University of Verona
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Type 2 diabetes, prediabetes, and MASLD: who and when to screen and how to treat?
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MALAT1 Expression Is Deregulated in miR-34a Knockout Cell Lines
Get PDFBackground/Objectives: Non-coding microRNA-34a (miR-34a) regulates the expression of key factors involved in several cellular processes, such as differentiation, apoptosis, proliferation, cell cycle, and senescence. Deregulation of the expression of these factors is implicated in the onset and progression of several human diseases, including cancer, neurodegenerative disorders, and pathologies associated with viral infections and inflammation. Despite numerous studies, the molecular mechanisms regulated by miR-34a remain to be fully understood. The present study aimed to generate miR-34a knockout cell lines to identify novel genes potentially regulated by its expression. Methods: We employed the CRISPR-Cas9 gene editing system to knock out the hsa-miR-34a gene in HeLa and 293T cell lines, two widely used models for studying molecular and cellular mechanisms. We compared proliferation rates and gene expression profiles via RNA-seq and qPCR analyses between the wild-type and miR-34a KO cell lines. Results: Knockout of miR-34a resulted in a decreased proliferation rate in both cell lines. Noteworthy, the ablation of miR-34a resulted in increased expression of the long non-coding RNA MALAT1. Additionally, miR-34a-5p silencing in the A375 melanoma cell line led to MALAT1 overexpression. Conclusions: Our findings support the role of the miR-34a/MALAT1 axis in regulating proliferation processes
Robot‐assisted partial nephrectomy using the HugoTM RAS System: first multicentre study and Tetrafecta achievement
No full textObjective To evaluate the perioperative outcomes and the rate of Tetrafecta achievement in robot-assisted partial nephrectomy (RAPN) cases performed using the Hugo (TM) robot-assisted surgery (RAS) system (Medtronic, Minneapolis, MN, USA). Patients and Methods Data from five tertiary care referral centres performing RAPN with the Hugo RAS System since October 2022 were collected. For the study purpose, a novel Tetrafecta was defined as a proxy for surgical quality. This included the coexistence of negative surgical margins, absence of intraoperative and Clavien-Dindo Grade >= II postoperative complications, and 90-day decline in estimated glomerular filtration rate of no more than 30% from baseline. Results A total of 140 patients, who underwent RAPN with the Hugo RAS system, were included. The median (interquartile range [IQR]) docking, console, and total operative times were 5 (4-7) min, 79 (45.5-135) min, and 150 (96-205) min, respectively. The median (IQR) estimated blood loss was 150 (100-300) mL. No additional port placements were required, and no conversions to open surgery occurred. Overall, postoperative complications were observed in 20.7% of cases, 5% of which were classified as major (Clavien-Dindo Grade >II). Tetrafecta was achieved in 80% of cases. Multivariate logistic regression analysis showed that R.E.N.A.L. (Radius, Exophytic/Endophytic, Nearness to collecting system or sinus, Anterior/Posterior, Location) nephrometry score (odds ratio [OR] 0.69; P = 0.01) and Hugo RAS surgical experience (OR 1.03; P = 0.02) were independent predictors of Tetrafecta achievement. Conclusions Relying on the largest multicentre series, our findings demonstrate that this novel robotic platform enables safe and effective RAPN, achieving a satisfactory Tetrafecta rate. These results would support the adoption of the Hugo RAS system to perform RAPN
Teoria tecnica e didattica delle attività motorio-espressive
No full textIl volume propone una ricca riflessione sulle attività motorio-espressive come strumento educativo capace di coniugare corpo, movimento e didattica. L’opera mette in luce come il corpo, oltre a essere dimensione fisica, rappresenti uno spazio di espressione, comunicazione e relazione, in cui si intrecciano emozioni, pensiero e crescita personale. Attraverso un approccio innovativo e multidisciplinare, il testo analizza le pratiche motorie e la loro applicazione in contesti educativi, evidenziando le potenzialità formative delle attività espressive sul piano fisico, emotivo, cognitivo e sociale. Il volume invita a riconsiderare il valore del movimento non solo come mezzo per il benessere, ma come via per esplorare la complessità dell’esperienza umana, offrendo strumenti preziosi a chi opera nei campi dell’educazione fisica, della psicomotricità e della didattica delle attività motori
Role of Non-Invasive Ventilation in Elderly Patients: Therapeutic Opportunity or Medical Futility? An Updated Narrative Review
No full textBackground and Objectives: Acute respiratory failure (ARF) represents an increasingly relevant clinical challenge in older subjects due to population aging and the high prevalence of cardiopulmonary comorbidities. Non-invasive ventilation (NIV), developed as continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP), has become a first-line treatment in various forms of ARF, including acute cardiogenic pulmonary oedema (ACPE) and acute exacerbations of COPD (AECOPD), offering several clinical advantages. In this context, the limited evidence on the efficacy of NIV in older patients leaves considerable uncertainty as to whether it constitutes a valid therapeutic option or represents medical futility in these patients. Materials and Methods: This narrative review explores the use of NIV and its outcomes in four key clinical scenarios in the elderly: ARF due to ACPE, AECOPD, community-acquired pneumonia (CAP), and palliative/end-of-life care. Results: Strong evidence supports NIV use with improved outcomes in ACPE and AECOPD, even in older populations. Conversely, data on its use in pneumonia are inconclusive, with potential harm if applied inappropriately. In palliative care, NIV can help relieve symptoms, but if not used appropriately, it may extend suffering. Conclusions: Age alone does not appear to be a sufficient factor to determine whether or not to use NIV; it becomes relevant only when considered in conjunction with the purpose of its use and the patient's clinical history and condition. Data remain limited and often conflicting, particularly when investigating the elderly population and patients with a "do not intubate" (DNI) order. There is a need for additional research on these patients, focusing on long-term outcomes and quality of life
Empowering Public Interest Communication with Argumentation - Project Report
No full textThe EPICA (Empowering Public Interest Communication with Argumentation) project aims to improve Public
Interest Communication (PIC) through the use of advanced Computational Argumentation (CA) techniques. This
paper provides a summary of the technical results of the project and discusses future research direction
Management in a post +4°C environment
No full textEven if some still deny the global warming phenomenon, for purely short-term political reasons, facts and figures are now numerous enough to be absolutely sure that the increase in temperature on the surface of the Earth will be several degrees at the end of the 21st century. The only unknown fact is exactly how big this rise will be. The range is between 3 and 4°C, and more and more climate scientists think that 4°C is more and more probable considering the measures which have not been taken and are still not taken. Consequently, this drastic change, unseen since man appeared on Earth, will have huge impacts on all walks of life for the environment in a broad sense and of course for mankind in social and economic terms. This study first examines what the climatic situation would be at the end of the 21st century in the light of the scientific evidence available. Then, in the hypothesis of a +4°C world, the social, economic and management consequences are investigated. Finally, in front of this never seen challenge, a number of solutions to cope with this +4°C world are examined and proposed. The conclusions are that huge changes are needed to build new economic and management models and practices. Otherwise, the outcome is simple enough; mankind will not be able to survive, at least as it has been known since the appearance of homo sapien
La Laguna del Mar Menor como sujeto de derechos: comentario de la Sentencia del Tribunal Constitucional 142/2024, de 20 de noviembre
No full textLa Ley 19/2022 para el reconocimiento de la personalidad jurídica de la laguna del Mar Menor y su cuenca representa una gran innovación para nuestro ordenamiento jurídico, pero no sólo, también a nivel europeo. Esta norma, que reconoce por primera vez derechos a un ente natural en nuestro continente, ha sido avalada por la STC 142/2024. En este artículo se analiza esta importante sentencia, dando especial relevancia a su opinión acerca del reconocimiento de derechos a la laguna
A MULTI‐CENTER REAL‐LIFE ANALYSIS ON PATIENTS WITH LARGE B‐CELL LYMPHOMA AFTER FAILURE OF CAR‐T CELLS THERAPY
No full textIntroduction: CAR-T therapy has changed relapsed/refractory (R/R) Large B Cell Lymphoma (LBCL) treatment, yet nearly 60% of patients (pts) relapse. Several therapeutic options exist post-CAR-T, but their optimal use and accessibility remain unclear. This study evaluates the incidence, treatment strategies and outcomes for LBCL pts relapsing after CAR-T.
Methods: We retrospectively analyzed LBCL pts treated post-CAR-T failure across 15 centers of the Italian Lymphoma Foundation. All received commercial CAR-T cells (axicabtagene ciloleucel, axi-cel, or tisagenlecleucel, tisa-cel) by December 31, 2023. Pts provided EBMT informed consent.
Results: Among 241 CAR-T recipients, 119 (61 axi-cel, 58 tisa-cel) relapsed or were refractory. Most had Diffuse Large B-cell Lymphoma (72%), advanced stage (76%) and IPI ≥ 3 (59%). CRS occurred in 83% (severe 12%), ICANS in 23% (severe 8%). Relapse/progression was histologically confirmed in 50%, with CD19 loss in 48%.
At relapse, 77% (n = 92) received curative-intent therapy. Although 67% were intended for bispecific antibodies (BiAB), only 19% accessed them due to limited availability. Other therapies included polatuzumab-based regimens (27%), chemotherapy (22%), immunomodulatory agents (15%), radiotherapy (6%) and experimental drugs (11%). Outcomes were poor, with a median overall survival (OS) of 6.5 months in treated pts and 0.7 months in palliative care (Figure 1). OS was longest with BiAB (12.5 months) and polatuzumab regimens (8.7 months), outperforming chemotherapy (3.4 months, p = 0.003). Progression free survival (PFS) was also superior with BiAB (6 months) versus polatuzumab (3.9 months), Immunomodulants (2.1 months), or chemotherapy (1.2 months; p < 0.001). Best response rates were seen with BiAB (72.5% ORR, 50% CR) and polatuzumab (37% ORR, 33% CR).
At CAR-T infusion, bridging therapy response, IPI, CARHEMATOTOX score, stage, CRS, and ICANS correlated with post-CAR-T outcomes, but multivariate analysis confirmed only PET positivity at day 30. At CAR-T failure, ECOG > 1, LDH > 2× ULN, > 2 extranodal sites, relapse < 4 months, platelets < 100 × 109/L, and high EASIX score predicted poor prognosis. Multivariate analysis identified LDH, extranodal sites, and early relapse as OS predictors, while LDH and relapse timing were linked to PFS. Developed prognostic models for OS and PFS stratified pts into 3 risk categories (p < 0.001, Figure 1). The PC-PI score proposed by Iacoboni was also validated (Figure 1).
Pts in CR after salvage therapy had better PFS when consolidated with allogeneic stem-cell transplantation (allo-SCT; n = 16) (not reached vs. 15.9 months, p = 0.016), although OS was not significantly improved.
Conclusion: Post-CAR-T relapse in LBCL is associated with poor outcomes. BiAB show the most promise but have been difficult to access. Prognostic factors such as LDH, extranodal involvement, and early relapse can guide therapy. While allo-SCT may improve PFS in selected pts, its impact on OS requires further investigation
Psychological distress and well-being in university and high school students: a cross-sectional study in Italy
Get PDFObjective: Adolescence is a transitional period marked by psychosocial changes that can impact well-being. Mental disorders before university are linked to dropout and lower employment rates, affecting long-term outcomes. This study examines the psychological well-being of Italian students aged 18-25, exploring factors related to distress. Design: Cross-sectional survey. Setting: High schools and university in Verona, northern Italy. Participants: A total of 1766 students (88.96% university students and 11.04% high school students in their final year) were recruited. Inclusion criteria were being enrolled in high school or university in Verona, aged 18-25, with adequate Italian language proficiency and informed consent. No exclusion criteria were applied. Primary and secondary outcome measures: Primary outcomes were levels of psychological distress (Kessler Psychological Distress Scale-10-item - Kessler-10), anxiety and depression (Patient Health Questionnaire Anxiety and Depression Scale - PHQ-ADS) and well-being (WHO-Five Well-Being Index - WHO-5). Secondary analyses examined the association of these outcomes with sociodemographic and educational variables. Results: Most participants (88.6%) reported psychological distress (mean K-10=22.95, SD=6.64). Mild symptoms of anxiety and depression were reported by 47.1% and 43.3% of participants, respectively. Only 16.5% reported high psychological well-being. Female and non-binary students had worse mental health outcomes than males (p value <0.001). Students in their first 3 years of university exhibited better mental health compared with those in later years or high school (p value <0.001). Students living in owned properties had lower levels of anxiety and depression (p value=0.004). Conclusions: Psychological distress, anxiety and depression are widespread among Italian students. Gender, academic stage and living situation significantly impact mental health outcomes. The findings emphasise the need for targeted mental health interventions, particularly for non-binary and female students, as well as those in advanced academic years