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Contains fulltext : 235105.pdf (Publisher’s version ) (Open Access) AIM: Anastomotic leakage is a severe complication after low anterior resection (LAR) for rectal cancer and occurs in up to 20% of patients. Most research focuses on reducing its incidence and finding predictive factors for anastomotic leakage. There are no robust data on severity and treatment strategies with associated outcomes. The aims of this work were (1) to investigate the factors that contribute to severity of anastomotic leakage and to compose an anastomotic leakage severity score and (2) to evaluate the effects of different treatment approaches on prespecified outcome parameters, stratified for severity score and other leakage characteristics. METHOD: TENTACLE-Rectum is an international multicentre retrospective cohort study. Patients with anastomotic leakage after LAR for primary rectal cancer between 1 January 2014 and 31 December 2018 will be included by each centre. We aim to include 1246 patients in this study. The primary outcome is 1-year stoma-free survival (i.e. patients alive at 1 year without a stoma). Secondary outcomes include number of reinterventions and unplanned readmissions within 1 year, total length of hospital stay, total time with a stoma, the type of stoma present at 1 year (defunctioning, permanent), complications related to secondary leakage and mortality. For aim (1) regression models will be used to create an anastomotic leakage severity score. For aim (2) the effectiveness of different treatment strategies for leakage will be tested after correction for severity score and leakage characteristics, in addition to other potential related confounders. CONCLUSION: TENTACLE-Rectum will be an important step towards drawing up evidence-based recommendations and improving outcomes for patients who experience severe treatment-related morbidity.

Family archives are a common element of the cultural-documentary heritage of all European countries. Public policies must manage programs of support, investment, recovery and diffusion of these archives, in cooperation with their owners. For 30 years, the Basque Government has been developing a program of these characteristics, to which it dedicates approximately € 450,000 each year. The elements that define this specific policy: (1) is a proactive policy, which has mapped these archives, located and identified them, and proposed a specific work program to their owners; (2) the objective is to order, describe and digitize them; (3) the archives are integrated into the website of the Archives System of the Basque Country (4 million digital images, 700,000 descriptions and 5.5 million sacramental records). This policy of promotion and investment, which is sustained over time, has been a success.

Background In recent years, a remarkable trend in neurorehabilitation is the combination of conventional methods and emerging technologies, such as robotic platforms with virtual reality (VR), Serious Games (SG) and other types of sophisticated graphic interfaces. The aim of the present study is to evaluate the influence on the user's mental workload of the degree of graphic detail present in this kind of environments, comparing the experience of subjects working with two graphical environments with the same physical load but radically different graphic detail levels. Methods The same therapy is performed by 52 healthy subjects in two totally different graphic environments, one rich in details and visual stimuli, and its schematic version focusing just in the target graphic elements. Autonomic Nervous System (ANS) activity, related to emotional state, is analyzed through the capture and processing of associated physiological signals. The SAM test is used to assess the subjective perception of the participants in order to establish a relationship with the calculated physiological parameters. Results Indexes calculated from the ANS physiological signals show significant differences between the basal state and those corresponding to the performance of the therapies but do not allow discriminating between the effects of performing a therapy based on an environment rich in stimuli and an austere one. In the case of subjective perceptions, based on the results of the SAM test, the subjects perceive significant differences between the basal stage and the therapies, and also between each of the two graphic environments. Conclusions Users reflected that a graphic environment rich in detail was more pleasant and attractive than a schematic one. However, this is not reflected in values obtained from their physiological activity, which suggests that more research is needed about the online inference of the emotional state of the subject from the record of his physiological activity.

Summary The immunosuppressive transmembrane protein PD-L1 was shown to traffic via the multivesicular body (MVB) and to be released on exosomes. A high-content siRNA screen identified the endosomal sorting complexes required for transport (ESCRT)-associated protein ALIX as a regulator of both EGFR activity and PD-L1 surface presentation in basal-like breast cancer (BLBC) cells. ALIX depletion results in prolonged and enhanced stimulation-induced EGFR activity as well as defective PD-L1 trafficking through the MVB, reduced exosomal secretion, and its redistribution to the cell surface. Increased surface PD-L1 expression confers an EGFR-dependent immunosuppressive phenotype on ALIX-depleted cells. An inverse association between ALIX and PD-L1 expression was observed in human breast cancer tissues, while an immunocompetent mouse model of breast cancer revealed that ALIX-deficient tumors are larger and show an increased immunosuppressive environment. Our data suggest that ALIX modulates immunosuppression through regulation of PD-L1 and EGFR and may, therefore, present a diagnostic and therapeutic target for BLBC., Graphical Abstract, Highlights • ALIX regulates EGFR activity and PD-L1 surface presentation in breast cancer cells • PD-L1 is packaged into the exosomes of breast cancer cells • ALIX depletion results in reduced exosomal and increased surface PD-L1 expression • Increased surface PD-L1 is associated with an enhanced immunosuppressive phenotype, Monypenny et al. show that the ESCRT-related protein ALIX regulates two clinically important proteins in breast cancer; namely, EGFR, a receptor linked to cell survival, and PD-L1, an immune checkpoint protein. ALIX is, therefore, associated with pathways that drive both cell-autonomous and non-cell-autonomous mechanisms of tumor survival.

The interaction of fluorescein‐5‐isothiocyanate (F5ITC) with gold surfaces—either uncoated or pre‐coated with passivating layers of either sodium citrate (citrate), bis(p‐sulfonatophenyl)phenylphosphine dihydrate dipotassium (BSPP), Pluronic P123 (EO20PO70EO20), or Pluronic F127 (EO100PO70EO100)—was studied using quartz crystal microbalance (QCM) measurements in order to determine the surface coverage of F5ITC in each case. Adsorption isotherms of the polymers (P123 and F127) binding to a gold surface were also obtained. Binding of F5ITC to the gold surfaces was found to be highly dependent on the passivating layer. The surface coverage ΓF5ITC of F5ITC on gold surfaces can be listed in decreasing order as ΓF5ITC, Au>ΓF5ITC, citrate>ΓF5ITC, P123>ΓF5ITC, BSPP>ΓF5ITC, F127. Mechanisms for binding of F5ITC to the gold surfaces are also discussed.

La terminologia i el concepte d'Error Congènit del Metabolisme (ECM), van ser establerts per A. Garrod a principis de segle. Avui día sabem que estan causats per errors o mutacions en els gens. Degut a la naturalesa del nostre codi genètic, segons el qual les instruccions del DNA són traduïdes a un producte gènic, les proteïnes, que seran les encarregades d'executar-lo; les mutacions del DNA es tradueixen en proteïnes anòmales amb la corresponent...