Integrative Multi-omics Analysis to Characterize Human Brain Ischemia

Stroke is a major cause of death and disability. A better comprehension of stroke pathophysiology is fundamental to reduce its dramatic outcome. The use of high-throughput unbiased omics approaches and the integration of these data might deepen the knowledge of stroke at the molecular level, depicting the interaction between different molecular units. We aimed to identify protein and gene expression changes in the human brain after ischemia through an integrative approach to join the information of both omics analyses. The translational potential of our results was explored in a pilot study with blood samples from ischemic stroke patients. Proteomics and transcriptomics discovery studies were performed in human brain samples from six deceased stroke patients, comparing the infarct core with the corresponding contralateral brain region, unveiling 128 proteins and 2716 genes significantly dysregulated after stroke. Integrative bioinformatics analyses joining both datasets exposed canonical pathways altered in the ischemic area, highlighting the most influential molecules. Among the molecules with the highest fold-change, 28 genes and 9 proteins were selected to be validated in five independent human brain samples using orthogonal techniques. Our results were confirmed for NCDN, RAB3C, ST4A1, DNM1L, A1AG1, A1AT, JAM3, VTDB, ANXA1, ANXA2, and IL8. Finally, circulating levels of the validated proteins were explored in ischemic stroke patients. Fluctuations of A1AG1 and A1AT, both up-regulated in the ischemic brain, were detected in blood along the first week after onset. In summary, our results expand the knowledge of ischemic stroke pathology, revealing key molecules to be further explored as biomarkers and/or therapeutic targets

Eating behavior style predicts craving and anxiety experienced in food-related virtual environments by patients with eating disorders and healthy controls

Eating behavior style (emotional, restrictive, or external) has been proposed as an explanation for the differences in response to food-related cues between people who overeat and those who do not, and has been also considered a target for the treatment of eating disorders (EDs) characterized by lack of control over eating and weight-related (overweight/obesity) conditions. The aim of this study was to analyze the relationship between eating behavior style and psychophysiological responses (self-reported food craving and anxiety) to food-related virtual reality (VR) environments in outpatients with bulimia nervosa (BN) and binge eating disorder (BED) and to compare them with healthy participants. Fifty-eight outpatients and 135 healthy participants were exposed to palatable foods in four experimental everyday real-life VR environments (kitchen, dining room, bedroom and cafe). During exposure, cue-elicited food craving and anxiety were assessed. Participants also completed standardized instruments for the study purposes. ED patients reported significantly higher levels of craving and anxiety when exposed to the virtual food than healthy controls. Eating behavior styles showed strong associations with cue-elicited food craving and anxiety. In the healthy group, external eating was the only predictor of cue-elicited craving and anxiety. In participants with BN and BED, external and emotional eating were the best predictors of cue-elicited craving and anxiety, respectively. 2017 Elsevier Ltd. All rights reserved

A Randomised Controlled Comparison of Second-Level Treatment Approaches for Treatment-Resistant Adults with Bulimia Nervosa and Binge Eating Disorder: Assessing the Benefits of Virtual Reality Cue Exposure Therapy

A question that arises from the literature on therapy is whether second-level treatment is effective for patients with recurrent binge eating who fail first-level treatment. It has been shown that subjects who do not stop binge eating after an initial structured cognitive-behavioural treatment (CBT) programme benefit from additional CBT (A-CBT) sessions; however, it has been suggested that these resistant patients would benefit even more from cue exposure therapy (CET) targeting features associated with poor response (e.g. urge to binge in response to a cue and anxiety experienced in the presence of binge-related cues). We assessed the effectiveness of virtual reality-CET as a second-level treatment strategy for 64 patients with bulimia nervosa and binge eating disorder who had been treated with limited results after using a structured CBT programme, in comparison with A-CBT. The significant differences observed between the two groups at post-treatment in dimensional (behavioural and attitudinal features, anxiety, food craving) and categorical (abstinence rates) outcomes highlighted the superiority of virtual reality-CET over A-CBT. Copyright (c) 2017 John Wiley & Sons, Ltd and Eating Disorders Association

A Randomized Trial of Virtual Reality-Based Cue Exposure Second-Level Therapy and Cognitive Behavior Second-Level Therapy for Bulimia Nervosa and Binge-Eating Disorder: Outcome at Six-Month Followup

This article reviews the 6-month followup data of a randomized, multicenter, parallel-group study conducted at five clinical sites in three European cities, which compared two second-level treatments for bulimia nervosa (BN) and binge eating disorder (BED): virtual reality-based cue exposure therapy (VR-CET) versus additional cognitive behavioral therapy (A-CBT). Post-treatment outcomes of this study were previously published and details of its design can be found at clinicaltrials.gov (identifier: NCT02237300). This article focuses on the evolution of symptoms assessed after 6 months of followup in a subgroup of 58 patients from the original study. In this study 64 patients with eating disorders (EDs) (35 with BN and 29 with BED), who still showed active episodes of binge eating by the end of a structured CBT program (first-level treatment), were randomly assigned to one of two second-level treatments (A-CBT or VR-CET). Frequency of binge and purge episodes, and attitudinal features of binge-related EDs (bulimia, drive for thinness, and body dissatisfaction) were assessed before starting the second-level treatment (n = 64), at the end (n = 64), and at 6-month followup (n = 58). Mixed between-within subject analyses of variance were used to compare outcomes of both second-level treatments over time. Although both treatment conditions showed statistically significant improvements at the end and after 6-month followup, obtained reductions were greater after VR-CET, regarding binge and purge episodes, as well as the decrease of self-reported tendency to engage in overeating episodes. Accordingly, abstinence from binge episodes were higher in VR-CET than A-CBT at followup (70 percent vs. 26 percent, respectively; chi(2) = 11.711, p = 0.001). These results provide further support for the use of VR-CET as an effective second-level intervention for BN and BED treatment-resistant patients

Testing virtual reality-based cue-exposure software: Which cue-elicited responses best discriminate between patients with eating disorders and healthy controls?

Purpose: Virtual reality (VR) technologies have been proposed as a new tool able to improve on in vivo exposure in patients with eating disorders. This study assessed the validity of a VR-based software for cue exposure therapy (CET) in people with bulimia nervosa (BN) and binge eating disorder (BED). Methods: Fifty eight outpatients (33 BN and 25 BED) and 135 healthy participants were exposed to 10 craved virtual foods and a neutral cue in four experimental virtual environments (kitchen, dining room, bedroom, and cafeteria). After exposure to each VR scenario, food craving and anxiety were assessed. The frequency/severity of episodes of uncontrollable overeating was also assessed and body mass index was measured prior to the exposure. Results: In both groups, craving and anxiety responses when exposed to the food-related virtual environments were significantly higher than in the neutral-cue virtual environment. However, craving and anxiety levels were higher in the clinical group. Furthermore, cue-elicited anxiety was better at discriminating between clinical and healthy groups than cue-elicited craving. Conclusions: This study provides evidence of the ability of food-related VR environments to provoke food craving and anxiety responses in BN and BED patients and highlights the need to consider both responses during treatment. The results support the use of VR-CET in the treatment of eating disorder patients characterized by binge-eating and people with high bulimic symptoms