Chemotherapy accelerates immune-senescence and functional impairments of Vδ2pos T cells in elderly patients affected by liver metastatic colorectal cancer.

Human (gamma delta) γδ T cells are unconventional innate-like lymphocytes displaying a broad array of anti-tumor activities with promising perspectives in cancer immunotherapy. In this context, Vδ2pos T cells represent the preferential target of several immunotherapy protocols against solid tumors. However, the impact of both aging and chemotherapy (CHT) on Vδ2pos T cells is still unknown. The present study evaluates with multi-parametric flow cytometry the frequencies, terminal differentiation, senescence and effector-functions of peripheral blood and tumor infiltrating Vδ2pos T cells purified from liver metastases (CLM) of patients affected by colorectal cancer (CRC) compared to those of sex- and age-matched healthy donors. The peripheral blood of CLM patients underwent CHT is characterized by decreased amounts of Vδ2pos T cells showing a relative increase of terminally-differentiated CD27neg/CD45RApos (TEMRA) cells. The enrichment of this latter subset is associated with an increased expression of the senescent marker CD57. The acquisition of CD57 on TEMRA Vδ2pos T cells is also coupled with impairments in cytotoxicity and production of TNF-α and IFN-γ. These features resemble the acquisition of an immune-senescent profile by Vδ2pos T cells from CLM patients that received CHT, a phenomenon that is also associated with the loss of the co-stimulatory marker CD28 and with the induced expression of CD16. The group of CLM patients underwent CHT and older than 60 years old showed higher frequencies of CD57pos and TEMRA Vδ2pos T cells. Similar results were found for tumor infiltrating Vδ2pos T cell subset purified from CLM specimens of patients treated with CHT. The toxicity of CHT regimens also affects the homeostasis of Vδ2pos T cells by inducing higher frequencies of circulating CD57pos TEMRA subset in CLM underwent CHT and younger than 60 years old. Taken together, our data demonstrate that the enrichment of senescent Vδ2pos T cells in CLM patients is not only induced by patients' aging but also by the toxicity of CHT that further accelerates the accumulation of CD57pos TEMRA cells highly dysfunctional in their anti-tumor activities. These results are important to both predict the clinical outcome of CLM and to optimize those protocols of cell cancer immunotherapy employing unconventional Vδ2pos T cells

Risk perception and media in shaping protective behaviors: insights from the early phase of COVID-19 Italian outbreak

In the absence of target treatments or vaccination, the SARS-CoV-2 pandemic can be impeded by effectively implementing containment measures and behaviors. This relies on individuals’ adoption of protective behaviors, their perceived risk, and the use and trust of information sources. During a health emergency, receiving timely and accurate information enables individuals to take appropriate actions to protect themselves, shaping their risk perception. Italy was the first western country plagued by COVID-19 and one of the most affected in the early phase. During this period, we surveyed 2,223 Italians before the national lockdown. A quarter of the sample perceived COVID-19 less threatening than flu and would not vaccinate, if a vaccine was available. Besides, most people perceived containment measures, based on social distancing or wearing masks, not useful. This perceived utility was related to COVID-19 threat perception and efficacy beliefs. All these measures were associated with the use of media and their truthfulness: participants declared to mainly use the Internet, while health organizations’ websites were the most trusted. Although social networks were frequently used, they were rated lower for trustfulness. Our data differ from those obtained in other community samples, suggesting the relevance to explore changes across different countries and during the different phases of the pandemic. Understanding these phenomena, and how people access the media, may contribute to improve the efficacy of containment measures, tailoring specific policies and health communications

Prevalence of hepatic steatosis in patients with type 2 diabetes and response to glucose-lowering treatments. A multicenter retrospective study in Italian specialist care

Type 2 diabetes (T2D) is a risk factor for metabolic dysfunction-associated fatty liver disease (MAFLD), which is becoming the commonest cause of chronic liver disease worldwide. We estimated MAFLD prevalence among patients with T2D using the hepatic steatosis index (HSI) and validated it against liver ultrasound. We also examined whether glucose-lowering medications (GLM) beneficially affected HSI

Codice nazionale e "vocabolario mentale" dei giuristi

Sommario - 1. Il dono dello straniero; - 2. Imposizione e persuasione; - 3. Una seconda vita; - 4. ‘Gius comune’ e codice; - 5. Tra Bentham e Savigny; - 6. ‘Codice perfetto’ e limiti al legislatore; - 7. Un ordine provvidenziale; - 8. Un destino per la scienza giuridica nazionale. La vicenda del diritto italiano nel corso del XIX secolo è strettamente legata alla presenza di contrastanti rappresentazioni del codice civile che ora è esaltato come strumento giuridico universale di progresso e di civilizzazione, ora come autentica espressione di un diritto «veramente nazionale». Imposto in Italia dalle armate francese, il modello-codice si affermò grazie a una composita strategia di persuasione, a una trasformazione del «dono dello straniero» in un simbolo di identità. Il saggio considera alcune costruzioni retoriche del «codice nazionale» evidenziando i nessi con i mutamenti del «vocabolario mentale» dei giureconsulti

Prolusioni, prelezioni, discorsi. L'identità nazionale nella retorica dei giuristi

introduzione al volum

“O preço da tranquilidade”. Ordem jurídica e injustiça do dano.

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Diritto comune civilistico e critiche sociali al Codice: la crisi del modello ottocentesco di unità del diritto.

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Natura delle cose e superbia del legislatore. Giuseppe Capograssi e il diritto agrario italiano di metà Novecento,

Il saggio analizza l'autonomia disciplinare del diritto agrario nel contributo di Capograssi, con riferimento alla riscoperta "natura delle cose" e con l'acquisita consapevolezza dell'insufficienza delle categorie codicistiche

Contratto e status. Uguaglianza e differenze tra Otto e Novecento

1. Status e contratto fra Otto e Novecento. - 2 IL libero contratto e "il nuovo ordine delle cose". - 3. Le leggi naturali in campo economico e il diritto comune. - 4. Rileggere Maine: dalla "prevalente dipendenza" alla "prevalente autonomia". - 5. Le leggi sociali, l'inversione del moto e i confini del diritto comune. - 6. I confini del diritto 'di tutti'

Codice civile e nazione. Da Risorgimento al tramonto dello Stato liberale.

1. L’Unità nelle leggi. – 2. Codice civile, unità nazionale e unità del diritto – 3. Codice civile e cittadinanza proprietaria – 4. Codice nazionale e universalità del diritto – 5. Codice civile e riforme. – 6. Codice civile e sistema. – 7. Tramonto dello Stato liberale e frammentazione dell’unità del diritto