A Schwarz Waveform Relaxation Method for Advection—Diffusion—Reaction Problems with Discontinuous Coefficients and Non-matching Grids

International audienceWe present a non-overlapping Schwarz waveform relaxation method for solving advection-reaction-diffusion problems in heterogeneous media. The do-main decomposition method is global in time, which permits the use of different time steps in different subdomains. We determine optimal non-local, and optimized Robin transmission conditions. We also present a space-time finite volume scheme es-pecially designed to handle such transmission conditions. We show the performance of the method on an example inspired from nuclear waste disposal simulations

Which dimensions of impulsivity are related to problematic practice of physical exercise?

Problematic practice of physical exercise (PPPE) has been suggested to be a behavioral addiction. Impulsivity represents a core dimension of behavioral addictions. However, little is known about impulsivity facets in PPPE. The aim of this study was to investigate the role of impulsivity facets in PPPE. Methods A total of 684 students (between 18 and 25 years) took part in this study and filled up a battery of questionnaire, which consisted of following measures – Global Physical Activity Questionnaire, Exercise Dependence Scale – Revised, and the UPPS Impulsive Behavior Scale. Multiple regression analyses were utilized to investigate the predictive role of each impulsivity facet in PPPE. Results Age, the total level of physical activity per day, sex (male), negative urgency, and sensation seeking were found to be significant predictors of PPPE. A categorical analysis of PPPE revealed that negative urgency, positive urgency, and sensation seeking were significantly higher in the dependent category of PPPE. Discussion and conclusions Associations to negative urgency and sensation seeking might indicate that PPPE serves to regulate or alleviate negative affect or aversive emotional states. Thus, PPPE could be conceptualized as a short-term coping strategy dedicated to relieving negative affective states, like other maladaptive behaviors such as binge eating, binge drinking, or compulsive buying

Preventive fraction of physical fitness on risk factors in cardiac patients: Retrospective epidemiological study

International audienceAIM: To quantify the preventive fraction of physical fitness on the risk factors in patients with cardiovascular diseases (CVDs).METHODS: A total of 249 subjects (205 men and 44 women) suffering from CVD were categorized into four groups, according to their percentage of physical fitness. We calculated the odds ratio to obtain the preventive fraction in order to evaluate the impact of the physical fitness level on the risk factors (i.e. , abdominal obesity, depression, diabetes, dyslipidemia, hypertension, obesity, overweight and smoking).RESULTS: It is observed that a normal physical fitness level is sufficient to induce a preventive action on abdominal obesity (38%), diabetes (12%), hypertension (33%), obesity (12%) and overweight (11%). Also, the preventive fraction increases with the level of physical fitness, in particular for hypertension (36%) and overweight (16%). A high physical fitness level does not necessarily induce a preventive action in most risk factors, excluding depression.CONCLUSION: This is the first study which demonstrates that reaching a normal physical fitness level is enough to induce aprotection for some risk factors, despite having a CVD

Risk perception and risk-taking among skateboarders

International audienceSkateboarding is considered to be a high risk activity. Although many studies have identified risk factors associated with skateboarding injuries, few have provided detailed in-depth knowledge on participants' psychological dispositions towards risk behaviors. The aim of this study was to identify individual factors associated with risk perception and risk-taking among skateboarders. Telephone interviews were conducted with 158 skateboarders (mean age = 18.1 years) recruited in 11 Montreal skateparks. Age, self-efficacy, previous injuries, fear of being injured, sensation seeking and experience level were all included in two linear regression models that were run for risk perception and risk-taking. Age, experience level, sensation seeking, and risk perception are significant explanatory variables of risk-taking. Results show that sensation seeking was the only significant factor associated with risk perception. These results allow for a better understanding of the behavior of skateboarders, they highlight the importance of impulsive sensation seeking in risk perception as well as risk-taking. This study characterizes skateboarders who take risks and provides additional information on interventions for injury prevention

Metabolic role of the hepatic valine/3-hydroxyisobutyrate (3-HIB) pathway in fatty liver disease

Background: The valine (branched-chain amino acid) metabolite 3-hydroxyisobutyrate (3-HIB), produced by 3-Hydroxyisobutyryl-CoA Hydrolase (HIBCH), is associated with insulin resistance and type 2 diabetes, but implicated tissues and cellular mechanisms are poorly understood. We hypothesized that HIBCH and 3-HIB regulate hepatic lipid accumulation. Methods: HIBCH mRNA in human liver biopsies (“Liver cohort”) and plasma 3-HIB (“CARBFUNC” cohort) were correlated with fatty liver and metabolic markers. Human Huh7 hepatocytes were supplemented with fatty acids (FAs) to induce lipid accumulation. Following HIBCH overexpression, siRNA knockdown, inhibition of PDK4 (a marker of FA β-oxidation) or 3-HIB supplementation, we performed RNA-seq, Western blotting, targeted metabolite analyses and functional assays. Findings: We identify a regulatory feedback loop between the valine/3-HIB pathway and PDK4 that shapes hepatic FA metabolism and metabolic health and responds to 3-HIB treatment of hepatocytes. HIBCH overexpression increased 3-HIB release and FA uptake, while knockdown increased cellular respiration and decreased reactive oxygen species (ROS) associated with metabolic shifts via PDK4 upregulation. Treatment with PDK4 inhibitor lowered 3-HIB release and increased FA uptake, while increasing HIBCH mRNA. Implicating this regulatory loop in fatty liver, human cohorts show positive correlations of liver fat with hepatic HIBCH and PDK4 expression (Liver cohort) and plasma 3-HIB (CARBFUNC cohort). Hepatocyte 3-HIB supplementation lowered HIBCH expression and FA uptake and increased cellular respiration and ROS. Interpretation: These data implicate the hepatic valine/3-HIB pathway in mechanisms of fatty liver, reflected in increased plasma 3-HIB concentrations, and present possible targets for therapeutic intervention.publishedVersio

Attention-deficit hyperactivity disorder and addictions (substance and behavioral): Prevalence and characteristics in a multicenter study in France

Aim The aim of this study is to determine the possible links between attention-deficit hyperactivity disorder (ADHD) and the presence of concomitant addictions with or without substance use in a French student population. Measures A battery of questionnaire measuring socioeconomic characteristics, university curriculum, ADHD (Wender Utah Rating Scale and Adult ADHD Self-Report Scale), substance consumptions (alcohol, tobacco, and cannabis), and behavioral addictions [(eating disorders (SCOFF)], Internet addiction (Internet Addiction Test), food addiction (Yale Food Addiction Scale), compulsive buying (Echeburua’s), and problem gambling (The Canadian Problem Gambling Index)] and measures of physical activity (Godin’s Leisure Time Exercise Questionnaire) was filled up by university students in Rouen and Nanterre in France. Results A total of 1,517 students were included (472 from Paris Nanterre and 1,042 from Rouen). The mean age was 20.6 years (SD = 3.6) and the sex ratio male to female was 0.46. The prevalence of ADHD among the students (current ADHD with a history of ADHD in childhood) was 5.6%. A quarter (25.7%) of students had already repeated their university curriculum, compared to 42.2% among the students with ADHD. Students with possible ADHD had repeated classes more often and believed to have a lower academic level than the students without ADHD. Significant differences were found as students with ADHD were less likely to succeed in their studies (repeated classes more often) than non-ADHD students, and considered their academic level to be lower. They also had significantly higher scores on substance (alcohol, cannabis, and tobacco) as well as behavioral addictions (gambling, compulsive buying disorder, eating disorders, and Internet addiction). Conclusion It seems essential to determine students’ problems and propose interventions adapted to students’ needs, in order to reduce the negative impact on their future academic and global successes

PLoS ONE

Lyme disease is a multisystemic disorder caused by B. burgdorferi sl. The molecular basis for specific organ involvement is poorly understood. The skin plays a central role in the development of Lyme disease as the entry site of B. burgdorferi in which specific clones are selected before dissemination. We compared the skin inflammatory response (antimicrobial peptides, cytokines and chemokines) elicited by spirochete populations recovered from patients presenting different clinical manifestations. Remarkably, these spirochete populations induced different inflammatory profiles in the skin of C3H/HeN mice. As spirochete population transmitted into the host skin is heterogeneous, we isolated one bacterial clone from a population recovered from a patient with neuroborreliosis and compared its virulence to the parental population. This clone elicited a strong cutaneous inflammatory response characterized by MCP-1, IL-6 and antimicrobial peptides induction. Mass spectrometry of this clone revealed 110 overexpressed proteins when compared with the parental population. We further focused on the expression of nine bacterial surface proteins. bb0347 coding for a protein that interacts with host fibronectin, allowing bacterial adhesion to vascular endothelium and extracellular matrix, was found to be induced in host skin with another gene bb0213 coding for a hypothetical protein. These findings demonstrate the heterogeneity of the B. burgdorferi ss population and the complexity of the interaction involved early in the skin

Cognitive impairment induced by delta9-tetrahydrocannabinol occurs through heteromers between cannabinoid CB1 and serotonin 5-HT2A receptors

Delta-9-tetrahydrocannabinol (THC), the main psychoactive compound of marijuana, induces numerous undesirable effects, including memory impairments, anxiety, and dependence. Conversely, THC also has potentially therapeutic effects, including analgesia, muscle relaxation, and neuroprotection. However, the mechanisms that dissociate these responses are still not known. Using mice lacking the serotonin receptor 5-HT2A, we revealed that the analgesic and amnesic effects of THC are independent of each other: while amnesia induced by THC disappears in the mutant mice, THC can still promote analgesia in these animals. In subsequent molecular studies, we showed that in specific brain regions involved in memory formation, the receptors for THC and the 5-HT2A receptors work together by physically interacting with each other. Experimentally interfering with this interaction prevented the memory deficits induced by THC, but not its analgesic properties. Our results highlight a novel mechanism by which the beneficial analgesic properties of THC can be dissociated from its cognitive side effects

Positive and Negative Urgency as a single coherent construct: Evidence from a large‐scale network analysis in clinical and non‐clinical samples

Aims: Negative and positive urgency are emotion-related impulsivity traits that are thought to be transdiagnostic factors in psychopathology. However, it has recently been claimed that these two traits are closely related to each other and that considering them separately might have limited conceptual and methodological value. The present study aimed to examine whether positive and negative urgency constructs constitute separate impulsivity traits. Methods: In contrast to previous studies that have used latent variable approaches, this study employed an item-based network analysis conducted in two different samples: a large sample of non-clinical participants (N = 18,568) and a sample of clinical participants with psychiatric disorders (N = 385). Results: The network analysis demonstrated that items denoting both positive and negative urgency cohere as a single cluster of items termed “general urgency” in both clinical and non-clinical samples, thereby suggesting that differentiating positive and negative urgency as separate constructs is not necessary. Conclusion: These findings have important implications for the conceptualization and assessment of urgency and, more broadly, for future research on impulsivity, personality, and psychopathology

Phase III randomized trial of sunitinib versus capecitabine in patients with previously treated HER2-negative advanced breast cancer

This multicenter, randomized, open-label phase III trial (planned enrollment: 700 patients) was conducted to test the hypothesis that single-agent sunitinib improves progression-free survival (PFS) compared with capecitabine as treatment for advanced breast cancer (ABC). Patients with HER2-negative ABC that recurred after anthracycline and taxane therapy were randomized (1:1) to sunitinib 37.5 mg/day or capecitabine 1,250 mg/m2 (1,000 mg/m2 in patients >65 years) BID on days 1–14 q3w. The independent data-monitoring committee (DMC) determined during the first interim analysis (238 patients randomized to sunitinib, 244 to capecitabine) that the trial be terminated due to futility in reaching the primary endpoint. No statistical evidence supported the hypothesis that sunitinib improved PFS compared with capecitabine (one-sided P = 0.999). The data indicated that PFS was shorter with sunitinib than capecitabine (median 2.8 vs. 4.2 months, respectively; HR, 1.47; 95% CI, 1.16–1.87; two-sided P = 0.002). Median overall survival (15.3 vs. 24.6 months; HR, 1.17; two-sided P = 0.350) and objective response rates (11 vs. 16%; odds ratio, 0.65; P = 0.109) were numerically inferior with sunitinib versus capecitabine. While no new or unexpected safety findings were reported, sunitinib treatment was associated with higher frequencies and greater severities of many common adverse events (AEs) compared with capecitabine, resulting in more temporary discontinuations due to AEs with sunitinib (66 vs. 51%). The relative dose intensity was lower with sunitinib than capecitabine (73 vs. 95%). Based on these efficacy and safety results, sunitinib should not be used as monotherapy for patients with ABC