In vitrodifferentiation of human cardiac fibroblasts into myofibroblasts: characterization using electrical impedance.

Cardiac arrhythmias represent about 50% of the cardiovascular diseases which are the first cause of mortality in the world. Implantable medical devices play a major role for treating these arrhythmias. Nevertheless the leads induce an unwanted biological phenomenon called fibrosis. This phenomenon begins at a cellular level and is effective at a macroscopic scale causing tissue remodelling with a local modification of the active cardiac tissue. Fibrosis mechanism is complex but at the cellular level, it mainly consists in cardiac fibroblasts activation and differentiation into myofibroblasts. We developed a simplifiedin vitromodel of cardiac fibrosis, with human cardiac fibroblasts whom differentiation into myofibroblasts was promoted with TGF-ß1. Our study addresses an unreported impedance-based method for real-time monitoring ofin vitrocardiac fibrosis. The objective was to study whether the differentiation of cardiac fibroblasts in myofibroblasts had a specific signature on the cell index, an impedance-based feature measured by the xCELLigence system. Primary human cardiac fibroblasts were cultured along 6 days, with or without laminin coating, to study the role of this adhesion protein in cultures long-term maintenance. The cultures were characterized in the presence or absence of TGF-ß1 and we obtained a significant cell index signature specific to the human cardiac fibroblasts differentiation.

Accuracy of prenatal ultrasound screening to identify fetuses infected by cytomegalovirus which will develop severe long-term sequelae.

OBJECTIVES: To compare the ability of detailed routine ultrasound examination, performed without knowledge of maternal serology and fetal status, with that of targeted prenatal imaging performed in prenatal diagnostic units in cases of known fetal infection to identify cytomegalovirus (CMV)-infected fetuses that will develop long-term sequelae. METHODS: All prenatal imaging reports were collected for 255 children with congenital CMV in a registered cohort between 2013 and 2017 (NCT01923636). All women had undergone detailed routine fetal ultrasound examination at 20-24 and 30-34 weeks as part of routine antenatal care. All cases of known fetal CMV infection had also undergone targeted prenatal ultrasound examination. Postnatal structured follow-up for up to 48 months of age involved clinical, audiological and neurological assessment, including Brunet-Lezine scoring. Long-term sequelae (> 12 months) were considered to be mild in cases with isolated unilateral hearing loss and/or vestibular disorders, and severe in cases with bilateral hearing loss and/or neurological sequelae. All imaging reports were analyzed retrospectively with the knowledge of congenital CMV infection, searching for reference to findings that were, or could have been, related to fetal infection. Findings were analyzed in relation to whether the cases were diagnosed with CMV in utero or only postnatally. RESULTS: There were 237 children with complete follow-up data (> 12 months), for a median of 24 (range, 12-48) months. Of these, 30% (71/237) were diagnosed with CMV prenatally and 70% (166/237) were diagnosed within 3 weeks after birth. 72.5% (29/40) of children with long-term sequelae, including 74% (14/19) with severe long-term sequelae, were not identified in the prenatal period. Among those diagnosed prenatally, the sensitivity of prenatal imaging for predicting long-term sequelae and severe long-term sequelae was 91% and 100%, respectively, while, in the group diagnosed only postnatally, non-specific infection-related ultrasound findings had been reported without raising suspicion in 48% of cases with long-term sequelae and 64% of those with severe long-term sequelae. CONCLUSIONS: Routine detailed ultrasound examination in pregnancy is not an appropriate screening tool for congenital CMV infection that leads to long-term sequelae, in contrast with the high performance of targeted prenatal imaging in known cases of fetal infection. The non-specific nature of ultrasound features of CMV and their evolution, and a lack of awareness of caregivers about congenital CMV, are likely explanations. Awareness of the sonologist regarding congenital CMV and knowledge of the maternal serological status in the first trimester seem key to the performance of prenatal ultrasound. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Interaction between cognitive and motor cortico-basal ganglia loops during decision making: a computational study.

In a previous modeling study, Leblois et al. (2006) demonstrated an action selection mechanism in cortico-basal ganglia loops based on competition between the positive feedback, direct pathway through the striatum and the negative feedback, hyperdirect pathway through the subthalamic nucleus. The present study investigates how multiple level action selection could be performed by the basal ganglia. To do this, the model is extended in a manner consistent with known anatomy and electrophysiology in three main areas. First, two-level decision making has been incorporated, with a cognitive level selecting based on cue shape and a motor level selecting based on cue position. We show that the decision made at the cognitive level can be used to bias the decision at the motor level. We then demonstrate that, for accurate transmission of information between decision-making levels, low excitability of striatal projection neurons is necessary, a generally observed electrophysiological finding. Second, instead of providing a biasing signal between cue choices as an external input to the network, we show that the action selection process can be driven by reasonable levels of noise. Finally, we incorporate dopamine modulated learning at corticostriatal synapses. As learning progresses, the action selection becomes based on learned visual cue values and is not interfered with by the noise that was necessary before learning.

High-resolution MEA platform for in-vitro electrogenic cell networks imaging.

A platform based on an active-pixel-sensor electrode array (APS-MEA) for high-resolution imaging of in-vitro electrogenic cell cultures is presented, characterized and validated under culture conditions. The system enables full frame acquisition at 8 kHz from 4096 microelectrodes integrated with separations of 21 microm and zoomed area acquisition with temporal resolutions down to 8 micros. This bi-modal acquisition feature opens new perspectives in particular for neuronal activity analysis and for the correlation of micro-scale and macro-scale behaviors. The low-noise performances of the integrated amplifier (11 microVRMS) combined with a hardware implementation reflecting image-/video-concepts enable high-resolution acquisitions with real-time processing capabilities adapted to the handling of the large amount of acquired data.

A real-time closed-loop setup for hybrid neural networks.

Hybrid living-artificial neural networks are an efficient and adaptable experimental support to explore the dynamics and the adaptation process of biological neural systems. We present in this paper an innovative platform performing a real-time closed-loop between a cultured neural network and an artificial processing unit like a robotic interface. The system gathers bioware, hardware, and software components and ensures the closed-loop data processing in less than 50 micros. We detail here the system components and compare its performances to a recent commercial platform.