Alzheimer’s disease (AD) is one of most devastating diseases affecting elderly people. Amyloid-β (Aβ) accumulation and the downstream pathological events such as oxidative stress play critical roles in pathogenesis of AD. Lessons from failures of current clinical trials suggest that targeting multiple key pathways of the AD pathogenesis is necessary to halt the disease progression. Here we show that Edaravone, a free radical scavenger that is marketed for acute ischemic stroke, has a potent capacity of inhibiting Aβ aggregation and attenuating Aβ-induced oxidation in vitro. When given before or after the onset of Aβ deposition via i.p. injection, Edaravone substantially reduces Aβ deposition, alleviates oxidative stress, attenuates the downstream pathologies including Tau hyperphosphorylation, glial activation, neuroinflammation, neuronal loss, synaptic dysfunction, and rescues the behavioral deficits of APPswe/PS1 mice. Oral administration of Edaravone also ameliorates the AD-like pathologies and memory deficits of the mice. These findings suggest that Edaravone holds a promise as a therapeutic agent for AD by targeting multiple key pathways of the disease pathogenesis.

Key pointsr Critical power represents an important threshold for neuromuscular fatigue development and may, therefore, dictate intensities for which exercise tolerance is determined by the magnitude of fatigue accrued.r Peripheral fatigue appears to be constant across O 2 delivery conditions for large muscle mass exercise, but this consistency is equivocal for smaller muscle mass exercise.r We sought to determine the influence of blood flow occlusion during handgrip exercise on neuromuscular fatigue development and to examine the relationship between neuromuscular fatigue development and W .r Blood flow occlusion influenced the development of both peripheral and central fatigue, thus providing further evidence that the magnitude of peripheral fatigue is not constant across O 2 delivery conditions for small muscle mass exercise.r W appears to be related to the magnitude of fatigue accrued during exercise, which may explain the reported consistency of intramuscular metabolic perturbations and work performed for severe-intensity exercise.Abstract The influence of the muscle metabolic milieu on peripheral and central fatigue is currently unclear. Moreover, the relationships between peripheral and central fatigue and the curvature constant (W ) have not been investigated. Six men (age: 25 ± 4 years, body mass: 82 ± 10 kg, height: 179 ± 4 cm) completed four constant power handgrip tests to exhaustion under conditions of control exercise (Con), blood flow occlusion exercise (Occ), Con with 5 min post-exercise blood flow occlusion (Con + Occ), and Occ with 5 min post-exercise blood flow occlusion (Occ + Occ). Neuromuscular fatigue measurements and W were obtained for each subject. Each trial resulted in significant peripheral and central fatigue. Significantly greater peripheral (79.7 ± 5.1% vs. 22.7 ± 6.0%) and central (42.6 ± 3.9% vs. 4.9 ± 2.0%) fatigue occurred for Occ than for Con. In addition, significantly greater peripheral (83.0 ± 4.2% vs. 69.0 ± 6.2%) and central (65.5 ± 14.6% vs. 18.6 ± 4.1%) fatigue occurred for Occ + Occ than for Con + Occ. W was significantly related to the magnitude of global (r = 0.91) and peripheral (r = 0.83) fatigue. The current findings demonstrate that blood flow occlusion exacerbated the development of both peripheral and central fatigue and that post-exercise blood flow occlusion prevented the recovery of both peripheral and central fatigue. Moreover, the current findings suggest that W may be determined by the magnitude of fatigue accrued during exercise.

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Background: Examining the analytical worth of the preoperative hemoglobin, albumin, lymphocyte, platelet (HALP) score and lymphocyte-to-monocyte ratio (LMR) within diseased persons having non-small cell lung cancer (NSCLC) after radical lung cancer surgery.Methods: Clinical data concerning 238 diseased persons with NSCLC who underwent radical lung cancer resection within Nantong Cancer Hospital between January 2009 and October 2015 had been looking back studied. ROC curve had been employed in regulating optimal critical worth of HALP and LMR that had been 48.00 and 6.30 singly. A 5-year amplification observed survival concerning diseased persons, and clinicopathological stuff assessed using statistics procedure. Kaplan Meier method, log rank test had been exploited from the point of view to analyze for surviving, and Cox regression analysis had been exploited for univariate and multivariate analysis. Eventually, a nomogram had been produced to examine the confirmation internally.Results: Kaplan Meier survival assessment revealed top HALP class's overall survival (OS) was significantly higher than below HALP class's (P<0.001), and high LMR group's OS was also greater than below LMR class's (P=0.001). Patients possessing average continuance period of 4 years. Further stratified study revealed high HALP class possessed notable OS as compared below HALP class (P=0.0002), and top LMR class possessed considerable OS as compared to below LMR class (P=0.003) in lung adenocarcinoma. In nonadenocarcinoma, there was no substantial difference in OS between two classes (P>0.05). Preoperative HALP and LMR remained independent risk constituents for tumor progression (P=0.005, P=0.028), lymph node metastasis and level of differentiation also had a certain effect on tumor progression (P<0.05), according to Cox multivariate analysis. Rise in HALP and LMR will help diseased persons having NSCLC live longer. The nomogram's c-index in inside validation was 0.672 (95% confidence interval: 0.626-0.718).Conclusions: Preoperative HALP versus LMR are independent predictive aspect within NSCLC diseased persons linked to clinicopathological features, and has a particular value in determining bodement.

Objectives: To compare the clinical efficacy of heated, humidified high-flow nasal cannula (HHHFNC) and nasal continuous positive airway pressure (NCPAP) in extremely low-birth-weight preterm infants (ELBWI) after extubation. Methods: This trial included 94 extremely low-birth-weight infants (ELBWI), within 7 days after birth, and prepared for tracheal extubation and a change to non-invasive ventilation in the neonatal intensive care unit (NICU) admitted to our hospital from January 2015 to December 2018, with 48 infants in the HHHFNC group and 46 infants in the NCPAP group. Reintubation rate within 72 h after initial extubation, total ventilation time, non-invasive ventilation time, total oxygen inhalation time, and the time to reach full enteral feeding were the primary outcome measures. Total intestinal feeding time, average weight gain rate, days of hospitalization, costs of hospitalization, and complication rates, including nasal injury, IVH, BPD, NEC, ROP, and PDA, were used as secondary outcomes. Data were analyzed using Student's t -test or the Mann-Whitney U -test with a Chi-square test or Fisher's exact test, as appropriate, in SPSS (25.0). Results: HHHFNC not only shortened the oxygen exposure time but also effectively reduced the incidence of nasal injury (6.25 vs. 36.96%) and NEC (10.42 vs. 28.26%) ( P < 0.05). Additionally, HHHFNC achieved a significant advance in the time to reach full enteral feeding (31.24 ± 11.35 vs. 34.21 ± 14.09 days); increased the average weight gain rate (16.07 ± 3.10 vs. 13.74 ± 4.21) and reduced the days of hospitalization (73.45 ± 18.84 vs. 79.24 ± 19.75), with a lower cost of hospitalization (16.04 ± 3.64 vs.18.79 ± 4.13) thousand dollars (all P < 0.05). Conclusions: Compared with NCPAP, HHHFNC was effective in preventing extubation failure in mechanically ventilated preterm ELBWI. HHHFNC shortens oxygen consumption time and significantly reduces the incidence of nasal injury and necrotizing enterocolitis; moreover, it can also reduce the length of stay and the hospitalization costs.