107 research outputs found

    Combating early school leaving: A qualitative study of compulsory training in Italy

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    The rate of early school leavers became a benchmark for the European Union in 2008, as part of the strategy to make the EU the world’s most competitive and dynamic knowledge-based economy by 2010 (Lisbon Agenda). The objective to decrease the average share of early school leavers by at least 10%, and to guarantee a high number of 22 year-olds who have completed their secondary education, stated in 2008 during the Lisbon Council was re-confirmed in the Europe 2020 Strategy, when it was used as a proxy for social inclusion. The scientific literature on the subject shows how the phenomenon of early school leaving is influenced by education-related factors, individual circumstances and socio-economic conditions. To date, research studies have focused on the characteristics of dropouts or the characteristics of their schools. However, relatively few qualitative studies on the phenomenon in a specific setting have been carried out. The paper presents a small-scale qualitative study based on the concept of “Dropout Factories” (Balfanz, Letgers 2004). Our study founds as the Local Community Dropout Factories influences the translation process (Czarniawska, Joerges 1996) of the regulations dedicated to combating early school leaving, without hindering their positive effect, and increases the risk of becoming dropouts: this seems to have been confirmed by the presence of not-at-risk young people within the group of dropouts

    La Partecipazione in SanitĂ . I modelli europei e le SocietĂ  della Salute toscane

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    Il concetto di partecipazione, entrato prepotentemente nell’immaginario collettivo occidentale alla fine degli anni Sessanta del secolo scorso, è stato protagonista nel corso degli ultimi quarant’anni di mutevoli vicende e alterne fortune. Negli anni più recenti abbiamo assistito al diffondersi di processi di partecipazione e al proliferare di sempre nuovi meccanismi di coinvolgimento della popolazione. La letteratura in materia ha, però, sottolineato da tempo come questo successo e la crescente diffusione dell’approccio partecipativo sia stato e continui ad essere del tutto indipendente dalla presenza di adeguate informazioni relative all’efficacia delle strategie e degli strumenti attivati (Rosener 1978; Mitton et al. 2009). Nel nostro percorso di ricerca abbiamo tentato di affrontare la questione e di offrire un primo, per quanto interlocutorio, strumento di analisi. A partire da un'analisi teorica della polisemia intrinseca ai concetti di riferimento (governance e partecipazione) che ha supportato il processo di definizione dell'orizzonte teorico di riferimento, abbiamo costruito un modello analitico-valutativo orientato a verificare la capacità dei processi partecipativi adottati in ambito sanitario, di operare una re-distribuzione del potere decisionale coerente con l'approccio collaborativo (Community Health Governance). Il modello elaborato è stato utilizzato per verificare le strategie di partecipazione adottate dai paesi europei - che sono state così tipizzate - e per studiare in profondità i funzionamenti degli organismi di partecipazione previsti dalla Regione Toscana all'interno delle Società della Salute (l.r.40/2005, come modif. l.r.60/2008)

    Nuove povertĂ . VulnerabilitĂ  sociale e disuguaglianze di genere e generazioni

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    L’attuale crisi economica ha innescato traiettorie inedite di vulnerabilità, tanto più gravi quanto più associate a sistemi di welfare poco generosi e residuali. Si parla, infatti, di “nuove povertà” per indicare come la crescente disoccupazione, la contrazione dei consumi e della produzione, la precarizzazione delle condizioni di vita e di lavoro espongano strati crescenti di popolazione al rischio di impoverimento. Il volume intende evidenziare, attraverso un’indagine ecologica e una lettura critica, come l’appartenenza di genere e generazione contribuisca ad acuire i vincoli di contesto, soprattutto in riferimento al mercato del lavoro e ai ruoli famigliari. I dati raccolti rilevano, infatti, la presenza di dinamiche perverse che innescano processi cumulativi di esclusione da cui, soprattutto per le donne e i giovani, risulta difficile uscire anche a causa di un sistema di protezione sociale sempre più inadeguato

    Looking at Covid-19 vaccine hesitancy through a macro perspective. A comparative study of Italy, Poland and Portugal

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    This article aims to overcome the most common interpretive paradigms on vaccine hesitancy and refusal when are limited to consider the individual or group level and provide a contextual reading. For the purpose of this study, cultural, economic and political conditions are considered constituent materials of "thinking" and "doing" in everyday life and of "problematizing" the issue of vaccines in the Covid-19 era. By adopting an analytical model derived from Sewell's pattern of contextualized structures (as a result of schemas and resources), the article compares three exemplary cases: Portugal, the country with the highest rate of Covid-19 vaccination; Italy, one of the most vaccine-hesitant western countries in Europe; and Poland, which with its vaccination rate well exemplifies vaccine-hesitant post-socialist CEE countries. By combining the schemas and resources, this study gives a social map with types of context-driven structures and offers an initial interpretative key useful to understanding the complexity of problem framing and structuring in the Covid-19 pandemic era in different sociocultural and political contexts

    Interleukin 18 in the CNS

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    Interleukin (IL)-18 is a cytokine isolated as an important modulator of immune responses and subsequently shown to be pleiotropic. IL-18 and its receptors are expressed in the central nervous system (CNS) where they participate in neuroinflammatory/neurodegenerative processes but also influence homeostasis and behavior. Work on IL-18 null mice, the localization of the IL-18 receptor complex in neurons and the neuronal expression of decoy isoforms of the receptor subunits are beginning to reveal the complexity and the significance of the IL-18 system in the CNS. This review summarizes current knowledge on the central role of IL-18 in health and disease

    Looking at Covid-19 vaccine hesitancy through a macro perspective. A comparative study of Italy, Poland and Portugal

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    This article aims to overcome the most common interpretive paradigms on vaccine hesitancy and refusal when are limited to consider the individual or group level and provide a contextual reading. For the purpose of this study, cultural, economic and political conditions are considered constituent materials of "thinking" and "doing" in everyday life and of "problematizing" the issue of vaccines in the Covid-19 era. By adopting an analytical model derived from Sewell's pattern of contextualized structures (as a result of schemas and resources), the article compares three exemplary cases: Portugal, the country with the highest rate of Covid-19 vaccination; Italy, one of the most vaccine-hesitant western countries in Europe; and Poland, which with its vaccination rate well exemplifies vaccine-hesitant post-socialist CEE countries. By combining the schemas and resources, this study gives a social map with types of context-driven structures and offers an initial interpretative key useful to understanding the complexity of problem framing and structuring in the Covid-19 pandemic era in different sociocultural and political contexts

    The Natural Compound Climacostol as a Prodrug Strategy Based on pH Activation for Efficient Delivery of Cytotoxic Small Agents

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    We synthesized and characterized MOMO as a new small molecule analog of the cytotoxic natural product climacostol efficiently activated in mild extracellular acidosis. The synthesis of MOMO had a key step in the Wittig olefination for the construction of the carbon-carbon double bond in the alkenyl moiety of climacostol. The possibility of obtaining the target (Z)-alkenyl MOMO derivative in very good yield and without presence of the less active (E)-diastereomer was favored from the methoxymethyl ether (MOM)-protecting group of hydroxyl functions in aromatic ring of climacostol aldehyde intermediate. Of interest, the easy removal of MOM-protecting group in a weakly acidic environment allowed us to obtain a great quantity of climacostol in biologically active (Z)-configuration. Results obtained in free-living ciliates that share the same micro-environment of the climacostol natural producer Climacostomum virens demonstrated that MOMO is well-tolerated in a physiological environment, while its cytotoxicity is rapidly and efficiently triggered at pH 6.3. In addition, the cytostatic vs. cytotoxic effects of acidified-MOMO can be modulated in a dose-dependent manner. In mouse melanoma cells, MOMO displayed a marked pH-sensitivity since its cytotoxic and apoptotic effects become evident only in mild extracellular acidosis. Data also suggested MOMO being preferentially activated in the unique extra-acidic microenvironment that characterizes tumoural cells. Finally, the use of the model organism Drosophila melanogaster fed with an acidic diet supported the efficient activity and oral delivery of MOMOmolecule in vivo.MOMO affected oviposition ofmating adults and larvae eclosion. Reduced survival of flies was due to lethality during the larval stages while emerging larvae retained their ability to develop into adults. Interestingly, the gut of eclosed larvae exhibited an extended damage (cell death by apoptosis) and the brain tissue was also affected (reduced mitosis), demonstrating that orally activated MOMO efficiently targets different tissues of the developing fly. These results provided a proof-of-concept study on the pHdependence of MOMO effects. In this respect, MOM-protection emerges as a potential prodrug strategy which deserves to be further investigated for the generation of efficient pH-sensitive small organic molecules as pharmacologically active cytotoxic compounds

    Reversal of Defective Mitochondrial Biogenesis in Limb-Girdle Muscular Dystrophy 2D by Independent Modulation of Histone and PGC-1α Acetylation

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    Mitochondrial dysfunction occurs in many muscle degenerative disorders. Here, we demonstrate that mitochondrial biogenesis was impaired in limb-girdle muscular dystrophy (LGMD) 2D patients and mice and was associated with impaired OxPhos capacity. Two distinct approaches that modulated histones or peroxisome proliferator-activated receptor-gamma coactivator 1 \u3b1 (PGC-1\u3b1) acetylation exerted equivalent functional effects by targeting different mitochondrial pathways (mitochondrial biogenesis or fatty acid oxidation[FAO]). The histone deacetylase inhibitor Trichostatin A (TSA) changed chromatin assembly at the PGC-1\u3b1 promoter, restored mitochondrial biogenesis, and enhanced muscle oxidative capacity. Conversely, nitric oxide (NO) triggered post translation modifications of PGC-1\u3b1 and induced FAO, recovering the bioenergetics impairment of muscles but shunting the defective mitochondrial biogenesis. In conclusion, a transcriptional blockade of mitochondrial biogenesis occurred in LGMD-2D and could be recovered by TSA changing chromatin conformation, or it could be overcome by NO activating a mitochondrial salvage pathway

    Nitric Oxide Generated by Tumor-Associated Macrophages Is Responsible for Cancer Resistance to Cisplatin and Correlated With Syntaxin 4 and Acid Sphingomyelinase Inhibition

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    Tumor microenvironment is fundamental for cancer progression and chemoresistance. Among stromal cells tumor-associated macrophages (TAMs) represent the largest population of infiltrating inflammatory cells in malignant tumors, promoting their growth, invasion, and immune evasion. M2-polarized TAMs are endowed with the nitric oxide (NO)-generating enzyme inducible nitric oxide synthase (iNOS). NO has divergent effects on tumors, since it can either stimulate tumor cells growth or promote their death depending on the source of it; likewise the role of iNOS in cancer differs depending on the cell type. The role of NO generated by TAMs has not been investigated. Using different tumor models in vitro and in vivo we found that NO generated by iNOS of M2-polarized TAMs is able to protect tumor cells from apoptosis induced by the chemotherapeutic agent cisplatin (CDDP). Here, we demonstrate that the protective effect of NO depends on the inhibition of acid sphingomyelinase (A-SMase), which is activated by CDDP in a pathway involving the death receptor CD95. Mechanistic insights indicate that NO actions occur via generation of cyclic GMP and activation of protein kinase G (PKG), inducing phosphorylation of syntaxin 4 (synt4), a SNARE protein responsible for A-SMase trafficking and activation. Noteworthy, phosphorylation of synt4 at serine 78 by PKG is responsible for the proteasome-dependent degradation of synt4, which limits the CDDP-induced exposure of A-SMase to the plasma membrane of tumor cells. This inhibits the cytotoxic mechanism of CDDP reducing A-SMase-triggered apoptosis. This is the first demonstration that endogenous NO system is a key mechanism through which TAMs protect tumor cells from chemotherapeutic drug-induced apoptosis. The identification of the pathway responsible for A-SMase activity downregulation in tumors leading to chemoresistance warrants further investigations as a means to identify new anti-cancer molecules capable of specifically inhibiting synt4 degradation
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