Fabrication of ferrogels using different magnetic nanoparticles and their performance on protein adsorption

Magnetic biomaterials were prepared using magnetite and chitosan-coated magnetite nanoparticles (CSNPs) dispersed in poly(vinyl alcohol) gels. Two different methods were developed to obtain ferrogels: in situ co-precipitation of magnetite (Ferro-IS) and by adding previously synthesized CSNPs to the neat matrix (Ferro-CSNPs). In both cases, the crosslinking was carried out by freezing −thawing (F-T). The as-prepared materials as well as precursor CSNPs were characterized by Fourier transform infrared spectroscopy, electronic microscopy (scanning and transmission), X-ray diffraction, ζ potential, dynamic light scattering, thermogravimetric analysis, differential scanning calorimetry and magnetic properties. The performance of these gels as protein adsorbents was evaluated. Batch adsorption experiments were carried out using bovine serum albumin (BSA) as a model. Substantially different adsorption behaviour was found using Ferro-IS and Ferro-CSNPs. This was assigned to dissimilar bonding mechanisms of BSA to the ferrogel matrix. Hence, biomaterials potentially useful in drug delivery as well as in protein purification fields may be prepared by a relatively simple, non-toxic and low cost method.Fil: Gonzalez, Jimena Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigación en Ciencia y Tecnología de Materiales (i); ArgentinaFil: Nicolás, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Instituto de Química del Sur; ArgentinaFil: Ferreira, Maria Lujan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Planta Piloto de Ingeniería Química (i); ArgentinaFil: Avena, Marcelo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Instituto de Química del Sur; ArgentinaFil: Lassalle, Verónica Leticia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Instituto de Química del Sur; ArgentinaFil: Alvarez, Vera Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigación en Ciencia y Tecnología de Materiales (i); Argentin

Connexin 43 deficiency is associated with reduced myocardial scar size and attenuated tgfβ1 signaling after transient coronary occlusion in conditional knock-out mice

Funding: This research was funded by Fundació La Marató de TV3 (n◦. 201536-10) and the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III (CIBERCV), cofinanced by the European Regional Development Fund (ERDF-FEDER, a way to build Europe). Antonio Rodríguez-Sinovas has a consolidated Miguel Servet contract.Previous studies demonstrated a reduction in myocardial scar size in heterozygous Cx43-mice subjected to permanent coronary occlusion. However, patients presenting with ST segment elevation myocardial infarction often undergo rapid coronary revascularization leading to prompt restoration of coronary flow. Therefore, we aimed to assess changes in scar size and left ventricular remodeling following transient myocardial ischemia (45 min) followed by 14 days of reperfusion using Cx43 (controls) and Cx43 inducible knock-out (Cx43 content: 50%) mice treated with vehicle or 4-hydroxytamoxifen (4-OHT) to induce a Cre-ER(T)-mediated global deletion of the Cx43 floxed allele. The scar area (picrosirius red), measured 14 days after transient coronary occlusion, was similarly reduced in both vehicle and 4-OHT-treated Cx43 mice, compared to Cx43 animals, having normal Cx43 levels (15.78% ± 3.42% and 16.54% ± 2.31% vs. 25.40% ± 3.14% and 22.43% ± 3.88% in vehicle and 4-OHT-treated mice, respectively, p = 0.027). Left ventricular dilatation was significantly attenuated in both Cx43-deficient groups (p = 0.037 for left ventricular end-diastolic diameter). These protective effects were correlated with an attenuated enhancement in pro-transforming growth factor beta 1 (TGFβ1) expression after reperfusion. In conclusion, our data demonstrate that Cx43 deficiency induces a protective effect on scar formation after transient coronary occlusion in mice, an effect associated with reduced left ventricular remodeling and attenuated enhancement in pro-TGFβ1 expression

Single breath-hold saturation recovery 3D cardiac T1 mapping via compressed SENSE at 3T.

To propose and validate a novel imaging sequence that uses a single breath-hold whole-heart 3D T1 saturation recovery compressed SENSE rapid acquisition (SACORA) at 3T. The proposed sequence combines flexible saturation time sampling, compressed SENSE, and sharing of saturation pulses between two readouts acquired at different RR intervals. The sequence was compared with a 3D saturation recovery single-shot acquisition (SASHA) implementation with phantom and in vivo experiments (pre and post contrast; 7 pigs) and was validated against the reference inversion recovery spin echo (IR-SE) sequence in phantom experiments. Phantom experiments showed that the T1 maps acquired by 3D SACORA and 3D SASHA agree well with IR-SE. In vivo experiments showed that the pre-contrast and post-contrast T1 maps acquired by 3D SACORA are comparable to the corresponding 3D SASHA maps, despite the shorter acquisition time (15s vs. 188s, for a heart rate of 60 bpm). Mean septal pre-contrast T1 was 1453 ± 44 ms with 3D SACORA and 1460 ± 60 ms with 3D SASHA. Mean septal post-contrast T1 was 824 ± 66 ms and 824 ± 60 ms. 3D SACORA acquires 3D T1 maps in 15 heart beats (heart rate, 60 bpm) at 3T. In addition to its short acquisition time, the sequence achieves good T1 estimation precision and accuracy.TFdS has received funding from the European Union Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement N722427. CGA is a P-FIS fellow (Instituto deSalud Carlos III). This study was partially supported by the Comunidad de Madrid (S2017/BMD-3867 RENIM-CM) and cofunded with European structural and investment funds. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia, Innovación y Universidades (MCNU) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505).S

European (energy) data exchange reference architecture 3.0

This is the third version of Data Exchange Reference Architecture – DERA 3.0. BRIDGE report on energy data exchange reference architecture aims at contributing to the discussion and practical steps towards truly interoperable and business process agnostic data exchange arrangements on European scale both inside energy domain and across different domains.DERA 3.0Recommendations related to the implementation of DERA:A. Leverage Smart Grid Architecture Model (SGAM) usage by completing it with data governance requirements, specifically from end-customer perspective, and map it to the reference architectures of other sectors (similar to the RAMI4.0 for industry – Reference Architecture Model Industrie 4.0; and CREATE-IoT 3D RAM for health – Reference Architecture Model of CREATE-IoT project), incl. for basic interoperability vocabulary with non-energy sectors.B. Facilitate European strategy, regulation (harmonisation of national regulations) and practical tools for cross-sector exchange of any type of both private data and public data, e.g. through reference models for data space, common data governance and data interoperability implementing acts.C. Ensure cooperation between appropriate associations, countries and sector representatives to work on cross-sector and cross-border data management by establishing European data cooperation agency. This involves ongoing empowering/restructuring of the Data Management WG of the BRIDGE Initiative to engage other sectors and extend cooperation with projects that are not EU-funded and with European Standardisation Organisations (CEN-CENELEC-ETSI).D. Harmonise the development, content and accessibility of data exchange business use cases for cross-sector domain through BRIDGE use case repository. Track tools that identify common features on use cases, e.g. interfaces between sectors, and enable the alignment with any potential peer repositories for other domains. Also, the use case repository must rely on the HEMRM with additional roles created by some projects or roles coming from other associations (related to another sector than the electricity/energy sector).E. Use BRIDGE use case repository for aligning the role selection. Harmonise data roles across electricity and other energy domains by developing HERM – Harmonised Energy Role Model and ensure access to model files. Look for consistency with other domains outside energy based on this HERM – cross-sectoral roles. Harmonised EnergyData EndpointsData SpaceConnectorData ProcessingStandard CommunicationProtocols& FormatsData HarmonizationData PersistanceVocabularyProviderCredentialManagerIdentityManagerMonitoring& OrchestrationData DiscoveryData IndexerLocal AI/ML ServicesDigital TwinsMarketplace BackendStandard CommunicationProtocols& FormatsMarketplace FrontendFederatedUse Cases and Business needsLocal Use Cases and Business needsEnergy RegulationEU Re-gulationActorsBusinessFunctionInformationComp.CommsNon-personal dataSecurity/ResilienceUserAcceptanceSovereigntyOpen SourceInteroperabilityLocalFederatedInteroperabilityTrustData valueGovernance9DATA MANAGEMENT WORKING GROUPEuropean (energy) data exchange reference architecture 3.0Role Model shall have clear implications and connections with data (space) roles such as data provider/consumer, service provider etc.F. Define and harmonise functional data processes for cross-sector domain, using common vocabulary, template and repository for respective use cases’ descriptions. Harmonisation of functional data processes for cross-sector data ecosystems including Vocabulary provider, Federated catalogue, Data quality, Data accounting processes, Clearing process (audit, logging, etc.) and Data tracking and provenance.G. Define and maintain a common reference semantic data model, and ensure access to its model files facilitating cross-sector data exchange, by leveraging existing data models like Common Information Model (CIM) of International Electrotechnical Commission (IEC) and ontologies like Smart Appliances Reference Ontology (SAREF).H. Develop cross-sector data models and profiles, with specific focus on private data exchange. Enable open access to model files whenever possible.I. Ensure protocol agnostic approach to cross-sector data exchange by selecting standardised and open ones.J. Ensure data format agnostic approach to cross-sector data exchange. The work done by projects like TDX-ASSIST and EU-SysFlex (using IEC CIM), and PLATOON (using SAREF) must be shared and made known to consolidate the approach in order to reach semantic interoperability. Metadata must also be taken into account.K. Promote business process agnostic DEPs (Data Exchange Platforms) and make these interoperable by developing APIs (Application Programming Interfaces) which enable for data providers and data users easy connection to any European DEP but also create the possibility whereby connecting to one DEP ensures data exchange with any other stakeholder in Europe. DEPs shall explore the integration of data space connectors towards their connectivity with other DEPs including cross-sector ones.L. Develop universal data applications which can serve any domain. Develop open data driven services that promote also cross-sector integration collectively available in application repositories.Possible next steps (“sub-actions”) for 2023/2024:➢ Release BRIDGE Federated Service Catalogue tool and associated process.➢ Release DERA interactive visualisation tool.➢ Follow up the implementation of DERA 3.0 in BRIDGE projects (mapping to DERA)➢ Update recommendations to comply with DERA 3.0.➢ Develop / enhance the “data role model”

Spontaneous reperfusion enhances succinate concentration in peripheral blood from stemi patients but its levels does not correlate with myocardial infarct size or area at risk

Cardiovascular biology; Diagnostic markers; Prognostic markersBiología cardiovascular; Marcadores de diagnóstico; Marcadores pronósticosBiologia cardiovascular; Marcadors diagnòstics; Marcadors pronòsticsSuccinate is enhanced during initial reperfusion in blood from the coronary sinus in ST-segment elevation myocardial infarction (STEMI) patients and in pigs submitted to transient coronary occlusion. Succinate levels might have a prognostic value, as they may correlate with edema volume or myocardial infarct size. However, blood from the coronary sinus is not routinely obtained in the CathLab. As succinate might be also increased in peripheral blood, we aimed to investigate whether peripheral plasma concentrations of succinate and other metabolites obtained during coronary revascularization correlate with edema volume or infarct size in STEMI patients. Plasma samples were obtained from peripheral blood within the first 10 min of revascularization in 102 STEMI patients included in the COMBAT-MI trial (initial TIMI 1) and from 9 additional patients with restituted coronary blood flow (TIMI 2). Metabolite concentrations were analyzed by 1H-NMR. Succinate concentration averaged 0.069 ± 0.0073 mmol/L in patients with TIMI flow ≤ 1 and was significantly increased in those with TIMI 2 at admission (0.141 ± 0.058 mmol/L, p < 0.05). However, regression analysis did not detect any significant correlation between most metabolite concentrations and infarct size, extent of edema or other cardiac magnetic resonance (CMR) variables. In conclusion, spontaneous reperfusion in TIMI 2 patients associates with enhanced succinate levels in peripheral blood, suggesting that succinate release increases overtime following reperfusion. However, early plasma levels of succinate and other metabolites obtained from peripheral blood does not correlate with the degree of irreversible injury or area at risk in STEMI patients, and cannot be considered as predictors of CMR variables. Trial registration: Registered at www.clinicaltrials.gov (NCT02404376) on 31/03/2015. EudraCT number: 2015-001000-58.This work was supported by the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III (Grants PI17/01397 and CIBERCV) and the Spanish Society of Cardiology (Proyectos de la FEC para Investigación Básica en Cardiología 2018, Sociedad Española de Cardiología), and was cofinanced by the European Regional Development Fund (ERDF-FEDER, a way to build Europe). Antonio Rodríguez-Sinovas has a consolidated Miguel Servet contract

Potential spironolactone effects on collagen metabolism biomarkers in patients with uncontrolled blood pressure.

BACKGROUND: An increase in myocardial collagen content may contribute to the development of heart failure; this might be inhibited or reversed by mineralocorticoid receptor antagonists (MRAs). We investigated changes in serum concentrations of the collagen synthesis biomarkers N-terminal propeptide of procollagen type III (PIIINP) (primary outcome) and C-terminal propeptide of procollagen type I (PICP) (secondary outcome) after non-randomised initiation of spironolactone as add-on therapy among patients with resistant hypertension enrolled in the 'Anglo-Scandinavian Cardiac Outcomes' trial (ASCOT). METHODS: An age/sex matching plus propensity-scored logistic regression model incorporating variables related to the outcome and spironolactone treatment was created to compare patients treated with spironolactone for a 9-month period versus matched controls. A within-person analysis comparing changes in serum biomarker concentrations in the 9 months before versus after spironolactone treatment was also performed. RESULTS: Patients included in the between-person analysis (n=146) were well matched: the mean age was 63±7 years and 11% were woman. Serum concentrations of PIIINP and PICP rose in 'controls' and fell during spironolactone treatment (adjusted means +0.52 (-0.05 to 1.09) vs -0.41 (-0.97 to 0.16) ng/mL, p=0.031 for PIIINP and +4.54(-1.77 to 10.9) vs -6.36 (-12.5 to -0.21) ng/mL, p=0.023 for PICP). For the within-person analysis (n=173), spironolactone treatment was also associated with a reduction in PICP (beta estimate=-11.82(-17.53 to -6.10) ng/mL, p<0.001) but not in PIIINP levels. CONCLUSIONS: Treatment with spironolactone was associated with a reduction in serum biomarkers of collagen synthesis independently of blood pressure in patients with hypertension, suggesting that spironolactone might exert favourable effects on myocardial collagen synthesis and fibrosis. Whether this effect might contribute to slowing the progression to heart failure is worth investigating

A candidate gene approach identifies an IL33 genetic variant as a novel genetic risk factor for GCA

INTRODUCTION: Increased expression of IL-33 and its receptor ST2, encoded by the IL1RL1 gene, has been detected in the inflamed arteries of giant cell arteritis (GCA) patients. The aim of the present study was to investigate for the first time the potential influence of the IL33 and IL1RL1 loci on GCA predisposition. METHODS: A total of 1,363 biopsy-proven GCA patients and 3,908 healthy controls from four European cohorts (Spain, Italy, Germany and Norway) were combined in a meta-analysis. Six genetic variants: rs3939286, rs7025417 and rs7044343, within the IL33 gene, and rs2058660, rs2310173 and rs13015714, within the IL1RL1 gene, previously associated with immune-related diseases, were genotyped using predesigned TaqMan assays. RESULTS: A consistent association between the rs7025417 polymorphism and GCA was evident in the overall meta-analysis, under both allele (P(MH) = 0.041, OR = 0.88, CI 95% 0.78-0.99) and recessive (P(MH) = 3.40E-03, OR = 0.53, CI 95% 0.35-0.80) models. No statistically significant differences between allele or genotype frequencies for the other IL33 and IL1RL1 genetic variants were detected in this pooled analysis. CONCLUSIONS: Our results clearly evidenced the implication of the IL33 rs7025417 polymorphism in the genetic network underlying GCA

Hugo Chávez: una década en el poder

Una década de Hugo Chávez Frías y su proyecto político en Venezuela trajo consigo un cambio de paradigmas que llama la atención de la sociedad en general. Este libro es el resultado del esfuerzo conjunto de un grupo de académicos de distintas nacionalidades que desde sus líneas de investigación realizan análisis que le brindan al lector elementos para comprender de manera global lo que significa una década de gobierno del Presidente Chávez en Venezuela.Este libro es el resultado del esfuerzo conjunto de un grupo de académicos de distintas nacionalidades que desde sus líneas de investigación realizan análisis que le brindan al lector elementos para comprender de manera global lo que significa una década de gobierno del Presidente Chávez en Venezuela

High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis.

Using the Immunochip custom SNP array, which was designed for dense genotyping of 186 loci identified through genome-wide association studies (GWAS), we analyzed 11,475 individuals with rheumatoid arthritis (cases) of European ancestry and 15,870 controls for 129,464 markers. We combined these data in a meta-analysis with GWAS data from additional independent cases (n = 2,363) and controls (n = 17,872). We identified 14 new susceptibility loci, 9 of which were associated with rheumatoid arthritis overall and five of which were specifically associated with disease that was positive for anticitrullinated peptide antibodies, bringing the number of confirmed rheumatoid arthritis risk loci in individuals of European ancestry to 46. We refined the peak of association to a single gene for 19 loci, identified secondary independent effects at 6 loci and identified association to low-frequency variants at 4 loci. Bioinformatic analyses generated strong hypotheses for the causal SNP at seven loci. This study illustrates the advantages of dense SNP mapping analysis to inform subsequent functional investigations

Genetics of rheumatoid arthritis contributes to biology and drug discovery

A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological datasets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)1. Here, we performed a genome-wide association study (GWAS) meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating ~10 million single nucleotide polymorphisms (SNPs). We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 1012–4. We devised an in-silico pipeline using established bioinformatics methods based on functional annotation5, cis-acting expression quantitative trait loci (cis-eQTL)6, and pathway analyses7–9 – as well as novel methods based on genetic overlap with human primary immunodeficiency (PID), hematological cancer somatic mutations and knock-out mouse phenotypes – to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery