Novel perspectives in redox biology and pathophysiology of failing myocytes: modulation of the intramyocardial redox milieu for therapeutic interventions - A review article from the Working Group of Cardiac Cell Biology, Italian Society of Cardiology

The prevalence of heart failure (HF) is still increasing worldwide, with enormous human, social, and economic costs, in spite of huge efforts in understanding pathogeneticmechanisms and in developing effective therapies that have transformed this syndrome into a chronic disease. Myocardial redox imbalance is a hallmark of this syndrome, since excessive reactive oxygen and nitrogen species can behave as signaling molecules in the pathogenesis of hypertrophy and heart failure, leading to dysregulation of cellular calcium handling, of the contractile machinery, of myocardial energetics and metabolism, and of extracellular matrix deposition. Recently, following new interesting advances in understanding myocardial ROS and RNS signaling pathways, new promising therapeutical approaches with antioxidant properties are being developed, keeping in mind that scavenging ROS and RNS tout court is detrimental as well, since these molecules also play a role in physiological myocardial homeostasis

Multi-Scale Modelling of Aggregation of TiO2 Nanoparticle Suspensions in Water

Titanium dioxide nanoparticles have risen concerns about their possible toxicity and the European Food Safety Authority recently banned the use of TiO2 nano-additive in food products. Following the intent of relating nanomaterials atomic structure with their toxicity without having to conduct large-scale experiments on living organisms, we investigate the aggregation of titanium dioxide nanoparticles using a multi-scale technique: starting from ab initio Density Functional Theory to get an accurate determination of the energetics and electronic structure, we switch to classical Molecular Dynamics simulations to calculate the Potential of Mean Force for the connection of two identical nanoparticles in water; the fitting of the latter by a set of mathematical equations is the key for the upscale. Lastly, we perform Brownian Dynamics simulations where each nanoparticle is a spherical bead. This coarsening strategy allows studying the aggregation of a few thousand nanoparticles. Applying this novel procedure, we find three new molecular descriptors, namely, the aggregation free energy and two numerical parameters used to correct the observed deviation from the aggregation kinetics described by the Smoluchowski theory. Ultimately, molecular descriptors can be fed into QSAR models to predict the toxicity of a material knowing its physicochemical properties, enabling safe design strategies

Position Sense Deficits at the Lower Limbs in Early Multiple Sclerosis: Clinical and Neural Correlates

Background/Objective. Position sense, defined as the ability to identify joint and limb position in space, is crucial for balance and gait but has received limited attention in patients with multiple sclerosis (MS). We investigated lower limb position sense deficits, their neural correlates, and their effects on standing balance in patients with early MS. Methods. A total of 24 patients with early relapsing-remitting MS and 24 healthy controls performed ipsilateral and contralateral matching tasks with the right foot during functional magnetic resonance imaging. Corpus callosum (CC) integrity was estimated with diffusion tensor imaging. Patients also underwent an assessment of balance during quiet standing. We investigated differences between the 2 groups and the relations among proprioceptive errors, balance performance, and functional/structural correlates. Results. During the contralateral matching task, patients demonstrated a higher matching error than controls, which correlated with the microstructural damage of the CC and with balance ability. In contrast, during the ipsilateral task, the 2 groups showed a similar matching performance, but patients displayed a functional reorganization involving the parietal areas. Neural activity in the frontoparietal regions correlated with the performance during both proprioceptive matching tasks and quiet standing. Conclusion. Patients with early MS had subtle, clinically undetectable, position sense deficits at the lower limbs that, nevertheless, affected standing balance. Functional changes allowed correct proprioception processing during the ipsilateral matching task but not during the more demanding bilateral task, possibly because of damage to the CC. These findings provide new insights into the mechanisms underlying disability in MS and could influence the design of neurorehabilitation protocols

Effects of divalent dopants on the microstructure and conversion efficiency of Cr4+ ions in Cr,Me:YAG (Me – Ca, Mg, Ca/Mg) transparent ceramics

The efficiency of Cr4+:YAG is directly proportional to the transparency and concentration of Cr4+ which can be tuned by changing the divalent dopant. The aim of this study was to investigate the influence of different kinds of divalent dopants on the properties of Cr,Me:YAG (Me = Ca, Mg or Ca/Mg) ceramics made by solid-state sintering in vacuum. Pure YAG phases with an in-line transmittance of 80% at 1064nm were prepared. It was revealed that the Cr4+ concentration is directly proportional to the concentration of divalent dopants and it does not depend on the type of dopant. Our experiment proves that the efficiency of high optical quality Cr4+:YAG ceramics preparedby sintering does not change when different kinds of divalent additives are used

Light Commercial Vehicle ADAS-Oriented Modelling: An Optimization-Based Conversion Tool from Multibody to Real-Time Vehicle Dynamics Model

In the last few years, the number of Advanced Driver Assistance Systems (ADAS) on road vehicles has been increased with the aim of dramatically reducing road accidents. Therefore, the OEMs need to integrate and test these systems, to comply with the safety regulations. To lower the development cost, instead of experimental testing, many virtual simulation scenarios need to be tested for ADAS validation. The classic multibody vehicle approach, normally used to design and optimize vehicle dynamics performance, is not always suitable to cope with these new tasks; therefore, real-time lumped-parameter vehicle models implementation becomes more and more necessary. This paper aims at providing a methodology to convert experimentally validated light commercial vehicles (LCV) multibody models (MBM) into real-time lumped-parameter models (RTM). The proposed methodology involves the definition of the vehicle subsystems and the level of complexity required to achieve a good match between the simulation results obtained from the two models. Thus, an automatic vehicle model converter will be presented together with the assessment of its accuracy. An optimization phase is included into the conversion tool, to fine-tune uncertain vehicle parameters and to compensate for inherent modelling differences. The objective function of the optimization is based on typical performance indices used for vehicle longitudinal and lateral dynamics assessment. Finally, the simulation results from the original and converted models are compared during steady-state and transient tests, to prove the conversion fidelity

Noninvasive Assessment of Hemodynamic Stress Distribution after Indirect Revascularization for Pediatric Moyamoya Vasculopathy

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