Archivio Istituzionale della Ricerca - Università degli Studi della Campania "Luigi Vanvitelli"
Not a member yet
116395 research outputs found
Sort by
Effects of intraoperative higher versus lower positive end-expiratory pressure during one-lung ventilation for thoracic surgery on postoperative pulmonary complications (PROTHOR): a multicentre, international, randomised, controlled, phase 3 trial
No full textBackground The effect of higher positive end-expiratory pressure (PEEP) and recruitment manoeuvres aimed at lung expansion as compared with lower PEEP without recruitment manoeuvres aimed at permissive atelectasis on postoperative pulmonary complications (PPCs) in patients undergoing one-lung ventilation (OLV) during thoracic surgery is unclear. We aimed to determine the contribution of an intraoperative lung expansion strategy to preventing PPCs. Methods In this multicentre, randomised, controlled, international phase 3 trial (PROTHOR) conducted at 74 sites in 28 countries, we enrolled adult patients (aged >= 18 years) with a BMI of less than 35 kg/m2 who were scheduled for open thoracic or video-assisted thoracoscopic surgery under general anaesthesia requiring one-lung ventilation with a double-lumen tube, with a planned operative time of more than 60 min, and an expected duration of one-lung ventilation longer than that of two-lung ventilation. Patients were randomly assigned (1:1), using permuted blocks of random size (4, 6, and 8) and stratified by study site, to receive one-lung ventilation with either a higher PEEP of 10 cm H2O and periodic lung recruitment manoeuvres (high PEEP group) or a lower PEEP of 5 cm H2O without routine recruitment manoeuvres (low PEEP group). All patients received protective tidal volumes of 5 mL/kg predicted body weight during one-lung ventilation and 7 mL/kg predicted body weight during two-lung ventilation. Postoperative assessors were masked to treatment allocation. The primary outcome was a composite of PPCs during the first 5 postoperative days, including aspiration pneumonia, moderate or severe respiratory failure, acute respiratory distress syndrome (ARDS), pulmonary infection, atelectasis, cardiopulmonary oedema, pleural effusion, non-operative pneumothorax, pulmonary infiltrates, prolonged air leak, purulent pleuritis, pulmonary embolism, and pulmonary haemorrhage. A modified intention-to-treat analysis was performed, with patients analysed according to their assigned treatment group, except in cases of withdrawal of informed consent, cancellation of surgery, and or loss to follow-up. This trial is registered with ClinicalTrials.gov (NCT02963025) and is completed. Findings Between Jan 3, 2017, and Feb 12, 2024, 2200 patients were randomly allocated: 1099 to the high PEEP group and 1101 to the low PEEP group. 43 patients in the high PEEP group and 33 in the low PEEP group were excluded from the modified intention-to-treat analysis after randomisation. The primary outcome occurred in 555 (536%) of 1036 patients in the high PEEP group and 592 (564%) of 1049 patients in the low PEEP group (absolute risk difference-268 percentage points [95% CI-636 to 101]; p=0155). Intraoperative complications occurred in 484 (498%) of 972 patients in the high PEEP group and in 305 (313%) of 974 patients in the low PEEP group (absolute risk difference 1809 percentage points [95% CI 1441-2177]), among which hypotension (360 [373%] of 966 patients in the high PEEP group vs 140 [143%] of 978 in the low PEEP group) and new arrhythmias (89 [99%] of 899 vs 37 [39%] of 956) were more frequent in the high PEEP group, while hypoxaemia rescue manoeuvres were more frequent in the low PEEP group (29 [33%] of 888 vs 86 [88%] of 982).The proportions of patients with extrapulmonary postoperative complications (110 [106%] of 1036 vs 107 [102%] of 1049 patients), and the numbers of adverse events (209 vs 204 events), did not differ between groups. Interpretation In patients with a BMI of less than 35 kg/m2 undergoing thoracic surgery, one-lung ventilation using higher PEEP with recruitment manoeuvres, compared with lower PEEP without recruitment manoeuvres, did not reduce PPCs. The choice for intraoperative lung expansion or permissive atelectasis should take the individual gas-exchange and haemodynamic conditions into account, which might vary during the intraoperative period. Funding Clinical Trials Network of the European Society of Anaesthesiology and Intensive Care; Department of Anaesthesiology and Intensive Care, University Hospital Carl Gustav Carus, Technische Universit & auml;t Dresden (Dresden, Germany); Conselho Nacional de Desenvolvimento Cientifico e Tecnol & oacute;gico (Brasilia, Brazil); and the Association of Anaesthetists of GB and Ireland. Copyright (c) 2025 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies
R.E.Pr.I.S.E. - Research on Entrepreneurship Processes, Innovation, and Startup Enterprises | Vol. 1
No full text
Vasculogenic Mimicry in Glioblastoma: Investigating the impact of natural and synthetic compounds and the role of tumor microenvironment
No full textGlioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults. Standard therapy, consisting of maximal surgical resection followed by radiotherapy and chemotherapy with agents such as temozolomide (TMZ) and cisplatin, provides only modest benefits, and recurrence is almost inevitable. A major limitation of current chemotherapeutics lies in their lack of selectivity, as they damage normal cells in addition to tumor cells, and their prolonged use is associated with toxicity and the development of chemoresistance. Furthermore, GBM progression is accompanied by neuronal loss (Rawal et al., 2025), which further contributes to the devastating impact of the disease.
The remarkable resilience of GBM derives not only from intrinsic features—such as high migratory and invasive potential and cellular plasticity—but also from the supportive role of the tumor microenvironment (TME). In particular, astrocytes secrete factors that promote GBM migration, invasion, stemness, and therapy resistance. Moreover, GBM cells are capable of engaging in vasculogenic mimicry (VM), forming vessel-like networks independently of endothelial cells. VM sustains tumor perfusion, therapeutic resistance, and recurrence, thereby representing a crucial adaptive mechanism. Targeting both tumor-intrinsic adaptations and microenvironmental support thus emerges as an essential therapeutic challenge.
Natural products are valuable sources of novel compounds with therapeutic potential in several human diseases, including cancer. In this context, previous studies from our laboratory investigated the activity of natural extracts from Ruta graveolens (RGWE), which were shown to selectively induce the death of glioblastoma cells and neural progenitors while sparing mature neurons. Interestingly, upon differentiation, A1 cells became resistant to rue’s toxic effects but not to those of TMZ and cisplatin, the two alkylating agents commonly used in glioblastoma therapy. These findings demonstrated that rue extracts induce glioma cell death by discriminating between proliferating/undifferentiated and non-proliferating/differentiated neuronal cells, representing a promising tool both for isolating novel therapeutic compounds and for identifying potential targets for intervention (Gentile et al., 2015). More recently, RGWE was also shown to exert neuroprotective effects in vivo, ameliorating ischemic damage and improving neurological deficits in a rat model of transient focal brain ischemia (Campanile et al., 2022). Building on these observations, our first aim was to assess whether RGWE could exert differential effects on primary glial cells. To this end, we analyzed its activity in primary neurons, oligodendrocytes, astrocytes, and microglia, comparing the results to those obtained in rat C6 glioma cells. Dose–response experiments revealed that RGWE reduced proliferation in glioma cells without detectable effects on healthy neurons or glial cells. By contrast, TMZ at comparable doses impaired the viability of both glioma and normal glial cells, underscoring its lack of selectivity.
Having established the selective action of RGWE, we next sought to broaden our investigation beyond its effects. Since our main focus was to further explore the adaptive properties of GBM and strategies to counteract them, we extended our analysis to additional classes of compounds. In particular, we reasoned that applying natural (e.g., RGWE), synthetic (e.g., uPAcyclin and its derivatives), and clinically approved chemotherapeutics (e.g., TMZ and cisplatin) at sub-lethal concentrations could help minimize toxicity while unveiling novel therapeutic windows. This approach allowed us not only to confirm the discriminatory activity of RGWE, but also to comparatively assess other agents with distinct mechanisms of action.
These studies revealed that RGWE significantly impaired GBM migration, invasion, and VM. Importantly, RGWE also proved effective against patient-derived cancer stem cells (CSCs), which are recognized as the main drivers of tumor aggressiveness and therapy resistance. Similarly, uPAcyclin and its derivatives consistently reduced GBM invasiveness by interfering with αV-integrin–dependent pathways. TMZ, at sub-lethal concentrations, attenuated migration, stemness, and VM, indicating a potential therapeutic window with lower cytotoxicity; however, its poor selectivity remained a concern. In contrast, sub-lethal doses of cisplatin paradoxically enhanced VM formation, raising caution regarding its use in this context.
To better capture the complexity of GBM, we further employed advanced 3D co-culture models to evaluate the effects of our compounds in a more physiologically relevant setting. These experiments confirmed the pivotal role of astrocytes in driving GBM aggressiveness. Astrocyte-conditioned media and direct co-cultures enhanced migration, invasion, and spheroid expansion. Interestingly, TMZ partially counteracted these astrocyte-driven effects, highlighting its dual capacity to act not only on tumor cells but also on TME-derived support.
In conclusion, this thesis identifies RGWE and uPAcyclin derivatives as promising anti-GBM candidates capable of impairing invasive and adaptive features while sparing healthy brain cells. It also emphasizes the dual, yet limited, action of TMZ—effective at reducing aggressiveness but lacking selectivity—and the potential risks of cisplatin in promoting pro-tumor adaptations. By integrating both tumor plasticity and astrocyte-mediated support, this work provides a rationale for the development of therapeutic strategies that are at once more effective and less toxic in the treatment of glioblastoma
Stellar and dynamical evolution in Globular Clusters
No full textGlobular Clusters (GCs) are stellar systems orbiting around galaxies, that present a spherical shape and are characterized by an intriguing dynamical evolution. The high stellar density makes gravitational encounters between stars frequent, driving these system toward two-body relaxation. This process alters the structural, spatial, and kinematic properties of stars during the long life of GCs, that is ∼ 10 Gyr. In this work, we first present and examine the past and current knowledge on Galactic GCs (Chapter 1). We begin by considering these systems as made of a single stellar population, to introduce the physical effects connected with relaxation, such as energy equipartition and mass segregation as well as stellar evaporation, produced by the Galactic tidal field. The already intricate evolution of GCs is further complicated by the presence of Multiple Populations (MPs), that is, generations of stars showing a different chemical content, detected in almost all GCs. The scenario behind their formation is still not known and widely discussed, as are the early conditions and their impact in the following evolution of these systems and the Galactic environment. We outline the observational evidence, the proposed formation scenarios, and MPs evolution, focusing on the main open problems.
In Chapter 2 we present the methods and tools used for studying the evolution of GCs and their dynamical state. As collisional systems, GCs evolution must be described through direct N-body simulations, that integrate the N-point mass dynamics subject to the mutual gravitational attraction between stars, as we outline in Sect. 2.1. In addition, also stellar evolution must be taken into account, as it alters the properties of individual objects, causing important effects on the system behavior, in particular in the early phases. Furthermore, dynamical models offer a robust tool to analyze and describe GCs and their physical process. In Sect. 2.2, we present our multi-mass King-like dynamical model, that can appropriately predict and quantify mass-based processes, such as energy equipartition and mass segregation. In particular, we use the model
to estimate the energy equipartition degree in a subset of Galactic GCs, for which we fit the available data on internal kinematics (Sect. 2.3). Our work reveals that the multi-mass model equilibrium parameter Φ_0, connected with the gravitational potential and the dynamical state, correlates with the equipartition mass m_eq, an empirical estimator of the energy equipartition degree adopted in the literature, as well as other structural quantities. In addition, we successfully fit the observed surface brightness profiles of the same GCs, further validating our approach and confirming the goodness of our description.
Concerning mass segregation, we find that our dynamical model can predict its degree through the relation between the half-mass radius and stellar mass. The shape of this function predicted by the model is also well described by a linear relation, whose slope β is an empirical quantifier of the segregation degree and results correlated with Φ_0 (Sect. 2.4.2).
As a consequence, we use our model to determine initial conditions for N-body simulations (Sect. 2.5), to set an initial degree of primordial segregation in GCs, as expected from the violent relaxation phase, that is, the early dynamical evolution that sets the monolithic structure of the system after stellar formation.
In Chapter 3, we take advantage of the aforementioned results to simulate the dynamical evolution of MPs, assuming one of the most appealing formation scenarios, the AGB one. It sees a First Generation (FG) formed by the original cluster composition. Once AGB stars of the FG evolve, they pollute the cluster with a chemically altered material, that contributes to the formation of a Second Generation (SG). We consider for the first time the impact of a primordial segregation degree in FG stars, imprinted by the violent relaxation phase. We also take into account the age of FG stars after the formation of SG stars, that is ∼ 100 Myr in the AGB pollution scenario. In addition, we explore the effects of a different relative spatial concentration between MPs in the initial conditions, taking advantage of quantitative estimates from SG formation studies.
Our results highlight that primordial segregation and age difference alter the early dynamical evolution, that is, the feedback from stellar evolution (Sect. 3.3). The expansion of FG stars is stronger for the aged cases and weaker for segregated ones. This affects the MPs radial mixing efficiency and the evolution toward mass segregation and energy equipartition, with the SG typically showing a higher degree of both. Interestingly, our different initial conditions also affect the behavior of the half-mass radius of FG black holes, which sink in the core. Furthermore, a higher initial relative concentration between MPs severely changes the early
dynamics, bringing to a strong predominance of SG stars in the most extreme case, that also show a more advanced dynamical state (Sect. 3.4).
Finally, we discuss the challenges of more realistic simulations in Sect. 3.5, targeting the mass budget problem with direct N-body simulations, likely requiring a very high number of stars and several computational resources to perform simulations where both the strong early loss of FG stars as well as the final internal dynamics are well described.
Our work underline the importance of considering the effect of a primordially segregated and aged FG, aspects that both influence the observational and structural features of MPs observable today. Thus, future research should focus on setting more realistic and consistent initial conditions, taking advantage of multi-mass dynamical models and appropriately considering the initial differences between FG and SG. This would shed further light on the formation scenario of MPs, the early conditions of GCs and the role of these systems in
the galactic context
Affective and Sexual Citizenship in Mental Disability. Voices, Practices, and Psycho-Educational Interventions for Young Adults with Intellectual Disabilities, Autism, and Severe Mental Illness
No full textThis doctoral dissertation investigates the intersection between mental disability—including intellectual disability, autism spectrum conditions, and severe psychiatric disorders—and the right to affective and sexual citizenship. Although sexuality is widely recognized as a constitutive dimension of both health and citizenship, it often remains a neglected “gap” within care pathways for young adults, who are frequently trapped in the paradox of the “eternal child.”
Using a qualitative, multi-method research design informed by Participatory Action Research (PAR), the study involved 13 young adults aged 18–40 in semi-structured interviews and 10 primary caregivers in six focus groups. Data were analyzed through Braun and Clarke’s Reflexive Thematic Analysis (RTA), revealing a profound tension between young people’s desire for autonomy and the dynamics of control, infantilization, and educational reticence exercised within familial and institutional microsystems.
The research also included the development, implementation, and evaluation of a modular psycho-educational intervention grounded in the principles of Comprehensive Sexuality Education (UNESCO). Results from the pilot project showed a significant increase in participants’ knowledge and awareness (average +30%), particularly regarding the management of personal boundaries (the Circles Model), privacy, and autonomy in body care.
The original contribution of this work lies in the proposal of an Integrated Ecological Model for Mental Disability, which expands Bronfenbrenner’s framework by introducing concepts such as the “Defensive Mesosystem” and the “Permeability of the Exosystem” as conditioned by social capital.
In conclusion, the dissertation argues for the necessity of Relational Justice, calling for a paradigm shift from a logic of “risk containment” to one of “enabling subjectivity,” in which affective inclusion is recognized not as rhetoric, but as an everyday practice of rights recognition
ANTI-SEISMIC CONCEPTS IN VERNACULAR ARCHITECTURE: THE CASE OF THE VESUVIAN MASSERIE
No full textThe first agricultural settlements on the slopes of Vesuvius date back to the 1st century BC, coinciding with the Roman colonisation of the territory. However, it was between the 11th and 12th centuries that these settlements gradually consolidated their typological and constructional characteristics, giving rise to a complex and lasting settlement system. The history of the Vesuvian Masserie is therefore a complex and layered process, constantly influenced by the imposing presence of the volcano, whose latent threat has had a significant impact on the structural organisation of the buildings and the way of life of their inhabitants. The research lays the foundations for the study of Vesuvian farmhouses in relation to seismic risk, highlighting how the concept of “earthquake-proof construction,” although achieved through empirical practices, was already present in embryonic form in the construction techniques used at the time
Semantic Modulation of Spatial Judgments in Augmented Reality: Evidence from fNIRS
No full textThis study examined how different types of semantic relationships modulate cortical activity during spatial judgments in an augmented reality (AR) setting. Participants viewed triads of everyday objects that were either thematically (co-occurring) or functionally (sharing a purpose) related and made spatial judgments varying in reference frame, egocentric (object closest to you?) vs. allocentric (object closest to another? ), and relation type, coordinate (distance-based) vs.categorical (left-right). Cortical activity was measured using functional near-infrared spectroscopy (fNIRS). Results showed that semantic modulation was most evident during allocentric-coordinate judgments, with increased activation in temporal regions for thematic triads compared to functional ones. In general, functionally related triads engaged parietal regions more broadly across conditions, while egocentric judgments elicited widespread parietal activity with reduced semantic modulation. Finally, categorical judgments showed minimal differences between semantic conditions. By combining AR with fNIRS, this study provides evidence that semantic knowledge influences cortical recruitment during spatial processing, offering a novel window into how meaning and spatial representation interact
