Redox Modulation of Meniere Disease by Coriolus Versicolor Treatment, a Nutritional Mushroom Approach with Neuroprotective Potential.

BACKGROUND: Meniere's disease (MD) is a cochlear neurodegenerative disease. Hearing loss appears to be triggered by oxidative stress in the ganglion neurons of the inner ear. OBJECTIVE: Here, we confirm the variation of markers of oxidative stress and inflammation in patients with Meniere and hypothesize that chronic treatment with Coriolus mushroom helps in the response to oxidative stress and acts on α-synuclein and on NF-kB-mediated inflammatory processes. METHODS: Markers of oxidative stress and inflammation were evaluated in MD patients with or without Coriolus treatment for 3 or 6 months. RESULTS: MD patients had a small increase in Nrf2, HO-1, γ-GC, Hsp70, Trx and sirtuin-1, which were further increased by Coriolus treatment, especially after 6 months. Increased markers of oxidative damage, such as protein carbonyls, HNE, and ultraweak chemiluminescence, associated with a decrease in plasma GSH/GSSG ratio, were also observed in lymphocytes from MD patients. These parameters were restored to values similar to the baseline in patients treated with Coriolus for both 3 and 6 months. Furthermore, treated MD subjects showed decreased expression of α-synuclein, GFAP and Iba-1 proteins and modulation of the NF-kB pathway, which were impaired in MD patients. These changes were greatest in subjects taking the supplements for 6 months. CONCLUSIONS: Our study suggests MD as a model of cochlear neurodegenerative disease for the identification of potent inducers of the Nrf2-vitagene pathway, able to reduce the deleterious consequences associated with neurodegenerative damage, probably by indirectly acting on α-synuclein expression and on inflammatory processes NF- kB-mediated.

Antioxidants, Hormetic Nutrition, and Autism.

Autism spectrum disorder (ASD) includes a heterogeneous group of complex neurodevel opmental disorders characterized by atypical behaviors with two core pathological manifestations: deficits in social interaction/communication and repetitive behaviors, which are associated with disturbed redox homeostasis. Modulation of cellular resilience mechanisms induced by low levels of stressors represents a novel approach for the development of therapeutic strategies, and in this context, neuroprotective effects of a wide range of polyphenol compounds have been demonstrated in several in vitro and in vivo studies and thoroughly reviewed by [2, 3]. Mushrooms have been used in traditional medicine for many years and have been associated with a long list of therapeutic properties, including antitumor, immunomodulatory, antioxidant, antiviral, antibacterial, and hepatoprotective effects [4]. Our recent studies have strikingly indicated the presence of polyphenols in nutritional mushrooms and demonstrated their protective effects in different models of neurodegenerative disorders in humans and rats [5, 6]. Although their therapeutic effects are exerted through multiple mechanisms, increasing attention is focusing on their capacity to induce endogenous defense systems by modulating cellular signaling processes, such as nuclear factor erythroid 2 related factor 2 (Nrf2) and nuclear factor-kappa B (NF-κB) pathways. Here we discuss the protective role of hormesis and its modulation by hormetic nutrients in ASD.

Is Satellite Ahead of Terrestrial in Deploying NOMA for Massive Machine-Type Communications?

Non-orthogonal multiple access (NOMA) technologies are considered key technologies for terrestrial 5G massive machine-type communications (mMTC) applications. It is less known that NOMA techniques were pioneered about ten years ago in the satellite domain to match the growing demand for mMTC services. This paper presents the key features of the first NOMA-based satellite network, presenting not only the underlying technical solutions and measured performance but also the related deployment over the Eutelsat satellite fleet. In particular, we describe the specific ground segment developments for the user terminals and the gateway station. It is shown that the developed solution, based on an Enhanced Spread ALOHA random access technique, achieves an unprecedented throughput, scalability and service cost and is well matched to several mMTC satellite use cases. The ongoing R&D lines covering both the ground segment capabilities enhancement and the extension to satellite on-board packet demodulation are also outlined. These pioneering NOMA satellite technology developments and in-the-field deployments open up the possibility of developing and exploiting 5G mMTC satellite- and terrestrial-based systems in a synergic and interoperable architecture.

A Network Medicine Approach for Drug Repurposing in Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is a progressive hereditary muscular disease caused by a lack of dystrophin, leading to membrane instability, cell damage, and inflammatory response. However, gene-editing alone is not enough to restore the healthy phenotype and additional treatments are required. In the present study, we have first conducted a meta-analysis of three microarray datasets, GSE38417, GSE3307, and GSE6011, to identify the differentially expressed genes (DEGs) between healthy donors and DMD patients. We have then integrated this analysis with the knowledge obtained from DisGeNET and DIAMOnD, a well-known algorithm for drug-gene association discoveries in the human interactome. The data obtained allowed us to identify novel possible target genes and were used to predict potential therapeutical options that could reverse the pathological condition.

A waves in electroneurography: differential diagnosis with other late responses.

Neurographic studies are an extension of clinical examination and are performed for the functional assessment of peripheral nerves. The study of motor and sensory conduction velocity and the presence, amplitude, morphology and symmetry of the response to electrical stimulation are crucial for the diagnosis and management of peripheral neuromuscular disorders. Neurography also plays an important role in the search for so-called late responses comprising the F wave, H reflex, axonal response and A wave. By analysing the parameters of each late wave, this paper addresses the pathophysiological features and the most common conditions impairing the physiology of late responses, with a special focus on A waves.

A Waves in Diabetic Neuropathy: Pathophysiology and Neurographic Images.

PURPOSE: To evaluate the presence of A waves in diabetic neuropathy, we designed a retrospective observational study recruiting patients with type II diabetes and chronic diabetic distal sensorimotor polyneuropathy. METHODS: We recruited 238 patients of both sexes aged between 41 and 89 years. Neurography was undertaken on two bilateral upper (median and ulnar) and lower (peroneal and tibial) limb nerves. As controls, we considered that neurographs performed bilaterally on the same nerves of 40 healthy subjects. RESULTS: In addition to neurographic changes typical of chronic distal sensorimotor neuropathy, patients had a 32.77% incidence of A waves, mostly found in the tibial (16.38%) and peroneal (8.8%) nerves. Among controls, A waves were found only in the tibial nerve of a single subject (2.5%). Chi-square test with Yates correction to compare the two percentages (32.77% of patients and 2.5% of healthy subjects): 13.98, P = 0.0002, highly significant. CONCLUSIONS: We postulate that demyelination may be the site of backfiring or slowing of nerve conduction velocity, explaining the appearance of A waves in their different varieties. Implementing the search for A waves in routine neurographic examination can be a useful option for the diagnosis of neuropathy and the prediction of possible latent neuropathic processes.

Early results of MitraClip system implantation by real-time three-dimensional speckle-tracking left ventricle analysis.

AIMS: To appraise the early effect of percutaneous mitral valve repair with the MitraClip system on myocardial function using real-time three-dimensional speckle-tracking echocardiography (3D-STE). METHODS: Consecutive patients with moderate-to-severe or severe mitral regurgitation, undergoing mitral valve repair with the MitraClip system, were prospectively evaluated during the peri-procedural workout and follow-up. Left ventricular deformation was evaluated by a two-dimensional and 3D speckle-tracking analysis. 3D-STE acquisitions were elaborated obtaining real-time 3D global longitudinal strain evaluation, and by appraising both volumetric and hemodynamic parameters (i.e. left ventricular end-diastolic volume, left ventricular end-systolic volume, left ventricular ejection fraction, cardiac output, and stroke volume). RESULTS: In all, 30 patients were included. At 1-month follow-up, 3D-STE analysis revealed no changes in left ventricular end-diastolic volume (162.6 ±â€Š73.7 ml at baseline vs. 159.8 ±â€Š64.5 ml at 1-month follow-up; P = 0.63) and a downward trend in left ventricular end-systolic volume (104.7 ±â€Š52.0 vs. 100.1 ±â€Š50.4 ml, respectively; P = 0.06). Left ventricular ejection fraction did not significantly increase (38.1 ±â€Š11.3% at baseline vs. 39.4 ±â€Š11.0% at 1-month follow-up; P = 0.20). No significant changes were reported in cardiac output (4.3 ±â€Š2.0 l/min at baseline vs. 4.0 ±â€Š1.5 l/min at follow-up; P = 0.377) and in stroke volume (59.5 ±â€Š25.5 ml at baseline vs. 59.9 ±â€Š20.7 ml at follow-up; P = 0.867). On the contrary, left ventricular deformation capability significantly improved, with the real-time 3D global longitudinal strain value changing from -9.8 ±â€Š4.1% at baseline to -11.0 ±â€Š4.4% at follow-up (P = 0.018). CONCLUSIONS: Accurately assessing myocardial function by the use of 3D-STE, this study reported irrelevant early changes in left ventricular size, but a positive effect on left ventricular deformation capability following mitral valve repair with the MitraClip system. These preliminary results need to be confirmed in larger series and extended to long-term follow-up.

Myocardial deformational adaptations to different forms of training: a real-time three-dimensional speckle tracking echocardiographic study.

The hemodynamic load due to physical activity leads to structural and functional cardiac adaptations known as "Athlete's heart". We aimed to compare myocardial performance in different groups of trained athletes by means of 3D echocardiography and 3D speckle tracking echocardiography (3D-STE). 66 athletes [26 strength-trained athletes (STA) and 40 endurance athletes (ETA)] were prospectively enrolled. A control group of 40 sedentary subjects (sedentary group) was also included. All subjects underwent both standard and 3D evaluation of left ventricular (LV) function including 3D-STE. Left ventricular mass indexed for body surface area, LV end-diastolic (LV Dd) thickness of interventricular septum and posterior wall thickness mean values were significantly increased in athletes (p < 0.001, p < 0.01 and p < 0.001, respectively). LV diastolic diameter index had a significantly higher mean value in ETA in respect to sedentary group (p = 0.001). Despite a preserved mean value of LV ejection fraction (LV EF) in all the groups, subjects in STA group showed a significant reduction of strain in the longitudinal, radial and circumferential directions (p < 0.05 for all). Area strain mean value was also reduced in STA group (p < 0.01). In the overall population, an inverse relationship between longitudinal strain and LV Dd index (r = -0.260, p = 0.008), the E/A ratio (r = -0.249, p = 0.010) and the E' velocity (r = -0.259, p = 0.009) has been identified. Sport-specific patterns of ventricular morphological and functional remodeling are present in athletes performing different kinds of training. 3D-STE is a useful and feasible echocardiographic technique for the assessment of sport-specific pattern of deformational adaptations.

Early changes of left ventricular geometry and deformational analysis in obese subjects without cardiovascular risk factors: a three-dimensional and speckle tracking echocardiographic study.

Subclinical myocardial dysfunction has been identified in obese subjects without cardiovascular risks factors and has been defined as "obesity cardiomyopathy". We evaluated left ventricular (LV) function and geometry in obese patients by using a 3 dimensional echocardiography (3DE). We also aimed to look at the influence of ventricular geometry upon functional parameters of the LV by using 3D speckle tracking imaging (3D-STI). 30 consecutive and asymptomatic obese cases (OB group) with no comorbidities were prospectively enrolled. The control group included 30 healthy volunteers (HS group), matched for age and sex. All subjects underwent 3DE and 3D-STI. Ventricular geometry was evaluated with the LV sphericity index (LV SpI) and the LV diastolic volume to mass ratio (LV EDV/Mass ratio). LV Mass was significantly increased in OB group and the LV EDV/Mass ratio had a significantly lower mean value in this group (p < 0.001 and p = 0.002, respectively). LV SpI was significantly reduced in obese subjects (p < 0.001). A significant reduction in longitudinal (GLS), radial (GRS) and area strain (GAS) was observed in OB group (p = 0.001 for all) while circumferential mechanic (GCS) was not different between the two groups (p = 0.052). LV EDV to mass ratio was significantly related to GLS (r = -0.298, p = 0.022) and GAS (r = -0.289, p = 0.026). On multivariate analysis, GRS and GAS were independently related to LV SpI (ß = 0.222, p = 0.031 and ß = -0.222, p = 0.034, respectively). Geometrical and structural ventricular remodeling negatively influences functional properties of the LV in obese subjects without cardiovascular risks factors. Further studies are needed to assess the prognostic value of our findings.

Three-dimensional echocardiographic and surgical findings in mitral mechanical valve dysfunction.

Periodic echocardiographic evaluation of valve function is recommended in all patients with prosthetic valves. Usually trans-thoracic echocardiography (TTE) is satisfactory to assess prosthetic function. Nevertheless when the TTE is suboptimal or in case of strong clinical doubt of prosthetic valve dysfunction, trans-esophageal echocardiography (TEE) remains the gold standard of imaging. Recent advancements in echocardiography, with the three-dimensional (3D) reconstruction, provide an incremental diagnostic value as compared to two-dimensional TEE. In addition, 3D-TEE gives unique views that add extra morphological and anatomical information, providing a very accurate presurgical evaluation.