Urinary exosomes reveal protein signatures in hypertensive patients with albuminuria

Albuminuria is an indicator of cardiovascular risk and renal damage in hypertensive individuals. Chronic renin-angiotensin system (RAS) suppression facilitates blood pressure control and prevents development of new-onset-albuminuria. A significant number of patients, however, develop albuminuria despite chronic RAS blockade, and the physiopathological mechanisms are underexplored. Urinary exosomes reflect pathological changes taking place in the kidney. The objective of this work was to examine exosomal protein alterations in hypertensive patients with albuminuria in the presence of chronic RAS suppression, to find novel clues underlying its development. Patients were followed-up for three years and were classified as: a) patients with persistent normoalbuminuria; b) patients developing de novo albuminuria; and c) patients with maintained albuminuria. Exosomal protein alterations between groups were identified by isobaric tag quantitation (iTRAQ). Confirmation was approached by target analysis (SRM). In total, 487 proteins were identified with high confidence. Specifically, 48 proteins showed an altered pattern in response to hypertension and/or albuminuria. Out of them, 21 proteins interact together in three main functional clusters: glycosaminoglycan degradation, coagulation and complement system, and oxidative stress. The identified proteins constitute potential targets for drug development and may help to define therapeutic strategies to evade albuminuria progression in hypertensive patients chronically treated.Instituto de Salud Carlos III, fondos FEDER/FSE (PI11/01401, PI13/01873, PI14/01841, IF08/3667-1, PI11-02239, PI 14/0917, PI11/02432, PI13/01746, PI14/01650, PI16/01334, PT13/0001/0013, CP09/00229, CP15/00129, CPII15/00027), Fundacion SENEFRO, Fundacion Conchita Rabago de Jimenez Diaz, and Redes Tematicas de Investigacion Cooperativa (fondos FEDER/FSE, RD12/0021/0001, RD12/0042/0071). These results are lined up with the Spanish initiative on the Human Proteome Project (SpHPP).S

Nitrogen deposition alters nitrogen cycling and reduces soil carbon content in low-productivity semiarid Mediterranean ecosystems.

Anthropogenic N deposition poses a threat to European Mediterranean ecosystems. We combined data from an extant N deposition gradient (4.3–7.3 kg N ha−1 yr−1) from semiarid areas of Spain and a field experiment in central Spain to evaluate N deposition effects on soil fertility, function and cyanobacteria community. Soil organic N did not increase along the extant gradient. Nitrogen fixation decreased along existing and experimental N deposition gradients, a result possibly related to compositional shifts in soil cyanobacteria community. Net ammonification and nitrification (which dominated N-mineralization) were reduced and increased, respectively, by N fertilization, suggesting alterations in the N cycle. Soil organic C content, C:N ratios and the activity of β-glucosidase decreased along the extant gradient in most locations. Our results suggest that semiarid soils in low-productivity sites are unable to store additional N inputs, and that are also unable to mitigate increasing C emissions when experiencing increased N deposition

Biogeochemical indicators of elevated nitrogen deposition in semiarid Mediterranean ecosystems

Nitrogen (N) deposition has doubled the natural N inputs received by ecosystems through biological N fixation and is currently a global problem that is affecting the Mediterranean regions. We evaluated the existing relationships between increased atmospheric N deposition and biogeochemical indicators related to soil chemical factors and cryptogam species across semiarid central, southern, and eastern Spain. The cryptogam species studied were the biocrust-forming species Pleurochaete squarrosa (moss) and Cladonia foliacea (lichen). Sampling sites were chosen in Quercus coccifera (kermes oak) shrublands and Pinus halepensis (Aleppo pine) forests to cover a range of inorganic N deposition representative of the levels found in the Iberian Peninsula (between 4.4 and 8.1 kg N ha(-1) year(-1)). We extended the ambient N deposition gradient by including experimental plots to which N had been added for 3 years at rates of 10, 20, and 50 kg N ha(-1) year(-1). Overall, N deposition (extant plus simulated) increased soil inorganic N availability and caused soil acidification. Nitrogen deposition increased phosphomonoesterase (PME) enzyme activity and PME/nitrate reductase (NR) ratio in both species, whereas the NR activity was reduced only in the moss. Responses of PME and NR activities were attributed to an induced N to phosphorus imbalance and to N saturation, respectively. When only considering the ambient N deposition, soil organic C and N contents were positively related to N deposition, a response driven by pine forests. The PME/NR ratios of the moss were better predictors of N deposition rates than PME or NR activities alone in shrublands, whereas no correlation between N deposition and the lichen physiology was observed. We conclude that integrative physiological measurements, such as PME/NR ratios, measured on sensitive species such as P. squarrosa, can provide useful data for national-scale biomonitoring programs, whereas soil acidification and soil C and N storage could be useful as additional corroborating ecosystem indicators of chronic N pollution

Eurodelta multi-model simulated and observed particulate matter trends in Europe in the period of 1990-2010

The Eurodelta-Trends (EDT) multi-model experiment, aimed at assessing the efficiency of emission mitigation measures in improving air quality in Europe during 1990-2010, was designed to answer a series of questions regarding European pollution trends; i.e. were there significant trends detected by observations? Do the models manage to reproduce observed trends? How close is the agreement between the models and how large are the deviations from observations? In this paper, we address these issues with respect to particulate matter (PM) pollution. An in-depth trend analysis has been performed for PM10 and PM2.5 for the period of 2000-2010, based on results from six chemical transport models and observational data from the EMEP (Cooperative Programme for Monitoring and Evaluation of the Long-range Transmission of Air Pollutants in Europe) monitoring network. Given harmonization of set-up and main input data, the differences in model results should mainly result from differences in the process formulations within the models themselves, and the spread in the model-simulated trends could be regarded as an indicator for modelling uncertainty.The model ensemble simulations indicate overall decreasing trends in PM10 and PM2.5 from 2000 to 2010, with the total reductions of annual mean concentrations by between 2 and 5 (7 for PM10) mu g m(-3) (or between 10 % and 30 %) across most of Europe (by 0.5-2 mu g m(-3) in Fennoscandia, the north-west of Russia and eastern Europe) during the studied period. Compared to PM2.5, relative PM10 trends are weaker due to large interannual variability of natural coarse PM within the former. The changes in the concentrations of PM individual components are in general consistent with emission reductions. There is reasonable agreement in PM trends estimated by the individual models, with the inter-model variability below 30 %-40 % over most of Europe, increasing to 50 %-60 % in the northern and eastern parts of the EDT domain.Averaged over measurement sites (26 for PM10 and 13 for PM2.5), the mean ensemble-simulated trends are - 0.24 and -0.22 mu g m(-3) yr(-1) for PM10 and PM2.5, which are somewhat weaker than the observed trends of - 0.35 and -0.40 mu g m(-3) yr(-1) respectively, partly due to model underestimation of PM concentrations. The correspondence is better in relative PM10 and PM2.5 trends, which are -1.7 % yr(-1) and -2.0 % yr(-1) from the model ensemble and -2.1 % yr(-1) and -2.9 % yr(-1) from the observations respectively. The observations identify significant trends (at the 95 % confidence level) for PM10 at 56 % of the sites and for PM2.5 at 36 % of the sites, which is somewhat less that the fractions of significant modelled trends. Further, we find somewhat smaller spatial variability of modelled PM trends with respect to the observed ones across Europe and also within individual countries.The strongest decreasing PM trends and the largest number of sites with significant trends are found for the summer season, according to both the model ensemble and observations. The winter PM trends are very weak and mostly insignificant. Important reasons for that are the very modest reductions and even increases in the emissions of primary PM from residential heating in winter. It should be kept in mind that all findings regarding modelled versus observed PM trends are limited to the regions where the sites are located.The analysis reveals considerable variability of the role of the individual aerosols in PM10 trends across European countries. The multi-model simulations, supported by available observations, point to decreases in SO42- concentrations playing an overall dominant role. Also, we see relatively large contributions of the trends of NH4+ and NO3- to PM10 decreasing trends in Germany, Denmark, Poland and the Po Valley, while the reductions of primary PM emissions appear to be a dominant factor in bringing down PM10 in France, Norway, Portugal, Greece and parts of the UK and Russia. Further discussions are given with respect to emission uncertainties (including the implications of not accounting for forest fires and natural mineral dust by some of the models) and the effect of inter-annual meteorological variability on the trend analysis.Peer reviewe

Assessment of the sensitivity of model responses to urban emission changes in support of emission reduction strategies

© 2023 The Author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/The sensitivity of air quality model responses to modifications in input data (e.g. emissions, meteorology and boundary conditions) or model configurations is recognized as an important issue for air quality modelling applications in support of air quality plans. In the framework of FAIRMODE (Forum of Air Quality Modelling in Europe, https://fairmode.jrc.ec.europa.eu/) a dedicated air quality modelling exercise has been designed to address this issue. The main goal was to evaluate the magnitude and variability of air quality model responses when studying emission scenarios/projections by assessing the changes of model output in response to emission changes. This work is based on several air quality models that are used to support model users and developers, and, consequently, policy makers. We present the FAIRMODE exercise and the participating models, and provide an analysis of the variability of O3 and PM concentrations due to emission reduction scenarios. The key novel feature, in comparison with other exercises, is that emission reduction strategies in the present work are applied and evaluated at urban scale over a large number of cities using new indicators such as the absolute potential, the relative potential and the absolute potency. The results show that there is a larger variability of concentration changes between models, when the emission reduction scenarios are applied, than for their respective baseline absolute concentrations. For ozone, the variability between models of absolute baseline concentrations is below 10%, while the variability of concentration changes (when emissions are similarly perturbed) exceeds, in some instances 100% or higher during episodes. Combined emission reductions are usually more efficient than the sum of single precursor emission reductions both for O3 and PM. In particular for ozone, model responses, in terms of linearity and additivity, show a clear impact of non-linear chemistry processes. This analysis gives an insight into the impact of model’ sensitivity to emission reductions that may be considered when designing air quality plans and paves the way of more in-depth analysis to disentangle the role of emissions from model formulation for present and future air quality assessments.Peer reviewe

Modeled deposition of nitrogen and sulfur in Europe estimated by 14 air quality model systems: evaluation, effects of changes in emissions and implications for habitat protection

The evaluation and intercomparison of air quality models is key to reducing model errors and uncertainty. The projects AQMEII3 and EURODELTA-Trends, in the framework of the Task Force on Hemispheric Transport of Air Pollutants and the Task Force on Measurements and Modelling, respectively (both task forces under the UNECE Convention on the Long Range Transport of Air Pollution, LTRAP), have brought together various regional air quality models to analyze their performance in terms of air concentrations and wet deposition, as well as to address other specific objectives. This paper jointly examines the results from both project communities by intercomparing and evaluating the deposition estimates of reduced and oxidized nitrogen (N) and sulfur (S) in Europe simulated by 14 air quality model systems for the year 2010. An accurate estimate of deposition is key to an accurate simulation of atmospheric concentrations. In addition, deposition fluxes are increasingly being used to estimate ecological impacts. It is therefore important to know by how much model results differ and how well they agree with observed values, at least when comparison with observations is possible, such as in the case of wet deposition. This study reveals a large variability between the wet deposition estimates of the models, with some performing acceptably (according to previously defined criteria) and others underestimating wet deposition rates. For dry deposition, there are also considerable differences between the model estimates. An ensemble of the models with the best performance for N wet deposition was made and used to explore the implications of N deposition in the conservation of protected European habitats. Exceedances of empirical critical loads were calculated for the most common habitats at a resolution of 100  ×  100 m2 within the Natura 2000 network, and the habitats with the largest areas showing exceedances are determined. Moreover, simulations with reduced emissions in selected source areas indicated a fairly linear relationship between reductions in emissions and changes in the deposition rates of N and S. An approximate 20 % reduction in N and S deposition in Europe is found when emissions at a global scale are reduced by the same amount. European emissions are by far the main contributor to deposition in Europe, whereas the reduction in deposition due to a decrease in emissions in North America is very small and confined to the western part of the domain. Reductions in European emissions led to substantial decreases in the protected habitat areas with critical load exceedances (halving the exceeded area for certain habitats), whereas no change was found, on average, when reducing North American emissions in terms of average values per habitat

Results of the first European Source Apportionment intercomparison for Receptor and Chemical Transport Models

In this study, the performance of the source apportionment model applications were evaluated by comparing the model results provided by 44 participants adopting a methodology based on performance indicators: z-scores and RMSEu, with pre-established acceptability criteria. Involving models based on completely different and independent input data, such as receptor models (RMs) and chemical transport models (CTMs), provided a unique opportunity to cross-validate them. In addition, comparing the modelled source chemical profiles, with those measured directly at the source contributed to corroborate the chemical profile of the tested model results. The most used RM was EPA- PMF5. RMs showed very good performance for the overall dataset (91% of z-scores accepted) and more difficulties are observed with SCE time series (72% of RMSEu accepted). Industry resulted the most problematic source for RMs due to the high variability among participants. Also the results obtained with CTMs were quite comparable to their ensemble reference using all models for the overall average (>92% of successful z-scores) while the comparability of the time series is more problematic (between 58% and 77% of the candidates’ RMSEu are accepted). In the CTM models a gap was observed between the sum of source contributions and the gravimetric PM10 mass likely due to PM underestimation in the base case. Interestingly, when only the tagged species CTM results were used in the reference, the differences between the two CTM approaches (brute force and tagged species) were evident. In this case the percentage of candidates passing the z-score and RMSEu tests were only 50% and 86%, respectively. CTMs showed good comparability with RMs for the overall dataset (83% of the z-scores accepted), more differences were observed when dealing with the time series of the single source categories. In this case the share of successful RMSEu was in the range 25% - 34%.JRC.C.5-Air and Climat

Association of Endovascular Thrombectomy vs Medical Management With Functional and Safety Outcomes in Patients Treated Beyond 24 Hours of Last Known Well: The SELECT Late Study

IMPORTANCE: The role of endovascular thrombectomy is uncertain for patients presenting beyond 24 hours of the time they were last known well. OBJECTIVE: To evaluate functional and safety outcomes for endovascular thrombectomy (EVT) vs medical management in patients with large-vessel occlusion beyond 24 hours of last known well. DESIGN, SETTING, AND PARTICIPANTS: This retrospective observational cohort study enrolled patients between July 2012 and December 2021 at 17 centers across the United States, Spain, Australia, and New Zealand. Eligible patients had occlusions in the internal carotid artery or middle cerebral artery (M1 or M2 segment) and were treated with EVT or medical management beyond 24 hours of last known well. INTERVENTIONS: Endovascular thrombectomy or medical management (control). MAIN OUTCOMES AND MEASURES: Primary outcome was functional independence (modified Rankin Scale score 0-2). Mortality and symptomatic intracranial hemorrhage (sICH) were safety outcomes. Propensity score (PS)-weighted multivariable logistic regression analyses were adjusted for prespecified clinical characteristics, perfusion parameters, and/or Alberta Stroke Program Early CT Score (ASPECTS) and were repeated in subsequent 1:1 PS-matched cohorts. RESULTS: Of 301 patients (median [IQR] age, 69 years [59-81]; 149 female), 185 patients (61%) received EVT and 116 (39%) received medical management. In adjusted analyses, EVT was associated with better functional independence (38% vs control, 10%; inverse probability treatment weighting adjusted odds ratio [IPTW aOR], 4.56; 95% CI, 2.28-9.09; P \u3c .001) despite increased odds of sICH (10.1% for EVT vs 1.7% for control; IPTW aOR, 10.65; 95% CI, 2.19-51.69; P = .003). This association persisted after PS-based matching on (1) clinical characteristics and ASPECTS (EVT, 35%, vs control, 19%; aOR, 3.14; 95% CI, 1.02-9.72; P = .047); (2) clinical characteristics and perfusion parameters (EVT, 35%, vs control, 17%; aOR, 4.17; 95% CI, 1.15-15.17; P = .03); and (3) clinical characteristics, ASPECTS, and perfusion parameters (EVT, 45%, vs control, 21%; aOR, 4.39; 95% CI, 1.04-18.53; P = .04). Patients receiving EVT had lower odds of mortality (26%) compared with those in the control group (41%; IPTW aOR, 0.49; 95% CI, 0.27-0.89; P = .02). CONCLUSIONS AND RELEVANCE: In this study of treatment beyond 24 hours of last known well, EVT was associated with higher odds of functional independence compared with medical management, with consistent results obtained in PS-matched subpopulations and patients with presence of mismatch, despite increased odds of sICH. Our findings support EVT feasibility in selected patients beyond 24 hours. Prospective studies are warranted for confirmation

Association of Endovascular Thrombectomy vs Medical Management With Functional and Safety Outcomes in Patients Treated Beyond 24 Hours of Last Known Well: The SELECT Late Study

IMPORTANCE: The role of endovascular thrombectomy is uncertain for patients presenting beyond 24 hours of the time they were last known well. OBJECTIVE: To evaluate functional and safety outcomes for endovascular thrombectomy (EVT) vs medical management in patients with large-vessel occlusion beyond 24 hours of last known well. DESIGN, SETTING, AND PARTICIPANTS: This retrospective observational cohort study enrolled patients between July 2012 and December 2021 at 17 centers across the United States, Spain, Australia, and New Zealand. Eligible patients had occlusions in the internal carotid artery or middle cerebral artery (M1 or M2 segment) and were treated with EVT or medical management beyond 24 hours of last known well. INTERVENTIONS: Endovascular thrombectomy or medical management (control). MAIN OUTCOMES AND MEASURES: Primary outcome was functional independence (modified Rankin Scale score 0-2). Mortality and symptomatic intracranial hemorrhage (sICH) were safety outcomes. Propensity score (PS)-weighted multivariable logistic regression analyses were adjusted for prespecified clinical characteristics, perfusion parameters, and/or Alberta Stroke Program Early CT Score (ASPECTS) and were repeated in subsequent 1:1 PS-matched cohorts. RESULTS: Of 301 patients (median [IQR] age, 69 years [59-81]; 149 female), 185 patients (61%) received EVT and 116 (39%) received medical management. In adjusted analyses, EVT was associated with better functional independence (38% vs control, 10%; inverse probability treatment weighting adjusted odds ratio [IPTW aOR], 4.56; 95% CI, 2.28-9.09; P \u3c .001) despite increased odds of sICH (10.1% for EVT vs 1.7% for control; IPTW aOR, 10.65; 95% CI, 2.19-51.69; P = .003). This association persisted after PS-based matching on (1) clinical characteristics and ASPECTS (EVT, 35%, vs control, 19%; aOR, 3.14; 95% CI, 1.02-9.72; P = .047); (2) clinical characteristics and perfusion parameters (EVT, 35%, vs control, 17%; aOR, 4.17; 95% CI, 1.15-15.17; P = .03); and (3) clinical characteristics, ASPECTS, and perfusion parameters (EVT, 45%, vs control, 21%; aOR, 4.39; 95% CI, 1.04-18.53; P = .04). Patients receiving EVT had lower odds of mortality (26%) compared with those in the control group (41%; IPTW aOR, 0.49; 95% CI, 0.27-0.89; P = .02). CONCLUSIONS AND RELEVANCE: In this study of treatment beyond 24 hours of last known well, EVT was associated with higher odds of functional independence compared with medical management, with consistent results obtained in PS-matched subpopulations and patients with presence of mismatch, despite increased odds of sICH. Our findings support EVT feasibility in selected patients beyond 24 hours. Prospective studies are warranted for confirmation