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Maxillary lateral incisors are frequently missing in patients with cleft lip and/or palate. The aim of this study was to assess how orthodontic gap closure or prosthetic rehabilitation of the missing maxillary lateral incisor affected dental arch relationships and symmetry at the end of treatment. The authors also aimed to determine the effect of the level of oral hygiene on the decision made to manage the missing maxillary lateral incisor gap.A descriptive, retrospective cohort study including all patients with cleft lip and/or palate born between 1980 and 1999 and treated at Nantes Cleft Center was performed. Patients presenting unilateral or bilateral missing maxillary lateral incisors were reviewed. Data on management of the missing incisor gap, dental arch relationships, symmetry, and level of oral hygiene were collected.A total of 486 patients with cleft lip and/or palate were reviewed, including 212 patients with unilateral or bilateral missing maxillary lateral incisors. When compared with orthodontic gap closure, prosthetic replacement of the gap was associated with better final dental arch relationships (59.8 percent versus 10.3 percent; p0.01) and better dental arch symmetry (88.1 percent versus 44.0 percent; p0.01) for patients with unilateral missing incisors but not for patients with bilateral missing incisors. A higher level of oral hygiene was associated with more cases of prosthetic replacement for patients with unilateral missing incisors ( p = 0.03) but had no effect for patients with bilateral missing incisors.Prosthetic replacement of the missing maxillary lateral incisor gap provided better functional and aesthetic results for patients with cleft lip and/or palate presenting with unilateral missing maxillary lateral incisor.

International audience; Background and objectives Age and comorbidity-related sarcopenia represent a main cause of muscle dysfunction in patients on long-term hemodialysis. However, recent findings suggest muscle abnormalities that are not associated with sarcopenia. The aim of this study was to isolate functional and cellular muscle abnormalities independently of other major confounding factors, including malnutrition, age, comorbidity, or sedentary lifestyle, which are common in patients on maintenance hemodialysis. To overcome these confounding factors, alterations in skeletal muscle were analyzed in highly selected patients on long-term hemodialysis undergoing kidney transplantation. Design, setting, participants, & measurements In total, 22 patients on long-term hemodialysis scheduled for kidney transplantation with few comorbidities, but with a long-term uremic milieu exposure, and 22 age, sex, and physical activity level frequency-matched control participants were recruited. We compared biochemical, functional, and molecular characteristics of the skeletal muscle using maximal voluntary force and endurance of the quadriceps, 6-minute walking test, and muscle biopsy of vastus lateralis . For statistical analysis, mean comparison and multiple regression tests were used. Results In patients on long-term hemodialysis, muscle endurance was lower, whereas maximal voluntary force was not significantly different. We observed a transition from type I (oxidative) to type II (glycolytic) muscle fibers, and an alteration of mitochondrial structure (swelling) without changes in DNA content, genome replication (peroxisome proliferator activator receptor γ coactivator-1 α and mitochondrial transcription factor A), regulation of fusion (mitofusin and optic atrophy 1), or fission (dynamin-related protein 1). Notably, there were autophagosome structures containing glycogen along with mitochondrial debris, with a higher expression of light chain 3 (LC3) protein, indicating phagophore formation. This was associated with a greater conversion of LC3-I to LC3-II and the expression of Gabaralp1 and Bnip3l genes involved in mitophagy. Conclusions In this highly selected long-term hemodialysis population, a low oxidative phenotype could be defined by a poor endurance, a fiber-type switch, and an alteration of mitochondria structure, without evidence of sarcopenia. This phenotype could be related to uremia through the activation of autophagy/mitophagy. Clinical Trial registration numbers: NCT02794142 and NCT02040363 .

Background: Obstructive sleep apnea syndrome (OSA) is common in patients with acute myocardial infarction (AMI). Whether OSA impacts on the ventricular remodeling post-AMI remains unclear. We compared cardiac ventricular remodeling in patients assessed by cardiac magnetic resonance (CMR) imaging at baseline and six months after AMI based on the presence and severity of OSA. Methods: This prospective study included 47 patients with moderate to severe AMI. They all underwent CMR at inclusion and at six months after an AMI, and a polysomnography was performed three weeks after AMI. Left and right ventricular remodeling parameters were compared between patients based on the AHI, AHI in REM and NREM sleep, oxygen desaturation index, and daytime sleepiness. Results: Of the 47 patients, 49% had moderate or severe OSA with an AHI ≥ 15/h. No differences were observed between these patients and those with an AHI < 15/h for left ventricular end-diastolic and end-systolic volumes at six months. No association was found for left and right ventricular remodeling parameters at six months or for the difference between baseline and six months with polysomnographic parameters of OSA severity, nor with daytime sleepiness. Conclusions: Although with a limited sample size, our proof-of-concept study does not report an association between OSA and ventricular remodeling in patients with AMI. These results highlight the complexity of the relationships between OSA and post-AMI morbi-mortality.

International audience; Improvements in skeletal muscle endurance and oxygen uptake are blunted in patients with chronic obstructive pulmonary disease (COPD), possibly because of a limitation in the muscle capillary oxygen supply. Pericytes are critical for capillary blood flow adaptation during angiogenesis but may be impaired by COPD systemic effects, which are mediated by circulating factors. This study compared the pericyte coverage of muscle capillaries in response to 10 wk of exercise training in patients with COPD and sedentary healthy subjects (SHS). Fourteen patients with COPD were compared with seven matched SHS. SHS trained at moderate intensity corresponding to an individualized moderate-intensity patient with COPD trained at the same relative (%V̇o2: COPD-RI) or absolute (mL·min-1·kg-1: COPD-AI) intensity as SHS. Capillary-to-fiber ratio (C/F) and NG2+ pericyte coverage were assessed from vastus lateralis muscle biopsies, before and after 5 and 10 wk of training. We also tested in vitro the effect of COPD and SHS serum on pericyte morphology and mesenchymal stem cell (MSC) differentiation into pericytes. SHS showed greater improvement in aerobic capacity (V̇o2VT) than both patients with COPD-RI and patients with COPD-AI (Group × Time: P = 0.004). Despite a preserved increase in the C/F ratio, NG2+ pericyte coverage did not increase in patients with COPD in response to training, contrary to SHS (Group × Time: P = 0.011). Conversely to SHS serum, COPD serum altered pericyte morphology (P < 0.001) and drastically reduced MSC differentiation into pericytes (P < 0.001). Both functional capacities and pericyte coverage responses to exercise training are blunted in patients with COPD. We also provide direct evidence of the deleterious effect of COPD circulating factors on pericyte morphology and differentiation.NEW & NOTEWORTHY This work confirms the previously reported impairment in the functional response to exercise training of patients with COPD compared with SHS. Moreover, it shows for the first time that pericyte coverage of the skeletal capillaries is drastically reduced in patients with COPD compared with SHS during training-induced angiogenesis. Finally, it provides experimental evidence that circulating factors are involved in the impaired pericyte coverage of patients with COPD.

Pressure therapy (PT) is commonly used to manage hypertrophic scars. It is often based on the use of elastic pressure garments, which are poorly suited for a facial localization. We describe the conception, fabrication, and use of a custom-made PT facial mask for primary prevention of hypertrophic scarring of complex facial wounds. The main advantage of the device is that it is quick and easy to manufacture in a conventional prosthetics laboratory, with a good level of observance and tolerance in our experience of 20 treated patients.

International audience; Myogenic differentiation mechanisms are generally assessed using a murine cell line placed in low concentrations of an animal-derived serum. To more closely approximate in vivo pathophysiological conditions, recent studies have combined the use of human muscle cells with human serum. Nevertheless, the in vitro studies of the effects of a human microenvironment on the differentiation process of human myoblasts require the identification of the culture conditions that would provide an optimal and reproducible differentiation process of human muscle cells. We assessed the differentiation variability resulting from the use of human myoblasts and serums from healthy subjects by measuring the myotube diameter, fusion index and surface covered by myotubes. We showed the preserved cell-dependent variability of the differentiation response of myoblasts cultured in human serums compared to FBS. We found that using a pool of serums reduced the serum-dependent variability of the myogenic response compared to individual serums. We validated our methodology by showing the atrophying effect of pooled serums from COPD patients on healthy human myotubes. By replacing animal-derived tissues with human myoblasts and serums, and by validating the sensitivity of cultured human muscle cells to a pathological microenvironment, this human cell culture model offers a valuable tool for studying the role of the microenvironment in chronic disease.

Unilateral posterior vertical insufficiency (PVI) is a growth defect of the mandibular condyle that results in a facial asymmetry. Various surgical procedures can be used to elongate the hypoplastic ramus. The aim of this study was to evaluate long-term aesthetic and architectural outcomes of vertical ramus osteotomy (VRO) in patients with unilateral PVI.Patients operated on with unilateral VRO were included in this retrospective study. Aesthetic and architectural parameters were evaluated on frontal photographs as well as on frontal and lateral cephalograms preoperatively, postoperatively, at 1-year and at the end of the follow-up.A total of 48 patients were analyzed. The aesthetic assessment revealed significant correction of the chin deviation (CD) and of the lip commissural line tilt after VRO (p1 = 0.0038 and p2 = 0.0067, respectively) with stable results. The architectural analysis revealed significant improvement in the maxillary and mandibular occlusal planes, as well as the chin deviation (p 0.0001). A tendency to relapse was noted for the mandibular canting and the CD during the follow-up. VRO allowed for a mean mandibular lengthening of 8.39 mm (ranging from 2.5 to 14 mm).VRO allows for immediate restoration of the symmetry of the lower third of the face in patients with unilateral PVI. A revisional procedure may be needed due to a tendency for the chin deviation to relapse.

BackgroundOver-testing of patients is a significant problem in clinical medicine that can be tackled by education. Clinical reasoning learning (CRL) is a potentially relevant method for teaching test ordering and interpretation. The feasibility might be improved by using an interactive whiteboard (IWB) during the CRL sessions to enhance student perceptions and behaviours around diagnostic tests. Overall, IWB/CRL could improve their skills.MethodsThird-year undergraduate medical students enrolled in a vertically integrated curriculum were randomized into two groups before clinical placement in either a respiratory disease or respiratory physiology unit: IWB-based CRL plus clinical mentoring (IWB/CRL + CM:n = 40) or clinical mentoring only (CM-only:n = 40). Feasibility and learning outcomes were assessed. In addition, feedback via questionnaire of the IWB students and their classmates (n = 233) was compared.ResultsAnalyses of the IWB/CRL sessions (n = 40, 27 paperboards) revealed that they met validated learning objectives. Students perceived IWB as useful and easy to use. After the IWB/CRL + CM sessions, students mentioned more hypothesis-based indications in a test ordering file (p p n = 23), the number of diagnostic tests ordered did not change in the IWB/CRL + CM group (+ 7%; p = N.S), whereas it increased among CM-only students (+ 30%;p p p = 0.36).ConclusionsIntegrating IWB into CRL sessions is feasible to teach test ordering and interpretation to undergraduate students. Moreover, student feedback and prospective assessment suggested a positive impact of IWB/CRL sessions on students’ learning.

International audience; Sleep disturbances are frequent among patients with heart failure (HF). We hypothesized that self-reported sleep disturbances are associated with a poor prognosis in patients with HF. A longitudinal study of 119 patients with HF was carried out to assess the association between sleep disturbances and the occurrence of major cardiovascular events (MACE). All patients with HF completed self-administered questionnaires on sleepiness, fatigue, insomnia, quality of sleep, sleep patterns, anxiety and depressive symptoms, and central nervous system (CNS) drugs intake. Patients were followed for a median of 888 days. Cox models were used to estimate the risk of MACE associated with baseline sleep characteristics. After adjustment for age, the risk of a future MACE increased with CNS drugs intake, sleep quality and insomnia scores as well with increased sleep latency, decreased sleep efficiency and total sleep time. However, after adjustment for left ventricular ejection fraction and hypercholesterolemia the HR failed to be significant except for CNS drugs and total sleep time. CNS drugs intake and decreased total sleep time were independently associated with an increased risk of MACE in patients with HF. Routine assessment of self-reported sleep disturbances should be considered to prevent the natural progression of HF.

International audience; Introduction: The treatment of fractures of the mandibular condylar process remains controversial, especially in children. The aim of this study was to assess the long-term clinical and radiographic outcomes of functional treatments for mandibular condylar fractures with an articular impact.Materials and methods: Young patients (< 15 years of age) presenting with either a unilateral or a bilateral mandibular fracture of the condylar process were included in this retrospective study. The clinical analysis focused on investigation of joint amplitudes at 1, 2, 6, 12, and 24 months after the beginning of the treatment, and at the end of their physical growth for the long-term study. Other clinical parameters included temporomandibular joint (TMJ) disorders and facial asymmetry. Photographs of patients and panoramic X-rays were assessed to identify any growth disorders at the end of the follow-up.Results: One hundred and eight patients were included in this study, and 33 patients who were no longer undergoing mandibular growth at the time of the last follow-up were included in the long-term study. The mean age at the time of the trauma was 9.33 years, and the mean follow-up was 82.2 months. A significant improvement was observed in the maximal mouth opening (MMO), diduction, and propulsion in the first months after the trauma, reaching 44.31 mm (p < 0.0001), 10.50 mm (p=0.0001), and 6.33 mm (p=0.01), respectively, at 6 months. Three patients experienced a clinical posterior vertical insufficiency, one of which required a surgical procedure, while four patients exhibited a ramus asymmetry of up to 10 mm, albeit with no clinical consequences. One case of TMJ ankylosis was noted.Conclusion: Our study suggests that functional treatment is appropriate for fractures of the mandibular condyle with an articular impact in children, as it promotes mandibular growth and good functional recovery. Children have to be followed up, however, until completion of growth.

Background and Purpose: Sleeve gastrectomy is a major therapy of morbid obesity, but recent reports suggest that its effects on weight loss are improved when patients increase their muscular activity, while a weight regain may occur in more than 30% of patients after 40 months. Exercise is an effective mean of preventing weight regain. In a recent preliminary study, we reported that exercise training targeted at the level of maximal lipid oxidation (LIPOXmax) improved weight loss and weight stabilization at 30 months. This study extends this previous one and aims at describing the kinetics of weight loss on 60 months after sleeve in people performing or not a LIPOXmax training and to see whether this variety of training exerts a satietogenic effect in sleeve patientsas has been evidenced in nonoperated obese subjects.

BACKGROUND Obesity is a major public health issue. Combining exercise training, nutrition, and therapeutic education in metabolic rehabilitation (MR) is recommended for obesity management. However, evidence from randomized controlled studies is lacking. In addition, MR is associated with poor patient adherence. Mobile health devices improve access to MR components. OBJECTIVE The aim of this study is to compare the changes in body composition, anthropometric parameters, exercise capacity, and quality of life (QOL) within 12 weeks of patients in the telerehabilitation (TR) program to those of usual care patients with obesity. METHODS This was a parallel-design randomized controlled study. In total, 50 patients with obesity (BMI>30 kg/m²) were included in a TR group (TRG) or a usual care group (UCG) for 12 weeks. Patients underwent biometric impedance analyses, metabolic exercise tests, actimetry, and QOL and satisfaction questionnaires. The primary outcome was the change in fat mass at 12 weeks from baseline. Secondary outcomes were changes in body weight, metabolic parameters, exercise capacity, QOL, patients’ adhesion, and satisfaction. RESULTS A total of 49 patients completed the study. No significant group × time interaction was found for fat mass (TRG: mean 1.7 kg, SD 2.6 kg; UCG: mean 1.2 kg, SD 2.4 kg; P=.48). Compared with the UCG, TRG patients tended to significantly improve their waist to hip ratios (TRG: −0.01 kg, SD 0.04; UCG: +0.01 kg, SD 0.06; P=.07) and improved QOL physical impact (TRG: +21.8, SD 43.6; UCG: −1.2, SD 15.4; P=.005). Significant time effects were observed for body composition, 6-minute walk test distance, exercise metabolism, sedentary time, and QOL. Adherence (95%) and satisfaction in the TRG were good. CONCLUSIONS In adults with obesity, the TR program was not superior to usual care for improving body composition. However, TR was able to deliver full multidisciplinary rehabilitation to patients with obesity and improve some health outcomes. Given the patients’ adherence and satisfaction, pragmatic programs should consider mobile health devices to improve access to MR. Further studies are warranted to further establish the benefits that TR has over usual care. CLINICALTRIAL ClinicalTrials.gov NCT03396666; http://clinicaltrials.gov/ct2/show/NCT03396666

International audience; No abstract available

Exercise training (ET) is a major part of pulmonary rehabilitation for Chronic Obstructive Pulmonary Disease (COPD) patients. However, ET for COPD patients has limited beneficial effects on peripheral muscles. Our objective was to assess the cellular mechanisms that could lead to the limited beneficial effects of ET in COPD using in vitro Electrical Pulse Stimulation (EPS) of cultured human myotubes. Myotubes from 9 healthy subjects (FEV1%: 102.4±14.7%) or 9 COPD patients (FEV1%: 36.3±14.6%) were subjected to an EPS protocol during 24 hours at 1 Hz and 11.5 V. We compared the variations (EPS - noEPS) of the myotube diameter, surface covered by myotubes, fusion index, and expression of differentiation, catabolic, anabolic and oxidative metabolism markers in healthy and COPD myotubes. EPS induced an increase of the differentiation characteristics (diameter +3.8 vs -4.6%; surface +4.5 vs -5.3%; fusion +4.4 vs -4.9%; p We showed that, unlike healthy myotubes, COPD myotubes have a limited response to EPS with alteration of differentiation, protein synthesis and oxidative metabolism adaptation. This altered response to EPS in vitro could reflect impaired regenerative capacities of satellite cells leading to a lack of muscle adaptation and therefore to the limited effects of in vivo ET in COPD patients.

Background Sarcopaenia, defined as a decline in both muscle mass and function, has been recognized as a major determinant of poor outcome in haemodialysis (HD) patients. It is generally assumed that sarcopaenia is driven by muscle atrophy related to protein-energy wasting. However, dynapaenia, defined as weakness without atrophy, has been characterized by a different disease phenotype from sarcopaenia. The aim of this study was to compare the characteristics and prognosis of sarcopaenic and dynapaenic patients among a prospective cohort of chronic HD (CHD) patients. Methods Two hundred and thirty-two CHD patients were enrolled from January to July 2016 and then followed prospectively until December 2018. At inclusion, weakness and atrophy were, respectively, evaluated by maximal voluntary force (MVF) and creatinine index (CI). Sarcopaenia was defined as the association of weakness and atrophy (MVF and CI below the median) while dynapaenia was defined as weakness not related to atrophy (MVF below the median, and CI above the median). Results From a total of 187 prevalent CHD patients [65% of men, age 65.3 (49.7–82.0) years], 44 died during the follow-up period of 23.7 (12.4–34.9) months. Sarcopaenia and dynapaenia were observed in 33.7 and 16% of the patients, respectively. Compared with patients with sarcopaenia, patients with dynapaenia were younger and with a lower Charlson score. In contrast, mortality rate was similar in both groups (38 and 27%, respectively). After adjustment for age, sex, lean tissue index, serum albumin, high-sensitivity C-reactive protein (hs-CRP), haemoglobin (Hb), normalized protein catabolic rate (nPCR), dialysis vintage and Charlson score, only patients with dynapaenia were at increased risk of death [hazard ratio (HR) = 2.99, confidence interval 1.18–7.61; P = 0.02]. Conclusions Screening for muscle functionality is highly warranted to identify patients with muscle functional impairment without muscle atrophy. In contrast to sarcopaenia, dynapaenia should appear as a phenotype induced by uraemic milieu, characterized by young patients with low Charlson score and poor prognosis outcome independently of serum albumin, hs-CRP, Hb, nPCR and dialysis vintage.

International audience; Introduction: Camel-hump condylo-mandibular dysplasia is a specific form of condyle dysostosis, first described by Delaire. The aim of this study was to describe the clinical and radiographic phenotype of the disease, and to discuss therapeutic options.Case series: Twenty-one patients were analyzed retrospectively. They exhibited the same unilateral facial asymmetry, which was of mandibular origin, with an elevated commissural line and occlusal cant, and a deviated chin on the side of the deformity. The soft tissues and the ears were always normal in terms of their physical appearance. Radiographic analysis generally revealed a short, curved, and anteriorly displaced condyle, with a high and sharp coronoid process. CT scans revealed that the glenoid fossa was empty. Twelve patients exhibited dental abnormalities, consisting mainly of dental inclusions affecting the lower first and/or second molars (10 patients). A good response to functional orthodontic treatment was achieved in eight patients, while 13 patients required a surgical mandibular lengthening procedure.Conclusion: Condylo-mandibular dysplasia is a congenital condyle deformity that needs to be recognized and differentiated from craniofacial microsomia in order to be able to provide patient-specific treatments.

We present a carbon monoxide (CO) sensor dedicated to human breath analysis, based on quartz enhanced photo-acoustic spectroscopy (QEPAS). An off-beam configuration was chosen for the sensor, using a quantum cascade laser emitting at 4.7 μm. The detection was based on a second harmonic wavelength modulation scheme. A minimum detection limit of 20 parts per billions in volume (ppbv) in 1 s was obtained. First tests were performed on smokers/non smokers to validate the stability and the ability of the sensor to be used in vivo. Then a detailed validation of the sensor was performed in Montpellier Hospital by testing the CO-QEPAS performance versus reference methods: blood carboxy-hemoglobin (COHb %) and clinical status. Additionally, the performance was compared with commercial exhaled CO analyzer measurements. A full clinical evaluation of the sensor showed good reliability and agreement with the reference method (COHb %) of the CO-QEPAS in healthy subjects, confirming the ability of our CO sensor for measuring low level endogenous exhaled CO concentrations.

International audience; Objective: Six- minutes’ walk-test (6MWT) is a measure of physical fitness widely studied and validated in chronic pathologies with sedentary lifestyles. It is an aerobic fitness test, correlated with maximum oxygen consumption (VO2max) in some studies, but this correlation is not well established in diabetes. We assessed the extent to which it predicts VO2max and its training-induced changes in type 2 diabetics.Materials and methods: Twenty-five type 2 diabetics were randomized and divided into two groups: 13 completed a physical training program (eight hospital education sessions continued at home through two weekly 30-45-minute sessions at an intensity corresponding to the first ventilatory threshold VT1) and the remaining 12 continued their usual treatment unchanged.Results: After 1 year training maintained maximum aerobic capacity, while it decreased significantly in the untrained group (p=0.014). Voorrips’ activity score was correlated with VO2max (r= 0.44, p= 0.05) and with the distance walked at 6MWT (r=0.446, p=0.05). The distance walked during 6MWT is correlated with VO2max before (r= 0.456 p= 0.05) and after (r= 0.714 p

International audience; Objective: Obstructive sleep apnea (OSA) is a high prevalent disorder with severe consequences including sleepiness, metabolic, and cardiovascular disorders. The aim of this study was to assess the effect of an individualized exercise-training (IET) program with educational sessions vs educational sessions alone on severity markers of OSA over an eight-week duration.Methods: This was a randomised, controlled, parallel-design study. In sum, 64 patients with moderate-to-severe OSA (apnea-hypopnea index AHI 15–45/hour), low physical activity level (Voorrips

Subjects with hypothyroidism substituted with levothyroxine (HS) are known to be poor responders to weight reducing strategies. Since muscle energy metabolism is regulated by thyroid hormones we compared the oxidation of fat and carbohydrates (CHO) during exercise in HS versus controls. We compared 52 patients (48 women, 4 men, age 49 t years, levothyroxine dose 25-250 micrograms / day) to a control group of 2081 patients matched for sex, age, BMI and percentage of fat during an exercise calorimetry with 4 submaximal 6 minutes steps. At the same power intensity HS on the average oxidize more fat (p = 0.009) and use more oxygen (p = 0.00019). Lipid oxidation culminates at the same power intensity(39,4±2,4 vs 38,6±0,3 watts) but its maximal oxidation rate is significantly higher in the HS group (10.32±0.47 vs. 9, 06±0.10 mg / min / kg muscle p = 0.02) and carbohydrate oxidation during the final level (1866.6 ± 77.3 vs1705.45 ± 11.5 mg / min p = 0.029 ). The maximal lipid oxidation rate is correlated with the dose of levothyroxine (r = 0.331, p

International audience; The proteolytic autophagy pathway is enhanced in the lower limb muscles of patients with chronic obstructive pulmonary disease (COPD). Reactive oxygen species (ROS) have been shown to regulate autophagy in the skeletal muscles, but the role of oxidative stress in the muscle autophagy of patients with COPD is unknown. We used cultured myoblasts and myotubes from the quadriceps of eight healthy subjects and twelve patients with COPD (FEV1% predicted: 102.0% and 32.0%, respectively; p

Context Toll-like receptor 4 (TLR4) activation contributes to obesity-associated insulin resistance in skeletal muscles (SM). TLR4 signaling involves two pathways: the myeloid differentiation primary response gene 88 (MyD88) leading to inflammatory cytokines production and the toll/interleukin-1 receptor domain-containing adapter-inducing interferon (IFN) I (TRIF)-dependent pathways leading to type 1 interferon (IFNI) and interferon stimulated genes (ISG) expression. The E3 ubiquitin ligase RNF41 allows the preferential activation of the TRIF-IFNI pathway; however, its role in insulin response has not been reported. Methods We measured RNF41 level and IFNI pathway activation (ISG expression) in SM biopsies of obese insulin sensitive (OIS) and obese insulin resistant (OIR) women. Then we isolated and differentiated in myotubes, primary human SM cell progenitors from OIS and OIR SM biopsies. We modulated RNF41 and ISG expression in these myotubes and investigated their effects on insulin response. Results RNF41 expression is down-regulated in vivo in OIR SM and myotubes compared to OIS SM and myotubes. TLR4 activation with palmitate induces TRIF-IFNI pathway and ISG in OIS myotubes but not in OIR myotubes. Inhibition of RNF41 expression with siRNF41 in OIS myotubes treated with palmitate attenuates insulin response, IFNI pathway activation and ISG induction, mimicking OIR phenotype. Further, overexpression of RNF41 in OIR myotubes increases insulin response and ISG expression. Exposure to IFNI or to its inducer polyinosinic-polycytidylic acid, restores ISG expression and insulin sensitivity in OIR myotubes and OIS myotubes transfected with siRNF41. Conclusion Our results identify RNF41 as essential to IFNI pathway activation in order to maintain muscle insulin sensitivity during human obesity.

Resume Actualites La chirurgie bariatrique a pris une place importante dans le traitement de l’obesite mais son efficacite a long terme est compromise dans 20–30 % des cas par des reprises de poids. L’activite physique pourrait etre une strategie preventive et/ou curative de ces echecs secondaires. Nous presentons une revue generale des etudes portant sur l’activite physique apres chirurgie bariatrique. Pour cela, nous avons selectionne 11 articles ayant etudie l’effet d’un protocole d’activite physique postoperatoire. De maniere globale, l’activite physique a des effets positifs sur le systeme cardiovasculaire, le maintien de la capacite fonctionnelle et musculaire, l’insulino-sensibilite et le metabolisme des lipides. Les effets sur le poids sont un peu discordants mais les protocoles realises apres la phase initiale de perte de poids rapide et sur une duree suffisante retrouvent perte de poids superieure a celle qu’induit la chirurgie bariatrique seule. Cet effet renforcant celui de la chirurgie sur la perte de poids est observe avec l’activite en endurance a faible intensite et notamment celle qui est ciblee au LIPOXmax, et n’est pas retrouvee avec l’endurance a plus haute intensite ou la resistance. Conclusion En resume, l’ensemble des articles presentes montrent des effets benefiques sur les comorbidites et complications de l’obesite. Cependant, les protocoles d’entrainement sont heterogenes entre les etudes. Des etudes complementaires sont necessaires afin de mieux preciser les strategies les plus adaptees.

Background Obesity is a major public health issue. Combining exercise training, nutrition, and therapeutic education in metabolic rehabilitation (MR) is recommended for obesity management. However, evidence from randomized controlled studies is lacking. In addition, MR is associated with poor patient adherence. Mobile health devices improve access to MR components. Objective The aim of this study is to compare the changes in body composition, anthropometric parameters, exercise capacity, and quality of life (QOL) within 12 weeks of patients in the telerehabilitation (TR) program to those of usual care patients with obesity. Methods This was a parallel-design randomized controlled study. In total, 50 patients with obesity (BMI>30 kg/m²) were included in a TR group (TRG) or a usual care group (UCG) for 12 weeks. Patients underwent biometric impedance analyses, metabolic exercise tests, actimetry, and QOL and satisfaction questionnaires. The primary outcome was the change in fat mass at 12 weeks from baseline. Secondary outcomes were changes in body weight, metabolic parameters, exercise capacity, QOL, patients’ adhesion, and satisfaction. Results A total of 49 patients completed the study. No significant group × time interaction was found for fat mass (TRG: mean 1.7 kg, SD 2.6 kg; UCG: mean 1.2 kg, SD 2.4 kg; P=.48). Compared with the UCG, TRG patients tended to significantly improve their waist to hip ratios (TRG: −0.01 kg, SD 0.04; UCG: +0.01 kg, SD 0.06; P=.07) and improved QOL physical impact (TRG: +21.8, SD 43.6; UCG: −1.2, SD 15.4; P=.005). Significant time effects were observed for body composition, 6-minute walk test distance, exercise metabolism, sedentary time, and QOL. Adherence (95%) and satisfaction in the TRG were good. Conclusions In adults with obesity, the TR program was not superior to usual care for improving body composition. However, TR was able to deliver full multidisciplinary rehabilitation to patients with obesity and improve some health outcomes. Given the patients’ adherence and satisfaction, pragmatic programs should consider mobile health devices to improve access to MR. Further studies are warranted to further establish the benefits that TR has over usual care. Trial Registration ClinicalTrials.gov NCT03396666; http://clinicaltrials.gov/ct2/show/NCT03396666

La modelisation mathematique des repas test quantifie les deux phases de l’insulinosecretion ainsi qu’un parametre appele potentiation qui indique que la reponse insulinosecretrice s’amplifie lorsque le stimulus glucose persiste. Nous avons examine si cette potentiation est associee a la survenue d’hypoglycemies reactionnelles sur une base de donnees de 620 petits dejeuners standardises realises pour caracterisation d’anomalies de la glucoregulation avec analyse mathematique de l’insulinosecretion et de ses composantes (modeles de Mari et de Cobelli) ainsi que de l’insulinosensibilite (SI) avec l’oral minimal model. Le quartile superieur de potentiation correspond a des nadirs de glycemie 2 fois plus souvent