A systematic review investigating fatigue, psychological and cognitive impairment following TIA and minor stroke:protocol paper

Approximately 20,000 people have a transient ischemic attack (TIA) and 23,375 have a minor stroke in England each year. Fatigue, psychological and cognitive impairments are well documented post-stroke. Evidence suggests that TIA and minor stroke patients also experience these impairments; however, they are not routinely offered relevant treatment. This systematic review aims to: (1) establish the prevalence of fatigue, anxiety, depression, post-traumatic stress disorder (PTSD) and cognitive impairment following TIA and minor stroke and to investigate the temporal course of these impairments; (2) explore impact on quality of life (QoL), change in emotions and return to work; (3) identify where further research is required and to potentially inform an intervention study

Fatigue after Stroke: Baseline Predictors and Influence on Survival. Analysis of Data from UK Patients Recruited in the International Stroke Trial

Little is known about the associations of post-stroke fatigue or its influence on survival. The vitality component of the Short Form 36 (SF-36) is a valid and reliable measure of post-stroke fatigue. We sought to identify associates of post-stroke fatigue and determine whether fatigue predicted survival.We used SF-36 vitality scores obtained by postal questionnaires from 1080 UK patients randomised in the International Stroke Trial, at a mean of 64 weeks after stroke onset. We used logistic regression to explore factors at randomisation which predicted SF-36 vitality at follow-up, and the relationship between SF-36 vitality and both SF-36 mental health and SF-36 emotional role function at follow-up. We used Cox proportional hazards to explore the influence of SF-36 vitality at follow-up on subsequent survival, using four different statistical models for handling missing data.Female sex, increasing age, lower mental health and lower emotional role function scores were associated with greater degrees of fatigue after stroke (i.e. lower vitality scores) but these factors explained <30% of the variance (R(2)) in fatigue. In two models, fatigue at follow-up was associated with shorter subsequent survival.Increasing age, female sex, emotional role function and mental health were associated with increased fatigue at a mean of 64 weeks after stroke onset, but explained less than 30% of the variance. Fatigue was associated with reduced subsequent long-term survival in 2/4 models. Further work is needed to identify the biological substrate of fatigue and to clarify its influence on survival

NUDT2 Disruption Elevates Diadenosine Tetraphosphate (Ap4A) and Down-Regulates Immune Response and Cancer Promotion Genes.

Regulation of gene expression is one of several roles proposed for the stress-induced nucleotide diadenosine tetraphosphate (Ap4A). We have examined this directly by a comparative RNA-Seq analysis of KBM-7 chronic myelogenous leukemia cells and KBM-7 cells in which the NUDT2 Ap4A hydrolase gene had been disrupted (NuKO cells), causing a 175-fold increase in intracellular Ap4A. 6,288 differentially expressed genes were identified with P < 0.05. Of these, 980 were up-regulated and 705 down-regulated in NuKO cells with a fold-change ≥ 2. Ingenuity® Pathway Analysis (IPA®) was used to assign these genes to known canonical pathways and functional networks. Pathways associated with interferon responses, pattern recognition receptors and inflammation scored highly in the down-regulated set of genes while functions associated with MHC class II antigens were prominent among the up-regulated genes, which otherwise showed little organization into major functional gene sets. Tryptophan catabolism was also strongly down-regulated as were numerous genes known to be involved in tumor promotion in other systems, with roles in the epithelial-mesenchymal transition, proliferation, invasion and metastasis. Conversely, some pro-apoptotic genes were up-regulated. Major upstream factors predicted by IPA® for gene down-regulation included NFκB, STAT1/2, IRF3/4 and SP1 but no major factors controlling gene up-regulation were identified. Potential mechanisms for gene regulation mediated by Ap4A and/or NUDT2 disruption include binding of Ap4A to the HINT1 co-repressor, autocrine activation of purinoceptors by Ap4A, chromatin remodeling, effects of NUDT2 loss on transcript stability, and inhibition of ATP-dependent regulatory factors such as protein kinases by Ap4A. Existing evidence favors the last of these as the most probable mechanism. Regardless, our results suggest that the NUDT2 protein could be a novel cancer chemotherapeutic target, with its inhibition potentially exerting strong anti-tumor effects via multiple pathways involving metastasis, invasion, immunosuppression and apoptosis

Sensory Impairments of the Lower Limb after Stroke: A Pooled Analysis of Individual Patient Data

To obtain more generalizable information on the frequency and factors influencing sensory impairment after stroke and their relationship to mobility and function. Method: A pooled analysis of individual data of stroke survivors (N = 459); mean (SD) age = 67.2 (14.8) years, 54% male, mean (SD) time since stroke = 22.33 (63.1) days, 50% left-sided weakness. Where different measurement tools were used, data were recoded. Descriptive statistics described frequency of sensory impairments, kappa coefficients investigated relationships between sensory modalities, binary logistic regression explored the factors influencing sensory impairments, and linear regression assessed the impact of sensory impairments on activity limitations. Results: Most patients’ sensation was intact (55%), and individual sensory modalities were highly associated (κ = 0.60, P < .001). Weakness and neglect influenced sensory impairment (P < .001), but demographics, stroke pathology, and spasticity did not. Sensation influenced independence in activities of daily living, mobility, and balance but less strongly than weakness. Conclusions: Pooled individual data analysis showed sensation of the lower limb is grossly preserved in most stroke survivors but, when present, it affects function. Sensory modalities are highly interrelated; interventions that treat the motor system during functional tasks may be as effective at treating the sensory system as sensory retraining alone.

A comparative study of the water budgets of lawns under three management scenarios

The fate of irrigation in urban ecosystems is highly uncertain, due to uncertainties in urban ecohydrology. We compared irrigation rates, soil moisture, evapotranspiration (ET), stomatal conductance, and water budgets of landscape ecosystems managed with different turfgrass species and irrigation technologies. The “Typical” landscape had a cool-season fescue and was irrigated by an automatic timer. The “Alternative1” landscape had a warm-season paspalum and a “smart” soil moisture sensor-based irrigation system. The “Alternative2” landscape had a cool-season native sedge and a “smart” weather station-based drip irrigation system. ET was measured with a portable closed chamber and modeled using a Penman-Monteith approach, and the two methods agreed well. The water applied to the Alternative1 was 54 % less than the water applied to the Typical landscape, and the water applied to the Alternative2 was 24 % less. Soil moisture was similar in the Typical and Alternative2, while Alternative1 was drier in spring. The stomatal conductance of sedge was lower than the other two species, but its ET was not lower due to higher leaf area. Irrigation efficiencies (ET/applied irrigation) were 57 - 58&nbsp;%, 86 – 97&nbsp;%, and 78 - 80&nbsp;% for the Typical, Alternative1, and Alternative2 landscapes, respectively. Runoff was less than 2&nbsp;% in each landscape, and excess irrigation primarily drained below the root zone. Differences in irrigation efficiency between landscapes were due mainly to irrigation application, which varied more than species water use. Smart irrigation systems provided substantial water savings relative to a timer-based system, and prevented significant drainage losses. The utilization of smart sensors was more important than the choice of turfgrass species for irrigation efficiency