NLRP3 Inflammasome Inhibitors for Antiepileptogenic Drug Discovery and Development.

Epilepsy is one of the most prevalent and serious brain disorders and affects over 70 million people globally. Antiseizure medications (ASMs) relieve symptoms and prevent the occurrence of future seizures in epileptic patients but have a limited effect on epileptogenesis. Addressing the multifaceted nature of epileptogenesis and its association with the Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated neuroinflammation requires a comprehensive understanding of the underlying mechanisms of these medications for the development of targeted therapeutic strategies beyond conventional antiseizure treatments. Several types of NLRP3 inhibitors have been developed and their effect has been validated both in in vitro and in vivo models of epileptogenesis. In this review, we discuss the advances in understanding the regulatory mechanisms of NLRP3 activation as well as progress made, and challenges faced in the development of NLRP3 inhibitors for the treatment of epilepsy.

Distribution and trends of mercury in aquatic and terrestrial biota of New York, USA: a synthesis of 50 years of research and monitoring.

Mercury (Hg) inputs have particularly impacted the northeastern United States due to its proximity to anthropogenic emissions sources and abundant habitats that efficiently convert inorganic Hg into methylmercury. Intensive research and monitoring efforts over the past 50 years in New York State, USA, have informed the assessment of the extent and impacts of Hg exposure on fishes and wildlife. By synthesizing Hg data statewide, this study quantified temporal trends of Hg exposure, spatiotemporal patterns of risk, the role that habitat and Hg deposition play in producing spatial patterns of Hg exposure in fish and other wildlife, and the effectiveness of current monitoring approaches in describing Hg trends. Most temporal trends were stable, but we found significant declines in Hg exposure over time in some long-sampled fish. The Adirondack Mountains and Long Island showed the greatest number of aquatic and terrestrial species with elevated Hg concentrations, reflecting an unequal distribution of exposure risk to fauna across the state. Persistent hotspots were detected for aquatic species in central New York and the Adirondack Mountains. Elevated Hg concentrations were associated with open water, forests, and rural, developed habitats for aquatic species, and open water and forested habitats for terrestrial species. Areas of consistently elevated Hg were found in areas driven by atmospheric and local Hg inputs, and habitat played a significant role in translating those inputs into biotic exposure. Continued long-term monitoring will be important in evaluating how these patterns continue to change in the face of changing land cover, climate, and Hg emissions.

All about oxygen: using near-infrared spectroscopy to understand bioenergetics.

The interchange among the energy-providing phosphagen, glycolytic, and aerobic systems during exercise is often poorly understood by beginning students in exercise physiology. Exercise is oftentimes thought of as being aerobic or anaerobic, with the body progressing sequentially from one system to the next, although the energy systems work synergistically to produce energy from the onset of exercise, and all ultimately use oxygen. Traditional methods of teaching these concepts using only indirect calorimetry and a metabolic cart can be misleading. Relatively inexpensive noninvasive monitors of muscle oxygenation levels ([Formula: see text]) provide a useful tool to help students better understand the contribution and timing of these three systems of ATP generation and convey the concept that ultimately all energy production in the human body is oxygen dependent. In this laboratory, students use near-infrared spectroscopy (NIRS) to visualize oxygen utilization by skeletal muscle during exercise by devising three exercise unique protocols, with each designed to stress a different energy system. Students then perform their protocols while using NIRS to measure and analyze [Formula: see text]. Students generate graphs with collected data, allowing them to visualize and appreciate oxygen consumption during all three protocols as well as elevated oxygen consumption after exercise. The students learn that any exercise is really all about oxygen.NEW & NOTEWORTHY Traditional methods of teaching bioenergetics using indirect calorimetry and a metabolic cart may be misleading. Recent advances in technology have made near-infrared spectroscopy (NIRS) a relatively inexpensive, noninvasive means of monitoring muscle oxygen levels during exercise. In this laboratory activity, NIRS devices are used for hands-on exploration of the synergistic nature of the energy systems, allowing students to appreciate the synergistic nature of the energy systems and how all exercise is really all about oxygen.

Atmospheric nitrogen deposition in the Chesapeake Bay watershed: A history of change.

The Chesapeake Bay watershed has been the focus of pioneering studies of the role of atmospheric nitrogen (N) deposition as a nutrient source and driver of estuarine trophic status. Here, we review the history and evolution of scientific investigations of the role of atmospheric N deposition, examine trends from wet and dry deposition networks, and present century-long (1950-2050) atmospheric N deposition estimates. Early investigations demonstrated the importance of atmospheric deposition as an N source to the Bay, providing 25%-40% among all major N sources. These early studies led to the unprecedented inclusion of targeted decreases in atmospheric N deposition as part of the multi-stakeholder effort to reduce N loads to the Bay. Emissions of nitrogen oxides (NOx) and deposition of wet nitrate, oxidized dry N, and dry ammonium ( NH 4 + ) sharply and synchronously declined by 60%-73% during 1995-2019. These decreases largely resulted from implementation of Title IV of the 1990 Clean Air Act Amendments, which began in 1995. Wet NH 4 + deposition shows no significant trend during this period. The century-long atmospheric N deposition estimates indicate an increase in total atmospheric N deposition in the Chesapeake watershed from 1950 to a peak of ~15 kg N/ha/yr in 1979, trailed by a slight decline of <10% through the mid-1990s, and followed by a sharp decline of about 40% thereafter through 2019. An additional 21% decline in atmospheric N deposition is projected from 2015 to 2050. A comparison of the Potomac River and James River watersheds indicates higher atmospheric N deposition in the Potomac, likely resulting from greater emissions from higher proportions of agricultural and urban land in this basin. Atmospheric N deposition rose from 30% among all N sources to the Chesapeake Bay watershed in 1950 to a peak of 40% in 1973, and a decline to 28% by 2015. These data highlight the important role of atmospheric N deposition in the Chesapeake Bay watershed and present a potential opportunity for decreases in deposition to contribute to further reducing N loads and improving the trophic status of tidal waters.

The impact of lime additions on mercury dynamics in stream chemistry and macroinvertebrates: a comparison of watershed and direct stream addition management strategies.

Acid deposition has declined across eastern North America and northern Europe due to reduced emissions of sulfur and nitrogen oxides. Ecosystem recovery has been slow with limited improvement in surface water chemistry. Delayed recovery has encouraged acid-neutralization strategies to accelerate recovery of impaired biological communities. Lime application has been shown to increase pH and dissolved organic carbon (DOC), which could also drive increased mobilization of mercury (Hg) to surface waters. A four-year study was conducted within Honnedaga Lake's watershed in the Adirondack region of New York to compare the effects of watershed and direct channel lime additions on Hg in stream water and macroinvertebrates. All treatments sharply increased stream pH and DOC concentrations, but large differences in the duration of impacts were apparent. The watershed treatment resulted in multi-year increases in concentrations and loads of total Hg (150%; 390%), DOC (190%; 350%) and nutrients, whereas total Hg and DOC increased for short periods (72-96 h) after channel treatments. No response of Hg in macroinvertebrates was evident following the watershed treatment, but a potential short-term and spatially constrained increase occurred after the channel treatment. Our observations indicate that both treatment approaches mobilize Hg, but that direct channel liming mobilizes considerably less than watershed liming over any period longer than a few days. During the final study year, increased methyl Hg concentrations were observed across reference and treated streams, which may reflect an extended dry period, highlighting that climate variation may also affect Hg dynamics.

Mercury in fish from streams and rivers in New York State: Spatial patterns, temporal changes, and environmental drivers.

Mercury (Hg) concentrations in freshwater fish across the state of New York frequently exceed guidelines considered harmful to humans and wildlife, but statewide distribution and temporal changes are not well known for the state's streams and rivers. We analyzed existing data to describe recent spatial patterns, identify key environmental drivers, and assess temporal changes. Size classes within sportfishes and prey fishes formed 'functional taxa' (FT), and standardized scores were generated from 2007-2016 data for 218 sites. Muscle Hg in ≥1 sportfish FT exceeded human-health guidelines of 50 ng/g (sensitive populations) and 300 ng/g (general population, GP) at 93 and 56% of sites, respectively, but exceeded 1000 ng/g (a state threshold) at only 10% of sites. Whole-body Hg in ≥1 prey fish FT exceeded wildlife thresholds of 40 ng/g and 100 ng/g at 91 and 51% of sites, respectively. Environmental drivers of recent spatial patterns include extent of forest cover and storage, the latter an indicator of wetlands. Standardized Hg scores increased with increasing atmospheric Hg deposition and storage across rural 'upland' regions of New York. However, scores were not related to atmospheric deposition in more-developed 'lowland' regions due to the limited methylation potential of urban landscapes. Comparisons of 2010-2015 sportfish Hg concentrations with those of 1998 and 2000-2005 showed inconsistent temporal changes both among and within eight sites examined. Some recent stream and river fish Hg spatial patterns differed from those of lake-based studies, highlighting the importance of New York's flowing waters to future Hg monitoring and risk assessment.

Unprocessed Atmospheric Nitrate in Waters of the Northern Forest Region in the U.S. and Canada.

Little is known about the regional extent and variability of nitrate from atmospheric deposition that is transported to streams without biological processing in forests. We measured water chemistry and isotopic tracers (δ18O and δ15N) of nitrate sources across the Northern Forest Region of the U.S. and Canada and reanalyzed data from other studies to determine when, where, and how unprocessed atmospheric nitrate was transported in catchments. These inputs were more widespread and numerous than commonly recognized, but with high spatial and temporal variability. Only 6 of 32 streams had high fractions (>20%) of unprocessed atmospheric nitrate during baseflow. Seventeen had high fractions during stormflow or snowmelt, which corresponded to large fractions in near-surface soil waters or groundwaters, but not deep groundwater. The remaining 10 streams occasionally had some (<20%) unprocessed atmospheric nitrate during stormflow or baseflow. Large, sporadic events may continue to be cryptic due to atmospheric deposition variation among storms and a near complete lack of monitoring for these events. A general lack of observance may bias perceptions of occurrence; sustained monitoring of chronic nitrogen pollution effects on forests with nitrate source apportionments may offer insights needed to advance the science as well as assess regulatory and management schemes.

Long-term Changes in Soil and Stream Chemistry across an Acid Deposition Gradient in the Northeastern United States.

Declines in acidic deposition across Europe and North America have led to decreases in surface water acidity and signs of chemical recovery of soils from acidification. To better understand the link between recovery of soils and surface waters, chemical trends in precipitation, soils, and streamwater were investigated in three watersheds representing a depositional gradient from high to low across the northeastern United States. Significant declines in concentrations of H (ranging from -1.2 to -2.74 microequivalents [µeq] L yr), NO (ranging from -0.6 to -0.84 µeq L yr), and SO (ranging from -0.95 to -2.13 µeq L yr) were detected in precipitation in the three watersheds during the period 1999 to 2013. Soil chemistry in the A horizon of the watershed with the greatest decrease in deposition showed significant decreases in exchangeable Al and increases in exchangeable bases. Soil chemistry did not significantly improve during the study in the other watersheds, and base saturation in the Oa and upper B horizons significantly declined in the watershed with the smallest decrease in deposition. Streamwater SO concentrations significantly declined in all three streams (ranging from -2.01 to -2.87 µeq L yr) and acid neutralizing capacity increased (ranging from 1.38 to 1.60 µeq L yr) in the two streams with the greatest decreases in deposition. Recovery of soils has likely been limited by decades of acid deposition that have leached base cations from soils with base-poor parent material.

Modeled ecohydrological responses to climate change at seven small watersheds in the northeastern United States.

A cross-site analysis was conducted on seven diverse, forested watersheds in the northeastern United States to evaluate hydrological responses (evapotranspiration, soil moisture, seasonal and annual streamflow, and water stress) to projections of future climate. We used output from four atmosphere-ocean general circulation models (AOGCMs; CCSM4, HadGEM2-CC, MIROC5, and MRI-CGCM3) included in Phase 5 of the Coupled Model Intercomparison Project, coupled with two Representative Concentration Pathways (RCP 8.5 and 4.5). The coarse resolution AOGCMs outputs were statistically downscaled using an asynchronous regional regression model to provide finer resolution future climate projections as inputs to the deterministic dynamic ecosystem model PnET-BGC. Simulation results indicated that projected warmer temperatures and longer growing seasons in the northeastern United States are anticipated to increase evapotranspiration across all sites, although invoking CO2 effects on vegetation (growth enhancement and increases in water use efficiency (WUE)) diminish this response. The model showed enhanced evapotranspiration resulted in drier growing season conditions across all sites and all scenarios in the future. Spruce-fir conifer forests have a lower optimum temperature for photosynthesis, making them more susceptible to temperature stress than more tolerant hardwood species, potentially giving hardwoods a competitive advantage in the future. However, some hardwood forests are projected to experience seasonal water stress, despite anticipated increases in precipitation, due to the higher temperatures, earlier loss of snow packs, longer growing seasons, and associated water deficits. Considering future CO2 effects on WUE in the model alleviated water stress across all sites. Modeled streamflow responses were highly variable, with some sites showing significant increases in annual water yield, while others showed decreases. This variability in streamflow responses poses a challenge to water resource management in the northeastern United States. Our analyses suggest that dominant vegetation type and soil type are important attributes in determining future hydrological responses to climate change.

X-ray and ultraviolet C irradiation-induced γ-H2AX and p53 formation in normal human periosteal cells in vitro: markers for quality control in cell therapy.

BACKGROUND AIMS: For successful cell transplantation therapy, the quality of cells must be strictly controlled. Unfortunately, to exclude inappropriate cells that possess structurally abnormal chromosomes, currently only karyotyping functions as an assessment. Unfortunately, this methodology is time-consuming and only effective for metaphasic cells. To develop a more efficient, inclusive and sensitive methodology, we examined the phosphorylation of histone H2AX and the p53 levels in normal human periosteal cells exposed to x-rays or other oxidative stressors. METHODS: Periosteal cells were obtained from human alveolar bone before being exposed to x-rays, ultraviolet C or hydrogen peroxide. The cell cycle, electric nuclear volume and CD44 expression were evaluated using flow cytometry, and the phosphorylated H2AX (γ-H2AX), p53, p21 and proliferating cell nuclear antigen (PCNA) levels were evaluated by Western blot analyses. RESULTS: Each oxidative stress dose-dependently arrested cell growth and partially induced premature cellular senescence. In parallel, each oxidative stress rapidly phosphorylated H2AX and stabilized p53, and intense stress sustained these high levels for at least 8 days. CONCLUSIONS: Intensive oxidative stress induces sustained high levels of γ-H2AX and p53, which force cells toward senescence or non-apoptotic cell death. Lower doses of oxidative stress induced more modest and transient increases in γ-H2AX and p53, and these cells eventually survive. However, because DNA is repaired without a template in the majority of these cells, G1 mutations accumulate. Therefore, we recommend that any cell population expressing elevated γ-H2AX and p53 levels be excluded from cell transplantation therapy.

Real-time quantitative polymerase chain reaction and flow cytometric analyses of cell adhesion molecules expressed in human cell-multilayered periosteal sheets in vitro.

BACKGROUND AIMS: Cultured human periosteal sheets more effectively function as an osteogenic grafting material at implantation sites than do dispersed periosteal cells. Because adherent cell growth and differentiation are regulated by cell-cell and cell-extracellular matrix contacts, we hypothesized that this advantage is a result of the unique cell adhesion pattern formed by their multiple cell layers and abundant extracellular matrix. To test this hypothesis, we prepared three distinct forms of periosteal cell cultures: three-dimensional cell-multilayered periosteal sheets, two-dimensional dispersed cell cultures, and three-dimensional hybrid mock-ups of cells dispersed onto collagen sponges. METHODS: Periosteal cells were obtained from human alveolar bone. Cell adhesion and extracellular matrix molecules were quantitatively determined at the messenger RNA and protein levels by means of real-time quantitative polymerase chain reaction and flow cytometry, respectively. RESULTS: Real-time quantitative polymerase chain reaction analysis demonstrated that regardless of culture media α1 integrin, vascular cell adhesion molecule-1, fibronectin and collagen type 1 were substantially upregulated, whereas CD44 was strongly downregulated in periosteal sheets compared with dispersed cell monolayers. With increased thickness, stem cell medium upregulated several integrins (ß1, α1 and α4), CD146, vascular cell adhesion molecule-1, fibronectin and collagen type 1 in the periosteal sheets. Flow cytometric analysis revealed that the active configuration of ß1 integrin was substantially downregulated in the stem cell medium-expanded cell cultures. The cell adhesion pattern found in the mock-up cultures was almost identical to that of genuine periosteal sheets. CONCLUSIONS: Integrin α1ß1 and CD44 function as the main cell adhesion molecule in highly cell-multilayered periosteal sheets and dispersed cells, respectively. This difference may account for the more potent osteogenic activity shown by the thicker periosteal sheets.

Hydrogeomorphology explains acidification-driven variation in aquatic biological communities in the Neversink Basin, USA.

Describing the distribution of aquatic habitats and the health of biological communities can be costly and time-consuming; therefore, simple, inexpensive methods to scale observations of aquatic biota to watersheds that lack data would be useful. In this study, we explored the potential of a simple "hydrogeomorphic" model to predict the effects of acid deposition on macroinvertebrate, fish, and diatom communities in 28 sub-watersheds of the 176-km2 Neversink River basin in the Catskill Mountains of New York State. The empirical model was originally developed to predict stream-water acid neutralizing capacity (ANC) using the watershed slope and drainage density. Because ANC is known to be strongly related to aquatic biological communities in the Neversink, we speculated that the model might correlate well with biotic indicators of ANC response. The hydrogeomorphic model was strongly correlated to several measures of macroinvertebrate and fish community richness and density, but less strongly correlated to diatom acid tolerance. The model was also strongly correlated to biological communities in 18 sub-watersheds independent of the model development, with the linear correlation capturing the strongly acidic nature of small upland watersheds (< 1 km2). Overall, we demonstrated the applicability of geospatial data sets and a simple hydrogeomorphic model for estimating aquatic biological communities in areas with stream-water acidification, allowing estimates where no direct field observations are available. Similar modeling approaches have the potential to complement or refine expensive and time-consuming measurements of aquatic biota populations and to aid in regional assessments of aquatic health.

Shallow groundwater mercury supply in a Coastal Plain stream.

Fluvial methylmercury (MeHg) is attributed to methylation in up-gradient wetland areas. This hypothesis depends on efficient wetland-to-stream hydraulic transport under nonflood and flood conditions. Fluxes of water and dissolved (filtered) mercury (Hg) species (FMeHg and total Hg (FTHg)) were quantified in April and July of 2009 in a reach at McTier Creek, South Carolina to determine the relative importance of tributary surface water and shallow groundwater Hg transport from wetland/floodplain areas to the stream under nonflood conditions. The reach represented less than 6% of upstream main-channel distance and 2% of upstream basin area. Surface-water discharge increased within the reach by approximately 10%. Mean FMeHg and FTHg fluxes increased within the reach by 23-27% and 9-15%, respectively. Mass balances indicated that, under nonflood conditions, the primary supply of water, FMeHg, and FTHg within the reach (excluding upstream surface water influx) was groundwater discharge, rather than tributary transport from wetlands, in-stream MeHg production, or atmospheric Hg deposition. These results illustrate the importance of riparian wetland/floodplain areas as sources of fluvial MeHg and of groundwater Hg transport as a fundamental control on Hg supply to Coastal Plain streams.

Spatial and seasonal variability of dissolved methylmercury in two stream basins in the eastern United States.

We assessed methylmercury (MeHg) concentrations across multiple ecological scales in the Edisto (South Carolina) and Upper Hudson (New York) River basins. Out-of-channel wetland/floodplain environments were primary sources of filtered MeHg (F-MeHg) to the stream habitat in both systems. Shallow, open-water areas in both basins exhibited low F-MeHg concentrations and decreasing F-MeHg mass flux. Downstream increases in out-of-channel wetlands/floodplains and the absence of impoundments result in high MeHg throughout the Edisto. Despite substantial wetlands coverage and elevated F-MeHg concentrations at the headwater margins, numerous impoundments on primary stream channels favor spatial variability and lower F-MeHg concentrations in the Upper Hudson. The results indicated that, even in geographically, climatically, and ecologically diverse streams, production in wetland/floodplain areas, hydrologic transport to the stream aquatic environment, and conservative/nonconservative attenuation processes in open water areas are fundamental controls on dissolved MeHg concentrations and, by extension, MeHg availability for potential biotic uptake.

Theoretical methodology for prediction of tropospheric oxidation of dimethyl phosphonate and dimethyl methylphosphonate.

Rate constants for the reactions of OH radicals with dimethyl phosphonate [DMHP, (CH(3)O)(2)P(O)H] and dimethyl methylphosphonate [DMMP, (CH(3)O)(2)P(O)CH(3)] have been calculated by ab initio structural methods and semiclassical dynamics modeling and compared with experimental measurements over the temperature range 250-350 K. The structure and energetics of reactants and transition structures are determined for all hydrogen atom abstraction pathways that initiate the atmospheric oxidation mechanism. Structures are obtained at the CCSD/6-31++G** level of chemical theory, and the height of the activation barrier is determined by a variant of the G2MP2 method. A Transfer Hamiltonian is used to compute the minimum energy path in the neighborhood of the transition state (TS). This calculation provides information about the curvature of the potential energy surface in the neighborhood of the TS, as well as the internal forces that are needed by the semiclassical flux-flux autocorrelation function (SCFFAF) dynamics model used to compute the temperature-dependent reaction rate constants for the various possible abstraction pathways. The computed temperature-dependent rate curves frequently lie within the experimental error bars.

Manual cryopreservation of human alveolar periosteal tissue segments: Effects of pre-culture on recovery rate.

Cultured human periosteal sheets constitute a promising grafting material for periodontal tissue regenerative therapy. However, preparation of these sheets usually requires six weeks or longer, and this lengthy commitment and delay limits both clinical applicability and availability. The aim of this study is to develop an efficient, practical, cost-effective cryopreservation method for periosteal tissue segments (PTSs). Human PTSs were aseptically excised from alveolar bone and pre-cultured in Medium 199+10% fetal bovine serum (FBS) for the indicated number of days before they were slowly frozen down to -75°C in a commercial freezing vessel using medium containing 10% dimethyl sulfoxide (Me(2)SO) and various concentrations of FBS. After fast-thawing at 37°C, PTSs were again cultured, and their growth and responses to standard osteogenic induction were evaluated (vs. freshly excised PTSs). Proliferating cells were obtained at the highest levels from cryopreserved PTSs that were pre-cultured for 14 days before freezing. When a concentration of 50% or more FBS was included in the cryopreservation solution, cells migrated out more actively and grew faster. Importantly, osteoinduction up-regulated alkaline phosphatase (ALP) activity and osteoblastic marker mRNAs in cryopreserved PTS-derived sheets just as effectively as it did in native PTS-derived ones. These data suggest that pre-conditioned PTSs can be efficiently cryopreserved in a freezing solution containing high FBS by traditional manual cryopreservation methods without aid of a program freezer or more elaborate equipment.

Spatial patterns of mercury in macroinvertebrates and fishes from streams of two contrasting forested landscapes in the eastern United States.

Controls on mercury bioaccumulation in lotic ecosystems are not well understood. During 2007-2009, we studied mercury and stable isotope spatial patterns of macroinvertebrates and fishes from two medium-sized (<80 km(2)) forested basins in contrasting settings. Samples were collected seasonally from multiple sites across the Fishing Brook basin (FB(NY)), in New York's Adirondack Mountains, and the McTier Creek basin (MC(SC)), in South Carolina's Coastal Plain. Mean methylmercury (MeHg) concentrations within macroinvertebrate feeding groups, and mean total mercury (THg) concentrations within most fish feeding groups were similar between the two regions. However, mean THg concentrations in game fish and forage fish, overall, were much lower in FB(NY) (1300 and 590 ng/g dw, respectively) than in MC(SC) (2300 and 780 ng/g dw, respectively), due to lower trophic positions of these groups from FB(NY) (means 3.3 and 2.7, respectively) than MC(SC) (means 3.7 and 3.3, respectively). Much larger spatial variation in topography and water chemistry across FB(NY) contributed to greater spatial variation in biotic Hg and positive correlations with dissolved MeHg and organic carbon in streamwater. Hydrologic transport distance (HTD) was negatively correlated with biotic Hg across FB(NY), and was a better predictor than wetland density. The small range of landscape conditions across MC(SC) resulted in no consistent spatial patterns, and no discernable correspondence with local-scale environmental factors. This study demonstrates the importance of local-scale environmental factors to mercury bioaccumulation in topographically heterogeneous landscapes, and provides evidence that food-chain length can be an important predictor of broad-scale differences in Hg bioaccumulation among streams.

The response of streams in the Adirondack region of New York to projected changes in sulfur and nitrogen deposition under changing climate.

Modeling studies project that in the future surface waters in the northeast US will continue to recover from acidification over decades following reductions in atmospheric sulfur dioxide and nitrogen oxides emissions. However, these studies generally assume stationary climatic conditions over the simulation period and ignore the linkages between soil and surface water recovery from acid deposition and changing climate, despite fundamental impacts to watershed processes and comparable time scales for both phenomena. In this study, the integrated biogeochemical model PnET-BGC was applied to two montane forest watersheds in the Adirondack region of New York, USA to evaluate the recovery of surface waters from historical acidification in response to possible future changes in climate and atmospheric sulfur and nitrogen deposition. Statistically downscaled climate scenarios on average project warmer temperatures and greater precipitation for the Adirondack by the end of the century. Model simulations suggest under constant climate, acid-sensitive Buck Creek would gain 12.8 µeq L-1 of acid neutralizing capacity (ANC) by 2100 from large reductions in deposition, whereas acid insensitive Archer Creek is projected to gain 7.9 µeq L-1 of ANC. However, climate change could limit those improvements in acid-base status. Under climate change, a negative offset relative to the ANC increases with no climate change are projected for both streams by 2100. In acid-insensitive Archer Creek the negative offset (-8.5 µeq L-1) was large enough that ANC is projected to decrease by -0.6 µeq L-1, whereas in acid-sensitive Buck Creek, the negative offset (-0.4 µeq L-1) resulted in a slight decline of the projected future ANC increase to 12.4 µeq L-1. Calculated target loads for 2150 for both sites decreased when future climate change was considered in model simulations, which suggests further reductions in acid deposition may be necessary to restore ecosystem structure and function under a changing climate.

Demographic Profile and Service-Connection Trends of Posttraumatic Stress Disorder and Traumatic Brain Injury in US Veterans Pre- and Post-9/11.

INTRODUCTION: This study seeks to understand the demographic changes in the active-duty service member profile, both prior to and following September 11, 2001 (9/11). The study analyzed diagnosis of posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) and measures of severity of those diagnoses as recorded in service-connection ratings (percent disability). METHODS: A retrospective cohort-study of military veterans who received care at Veterans Health Administration medical centers between December 1998 and May 2014 was conducted based on clinical data recorded and stored within the Corporate Data Warehouse. RESULTS: A cohort of 1,339,937 veterans received an inpatient or outpatient diagnosis of PTSD and/or TBI. The cohort was divided into 4 service period groups and 3 diagnosis categories. The service periods included pre-9/11 (n = 1,030,806; 77%), post-9/11 (n = 204,083; 15%), overlap-9/11 (n = 89,953; 7%), and reentered post-9/11 (n = 15,095; 1%). The diagnosis categories included PTSD alone (n = 1,132,356; 85%), TBI alone (n = 100,789; 7%) and PTSD+TBI (n = 106,792; 8%). Results of the post-9/11 group revealed significant changes, including (1) increase of veterans with PTSD+TBI; (2) increase of female veterans with PTSD+TBI; and (3) increase of severity level of diagnosed PTSD/TBI as evidenced by higher service-connected disability pensions at younger age in the post-9/11 group. Additionally, data revealed unequal distribution of veterans with PTSD+TBI across geographic areas. CONCLUSIONS: The veteran of the post-9/11 service period does not mirror the veteran of the pre-9/11 service period. Findings are valuable for policy making, allocation of resources, and for reconsidering the prevailing paradigm for treating veterans with PTSD and/or TBI.

The response of stream ecosystems in the Adirondack region of New York to historical and future changes in atmospheric deposition of sulfur and nitrogen.

The present-day acid-base chemistry of surface waters can be directly linked to contemporary observations of acid deposition; however, pre-industrial conditions are key to predicting the potential future recovery of stream ecosystems under decreasing loads of atmospheric sulfur (S) and nitrogen (N) deposition. The integrated biogeochemical model PnET-BGC was applied to 25 forest watersheds that represent a range of acid sensitivity in the Adirondack region of New York, USA to simulate the response of streams to past and future changes in atmospheric S and N deposition, and calculate the target loads of acidity for protecting and restoring stream water quality and ecosystem health. Using measured data, the model was calibrated and applied to simulate soil and stream chemistry at all study sites. Model hindcasts indicate that historically stream water chemistry in the Adirondacks was variable, but inherently sensitive to acid deposition. The median model-simulated acid neutralizing capacity (ANC) of the streams was projected to be 55 µeq L-1 before the advent of anthropogenic acid deposition (~1850), decreasing to minimum values of 10 µeq L-1 around the year 2000. The median simulated ANC increased to 13 µeq L-1 by 2015 in response to decreases in acid deposition that have occurred over recent decades. Model projections suggest that simultaneous decreases in sulfate, nitrate and ammonium deposition are more effective in restoring stream ANC than individual decreases in sulfur or nitrogen deposition. However, the increases in stream ANC per unit equivalent decrease in S deposition is greater compared to decreases in N deposition. Using empirical algorithms, fish community density and biomass are projected to increase under several deposition-control scenarios that coincide with increases in stream ANC. Model projections suggest that even under the most aggressive deposition-reduction scenarios, stream chemistry and fisheries will not fully recover from historical acidification by 2200.