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Electrocardiography imaging (ECGi) is a non‐invasive inverse reconstruction procedure which employs body surface potential maps (BSPM) obtained from surface electrode array measurements to improve the spatial resolution and interpretability of conventional electrocardiography (ECG) for the diagnosis of cardiac dysfunction. ECGi currently lacks precision, which has prevented its adoption in clinical setups. The introduction of high‐density electrode arrays could increase ECGi reconstruction accuracy but is not attempted before due to manufacturing and processing limitations. Advances in multiple fields have now enabled the implementation of such arrays which poses questions on optimal array design parameters for ECGi. In this work, a novel conducting polymer electrode manufacturing process on flexible substrates is proposed to achieve high‐density, mm‐sized, conformable, long‐term, and easily attachable electrode arrays for BSPM with parameters optimally selected for ECGi applications. Temporal, spectral, and correlation analysis are performed on a prototype array demonstrating the validity of the chosen parameters and the feasibility of high‐density BSPM, paving the way for ECGi devices fit for clinical application.

Eutectogels are an emerging family of soft ionic materials alternative to ionic liquid gels and organogels, offering fresh perspectives for designing functional dynamic platforms in water-free environments. Herein, the first example of mixed ionic and electronic conducting supramolecular eutectogel composites is reported. A fluorescent glutamic acid-derived low-molecular-weight gelator (LMWG) was found to self-assemble into nanofibrillar networks in deep eutectic solvents (DES)/poly(3,4-ethylenedioxythiophene) (PEDOT): chondroitin sulfate dispersions. These dynamic materials displayed excellent injectability and self-healing properties, high ionic conductivity (up to 10−2 S cm−1), good biocompatibility, and fluorescence imaging ability. This set of features turns the mixed conducting supramolecular eutectogels into promising adaptive materials for bioimaging and electrostimulation applications. This work was supported by Marie Sklodowska-Curie Research and Innovation Staff Exchanges (RISE) under the grant agreement No 823989 “IONBIKE”. The financial support received from CONICET and ANPCyT (Argentina) is also gratefully acknowledged. M. C.-G. thanks Emakiker Grant Program of POLYMAT. L. C. T. is grateful to Fundação para a Ciência e a Tecnologia (FCT/MCTES) in Portugal for her research contract under Scientific Employment Stimulus (2020.01555.CEECIND), and Associate Laboratory for Green Chemistry—LAQV, which is also financed by FCT/MCTES (UIDB/50006/2020 and UIDP/50006/2020). D. M. thanks “Ayuda RYC2021-031668-I financiada por MCIN/AEI/10.13039/501100011033 y por la Unión Europea NextGenerationEU/PRTR”. The authors thank the technical and human support provided by SGIker (UPV/EHU/ERDF, EU).

We study the effect of childbirth and birth timing on female labor market outcomes in Italy. The impact is traced up to 21 years since school completion by estimating a factor analytic model with dynamic selection into treatments. We find that childbirth, especially the first delivery, negatively affects female earnings and participation. Women having their first child soon after school exit catch up with childless women after 12–15 years. The negative consequences are smaller if the first child is delayed up to 7–9 years after school completion or if a second childbirth occurs within 6 years since school exit.

In 2007 the Italian central government started a programme by transferring funds to regional governments to develop both private and public early childcare services. Exploiting the different timing of programme implementation across regions, we evaluate its effectiveness in boosting the public supply of early childhood educational services. We find that the ratio between the available slots in public early childhood education and the population aged 0–2 increased by 18% 3 years after the start of the programme, with respect to the pre‐programme level. The programme impact was, however, limited in the South and mostly driven by the Center‐North.

Cardiac stromal cells (CSCs) are the main players in fibrosis. Dysmetabolic conditions (metabolic syndrome-MetS, and type 2 diabetes mellitus-DM2) are strong pathogenetic contributors to cardiac fibrosis. Moreover, modulation of the oxidative state (OxSt) and autophagy is a fundamental function affecting the fibrotic commitment of CSCs, that are adversely modulated in MetS/DM2. We aimed to characterize CSCs from dysmetabolic patients, and to obtain a beneficial phenotypic setback from such fibrotic commitment by modulation of OxSt and autophagy. CSCs were isolated from 38 patients, stratified as MetS, DM2, or controls. Pharmacological modulation of OxSt and autophagy was obtained by treatment with trehalose and NOX4/NOX5 inhibitors (TREiNOX). Flow-cytometry and real-time quantitative polymerase chain reaction (RT-qPCR) analyses showed significantly increased expression of myofibroblasts markers in MetS-CSCs at baseline (GATA4, ACTA2, THY1/CD90) and after starvation (COL1A1, COL3A1). MetS- and DM2-CSCs displayed a paracrine profile distinct from control cells, as evidenced by screening of 30 secreted cytokines, with a significant reduction in vascular endothelial growth factor (VEGF) and endoglin confirmed by enzyme-linked immunoassay (ELISA). DM2-CSCs showed significantly reduced support for endothelial cells in angiogenic assays, and significantly increased Hsub2/subOsub2/subrelease and NOX4/5 expression levels. Autophagy impairment after starvation (reduced ATG7 and LC3-II proteins) was also detectable in DM2-CSCs. TREiNOX treatment significantly reduced ACTA2, COL1A1, COL3A1, and NOX4 expression in both DM2- and MetS-CSCs, as well as GATA4 and THY1/CD90 in DM2, all versus control cells. Moreover, TREiNOX significantly increased VEGF release by DM2-CSCs, and VEGF and endoglin release by both MetS- and DM2-CSCs, also recovering the angiogenic support to endothelial cells by DM2-CSCs. In conclusion, DM2 and MetS worsen microenvironmental conditioning by CSCs. Appropriate modulation of autophagy and OxSt in human CSCs appears to restore these features, mostly in DM2-CSCs, suggesting a novel strategy against cardiac fibrosis in dysmetabolic patients. © 2022 The Authors. The Journal of Pathology published by John Wileyamp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Extracellular vesicles (EVs) are key biological mediators of several physiological functions within the cell microenvironment. Platelets are the most abundant source of EVs in the blood. Similarly, platelet lysate (PL), the best platelet derivative and angiogenic performer for regenerative purposes, is enriched of EVs, but their role is still too poorly discovered to be suitably exploited. Here, we explored the contribution of the EVs in PL, by investigating the angiogenic features extrapolated from that possessed by PL.We tested angiogenic ability and molecular cargo in 3D bioprinted models and by RNA sequencing analysis of PL-derived EVs.A subset of small vesicles is highly represented in PL. The EVs do not retain aggregation ability, preserving a low redox state in human umbilical vein endothelial cells (HUVECs) and increasing the angiogenic tubularly-like structures in 3D endothelial bioprinted constructs. EVs resembled the miRNome profile of PL, mainly enriched with small RNAs and a high amount of miR-126, the most abundant angiogenic miRNA in platelets. The transfer of miR-126 by EVs in HUVEC after the in vitro inhibition of the endogenous form, restored angiogenesis, without involving VEGF as a downstream target in this system.PL is a biological source of available EVs with angiogenic effects involving a miRNAs-based cargo. These properties can be exploited for targeted molecular/biological manipulation of PL, by potentially developing a product exclusively manufactured of EVs.

Current electrolytes for lithium batteries are usually composed of at least two chemical compounds, an organic solvent such as a cyclic carbonate and a lithium salt such as LiPF6. Here, the concept of using a single-component electrolyte is demonstrated in lithium batteries based on new lithium borate ionic liquids at room temperature. The design concept of this class of lithium ionic liquids (LiILs) is based on an asymmetrically substituted central tetracoordinate boron atom with oligoethylene glycol groups, fluorinated electron-attracting groups, and one alkane group. The optimized borateLi+ LiILs show a high ionic conductivity value of >10−4 S cm−1 at 25 °C, high lithium transference numbers ( = 0.4 – 0.5) and electrochemical stability (>4 V). Some of the LiILs present high compatibility with lithium-metal electrodes showing stable polarization profiles in platting/stripping tests. The selected LiIL is investigated as single-component electrolytes in lithium-metal battery cells showing discharge capacity values in Li0/LiIL/lithium–iron phosphate and Li0/LiIL/lithium titanate cells of 124 and 75 mAh g−1, respectively, at a C-rate of 0.2 C and 65 °C with low-capacity loss. This work was funded and supported by a Grant for Basque Government through grant IT1309-19, and European Commission's funded Marie Skłodowska–Curie project POLYTE-EID (Project No. 765828) and Spanish MCIN/AEI/PID2020-119026GB-I00. G.G.-G. is grateful to “Secretaría de Educación, Ciencia, Tecnología e Innovación” from Ciudad de México for the postdoctoral fellowship through grant SECTEI/133/2019. G.G.-G. also thanks the PhD. IOSM for being the driving force and constant support.

Unformatted preprint Iongels have attracted much attention over the years as ion-conducting soft materials for applications in several technologies including stimuli-responsive drug release and flexible (bio)electronics. Nowadays, iongels with additional functionalities such as electronic conductivity, self-healing, thermo-responsiveness or biocompatibility are actively being searched for high demanding applications. In this work, we present a simple and rapid synthetic pathway to prepare hyperelastic and thermoreversible iongels. These iongels were prepared by supramolecular crosslinking between polyphenols biomolecules with a hydroxyl-rich biocompatible polymer such as poly(vinyl alcohol) (PVA) in the presence of ionic liquids. Using this strategy, a variety of iongels were obtained by combining different plant-derived polyphenol compounds such as gallic acid, pyrogallol, and tannic acid with imidazolium-based ionic liquids, namely [C2mim][N(CN)2] and [C2mim][Br]. A suite of characterization tools was used to study the structural, morphological, mechanical, rheological and thermal properties of the supramolecular iongels. These iongels can withstand large deformations (40 % under compression) with full recovery, revealing reversible transitions from solid to liquid state between 87 to 125 °C. Finally, the polyphenol-based thermoreversible iongels shows appropriated properties for their potential application as printable electrolytes for bioelectronics. This work was supported by Marie Sklodowska-Curie Research and Innovation Staff Exchanges (RISE) under the grant agreement No 823989 “IONBIKE”. Also, the financial support received from CONICET, UNL, and ANPCyT (all of Argentina) is gratefully acknowledged. Liliana C. Tomé has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement no. 745734.

Eutectogels are a new class of soft ion conductive materials that are attracting attention as an alternative to conventional hydrogels and costly ionic liquid gels to build wearable sensors and bioelectrodes. Herein, the first example of mixed ionic and electronic conductive eutectogels showing high adhesion, flexibility, nonvolatility, and reversible low-temperature gel transition for 3D printing manufacturing is reporting. The eutectogels consist of choline chloride/glycerol deep eutectic solvent, poly(3,4-ethylenedioxythiophene): lignin sulfonate, and gelatin as the biocompatible polymer matrix. These soft materials are flexible and stretchable, show high ionic and electronic conductivities of 7.3 and 8.7 mS cm−1, respectively, and have high adhesion energy. Due to this unique combination of properties, they could be applied as strain sensors to precisely detect physical movements. Furthermore, these soft mixed ionic electronic conductors possess excellent capacity as conformal electrodes to record epidermal physiological signals, such as electrocardiograms and electromyograms, over a long time. M.L.P. and A.G. contributed equally to this work. This work was supported by Marie Sklodowska-Curie Research and Innovation Staff Exchanges (RISE) under the grant agreement No 823989 “IONBIKE.” The financial support received from CONICET and ANPCyT (Argentina) is also gratefully acknowledged. Thanks to the Flexible Electronic Department (FEL) of Ecole des Mines de Saint-Etienne (EMSE) for the combined mechanical/electrical characterization.

Soft-ionic materials with biocompatibility and 3D printability are needed to develop next-generation devices to interface between electronic and biological signals. Herein, thermoreversible and biocompatible ionic liquid gels or iongels, which can be processed by direct ink writing are reported. The iongels are designed by taking advantage of polyvinyl alcohol/phenol interactions to gelify biocompatible cholinium carboxylate ionic liquids. The obtained iongels are stable, soft, and flexible materials (Young modulus between 14 and 70 kPa) with high ionic conductivity (1.8 x 10(-2) S cm(-1)). Interestingly, they presented thermoreversible properties with gel-sol transitions ranging from 85 and 110 degrees C, which allows the iongel processing via direct ink writing 3D printing by material extrusion at temperatures over its transition. These 3D printable iongels are integrated into a variety of body sensors applications, namely pressure sensors, motion sensors and electrodes for electrophysiological recordings. The iongels are used as pressure sensors with a sensitivity of 0.1 kPa(-1), ten times higher than that of others similar materials reported so far; showing its ability to detect human motion. Furthermore, the iongels showed excellent performance in electrodes for electrocardiography (ECG) recording, presenting good stability over time with electrocardiographic waves maintained their typical shape even after weeks. This work was supported by Marie Sklodowska-Curie Research and Innovation Staff Exchanges (RISE) under the grant agreement No 823989 "IONBIKE". The financial support received from CONICET, UNL, and ANPCyT (Argentina) is also gratefully acknowledged. L.C.T. has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie SklodowskaCurie grant agreement no. 745734 and from FCT (Fundacao para a Ciencia e a Tecnologia) in Portugal under the research contract CEECIND/01697/2018.

Background & Aims Predictors of response to treatment with peginterferon plus ribavirin are well established. In these post-hoc analyses of the REALIZE study, we sought to identify predictors of response for telaprevir-based triple therapy. Methods Patients from the REALIZE study with baseline data for all predictors evaluated (including baseline disease characteristics and demographics, prior treatment response and baseline laboratory assessments) were included in the post-hoc analyses (n = 465). Univariate and multivariate analyses were used to evaluate factors predicting treatment outcomes. Results Sustained viral response (SVR) rates were 86% in prior relapsers, 63% in prior partial responders and 32% in prior null-responders. In the final multivariate analysis, baseline factors predicting SVR were prior response to treatment [Odds ratio (OR) = 2.80; 95% confidence interval (CI), 2.13–3.69], low-density lipoprotein (LDL) (≥2.6 mmol/L) (OR = 2.11; 95% CI, 1.52–2.93), HCV genotype (OR = 0.58; 95% CI, 0.36–0.93), and maximum alanine amino transferase and aspartate amino transferase (OR = 0.62; 95% CI, 0.40–0.97). Conclusions Prior response to peginterferon plus ribavirin treatment and LDL levels are the main independent predictive markers of response with telaprevir-based triple therapy.

Basic and translational research on lung biology has discovered multiple progenitor cell types, specialized or facultative, responsible for turnover, renewal, and repair. Isolation of populations of resident lung progenitor cells (LPCs) has been described by multiple protocols, and some have been successfully applied to healthy human lung tissue. We aimed at understanding how different cell culture conditions may affect, in vitro, the phenotype of LPCs to create an ideal niche-like microenvironment. The influence of different substrates (i.e., fibronectin, gelatin, laminin) and the impact of a three-dimensional/two-dimensional (3D/2D) culture switch on the biology of LPCs isolated as lung spheroids (LSs) from normal adult human lung biopsy specimens were investigated. We applied a spheroid culture system as the selective/inductive step for progenitor cell culture, as described in many biological systems. The data showed a niche-like proepithelial microenvironment inside the LS, highly sensitive to the 3D culture system and significantly affecting the phenotype of adult LPCs more than culture substrate. LSs favor epithelial phenotypes and LPC maintenance and contain cells more responsive to specific commitment stimuli than 2D monolayer cultures, while secreting a distinctive set of paracrine factors. We have shown for the first time, to our knowledge, how culture as 3D LSs can affect LPC epithelial phenotype and produce strong paracrine signals with a distinctive secretomic profile compared with 2D monolayer conditions. These findings suggest novel approaches to maintain ex vivo LPCs for basic and translational studies.

Minority variants (1.0-25.0%) were evaluated by deep sequencing (DS) at baseline and virological failure (VF) in a selection of antiretroviral treatment-naive, HIV-1-infected patients from the rilpivirine ECHO/THRIVE phase III studies. Linkage between frequently emerging resistance-associated mutations (RAMs) was determined. DS (llIumina®) and population sequencing (PS) results were available at baseline for 47 VFs and time of failure for 48 VFs; and at baseline for 49 responders matched for baseline characteristics. Minority mutations were accurately detected at frequencies down to 1.2% of the HIV-1 quasispecies. No baseline minority rilpivirine RAMs were detected in VFs; one responder carried 1.9% F227C. Baseline minority mutations associated with resistance to other non-nucleoside reverse transcriptase inhibitors (NNRTIs) were detected in 8/47 VFs (17.0%) and 7/49 responders (14.3%). Baseline minority nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) RAMs M184V and L210W were each detected in one VF (none in responders). At failure, two patients without NNRTI RAMs by PS carried minority rilpivirine RAMs K101E and/or E138K; and five additional patients carried other minority NNRTI RAMs V90I, V106I, V179I, V189I, and Y188H. Overall at failure, minority NNRTI RAMs and NRTI RAMs were found in 29/48 (60.4%) and 16/48 VFs (33.3%), respectively. Linkage analysis showed that E138K and K101E were usually not observed on the same viral genome. In conclusion, baseline minority rilpivirine RAMs and other NNRTI/NRTI RAMs were uncommon in the rilpivirine arm of the ECHO and THRIVE studies. DS at failure showed emerging NNRTI resistant minority variants in seven rilpivirine VFs who had no detectable NNRTI RAMs by PS.

Hybrid nanoparticles containing proteins have a technological interest because they attempt to achieve improved properties with respect to the single materials by chemically linking both components. In this article, the batch emulsion polymerization of methyl methacrylate in the presence of varied concentration of casein and tert-butyl hydroperoxide as initiator was investigated. A detailed characterization of the molecular microstructure and morphology of the hybrid nanoparticles allowed the identification of two competitive particle formation mechanisms. Compatibilized nanoparticles were produced at the beginning of the polymerization, while uncompatibilized particles could be generated by a second way of nucleation, which is promoted by the ungrafted protein and depends on its concentration. Fil: Picchio, Matías Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química (i); Argentina Fil: Minari, Roque Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química (i); Argentina Fil: Gonzalez, Veronica Doris Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química (i); Argentina Fil: Passeggi, Mario Cesar Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto de Investigaciones en Tecnología Química; Argentina Fil: Vega, Jorge Ruben. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química (i); Argentina Fil: Barandiaran, María. Universidad del Pais Vasco; España Fil: Gugliotta, Luis Marcelino. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química (i); Argentina

Aim Inflammation and fibrosis are present in both colonic diverticulitis and Crohn's disease (CD). The molecular pattern of basic fibroblastic growth factor (bFGF) and syndecan 1 (SD1) expression is altered in stenosing CD, but their expression in resected complicated colonic diverticulitis (ACD) is unknown. Method The expression of bFGF, SD1 and tumour necrosis factor α (TNF-α) in 20 patients after resection of ACD was compared with 15 patients having a resection for CD. Analysis was conducted using real-time reverse transcriptase polymerase chain reaction in biopsy samples. Results Lymphocytic and neutrophil inflammation scores were similar in both groups (P = 0.771 and P = 0.562). TNF-α and bFGF expression was significantly higher in ACD than in CD (P

Objectives: To evaluate the safety and efficacy profile of the new Premere patent foramen ovale (PFO) occlusion system. Background: Several different devices have been used so far for transcatheter PFO closure but no data has been published so far on the efficacy and safety of the Premere PFO occlusion system. Methods: Since September 2005, 15 patients (seven males, eight females; mean age 51.2 ± 10.8 years) at our institution underwent transcatheter PFO closure because of cryptogenic stroke, using the Premere PFO occlusion system. The procedure was performed under fluoroscopic and transesophageal echocardiographic (TEE) guidance in all patients. Seven patients (47%) had an associated atrial septal aneurysm and two patients had had >1 stroke. Five patients (33%) had an associated thrombophilia, whereas three patients (20%) had a diagnosis of migraine headache with aura, by the referring neurologist. Residual shunt was assessed immediately after and 1 month (only in 11 patients) after the procedure by both transcranial Doppler and TEE. Results: Premere PFO devices could be implanted in all patients (20 mm size in seven patients, 25 mm size in eight). Fluoroscopy time was 7.3 ± 1.9 and procedural time was 11 ± 3 min (range 7–17 min), reflecting our initial learning curve with this device. No complication occurred during the procedure or at follow-up. A residual shunt was noted immediately after the procedure in eight patients (53%) and at 1 month in 4/11 patients (36%). Residual shunt was mild in all patients. After a median follow-up of 4.2 months (0.2–5.8 months), no patient had a recurrent stroke. All patients with migraine headache with aura had resolution of symptoms. Conclusions: Our preliminary experience with the Premere PFO occlusion system shows that this device is safe and effective. © 2006 Wiley-Liss, Inc.

We report on a 17-year-old patient with a residual ventricular septal defect and a significant pressure gradient across the pulmonary homograft after Rastelli-type operation. Device closure of the defect was associated with a considerable reduction of right ventricular hypertension and of the pressure gradient across the right ventricle-to-pulmonary artery conduit. © 2005 Wiley-Liss, Inc.