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The present study aimed to investigate the pharyngeal and nasal microbiota composition in children with adenotonsillar hypertrophy (AH) and assess longitudinal alterations in both microbiota after a probiotic oral spray treatment. A cohort of 57 AH patients were enrolled and randomly assigned to the probiotic and placebo groups for a 5-month treatment course. Pharyngeal and nasal swabs were collected before and after treatment and analyzed by 16S rRNA-based metataxonomics and axenic cultures for pathobiont identification. 16S rRNA sequences from pharyngeal and nasal swabs of 65 healthy children (HC) were used as microbiota reference profiles. We found that the pharyngeal and nasal microbiota of AH children were similar. When compared to HC, we observed an increase of the genera Rothia, Granulicatella, Streptococcus, Neisseria, and Haemophilus, as well as a reduction of Corynebacterium, Pseudomonas, Acinetobacter, and Moraxella in both microbiota of AH patients. After probiotic treatment, we confirmed the absence of adverse effects and a reduction of upper respiratory tract infections (URTI). Moreover, the composition of pharyngeal microbiota was positively influenced by the reduction of potential pathobionts, like Haemophilus spp., with an increase of beneficial microbial metabolic pathways. Finally, the probiotic reduced the abundance of the pathobionts Streptococcus mitis and Gemella haemolysans in relation to AH severity. In conclusion, our results highlight the alterations of the pharyngeal and nasal microbiota associated with AH. Moreover, probiotic administration conferred protection against URTI and reduced the presence of potential pathobionts in patients with AH. IMPORTANCE: Adenotonsillar hypertrophy (AH) is considered the main cause of breathing disorders during sleep in children. AH patients, after significant morbidity and often multiple courses of antibiotics, often proceed to tonsillectomy and/or adenoidectomy. Given the potential risks associated with these procedures, there is a growing interest in the use of nonsurgical adjuvant therapies, such as probiotics, that could potentially reduce their need for surgical intervention. In this study, we investigated the pharyngeal and nasal microbiota in patients with AH compared with healthy children. Furthermore, we tested the effects of probiotic spray administration on both disease symptoms and microbiota profiles, to evaluate the possible use of this microbial therapy as an adjuvant for AH patients.

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In this work, we analyze the way concentric hypertrophy, triggered by mild aortic stenosis, affects the electromechanical activity of the left ventricle during a cardiac cycle by employing a 3D finite-element strongly-coupled model. Three mechanical feedbacks on electrophysiology are considered: the conduction feedback, acting on conductivity tensors, the convection feedback, dependent on the deformation rate, and the mechanoelectric feedback due to stretch-activated membrane channels. In case of a multiple endocardial electrical stimulation for a healthy ventricle, the convection feedback raises the values of action potential duration APD while modifying the corresponding distribution patterns, mainly in the latest activated regions. Hypertrophy stresses the latter effect. If an endocardial ectopic stimulation is applied to the healthy ventricle, the convection feedback enhances its effects on APD (by increasing the corresponding dispersion too), especially on the opposite side with respect to the stimulation site; the mechanoelectric feedback reduces APD values on the midmyocardium instead. By including all feedbacks, it turns out that the hypertrophic ventricle exhibits lower values and a modified epicardial pattern of APD if compared with the healthy and stenotic (without growth) ventricles, but its transmural dispersion of repolarization does not increase and its epicardial electrograms have the same morphological features. Despite a decrease of the end-diastolic volume, hypertrophy compensates for the stenotic increase of the end-systolic volume and of the internal pressure during the efflux phase, while normalizing stroke work.

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Mechanical function of the heart during open-chest cardiac surgery is exclusively monitored by echocardiographic techniques. However, little is known about local kinematics, particularly for the reperfused regions after ischemic events. We report a novel imaging modality, which extracts local and global kinematic parameters from videos of in situ beating hearts, displaying live video cardiograms of the contraction events. A custom algorithm tracked the movement of a video marker positioned ad hoc onto a selected area and analyzed, during the entire recording, the contraction trajectory, displacement, velocity, acceleration, kinetic energy and force. Moreover, global epicardial velocity and vorticity were analyzed by means of Particle Image Velocimetry tool. We validated our new technique by i) computational modeling of cardiac ischemia, ii) video recordings of ischemic/reperfused rat hearts, iii) videos of beating human hearts before and after coronary artery bypass graft, and iv) local Frank-Starling effect. In rats, we observed a decrement of kinematic parameters during acute ischemia and a significant increment in the same region after reperfusion. We detected similar behavior in operated patients. This modality adds important functional values on cardiac outcomes and supports the intervention in a contact-free and non-invasive mode. Moreover, it does not require particular operator-dependent skills.

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In this paper, we analyze the epicardial electromechanical response of an in silico cardiac ventricular wedge under both healthy and concentric hypertrophic conditions. This is achieved by taking into account the growth of the wedge thickness and the fiber dispersion that may follow. The electromechanical response is described in terms of some macroscopic measures, i.e. the action potential duration, the conduction velocity, the contractility and the contraction force. Our results suggest that growth reduces the action potential duration and conduction velocity, whilst it increases the contractility and contraction force, yielding an overall negative effect. In presence of fiber dispersion, the action potential duration and conduction velocity are not affected further, whilst the effect on the contractility and contraction force is enhanced.

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Nowadays, in vitro cardiac cultures offer a valid tool to study the bioelectrical activity and the biomechanics of the heart tissue. Modelling their properties could be helpful for researchers involved in this field. In this paper, we develop a three-dimensional electromechanical model to study how thickness affects the bioelectrical and biomechanical performances of an in vitro culture made of ventricular cells. In particular, by our in silico simulations we want to verify if thickness variations can be a key factor in modifying the response of the whole culture when this one is grown to become a cardiac patch. Therefore, for this parameter we choose three increasing values while keeping a fiber architecture among layers that is similar to the one of the in vivo heart but it is randomly stated at the beginning of each simulation. We prove that, independently from the selected architectures, the more thickness increases the more mechanical improvements are attained, but the more electrical problems may arise too.

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Today, in vitro cardiac cultures are widely exploited to investigate several aspects of the electromechanical behavior of the cardiac tissue. Thus, new forecasts may derive from modelling their properties. In particular, in this paper, we focus on the fiber architecture of cultures, i.e. on the way cellular sarcomeres are locally oriented, when they are designed to be cardiac patches. We employ a three-dimensional model to simulate the bioelectrical activity and the biomechanics of a multilayered culture made of ventricular cells and with four possible architectures consisting of: i) random fibers in all cells; ii) randomly rotating fibers among layers; iii) structurally rotating fibers from the bottom layer to the top one; iv) parallel fibers among layers. Our results suggest that the best configuration for a patch may be the architecture with structurally rotating fibers, which is the one that most approaches the anisotropic structure of the in vivo heart, thanks to its better electrical and mechanical performances.

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