Ruolo della Nox2 nelle demenze: nuove strategie di neuroprotezione

Le demenze sono patologie croniche ad incidenza crescente all’interno della popolazione geriatrica. L’indagine EURODEM ha riscontrato una prevalenza media delle demenze nella popolazione ultrasessantacinquenne, in Europa, che varia, a seconda delle classi di età, dal 5.9 al 9.4%. La ricerca scientifica ha compiuto grandi progressi nell’ultimo decennio nell’individuare meccanismi patogenetici, criteri diagnostici, clinici e neuroradiologici, strategie di prevenzione e trattamento delle demenze. Dall’introduzione nella pratica clinica di farmaci a dimostrata efficacia sulla sintomatologia cognitiva del paziente con demenza (inibitori delle colinesterasi, memantina), la ricerca rivolge oggi il suo oggetto di interesse verso le cosiddette “disease modifying therapies”, strategie terapeutiche in grado di agire sui meccanismi patogenetici della malattia, arrestando a diversi livelli la cascata di eventi che porta come conseguenza finale la morte neuronale. Tali farmaci, molti dei quali ancora in sperimentazione clinica, sono tanto più efficaci quanto più precocemente somministrati. Nell’ottica di identificare nuove strategie terapeutiche che abbiano un impatto sul processo neuropatologico che conduce alla morte neuronale, il presente studio ha il fine di analizzare il ruolo dello stress ossidativo nella patogenesi delle demenze, attraverso l’analisi dei livelli sierici della NOX2 o gp91-FOX, parte dell’enzima NADPH-ossidasi in pazienti affetti da demenza di Alzheimer (AD) o da demenza vascolare (VaD) e in controlli sani, omogenei tra loro per età, sesso e fattori di rischio cardiovascolari. Tale risultato, associato all’analisi dei livelli di isoprostani urinari nei tre gruppi, rappresenta uno specchio dell’attivazione di processi di neuroinfiammazione mediati dallo stress ossidativo. Alcuni studi in letteratura effettuati post-mortem sul cervello di pazienti con AD hanno mostrato la presenza di una risposta infiammatoria da parte della microglia attivata dalla beta-amiloide in stadi precoci di malattia. La NADPH-ossidasi è stata implicata come attore principale di questo processo di neuroinfiammazione e danno neuronale. Riconoscere la via mediata dalla NADPH-ossidasi microgliale come una delle vie principali della cascata neuropatologica dell’AD consentirebbe di sviluppare terapie mirate a bloccare l’attivazione del suddetto enzima per rallentare o addirittura arrestare la progressione della malattia. Ultima fase del nostro studio consisterà proprio nel trattare i pazienti arruolati che esprimeranno il loro consenso con fonti alimentari di polifenoli, potenti inibitori della NADPH ossidasi ed osservarne in acuto ed in cronico gli effetti a livello biochimico, strumentale e clinico

Heart Rate Control in Non-Paroxysmal Atrial Fibrillation. A New Indication for Ivabradine?

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Management of Painful Shoulder Arthroplasty: A Narrative Review

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Glyco-metabolic Effects of Ranolazine: A truly Multifaceted Drug?

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Executive Functioning and Personality Traits in Insomnia Disorder: A Preliminary Report on the Clinical Importance of Objective and Subjective Reduction of Total Sleep Time

To confirm and extend previous findings on the relationships between executive functioning (EF) and insomnia, as well as the available evidence on the associations between personality traits and insomnia, 30 consecutively-admitted insomnia participants and 30 community dwelling adult participants matched on age, gender and educational level, were administered a battery of EF measures and the Personality Inventory for DSM-5 (PID-5). Insomnia participants underwent two full-night polysomnographic (PSG) recording, followed by a morning assessment of subjective sleep parameters. A misperception index (MI) was computed in order to identify participants characterized by objective insomnia and non-objective insomnia. The EF performance associations between insomnia and poor performance on selected executive functions was confirmed. However, the objective insomnia and non-objective insomnia sub-groups show significant differences on specific EF indices, as well as on dysfunctional personality dimensions

A peculiar formula of essential amino acids prevents rosuvastatin myopathy in mice

Aims: Myopathy, characterized by mitochondrial oxidative stress, occurs in ∼10% of statin-treated patients, and a major risk exists with potent statins such as rosuvastatin (Rvs). We sought to determine whether a peculiar branched-chain amino acid-enriched mixture (BCAAem), found to improve mitochondrial function and reduce oxidative stress in muscle of middle-aged mice, was able to prevent Rvs myopathy. Results: Dietary supplementation of BCAAem was able to prevent the structural and functional alterations of muscle induced by Rvs in young mice. Rvs-increased plasma 3-methylhistidine (a marker of muscular protein degradation) was prevented by BCAAem. This was obtained without changes of Rvs ability to reduce cholesterol and triglyceride levels in blood. Rather, BCAAem promotes de novo protein synthesis and reduces proteolysis in cultured myotubes. Morphological alterations of C2C12 cells induced by statin were counteracted by amino acids, as were the Rvs-increased atrogin-1 mRNA and protein levels. Moreover, BCAAem maintained mitochondrial mass and density and citrate synthase activity in skeletal muscle of Rvs-treated mice beside oxygen consumption and ATP levels in C2C12 cells exposed to statin. Notably, BCAAem assisted Rvs to reduce oxidative stress and to increase the anti-reactive oxygen species (ROS) defense system in skeletal muscle. Innovation and Conclusions: The complex interplay between proteostasis and antioxidant properties may underlie the mechanism by which a specific amino acid formula preserves mitochondrial efficiency and muscle health in Rvs-treated mice. Strategies aimed at promoting protein balance and controlling mitochondrial ROS level may be used as therapeutics for the treatment of muscular diseases involving mitochondrial dysfunction, such as statin myopathy

Stellar metallicity from optical and UV spectral indices: test case for WEAVE-StePS

Context. The upcoming generation of optical spectrographs on four meter-class telescopes, with their huge multiplexing capabilities, excellent spectral resolution, and unprecedented wavelength coverage, will provide high-quality spectra for thousands of galaxies. These data will allow us to examine of the stellar population properties at intermediate redshift, an epoch that remains unexplored by large and deep surveys. Aims. We assess our capability to retrieve the mean stellar metallicity in galaxies at different redshifts and signal-to-noise ratios (S/N), while simultaneously exploiting the ultraviolet (UV) and optical rest-frame wavelength coverage. Methods. The work is based on a comprehensive library of spectral templates of stellar populations, covering a wide range of age and metallicity values and built assuming various star formation histories (SFHs), to cover an observable parameter space with diverse chemical enrichment histories and dust attenuation. We took into account possible observational errors, simulating realistic observations of a large sample of galaxies carried out with WEAVE at the William Herschel Telescope at different redshifts and S/N values. We measured all the available and reliable indices on the simulated spectra and on the comparison library. We then adopted a Bayesian approach to compare the two sets of measurements in order to obtain the probability distribution of stellar metallicity with an accurate estimate of the uncertainties. Results. The analysis of the spectral indices has shown how some mid-UV indices, such as BL3580 and Fe3619, can provide reliable constraints on stellar metallicity, along with optical indicators. The analysis of the mock observations has shown that even at S/N = 10, the metallicity can be derived within 0.3 dex, in particular, for stellar populations older than 2 Gyr. The S/N value plays a crucial role in the uncertainty of the estimated metallicity and so, the differences between S/N = 10 and S/N = 30 are quite large, with uncertainties of ∼ 0.15 dex in the latter case. On the contrary, moving from S/N = 30 to S/N = 50, the improvement on the uncertainty of the metallicity measurements is almost negligible. Our results are in good agreement with other theoretical and observational works in the literature and show how the UV indicators, coupled with classic optical ones, can be advantageous in constraining metallicities. Conclusions. We demonstrate that a good accuracy can be reached on the spectroscopic measurements of the stellar metallicity of galaxies at intermediate redshift, even at low S/N, when a large number of indices can be employed, including some UV indices. This is very promising for the upcoming surveys carried out with new, highly multiplexed, large-field spectrographs, such as StePS at the WEAVE and 4MOST, which will provide spectra of thousands of galaxies covering large spectral ranges (between 3600 and 9000 Å in the observed frame) at relatively high S/N (> 10 Å−1 )

The potential of blood flow restriction exercise to overcome Jetlag : important implications for Tokyo 2020

The decision taken by the International Olympic Committee (IOC) to host the Olympic Games this summer brings new challenges for event organisers and athletes. One such measure taken by the IOC is to mandate that athletes may not enter the Olympic Village more than five days before competing at the Games in order to prevent the spread of COVID-19. As a result, athletes from around the globe that are unable to make alternative plans will need to travel to Tokyo and acclimatize within only 5 days before their event. Of particular concern are the adverse health and performance effects elicited by flight dysrhythmia, also known as jetlag, on those athletes travelling to the Olympic Games across multiple times zones. Blood flow restriction (BFR) is a safe exercise mode that can potentially diminish the impact of jetlag on performance through its numerous beneficial physiological adaptations that overlap with those of other jetlag mitigation strategies. Experimental data are required to confirm this intriguing possibility. The present commentary aims to encourage more research into the effects of BFR training in conjunction with other strategies to overcome the effects of jetlag prior, during and after a long-haul flight on the subsequent performance of elite athletes, particularly during these difficult times of the COVID19 pandemic.https://www.minervamedica.it/en/journals/medicina-dello-sport2022-07-17hj2021Sports Medicin

Drastic Reductions in Mental Well-Being Observed Globally During the COVID-19 Pandemic: Results From the ASAP Survey

Most countries affected by the COVID-19 pandemic have repeatedly restricted public life to control the contagion. However, the health impact of confinement measures is hitherto unclear. We performed a multinational survey investigating changes in mental and physical well-being (MWB/PWB) during the first wave of the pandemic. A total of 14,975 individuals from 14 countries provided valid responses. Compared to pre-restrictions, MWB, as measured by the WHO-5 questionnaire, decreased considerably during restrictions (68.1 +/- 16.9 to 51.9 +/- 21.0 points). Whereas 14.2% of the participants met the cutoff for depression screening pre-restrictions, this share tripled to 45.2% during restrictions. Factors associated with clinically relevant decreases in MWB were female sex (odds ratio/OR = 1.20, 95% CI: 1.11-1.29), high physical activity levels pre-restrictions (OR = 1.29, 95% CI 1.16-1.42), decreased vigorous physical activity during restrictions (OR = 1.14, 95% CI: 1.05-1.23), and working (partially) outside the home vs. working remotely (OR = 1.29, 95% CI: 1.16-1.44/OR = 1.35, 95% CI: 1.23-1.47). Reductions, although smaller, were also seen for PWB. Scores in the SF-36 bodily pain subscale decreased from 85.8 +/- 18.7% pre-restrictions to 81.3 +/- 21.9% during restrictions. Clinically relevant decrements of PWB were associated with female sex (OR = 1.62, 95% CI: 1.50-1.75), high levels of public life restrictions (OR = 1.26, 95% CI: 1.18-1.36), and young age (OR = 1.10, 95% CI: 1.03-1.19). Study findings suggest lockdowns instituted during the COVID-19 pandemic may have had substantial adverse public health effects. The development of interventions mitigating losses in MWB and PWB is, thus, paramount when preparing for forthcoming waves of COVID-19 or future public life restrictions.DJ-P is supported by a grant from the Spanish Ministry of Science and Innovation-MINECO (RYC-2014-16938). The research fellowship of KH was funded by the German Research Foundation (Grant no. HO 6214/2-1)

Restrictercise! Preferences Regarding Digital Home Training Programs during Confinements Associated with the COVID-19 Pandemic

Confinement measures during the COVID-19 pandemic have caused substantial reductions in global physical activity (PA) levels. In view of the manifold health benefits of PA, the development of interventions counteracting this trend is paramount. Our survey with 15,261 participants (38 +/- 15 years, 58.5% females) examined preferences towards digital home exercise programs in 14 countries affected by COVID-19. More than two-thirds of the sample (68.4%, n = 10,433) indicated being interested in home exercise, and most participants were willing to work out at least three times per week (89.3%, n = 9328). Binary logistic regression revealed that female sex, working part-time, younger age, and being registered in a gym were associated with willingness to exercise. Flexibility (71.1%, n = 7377), resistance (68.6%, n = 7116), and endurance training (62.4%, n = 6478) were the most preferred types of exercise. Our results may guide health providers in developing individually tailored PA interventions during the current and future pandemic