Climate change adaptation mainstreaming through strategic environmental assessments. An in-depth analysis of environmental indicators from spatial plans in Friuli Venezia Giulia Region (Italy)

Climate change adaptation, CCA henceforth, is nowadays a shared concern, deeply investigated and advocated by international research and political organisations. However, both CCA implementation and its monitoring and evaluation (M&E) are challenges yet to be properly addressed. From a spatial planning perspective, local plans are the land-use-oriented tools with the highest potential to enhance CCA operativity. Strategic Environmental Assessment (SEA) is also acknowledged to be a key instrument to integrate climate change concerns and hence, to monitor and evaluate climate change (CC) risks and CCA efforts. This study addresses two hypotheses, i.e., i) indicators included in SEAs' spatial plans may be used at the service of CCA M&E, ii) the full extent of indicators can be captured by multi-level planning analyses. To this aim, this study provides an in-depth analysis, through a multi-step systematic categorization, of the indicators used within the SEA of regional and municipal plans in the Friuli Venezia Giulia Region (Italy). This study brings novelty in the SEA research field by bridging the climate risk theoretical principles to the methodological approach for analysing SEAs' indicators, which are classified within the risk function frame. Key insights come from the metrics, the indicators' explicitness for CCA, and the indicators' extent into the climate risk function. Finally, the paper paves the way for further research of CC- and CCA-related indicators in both spatial planning and other public sectors to support CCA mainstreaming through SEAs

Reactive gamma-ketoaldehydes as novel activators of hepatic stellate cells in vitro

Aims: Products of lipid oxidation, such as 4-hydroxynonenal (4-HNE), are key activators of hepatic stellate cells (HSC) to a pro-fibrogenic phenotype. Isolevuglandins (IsoLG) are a family of acyclic γ-ketoaldehydes formed through oxidation of arachidonic acid or as by-products of the cyclooxygenase pathway. IsoLGs are highly reactive aldehydes which are efficient at forming protein adducts and cross-links at concentrations 100-fold lower than 4-hydroxynonenal. Since the contribution of IsoLGs to liver injury has not been studied, we synthesized 15-E2-IsoLG and used it to investigate whether IsoLG could induce activation of HSC. / Results: Primary human HSC were exposed to 15-E2-IsoLG for up to 48 hours. Exposure to 5 μM 15-E2-IsoLG in HSCs promoted cytotoxicity and apoptosis. At non-cytotoxic doses (50 pM-500 nM) 15-E2-IsoLG promoted HSC activation, indicated by increased expression of α-SMA, sustained activation of ERK and JNK signaling pathways, and increased mRNA and/or protein expression of cytokines and chemokines, which was blocked by inhibitors of JNK and NF-kB. In addition, IsoLG promoted formation of reactive oxygen species, and induced an early activation of ER stress, followed by autophagy. Inhibition of autophagy partially reduced the pro-inflammatory effects of IsoLG, suggesting that it might serve as a cytoprotective response. / Innovation: This study is the first to describe the biological effects of IsoLG in primary HSC, the main drivers of hepatic fibrosis. / Conclusions: IsoLGs represent a newly identified class of activators of HSC in vitro, which are biologically active at concentrations as low as 500 pM, and are particularly effective at promoting a pro-inflammatory response and autophagy

Populene D Analogues: Design, Concise Synthesis and Antiproliferative Activity

An efficient and concise synthesis of nine populene D analogues was performed using an iodine-catalyzed Prins cyclization as the key transformation. The antiproliferative activity of these new pyrans against several cancer cell lines was then investigated. Among them, an isochromene with moderate activity (mean logGI(50) = 0.91) was found. Additionally, compounds with selectivity toward the tumor cell lines NCI-ADR/RES, OVCAR-3, and HT29 were discovered.CAPESCAPESCNPqCNPqFAPESPFAPES

Association of total energy intake and macronutrient consumption with colorectal cancer risk: results from a large population-based case-control study in Newfoundland and Labrador and Ontario, Canada

<p>Abstract</p> <p>Background</p> <p>Diet is regarded as one of the most important environmental factors associated with colorectal cancer (CRC) risk. A recent report comprehensively concluded that total energy intake does not have a simple relationship with CRC risk, and that the data were inconsistent for carbohydrate, cholesterol and protein. The objective of this study was to identify the associations of CRC risk with dietary intakes of total energy, protein, fat, carbohydrate, fiber, and alcohol using data from a large case-control study conducted in Newfoundland and Labrador (NL) and Ontario (ON), Canada.</p> <p>Methods</p> <p>Incident colorectal cancer cases (n = 1760) were identified from population-based cancer registries in the provinces of ON (1997-2000) and NL (1999-2003). Controls (n = 2481) were a random sample of residents in each province, aged 20-74 years. Family history questionnaire (FHQ), personal history questionnaire (PHQ), and food frequency questionnaire (FFQ) were used to collect study data. Logistic regression was used to evaluate the association of intakes of total energy, macronutrients and alcohol with CRC risk.</p> <p>Results</p> <p>Total energy intake was associated with higher risk of CRC (OR: 1.56; 95% CI: 1.21-2.01, <it>p</it>-trend = 0.02, 5^thversus 1^stquintile), whereas inverse associations emerged for intakes of protein (OR: 0.85, 95%CI: 0.69-1.00, <it>p</it>-trend = 0.06, 5^thversus 1^stquintile), carbohydrate (OR: 0.81, 95%CI: 0.63-1.00, <it>p</it>-trend = 0.05, 5^thversus 1^stquintile) and total dietary fiber (OR: 0.84, 95% CI:0.67-0.99, <it>p</it>-trend = 0.04, 5^thversus 1^stquintile). Total fat, alcohol, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, and cholesterol were not associated with CRC risk.</p> <p>Conclusion</p> <p>This study provides further evidence that high energy intake may increase risk of incident CRC, whereas diets high in protein, fiber, and carbohydrate may reduce the risk of the disease.</p

Development and First Validation of a Disease Activity Score for Gout

Objective: To develop a new composite disease activity score for gout and provide its first validation. Methods: Disease activity has been defined as the ongoing presence of urate deposits that lead to acute arthritis and joint damage. Every measure for each Outcome Measures in Rheumatology core domain was considered. A 3-step approach (factor analysis, linear discriminant analysis, and linear regression) was applied to derive the Gout Activity Score (GAS). Decision to change treatment or 6-month flare count were used as the surrogate criteria of high disease activity. Baseline and 12-month followup data of 446 patients included in the Kick-Off of the Italian Network for Gout cohort were used. Construct- and criterion-related validity were tested. External validation on an independent sample is reported. Results: Factor analysis identified 5 factors: patient-reported outcomes, joint examination, flares, tophi, and serum uric acid (sUA). Discriminant function analysis resulted in a correct classification of 79%. Linear regression analysis identified a first candidate GAS including 12-month flare count, sUA, visual analog scale (VAS) of pain, VAS global activity assessment, swollen and tender joint counts, and a cumulative measure of tophi. Alternative scores were also developed. The developed GAS demonstrated a good correlation with functional disability (criterion validity) and discrimination between patient- and physician-reported measures of active disease (construct validity). The results were reproduced in the external sample. Conclusion: This study developed and validated a composite measure of disease activity in gout. Further testing is required to confirm its generalizability, responsiveness, and usefulness in assisting with clinical decisions

The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients

The cause of Huntington disease (HD) is a polyglutamine repeat expansion of more than 36 units in the huntingtin protein, which is inversely correlated with the age at onset of the disease. However, additional genetic factors are believed to modify the course and the age at onset of HD. Recently, we identified the V471A polymorphism in the autophagy-related gene ATG7, a key component of the autophagy pathway that plays an important role in HD pathogenesis, to be associated with the age at onset in a large group of European Huntington disease patients. To confirm this association in a second independent patient cohort, we analysed the ATG7 V471A polymorphism in additional 1,464 European HD patients of the “REGISTRY” cohort from the European Huntington Disease Network (EHDN). In the entire REGISTRY cohort we could not confirm a modifying effect of the ATG7 V471A polymorphism. However, analysing a modifying effect of ATG7 in these REGISTRY patients and in patients of our previous HD cohort according to their ethnic origin, we identified a significant effect of the ATG7 V471A polymorphism on the HD age at onset only in the Italian population (327 patients). In these Italian patients, the polymorphism is associated with a 6-years earlier disease onset and thus seems to have an aggravating effect. We could specify the role of ATG7 as a genetic modifier for HD particularly in the Italian population. This result affirms the modifying influence of the autophagic pathway on the course of HD, but also suggests population-specific modifying mechanisms in HD pathogenesis