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RIABILITAZIONE UDITIVA DI TIPO CHIRURGICO NELLE SORDITà TRASMISSIVE DELL’ORECCHIO MEDIO
No full textLo studio retrospettivo ha confrontato le principali tecniche di riabilitazione uditiva di tipo chirurgico
nelle ipoacusie trasmissive derivanti da patologie dell’orecchio medio, otiti croniche, discontinuità
della catena ossiculare, otosclerosi, prendendo in esame le procedure tradizionali di stapedoplastica,
ossiculoplastica (PORP e TORP) eseguite in primo e secondo tempo, sia con materiali autologhi che
sintetici, e l’impiego di sistemi protesici di ultima generazione, CochlearTM Osia System, come
alternativa per i casi non candidabili a chirurgia convenzionale. Sono stati analizzati i risultati
audiologici pre- e post-operatori in un campione di pazienti sottoposti a tali interventi, con valutazione
del guadagno uditivo a medio termine in una casistica monocentrica, i dati raccolti confermano un
significativo miglioramento dell’outcome audiologico nei pazienti trattati in tutti i gruppi chirurgici, con
una riduzione statisticamente significativa dell’air–bone gap medio residuo (18 dB) e migliore rispetto
alle raccomandazioni dell’AAO-HNS. La chirurgia dell’orecchio medio costituisce un cardine nella
gestione delle sordità trasmissive, l’evoluzione tecnologica dei dispositivi impiantabili come l’Osia2
trova spazio quando né la protesizzazione tradizionale né la risoluzione chirurgica è possibile e
consente oggi di estendere l’efficacia riabilitativa anche a pazienti tradizionalmente esclusi dal
trattamento convenzionale. Il carattere retrospettivo dello studio e il follow-up limitato a 6 mesi non
consentono una valutazione completa della stabilità a lungo termine dei risultati. Studi prospettici, con
campioni più ampi e follow-up esteso, potranno chiarire meglio l’impatto del materiale protesico sulla
durata del risultato uditivo e il ruolo del timing chirurgico (primo tempo vs second look
Blunt ADrenal Gland injUrY in major trauma. BAD GUY project
No full textThe Blunt ADrenal Gland injUrY (BAD GUY) project is a structured, multi-phase research program designed to clarify the epidemiology, clinical significance, and prognostic implications of blunt adrenal gland injury (BAGI) in major trauma. Given the increasing detection of adrenal injuries with modern computed tomography and the absence of standardized management or prognostic frameworks, the project aimed to determine whether BAGI represents an independent determinant of adverse outcomes or primarily a marker of overall trauma severity .
The first phase consisted of a systematic review and meta-analysis conducted according to PRISMA and AMSTAR guidelines, registered on PROSPERO. Eight retrospective studies encompassing over 379,000 trauma patients were analyzed. BAGI was consistently associated with higher Injury Severity Scores, supporting its role as a marker of high-energy trauma. However, no robust independent association with in-hospital mortality or length of stay was demonstrated after sensitivity analyses, and the certainty of evidence ranged from moderate to low. A major gap identified was the lack of standardized adrenal injury grading and limited evaluation of adrenal insufficiency in trauma populations .
The second phase addressed these gaps through a multicenter European retrospective cohort study involving nine trauma centers in Italy and Spain and nearly 2,000 patients with blunt thoraco-abdominal trauma. Using propensity-score matching, the study showed that BAGI was not independently associated with increased mortality or overall injury severity but clustered with complex thoracic and abdominal solid-organ injuries and higher utilization of angiography and interventional procedures. Stratification by Organ Injury Scale (OIS) demonstrated a graded relationship between adrenal injury severity and physiological derangement, transfusion requirements, and operative burden, while laterality analyses revealed distinct anatomical and resource-use patterns .
Overall, the BAD GUY project demonstrates that BAGI should not be regarded as a benign incidental finding, nor as an isolated prognostic determinant. Instead, its detection refines trauma severity assessment by signaling injury complexity and resource needs. The findings support the adoption of standardized adrenal injury grading, systematic reporting of laterality, and integration of endocrine evaluation in future prospective, multicenter trauma research
Nuovi approcci terapeutici nel melanoma e adenocarcinoma polmonare attraverso la generazione di organoidi da pazienti sottoposti ad intervento chirurgico
No full textIl cancro rappresenta un ecosistema complesso costituito non solo da cellule neoplastiche, ma anche da numerose cellule non tumorali come componenti stromali ed immunitarie che definiscono il microambiente tumorale (TME, Tumor Microenvironment). Le interazioni tra cellule tumorali, matrice extracellulare (ECM) e cellule non neoplastiche modulano in modo cruciale la progressione della malattia, la metastatizzazione e la risposta terapeutica. Tra i processi cellulari maggiormente alterati, il reprogramming metabolico e, in particolare il metabolismo lipidico, è emerso come un determinante chiave della sopravvivenza e dell’adattabilità tumorale.
L’enzima Stearoyl-CoA Desaturasi 1 (SCD1), coinvolto nella sintesi di acidi grassi monoinsaturi (MUFA) a partire da grassi saturi (SFA), gioca un ruolo fondamentale nel mantenimento della plasticità metabolica e nella regolazione delle cellule staminali tumorali (CSCs). La sua over-espressione è stata associata a proliferazione, invasività e resistenza farmacologica in diversi tumori, tra cui melanoma e adenocarcinoma polmonare non a piccole cellule (NSCLC). L’inibizione di SCD1, sia farmacologica sia genica, si è dimostrata capace di ridurre la vitalità delle CSCs, di indurre apoptosi e di ripristinare la sensibilità ai trattamenti convenzionali.
Parallelamente, il metabolismo lipidico influenza profondamente anche le cellule immunitarie e stromali del TME, contribuendo alla formazione di un ambiente immunosoppressivo che favorisce la progressione neoplastica e la resistenza ai farmaci. Lo studio integrato delle interazioni metaboliche e immunologiche nel TME rappresenta quindi una prospettiva promettente per l’identificazione di nuovi biomarcatori predittivi e lo sviluppo di strategie terapeutiche innovative.
In questo contesto, il presente progetto di ricerca si propone di indagare le interazioni tra metabolismo lipidico, microambiente tumorale e CSCs nel melanoma e nell’adenocarcinoma polmonare, con l’obiettivo di individuare nuovi bersagli molecolari e approcci terapeutici personalizzati. A tal fine, sono stati sviluppati e caratterizzati modelli tridimensionali (3D) in vitro, comprendenti organoidi derivati da paziente (PDOs), che riproducono fedelmente l’eterogeneità genetica, molecolare e funzionale del tumore originario. La generazione e l’impiego di tali modelli sono resi possibili dalla raccolta sistematica e dalla conservazione di campioni biologici all’interno di biobanche, che rappresentano infrastrutture fondamentali per la medicina di precisione. Le biobanche consentono di integrare materiale biologico e dati clinico-molecolari, favorendo la stratificazione dei pazienti e la validazione di approcci terapeutici mirati. In questo senso, i modelli 3D derivati da pazienti, conservati secondo procedure standard ben definite, tali da garantirne la qualità, la coerenza e la tracciabilità, costituiscono potenti strumenti preclinici per lo studio dei meccanismi di resistenza farmacologica e per la valutazione della risposta ai trattamenti, contribuendo in modo significativo al progresso della medicina personalizzata in oncologia
Cybersecurity with LLMs and RAGs: Challenges and Innovations
No full textDespite the significant advances that Large Language Models (LLMs) offer in processing vast amounts of data and providing actionable insights quickly, their application in the technical field of cybersecurity poses significant challenges. These include the tendency to produce hallucinatory and unreliable results when these models are tested on questions where factuality is important. Furthermore, while Retrieval Augmented Generation (RAG) systems are useful in enriching model answers with relevant information, they struggle with issues related to retrieval speed, choice of embeddings and thresholds and handling multi-hop queries. This paper describes these challenges and discusses strategies to overcome them in order to improve the adaptability and reliability of these models in responding to rapidly evolving cybersecurity threats
Critica e costruttivismo. Butler, Foucault e l'eredità di Kant
No full textNegli ultimi trent’anni, studi kantiani e studi femministi hanno cominciato a incontrarsi: esiste oggi un
femminismo kantiano. Esso si colloca però quasi interamente all’interno della tradizionale liberale
analitica. Ne derivano una serie di limiti significativi: un kantismo privato della sua strutturale
sistematicità e come ridotto a ricettacolo di argomenti morali e giuridici; un femminismo estraneo alle
recenti elaborazioni concettuali della sua stessa tradizione; la fondamentale assenza di ogni prospettiva
storica. Il mio lavoro si propone di guardare oltre questi limiti, ponendo l’opera kantiana in relazione con la
critica costruttivista foucaultiana di Judith Butler. A partire da alcune affermazioni di Butler, solo
marginalmente indagate dalle interpreti, esso si muove a ricostruire l’«eredità di Kant» all’interno della
sua concezione della critica. Questa appare ovviamente mediata dall’originale appropriazione kantiana
operata da Michel Foucault. La ricerca finisce così per ricostruire una precisa genealogia della critica
costruttivista di Butler e Foucault, che si presenta come un recupero trasformativo della riflessione
kantiana. Indagine trascendentale e trasformazione illuminista del mondo, il cui nesso fonda il senso
ultimo dell’opera di Kant, ritornano entrambe in modo originale nella loro concezione della critica, in
un «groviglio di continuità e discontinuità» che consente di riconoscervi una tradizione di sviluppo del
kantismo alternativa a quella dominante, ma non per questo illegittima. Su questo riconoscimento si
fonda il contributo propriamente teorico all’interpretazione dell’opera di Butler: che cioè la sua
peculiare concezione costruttivista, fondata sull’attestazione di un'inevitabile finitezza della
costituzione e sul rifiuto di fondarla in una realtà in sé stessa, divenga realmente comprensibile, contro i
consueti fraintendimenti, a partire da una ben diffusa lettura dell’idealismo trascendentale
Multifunctional poly(vinyl alcohol) gel systems for radiation protection and sensing in space environment
No full textProtecting astronauts from the extreme radiation environment during long duration missions to the Moon or Mars is a fundamental challenge. Space agencies are currently evaluating the possibility of establishing permanent lunar bases as staging points for crewed missions into deep space, where exposure to solar particle events (SPEs) and galactic cosmic radiation (GCR) poses critical health and safety risks. In this context, the development of lightweight, flexible, hydrogen-rich materials with high stopping power for radiation protection has become a key priority. This doctoral research focuses on the design, fabrication and characterization of poly(vinyl alcohol) (PVA)-based gelled systems designed for various space applications. Two main experimental approaches were used for the fabrication of PVA-based gels. First, physically cross-linked PVA gels were fabricated through controlled freeze-thaw (FT) cycles to study the influence of water content on structural and mechanical properties. Subsequently, gels chemically cross-linked with boric acid (BA) were synthesised to improve radiation attenuation. Comprehensive experimental characterization was conducted to assess mechanical, thermal, electrical, and spectroscopic properties, confirming the potential of these gels as multifunctional materials.
This study pursues three main objectives: the development of self-healing, thermally insulating layers for extravehicular spacesuits, the enhancement of neutron shielding performance for radiation protection in space, and the fabrication of electrically conductive gels capable of supporting embedded sensing for structural health monitoring. First, PVA/BA gels were studied as intermediate layers between the pressure bladder garment (PBG) and the liquid cooling and ventilation garment (LCVG) of spacesuits, with the aim of improving radiation shielding during extravehicular activities (EVA) on the Moon without altering the ergonomics or geometry of the suit. Thanks to their high-water content, these gels combine softness and ductility with strong radiation attenuation. Experiments demonstrated comparable density and thermal conductivity, but markedly superior flexibility in the gels, highlighted by higher local strain under tensile stress with elongations up to ∼ 65%. Simulations with NASA’s On-Line Tool for the Assessment of Radiation in Space (OLTARIS)
confirmed effective protection against SPE protons on the lunar surface. To improve neutron attenuation in long-duration missions, PVA/polyethylene glycol (PVA/PEG) composite hydrogels filled with boron carbide (B4C) were fabricated through physical cross-linking. Characterization by infrared spectroscopy and thermal conductivity measurements confirmed good structural integrity and stability. Numerical simulations performed with OLTARIS tool and NGCal software showed that these gels achieve dose reductions comparable to water and superior to aluminum, owing to the high hydrogen and boron concentrations. Finally, multifunctional PVA–MWCNTs gels were designed for combined radiation shielding and strain sensing. Compression tests and quasi-static tensile tests coupled with impedance monitoring were used to evaluate electromechanical stability
Proteomic Profiling of Non-Muscle Invasive Bladder Cancer Reveals Stage-Specific Molecular Signatures and Prognostic Biomarkers
No full textBackground: Non-muscle invasive bladder cancer (NMIBC) comprises high-grade (HG) and low-grade (LG) variants, classified by aggressiveness, recurrence risk, and stage—either non-invasive (pTa) or invading the lamina propria (pT1). Cystoscopy remains the diagnostic gold standard, with no less-invasive alternatives, while molecular mechanisms driving tumorigenesis and treatment response are poorly understood. Methods: To address this gap, we conducted a preliminary top-down proteomic study on fresh biopsies from pTa-LG and pT1-HG NMIBC at initial diagnosis to identify molecular differences and potential prognostic biomarkers. Results: Distinct protein profiles were observed between stages. Highly abundant proteins in pT1-HG were associated with nitric oxide biosynthesis, signal transduction, inhibition of apoptosis, protein folding, and immune response. Proteins of low abundance were related to cellular localization, cytoskeleton organization, cell adhesion, phagocytosis, and tissue development. Notably, multiple proteoforms of PDC6I/ALIX, a protein implicated in the regulation of apoptosis, proliferation, and PD-L1 surface presentation, were significantly downregulated in pT1-HG tumors. Furthermore, the abundance of proteins such as GANAB, GALE, THIC, SEPT8, and MYDGF/C19orf10 correlated with tumor size, suggesting their potential as prognostic biomarkers. Conclusions: These proteins, taken together, indicate that they may serve as valuable prognostic markers, offering a path toward more personalized management of NMIBC beyond the traditional one-size-fits-all approac
Maintenance and Safety of the Road Infrastructure by a New Robotised System for Pothole Repair
No full textThe essential needs to maintain the integrity, performance, and safety of road infrastructures have been tackled in InfraROB, a research project funded by the EU research programme Horizon 2020 that aims to reach that objective through autonomous robotised solutions. A specific task of the project is the development of a 3D printer able to extrude a mixture for filling in small potholes. The printer is integrated into a small carrier that can autonomously reach the pothole while the operator remains in a safe roadside area. The study about the mixture was focused on material that, immediately after the laying, can be compacted by the wheels of the maintenance vehicle itself and later by the traffic vehicles. The development of the novel system, and its integration into an autonomous carrier was divided into four different phases: i) definition of the constraints due to the autonomous carrier; ii) definition of the parameters of the 3D printer system and repairing mixture; iii) design and construction of the 3D printer, and iv) system integration with the autonomous carrier. The final choice led to a mixture composed of 100% Reclaimed Asphalt Pavement and rejuvenator to be extruded through a head complying with the requested dimensions and weight. This paper also describes the printer’s design consistent with the robot dimension and the preliminary phase of its integration with the autonomous carrier
Shear viscosity assessment in nanoconfined water inside 3D model human mineralized collagen fibril
No full textThis work presents a 3D numerical model of the human mineralized collagen fibril developed to quantitatively analyse the shear viscosity and diffusion of nanoconfined water within bone tissue at the nanoscale based on a 3D random walk approach. The analysis of transport properties has been conducted at different longitudinal reference quotes and along the three main directions of the fibril to quantify the tissue non-homogeneity and anisotropy by considering a physiological volume fraction. The diffusion has been characterised by analysing the Brownian motion of water molecules, and the shear viscosity by using the Stokes-Einstein-Sutherland relation. The results indicate non-homogeneous and anisotropic properties of water within the bone nanostructure, and notably different values than the bulk water at the macroscale with no structural confinements. Transport properties of water play a key role in the bone mechanobiology by influencing the supply of mineral ions and growth factors, the nucleation process and the tissue remodelling activity. This model can support the design and features of biomimetic scaffolds and enhance the understanding of bone mechanobiology at the nanoscale
Advancing the understanding of performance monitoring with conventional and cutting-edge non-invasive brain stimulation techniques
No full textmonitoring is a fundamental cognitive function that enables individuals to evaluate and adjust their actions in pursuit of goals. Dysfunction in this system can lead to deficits in goal-directed behaviour, conflict resolution, and error processing, as observed in several clinical conditions. Moreover, growing evidence indicates that body representation may also play a role in performance monitoring. The present work adopts a multimodal approach combining behavioural, electrophysiological, and non-invasive brain stimulation (NIBS) methods to investigate the neural mechanisms underlying performance monitoring and embodiment. In the first study, theta transcranial alternating current stimulation was applied over fronto-parietal areas to entrain endogenous theta rhythms during a Flanker-like task. The stimulation led to improved conflict adaptation reflected by faster reactions times following conflict conditions, suggesting a state-dependent facilitation of fronto-parietal communication during high-conflict processing. The second study employed transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex combined with electroencephalographic recording, during action observation of an embodied virtual avatar in an immersive virtual reality environment. High-embodiment conditions elicited an enhanced contralateral fronto-parietal activation and concurrent ipsilateral inhibition, consistent with neural embodiment processes and optimized motor control. Moreover, early modulations of TMS-evoked potentials likely reflected neurotransmitter fluctuations associated with error processing, and embodiment-related variations driven by action outcome. Finally, the third study tested an excitatory transcranial focused ultrasound stimulation protocol to evaluate its capability to modulate corticospinal excitability via motor-evoked potentials. Although preliminary, the results identified an effective control condition mitigating auditory confounds. Overall, this work highlights the complementary potential of standard and innovative NIBS techniques to elucidate the neural dynamics of performance monitoring