Photoactive nanodevices for potential biological applications

Biological systems are complex and highly organized architectures governed by noncovalent interactions, which are responsible for molecular recognition, self-assembly, self-organization, adaptation and evolution processes. These systems provided the inspiration for the development of supramolecular chemistry, that aimed at the design of artificial multicomponent molecular assemblies, namely supramolecular systems, properly designed to perform different operations: each constituting unit performs a single act, whereas the entire supramolecular system is able to execute a more complex function, resulting from the cooperation of the constituting components. Supramolecular chemistry deals with the development of molecular systems able to mimic naturally occurring events, for example complexation and self-assembly through the establishment of noncovalent interactions. Moreover, the application of external stimuli, such as light, allows to perform these operations in a time- and space-controlled manner. These systems can interact with biological systems and, thus, can be applied for bioimaging, therapeutic and drug delivery purposes. In this work the study of biocompatible supramolecular species able to interact with light is presented. The first part deals with the photophysical, photochemical and electrochemical characterization of water-soluble blue emitting triazoloquinolinium and triazolopyridinium salts. Moreover, their interaction with DNA has been explored, in the perspective of developing water-soluble systems for bioimaging applications. In the second part, the effect exerted by the presence of azobenzene-bearing supramolecular species in liposomes, inserted both in the phospholipid bilayer and in the in the aqueous core of vesicles has been studied, in order to develop systems able to deliver small molecules and ions in a photocontrolled manner. Moreover, the versatility of azobenzene and its broad range of applications have been highlighted, since conjugated oligoazobenzene derivatives proved not to be adequate to be inserted in the phospholipid bilayer of liposomes, but their electrochemical properties made them interesting candidates as electron acceptor materials for photovoltaic applications

Modeling high-resolution climate change impacts on wheat and maize in Italy

Abstract The Mediterranean basin has been identified as a prominent hotspot of climate change, with expected negative impacts on crop productivity, among others. Given the primary role that agriculture has to sustain cultural values, economic opportunities, and food security, it is crucial to identify specific risks in agriculture due to climate change, which can address more effective adaptation strategies and policies to cope with climate change. This study aims to evaluate the high-resolution impacts of climate change on the length of the growing cycle and yield of durum wheat, common wheat, and maize in Italy by using the CERES-Wheat and CERES-Maize crop models implemented in the Decision Support System for Agrotechnology Transfer (DSSAT) software. A digital platform (GIS-DSSAT) was developed to couple crop simulation models with dynamically downscaled climate projections at high resolution for Italy, which can better represent the Italian landscape complexity and the spatial distribution of different pedological and crop management features, providing more detailed information on the expected impacts on crops respect to previous studies at a coarser resolution. The projections have been extended for two climate change scenarios and accounting for uncertainty, either considering or not the potential direct effects of increasing atmospheric CO2 concentrations ([CO2]). Results show that climate change may affect Italian cereal production in the medium to long term periods. Maize is the main affected crop, with yield reductions homogeneously distributed from North to South Italy. Wheat yield is expected to decrease mainly in southern Italy, while northern Italy may benefit from higher precipitation regimes. Higher levels of atmospheric CO2 concentrations may partially offset the negative impact posed by climate change and increase the benefits in the northern regions, especially for common and durum wheat

Lymphatic Mapping for Endometrial Cancer

The staging for endometrial cancer is surgical and it should include both pelvic and para-aortic lymphadenectomy. The majority of endometrial cancers are diagnosed at early stage and lymphadenectomy gives no benefit for staging while adding surgical risks. Performing a systematic lymphadenectomy in very obese women is almost impossible. Preoperative lymphatic mapping (via planar lymphoscintigraphy, single photon emission computed tomography, or positron emission tomography) has poor correlation with surgical mapping of sentinel lymph nodes (SLNs), that has been proposed to avoid systematic lymphadenectomy in early stages. However, surgical SLN mapping is a very challenging procedure in endometrial cancer because the uterus has a complex lymphatic drainage. In the last 20 years, different authors used different tracers (vital stains, radioactive isotopes, or fluorescent dye), different sites of tracer injection (cervix, endometrium, or myometrium), and different surgical approaches (laparotomic, laparoscopic, or robotic) to find out the best procedure for SLNs identification. A well-designed, prospective, randomized, international multicenter tri¬al aimed at validating the accuracy of a uniform procedure is still lacking. In the meantime, to reduce the false-negative rate of intra-operative SLN mapping a surgical algorithm limits systematic pelvic lymphadenectomy to the hemi-pelvis without SLNs mapping and includes removal of any suspicious, although not mapped, node together with mapped SLNs

Valproic acid triggers erythro/megakaryocyte lineage decision through induction of GFI1B and MLLT3 expression

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Intercultural Mentoring tools to support migrant integration at school (INTO)

[ES] Within the scope of European policies and to combat educational disadvantages for migrant children, numerous actions have been taken to improve the position of migrant children in education. In secondary education the emphasis lies on diversification of the offered teaching methods and extra guidance of the pupils. Some schools in Europe have set up measures to increase the continuity of the educational support in terms of migrant pupil inclusion and orientation. Despite these measures, dropout rates are still high among migrant youth and compared to their native peers a disproportionately large number attend the lowest levels of secondary school after completing primary school. The disappointing results of regular guidance are partly the reason for the development of more innovative forms of guidance. The project aims to promote strategies and methods that help students with a migrant background at risk of ESL to maintain their motivation through the development, testing and validation of an Intercultural Mentoring Programme based on the empowered peer education methodology.The Intercultural mentor profile will be adapted to different European contexts, developed in collaboration with at least 100 school staff members (headmaster and secondary school teachers from 5 different European countries) and tested with at least 50 students with a migrant background trained as Intercultural Mentors. The impact of the project will be sustained thanks to its outcomes: (i) Didactic Kit: conceived as self-teaching materials will contain the training framework to directly implement the model of intervention in secondary schools system; (ii) Guideline Handbook: support the future implementation of training courses – by other education organizations and secondary school, (iii) Project website: it will include not only the results and materials of the project (handbooks, e-learning platform, reports, etc.) but will also include updated information on young migrants

Intercultural Education through Religious Studies (IERS): COMENIUS Multilateral project

[EN] Religious and cultural diversity are today more than ever a critical and political challenge as the recent emergencies related to geo-political and economical global transformations clearly show. European countries are concerned by a big immigration flow that demands an educational effort in order to foster the mutual understanding and integration. According to Toledo guiding principles, IERS project meets the needs of an innovative approach in teaching about religions and beliefs at school by providing teachers of humanistic disciplines with new tools that help teachers and pupils to plunge deeper into religions and cultures of non-european countries, as well as raising the knowledge of the religious traditions that contributed to the common European cultural Identity, promoting it in the best way suited for encourage intra -and extra- European cultural dialogue attitudes. The Project aims to support the development of social, civic and intercultural transversal key competences by educating towards a positive understanding of cultural and religious differences, a readiness to engage in dialogue and to avoid or manage conflicts. By encouraging teachers and pupils to expose themselves to the differences and commonalities of religious topics, it promotes also the values of democracy, equality and human rights as it deals with social and civic dimensions of both intercultural and interreligious dialogue. The project will involve high school in-service teachers by developing a complete set of didactical tools and training experiences. The results will be: 1. A baseline study which analyzes the actual situation of teaching about religions throughout Europe; 2. New innovative didactic tools such as Multimedia Digital Modules to be used in classroom activities, accompanied by a Handbook with didactical guidelines for teachers. 3. Teacher support activities (virtual community, training activities, developing of didactical projects to apply in classroom)

Modeling Parkinson's Disease Neuropathology and Symptoms by Intranigral Inoculation of Preformed Human α-Synuclein Oligomers.

The accumulation of aggregated α-synuclein (αSyn) is a hallmark of Parkinson's disease (PD). Current evidence indicates that small soluble αSyn oligomers (αSynOs) are the most toxic species among the forms of αSyn aggregates, and that size and topological structural properties are crucial factors for αSynOs-mediated toxicity, involving the interaction with either neurons or glial cells. We previously characterized a human αSynO (H-αSynO) with specific structural properties promoting toxicity against neuronal membranes. Here, we tested the neurotoxic potential of these H-αSynOs in vivo, in relation to the neuropathological and symptomatic features of PD. The H-αSynOs were unilaterally infused into the rat substantia nigra pars compacta (SNpc). Phosphorylated αSyn (p129-αSyn), reactive microglia, and cytokine levels were measured at progressive time points. Additionally, a phagocytosis assay in vitro was performed after microglia pre-exposure to αsynOs. Dopaminergic loss, motor, and cognitive performances were assessed. H-αSynOs triggered p129-αSyn deposition in SNpc neurons and microglia and spread to the striatum. Early and persistent neuroinflammatory responses were induced in the SNpc. In vitro, H-αSynOs inhibited the phagocytic function of microglia. H-αsynOs-infused rats displayed early mitochondrial loss and abnormalities in SNpc neurons, followed by a gradual nigrostriatal dopaminergic loss, associated with motor and cognitive impairment. The intracerebral inoculation of structurally characterized H-αSynOs provides a model of progressive PD neuropathology in rats, which will be helpful for testing neuroprotective therapies

‘Capturing Anarchists Across Borders’: the transnational dimensions of Italian antimilitarist campaigns, 1911-1914

This article stems from the vibrant debate on methodological developments and new perspectives that has been inspired by a recent upsurge of interest in the transnational history of labour and radical movements. It engages with the problematic question of the integration between different scales of analysis in the study of radicalism: the ‘transnational’, ‘national’ and ‘local’ or ‘trans-local’. The article reverts the study of transnational anarchism back to a ‘national’ and ‘trans-local’ perspective: the analysis of the intersection between the networks of those who migrated from Italy and those who stayed there provides a fruitful way to uncover the dynamics within the transnational anarchist movement and the inter-playing, in both directions, between: home country - exiles’ communities - host countries. The article focuses on the crucial - but still unexplored - contributions in terms of propaganda, theoretical debate, financing, and counterculture production that the communities of Italian anarchists abroad (among them London, Paris, Berne, Marseille, Barre, and Buenos Aires) gave to the antimilitarist campaigns against the Italian colonial enterprise in Libya and for the release of Augusto Masetti - the soldier who shot at his colonel whilst addressing troops leaving for the frontline - from 1911 to 1914. The investigation of the initiatives that the anarchist exiles established and coordinated with their comrades in Italy provides a significant case study not only for the understanding of network-based transnational anarchism but also to reflect on the mechanisms of political migration and its influence in the development of social conflicts

Effect of RNS60 in amyotrophic lateral sclerosis: a phase II multicentre, randomized, double-blind, placebo-controlled trial

Background and purpose Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with limited treatment options. RNS60 is an immunomodulatory and neuroprotective investigational product that has shown efficacy in animal models of ALS and other neurodegenerative diseases. Its administration has been safe and well tolerated in ALS subjects in previous early phase trials. Methods This was a phase II, multicentre, randomized, double-blind, placebo-controlled, parallel-group trial. Participants diagnosed with definite, probable or probable laboratory-supported ALS were assigned to receive RNS60 or placebo administered for 24 weeks intravenously (375 ml) once a week and via nebulization (4 ml/day) on non-infusion days, followed by an additional 24 weeks off-treatment. The primary objective was to measure the effects of RNS60 treatment on selected biomarkers of inflammation and neurodegeneration in peripheral blood. Secondary objectives were to measure the effect of RNS60 on functional impairment (ALS Functional Rating Scale-Revised), a measure of self-sufficiency, respiratory function (forced vital capacity, FVC), quality of life (ALS Assessment Questionnaire-40, ALSAQ-40) and survival. Tolerability and safety were assessed. Results Seventy-four participants were assigned to RNS60 and 73 to placebo. Assessed biomarkers did not differ between arms. The mean rate of decline in FVC and the eating and drinking domain of ALSAQ-40 was slower in the RNS60 arm (FVC, difference 0.41 per week, standard error 0.16, p = 0.0101; ALSAQ-40, difference -0.19 per week, standard error 0.10, p = 0.0319). Adverse events were similar in the two arms. In a post hoc analysis, neurofilament light chain increased over time in bulbar onset placebo participants whilst remaining stable in those treated with RNS60. Conclusions The positive effects of RNS60 on selected measures of respiratory and bulbar function warrant further investigation

COVID-19 in rheumatic diseases in Italy: first results from the Italian registry of the Italian Society for Rheumatology (CONTROL-19)

OBJECTIVES: Italy was one of the first countries significantly affected by the coronavirus disease 2019 (COVID-19) epidemic. The Italian Society for Rheumatology promptly launched a retrospective and anonymised data collection to monitor COVID-19 in patients with rheumatic and musculoskeletal diseases (RMDs), the CONTROL-19 surveillance database, which is part of the COVID-19 Global Rheumatology Alliance. METHODS: CONTROL-19 includes patients with RMDs and proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) updated until May 3rd 2020. In this analysis, only molecular diagnoses were included. The data collection covered demographic data, medical history (general and RMD-related), treatments and COVID-19 related features, treatments, and outcome. In this paper, we report the first descriptive data from the CONTROL-19 registry. RESULTS: The population of the first 232 patients (36% males) consisted mainly of elderly patients (mean age 62.2 years), who used corticosteroids (51.7%), and suffered from multi-morbidity (median comorbidities 2). Rheumatoid arthritis was the most frequent disease (34.1%), followed by spondyloarthritis (26.3%), connective tissue disease (21.1%) and vasculitis (11.2%). Most cases had an active disease (69.4%). Clinical presentation of COVID-19 was typical, with systemic symptoms (fever and asthenia) and respiratory symptoms. The overall outcome was severe, with high frequencies of hospitalisation (69.8%), respiratory support oxygen (55.7%), non-invasive ventilation (20.9%) or mechanical ventilation (7.5%), and 19% of deaths. Male patients typically manifested a worse prognosis. Immunomodulatory treatments were not significantly associated with an increased risk of intensive care unit admission/mechanical ventilation/death. CONCLUSIONS: Although the report mainly includes the most severe cases, its temporal and spatial trend supports the validity of the national surveillance system. More complete data are being acquired in order to both test the hypothesis that RMD patients may have a different outcome from that of the general population and determine the safety of immunomodulatory treatments