GLI EFFETTI DELL’ACAMPROSATO SULLA RIMODULAZIONE DELLA TRASMISSIONE GLUTAMMATERGICA ECCITATORIA ED IL SUO IMPIEGO NEL TRATTAMENTO DEL CRAVING DA ALCOLISMO NEL TERRITORIO DELL’A.S.P. 1 AG

Secondo l’OMS definiamo l’alcolismo quel disturbo a genesi multifattoriale (bio-psico-sociale) associato all’assunzione episodica e/o cronica di bevande alcoliche con presenza o meno di dipendenza capace di determinare una sofferenza multidimensionale che si manifesta in maniera diversa da Soggetto a Soggetto. L’assunzione cronica di alcol modifica la normale attività neuronale attraverso il potenziamento dell’attività inibitoria del GABA e l’inibizione dell’effetto eccitatorio del Glutammato che induce il neuro-adattamento attraverso una over-espressione dei recettori del glutammato in modo da ripristinare l’equilibrio del sistema in presenza di alcol. Quando l’assunzione di alcol viene interrotta l’attività neuronale è caratterizzata sia da un aumento dell’eccitabilità dei recettori del glutammato sia dall’attività dei recettori NMDA che rappresenta invece la causa dei caratteristici sintomi dell’astinenza: le convulsioni. L’Acamprosato è un neuro modulatore specifico per il trattamento della dipendenza da alcol determinando il ripristino dell’equilibrio della trasmissione glutammatergica e l’inibizione dell’attività del glutammato agendo su due recettori: NMDA e mGluR5 rispettivamente ionotropico e metabotropico. Contrastando l’iperattività glutammatergica l’Acamprosato riduce il craving negativo e conseguenzialmente diminuisce l’incidenza, la severità e la frequenza delle ricadute. Nello studio clinico effettuato sono stati osservati 30 Pazienti reclutati nel territorio dell’A.S.P.1 di Agrigento suddivisi rispettivamente : > 9 Pazienti di cui 2 donne e 7 uomini presso il Ser.T di Sciacca, > 6 Pazienti di cui 1 donna e 5 uomini presso il Ser.T di Ribera, > 7 Pazienti di cui 2 donne e 5 uomini presso il Ser.T di Agrigento, > 8 Pazienti di cui 4 donne e 4 uomini presso il Ser.T di Canicattì. Riportiamo i dati di alcuni Pazienti reclutati e seguiti ambulatorialmente presso i Ser.T che erano già stati sottoposti a precedenti trattamenti farmacologici con GHB: * 4 Pazienti sui 30 – pari al 13,33% - esito negativo, * 9 Pazienti sui 30 – pari al 30 % - esito positivo, *17 Pazienti sui 30 – pari al 56,67 % - si sottoponevano per la prima volta alla terapia con Acamprosato. Ciascun Paziente è stato valutato mediante 2 questionari: OCDS (Obsessive Compulsive Drinking Scale) costituito da 14 item e SHORT SLEEP INDEX composto da 4 item. Tutti sono stati sottoposti a controlli seriati nel tempo che così abbiamo identificato: – T0 – prima dell’assunzione di Acamprosato; il primo follow –up al 4° mese – T1 - ed all’8 mese – T2 - il secondo. Per quanto riguarda la valutazione del craving si è osservato al T0 una percentuale dell’86,67% ricovero ed una del 13,33% ambulatoriale. Dove per ricovero si intende la percentuale di Pazienti che, rispondendo alle domande del test, ha totalizzato un punteggio relativo al craving >22, valore che richiede un monitoraggio costante da parte del Medico Responsabile del Ser.T e contemporaneamente anche di un maggiore supporto psicologico. Con il termine ambulatoriale si indicano tutti quei Pazienti il cui grado di craving risulta al di sotto dei valori considerati a “rischio ricadute” e tali da permettere al Paziente di proseguire un trattamento esclusivamente diurno ma che prevede comunque l’adeguato supporto psicologico all’interno del Ser.T. Al termine dell’odierno lavoro ed alla luce dei risultati ottenuti è innegabile l’efficacia dell’Acamprosato nel mantenimento dell’astinenza nei Soggetti dipendenti dall’alcol. Efficacia che si è manifestata riducendo il rischio di ricadute da un lato e, dall’altro per i ridotti effetti indesiderati registrati (la diarrea – il prurito) e per la notevole riduzione del craving negativo. Possiamo pertanto concludere dicendo che l’Acamprosato, associato ad un opportuno supporto psicologico, può senza dubbio rappresentare la terapia d’elezione che, certamente, in un futuro prossimo, sarà completata da altri supporti farmacologici-psicologici o altro per la riduzione/annientamento del problema: dipendenza dall’alcol

Effects of an intervention to prevent the bullying in first-grade secondary schools of Palermo, Italy: the BIAS study

Background: Bullying is one of the most common expressions of violence in the peer context during school years. This study investigates the prevalence of bullying and the short-term effects on students’ bullying perceptions of a preventive intervention conducted among teachers of first-grade secondary schools in Palermo, Sicily (Italy). Methods: Between the 2017/2018 and 2018/2019 school years, a pre-post intervention study was conducted among nine school institutions, sampled and categorized by neighbourhood socioeconomic index. A questionnaire investigating physical, verbal, and indirect bullying, the role of observers, prosociality, and resiliency in bullying was administered before and after intervention with formative cascade training of the teachers of the selected classes. Three different methods (sentinel questions, the five-question method, the ‘score of seven’ method) were used to detect the baseline level of bullying. Results: A total of 402 students participated in the study (72.7% response rate). A decrease in the number of bullying episodes after the intervention was reported by the students in all types of bullying explored (physical, verbal, and indirect bullying, observers, resiliency, and prosociality), with all three methods. In particular, a statistically significant decrease in all the bullying areas investigated (except for resiliency) was reported for students attending schools of an intermediate socioeconomic level. Conclusions: Even if many school-based interventions have been implemented to reduce school bullying throughout the world, this is one of the first conducted in Europe and it assesses the effectiveness among students of an antibullying intervention tailored for teachers. The encouraging results in reducing the number of bullying episodes together with the low cost in terms of human and economic resources could suggest an extension of this research on a regional/national scale

THE BIAS (BULLYING IN SICILIAN SCHOOL) PILOT STUDY: INVESTIGATING THE PREVALENCE OF BULLYING IN SCHOOL OF PALERMO CITY. A RESEARCH STUDY PROTOCOL

Being a serious threat to physical and emotional health of children and adolescents all over the world, bullying in school represents an important public health issue. Since 2007, in Italy, the Ministry of Education (MIUR) has promoted activities to face and prevent bullying in schools of all levels while at the same time national and local Health Authorities have implemented effective social-health strategies. To date, the lack of consistent data needed to properly describe the concerning increase of this Public Health phenomenon prevents both the ability to systematically survey and measure the effectiveness of the public health strategies against bullying. The Bullying In Sicilian Schools (BIAS) pilot study’s aims: i) to estimate the prevalence of bullying in a sample of secondary first-grade schools of Palermo, the largest city in Sicily, investigating its characteristics, and ii) to assess the feasibility of alternative methods for the detection of the prevalence of bullying in schools. Here we present the research protocol and the questionnaires that will be used

Silk fibroin microgels as a platform for cell microencapsulation

: Cell microencapsulation has been utilized for years as a means of cell shielding from the external environment while facilitating the transport of gases, general metabolites, and secretory bioactive molecules at once. In this light, hydrogels may support the structural integrity and functionality of encapsulated biologics whereas ensuring cell viability and function and releasing potential therapeutic factors once in situ. In this work, we describe a straightforward strategy to fabricate silk fibroin (SF) microgels (µgels) and encapsulate cells into them. SF µgels (size ≈ 200 µm) were obtained through ultrasonication-induced gelation of SF in a water-oil emulsion phase. A thorough physicochemical (SEM analysis, and FT-IR) and mechanical (microindentation tests) characterization of SF µgels were carried out to assess their nanostructure, porosity, and stiffness. SF µgels were used to encapsulate and culture L929 and primary myoblasts. Interestingly, SF µgels showed a selective release of relatively small proteins (e.g., VEGF, molecular weight, MW = 40 kDa) by the encapsulated primary myoblasts, while bigger (macro)molecules (MW = 160 kDa) were hampered to diffusing through the µgels. This article provided the groundwork to expand the use of SF hydrogels into a versatile platform for encapsulating relevant cells able to release paracrine factors potentially regulating tissue and/or organ functions, thus promoting their regeneration

The place of allogeneic stem cell transplantation in aggressive B-cell non-Hodgkin lymphoma in the era of CAR-T-cell therapy

Chimeric antigen receptor T (CAR-T) cells are a treatment option for patients with relapse/refractory (R/R) non-Hodgkin lymphoma (NHL), acute lymphoid leukemia and multiple myeloma. To date, diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and chronic lymphocytic leukemia (CLL) have been successfully treated with CAR-T cells directed against the CD19 antigen. However, when R/R disease persists after several treatment lines, patients with these diseases are often referred to transplantation centres to receive allogeneic stem cell transplantation (ALLO-SCT). ALLO-SCT and CAR-T cells share mechanism of actions, inducing immune effects of T-cells (and other cells after transplantation) against lymphoma cells, but they differ in several other characteristics. These differences justify unique positioning of each therapy within treatment algorithms. In this paper, we analyzed the results obtained after ALLO-SCT and CAR-T-cell therapy in patients with aggressive lymphomas (large B-cell lymphoma and MCL) to identify the ideal scenarios in which these 2 immunological therapies should be employed

GEN-O-MA project: an Italian network studying clinical course and pathogenic pathways of moyamoya disease—study protocol and preliminary results

Background: GENetics of mOyaMoyA (GEN-O-MA) project is a multicenter observational study implemented in Italy aimed at creating a network of centers involved in moyamoya angiopathy (MA) care and research and at collecting a large series and bio-repository of MA patients, finally aimed at describing the disease phenotype and clinical course as well as at identifying biological or cellular markers for disease progression. The present paper resumes the most important study methodological issues and preliminary results. Methods: Nineteen centers are participating to the study. Patients with both bilateral and unilateral radiologically defined MA are included in the study. For each patient, detailed demographic and clinical as well as neuroimaging data are being collected. When available, biological samples (blood, DNA, CSF, middle cerebral artery samples) are being also collected for biological and cellular studies. Results: Ninety-eight patients (age of onset mean ± SD 35.5 ± 19.6 years; 68.4% females) have been collected so far. 65.3% of patients presented ischemic (50%) and haemorrhagic (15.3%) stroke. A higher female predominance concomitantly with a similar age of onset and clinical features to what was reported in previous studies on Western patients has been confirmed. Conclusion: An accurate and detailed clinical and neuroimaging classification represents the best strategy to provide the characterization of the disease phenotype and clinical course. The collection of a large number of biological samples will permit the identification of biological markers and genetic factors associated with the disease susceptibility in Italy

Non-Small Cell Lung Cancer Harboring Concurrent EGFR Genomic Alterations: A Systematic Review and Critical Appraisal of the Double Dilemma

The molecular pathways which promote lung cancer cell features have been broadly explored, leading to significant improvement in prognostic and diagnostic strategies. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have dramatically altered the treatment approach for patients with metastatic non-small cell lung cancer (NSCLC). Latest investigations by using next-generation sequencing (NGS) have shown that other oncogenic driver mutations, believed mutually exclusive for decades, could coexist in EGFR-mutated NSCLC patients. However, the exact clinical and pathological role of concomitant genomic aberrations needs to be investigated. In this systematic review, we aimed to summarize the recent data on the oncogenic role of concurrent genomic alterations, by specifically evaluating the characteristics, the pathological significance, and their potential impact on the treatment approach

Ropinirole and pramipexole promote structural plasticity in human iPSC- derived dopaminergic neurons via BDNF and mTOR signaling

The antiparkinsonian ropinirole and pramipexole are D3 receptor- (D3R-) preferring dopaminergic (DA) agonists used as adjunctive therapeutics for the treatment resistant depression (TRD). While the exact antidepressant mechanism of action remains uncertain, a role for D3R in the restoration of impaired neuroplasticity occurring in TRD has been proposed. Since D3R agonists are highly expressed on DA neurons in humans, we studied the effect of ropinirole and pramipexole on structural plasticity using a translational model of human-inducible pluripotent stem cells (hiPSCs). Two hiPSC clones from healthy donors were differentiated into midbrain DA neurons. Ropinirole and pramipexole produced dose-dependent increases of dendritic arborization and soma size after 3 days of culture, effects antagonized by the selective D3R antagonists SB277011-A and S33084 and by the mTOR pathway kinase inhibitors LY294002 and rapamycin. All treatments were also effective in attenuating the D3R-dependent increase of p70S6-kinase phosphorylation. Immunoneutralisation of BDNF, inhibition of TrkB receptors, and blockade of MEK-ERK signaling likewise prevented ropinirole-induced structural plasticity, suggesting a critical interaction between BDNF and D3R signaling pathways. The highly similar profiles of data acquired with DA neurons derived from two hiPSC clones underpin their reliability for characterization of pharmacological agents acting via dopaminergic mechanisms

IAU Office of Astronomy for Education OAE Center Italy - Quarterly Report 1 January-March 2022

The IAU O!ce of Astronomy for Education Center Italy (I-OAE) is a joint project of a consortium of Italian partners led and represented by Istituto Nazionale di Astrofisica (INAF, National Institute for Astrophysics), the International Astronomical Union (IAU) and the IAU O!ce of Astronomy for Education. The Italian consortium is constituted by: INAF, the Italian Astronomical Society (SAIt) and the University of Rome Tor Vergata (ToV). I-OAE HQ are hosted by the INAF - Rome Astronomical Observatory, in Monteporzio. Personnel is selected on voluntary bases according to their interests and competence, in agreement with the Institutes they work for. Brochure of the 2021 activities: https://www.flipsnack.com/eduinaf/oaei-brochure.htmlQuarterly Report 1 January-March 2022 is the report of the activities from January to March 2022 of the IAU Office of Astronomy for Education OAE Center Italy Attachment: brochure of the activities and project 202

Chromosome microarray analysis as first-line test in pregnancies with a priori low risk for detection of submicroscopic chromosomal abnormalities

n this study, we aimed to explore the utility of chromosomal microarray analysis (CMA) in groups of pregnancies with a priori low risk for detection of submicroscopic chromosome abnormalities, usually not considered an indication for testing, in order to assess whether CMA improves the detection rate of prenatal chromosomal aberrations. A total of 3000 prenatal samples were processed in parallel using both whole-genome CMA and conventional karyotyping. The indications for prenatal testing included: advanced maternal age, maternal serum screening test abnormality, abnormal ultrasound findings, known abnormal fetal karyotype, parental anxiety, family history of a genetic condition and cell culture failure. The use of CMA resulted in an increased detection rate regardless of the indication for analysis. This was evident in high risk groups (abnormal ultrasound findings and abnormal fetal karyotype), in which the percentage of detection was 5.8% (7/120), and also in low risk groups, such as advanced maternal age (6/1118, 0.5%), and parental anxiety (11/1674, 0.7%). A total of 24 (0.8%) fetal conditions would have remained undiagnosed if only a standard karyotype had been performed. Importantly, 17 (0.6%) of such findings would have otherwise been overlooked if CMA was offered only to high risk pregnancies.The results of this study suggest that more widespread CMA testing of fetuses would result in a higher detection of clinically relevant chromosome abnormalities, even in low risk pregnancies. Our findings provide substantial evidence for the introduction of CMA as a first-line diagnostic test for all pregnant women undergoing invasive prenatal testing, regardless of risk factors