Le misure alternative prima del carcere (ovvero il prevalere dell'istanza deflattiva)

Questo lavoro cercherà di affrontare quello che è stato l’iter di nascita e sviluppo dell’applicazione anticipata delle misure alternative alla detenzione, e di come tale istituto sia finito col rappresentare un vero e proprio ‘’ rimedio ‘’ atto ad ovviare al grave problema del sovraffollamento carcerario. L’alternatività della misura nacque, in origine, per rispondere ad una grave situazione che, nel corso degli anni Ottanta, parallelamente ad un graduale accrescimento del consumo di droga tra la popolazione, fece assistere ad un notevole aumento dei soggetti tossicodipendenti che affollavano gli istituti penitenziari del nostro Paese. Tutto questo diede l’input che portò a domandarsi se fosse opportuno intraprendere una via differente ed alternativa al carcere, cercando di andare in aiuto ai soggetti tossicodipendenti, abbracciando un regime volto a favorire anche la cura della dipendenza dalla droga. Negli anni che seguirono, l’istituto in oggetto ha subito incisive modifiche, spinte, purtroppo, dall'esigenza di rimediare alla grave situazione venutasi a creare per via del sovraffollamento carcerario. Tutto ciò ha praticamente snaturato quello che era il significato alla base dell’istituto in questione, giunto adesso a rappresentare un ‘’rimedio ‘’ diretto ad alleggerire il grande carico di soggetti detenuti presenti all'interno delle carceri del nostro paese

Sustainability in urban logistics : a literature review

Purpose: The importance of urban logistics is on the rise. On the one hand, the population in cities is growing due to urbanization processes. On the other hand, there is a significant increase in the flow of goods (e.g., a boost in online purchases). Such changes are leading cities to face social, economic, and environmental issues, which urge to be addressed. Based on these premises, this study aims to identify, classify and provide an overview of the environmentally sustainable logistics solutions for urban contexts. Methodology: This study performs a systematic literature review. First, it provides a quantitative description of the results, highlighting eventual trends; second, it displays a narrative description of the papers considered to map the current solution and of the related methodology. Findings: The study highlights the maturity and interest in adopting more sustainable delivery options in urban logistics. The selection of suitable transport means, the engagement of stakeholders, as well as the definition of norms and regulations, emerge as the most discussed and promising solutions. Originality: This study is a first attempt to classify the existing body of knowledge related to urban logistics, analysing contributions based on different axes of classification and highlighting cutting-edge solutions to propose possible research directions

Differente impatto sul rimodellamento cellulare e strutturale del ventricolo sinistro dell'ipertrofia geneticamente determinata e da sovraccarico pressorio.

La cardiomiopatia ipertrofica è una patologia ereditaria caratterizzata da una massiva ipertrofia del setto interventricolare, associata a mutazioni nei geni che codificano prevalentemente per proteine sarcomeriche. Al giorno d’oggi sono conosciute più di 100 mutazioni in oltre 36 geni che sono causativi della patologia, con una trasmissione autosomica dominante; le mutazioni più frequenti sono quella a carico della myosin binding protein C (MYBPC3) e myosin heavy chain  (MYH7). L’ipertrofia viene definita dalla presenza di un ventricolo sinistro ipertrofico non dilatato in assenza di altre cause cardiache o sistemiche che potrebbero portare ad un fenotipo similare. L’ipertrofia è spesso presente in forma asimmetrica, con inspessimento maggiore a carico della regione del setto adiacente alla valvola aortica. Questa alterata geometria ventricolare fa si che durante la sistole il lembo anteriore della valvola mitrale sia spinto verso la regione inspessita del setto provocando l’ostruzione del tratto di efflusso configurando una condizione definita come cardiomiopatia ipertrofica ostruttiva (HOCM). Nonostante la continua scoperta di geni associati allo sviluppo della patologia, la fisiopatologia di HOCM rimane ancora oscura. Molti geni infatti, trasmessi in maniera ereditabile, responsabili di mutazioni a carico di proteine sarcomeriche, possono causare in soggetti della stessa famiglia da una parte fenotipo ipertrofico e dall’altra una totale assenza di sintomatologia. Abbiamo ipotizzato che alla base della massiva e focale ipertrofia della HOCM sia presente una alterazione del turnover cellulare con marcata proliferazione cardiomiocitaria consentita da una adeguata risposta vasculogenica. Inoltre, per comprendere se questi eventi cellulari fossero specifici della HOCM, abbiamo analizzato campioni di cuori ipertrofici da sovraccarico pressorio ottenuti da miectomie del setto di pazienti con stenosi aortica (AoS) grave. La HOCM è la maggior causa di morte cardiaca improvvisa nei giovani adulti mentre la stenosi aortica è la maggiore causa di morte tra le cardiopatie da difetti valvolari, Le analisi morfometriche effettuate su sezioni colorate con tricromica di Masson hanno evidenziato un deposito di collagene a livello interstiziale e perivascolare in entrambe le patologie con un aumento più marcato nella stenosi aortica. Inoltre, studi effettuati sul compartimento vascolare, hanno rivelato una diminuzione della densità dei capillari del 38% nei soggetti affetti da HOCM e del 46% in pazienti con AoS. E’ stato interessante notare che a livello tessutale i precursori vascolari PDGFR positivi risultavano significativamente aumentati (+27%) nel miocardio di soggetti affetti da HOCM rispetto ai valori riscontrati nelle miectomie da AoS e nei controlli. Infine, abbiamo analizzato la proliferazione cellulare mediante marcatura con Ki67,e l’incidenza di apoptosi con TUNEL assay. Rispetto al miocardio di controllo, abbiamo riscontrato valori di proliferazione dei cardiomiociti 10 volte superiori nei soggetti con HOCM e 3.9 volte superiori in pazienti con AoS. Per contro, l’apoptosi risultava significativamente maggiore nelle due patologie ma era più elevata nella AoS. I nostri dati confermano l’ipotesi iniziale secondo la quale una localizzata massiva ipertrofia cardiaca possa essere originata da un alterato turnover cellulare. Paragonata ad una ipertrofia da sovraccarico pressorio, HOCM mostra una riduzione di deposito di collagene e di morte cellulare programmata, associate ad un notevole incremento della proliferazione cardiomiocitaria. Una eccessiva crescita non accompagnata da una consensuale morte cellulare potrebbe anche implicare un sovraffollamento e disarray dei cardiomiociti a livello tissutale

Corticostriate Projections from Areas of the "Lateral Grasping Network": Evidence for Multiple Hand-Related Input Channels

Corticostriatal projections from the primate cortical motor areas partially overlap in different zones of a large postcommissural putaminal sector designated as "motor" putamen. These zones are at the origin of parallel basal ganglia-thalamocortical subloops involved in modulating the cortical motor output. However, it is still largely unknown how parietal and prefrontal areas, connected to premotor areas, and involved in controlling higher order aspects of motor control, project to the basal ganglia. Based on tracer injections at the cortical level, we analyzed the corticostriatal projections of the macaque hand-related ventrolateral prefrontal, ventral premotor, and inferior parietal areas forming a network for controlling purposeful hand actions (lateral grasping network). The results provided evidence for partial overlap or interweaving of these projections in correspondence of 2 putaminal zones, distinct from the motor putamen, one located just rostral to the anterior commissure, the other in the caudal and ventral part. Thus, the present data provide evidence for partial overlap or interweaving in specific striatal zones (input channels) of projections from multiple, even remote, areas taking part in a large-scale functionally specialized cortical network. Furthermore, they suggest the presence of multiple hand-related input channels, possibly differentially involved in controlling goal-directed hand actions

Impact of Vaccination on Rotavirus Genotype Diversity: A Nearly Two-Decade-Long Epidemiological Study before and after Rotavirus Vaccine Introduction in Sicily, Italy

Sicily was the first Italian region to introduce rotavirus (RV) vaccination with the monovalent G1P[8] vaccine Rotarix® in May 2012. In this study, the seasonal distribution and molecular characterization of RV strains detected over 19 years were compared to understand the effect of Rotarix® on the evolutionary dynamics of human RVs. A total of 7846 stool samples collected from children < 5 years of age, hospitalized with acute gastroenteritis, were tested for RV detection and genotyping. Since 2013, vaccine coverage has progressively increased, while the RV prevalence decreased from 36.1% to 13.3% with a loss of seasonality. The local distribution of RV genotypes changed over the time possibly due to vaccine introduction, with a drastic reduction in G1P[8] strains replaced by common and novel emerging RV strains, such as equine-like G3P[8] in the 2018-2019 season. Comparison of VP7 and VP4 amino acid (aa) sequences with the cognate genes of Rotarix® and RotaTeq® vaccine strains showed specific aa changes in the antigenic epitopes of VP7 and of the VP8* portion of VP4 of the Italian RV strains. Molecular epidemiological surveillance data are required to monitor the emergence of novel RV strains and ascertain if these strains may affect the efficacy of RV vaccines

Time-course transcriptome analysis of a double challenge bleomycin-induced lung fibrosis rat model uncovers ECM homoeostasis-related translationally relevant genes

Background Idiopathic pulmonary fibrosis (IPF) is an irreversible disorder with a poor prognosis. The incomplete understanding of IPF pathogenesis and the lack of accurate animal models is limiting the development of effective treatments. Thus, the selection of clinically relevant animal models endowed with similarities with the human disease in terms of lung anatomy, cell biology, pathways involved and genetics is essential. The bleomycin (BLM) intratracheal murine model is the most commonly used preclinical assay to evaluate new potential therapies for IPF. Here, we present the findings derived from an integrated histomorphometric and transcriptomic analysis to investigate the development of lung fibrosis in a time-course study in a BLM rat model and to evaluate its translational value in relation to IPF.Methods Rats were intratracheally injected with a double dose of BLM (days 0–4) and sacrificed at days 7, 14, 21, 28 and 56. Histomorphometric analysis of lung fibrosis was performed on left lung sections. Transcriptome profiling by RNAseq was performed on the right lung lobes and results were compared with nine independent human gene-expression IPF studies.Results The histomorphometric and transcriptomic analyses provided a detailed overview in terms of temporal gene-expression regulation during the establishment and repair of the fibrotic lesions. Moreover, the transcriptomic analysis identified three clusters of differentially coregulated genes whose expression was modulated in a time-dependent manner in response to BLM. One of these clusters, centred on extracellular matrix (ECM)-related process, was significantly correlated with histological parameters and gene sets derived from human IPF studies.Conclusions The model of lung fibrosis presented in this study lends itself as a valuable tool for preclinical efficacy evaluation of new potential drug candidates. The main finding was the identification of a group of persistently dysregulated genes, mostly related to ECM homoeostasis, which are shared with human IPF

Blood and lymphatic vessels contribute to the impact of the immune microenvironment on clinical outcome in non-small-cell lung cancer

OBJECTIVES: Lymphangiogenesis plays a critical role in the immune response, tumour progression and therapy effectiveness. The aim of this study was to determine whether the interplay between the lymphatic and the blood microvasculature, tumour-infiltrating lymphocytes and the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) immune checkpoint constitutes an immune microenvironment affecting the clinical outcome of patients with non-small-cell lung cancer. METHODS: Samples from 50 squamous cell carcinomas and 42 adenocarcinomas were subjected to immunofluorescence to detect blood and lymphatic vessels. CD3pos, CD8pos and PD-1pos tumour-infiltrating lymphocytes and tumour PD-L1 expression were assessed by immunohistochemical analysis. RESULTS: Quantification of vascular structures documented a peak of lymphatics at the invasive margin together with a decreasing gradient of blood and lymphatic vessels from the peritumour area throughout the neoplastic core. Nodal involvement and pathological stage were strongly associated with vascularization, and an increased density of vessels was detected in samples with a higher incidence of tumour-infiltrating lymphocytes and a lower expression of PD-L1. Patients with a high PD-L1 to PD-1 ratio and vascular rarefaction had a gain of 10 months in overall survival compared to those with a low ratio and prominent vascularity. CONCLUSIONS: Microvessels are an essential component of the cancer immune microenvironment. The clinical impact of the PD-1/PD-L1-based immune contexture may be implemented by the assessment of microvascular density to potentially identify patients with non-small-cell lung cancer who could benefit from immunotherapy and antiangiogenic treatment

Low PD-1 expression in Cytotoxic CD8+ Tumor infiltrating Lymphocytes Confers an Immune Privileged Tissue Microenvironment in NSCLC with a Prognostic and Predictive Value

The success of immune checkpoint inhibitors strengthens the notion that tumor growth and regression are immune regulated. To determine whether distinct tissue immune microenvironments differentially impact on clinical outcome in Non Small Cell Lung Cancer (NSCLC), an extended analysis of PD-L1 and Tumor Infiltrating Lymphocytes (TILs) was performed. Experimental Design Samples from resected adenocarcinoma (ADC 42) and squamous cell carcinoma (SCC 58) and from 26 advanced diseases (13 ADC, 13 SCC) treated with nivolumab were analyzed. PD-L1 expression and the incidence of CD3, CD8, CD4, PD-1, CD57, FOXP3, CD25 and Granzyme B TILs was immunohistochemically assessed. Results PD-L1 levels inversely correlated with N involvement although did not show a statistical significant prognostic value in resected patients. The incidence and phenotype of TILs differed in SCC vs ADC in which EGFR and KRAS mutations conditioned a different frequency and tissue localization of lymphocytes. NSCLC resected patients with high CD8 pos lymphocytes lacking PD-1 inhibitory receptor had a longer Overall Survival (OS:HR=2.268, 95%CI 1.056-4.871,p=0.03). PD-1-to-CD8 ratio resulted a prognostic factor both on univariate (HR=1.952, 95%CI 1.34-3.12,p=0.001) and multivariate (HR=1.943, 95%CI 1.38-2.86,p=0.009) analysis. Moreover, low PD-1 incidence among CD8(pos) cells was a distinctive feature of nivolumab treated patients showing clinical benefit with a prolonged Progression-Free Survival (PFS:HR=4.51, 95%CI 1.45-13.94,p=0.004). Conclusions In the presence of intrinsic variability in PD-L1 expression, the reservoir of PD-1 negative effector T-lymphocytes provides an immune-privileged microenvironment with a positive impact on survival of patients with resected disease and response to immunotherapy in advanced NSCLC