MALDI-MSI for the analysis of a 3D tissue-engineered psoriatic skin model

MALDI-MS Imaging is a novel label-free technique that can be used to visualize the changes in multiple mass responses following treatment. Following treatment with proinflammatory cytokine interleukin-22 (IL-22), the epidermal differentiation of Labskin, a living skin equivalent (LSE), successfully modeled psoriasis in vitro. Masson’s trichrome staining enabled visualization and quantification of epidermal differentiation between the untreated and IL-22 treated psoriatic LSEs. Matrix-assisted laser desorption ionization mass spectrometry imaging was used to observe the spatial location of the psoriatic therapy drug acetretin following 48 h treatments within both psoriatic and normal LSEs. After 24 h, the drug was primarily located in the epidermal regions of both the psoriatic and nonpsoriatic LSE models whereas after 48 h it was detectible in the dermis

Recommendations for the application and follow-up of quality controls in medical laboratories

This is a translation of the paper “Recommendations for the application and follow-up of quality controls in medical biology laboratories” published in French in the journal Annales de Biologie Clinique (Recommandations pour la mise en place et le suivi des contrôles de qualité dans les laboratoires de biologie médicale. Ann Biol Clin (Paris). 2019;77:577-97.). The recommendations proposed in this document are the result of work conducted jointly by the Network of Accredited Medical Laboratories (LABAC), the French Society of Medical Biology (SFBC) and the Federation of Associations for External Quality Assessment (FAEEQ). The different steps of the implementation of quality controls, based on a risk analysis, are described. The changes of reagent or internal quality control (IQC) materials batches, the action to be taken in case of non-conform IQC results, the choice of external quality assessment (EQA) scheme and interpretation of their results as well as the new issue of analyses performed on several automatic systems available in the same laboratory are discussed. Finally, the concept of measurement uncertainty, the robustness of the methods as well as the specificities of near-patient testing and rapid tests are described. These recommendations cannot apply for all cases we can find in medical laboratories. The implementation of an objective alternative strategy, supported with documented evidence, might be equally considered

IFNAR1-Signalling Obstructs ICOS-mediated Humoral Immunity during Non-lethal Blood-Stage Plasmodium Infection

Funding: This work was funded by a Career Development Fellowship (1028634) and a project grant (GRNT1028641) awarded to AHa by the Australian National Health & Medical Research Council (NHMRC). IS was supported by The University of Queensland Centennial and IPRS Scholarships. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

25-OH Vitamin D Levels and Cognitive Performance: Longitudinal Assessment in a Healthy Aging Cohort

Background: Declining serum levels of 25-hydroxyvitamin D [25(OH)D, a biomarker of vitamin D status] with aging is a well-recognized phenomenon. However, scarce information is available on the relation between 25(OH)D levels and cognitive performance over time in older individuals. Our purpose was to evaluate, longitudinally, the association of 25(OH)D with cognitive function in a healthy older adults' cohort. Methods: Sixty-four individuals over 55 years-old with no cognitive impairment, clustered as healthy "Poor" and "Good" cognitive performers, were followed for an average of 18 months. Seasonal-adjusted 25(OH)D serum levels (measured by high-performance liquid chromatography-tandem mass spectrometry) were related, longitudinally, with cognitive (memory and general/executive) composite scores. Results: Overall seasonal-adjusted median serum 25(OH)D level was of 47 nmol/l [interquartile range (IQR), 38-60 nmol/l]. A negative correlation between baseline 25(OH)D and the general/executive composite score was found in the "Poor" cognitive performers (rs = -0.52, p = 0.006), an association lost after adjusting 25(OH)D levels for the season. No effect was found in both groups between seasonal-adjusted 25(OH)D levels and the variation of both memory and general/executive composites during follow-up when adjusted for age, gender and education level. Conclusion: In this healthy older population with no cognitive impairment, lower serum levels of 25(OH)D were not longitudinally associated with poorer cognitive scores.Project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER), and was funded by the European Commission (FP7) “SwitchBox—Maintaining health in old age through homeostasis” (Contract HEALTH-F2-2010-259772), and co-financed by the Portuguese North Regional Operational Program (ON.2—O Novo Norte), under the National Strategic Reference Framework (QREN), through FEDER, and by the Fundação Calouste Gulbenkian (Portugal; Contract grant number: P-139977; project “TEMPO—Better mental health during aging based on temporal prediction of individual brain aging trajectories”). NCS was supported during the work by a Research Assistantship by the Portuguese Foundation for Science and Technology (FCT, Portugal) through the “FCT Investigator Programme (200∞ Ciência),” CP-N by a “MyHealth” project (Contract DoIT-13853) research fellowship, and TC by a FCT doctoral fellowship (SFRH/BD/90078/2012

When Patrolmen Become Corrupted: Monitoring a Graph using Faulty Mobile Robots

International audienceA team of k mobile robots is deployed on a weighted graph whose edge weights represent distances. The robots perpetually move along the domain, represented by all points belonging to the graph edges, not exceeding their maximal speed. The robots need to patrol the graph by regularly visiting all points of the domain. In this paper, we consider a team of robots (patrolmen), at most f of which may be unreliable, i.e. they fail to comply with their patrolling duties. What algorithm should be followed so as to minimize the maximum time between successive visits of every edge point by a reliable patrolmen? The corresponding measure of efficiency of patrolling called idleness has been widely accepted in the robotics literature. We extend it to the case of untrusted patrolmen; we denote by Ifk (G) the maximum time that a point of the domain may remain unvisited by reliable patrolmen. The objective is to find patrolling strategies minimizing Ifk (G). We investigate this problem for various classes of graphs. We design optimal algorithms for line segments, which turn out to be surprisingly different from strategies for related patrolling problems proposed in the literature. We then use these results to study the case of general graphs. For Eulerian graphs G, we give an optimal patrolling strategy with idleness Ifk (G) = (f + 1)|E|/k, where |E| is the sum of the lengths of the edges of G. Further, we show the hardness of the problem of computing the idle time for three robots, at most one of which is faulty, by reduction from 3-edge-coloring of cubic graphs — a known NP-hard problem. A byproduct of our proof is the investigation of classes of graphs minimizing idle time (with respect to the total length of edges); an example of such a class is known in the literature under the name of Kotzig graphs

Functional Hemispheric (A)symmetries in the Aged Brain-Relevance for Working Memory

Functional hemispheric asymmetries have been described in different cognitive processes, such as decision-making and motivation. Variations in the pattern of left/right activity have been associated with normal brain functioning, and with neuropsychiatric diseases. Such asymmetries in brain activity evolve throughout life and are thought to decrease with aging, but clear associations with cognitive function have never been established. Herein, we assessed functional laterality during a working memory task (N-Back) in a healthy aging cohort (over 50 years old) and associated these asymmetries with performance in the test. Activity of lobule VI of the cerebellar hemisphere and angular gyrus was found to be lateralized to the right hemisphere, while the precentral gyrus presented left > right activation during this task. Interestingly, 1-Back accuracy was positively correlated with left > right superior parietal lobule activation, which was mostly due to the influence of the left hemisphere. In conclusion, although regions were mostly symmetrically activated during the N-Back task, performance in working memory in aged individuals seems to benefit from lateralized involvement of the superior parietal lobule.NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER), and was funded by the European Commission (FP7) “SwitchBox—Maintaining health in old age through homeostasis” (Seventh Framework Programme; Contract HEALTH-F2-2010-259772), by FEDER through the Competitiveness Factors Operational Programme (COMPETE) and by National Funds, through the Foundation for Science and Technology (FCT) under the scope of the project POCI-01-0145-FEDER-007038, by the Fundação Calouste Gulbenkian (Portugal; Contract Grant No: P-139977; project “TEMPO—Better mental health during ageing based on temporal prediction of individual brain ageing trajectories”) and by “PANINI—Physical Activity and Nutrition Influences In Ageing” (European Commission (Horizon 2020), Contract GA 675003); Fundação para a Ciência e a Tecnologia (FCT) (Grant Nos. SFRH/BD/52291/2013 to ME and PD/BD/106050/2015 to CP-N via Inter-University Doctoral Programme in Ageing and Chronic Disease (PhDOC), SFRH/BPD/80118/2011 to HL-A and SFRH/BD/90078/2012 to TCC); and FCT/MEC and ON.2–ONOVONORTE—North Portugal Regional Operational Programme 2007/2013, of the National Strategic Reference Framework (NSRF) 2007/2013, through FEDER (project FCTANR/NEU-OSD/0258/2012 to RM)info:eu-repo/semantics/publishedVersio

Reduced hedonic valuation of rewards and unaffected cognitive regulation in chronic stress

Cognition can influence choices by modulation of decision-making processes. This cognitive regulation is defined as processing information, applying knowledge, and changing preferences to consciously modulate decisions. While cognitive regulation of emotions has been extensively studied in psychiatry, few works have detailed cognitive regulation of decision-making. Stress may influence emotional behavior, cognition, and decision-making. In addition, the brain regions responsible for decision-making are sensitive to stress-induced changes. Thus, we hypothesize that chronic stress may disrupt the ability to regulate choices. Herein, we used a functional magnetic resonance imaging task where fourteen control and fifteen chronically stressed students had to cognitively upregulate or downregulate their craving before placing a bid to obtain food. We found that stressed participants placed lower bids to get the reward and chose less frequently higher bid values for food. Nevertheless, we did not find neural and behavioral differences during cognitive regulation of craving. Our outcomes revealed that chronic stress impacts decision-making after cognitive regulation of craving by reducing the valuation of food rewards but not cognitive modulation itself. Importantly, our results need further validation with larger sample sizes.MyHealth project (DoIT – Desenvolvimento e Operacionalização da Investigação de Translação, Contract DoIT-13853) and the BIAL Foundation, Porto, Portugal (Grant No. PT/FB/BL-2016-206). This work was also funded by the FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and by national funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-007038. This manuscript has been developed under the scope of the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). PaM was supported by a fellowship of the project “SwitchBox” (Contract HEALTH-F2-2010-259772). SF was supported by a combined Ph.D. scholarship from the FCT and the company iCognitus4ALL – IT Solutions, Lda (PD/BDE/127839/2016). RM was supported by the combined FCT and Enlightenment, Lda fellowship (PDE/BDE/113604/2015) from the PhDiHES progra

Saccade dysmetria indicates attenuated visual exploration in autism spectrum disorder

Background: Visual exploration in autism spectrum disorder (ASD) is characterized by attenuated social attention. The underlying oculomotor function during visual exploration is understudied, whereas oculomotor function during restricted viewing suggested saccade dysmetria in ASD by altered pontocerebellar motor modulation. Methods: Oculomotor function was recorded using remote eye tracking in 142 ASD participants and 142 matched neurotypical controls during free viewing of naturalistic videos with and without human content. The sample was heterogenous concerning age (6–30 years), cognitive ability (60–140 IQ), and male/female ratio (3:1). Oculomotor function was defined as saccade, fixation, and pupil-dilation features that were compared between groups in linear mixed models. Oculomotor function was investigated as ASD classifier and features were correlated with clinical measures. Results: We observed decreased saccade duration (∆M = −0.50, CI [−0.21, −0.78]) and amplitude (∆M = −0.42, CI [−0.12, −0.72]), which was independent of human video content. We observed null findings concerning fixation and pupil-dilation features (POWER =.81). Oculomotor function is a valid ASD classifier comparable to social attention concerning discriminative power. Within ASD, saccade features correlated with measures of restricted and repetitive behavior. Conclusions: We conclude saccade dysmetria as ASD oculomotor phenotype relevant to visual exploration. Decreased saccade amplitude and duration indicate spatially clustered fixations that attenuate visual exploration and emphasize endogenous over exogenous attention. We propose altered pontocerebellar motor modulation as underlying mechanism that contributes to atypical (oculo-)motor coordination and attention function in ASD