Publications by authors named "Frédéric Roche"

207 Publications

OSAHS phenotypes after night sleep recordings: How to get to precision medicine in 2021.

Sleep 2021 Jun 18. Epub 2021 Jun 18.

Clinical Physiology, Visas Center, University Hospital, Saint-Etienne, France.

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http://dx.doi.org/10.1093/sleep/zsab154DOI Listing
June 2021

Efficiency of an Optimized Care Organization in Fibromyalgia Patients: The From Intent to Move (FIMOUV) Study Protocol of a Randomized Controlled Trial.

Front Public Health 2021 25;9:554291. Epub 2021 May 25.

University Lyon, UJM-Saint-Etienne Sainbiose Laboratory, INSERM U1059, Saint-Étienne, France.

Fibromyalgia (FM) is characterized by multiple symptoms including pain, fatigue, and sleep disorders, altering patient's quality of life. In the absence of effective pharmacological therapy, the last European guidelines recommend a multidisciplinary management based on exercise and education. Thus, our main objective was to measure the effectiveness of a healthcare organization offering a specific program of adapted physical activity combined with a therapeutic education program for FM patients. The From Intent To Move (FIMOUV) study will recruit 330 FM patients randomized into two groups: test and control. The test group will benefit from a 1-month mixed exercise training program supervised at the hospital, followed by 2 months in a community-based relay in a health-sport structure. In addition, each of the two groups will benefit from therapeutic patient education sessions. The main endpoint is the measurement of the level of physical activity by accelerometry at 1 year. The secondary endpoints concern adherence to the practice of physical activity, impact on lifestyle, state of health, and physical capacity, as well as an estimate of the budgetary impact of this management strategy. This interventional research will allow us to assess the evolution of behaviors in physical activity after an FM syndrome management based solely on patient education or based on a supervised and adapted practice of physical activity associated with this same therapeutic education program. It seems to be the first study evaluating the impact of its intervention on objective data for measuring physical activity and sedentary behavior accelerometry among FM patients. ClinicalTrials.gov NCT04107948.
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http://dx.doi.org/10.3389/fpubh.2021.554291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185292PMC
June 2021

Associations between physical activity types and multi-domain cognitive decline in older adults from the Three-city cohort.

PLoS One 2021 1;16(6):e0252500. Epub 2021 Jun 1.

Institute for Neurosciences of Montpellier, Inserm, Univ. Montpellier, Montpellier, France.

Several studies suggest that physical activity improves cognitive functions and reduces cognitive decline, whereas others did not find any evidence of a neuroprotective effect. Furthermore, few cohort studies have analyzed the different physical activity types and particularly household activities. Our objective was to assess the association of two physical activity types with the decline in different cognitive domains in a large prospective cohort of community-dwelling older adults from the Three-city study. Physical activity (domestic/transportation activities and leisure/sport activities) was assessed with the Voorrips questionnaire, specific for older adults. Baseline sociodemographic and health history variables as well as cognitive performance data at baseline and during the 8-year follow-up (Mini-Mental State Examination, Benton Visual Retention Test, Trail Making Tests A and B, Isaac's Set Test and Free and Cued Selective Reminding Test) were also available. Associations between physical activity scores and cognitive decline in different domains were tested using minimally- and multi-adjusted linear mixed models. The analysis included 1697 participants without dementia at baseline and with at least one follow-up visit. At baseline, participants with higher sub-scores for the two physical activity types had better cognitive performances. Interaction with time showed that decline in some cognitive scores (Trail Making Test B and Isaac's Set Test) was significantly less pronounced in participants with higher household/transportation activity sub-scores. No significant effect over time was found for leisure/sport activities. This study shows that during an 8-year follow-up, executive functions and verbal fluency were better preserved in older adults who performed household/transportation activities at moderate to high level. Participation in domestic activities and using adapted transport means could allow older adults to maintain specific cognitive abilities.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252500PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168837PMC
June 2021

Muscle Proteomic and Transcriptomic Profiling of Healthy Aging and Metabolic Syndrome in Men.

Int J Mol Sci 2021 Apr 19;22(8). Epub 2021 Apr 19.

Université Clermont Auvergne, INRAE, UNH, Unité de Nutrition Humaine, CRNH Auvergne, 63000 Clermont-Ferrand, France.

(1) Background: Aging is associated with a progressive decline in muscle mass and function. Aging is also a primary risk factor for metabolic syndrome, which further alters muscle metabolism. However, the molecular mechanisms involved remain to be clarified. Herein we performed omic profiling to decipher in muscle which dominating processes are associated with healthy aging and metabolic syndrome in old men. (2) Methods: This study included 15 healthy young, 15 healthy old, and 9 old men with metabolic syndrome. Old men were selected from a well-characterized cohort, and each vastus lateralis biopsy was used to combine global transcriptomic and proteomic analyses. (3) Results: Over-representation analysis of differentially expressed genes (ORA) and functional class scoring of pathways (FCS) indicated that healthy aging was mainly associated with upregulations of apoptosis and immune function and downregulations of glycolysis and protein catabolism. ORA and FCS indicated that with metabolic syndrome the dominating biological processes were upregulation of proteolysis and downregulation of oxidative phosphorylation. Proteomic profiling matched 586 muscle proteins between individuals. The proteome of healthy aging revealed modifications consistent with a fast-to-slow transition and downregulation of glycolysis. These transitions were reduced with metabolic syndrome, which was more associated with alterations in NADH/NAD shuttle and β-oxidation. Proteomic profiling further showed that all old muscles overexpressed protein chaperones to preserve proteostasis and myofiber integrity. There was also evidence of aging-related increases in reactive oxygen species but better detoxifications of cytotoxic aldehydes and membrane protection in healthy than in metabolic syndrome muscles. (4) Conclusions: Most candidate proteins and mRNAs identified herein constitute putative muscle biomarkers of healthy aging and metabolic syndrome in old men.
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http://dx.doi.org/10.3390/ijms22084205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074053PMC
April 2021

Longer-term effects of supervised physical activity on obstructive sleep apnea and subsequent health consequences.

Scand J Med Sci Sports 2021 Jul 2;31(7):1534-1544. Epub 2021 May 2.

SNA-EPIS Laboratory, University of Lyon, Saint-Etienne, France.

Although recent trials have shown promising benefits of exercise on obstructive sleep apnea (OSA) severity, the long-term effect of these interventions remains unknown. The aim of this study was to assess the effect of a 9-month community physical activity program on OSA severity one year later in free-living conditions. OSA patients, previously included in a 9-month randomized controlled trial (EXESAS study) evaluating the effects of supervised community physical activity on OSA severity, were invited to participate in an extra one-year observational study. Twenty-eight patients completed the study. Although OSA severity did not significantly worsen over the real-life period (9 to 21 months of follow-up), reductions in apnea-hypopnea index (AHI) and oxygen desaturation index were no longer significant after 21 months of follow-up compared to baseline (baseline AHI: 22.2 ± 6.3 /h; 9 months: 16.3 ± 6.4 /h; 21 months: 18.7 ± 8.9 /h). Benefits observed at 9 months on daytime sleepiness and mental health were preserved at 21 months, whereas cardiorespiratory fitness slightly decreased. Per-protocol analysis revealed that patients who stopped exercise at 9 months had worsened OSA severity compared to those who continued exercise during the real-life period (AHI: +9.0 ± 8.8 vs. -1.3 ± 5.3 /h; p < .01). In conclusion, our study suggested that improvements in OSA severity remain transient and is dependent on long-term adherence to regular physical activity practice.
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http://dx.doi.org/10.1111/sms.13961DOI Listing
July 2021

Sleep quality and sleep disturbances among volunteer and professional French firefighters: FIRESLEEP study.

Sleep Med 2021 Apr 2;80:228-235. Epub 2021 Feb 2.

Clinical and Exercise Physiology, EA 4607 SNA EPIS, University Hospital and Jean Monnet University, PRES Lyon, 42023 Saint-Etienne, France. Electronic address:

Background: Although insufficient sleep among firefighters reduces work efficiency and increases the risk of injury, little is known about the sleep quality of French firefighters in the Loire department. The aim of the FIRESLEEP study was to evaluate sleep quality and sleep disturbances among professional and voluntary French firefighters.

Methods: A cross-sectional observational study was conducted between November 2018 and May 2019. Firefighters were invited to complete a questionnaire on a secure platform including clinical questions and validated questionnaires (Pittsburgh Sleep Quality Index [PSQI], Epworth sleepiness scale [ESS], Insomnia Severity Index [ISI] and the STOP-Bang score) during their periodic medical examination.

Results: 193 firefighters were included in this study, of which 29% were of professional status and 71% were volunteer firefighters. Among them, 26.9% had poor sleep quality, 27.7% showed excessive daytime sleepiness (EDS), 18.8% reported moderate-to-severe symptoms of insomnia, and 1.6% had moderate-to-high risk of obstructive sleep apnea. Subgroup analysis revealed that professional firefighters had poorer sleep quality and higher sleep disturbances than volunteer firefighters. The independent risk factors associated with poor sleep quality were known sleep disorder, treated anxiety/depression, night calls, and insomnia symptoms. Moreover, the independent risk factors associated with EDS were short sleep duration, taking a nap, and insomnia symptoms; while older age was a protective factor for EDS.

Conclusions: Poor sleep quality and sleep disturbances are highly frequent in French firefighters and underdiagnosed. Prevention through education and systematic screening could limit the impact of sleep disturbances on firefighters' global health.
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http://dx.doi.org/10.1016/j.sleep.2021.01.041DOI Listing
April 2021

Domestic Activities Associated With a Decreased Risk of Cognitive Disorders: Results of the "Fréle" Cohort.

Front Public Health 2020 9;8:602238. Epub 2020 Dec 9.

Centre technique d'appui et de formation (CETAF), Saint-Etienne, France.

Previous cohorts studied the association of various types of physical activities with the incidence of cognitive disorders. The objective of this work was to analyze the association of leisure, domestic and professional physical activities with mild and moderate cognitive disorders in older people living in the community. We used retrospective data from the "FRéLE" (FRagilité: étude Longitudinale de ses Expressions) a longitudinal and observational study. Data collected included socio-demographic variables, lifestyle and health status. Cognitive disorders were assessed using the Montreal Cognitive Assessment (MoCA). Two cut-offs of MoCA were used to analyze mild and moderate cognitive disorders. Physical activity was assessed by the Physical Activity Scale for the Elderly (PASE) structured in three sections: leisure, household, and professional activities. Spline and logistic regression models were used to estimate the risk of cognitive disorders. At baseline, 428 participants (for study of mild disorders) and 1,271 participants (for study of moderate disorders) without cognitive disorders were included in the analysis. The mean ages were 74 and 78 years, respectively. After a 2-year follow-up, we found mild cognitive disorders in 154 participants (36%) and 71 cases of moderate cognitive disorders (5.6%). In multi-adjusted logistic models, domestic activities were associated with cognitive disorders, but not leisure and professional activities. We found an inverse relation between domestic sub-score and cognitive disorders defined by MoCA < 18. With a specific questionnaire and quantitative information on the type of activities, this study contributed to the debate on the beneficial effects of physical activity on cognition.
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http://dx.doi.org/10.3389/fpubh.2020.602238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793943PMC
May 2021

Prevalence and prognostic value of autonomic neuropathy assessed by Sudoscan® in transthyretin wild-type cardiac amyloidosis.

ESC Heart Fail 2021 Apr 22;8(2):1656-1665. Epub 2020 Dec 22.

Cardiology Department, AP-HP (Assistance Publique-Hôpitaux de Paris), Henri Mondor University Hospital, 51 Avenue du Marechal de Lattre de Tassigny, Créteil, F-94010, France.

Aims: The prevalence of autonomic neuropathy (AN) is high in patients with hereditary transthyretin amyloidosis but remains unknown in transthyretin wild-type cardiac amyloidosis (ATTRwt-CA). This study aimed to determine the prevalence of AN in patients with ATTRwt-CA using Sudoscan®, a non-invasive method used to provide evidence of AN in clinical practice and based on measurement of electrochemical skin conductance at the hands and feet (fESC).

Methods And Results: A series of 62 non-diabetic patients with ATTRwt-CA was prospectively included over 2 years and compared with healthy elderly subjects, matched by age, gender, and body mass index. The presence of AN was defined as electrochemical skin conductance at the hands <60 μS and/or fESC <70 μS, and conductances were analysed according to clinical, biological, and echocardiographic data. Mean fESC was significantly lower in patients with ATTRwt-CA compared with elderly controls: 68.3 (64.1-72.5) vs. 76.9 (75.6-78.1) μS (P < 0.0001), respectively. Prevalence of fESC <70 μS was higher in ATTRwt-CA patients than in controls: 48.4% vs. 19.9%, P < 0.05. Univariate analysis showed that fESC, N-terminal pro-B-type natriuretic peptide, creatinine plasma levels, and echocardiographic global longitudinal strain were associated with decompensated cardiac failure and death. Multivariate analysis revealed that fESC was an independent prognostic factor, and Kaplan-Meier estimator evidenced a greater occurrence of cardiac decompensation and death in patients with fESC <70 μS, P = 0.046.

Conclusions: Reduced fESC was observed in almost 50% of patients with ATTRwt-CA and was associated with a worse prognosis. Sudoscan® could easily be used to screen ATTRwt-CA patients for the presence of AN and identify patients at higher risk for a poor outcome.
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http://dx.doi.org/10.1002/ehf2.13131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006719PMC
April 2021

Intermittent Hypoxia and Its Impact on Nrf2/HIF-1α Expression and ABC Transporters: An in Vitro Human Blood-Brain Barrier Model Study.

Cell Physiol Biochem 2020 Dec;54(6):1231-1248

INSERM, U1059, Sainbiose, Dysfonction Vasculaire et Hémostase, Université de Lyon, Université Jean Monnet, Saint-Etienne, France.

Background/aims: Obstructive sleep apnea (OSA) is characterized by repeated episodes of complete or partial obstruction of the upper airways, leading to chronic intermittent hypoxia (IH). OSA patients are considered at high cerebrovascular risk and may also present cognitive impairment. One hypothesis explored is that disturbances may be linked to blood-brain barrier (BBB) dysfunction. The BBB is a protective barrier separating the brain from blood flow. The BBB limits the paracellular pathway through tight and adherens junctions, and the transcellular passage by efflux pumps (ABC transporters). The aims of this study were to evaluate the impact of IH and sustained hypoxia (SH) on a validated in vitro BBB model and to investigate the factors expressed under both conditions.

Methods: Exposure of endothelial cells (HBEC-5i) in our in vitro model of BBB to hypoxia was performed using IH cycles: 1% O2-35 min/18% O2-25 min for 6 cycles or 6 h of SH at 1% O2. After exposure, we studied the cytotoxicity and the level of ROS in our cells. We measured the apparent BBB permeability using sodium fluorescein, FITC-dextran and TEER measurement. Whole cell ELISA were performed to evaluate the expression of tight junctions, ABC transporters, HIF-1α and Nrf2. The functionality of ABC transporters was evaluated with accumulation studies. Immunofluorescence assays were also conducted to illustrate the whole cell ELISAs.

Results: Our study showed that 6 h of IH or SH induced a BBB disruption marked by a significant decrease in junction protein expressions (claudin-5, VE-cadherin, ZO-1) and an increase in permeability. We also observed an upregulation in P-gp protein expression and functionality and a downregulation in BCRP. Hypoxia induced production of ROS, Nrf2 and HIF-1α. They were expressed in both sustained and intermittent conditions, but the expression and the activity of P-gp and BCRP were different.

Conclusion: Understanding these mechanisms seems essential in order to propose new therapeutic strategies for patients with OSA.
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http://dx.doi.org/10.33594/000000311DOI Listing
December 2020

Vigilance and sleepiness in nurses working 12-hr shifts and their coping strategies.

J Nurs Manag 2020 Dec 10. Epub 2020 Dec 10.

Univ Lyon, Univ Lyon 1, Univ St Etienne, IFSTTAR, UMRESTTE, UMR_T9405, Saint Etienne, France.

Aim: To describe the progression of vigilance and sleepiness over the shift and the coping strategies of nurses working 12-hr day or night shifts.

Background: The spread of 12-hr shift work in nursing raises the question of whether sufficient vigilance can be maintained to ensure quality of care.

Method: 18 nurses working 12-hr shifts filled out a Karolinska Sleepiness Scale questionnaire and a Brief Psychomotor Vigilance Test, at the beginning of the shift and then every 3 hr. Coping strategies and quality of care were assessed on self-administered questionnaires, filled out at 3 hr, 6 hr, 9 hr and 12 hr after the start of the shift.

Results: The present investigation did not show significantly excessive sleepiness or vigilance impairment or poor self-perception of quality of work during 12-hr nursing work shifts, although Psychomotor Vigilance Test results gradually deteriorated slightly over duty time (from start to end of shift). Certain coping strategies were preferred such as 'having a nap' later in the night shift.

Conclusion: Attention needs to be paid to the health status of nurses working 12-hr shifts, with regular medical monitoring by the occupational health service.

Implications For Nursing Management: Coping strategies to maintain sufficient vigilance to ensure quality of care should be facilitated.
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http://dx.doi.org/10.1111/jonm.13233DOI Listing
December 2020

Surveillance of Cardiovascular Risk Factors in the Fifth Military Sector Health Center, Ngaoundéré, Cameroon: Observational Study.

JMIR Form Res 2020 Nov 26;4(11):e18567. Epub 2020 Nov 26.

Autonomic Nervous System Research Laboratory, University of Jean Monnet, Saint-Etienne, France.

Background: Noncommunicable diseases (NCDs) are the leading causes of death worldwide. They were responsible for 40 million of the 57 million deaths recorded worldwide in 2016. In Cameroon, epidemiological studies have been devoted to NCDs and their risk factors. However, none provides specific information on their extent or the distribution of their risk factors within the Cameroonian defense forces.

Objective: The objective of our study was to assess the cardiovascular risk of a Cameroonian military population compared with that of its neighboring civilian population.

Methods: We conducted a cross-sectional study that involved subjects aged 18 to 58 years, recruited from October 2017 to November 2018 at the Fifth Military Sector Health Center in Ngaoundéré, Cameroon. Data collection and assessment were done according to the World Health Organization (WHO)'s STEPS manual for surveillance of risk factors for chronic NCDs and the Alcohol Use Disorders Identification Test. Five cardiovascular risk factors were assessed: smoking, harmful alcohol consumption, obesity/overweight, hypertension, and diabetes. The risk was considered high in subjects with 3 or more of the factors. Univariate analysis and multivariate logistic regression were carried out according to their indications.

Results: Our study sample of 566 participants included 295 soldiers and 271 civilians of the same age group (median age 32 years versus 33 years, respectively; P=.57). The military sample consisted of 31 officers and 264 noncommissioned officers (NCOs). Soldiers were more exposed to behavioral risk factors than civilians, with a prevalence of smoking of 13.9% versus 4.4% (P<.001) and excessive alcohol consumption of 61.7% versus 14.8% (P<.001). They also presented with a higher cardiovascular risk than civilians (odds ratio 2.7, 95% CI 1.50-4.81; P<.001), and among the military participants, the cardiovascular risk was higher for officers than for NCOs (51.6% versus 14.0%, respectively; P<.001).

Conclusions: Cameroonian soldiers are particularly exposed to cardiovascular behavioral risk factors and consequently are at higher risk of NCDs.

Trial Registration: ClinicalTrials.gov NCT04315441; https://clinicaltrials.gov/ct2/show/NCT04315441.
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http://dx.doi.org/10.2196/18567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728542PMC
November 2020

Correction to: Social marketing interventions to promote physical activity among 60 years and older: a systematic review of the literature.

BMC Public Health 2020 Oct 28;20(1):1622. Epub 2020 Oct 28.

Laboratoire SNA EPIS EA 4607, Université Jean Monnet, Saint-Étienne, France.

An amendment to this paper has been published and can be accessed via the original article.
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http://dx.doi.org/10.1186/s12889-020-09742-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594420PMC
October 2020

Management of sleep apnoea syndrome (SAS) in patients with vasovagal syncope (VVS): a protocol for the VVS-SAS cohort study.

BMJ Open 2020 09 30;10(9):e038791. Epub 2020 Sep 30.

Department of Medical Information, IMAG, CNRS, Univ Montpellier, Centre Hospitalier Universitaire de Montpellier, Montpellier, France.

Introduction: Recurrent vasovagal syncope (VVS) is associated with decreased quality-of-life and frequent use of emergency services. The evidence base for causality, diagnostic procedures and potential VVS treatments is poor. Scattered observations in the literature suggest a link between respiratory disturbances during sleep and VVS. Empirical observations lead us to further hypothesise that the appropriate management of sleep apnoea syndrome (SAS) may help resolve comorbid recurrent VVS in certain patients. We therefore designed this pilot study to provide a framework for the observation of changes in outcomes accompanying the deployment of SAS treatments in patients with VVS.

Methods And Analysis: This is a multicentre, registry-based study whose primary objective is to evaluate the effect of SAS management on the number of syncope/presyncope episodes in a population suffering from both VVS and SAS. To this effect, syncope rates prior to the treatment of SAS will be compared with those occurring after the initiation of the latter. In addition, yearly assessments will collect data for echocardiography, polysomnography, Holter monitoring, table tilt tests, multiple sleep latency tests, SAS management parameters and questionnaires describing fatigue, depression and quality-of-life. Sixty patients will be included with a minimum follow-up period of 12 months. The primary analysis will use comparisons of centrality for paired data to describe the changes in syncope rates before versus after the initiation of SAS management. Longitudinal data will be analysed using mixed models with patients set as a random effect. Subgroup analyses will be performed for SAS-treatment adherence and efficacy.

Ethics And Dissemination: The VVS-SAS registry was approved by an ethics committee (Comité pour la Protection des Personnes Ile-de-France VI, Reference number CPP/2-18) in accordance with French law. The princeps publication will present before-after SAS management results and longitudinal analyses.

Trial Registration Number: NCT04294524. Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2020-038791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7528365PMC
September 2020

Social marketing interventions to promote physical activity among 60 years and older: a systematic review of the literature.

BMC Public Health 2020 Aug 28;20(1):1312. Epub 2020 Aug 28.

Laboratoire SNA EPIS EA 4607, Université Jean Monnet, Saint-Étienne, France.

Background: Falls are a significant source of morbidity in people aged 65 and over, affecting one in three people in this age group. The scientific evidence indicates that physical activity is the most effective method for preventing falls among seniors. Although public health professionals often use social marketing to design and plan successful interventions, its use to promote physical activity and prevent falls among older people remains low. This article aims to provide a new systematic literature review of social marketing interventions promoting physical activity and targeting people aged 60 and over.

Methods: Following CRD's guidance and PRISMA guidelines, we searched between January 2008 and July 2019 for relevant articles in five primary databases using predefined search and inclusion criteria. Two independent reviewers analysed the selected articles to identify evidence of the seven social marketing benchmark criteria, defined by experts in the field as the common elements that contribute to social marketing success.

Results: The final review included nine studies. Of the studies selected, three specifically targeted over 60-year-olds, whereas the others segmented the population into several age-based subcategories, including over 60-year-olds. Eight studies highlighted positive results for the participants with an increase in participation or an increase in physical activity level. None of the nine studies selected for this systematic review implemented the entire social marketing approach.

Conclusion: Few published interventions use the seven social marketing criteria. Further research is required to encourage uptake and inclusion in successful social marketing interventions to increase program effectiveness in this target population.
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http://dx.doi.org/10.1186/s12889-020-09386-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456007PMC
August 2020

Perinatal inflammation is associated with social and motor impairments in preterm children without severe neonatal brain injury.

Eur J Paediatr Neurol 2020 Sep 13;28:126-132. Epub 2020 Jul 13.

Neonatal Intensive Care Unit, Department of Pediatrics, Centre Hospitalier Universitaire de Saint-Étienne, Saint-Étienne, France; EA 4607 SNA EPIS, Université de Lyon, Université Jean Monnet, Saint-Étienne, France.

Objective: To test the association between exposure to perinatal inflammation - i.e. clinical chorioamnionitis or early-onset neonatal infection - in preterm children without severe neonatal brain injury and neurodevelopmental outcome at 30 months of corrected age (CA).

Design: Cross-sectional study from a French regional cohort of clinical follow-up (SEVE Network).

Patients: One hundred sixty-four surviving neonates without severe brain injury - namely, grade III and IV cerebral hemorrhage and cystic periventricular leukomalacia - and without late-onset neonatal inflammation exposure - namely, late-onset neonatal infection and necrotizing enterocolitis -, born at less than 33 weeks of gestational age from November 2011 to June 2015 and enrolled in the SEVE Network.

Main Outcome Measure: Global developmental quotient (DQ) score of the revised Brunet-Lézine scale and its four indices measured by the same neuropsychologist at 30 months of CA.

Results: After multivariate analysis, exposure to perinatal inflammation was not found significantly associated with a modification of the global DQ score (coefficient -1.7, 95% CI -4.8 to 1.3; p = 0.26). Exposure to perinatal inflammation was associated with a decrease of the gross motor function DQ score (coefficient -6.0, 95% CI -9.9 to -2.1; p < 0.01) and a decrease of the sociability DQ score (coefficient -5.1, 95% CI -9.2 to -0.9; p = 0.02). Language and visuospatial coordination DQ scores were not affected by exposure to perinatal inflammation.

Conclusion: Exposure to perinatal inflammation in preterm children without severe neonatal brain injury is independently associated with decreased motor and social abilities at 30 months of CA.
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http://dx.doi.org/10.1016/j.ejpn.2020.06.008DOI Listing
September 2020

Role of Gender and Physical Activity Level on Cardiovascular Risk Factors and Biomarkers of Oxidative Stress in the Elderly.

Oxid Med Cell Longev 2020 19;2020:1315471. Epub 2020 Jun 19.

Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM) EA7424, Team « Vascular Biology and Red Blood Cell », Univ Lyon, Université Claude Bernard Lyon 1, Villeurbanne, France.

Background: Cardiovascular diseases remain as the leading cause of morbidity and mortality in industrialized countries. Ageing and gender strongly modulate the risk to develop cardiovascular diseases but very few studies have investigated the impact of gender on cardiovascular diseases in the elderly, which represents a growing population. The purpose of this study was to test the impact of gender and physical activity level on several biochemical and clinical markers of cardiovascular risk in elderly individuals.

Methods: Elderly individuals (318 women (75.8 ± 1.2 years-old) and 227 men (75.8 ± 1.1 years-old)) were recruited. Physical activity was measured by a questionnaire. Metabolic syndrome was defined using the National Cholesterol Education Program Expert Panel's definition. Polysomnography and digital tonometry were used to detect obstructive sleep apnea and assess vascular reactivity, respectively. Blood was sampled to measure several oxidative stress markers and adhesion molecules.

Results: The frequency of cardiovascular diseases was significantly higher in men (16.4%) than in women (6.1%) ( < 0.001). Body mass index (25.0 ± 4.3 vs. 25.8 ± 3.13 kg.m) and glycaemia (94.9 ± 16.5 vs. 101.5 ± 22.6 mg.dL) were lower, and High Density Lipoprotein (HDL) (74.6 ± 17.8 vs. 65.0 ± 17.2 mg.dL) was higher in women compared to men ( < 0.05). Oxidative stress was lower in women than in men (uric acid: 52.05 ± 13.78 vs. 59.84 ± 13.58, advanced oxidation protein products: 223 ± 94 vs. 246 ± 101 mol.L, malondialdehyde: 22.44 ± 6.81 vs. 23.88 ± 9.74 nmol.L). Physical activity was not associated with lower cardiovascular risk factors in both genders. Multivariate analyses showed an independent effect of gender on acid uric ( = 0.182; = 0.020), advanced oxidation protein products ( = 0.257; < 0.001), and HDL concentration ( = -0.182; = 0.026).

Conclusion: These findings suggest that biochemical cardiovascular risk factors are lower in women than men which could explain the lower cardiovascular disease proportion observed in women in the elderly.
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http://dx.doi.org/10.1155/2020/1315471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7321518PMC
May 2021

Sera of elderly obstructive sleep apnea patients alter blood-brain barrier integrity in vitro: a pilot study.

Sci Rep 2020 07 9;10(1):11309. Epub 2020 Jul 9.

Clinical Physiology, University Hospital (CHU), Saint-Étienne, France.

Obstructive sleep apnea syndrome (OSAS) is characterized by repeated episodes of hypoxia during the night. The severity of the disorder can be evaluated using an apnea-hypopnea index (AHI). The physiological consequences are mainly cardiovascular and neuronal dysfunctions. One hypothesis to explain such associated neurological disorders is disruption of the blood-brain barrier (BBB), which protects the brain from endovascular cytotoxic compounds. We selected two subgroups of volunteers from the PROOF cohort study (France), a group of patients suffering newly diagnosed severe OSAS (AHI > 30/h) and a group showing no sleep apnea (AHI < 5/h). We exposed a human in vitro BBB model of endothelial cells (HBEC-5i) with sera of patients with and without OSAS. After exposure, we measured the apparent BBB permeability as well as tight junction and ABC transporter expression using whole cell ELISA. We showed that after incubation with sera from OSAS patients, there was a loss of integrity in the human in vitro BBB model; this was reflected by an increase in permeability (43%; p < 0.001) and correlated with a 50% and 40% decrease in tight junction protein expression of ZO-1 and claudin-5, respectively. At the same time, we observed an upregulation in Pgp protein expression (52%) and functionality, and a downregulation in BCRP expression (52%). Our results demonstrated that severe BBB disorder after exposure to sera from OSAS patients was reflected by an opening of the BBB.
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http://dx.doi.org/10.1038/s41598-020-68374-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347951PMC
July 2020

Prevalence of cardiovascular risk factors in a population of French firefighters.

Arch Environ Occup Health 2021 16;76(1):45-51. Epub 2020 Jun 16.

Department of Occupational Health, University Hospital, Saint-Priest-en-Jarez cedex, France.

Firefighters' activities increase the risk of sudden cardiac events. The main objective of this study was to describe the Loire firefighters' cardiovascular risk factors according to their cardiovascular risk and to their professional status. A retrospective study of the entire population of firefighters of the Loire department was conducted. Risk factors derived from the data collected during the occupational health follow-up medical examinations were described and the cardiovascular risk was assessed for 417 firefighters. The most frequent cardiovascular risk factors were: overweight and obesity (62.1%), high blood pressure (27.8%) and active smoking (16,1%). There were no significant differences between career firefighters and volunteers. The prevalence of risk factors for cardiovascular diseases is less than in the general population. Obesity remains the most common risk factor, especially among firefighters with high cardiovascular risk.
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http://dx.doi.org/10.1080/19338244.2020.1779017DOI Listing
March 2021

Using 99mTc-(V)-DMSA to follow the vascular calcification process in vascular smooth muscle cells based on pit-1 expression.

Q J Nucl Med Mol Imaging 2020 Jun 15. Epub 2020 Jun 15.

INSERM U1059 Dysfonction Vasculaire et Hémostase, Université de Lyon, UJM-Saint-Etienne, Saint-Étienne, France.

Background: Vascular calcification is an established feature of atherosclerosis process. The sodium/phosphate transporter PiT-1 acts as a biosensor in vascular calcification of VSMCs. [99mTc]-Pentavalent dimercaptosuccinic acid (99mTc-(V)-DMSA) was mediated by PiT-1 transporter in tumoral cells and we propose its evaluation in a vascular calcification in vitro model. The aim of this study was to determine if 99mTc-(V)-DMSA can follow the vascular calcification process in vascular smooth muscle cells (VSMCs) based on PiT-1 expression.

Methods: From a rat aortic VSMC cell line (A7r5), we set up a model of calcification within 7 days using a calcifying medium containing a high inorganic phosphate concentration. Phosphocalcic deposits were monitored with Alizarin red and Von Kossa staining and with phase contrast microscopy. PiT-1 expression was evaluated with an immunofluorescence assay and osteopontin expression, with whole cell ELISA assay. 99mTc-(V)-DMSA uptake was measured in control and calcifying conditions and compared with optical microscopy evaluation.

Results: Under hyperphosphatemia conditions, the VSMC cells progressively overexpressed osteopontin protein, PiT-1 transporter, and synthetized mineralized matrix with phosphocalcic deposition. 99mTc-(V)-DMSA uptake was to 2.8+/-2.08%DA/mg-protein in control cells and 42+/-24%DA/mg-protein in calcified cells (p<0,001). PiT-1 inhibition with phosphonoformic acid completely reverse the calcium deposition as well as the 99mTc-(V)- DMSA uptake. These results demonstrated that 99mTc-(V)-DMSA in vitro uptake is mediated by PiT-1 transporter and follow the VSMC calcification process.

Conclusions: These preliminary in vitro results showed 99mTc-(V)-DMSA uptake follow the phospho-calcic deposition mediated by PiT-1 transporter. This radiotracer may have some potential to detect changes of VSMC metabolism occurring in the atherosclerosis process.
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http://dx.doi.org/10.23736/S1824-4785.20.03225-2DOI Listing
June 2020

Causal analyses to study autonomic regulation during acute head-out water immersion, head-down tilt and supine position.

Exp Physiol 2020 08 12;105(8):1216-1222. Epub 2020 Jun 12.

Saint-Etienne Jean Monnet University, CHU de Saint-Etienne, Department of Clinical and Exercise Physiology, University of Lyon, SNA-EPIS (EA4607), Saint-Etienne, F-42055, France.

New Findings: What is the central question of this study? Can Granger causality analysis of R-R intervals, systolic blood pressure and respiration provide evidence for the different physiological mechanisms induced during thermoneutral water immersion, 6 deg head-down tilt and supine position tests that are not accessible using traditional heart rate variability and baroreflex methods? What is the main finding and its importance? The Granger analysis demonstrated a significant difference in the causal link from R-R intervals to respiration between water immersion and head-down tilt. The underlying physiological mechanism explaining this difference could be the variation in peripheral resistances.

Abstract: Thermoneutral head-out water immersion (WI) and 6 deg head-down tilt (HDT) are used to simulate SCUBA diving, swimming and microgravity, because these models induce an increase in central blood volume. Standard methods to analyse autonomic regulation have demonstrated an increase in parasympathetic activity and baroreflex sensitivity during these experimental conditions. However, such methods are not adapted to quantify all closed-loop interactions involved in respiratory and cardiovascular regulation. To overcome this limitation, we used Granger causality analysis between R-R intervals (RR), systolic blood pressure (SBP) and respiration (RE) in eight young, healthy subjects, recorded during 30 min periods in the supine position, WI and HDT. For all experimental conditions, we found a bidirectional causal relationship between RE and RR and between RR and SBP, with a dominant direction from RR to SBP, and a unidirectional causality from RE to SBP. These causal relationships remained unchanged for the three experimental tests. Interestingly, there was a lower causal relationship from RR to RE during WI compared with HDT. This causal link from RR to RE could be modulated by peripheral resistances. These results highlight differences in cardiovascular regulation during WI and HDT and confirm that Granger causality might reveal physiological mechanisms not accessible with standard methods.
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http://dx.doi.org/10.1113/EP088640DOI Listing
August 2020

Ampicillin Treatment Increases Placental Interleukin-1 Beta Concentration and Polymorphonuclear Infiltration in Group B Streptococcus-Induced Chorioamnionitis: A Preclinical Study.

Neonatology 2020 6;117(3):369-373. Epub 2020 May 6.

Child Neurology Division, Department of Pediatrics, McGill University, Montreal, Québec, Canada.

Background: Antibiotic therapy during preterm labor with intact membranes has been associated with an increased risk of neonatal death.

Objectives: Using an established rat model of group B Streptococcus (GBS)-induced chorioamnionitis, we hypothesized that ampicillin treatment increases placental inflammation, as shown in other bacterial infections.

Methods: At gestational day 19, 19 Lewis dams were intraperitoneally (i.p.) inoculated by 108 CFU of β-hemolytic serotype Ia GBS (strain #16955 susceptible to ampicillin). Dams were treated i.p. with either 200 mg/kg of ampicillin (n = 9) or 0.9% saline (n = 10) at 48 and 60 h post-GBS inoculation. Cesarean sections were performed 72 h post-GBS inoculation.

Results: Ampicillin treatment was associated with an increased number of polymorphonuclear cells (PMN) infiltrating the decidua (mean 1,536 vs. 532 PMN/mm2; p < 0.001) and a higher placental concentration of IL-1β (mean 26.4 vs. 7.9 pg/mg; p < 0.01) compared to saline-treated dams. These effects were observed in dams without GBS bacteremia. Conversely, ampicillin treatment was associated with a decreased placental concentration of proinflammatory cytokines in dams with GBS bacteremia.

Conclusions: Ampicillin increases placental inflammation in a rat model of GBS-induced chorioamnionitis without bacteremia. This proinflammatory effect of ampicillin could be due to bacterial lysis. Our findings do not query the intrapartum antibiotic prophylaxis against GBS disease. They pave the way for future preclinical studies combining anti-inflammatory treatments and antibiotic therapy for GBS-induced chorioamnionitis.
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http://dx.doi.org/10.1159/000506906DOI Listing
May 2020

Physical activity types and risk of dementia in community-dwelling older people: the Three-City cohort.

BMC Geriatr 2020 04 10;20(1):132. Epub 2020 Apr 10.

Univ. Montpellier, Inserm U1061, Neuropsychiatry: epidemiological and clinical research, PSNREC, 39 avenue Charles Flahault, BP 34493, 34093, Montpellier cedex 05, France.

Background: Physical activity may decrease the risk of dementia; however, previous cohort studies seldom investigated the different types of physical activity and household activities. Our objective was to analyze the links between two physical activity types and dementia in older people.

Methods: The study used data from the prospective observational Three-city cohort and included 1550 community-dwelling individuals aged 72 to 87 without dementia at baseline. Physical activity was assessed with the Voorrips questionnaire. Two sub-scores were calculated to assess household/transportation activities and leisure/sport activities. Restricted cubic spline and proportional hazard Cox models were used to estimate the non-linear exposure-response curve for the dementia risk and the appropriate activity level thresholds. Models were adjusted for possible confounders, including socio-demographic variables, comorbidities, depressive symptoms and APOE genotype.

Results: The median age was 80 years, and 63.6% of participants were women. After a median follow-up of 4.6 years, dementia was diagnosed in 117 participants (7.6%). An inverse J-shaped association was found between household/transportation physical activity sub-score and dementia risk, which means that the risk is lowest for the moderately high values and then re-increases slightly for the highest values. The results remained significant when this sub-score was categorized in three classes (low, moderate, and high), with hazard ratios (95% confidence interval) of 0.55 (0.35-0.87) and 0.62 (0.38-1.01) for moderate and high activity levels, respectively. No significant effect was found for leisure/sport activities.

Conclusions: The 5-year risk of dementia was significantly and negatively associated with the household/transportation activity level, but not with the leisure and sport activity sub-score. This highlights the importance of considering all physical activity types in 72 years or older people.
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http://dx.doi.org/10.1186/s12877-020-01538-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146952PMC
April 2020

Sleep apnoea and endothelial dysfunction: An individual patient data meta-analysis.

Sleep Med Rev 2020 08 13;52:101309. Epub 2020 Mar 13.

INSERM U1063, SOPAM, Angers University, F-49045, Angers, France; Department of Respiratory and Sleep Medicine, Angers University Hospital, Angers, France. Electronic address:

We performed an individual patient data meta-analysis to investigate the association between obstructive sleep apnoea (OSA) severity and the reactive hyperaemia index (RHI) measured by peripheral arterial tonometry (PAT), a validated measurement of endothelial function, and a strong predictor of late cardiovascular (CV) events. Patients from 12 studies underwent PAT and overnight polysomnography or respiratory polygraphy for suspected OSA. Endothelial dysfunction was defined by a log-transformed RHI<0.51. Subgroup analyses were performed to investigate this relationship in specific populations. Among 730 patients without overt CV disease, 387 (53.0%) had severe OSA (apnoea-hypopnea index ≥30) and 164 (22.5%) exhibited endothelial dysfunction. After adjustment for age, gender, diastolic blood pressure, obesity, diabetes and chronic obstructive pulmonary disease, endothelial dysfunction was associated with severe OSA (odds ratio, OR [95% confidence interval]: 2.27 [1.12-4.60]; p = 0.02), and nocturnal hypoxemia defined by >20 min with oxygen saturation <90% (OR: 1.83 [1.22-2.92]; p = 0.004) or mean oxygen saturation <92% (OR: 1.52 [1.17-1.96]; p = 0.002). On subgroup analyses, the association between severe OSA and endothelial dysfunction was not significant in patients with hypertension, obesity and/or diabetes. Among adults without overt CV disease, severe OSA is independently associated with an increased risk of endothelial dysfunction that may predispose to late CV events.
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http://dx.doi.org/10.1016/j.smrv.2020.101309DOI Listing
August 2020

Magnesium transport and homeostasis-related gene expression in skeletal muscle of young and old adults: analysis of the transcriptomic data from the PROOF cohort Study.

Magnes Res 2019 Aug;32(3):72-82

Université Clermont Auvergne, INRA, UNH, Unité de Nutrition Humaine, CRNH Auvergne, F-63000 Clermont-Ferrand, France.

Magnesium (Mg) is critical for a number of biological processes and 25% body Mg is located in the skeletal muscle. Mg transport and homeostasis systems (MgTHs) regulate intracellular Mg concentration and muscle MgTHs are thus related to whole body Mg homeostasis. Nonetheless, few studies have investigated the regulation of muscle MgTHs under (patho)physiological conditions. Herein, we assessed the relationship between the expression of MgTHs genes (Trpm6, Trpm7, Magt1, Mrs2, Cnnm1-4, Slc41a1-3) and relevant pathways in human sarcopenia, which is one of the most dramatic physiologic changes affecting the human body. Transcriptomic data were compared between young adult (YO, 22 y, n = 11) and old (EL, 73 y, n = 13) men from the PROOF cohort. MgTH mRNA levels did not change with aging, with the exception of a slight decrease for Slc41a3. Nevertheless, interindividual variations of mRNA levels revealed strong correlations between MgTHs in the YO group, while few were maintained in the EL muscle. Moreover, in the YO muscle, different clusters of MgTH mRNAs strongly correlated with divers physiological (BMI, blood pressure) and muscle characteristics (intramyocellular droplets, capillarization); however, most correlations changed or disappeared in the EL muscle. Further investigations of the whole transcriptome identified several sets of mRNAs correlated with defined MgTHs. There again was a sharp difference between YO and EL muscles, as the number of mRNAs correlated with MgTHs strongly decreased with aging. Gene ontology analyses of these sets of correlated mRNAs revealed 6 biological processes common to YO and EL, 3 specific to the YO (RNA processing, translation, respiration), and 2 (regulation of catabolic process, Wnt signaling) to the EL muscle. Overall, these observations lead to questions about potential resilience to muscle Mg homeostasis in the elderly.
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http://dx.doi.org/10.1684/mrh.2019.0458DOI Listing
August 2019

Dynamic Force Production Capacities Between Coronary Artery Disease Patients vs. Healthy Participants on a Cycle Ergometer.

Front Physiol 2019 24;10:1639. Epub 2020 Jan 24.

UJM-Saint-Etienne Autonomic Nervous System Research Laboratory, EA 4607 SNA-EPIS, University of Lyon, Saint-Étienne, France.

Background: The force-velocity-power (FVP) profile is used to describe dynamic force production capacities, which is of great interest in training high performance athletes. However, FVP may serve a new additional tool for cardiac rehabilitation (CR) of coronary artery disease (CAD) patients. The aim of this study was to compare the FVP profile between two populations: CAD patients vs. healthy participants (HP).

Methods: Twenty-four CAD patients (55.8 ± 7.1 y) and 24 HP (52.4 ± 14.8 y) performed two sprints of 8 s on a Monark cycle ergometer with a resistance corresponding to 0.4 N/kg × body mass for men and 0.3 N/kg × body mass for women. The theoretical maximal force () and velocity (), the slope of the force-velocity relationship () and the maximal mechanical power output () were determined.

Results: The (CAD: 6.86 ± 2.26 W.kg vs. HP: 9.78 ± 4.08 W.kg, = 0.003), (CAD: 5.10 ± 0.82 m.s vs. HP: 5.79 ± 0.97 m.s, = 0.010), and (CAD: 1.35 ± 0.38 N.kg vs. HP: 1.65 ± 0.51 N.kg, = 0.039) were significantly higher in HP than in CAD. No significant difference appeared in S (CAD: -0.27 ± 0.07 N.kg.m.s vs. HS: -0.28 ± 0.07 N.kg.m.s, = 0.541).

Conclusion: The lower maximal power in CAD patients was related to both a lower and . Physical inactivity, sedentary time and high cardiovascular disease (CVD) risk may explain this difference of force production at both high and low velocities between the two groups.
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http://dx.doi.org/10.3389/fphys.2019.01639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6993059PMC
January 2020

Pulse wave amplitude drops during sleep: clinical significance and characteristics in a general population sample.

Sleep 2020 07;43(7)

Center for Investigation and Research in Sleep (CIRS), Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland (Institution where the work was performed).

Study Objectives: To explore the clinical significance of pulse wave amplitude (PWA)-drops during sleep as a biomarker for cardiometabolic disorders and describe their main characteristics in a general population sample.

Methods: Cross-sectional study of HypnoLaus cohort, in which 2162 individuals underwent clinical assessment and in-home full polysomnography. PWA-drops were derived from photoplethysmography and processed using a validated automated algorithm. Associations between PWA-drop features (index, mean duration, and mean area under the curve [AUC]) with hypertension, diabetes, and previous cardiovascular (CV) event were analyzed using multivariable-adjusted logistic regression.

Results: Two thousand one hundred forty-nine participants (59 ± 11 years, 51% women, 9.9% diabetes, 41.3% hypertension, 4.4% CV event) were included. Mean ± standard deviation (SD) of PWA-drop index, duration, and AUC during sleep were 51.0 ± 20.3 events/hour, 14.0 ± 2.7 seconds, and 527±115 %seconds, respectively. PWA-drop index was lower in women and decreased with age, while its mean duration and AUC increased in men and elderly. Overall, lower PWA-drop index, longer duration and greater AUC were associated with increased odds of hypertension, diabetes, or CV event after adjustment for confounders. Participants in the lowest quartile of mean duration-normalized PWA-drop index had a significantly higher odds ratio (OR) of hypertension (OR = 1.60 [1.19-2.16]), CV event (OR = 3.26 [1.33-8.03]), and diabetes (OR = 1.71 [1.06-2.76]) compared to those in the highest quartile. Similar results were observed for mean AUC-normalized PWA-drop index regarding hypertension (OR = 1.59 [1.19-2.13]), CV event (OR = 2.45 [1.14-5.26]) and diabetes (OR = 1.76 [1.10-2.83]).

Conclusions: PWA-drop features during sleep seem to be an interesting biomarker independently associated with cardiometabolic outcomes in the general population.
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http://dx.doi.org/10.1093/sleep/zsz322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355400PMC
July 2020

Inflammatory stress induced by a combination of cytokines (IL-6, IL-17, TNF-α) leads to a loss of integrity on bEnd.3 endothelial cells in vitro BBB model.

Brain Res 2020 03 3;1730:146647. Epub 2020 Jan 3.

Univ Lyon, UJM-Saint-Étienne, SNA-EPIS, EA4607 Saint-Étienne, France.

The brain is a complex organ protected by the blood-brain barrier (BBB), which also has a complex organization. To play its protective role, the BBB acts by limiting the paracellular passage of potentially cytotoxic compounds through tight junctions as well as limiting transcellular passage by efflux pumps (ABC transporters). In many conditions such as sleep apnea or Alzheimer's disease, there is chronic inflammation, resulting in the presence of pro-inflammatory cytokines in the bloodstream. The effect of this chronic inflammation on the integrity of the BBB has been studied mainly through a single inflammatory molecule; but in physiological and pathological conditions, it is a combination of inflammatory cytokines. We investigated the effect of three major pro-inflammatory cytokines (IL-17, IL-6, TNF-α) used alone or in combination on the integrity of an in vitro model of BBB. Our study showed 24 h of inflammatory stress led to a BBB's opening, reflected by a significant increase of permeability, which was correlated to a significant decrease of tight junction protein expressions (ZO-1, claudin-5), involving a possible entry of cytotoxic compounds into the brain. To compensate the loss of integrity, one of defense mechanism of endothelial cells was efflux transport, which showed a significant increase in expression and functionality of ABC transport proteins (MRP-1, Pgp). This opening of the BBB was more important when pro-inflammatory cytokines were combined, which could be explained by the interaction between cytokines and the potentiation of their effect.
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http://dx.doi.org/10.1016/j.brainres.2020.146647DOI Listing
March 2020

Autonomic cardiovascular adaptations to acute head-out water immersion, head-down tilt and supine position.

Eur J Appl Physiol 2020 Feb 7;120(2):337-347. Epub 2019 Dec 7.

EA 4607 SNA-EPIS, Service de Physiologie Clinique et de l'Exercice, Pole NOL, CHU Nord, Faculté de Médecine Jacques Lisfranc, Université Jean Monnet, PRES Université de Lyon, Saint-Étienne, France.

Purpose: Thermoneutral head-out water immersion (WI) and 6° head-down tilt (HDT) have been considered as suitable models to increase central blood volume and simulate autonomic cardiovascular adaptations to microgravity, swimming or scuba diving. However, any differences in autonomic cardiovascular adaptations are still unclear. In this study, we hypothesized that WI induces a higher activation of arterial baroreceptors and the parasympathetic system.

Methods: Ten healthy men underwent 30 min of WI, HDT, and a supine position (SP). RR intervals (RRI) and blood pressure (BP) were continuously monitored. High frequency power (HF), low frequency power (LF) and LF/HF ratio were calculated to study sympathetic and parasympathetic activities, and a spontaneous baroreflex method was used to study arterial baroreflex sensitivity (aBRS). Lung transfer of nitric oxide and carbon monoxide (TLNO/TLCO), vital capacity and alveolar volume (Vc/VA) were measured to study central blood redistribution.

Results: We observed (1) a similar increase in RRI and decrease in BP; (2) a similar increase in HF power during all experimental conditions, whereas LF increased after; (3) a similar rise in aBRS; (4) a similar increase in Vc/VA and decrease in TLNO/TLCO in all experimental conditions.

Conclusions: These results showed a cardiac parasympathetic dominance to the same extent, underpinned by a similar arterial baroreflex activation during WI and HDT as well as control SP. Future studies may address their association with cold or hyperoxia to assess their ability to replicate autonomic cardiovascular adaptations to microgravity, swimming or scuba diving.
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http://dx.doi.org/10.1007/s00421-019-04278-4DOI Listing
February 2020

Determinants of Nocturnal Cardiovascular Variability and Heart Rate Arousal Response in Restless Legs Syndrome (RLS)/Periodic Limb Movements (PLMS).

J Clin Med 2019 Oct 4;8(10). Epub 2019 Oct 4.

EA SNA-EPIS Service de Physiologie Clinique et de l'Exercice (Pole Hospitalier NOL), CHU de Saint-Étienne, Faculté de Médecine Jacques Lisfranc, Université Jean Monnet, Université de Lyon, 42055 Saint-Étienne, France.

Recent studies have suggested that restless legs syndrome is associated with an increased prevalence of cardiovascular diseases mediated by sympathetic activation occurring during periodic limb movements. The aim of this study was to establish which factors affect the degree of sympathetic activation during the basal condition and during periodic limb movements that may contribute to increased vascular risk. Fifty untreated restless legs syndrome patients aged 62.6 ± 11.1 y, free of cardiovascular diseases, were examined. Heart rate variability was calculated during wakefulness and all sleep stages, during periods with and without periodic limb movements. Heart rate changes before and after periodic limb movement onset were analyzed to assess the arousal response to periodic limb movements. Both analyses took into account the effects of age, gender, periodic limb movement duration, periodic limb movement index, periodic limb movement interval and periodicity, and magnitude of muscular activity (electromyogram power). Compared to periods without periodic limb movements, a significant increase in sympathetic activity occurred in periods with periodic limb movements, independent of age, sex and periodic limb movement characteristics. Data obtained from the cardiac arousal response to periodic limb movements showed that electromyogram power is the factor affecting sympathetic tonus. These results suggest that other factors, such as electromyogram power and individual susceptibility, should be considered in the assessment of the vascular risk related to restless legs syndrome.
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http://dx.doi.org/10.3390/jcm8101619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832401PMC
October 2019

Factors Influencing Adherence to Auto-CPAP: An Observational Monocentric Study Comparing Patients With and Without Cardiovascular Diseases.

Front Neurol 2019 2;10:801. Epub 2019 Aug 2.

Service de Physiologie Clinique et de l'Exercice, CHU de Saint-Etienne, Saint-Étienne, France.

Obstructive sleep apnea/hypopnea (OSAH) affects more than 15% of the general population and increases the occurrence of cardiovascular (CV) and metabolic events. Continuous positive airway pressure (CPAP) treatment is currently the gold standard treatment of OSAH and could prevent the occurrence of such events. However, long-term adherence to CPAP is a problem where a significant rate stop device treatment use. OSAH patients suffering CV disease could be less compliant due to less diurnal symptoms. We performed a prospective study of 408 non-CV or CV disease patients suffering severe OSAH syndrome and followed them during the first 5 months as well as a mean of 3 years of CPAP treatment use. We demonstrated that in adult OSAH patients that two variables were associated with a low compliance (<5 h/night): age <60 y and lower maximal positive airway pressure level used. There was no significant impact of the presence of CV disease on compliance of 5 months. After 3 years of CPAP, age <60 y as well as diabetes were independent factors of low compliance. There was no significant association between gender, mask types, 90th centile positive airway pressure level, apnea/hypopnea index and short- or long-term compliance in our population. We did not find lower compliance of CPAP in CV OSAH patients. Most of our population (68-73%) demonstrated an optimal night treatment duration at 3 years of follow-up, allowing a reduction of CV occurrence or recurrence. We hypothesize that an early and short education of OSAH as we routinely proposed could allow a significant increase in the optimal observance of CPAP in at-risk populations.
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http://dx.doi.org/10.3389/fneur.2019.00801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6688161PMC
August 2019