Does motor cortex engagement during movement preparation differentially inhibit nociceptive processing in patients with chronic whiplash associated disorders, chronic fatigue syndrome and healthy controls? An experimental study

Background: Patients with chronic fatigue syndrome (CFS) and chronic whiplash associated disorders (cWAD) present a reduced ability to activate central descending nociceptive inhibition after exercise, compared to measurements before exercise. It was hypothesised that a dysfunctional motor-induced inhibition of nociception partly explains this dysfunctional exercise-induced hypoalgesia. This study investigates if engagement of the motor system during movement preparation inhibits nociception-evoked brain responses in these patients as compared to healthy controls (HC). Methods: The experiment used laser-evoked potentials (LEPs) during three conditions (no task, mental task, movement preparation) while recording brain activity with a 32-channel electroencephalogram in 21 patients with cWAD, 20 patients with CFS and 18 HC. Two-factor mixed design Analysis of variance were used to evaluate differences in LEP amplitudes and latencies. Results: No differences in N1, N2, N2P2, and P2 LEP amplitudes were found between the HC, CFS, and cWAD groups. After nociceptive stimulation, N1, N2 (only at hand location), N2P2, and P2 LEP amplitudes significantly decreased during movement preparation compared to no task (within group differences). Conclusion: Movement preparation induces a similar attenuation of LEPs in patients with CFS, patients with cWAD and HC. These findings do not support reduced motor-induced nociceptive inhibition in these patients

Feasibility and impact study of a reward-based mobile application to improve adolescents’ snacking habits

AbstractObjectiveAdolescents’ snacking habits are driven by both explicit reflective and implicit hedonic processes. Hedonic pathways and differences in sensitivity to food rewards in addition to reflective determinants should be considered. The present study evaluated the feasibility and impact of a mobile phone-delivered intervention, incorporating explicit reflective and implicit rewarding strategies, on adolescents’ snack intake.DesignAdolescents (n 988; mean age 14·9 (sd 0·70) years, 59·4 % boys) completed a non-randomized clustered controlled trial. Adolescents (n 416) in the intervention schools (n 3) were provided with the intervention application for four weeks, while adolescents (n 572) in the control schools (n 3) followed the regular curriculum. Outcomes were differences in healthy snacking ratio and key determinants (awareness, intention, attitude, self-efficacy, habits and knowledge). Process evaluation data were collected via questionnaires and through log data of the app.ResultsNo significant positive intervention effects on the healthy snack ratio (b=−3·52 (se 1·82), P&gt;0·05) or targeted determinants were observed. Only 268 adolescents started using the app, of whom only fifty-five (20·5 %) still logged in after four weeks. Within the group of users, higher exposure to the app was not significantly associated with positive intervention effects. App satisfaction ratings were low in both high and low user groups. Moderation analyses revealed small positive intervention effects on the healthy snack ratio in high compared with low reward-sensitive boys (b=1·38 (se 0·59), P&lt;0·05).ConclusionsThe intervention was not able to improve adolescents’ snack choices, due to low reach and exposure. Future interventions should consider multicomponent interventions, teacher engagement, exhaustive participatory app content development and tailoring.</jats:sec

Impact of metformin and Dysosmobacter welbionis on diet-induced obesity and diabetes: from clinical observation to preclinical intervention.

peer reviewed[en] AIMS/HYPOTHESIS: We aimed to investigate the association between the abundance of Dysosmobacter welbionis, a commensal gut bacterium, and metabolic health in human participants with obesity and diabetes, and the influence of metformin treatment and prebiotic intervention. METHODS: Metabolic variables were assessed and faecal samples were collected from 106 participants in a randomised controlled intervention with a prebiotic stratified by metformin treatment (Food4Gut trial). The abundance of D. welbionis was measured by quantitative PCR and correlated with metabolic markers. The in vitro effect of metformin on D. welbionis growth was evaluated and an in vivo study was performed in mice to investigate the effects of metformin and D. welbionis J115T supplementation, either alone or in combination, on metabolic variables. RESULTS: D. welbionis abundance was unaffected by prebiotic treatment but was significantly higher in metformin-treated participants. Responders to prebiotic treatment had higher baseline D. welbionis levels than non-responders. D. welbionis was negatively correlated with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and fasting blood glucose levels in humans with obesity and type 2 diabetes. In vitro, metformin had no direct effect on D. welbionis growth. In mice, D. welbionis J115T treatment reduced body weight gain and liver weight, and improved glucose tolerance to a better level than metformin, but did not have synergistic effects with metformin. CONCLUSIONS/INTERPRETATION: D. welbionis abundance is influenced by metformin treatment and associated with prebiotic response, liver health and glucose metabolism in humans with obesity and diabetes. This study suggests that D. welbionis may play a role in metabolic health and warrants further investigation. CLINICAL TRIAL: NCT03852069

Common genetic variation drives molecular heterogeneity in human iPSCs.

Technology utilizing human induced pluripotent stem cells (iPS cells) has enormous potential to provide improved cellular models of human disease. However, variable genetic and phenotypic characterization of many existing iPS cell lines limits their potential use for research and therapy. Here we describe the systematic generation, genotyping and phenotyping of 711 iPS cell lines derived from 301 healthy individuals by the Human Induced Pluripotent Stem Cells Initiative. Our study outlines the major sources of genetic and phenotypic variation in iPS cells and establishes their suitability as models of complex human traits and cancer. Through genome-wide profiling we find that 5-46% of the variation in different iPS cell phenotypes, including differentiation capacity and cellular morphology, arises from differences between individuals. Additionally, we assess the phenotypic consequences of genomic copy-number alterations that are repeatedly observed in iPS cells. In addition, we present a comprehensive map of common regulatory variants affecting the transcriptome of human pluripotent cells

Identifying Extrinsic versus Intrinsic Drivers of Variation in Cell Behavior in Human iPSC Lines from Healthy Donors.

Large cohorts of human induced pluripotent stem cells (iPSCs) from healthy donors are a potentially powerful tool for investigating the relationship between genetic variants and cellular behavior. Here, we integrate high content imaging of cell shape, proliferation, and other phenotypes with gene expression and DNA sequence datasets from over 100 human iPSC lines. By applying a dimensionality reduction approach, Probabilistic Estimation of Expression Residuals (PEER), we extracted factors that captured the effects of intrinsic (genetic concordance between different cell lines from the same donor) and extrinsic (cell responses to different fibronectin concentrations) conditions. We identify genes that correlate in expression with intrinsic and extrinsic PEER factors and associate outlier cell behavior with genes containing rare deleterious non-synonymous SNVs. Our study, thus, establishes a strategy for examining the genetic basis of inter-individual variability in cell behavior

Revealing the influence of tempering on polymorphism and crystal arrangement in semicrystalline oil-in-water emulsions

The influence of tempering (i.e., successive heating and cooling) on crystallization properties of semicrystalline milk fat-in-water emulsions was studied by X-ray diffraction (XRD), differential scanning calorimetry (DSC), and cryoscanning electron microscopy. Melting profiles obtained by DSC indicate a fractionation process of milk fat in every individual fat droplet. The long spacings, as observed by XRD, were useful in the designation of polymorphic changes to a shift in fatty acid composition of the crystals. An increased layer thickness of the 3L-crystals at 20 and 30 degrees C tempering points to a preferential incorporation of long-chain unsaturated fatty acids over short-chain fatty acids. Additionally, at 30 degrees C, an increased layer thickness of the 2L-crystals assumes the incorporation of longer-chain saturated fatty acids. The highly mixed crystals, an inherent property of milk fat, seem to be fractionated in purer crystals grouping triacylglycerols with a similar fatty acid composition. Moreover, a A different crystal organization was obtained for both tempering temperatures, where tempering at 20 degrees C appears to result in a coarser structure with well-defined lamellar regions near the interface, while tempering at 30 degrees C seems to lead to a finer, more homogeneous crystal structure. The observed effects on the microstructural level will have implications on storage stability and applicability

Investigation of pigment degradation due to acetic acid vapours : Raman spectroscopic analysis

The preservation of moveable cultural heritage objects inside museums includes trying to keep these objects under the best conditions as possible. This is done, amongst others, by controlling the atmospheric conditions under which the objects are preserved: the amount of light, temperature and relative humidity, etc. should be carefully monitored in exhibitions as well as in storage rooms. However, other atmospheric components may as well be important for the optimal preservation of cultural heritage materials, such as acetic compounds derived from wood package. A study of the degradation of malachite, leadwhite, lead-tin yellow type I, red lead and pigment orange 36 is performed using Raman spectroscopy. The degradation of these pigments was analyzed after exposure to acetic acid vapours. Three different acetic acid concentrations in the atmosphere were tested: ca. 150 ppm, ca. 300 ppm and ca. 500 ppm. In all conditions, the relative humidity was kept constant at ca. 75 %. A possible colour change, which can go hand in hand with the degradation process, was evaluated by observing the change of the RGB values of the sample colour. Besides pigment orange 36, which showed to be unreactive towards the acid atmosphere, acetate species were generated for each pigment: malachite reacted towards a verdigris variety; red lead, leadwhite and lead-tin yellow degraded towards lead acetate. At high doses, red lead alters towards a black pigment, which is presumed to be plattnerite