17 research outputs found

    Qualitative research in social and organizational psychology: the Italian way

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    Our paper provides a mapping of qualitative research in social and organizational psychology. This mapping was directed by the authors’ choices and this means that scholars from other perspectives are likely to offer different readings of the same topic. The first choice was to not consider the clinical and developmental psychological research, so to deepen our exploration of the two areas in which we work on, and on which we have a more articulated perspective. These two areas differ for some aspects, but they also present some relevant common elements, as it is demonstrated by the fact that scholars working in social and organizational psychology are part of the same academic recruitment field (“11/E3 Social psychology and work and organizational psychology”). The first section of the article consists of a short history of qualitative research in Italian psychology. To deepen the focus on the most recent developments, in the second section we present a review of the scientific articles published in the last five years

    Functional reconstitution of HBV-specific CD8 T cells by in vitro polyphenol treatment in chronic hepatitis B.

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    Background & aims In chronic HBV infection, mitochondrial functions and proteostasis are dysregulated in exhausted HBV-specific CD8 T cells. To better characterise the potential involvement of deregulated protein degradation mechanisms in T cell exhaustion, we analysed lysosome-mediated autophagy in HBV-specific CD8 T cells. Bioactive compounds able to simultaneously target both mitochondrial functions and proteostasis were tested to identify optimal combination strategies to reconstitute efficient antiviral CD8 T cell responses in patients with chronic HBV infection. Methods Lysosome-mediated degradation pathways were analysed by flow cytometry in virus-specific CD8 T cells from patients with chronic HBV infection. Mitochondrial function, intracellular proteostasis, and cytokine production were evaluated in HBV-peptide-stimulated T cell cultures, in the presence or absence of the polyphenols resveratrol (RSV) and oleuropein (OLE) and their metabolites, either alone or in combination with other bioactive compounds. Results HBV-specific CD8 T cells from patients with CHB showed impaired autophagic flux. RSV and OLE elicited a significant improvement in mitochondrial, proteostasis and antiviral functions in CD8 T cells. Cytokine production was also enhanced by synthetic metabolites, which correspond to those generated by RSV and OLE metabolism in vivo, suggesting that these polyphenols may also display an effect after transformation in vivo. Moreover, polyphenolic compounds improved the T cell revitalising effect of mitochondria-targeted antioxidants and of programmed cell death protein 1/programmed cell death ligand 1 blockade. Conclusions Simultaneously targeting multiple altered intracellular pathways with the combination of mitochondria-targeted antioxidants and natural polyphenols may represent a promising immune reconstitution strategy for the treatment of chronic HBV infection. Lay summary In chronic hepatitis B, antiviral T lymphocytes are deeply impaired, with many altered intracellular functions. In vitro exposure to polyphenols, such as resveratrol and oleuropein, can correct some of the deregulated intracellular pathways and improve antiviral T cell function. This effect can be further strengthened by the association of polyphenols with antioxidant compounds in a significant proportion of patients. Thus, the combination of antioxidants and natural polyphenols represents a promising strategy for chronic hepatitis B therapy

    Short-term TNF-alpha treatment induced A2B adenosine receptor desensitization in human astroglial cells

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    Long-term glial cell treatment with the proinflammatory cytokine TNF-alpha has been demonstrated to increase the functional responsiveness of A 2B adenosine receptors (A2B ARs), which in turn synergize with the cytokine inducing chronic astrogliosis. In the present study, we investigated the short-term effects of TNF-alpha on A2B AR functional responses in human astroglial cells (ADF), thus simulating the acute phase of cerebral damage which is characterized by both cytokine and adenosine high level release. Short-term TNF-alpha cell treatment caused A2B AR phosphorylation inducing, in turn, impairment in A2B AR-G protein coupling and cAMP production. These effects occurred in a time-dependent manner with a maximum following 3-h cell exposure. Moreover, we showed PKC intracellular kinase is mainly involved in the TNF-alpha-mediated regulation of A2B AR functional responses. The results may indicate the A 2B AR functional impairment as a cell defense mechanism to counteract the A2B receptor-mediated effects during the acute phase of brain damage, underlying A2B AR as a target to modulate early inflammatory responses. © 2007 Wiley-Liss, Inc

    Is medical perspective on clinical governance practices associated with clinical units’ performance and mortality? A cross-sectional study through a record-linkage procedure

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    Objective: Assessment of the knowledge and application as well as perceived utility by doctors of clinical governance tools in order to explore their impact on clinical units’ performance measured through mortality rates and efficiency indicators. Methods: This research is a cross-sectional study with a deterministic record-linkage procedure. The sample includes n = 1250 doctors (n = 249 chiefs of clinical units; n = 1001 physicians) working in six public hospitals located in the Emilia-Romagna Region in Italy. Survey instruments include a checklist and a research-made questionnaire which were used for data collection about doctors’ knowledge and application as well as perceived utility of clinical governance tools. The analysis was based on clinical units’ performance indicators which include patients’ mortality, extra-region active mobility rate, average hospital stay, bed occupancy, rotation and turnover rates, and the comparative performance index as efficiency indicators. Results: The clinical governance tools are known and applied differently in all the considered clinical units. Significant differences emerged between roles and organizational levels at which the medical leadership is carried out. The levels of knowledge and application of clinical governance practices are correlated with the clinical units’ efficiency indicators (bed occupancy rate, bed turnover interval, and extra-region mobility). These multiple linear regression analyses highlighted that the clinical governance knowledge and application is correlated with clinical units’ mortality rates (odds ratio, −8.677; 95% confidence interval, −16.654, −0.700). Conclusion: The knowledge and application, as well as perceived utility by medical professionals of clinical governance tools, are associated with the mortality rates of their units and with some efficiency indicators. However, the medical frontline staff seems to not consider homogeneously useful the clinical governance tools application on its own clinical practice

    FluoroSpot assay to analyze SARS-CoV-2-specific T cell responses

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    Summary: Monitoring antigen-specific T cell frequency and function is essential to assess the host immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we present a FluoroSpot assay for concurrently detecting ex vivo antiviral cytokine production by SARS-CoV-2-specific T cells following peptide stimulation. We then detail intracellular cytokine staining by flow cytometry to further validate the FluoroSpot assay results and define the specific T cell subpopulations.For complete details on the use and execution of this protocol, please refer to Tiezzi et al. (2023).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics

    Le ceramiche a vernice nera nel IV e III secolo a.C. dell’Ager Portuensis e di Ostia: notizie preliminari sulle ricerche archeologiche e archeometriche

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    none8Olcese, G.; Capelli, C.; Carconi, A.; Ceccarelli, L.; Giunta, S.; Manzini, I.; Montali, I.; Scorrano, A.Olcese, G.; Capelli, C.; Carconi, A.; Ceccarelli, L.; Giunta, S.; Manzini, I.; Montali, I.; Scorrano, A

    Unraveling the Multifaceted Nature of CD8 T Cell Exhaustion Provides the Molecular Basis for Therapeutic T Cell Reconstitution in Chronic Hepatitis B and C

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    In chronic hepatitis B and C virus infections persistently elevated antigen levels drive CD8+ T cells toward a peculiar differentiation state known as T cell exhaustion, which poses crucial constraints to antiviral immunity. Available evidence indicates that T cell exhaustion is associated with a series of metabolic and signaling deregulations and with a very peculiar epigenetic status which all together lead to reduced effector functions. A clear mechanistic network explaining how intracellular metabolic derangements, transcriptional and signaling alterations so far described are interconnected in a comprehensive and unified view of the T cell exhaustion differentiation profile is still lacking. Addressing this issue is of key importance for the development of innovative strategies to boost host immunity in order to achieve viral clearance. This review will discuss the current knowledge in HBV and HCV infections, addressing how innate immunity, metabolic derangements, extensive stress responses and altered epigenetic programs may be targeted to restore functionality and responsiveness of virus-specific CD8 T cells in the context of chronic virus infections

    Antigen Load and T Cell Function: A Challenging Interaction in HBV Infection

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    Current treatment for chronic HBV infection is mainly based on nucleos(t)ide analogues, that in most cases need to be administered for a patient's lifetime. There is therefore a pressing need to develop new therapeutic strategies to shorten antiviral treatments. A severe dysfunction of virus-specific T cell responses contributes to virus persistence; hence, immune-modulation to reconstitute an efficient host antiviral response is considered a potential approach for HBV cure. In this perspective, a detailed understanding of the different causes of T cell exhaustion is essential for the design of successful functional T cell correction strategies. Among many different mechanisms which are widely believed to play a role in T cell dysfunction, persistent T cell exposure to high antigen burden, in particular HBsAg, is expected to influence T cell differentiation and function. Definitive evidence of the possibility to improve anti-viral T cell functions by antigen decline is, however, still lacking. This review aims at recapitulating what we have learned so far on the complex T cell-viral antigen interplay in chronic HBV infection

    FUNCTIONAL AND TRANSCRIPTIONAL RESTORATION OF EXHAUSTED VIRUS-SPECIFIC T LYMPHOCYTES FROM PATIENTS WITH CHRONIC HEPATITIS B

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    Background and Aims: The current therapy for chronic hepatitis B (CHB) is mainly based on direct acting antiviral drugs that efficiently suppress virus replication, but don’t eradicate HBV and frequently require lifelong administration. Therefore, novel anti-HBV therapies should induce complete HBV cure in a short definite time of treatment. During CHB, HBV-specific T cells gradually lose their anti-viral functions in a process known as T cell exhaustion, which is associated with a deregulated CD8 transcriptional profile that underlies a number of altered biological processes. Among them, an impaired mitochondrial function with ROS overproduction as well as NAD depletion are believed to be crucial. These observations suggest that mitochondrial antioxidants, such as Mitoquinone, and NAD precursors, such as nicotinamide mononucleotide (NMN), perhaps in combination with inhibition of CD38, one of the principal NAD consumers, may represent possible therapeutic strategies aimed at restoring HBV-specific CD8 T cell functions. Methods: HBV Core18-27- specific CD8 T cells from chronic HBV patients were expanded in vitro by HBV peptide stimulation in the presence or absence of Mitoquinone or NMN plus CD38 inhibitors (CD38i). Influenza(Flu)- specific CD8 cells from the same patients were expanded at the same experimental conditions without any treatment and used as controls for the definition of reference transcriptional features of memory CD8 T cells associated with control of infection. Virus-specific CD8 T cells were then sorted and subjected to low input RNASeq analysis by SMART-Seq. Differentially expressed genes were identified by DESeq2 v1.34.0, with the lfcShrink analysis (s value<0.05). The softwares Shinygo and GSEA were also used. Results: HBV-specific CD8 cells from cultures treated with either therapy showed a significant reduction of PD1 expression and a trend towards a decreased CD38 expression. In addition, a number of differentially expressed genes were identified comparing cultures treated with immune-modulating strategies and untreated control cells. Interestingly, in parallel with antiviral function enhancement, both treatments induced the development of transcriptional memory T cell features. Among these, the down-regulation of several genes controlling intracellular Ca2+ uptake, which may be potentially responsible for reduced T cell activation, and regulating the glycolytic metabolism could be observed, with an enhancement of the fatty-acid ÎČ-oxidation. Interestingly, GSEA analysis showed a significant association of gene expression profiles in HBV-specific CD8 T cells from treated cultures with control fully functional FLU-specific CD8 T cells. Conclusions: Administration of mitochondria-targeted antioxidant compounds and NAD supplementation represent strategies able to correct the deregulated transcriptional profile in exhausted HBV-specific CD8 T cells from CHB patients, by acting at several levels, including T cell metabolism

    The Good and the Bad of Natural Killer Cells in Virus Control: Perspective for Anti-HBV Therapy

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    Immune modulatory therapies are widely believed to represent potential therapeutic strategies for chronic hepatitis B infection (CHB). Among the cellular targets for immune interventions, Natural Killer (NK) cells represent possible candidates because they have a key role in anti-viral control by producing cytokines and by exerting cytotoxic functions against virus-infected cells. However, in patients with chronic hepatitis B, NK cells have been described to be more pathogenic than protective with preserved cytolytic activity but with a poor capacity to produce anti-viral cytokines. In addition, NK cells can exert a regulatory activity and possibly suppress adaptive immune responses in the setting of persistent viral infections. Consequently, a potential drawback of NK-cell targeted modulatory interventions is that they can potentiate the suppressive NK cell effect on virus-specific T cells, which further causes impairment of exhausted anti-viral T cell functions. Thus, clinically useful NK-cell modulatory strategies should be not only suited to improve positive anti-viral NK cell functions but also to abrogate T cell suppression by NK cell-mediated T cell killing. This review outlines the main NK cell features with a particular focus on CHB infection. It describes different mechanisms involved in NK-T cell interplay as well as how NK cells can have positive anti-viral effector functions and negative suppressive effects on T cells activity. This review discusses how modulation of their balance can have potential therapeutic implications
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