CD5L promotes M2 macrophage polarization through autophagy-mediated upregulation of ID3

CD5L (CD5 molecule-like) is a secreted glycoprotein that controls key mechanisms in inflammatory responses, with involvement in processes such as infection, atherosclerosis, and cancer. In macrophages, CD5L promotes an anti-inflammatory cytokine profile in response to TLR activation. In the present study, we questioned whether CD5L is able to influence human macrophage plasticity, and drive its polarization toward any specific phenotype. We compared CD5L-induced phenotypic and functional changes to those caused by IFN/LPS, IL4, and IL10 in human monocytes. Phenotypic markers were quantified by RT-qPCR and flow cytometry, and a mathematical algorithm was built for their analysis. Moreover, we compared ROS production, phagocytic capacity, and inflammatory responses to LPS. CD5L drove cells toward a polarization similar to that induced by IL10. Furthermore, IL10- and CD5L-treated macrophages showed increased LC3-II content and colocalization with acidic compartments, thereby pointing to the enhancement of autophagy-dependent processes. Accordingly, siRNA targeting ATG7 in THP1 cells blocked CD5L-induced CD163 and Mer tyrosine kinase mRNA and efferocytosis. In these cells, gene expression profiling and validation indicated the upregulation of the transcription factor ID3 by CD5L through ATG7. In agreement, ID3 silencing reversed polarization by CD5L. Our data point to a significant contribution of CD5L-mediated autophagy to the induction of ID3 and provide the first evidence that CD5L drives macrophage polarization.Peer ReviewedPostprint (published version

Protagonitza Barcelona

Treballs de l'alumnat del Grau de Comunicació Audiovisual, Facultat de Biblioteconomia i Documentació, Universitat de Barcelona, [Projectes I - Grup VI]. Curs: 2015-2016, Tutor: Jaume Vilaseca Corderroure.Directors: Núria Barba, Aran Comín, Gemma Burgos, Mar Fernández, Raquel Gil, Alba Pedrerol i Berta Salvat; Productora: Alba Pedrerol; Aj. Producció: Núria Barba; Guionista: Berta Salvat; Directora de fotografia: Mar Fernández; Càmera: Gemma Burgos; Aj. càmera; Alba Pedrerol; Il·luminadora: Raquel Gil; Direcció de so: Aran Comín; Muntatge: Gemma Burgos; Música: Aran Comín; Equip artístic: Aran Comín, Josh Pricard, Raquel Gil, Núria Barba, Alba Pedrerol.Un grup de cinc amics participen en un joc d’atzar que consisteix a representar pel·lícules en llocs emblemàtics de Barcelona: la Sagrada Família, el Passeig de Gràcia, la Barceloneta, les Rambles, els Búnkers del Caramel, Plaça Catalunya i el Park Güell. Junts representen experiències de vida com l’amor, la diversió o el misteri a través de les pel·lícules Forrest Gump, Singin’ in the rain, Titanic, The Birds, The Lion King, The Lord of the Rings i Per qualche dollaro in più. El punt culminant és quan, després d’haver representat les escenes més mítiques dels films, van als cinemes Comedia per gaudir en companyia de les pel·lícules que els ofereix

The effectiveness of a digital shared decision-making tool in hormonal contraception during clinical assessment: study protocol of a randomized controlled trial in Spain

Decision-making tools represent a paradigm shift in the relationship between the clinician and the user/patient. Some of their advantages include patient commitment, the promotion of preferences and values, and increased treatment adherence. This study protocol aims to assess the effectiveness of a decision-making tool in contraception (SHARECONTRACEPT) concerning: a) Improvement in counselling on hormonal contraception at the medical consultation, measured in terms of decreasing decisional conflict and improving knowledge of available contraceptive options; b) Improvement in adherence to treatment measured in terms of: persistence in the chosen treatment, compliance with dose or procedure of use, and ability to deal with incidents related to the use of the contraceptive method; and decreasing unwanted pregnancies and voluntary interruption of pregnancy. The SHARECONTRACEPT tool, developed by previous phases of this project, is available at: http://decisionscompartides.gencat.cat/en/decidir-sobre/anticoncepcio_hormonal/ METHODS/DESIGN: A longitudinal, prospective-type, randomized, controlled community clinical trial, carried out in the clinical contraceptive counselling units of 6 autonomous regions in Spain, with an experimental group and a control group. Description of the intervention: The health professionals participating will be randomly assigned to one of the two groups. Clinicians assigned to the experimental group will perform contraceptive counselling assisted by SHARECONTRACEPT, and those of the control group will follow the conventional contraceptive counselling provided in their clinical unit. It is planned to study 1708 users (control group n = 854 and intervention group n = 854), recruited from women who attend the consultations of the health professionals. The selected users will be followed up for one year. The data will be collected through ad-hoc questionnaires, and validated instruments for measuring decisional conflict and adherence to treatment.info:eu-repo/semantics/publishedVersio

Development of a reliable clinical assessment tool for meningoencephalitis in dogs: The neurodisability scale.

BackgroundMeningoencephalitis of unknown origin (MUO) comprises a group of debilitating inflammatory diseases affecting the central nervous system of dogs. Currently, no validated clinical scale is available for the objective assessment of MUO severity.ObjectivesDesign a neurodisability scale (NDS) to grade clinical severity and determine its reliability and whether or not the score at presentation correlates with outcome.AnimalsOne hundred dogs with MUO were included for retrospective review and 31 dogs were subsequently enrolled for prospective evaluation.MethodsMedical records were retrospectively reviewed for 100 dogs diagnosed with MUO to identify the most frequent neurological examination findings. The NDS was designed based on these results and evaluated for prospective and retrospective use in a new population of MUO patients (n = 31) by different groups of independent blinded assessors, including calculation of interobserver agreement and association with outcome.ResultsThe most common clinical signs in MUO patients were used to inform categories for scoring in the NDS: seizure activity, ambulatory status, posture and cerebral, cerebellar, brainstem, and visual functions. The intraclass correlation coefficient (ICC) for prospective use of the NDS was 0.83 (95% confidence interval [CI], 0.68-0.91) indicating good agreement, and moderate agreement was found between prospective and retrospective assessors (ICC, 0.71; 95% CI, 0.56-0.83). No association was found between NDS score and long-term outcome.Conclusions and clinical importanceThe NDS is a novel clinical measure for objective assessment of neurological dysfunction and showed good reliability when used prospectively in MUO patients but, in this small population, no association with outcome could be identified

Detection of lesions in the optic nerve with magnetic resonance imaging using a 3D convolutional neural network

Deep learning; Multiple sclerosis, Optic nerveAprendizaje profundo; Esclerosis múltiple; Nervio ópticoAprenentatge profund; Esclerosi múltiple; Nervi òpticBackground Optic neuritis (ON) is one of the first manifestations of multiple sclerosis, a disabling disease with rising prevalence. Detecting optic nerve lesions could be a relevant diagnostic marker in patients with multiple sclerosis. Objectives We aim to create an automated, interpretable method for optic nerve lesion detection from MRI scans. Materials and Methods We present a 3D convolutional neural network (CNN) model that learns to detect optic nerve lesions based on T2-weighted fat-saturated MRI scans. We validated our system on two different datasets (N = 107 and 62) and interpreted the behaviour of the model using saliency maps. Results The model showed good performance (68.11% balanced accuracy) that generalizes to unseen data (64.11%). The developed network focuses its attention to the areas that correspond to lesions in the optic nerve. Conclusions The method shows robustness and, when using only a single imaging sequence, its performance is not far from diagnosis by trained radiologists with the same constraint. Given its speed and performance, the developed methodology could serve as a first step to develop methods that could be translated into a clinical setting.This project was developed as a part of Gerard Martí-Juan ECTRIMS Research Fellowship Program 2021–2022. This study was partially supported by the Projects (PI18/00823, PI19/00950), from the Fondo de Investigación Sanitaria (FIS), Instituto de Salud Carlos III

Combining biocatalysts to achieve new phase change materials. Application to non-edible animal fat

"Formerly known as Journal of Molecular Catalysis A: Chemical"The thermal properties of various alkyl threo-9, 10-dihydroxystearates (DHSEs) prepared from non-edible fat were studied. Non-edible animal fat was hydrolyzed in a 93% yield with R. oryzae resting cells. Crude unsaturated fatty acids were recovered from the matter liquor resulting from a crystallization performed to achieve the saturated fatty acids. These unsaturated free fatty acids were epoxidized with 30% H2O2 using immobilized Candida antarctica Lipase-B (CAL-B) as biocatalyst. The epoxy ring was cleaved with hot water in the presence of tert-butanol (t-BuOH). Pure threo-9, 10-dihydroxystearic acid (DHSA) from animal fat was recovered by crystallization (51% yield). Subsequently, DHSA was esterified in alpha-limonene using biocatalysts yielding twelve DHSEs (58-90% yield). Differential scanning calorimetry (DSC) analysis of these esters revealed potential latent heats ranging from 136.83 kJ kg−1 to 234.22 kJ kg−1 and melting temperatures from 52.45 ◦C to 76.88 ◦C. Finally, the compounds with enthalpies above 200 kJ kg−1 were subjected to 100 and 1000 thermal cycles. These experiments showed that these products present good thermal reliability.GREA and DBA are certified agents TECNIO in the category of technology developers from the Government of Catalonia. We thanks to Subproductos Cárnicos Echevarria y Asociados S.L (Cervera, Spain) for supplying the non-edible fat. Moreover, the research leading to these results has received funding from the European Commission Seventh Framework Programme (FP/2007-2013) under grant agreement no PIRSES-GA-2013-610692 (INNOSTORAGE) and from the European Union’s Horizon 2020 research and innovation program under grant agreement no 657466 (INPATH-TES). The authors would like to thank the Catalan Government for the quality accreditation given to their research groups GREA (2014 SGR 123) and Agricultural Biotechnology Research Group (2014 SGR 1296). This work has been partially funded by the Spanish government (CTQ2015-70982-C3-1-R (MINECO/FEDER) and ENE2015-64117-C5-1-R (MINECO/FEDER). Aran Solé would like to thank Ministerio de Economía y Competitividad de España for Grant Juan de la Cierva, FJCI-2015-25741

Nanosized UCMSC-derived extracellular vesicles but not conditioned medium exclusively inhibit the inflammatory response of stimulated T cells: implications for nanomedicine

Altres ajuts: La Marató TV3 (201502 i 201516). This work has been developed in the context of AdvanceCat with the support of ACCIÓ (Catalonia Trade & Investment; Generalitat de Catalunya) under the Catalonian ERDF operational program (European Regional Development Fund) 2014-2020. FEB is sponsored by the "Researchers Stabilization Program" from the Spanish "Sistema Nacional de Salud" (SNS-ISCIII) and "Direcció d'Estratègia i Coordinació" Catalan Health Department (CES07/015).Undesired immune responses have drastically hampered outcomes after allogeneic organ transplantation and cell therapy, and also lead to inflammatory diseases and autoimmunity. Umbilical cord mesenchymal stem cells (UCMSCs) have powerful regenerative and immunomodulatory potential, and their secreted extracellular vesicles (EVs) are envisaged as a promising natural source of nanoparticles to increase outcomes in organ transplantation and control inflammatory diseases. However, poor EV preparations containing highly-abundant soluble proteins may mask genuine vesicular-associated functions and provide misleading data. Here, we used Size-Exclusion Chromatography (SEC) to successfully isolate EVs from UCMSCs-conditioned medium. These vesicles were defined as positive for CD9, CD63, CD73 and CD90, and their size and morphology characterized by NTA and cryo-EM. Their immunomodulatory potential was determined in polyclonal T cell proliferation assays, analysis of cytokine profiles and in the skewing of monocyte polarization. In sharp contrast to the non-EV containing fractions, to the complete conditioned medium and to ultracentrifuged pellet, SEC-purified EVs from UCMSCs inhibited T cell proliferation, resembling the effect of parental UCMSCs. Moreover, while SEC-EVs did not induce cytokine response, the non-EV fractions, conditioned medium and ultracentrifuged pellet promoted the secretion of pro-inflammatory cytokines by polyclonally stimulated T cells and supported Th17 polarization. In contrast, EVs did not induce monocyte polarization, but the non-EV fraction induced CD163 and CD206 expression and TNF-α production in monocytes. These findings increase the growing evidence confirming that EVs are an active component of MSC's paracrine immunosuppressive function and affirm their potential for therapeutics in nanomedicine. In addition, our results highlight the importance of well-purified and defined preparations of MSC-derived EVs to achieve the immunosuppressive effect

PANC Study (Pancreatitis: A National Cohort Study): national cohort study examining the first 30 days from presentation of acute pancreatitis in the UK

Abstract Background Acute pancreatitis is a common, yet complex, emergency surgical presentation. Multiple guidelines exist and management can vary significantly. The aim of this first UK, multicentre, prospective cohort study was to assess the variation in management of acute pancreatitis to guide resource planning and optimize treatment. Methods All patients aged greater than or equal to 18 years presenting with acute pancreatitis, as per the Atlanta criteria, from March to April 2021 were eligible for inclusion and followed up for 30 days. Anonymized data were uploaded to a secure electronic database in line with local governance approvals. Results A total of 113 hospitals contributed data on 2580 patients, with an equal sex distribution and a mean age of 57 years. The aetiology was gallstones in 50.6 per cent, with idiopathic the next most common (22.4 per cent). In addition to the 7.6 per cent with a diagnosis of chronic pancreatitis, 20.1 per cent of patients had a previous episode of acute pancreatitis. One in 20 patients were classed as having severe pancreatitis, as per the Atlanta criteria. The overall mortality rate was 2.3 per cent at 30 days, but rose to one in three in the severe group. Predictors of death included male sex, increased age, and frailty; previous acute pancreatitis and gallstones as aetiologies were protective. Smoking status and body mass index did not affect death. Conclusion Most patients presenting with acute pancreatitis have a mild, self-limiting disease. Rates of patients with idiopathic pancreatitis are high. Recurrent attacks of pancreatitis are common, but are likely to have reduced risk of death on subsequent admissions. </jats:sec