Validation of the Back-table Graft Arterial Anastomosis between the Splenic Artery and Superior Mesenteric Artery: Arterial Complications after a 21-year Single-center Experience of Pancreas Transplantation.

OBJECTIVE: To determine the role of the arterial splenomesenteric anastomosis (ASMA) vascular reconstruction technique in terms of arterial vascular complications in pancreas transplant (PT) recipients. SUMMARY BACKGROUND DATA: The ASMA technique was first described in 1992 by Hospital Clínic Barcelona group. Regardless that the iliac Y-graft technique is the most frequently used worldwide, evidence of arterial complications and implications of using a different back-table reconstruction is conspicuously absent in the literature. METHODS: Descriptive review of 407 PTs performed at a single center (1999-2019) by analyzing the type of arterial reconstruction technique, focusing on ASMA. The endpoints were the management of arterial complications and long-term patient and graft survival. RESULTS: ASMA was performed in 376 cases (92.4%) and a Y-graft in 31 cases (7.6%). A total of 34 arterial complications (8.3%) were diagnosed. In the ASMA group (n=30, 7.9%) they comprised: 15 acute thrombosis; 4 stenosis; 1 pseudoaneurysm and 10 diverse chronic arterial complications while in the Y-graft group (n=4, 12.9%) 3 acute thrombosis and 1 chronic artery-duodenal fistula occurred. Graft salvage was achieved in 16 patients (53.3%) from the ASMA group and in 2 (50%) from the Y-graft. After a median follow-up of 129.2 (IQR 25-75%, 77.2 -182) months the overall graft and patient survival for the whole cohort at 1, 5, and 10 years was 86.7%, 79.5%, 70.5%, and 98.5%, 95.3%, 92.5%, respectively. CONCLUSIONS: The ASMA proves to be a safe and more easily reproducible technique and should therefore be considered for first-line back-table reconstruction in the PT population.

Recent PELE Developments and Applications in Drug Discovery Campaigns.

Computer simulation techniques are gaining a central role in molecular pharmacology. Due to several factors, including the significant improvements of traditional molecular modelling, the irruption of machine learning methods, the massive data generation, or the unlimited computational resources through cloud computing, the future of pharmacology seems to go hand in hand with in silico predictions. In this review, we summarize our recent efforts in such a direction, centered on the unconventional Monte Carlo PELE software and on its coupling with machine learning techniques. We also provide new data on combining two recent new techniques, aquaPELE capable of exhaustive water sampling and fragPELE, for fragment growing.

Frequency of health-care service use and severity of illness in undocumented migrants in Catalonia, Spain: a population-based, cross-sectional study.

BACKGROUND: In Spain, legislation was passed in 2012 excluding undocumented migrants from the public health-care system. Catalonia was one of the Spanish regions that did not implement this legislation, and continued to guarantee access to health care to the whole population. We aimed to analyse health-care use and health status among undocumented migrants in Catalonia, and compare health-care use and health status with legal residents classified according to their socioeconomic position (SEP). METHODS: We did a population-based, cross-sectional study, with administrative individual data. The study included the resident population in Catalonia, Spain, in 2017, aged younger than 65 years and with a maximum annual income of less than €18 000 per year, and classified into three socioeconomic (SEP) groups-low SEP, very low SEP, and undocumented migrants. Indicators regarding health-care service use (primary care, emergency care, mental health care, acute care), drug prescriptions, and selected chronic and infectious diseases were analysed. FINDINGS: Between Jan 1 and Dec 31, 2017, 4 071 988 residents of Catalonia were included in this study; undocumented migrants represented 2·8% (n=113 450) of this population. Of all undocumented migrants, 25 942 (61·0%) female participants aged 15-64 years and 19 819 (46·0%) male participants aged 15-64 years attended primary health-care centres: these rates were lower than in individuals with a very low SEP (84·8% in female participants and 72·1% in male participants). Hospital admission rates among male participants aged 15-64 years in the very low SEP group were more than three times as high as in undocumented migrants (111·6 vs 35·7). The highest tuberculosis rate was found in undocumented male migrants (incidence rate 4·35 [95% CI 3·55-5·16]). INTERPRETATION: Undocumented migrants made less use of health-care services than those in the low and very low SEP groups, but for some infectious diseases, incidence was higher in undocumented migrants. These results constitute an additional argument to support the maintenance of universal health coverage for all citizens. FUNDING: None.

Identification of Plitidepsin as Potent Inhibitor of SARS-CoV-2-Induced Cytopathic Effect After a Drug Repurposing Screen.

There is an urgent need to identify therapeutics for the treatment of Coronavirus disease 2019 (COVID-19). Although different antivirals are given for the clinical management of SARS-CoV-2 infection, their efficacy is still under evaluation. Here, we have screened existing drugs approved for human use in a variety of diseases, to compare how they counteract SARS-CoV-2-induced cytopathic effect and viral replication in vitro. Among the potential 72 antivirals tested herein that were previously proposed to inhibit SARS-CoV-2 infection, only 18 % had an IC50 below 25 µM or 102 IU/ml. These included plitidepsin, novel cathepsin inhibitors, nelfinavir mesylate hydrate, interferon 2-alpha, interferon-gamma, fenofibrate, camostat along the well-known remdesivir and chloroquine derivatives. Plitidepsin was the only clinically approved drug displaying nanomolar efficacy. Four of these families, including novel cathepsin inhibitors, blocked viral entry in a cell-type specific manner. Since the most effective antivirals usually combine therapies that tackle the virus at different steps of infection, we also assessed several drug combinations. Although no particular synergy was found, inhibitory combinations did not reduce their antiviral activity. Thus, these combinations could decrease the potential emergence of resistant viruses. Antivirals prioritized herein identify novel compounds and their mode of action, while independently replicating the activity of a reduced proportion of drugs which are mostly approved for clinical use. Combinations of these drugs should be tested in animal models to inform the design of fast track clinical trials.

FragPELE: Dynamic Ligand Growing within a Binding Site. A Novel Tool for Hit-To-Lead Drug Design.

The early stages of drug discovery rely on hit-to-lead programs, where initial hits undergo partial optimization to improve binding affinities for their biological target. This is an expensive and time-consuming process, requiring multiple iterations of trial and error designs, an ideal scenario for applying computer simulation. However, most state-of-the-art modeling techniques fail to provide a fast and reliable answer to the Induced-Fit protein-ligand problem. To aid in this matter, we present FragPELE, a new tool for in silico hit-to-lead drug design, capable of growing a fragment from a bound core while exploring the protein-ligand conformational space. We tested the ability of FragPELE to predict crystallographic data, even in cases where cryptic sub-pockets open because of the presence of particular R-groups. Additionally, we evaluated the potential of the software on growing and scoring five congeneric series from the 2015 FEP+ dataset, comparing them to FEP+, SP and Induced-Fit Glide, and MMGBSA simulations. Results show that FragPELE could be useful not only for finding new cavities and novel binding modes in cases where standard docking tools cannot but also to rank ligand activities in a reasonable amount of time and with acceptable precision.

Metric Goodness of the Adult Prosocialness Scale. Comparative Study of Italy and Spain.

The main goal of the study is to analyze the metric goodness of the Spanish version of the Adult Prosocialness Scale (Caprara, Steca, Zelli, & Capanna, 2005). Analysis of construct and concurrent validity in two similar samples of young adults, a Spanish sample (target of the adaptation) and an Italian sample (source language), revealed the adequacy of the Spanish version of instrument, with adequate fit of the model in the Spanish group, χ2(96) = 405.28, p = .001, RMSEA = .071, CFI = .94, GFI = .93, and the Italian group χ2(97) = 224.5, p = .001, RMSEA = .075, CFI = .91, GFI = .90. The results also replicated the adequacy of the instrument found in the Italian sample, as the configural and metric invariance was verified in both groups. Analyses of benevolent and power values related to prosociality and differences between genders supported the validity of the scale. In short, the present study confirms the adequacy and sensitivity of the instrument to study prosociality in young adults in a Spanish sample.

Metric goodness of the adult prosocialness scale. Comparative study of Italy and Spain

The main goal of the study is to analyze the metric goodness of the Spanish version of the Adult Prosocialness Scale (Caprara, Steca, Zelli, & Capanna, 2005). Analysis of construct and concurrent validity in two similar samples of young adults, a Spanish sample (target of the adaptation) and an Italian sample (source language), revealed the adequacy of the Spanish version of instrument, with adequate fit of the model in the Spanish group, χ2(96) = 405.28, p = .001, RMSEA = .071, CFI = .94, GFI = .93, and the Italian group χ2(97) = 224.5, p = .001, RMSEA = .075, CFI = .91, GFI = .90. The results also replicated the adequacy of the instrument found in the Italian sample, as the configural and metric invariance was verified in both groups. Analyses of benevolent and power values related to prosociality and differences between genders supported the validity of the scale. In short, the present study confirms the adequacy and sensitivity of the instrument to study prosociality in young adults in a Spanish sample

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