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Italian clinical practice GRADE-based guidelines on the diagnosis and treatment of overweight and obesity, endorsed by the Italian National Institute of Health
No full text: Obesity is a chronic relapsing disease associated with increased morbidity and mortality and reduced quality of life. The present GRADE-based guidelines have been commissioned by the Italian Society of Obesity (SIO) by the Italian National Health Institute to provide evidence-based recommendations on obesity diagnosis and treatment. The panel identified 13 clinical questions, organised into four domains: A. diagnostic criteria (4 questions); B. medical nutrition therapy (4 questions); C. pharmacological, surgical, and endoscopic treatments (4 questions); and D. miscellaneous (1 question). The expert panel recommends adopting at least one anthropometric index of abdominal visceral fat distribution beyond body mass index (BMI) for better clinical risk stratification. A structured lifestyle intervention (i.e., medical-nutritional treatment-MNT), preferably based on cognitive-behavioural therapeutic approach and including physical activity and a balanced diet, should be offered to all subjects living with obesity. Pharmacological or surgical treatment should be offered in addition to MNT when MNT is unable to reach clinical goals. In particular, pharmacological treatment should be considered as the preferred option for subjects with BMI > 27 kg/m2 with comorbidities, and for those with BMI 30-39.9 kg/m2, based on individual therapeutic goals and needs, adopting surgical treatment in selected cases or in case of OMM failure to reach clinical goals. For subjects with a BMI > 40 kg/m2, surgical treatment may be considered conversely as a preferable option. Reduction of at least 10% of the initial body weight is associated with a better quality of life and a reduced risk of incident depression. The current guideline is endorsed by the Italian National Institute of Health, providing the new, updated clinical and legal reference for professionals involved in the management of subjects living with obesity in Italy
Development of Sustainable Polymer Materials for Packaging Applications
No full textIn recent years, global plastic production has achieved record levels, reaching over 400 million tons per year. Indeed, nowadays, one of the most significant global challenges is undoubtedly plastic pollution. Clearly, a significant proportion of these materials, often from packaging, ends up in the environment, contributing to the accumulation of urban waste and the release of microplastics, which have a negative impact on marine and land ecosystems.This thesis aims to explore strategies to make the packaging sector more sustainable, thus integrating innovative approaches that can reduce the environmental impact of current products and promote a circular economy model. The study focuses on three main pathways, such as: recycling current manufactured products, aimed at reducing dispersion in the environment and giving them a second life; the development of new biodegradable systems with the added possibility of recycling for packaging applications; and finally, the use of agricultural waste for the production of sustainable and environmentally friendly biocomposites. These combined approaches represent not only a strategy to address the problem of packaging waste dispersion in the environment, but also to reduce its impact on ecosystems.The study uses established methodologies in the packaging sector, such as single-screw and twin-screw extruders and melt compounding, in order to investigate the relationship between structure process–property relationships of the materials. Analysis of all systems obtained provides insight into how to optimize performance and develop more sustainable materials.Hence, this thesis is not limited to contributing to the transition towards reducing environmental impact, but also aims to propose concrete solutions applicable in the packaging sector. Indeed, the adoption of models for recycling complex products, such as multilayers packaging, and the use of agricultural waste for the development of sustainable biocomposites represent a step towards the creation of a circular economy model, in which waste reduction, innovation and valorization combine to generate both industrial and environmental benefits
Introduzione all'analisi di bilancio delle aziende sportive
No full textIl testo introduce l’analisi di bilancio applicata alle aziende sportive, interpretando lo sport come un vero e proprio settore economico, popolato da organizzazioni differenti e caratterizzato da modelli di business eterogenei. A partire dal bilancio d’esercizio e dalle sue funzioni informative e gestionali nei confronti degli stakeholder, vengono chiariti struttura, contenuti e principali riferimenti normativi. La parte centrale sviluppa un set di strumenti operativi: riclassificazione di Stato patrimoniale e Conto economico, analisi per indici e lettura dei flussi di cassa, con particolare attenzione alle criticità tipiche del comparto (stagionalità dei risultati, investimenti in impianti e atleti, sostenibilità del debito e tenuta finanziaria). Il testo si chiude con un focus sul sistema FIGC e sui controlli di sostenibilità economico-finanziaria, oltre a casi, esercizi ed esperienze di benchmarking utili per applicare in modo concreto i metodi proposti
SGSS05-NS3, a covalent SETD8 inhibitor that activates p53 pathway in neuroblastoma
No full textBackground
High-risk neuroblastoma (NB) is one of the most aggressive pediatric tumors accounting for 15% of all pediatric oncology deaths, and with less than 50% of patients experience long-term survival despite intense multimodal treatment. The tumor suppressor p53 is rarely (2%) mutated in NB but its functions are diminished in the majority of these tumors. Multiple mechanisms have been identified that attenuate the activity of p53 in MYCN-amplified (MYCN-amp) NB cells, but fewer mechanisms of p53 inactivation have been revealed in MYCN-WT NBs. Thus, a major challenge is to identify novel targeted therapies for high-risk NB (HR-NB) patients, specifically for the large fraction (70%) that present with MYCN-WT. Previously, we identified SETD8, the H4K20me1 methyltransferase, as a crucial epigenetic regulator of growth and differentiation in NB. In addition to targeting other non-histone proteins, SETD8 monomethylates p53 on lysine 382 (p53K382me1), attenuating its pro-apoptotic and growth arrest functions. Genetic and pharmacological (UNC0379) inhibition of SETD8 impairs NB growth in vivo.
Methods
IC50 and IVTI (in vitro therapeutic index) of SGSS05-NS3, a SETD8 inhibitor, were measured in a broad collection of MYCN-WT and MYCN-amp NB cell lines. We took advantage of RNA-seq transcriptome analysis, in vitro functional assays and in vivo preclinical NB models.
Results
To identify targeted therapies that are less toxic for HR-NB, we evaluated a more specific SETD8 inhibitor with enhanced activity and selectivity, SGSS05-NS3. Our results indicated that in NB cells in vitro treatment with SGSS05-NS3 rescues the canonical p53 functions leading to increases in p53 protein levels and of its target p21 by decreasing p53K382me1, impairing NB cell viability and inducing caspase-dependent cell death. Gene expression profile (RNA-seq analysis) confirmed that the most significantly upregulated genes upon SGSS05-NS3 treatment were among the p53 pathway targets. Pharmacological and genetic SETD8 inhibition restores p53-mediated DNA damage response. In pre-clinical xenograft NB models, pharmacological SETD8 inhibition by SGSS05-NS3 conferred a significant survival advantage in MYCN-WT NB.
Conclusions
Our study provides further evidence for targeting SETD8 as a therapeutic strategy in NB, alone or in combination with Topotecan
Spontaneous breathing trials as predictors of extubation outcomes in neurocritical care: insights from the ENIO study
No full textPurpose: In critically ill patients, extubation readiness is typically assessed using a spontaneous breathing trial (SBT). Among patients with acute brain injury (ABI), the optimal SBT method remains uncertain. Methods: We conducted a post-hoc analysis of the ENIO study (NCT03400904), including mechanically ventilated ABI patients with available SBT data, undergoing extubation attempt. SBTs were classified as T-piece, pressure support ventilation (PSV), or continuous positive airway pressure (CPAP). The primary outcome was extubation failure within 5 days. Associations between SBT modality and extubation failure were assessed using multivariable logistic regression and inverse probability of treatment weighting. Results: Of 1,512 patients enrolled in ENIO, 839 met the inclusion criteria, of whom 270 (32.2%) were female and 396 (47.2%) had traumatic brain injury as the cause of admission. SBTs were performed with PSV in 430 (51.3%), T-piece in 329 (39.2%), and CPAP in 80 (9.5%). SBT median duration was 60 min in PSV and T-piece, while 120 min in CPAP. Extubation failure occurred in 177 (21.1%) cases. In multivariable analyses, there was no significant association between SBT modality or duration and extubation outcome. Results were similar in ABI subgroup analyses. After inverse probability weighting, vigorous cough remained the only significant predictor of extubation success. Conclusions: In this large international ABI cohort, neither SBT mode nor duration was associated with extubation failure
Completing Wheeler Automata
No full textWe consider the problem of embedding a Wheeler Deterministic Finite Automaton (WDFA, in short) into an equivalent complete WDFA, preserving the order of states and the accepted language. In some cases, such a complete WDFA does not exist. We say that a WDFA is Wheeler-complete (W-complete, in short) if it cannot be properly embedded into an equivalent WDFA. We give an algorithm that, given as input a WDFA A, returns the smallest W-complete DFA containing A: it is called the minimal W-completion of A. We derive some interesting applications of this algorithm concerning the construction of a WDFA for the union and a WDFA for the complement of Wheeler languages
STARTUP TRAJECTORIES IN CORPORATE ACCELERATORS: FROM SPRINGBOARD ACCELERATION TO POTENTIAL SANDTRAPS.
No full textThe effects of rail network development on the reduction of spatial inequalities. Analyzing accessibility changes in the cities of Palermo and Naples
No full textPublic transport has been historically conceived to make cities more accessible to people, creating networks to effectively serve urban areas where the mobility demand is stronger and to reduce the distance between core and marginal neighborhoods. Lacking a proper planning strategy for these objectives can create additional dysfunctions within urban areas, with the result of increasing the use of private means of transport and additional forms of exclusion for large social strata. In the last decades, several cities in Europe and beyond have implemented huge action plans to improve their own mobility systems, looking at public transportation as a driver for a more just and sustainable urban development. However, because urban areas are very intricate intersections of social, economic, and environmental factors, wide knowledge gaps still exist in the way change in the mobility system can impact the social function of a city as a whole.
In the context of multidisciplinary research projects such as ‘Sustainable Mobility Centre (MOST)’ and ‘Mapping the new Spatial Inequalities within Southern European Cities’, this article presents an analysis that seeks to understand how the development of the rail system in the two largest cities of Southern Italy (Palermo and Naples) can positively affect accessibility and the reduction of spatial inequalities. The work is based on a methodology that takes into consideration multiple indicators of urban development and looks at the present and evolving accessibility scenario in the two cities in order to (implicitly) suggest strategies for future policies.
The preliminary results presented in this paper suggest that ongoing development plans for the rail systems are expected to have a positive impact on the overall accessibility in both cities. At the same time, if it comes to understanding the impact of infrastructure projects on the social structure of the two urban areas, evidence suggests that such increased accessibility interacts with a variety of patterns of socio-economic development