Innovatività e sostenibilità della ricerca e dello sviluppo dei farmaci per il trattamento delle malattie rare: un'analisi comparata.

La 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

The multiple facets of ovarian high grade serous carcinoma: A review on morphological, immunohistochemical and molecular features

High-grade serous ovarian carcinoma (HGSOC) is the most aggressive subtype of epithelial ovarian cancer and a leading cause of mortality among gynecologic malignancies. This review aims to comprehensively analyze the morphological, immunohistochemical, and molecular features of HGSOC, highlighting its pathogenesis and identifying biomarkers with diagnostic, prognostic, and therapeutic significance. Special emphasis is placed on the role of tumor microenvironment (TME) and genomic instability in shaping the tumor's behavior and therapeutic vulnerabilities. Key advancements, such as the identification of TP53 and BRCA mutations, the classification of homologous recombination repair (HRR) deficiencies, and the clinical implications of biomarkers like folate receptor alpha (FRα) and PD-L1 are discussed. These findings reveal actionable insights into targeted therapies, including immune checkpoint inhibitors and PARP inhibitors, which hold promise for improving outcomes in HGSOC. This synthesis of knowledge aims to bridge gaps in understanding HGSOC's multifaceted biology, enhance clinical decision-making, and foster the development of precision therapies

Comprehensive Assessment of Pollution Dynamics in Lake Como: Zooplankton, Microplastics, and Sustainable Water Management Strategies.

Lake Como in Northern Italy is a vital freshwater ecosystem that supports a range of socioeconomic activities, including tourism, agriculture, and energy generation. This multifunctional role, however, has led to increased pollution pressures, particularly through the influx of microplastics and other aquatic debris, exacerbated by high tourism volume impacts. Despite growing concerns over microplastic contamination in freshwater systems, most existing research focuses on marine environments, leaving a critical knowledge gap regarding lakes. This thesis aims to address this gap by investigating the sources, distribution, and ecological impacts of plastic debris (and its derivatives e.g. microplastics) pollution in Lake Como, with a particular emphasis on effects on zooplankton, an essential component of the lake's food web and a key bioindicator of water quality. This research pursues four main objectives: (1) to analyze the concentration, composition, and spatial distribution of microplastics in Lake Como through systematic sampling and laboratory analysis; (2) to assess how climate change is affecting the functioning of wastewater treatment plants (WWTPs) in the region and their ability to manage microplastic loads; (3) to explore the effects of algal bloom-induced turbidity on debris detection and ecological assessment, using advanced remote operating vehicle (ROV) technology for monitoring; and (4) to investigate the application of circular economy principles in waste management, with a specific focus on recycling textile waste as a strategy to curb pollution in freshwater systems. Fieldwork conducted over multiple seasons involved sampling eight sites across Lake Como, coupled with ROV monitoring to document both floating and submerged debris. Preliminary results reveal a heterogeneous distribution of plastics, with higher concentrations near populated and tourist areas, indicating localized pollution sources. Analysis shows that the types of microplastics range from fragments to fibres, implicating both municipal waste and industrial discharge as contributors. Furthermore, climate-related stressors, such as extreme weather events and increased runoff, have been shown to impair WWTP efficiency, complicating efforts to control microplastic contamination. The findings highlight an urgent need for 4 innovative waste management strategies. Circular economy practices, particularly textile waste recycling, are proposed as viable solutions to reduce microplastic inputs and enhance sustainable waste utilization. This study not only contributes to the limited but growing literature on freshwater microplastic pollution but also offers practical recommendations for pollution mitigation and ecosystem health preservation in Lake Como and similar freshwater bodies. These recommendations include policy interventions and infrastructure improvements that can help manage anthropogenic pressures on freshwater ecosystems in a changing climate.Lake Como in Northern Italy is a vital freshwater ecosystem that supports a range of socioeconomic activities, including tourism, agriculture, and energy generation. This multifunctional role, however, has led to increased pollution pressures, particularly through the influx of microplastics and other aquatic debris, exacerbated by high tourism volume impacts. Despite growing concerns over microplastic contamination in freshwater systems, most existing research focuses on marine environments, leaving a critical knowledge gap regarding lakes. This thesis aims to address this gap by investigating the sources, distribution, and ecological impacts of plastic debris (and its derivatives e.g. microplastics) pollution in Lake Como, with a particular emphasis on effects on zooplankton, an essential component of the lake's food web and a key bioindicator of water quality. This research pursues four main objectives: (1) to analyze the concentration, composition, and spatial distribution of microplastics in Lake Como through systematic sampling and laboratory analysis; (2) to assess how climate change is affecting the functioning of wastewater treatment plants (WWTPs) in the region and their ability to manage microplastic loads; (3) to explore the effects of algal bloom-induced turbidity on debris detection and ecological assessment, using advanced remote operating vehicle (ROV) technology for monitoring; and (4) to investigate the application of circular economy principles in waste management, with a specific focus on recycling textile waste as a strategy to curb pollution in freshwater systems. Fieldwork conducted over multiple seasons involved sampling eight sites across Lake Como, coupled with ROV monitoring to document both floating and submerged debris. Preliminary results reveal a heterogeneous distribution of plastics, with higher concentrations near populated and tourist areas, indicating localized pollution sources. Analysis shows that the types of microplastics range from fragments to fibres, implicating both municipal waste and industrial discharge as contributors. Furthermore, climate-related stressors, such as extreme weather events and increased runoff, have been shown to impair WWTP efficiency, complicating efforts to control microplastic contamination. The findings highlight an urgent need for 4 innovative waste management strategies. Circular economy practices, particularly textile waste recycling, are proposed as viable solutions to reduce microplastic inputs and enhance sustainable waste utilization. This study not only contributes to the limited but growing literature on freshwater microplastic pollution but also offers practical recommendations for pollution mitigation and ecosystem health preservation in Lake Como and similar freshwater bodies. These recommendations include policy interventions and infrastructure improvements that can help manage anthropogenic pressures on freshwater ecosystems in a changing climate

Dupilumab Effectiveness in Patients with Severe Allergic Asthma Non-Responsive to Omalizumab

Background/Objectives: Severe allergic asthma is usually treated with omalizumab; however, this drug may not be effective for every patient. By its action, dupilumab could be an alternative in these patients. The objective of this study was to evaluate the efficacy of dupilumab in patients with severe allergic asthma, non-responsive to omalizumab, according to the maintenance of their oral corticosteroid (OCS) dose, an exacerbation rate decrease, or poor control of the disease, despite optimized treatment. Methods: A retrospective analysis of data from severe asthma clinics was performed, observing the efficacy of the switch to dupilumab in patients who experienced a failed treatment with omalizumab. Results: Forty-two patients were included. Dupilumab proved to be effective in patients who experienced a failed omalizumab treatment, with a significant reduction in the exacerbation number and OCS use. Furthermore, remission of the disease, according to the Severe Asthma Network of Italy (SANI) criteria, was achieved in 35 patients, with complete remission in 19 (45%) and partial remission in 16 (38%). The analysis of the predictors of the success of dupilumab therapy in achieving clinical remission, through univariate analysis of the data at baseline, showed that complete remission was more easily reached in patients with concomitant aspirin (ASA) intolerance or in those with nasal polyposis. Conclusions: Dupilumab is an effective drug for the treatment of patients with severe asthma with an allergic component, with better benefits in patients with an ASA intolerance or nasal polyposis

Creative city narratives vs. lived realities: an ethnographic study of UNESCO designation in Como, Italy

Introduction: This study examines how cultural producers perceive and interpret the UNESCO Creative City designation, focusing on Como, Italy, following its 2021 inclusion in the network. Anchored in critical urban theory and cultural sociology, the research investigates how institutional narratives of creativity intersect with the interpretive frameworks through which cultural actors understand their work. Methods: The research employed ethnographic methods, including semi-structured interviews with diverse cultural producers (theatrical practitioners, visual artists, craftspeople, musicians, filmmakers, venue operators), participant observation at cultural events, and document analysis. Data were analyzed using constructivist grounded theory principles. Results: Findings reveal three interrelated disjunctures: (1) institutional disconnection, expressed through parallel cultural worlds governed by conflicting evaluative logics; (2) spatial constraints, exacerbated by tourism intensification, that undermine conditions for creative practice; and (3) network fragmentation, which cultural producers seek to overcome through emergent forms of solidarity. The study demonstrate these tensions exist alongside the potential for virtuous relationships between Creative City designations and cultural tourism development, while also reflecting how local cultural forms are transformed into symbolic capital within broader urban development projects. Discussion: The study highlights significant tensions between top-down policy frameworks and bottom-up cultural labor, showing how local creative communities actively reinterpret, resist, and reshape institutional discourses. By centering cultural producers’ meaning-making practices, the research contributes to debates on culture’s instrumentalization in urban governance and offers insights for more inclusive, sustainable, and dialogic cultural policy approaches

Temperature-driven flows in nanochannels: Theory and simulations

The motion of a fluid induced by thermal gradients in the absence of external forces is known as thermo-osmosis. The physical explanation of this phenomenon stems from the emergence of gradients in the tangential pressure due to the presence of a confining surface. The microscopic origin of the effect has recently been elucidated in the framework of linear response theory. Here, by use of conservation laws, we provide an explicit solution of the equations governing the fluid flow at stationarity in slab geometry, expressing the thermo-osmotic coefficient as the integrated mass current-heat current correlation function (which vanishes in the bulk). A very simple expression for the pressure gradient in terms of equilibrium properties is also derived. To test the theoretical predictions in a controlled setting, we performed extensive nonequilibrium molecular dynamics simulations in two dimensions. Few simple models of wall-particle interactions are examined, and the resulting pressure drop and velocity profile are compared with the theoretical predictions both in the liquid regime and in the gas regime

Gender inequities in speaker representation and academic recognition: A cross-sectional observational study

Aim: This study evaluates gender disparities in speaker representation at the Italian Society of Orthodontists (SIDO) congresses (2020–2024) and the International Orthodontic Congress (IOC) 2020, focusing on gender distribution and academic impact, measured by the h-index. Materials and Methods: The SIDO congress programs (2020–2024) and IOC 2020 were analyzed to count male and female invited speakers. The h-index for each speaker was retrieved from the Scopus database to assess academic productivity. Statistical tests, including the Shapiro-Wilk test, independent samples t-test, and Kruskal-Wallis test, were used to analyze gender-based differences in representation and h-index values. Results: Data from the SIDO congresses showed a persistent gender imbalance in both representation and academic recognition. In 2020, only 6 out of 29 speakers were female, with their average h-index (7.33) significantly lower than that of male speakers (13.13). Female representation increased to 31 % in 2024, but their average h-index (8.95) still lagged behind males (11.13). At the IOC 2020, female speakers represented 24 % but had a higher average h-index (22.62) than males (20.91). Conclusions: This study highlights significant gender disparities in both speaker representation and academic recognition in orthodontics. Despite increased female participation at SIDO congresses, their academic impact remains lower than that of their male counterparts. These findings emphasize the need for initiatives promoting gender equality, such as mentorship programs and inclusive policies, to empower women and reduce the gender gap in academic and professional settings