Neuropsychiatric performance and treatment of hepatitis C with direct-acting antivirals: a prospective study

Background: Since direct-acting antivirals (DAAs) have been approved for the treatment of hepatitis C virus (HCV) infection, a small series of patients with new-onset neuropsychiatric alterations have been referred to us. We therefore set out to study neuropsychiatric function in relation to DAAs prospectively. Methods: Ten patients with cirrhosis and 12 post-liver transplant (post-LT) patients were enrolled. All underwent wake electroencephalography (EEG) and a neuropsychological evaluation (paper and pencil battery, simple/choice reaction times, working memory task) at baseline, at the end of treatment with DAAs and after 6 months. At the same time points, full blood count, liver/kidney function tests, quantitative HCV RNA, ammonia and immunosuppressant drug levels were obtained, as appropriate. Results: Patients with cirrhosis were significantly older than post-LT patients (65\ub112 vs 55\ub17 years; P<0.05). Neuropsychological performance and wake EEG were comparable in the two groups at baseline. At the end of a course of treatment with DAAs, a significant slowing in choice reaction times and in the EEG (increased relative delta power) was observed in patients with cirrhosis, which resolved after 6 months. In contrast, no significant changes over time were observed in the neuropsychiatric performance of post-LT patients. No significant associations were observed between neuropsychiatric performance and stand-alone/combined laboratory variables. Conclusion: Some degree of neuropsychiatric impairment was observed in relation to treatment with DAAs in patients with cirrhosis, but not in post-LT patients, suggesting that the former may be sensitive to mild DAA neurotoxicity

FIP200 Claw Domain Binding to p62 Promotes Autophagosome Formation at Ubiquitin Condensates

The autophagy cargo receptor p62 facilitates the condensation of misfolded, ubiquitin-positive proteins and their degradation by autophagy, but the molecular mechanism of p62 signaling to the core autophagy machinery is unclear. Here, we show that disordered residues 326–380 of p62 directly interact with the C-terminal region (CTR) of FIP200. Crystal structure determination shows that the FIP200 CTR contains a dimeric globular domain that we designated the “Claw” for its shape. The interaction of p62 with FIP200 is mediated by a positively charged pocket in the Claw, enhanced by p62 phosphorylation, mutually exclusive with the binding of p62 to LC3B, and it promotes degradation of ubiquitinated cargo by autophagy. Furthermore, the recruitment of the FIP200 CTR slows the phase separation of ubiquitinated proteins by p62 in a reconstituted system. Our data provide the molecular basis for a crosstalk between cargo condensation and autophagosome formation

Financial dependence and growth: The role of input-output linkages

We widen the understanding of the finance-growth nexus by accounting for the indirect effect of financial development through input-output (IO) linkages in determining the growth of industries across countries. If financial development is expected to promote disproportionately more the growth of industrial sectors that are more in need of external finance, it also favours more the industries that are linked by IO relations to more financially dependent industries. We explore this new channel in a sample of countries at different development stages over the period 1995–2007. Our results highlight that financial development, besides easing the growth of industries highly dependent on external finance, also fosters the growth of industries strongly linked to highly financially dependent upstream industries. Moreover, the indirect effect - propagated through IO linkages - of finance has a higher and non-negligible role compared to the direct effect and its omission leads to a biased and underestimated perception of the role of finance for industries’ growth

Risk factors for persistent enterococcal bacteraemia: a multicentre retrospective study

Enterococcal bacteraemia; Enterococcus; Persistent bacteraemiaBacteriemia enterocócica, Enterococo; Bacteriemia persistenteBacterèmia enterocòccica; Enterococ; Bacterèmia persistentObjectives Conditions favouring persistent enterococcal bacteraemia (p-EB) have not been fully investigated yet. The aim of our study is to analyse risk factors for p-EB and its impact on mortality. Methods International two-centre retrospective study of all hospitalised adults with enterococcal bacteraemia managed with follow-up blood cultures (BCs) during the period 2011–2019. Exclusion criteria were: (1) death within 72 hours from index BCs and (2) polymicrobial bacteraemia. Primary endpoint was p-EB, defined as further isolation of the same species of Enterococcus spp. from BCs after at least 72 hours of appropriate antibiotic therapy. Multivariable logistic regression model was performed to assess risk factors for p-EB. The impact of p-EB on 30-day mortality was assessed by Kaplan-Meier survival curve and Cox regression multivariable model. Results During the study period, 244 enterococcal bacteraemia were diagnosed. P-EB were 13.5% (33/244). At multivariable analysis, factors independently associated with p-EB were hematologic malignancy (OR 4.60 [95% CI 1.32–16.00], P = 0.01), infective endocarditis (OR 7.99 [95% CI 2.20–28.9], P = 0.002), and use of daptomycin as initial treatment (OR 4.50 [95% CI 1.29–15.61], P = 0.018). Mortality rate was higher in the p-EB group (32% vs. 18%). Kaplan-Meier survival curve showed that patients with p-EB were less likely to survive at 30 days from index BCs (log-rank P = 0.002). Using a Cox regression model, independent predictors of 30-day mortality were hematologic malignancy (HR 2.30 [95% CI 1.02–4.11], P = 0.043), p-EB (HR 1.93 [95% CI 0.92–4.04], P = 0.08), and septic shock (HR 5.92 [95% CI 2.17–16.30], P = 0.001). Conclusion P-EB was diagnosed mainly in very fragile patients and in those receiving daptomycin as frontline therapy. P-EB may have an impact on mortality

Beyond the Concepts of Elder and Marginal in DCD Liver Transplantation: A Prospective Observational Matched-Cohort Study in the Italian Clinical Setting

Donation after circulatory determination of death (DCD) is a valuable strategy to increase the availability of grafts for liver transplantation (LT). As the average age of populations rises, the donor pool is likely to be affected by a potential increase in DCD donor age in the near future. We conducted a prospective cohort study to evaluate post-transplantation outcomes in recipients of grafts from elderly DCD donors compared with younger DCD donors, and elderly donors after brainstem determination of death (DBD). From August 2020 to May 2022, consecutive recipients of deceased donor liver-only transplants were enrolled in the study. DCD recipients were propensity score matched 1:3 to DBD recipients. One-hundred fifty-seven patients were included, 26 of whom (16.6%) were transplanted with a DCD liver graft. After propensity score matching and stratification, three groups were obtained: 15 recipients of DCD donors &amp; GE;75 years, 11 recipients of DCD donors &lt;75 years, and 28 recipients of DBD donors &amp; GE;75 years. Short-term outcomes, as well as 12 months graft survival rates (93.3%, 100%, and 89.3% respectively), were comparable among the groups. LT involving grafts retrieved from very elderly DCD donors was feasible and safe in an experienced high-volume center, with outcomes comparable to LTs from younger DCD donors and age-matched DBD donors

Il processo edilizio supportato dal BIM: l'approccio innovance

Il terzo volume della collana dedicata a INNOVance, presenta l’interpretazione del concetto di BIM elaborata durante il progetto. Una prima parte del documento illustra le esperienze del capitolo italiano IAI, nate in seno al Dipartimento BEST del Politecnico di Milano – poi confluito nel dipartimento ABC - e che sono state premessa del progetto INNOVance. Vengono poi mostrati i concetti di BIM e gli esiti del progetto, in particolare le procedure e i requisiti per la produzione di librerie BIM Interoperabili che sono state definite da INNOVance, aspetto quest’ultimo che ha caratterizzato profondamente il lavoro. La questione del BIM e delle librerie BIM è oggetto di particolare attenzione da parte degli operatori dell’industria edilizia, anche grazie a diversi programmi di ricerca internazionali, tra i quali spicca l’esperienza della National BIM Library britannica sotto l’egida del NBS. La tecnologia BIM, oggi vista da molti come forza propulsiva per lo sviluppo e l’innovazione del settore edilizio, richiede standard operativi utili a garantire che l’informazione possa essere condivisa e soprattutto che possa essere utilizzata da tutti gli operatori del processo. Lo sviluppo di librerie BIM interoperabili è una premessa necessaria per questo ed è un passo fondamentale per facilitare la diffusione del BIM nell’intero processo. L’interpretazione del BIM da parte di INNOVance parte da tale assunto. Si è perciò dedicata grande attenzione allo sviluppo delle librerie, per definire le quali si sono prima di tutto individuati alcuni modelli di riferimento da utilizzare come casi studio nei quali sperimentare le soluzioni tecnologiche digitali costruite come oggetti BIM. Questi ultimi, codificati secondo gli standard INNOVance, sono stati verificati in termini di interoperabilità, requisito fondamentale per garantire condivisione e usabilità dell’informazione lungo la filiera edilizia. L’esito del lavoro, per qualità e approfondimento nonché per le proposte avanzate, colloca a buon diritto INNOVance all’avanguardia in ambito internazionale INNOVance ha inoltre tracciato i requisiti, in termini di standard e norme, che hanno portato allo sviluppo della normativa italiana sul BIM attualmente in fase di gestazione e di cui si anticipano alcuni contenuti nel presente testo

Urban Water Tariffs in Spain: What Needs to Be Done?

Recently, in the context of the Integrated Water Resources Management, demand policies are playing a more important role as opposed to traditional supply policies based on the construction of large hydraulic infrastructures. In this new context, water tariffs have become an important tool in achieving economic efficiency, environmental sustainability, and social equity. This paper reviews the situation of urban water tariffs in Spain, a country subject to high water stress. It analyzes the capacity of urban water tariffs to recover service costs and to promote efficiency, sustainability, affordability, and equity. Although it has made significant progress in recent years, the Spanish urban water tariff system still faces many challenges. Many of these challenges would be better addressed by a national independent regulatory body.The authors also gratefully acknowledge the financial support from the following Spanish institutions: the Consejería de Economía, Innovación, Ciencia y Empleo from the Government of Andalusia (P11-SEJ-7039), the Spanish Ministry of Economics and Competitiveness of Spain (Project ECO2012‐32189), and the CEI BioTIC program from Universidad de Granada (mP_CP_3). Finally, the authors acknowledge the assistance granted under the Programa de Fortalecimiento de las Capacidades de I + D + i, jointly funded by the European Regional Development Fund (ERDF) and the Junta de Andalucía (The Regional Government)

Utilización de herramientas para el control de parámetros ambientales de sistemas eléctricos

En el presente trabajo se exponen aspectos vinculados al manejo de herramientas desarrolladas e implementadas por el ENRE (Ente Nacional Regulador de la Electricidad) para el monitoreo y control de diferentes parámetros ambientales vinculados a empresas del sector eléctrico, como ser Campo Magnético, Campo Eléctrico, Radio Interferencia, etc. En este sentido, se destacan las ventajas de contar con una herramienta que centralice la información correspondiente a diferentes tipos de instalaciones, incluyendo valores medidos de los parámetros mencionados y demás datos complementarios de dichas instalaciones, de manera de constituir una verdadera base de datos que facilita la forma de acceder a la información y que posibilita realizar un seguimiento efectivo. Entre las atribuciones que le corresponden al ENRE se encuentran el dictado de regulaciones y procedimientos técnicos para ser seguidos por los agentes, verificar el cumplimiento de esas regulaciones y aplicar sanciones en los casos de incumplimiento. El Departamento Ambiental del ENRE tiene entre sus múltiples actividades la tarea de analizar la información obtenida por distintos canales y dar respuesta a los reclamos producidos en su ámbito de competencia y jurisdicción, entre otras tareas. En este sentido, la creciente demanda de información por parte del público en general respecto de parámetros ambientales, tales como los campos magnético y eléctrico, confirman la necesidad de disponer de una herramienta como la presentada que contribuya a la administración ágil de esta información y a su vez, prestar una respuesta rápida y concreta ante situaciones que, en algunos casos, pueden afectar a comunidades enteras. Por otro lado también se considera la utilización de la información disponible en la herramienta desarrollada para lograr una interacción efectiva, utilizando datos reales y actualizados, con otros organismos gubernamentales. En el presente trabajo también se vuelcan algunos ejemplos de la información que puede ser obtenida a partir de lo almacenado en la base de datos creada por el ENRE y en la cual ya se cuenta con gran cantidad de mediciones de campos eléctrico y magnético. El IITREE (Instituto de Investigaciones Tecnológicas para Redes y Equipos Eléctricos), mediante un convenio que mantiene la Universidad Nacional de La Plata con el ENRE, ha venido prestando su colaboración en este emprendimiento y ha realizado un gran número de mediciones en distintas instalaciones del país, donde el ENRE tiene incumbencia, siendo dichas mediciones parte sustancial del contenido de la herramienta desarrollada por el ENRE, con la colaboración del IITREE.Comité de estudio C3: Desempeño ambiental del sistema.Instituto de Investigaciones Tecnológicas para Redes y Equipos Eléctricos (IITREE

Risk factors for persistent enterococcal bacteraemia: a multicentre retrospective study

Objectives: Conditions favouring persistent enterococcal bacteraemia (p-EB) have not been fully investigated yet. The aim of our study is to analyse risk factors for p-EB and its impact on mortality.Methods: International two-centre retrospective study of all hospitalised adults with enterococcal bacteraemia managed with follow-up blood cultures (BCs) during the period 2011-2019. Exclusion criteria were: (1) death within 72 hours from index BCs and (2) polymicrobial bacteraemia. Primary endpoint was p-EB, defined as further isolation of the same species of Enterococcus spp. from BCs after at least 72 hours of appropriate antibiotic therapy. Multivariable logistic regression model was performed to assess risk factors for p-EB. The impact of p-EB on 30-day mortality was assessed by Kaplan-Meier survival curve and Cox regression multivariable model.Results: During the study period, 244 enterococcal bacteraemia were diagnosed. P-EB were 13.5% (33/244). At multivariable analysis, factors independently associated with p-EB were hematologic malignancy (OR 4.60 [95% CI 1.32-16.00], P = 0.01), infective endocarditis (OR 7.99 [95% CI 2.20-28.9], P = 0.002), and use of daptomycin as initial treatment (OR 4.50 [95% CI 1.29-15.61], P = 0.018). Mortality rate was higher in the p-EB group (32% vs. 18%). Kaplan-Meier survival curve showed that patients with p-EB were less likely to survive at 30 days from index BCs (log-rank P = 0.002). Using a Cox regression model, independent predictors of 30-day mortality were hematologic malignancy (HR 2.30 [95% CI 1.02-4.11], P = 0.043), p-EB (HR 1.93 [95% CI 0.92-4.04], P = 0.08), and septic shock (HR 5.92 [95% CI 2.17-16.30], P = 0.001).Conclusion: P-EB was diagnosed mainly in very fragile patients and in those receiving daptomycin as frontline therapy. P-EB may have an impact on mortality.(c) 2022 Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/

Preoperative Fibrinogen-to-Albumin Ratio as Potential Predictor of Bladder Cancer: A Monocentric Retrospective Study

: Background and objective: Fibrinogen and albumin are two proteins widely used, singularly and in combination, in cancer patients as biomarkers of nutritional status, inflammation and disease prognosis. The aim of our study was to investigate the preoperative fibrinogen-to-albumin ratio (FAR) as a preoperative predictor of malignancy as well as advanced grade in patients with bladder cancer. Materials and Methods: A retrospective analysis of patients who underwent TURBT at our institution between 2017 and 2021 was conducted. FAR was obtained from preoperative venous blood samples performed within 30 days from scheduled surgery and was analyzed in relation to histopathological reports, as was the presence of malignancy. Statistical analysis was performed using a Kruskal−Wallis Test, and univariate and multivariate logistic regression analysis, assuming p < 0.05 to be statistically significant. Results: A total of 510 patients were included in the study (81% male, 19% female), with a mean age of 71.66 ± 11.64 years. The mean FAR was significantly higher in patients with low-grade and high-grade bladder cancer, with values of 80.71 ± 23.15 and 84.93 ± 29.96, respectively, compared to patients without cancer (75.50 ± 24.81) (p = 0.006). Univariate regression analysis reported FAR to be irrelevant when considered as a continuous variable (OR = 1.013, 95% CI = 1.004−1.022; p = 0.004), while when considered as a categorical variable, utilizing a cut-off set at 76, OR was 2.062 (95% CI = 1.378−3.084; p < 0.0001). Nevertheless, the data were not confirmed in the multivariate analysis. Conclusions: Elevated preoperative FAR is a potential predictor of malignancy as well as advanced grade in patients with bladder cancer. Further data are required to suggest a promising role of the fibrinogen-to-albumin ratio as a diagnostic biomarker for bladder tumors