Alternative avenues in the assessment of driving capacities in older drivers and implications for training

The population aging, combined with the overrepresentation of older drivers in car crashes, engendered a whole body of research destined at finding simple and efficient assessment methods of driving capacities. However, this quest is little more than a utopian dream, given that car crashes and unsafe driving behaviours can result from a plethora of interacting factors. This review highlights the main problems of the current assessment methods and training programs, and presents theoretical and empirical arguments justifying the need of reorienting the research focus. Our discussion is elaborated in light of the fundamental principle of specificity in learning and practice. We also identify overlooked variables that are deterministic when assessing, and training, a complex ability like driving. We especially focus on the role of the sensorimotor transformation process. Finally, we propose alternative methods that are in-line with the recent trends in educational programs that use virtual reality and simulation technologies

Small critical RNAs in the scrapie agent

Unconventional infectious agents cause transmissible spongiform encephalopathy (TSE) diseases including scrapie and bovine spongiform encephalopathy (BSE) in animals and Creutzfeldt-Jakob disease in humans. The protein only hypothesis claims that the TSE agent is composed solely of the protein called prion (PrP^sc^)^1^. This protein is the misfolded form of a host-encoded cellular protein, PrP^c^ exerting presumably a vital role at the synapse^2^. Even though now widely accepted, the prion concept fails to provide in certain circumstances^3-6^, a satisfying interpretation of the infectious phenomenon. Using the 263K scrapie-hamster model, we conducted a transmission study to search for a putative prion-associated factor indispensable for infectivity. Here we show that innocuous recombinant prion protein (recPrP) was capable, in a reproducible manner, of transmitting scrapie disease when the protein was [beta]–sheet converted in a solution containing PrP^sc^-derived RNA material. Analysis of the PrP-RNA mixture revealed the association of recPrP with two prominent populations of small RNA molecules having an average length of about ~27 and ~55 nucleotides. We conclude that the nature of the TSE agent seems to be composed of a nucleoprotein molecular complex, in which informative RNA molecules of small sizes are associated with the misfolded prion protein (PrP^sc^)

Evidence for cognitive vestibular integration impairment in idiopathic scoliosis patients

<p>Abstract</p> <p>Background</p> <p>Adolescent idiopathic scoliosis is characterized by a three-dimensional deviation of the vertebral column and its etiopathogenesis is unknown. Various factors cause idiopathic scoliosis, and among these a prominent role has been attributed to the vestibular system. While the deficits in sensorimotor transformations have been documented in idiopathic scoliosis patients, little attention has been devoted to their capacity to integrate vestibular information for cognitive processing for space perception. Seated idiopathic scoliosis patients and control subjects experienced rotations of different directions and amplitudes in the dark and produced saccades that would reproduce their perceived spatial characteristics of the rotations (vestibular condition). We also controlled for possible alteration of the oculomotor and vestibular systems by measuring the subject's accuracy in producing saccades towards memorized peripheral targets in absence of body rotation and the gain of their vestibulo-ocular reflex.</p> <p>Results</p> <p>Compared to healthy controls, the idiopathic scoliosis patients underestimated the amplitude of their rotations. Moreover, the results revealed that idiopathic scoliosis patients produced accurate saccades to memorized peripheral targets in absence of body rotation and that their vestibulo-ocular reflex gain did not differ from that of control participants.</p> <p>Conclusion</p> <p>Overall, results of the present study demonstrate that idiopathic scoliosis patients have an alteration in cognitive integration of vestibular signals. It is possible that severe spine deformity developed partly due to impaired vestibular information travelling from the cerebellum to the vestibular cortical network or alteration in the cortical mechanisms processing the vestibular signals.</p

Responses to hydric stress in the seed-borne necrotrophic fungus Alternaria brassicicola

Alternaria brassicicola is a necrotrophic fungus causing black spot disease and is an economically important seed-borne pathogen of cultivated brassicas. Seed transmission is a crucial component of its parasitic cycle as it promotes long-term survival and dispersal. Recent studies, conducted with the Arabidopsis thaliana/A. brassicicola pathosystem, showed that the level of susceptibility of the fungus to water stress strongly influenced its seed transmission ability. In this study, we gained further insights into the mechanisms involved in the seed infection process by analyzing the transcriptomic and metabolomic responses of germinated spores of A. brassicicola exposed to water stress. Then, the repertoire of putative hydrophilins, a group of proteins that are assumed to be involved in cellular dehydration tolerance, was established in A. brassicicola based on the expression data and additional structural and biochemical criteria. Phenotyping of single deletion mutants deficient for fungal hydrophilin-like proteins showed that they were affected in their transmission to A. thaliana seeds, although their aggressiveness on host vegetative tissues remained intact

Early stages of fat crystallisation evaluated by low‐field NMR and small‐angle X‐ray scattering

Low‐field time‐domain nuclear magnetic resonance (NMR; 20 MHz) is commonly used in the studies of fats in the form of solid fat content (SFC) measurements. However, it has the disadvantage of low sensitivity to small amounts of crystalline material (0.5%), thus often incorrectly determining crystallisation induction times. From spin–lattice relaxation rate measurements (R1) during the isothermal crystallisation measurements of cocoa butter between 0.01 and 10 MHz using fast field cycling NMR, we learnt previously that the most sensitive frequency region is below 1 MHz. Thus, we focused on analysing our 10‐kHz data in detail, by observing the time dependence of R1 and comparing it with standard SFCNMR and SFC determinations from small‐angle X‐ray scattering (SFCSAXS). Although not reflecting directly the SFC, the R1 at this low frequency is very sensitive to changes in molecular aggregation and hence potentially serving as an alternative for determination of crystallisation induction times. Alongside R1, we also show that SFCSAXS is more sensitive to early stages of crystallisation, that is, standard SFCNMR determinations become more relevant when crystal growth starts to dominate the crystallisation process but fail to pick up earlier crystallisation steps. This paper thus demonstrates the potential of studying triacylglycerols at frequencies below 1 MHz for obtaining further understanding of the early crystallisation stages of fats and presents an alternative and complementary method to estimate SFC by SAXS

Altered sensory-weighting mechanisms is observed in adolescents with idiopathic scoliosis

BACKGROUND: Scoliosis is the most common type of spinal deformity. In North American children, adolescent idiopathic scoliosis (AIS) makes up about 90% of all cases of scoliosis. While its prevalence is about 2% to 3% in children aged between 10 to 16 years, girls are more at risk than boys for severe progression with a ratio of 3.6 to 1. The aim of the present study was to test the hypothesis that idiopathic scoliosis interferes with the mechanisms responsible for sensory-reweighting during balance control. METHODS: Eight scoliosis patients (seven female and one male; mean age: 16.4 years) and nine healthy adolescents (average age 16.5 years) participated in the experiment. Visual and ankle proprioceptive information was perturbed (eyes closed and/or tendon vibration) suddenly and then returned to normal (eyes open and/or no tendon vibration). An AMTI force platform was used to compute centre of pressure root mean squared velocity and sway density curve. RESULTS: For the control condition (eyes open and no tendon vibration), adolescent idiopathic scoliosis patients had a greater centre of pressure root mean squared velocity (variability) than control participants. Reintegration of ankle proprioception, when vision was either available or removed, led to an increased centre of pressure velocity variability for the adolescent idiopathic scoliosis patients whereas the control participants reduced their centre of pressure velocity variability. Moreover, in the absence of vision, adolescent idiopathic scoliosis exhibited an increased centre of pressure velocity variability when ankle proprioception was returned to normal (i.e. tendon vibration stopped). The analysis of the sway density plot suggests that adolescent idiopathic scoliosis patients, during sensory reintegration, do not scale appropriately their balance control commands. CONCLUSION: Altogether, the present results demonstrate that idiopathic scoliosis adolescents have difficulty in reweighting sensory inputs following a brief period of sensory deprivation

Calorie Restriction Increases Muscle Mitochondrial Biogenesis in Healthy Humans

BACKGROUND: Caloric restriction without malnutrition extends life span in a range of organisms including insects and mammals and lowers free radical production by the mitochondria. However, the mechanism responsible for this adaptation are poorly understood. METHODS AND FINDINGS: The current study was undertaken to examine muscle mitochondrial bioenergetics in response to caloric restriction alone or in combination with exercise in 36 young (36.8 ± 1.0 y), overweight (body mass index, 27.8 ± 0.7 kg/m(2)) individuals randomized into one of three groups for a 6-mo intervention: Control, 100% of energy requirements; CR, 25% caloric restriction; and CREX, caloric restriction with exercise (CREX), 12.5% CR + 12.5% increased energy expenditure (EE). In the controls, 24-h EE was unchanged, but in CR and CREX it was significantly reduced from baseline even after adjustment for the loss of metabolic mass (CR, −135 ± 42 kcal/d, p = 0.002 and CREX, −117 ± 52 kcal/d, p = 0.008). Participants in the CR and CREX groups had increased expression of genes encoding proteins involved in mitochondrial function such as PPARGC1A, TFAM, eNOS, SIRT1, and PARL (all, p < 0.05). In parallel, mitochondrial DNA content increased by 35% ± 5% in the CR group (p = 0.005) and 21% ± 4% in the CREX group (p < 0.004), with no change in the control group (2% ± 2%). However, the activity of key mitochondrial enzymes of the TCA (tricarboxylic acid) cycle (citrate synthase), beta-oxidation (beta-hydroxyacyl-CoA dehydrogenase), and electron transport chain (cytochrome C oxidase II) was unchanged. DNA damage was reduced from baseline in the CR (−0.56 ± 0.11 arbitrary units, p = 0.003) and CREX (−0.45 ± 0.12 arbitrary units, p = 0.011), but not in the controls. In primary cultures of human myotubes, a nitric oxide donor (mimicking eNOS signaling) induced mitochondrial biogenesis but failed to induce SIRT1 protein expression, suggesting that additional factors may regulate SIRT1 content during CR. CONCLUSIONS: The observed increase in muscle mitochondrial DNA in association with a decrease in whole body oxygen consumption and DNA damage suggests that caloric restriction improves mitochondrial function in young non-obese adults

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Pétrographie, sédimentologie et analyse des facies de la formation de Daubrée, Chapais, Québec

Une formation sédimentaire se situe au sud-ouest du lac Opémisca dans le canton de Daubrée. Elle fut identifiée comme la Formation de Daubrée dans le synclinal de Chapais par Wolhuter qui cartographia la moitié sud du canton de Daubrée en 1962. Le présent travail consiste à faire des coupes stratigraphiques au travers de cette formation, à en étudier la pétrographie, la pétrologie sédimentaire et finalement à en préciser la paléogéographie. La formation se compose en prédominance de grès feldspathiques (grauwackes) et pauvres en quartz. Approximativement 60 à 70% de la Formation de Daubrée consiste en turbidites classiques (lits de grès de 5 à 100cm d'épaisseur) montrant des séquences cycliques de Bouma (Ta-d ou Tb-d). Des laminations convolutées dans la partie supérieure des lits, des dykes de grès, des structures d'échappement d'eau et des injections de shales dans les lits de grès sus-jacents prouvent la grande vitesse de sédimentation. La base de la Formation de Daubrée est composée sensiblement des mêmes lithologies (shales noirs, grès volcanoclastiques, dérivés des roches pyroclastiques felsiques, et quelques couches de conglomérats volcanoclastiques mono- et hétérolithiques) que celles du sommet de la Formation de Blondeau sous-jacente, ce qui fait penser que le contact est transitionnel. Les conglomérats sont composés principalement (95%) de cailloux dérivés de la Formation de Blondeau sous-jacente, impliquant qu'une partie de la Formation de Daubrée a une base érosionnelle. Des études sédimentologiques suggèrent un contact net, sans discordance angulaire mais non-concordant, entre le sommet de la Formation de Daubrée et la base de la Formation de Hatty dans les cantons de Daubrée et de Dolomieu. Il est suggéré que la Formation de Daubrée représente un cône alluvionnaire de matériel pyroclastique, sus-jacent à la sédimentation de fond représentée par la Formation de Blondeau. Durant cette période, des îles étendues se formaient, accompagnées d'une activité pyroclastique extensive. Les produits de l'érosion de ces îles furent déposés dans des bassins de failles créant des turbidites. Une faible discordance entre les Formations de Blondeau et Daubrée, visible en certains endroits, suggère également des mouvements tectoniques. La Formation de Daubrée est placée au sommet du Groupe de Roy, mais se classe principalement comme unité de transition entre le Groupe de Roy et le Groupe d'Opémisca