Effect of the Purinergic Inhibitor Oxidized ATP in a Model of Islet Allograft Rejection

The lymphocytic ionotropic purinergic P2X receptors (P2X1R-P2X7R, or P2XRs) sense ATP released during cell damage-activation, thus regulating T-cell activation. We aim to define the role of P2XRs during islet allograft rejection and to establish a novel anti-P2XRs strategy to achieve long-term islet allograft function. Our data demonstrate that P2X1R and P2X7R are induced in islet allograft-infiltrating cells, that only P2X7R is increasingly expressed during alloimmune response, and that P2X1R is augmented in both allogeneic and syngeneic transplantation. In vivo short-term P2X7R targeting (using periodate-oxidized ATP [oATP]) delays islet allograft rejection, reduces the frequency of Th1/Th17 cells, and induces hyporesponsiveness toward donor antigens. oATP-treated mice displayed preserved islet grafts with reduced Th1 transcripts. P2X7R targeting and rapamycin synergized in inducing long-term islet function in 80% of transplanted mice and resulted in reshaping of the recipient immune system. In vitro P2X7R targeting using oATP reduced T-cell activation and diminished Th1/Th17 cytokine production. Peripheral blood mononuclear cells obtained from long-term islet-transplanted patients showed an increased percentage of P2X7R+CD4+ T cells compared with controls. The beneficial effects of oATP treatment revealed a role for the purinergic system in islet allograft rejection, and the targeting of P2X7R is a novel strategy to induce long-term islet allograft function

Effect of the Purinergic Inhibitor Oxidized ATP in a Model of Islet Allograft Rejection

The lymphocytic ionotropic purinergic P2X receptors (P2X1R-P2X7R, or P2XRs) sense ATP released during cell damage-activation, thus regulating T-cell activation. We aim to define the role of P2XRs during islet allograft rejection and to establish a novel anti-P2XRs strategy to achieve long-term islet allograft function. Our data demonstrate that P2X1R and P2X7R are induced in islet allograft-infiltrating cells, that only P2X7R is increasingly expressed during alloimmune response, and that P2X1R is augmented in both allogeneic and syngeneic transplantation. In vivo short-term P2X7R targeting (using periodate-oxidized ATP [oATP]) delays islet allograft rejection, reduces the frequency of Th1/Th17 cells, and induces hyporesponsiveness toward donor antigens. oATP-treated mice displayed preserved islet grafts with reduced Th1 transcripts. P2X7R targeting and rapamycin synergized in inducing long-term islet function in 80% of transplanted mice and resulted in reshaping of the recipient immune system. In vitro P2X7R targeting using oATP reduced T-cell activation and diminished Th1/Th17 cytokine production. Peripheral blood mononuclear cells obtained from long-term islet-transplanted patients showed an increased percentage of P2X7R+CD4+ T cells compared with controls. The beneficial effects of oATP treatment revealed a role for the purinergic system in islet allograft rejection, and the targeting of P2X7R is a novel strategy to induce long-term islet allograft function

Family burden, emotional distress and service satisfaction in first episode psychosis. Data from the GET UP trial

Background: Literature has documented the role of family in the outcome of chronic schizophrenia. In the light of this, family interventions (FIs) are becoming an integral component of treatment for psychosis. The First Episode of Psychosis (FEP) is the period when most of the changes in family atmosphere are observed; unfortunately, few studies on the relatives are available. Objective: To explore burden of care and emotional distress at baseline and at 9-month follow-up and the levels of service satisfaction at follow-up in the two groups of relatives (experimental treatment EXP vs. treatment as usual TAU) recruited in the cluster-randomized controlled GET UP PIANO trial. Methods: The experimental treatment was provided by routine public Community Mental Health Centers (Italian National Health Service) and consisted of Treatment as Usual plus evidence-based additional treatment (Cognitive Behavioral Therapy for psychosis for patients, Family Intervention for psychosis, and Case Management). TAU consisted of personalized outpatient psychopharmacological treatment, combined with non-specific supportive clinical management and informal support/educational sessions for families. The outcomes on relatives were assessed by the Involvement Evaluation Questionnaire (IEQ-EU), the General Health Questionnaire (GHQ-12), and the Verona Service Satisfaction Scale (VSSS-EU). Differences within and between groups were evaluated. Results: At baseline, 75 TAU and 185 EXP caregivers were assessed. In the experimental group 92% of relatives participated in at least 1 family session. At follow-up both groups experienced improvement in all IEQ and GHQ items, but caregivers belonging to the EXP arm experienced a significantly greater change in 10 IEQ items (mainly pertaining to the "Tension" dimension) and in GHQ items. Due to the low sample size, a significant effectiveness was only observed for 2 IEQ items and 1 GHQ-12 item. With respect to VSSS data at follow-up, caregivers in the EXP arm experienced significantly greater satisfaction in 8 items, almost all pertaining to the dimensions "Relatives' Involvement" and "Professionals' Skills and Behavior." Conclusions: The Family intervention for psychosis delivered in the GET UP PIANO trial reduced family burden of illness and improved emotional distress and satisfaction with services. These results should encourage to promote FIs on caregivers of first-episode psychosis patients

A multi-element psychosocial intervention for early psychosis (GET UP PIANO TRIAL) conducted in a catchment area of 10 million inhabitants: study protocol for a pragmatic cluster randomized controlled trial

Multi-element interventions for first-episode psychosis (FEP) are promising, but have mostly been conducted in non-epidemiologically representative samples, thereby raising the risk of underestimating the complexities involved in treating FEP in 'real-world' services

L’esternalizzazione ai privati delle attività di valorizzazione e dei servizi per il pubblico negli istituti e luoghi di cultura

L'esternalizzazione ai privati delle attività di valorizzazione e dei servizi per il pubblico negli istituti e luoghi di cultura costituisce la forma tradizionalmente più rilevante di collaborazione tra pubblico e privato nei processi di valorizzazione dei beni culturali pubblici. Il coinvolgimento dei privati nella gestione dei servizi di valorizzazione ha determinato indubbi vantaggi, contribuendo all'innalzamento del livello qualitativo medio dell'offerta culturali di musei e siti del nostro Paese. Tuttavia, tale collaborazione ha sollevato molteplici criticità, talune connesse all'incertezza del quadro normativo, altre emerse nella concreta prassi applicativa

Il sindacato del giudice amministrativo sulle valutazioni tecniche dell’amministrazione in materia di salute

Il contributo si pone l'obiettivo di analizzare il sindacato del giudice amministrativo sulle valutazioni tecniche in materia di salute, con particolare riferimento alle valutazioni medico-legali e alle valutazioni circa la sussistenza di una situazione di pericolo o di pregiudizio per l'integrità psico-fisica della collettività, poste a fondamento delle ordinanze adottate dalle Amministrazioni centrali e locali a tutela della salute pubblica. L'indagine è volta a verificare l’effettivo tipo di controllo giurisdizionale effettuato su tali valutazioni, al di là delle formule astratte utilizzate nelle pronunce e, a tal fine, sono stati esaminati nel dettaglio le modalità e gli strumenti attraverso i quali il giudice valuta l’attendibilità dei giudizi tecnici, tenendo conto delle peculiarità e delle differenze dei singoli provvedimenti presi in esame

Eva Steiner, French Law. A Comparative Approach, new York, Oxford University Press, 2018, 312 p.

Le distanze tra gli ordinamenti giuridici nazionali, in particolare tra quelli di common law e quelli di civil law, si sono gradualmente attenuate, ma ancora permangono alcune differenze, che riflettono le diverse tradizioni giuridiche e culturali dei singoli Paesi. Tali differenze possono costituire un ostacolo alla conoscenza e alla comprensione del funzionamento dei sistemi giuridici da parte di giuristi di altri ordinamenti. Il libro di Eva Steiner tenta di superare tali ostacoli fornendo al lettore le coordinate essenziali per conoscere e comprendere il funzionamento dell'ordinamento giuridico francese e per muoversi al suo interno

Errol P. Mendes, Peace and Justice at the International Criminal Court. A Court of Last Resort, Cheltenham, Edward Elgar, 2019

Mendes offre un’analisi critica dettagliata dell’azione e del ruolo svolto dalla Corte penale internazionale nella repressione dei più gravi crimini internazionali. La prospettiva di fondo accolta dall’autore è che una pace sostenibile e duratura non possa essere raggiunta senza il perseguimento della giustizia; tali distinti interessi, infatti, lungi dall’essere in conflitto tra di loro, sono profondamente interconnessi e complementari: come rileva Mendes nella prefazione, non vi può essere «a zero-sum game between peace and justice»