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BackgroundThere’s scarce evidence about cardiovascular events (CV) in patients with hospitalization for acute heart failure (HF) and no indication for immediate device implant. ObjectiveThe CARdiac RhYthm monitorING after acute decompensatiON for Heart Failure study was designed to assess the incidence of prespecified clinical and arrhythmic events in this patient population. MethodsIn this pilot study, 18 patients (12 (67%) male; age 72±10; 16 (89%) NYHA II-III), who were hospitalized for HF with low left ventricular ejection fraction (LVEF) (

Nosocomial infections affect implanted medical devices and greatly challenge their functional outcomes, becoming sometimes life threatening for the patients. Therefore, aggressive antibiotic therapies are administered, which often require the use of last‐resort drugs, if the infection is caused by multi‐drug‐resistant bacteria. Reducing the risk of bacterial contamination of medical devices in the hospitals has thus become an emerging issue. Promising routes to control these infections are based on materials provided with intrinsic bactericidal properties (i.e., chemical action) and on the design of surface coatings able to limit bacteria adhesion and fouling phenomena (i.e., physical action), thus preventing bacterial biofilm formation. Here, we report the development and validation of coatings made of layer‐by‐layer deposition of electrospun poly(vinylidene fluoride‐co‐trifluoro ethylene) P(VDF‐TrFE) fibers with controlled orientations, which ultimately gave rise to antifouling surfaces. The obtained 10‐layer surface morphology with 90° orientation fibers was able to efficiently prevent the adhesion of bacteria, by establishing a superhydrophobic‐like behavior compatible with the Cassie‐Baxter regimen. Moreover, the results highlighted that surface wettability and bacteria adhesion could be controlled using fibers with diameter comparable to bacteria size (i.e., achievable via electrospinning process), by tuning the intra‐fiber spacing, with relevant implications in the future design of biomedical surface coatings. [ABSTRACT FROM AUTHOR]

Recently, in vitro models emerge as valuable tools in biomedical research by enabling the investigation of complex physiological processes in a controlled environment, replicating some traits of interest of the biological tissues. This study focuses on the development of tubular polymeric scaffolds, made of electrospun fibers, aimed to generate three‐dimensional (3D) in vitro intestinal models resembling the lumen of the gut. Polycaprolactone (PCL) and polyacrylonitrile (PAN) are used to produce tightly arranged ultrafine fiber meshes via electrospinning in the form of continuous tubular structures, mimicking the basement membrane on which the epithelial barrier is formed. Morphological, physical, mechanical, and piezoelectric properties of the PCL and PAN tubular scaffolds are investigated. They are cultured with Caco‐2 cells using different biological coatings (i.e., collagen, gelatin, and fibrin) and their capability of promoting a compact epithelial layer is assessed. PCL and PAN scaffolds show 42% and 50% porosity, respectively, with pore diameters and size suitable to impede cell penetration, thus promoting an intestinal epithelial barrier formation. Even if both polymeric structures allow Caco‐2 cell adhesion, PAN fiber meshes best suit many requirements needed by this model, including highest mechanical strength upon expansion, porosity and piezoelectric properties, along with the lowest pore size. [ABSTRACT FROM AUTHOR]

We previously estimated that 42% of patients with severe developmental disorders carry pathogenic de novo mutations in coding sequences. The role of de novo mutations in regulatory elements affecting genes associated with developmental disorders, or other genes, has been essentially unexplored. We identified de novo mutations in three classes of putative regulatory elements in almost 8,000 patients with developmental disorders. Here we show that de novo mutations in highly evolutionarily conserved fetal brain-active elements are significantly and specifically enriched in neurodevelopmental disorders. We identified a significant twofold enrichment of recurrently mutated elements. We estimate that, genome-wide, 1-3% of patients without a diagnostic coding variant carry pathogenic de novo mutations in fetal brain-active regulatory elements and that only 0.15% of all possible mutations within highly conserved fetal brain-active elements cause neurodevelopmental disorders with a dominant mechanism. Our findings represent a robust estimate of the contribution of de novo mutations in regulatory elements to this genetically heterogeneous set of disorders, and emphasize the importance of combining functional and evolutionary evidence to identify regulatory causes of genetic disorders.

De novo mutations in protein-coding genes are a well-established cause of developmental disorders.sup.1. However, genes known to be associated with developmental disorders account for only a minority of the observed excess of such de novo mutations.sup.1,2. Here, to identify previously undescribed genes associated with developmental disorders, we integrate healthcare and research exome-sequence data from 31,058 parent-offspring trios of individuals with developmental disorders, and develop a simulation-based statistical test to identify gene-specific enrichment of de novo mutations. We identified 285 genes that were significantly associated with developmental disorders, including 28 that had not previously been robustly associated with developmental disorders. Although we detected more genes associated with developmental disorders, much of the excess of de novo mutations in protein-coding genes remains unaccounted for. Modelling suggests that more than 1,000 genes associated with developmental disorders have not yet been described, many of which are likely to be less penetrant than the currently known genes. Research access to clinical diagnostic datasets will be critical for completing the map of genes associated with developmental disorders. By integrating healthcare and exome-sequencing data from parent-offspring trios of patients with developmental disorders, 28 genes that had not previously been associated with developmental disorders were identified., Author(s): Joanna Kaplanis [sup.1] , Kaitlin E. Samocha [sup.1] , Laurens Wiel [sup.2] [sup.3] , Zhancheng Zhang [sup.4] , Kevin J. Arvai [sup.4] , Ruth Y. Eberhardt [sup.1] , Giuseppe [...]

Bone defects are a significant health problem worldwide. Novel treatment approaches in the tissue engineering field rely on the use of biomaterial scaffolds to stimulate and guide the regeneration of damaged tissue that cannot repair or regrow spontaneously. This work aimed at developing and characterizing new piezoelectric scaffolds to provide electric bio-signals naturally present in bone and vascular tissues. Mixing and extrusion were used to obtain nanocomposites made of polyhydroxybutyrate (PHB) as a matrix and barium titanate (BaTiO3) nanoparticles as a filler, at BaTiO3/PHB compositions of 5/95, 10/90, 15/85 and 20/80 (w/w%). The morphological, thermal, mechanical and piezoelectric properties of the nanocomposites were studied. Scanning electron microscopy analysis showed good nanoparticle dispersion within the polymer matrix. Considerable increases in the Young's modulus, compressive strength and the piezoelectric coefficient d31 were observed with increasing BaTiO3 content, with d31 = 37 pm/V in 20/80 (w/w%) BaTiO3/PHB. 3D printing was used to produce porous cubic-shaped scaffolds using a 90° lay-down pattern, with pore size ranging in 0.60–0.77 mm and good mechanical stability. Biodegradation tests conducted for 8 weeks in saline solution at 37 °C showed low mass loss (∼4%) for 3D printed scaffolds. The results obtained in terms of piezoelectric, mechanical and chemical properties of the nanocomposite provide a new promising strategy for vascularized bone tissue engineering. [ABSTRACT FROM AUTHOR]

Abstract Background Protein-protein interaction (PPI) data are widely used to generate network models that aim to describe the relationships between proteins in biological systems. The fidelity and completeness of such networks is primarily limited by the paucity of protein interaction information and by the restriction of most of these data to just a few widely studied experimental organisms. In order to extend the utility of existing PPIs, computational methods can be used that exploit functional conservation between orthologous proteins across taxa to predict putative PPIs or 'interologs'. To date most interolog prediction efforts have been restricted to specific biological domains with fixed underlying data sources and there are no software tools available that provide a generalised framework for 'on-the-fly' interolog prediction. Results We introduce Bio::Homology::InterologWalk, a Perl module to retrieve, prioritise and visualise putative protein-protein interactions through an orthology-walk method. The module uses orthology and experimental interaction data to generate putative PPIs and optionally collates meta-data into an Interaction Prioritisation Index that can be used to help prioritise interologs for further analysis. We show the application of our interolog prediction method to the genomic interactome of the fruit fly, Drosophila melanogaster. We analyse the resulting interaction networks and show that the method proposes new interactome members and interactions that are candidates for future experimental investigation. Conclusions Our interolog prediction tool employs the Ensembl Perl API and PSICQUIC enabled protein interaction data sources to generate up to date interologs 'on-the-fly'. This represents a significant advance on previous methods for interolog prediction as it allows the use of the latest orthology and protein interaction data for all of the genomes in Ensembl. The module outputs simple text files, making it easy to customise the results by post-processing, allowing the putative PPI datasets to be easily integrated into existing analysis workflows. The Bio::Homology::InterologWalk module, sample scripts and full documentation are freely available from the Comprehensive Perl Archive Network (CPAN) under the GNU Public license.