Consorzio Italiano per la Ricerca in Medicina

ABSTRACT Chromatin folding below the scale of topologically associating domains (TADs) remains largely unexplored in mammals. Here, we used a high-resolution 3C-based method, Micro-C, to probe links between 3D-genome organization and transcriptional regulation in mouse stem cells. Combinatorial binding of transcription factors, cofactors, and chromatin modifiers spatially segregate TAD regions into “microTADs” with distinct regulatory features. Enhancer-promoter and promoter-promoter interactions extending from the edge of these domains predominantly link co-regulated loci, often independently of CTCF/Cohesin. Acute inhibition of transcription disrupts the gene-related folding features without altering higher-order chromatin structures. Intriguingly, we detect “two-start” zig-zag 30-nanometer chromatin fibers. Our work uncovers the finer-scale genome organization that establishes novel functional links between chromatin folding and gene regulation. ONE SENTENCE SUMMARY Transcriptional regulatory elements shape 3D genome architecture of microTADs.

Abstract It remains unclear why acute depletion of CTCF and cohesin only marginally affects expression of most genes despite substantially perturbing 3D genome folding at the level of domains and structural loops. To address this conundrum, we used high-resolution Micro-C and nascent transcript profiling to find that enhancer-promoter (E-P) interactions are largely insensitive to acute (3-hour) depletion of CTCF, cohesin, and WAPL. YY1 has been proposed to be a structural regulator of E-P loops, but acute YY1 depletion also had minimal effects on E-P loops, transcription, and 3D genome folding. Strikingly, live-cell single-molecule imaging revealed that cohesin depletion reduced transcription factor binding to chromatin. Thus, although neither CTCF, cohesin, WAPL, nor YY1 are required for the short-term maintenance of most E-P interactions and gene expression, we propose that cohesin may serve as a “transcription factor binding platform” that facilitates transcription factor binding to chromatin.

Increasing intracellular drug concentration using nanocarriers can be a potential strategy to improve efficacy against glioblastoma (GBM). Here, the fluorescent-labelled NFL-TBS·40-63 peptide (fluoNFL) concentration on a lipid nanocapsule (LNC) was studied to enhance nanovector internalization into human GBM cells. LNC surface-functionalization with various fluoNFL concentrations was performed by adsorption. LNC size and surface charge altered gradually with increasing peptide concentration, but their complement protein consumption remained low. Desorption of fluoNFL from the LNC surface was found to be slow. Furthermore, it was observed that the rate and extent of LNC internalization in the U87MG human glioblastoma cells were dependent on the surface-functionalizing fluoNFL concentration. In addition, we showed that the uptake of fluoNFL-functionalized LNCs was preferential towards U87MG cells compared to healthy human astrocytes. The fluoNFL-functionalized LNC internalization into the U87MG cells was energy-dependent and occurred possibly by macropinocytosis and clathrin-mediated and caveolin-mediated endocytosis. A new ferrocifen-type molecule (FcTriOH), as a potent anticancer candidate, was then encapsulated in the LNCs and the functionalization improved its in vitro efficacy compared to other tested formulations against U87MG cells. In the preliminary study, on subcutaneous human GBM tumor model in nude mice, a significant reduction of relative tumor volume was observed at one week after the second intravenous injection with FcTriOH-loaded LNCs. These results showed that enhancing NFL peptide concentration on the LNC surface is a promising approach for increased and preferential nanocarrier internalization into human GBM cells, and the FcTriOH-loaded LNCs are a promising therapy approach for GBM.

Immune correlates of protection against human cytomegalovirus (HCMV) infection are still debated. This study aimed to investigate which arm of the immune response plays a major role in protection against HCMV infection in kidney transplant recipients (n = 40) and heart transplant recipients (n = 12). Overall, patients were divided into 2 groups: one including 37 patients with low viral load (LVL), and the other including 15 patients with high viral load (HVL). All LVL patients resolved the infection spontaneously, whereas HVL patients were all treated with one or more courses of antivirals. In HVL patients, viral DNAemia, which was more than 100 times higher than LVL, appeared and peaked at significantly earlier times, but disappeared much later than in LVL patients. During a 1‐year follow‐up, all LVL patients had levels of HCMV‐specific CD4 + (and CD8 + ) T cells significantly higher than HVL patients. On the contrary, titers of neutralizing antibodies and enzyme‐linked immunosorbent assay‐IgG antibodies to gB, gHgLgO, and pentamer gHgLpUL128L were overlapping in the 2 patient groups. In conclusion, while a valid HCMV‐specific T‐cell response was detected in more than 90% of LVL patients, >90% of HVL patients lacked an adequate T‐cell response. Antibody responses did not appear to be associated directly or indirectly with protection.

L’autorité, thème majeur de la philosophie politique, apparaît comme un mystère (ou une mystification) dans nos sociétés modernes où l’on déplore (ou célèbre) sa disparition, au moment même où les « relations de pouvoir » paraissent s’imposer dans certaines théories comme la clé ouvrant toutes les portes du savoir sociologique, par ses capacités infinies de dévoilement des intérêts cachés au cœur de toute relation sociale. Pourtant, à l’issue d’un examen approfondi, réunissant des lieux aussi divers que la Chine, l’Inde, la Nouvelle-Calédonie, la Nouvelle-Guinée, les Philippines, la Russie, la Tunisie et Wallis, des sociétés aux régimes politiques allant de l’empire à la « société sans État » en passant par la démocratie et des religions allant de l’islam au chamanisme, l’autorité se révèle être une dimension nécessaire et consubstantielle à la vie sociale, articulant et ordonnant les valeurs fondamentales qui régissent la pensée et l’action collectives. En plaçant chaque forme d’autorité observée dans le tout de chaque culture, ce travail dégage non seulement certaines conclusions quant à la nature de l’autorité, mais invite également à des considérations méthodologiques générales en soulignant les impasses des « anthropologies potestatives » pour lesquelles seuls les rapports de pouvoir sont au fondement de l’ordre social.

We report the current situation regarding the COVID-19 pandemic with particular regard to seafarers and with the indications drawn up by the Centro Internazionale Radio Medico (C.I.R.M.) in this regard.

It is common practice nowadays to associate the measurement uncertainty to the measurand, in order to judge the quality of a result related to the measurement process. However, the improvement of this parameter as well as the adaptation of its estimation modes always remain an analytical challenge, especially in chemical testing. In this paper, we outline a measurement uncertainty estimation mode based on the one-point linear calibration equation to fully establish a "bottom-up" approach for estimating the measurement uncertainty of a multi-point calibration-based HPLC-UV quantitative method. To demonstrate this estimation mode, we have followed as an example of interest the influences resulting from the simultaneous determination of two biochemical indicators, namely the human plasma vitamers retinol and α-tocopherol. Results from this estimation showed consistency when compared to those obtained from the validation-based alternative method, where the relative expanded uncertainties were found, at a 95% confidence level, to be less than 15% for the low concentration ranges of the two molecules. However, the modelling approach shows all the benefits of its use to identify and quantify all the uncertainty contributions arising from the different steps of the analytical process and seems to be quite achievable for comparative HPLC methods.

Depuis son émergence au milieu du xxe siècle comme champ disciplinaire autonome, « l’anthropologie politique » a souhaité montrer qu’il existait hors de l’État et des catégories occidentales des « formes politiques » dont il importait de saisir la logique interne (sociétés segmentaires, chefferies sans pouvoir, big men, etc.). Néanmoins, plutôt que d’approfondir ces spécificités culturelles, l’évolution « postmoderne » des théories, depuis une trentaine d’années, s’appuie une extension illimitée des « rapports de pouvoir », désormais considérés comme l’axiome de toute analyse critique et le soubassement implicite de toute relation sociale. À l’encontre d’une telle généralisation abusive – qui en revient à proposer une « anthropologie potestative » centrée sur la dénonciation d’une « domination » universelle et omniprésente –, le « holisme structural » de Louis Dumont et Daniel de Coppet, en écho à certaines préoccupations semblables en philosophie politique (Lefort, Revault d’Allonnes, Descombes), s’attache à distinguer les notions d’autorité et de pouvoir, afin de comprendre les institutions et valeurs centrales d’une totalité sociale, « domaine et condition du sens ». C’est dans cette orientation épistémologique qu’ont voulu s’inscrire les auteurs de cet ouvrage collectif, à travers diverses études monographiques et des réflexions comparatives.

Bronchiolitis is an acute viral infection of the lower respiratory tract that affects infants and young children. Respiratory syncytial virus (RSV) is the most common causative agent, however other viruses can be the reason of the disease. We retrospectively reviewed the clinical features of infants aged less than 12 months referred to our Pediatric Units of Chivasso, Cirié and Ivrea for acute bronchiolitis requiring hospitalization over two consecutive bronchiolitis seasons. Patient-, disease-
 and treatment related variables were analyzed in this retrospective study. We were able to show how with the high flow oxygen support (HFNC) only a very low number of children (8 out of 192) need to be trasferred to our HUB referral centers. The probability of success were 96% for all patients and 93% for RSV vs. 98% for non-RSV patients (P=NS). Factor associated to failure of treatment were age below 1 months and the failure of HFNC. The wide and increasing use of HFNC in pediatric inpatients improved management of bronchiolitis in Spoke hospitals, reducing transfer to a Hub hospital provided with Intensive Care Units.

<br/>LITERATURE REVIEW ON THE TELEMEDICAL ADVICE FOR SHIPS (TMAS) 2005-2015 <br/><br/>M. Luisa Canals*, Olaf Jensen**, Dominique Jégaden*, Francesco Amenta*, Ilona Denisenko**, Don Eliseo Prisno-III***. <br/>IMHA Research Group, *Mediterranean-**Atlantic-***Indopacific<br/><br/>ABSTRACT<br/><br/>INTRODUCTION<br/>The presentation will provide a review of the international scientific literature on telemedical assistance for ships (TMAS) during the latest 10 years. <br/><br/>OBJECTIVES<br/>1) to improve the quality of the maritime telemedical services 2) to identify research gabs 3) to prepare a draft that can be developed later as a systematic review. <br/><br/>METHODS<br/>The literature search was done in collaboration in the three geographical IMHA-research groups by using PubMed and the respective national scientific journals. The search terms used: "telemedicine AND maritime, seafarers, ships, shipping, fishermen, fisherman, fishing, passengers".<br/><br/>RESULTS<br/>All the abstracts (n= 54) were entered in the Zotero database and distributed in 5 categories: TMAS cross-sectional studies, n=14, Guides on TMAS systems, n=12, not TMAS relevant n= 2, telemedicine but not at sea = 9, no telemedicine- but other maritime relevant issues = 18. Futher the abstracts are scrutinised and the main conclusions summed up. Analysis of other national journals related to maritime medicine show that other interesting articles can be found.<br/><br/>CONCLUSION <br/>The cross-sectional studies show that cardio-vascular disease and injuries form the main parts of the radio medical advice in the merchant, the fishing and the passenger/cruise ships segments. Even if the national TMAS centres have highly technical developed communication systems and skilled personal, there are still many challenges to overcome. <br/><br/>KEY WORDS<br/>Telemedicine, Remote Consultation, Ships <br/>

Objectives: Commonly, general anesthesia (GA) with endotracheal intubation is the standard anesthesiology approach in gynecological laparoscopic surgery; neuraxial anesthesia (NA) can also be used, but its application is very low and limited to few indications. This study assessed NA feasibility for almost all kinds of gynecologic laparoscopies. Materials and Methods: Data on laparoscopic surgeries performed under NA were collected retrospectively. A total of 76 patients had laparoscopic interventions at the Donatello Clinic in Florence, Italy, between October 2019 and August 2022. Adnexectomies, ovarian cyst enucleations, multiple myomectomies, total hysterectomies, radical hysterectomies with sentinel lymph-node biopsies, and complete excisions of endometriosis and adhesiolysis were performed under regional anesthesia. All procedures but 1 were completed with no change from NA. Results: All cases but 1 were completed under NA. There were (1) spontaneously breathing patients; (2) no pulmonary complications; (3) satisfactory muscle relaxation; (4) fast postoperative bowel function recovery; (5) reduced postoperative pain; (6) reduced postoperative narcotics use; and (6) absence of postoperative nausea and vomiting. Conclusions: These procedures appear to comprise the largest series of complex gynecologic laparoscopies performed under NA reported in the literature. Preliminary data seems to support the concept that this approach might be feasible and safe in selected and motivated patients, but further research is needed to confirm these encouraging data. (J GYNECOL SURG 20XX:000)

Background/Objectives: Arrhythmic recurrence is a common issue affecting a significant percentage of patients undergoing transcatheter ablation (TCA) of Atrial Fibrillation (AF). The use of artificial intelligence (AI) for the identification of electrocardiographic predictors of post-ablation recurrence may offer a valuable and cost-effective approach to improve risk stratification and optimize follow-up. This study aims to investigate the relationship between post-procedural electrocardiographic (ECG) P-wave parameters, measured using AI, and AF recurrence in patients undergoing transcatheter ablation (TCA). Methods: Seventy-four patients (age 62.36 ± 10.4 years) with a diagnosis of AF were retrospectively analyzed. ECGs were processed using AI software to analyze P-wave-related variables. All patients had either an implantable loop recorder (ILR) or another form of cardiac implantable electronic device (CIED). Results: Post-procedural P-wave amplitude in lead II (PwA in lead II) showed a significant association with AF recurrence, defined as an average arrhythmic burden &gt;6% at one-year follow-up. Conclusions: These findings underscore the potential of PwA in lead II as a biomarker for the follow-up of patients undergoing TCA and highlight the contribution of AI in the analysis of electrocardiographic parameters predictive of AF recurrence. Together, these results may contribute to the development of early risk-stratification strategies following catheter ablation.

Le texte vise à comprendre le processus de sacralisation des tsars russes durant le xvie siècle, d’Ivan III au Temps des troubles, par une étude de l’aspect « divino-humain » hérité du byzantinisme et les conséquences impliquées dans la perception sociale de l’autorité du Prince, notamment l’anti-conduite (rituels d’inversion) qui émerge à un niveau subordonné. Dans un second temps, le phénomène de « l’imposture » reconduit sous une autre forme cette sacralisation du pouvoir politique, en la disjoignant de son incarnation officielle. D’où l’apparition de « faux-tsars » qui créent autour d’eux un « espace sacré » (comme les fols-en-Christ) et renvoient le possesseur du trône à l’illégitimité, portés par une dynamique qui accorde une autorité messianique au Peuple, devant faire instamment advenir la Vérité révélée au sein d’un horizon social corrompu par l’hérésie au pouvoir.

ABSTRACT: Beta-blockers are a crucial part of post-myocardial infarction (MI) pharmacological therapy. Recent studies have raised questions about their efficacy in patients without reduced left ventricular ejection fraction (LVEF). This study aims to assess adherence to beta-blockers after discharge for ST-segment elevation myocardial infarction (STEMI) and the impact of adherence on outcomes based on LVEF at discharge. The retrospective registry FAST-STEMI evaluated real-world adherence to main cardiovascular drugs in patients with STEMI between 2012 and 2017 by comparing purchased tablets with expected ones at 1 year through pharmacy registries. Optimal adherence was defined as ≥80%. Primary outcomes included all-cause and cardiovascular death while secondary outcomes were MI, major/minor bleeding events, and ischemic stroke. The study included 4688 patients discharged on beta-blockers. The mean age was 64 ± 12.3 years, 76% were male, and the mean LVEF was 49.2 ± 8.8%. The mean adherence at 1 year was 87.1%. Optimal adherence was associated with lower all-cause (adjusted hazard ratio, 0.62, 95% confidence interval, 0.41-0.92, P : 0.02) and cardiovascular (adjusted hazards ratio, 0.55, 95% confidence interval, 0.26-0.98, P : 0.043) mortality. In patients with LVEF ≤40%, optimal adherence was linked to reduced all-cause and cardiovascular mortality, but this was not found in patients with either preserved or mildly reduced LVEF. Predictors of cardiovascular mortality included older age, chronic kidney disease, male gender, and atrial fibrillation. Optimal adherence to beta-blocker therapy in patients with all-comers STEMI reduced all-cause and cardiovascular mortality at 1 year; once stratified by LVEF, this effect was confirmed only in patients with reduced LVEF (<40%) at hospital discharge. Impact of adherence to beta-blockers in all-comers STEMI patients and according to LVEF at discharge: results from the real-world registry FAST-STEMI.

FTTO means Fiber To The Office, in reference to FTTH (Fibre To The Home), deployed in France for individuals. The principle of FTTO is to cable a building totally in fibre optic, to remove as much copper cabling as possible and install microswitches in each office (duct or adjacent), as near the machines as possible. Users are still connected with standard RJ45 copper wiring. Through questions and answers, we will highlight the reasons why FFTO is a controlled and future-oriented technology.Over the last six years, several building projects within the perimeter of Higher Education and Research have chosen this technology and have seen or will see the light of day. Depending on the project, different topologies and technologies are possible. What is the feedback after these years? Is the result as expected? How is the solution experienced on a day-to-day basis? What security, how is a large switch assembly configured and maintained, what high availability is possible? How is Wi-Fi, IP telephony and all PoE devices integrated? Does FTTO contribute to eco-consumption? How can a FTTO call for tender be set up for a project, what are the essential elements to be included and what are the errors to be avoided at all costs? In the future, what is the life expectancy for its infrastructure and what speeds can be envisaged? The RESINFO FTTO Group is working to provide clear answers to all these questions and to share its experience with the community.

[This corrects the article DOI: 10.1021/acsmedchemlett.3c00452.].

L’œuvre de Daniel de Coppet est inséparable de sa connaissance de la société ‘aré’aré de Malaita (îles Salomon) qu’il étudia et fit entendre pour y avoir séjourné dès 1963. Chercheur au CNRS, il dirigea l’équipe Érasme dont les analyses se présentent résolument dans le prolongement des œuvres de Marcel Mauss et de Louis Dumont. Directeur d’études à l’École des hautes études en sciences sociales, son enseignement contribua à former de nombreux étudiants qu’il sut orienter et encourager en leu...