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The aim of this essay is to present an idea of theatre pedagogy for the use of theatre in the educational context (first-grade secondary school): this work is offering a reflection, with no claim to exhaustiveness, but with the promise of a coherent exercise, aimed at guiding the structuring of articulated and effective didactic-theatre projects. There are numerous studies on the pedagogy of theatre: among the most recent, Mango’s experience appeared as a monograph in “Costellazioni”, issue 24, Theatre and pedagogical processes, to which must be added Rivoltella’s latest volume Drammaturgia didattica, as well as the text edited by Pontremoli Elementi di teatro educativo, sociale e di comunità. In such an encouraging and stimulating framework we can move not only in a reconnaissance logic, but also in a propositional direction, also interpreting the Italian ministerial indication of Law 107/2015 (paragraph 181) on theatre education in schools. The essay will start from the definition of the third millennium school’s didactic needs and the opportunities offered by the object Theatre. Ultimately, an annotated operational project is presented, through the classic scheme of the interdisciplinary learning unit.

Abstract Mutations in BAP1 have been identified in a hereditary cancer predisposition syndrome and in sporadic tumours. Individuals carrying familiar BAP1 monoallelic mutations display hypersusceptibility to exposure-associated cancers, such as asbestos-driven mesothelioma, thus BAP1 status has been postulated to participate in gene-environment interaction. Intriguingly, BAP1 functions display also a high degree of tissue dependency, associated to a peculiar cancer spectrum and cell types of specific functions. Mechanistically, BAP1 functions as an ubiquitin carboxy-terminal hydrolase (UCH) and controls regulatory ubiquitination of histones as well as degradative ubiquitination of a range of protein substrates. In this article we provide an overview of the most relevant findings on BAP1, underpinning its tissue specific tumour suppressor function. We also discuss the importance of its epigenetic role versus the control of protein stability in the regulation of genomic integrity.

Objectives This study investigates the diagnostic role of synovial tissue analysis in children presenting with arthritis and assesses its prognostic significance to predict clinical outcome in juvenile idiopathic arthritis (JIA).Methods Synovial samples of paediatric patients undergoing synovial biopsy between 1995 and 2020 were analysed histologically and immunohistochemically. Relationships between histological/immunohistochemical parameters and clinical variables were assessed.Results Synovial biopsy was performed for diagnosis in 65 cases allowing to correctly classify 79% of patients.At histological analysis on 42 JIA samples, any difference in the number of synovial lining layers, subsynovial elementary lesions, fibrin deposit, Krenn Synovitis Score, inflammatory infiltrate score and pattern emerged between JIA subsets or on treatment exposure. Synovial tissue analysis predicted outcome: higher number of synovial layers predicted worse disease course (>4 flares during follow-up; 4.5 vs 3.0, p=0.035), even after adjusting for age at diagnosis and observation time (OR 2.2, p=0.007); subjects who had switched>2 biological disease-modifying antirheumatic drugs had higher prevalence of subsynovial elementary lesions (55.6% vs 10.3%, p=0.005) and fibrin deposits in synovial lining (60.0% vs 22.6%, p=0.049), even after adjustment for observation time and age at diagnosis (OR 8.1, p=0.047). At immunohistochemistry on 31 JIA samples, higher CD3 expression was described in polyarticular compared with oligoarticular subset (p=0.040). Patients with severe disease course had higher CD20+ rate (OR 7, p=0.023), regardless of JIA subset and treatment exposure.Conclusions Synovial tissue analysis might support the clinicians in the diagnostic approach of paediatric patients presenting with arthritis and guide the clinical management in JIA.

IntroductionSound therapy is a common tinnitus treatment, where the tinnitus percept is either fully or partially masked by an external sound. Some tinnitus patients experience a decrease in tinnitus related distress after the use of sound therapy. Differences in the neural response to sound therapy may form a basis for classifying tinnitus patients.MethodsIn this study, the long-term (2 months) effects of sound therapy on the oscillatory brain activity and tinnitus related distress were investigated in chronic tinnitus patients. Baseline oscillatory activity in the group of tinnitus participants was also compared to a matched control group.ResultsNo differences were found in the oscillatory activity when comparing the tinnitus group to the control group. Differences were found for the frequency range between 27.5 and 41.5 Hz corresponding to high beta and gamma power when comparing the tinnitus group before and after the use of sound therapy. Furthermore, a reduction of the tinnitus-related distress was found after the long-term use of sound therapy. However, there was no correlation between the changes in the oscillatory activity and the reductions of the tinnitus-related distress.DiscussionOverall, the lack of correlation between the changes in tinnitus-related distress and changes in power activity hampers the interpretability of the findings and undermines the utility of using oscillatory activity as a biomarker for the effect of sound therapy treatment.

ObjectiveTo evaluate in patients with rheumatoid arthritis (RA) the impact of EMA recommendations on the real-life prescription of JAK inhibitors (JAKis) and the use of the Expanded Risk Score in RA (ERS-RA) to quantify the risk of major adverse cardiac events (MACE).MethodsWe conducted a retrospective analysis of real-life RA patients treated with JAKis. Patients were classified as ineligible for JAKis if they fulfilled EMA criteria (>65 years-old, history of malignancy, or increased risk of venous thromboembolic events [VTE] or MACE including smoking). Risk of MACE was defined according to ORAL Surveillance trial inclusion criteria (ORALSURV) or by using the ERS-RA.ResultsOf 194 patients enrolled, 57.9% were classified as ineligible according to EMA definition (ORALSURV criteria). The most frequent reason for ineligibility was increased MACE risk (70.2%), followed by age>65 (34.2%), smoking (30.7%), and increased risk of VTE (20.2%) or malignancy (7%). The use of the ERS-RA reduced the rate of patients carrying an increased CV risk to 18.6% (p

Sound therapy is one of the most common tinnitus treatments that can be used either to mask or to shift attention away from the tinnitus percept. However, the actual benefit of sound therapy and the mechanisms leading to the benefits remain limited. The objective of this study was to investigate the short-term (15 min) and long-term (2 months) effects of sound therapy on visual attention in chronic tinnitus patients. Visual attention was evaluated with the behavioral Attention Network Task, while the tinnitus-related distress was evaluated with the Tinnitus Handicap Inventory (THI) to quantify the effect of sound therapy. The study included 20 participants with chronic and bothersome tinnitus (>6 months, THI > 18) and 20 matched control participants. All participants took part in a first session consisting of a baseline condition, a short-term sound therapy condition and a silent control condition. The tinnitus participants also took part in a second session that evaluated the long-term effect of the therapy. A reduction in the tinnitus-related distress was found after the long-term use of sound therapy. Furthermore, a reduction in the differential index of the executive control (EC) attention network, indicating improved attention, was found after long-term use of sound therapy in the sound condition but not in the silent control condition. In contrast to earlier research, no differences were found between the tinnitus group and the control group for the baseline measurement of the EC attention network. Overall, the results suggest that there is no link between the visual attention networks and the sound therapy’s effect on tinnitus-related distress.

Abstract Background Myoclonus, Epilepsy and Ragged-Red-Fibers (MERRF) is a mitochondrial encephalomyopathy due to heteroplasmic mutations in mitochondrial DNA (mtDNA) most frequently affecting the tRNA Lys gene at position m.8344A > G. Defective tRNALys severely impairs mitochondrial protein synthesis and respiratory chain when a high percentage of mutant heteroplasmy crosses the threshold for full-blown clinical phenotype. Therapy is currently limited to symptomatic management of myoclonic epilepsy, and supportive measures to counteract muscle weakness with co-factors/supplements. Methods We tested two therapeutic strategies to rescue mitochondrial function in cybrids and fibroblasts carrying different loads of the m.8344A > G mutation. The first strategy was aimed at inducing mitochondrial biogenesis directly, over-expressing the master regulator PGC-1α, or indirectly, through the treatment with nicotinic acid, a NAD+ precursor. The second was aimed at stimulating the removal of damaged mitochondria through prolonged rapamycin treatment. Results The first approach slightly increased mitochondrial protein expression and respiration in the wild type and intermediate-mutation load cells, but was ineffective in high-mutation load cell lines. This suggests that induction of mitochondrial biogenesis may not be sufficient to rescue mitochondrial dysfunction in MERRF cells with high-mutation load. The second approach, when administered chronically (4 weeks), induced a slight increase of mitochondrial respiration in fibroblasts with high-mutation load, and a significant improvement in fibroblasts with intermediate-mutation load, rescuing completely the bioenergetics defect. This effect was mediated by increased mitochondrial biogenesis, possibly related to the rapamycin-induced inhibition of the Mechanistic Target of Rapamycin Complex 1 (mTORC1) and the consequent activation of the Transcription Factor EB (TFEB). Conclusions Overall, our results point to rapamycin-based therapy as a promising therapeutic option for MERRF.

The objective of this study was to evaluate biological disease-modifying anti-rheumatic drugs (bDMARDs) survival in several therapy courses of patients affected by psoriatic arthritis (PsA) and to compare tumor necrosis factor inhibitors (TNFi) and non-TNFi retention rates. A total of 241 bDMARD therapy courses (155 TNFi drugs, 65 anti-interleukin (IL)-17 drugs, and 21 anti-IL12/23) were analyzed. Bivariate analyses were performed to assess the presence of demographic and clinical features, as well as comorbidities, associated with bDMARD discontinuation in TNFi and non-TNFi groups. In the bivariate analyses of TNFi and non-TNFi groups, we found a lower age at the start of TNFi therapy in the former group [46 years, interquartile range (IQR) 45-54 vs 50.5 years, IQR 42-61; p=0.004] as well as a lower proportion of patients with skin psoriasis (65.8% vs 88.4%; p

Maize silks, the stigmatic portions of the female flowers, have an important role in reproductive development. Silks also provide entry points for pathogens into host tissues since fungal hyphae move along the surface of the silks to reach the site of infection, i.e., the developing kernel. The outer extracellular surface of the silk is covered by a protective hydrophobic cuticle, comprised of a complex array of long-chain hydrocarbons and small amounts of very long chain fatty acids and fatty alcohols. This work illustrates that two previously characterized cuticle-related genes separately exert roles on maize silk cuticle deposition and function. ZmMYB94/FUSED LEAVES 1 (ZmFDL1) MYB transcription factor is a key regulator of cuticle deposition in maize seedlings. The ZmGLOSSY2 (ZmGL2) gene, a putative member of the BAHD superfamily of acyltransferases with close sequence similarity to the Arabidopsis AtCER2 gene, is involved in the elongation of the fatty acid chains that serve as precursors of the waxes on young leaves. In silks, lack of ZmFDL1 action generates a decrease in the accumulation of a wide number of compounds, including alkanes and alkenes of 20 carbons or greater and affects the expression of cuticle-related genes. These results suggest that ZmFDL1 retains a regulatory role in silks, which might be exerted across the entire wax biosynthesis pathway. Separately, a comparison between gl2-ref and wild-type silks reveals differences in the abundance of specific cuticular wax constituents, particularly those of longer unsaturated carbon chain lengths. The inferred role of ZmGL2 is to control the chain lengths of unsaturated hydrocarbons. The treatment of maize silks with Fusarium verticillioides conidia suspension results in altered transcript levels of ZmFDL1 and ZmGL2 genes. In addition, an increase in fungal growth was observed on gl2-ref mutant silks 72 hours after Fusarium infection. These findings suggest that the silk cuticle plays an active role in the response to F. verticillioides infection.

Intro: Dengue virus (DENV) is a mosquito-borne human pathogen endemic in 129 countries. In Italy, presence of the competent vector increases the risk of autochthonous transmission from imported cases, and a surveillance national plan for Arboviruses (PNA 2020-2025) is in place. The results of laboratory diagnosis of DENV in Italy from November 2015 to November 2021 are presented. Methods: Samples from 502 suspected DENV cases were tested by both molecular/antigen NS1 and serological assays, including Plaque Reduction Neutralization Test (PRNT). Samples were tested in parallel for DENV, Chikungunya (CHIKV)and Zika virus (ZIKV). Cases were classified based on laboratory results according to the Italian National Plan for Arboviruses (PNA) criteria. Findings: After evaluation of laboratory results, there were 140/502 confirmed and 7/502 probable cases (DENV cases). A positive molecular test was found in 27.1% of cases and 66.7% had a positive antigen NS1 test. The lag time from symptoms to collection was 4 and 6 days, respectively, with a higher range of day detection limit for antigen NS1. DENV cases gave 87.8% IgM and 82.9% PRNT positive/border line results: samples positivity of 72.20% and 33.9% in IgM and PRNT, respectively, was observed within the first 7 days of disease. Overall, 10.9% IgM positive results were not confirmed as positive in PRNT or molecular test among excluded cases (274/502). 26/502 suspected cases were both DENV and ZIKV positive by IgM and/or PRNT, making it difficult to provide a final differential diagnosis. None had a possible co-infection of DENV and CHIKV. Conclusion: DENV diagnosis by molecular/antigen tests is the gold standard but the sample collection time is a limitation. Serological tests are thus necessary. However, IgM results need PRNT confirmation. Co-circulation of DENV and ZIKV increases diagnostic difficulty. Continuous evaluation of diagnostic strategies is essential against future DENV autochthonous outbreaks.

Abstract Background Preterm extremely low birth weight infants (ELBWi) are known to be at greater risk of developing neuropsychiatric diseases. Identifying early predictors of outcome is essential to refer patients for early intervention. Few studies have investigated neurodevelopmental outcomes in Italian ELBWi. This study aims to describe neurodevelopmental outcome at 24 months of corrected age in an eleven-year single-center cohort of Italian ELBWi and to identify early risk factors for adverse neurodevelopmental outcomes. Methods All infants born with birth weight

Florenzo Iannone,1 Fabrizio Conti,2 Alberto Cauli,3 Alberto Farina,4 Roberto Caporali5 1Rheumatology Unit, Department of Emergency and Organ Transplantation, Università Degli Studi Di Bari Aldo Moro, Bari, Italy; 2Rheumatology Unit, Department of Clinical, Internal, Anesthetic and Cardiovascular Sciences, Sapienza Università di Roma, Rome, Italy; 3Rheumatology Unit, Department of Medical Sciences and Public Health, AOU and University of Cagliari, Monserrato, Italy; 4Medical Affairs Department, Celltrion Healthcare Italy srl, Milan, Italy; 5Department of Clinical Sciences and Community Health, Research Centre for Adult and Pediatric Rheumatic Diseases, University of Milan, Milan, ItalyCorrespondence: Florenzo Iannone, Rheumatology Unit, Department of Emergency and Organ Transplantation, Università Degli Studi Di Bari Aldo Moro, 11, Piazza Giulio Cesare, Bari (BA), 70124, Italy, Tel +39 080 5592775, Fax +39 080 5478802, Email florenzo.iannone@uniba.itAbstract: The first subcutaneous (SC) formulation of infliximab CT-P13 has been authorized for the treatment of rheumatoid arthritis (RA) in Europe in 2019. Later, in 2020, approved indications were extended also to ankylosing spondylitis, psoriatic arthritis, psoriasis, Crohn’s disease (CD) and ulcerative colitis (UC). The present review provides summary of the key features of SC infliximab, with particular focus on pharmacokinetic profile, clinical development program in comparison with the intravenous (IV) formulation, and the latest evidence in the literature. We conclude that SC infliximab represents a new and promising approach in the treatment of patients with RA, offering an optimized clinical profile and a more practical option in comparison to the IV formulation. Nevertheless, SC formulation can improve the use of national health systems resources (e.g., through the time of healthcare workers not having to supervise infusions) and facilitate social distancing measures during the COVID-19 pandemic, as the patient can self-inject the medicine at home without going to the hospital. The limitations of the SC infliximab are mainly due to the limited experience of use in clinical practice and the absence of long-term drug retention data.Keywords: rheumatoid arthritis, TNF inhibitors, infliximab, subcutaneous, intravenous, SC, IV, RA