Evaluation of the optical and biomechanical properties of bioengineered human skin generated with fibrin-agarose biomaterials

Significance: Recent generation of bioengineered human skin allowed the efficient treatment of patients with severe skin defects. However, the optical and biomechanical properties of these models are not known. Aim: Three models of bioengineered human skin based on fibrin-agarose biomaterials (acellular, dermal skin substitutes, and complete dermoepidermal skin substitutes) were generated and analyzed. Approach: Optical and biomechanical properties of these artificial human skin substitutes were investigated using the inverse adding-doubling method and tensile tests, respectively. Results: The analysis of the optical properties revealed that the model that most resembled the optical behavior of the native human skin in terms of absorption and scattering properties was the dermoepidermal human skin substitutes after 7 to 14 days in culture. The time-course evaluation of the biomechanical parameters showed that the dermoepidermal substitutes displayed significant higher values than acellular and dermal skin substitutes for all parameters analyzed and did not differ from the control skin for traction deformation, stress, and strain at fracture break. Conclusions: We demonstrate the crucial role of the cells from a physical point of view, confirming that a bioengineered dermoepidermal human skin substitute based on fibrin-agarose biomaterials is able to fulfill the minimal requirements for skin transplants for future clinical use at early stages of in vitro development.Ministry of Science, Innovation and Universities of Spain PGC2018-101904-A-I0Instituto de Salud Carlos III (ISCIII), Ministry of Science, Innovation and Universities, through AES 2017 AC17/00013Instituto de Salud Carlos III (ISCIII), Ministry of Science, Innovation and Universities within EuroNanoMed framework, EU AC17/00013University of Granada A.TEP.280.UGR18Junta de Andalucía PE-0395-2019Fundación Benéfica Anticancer San Francisco Javier y Santa Cándida, Granada, SpainOTRI.35A-0

Ser o no ser y estar o no estar en Internet.

Objective: To reflect the situation of the websites of the hospital libraries in Spain in 2003. Material and methods: The websites of the hospital libraries have been located through C-17 directory, various hospital directories and searching Google, Altavista and Alltheweb. It has been applied the questionnaire of evaluation of websites with pondered punctuation by Lluís Codina. Visibility indicators have been obtained as well as accessibility according TAW. Results: From the C-17 catalogue have been retrieved 176 hospital libraries, of which 13 have a website; we added to these other 19 websites found through other directories and search engines. Of those 32 websites, 2 were not active; the remaining 30 were analyzed. Five of them passed the Codina's test of level I. In the TAW priority level 1, the problems detected automatically oscillated between 0 and 77. Conclusions: The results show the low number of hospital libraries with websites on the internet. The websites quality should be improved following the recommendations of the checkup lists to evaluate digital resources on the internet. The scarce visibility of these webs, hinders greatly its localization. On the other hand, the low accessibility rate of these webs blocks their visualization to handicapped people

Safety of switching from intravenous to subcutaneous rituximab during first-line treatment of patients with non-Hodgkin lymphoma: the Spanish population of the MabRella study

Rituximab is a standard treatment for non-Hodgkin diffuse large B-cell (DLBCL) and follicular (FL) lymphomas. A subcutaneous formulation was developed to improve the resource use of intravenous rituximab, with comparable efficacy and safety profiles except for increased administration-related reactions (ARRs). MabRella was a phase IIIb trial to assess the safety of switching from intravenous to subcutaneous administration of rituximab during first-line induction/maintenance for DLBCL or FL, focusing on ARRs. Efficacy, satisfaction and quality of life were also assessed. Patients received subcutaneous rituximab plus standard induction chemotherapy for DLBCL or FL for 4–7 cycles, and/or every 2 months maintenance monotherapy for FL for 6–12 cycles. The study included 140 patients: DLBCL, n = 29; FL, n = 111. Ninety-five percent of patients experienced adverse events, reaching grade ≥3 in 38 6% and were serious in 30 0%. AARs occurred in 48 6%, mostly (84 9%) at the injection site, with only 2 1% of patients reaching grade 3. The end-of-induction complete/unconfirmed complete response rate was 69 6%. After a median follow-up of 33 5 months, median disease-/event-/progression-free and overall survivals were not attained. The Rituximab Administration Satisfaction Questionnaire showed improvements in overall satisfaction and the EuroQoL-5D a good quality-of-life perception at induction/maintenance end. Therefore, switching to subcutaneous rituximab showed no new safety issues and maintained efficacy with improved satisfaction and quality of life

Exploring the relation between childhood trauma, temperamental traits and mindfulness in borderline personality disorder

Background: Deficits in mindfulness-related capacities have been described in borderline personality disorder (BPD). However, little research has been conducted to explore which factors could explain these deficits. This study assesses the relationship between temperamental traits and childhood maltreatment with mindfulness in BPD. Methods: A total of 100 individuals diagnosed with BPD participated in the study. Childhood maltreatment was assessed using the Childhood Trauma Questionnaire (CTQ-SF), temperamental traits were assessed using the Zuckerman-Khulman Personality Questionnaire (ZKPQ), and mindfulness capabilities were evaluated with the Five Facet Mindfulness Questionnaire (FFMQ). Results: Hierarchical regression analyses were performed including only those CTQ-SF and ZKPQ subscales that showed simultaneous significant correlations with mindfulness facets. Results indicated that neuroticism and sexual abuse were predictors of acting with awareness; and neuroticism, impulsiveness and sexual abuse were significant predictors of non-judging. Temperamental traits did not have a moderator effect on the relationship between childhood sexual abuse and mindfulness facets. Conclusions: These results provide preliminary evidence for the effects of temperamental traits and childhood trauma on mindfulness capabilities in BPD individuals. Further studies are needed to better clarify the impact of childhood traumatic experiences on mindfulness capabilities and to determine the causal relations between these variables

Myxomatosis and rabbit Haemorrhagic disease: A 30-year study of the occurrence on commercial farms in Spain

In this retrospective study, we describe the relative occurrence of clinical myxomatosis, and rabbit haemorrhagic disease (RHD), on 1714 commercial farms visited in Spain, between 1988 and 2018. We determined the annual prevalence based on 817 visits to 394 farms affected by myxomatosis. Myxomatosis was more prevalent from August to March, being lowest in June (3%) and highest in September (8.9%). With regard to RHD, we assessed 253 visits to 156 affected farms. We analyzed mean annual and monthly incidence. Two important RHD epidemics occurred; the first in 1988-1989 due to RHDV GI.1 (also known as RHDV), and the second from 2011 to 2013 due to RHDV GI.2 (RHDV2 or RHDVb). These epidemics occurred at times when effective vaccination had not been carried out. Relative monthly incidence in 2011-2018 was higher from April to August (p < 0.001). The results we obtained from 1404 necropsies on 102 farms did not clearly relate serosanguinous nasal discharge in rabbits with disease caused by GI.2 infection. We also assessed vaccination schedules used on 200 doe farms visited from the end of 2014 to 2018; 95.5% vaccinated against myxomatosis and 97.5% against RHD. Both diseases remain prevalent; however, effective vaccination has produced a steady decline in myxomatosis and RHDV GI.1 and GI.2 on-farm detection. The maintenance of high hygienic standards will be needed to continue and improve this control. However, further studies are required to investigate the causes of sustained virus presence and vaccine breaks.info:eu-repo/semantics/publishedVersio

Apoptotic microtubules delimit an active caspase free area in the cellular cortex during the execution phase of apoptosis

This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License.Apoptotic microtubule network (AMN) is organized during apoptosis, forming a cortical structure beneath plasma membrane, which has an important role in preserving cell morphology and plasma membrane permeability. The aim of this study was to examine the role of AMN in maintaining plasma membrane integrity during the execution phase of apoptosis. We demonstrated in camptothecin-induced apoptosis in H460 cells that AMN delimits an active caspase free area beneath plasma membrane that permits the preservation of cellular cortex and transmembrane proteins. AMN depolymerization in apoptotic cells by a short exposure to colchicine allowed active caspases to reach the cellular cortex and cleave many key proteins involved in plasma membrane structural support, cell adhesion and ionic homeostasis. Cleavage of cellular cortex and plasma membrane proteins, such as α-spectrin, paxilin, focal adhesion kinase (FAK), E-cadherin and integrin subunit β4 was associated with cell collapse and cell detachment. Otherwise, cleavage-mediated inactivation of calcium ATPase pump (PMCA-4) and Na(+)/Ca(2+) exchanger (NCX) involved in cell calcium extrusion resulted in calcium overload. Furthermore, cleavage of Na(+)/K(+) pump subunit β was associated with altered sodium homeostasis. Cleavage of cell cortex and plasma membrane proteins in apoptotic cells after AMN depolymerization increased plasma permeability, ionic imbalance and bioenergetic collapse, leading apoptotic cells to secondary necrosis. The essential role of caspase-mediated cleavage in this process was demonstrated because the concomitant addition of colchicine that induces AMN depolymerization and the pan-caspase inhibitor z-VAD avoided the cleavage of cortical and plasma membrane proteins and prevented apoptotic cells to undergo secondary necrosis. Furthermore, the presence of AMN was also critical for proper phosphatidylserine externalization and apoptotic cell clearance by macrophages. These results indicate that AMN is essential to preserve an active caspase free area in the cellular cortex of apoptotic cells that allows plasma membrane integrity during the execution phase of apoptosis.This work was supported by FIS PI10/00543 grant, FIS EC08/00076 grant, Ministerio de Sanidad, Spain and Fondo Europeo de Desarrollo Regional (FEDER-Unión Europea), SAS 111242 grant, Servicio Andaluz de Salud Junta de Andalucía, Proyecto de Investigación de Excelencia de la Junta de Andalucía CTS-5725, and by AEPMI (Asociación de Enfermos de Patología Mitocondrial).Peer reviewe

Demonstrating public value to funders and other stakeholders—the journey of ELIXIR, a virtual and distributed research infrastructure for life science data

Open Science is a founding principle of ELIXIR, a pan-European research infrastructure for life science data, with 21 Member countries plus the European Molecular Biology Laboratory. The mission of ELIXIR is to coordinate bioinformatics resources so that they form a single, integrated and pan-European infrastructure, which can be used freely by academic and private-sector researchers across the globe. As a recipient of public and charitable funding, ELIXIR must demonstrate its value, and the need to produce evidence in support of this is intensifying. Our practice-led journey towards demonstrating public value is articulated around five main challenges and, for each, we present our pragmatic approach for tackling it. We begin by showing how we are working towards demystifying what research infrastructures do. We then shed light on the sort of evidence our funders and other stakeholders are asking us for, how this evidence varies in nature and scope, and our tactics to satisfy them. We follow-on by providing our thoughts on possible barriers and solutions to embedding impact evaluation in our activities. Finally, we provide lessons learned, which we believe are sufficiently transferable and will be inspirational to other research infrastructures as they embark on their own journeys to demonstrate public value.publishedVersio

Ser o no ser y estar o no estar en Internet.

Objective: To reflect the situation of the websites of the hospital libraries in Spain in 2003. Material and methods: The websites of the hospital libraries have been located through C-17 directory, various hospital directories and searching Google, Altavista and Alltheweb. It has been applied the questionnaire of evaluation of websites with pondered punctuation by Lluís Codina. Visibility indicators have been obtained as well as accessibility according TAW. Results: From the C-17 catalogue have been retrieved 176 hospital libraries, of which 13 have a website; we added to these other 19 websites found through other directories and search engines. Of those 32 websites, 2 were not active; the remaining 30 were analyzed. Five of them passed the Codina's test of level I. In the TAW priority level 1, the problems detected automatically oscillated between 0 and 77. Conclusions: The results show the low number of hospital libraries with websites on the internet. The websites quality should be improved following the recommendations of the checkup lists to evaluate digital resources on the internet. The scarce visibility of these webs, hinders greatly its localization. On the other hand, the low accessibility rate of these webs blocks their visualization to handicapped people

Infant Formula Supplemented With Milk Fat Globule Membrane, Long-Chain Polyunsaturated Fatty Acids, and Synbiotics Is Associated With Neurocognitive Function and Brain Structure of Healthy Children Aged 6 Years: The COGNIS Study

Background: Adequate nutrient intake during the first few months of life plays a critical role on brain structure and function development. Objectives: To analyze the long-term effects of an experimental infant formula (EF) on neurocognitive function and brain structure in healthy children aged 6 years compared to those fed with a standard infant formula or breastfed. Methods: The current study involved 108 healthy children aged 6 years and participating in the COGNIS Study. At 0-2 months, infants were randomized to receive up to 18 months of life a standard infant formula (SF) or EF enriched with milk fat globule membrane (MFGM), long-chain polyunsaturated fatty acids (LC-PUFAs) and synbiotics. Furthermore, a reference group of breastfed (BF) infants were also recruited. Children were assessed using neurocognitive tests and structural Magnetic Resonance Imaging (MRI) at 6 years old. Results: Experimental infant formula (EF) children showed greater volumes in the left orbital cortex, higher vocabulary scores and IQ, and better performance in an attention task than BF children. EF children also presented greater volumes in parietal regions than SF kids. Additionally, greater cortical thickness in the insular, parietal, and temporal areas were found in children from the EF group than those fed with SF or BF groups. Further correlation analyses suggest that higher volumes and cortical thickness of different parietal and frontal regions are associated with better cognitive development in terms of language (verbal comprehension) and executive function (working memory). Finally, arachidonic acid (ARA), adrenic acid (AdA), docosahexaenoic acid (DHA) levels in cheek cell glycerophospholipids, ARA/DHA ratio, and protein, fatty acid, and mineral intake during the first 18 months of life seem to be associated with changes in the brain structures at 6 years old. Conclusions: Supplemented infant formula with MFGM components, LC-PUFAs, and synbiotics seems to be associated to long-term effects on neurocognitive development and brain structure in children at 6 years old.This project has been funded by Laboratorios Ordesa, S.L. Contract University of Granada General Foundation, No. 3349 and SMARTFOODS (CIEN) Contract University of Granada General Foundation, No. 4003, Spanish Ministry of Economy, Industry and Competitiveness. Furthermore, the project has been partially funded by HORIZON 2020 EU DynaHEALTH Project (GA No. 633595).S