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Background O6-methylguanine (O6-MeG)-DNA methyltransferase (MGMT) methylation status is a predictive factor for alkylating treatment efficacy in glioblastoma patients, but its prognostic role is still unclear. We performed a large, multicenter study to evaluate the association between MGMT methylation value and survival. Methods We evaluated glioblastoma patients with an assessment of MGMT methylation status by pyrosequencing from nine Italian centers. The inclusion criteria were histological diagnosis of IDH wild-type glioblastoma, Eastern Cooperative Oncology Group Performance Status (ECOG-PS) ≤2, and radio-chemotherapy treatment with temozolomide. The relationship between OS and MGMT was investigated with a time-dependent Receiver Operating Characteristics (ROC) curve and Cox regression models. Results In total, 591 newly diagnosed glioblastoma patients were analyzed. The median OS was 16.2 months. The ROC analysis suggested a cut-off of 15% for MGMT methylation. The 2-year Overall Survival (OS) was 18.3% and 51.8% for MGMT methylation Conclusions Our findings suggested a non-linear relationship between OS and MGMT promoter methylation, which implies a varying magnitude of prognostic effect across values of MGMT promoter methylation by pyrosequencing in newly diagnosed IDH wild-type glioblastoma patients treated with chemoradiotherapy.

The formation of three oxidative DNA 5-methylcytosine (5mC) modifications (oxi-mCs), 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), by the TET/JBP family of dioxygenases, prompted intensive studies of their functional roles in mammalian cells. However, the functional interplay of these less abundant modified nucleotides in other eukaryotic lineages remains poorly understood. We carried out a systematic study of the content and distribution of oxi-mCs in DNA and RNA of the basidiomycetes Laccaria bicolor and Coprinopsis cinerea which are established models to study DNA methylation, developmental and symbiotic processes. Quantitative liquid chromatography-tandem mass spectrometry revealed persistent but uneven occurrence of 5hmC, 5fC and 5caC in DNA and RNA of the two organisms, which could be upregulated by vitamin C. 5caC in RNA (5carC) was predominantly found in non-ribosomal RNA fractions which potentially include non-coding, messenger and small RNA species. Mapping of 5hmC and 5fC genome-wide using the single CG analysis techniques hmTOP-seq and foTOP-seq pointed at involvement of oxi-mCs in regulation of gene expression and silencing of transposable elements. The implicated diverse roles of 5mC and oxi-mCs in the two fungi highlight the epigenetic importance of the latter modifications which are often neglected in standard whole-genome bisulfite analyses.

Cells 11(4), 664 (2022). doi:10.3390/cells11040664 special issue: "Special Issue "Common Denominators of Extracellular Matrix across Tissues as Inter-Tissue Messengers and Targets for Drug Repurposing" / Special Issue Editors: Prof. Dr. Alexander Dityatev, Guest Editor; Prof. Dr. Jessica Bertrand, Guest Editor; Prof. Dr. Peter R. Mertens, Guest Editor", Published by MDPI, Basel

IntroductionFor end-stage lung diseases, double lung transplantation (DLTx) is the ultimate curative treatment option. However, acute and chronic rejection and chronic dysfunction are major limitations in thoracic transplantation medicine. Thus, a better understanding of the contribution of immune responses early after DLTx is urgently needed. Passenger cells, derived from donor lungs and migrating into the recipient periphery, are comprised primarily by NK and T cells. Here, we aimed at characterizing the expression of killer cell immunoglobulin-like receptors (KIR) on donor and recipient NK and T cells in recipient blood after DLTx. Furthermore, we investigated the functional status and capacity of donor vs. recipient NK cells.MethodsPeripheral blood samples of 51 DLTx recipients were analyzed pre Tx and at T0, T24 and 3wk post Tx for the presence of HLA-mismatched donor NK and T cells, their KIR repertoire as well as activation status using flow cytometry.ResultsWithin the first 3 weeks after DLTx, donor NK and T cells were detected in all patients with a peak at T0. An increase of the KIR2DL/S1-positive subset was found within the donor NK cell repertoire. Moreover, donor NK cells showed significantly higher frequencies of KIR2DL/S1-positive cells (p+ T cells 3wk after DLTx with higher proportions of KIR2DL/S1 (pvia CD25 expression as well as a higher degranulation capacity upon activation by K562 target cells.ConclusionHigher frequencies of donor NK and T cells expressing KIR compared to recipient NK and T cells argue for their origin in the lung as a part of a highly specialized immunocompetent compartment. Despite KIR expression, higher activation levels of donor NK and T cells in the periphery of recipients suggest their pre-activation during the ex situ phase. Taken together, donor NK and T cells are likely to have a regulatory effect in the balance between tolerance and rejection and, hence, graft survival after DLTx.

Background: The risk of surgery in eloquent areas is related to neuropsychological dysfunctions. Maximizing the extent of resection increases the overall survival. The onco-functional balance is mandatory when surgery involves cognitive areas, and maximal information on the cognitive status of patients during awake surgery is needed. This can be achieved using direct cortical stimulation mapping and, in addition to this, a neuropsychological monitoring technique called real-time neuropsychological testing (RTNT). The RTNT includes testing protocols based on the area where the surgery is performed. We reported on tests used for left temporal lobe surgery and our RTNT decision tree.Case Report: We reported our RTNT experience with a 25-year-old right-handed man with 13 years of schooling. He reported daily partial seizures. MRI revealed the presence of a low-grade glioma involving the temporo-insular cortex. The neuropsychological status presurgery which was within the normal range was combined with functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) information. Awake surgery plus RTNT was performed. Direct electrical stimulation during object naming elicited a motor speech arrest. Resection was continuously accompanied by the RTNT. The RTNT provided enriched information to the surgeon. Performance never dropped. A slight decrement in accuracy emerged for pseudoword repetition, short-term memory and working memory, phonological processing, and verbal comprehension. Total resection was performed, and the histological examination confirmed the nature of the lesion. Immediate postsurgery performance was within the normal range as it was the fMRI and DTI assessment.Conclusion: The RTNT provides essential information that can be used online, during surgery, for clinical aims to provide the surgeon with useful feedback on the cognitive status of patients.

ESC heart failure 8(6), 5542-5550 (2021). doi:10.1002/ehf2.13574, Published by Wiley, Chichester

The present investigation aimed to characterize the protein profile of cavitating ultrasound aspirator fluid of newly diagnosed and recurrent glioblastoma comparing diverse zones of collection, i.e., tumor core and tumor periphery, with the aid of 5-aminolevulinic acid fluorescence. The samples were pooled and analyzed in triplicate by LC-MS following the shotgun proteomic approach. The identified proteins were then grouped to disclose elements exclusive and common to the tumor state or tumor zones and submitted to gene ontology classification and pathway overrepresentation analysis. The proteins common to the distinct zones were further investigated by relative quantitation, following a label free approach, to disclose possible differences of expression. Nine proteins, i.e., tubulin 2B chain, CD59, far upstream element-binding, CD44, histone H1.4, caldesmon, osteopontin, tropomyosin chain and metallothionein-2, marked the core of newly diagnosed glioblastoma with respect to tumor periphery. Considering the tumor zone, including the core and the fluorescence positive periphery, the serine glycine biosynthesis, pentose phosphate, 5-hydroxytryptamine degredation, de novo purine biosynthesis and huntington disease pathways resulted statistically significantly overrepresented with respect to the human genome of reference. The fluorescence negative zone shared several protein elements with the tumor zone, possibly indicating the presence of pathological aspects of glioblastoma rather than of normal brain parenchyma. On the other hand, its exclusive protein elements were considered to represent the healthy zone and, accordingly, exhibiting no pathways overrepresentation. On the contrary to newly diagnosed glioblastoma, pathway overrepresentation was recognized only in the healthy zone of recurrent glioblastoma. The TGF&beta, signaling pathway, exclusively classified in the fluorescence negative periphery in newly diagnosed glioblastoma, was instead the exclusive pathway classified in the tumor core of recurrent glioblastoma. These results, preliminary obtained on sample pools, demonstrated the potential of cavitron ultrasonic sur

Background: Tracking the white matter principal tracts is routinely typically included during the pre-surgery planning examinations and has revealed to limit functional resection of low-grade gliomas (LGGs) in eloquent areas.Objective: We examined the integrity of the Superior Longitudinal Fasciculus (SLF) and Inferior Fronto-Occipital Fasciculus (IFOF), both known to be part of the language-related network in patients with LGGs involving the temporo-insular cortex. In a comparative approach, we contrasted the main quantitative fiber tracking values in the tumoral (T) and healthy (H) hemispheres to test whether or not this ratio could discriminate amongst patients with different post-operative outcomes.Methods: Twenty-six patients with LGGs were included. We obtained quantitative fiber tracking values in the tumoral and healthy hemispheres and calculated the ratio (HIFOF–TIFOF)/HIFOF and the ratio (HSLF–TSLF)/HSLF on the number of streamlines. We analyzed how these values varied between patients with and without post-operative neurological outcomes and between patients with different post-operative Engel classes.Results: The ratio for both IFOF and SLF significantly differed between patient with and without post-operative neurological language deficits. No associations were found between white matter structural changes and post-operative seizure outcomes.Conclusions: Calculating the ratio on the number of streamlines and fractional anisotropy between the tumoral and the healthy hemispheres resulted to be a useful approach, which can prove to be useful during the pre-operative planning examination, as it gives a glimpse on the potential clinical outcomes in patients with LGGs involving the left temporo-insular cortex.

Questo taccuino è dedicato ai coach che, in P.I.P.P.I., svolgono la funzione di facilitare i componenti delle équipe multidisciplinari nell’implementazione del framework teorico e metodologico del programma, attraverso un accompagnamento in presenza e a distanza definito “tutoraggio”. Il taccuino rappresenta una mappa per i coach che è complementare al “Quaderno di P.I.P.P.I.” e che contiene le informazioni utili per organizzare l’accompagnamento delle EEMM. In esso sono presenti il “Modello ecologico e aree di lavoro del coach”, il “Piano di lavoro di lavoro del coach” e una serie di 15 “Schede Metodologiche” che raccolgono in maniera specifica i contenuti “irrinunciabili” rispetto alle diverse dimensioni e funzioni del coach.

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All’interno di un percorso laboratoriale in cui ricercatori dell’università di Padova e operatori dei servizi socioeducativi della regione Emilia-Romagna hanno esplorato il tema del benessere dei professionisti che operano con famiglie in situazione di vulnerabilità, è nata l’esigenza di offrire uno strumento utile ad orientare percorsi autonomi di autocura al fine di contrastare lo sviluppo di disturbi vicari cui sono costantemente esposti questi professionisti. Il testo, lontano dal proporre di proporre un manuale o una guida, è volto ad offrire un luogo in cui trovare orientamenti teorici e proposte operative a partire dalle quali sviluppare in autonomia, nei singoli gruppi di lavoro, percorsi di promozione del benessere professionale. La prima parte delinea la cornice teorica presentando il costrutto di resilienza ed esaminando i disturbi vicari che possono insorgere nei professionisti a partire dall’esposizione ripetuta e continuata alla sofferenza, alle difficoltà e fragilità altrui; vengono inoltre esplorati i costrutti di lavoro emotivo ed euristica del giudizio (bias cognitivi) per consentire di disinnescare trappole cognitive, comunicative e relazionali foriere di malessere professionale, identitario ed emotivo. La seconda parte è volta all’operatività ed è destinata a responsabili o coordinatori dei servizi o altri facilitatori di gruppi impegnati a promuovere comunità professionali mutuamente supportive per il lavoro di cura. Vengono presentate attività da utilizzare o a cui ispirarsi per progettare e proporre pe a favorire benessere, cura e autocura nei diversi gruppi di lavoro.

P.IP.P.I (Programma di Intervento Per la Prevenzione dell’Istituzionalizzazione; Programme of Intervention to Prevent Institutionalization) is an action-research programme that provides intensive intervention for families facing child neglect. Its acronym is inspired by the resilience of P.IP.P.I Longstocking as a metaphor for children’s ability to cope with life’s adverse situations. The programme was founded through a collaboration between the Ministry of Labour and Social Affairs and the Laboratory of Research and Intervention in Family Education (LabRIEF) at the University of Padua, with the aim of meeting two main objectives of the social protection system in Europe, in relation to the EU2020 strategy: 1. to decrease in out-of-home placement of children. 2. to fight against poverty and social exclusion. These two objectives are in line with European Recommendation 2006/19 on “creating the conditions for positive parenting” and Recommendation 2013/112, which proposes “investing in children to break the cycle of social disadvantage”. From 2011 to 2018, the Ministry funded seven institutions in an average of 50 participating municipalities (the city and its conurbations) every year. Each implementation of the in loco programme lasts 24 months. It provides for the participation of ten target families, at least four multidisciplinary teams, two coaches who are specially trained in the programme’s method, and a managerial executive. In the first four implementations, carried out from 2011 to 2016, the Ministry provided national funding for the programme in 120 municipalities, belonging to 18 Italian regions, with 1361 children living in 1091 families. Seventy municipalities participated in two or three institutions. The data presented in this chapter relate to the fourth implementation (2015-2016). These data concern the national level as well as the in-depth group presented below. The team is currently carrying out the seventh implementation (2018-2019). The general target of the programme is to foster investment in services for families facing child neglect, promoting innovation and harmonisation of intervention practices with families of children aged from birth to 11 years old, in different geographical areas and in the different organisational systems in Italy at a regional level. By targeting situations of child neglect, the aim is to reduce the risk of violence against children and to improve the relevance of out-of-home placements for children through the coordination of social, health, educational and school sectors, the justice system, and civil society support networks, particularly by considering the point of view of parents and children in the analysis and response to needs (Serbati, Ius and Milani, 2016). Child neglect is conceived as: “a significant failure or lack of response to a child’s needs that are recognized as fundamental on the basis of current scientific knowledge or, in the absence of such knowledge, a lack of consensus about it, social values adopted by the community to which the child belongs” (Lacharité, Ethier and Nolin, 2006, p. 387), whereas vulnerability is a potential situation which, on the one hand, concerns us all as human beings, and which, on the other hand, does not concern individuals as much as the relationships between individuals and social contexts (Soulet, 2013). In any case, children and families in situations of vulnerability and neglect can also find answers in action mechanisms that are not strictly related to the field of child protection (Vinay and Zaouche Gaudron, 2017). The phenomenon of child neglect in particular remains a grey area that is still rather unknown in Italy: neglect is the primary cause of out-of-home placements, most of the problems that concern health and social services and the school increasingly refer to this phenomenon, but we have not yet developed empirical knowledge on the phenomenon nor on the interventions that are able to respond to it in an appropriate way. Indeed, a government computerised system on children subject to child protection is still in an experimental phase. The latest national data only date back to 2014 (MLPS, 2014), but the fact that neglect is the cause of 37 % of child placements in the country and that the second cause – parental substance abuse – accounts for “only” 9 % of placements, underscores the growing importance of this phenomenon.

Il contributo presenta una riflessione sulle pratiche di incontro tra scuola e famiglia all'interno dell'esperienza della scuola nel bosco di Riva del Garda (TN).

BACKGROUND: The aim of this study was to understand the impact of SARS-COVID-19 disease on neurosurgeons and our profession; specifically, to trace the role of women, in particular young neurosurgeons, in addressing this health emergency. METHODS: This cross-sectional study evaluated the impact of SARS-COVID-19 disease on Italian neurosurgeons stratified by gender [44 (49.9%) males and 49 (52,1%) females] enrolled through a questionnaire-based online survey. RESULTS: Ninety-three Italian neurosurgeons were included in this study. The percentage of female participants was 52,1%(49) and 53%(50) were younger than 40 years. Men were significantly more affected than women by complications (14 versus 3), while there was no gender difference in the Covid infection rate. Furthermore the social impact of the Pandemia was the same between men and women. CONCLUSIONS: Our analysis did not show significant differences between the two genders in the susceptibility, and mortality from COVID-19. The possible and immediate implementation of anti-COVID-19 measures and devices, associated with a lower risk of transmission in the treatment of neurosurgical pathologies, has likely, moderated and disregarded the socio-psychological "gender gap" of the Covid-19 pandemic.

Il contributo offre una cornice teorica relativa al ruolo dell'educatore nei percorso di outdoor education secondo una chiave resiliente.

Nello scenario creatosi in seguito all’emergenza Coronavirus le esigenze socio-assistenziali ed educative delle fasce più fragili della società si sono ulteriormente ampliate e diversificate, ponendo enormi sfide al sistema dei servizi e, parallelamente, alle loro infrastrutture informatiche. Si è pertanto assistito a una riorganizzazione delle modalità di offerta ed erogazione di servizi e interventi professionali (a distanza, o in presenza ma con i dovuti dispositivi di protezione) e la nascita o il consolidamento di nuove connessioni tra enti pubblici e privati, professionisti e società civile, gruppi formali e informali, al fine di garantire continuità ai percorsi di accompagnamento e di diversificare la programmazione del welfare locale. Pertanto, nel campo dei servizi socio-educativi e sociosanitari, è osservabile una riconfigurazione in prospettiva smart potenzialmente in grado di fornire risposte via via più coerenti con i bisogni della cittadinanza. Si prefigura così il consolidamento del paradigma dello smart welfare, caratterizzato dall’utilizzo delle Digital Humanities (DH), dalle Information and Communication Technologies (ICT) e da una reinterpretazione delle prassi operative sia tra operatori e famiglie che all’interno dei servizi stessi.

This article accompanies a Roadmap on the judicial use of comparative law, which was developed by judges from different European supreme courts. This document is published in this issue of Utrecht Law Review. Brief reflections on relevant scholarly aspects help the reader to appreci- ate the meaning and value of this Roadmap for contemporary judicial functioning in Member States of the European Union. Addressed aspects concern the legitimacy of judicial comparativ- ism and the methodological quality of the Roadmap. This analysis leads to a conclusion about the Roadmap’s potential to enhance the quality of judicial decision-making and support dialogues of courts with their foreign counterparts as well as with other legal and societal audiences.

Inspiré de l’expérience du Programme d’aide personnelle, familiale et communautaire (PAPFC2 : Lacharité, 2014) et de l’initiative AIDES (Chamberland et al., 2012) au Québec, le Laboratoire de recherche et d’intervention en éducation familiale (LabRIEF) de l’Université de Padoue met en œuvre, depuis 2011, le Programme d’Intervention Précoce pour Prévenir l’Institutionnalisation (P.I.P.P.I.), grâce au soutien du Ministère italien du travail et des affaires sociales. L’acronyme fait référence à la résilience de Pippi Longstocking1. L’objectif de ce chapitre est de présenter une évaluation des processus et des résultats de l’implantation du programme, axée spécifiquement sur les familles ayant des enfants âgés de 0 à 2 ans qui ont participé à celui-ci. Les questions suivantes seront abordées : quelles sont les conditions de vulnérabilité spécifiques de ces familles? Quels sont les dispositifs du programme planifiés et mis en œuvre avec ces familles? En quoi les processus d’intervention et les résultats obtenus diffèrent-ils selon l’âge des enfants? Y a-t-il des effets différentiels du programme au sein du groupe d’enfants les plus jeunes?

Il presente contributo si prefigge di presentare e discutere gli aspetti metodologici e i risultati di una pratica educativa utilizzata nell’insegnamento di pedagogia interculturale. Tale insegnamento ha avuto come cornice la proposta delineata da Milan (2020) a partire dal service-learning dal quale sono derivati il “decalogo pedagogico” e i “dieci passi della relazionalità autentica” volti a compiere il “viaggio dell’incontro ospitale” che lo sguardo interculturale evidenzia come fondamentale educativo. In tale viaggio, l’educatore è chiamato a far propria la dimensione “inter”, non solo nella relazione con l’altro da sé, per accompagnarlo intenzionalmente nel suo divenire, ma anche in quella con l’altro in sé, per continuare a conoscere, comprendere e compiere il proprio divenire come elemento essenziale per poter incontrare autenticamente l’altro. Come offrire agli educatori in formazione un’occasione per sperimentarsi all’interno dei confini e delle frontiere delle loro differenze (Agostinetto, 2013) grazie ad un contesto in cui sostare per incontrare se stessi e incontrare gli altri, promuovendo coesione sociale e scambio culturale in modo coerente con la cornice teorica di riferimento?

The paper aims at reflecting on relation and communication in education. The first part proposes a brief pedagogical theoretical framework on the topic of communication within the educational relationship, and it underlines the concept of empathy. A discussion on the role of the educator follows to focus on the helping relationship to explore the topic of the management of communicative and relational dynamics. By arguing on the etymology and the misuse of the word “dynamic”, a reflection is proposed on the concept of strength and of communication as the meeting between two strengths. The third part discusses about the communication skills and, according to what shown before, proposes and reflects on counselling microskills that have been taught on University lectures for educators. Conclusions underline possible developments and attentions to be integrated in designing university training on communicational and relational skills for educators., Rivista Italiana di Educazione Familiare, Vol. 17 No. 2 (2020): n° 2 luglio-dicembre 2020

Simple Summary Diffuse low-grade gliomas (LGG) are relatively uncommon primary brain cancers. In recent years, the molecular, diagnostic, and therapeutic approaches have evolved. IDH (isocitrate dehydrogenase) mutations can affect the great majority of these tumors with distinct genetic and clinical characteristics, carrying a more favorable prognosis compared with wild-type IDH. In patients with LGG, the most common manifestation is seizure and new neuroradiological tools are available to improve the diagnostic and therapeutic pathways. Surgical intervention is performed with the goal of maximum safe resection; postoperative chemoradiotherapy showed benefits in selected patients. New treatments based on molecular profiling, new small molecule and immunotherapy approaches could improve survival and quality of life. In this review, in order to identify the optimal clinical management of patients with LGG, we discuss the relevant biological and clinical characteristics, new therapeutic approaches, and future research directions for these tumors. Abstract Diffuse low-grade gliomas (LGG) represent a heterogeneous group of primary brain tumors arising from supporting glial cells and usually affecting young adults. Advances in the knowledge of molecular profile of these tumors, including mutations in the isocitrate dehydrogenase genes, or 1p/19q codeletion, and in neuroradiological techniques have contributed to the diagnosis, prognostic stratification, and follow-up of these tumors. Optimal post-operative management of LGG is still controversial, though radiation therapy and chemotherapy remain the optimal treatments after surgical resection in selected patients. In this review, we report the most important and recent research on clinical and molecular features, new neuroradiological techniques, the different therapeutic modalities, and new opportunities for personalized targeted therapy and supportive care.

We address existing controversies regarding neuroanatomical substrates of reading‐aloud processes according to the dual‐route processing models, in this particular instance in a series of 49 individuals with brain tumors who performed several reading tasks of real‐time neuropsychological testing during surgery (low‐ to high‐grade cerebral neoplasms involving the left hemisphere). We explored how reading abilities in individuals with brain tumors evolve during and after surgery for a brain tumor, and we studied the reading performance in a sample of 33 individuals in a 4‐month follow‐up after surgery. Impaired reading performance was seen pre‐surgery in 7 individuals with brain tumors, intra‐surgery in 18 individuals, at immediate post‐surgery testing in 26 individuals, and at follow‐up in 5 individuals. We classified their reading disorders according to operational criteria for either phonological or surface dyslexia. Neuroimaging results are discussed within the theoretical framework of the dual‐route model of reading. Lesion‐mask subtraction analyses revealed that areas selectively related with phonological dyslexia were located—along with the left hemisphere dorsal stream—in the Rolandic operculum, the inferior frontal gyrus, the precentral gyrus, the supramarginal gyrus, the insula (and/or the underlying external capsule), and parts of the superior longitudinal fasciculus, whereas lesions related to surface dyslexia involved the ventral stream, that is, the left middle and inferior temporal gyrus and parts of the left inferior longitudinal fasciculus., We explored how reading abilities in individuals with neurosurgical lesions evolve during and after surgery for a brain tumor, and we studied the reading performance in a sample of 33 individuals in a 4‐month follow‐up after surgery.