The COVID-19 epidemic that emerged in China in December 2019 has spread pandemically around the world. At this time, France has recorded 16,689 confirmed cases of SARS-CoV2 and 614 deaths. In the Occitania region, 86 patients are hospitalized in intensive care units for severe pulmonary disease. In this epidemic context, the SAMU-center 15 is the essential triage platform to limit the inappropriate use of emergency services. The current challenge is to be able to identify among all patients calling at the dispatching center for a reason of low or high respiratory infection, those at risk of complications that will require hospitalization with appropriate management. The objective of this study is therefore to identify predictive factors of aggravation for patients presenting a low or high respiratory infection suspected of COVID-19 during medical phone regulation. A predictive model of the aggravation of these patients, a description of the characteristics of the symptoms experienced and their status 30 days after the call will also be proposed. The predictive criteria identified in this study will help detect patients at risk of aggravation during the first medical phone consultation in order to optimize their management and be more efficient in their use of care.

The cochlear implant (CI) in congenital deaf children is now widely considered as a highly efficient means to restore auditory functions. However, after several decades of retrospective analysis, it is clear that there is a large range of recuperation levels, and in extreme cases some CI recipients never develop adequate oral language skills. The major goal of HearCog to improve rehabilitation strategies in CI children, it is to better understand and circumscribe the origins of such variability in CI outcomes. The originality of HearCog project is to consider CI outcomes in a broad range of interdependent aspects, from speech perception to speech production and the associated cognitive mechanism embedded in executive functions. The novelty of the proposal is both theoretical and methodological. The goals will be first to evaluate the capacities of the visual and auditory system to respond to natural environmental stimuli and to analyse neuronal mechanisms induced by sensory loss and recovery through the CI using brain imaging techniques (Functional Near-Infrared Spectroscopy, fNIRS). In view of the co-structuration of speech perception and production during development, we will assess how deafness and CI recovery can alter speech production. But congenital deafness has deleterious impacts that extend beyond the auditory functions and encompass cognitive systems including higher-order executive processes. Based on the disconnecting model (Kral et al., 2016), our objective will be to relate neuronal assessment, using the fNIRS technique, of executive functions to auditory restoration in CI children. HearCog is based on longitudinal assessment on CI infants and age-matched controls, to search for prognosis factors of auditory restoration. We will also compare these measurements to data acquired in older CI children implanted for several years, and controls. In fine our goal is to acquire objective measures of brain reorganization that could be linked to variability in CI outcomes and therefore would constitute a predictive factor. HearCog is at the crossroad of cognitive neuropsychology, clinical research with a strong opening toward education. Consequently HearCog is translational and multidisciplinary with the unique objective to understand the compensatory mechanisms induced by congenital hearing loss to support both the social insertion as well as the insertion within the school system of cochlear implanted deaf children.

The adolescent idiopathic scoliosis (AIS) is a multifactorial disease which up to 3% of adolescent population in the growth spurt with a female prevalence. The project aims at correlating growth-related factors, metabolic factors and biomechanical factors in a cohort of adolescent idiopathic scoliosis (AIS). In a innovative methodology, we hypothesize that the interdisciplinary approach combining clinical data image-base clinical data, metabolic factors and biomechanical models give access a) to plausible mechano-biological scenarios to describe AIS evolution, and b) to the proposal of new mechano-biological markers. The clinical relevance concerns distinction between stable and progressive deformation requiring invasive surgery.

Heart failure (HF) with preserved ejection fraction (HFpEF) is a leading cause of morbidity and mortality throughout the industrialized world. HFpEF, characterized by a diastolic dysfunction, is considered as the predominant form of HF and currently accounts for ~50 % of all HF. This is a multi-organ syndrome and thus a complex and heterogeneous pathology that complicates its diagnosis. . Interestingly, HFpEF is sexually dimorphic with higher prevalence in old/hypertensive/obese/diabetic women. Our understanding of this condition is still limited and, accordingly, specific prevention and treatment strategies are lacking, thus justifying the urgent need to identify the molecular mechanisms underlying HFpEF. Only recently, SGLT2 inhibitors were shown to reduce the associated morbi-mortality, highlighting a heart-remote but unknown mechanism. These last years, the development of a specific expertise in high-resolution microscopy to explore the cardiac tissue (rodents and human) led us to accurately characterize the cell surface of the cardiomyocytes (CM) in periodic crests field by subsarcolemmal mitochondria (SSM) whose role is unknown and to demonstrate for the first time crest-crest intermittent interactions between neighbor CMs. More recently, we identified a specific crest determinant. By using a CM-specific KO mouse model, we found that the crests/SSM participate to the cardiac beta-oxidation of fatty acids and regulate specifically the diastolic function. Interestingly, we determined that crest maturity is sexually dimorphic with a high metabolic plasticity (SSM shrinking/swelling) in female during physiological cardiac stress such as pregnancy. Similar plasticity was also observed in male during the postnatal period but is lost at adulthood. All these data questioned about the metabolic fuel used by the specific SSM. The heart displays a high metabolic flexibility allowing it to switch between different energy substrates according to their availability, the workload and the hormonal status. Especially, ketone bodies, produced by the liver, have been recently recognized as key fuel for the heart function. Preliminary data from our consortium demonstrated that, i/ liver PPARa, a major fatty acid and ketone generator, regulates CM crest maturity in male hearts, and ii/ ERa (Estrogen Receptor alpha), a major determinant of sexual dimorphism, controls hepatic PPARa activity acting as nutritional sensor specifically in female mice. In line with these preliminary results and using the expertise of our consortium mixing researchers and clinicians experts in cardiology, hepatology and metabolism, this proposal aims at investigating the liver to heart dialog and more specifically how sex, by influencing hepatic PPARa/ERa-dependent lipid metabolism, modulates crest/SSM maturity in the heart and the related diastolic function in physiology and in metabolic diseases. In the preclinical study using male and female mouse models, 3 main questions will be answered: i/ Do estrogens inhibit crest/SSM maturity and turn down the cardiac diastolic function?; ii/ Where estrogens modulate crest/SSM maturity/diastolic function and how? This will be explored taking advantage of ERa-hepato-/- and PPARa-hepato-/- mice already available within the consortium; iii/ How diet-induced Non Alcoholic Fatty Liver Disease (NAFLD), which disturbs liver lipid metabolism, sex-dependently impacts crest maturity and diastolic function? Finally, the clinical study will explore the cardiac function in relation to the liver function in a cohort of young obese male and female patients to establish the proof of concept of a potential correlation between NAFLD progression and HFpEF. This fundamental and clinical project exploring the liver-to-heart dialog should have major impact in the understanding of the diastolic function and HFpEF and should pave the way in the future for the development of new original sex-specific therapies for HFpEF.

The AgeHear project is firmly based on the perspective of access to speech comprehension for the elderly suffering of Age-related hearing loss in a dual framework of both basic and clinical research. Hearing loss is a growing challenge in our modern society, and has a significant socio-economic impact, particularly with regard to the ageing population. Age-related hearing loss (ARHL or presbycusis) is present in about two thirds of the elderly, causing serious communication difficulties and leading to social isolation and depression. This difficulty in communicating is worsened by a cognitive decline related to the listening effort which depletes the person's cognitive resources. These demographic and clinical issues are at the heart of AgeHear project, which focuses on understanding the mechanisms of rehabilitation of presbycusis subjects with hearing aids (HAs). Thanks to technological advances, hearing aids enable the elderly to have access to oral communication and to return to an enriched social life. From a fundamental point of view, based on a multidisciplinary approach combining psychophysics, neuropsychology and brain imaging, AgeHear will seek to understand the mechanisms of brain plasticity involved in the rehabilitation of speech in the noise of the presbycusis subject and the links with a reduction in cognitive effort. From a clinical point of view, AgeHear will make it possible to use this experimental and theoretical understanding to support and guide the implementation of rehabilitation strategies. The central theme of AgeHear thus concerns the mechanisms of spatial hearing and neurocognitive compensation and their impact on the recovery of speech comprehension by hearing aids. The originality of AgeHear is both technological and theoretical. Conceptually, AgeHear proposes to study the mechanisms of spatial hearing restoration in a natural ecological context including dynamic and multisensory components. The impact and strategies supporting the rehabilitation of speech understanding in noise will be evaluated using a 3D virtual system (HTC ViveTM) allowing the patient to be immersed in a controlled vivid visuo-auditory environment. At the heart of AgeHear is the strong hypothesis that the success of rehabilitation of the presbycusis subject depends on his potential of brain plasticity. Based on a longitudinal approach, we will search for neural markers through PET scan brain imaging which would be predictive of the level of recovery by HAs and could consequently guide individual rehabilitation strategies. PET imaging will also allow us to determine whether spatial hearing and speech in noise comprehension share the same cognitive resources. This aspect will be reinforced by analyzing the links between hearing loss and its recovery with deficits in executive functions. Thus, AgeHear is a definitely a multidisciplinary and translational project that brings together two laboratories with expertise in brain imaging and psychophysics of deafness associated with an ENT service in addition to the participation of an industrial partner specialized in hearing aids. This consortium will enable a complementary approach, from psychophysics to clinical neurosciences, with a single common objective of a better understanding of the mechanisms of rehabilitation of presbycusis in its perceptive and cognitive aspects in order to optimize the rehabilitation of the elderly, thus promoting their social reintegration.