Where the not-so-wild things are in cities? The influence of social-ecological factors in urban trees at multiple scales.

Green infrastructure plays an essential role in cities due to the ecosystem services it provides. However, these elements are shaped by social and ecological factors that influence their distribution and diversity, affecting ecological functions and human well-being. Here, we analyzed neighborhood tree distribution - trees in pocket parks, squares and along streets - in Lisbon (Portugal) and modelled tree abundance and taxonomic and functional diversity, at the parish and local scales, considering a comprehensive list of social and ecological factors. For the functional analyses, we included functional traits linked to dispersal, resilience to important perturbations in coastal Mediterranean cities, and ecosystem services delivery. Our results show not only that trees are unevenly distributed across the city, but that there is a strong influence of social factors on all biological indices considered. At the parish and local scales, abundance and diversity responded to different factors, with abundance being linked to both social and ecological variables. Although the influence of social factors on urban trees can be expected, by modelling their influence we can quantify how much humans modify urban landscapes at a structural and functional level. These associations can underlie potential biodiversity filters and should be analyzed over time to inform decisions that support long-term ecological resilience, maximize trait functional expression, and increase equity in ecosystem services delivery.

Shifts in plant functional groups along an aridity gradient in a tropical dry forest.

Increasing aridity associated with climate change may lead to the crossing of critical ecosystem thresholds in drylands, compromising ecosystem services for millions of people. In this context, finding tools to detect at early stages the effects of increasing aridity on ecosystems is extremely urgent to avoid irreversible damage. Here, we assess shifts in plant community functional structure along a spatial aridity gradient in tropical dryland (Brazilian Caatinga), to select the most appropriate plant functional groups as ecological indicators likely useful to predict temporal ecosystem trajectories in response to aridity. We identified seven plant functional groups based on 13 functional traits associated with plant establishment, defense, regeneration, and dispersal, whose relative abundances changed, linearly and non-linearly, with increasing aridity, showing either increasing or decreasing trends. Of particular importance is the increase in abundance of plants with high chemical defense and Crassulacean Acid Metabolism (CAM) photosynthetic pathway, with increasing aridity. We propose the use of these functional groups as early warning indicators to detect aridity impacts on these dryland ecosystems and shifts in ecosystem functioning. This information can also be used in the elaboration of mitigation and ecological restoration measures to prevent and revert current and future climate change impacts on tropical dry forests.

More than trees: Stand management can be used to improve ecosystem diversity, structure and functioning 20 years after forest restoration in drylands.

In Mediterranean drylands, extensive areas have been restored by reforestation over the past decades to improve diversity, soil fertility, and tree natural regeneration, contributing to halting desertification and land degradation. However, evaluating reforestation success usually relies on tree survival, while holistic and long-term evaluations of reforestation success based on ecosystem diversity, structure and functioning are scarce. In this work, we provide the first assessment that combines the evaluation of planted trees and indicators of ecosystem diversity, structure, and functioning in established reforestations with three native Mediterranean species along a climatic gradient. We sampled 43 20-year-old stands with umbrella pine, holm oak and cork oak in Portugal, and tested the effects of tree species composition, stand management (i.e., differences in tree density and shrub cover), and edaphoclimatic conditions, on the size of planted trees, species diversity, structural complexity and indicators of ecosystem functioning related to productivity, soil nutrients and tree natural regeneration. Our results show that, after 20 years of reforestation, stand management was an essential driver of plant diversity and ecosystem functioning. Higher tree density, particularly of oaks, and higher shrub cover improved plant diversity, ecosystem productivity, and oak regeneration. The latter was also improved by structural complexity. Tree composition effects highlighted the importance of pine management to avoid competition. Since we evaluated these reforestations along a climatic gradient, we also conclude that climate influenced pine and holm oak size, ecosystem productivity, and soil C/N. Our research, by being based on assessing the long-term reforestation success in a more holistic way, highlighted the importance of stand management for improving ecosystem diversity and functioning in these restored systems. Practices such as increasing tree density up to ~800 trees/ha and allowing a shrub cover of ca. 30 %, may improve the ecological condition of future and currently reforested areas across the Mediterranean region.

How Do Taxonomic and Functional Diversity Metrics Change Along an Aridity Gradient in a Tropical Dry Forest?

Ecological indicators based on biodiversity metrics are valuable and cost-effective tools to quantify, track and understand the effects of climate change on ecosystems. Studying changes in these indicators along climatic gradients in space is a common approach to infer about potential impacts of climate change over time, overcoming the limitations of lack of sufficiently long time-series data. Here, we studied the response of complementary biodiversity metrics in plants: taxonomic diversity (species richness and Simpson index) and functional diversity (diversity and redundancy) in 113 sampling sites along a spatial aridity gradient (from 0.27 to 0.69 of aridity index-AI) of 700 km in a Tropical dry forest. We found different responses of taxonomic and functional diversity metrics to aridity. Species diversity showed a hump-shaped curve peaking at intermediate levels of aridity between 0.38 and 0.52 AI as an ecotone, probably because it is where most species, from both drier and more mesic environments, still find conditions to co-exist. Functional diversity showed a positive linear relation with increasing aridity, suggesting higher aridity favors drought-adapted species with diverse functional traits. In contrast, redundancy showed a negative linear relation with increasing aridity, indicating that drier sites have few species sharing the same functional traits and resource acquisition strategies. Thus, despite the increase in functional diversity toward drier sites, these communities are less resilient since they are composed of a small number of plant species with unique functions, increasing the chances that the loss of one of such "key species" could lead to the loss of key ecosystem functions. These findings show that the integration of complementary taxonomic and functional diversity metrics, beyond the individual response of each one, is essential for reliably tracking the impacts of climate change on ecosystems. This work also provides support to the use of these biodiversity metrics as ecological indicators of the potential impact of climate change on drylands over time.

Local-scale factors matter for tree cover modelling in Mediterranean drylands.

Forests contribute directly to ecosystem structure and functioning, maintaining biodiversity, acting as a climate regulator and reducing desertification. To better manage forests, it is essential to have high-resolution forest models and appropriate spatial-explicit variables able to explain tree cover at different scales, including the management scale. Most tree cover models rely only on broad-scale variables (>500 m), such as macroclimate, while only few studies include also local-scale variables (<500 m). This study aimed to identify the importance of local-scale factors relative to broad-scale factors and identify the environmental variables at different scales that explain tree cover in oak woodlands in Mediterranean drylands. Sixty sites previously identified as being covered with Holm oak or Cork oak were stratified by precipitation. Normalized Difference Vegetation Index, used here as a surrogate of tree cover, was modelled using simultaneously broad-scale factors (macroclimate) and local-scale factors (microclimatic and edaphic conditions). The percentage of variance explained by local- and broad-scale factors and the effect size of each environmental variable on tree cover was determined for the study site. It was found that local-scale factors and their interaction with broad-scale factors explained more variance than broad-scale factors alone. The most important local-scale factors explaining tree cover were elevation, potential solar radiation, used as a surrogate of microclimatic conditions, and wetness evaluated terrain used as an indicator of water flow accumulation. The main broad-scale factors were related to temperature and precipitation. The effect of some local-scale variables in tree cover seems to increase in areas where water as a limiting factor is more important. This study demonstrates the critical importance of including local-scale factors in multi-scale modelling of tree cover to obtain better predictions. These models will support well-suited forest management decisions, such as reforestation and afforestation plans to reverse evergreen oaks decline in Mediterranean drylands.

Bottom-up cascading effects of quarry revegetation deplete bird-mediated seed dispersal services.

Quarrying activities cause profound modifications on ecosystems, such as removal of vegetation cover, biodiversity loss and depletion of ecosystem services. Ecological restoration stands as a solution to revert such effects. Concomitantly, awareness is currently being given on ecosystem services and ecological processes to evaluate restoration efficiency. The objective of the study was to assess restoration success in a quarry subjected to restoration practices for the last 40 years involving the plantation of native Mediterranean vegetation and the non-native Aleppo pine Pinus halepensis. The study was carried out by assessing the effectiveness of seed dispersal service provided by birds in the restored quarry by comparing this service to neighbouring natural (shrubland) and other semi-natural areas (oak-pine mixed open and Aleppo pine forest) present at the landscape. For this purpose, we explored bird composition structure and seed dispersal networks using point counts and faecal samples of mist-netted birds. We also collected vegetation structure data and explored its effect on bird community composition. Our results showed that bird abundance in the restored quarry was significantly lower, and its bird community was compositionally different than natural shrubland and semi-natural areas. For instance, seed-dispersing birds, woody and shrub/ground foragers and partially migrators were the most affected groups at the restored area. Bird community composition and their traits were likely driven by vegetation characteristics, with higher native vegetation cover and fruit richness promoting higher bird abundance and Aleppo pine cover negatively influencing seed-dispersing birds. Concurrently, seed dispersal network in the restored quarry was less complex than in other areas. Seed dispersal services in the restored quarry were below the reported values for neighbouring natural and semi-natural areas and are likely driven by the low abundance of seed-dispersing birds. We consider that the causes affecting this group's low abundance can be related to revegetation measures favouring Aleppo pine, combined with a shallow soil depth and poor soil quality, which may have constrained native vegetation development. We conclude that seed dispersal services at the quarry are depleted, which may suggest a low restoration success concerning ecosystem functioning. Our results strengthen that quarry revegetation with non-native species must be avoided, since it alters bird community composition, and consequently, affects seed dispersal service provided by birds.

Local environmental variables are key drivers of ant taxonomic and functional beta-diversity in a Mediterranean dryland.

The decomposition of beta-diversity (ß-diversity) into its replacement (ßrepl) and richness (ßrich) components in combination with a taxonomic and functional approach, may help to identify processes driving community composition along environmental gradients. We aimed to understand which abiotic and spatial variables influence ant ß-diversity and identify which processes may drive ant ß-diversity patterns in Mediterranean drylands by measuring the percentage of variation in ant taxonomic and functional ß-diversity explained by local environmental, regional climatic and spatial variables. We found that taxonomic and functional replacement (ßrepl) primarily drove patterns in overall ß-diversity (ßtot). Variation partitioning analysis showed that respectively 16.8%, 12.9% and 21.6% of taxonomic ßtot, ßrepl and ßrich variation were mainly explained by local environmental variables. Local environmental variables were also the main determinants of functional ß-diversity, explaining 20.4%, 17.9% and 23.2% of ßtot, ßrepl and ßrich variation, respectively. Findings suggest that niche-based processes drive changes in ant ß-diversity, as local environmental variables may act as environmental filters on species and trait composition. While we found that local environmental variables were important predictors of ant ß-diversity, further analysis should address the contribution of other mechanisms, e.g. competitive exclusion and resource partitioning, on ant ß-diversity.

Phylogenetic structure of understorey annual and perennial plant species reveals opposing responses to aridity in a Mediterranean biodiversity hotspot.

Aridity is a critical driver of the diversity and composition of plant communities. However, how aridity influences the phylogenetic structure of functional groups (i.e. annual and perennial species) is far less understood than its effects on species richness. As perennials have to endure stressful conditions during the summer drought, as opposed to annuals that avoid it, they may be subjected to stronger environmental filtering. In contrast, annuals may be more susceptible to interannual climatic variability. Here we studied the phylogenetic structure of the annual and perennial components of understorey plant communities, along a regional aridity gradient in Mediterranean drylands. Specifically, we asked: (1) How do species richness (S) and phylogenetic structure (PS) of annuals and perennials in plant communities respond to aridity? (2) What is the contribution of other climatic and topo-edaphic variables in predicting S and PS for both components? (3) How does the taxonomic and phylogenetic turnover of annuals and perennials vary with spatial and environmental distances? We assessed annuals' and perennials' species richness, the phylogenetic structure at deep and shallow phylogenetic levels, and taxonomic and phylogenetic turnover along spatial and environmental distances. We found no relationship between annuals' richness and aridity, whereas perennials' richness showed a unimodal pattern. The phylogenetic structure of annuals and perennials showed contrasting responses to aridity and negatively correlated with topo-edaphic variables. We found phylogenetic clustering at intermediate-to-higher aridity levels for annuals, and at lower aridity levels for perennials. Both taxonomic and phylogenetic turnover in annuals and perennials correlated with the environmental distance rather than with spatial distance between communities, suggesting adaptation to local factors. Overall, our results show a decoupling in the response of the phylogenetic structure of annual and perennial components of plant communities to aridity in Mediterranean drylands. Our findings have significant implications for land management strategies under climate change.

The response of plant functional traits to aridity in a tropical dry forest.

Drylands are experiencing an overall increase in aridity that is predicted to intensify in the future due to climate change. This may cause changes in the structure and functioning of dryland ecosystems, affecting ecosystem services and human well-being. Therefore, detecting early signs of ecosystem change before irreversible damage takes place is important. Thus, here we used a space-for-time substitution approach to study the response of the plant community to aridity in a Tropical dry forest (Caatinga, Brazil), and infer potential consequences of climate change. We assessed plant functional structure using the community weighted mean (CWM) and functional diversity, measured through functional dispersion (FDis), along a 700 km climatic gradient. We studied 13 functional traits, reflecting strategies associated with establishment, defense, regeneration, and dispersal of the most abundant 48 plant species in 113 sampling sites. Spearman correlations were used to test the relation between aridity and single-trait functional metrics. Aridity was a major environmental filter of the plant community functional structure. We found a higher abundance of species with deciduous leaves, zoochorous dispersal, fleshy fruits, chemical defense exudation and spinescence, and crassulacean acid metabolism towards more arid sites, at the expense of species with evergreen and thicker leaves, autochory dispersal, and shrub growth-form. The FDis of leaf type and thickness decreased with aridity, whereas FDis of fruit type, photosynthetic pathway, and defense strategies increased. Our findings provide functional indicators to early detect climate change impacts on Caatinga structure and functioning, to timely adopt preventive measures (e.g. conservation of forest remnants) and restoration actions (e.g. introduction of species with specific functional traits) in this threatened and unique ecosystem.

Comparison of Heart Transplantation Outcomes: Adult Congenital Heart Disease vs Matched Cardiac Patients in a Quaternary Reference Centre.

BACKGROUND: The number of transplantations performed for adult congenital heart disease (ACHD) patients is increasing. We sought to compare survival and post-transplantation complications, including graft failure, rejection, dialysis, and use of a right ventricular assist device, between ACHD and a cohort of dilated (DCM) and ischemic (ICM) cardiomyopathy patients matched by age and year of transplantation. METHODS: We retrospectively reviewed our single-institution heart transplantation database and selected all patients who had surgery from 1988 to 2017. In our primary analysis, we looked at survival and post-transplantation complications across cardiomyopathy groups. Our secondary analysis was matched to mitigate era effects as well as differences in age at transplant. RESULTS: We analyzed a cohort consisting of 303 heart transplant patients with cardiomyopathy due to either 1) ACHD (n = 38), 2) ICM (n = 110), or 3) DCM (n = 155). Kaplan-Meier analysis and a multivariable Cox proportional hazard regression model were used for all-cause mortality, and cause-specific hazard regression for cause-specific mortality and morbidity. There was no statistically significant survival difference across groups. The 1-year survival was 68.5% for ACHD, 85.4% for ICM, and 85.5% for DCM. In multivariable analysis, ICM and DCM patients showed a 66% lower risk of death relative to the ACHD group. The matched analysis showed no significant difference in survival across groups. CONCLUSIONS: ACHD patients represent a growing high-risk patient cohort referred for transplantation. To improve survival outcomes we need to address modifiable risk factors.

Local topographic and edaphic factors largely predict shrub encroachment in Mediterranean drylands.

Shrub encroachment influences several ecosystem services in drylands worldwide. Yet, commonly used strategies to reduce encroachment show a low medium-term success, calling for a better understanding of its causes. Previous works identified multiple drivers responsible for this phenomenon, including anthropogenic and environmental causes. However, the relative effect of climate, topography and edaphic factors on shrub encroachment is not fully understood nor has been properly quantified in Mediterranean Basin drylands. Also, understanding how these drivers lead to changes in plant communities' functional traits associated to shrub encroachment is crucial, considering traits influence ecosystem processes and associated ecosystem services. Here, we studied the understory of a Mediterranean dryland ecosystem composed of savanna-like Holm-oak woodlands, along a regional climatic gradient. We specifically assessed (i) how climatic, topographic and edaphic factors influence understory relative shrub cover (RSC) and (ii) their direct and indirect effects (via RSC) on plant functional traits. We studied the mean and diversity of 12 functional traits related to plant regeneration, establishment, and dispersal, at the community-level. We found that, under similar low-intensity land use, topographic and edaphic factors, namely slope variations and soil C:N ratio, were the most important predictors of shrub encroachment, determining communities' functional characteristics. Climate, namely summer precipitation, had a much lesser influence. Our model explained 52% of the variation in relative shrub cover. Climate had a stronger effect on a set of functional traits weakly involved in shrub encroachment, related to flowering and dispersal strategies. We show that shrub encroachment is largely predicted by topo-edaphic factors in Mediterranean drylands subject to conventional low-intensity land use. Hence, management strategies to reduce encroachment need to take these drivers into account for efficient forecasting and higher cost-effectiveness. Our results suggest that climate change might not greatly impact shrub encroachment in the Mediterranean Basin, but may affect functional structure and reduce functional diversity of plant communities, thus affecting ecosystem functioning.

Ecological impacts of atmospheric pollution and interactions with climate change in terrestrial ecosystems of the Mediterranean Basin: Current research and future directions.

Mediterranean Basin ecosystems, their unique biodiversity, and the key services they provide are currently at risk due to air pollution and climate change, yet only a limited number of isolated and geographically-restricted studies have addressed this topic, often with contrasting results. Particularities of air pollution in this region include high O3 levels due to high air temperatures and solar radiation, the stability of air masses, and dominance of dry over wet nitrogen deposition. Moreover, the unique abiotic and biotic factors (e.g., climate, vegetation type, relevance of Saharan dust inputs) modulating the response of Mediterranean ecosystems at various spatiotemporal scales make it difficult to understand, and thus predict, the consequences of human activities that cause air pollution in the Mediterranean Basin. Therefore, there is an urgent need to implement coordinated research and experimental platforms along with wider environmental monitoring networks in the region. In particular, a robust deposition monitoring network in conjunction with modelling estimates is crucial, possibly including a set of common biomonitors (ideally cryptogams, an important component of the Mediterranean vegetation), to help refine pollutant deposition maps. Additionally, increased attention must be paid to functional diversity measures in future air pollution and climate change studies to establish the necessary link between biodiversity and the provision of ecosystem services in Mediterranean ecosystems. Through a coordinated effort, the Mediterranean scientific community can fill the above-mentioned gaps and reach a greater understanding of the mechanisms underlying the combined effects of air pollution and climate change in the Mediterranean Basin.

Association between Spirituality and Adherence to Management in Outpatients with Heart Failure / Associação entre Espiritualidade e Adesão ao Tratamento em Pacientes Ambulatoriais com Insuficiência Cardíaca

Abstract Background: Spirituality may influence how patients cope with their illness. Objectives: We assessed whether spirituality may influence adherence to management of outpatients with heart failure. Methods: Cross sectional study enrolling consecutive ambulatory heart failure patients in whom adherence to multidisciplinary treatment was evaluated. Patients were assessed for quality of life, depression, religiosity and spirituality utilizing validated questionnaires. Correlations between adherence and psychosocial variables of interest were obtained. Logistic regression models explored independent predictors of adherence. Results: One hundred and thirty patients (age 60 ± 13 years; 67% male) were interviewed. Adequate adherence score was observed in 38.5% of the patients. Neither depression nor religiosity was correlated to adherence, when assessed separately. Interestingly, spirituality, when assessed by both total score sum (r = 0.26; p = 0.003) and by all specific domains, was positively correlated to adherence. Finally, the combination of spirituality, religiosity and personal beliefs was an independent predictor of adherence when adjusted for demographics, clinical characteristics and psychosocial instruments. Conclusion: Spirituality, religiosity and personal beliefs were the only variables consistently associated with compliance to medication in a cohort of outpatients with heart failure. Our data suggest that adequately addressing these aspects on patient’s care may lead to an improvement in adherence patterns in the complex heart failure management.

Resumo Fundamento: A espiritualidade pode influenciar a maneira com que os pacientes lidam com sua doença. Objetivos: Avaliamos a possibilidade de a espiritualidade influenciar a adesão ao tratamento de pacientes ambulatoriais com insuficiência cardíaca. Métodos: Estudo transversal com pacientes ambulatoriais com insuficiência cardíaca, cuja adesão ao tratamento multidisciplinar foi avaliada. Os pacientes foram avaliados sobre qualidade de vida, depressão, religiosidade e espiritualidade, utilizando questionários validados. Foram obtidas correlações entre adesão e variáveis psicossociais de interesse. Modelos de regressão logística exploraram preditores independentes de adesão. Resultados: Cento e trinta pacientes (idade 60 ± 13 anos; 67% masculinos) foram entrevistados. Observou-se adequado escore de adesão em 38,5% dos pacientes. Nem a depressão ou a religiosidade foram correlacionados à adesão, quando avaliados separadamente. É interessante notar que quando a espiritualidade foi avaliada por ambos, o somatório total de score (r = 0,26; p = 0,003) e os domínios específicos, ela estava positivamente correlacionada à adesão. Por fim, a combinação de espiritualidade, religiosidade e crenças pessoais mostrou-se um preditor independente de adesão quando ajustado às características demográficas, clínicas e a instrumentos psicossociais. Conclusão: Espiritualidade, religiosidade e crenças pessoais foram as únicas variáveis consistentemente associadas à adesão em relação à medicação em uma coorte de pacientes ambulatoriais com insuficiência cardíaca. Nossos dados sugerem que abordar adequadamente esses aspectos no cuidado com o paciente pode auxiliar a melhorar o padrão de adesão no complexo tratamento da insuficiência cardíaca.

Ecological restoration across the Mediterranean Basin as viewed by practitioners.

Restoration efforts in the Mediterranean Basin have been changing from a silvicultural to an ecological restoration approach. Yet, to what extent the projects are guided by ecological restoration principles remains largely unknown. To analyse this issue, we built an on-line survey addressed to restoration practitioners. We analysed 36 restoration projects, mostly from drylands (86%). The projects used mainly soil from local sources. The need to comply with legislation was more important as a restoration motive for European Union (EU) than for non-EU countries, while public opinion and health had a greater importance in the latter. Non-EU countries relied more on non-native plant species than EU countries, thus deviating from ecological restoration guidelines. Nursery-grown plants used were mostly of local or regional provenance, whilst seeds were mostly of national provenance. Unexpected restoration results (e.g. inadequate biodiversity) were reported for 50% of the projects and restoration success was never evaluated in 22%. Long term evaluation (>6years) was only performed in 31% of cases, and based primarily on plant diversity and cover. The use of non-native species and species of exogenous provenances may: i) entail the loss of local genetic and functional trait diversity, critical to cope with drought, particularly under the predicted climate change scenarios, and ii) lead to unexpected competition with native species and/or negatively impact local biotic interactions. Absent or inappropriate monitoring may prevent the understanding of restoration trajectories, precluding adaptive management strategies, often crucial to create functional ecosystems able to provide ecosystem services. The overview of ecological restoration projects in the Mediterranean Basin revealed high variability among practices and highlighted the need for improved scientific assistance and information exchange, greater use of native species of local provenance, and more long-term monitoring and evaluation, including functional and ecosystem services' indicators, to improve and spread the practice of ecological restoration.

Association between Spirituality and Adherence to Management in Outpatients with Heart Failure.

BACKGROUND: Spirituality may influence how patients cope with their illness. OBJECTIVES: We assessed whether spirituality may influence adherence to management of outpatients with heart failure. METHODS: Cross sectional study enrolling consecutive ambulatory heart failure patients in whom adherence to multidisciplinary treatment was evaluated. Patients were assessed for quality of life, depression, religiosity and spirituality utilizing validated questionnaires. Correlations between adherence and psychosocial variables of interest were obtained. Logistic regression models explored independent predictors of adherence. RESULTS: One hundred and thirty patients (age 60 ± 13 years; 67% male) were interviewed. Adequate adherence score was observed in 38.5% of the patients. Neither depression nor religiosity was correlated to adherence, when assessed separately. Interestingly, spirituality, when assessed by both total score sum (r = 0.26; p = 0.003) and by all specific domains, was positively correlated to adherence. Finally, the combination of spirituality, religiosity and personal beliefs was an independent predictor of adherence when adjusted for demographics, clinical characteristics and psychosocial instruments. CONCLUSION: Spirituality, religiosity and personal beliefs were the only variables consistently associated with compliance to medication in a cohort of outpatients with heart failure. Our data suggest that adequately addressing these aspects on patient's care may lead to an improvement in adherence patterns in the complex heart failure management.

Harmine, a natural beta-carboline alkaloid, upregulates astroglial glutamate transporter expression.

Glutamate is the predominant excitatory amino acid neurotransmitter in the mammalian central nervous system (CNS). Glutamate transporter EAAT2/GLT-1 is the physiologically dominant astroglial protein that inactivates synaptic glutamate. Previous studies have shown that EAAT2 dysfunction leads to excessive extracellular glutamate and may contribute to various neurological disorders including amyotrophic lateral sclerosis (ALS). The recent discovery of the neuroprotective properties of ceftriaxone, a beta lactam antibiotic, suggested that increasing EAAT2/GLT-1 gene expression might be beneficial in ALS and other neurological/psychiatric disorders by augmenting astrocytic glutamate uptake. Here we report our efforts to develop a new screening assay for identifying compounds that activate EAAT2 gene expression. We generated fetal derived-human immortalized astroglial cells that are stably expressing a firefly luciferase reporter under the control of the human EAAT2 promoter. When screening a library of 1040 FDA approved compounds and natural products, we identified harmine, a naturally occurring beta-carboline alkaloid, as one of the top hits for activating the EAAT2 promoter. We further tested harmine in our in vitro cell culture systems and confirmed its ability to increase EAAT2/GLT1 gene expression and functional glutamate uptake activity. We next tested its efficacy in both wild type animals and in an ALS animal model of disease and demonstrated that harmine effectively increased GLT-1 protein and glutamate transporter activity in vivo. Our studies provide potential novel neurotherapeutics by modulating the activity of glutamate transporters via gene activation. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'.

Avaliação das atitudes dos estudantes de medicina frente ao abuso de drogas por colegas do meio acadêmico / Evaluation of medical students' attitudes towards drug abuse by colleagues in the academic environment

CONTEXTO: A prevalência do uso de drogas tem aumentado entre os jovens universitários, trazendo preocupação adicional aos estudantes de medicina que irão se deparar com as conseqüências desse problema durante o período de formação e na prática clínica. OBJETIVOS: Avaliar as atitudes dos estudantes de medicina diante do abuso de drogas por colegas do meio acadêmico, comparando-as quanto às diferentes drogas envolvidas (ilícitas, lícitas e exclusivamente álcool). MÉTODOS: Três versões de um questionário de auto-administração, aprovado pela Comissão de Ética para Análise de Projetos de Pesquisa, foram distribuídas em igual número para diferentes grupos de estudantes de medicina da Faculdade de Medicina da Universidade de São Paulo (FMUSP), sendo o enfoque de cada um deles as drogas lícitas, as ilícitas e o álcool. RESULTADOS: Os resultados mostraram que existe diferença na atitude intervencionista dos estudantes diante do abuso de diferentes drogas. Também houve diferença ao considerarem a participação dos colegas, familiares e profissionais na abordagem do problema e quanto ao plano de tratamento nos casos de abuso. CONCLUSÕES: Os estudantes são mais tolerantes e consideram-se menos vulneráveis ao abuso do álcool, e, portanto, os prejuízos podem não ser percebidos até que haja uma disfuncionalidade incapacitante no campo pessoal e profissional.

BACKGROUND: The prevalence of drug use among young college students is increasing. This gives cause for special concern to medical students who will later confront the consequences of the drug problems both in the classroom as well as in clinical practice. OBJECTIVES: The purpose of this paper is the evaluation of medical students ' attitudes towards drug abuse in the academic environment; comparing these with respect to different kinds of drugs - illegal, legal, and alcohol exclusively. METHODS: Three different versions of a self-completed questionnaire (approved by the Ethics Committee for Research Project Evaluation) were ministered to groups of equal numbers of medical students attending the University of Sao Paulo, School of Medicine - FMUSP (Brazil). Each questionnaire focused on illegal drugs, legal drugs, and alcohol. RESULTS: The results indicated a significant difference in the students ' attitudes regarding intervention for the different types of drug abuse. There was also indication of a difference in the students ' opinions regarding the roles that colleagues, relatives, and health professionals undertake in dealing with these issues, including the respective treatment plans for drug abuse. CONCLUSIONS: Medical students tend to be more tolerant of alcohol consumption, considering themselves to be less vulnerable to alcohol abuse. Therefore, harmful consequences may not be apparent until an incapacitating level of dysfunction affects the individual on both a personal and professional level.

Repeated sessions of noninvasive brain DC stimulation is associated with motor function improvement in stroke patients.

PURPOSE: Recent evidence has suggested that a simple technique of noninvasive brain stimulation - transcranial direct current stimulation (tDCS) - is associated with a significant motor function improvement in stroke patients. METHODS: We tested the motor performance improvement in stroke patients following 4 weekly sessions of sham, anodal- and cathodal tDCS (experiment 1) and the effects of 5 consecutive daily sessions of cathodal tDCS (experiment 2). A blinded rater evaluated motor function using the Jebsen-Taylor Hand Function Test. RESULTS: There was a significant main effect of stimulation condition (p=0.009) in experiment 1. Furthermore there was a significant motor function improvement after either cathodal tDCS of the unaffected hemisphere (p=0.016) or anodal tDCS of the affected hemisphere (p=0.046) when compared to sham tDCS. There was no cumulative effect associated with weekly sessions of tDCS, however consecutive daily sessions of tDCS (experiment 2) were associated with a significant effect on time (p< 0.0001) that lasted for 2 weeks after treatment. CONCLUSIONS: The findings of our study support previous research showing that tDCS is significantly associated with motor function improvement in stroke patients; and support that consecutive daily sessions of tDCS might increase its behavioral effects. Because the technique of tDCS is simple, safe and non-expensive; our findings support further research on the use of this technique for the rehabilitation of patients with stroke.

Hipertensão arterial sistêmica e acidente vascular encefálico: a magnitude do risco / hypertension and stroke: the extent of risk

O risco propiciado pela elevação da pressão arterial para a incidência de eventos cerebrovasculares é bem conhecido, mas não está esclarecido se a associação é linear ou se há faixas distintas de risco. A partir da análise convencional dos dados de grandes estudos de coorte, assumiu-se a primeira possibilidade. A reanálise dos dados de Framinghan, entretanto, sugere fortemente que até o percentil 70 da distribuição de pressão sistólica, para cada faixa etária e gênero, o risco para mortalidade cardiovascular e AVE permanecem estáveis. Acima desse ponto de corte, variando de 140 mmHg a 160 mmHg de acordo com o gênero e a idade, o risco sobe abruptamente com aumento de pressão. Esses resultados possuem implicações para o diagnóstico de hipertensão e para o estabelecimento de objetivos terapêuticos. Até que sejam confirmados em outras bases de dados, requer-se cautela para rotular indivíduos como hipertensos e estabelecer a intensidade d tratamento anti-hipertensivo.