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Age-related macular degeneration (AMD) is a leading cause of blindness. Laser-induced nonhuman primate choroidal neovascularization (CNV) is a widely used animal model of neovascular AMD. Subretinal fibrosis (SFb) is the major limiting factor of effective anti-VEGF therapy for neovascular AMD, yet SFb has never been systematically analyzed in the primate CNV model and if VEGF directly affect SFb is unknown. We recruited a large cohort of rhesus macaques to study the occurrence, multimodal imaging and electroretinography (ERG) features, and related cytokines of SFb. Here we show that among 33 rhesus macaques, 88% CNV eyes developed SFb. Spectral domain optical coherence tomography (SD-OCT) identified four types of subretinal hyper-reflective material (SHRM) of SFb in primate. Multimodal imaging is reliable for monitoring SFb and matches the histological results well. Reduced amplitude of oscillatory potentials correlates with the thinning of inner retina layers and is a possible SFb indicator. Iba1+ microglia/macrophage cells infiltrated in the fibrotic lesions, and aqueous cytokine analysis identified four fibrosis-related factors (GM-CSF, IL-10, TGFβ2 and VEGF). Unexpectedly, we found sustained expression of VEGF may be an important inducer of SFb, and anti-VEGF therapy actually partially suppresses SFb. Taken together, our data suggest the laser-induced primate SFb model, coupled with multimodal imaging and ERG recording, is a useful system to dissect the pathogenesis and explore the rationale of treatment for SFb; and combined therapy with anti-VEGF and anti-fibrosis agents is necessary for AMD treatment.We investigated the impact of spinal cord injury (SCI) on cough capacity in 10 children (Mean ± SD, age 8 ± 4 years) and compared it to 15 typically developing children (age 8 ± 3 years). Participants underwent spirometry, single and sequential cough assessment with surface-electromyography from respiratory muscles. Inspiratory phase duration, inspiratory phase peak flow, inspiratory phase rise time, compression phase duration, expiratory phase rise time, expiratory phase peak airflow (EPPF) and cough volume acceleration (CVA) parameters of single and sequential cough were measured. Root mean square (RMS) values of right pectoralis-major, intercostal, rectus-abdominus (RA), and oblique (OB) muscles were calculated and mean of three trials were compared. The significance criterion was set at P less then 0.05. The SCI group produced significantly lower lung volumes, EPPF, CVA, and RMS values of RA and OB during expiratory phases of single and sequential coughs. The decrease in activation in expiratory muscles in the SCI group accounts for the impaired expiratory flow and may contribute to risk of respiratory complications.Acute cardiovascular exercise has shown to promote neuroplastic processes supporting the consolidation of newly acquired motor skills in healthy adults. https://www.selleckchem.com/products/elexacaftor.html First results suggest that this concept may be transferred to populations with motor and cognitive dysfunctions. In this context, Parkinson's disease (PD) is highly relevant since patients demonstrate deficits in motor learning. Hence, in the present study we sought to explore the effect of a single post-practice exercise bout on motor memory consolidation in PD. For this purpose, 17 patients with PD (Hoehn and Yahr 1 - 2.5, age 60.1 ± 7.9 y) practiced a whole-body skill followed by either (i) a moderate-intense bout of cycling, or (ii) seated rest for a total of 30 min. The motor skill required the participants to balance on a tiltable platform (stabilometer) for 30 s. During skill practice, participants performed 15 trials followed by a retention test 1 day and 7 days later. We calculated time in balance (platform within ± 5° from horizontal) for each trial and within- and between-group differences in memory consolidation (i.e. offline learning = skill change from last acquisition block to retention tests) were analyzed. Groups revealed similar improvements during skill practice (F4,60 = 0.316, p = 0.866), but showed differences in offline learning, which were only evident after 7 days (F1,14 = 5.602, p = 0.033). Our results suggest that a single post-practice exercise bout is effective in enhancing long-term motor memory consolidation in a population with motor learning impairments. This may point at unique promoting effects of exercise on dopamine neurotransmission involved in memory formation. Future studies should investigate the potential role of exercise-induced effects on the dopaminergic system. Short fiber reinforced composites (SFRC) require a veneering layer of conventional composite when used as restorations in the oral environment. The current study investigates the toughening effects during the path of a preexisting crack propagating through the bilayer system as it confronts the interface, through the attempted alignment of fibers and matrix-fiber interactions in the SFRC, and the distance it travels in the SFRC. Bilayer systems of SFRC and conventional composite were produced with aligned fibers perpendicular to load direction. Single-edge-notched bend (SENB) specimens (25 × 5 × 2.5 mm ) with pre-crack length (a) to width (W) ratios (a/W = 0.2-0.8) were produced and tested in 3-point bending configuration until complete fracture. The specific work of fracture (w ) was deduced from calculating the area under the load-displacement curves. Fiber alignment was digitally evaluated from images taken from the top and side planes of the specimen. The toughness of the bilayer system is optimalted by wear behavior.Several alternative methods have been developed and regulatory adopted by OECD as in vitro alternatives to the Draize eye irritation assay either to detect chemicals not requiring classification (No Category) or inducing serious damage to the eye (Category 1) but none are sensitive enough to identify chemicals inducing reversible eye effects (category 2) which are categorised by default. Therefore, the discriminatory power of a genomic approach applied to the SkinEthic™ Human Corneal Epithelium (HCE) model was investigated to allow subcategorization capacity according to UN GHS classification. An algorithm based on gene expression modulation on a training (62) and a test (31 liquids) chemical set, tested neat and at 30%was evaluated in an assay called EyeIRR-IS. Its accuracy prediction to distinguish Cat1/Cat2 from No Cat was 95% with a specificity of 89% and a sensitivity of 98%. For subcategorization into the 3 GHS classes the accuracy reached 84% with 94% Cat1, 67% Cat2 and 89% No Cat correctly predicted. No Cat.
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