Memory function in multiple sclerosis

Multiple Sclerosis (MS) is a disease of the central nervous system. Its diffuse pathology results in a variety of physical and psychological symptoms. Memory dysfunction is one of the most prevalent cognitive deficits associated with MS. However, the accurate assessment of memory in MS is often compromised by the coincident physical and/or cognitive difficulties of the patients. Also, there are no conventional memory tests suitable for MS patients, which grade varying types of verbal and spatial memory ability. The aim of this thesis was to develop a new test of memory which reduced the handicap imposed by sensori-motor dysfunction on cognitive test performance, and assessed recall memory, paired association, and recognition memory using matched verbal and spatial tasks. The New Test Of Memory was standardised using a sample of 85 healthy controls, stratified for age, sex, and IQ. The measure demonstrated the effects of ageing on normal memory performance, and showed good internal reliability (Cronbach's alpha verbal sections: 0.76; spatial sections: 0.75), consistency, and construct and factorial validity. The validation sample comprised 100 MS patients. The applicability of the tasks for patients with MS was demonstrated by the absence of a relationship between memory performance and measures of visual integrity and manual dexterity. The patient assessments also showed good internal reliability (Cronbach's alpha verbal sections: 0.85; spatial sections: 0.74), consistency, and construct, factorial, convergent, and discriminant validity. Patient performance was significantly impaired relative to controls, with 23 % of patients scoring more than 2 standard deviations below the age group control mean on the verbal sections, and 15 % on the spatial sections. The patterns of impairment demonstrated by the patients did not provide support for either the acquisition or retrieval deficit hypotheses, suggesting that memory deficiencies in MS may not fit a simple, single deficit model

Behaviour of the clay cover of a site for storing nuclear waste of verylow activity submitted to differential settlement of underlying waste:laboratory and field bending tests

International audienceThe behaviour of the cover barrier of a site for storing nuclear waste of very low activity isstudied. The risk of a bending of the clay layer in case of differential settlements within underlying waste isparticularly studied. Laboratory and field bending tests are performed. Influence of the water content on themechanical behaviour of the clay is examined. Initialization and propagation of cracks are studied. The limitvalue of the extension strain of the clay layer without cracking is characterized. Results of field and laboratorybending tests are presented. The main aim is to optimize the use of clay as landfill cover, in terms ofconditions of implementation (water content, compaction energy)

Untargeted metabolomics to reveal red versus white meat‐associated gut metabolites in a prudent and western dietary context

Scope: To improve understanding of the epidemiological link between red and processed meat consumption and chronic diseases, more insight in the formation of metabolites during meat digestion is warranted.Methods and results: Untargeted MS-based metabolomics was applied to explore the impact of red and processed meat consumption (compared to chicken), combined with a prudent or Western dietary pattern. A pig feeding study (n=32), as a sentinel for humans, was conducted in a 2×2 factorial design for four weeks. The luminal content of the small intestine and colon of the pigs were collected to determine their metabolic fingerprints. Seventy-six unique metabolites (38 in small intestine, 32 in colon, and 6 in both intestinal compartments) contributing tothe distinct gut metabolic profiles of pigs fed either chicken or red and processed meat were (tentatively) identified. Consumption of red and processed meat resulted in higher levels of short-and medium-chain acylcarnitines and 3-dehydroxycarnitine, irrespective of dietary context, whereas long-chain acylcarnitines and monoacylglycerols were specifically associated with the red and processed-Western diet.Conclusion: The identification of red and processed meat-associated gut metabolites in this study contributes to the understanding of meat digestion in a complex but controlled dietary context and its potential health effect

Identifying Visible Tissue in Intraoperative Ultrasound Images during Brain Surgery: A Method and Application

Intraoperative ultrasound scanning is a demanding visuotactile task. It requires operators to simultaneously localise the ultrasound perspective and manually perform slight adjustments to the pose of the probe, making sure not to apply excessive force or breaking contact with the tissue, whilst also characterising the visible tissue. In this paper, we propose a method for the identification of the visible tissue, which enables the analysis of ultrasound probe and tissue contact via the detection of acoustic shadow and construction of confidence maps of the perceptual salience. Detailed validation with both in vivo and phantom data is performed. First, we show that our technique is capable of achieving state of the art acoustic shadow scan line classification - with an average binary classification accuracy on unseen data of 0.87. Second, we show that our framework for constructing confidence maps is able to produce an ideal response to a probe's pose that is being oriented in and out of optimality - achieving an average RMSE across five scans of 0.174. The performance evaluation justifies the potential clinical value of the method which can be used both to assist clinical training and optimise robot-assisted ultrasound tissue scanning

Impact of red versus white meat consumption in a prudent or Western dietary pattern on the oxidative status in a pig model

Human diets contain a complex mixture of antioxidants and pro-oxidants that contribute to the body's oxidative status. In this study, 32 pigs were fed chicken versus red and processed meat in the context of a prudent or Western dietary pattern for 4 weeks, to investigate their oxidative status. Lipid oxidation products (malondialdehyde, 4-hydroxy-2-nonenal, and hexanal) were higher in the chicken versus red and processed meat diets (1.7- to 8.3-fold) and subsequent in vitro (1.3- to 1.9-fold) and in vivo (1.4 to 3-fold) digests (P < 0.001), which was presumably related to the higher polyunsaturated fatty acid content in chicken meat and/or the added antioxidants in processed meat. However, diet had only a marginal or no effect on the systemic oxidative status, as determined by plasma oxygen radical absorbance capacity, malondialdehyde, glutathione, and glutathione peroxidase activity in blood and organs, except for alpha-tocopherol, which was higher after the consumption of the chicken-Western diet. In conclusion, in contrast to the hypothesis, the consumption of chicken in comparison to that of the red and processed meat resulted in higher concentrations of lipid oxidation products in the pig intestinal contents; however, this was not reflected in the body's oxidative status

Mutations in splicing factor genes are a major cause of autosomal dominant retinitis pigmentosa in Belgian families

Purpose : Autosomal dominant retinitis pigmentosa (adRP) is characterized by an extensive genetic heterogeneity, implicating 27 genes, which account for 50 to 70% of cases. Here 86 Belgian probands with possible adRP underwent genetic testing to unravel the molecular basis and to assess the contribution of the genes underlying their condition. Methods : Mutation detection methods evolved over the past ten years, including mutation specific methods (APEX chip analysis), linkage analysis, gene panel analysis (Sanger sequencing, targeted next-generation sequencing or whole exome sequencing), high-resolution copy number screening (customized microarray-based comparative genomic hybridization). Identified variants were classified following American College of Medical Genetics and Genomics (ACMG) recommendations. Results : Molecular genetic screening revealed mutations in 48/86 cases (56%). In total, 17 novel pathogenic mutations were identified: four missense mutations in RHO, five frameshift mutations in RP1, six mutations in genes encoding spliceosome components (SNRNP200, PRPF8, and PRPF31), one frameshift mutation in PRPH2, and one frameshift mutation in TOPORS. The proportion of RHO mutations in our cohort (14%) is higher than reported in a French adRP population (10.3%), but lower than reported elsewhere (16.5-30%). The prevalence of RP1 mutations (10.5%) is comparable to other populations (3.5%-10%). The mutation frequency in genes encoding splicing factors is unexpectedly high (altogether 19.8%), with PRPF31 the second most prevalent mutated gene (10.5%). PRPH2 mutations were found in 4.7% of the Belgian cohort. Two families (2.3%) have the recurrent NR2E3 mutation p.(Gly56Arg). The prevalence of the recurrent PROM1 mutation p.(Arg373Cys) was higher than anticipated (3.5%). Conclusions : Overall, we identified mutations in 48 of 86 Belgian adRP cases (56%), with the highest prevalence in RHO (14%), RP1 (10.5%) and PRPF31 (10.5%). Finally, we expanded the molecular spectrum of PRPH2, PRPF8, RHO, RP1, SNRNP200, and TOPORS-associated adRP by the identification of 17 novel mutations

Effect of streptozotocin-induced diabetes on myocardial blood flow reserve assessed by myocardial contrast echocardiography in rats

The role of structural and functional abnormalities of small vessels in diabetes cardiomyopathy remains unclear. Myocardial contrast echocardiography allows the quantification of myocardial blood flow at rest and during dipyridamole infusion. The aim of the study was to determine the myocardial blood flow reserve in normal rats compared with Streptozotocin-induced diabetic rats using contrast echocardiography

Impact of model resolution on tropical cyclone simulation using the HighResMIP–PRIMAVERA multimodel Ensemble

A multimodel, multiresolution set of simulations over the period 1950–2014 using a common forcing protocol from CMIP6 HighResMIP have been completed by six modeling groups. Analysis of tropical cyclone performance using two different tracking algorithms suggests that enhanced resolution toward 25 km typically leads to more frequent and stronger tropical cyclones, together with improvements in spatial distribution and storm structure. Both of these factors reduce typical GCM biases seen at lower resolution. Using single ensemble members of each model, there is little evidence of systematic improvement in interannual variability in either storm frequency or accumulated cyclone energy as compared with observations when resolution is increased. Changes in the relationships between large-scale drivers of climate variability and tropical cyclone variability in the Atlantic Ocean are also not robust to model resolution. However, using a larger ensemble of simulations (of up to 14 members) with one model at different resolutions does show evidence of increased skill at higher resolution. The ensemble mean correlation of Atlantic interannual tropical cyclone variability increases from ~0.5 to ~0.65 when resolution increases from 250 to 100 km. In the northwestern Pacific Ocean the skill keeps increasing with 50-km resolution to 0.7. These calculations also suggest that more than six members are required to adequately distinguish the impact of resolution within the forced signal from the weather noise

Targeting of vascular cell adhesion molecule-1 by18F-labelled nanobodies for PET/CT imaging of inflamed atherosclerotic plaques

Aims Positron emission tomography-computed tomography (PET-CT) is a highly sensitive clinical molecular imaging modality to study atherosclerotic plaque biology. Therefore, we sought to develop a new PET tracer, targeting vascular cell adhesion molecule (VCAM)-1 and validate it in a murine atherosclerotic model as a potential agent to detect atherosclerotic plaque inflammation. Methods and results The anti-VCAM-1 nanobody (Nb) (cAbVCAM-1-5) was radiolabelled with Fluorine-18 (F-18), with a radiochemical purity of >98%. In vitro cell-binding studies showed specific binding of the tracer to VCAM-1 expressing cells. In vivo PET/CT imaging of ApoE(-/-) mice fed aWestern diet or control mice was performed at 2h30 post-injection of [F-18]-FB-cAbVCAM-1-5 or F-18-control Nb. Additionally, plaque uptake in different aorta segments was evaluated ex vivo based on extent of atherosclerosis. Atherosclerotic lesions in the aortic arch of ApoE(-/-) mice, injected with [F-18]-FB-anti-VCAM-1 Nb, were successfully identified using PET/CT imaging, while background signal was observed in the control groups. These results were confirmed by ex vivo analyses where uptake of [F-18]-FB-cAbVCAM-1-5 in atherosclerotic lesions was significantly higher compared with control groups. Moreover, uptake increased with the increasing extent of atherosclerosis (Score 0: 0.68 +/- 0.10, Score 1: 1.18 +/- 0.36, Score 2: 1.49 +/- 0.37, Score 3: 1.48 +/- 0.38% ID/g, Spearman's r(2) = 0.675, P < 0.0001). High lesion-to-heart, lesion-to-blood, and lesion-to-control vessel ratios were obtained (12.4 +/- 0.4, 3.3 +/- 0.4, and 3.1 +/- 0.6, respectively). Conclusion The [F-18]-FB-anti-VCAM-1 Nb, cross-reactive for both mouse and human VCAM-1, allows non-invasive PET/CT imaging of VCAM-1 expression in atherosclerotic plaques in a murine model and may represent an attractive tool for imaging vulnerable atherosclerotic plaques in patients