Re-construction of action awareness depends on an internal model of action-outcome timing.

The subjective time of an instrumental action is shifted towards its outcome. This temporal binding effect is partially retrospective, i.e., occurs upon outcome perception. Retrospective binding is thought to reflect post-hoc inference on agency based on sensory evidence of the action - outcome association. However, many previous binding paradigms cannot exclude the possibility that retrospective binding results from bottom-up interference of sensory outcome processing with action awareness and is functionally unrelated to the processing of the action - outcome association. Here, we keep bottom-up interference constant and use a contextual manipulation instead. We demonstrate a shift of subjective action time by its outcome in a context of variable outcome timing. Crucially, this shift is absent when there is no such variability. Thus, retrospective action binding reflects a context-dependent, model-based phenomenon. Such top-down re-construction of action awareness seems to bias agency attribution when outcome predictability is low

Intracerebral Human Regulatory T Cells: Analysis of CD4+CD25+FOXP3+ T Cells in Brain Lesions and Cerebrospinal Fluid of Multiple Sclerosis Patients

Impaired suppressive capacity of CD4+CD25+FOXP3+ regulatory T cells (Treg) from peripheral blood of patients with multiple sclerosis (MS) has been reported by multiple laboratories. It is, however, currently unresolved whether Treg dysfunction in MS patients is limited to reduced control of peripheral T cell activation since most studies analyzed peripheral blood samples only. Here, we assessed early active MS lesions in brain biopsies obtained from 16 patients with MS by FOXP3 immunohistochemistry. In addition, we used six-color flow cytometry to determine numbers of Treg by analysis of FOXP3/CD127 expression in peripheral blood and cerebrospinal fluid (CSF) of 17 treatment-naïve MS patients as well as quantities of apoptosis sensitive CD45ROhiCD95hi cells in circulating and CSF Treg subsets. Absolute numbers of FOXP3+ and CD4+ cells were rather low in MS brain lesions and Treg were not detectable in 30% of MS biopsies despite the presence of CD4+ cell infiltrates. In contrast, Treg were detectable in all CSF samples and Treg with a CD45ROhiCD95hi phenotype previously shown to be highly apoptosis sensitive were found to be enriched in the CSF compared to peripheral blood of MS patients. We suggest a hypothetical model of intracerebral elimination of Treg by CD95L-mediated apoptosis within the MS lesion

“My Lung Disease Won’t Go Away, it’s There to Stay”: Profiles of Adaptation to Functional Limitations in Workers with Asthma and COPD

Purpose Earlier research has shown that adaptation (i.e., the way in which employees cope with limitations resulting from their disease) is associated with sick leave. Our aim was to investigate signs of adequate or inadequate adaptation in employees with asthma and COPD. Methods A Q-methodological study was carried out among 34 workers with asthma or COPD. Results Four adaptation profiles were distinguished: the eager, the adjusted, the cautious, and the worried workers. The adaptation profiles provide insight into the different ways in which workers with asthma and COPD cope with their illness at work. Conclusions The adaptation profiles serve as a starting point for the design of appropriate (occupational) care. The eager workers experience little difficulties at work; the cautious workers may need assistance in learning how to accept their disease; the worried workers need reassurance, and may need reactivation; the adjusted workers deserve extra attention, and, when necessary, advice on how to live with their asthma or COPD

Treatment with Natalizumab in Relapsing–Remitting Multiple Sclerosis Patients Induces Changes in Inflammatory Mechanism

Natalizumab is a widely accepted drug for the relapsing–remitting subtype of multiple sclerosis (RRMS). The present longitudinal exploratory study in RRMS patients analyzes the effects of natalizumab treatment on the levels of pro-inflammatory and anti-inflammatory cytokine protein levels and also the frequency and suppressor function of regulatory T cells. Flow cytometry was used to determine cytokines and regulatory T cell frequency while regulatory T cell suppressor function was assayed in vitro at different time-points after starting with natalizumab. Results showed serum levels of pro-inflammatory interferon gamma and interleukin (IL)-12p70, as well as anti-inflammatory IL-4 and IL-10, were elevated just a few hours or days after first IV infusion of natalizumab. Interestingly, other cytokines like IL-5 or IL-13 were also elevated while pro-inflammatory IL-17, IL-2, and IL-1β increased only after a long-term treatment, suggesting different immune mechanisms. In contrast, we did not observe any effect of natalizumab treatment on regulatory T cell frequency or activity. In conclusion, these results suggest natalizumab has other immunological effects beyond VLA-4 interaction and inhibition of CNS extravasation, the relevance of which is as yet unknown and warrants further investigation

Altered visual feedback from an embodied avatar unconsciously influences movement amplitude and muscle activity

Evidence suggests that the sense of the position of our body parts can be surreptitiously deceived, for instance through illusory visual inputs. However, whether altered visual feedback during limb movement can induce substantial unconscious motor and muscular adjustments is not known. To address this question, we covertly manipulated virtual body movements in immersive virtual reality. Participants were instructed to flex their elbow to 90° while tensing an elastic band, as their virtual arm reproduced the same, a reduced (75°), or an amplified (105°) movement. We recorded muscle activity using electromyography, and assessed body ownership, agency and proprioception of the arm. Our results not only show that participants compensated for the avatar’s manipulated arm movement while being completely unaware of it, but also that it is possible to induce unconscious motor adaptations requiring significant changes in muscular activity. Altered visual feedback through body ownership illusions can influence motor performance in a process that bypasses awareness

Approaches in biotechnological applications of natural polymers

Natural polymers, such as gums and mucilage, are biocompatible, cheap, easily available and non-toxic materials of native origin. These polymers are increasingly preferred over synthetic materials for industrial applications due to their intrinsic properties, as well as they are considered alternative sources of raw materials since they present characteristics of sustainability, biodegradability and biosafety. As definition, gums and mucilages are polysaccharides or complex carbohydrates consisting of one or more monosaccharides or their derivatives linked in bewildering variety of linkages and structures. Natural gums are considered polysaccharides naturally occurring in varieties of plant seeds and exudates, tree or shrub exudates, seaweed extracts, fungi, bacteria, and animal sources. Water-soluble gums, also known as hydrocolloids, are considered exudates and are pathological products; therefore, they do not form a part of cell wall. On the other hand, mucilages are part of cell and physiological products. It is important to highlight that gums represent the largest amounts of polymer materials derived from plants. Gums have enormously large and broad applications in both food and non-food industries, being commonly used as thickening, binding, emulsifying, suspending, stabilizing agents and matrices for drug release in pharmaceutical and cosmetic industries. In the food industry, their gelling properties and the ability to mold edible films and coatings are extensively studied. The use of gums depends on the intrinsic properties that they provide, often at costs below those of synthetic polymers. For upgrading the value of gums, they are being processed into various forms, including the most recent nanomaterials, for various biotechnological applications. Thus, the main natural polymers including galactomannans, cellulose, chitin, agar, carrageenan, alginate, cashew gum, pectin and starch, in addition to the current researches about them are reviewed in this article.. }To the Conselho Nacional de Desenvolvimento Cientfíico e Tecnológico (CNPq) for fellowships (LCBBC and MGCC) and the Coordenação de Aperfeiçoamento de Pessoal de Nvíel Superior (CAPES) (PBSA). This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit, the Project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462) and COMPETE 2020 (POCI-01-0145-FEDER-006684) (JAT)

TMS stimulation over the inferior parietal cortex disrupts prospective sense of agency

Sense of agency refers to the feeling of controlling an external event through one's own action. On one influential view, sense of agency is inferred after an action, by "retrospectively" comparing actual effects of actions against their intended effects. However, it has been recently shown that earlier processes, linked to action selection, may also contribute to sense of agency, in advance of the action itself, and independently of action effects. The inferior parietal cortex (IPC) may underpin this "prospective" contribution to agency, by monitoring signals relating to fluency of action selection in dorsolateral prefrontal cortex (DLPFC). Here, we combined transcranial stimulation (TMS) with subliminal priming of action selection to investigate the causal role of these regions in the prospective coding of agency. In a first experiment, we showed that TMS over left IPC at the time of action selection disrupts perceived control over subsequent effects of action. In a second experiment, we exploited the temporal specificity of single-pulse TMS to pinpoint the exact timing of IPC contribution to sense of agency. We replicated the reduction in perceived control at the point of action selection, while observing no effect of TMS-induced disruption of IPC at the time of action outcomes

Chapter 11 - Voluntary or involuntary? A neurophysiologic approach to functional movement disorders

Patients with functional movement disorders (FMD) experience movements as involuntary that share fundamental characteristics with voluntary actions. This apparent paradox raises questions regarding the possible sources of a subjective experience of action. In addition, it poses a yet unresolved diagnostic challenge, namely how to describe or even quantify this experience in a scientifically and clinically useful way. Here, we describe recent experimental approaches that have shed light on the phenomenology of action in FMD. We first outline the sources and content of a subjective experience of action in healthy humans and discuss how this experience may be created in the brain. Turning to FMD, we describe implicit, behavioral measures that have revealed specific abnormalities in the awareness of action in FMD. Based on these abnormalities, we propose a potential, new solution to the paradox of volition in FMD

Severe relapses after the first infusion of natalizumab in active relapsing-remitting multiple sclerosis

Abstract We describe three patients suffering from a very active form of relapsing-remitting multiple sclerosis (MS), who experienced severe disease worsening, associated with a marked increase in brain inflammation, a few days after the first administration of natalizumab. In line with preclinical studies, our observations suggest that natalizumab, when administered during active disease phases, may worsen disease evolution possibly by modifying the regulatory network in the brain. We suggest that relapsing-remitting MS patients having had a recent relapse should be treated with natalizumab only after achieving complete clinical and radiological remission