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Objective: Traumatic brain injury (TBI) is a multifactorial pathology with great interindividual variability in response to injury and outcome. Mitochondria contain their own DNA (mtDNA) with genomic variants that have different physiological and pathological characteristics, including susceptibility to neurodegeneration. Given the central role of mitochondria in the pathophysiology of neurological injury, we hypothesized that its genomic variants may account for the variability in outcome following TBI.Methods: We undertook an analysis of mitochondrial haplogroups in a large, well-characterized cohort of 1,094 TBI patients. A proportional odds model including age, brain computed tomography characteristics, injury severity, pupillary reactivity, mitochondrial haplogroups, and APOE was applied to Glasgow Outcome Score (GOS) data.Results: mtDNA had a significant association with 6-month GOS (p = 0.008). Haplogroup K was significantly associated with favorable outcome (odds ratio = 1.64, 95% confidence interval = 1.08–2.51, p = 0.02). There was also a significant interaction between mitochondrial genome and age (p = 0.002), with a strong protective effect of both haplogroups T (p = 0.015) and K (p = 0.017) with advancing age. We also found a strong interaction between APOE and mitochondrial haplogroups (p = 0.001), indicating a protective effect of haplogroup K in carriers of the APOE ε4 allele.Interpretation: These findings reveal an interplay between mitochondrial DNA, pathophysiology of TBI, and aging. Haplogroups K and T, which share a common maternal ancestor, are shown as protective in TBI. The data also suggest that the APOE pathways interact with genetically regulated mitochondrial functions in the response to acute injury, as previously reported in Alzheimer disease.

Neurodegenerative diseases (NDs) are becoming increasingly prevalent in the world, with an aging population. In the last few decades, due to the devastating nature of these diseases, the research of biomarkers has become crucial to enable adequate treatments and to monitor the progress of disease. Currently, gene mutations, CSF and blood protein markers together with the neuroimaging techniques are the most used diagnostic approaches. However, despite the efforts in the research, conflicting data still exist, highlighting the need to explore new classes of biomarkers, particularly at early stages. Small non-coding RNAs (MicroRNA, Small nuclear RNA, Small nucleolar RNA, tRNA derived small RNA and Piwi-interacting RNA) can be considered a "relatively" new class of molecule that have already proved to be differentially regulated in many NDs, hence they represent a new potential class of biomarkers to be explored. In addition, understanding their involvement in disease development could depict the underlying pathogenesis of particular NDs, so novel treatment methods that act earlier in disease progression can be developed. This review aims to describe the involvement of small non-coding RNAs as biomarkers of NDs and their potential role in future clinical applications.

The diagnosis of mild traumatic brain injury or sports-related concussion is a challenge for all clinicians, players, coaches and parents involved in contact sports. Currently, there is no validated objective biomarker available to assess the presence or severity of concussion in sport, and so it is necessary to rely on subjective measures like self-reporting of symptoms which depend on the cooperation of the athlete. There is a significant health risk associated with repetitive injury if the diagnosis is missed, and so there is great value in an objective biomarker to assist diagnostic and prognostic decisions. To establish a panel of non-invasive MicroRNA biomarkers in urine and saliva for the rapid diagnosis of sports-related concussion and investigate the kinetics and clinical utility of these biomarkers in assisting diagnostic, prognostic and return-to-play decisions. Observational, prospective, multicentre cohort study recruiting between the 2017-2018 and 2018-2019 Rugby Union seasons. Professional rugby players in the two highest tiers of senior professional domestic rugby competition in England will be recruited prospectively to the study. During the season, three groups will be identified: athletes entering the World Rugby Head Injury Assessment (HIA) protocol, uninjured control athletes and control athletes with musculoskeletal injuries. Saliva and urine will be collected from these athletes at multiple timepoints, coinciding with key times in the HIA protocol and return-to-play process. Ethics approval has been obtained. The compiled and analysed results will be presented at national and international conferences concerning the care of patients with traumatic brain injury. Results will also be submitted for peer review and publication in the subject journals/literature. [Abstract copyright: © Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY. Published by BMJ.]

Concussion is difficult to diagnose, particularly when symptoms are atypical or late in presenting. An accurate and timely initial assessment is crucial for clinical management. Cerebral spinal fluid (CSF) and blood markers of traumatic brain injury show promising results but their clinical applicability in concussion has significant limitations. In the study, we explored saliva as a new source of biomarkers of concussion. Saliva samples of concussed players were collected after 48–72 h from concussion and analyzed by high-throughput technologies. A discovery group of 10 concussed rugby professional and semiprofessional athletes and 10 non-concussed matched controls was used for the analysis of 92 inflammatory proteins by the Proseek-Multiplex-Inflammation technology. In addition, saliva samples of 6 concussed and 6 non-concussed athletes were used to screen 800 human microRNAs (miRNAs) by the Nanostring Technology. The results were then validated by RT-qPCR in an enlarged cohort (validation group) comprising 22 concussed athletes. Results showed, no significant variations of the 65 inflammatory proteins detected in saliva between groups but 5 microRNAs, miR-27b-3p (p = 0.016), let-7i-5p (p = 0.001), miR-142-3p (p = 0.008), miR-107 (p = 0.028), miR-135b-5p (p = 0.017) significantly upregulated in concussed athletes. Univariate ROC curve analysis showed that the differentially expressed miRNAs could be considered good classifiers of concussion. Further analyses showed significant correlation between these microRNAs and Reaction Time component of the ImPACT concussion assessment tool. In addition, biocomputation analysis predicted the involvement of these microRNAs in important biological processes that might be related to trauma, such as response to hypoxia, cell death, neurogenesis, axon repair and myelination. Ease of access and non-invasiveness of saliva samples make these biomarkers particularly suitable for concussion assessment.

International audience; Le vote du Brexit en juin 2016 a rappelé l’existence des 300 000 britanniques installés en France. Les medias ont ainsi relayé de nombreux témoignages d’expatriés exerçant une activité économique, inquiets des conséquences de la sortie de l’UE sur leurs affaires : augmentations des taxes et impôt, accès à certaines professions, instauration de visas...Malgré leur volonté de rester en France, l’insertion de ces entrepreneurs n’est pas flagrante selon les publications grand public (articles de presse, sites internet), qui évoquent des difficultés d’installation et même nombreux échecs (Lagarde & McElwee, 2016). D’après la presse, les causes seraient multiples : manque de préparation, manque de compétences, marché limité entre expatriés, problèmes familiaux, difficultés avec la langue et la règlementation (irrégularités, travail au noir), … Les rares études académiques sur ces britanniques entrepreneurs en France (Lardies, 1999 ; Stone & Stubbs 2007) ne permettent pas de trancher parmi les idées véhiculées par l’expression populaire.Cette question des difficultés connaissant une acuité particulière avec l’application du Brexit en 2019, nous proposons d’étudier les principaux déterminants des problèmes et des échecs des entreprises britanniques dans le Sud-Ouest de la France.L’état de l’art a consisté à extraire de la littérature géographique et sociologique sur ces expatriés, les informations éparses sur leurs activités et situations économiques. Puis, il s’est agi de faire converger 3 champs de la littérature entrepreneuriale, puisque ces entreprises cumulent certaines difficultés des néo-ruraux (Saleilles, 2006), des migrants (Waldinger et al., 1990 ; Stone & Stubb, 2007), et des petites entreprises en général (Levratto, 2011), notamment les plus récentes (Khelil et al., 2012).L’approche terrain en Nouvelle Aquitaine rurale, a consisté en une douzaine d’entretiens semi-directifs avec des témoins privilégiés (Quivy et Van Campenhoudt, 2006) (élus locaux, associations d’expatriés, agents immobilier, chambres consulaires) ; puis avec une dizaine d’entrepreneurs britanniques dans des situations économiques et sociales variées.En clé de lecture, nous utilisons le modèle de Gartner qui préconise d'étudier le phénomène entrepreneurial selon quatre dimensions : l'individu, le projet, le processus et son environnement (Gartner, 1985); parce qu’il est particulièrement adapté, à la fois à l’appréhension multidimensionnelle des difficultés (Khelil et al., 2012) et à l’approche des expatriés entrepreneurs (Stone & Stubb, 2007). La plupart des difficultés annoncées par la presse et la littérature sont vérifiées, mais dans des proportions variables selon les profils et les types d’activités. Comme il y a confusion du projet de vie (vivre en France, devenir propriétaire) et du projet économique, la notion d’échec est très subjective et très relative (Jenkins & McKelvie, 2016). L’entreprise n’est qu’un moyen de réaliser le principal projet familial de rester en France. Les micro-entreprises très souples (entretien parcs et jardin, bricolage maçonnerie et électricité, …) sont davantage dans une logique de subsistance. Elles sont donc moins affectées par les problèmes de compétence, de marché limité entre expatriés et de sous-investissement, que les plus importantes (bar, restaurant…). Les plus entreprenants ont de véritables stratégies et sont dans de meilleures situations économiques et sociales. Ils sont également mieux intégrés localement. La question du sens de la relation entre l’intégration du dirigeant est l’échec de l’entreprise est interrogée. Selon ses modalités finales, le Brexit pourrait avoir des effets importants sur ces entreprises, les fragiliser, voire en condamner certaines.