32,300 research outputs found

    Intrathecal versus peripheral inflammatory protein profile in MS patients at diagnosis: a comprehensive investigation on serum and CSF

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    Intrathecal inflammation plays a key role in the pathogenesis of multiple sclerosis (MS). To better elucidate its relationship with peripheral inflammation, we investigated the correlation between cerebrospinal fluid (CSF) and serum levels of 61 inflammatory proteins. Paired CSF and serum samples were collected from 143 treatment-naïve MS patients at diagnosis. A customized panel of 61 inflammatory molecules was analyzed by a multiplex immunoassay. Correlations between serum and CSF expression levels for each molecule were performed by Spearman's method. The expression of sixteen CSF proteins correlated with their serum expression (p-value < 0.001): only five molecules (CXCL9, sTNFR2, IFNα2, Pentraxin-3, and TSLP) showed a Rho value >0.40, suggesting moderate CSF/serum correlation. No correlation between inflammatory serum patterns and Qalb was observed. Correlation analysis of serum expression levels of these sixteen proteins with clinical and MRI parameters pinpointed a subset of five molecules (CXCL9, sTNFR2, IFNα2, IFNβ, and TSLP) negatively correlating with spinal cord lesion volume. However, following FDR correction, only the correlation of CXCL9 remained significant. Our data support the hypothesis that the intrathecal inflammation in MS only partially associates with the peripheral one, except for the expression of some immunomodulators that might have a key role in the initial MS immune response

    Designed acute physical activity to benefit primary school children’s cognition: Effects of cognitive challenge, bout duration and positive affect

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    Introduction Acute bouts of physical activity (PA) have the potential to transiently enhance children’s cognition (Ludyga et al., 2016). Although these positive results seem to be relatively consistent, there is considerable heterogeneity in the magnitude of effects (Lubans et al., 2022). Cognitive benefits are largely influenced by the interaction of quantitative and qualitative PA task characteristics (Lubans et al., 2022; Pesce, 2012), as well as by individual differences in responsiveness to PA bouts (Herold et al., 2021). Understanding the individual and joint effects of moderators is of great practical importance in the educational setting (Schmidt et al., 2021). This information could help to design and individualize PA breaks to enhance cognitive functions that are essential for learning and academic achievement, such as executive functions (EFs; responsible for self-regulation and goal-directed behavior) and attention (responsible for allocation of resources). Among PA task characteristics, the level of cognitive challenge has attracted increasing interest; however, a low comparability of PA studies varying in both quantitative parameters and qualitative modality do not allow for definitive conclusions (Paschen et al., 2019; Schmidt et al., 2021). Moreover, preliminary evidence highlights that positive affect induced by the PA bout may mediate PA effects on cognition (Schmidt et al., 2016). Thus, the aim of the research program was threefold: (1) shed light on which cognitive challenge level in acute PA may affect children’s EFs and attention (“cognitive challenge” study); (2) investigate which bout duration of the identified optimal cognitive challenge level is necessary to reap largest benefits (“bout duration” study); and (3) manipulate positive affect through supportive feedback (and music) to elucidate its influence on cognitive performance (“positive affect” study). Methods Three studies with within-subjects experimental design were conducted with 5th-6th graders (N = 110, N = 114, N = 102; determined by a-priori power analyses). Each study used an exergame (i.e., active video game that involves gross-motor PA) as intervention, performed at 65% maximum heart rate (HR). For the studies, the following experimental conditions were used: “Cognitive challenge” study: three sessions (15-min) with different cognitive challenge levels (low, mid, high), continuously adapted to the individual ongoing performance by an ascending number of distracting stimuli and misleading cues. “Bout duration” study: four sessions with the same, individually adapted cognitive challenge level (chosen according to “cognitive challenge” study) and different PA durations (5-, 10-, 15-, 20-min). “Positive affect” study: three sessions with the same cognitive challenge level and duration of the PA bout (chosen according to “cognitive challenge” and “bout duration” studies) and different affect-inducing feedback (no feedback, music with sound effects, music with sound effects and verbal supportive feedback). Each exergame session was performed individually during school hours (once a week). Children wore motion-based trackers and a HR sensor, while playing a virtual game that required performing different movements (e.g., jumps, squats, punches). During each session (every 5 minutes), perceived physical and cognitive challenge, as well as affective states were assessed. After the exergame, executive control (flanker effect), attentional alerting and orienting, and their interactive functioning were assessed by a child-adapted attention network test (ANT-R; Fan et al., 2009). Repeated measures ANOVAs were calculated to analyze intervention effects on reaction times (RTs) and accuracy data, with subsequent post-hoc Bonferroni-adjusted comparisons. Results “Cognitive challenge” study. A significant interaction for RTs between cognitive challenge and flanker conditions emerged [F(2, 100) = 4.16, p = .018, ƞ2p = .07], with no effects for accuracy. Post-hoc analyses of RT difference data (incongruent – congruent, i.e., flanker effect) revealed best performance after the high-challenge condition (ps < .045; ƞ2ps > .01). Regarding differential effects, adding sex to the model showed that it moderated the effect of cognitive challenge on the interactive functioning of executive control and attentional orienting [F(6, 96) = 2.33, p = .038, ƞ2p = .12]. “Bout duration” study. A significant effect of duration on overall RTs emerged [F(3, 101) = 4.04, p = .009, ƞ2p = .11], with no effects on accuracy. Post-hoc comparisons revealed significantly faster RTs after the 15-min compared to the 10-min condition (p = .019, ƞ2p = .09). Regarding differential effects, adding habitual PA level to the model showed that it moderated the effect of duration on the interactive functioning of executive control and attentional orienting [F(3, 100) = 4.81, p = .004, ƞ2p = .13]. “Positive affect” study. Ongoing – results will be presented at the SGS-meeting. Discussion The high-challenging bout benefited children’s executive control the most (“cognitive challenge” study), supporting the hypothesis that PA designed to generate cognitive engagement may facilitate performance in subsequent EF tasks (i.e., cognitive stimulation hypothesis; Pesce, 2012). However, attentional alerting and orienting were unaffected in the current study, which is in line with the absence of effects found for aerobic PA bouts (van den Berg et al., 2018). The 15-min cognitively high-challenging bout benefited children’s overall information processing speed the most, with no duration-dependent differences for executive control, alerting or orienting (“bout duration” study). Results extend to acute cognitively challenging PA the duration-dependent effects that have been found for acute high-intensity or aerobic PA bouts on overall information processing, but neither on EFs (Hatch et al., 2021), nor on alerting and orienting (van den Berg et al., 2018). Interestingly, in both “cognitive challenge” and “bout duration” studies an intriguing interplay between individual and tasks characteristics on the interactive functioning of executive control and orienting networks emerged. Indeed, the high-challenging bout benefited – for males only – also the efficiency of executive control under disadvantageous spatial attention conditions, consistent with previous adult studies without PA (Li et al., 2021). Whereas, the 15-min duration benefited the same interactive functioning for more active children only, which is in line with evidence that cognitively challenging PA bouts benefit EF efficiency more in children who are physically and cognitively better equipped to capitalize on it (Jäger et al., 2015). The added value of the present studies within an inconsistent evidence base (Paschen et al., 2019; Schmidt et al., 2021) is threefold. The studies allowed to (1) disentangle cognitive from physical challenge effects, while individualizing cognitive challenge; (2) identify the optimal duration for learning contexts; and (3) further the understanding of the interplay between individual and task characteristics. The “positive affect” study will complement the investigation of individual- and task-level moderators with information on positive affect as potential mediator for the acute PA-cognition relation. Results of the research program may inform the design of acute and chronic PA studies implemented in the school context, to capitalize jointly on physical and cognitive benefits of PA. References Fan, J., Gu, X., Guise, K. G., Liu, X., Fossella, J., Wang, H., & Posner, M. I. (2009). Testing the behavioral interaction and integration of attentional networks. Brain and Cognition, 70(2), 209–220. https://doi.org/10.1016/j.bandc.2009.02.002 Hatch, L. M., Dring, K. J., Williams, R. A., Sunderland, C., Nevill, M. E., & Cooper, S. B. (2021). Effect of differing durations of high-intensity intermittent activity on cognitive function in adolescents. International Journal of Environmental Research and Public Health, 18(21), Article 11594. https://doi.org/10.3390/ijerph182111594 Herold, F., Törpel, A., Hamacher, D., Budde, H., Zou, L., Strobach, T., Müller, N. G., & Gronwald, T. (2021). Causes and consequences of interindividual response variability: A call to apply a more rigorous research design in acute exercise-cognition studies. Frontiers in Physiology, 12, Article 682891. https://doi.org/10.3389/fphys.2021.682891 Jäger, K., Schmidt, M., Conzelmann, A., & Roebers, C. M. (2015). The effects of qualitatively different acute physical activity interventions in real-world settings on executive functions in preadolescent children. Mental Health and Physical Activity, 9, 1–9. https://doi.org/10.1016/j.mhpa.2015.05.002 Li, Y., Wang, Y., Jin, X., Niu, D., Zhang, L., Jiang, S. Y., Ruan, H. D., & Ho, G. W. (2021). Sex differences in hemispheric lateralization of attentional networks. Psychological Research, 85(7), 2697–2709. https://doi.org/10.1007/s00426-020-01423-z Lubans, D. R., Leahy, A. A., Mavilidi, M. F., & Valkenborghs, S. R. (2022). Physical activity, fitness, and executive functions in youth: Effects, moderators, and mechanisms. Current Topics in Behavioral Neurosciences, 53, 103–130. https://doi.org/10.1007/7854_2021_271 Ludyga, S., Gerber, M., Brand, S., Holsboer-Trachsler, E., & Pühse, U. (2016). Acute effects of moderate aerobic exercise on specific aspects of executive function in different age and fitness groups: A meta-analysis. Psychophysiology, 53(11), 1611–1626. https://doi.org/10.1111/psyp.12736 Paschen, L., Lehmann, T., Kehne, M., & Baumeister, J. (2019). Effects of acute physical exercise with low and high cognitive demands on executive functions in children: A systematic review. Pediatric Exercise Science, 31(3), 267–281. https://doi.org/10.1123/pes.2018-0215 Pesce, C. (2012). Shifting the focus from quantitative to qualitative exercise characteristics in exercise and cognition research. Journal of Sport & Exercise Psychology, 34(6), 766–786. https://doi.org/10.1123/jsep.34.6.766 Schmidt, M., Benzing, V., & Kamer, M. (2016). Classroom-based physical activity breaks and children's attention: Cognitive engagement works! Frontiers in Psychology, 7, Article 1474. https://doi.org/10.3389/fpsyg.2016.01474 Schmidt, M., Egger, F., Anzeneder, S., & Benzing, V. (2021). Acute cognitively challenging physical activity to promote children’s cognition. In R. Bailey (Ed.), ICSSPE perspectives. Physical activity and sport during the first ten years of life: Multidisciplinary perspectives (pp. 141–155). Routledge. van den Berg, V., Saliasi, E., Jolles, J., de Groot, R. H., Chinapaw, M. J. M., & Singh, A. S. (2018). Exercise of varying durations: No acute effects on cognitive performance in adolescents. Frontiers in Neuroscience, 12, Article 672. https://doi.org/10.3389/fnins.2018.0067

    Chronic use of cannabis might impair sensory error processing in the cerebellum through endocannabinoid dysregulation

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    Chronic use of cannabis leads to both motor deficits and the downregulation of CB1 receptors (CB1R) in the cerebellum. In turn, cerebellar damage is often related to impairments in motor learning and control. Further, a recent motor learning task that measures cerebellar-dependent adaptation has been shown to distinguish well between healthy subjects and chronic cannabis users. Thus, the deteriorating effects of chronic cannabis use in motor performance point to cerebellar adaptation as a key process to explain such deficits. We review the literature relating chronic cannabis use, the endocannabinoid system in the cerebellum, and different forms of cerebellar-dependent motor learning, to suggest that CB1R downregulation leads to a generalized underestimation and misprocessing of the sensory errors driving synaptic updates in the cerebellar cortex. Further, we test our hypothesis with a computational model performing a motor adaptation task and reproduce the behavioral effect of decreased implicit adaptation that appears to be a sign of chronic cannabis use. Finally, we discuss the potential of our hypothesis to explain similar phenomena related to motor impairments following chronic alcohol dependency

    Complement mediated synapse elimination in schizophrenia

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    Schizophrenia (SCZ) is a devastating psychiatric disorder with a typically age of onset in late adolescence. The heritability is estimated to be in between 60-80% and large-scale genome-wide studies have revealed a prominent polygenic component to SCZ risk and identified more than three-hundred common risk variants. Despite a better understanding of which genetic risk variants that increases SCZ risk, it has been challenging to map out the pathophysiology of the disorder. This has stalled the development of target drugs and current treatment options display moderate efficacy and are prone to produce side-effects. SCZ is generally considered a neurodevelopmental disorder and it was proposed more than forty years ago that physiological removal of less active synapses in adolescence, i.e., synaptic pruning, is increased in SCZ and hereby causes the core symptoms of the disorder. This theory has then been supported by post-mortem brain tissue and imaging studies displaying decreased synapse density in SCZ. More recently, it was then shown that the most strongly associated risk loci can largely be explained by copy numbers of a gene coding for the complement factor 4A (C4A). As microglia prune synapses with the help of complement signalling, we therefore decided to use a recently developed human 2D in vitro assay to assess microglial uptake of synaptic structures in models based on cells from individuals with SCZ and healthy controls (study I). We observed excessive uptake of synaptic structures in SCZ models and by mixing synapses from healthy controls with microglia from SCZ patients, and vice versa, we showed the contribution of microglial and neuronal factors contributing to this excessive uptake of synaptic structures. We then developed an in vitro assay to study neuronal complement deposition dependent on copy numbers of C4A in the neuronal lines. Complement 3 (C3) deposition increased by C4A copy numbers but was independent of C4B copy numbers (also unrelated to SCZ risk). Similar C4A copy numbers correlated with the extent of microglial uptake of synapses. Microglial uptake of synaptic structures could also be inhibited by the tetracycline minocycline that also decreased risk of developing SCZ in an electronic health record cohort. In study II, we cerebrospinal fluid (CSF) from first-episode psychosis patients to measure protein levels of C4A. In two independent cohorts, we observed elevated C4A levels (although not C4B levels) in first-episode patients that later were to develop SCZ and could show correlations with markers of synapse density. However, elevated C4A levels could not fully be explained by more copy numbers of C4A in individuals with SCZ and in vitro experiments revealed that SCZ-associated cytokines can induce C4A mRNA expression while also correlating with C4A in patient-derived CSF. In study III, we set-up a 3D brain organoid models to more fully comprehensively capture processes in the developing human brain and then also included innately developing microglia. We display synaptic pruning within these models and use single cell RNA sequencing to validate them. In conclusion, this thesis uses patient-derived cellular modelling to uncover a disease mechanism in SCZ that link genetic risk variants with bona fide protein changes in living patients

    Face processing in young adults with autism and ADHD: an event related potentials study

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    Background: Atypicalities in perception and interpretation of faces and emotional facial expressions have been reported in both autism and attention-deficit/hyperactivity disorder (ADHD) during childhood and adulthood. Investigation of face processing during young adulthood (18 to 25 years), a transition period to full-fledged adulthood, could provide important information on the adult outcomes of autism and ADHD. Methods: In this study, we investigated event-related potentials (ERPs) related to visual face processing in autism, ADHD, and co–occurring autism and ADHD in a large sample of young adults (N = 566). The groups were based on the Diagnostic Interview for ADHD in Adults 2.0 (DIVA-2) and the Autism Diagnostic Observation Schedule-2 (ADOS-2). We analyzed ERPs from two passive viewing tasks previously used in childhood investigations: (1) upright and inverted faces with direct or averted gaze; (2) faces expressing different emotions. Results: Across both tasks, we consistently found lower amplitude and longer latency of N170 in participants with autism compared to those without. Longer P1 latencies and smaller P3 amplitudes in response to emotional expressions and longer P3 latencies for upright faces were also characteristic to the autistic group. Those with ADHD had longer N170 latencies, specific to the face-gaze task. Individuals with both autism and ADHD showed additional alterations in gaze modulation and a lack of the face inversion effect indexed by a delayed N170. Conclusion: Alterations in N170 for autistic young adults is largely consistent with studies on autistic adults, and some studies in autistic children. These findings suggest that there are identifiable and measurable socio-functional atypicalities in young adults with autism

    Nonparametric Two-Sample Test for Networks Using Joint Graphon Estimation

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    This paper focuses on the comparison of networks on the basis of statistical inference. For that purpose, we rely on smooth graphon models as a nonparametric modeling strategy that is able to capture complex structural patterns. The graphon itself can be viewed more broadly as density or intensity function on networks, making the model a natural choice for comparison purposes. Extending graphon estimation towards modeling multiple networks simultaneously consequently provides substantial information about the (dis-)similarity between networks. Fitting such a joint model - which can be accomplished by applying an EM-type algorithm - provides a joint graphon estimate plus a corresponding prediction of the node positions for each network. In particular, it entails a generalized network alignment, where nearby nodes play similar structural roles in their respective domains. Given that, we construct a chi-squared test on equivalence of network structures. Simulation studies and real-world examples support the applicability of our network comparison strategy.Comment: 25 pages, 6 figure

    All-Optical Nonzero-Field Vector Magnetic Sensor For Magnetoencephalography

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    We present the concept and the results of an investigation of an all-optical vector magnetic field sensor scheme developed for biological applications such as non-zero field magnetoencephalography and magnetocardiography. The scheme differs from the classical two-beam Bell-Bloom scheme in that the detecting laser beam is split into two beams, which are introduced into the cell in orthogonal directions, and the ratio of the amplitudes of the magnetic resonance signals in these beams and their phase difference are measured; strong optical pumping from the lower hyperfine level of the ground state ensures the resonance line narrowing, and detection in two beams is carried out in a balanced schemes by measuring the beam polarization rotation. The proposed sensor is compact, resistant to variations of parameters of laser radiation and highly sensitive to the angle of deflection of the magnetic field vector - with an estimated scalar sensitivity of the order of 16 fT/Hz1/2 in 8x8x8 mm3 cell, an angular sensitivity of 4x10-7 rad, or 0.08'', was demonstrated

    Anxiety and hope: a study about the caregiver overload in the care of patients with stroke

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    Stroke involves injury to the central nervous system, presenting most frequently as cerebral infarction and intracerebral hemorrhage. It’s an important cause of disability worldwide, being associated with high burden to the patients’ caregivers, who are, frequently, family members. In that matter, it is reported that the main caregivers of stroke patients have the same, or even greater incidence of mental illnesses, such as depression and anxiety. Therefore, we present this study protocol aiming to observe the association between the patient’s type of stroke along with the severity of their sequelae, and the levels of anxiety and hope of their caregivers, in a descriptive, cross-sectional study with a quali-quantitative approach. For that purpose, patients of both sexes, over 18 years of age, who have had a stroke and are being followed up at the Cerebrovascular Diseases Ambulatory will be randomly selected. Then, data will be collected from the caregiver through questionnaires: Zarit Burden Interview (ZBI), Beck Hopelessness Scale (BHS), Beck Anxiety Inventory (BAI) and a socioeconomic questionnaire. The ZBI analyzes psychological, financial, social and physical aspects of the caregiver’s universe, while the BAI and BHS are used to quantify the caregiver’s anxiety state, and bring information about the individual’s hope and life expectations. Information about the patient will be obtained from medical records. Finally, we hope to find useful information for health services about the reality in which they are inserted, in order to promote the creation of disease prevention measures, which is essential to improve the quality of healthcare provided

    Trajectories of interleukin 10 and heart fatty acid-binding protein levels in traumatic brain injury patients with or without extracranial injuries

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    BackgroundInterleukin 10 (IL-10) and heart fatty acid-binding protein (H-FABP) have gained interest as diagnostic biomarkers of traumatic brain injury (TBI), but factors affecting their blood levels in patients with moderate-to-severe TBI are largely unknown.ObjectiveTo investigate the trajectories of IL-10 and H-FABP between TBI patients with and without extracranial injuries (ECI); to investigate if there is a correlation between the levels of IL-10 and H-FABP with the levels of inflammation/infection markers C-reactive protein (CRP) and leukocytes; and to investigate if there is a correlation between the admission level of H-FABP with admission levels of cardiac injury markers, troponin (TnT), creatine kinase (CK), and creatine kinase MB isoenzyme mass (CK-MBm).Materials and methodsThe admission levels of IL-10, H-FABP, CRP, and leukocytes were measured within 24 h post-TBI and on days 1, 2, 3, and 7 after TBI. The admission levels of TnT, CK, and CK-MBm were measured within 24 h post-TBI.ResultsThere was a significant difference in the concentration of H-FABP between TBI patients with and without ECI on day 0 (48.2 ± 20.5 and 12.4 ± 14.7 ng/ml, p = 0.02, respectively). There was no significant difference in the levels of IL-10 between these groups at any timepoints. There was a statistically significant positive correlation between IL-10 and CRP on days 2 (R = 0.43, p < 0.01) and 7 (R = 0.46, p = 0.03) after injury, and a negative correlation between H-FABP and CRP on day 0 (R = -0.45, p = 0.01). The levels of IL-10 or H-FABP did not correlate with leukocyte counts at any timepoint. The admission levels of H-FABP correlated with CK (R = 0.70, p < 0.001) and CK-MBm (R = 0.61, p < 0.001), but not with TnT.ConclusionInflammatory reactions during the early days after a TBI do not significantly confound the use of IL-10 and H-FABP as TBI biomarkers. Extracranial injuries and cardiac sources may influence the levels of H-FABP in patients with moderate-to-severe TBI

    Pour un accompagnement global en pension de famille : l’apport des capabilités d’Identité-Logement

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    Face à l’augmentation constante du nombre de personnes sans domicile en France, le « Plan Logement d'abord 2018-2022 » s’appuie sur les résultats du modèle « Housing First » (HF) pour proposer des solutions de logement pérennes. Il s'agit notamment de pensions de famille qui offrent un logement permanent aux personnes en situation de grande précarité, avec un accompagnement adapté. Si le modèle initial (HF) destiné à un public atteint de troubles psychiques propose un accompagnement orienté vers le rétablissement, l’accompagnement en pension de famille destiné à un public plus large, il nécessite d’être pensé autrement. Par une étude de cas menée en pension de famille, cet article présente une philosophie d’intervention différente où l’accompagnement prendrait appui sur l’approche par les capabilités et sur le concept d’Identité-logement, ouvrant la voie au pragmatisme critique.Faced with the ever-increasing number of homeless people in France, the "Housing First Plan 2018-2022" builds on the results of the "Housing First" (HF) model to propose sustainable solutions. These include boarding houses that provide permanent accommodation for people in very precarious situations, with appropriate support. While the Housing First (HF) model for people with mental health problems offers recovery-oriented support, support in boarding houses for a wider public needs to be considered differently. Through a case study in a boarding house, this article presents a different philosophy of intervention where the support would be based on the capability approach and on the concept of Home-identity, opening the way to critical pragmatism
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