Absence of Caspase 8 and High Expression of PED Protect Primitive Neural Cells from Cell Death

The mechanisms that control neural stem and progenitor cell survival are unknown. In several pathological conditions, death receptor (DR) ligands and inflammatory cytokines exert a deleterious effect on neurons, whereas primitive neural cells migrate and survive in the site of lesion. Here, we show that even in the presence of inflammatory cytokines, DRs are unable to generate death signals in primitive neural cells. Neural stem and progenitor cells did not express caspase 8, the presence of which is required for initiating the caspase cascade. However, exogenous or cytokine-mediated expression of caspase 8 was not sufficient to restore their DR sensitivity. Searching for molecules potentially able to block DR death-inducing signaling complex (DISC), we found that primitive neural cells expressed high levels of the death effector domain-containing protein PED (also known as PEA-15). PED localized in the DISC and prevented caspase 8 recruitment and activation. Moreover, lentiviral-mediated delivery of PED antisense DNA resulted in dramatic down-regulation of the endogenous gene expression and sensitization of primitive neural cells to apoptosis mediated by inflammatory cytokines and DRs. Thus, absence of caspase 8 and high expression of PED constitute two levels of protection from apoptosis induced by DRs and inflammatory cytokines in neural stem and progenitor cells

An Italian Multicenter Study on the Epidemiology of Respiratory Syncytial Virus During SARS-CoV-2 Pandemic in Hospitalized Children

Since the beginning of 2020, a remarkably low incidence of respiratory virus hospitalizations has been reported worldwide. We prospectively evaluated 587 children, aged <12 years, admitted for respiratory tract infections from 1 September 2021 to 15 March 2022 in four Italian pediatric hospitals to assess the burden of respiratory viruses during the COVID-19 pandemic in Italy. At admission, a Clinical Respiratory Score was assigned and nasopharyngeal or nasal washing samples were collected and tested for respiratory viruses. Total admissions increased from the second half of October 2021 to the first half of December 2021 with a peak in early November 2021. The respiratory syncytial virus (RSV) incidence curve coincided with the total hospitalizations curve, occurred earlier than in the pre-pandemic years, and showed an opposite trend with respect to the incidence rate of SARS-CoV-2. Our results demonstrated an early peak in pediatric hospitalizations for RSV. SARS-CoV-2 may exhibit a competitive pressure on other respiratory viruses, most notably RSV

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Transcranial electrical and magnetic stimulation (tES and TMS) for addiction medicine: A consensus paper on the present state of the science and the road ahead

There is growing interest in non-invasive brain stimulation (NIBS) as a novel treatment option for substance-use disorders (SUDs). Recent momentum stems from a foundation of preclinical neuroscience demonstrating links between neural circuits and drug consuming behavior, as well as recent FDA-approval of NIBS treatments for mental health disorders that share overlapping pathology with SUDs. As with any emerging field, enthusiasm must be tempered by reason; lessons learned from the past should be prudently applied to future therapies. Here, an international ensemble of experts provides an overview of the state of transcranial-electrical (tES) and transcranial-magnetic (TMS) stimulation applied in SUDs. This consensus paper provides a systematic literature review on published data – emphasizing the heterogeneity of methods and outcome measures while suggesting strategies to help bridge knowledge gaps. The goal of this effort is to provide the community with guidelines for best practices in tES/TMS SUD research. We hope this will accelerate the speed at which the community translates basic neuroscience into advanced neuromodulation tools for clinical practice in addiction medicine

Costruzione di un nuovo vettore genetico integrativo per l'espressione di proteine eterologhe in Hansenula polymorpha (sin. Pichia angusta)

Dottorato di ricerca in biotecnologia. 7. ciclo. Tutore N. Nicolai. Coordinatore V. PalliniConsiglio Nazionale delle Ricerche - Biblioteca Centrale - P.le Aldo Moro, 7, Rome; Biblioteca Nazionale Centrale - P.za Cavalleggeri, 1, Florence / CNR - Consiglio Nazionale delle RichercheSIGLEITItal

Engagement politique non traditionnel des militantes musulmanes pieuses illibérales en Tunisie en 2019

Cette étude contribue à la littérature sur le genre, la théorie des mouvements sociaux et le nationalisme en mettant en lumière l'engagement politique des femmes pieuses et leur compréhension de la citoyenneté dans la Tunisie post-révolutionnaire. Le cadre théorique de ce travail s'enracine dans le concept d'« autorité identitaire » élaboré par Nielsen (2020). Cette étude porte sur les stratégies de résistance des femmes contre ce qu'elles perçoivent comme un État impie leur imposant un modèle rigide d'identité nationale, la Tunisianité. La recherche empirique pour ce travail a été menée à Tunis, entre 2018 et 2020, à travers des entretiens semi-structurés avec de pieuses militantes musulmanes illibérales dans deux associations coraniques, les membres du parti non électoral Hizb ut-Tahrir, une femme salafiste, une militante indépendante, une S17, et des fonctionnaires d'État, les wa'ydhat. Au sein des associations coraniques, j'ai effectué l'observation participante pendant huit mois à Tunis. J'ai tendance à voir la population très hétérogène de cette étude comme une force car j'ai réussi à observer de multiples exemples de ce que j'appelle des femmes musulmanes pieuses et illibérales et leurs différentes revendications politiques. Les résultats de la recherche empirique montrent que: • Les « activistes musulmanes illibérales pieuses » ne rentrent pas dans la théorie de la soumission, car elles font preuve d'agence à travers leur engagement politique non traditionnel (voir Chapitre 1, 2) ; • Les « activistes musulmanes illibérales pieuses », en particulier celles des associations coraniques, sont, contrairement au sens commun, des citoyennes politiquement conscientes (voir chapitre 4) ; • Les « activistes musulmanes illibérales pieuses » s'opposent consciemment à la notion de Tunisianité (voir chapitres 5, 6, 7) • Les « activistes musulmanes illibérales pieuses » ont crée des espaces d'autonomie par rapport à leurs homologues masculins (voir chapitre 8). Sur le plan méthodologique, j'ai trouvé que: • L'enquête comme méthode de recherche n'est pas particulièrement efficace pour étudier de petits groupes où la confiance doit être mise en place avant l'enquête (voir chapitre 3).This study contributes to the literature on gender, social movement theory and nationalism in shedding light on the political engagement of pious women and their understanding of citizenship in post-revolutionary Tunisia. The theoretical frame of this work is rooted in the concept of "identity authority" elaborated by Nielsen (2020). This study focuses on women's strategies of resistance against what they perceive being an impious state imposing on them a rigid model of national identity, the Tunisianité. Empirical research for this work was conducted in Tunis, between 2018 and 2020, through semi-structured interviews with pious illiberal Muslim women activists in two koranic associations, the members of the non-electoral party Hizb ut-Tahrir, one Salafi woman, one independent activist, one S17, and religious civil servants, the wa'ydhat. Within the koranic associations, I carried out participant observation for eight months in Tunis. I tend to seethe highly heterogeneous population of this study as a strength as I managed to observe multiple examples of what I call pious, illiberal Muslim women and their different political claims. The empirical research findings show that: • "pious illiberal Muslim women activists" cannot fall under the submission theory, as they show agency through their non-traditional political engagement (see Chapter 1, 2); • "pious illiberal Muslim women activists", especially those in the koranic associations, are, against conventional wisodm, politically conscious citizens (see Chapter 4);• "pious illiberal Muslim women activists" consciously oppose the notion of Tunisianité (see Chapters 5, 6,7)• "pious illiberal Muslim women activists" managed to find spaces of autonomy from their male counterparts (see Chapter 8) On a methodological level, I found that: • survey as research method is not particularly efficacious for studying small groups where trust need to be implemented before the survey (see Chapter 3)

Mixed Reality Approach for the Management of Building Maintenance and Operation

Building Information Modelling (BIM) has been indicated as the right tool to provide the construction industry with the productivity boost that has been lacking in the last 40 years. This momentum finds its highest fulfilment in the support provided by BIM models to knowledge management and the automation of process. However, the management of information flow is still far from its automation breakthrough and, as far as operation and maintenance are concerned, knowledge about procedures is often incomplete. Moreover, processes are often do not undergo optimisation and the individual steps to be performed are not communicated, but in facility management (FM) the transmission of know-how is fundamental particularly because some operations are dangerous or risky. In this framework, Mixed Reality (MR) represents a powerful means to communicate the correct data concerning both geometric features to be considered and the standard procedure to be followed. The aim of this paper is to investigate the possibility of exploiting the benefits provided by these technologies to achieve automation in the transmission of information and optimisation of procedures, improving efficiency and productivity thanks to a better understanding of the operations to be carried out and the reduction of errors. With the support of a head-mounted display (HDM) device with a see-through screen capable of presenting 3D virtual objects, this research tries to combine information from a BIM model with reality to study the benefits for maintenance personnel

La violenza sessuale sui minorenni: indagine sulle denunce pervenute alla Procura della Repubblica presso il Tribunale per i minorenni di Perugia dal 1991 al 2006

The present survey emerges from the need to investigate a very complex phenomenon, that is sexual abuse of minors, pedophilia and crime against children and teenagers in general. The aim of the study was to deal with this topic, which has in recent years been given much attention by the media and public opinion, from a scientific point of view. Apart from the difficulties in defining and making diagnosis of sexual violence, the statistical-epidemiological aspects were problematic due to both the complexities in collecting data on this crime and evaluating the actual extent of the phenomenon. Considering the complex nature there of the main target of this investigation was to outline the Umbrian situation as accurately as possible by comparing it with the results of other national and international surveys in order to learn more about this phenomenon. Cases of sexual violence against minors reported to the police from 1991 to 2006 and filed in the Public Prosecutor’s Office at the Juvenile Court in Perugia were consulted. It has emerged from this research that the situation in Umbria partially reflects other Italian and international statistical data and in some aspects diverges from them.La presente indagine nasce dall’esigenza di far luce su un fenomeno altamente complesso e per molti aspetti ancora oscuro e di rispondere mediante rilevazioni scientifiche alla grande attenzione rivolta negli ultimi anni dai mezzi di comunicazione e dall’opinione pubblica a temi come gli abusi sessuali sui minorenni, la pedofilia e più in generale i delitti contro l’infanzia e l’adolescenza. Alle difficoltà definitorie e diagnostiche si affiancano quelle di origine statisticoepidemiologica, legate sia alle complicazioni nel reperimento dei dati relativi a questo reato, sia alla valutazione dell’entità reale del fenomeno.Alla luce di tale complessità, l’obiettivo principale di questa indagine è quello di tracciare un quadro quanto più fedele possibile della realtà umbra, comparandolo con quanto emerso da altre ricerche nazionali ed internazionali, allo scopo di raggiungere una maggior conoscenza del fenomeno. A tale finalità sono stati consultati i fascicoli relativi alle denunce di violenze sessuali sui minori pervenute dal 1991 al 2006 alla Procura della Repubblica presso il Tribunale per i Minorenni di Perugia. Da questo studio condotto sulle denunce di violenze sessuali su minorenni degli ultimi 16 anni nella regione Umbria deriva un quadro del fenomeno parzialmente corrispondente a quanto emerso da altre ricerche nazionali ed internazionali e per alcuni aspetti peculiare

First-time diagnosis after an emergency presentation in children with cancer

Aim: To determine the prevalence rate of cancer diagnoses by an emergency route, the related risk factors and whether the emergency diagnosis was associated with poorer outcome. Methods: Retrospective observational study with identification of patients diagnosed at the Pediatric Oncology Unit of "Sapienza" University between 2008 and 2018. The percentage of patients who received a first-time diagnosis after an emergency presentation was determined. Two-year survival and clinical factors, such as sex, age and histology, associated to emergency presentation were evaluated. Results: Of 207 patients (109 girls and 98 boys; median age, 120 months), with a first-time diagnosis of solid tumor, 5.8% were diagnosed during an emergency admission after a median latency time of 2.5 days. Cases with an emergency diagnosis were younger compared with those who were diagnosed electively (median age, 30 months vs 120 months, P < 0.005). Higher prevalence rate of emergency presentation was detected in patients with lymphoma compared with those with no lymphoma disease (28.6% vs 4.1%; P < 0.0001). All patients were managed to overcome their emergency presentation, 33.3% of these died later. No statistically significant difference for 2-year overall survival was found between patients with an emergency diagnosis and those with elective diagnosis (66.7% vs 81.0%; odds ratio, 2.1; confidence interval, 0.6-7.5; P = 0.22). Conclusions: A minor but not negligible number of pediatric patients come to a first-time diagnosis of cancer as result of a life-threatening event; risk factors were younger age and lymphoma disease. The emergency event can be successfully treated, and it was not related to a poorer survival