Combinatorial Polymer Electrospun Matrices Promote Physiologically-Relevant Cardiomyogenic Stem Cell Differentiation

Myocardial infarction results in extensive cardiomyocyte death which can lead to fatal arrhythmias or congestive heart failure. Delivery of stem cells to repopulate damaged cardiac tissue may be an attractive and innovative solution for repairing the damaged heart. Instructive polymer scaffolds with a wide range of properties have been used extensively to direct the differentiation of stem cells. In this study, we have optimized the chemical and mechanical properties of an electrospun polymer mesh for directed differentiation of embryonic stem cells (ESCs) towards a cardiomyogenic lineage. A combinatorial polymer library was prepared by copolymerizing three distinct subunits at varying molar ratios to tune the physicochemical properties of the resulting polymer: hydrophilic polyethylene glycol (PEG), hydrophobic poly(ε-caprolactone) (PCL), and negatively-charged, carboxylated PCL (CPCL). Murine ESCs were cultured on electrospun polymeric scaffolds and their differentiation to cardiomyocytes was assessed through measurements of viability, intracellular reactive oxygen species (ROS), α-myosin heavy chain expression (α-MHC), and intracellular Ca2+ signaling dynamics. Interestingly, ESCs on the most compliant substrate, 4%PEG-86%PCL-10%CPCL, exhibited the highest α-MHC expression as well as the most mature Ca2+ signaling dynamics. To investigate the role of scaffold modulus in ESC differentiation, the scaffold fiber density was reduced by altering the electrospinning parameters. The reduced modulus was found to enhance α-MHC gene expression, and promote maturation of myocyte Ca2+ handling. These data indicate that ESC-derived cardiomyocyte differentiation and maturation can be promoted by tuning the mechanical and chemical properties of polymer scaffold via copolymerization and electrospinning techniques

Should I stay or should I go? An exploration of the decision-making bhaviour of acute cardiac patients during the COVID-19 pandemic

Background: During the SARS-COV-2 (COVID-19) pandemic efforts to reduce virus transmission resulted in non-emergency patients being deterred from seeking help. The number of patients presenting with acute cardiac conditions reduced, significantly Objectives: To explore the decision-making process, and influential factors in that process, of patients and their family during an acute cardiac event. Methods: A qualitative research design was employed using purposive sampling of patients who experienced an acute cardiac event during the social containment mandates. Semi-structured interviews were conducted, with thematic analysis of interview transcripts. Results: Twenty-five participants were recruited from three UK hospitals. Themes identified were reliance on informal support network, lack of awareness of cardiac symptoms leading to delayed help-seeking, and an indirect COVID-19 effect (e.g. avoiding treatment). Conclusions: These results highlight the need for informed public health messages, targeting patients and their support networks, that allow those in need of treatment to access care

Should I stay or should I go? An exploration of the decision-making behaviour of acute cardiac patients during the COVID-19 pandemic

Background: During the SARS-COV-2 (COVID-19) pandemic efforts to reduce virus transmission resulted in non-emergency patients being deterred from seeking help. The number of patients presenting with acute cardiac conditions reduced, significantly Objectives: To explore the decision-making process, and influential factors in that process, of patients and their family during an acute cardiac event. Methods: A qualitative research design was employed using purposive sampling of patients who experienced an acute cardiac event during the social containment mandates. Semi-structured interviews were conducted, with thematic analysis of interview transcripts. Results: Twenty-five participants were recruited from three UK hospitals. Themes identified were reliance on informal support network, lack of awareness of cardiac symptoms leading to delayed help-seeking, and an indirect COVID-19 effect (e.g. avoiding treatment). Conclusions: These results highlight the need for informed public health messages, targeting patients and their support networks, that allow those in need of treatment to access care

<em>flp-32</em> Ligand/Receptor Silencing Phenocopy Faster Plant Pathogenic Nematodes

Restrictions on nematicide usage underscore the need for novel control strategies for plant pathogenic nematodes such as Globodera pallida (potato cyst nematode) that impose a significant economic burden on plant cultivation activities. The nematode neuropeptide signalling system is an attractive resource for novel control targets as it plays a critical role in sensory and motor functions. The FMRFamide-like peptides (FLPs) form the largest and most diverse family of neuropeptides in invertebrates, and are structurally conserved across nematode species, highlighting the utility of the FLPergic system as a broad-spectrum control target. flp-32 is expressed widely across nematode species. This study investigates the role offlp-32 in G. pallida and shows that: (i) Gp-flp-32 encodes the peptide AMRNALVRFamide; (ii)Gp-flp-32 is expressed in the brain and ventral nerve cord of G. pallida; (iii) migration rate increases in Gp-flp-32-silenced worms; (iv) the ability of G. pallida to infect potato plant root systems is enhanced in Gp-flp-32-silenced worms; (v) a novel putative Gp-flp-32 receptor (Gp-flp-32R) is expressed in G. pallida; and, (vi) Gp-flp-32R-silenced worms also display an increase in migration rate. This work demonstrates that Gp-flp-32 plays an intrinsic role in the modulation of locomotory behaviour in G. pallida and putatively interacts with at least one novel G-protein coupled receptor (Gp-flp-32R). This is the first functional characterisation of a parasitic nematode FLP-GPCR