Non-Vitamin K antagonist oral anticoagulants for mechanical heart valves is the door still open?

The estimated prevalence of mitral or aortic valvular heart disease is ≈2.5% in the general population of Western countries, and is expected to rise with population aging. A substantial proportion of patients with valvular heart disease undergoes surgical valve replacement. Mechanical heart valves are much more durable than bioprostheses, and are thus preferentially implanted in patients with a longer life expectancy, but have the major drawback of requiring lifelong anticoagulation to prevent valve thrombosis because of their higher thrombogenicity. The non-vitamin K antagonist oral anticoagulants (NOACs) are replacing vitamin K antagonists in many settings, including bioprostheses, because of their favorable safety and efficacy profiles. However, mechanical heart valves currently pose an absolute contraindication to NOACs based on the results of a single phase II study comparing dabigatran and warfarin (RE-ALIGN [Randomized, Phase II Study to Evaluate the Safety and Pharmacokinetics of Oral Dabigatran Etexilate in Patients after Heart Valve Replacement]). That trial was stopped prematurely because of an excess of both stroke and bleeding with the dabigatran doses tested. Because of such negative findings, research in this area has been halted. We believe that several aspects of both the preclinical studies and the RE-ALIGN trial should be critically reevaluated. In our opinion, 1 single trial with a single NOAC does not represent sufficient evidence for dismissing a therapeutic strategy, anticoagulation with NOACs, that has shown better safety and at least similar efficacy as warfarin in the setting of atrial fibrillation and venous thromboembolism,. Herein, we reevaluate this topic to identify the patient profile that has the greatest likelihood of benefit from some of the NOACs, with a focus on factor Xa inhibitors, thus providing some perspectives for basic and translational research

FFAs and QT intervals in obese women with visceral adiposity: Effects of sustained weight loss over 1 year

We evaluated 66 obese patients grouped by waist-to-hip ratio (WHR) into group A (WHR > 0.85, n = 30) and group B (WHR ≤ 0.85, n = 36), before and after 1 yr of diet-induced weight loss compared with 25 nonobese women. Before diet, the longest values of QT intervals and the highest levels of FFA and catecholamines were in group A (P < 0.01). In obese women (both groups), the corrected QT (QTc); interval correlated with plasma FFA (P < 0.01) and catecholamine (P < 0.02) concentrations. After 1 yr of diet, at the same levels of body weight reduction, the decrement of the QTc interval (P < 0.02), FFA (P < 0.01) and catecholamine (P < 0.02) levels were significantly greater in-group A than group B. In multivariate analysis, the decline of the QTc interval after weight loss was associated with changes in plasma FFA independently of changes in WHR and plasma catecholamines. Our data suggest that the QTc interval is tightly correlated with plasma FFA levels; shortening of cardiac repolarization times in the course of long-lasting weight reduction may reduce the risk of ventricular electrical instability, especially in women with abdominal adiposity

Il complesso di gallerie drenanti Chianatelle-Felice-Olivella nel Parco Nazionale del Vesuvio (Napoli)

The Chianatelle-Felice-Olivella drainage galleries complex in the Vesuvius National Park (Naples) The Chianatelle-Felice-Olivella complex, located close to the village of Sant’Anastasia on Mt. Vesuvius, is constituted of 4 drainage galleries, each several tens of meters long, with a total drainage of about 0,1 l/s. Their present structure is due to the hydraulic works made, at the end of the 19th century by the king Ferdinando II of Bourbon, whereas the presence of an underground aquifer in this area had been noticed before the 79 a.C. eruption. The underground complex is not only an important archaeological site, but it is nowadays a part of the monitoring network for the Vesuvius volcanic risk assessment managed by the Istituto Nazionale di Geofisica e Vulcanologia. Some important variation of the geochemical characteristics of the Olivella 1 gallery were recorded in coincidence with the October 11, 1999, earthquake

Enhancement of SSVEPs Classification in BCI-based Wearable Instrumentation Through Machine Learning Techniques

This work addresses the adoption of Machine Learning classifiers and Convolutional Neural Networks to improve the performance of highly wearable, single-channel instrumentation for Brain-Computer Interfaces. The proposed measurement system is based on the classification of Steady-State Visually Evoked Potentials (SSVEPs). In particular, Head-Mounted Displays for Augmented Reality are used to generate and display the flickering stimuli for the SSVEPs elicitation. Four experiments were conducted by employing, in turn, a different Head-Mounted Display. For each experiment, two different algorithms were applied and compared with the state-of-the-art-techniques. Furthermore, the impact of different Augmented Reality technologies in the elicitation and classification of SSVEPs was also explored. The experimental metrological characterization demonstrates (i) that the proposed Machine Learning-based processing strategies provide a significant enhancement of the SSVEP classification accuracy with respect to the state of the art, and (ii) that choosing an adequate Head-Mounted Display is crucial to obtain acceptable performance. Finally, it is also shown that the adoption of inter-subjective validation strategies such as the Leave-One-Subject-Out Cross Validation successfully leads to an increase in the inter-individual 1-σ reproducibility: this, in turn, anticipates an easier development of ready-to-use systems

Animals-assisted therapy: A brief review

In rehabilitative setting, the presence of animals can be considered as an important stimulus for verbal and social communication, and for mood regulation. Interaction with an animal is beneficial for children's development and numerous psychological tests have revealed that growing up with pets has a beneficial effect on children's self-esteem and self-confidence, can improve empathy, a sense of responsibility and cognitive development, as well as social status within the peer group

A ML-based Approach to Enhance Metrological Performance of Wearable Brain-Computer Interfaces

In this paper, the adoption of Machine Learning (ML) classifiers is addressed to improve the performance of highly wearable, single-channel instrumentation for Brain-Computer Interfaces (BCIs). The proposed BCI is based on the classification of Steady-State Visually Evoked Potentials (SSVEPs). In this setup, Augmented Reality Smart Glasses are used to generate and display the flickering stimuli for the SSVEP elicitation. An experimental campaign was conducted on 20 adult volunteers. Successively, a Leave-One-Subject-Out Cross Validation was performed to validate the proposed algorithm. The obtained experimental results demonstrate that suitable ML-based processing strategies outperform the state-of-the-art techniques in terms of classification accuracy. Furthermore, it was also shown that the adoption of an inter-subjective model successfully led to a decrease in the 3-σ uncertainty: this can facilitate future developments of ready-to-use systems

Single-cell and neuronal network alterations in an in vitro model of Fragile X syndrome

The Fragile X mental retardation protein (FMRP) is involved in many cellular processes and it regulates synaptic and network development in neurons. Its absence is known to lead to intellectual disability, with a wide range of comorbidities including autism. Over the past decades, FMRP research focused on abnormalities both in glutamatergic and GABAergic signaling, and an altered balance between excitation and inhibition has been hypothesized to underlie the clinical consequences of absence of the protein. Using Fmrp knockout mice, we studied an in vitro model of cortical microcircuitry and observed that the loss of FMRP largely affected the electrophysiological correlates of network development and maturation but caused less alterations in single-cell phenotypes. The loss of FMRP also caused a structural increase in the number of excitatory synaptic terminals. Using a mathematical model, we demonstrated that the combination of an increased excitation and reduced inhibition describes best our experimental observations during the ex vivo formation of the network connections

Psychopathological and psychodynamic hypotheses for pediatric stuttering

Stuttering is a common language alteration in pediatric age consisting in repetitions and blocks, which entail a break in the rhythm and melody of the speech. According to the WHO it is a disorder of the rhythm of the word, the subject knows precisely what he would like to say, but at the same time he is not able to say it. It is a great inconvenience for those affected, also because the slowing down of speaking is not about thought or cognitive skills

A brief review about anxiety and aggressive behavior in pediatric age

Anxiety can be considered a normal experience of the human being and as such also of the child. It manifests itself in different ways according to the level of development: in the smaller the child, the more anxiety is expressed with manifestations that involve the whole organism, becoming evident either with motor excitement or with physical discomfort. As the psychic apparatus is structured, anxiety is experienced as an inner phenomenon and is experienced as an unpleasant state. Fortunately, we are all a bit anxious, even if there are some people who are more, others less

Antiviral Properties of Moringa oleifera Leaf Extracts against Respiratory Viruses

: Moringa oleifera (M. oleifera) is a plant widely used for its beneficial properties both in medical and non-medical fields. Because they produce bioactive metabolites, plants are a major resource for drug discovery. In this study, two different cultivars of leaves of M. oleifera (Salento and Barletta) were obtained by maceration or microwave-assisted extraction (MAE). We demonstrated that extracts obtained by MAE exhibited a lower cytotoxic profile compared to those obtained by maceration at concentrations ranged from 25 to 400 μg/mL, on both Vero CCL-81 and Vero/SLAM cells. We examined their antiviral properties against two viruses, i.e., the human coronavirus 229E (HCoV-229E) and measles virus (MeV), which are both responsible for respiratory infections. The extracts were able to inhibit the infection of both viruses and strongly prevented their attack and entry into the cells in a range of concentrations from 50 to 12 μg/mL. Particularly active was the variety of Salento that registered a 50% inhibitory concentration (IC50) at 21 μg/mL for HCoV-229E and at 6 μg/mL for MeV. We identified the presence of several compounds through high performance liquid chromatography (HPLC); in particular, chlorogenic and neochlorogenic acids, quercetin 3-O-β-d-glucopyranoside (QGP), and glucomoringin (GM) were mainly observed. In the end, M. oleifera can be considered a promising candidate for combating viral infections with a very strong action in the early stages of viral life cycle, probably by destructuring the viral particles blocking the virus-cell fusion