Naturalistic visualization of reaching movements using head-mounted displays improves movement quality compared to conventional computer screens and proves high usability.

BACKGROUND The relearning of movements after brain injury can be optimized by providing intensive, meaningful, and motivating training using virtual reality (VR). However, most current solutions use two-dimensional (2D) screens, where patients interact via symbolic representations of their limbs (e.g., a cursor). These 2D screens lack depth cues, potentially deteriorating movement quality and increasing cognitive load. Head-mounted displays (HMDs) have great potential to provide naturalistic movement visualization by incorporating improved depth cues, reduce visuospatial transformations by rendering movements in the space where they are performed, and preserve eye-hand coordination by showing an avatar-with immersive VR (IVR)-or the user's real body-with augmented reality (AR). However, elderly populations might not find these novel technologies usable, hampering potential motor and cognitive benefits. METHODS We compared movement quality, cognitive load, motivation, and system usability in twenty elderly participants (>59 years old) while performing a dual motor-cognitive task with different visualization technologies: IVR HMD, AR HMD, and a 2D screen. We evaluated participants' self-reported cognitive load, motivation, and usability using questionnaires. We also conducted a pilot study with five brain-injured patients comparing the visualization technologies while using an assistive device. RESULTS Elderly participants performed straighter, shorter duration, and smoother movements when the task was visualized with the HMDs than screen. The IVR HMD led to shorter duration movements than AR. Movement onsets were shorter with IVR than AR, and shorter for both HMDs than the screen, potentially indicating facilitated reaction times due to reduced cognitive load. No differences were found in the questionnaires regarding cognitive load, motivation, or usability between technologies in elderly participants. Both HMDs proved high usability in our small sample of patients. CONCLUSIONS HMDs are a promising technology to be incorporated into neurorehabilitation, as their more naturalistic movement visualization improves movement quality compared to conventional screens. HMDs demonstrate high usability, without decreasing participants' motivation, and might potentially lower cognitive load. Our preliminary clinical results suggest that brain-injured patients may especially benefit from more immersive technologies. However, larger patient samples are needed to draw stronger conclusions.*

The modulation of reading strategies by language opacity in early bilinguals: an eye movement study

Converging evidences from eye movement experiments indicate that linguistic contexts influence reading strategies. However, the question of whether different linguistic contexts modulate eye movements during reading in the same bilingual individuals remains unresolved. We examined reading strategies in a transparent (German) and an opaque (French) language of early, highly proficient French–German bilinguals: participants read aloud isolated French and German words and pseudo- words while the First Fixation Location (FFL), its duration and latency were measured. Since transparent linguistic contexts and pseudo-words would favour a direct grapheme/phoneme conversion, the reading strategy should be more local for German than for French words (FFL closer to the beginning) and no difference is expected in pseudo-words’ FFL between contexts. Our results confirm these hypotheses, providing the first evidence that the same individuals engage different reading strategy depending on language opacity, suggesting that a given brain process can be modulated by a given context

Orthographic Depth Modulates Reading Route Selection: An Electrical Neuroimaging Study

Introduction The orthographic Depth Hypothesis (Katz and Feldman, 1983) posits that different reading routes are engaged depending on the expertise of the reader but also on the type of grapheme/phoneme correspondence of the language being read. Shallow orthographies (e.g. German and Italian) with consistent grapheme to phoneme correspondences favor encoding via non-lexical pathways, where each phoneme is sequentially mapped to its corresponding grapheme. In contrast, deep orthographies (e.g. French and English), with inconsistent grapheme to phoneme correspondences favor lexical pathways, where phonemes are retrieved from memory structures. Only few studies investigated the impact of orthographic depth on brain response while reading. Moreover, because they used between subject or cross-language designs, the interpretability of previous studies on the effect of orthographic depth is limited. The aim of the present study was to investigate the impact of orthographic depth on reading route selection using an experimental design enabling isolating the effect of orthographic depth. Method We presented the same pseudowords (PWs) to highly proficient bilinguals and manipulated the orthographic depth of PW reading by embedding them among two separated language contexts (German and French), implicating either shallow or deep orthography. High density 128-channel electroencephalography was recorded during the task. Results The topographies of the event-related potential were different between PWs read in deep orthographic context and PWs read in shallow orthographic context at 300-360ms after stimulus onset, indicating distinct brain networks engaged in reading during this time window. The brain source underlying these topographic effects were located within left inferior frontal, left parietal and left cingular areas. Conclusion We propose that in deep orthographic context, reading PWs cannot rely on the routine lexical pathways and thus switching to the non-lexical route is necessary. In controast, reading in a shallow orthographic context favors non-lexical route processing which fits PW reading. The topographic modulation might thus reflect the recruitment of lexical pathways in the deep but not in the shallow context. Analysis of electrical source estimation over the period of topographic modulation supports this hypothesis by showing that inferior frontal areas, a region shown to subserve phonological processing, is differentially engaged between the deep vs shallow conditions. In addition, a difference in the activity of parietal-cingular areas suggests a modulation of attentional demands related to route selection processes. Non-lexical route may be less automatized than lexical route processing. These collective results support a modulation of reading route selection by orthographic depth

Dietary factors and low-grade inflammation in relation to overweight and obesity

Low-grade inflammation is a characteristic of the obese state, and adipose tissue releases many inflammatory mediators. The source of these mediators within adipose tissue is not clear, but infiltrating macrophages seem to be especially important, although adipocytes themselves play a role. Obese people have higher circulating concentrations of many inflammatory markers than lean people do, and these are believed to play a role in causing insulin resistance and other metabolic disturbances. Blood concentrations of inflammatory markers are lowered following weight loss. In the hours following the consumption of a meal, there is an elevation in the concentrations of inflammatory mediators in the bloodstream, which is exaggerated in obese subjects and in type 2 diabetics. Both high-glucose and high-fat meals may induce postprandial inflammation, and this is exaggerated by a high meal content of advanced glycation end products (AGE) and partly ablated by inclusion of certain antioxidants or antioxidant-containing foods within the meal. Healthy eating patterns are associated with lower circulating concentrations of inflammatory markers. Among the components of a healthy diet, whole grains, vegetables and fruits, and fish are all associated with lower inflammation. AGE are associated with enhanced oxidative stress and inflammation. SFA and trans-MUFA are pro-inflammatory, while PUFA, especially long-chain n-3 PUFA, are anti-inflammatory. Hyperglycaemia induces both postprandial and chronic low-grade inflammation. Vitamin C, vitamin E and carotenoids decrease the circulating concentrations of inflammatory markers. Potential mechanisms are described and research gaps, which limit our understanding of the interaction between diet and postprandial and chronic low-grade inflammation, are identifie

International STakeholder NETwork (ISTNET): creating a developmental neurotoxicity (DNT) testing road map for regulatory purposes

A major problem in developmental neurotoxicity (DNT) risk assessment is the lack of toxicological hazard information for most compounds. Therefore, new approaches are being considered to provide adequate experimental data that allow regulatory decisions. This process requires a matching of regulatory needs on the one hand and the opportunities provided by new test systems and methods on the other hand. Alignment of academically and industrially-driven assay development with regulatory needs in the field of DNT is a core mission of the International STakeholder NETwork (ISNET) in DNT testing. The first meeting of ISTNET was held in Zurich on 23-24 January 2014 in order to explore the concept of adverse outcome pathway (AOP) to practical DNT testing. AOPs were considered promising tools to promote test systems development according to regulatory needs. Moreover, the AOP concept was identified as an important guiding principle to assemble predictive integrated testing strategies (ITSs) for DNT. The recommendations on a roadmap towards AOP-based DNT testing is considered a stepwise approach, operating initially with incomplete AOPs for compound grouping, and focussing on key events of neurodevelopment. Next steps to be considered in follow-up activities are the use of case studies to further apply the AOP concept in regulatory DNT testing, making use of AOP intersections (common key events) for economic development of screening assays, and addressing the transition from qualitative descriptions to quantitative network modelling.JRC.I.5-Systems Toxicolog

Iron Accumulation with Age, Oxidative Stress and Functional Decline

Identification of biological mediators in sarcopenia is pertinent to the development of targeted interventions to alleviate this condition. Iron is recognized as a potent pro-oxidant and a catalyst for the formation of reactive oxygen species in biological systems. It is well accepted that iron accumulates with senescence in several organs, but little is known about iron accumulation in muscle and how it may affect muscle function. In addition, it is unclear if interventions which reduced age-related loss of muscle quality, such as calorie restriction, impact iron accumulation. We investigated non-heme iron concentration, oxidative stress to nucleic acids in gastrocnemius muscle and key indices of sarcopenia (muscle mass and grip strength) in male Fischer 344 X Brown Norway rats fed ad libitum (AL) or a calorie restricted diet (60% of ad libitum food intake starting at 4 months of age) at 8, 18, 29 and 37 months of age. Total non-heme iron levels in the gastrocnemius muscle of AL rats increased progressively with age. Between 29 and 37 months of age, the non-heme iron concentration increased by approximately 200% in AL-fed rats. Most importantly, the levels of oxidized RNA in gastrocnemius muscle of AL rats were significantly increased as well. The striking age-associated increase in non-heme iron and oxidized RNA levels and decrease in sarcopenia indices were all attenuated in the calorie restriction (CR) rats. These findings strongly suggest that the age-related iron accumulation in muscle contributes to increased oxidative damage and sarcopenia, and that CR effectively attenuates these negative effects

Quantitative evaluation of the beneficial effects in the mdx mouse of epigallocatechin gallate, an antioxidant polyphenol from green tea

In two separate previous studies, we reported that subcutaneous (sc) or oral administration of (−)-epigallocatechin-3-gallate (EGCG) limited the development of muscle degeneration of mdx mice, a mild phenotype model for Duchenne muscular dystrophy (DMD). However, it was not possible to conclude which was the more efficient route of EGCG administration because different strains of mdx mice, periods of treatment and methods of assessment were used. In this study, we investigated which administration routes and dosages of EGCG are the most effective for limiting the onset of dystrophic lesions in the same strain of mdx mice and applying the same methods of assessment. Three-week-old mdx mice were injected sc for 5 weeks with either saline or a daily average of 3 or 6 mg/kg EGCG. For comparison, age-matched mdx mice were fed for 5 weeks with either a diet containing 0.1% EGCG or a control diet. The effects of EGCG were assessed quantitatively by determining the activities of serum muscle-derived creatine kinase, isometric contractions of triceps surae muscles, integrated spontaneous locomotor activities, and oxidative stress and fibrosis in selected muscles. Oral administration of 180 mg/kg/day EGCG in the diet was found the most effective for significantly improving several parameters associated with muscular dystrophy. However, the improvements were slightly less than those observed previously for sc injection started immediately after birth. The efficacy of EGCG for limiting the development of dystrophic muscle lesions in mice suggests that EGCG may be of benefit for DMD patients

Epigallocatechin-3-gallate: a useful, effective and safe clinical approach for targeted prevention and individualised treatment of neurological diseases?

Neurodegenerative disorders show an increasing prevalence in a number of highly developed countries. Often, these diseases require life-long treatment mostly with drugs which are costly and mostly accompanied by more or less serious side-effects. Their heterogeneous manifestation, severity and outcome pose the need for individualised treatment options. There is an intensive search for new strategies not only for treating but also for preventing these diseases. Green tea and green tea extracts seem to be such a promising and safe alternative. However, data regarding the beneficial effects and possible underlying mechanism, specifically in clinical trials, are rare and rather controversial or non-conclusive. This review outlines the existing evidence from preclinical studies (cell and tissue cultures and animal models) and clinical trials regarding preventive and therapeutic effects of epigallcatechin-3-gallate in neurodegenerative diseases and considers antioxidative vs. pro-oxidative properties of the tea catechin important for dosage recommendations

International STakeholder NETwork (ISTNET): creating a developmental neurotoxicity (DNT) testing road map for regulatory purposes

A major problem in developmental neurotoxicity (DNT) risk assessment is the lack of toxicological hazard information for most compounds. Therefore, new approaches are being considered to provide adequate experimental data that allow regulatory decisions. This process requires a matching of regulatory needs on the one hand and the opportunities provided by new test systems and methods on the other hand. Alignment of academically and industrially driven assay development with regulatory needs in the field of DNT is a core mission of the International STakeholder NETwork (ISTNET) in DNT testing. The first meeting of ISTNET was held in Zurich on 23-24 January 2014 in order to explore the concept of adverse outcome pathway (AOP) to practical DNT testing. AOPs were considered promising tools to promote test systems development according to regulatory needs. Moreover, the AOP concept was identified as an important guiding principle to assemble predictive integrated testing strategies (ITSs) for DNT. The recommendations on a road map towards AOP-based DNT testing is considered a stepwise approach, operating initially with incomplete AOPs for compound grouping, and focussing on key events of neurodevelopment. Next steps to be considered in follow-up activities are the use of case studies to further apply the AOP concept in regulatory DNT testing, making use of AOP intersections (common key events) for economic development of screening assays, and addressing the transition from qualitative descriptions to quantitative network modelling

Cardiovascular control and stabilization via inclination and mobilization during bed rest

Cardiovascular deconditioning has long been recognized as a characteristic of the physiological adaptation to long-term bed rest in patients. The process is thought to contribute to orthostatic intolerance and enhance secondary complications in a significant way. Mobilization is a cost-effective and simple method to maintain the cardiovascular parameters (i.e., blood pressure, heart rate) stable, counter orthostatic intolerance and reduce the risk of secondary problems in patients during long-term immobilization. The aim of this project is to control the cardiovascular parameters such as heart rate and blood pressure of bed rest patients via automated leg mobilization and body tilting. In a first step, a nonlinear model predictive control strategy was designed and evaluated on five healthy subjects and 11 bed rest patients. In a next step, a clinically feasible study was conducted on two patients. The mean values differed on average less than 1 bpm from the predetermined heart rate and less than 2.5 mmHg from the desired blood pressure values. These results of the feasibility study are promising, although heterogeneous disease etiologies and individual medication strongly influence the mechanically induced reactions. The long-term goal is an automation of the control of physiological signals and the mobilization of bed rest patients in an early phase of the rehabilitation process. Therefore, this new approach could help to strengthen the cardiovascular system and prevent secondary health problems arising from long-term bed rest