Archivio istituzionale della ricerca - Università dell'Insubria
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Editoriale
Full text linkEditoriale di presentazione del numero 69 della rivista Coscienza e Libertà, intitolato «L’abuso sulla persona nelle religioni», dedicato all’analisi delle forme di abuso all’interno delle istituzioni religiose
Energy communities – lessons learnt, challenges, and policy recommendations
Full text linkEnergy communities (ECs) are considered important in transitioning the energy system. They are of particular interest due to their potential to empower citizens and support a more just energy transition. However, experiences from ECs remain limited and vary across countries, thus raising questions on potential future advancements. In this article, we explore experiences from ECs in several European countries to inspire discussions on further evolvement and improvements. Insights into lessons learned and key challenges within the selected countries have been collected and analysed, and recommendations for advancing these efforts are provided to policy makers. The results indicate that ECs are making progress in producing and sharing renewable energy while supporting a more just energy transition by engaging a variety of actors within local communities. The challenges, however, often stem from limited national support and difficulties in fully achieving diversity within engaged local communities. The recommendations stress the importance of building on early learnings in community energy and further strengthening local anchoring to achieve a just transition. This in turn, generates fertile ground for discussions on how to localize energy policy and reinforce a multi-level policy approach beyond the European and national levels.Energy communities (ECs) are considered important for transitioning the energy system, and empowering citizens to support a more just energy transition. This article focuses on experiences in ECs across several European countries indicating progress in ECs supporting renewable energy and engaging a variety of actors. However, challenges often stem from limited national support and difficulties in achieving full diversity within engaged local communities. To enable further progress, it will be important to build on early learnings in community energy, strengthen local anchoring, and adopt a multi-level policy approach
Innovatività e sostenibilità della ricerca e dello sviluppo dei farmaci per il trattamento delle malattie rare: un'analisi comparata.
Full text linkLa tesi esamina i profili giuridici inerenti alla ricerca e allo sviluppo dei farmaci orfani, con particolare enfasi sulla determinazione del prezzo. Analizza il sistema giuridico degli Stati Uniti, con particolare riferimento all’Orphan Drug Act, confrontandolo con il regolamento europeo (CE) n. 141/2000. Successivamente, vengono esaminati i meccanismi di definizione del prezzo negli Stati Uniti e in Italia, evidenziando le dinamiche di mercato e i criteri di valutazione costo-efficacia, mettendo a confronto gli effetti prodotti dalle normative federali e europee sui sistemi sanitari dei due Paesi.The thesis examines the legal profiles associated with the research and development of orphan medicinal products, with a focus on pricing. It analyses the US legal system with particular reference to the Orphan Drug Act and compares it with the European Regulation (EC) No 141/2000. It then examines the pricing mechanisms in the United States and Italy, highlighting the market dynamics and the criteria for evaluating cost-effectiveness and comparing the impact of federal and European regulations on the healthcare systems of the two countries
Metabolic reprogrammed primary skin fibroblasts as patient specific cellular models for Parkinson's disease
Full text linkMitochondria are crucial organelles which undergo fusion and fission processes responsible for mitochondrial network rearrangements. Once mitochondria are damaged, they are selectively degraded by mitophagy. Collectively, these processes are referred to as mitochondrial dynamics, and dysregulations that hamper their function are often associated with neurodegenerative diseases like Parkinson’s disease (PD). Mutations in mitophagy-related PRKN gene, which encodes the E3 ubiquitin ligase Parkin, have been linked to autosomal recessive juvenile PD. Recently, molecular players of the endosomal-lysosomal pathway such as Rab proteins, have been linked to the mitophagic pathway, indeed, mutations in RAB32 and RAB39B have been identified to cause familial PD. In order to elucidate the interplay between Rab proteins and dysfunctional mitophagy in PD, we exploited PRKN-mutated and control human skin fibroblasts to evaluate levels and sub-cellular localization of a Rab protein subset. First of all, to make fibroblasts more sensitive to mitochondrial damages and metabolically more similar to neurons, we induced a metabolic reprogramming toward oxidative phosphorylation. The changes in CS and COX5B protein levels suggested that the protocol succeeded in the metabolic reprogramming of both control and PRKN-mutated fibroblasts. Moreover, we exploited mitochondrial toxins related to PD, Rotenone and 1-methyl-4-phenylpyridinium (MPP+), to induce mitophagy. Both treatments induced mitochondrial depolarisation and alterations in mitochondrial marker levels, but MPP+ was the selected toxin since it induced the higher mitochondrial depolarisation. Exploiting our final model, reprogrammed skin fibroblasts treated with a mitochondrial toxin, we evaluated the mitochondrial network morphology, the mitochondrial mass, and the Rab protein levels in PRKN-mutated fibroblasts. We observed increased RAB9 levels in PRKN-mutated fibroblasts especially after MPP+ treatment. RAB9 is usually associated to alternative PINK1/Parkin-mediated mitophagy, thus hinting a role of Rab proteins in mitochondrial dynamics related to PD. In conclusion, this thesis established a set-up (metabolic reprogramming and MPP+ treatment) that enables the use of skin fibroblasts as personalized cellular models to study mitochondrial dynamics related to PD. Furthermore, the preliminary study on Rab proteins involved in mitophagy revealed altered levels of these vesicular trafficking regulators in PRKN-mutated fibroblasts, particularly following mitophagy induction.Mitochondria are crucial organelles which undergo fusion and fission processes responsible for mitochondrial network rearrangements. Once mitochondria are damaged, they are selectively degraded by mitophagy. Collectively, these processes are referred to as mitochondrial dynamics, and dysregulations that hamper their function are often associated with neurodegenerative diseases like Parkinson’s disease (PD). Mutations in mitophagy-related PRKN gene, which encodes the E3 ubiquitin ligase Parkin, have been linked to autosomal recessive juvenile PD. Recently, molecular players of the endosomal-lysosomal pathway such as Rab proteins, have been linked to the mitophagic pathway, indeed, mutations in RAB32 and RAB39B have been identified to cause familial PD. In order to elucidate the interplay between Rab proteins and dysfunctional mitophagy in PD, we exploited PRKN-mutated and control human skin fibroblasts to evaluate levels and sub-cellular localization of a Rab protein subset. First of all, to make fibroblasts more sensitive to mitochondrial damages and metabolically more similar to neurons, we induced a metabolic reprogramming toward oxidative phosphorylation. The changes in CS and COX5B protein levels suggested that the protocol succeeded in the metabolic reprogramming of both control and PRKN-mutated fibroblasts. Moreover, we exploited mitochondrial toxins related to PD, Rotenone and 1-methyl-4-phenylpyridinium (MPP+), to induce mitophagy. Both treatments induced mitochondrial depolarisation and alterations in mitochondrial marker levels, but MPP+ was the selected toxin since it induced the higher mitochondrial depolarisation. Exploiting our final model, reprogrammed skin fibroblasts treated with a mitochondrial toxin, we evaluated the mitochondrial network morphology, the mitochondrial mass, and the Rab protein levels in PRKN-mutated fibroblasts. We observed increased RAB9 levels in PRKN-mutated fibroblasts especially after MPP+ treatment. RAB9 is usually associated to alternative PINK1/Parkin-mediated mitophagy, thus hinting a role of Rab proteins in mitochondrial dynamics related to PD. In conclusion, this thesis established a set-up (metabolic reprogramming and MPP+ treatment) that enables the use of skin fibroblasts as personalized cellular models to study mitochondrial dynamics related to PD. Furthermore, the preliminary study on Rab proteins involved in mitophagy revealed altered levels of these vesicular trafficking regulators in PRKN-mutated fibroblasts, particularly following mitophagy induction
Potential pharmacological effect of Quercetin PhytosomeTM in the management of hyperuricemia: results from real-life clinical studies
Full text linkBackground: Hyperuricemia is associated with several metabolic and cardiovascular disorders, and traditional treatments, such as xanthine oxidase (XO) inhibitors, often have limitations, such as severe hypersensitivity reactions or ineffectiveness in achieving target serum urate levels in some patients. Quercetin, a naturally occurring flavonoid, has shown potential as a hypouricemic agent through XO inhibition. Objective: This study aims to evaluate the potential hypouricemic effect of Quercetin PhytosomeTM (QP) supplementation across three cohort studies involving healthy adults with various metabolic health profiles, exploring its potential as a safe, effective intervention for hyperuricemia. Methods: Clinical data collected in various clinics in Italy between September 2021 and April 2024 under real-life clinical settings from three distinct cohort studies, were analyzed. Cohort 1 consisted of 164 healthy participants (87 QP-treated, 77 probiotic Streptococcus salivarius (S. salivarius) K12-treated) who were monitored for 90 days. Cohort 2 included 22 mildly hyperuricemic adults with metabolic disorders receiving QP, while Cohort 3 comprised 64 obese adults with hypercholesterolemia, further divided into moderately hyperuricemic QP-treated group (n = 20), a moderately hyperuricemic Berberine PhytosomeTM and monacolins (BM)-treated group (n = 22), and a normouricemic BM-treated group (n = 22). QP was administered at 400 mg of quercetin daily in all cohorts. Primary endpoints were reductions in serum uric acid levels, while secondary outcomes included effects on lipid profile, glycemia, liver enzymes, and treatment tolerability. Results: In Cohort 1, QP significantly reduced uric acid levels by 15.2% in males and 13.8% in females, with no significant changes observed in the probiotic group. Cohort 2 showed a significant 13.1% reduction in uric acid (p < 0.01) and a concurrent 10.2% reduction in triglycerides (p < 0.05). In Cohort 3, QP led to a 13.7% decrease in uric acid and a 20.8% reduction in triglycerides (p < 0.01), with no significant uric acid changes in the BM-treated group. QP was well tolerated across all cohorts, with minimal, transient side effects. Conclusion: QP supplementation demonstrates a significant hypouricemic effect. Additionally, triglyceride-lowering benefits were evident, particularly in metabolically compromised individuals (Cohorts 2 and 3), where these effects were statistically significant. With high tolerability, these findings highlight Quercetin PhytosomeTM's potential as a safe adjunctive therapy for hyperuricemia management, meriting further investigation in larger, randomized trials to confirm its efficacy and safety. Clinical trial registration: clinicaltrials.gov, identifier NCT06652035
Public grants beneficiaries and venture capital‐backed firms: a tale of two funding strategies
Full text linkAlthough firm characteristics play a crucial role in predicting future performance, public
agencies often overlook these factors in their funding decisions, unlike Venture Capital
investors. This oversight may have implications for the pay-offs from publicly allocated
funds and the achievement of policy objectives. To explore the role of firm characteris-
tics in receiving public grants and Venture Capital funding, we compare the characteristics
of beneficiaries of the SME Instrument—one of the most innovative funding instruments
for innovative companies in Europe—with those of VC-backed firms. Our findings reveal
different funding strategies: Venture Capitalists tend to fund younger and more innova-
tive firms, while SME Instrument grants lean towards smaller and older companies. These
trends persist even when considering factors such as bank indebtedness and profitability.
Additionally, firms that are more profitable are more likely to secure public grants than
VC-backed counterparts are. The difference in funding strategies may be related to the
varying levels of risk tolerance of public agencies and Venture Capitalists, with the pub-
lic agency potentially being more risk-averse than its private counterparts are. Our study
underscores the potential need to refine the selection criteria of the public funding program
to align it with the expected role of public funding in de-risking uncertain ventures in their
early development phase
Tropicalization through the lens of Łukasiewicz logic, with a topos theoretic perspective
No full textAcute kidney injury and aorta-related mortality during open surgery of the abdominal aorta with suprarenal clamping using different renal protection strategies
No full textOBJECTIVES: The aim was to evaluate the incidence of acute kidney injury in patients treated with open surgical repair and suprarenal cross-clamp comparing no-perfusion strategy versus the renal perfusion with the histidine-tryptophan-ketoglutarate solution. METHODS: It is a physician-initiated, multicentre, retrospective observational study including patients treated with open surgical repair for abdominal aortic aneurysm between 1 January 2015 and 31 December 2021. Patients already on dialysis were excluded from the final analysis. A coarsened exact match identified 2 cohorts: no-perfusion strategy versus renal perfusion with the histidine-tryptophan-ketoglutarate solution. Primary outcomes were acute kidney injury incidence and survival at 30 day. Secondary outcomes were freedom from haemodialysis and survival at 1 year. RESULTS: We analysed 125 (28.7%) patients: 63 (14.5%) who did not receive renal perfusion and 62 (14.2%) who received the histidine-tryptophan-ketoglutarate perfusion. At 30 day, acute kidney injury rate (37.6%) was not different between the 2 groups [n = 24 (38.7%) vs 23 (36.5%); OR: 1.1, P = 0.855]. At 30 day, acute kidney injury development was associated with aneurysm extent (pararenal, OR: 2.28, 95% CI: 1.031-5.031, P = 0.042) and total time of intervention (threshold: 365 min, OR: 1.008, 95% CI: 1.003-1.012, P = 0.001). At 1 year, postoperative acute kidney injury did not impact mortality (OR: 3.4, P = 0.556), and freedom from haemodialysis was 100%. CONCLUSIONS: Postoperative acute kidney injury remains high at nearly 38%, but it did not impact on freedom from haemodialysis at 1 year as well as on overall survival