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Background: The level of myelin disruption in multiple sclerosis patients may impact the capacity for training-induced neuroplasticity and the magnitude of therapeutic response to rehabilitation interventions. Downslope walking has been shown to increase functional mobility in individuals with multiple sclerosis, but it is unclear if myelin status influences therapeutic response. Objective: The current study aimed to examine the relationship between baseline myelin status and change in functional mobility after a walking intervention. Methods: The Timed Up and Go test was used to measure functional mobility before and after completion of a repeated, six-session slope walking intervention in 16 participants with relapsing–remitting multiple sclerosis. Multi-component T2 relaxation imaging was used to index myelin water fraction of overall water content in brain tissue compartments. Results: Results demonstrated that the ratio of the myelin water fraction in lesion to normal-appearing white matter (myelin water fraction ratio) significantly predicted 31% of the variance in change in Timed Up and Go score after the downslope walking intervention, where less myelin disruption was associated with greater intervention response. Conclusions: Myelin water content fraction ratio may offer a neural biomarker of myelin to identify potential responders to interventions targeting functional impairments in multiple sclerosis. [ABSTRACT FROM AUTHOR]

Background and Purpose: Due to their potent bronchodilator properties, beta(2)-adrenoceptor agonists are a mainstay of therapy in asthma. However, the effects of beta(2)-adrenoceptor agonists on inflammation are less clear. Accordingly, we have investigated the effects of beta(2)-adrenoceptor agonists on inflammatory mediator release.Experimental Approach: Transcription factor activation, and both release and mRNA expression of IL-6 and IL-8 were examined by luciferase reporter assay, elisa and real-time RT-PCR in bronchial human epithelial BEAS-2B cells or primary human bronchial epithelial cells grown at an air-liquid interface.Key Results: Pre-incubation with beta(2)-adrenoceptor agonists (salbutamol, salmeterol, formoterol) augmented the release and mRNA expression of IL-6 and IL-8 induced by IL-1beta and IL-1beta plus histamine, whereas NF-kappaB-dependent transcription was significantly repressed, and AP-1-dependent transcription was unaffected. These effects were mimicked by other cAMP-elevating agents (PGE(2), forskolin). Enhancement of cytokine release by beta(2)-adrenoceptor agonists also occurred in primary bronchial epithelial cells. Addition of dexamethasone with salmeterol repressed IL-6 and IL-8 release to levels that were similar to the repression achieved in the absence of salmeterol. IL-6 release was enhanced when salmeterol was added before, concurrently or after IL-1beta plus histamine stimulation, whereas IL-8 release was only enhanced by salmeterol addition prior to stimulation.Conclusions and Implications: Enhancement of IL-6 and IL-8 release may contribute to the deleterious effects of beta(2)-adrenoceptor agonists in asthma. As increased inflammatory mediator expression is prevented by the addition of glucocorticoid to the beta(2)-adrenoceptor, our data provide further mechanistic support for the use of combination therapies in asthma management. [ABSTRACT FROM AUTHOR]

Two greenhouse experiments were performed to investigate the effects of Summer-pruning in the first year, and cold-storage, on primocane-fruiting raspberry (Rubus idaeus L.) cultivars. In the first year in the greenhouse, primocanes were Summer-pruned when they were 60 cm tall which delayed fruiting by approx. 1 month, but decreased yields slightly. Plants cold-stored below 7℃C for 6 weeks, markedly and consistently out-yielded those that had not been cold-treated. In the second experiment, yields on the floricanes and primocanes were separated and clearly showed that floricane dormancy was broken, so that double-cropping could occur. ‘Heritage’ produced few fruits on its floricanes, which indicated that it requires a longer cold treatment than cvs. ‘Autumn Britten’, ‘Polana’ and ‘Summit’. In this system, 10 canes m⁻² appeared to be the optimum number of primocanes needed to produce the highest yields. These experiments confirmed that adventitious buds will eventually break dormancy without a chilling period, as daylength increases. Also, they show that primocane-fruiting raspberries can be manipulated to fruit all-year-round in the greenhouse. [ABSTRACT FROM AUTHOR]

The definitive diagnosis of Alzheimer's disease remains histopathological. To date many published studies have been limited by being based on clinical diagnosis alone, which has a significant false positive rate. In a prospective, longitudinal, clinicopathological study which aims to develop an antemortem diagnostic test for Alzheimer's disease, we have achieved 96% (250/260) consent and 97% (59/61) completion rates. We here describe some of the factors we believe are responsible for these high rates and which may be relevant to other studies requiring autopsy to verify clinical diagnoses. [ABSTRACT FROM AUTHOR]