Spectral Resting-State EEG (rsEEG) in Chronic Aphasia Is Reliable, Sensitive, and Correlates With Functional Behavior

We investigated spectral resting-state EEG in persons with chronic stroke-induced aphasia to determine its reliability, sensitivity, and relationship to functional behaviors. Resting-state EEG has not yet been characterized in this population and was selected given the demonstrated potential of resting-state investigations using other neuroimaging techniques to guide clinical decision-making. Controls and persons with chronic stroke-induced aphasia completed two EEG recording sessions, separated by approximately 1 month, as well as behavioral assessments of language, sensorimotor, and cognitive domains. Power in the classic frequency bands (delta, theta, alpha, and beta) was examined via spectral analysis of resting-state EEG data. Results suggest that power in the theta, alpha, and beta bands is reliable for use as a repeated measure. Significantly greater theta and lower beta power was observed in persons with aphasia (PWAs) than controls. Finally, in PWAs theta power negatively correlated with performance on a discourse informativeness measure, while alpha and beta power positively correlated with performance on the same measure. This indicates that spectral rsEEG slowing observed in PWAs in the chronic stage is pathological and suggests a possible avenue for directly altering brain activation to improve behavioral function. Taken together, these results suggest that spectral resting-state EEG holds promise for sensitive measurement of functioning and change in persons with chronic aphasia. Future studies investigating the utility of these measures as biomarkers of frank or latent aphasic deficits and treatment response in chronic stroke-induced aphasia are warranted

What has finite element analysis taught us about diabetic foot disease and its management?:a systematic review

Over the past two decades finite element (FE) analysis has become a popular tool for researchers seeking to simulate the biomechanics of the healthy and diabetic foot. The primary aims of these simulations have been to improve our understanding of the foot's complicated mechanical loading in health and disease and to inform interventions designed to prevent plantar ulceration, a major complication of diabetes. This article provides a systematic review and summary of the findings from FE analysis-based computational simulations of the diabetic foot.A systematic literature search was carried out and 31 relevant articles were identified covering three primary themes: methodological aspects relevant to modelling the diabetic foot; investigations of the pathomechanics of the diabetic foot; and simulation-based design of interventions to reduce ulceration risk.Methodological studies illustrated appropriate use of FE analysis for simulation of foot mechanics, incorporating nonlinear tissue mechanics, contact and rigid body movements. FE studies of pathomechanics have provided estimates of internal soft tissue stresses, and suggest that such stresses may often be considerably larger than those measured at the plantar surface and are proportionally greater in the diabetic foot compared to controls. FE analysis allowed evaluation of insole performance and development of new insole designs, footwear and corrective surgery to effectively provide intervention strategies. The technique also presents the opportunity to simulate the effect of changes associated with the diabetic foot on non-mechanical factors such as blood supply to local tissues.While significant advancement in diabetic foot research has been made possible by the use of FE analysis, translational utility of this powerful tool for routine clinical care at the patient level requires adoption of cost-effective (both in terms of labour and computation) and reliable approaches with clear clinical validity for decision making

Reduction of Pavlovian bias in schizophrenia: Enhanced effects in clozapine-administered patients

The negative symptoms of schizophrenia (SZ) are associated with a pattern of reinforcement learning (RL) deficits likely related to degraded representations of reward values. However, the RL tasks used to date have required active responses to both reward and punishing stimuli. Pavlovian biases have been shown to affect performance on these tasks through invigoration of action to reward and inhibition of action to punishment, and may be partially responsible for the effects found in patients. Forty-five patients with schizophrenia and 30 demographically-matched controls completed a four-stimulus reinforcement learning task that crossed action ("Go" or "NoGo") and the valence of the optimal outcome (reward or punishment-avoidance), such that all combinations of action and outcome valence were tested. Behaviour was modelled using a six-parameter RL model and EEG was simultaneously recorded. Patients demonstrated a reduction in Pavlovian performance bias that was evident in a reduced Go bias across the full group. In a subset of patients administered clozapine, the reduction in Pavlovian bias was enhanced. The reduction in Pavlovian bias in SZ patients was accompanied by feedback processing differences at the time of the P3a component. The reduced Pavlovian bias in patients is suggested to be due to reduced fidelity in the communication between striatal regions and frontal cortex. It may also partially account for previous findings of poorer "Go-learning" in schizophrenia where "Go" responses or Pavlovian consistent responses are required for optimal performance. An attenuated P3a component dynamic in patients is consistent with a view that deficits in operant learning are due to impairments in adaptively using feedback to update representations of stimulus value

Energy intake and expenditure assessed ‘in-season’ in an elite European rugby union squad.

This is an Accepted Manuscript of an article published by Taylor & Francis in European Journal of Sport Science on 09/06/2015, available online: http://www.tandfonline.com/doi/pdf/10.1080/17461391.2015.1042528Rugby union (RU) is a complex high-intensity intermittent collision sport with emphasis placed on players possessing high lean body mass and low body fat. After an 8 to 12-week pre-season focused on physiological adaptations, emphasis shifts towards competitive performance. However, there are no objective data on the physiological demands or energy intake (EI) and energy expenditure (EE) for elite players during this period. Accordingly, in-season training load using global positioning system and session rating of perceived exertion (sRPE), alongside six-day assessments of EE and EI were measured in 44 elite RU players. Mean weekly distance covered was 7827 ± 954 m and 9572 ± 1233 m with a total mean weekly sRPE of 1776 ± 355 and 1523 ± 434 AU for forwards and backs, respectively. Mean weekly EI was 16.6 ± 1.5 and 14.2 ± 1.2 megajoules (MJ) and EE was 15.9 ± 0.5 and 14 ± 0.5 MJ. Mean carbohydrate (CHO) intake was 3.5 ± 0.8 and 3.4 ± 0.7 g.kg-1 body mass, protein intake was 2.7 ± 0.3 and 2.7 ± 0.5 g.kg-1 body mass, and fat intake was 1.4 ± 0.2 and 1.4 ± 0.3 g.kg-1 body mass. All players who completed the food diary self-selected a 'low' CHO 'high' protein diet during the early part of the week, with CHO intake increasing in the days leading up to a match, resulting in the mean EI matching EE. Based on EE and training load data, the EI and composition seems appropriate, although further research is required to evaluate if this diet is optimal for match day performance

A Major Determinant of Cyclophilin Dependence and Cyclosporine Susceptibility of Hepatitis C Virus Identified by a Genetic Approach

Since the advent of genome-wide small interfering RNA screening, large numbers of cellular cofactors important for viral infection have been discovered at a rapid pace, but the viral targets and the mechanism of action for many of these cofactors remain undefined. One such cofactor is cyclophilin A (CyPA), upon which hepatitis C virus (HCV) replication critically depends. Here we report a new genetic selection scheme that identified a major viral determinant of HCV's dependence on CyPA and susceptibility to cyclosporine A. We selected mutant viruses that were able to infect CyPA-knockdown cells which were refractory to infection by wild-type HCV produced in cell culture. Five independent selections revealed related mutations in a single dipeptide motif (D316 and Y317) located in a proline-rich region of NS5A domain II, which has been implicated in CyPA binding. Engineering the mutations into wild-type HCV fully recapitulated the CyPA-independent and CsA-resistant phenotype and four putative proline substrates of CyPA were mapped to the vicinity of the DY motif. Circular dichroism analysis of wild-type and mutant NS5A peptides indicated that the D316E/Y317N mutations (DEYN) induced a conformational change at a major CyPA-binding site. Furthermore, nuclear magnetic resonance experiments suggested that NS5A with DEYN mutations adopts a more extended, functional conformation in the putative CyPA substrate site in domain II. Finally, the importance of this major CsA-sensitivity determinant was confirmed in additional genotypes (GT) other than GT 2a. This study describes a new genetic approach to identifying viral targets of cellular cofactors and identifies a major regulator of HCV's susceptibility to CsA and its derivatives that are currently in clinical trials