Centro Studi Luca d’Agliano

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    THE ROLE OF THE CLINICIAN¿S SUBJECTIVE EXPERIENCE IN THE INTERACTION WITH THE PATIENT: A PILOT STUDY ON NEUROBIOLOGICAL CORRELATES

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    Introduzione. L'Assessment of Clinician's Subjective Experience (ACSE) è un questionario progettato per valutare l'esperienza soggettiva del clinico durante le interazioni con il paziente. Sebbene studi precedenti ne abbiano supportato l'affidabilità e la validità clinica, i suoi fondamenti neurobiologici rimangono inesplorati. Metodi. Due medici e dieci pazienti sono stati reclutati in uno studio in tre fasi: (1) una prima intervista clinica, (2) la somministrazione dell'ACSE e (3) l'ascolto della registrazione dell'intervista clinica. I dati elettroencefalografici (EEG) sono stati acquisiti sui medici durante la prima intervista clinica e durante la somministrazione dell'ACSE. I dati EEG sono stati analizzati utilizzando la densità spettrale di potenza relativa, la forza dei nodi e l'efficienza globale derivata dalla coerenza immaginaria. Risultati. I medici erano psichiatri, mentre i pazienti avevano una diagnosi di depressione e disturbi d'ansia. I punteggi dell'ACSE sono stati più alti per le dimensioni Difficoltà di Sintonizzazione e Coinvolgimento, in linea con i risultati precedenti. Le analisi EEG hanno rivelato distinti pattern specifici per frequenza e regione associati a ciascuna dimensione ACSE: la dimensione della Disconferma ha suscitato le risposte neurali più eterogenee in tutte le metriche EEG ed in entrambi i clinici. Le analisi di connettività hanno evidenziato profili di rete divergenti: Il clinico di sesso femminile ha mostrato una maggiore variabilità nell'efficienza globale, mentre il clinico di sesso maschile ha mostrato pattern più stabili. Infine, le analisi correlazionali hanno identificato specifiche associazioni tra le dimensioni ACSE e le caratteristiche EEG. Conclusione. Questi risultati preliminari forniscono la prima evidenza neurobiologica che collega l'esperienza soggettiva del clinico con un'attività cerebrale misurabile. Emerge che le dimensioni soggettive negli incontri clinici possono essere parzialmente codificate in pattern EEG distinti, gettando le basi per future ricerche sulla neurobiologia dei processi di intersoggettività.Background. The Assessment of Clinician’s Subjective Experience (ACSE) is a questionnaire designed to assess the clinician’s subjective experience during patient interactions. Although previous studies have supported its reliability and clinical validity, its neurobiological underpinnings remain unexplored. Methods. Two clinicians and ten patients were recruited in a three-phase study: (1) a first clinical interview, (2) ACSE administration, and (3) listening to the first clinical interview recording. Electroencephalography (EEG) data were recorded from clinicians during both the first clinical interview and the ACSE administration. EEG data were analyzed using relative power spectral density, node strength, and global efficiency derived from imaginary coherence. Results. Clinicians were psychiatrists, while patients were diagnosed with depressive and anxiety disorders. ACSE scores were highest for Difficulty in Attunement and Engagement dimensions, aligning with prior findings. EEG analyses revealed distinct frequency- and region-specific patterns associated with each ACSE dimension: the dimension of Disconfirmation elicited the most heterogeneous neural responses across all EEG metrics and both clinicians. Connectivity analyses highlighted divergent network profiles: the female clinician showed higher variability in global efficiency, while the male clinician exhibited more stable patterns. Finally, correlational analyses identified specific associations between ACSE dimensions and EEG features. Conclusion. These preliminary findings provide the first neurobiological evidence linking the clinician’s subjective experience with measurable brain activity. They suggest that subjective dimensions in clinical encounters may be partially encoded in distinct EEG patterns, laying the groundwork for future research on the neurobiology of intersubjectivity processes

    Code Less to Code More: Streamlining Language Server Protocol and type system development for language families

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    Developing editing support for L languages in E editors is complex and time-consuming. Some languages do not provide dedicated editors, while others offer a single native editor. The language server protocol (LSP) reduces the language-editor combinations L×E to L+E, where a single language server communicates with editors via LSP plugins. However, overlapping implementations of linguistic components remain an issue. Existing language workbenches struggle with modularity, reusability, and leveraging type systems for language server generation. In this work, we propose: (i) Typelang, a family of domain-specific languages for modular, composable, and reusable type system implementation, (ii) a modular language server generation process, producing servers for languages built in a modular workbench, (iii) the variant-oriented programming paradigm and a cross-artifact coordination layer to manage interdependent software variants, and (iv) an LSP plugin generator, reducing E to 1 by automating plugin creation for multiple editors. To simplify editing support for language families, each language artifact integrates its own Typelang variant, used to generate language servers. This reduces combinations to T×1, where T=L represents the number of type systems. Further reuse of language artifacts across languages lowers this to N×1, where N&lt

    Tuning bismuth oxyhalides for efficient amoxicillin removal: insights from crystal facets, toxicity and sustainability

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    In recent decades, the increasing presence of antibiotics in wastewater has become a critical environmental issue, posing significant risks to both ecosystems and human health [1]. Among the available advanced oxidation processes, heterogeneous photocatalysis has emerged as an effective and versatile treatment technology. Within this framework, bismuth oxyhalides (BiOX, where X = Cl, Br, or I) have attracted substantial interest owing to their unique structural and electronic features [2]. These materials crystallize in a distinctive tetragonal structure in which positively charged [Bi2O2] layers alternate with double layers of halide anions, generating an internal static electric field perpendicular to the slabs [3]. This built-in electric field promotes the separation and migration of photoinduced electrons and holes, ultimately enhancing photocatalytic efficiency. The photocatalytic performance of BiOX can be further tuned by controlling their exposed crystal facets, which strongly influence surface reactivity, charge dynamics, and adsorption properties. Facet engineering can be achieved through rational design of synthesis conditions—modulating reaction temperature and time, selecting suitable solvents, introducing capping agents, and choosing appropriate halogen precursors [3]. In this study, BiOBr and BiOCl photocatalysts were synthesized using potassium (K) and calcium (Ca) salts as halogen sources, and their bulk and surface properties were comprehensively characterized using a wide set of physico-chemical techniques (FESEM, XRD, N2 physisorption, Raman, photoluminescence, XPS, UV-Vis DRS, point of zero charge, EIS, Mott–Schottky analysis, and VB-XPS). XRD patterns highlighted the influence of the halogen precursor on crystal growth, with K-derived samples showing an increased exposure of the (110) facet [4]. This structural feature correlates well with the photocatalytic results obtained for amoxicillin (AMX) degradation ([AMX] = 10 mg L−1; catalyst dosage = 0.25 g L−1; irradiance = 35 W m−2): K-based BiOBr achieved complete AMX removal within 30 minutes, while the Ca-derived analogue reached ~70% only after 180 minutes. A similar trend was observed for BiOCl. The intrinsic toxicity of the materials was assessed using zebrafish embryo tests, confirming the biocompatibility of all samples. Furthermore, a Life Cycle Assessment (LCA) was performed to compare the environmental impacts of BiOX materials synthesized from different halide precursors, providing insights into greener and more sustainable production routes. In conclusion, the combination of facet engineering, toxicity assessment, and environmental impact analysis represents a robust strategy for optimizing BiOX photocatalysts. These results support the development of efficient, safe, and sustainable materials for the removal of antibiotics from wastewater

    DUAL TARGETING OF RFAP AND FIMH IMPAIRS AIEC INTRACELLULAR SURVIVAL AND LIMITS OMV-DEPENDENT IL-23/PTH17 AXIS ACTIVATION, OFFERING A NOVEL THERAPEUTIC STRATEGY FOR CROHN¿S DISEASE

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    Crohn’s disease (CD) is a chronic inflammatory disorder characterized by an aberrant inflammatory response against a dysbiotic gut microbiota. Especially, intestinal enrichment of the adherent-invasive Escherichia coli strain (AIEC), together with a dysregulated activation of the IL-23/pTh17 axis, is a distinctive feature of CD. In this context, current therapies primarily suppress the exaggerated inflammation without directly targeting AIEC, and the only AIEC-based approach under investigation is the inhibition of FimH, which mediates adhesion to intestinal epithelial cells. However, whether FimH inhibitors also affect other key steps of AIEC-host interaction, such as intramacrophagic replication, the associated excessive TNF-α secretion, and especially the marked activation of the IL-23/pTh17 axis, remains unknown. Therefore, here we aimed to characterize the pleiotropic activity of specific AIEC virulence determinants to assess whether their simultaneous targeting can prevent the cascade of pathogenic events leading to chronic inflammation. To this aim, we generated and functionally characterized single and double mutants in the LF82 strain, focusing on ΔfimH, ΔrfaP, and ΔybaT for their specific inhibitory effect on distinct host-AIEC pathogenic interactions. Our functional analysis revealed that the ΔrfaPΔfimH double mutant strongly impairs intracellular persistence within macrophages and dendritic cells and, most notably, completely abolished intracellular survival within intestinal epithelial cells. Consistently, the associated pro-inflammatory response — including IL-8, CCL20, TNF-α, and the pTh17-polarizing cytokine IL-23/IL-1β, was markedly reduced in response to ΔrfaPΔfimH double mutant strain. Remarkably, we demonstrated for the first time that OMVs released by LF82 are sufficient to drive the pathogenic skewing of protective cTh17 cells into pathogenic IFN-γ-producing Th17 cells, thereby revealing a previously unrecognized mechanism through which AIEC promotes mucosal immune dysregulation. Strikingly, OMVs derived from the ΔrfaPΔfimH double mutant displayed a reduced ability to induce pTh17 generation. In conclusion, our study strongly proves that dual targeting of RfaP and FimH represents a novel and highly promising therapeutic strategy to simultaneously impair key mechanisms of AIEC virulence and to attenuate the exaggerated inflammatory response that characterizes CD patients

    DECIPHERING THE ORAL MICROBIOTA IN FOOD ALLERGY: INSIGHTS INTO THE CANDIDATE PHYLA RADIATION AND NOVEL METHODOLOGICAL APPROACHES

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    Food allergies are abnormal immune reactions to otherwise harmless food antigens, influenced by multiple factors, including the oral microbiota. During my PhD, I contributed to studies investigating the oral microbiota in food-allergic children, with a particular focus on the Candidate Phyla Radiation (CPR), an elusive bacterial group increasingly implicated in health and disease. We assessed available protocols for quantifying CPR in human salivary samples and performed in silico analyses to identify alternative genetic markers, highlighting RecA as a strong candidate. Building on this, we explored its potential for bacterial community profiling, developing a machine learning algorithm that accurately infers taxonomy from RecA sequences across bacterial diversity. This algorithm was implemented in a software that provides ultra-fast, accurate taxonomic profiling from raw shotgun metagenomic reads. In parallel, we analyzed the oral microbiota of allergic children using absolute rather than relative quantification, revealing patterns of microbial susceptibility and resilience to immune pressure. We also studied children who achieved antigen tolerance, observing microbial shifts that partially restored a healthy-like composition. Finally, I contributed to a study clarifying diagnostic markers for food-protein–induced allergic proctocolitis

    Assessment of genetically modified soybean MON 87769 for renewal authorisation under Regulation (EC) No 1829/2003 (dossier GMFF‐2023‐21253)

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    Following the submission of dossier GMFF-2023-21253 under Regulation (EC) No 1829/2003 from Bayer CropScience LP, the Panel on Genetically Modified Organisms of the European Food Safety Authority was asked to deliver a scientific risk assessment on the data submitted in the context of the renewal of authorisation application for the stearidonic acid producing genetically modified soybean MON 87769, for food and feed uses, excluding cultivation within the European Union. The data received in the context of this renewal application contained post-market environmental monitoring reports, post-market monitoring reports, an evaluation of the literature retrieved by a scoping review, a search for additional studies performed by or on behalf of the applicant and updated bioinformatics analyses. The GMO Panel assessed these data for possible new hazards, modified exposure or new scientific uncertainties identified during the authorisation period and not previously assessed in the context of the original application. Under the assumption that the DNA sequence of the event in soybean MON 87769 considered for renewal is identical to the sequence of the originally assessed event, the GMO Panel concludes that there is no evidence in renewal dossier GMFF-2023-21253 for new hazards, modified exposure or scientific uncertainties that would change the conclusions of the original risk assessment on soybean MON 87769

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