Efficacy of a hybrid assistive limb in post-stroke hemiplegic patients: a preliminary report

<p>Abstract</p> <p>Background</p> <p>Robotic devices are expected to be widely used in various applications including support for the independent mobility of the elderly with muscle weakness and people with impaired motor function as well as support for nursing care that involves heavy laborious work. We evaluated the effects of a hybrid assistive limb robot suit on the gait of stroke patients undergoing rehabilitation.</p> <p>Methods</p> <p>The study group comprised 16 stroke patients with severe hemiplegia. All patients underwent gait training. Four patients required assistance, and 12 needed supervision while walking. The stride length, walking speed and physiological cost index on wearing the hybrid assistive limb suit and a knee-ankle-foot orthosis were compared.</p> <p>Results</p> <p>The hybrid assistive limb suit increased the stride length and walking speed in 4 of 16 patients. The patients whose walking speed decreased on wearing the hybrid assistive limb suit either had not received sufficient gait training or had an established gait pattern with a knee-ankle-foot orthosis using a quad cane. The physiological cost index increased after wearing the hybrid assistive limb suit in 12 patients, but removal of the suit led to a decrease in the physiological cost index values to equivalent levels prior to the use of the suit.</p> <p>Conclusions</p> <p>Although the hybrid assistive limb suit is not useful for all hemiplegic patients, it may increase the walking speed and affect the walking ability. Further investigation would clarify its indication for the possibility of gait training.</p

Inhibition of 26S Protease Regulatory Subunit 7 (MSS1) Suppresses Neuroinflammation

Recently, researchers have focused on immunosuppression induced by rifampicin. Our previous investigation found that rifampicin was neuroprotective by inhibiting the production of pro-inflammatory mediators, thereby suppressing microglial activation. In this study, using 2-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS), we discovered that 26S protease regulatory subunit 7 (MSS1) was decreased in rifampicin-treated microglia. Western blot analysis verified the downregulation of MSS1 expression by rifampicin. As it is indicated that the modulation of the ubiquitin-26S proteasome system (UPS) with proteasome inhibitors is efficacious for the treatment of neuro-inflammatory disorders, we next hypothesized that silencing MSS1 gene expression might inhibit microglial inflammation. Using RNA interference (RNAi), we showed significant reduction of IkBα degradation and NF-kB activation. The production of lipopolysaccharides-induced pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS), nitric oxide, cyclooxygenase-2, and prostaglandin E2 were also reduced by MSS1 gene knockdown. Taken together, our findings suggested that rifampicin inhibited microglial inflammation by suppressing MSS1 protein production. Silencing MSS1 gene expression decreased neuroinflammation. We concluded that MSS1 inhibition, in addition to anti-inflammatory rifampicin, might represent a novel mechanism for the treatment of neuroinflammatory disorders

A Chaperone Trap Contributes to the Onset of Cystic Fibrosis

Protein folding is the primary role of proteostasis network (PN) where chaperone interactions with client proteins determine the success or failure of the folding reaction in the cell. We now address how the Phe508 deletion in the NBD1 domain of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein responsible for cystic fibrosis (CF) impacts the binding of CFTR with cellular chaperones. We applied single ion reaction monitoring mass spectrometry (SRM-MS) to quantitatively characterize the stoichiometry of the heat shock proteins (Hsps) in CFTR folding intermediates in vivo and mapped the sites of interaction of the NBD1 domain of CFTR with Hsp90 in vitro. Unlike folding of WT-CFTR, we now demonstrate the presence of ΔF508-CFTR in a stalled folding intermediate in stoichiometric association with the core Hsps 40, 70 and 90, referred to as a ‘chaperone trap’. Culturing cells at 30 C resulted in correction of ΔF508-CFTR trafficking and function, restoring the sub-stoichiometric association of core Hsps observed for WT-CFTR. These results support the interpretation that ΔF508-CFTR is restricted to a chaperone-bound folding intermediate, a state that may contribute to its loss of trafficking and increased targeting for degradation. We propose that stalled folding intermediates could define a critical proteostasis pathway branch-point(s) responsible for the loss of function in misfolding diseases as observed in CF

TYK2 Kinase Activity Is Required for Functional Type I Interferon Responses In Vivo

Tyrosine kinase 2 (TYK2) is a member of the Janus kinase (JAK) family and is involved in cytokine signalling. In vitro analyses suggest that TYK2 also has kinase-independent, i.e., non-canonical, functions. We have generated gene-targeted mice harbouring a mutation in the ATP-binding pocket of the kinase domain. The Tyk2 kinase-inactive (Tyk2K923E) mice are viable and show no gross abnormalities. We show that kinase-active TYK2 is required for full-fledged type I interferon- (IFN) induced activation of the transcription factors STAT1-4 and for the in vivo antiviral defence against viruses primarily controlled through type I IFN actions. In addition, TYK2 kinase activity was found to be required for the protein’s stability. An inhibitory function was only observed upon over-expression of TYK2K923E in vitro. Tyk2K923E mice represent the first model for studying the kinase-independent function of a JAK in vivo and for assessing the consequences of side effects of JAK inhibitors

How to use the world's scarce selenium resources efficiently to increase the selenium concentration in food

The world's rare selenium resources need to be managed carefully. Selenium is extracted as a by-product of copper mining and there are no deposits that can be mined for selenium alone. Selenium has unique properties as a semi-conductor, making it of special value to industry, but it is also an essential nutrient for humans and animals and may promote plant growth and quality. Selenium deficiency is regarded as a major health problem for 0.5 to 1 billion people worldwide, while an even larger number may consume less selenium than required for optimal protection against cancer, cardiovascular diseases and severe infectious diseases including HIV disease. Efficient recycling of selenium is difficult. Selenium is added in some commercial fertilizers, but only a small proportion is taken up by plants and much of the remainder is lost for future utilization. Large biofortification programmes with selenium added to commercial fertilizers may therefore be a fortification method that is too wasteful to be applied to large areas of our planet. Direct addition of selenium compounds to food (process fortification) can be undertaken by the food industry. If selenomethionine is added directly to food, however, oxidation due to heat processing needs to be avoided. New ways to biofortify food products are needed, and it is generally observed that there is less wastage if selenium is added late in the production chain rather than early. On these bases we have proposed adding selenium-enriched, sprouted cereal grain during food processing as an efficient way to introduce this nutrient into deficient diets. Selenium is a non-renewable resource. There is now an enormous wastage of selenium associated with large-scale mining and industrial processing. We recommend that this must be changed and that much of the selenium that is extracted should be stockpiled for use as a nutrient by future generations

Search for 10–1000 GeV Neutrinos from Gamma-Ray Bursts with IceCube

We present the results of a search for 10-1000 GeV neutrinos from 2268 gamma-ray bursts (GRBs) over 8 yr of IceCube-DeepCore data. This work probes burst physics below the photosphere where electromagnetic radiation cannot escape. Neutrinos of tens of giga electronvolts are predicted in sub-photospheric collision of free-streaming neutrons with bulk-jet protons. In a first analysis, we searched for the most significant neutrino-GRB coincidence using six overlapping time windows centered on the prompt phase of each GRB. In a second analysis, we conducted a search for a group of GRBs, each individually too weak to be detectable, but potentially significant when combined. No evidence of neutrino emission is found for either analysis. The most significant neutrino coincidence is for Fermi-GBM GRB bn 140807500, with a p-value of 0.097 corrected for all trials. The binomial test used to search for a group of GRBs had a p-value of 0.65 after all trial corrections. The binomial test found a group consisting only of GRB bn 140807500 and no additional GRBs. The neutrino limits of this work complement those obtained by IceCube at tera electronvolt to peta electronvolt energies. We compare our findings for the large set of GRBs as well as GRB 221009A to the sub-photospheric neutron-proton collision model and find that GRB 221009A provides the most constraining limit on baryon loading. For a jet Lorentz factor of 300 (800), the baryon loading on GRB 221009A is lower than 3.85 (2.13) at a 90% confidence level

Contrasting Responses to Harvesting and Environmental Drivers of Fast and Slow Life History Species

According to their main life history traits, organisms can be arranged in a continuum from fast (species with small body size, short lifespan and high fecundity) to slow (species with opposite characteristics). Life history determines the responses of organisms to natural and anthropogenic factors, as slow species are expected to be more sensitive than fast species to perturbations. Owing to their contrasting traits, cephalopods and elasmobranchs are typical examples of fast and slow strategies, respectively. We investigated the responses of these two contrasting strategies to fishing exploitation and environmental conditions (temperature, productivity and depth) using generalized additive models. Our results confirmed the foreseen contrasting responses of cephalopods and elasmobranchs to natural (environment) and anthropogenic (harvesting) influences. Even though a priori foreseen, we did expect neither the clear-cut differential responses between groups nor the homogeneous sensitivity to the same factors within the two taxonomic groups. Apart from depth, which affected both groups equally, cephalopods and elasmobranchs were exclusively affected by environmental conditions and fishing exploitation, respectively. Owing to its short, annual cycle, cephalopods do not have overlapping generations and consequently lack the buffering effects conferred by different age classes observed in multi-aged species such as elasmobranchs. We suggest that cephalopods are sensitive to short-term perturbations, such as seasonal environmental changes, because they lack this buffering effect but they are in turn not influenced by continuous, long-term moderate disturbances such as fishing because of its high population growth and turnover. The contrary would apply to elasmobranchs, whose multi-aged population structure would buffer the seasonal environmental effects, but they would display strong responses to uninterrupted harvesting due to its low population resilience. Besides providing empirical evidence to the theoretically predicted contrasting responses of cephalopods and elasmobranchs to disturbances, our results are useful for the sustainable exploitation of these resourcesVersión del editor4,411

Moving to capture children’s attention: developing a methodology for measuring visuomotor attention

Attention underpins many activities integral to a child’s development. However, methodological limitations currently make large-scale assessment of children’s attentional skill impractical, costly and lacking in ecological validity. Consequently we developed a measure of ‘Visual Motor Attention’ (VMA) - a construct defined as the ability to sustain and adapt visuomotor behaviour in response to task-relevant visual information. In a series of experiments, we evaluated the capability of our method to measure attentional processes and their contributions in guiding visuomotor behaviour. Experiment 1 established the method’s core features (ability to track stimuli moving on a tablet-computer screen with a hand-held stylus) and demonstrated its sensitivity to principled manipulations in adults’ attentional load. Experiment 2 standardised a format suitable for use with children and showed construct validity by capturing developmental changes in executive attention processes. Experiment 3 tested the hypothesis that children with and without coordination difficulties would show qualitatively different response patterns, finding an interaction between the cognitive and motor factors underpinning responses. Experiment 4 identified associations between VMA performance and existing standardised attention assessments and thereby confirmed convergent validity. These results establish a novel approach to measuring childhood attention that can produce meaningful functional assessments that capture how attention operates in an ecologically valid context (i.e. attention's specific contribution to visuomanual action)

Synthetic Biology: Mapping the Scientific Landscape

This article uses data from Thomson Reuters Web of Science to map and analyse the scientific landscape for synthetic biology. The article draws on recent advances in data visualisation and analytics with the aim of informing upcoming international policy debates on the governance of synthetic biology by the Subsidiary Body on Scientific, Technical and Technological Advice (SBSTTA) of the United Nations Convention on Biological Diversity. We use mapping techniques to identify how synthetic biology can best be understood and the range of institutions, researchers and funding agencies involved. Debates under the Convention are likely to focus on a possible moratorium on the field release of synthetic organisms, cells or genomes. Based on the empirical evidence we propose that guidance could be provided to funding agencies to respect the letter and spirit of the Convention on Biological Diversity in making research investments. Building on the recommendations of the United States Presidential Commission for the Study of Bioethical Issues we demonstrate that it is possible to promote independent and transparent monitoring of developments in synthetic biology using modern information tools. In particular, public and policy understanding and engagement with synthetic biology can be enhanced through the use of online interactive tools. As a step forward in this process we make existing data on the scientific literature on synthetic biology available in an online interactive workbook so that researchers, policy makers and civil society can explore the data and draw conclusions for themselves