.2. The CCF was modelled using a halo model description that depends on HOD and cosmological parameters. Then a Markov chain Monte Carlo method was used to estimate the parameters for different cases. Results. For the ΛCDM model the analysis yields a maximum posterior value at 0.26 with [0.17, 0.41] 68% C.I. for ωM and at 0.87 with [0.75, 1] 68% C.I. for σ8. With our current results H0 is not yet constrained. With a more general ω0CDM model, the constraints on ωM and σ8 are similar, but we found a maximum posterior value for ω0 at -1 with [ - 1.56, -0.47] 68% C.I. In the ω0ωaCDM model, the results are -1.09 with [ - 1.72, -0.66] 68% C.I. for ω0 and -0.19 with [ - 1.88, 1.48] 68% C.I. for ωa. Conclusions. The results on Mmin show a trend towards higher values at higher redshift confirming recent findings. The tomographic analysis presented in this work improves the constraints in the σ8 - ωM plane with respect to previous findings exploiting the magnification bias and it confirms that magnification bias results do not show the degeneracy found with cosmic shear measurements. Moreover, related to dark energy, we found a trend of higher ω0 values for lower H0 values