Effects of Repeated Sprint Training With Progressive Elastic Resistance on Sprint Performance and Anterior-Posterior Force Production in Elite Young Soccer Players.

ABSTRACT: Le Scouarnec, J, Samozino, P, Andrieu, B, Thubin, T, Morin, JB, and Favier, FB. Effects of repeated sprint training with progressive elastic resistance on sprint performance and anterior-posterior force production in elite young soccer players. J Strength Cond Res 36(6): 1675-1681, 2022-This study aimed to determine whether repeated sprint training with progressive high elastic resistance could improve sprint performance and anterior-posterior (AP) force production capacities of elite young soccer players. Seven elite U19 soccer players underwent 10 sessions of elastic-resisted repeated sprints on 8 weeks, whereas 8 U17 players from the same academy (control group) followed the same protocol without elastic bands. Sprint performance and mechanical parameters were recorded on a 30-m sprint before and after training. The control group did not show change for any of the measured variables. In contrast, the elastic-resisted training resulted in a significant improvement of the sprint time (-2.1 ± 1.3%; p = 0.026; Hedges' g = -0.49) and maximal velocity (Vmax; +3.9 ± 2%; p = 0.029; Hedges' g = 0.61) reached during the 30-m sprint. These enhancements were concurrent with an increase in the maximal power output related to AP force (Pmax; +4.9 ± 5.1%%; p = 0.026; Hedges' g = 0.42). Although the theoretical maximal AP force (F0) remained unchanged in both groups, there was a medium but nonsignificant increase in theoretical maximal velocity (V0; +3.7 ± 2.5%; p = 0.13; Hedges' g = 0.5) only in the elastic group. Therefore, the present results show that sprint capacity of elite young soccer players can be further improved by adding incremental resistance against runner displacement to raise the ability to produce AP force, rather at high velocity in the final phase of the acceleration.

REDD1 deficiency protects against nonalcoholic hepatic steatosis induced by high-fat diet.

Nonalcoholic fatty liver disease is a chronic liver disease which is associated with obesity and insulin resistance. We investigated the implication of REDD1 (Regulated in development and DNA damage response-1), a stress-induced protein in the development of hepatic steatosis. REDD1 expression was increased in the liver of obese mice and morbidly obese patients, and its expression correlated with hepatic steatosis and insulin resistance in obese patients. REDD1 deficiency protected mice from the development of hepatic steatosis induced by high-fat diet (HFD) without affecting body weight gain and glucose intolerance. This protection was associated with a decrease in the expression of lipogenic genes, SREBP1c, FASN, and SCD-1 in liver of HFD-fed REDD1-KO mice. Healthy mitochondria are crucial for the adequate control of lipid metabolism and failure to remove damaged mitochondria is correlated with liver steatosis. Expression of markers of autophagy and mitophagy, Beclin, LC3-II, Parkin, BNIP3L, was enhanced in liver of HFD-fed REDD1-KO mice. The number of mitochondria showing colocalization between LAMP2 and AIF was increased in liver of HFD-fed REDD1-KO mice. Moreover, mitochondria in liver of REDD1-KO mice were smaller than in WT. These results are correlated with an increase in PGC-1α and CPT-1 expression, involved in fatty acid oxidation. In conclusion, loss of REDD1 protects mice from the development of hepatic steatosis.

Is REDD1 a metabolic double agent? Lessons from physiology and pathology.

The Akt/mechanistic target of rapamycin (mTOR) signaling pathway governs macromolecule synthesis, cell growth, and metabolism in response to nutrients and growth factors. Regulated in development and DNA damage response (REDD)1 is a conserved and ubiquitous protein, which is transiently induced in response to multiple stimuli. Acting like an endogenous inhibitor of the Akt/mTOR signaling pathway, REDD1 protein has been shown to regulate cell growth, mitochondrial function, oxidative stress, and apoptosis. Recent studies also indicate that timely REDD1 expression limits Akt/mTOR-dependent synthesis processes to spare energy during metabolic stresses, avoiding energy collapse and detrimental consequences. In contrast to this beneficial role for metabolic adaptation, REDD1 chronic expression appears involved in the pathogenesis of several diseases. Indeed, REDD1 expression is found as an early biomarker in many pathologies including inflammatory diseases, cancer, neurodegenerative disorders, depression, diabetes, and obesity. Moreover, prolonged REDD1 expression is associated with cell apoptosis, excessive reactive oxygen species (ROS) production, and inflammation activation leading to tissue damage. In this review, we decipher several mechanisms that make REDD1 a likely metabolic double agent depending on its duration of expression in different physiological and pathological contexts. We also discuss the role played by REDD1 in the cross talk between the Akt/mTOR signaling pathway and the energetic metabolism.

Glucocorticoid-dependent REDD1 expression reduces muscle metabolism to enable adaptation under energetic stress.

BACKGROUND: Skeletal muscle atrophy is a common feature of numerous chronic pathologies and is correlated with patient mortality. The REDD1 protein is currently recognized as a negative regulator of muscle mass through inhibition of the Akt/mTORC1 signaling pathway. REDD1 expression is notably induced following glucocorticoid secretion, which is a component of energy stress responses. RESULTS: Unexpectedly, we show here that REDD1 instead limits muscle loss during energetic stresses such as hypoxia and fasting by reducing glycogen depletion and AMPK activation. Indeed, we demonstrate that REDD1 is required to decrease O2 and ATP consumption in skeletal muscle via reduction of the extent of mitochondrial-associated endoplasmic reticulum membranes (MAMs), a central hub connecting energy production by mitochondria and anabolic processes. In fact, REDD1 inhibits ATP-demanding processes such as glycogen storage and protein synthesis through disruption of the Akt/Hexokinase II and PRAS40/mTORC1 signaling pathways in MAMs. Our results uncover a new REDD1-dependent mechanism coupling mitochondrial respiration and anabolic processes during hypoxia, fasting, and exercise. CONCLUSIONS: Therefore, REDD1 is a crucial negative regulator of energy expenditure that is necessary for muscle adaptation during energetic stresses. This present study could shed new light on the role of REDD1 in several pathologies associated with energetic metabolism alteration, such as cancer, diabetes, and Parkinson's disease.

Prevalence, treatment and control of hypertension in La Réunion: the RÉDIA population-based cohort study.

A better knowledge of prevalence, management and determinants of hypertension is needed in regions in epidemiological transition to adapt the strategies of public health screening and prevention, and to reduce the burden of cardiovascular diseases. We conducted a prospective cohort study including 4610 participants aged between 18 and 69 years and representative of the general population of La Réunion, a French overseas island located in the western Indian Ocean. The median time between inclusion and follow-up was 7.4 years. Blood pressure data at baseline and follow-up of 3087 participants were analyzed. We found a high prevalence of hypertension, especially in women (36.7% [34.5-39.0]) and in men (40.3% [37.6-43.0]) and in the under 30s (17.1% [14.0-20.5]), with an increase of 10% at follow-up. Treatment rates were very low in men (19.5% versus 39.1% in women) as was awareness of their condition (25.7% versus 44.6%). Blood pressure control rates were similar (18% at baseline and 34% at follow-up for both sexes). Diagnosis of hypertension at follow-up among subjects normotensive at baseline was independently associated with obesity at baseline (relative risk (RR) = 1.40 [1.12-1.75] for BMI between 27 and 30 kg/m2 and 1.72 [1.33-2.25] for BMI ≥30 kg/m2 as compared with BMI <27 kg/m2) and HbA1C (RR =1.12 [1.05-1.19] per %), suggesting a prominent role of insulin resistance in our population. Our study provides original data that cannot be assimilated to any existing model and should guide the implementation of original community-based programs in such countries.

[To analyse the transferability of an intervention : applying the functions/implementation/context model on a diabetes prevention programme]. / Analyser la transférabilité d'une intervention : application du modèle fonctions clés/implémentation/contexte à un programme de prévention du diabète.

INTRODUCTION: A type 2 diabetes primary prevention programme that was shown to be feasible and effective in 2003 was transferred to another vulnerable district of Reunion Island in 2004, but its short-term effectiveness could not be reproduced. Based on this example, this article analyses whether the key functions/implementation/context model can be useful to : 1- more accurately describe an evaluated intervention ; and 2- identify the factors involved in the transferability of this intervention. METHODS: The causality model of the initial programme is described. We then identified the key functions (or theoretical processes) of this initial programme, implementation of these functions, and the context in which the intervention took place. Transfer was analysed by focusing on the differences between the initial programme and the transferred programme in terms of key functions, implementation and context. RESULTS: The causality model involves individual, meso-social, and environmental health determinants. Our analysis of programme transfer highlights differences in : key functions (two key functions dropped, one key function added, one key function modified), implementation (failure to implement, loss/improvement of quality), and context (population and socioeconomic level of the district concerned). CONCLUSION: This work supports the hypothesis that the key functions/implementation/context model can be useful to improve the description of an intervention, and analyse the factors involved in its transferability.

REDD1 deletion prevents dexamethasone-induced skeletal muscle atrophy.

REDD1 (regulated in development and DNA damage response 1) has been proposed to inhibit the mechanistic target of rapamycin complex 1 (mTORC1) during in vitro hypoxia. REDD1 expression is low under basal conditions but is highly increased in response to several catabolic stresses, like hypoxia and glucocorticoids. However, REDD1 function seems to be tissue and stress dependent, and its role in skeletal muscle in vivo has been poorly characterized. Here, we investigated the effect of REDD1 deletion on skeletal muscle mass, protein synthesis, proteolysis, and mTORC1 signaling pathway under basal conditions and after glucocorticoid administration. Whereas skeletal muscle mass and typology were unchanged between wild-type (WT) and REDD1-null mice, oral gavage with dexamethasone (DEX) for 7 days reduced tibialis anterior and gastrocnemius muscle weights as well as tibialis anterior fiber size only in WT. Similarly, REDD1 deletion prevented the inhibition of protein synthesis and mTORC1 activity (assessed by S6, 4E-BP1, and ULK1 phosphorylation) observed in gastrocnemius muscle of WT mice following single DEX administration for 5 h. However, our results suggest that REDD1-mediated inhibition of mTORC1 in skeletal muscle is not related to the modulation of the binding between TSC2 and 14-3-3. In contrast, our data highlight a new mechanism involved in mTORC1 inhibition linking REDD1, Akt, and PRAS40. Altogether, these results demonstrated in vivo that REDD1 is required for glucocorticoid-induced inhibition of protein synthesis via mTORC1 downregulation. Inhibition of REDD1 may thus be a strategy to limit muscle loss in glucocorticoid-mediated atrophy.

Depletion of the p43 mitochondrial T3 receptor in mice affects skeletal muscle development and activity.

In vertebrates, skeletal muscle myofibers display different contractile and metabolic properties associated with different mitochondrial content and activity. We have previously identified a mitochondrial triiodothyronine receptor (p43) regulating mitochondrial transcription and mitochondrial biogenesis. When overexpressed in skeletal muscle, it increases mitochondrial DNA content, stimulates mitochondrial respiration, and induces a shift in the metabolic and contractile features of muscle fibers toward a slower and more oxidative phenotype. Here we show that a p43 depletion in mice decreases mitochondrial DNA replication and respiratory chain activity in skeletal muscle in association with the induction of a more glycolytic muscle phenotype and a decrease of capillary density. In addition, p43(-/-) mice displayed a significant increase in muscle mass relative to control animals and had an improved ability to use lipids. Our findings establish that the p43 mitochondrial receptor strongly affects muscle mass and the metabolic and contractile features of myofibers and provides evidence that this receptor mediates, in part, the influence of thyroid hormone in skeletal muscle.

The influenza A (H1N1) pandemic in Reunion Island: knowledge, perceived risk and precautionary behaviour.

BACKGROUND: The effectiveness of preventive measures depends on prevailing attitudes and mindsets within a population. Perceived risk is central to a shift in mindset and behaviour. The present study aims to investigate the perceived severity, vulnerability and precautionary behaviour adopted in response to the influenza A (H1N1) epidemic that broke out in 2009 on Reunion Island (Indian Ocean). As no H1N1 vaccination was available at the time, non-medical interventions appeared of crucial importance to the control of the epidemic. METHODS: A cross sectional survey was conducted in Reunion Island between November 2009 and April 2010 within 2 months of the passage of the influenza A (H1N1) epidemic wave. Individual contacts representing 725 households (one contact per household) were interviewed by telephone using validated questionnaires on perceived risks. Mean scores were calculated for perceived severity, vulnerability, efficacy of preventive measures and precautionary behaviour. Univariate analysis was applied to identify preventive measures and attitudes and multivariate analysis was used to study the determinants of precautionary behaviour. RESULTS: More than 95% of contacted persons accepted to participate to the survey. Eighty seven percent of respondents believed that prevention was possible. On average, three out of six preventive measures were deemed effective. Spontaneously, 57% of the respondents reported that they took one or more preventive measures. This percentage increased to 87% after the interviewer detailed possible precautions one by one. The main precautions taken were frequent hand washing (59%) and avoidance of crowded places (34%). In multivariate logistic regression analysis the following factors were significantly associated with taking one or more preventive measures: young age, previous vaccination against seasonal influenza, having had seasonal influenza in the last five years, effectiveness of the preventive measures taken and low standards of education. CONCLUSION: Inhabitants of Reunion Island have expressed a preventive approach adapted to the realities of the H1N1 pandemic, a feature that likely reflects some preparedness gained after the large and severe chikungunya epidemic that hit the island in 2006. The degree of severity was well assessed despite the initial alarmist messages disseminated by national and international media. Precautions that were undertaken matched the degree of severity of the epidemic and the recommendations issued by health authorities. Further qualitative studies are needed to help adapting public messages to the social and cultural realities of diverse communities and to prevent misconceptions.

Structured self-management education maintained over two years in insufficiently controlled type 2 diabetes patients: the ERMIES randomised trial in Reunion Island.

BACKGROUND: Self-management education programs can reduce the complications and mortality in type 2 diabetes. The need to structure these programs for outpatient and community care with a vision for long-term maintenance has been recognised. In Reunion Island, an area affected by epidemiological and nutritional transition, diabetes affects 18% of the adult population over 30 years, with major social disparities, poor glycaemic control and frequent cardiovascular complications. METHODS/DESIGN: ERMIES is a randomised controlled trial designed to test the efficacy of a long-term (2 years) structured group self management educational intervention in improving blood glucose in non-recent, insufficiently controlled diabetes. After an initial structured educational cycle carried out blind for the intervention arm, patients will be randomised in two parallel group arms of 120 subjects: structured on-going group with educational intervention maintained over two years, versus only initial education. Education sessions are organised through a regional diabetes management network, and performed by trained registered nurses at close quarters. The educational approach is theoretically based (socio-constructivism, social contextualisation, empowerment, action planning) and reproducible, thanks to curricula and handouts for educators and learners. The subjects will be recruited from five hospital outpatient settings all over Reunion Island. The main eligibility criteria include: age ≥18 years, type 2 diabetes treated for more than one year, HbA1c ≥ 7.5% for ≥3 months, without any severe evolving complication (ischaemic or proliferative retinopathy, severe renal insufficiency, coronaropathy or evolving foot lesion), and absence of any major physical or cognitive handicap. The primary outcome measure is HbA1c evolution between inclusion and 2 years. The secondary outcome measures include anthropometric indicators, blood pressure, lipids, antidiabetic medications, level of physical activity, food ingestion, quality of life, social support, anxiety, depression levels and self-efficacy. An associated nested qualitative study will be conducted with 30 to 40 subjects in order to analyse the learning and adaptation processes during the education cycles, and throughout the study. CONCLUSIONS: This research will help to address the necessary but difficult issue of structuring therapeutic education in type 2 diabetes based on: efficacy and potential interest of organising on-going empowerment group-sessions, at close quarters, over the long term, in a heterogeneous socioeconomic environment. TRIAL REGISTRATION: ID_RCB number: 2011-A00046-35Clinicaltrials.gov number: NCT01425866.

Maximizing anaerobic performance with repeated-sprint training in hypoxia: In search of an optimal altitude based on pulse oxygen saturation monitoring.

Purpose: Repeated-sprint training in hypoxia (RSH) leads to great improvements in anaerobic performance. However, there is no consensus about the optimal level of hypoxia that should be used during training to maximize subsequent performances. This study aimed to establish whether such an optimal altitude can be determined and whether pulse oxygen saturation during RSH is correlated with training-induced improvement in performance. Methods: Peak and mean power outputs of healthy young males [age (mean ± SD) 21.7 ± 1.4 years] were measured during a Wingate (30 s) and a repeated-sprint ability (RSA; 10 x 6-s sprint with 24-s recovery) test before and after RSH. Participants performed six cycling sessions comprising three sets of 8 x 6-s sprint with 24-s recovery in normobaric hypoxia at a simulated altitude of either 1,500 m, 2,100 m, or 3,200 m (n = 7 per group). Heart rate variability was assessed at rest and during recovery from Wingate test before and after RSH. Results: The subjective rating of perceived exertion and the relative exercise intensity during training sessions did not differ between the three groups, contrary to pulse oxygen saturation (p < 0.001 between each group). Mean and peak power outputs were significantly increased in all groups after training, except for the mean power in the RSA test for the 3200 m group. Change in mean power on RSA test (+8.1 ± 6.6%) was the only performance parameter significantly correlated with pulse oxygen saturation during hypoxic training (p < 0.05, r = 0.44). The increase in LnRMSSD during recovery from the Wingate test was enhanced after training in the 1,500 m (+22%) but not in the two other groups (≈- 6%). Moreover, the increase in resting heart rate with standing after training was negatively correlated with SpO2 (p < 0.01, r =-0.63) suggesting that hypoxemia level during training differentially altered autonomic nervous system activity. Conclusion: These data indicate that RSH performed as early as 1,500 m of altitude is effective in improving anaerobic performance in moderately trained subjects without strong association with pulse oxygen saturation monitoring during training.

Usefulness of Home Screening for Promoting Awareness of Impaired Glycemic Status and Utilization of Primary Care in a Low Socio-Economic Setting: A Follow-Up Study in Reunion Island.

BACKGROUND: Low socio-economic settings are characterized by high prevalence of diabetes and difficulty in accessing healthcare. In these contexts, proximity health services could improve healthcare access for diabetes prevention. Our primary objective was to evaluate the usefulness of home screening for promoting awareness of impaired glycemic status and utilization of primary care among adults aged 18-79 in a low socio-economic setting. METHODS: This follow-up study was conducted in 2015-2016 in Reunion Island, a French overseas department in the Indian Ocean. Enrollment and screening occurred on the same day at the home of participants (N=907). Impaired glycemic status was defined as [glycated hemoglobin (HbA1c) ≥5.7%] OR [fasting capillary blood glucose (FCBG) ≥1.10 g/L] OR [HbA1c=5.5-5.6% and FCBG=1.00-1.09 g/L]. Medical, socio-cultural, and socio-economic characteristics were collected via a face-to-face questionnaire. A one-month telephone follow-up survey was conducted to determine whether participants had consulted a general practitioner (GP) for confirmation of screening results. A multinomial polytomous logistic regression model was used to identify factors independently associated with non-use of GP consultation for confirmation of screening results and nonresponse to the telephone follow-up survey. RESULTS: Prevalence of glycemic abnormalities was 46.0% (95% CI = 42.7-49.2%). Among participants with impaired glycemic status (N=417), 77.7% (95% CI=73.7-81.7%) consulted a GP for confirmation of screening results, 12.5% (95% CI=9.3-15.6%) did not, and 9.8% failed to respond to the follow-up survey. Factors independently associated with non-use of GP consultation for confirmation of screening results were self-reported unwillingness to consult a GP (adjusted odds ratio [OR]: 4.86, 95% CI=1.70-13.84), usual GP consultation frequency of less than once a year (adjusted OR: 4.13, 95% CI=1.56-10.97), and age 18-39 years (adjusted OR: 3.09, 95% CI=1.46-6.57). CONCLUSION: Home screening for glycemic abnormalities is a useful proximity health service for diabetes prevention in low socio-economic settings. Further efforts, including health literacy interventions, are needed to increase utilization of primary care.

Hypothalamic-pituitary-adrenal axis activation and glucocorticoid-responsive gene expression in skeletal muscle and liver of Apc mice.

BACKGROUND: Cancer patients at advanced stages experience a severe depletion of skeletal muscle compartment together with a decrease in muscle function, known as cancer cachexia. Cachexia contributes to reducing quality of life, treatment efficiency, and lifespan of cancer patients. However, the systemic nature of the syndrome is poorly documented. Here, we hypothesize that glucocorticoids would be important systemic mediators of cancer cachexia. METHODS: To explore the role of glucocorticoids during cancer cachexia, biomolecular analyses were performed on several tissues (adrenal glands, blood, hypothalamus, liver, and skeletal muscle) collected from ApcMin/+ male mice, a mouse model of intestine and colon cancer, aged of 13 and 23 weeks, and compared with wild type age-matched C57BL/6J littermates. RESULTS: Twenty-three-week-old Apc mice recapitulated important features of cancer cachexia including body weight loss (-16%, P < 0.0001), muscle atrophy (gastrocnemius muscle: -53%, P < 0.0001), and weakness (-50% in tibialis anterior muscle force, P < 0.0001), increased expression of atrogens (7-fold increase in MuRF1 transcript level, P < 0.0001) and down-regulation of Akt-mTOR pathway (3.3-fold increase in 4EBP1 protein content, P < 0.0001), together with a marked transcriptional rewiring of hepatic metabolism toward an increased expression of gluconeogenic genes (Pcx: +90%, Pck1: +85%), and decreased expression of glycolytic (Slc2a2: -40%, Gk: -30%, Pklr: -60%), ketogenic (Hmgcs2: -55%, Bdh1: -80%), lipolytic/fatty oxidation (Lipe: -50%, Mgll: -60%, Cpt2: -60%, Hadh: -30%), and lipogenic (Acly: -30%, Acacb: -70%, Fasn: -45%) genes. The hypothalamic pituitary-adrenal axis was activated, as evidenced by the increase in the transcript levels of genes encoding corticotropin-releasing hormone in the hypothalamus (2-fold increase, P < 0.01), adrenocorticotropic hormone receptor (3.4-fold increase, P < 0.001), and steroid biosynthesis enzymes (Cyp21a1, P < 0.0001, and Cyp11b1, P < 0.01) in the adrenal glands, as well as by the increase in corticosterone level in the serum (+73%, P < 0.05), skeletal muscle (+17%, P < 0.001), and liver (+24%, P < 0.05) of cachectic 23-week-old Apc mice. A comparative transcriptional analysis with dexamethasone-treated C57BL/6J mice indicated that the activation of the hypothalamic-pituitary-adrenal axis in 23-week-old ApcMin/+ mice was significantly associated with the transcription of glucocorticoid-responsive genes in skeletal muscle (P < 0.05) and liver (P < 0.001). The transcriptional regulation of glucocorticoid-responsive genes was also observed in the gastrocnemius muscle of Lewis lung carcinoma tumour-bearing mice and in KPC mice (tibialis anterior muscle and liver). CONCLUSIONS: These findings highlight the role of the hypothalamic-pituitary-adrenal-glucocorticoid pathway in the transcriptional regulation of skeletal muscle catabolism and hepatic metabolism during cancer cachexia. They also provide the paradigm for the design of new therapeutic strategies.

Perceived morbidity and community burden after a Chikungunya outbreak: the TELECHIK survey, a population-based cohort study.

BACKGROUND: Persistent disabilities are key manifestations of Chikungunya virus (CHIKV) infection, especially incapacitating polyarthralgia and fatigue. So far, little is known about their impact on health status. The present study aimed at describing the burden of CHIKV prolonged or late-onset symptoms on the self-perceived health of La Réunion islanders. METHODS: At 18 months after an outbreak of Chikungunya virus, we implemented the TELECHIK survey; a retrospective cohort study conducted on a random sample of the representative SEROCHIK population-based survey. A total of 1,094 subjects sampled for CHIKV-specific IgG antibodies in the setting of La Réunion island in the Indian Ocean, between August 2006 and October 2006, were interviewed about current symptoms divided into musculoskeletal/rheumatic, fatigue, cerebral, sensorineural, digestive and dermatological categories. RESULTS: At the time of interview, 43% of seropositive (CHIK+) subjects reported musculoskeletal pain (vs 17% of seronegative (CHIK-) subjects, P < 0.001), 54% fatigue (vs 46%, P = 0.04), 75% cerebral disorders (vs 57%, P < 0.001), 49% sensorineural impairments (vs 37%, P = 0.001), 18% digestive complaints (vs 15%, P = 0.21), and 36% skin involvement (vs 34%, P = 0.20) on average 2 years after infection (range: 15-34 months). After controlling for confounders such as age, gender, body mass index or major comorbidities in different Poisson regression models, 33% of joint pains were attributable to CHIKV, 10% of cerebral disorders and 7.5% of sensorineural impairments, while Chikungunya did not enhance fatigue states, digestive and skin disorders. CONCLUSIONS: On average, 2 years after infection 43% to 75% of infected people reported prolonged or late-onset symptoms highly attributable to CHIKV. These manifestations carry a significant burden in the community in the fields of rheumatology, neurology and sensorineural health.

Downregulation of Akt/mammalian target of rapamycin pathway in skeletal muscle is associated with increased REDD1 expression in response to chronic hypoxia.

Although it is well established that chronic hypoxia leads to an inexorable loss of skeletal muscle mass in healthy subjects, the underlying molecular mechanisms involved in this process are currently unknown. Skeletal muscle atrophy is also an important systemic consequence of chronic obstructive pulmonary disease (COPD), but the role of hypoxemia in this regulation is still debated. Our general aim was to determine the molecular mechanisms involved in the regulation of skeletal muscle mass after exposure to chronic hypoxia and to test the biological relevance of our findings into the clinical context of COPD. Expression of positive and negative regulators of skeletal muscle mass were explored 1) in the soleus muscle of rats exposed to severe hypoxia (6,300 m) for 3 wk and 2) in vastus lateralis muscle of nonhypoxemic and hypoxemic COPD patients. In rodents, we observed a marked inhibition of the mammalian target of rapamycin (mTOR) pathway together with a strong increase in regulated in development and DNA damage response 1 (REDD1) expression and in its association with 14-3-3, a mechanism known to downregulate the mTOR pathway. Importantly, REDD1 overexpression in vivo was sufficient to cause skeletal muscle fiber atrophy in normoxia. Finally, the comparative analysis of skeletal muscle in hypoxemic vs. nonhypoxemic COPD patients confirms that hypoxia causes an inhibition of the mTOR signaling pathway. We thus identify REDD1 as a negative regulator of skeletal muscle mass during chronic hypoxia. Translation of this fundamental knowledge into the clinical investigation of COPD shows the interest to develop therapeutic strategies aimed at inhibiting REDD1.

Endurance exercise decreases protein synthesis and ER-mitochondria contacts in mouse skeletal muscle.

Exercise is important to maintain skeletal muscle mass through stimulation of protein synthesis, which is a major ATP-consuming process for cells. However, muscle cells have to face high energy demand during contraction. The present study aimed to investigate protein synthesis regulation during aerobic exercise in mouse hindlimb muscles. Male C57Bl/6J mice ran at 12 m/min for 45 min or at 12 m/min for the first 25 min followed by a progressive increase in velocity up to 20 m/min for the last 20 min. Animals were injected intraperitoneally with 40 nmol/g of body weight of puromycin and euthanized by cervical dislocation immediately after exercise cessation. Analysis of gastrocnemius, plantaris, quadriceps, soleus, and tibialis anterior muscles revealed a decrease in protein translation assessed by puromycin incorporation, without significant differences among muscles or running intensities. The reduction of protein synthesis was associated with a marked inhibition of mammalian target of rapamycin complex 1 (mTORC1)-dependent phosphorylation of eukaryotic translation initiation factor 4E-binding protein 1, a mechanism consistent with reduced translation initiation. A slight activation of AMP-activated protein kinase consecutive to the running session was measured but did not correlate with mTORC1 inhibition. More importantly, exercise resulted in a strong upregulation of regulated in development and DNA damage 1 (REDD1) protein and gene expressions, whereas transcriptional regulation of other recognized exercise-induced genes (IL-6, kruppel-like factor 15, and regulator of calcineurin 1) did not change. Consistently with the recently discovered role of REDD1 on mitochondria-associated membranes, we observed a decrease in mitochondria-endoplasmic reticulum interaction following exercise. Collectively, these data raise questions concerning the role of mitochondria-associated endoplasmic reticulum membrane disruption in the regulation of muscle proteostasis during exercise and, more generally, in cell adaptation to metabolic stress.NEW & NOTEWORTHY How muscles regulate protein synthesis to cope with the energy demand during contraction is poorly documented. Moreover, it is unknown whether protein translation is differentially affected among mouse hindlimb muscles under different physiological exercise modalities. We showed here that 45 min of running decreases puromycin incorporation similarly in 5 different mouse muscles. This decrease was associated with a strong increase in regulated in development and DNA damage 1 protein expression and a significant disruption of the mitochondria and sarcoplasmic reticulum interaction.

Serious acute chikungunya virus infection requiring intensive care during the Reunion Island outbreak in 2005-2006.

OBJECTIVE: To report the clinical and laboratory findings of adults with serious chikungunya virus acute infection hospitalized in an intensive care unit. DESIGN: Case series study from August 2005 to May 2006. SETTING: Medical intensive care unit, South Reunion Hospital. PATIENTS: We observed 33 episodes of confirmed acute chikungunya virus infection (chikungunya virus-IgM or reverse transcription-polymerase chain reaction positive in the serum) admitted to the intensive care unit. INTERVENTIONS: We collected cerebrospinal fluid, serum, and sometimes tissue samples from patients with suspected chikungunya fever in our intensive care unit. These samples underwent viral testing for evidence of acute chikungunya virus infection. MEASUREMENTS AND MAIN RESULTS: Of the 33 patients, 19 (58%) had chikungunya virus specific manifestations, 8 (24%) had associated acute infectious disease and 6 (18%) exacerbations of previous complaints. Among the chikungunya virus specific manifestations, we identified 14 cases of encephalopathy, one case each of myocarditis, hepatitis and Guillain Barré syndrome. Eighty-five percent of patients had a McCabe score = 1 (for nonfatal or no underlying disease). Mortality was 48%. CONCLUSIONS: Chikungunya virus infection may be responsible for very severe clinical presentation, including young patients with unremarkable medical histories. Chikungunya virus infection is strongly suspected to have neurologic, hepatic, and myocardial tropism leading to dramatic complications and high mortality rate.

Estimating Chikungunya prevalence in La Réunion Island outbreak by serosurveys: two methods for two critical times of the epidemic.

BACKGROUND: Chikungunya virus (CHIKV) caused a major two-wave seventeen-month-long outbreak in La Réunion Island in 2005-2006. The aim of this study was to refine clinical estimates provided by a regional surveillance-system using a two-stage serological assessment as gold standard. METHODS: Two serosurveys were implemented: first, a rapid survey using stored sera of pregnant women, in order to assess the attack rate at the epidemic upsurge (s1, February 2006; n = 888); second, a population-based survey among a random sample of the community, to assess the herd immunity in the post-epidemic era (s2, October 2006; n = 2442). Sera were screened for anti-CHIKV specific antibodies (IgM and IgG in s1, IgG only in s2) using enzyme-linked immunosorbent assays. Seroprevalence rates were compared to clinical estimates of attack rates. RESULTS: In s1, 18.2% of the pregnant women were tested positive for CHIKV specific antibodies (13.8% for both IgM and IgG, 4.3% for IgM, 0.1% for IgG only) which provided a congruent estimate with the 16.5% attack rate calculated from the surveillance-system. In s2, the seroprevalence in community was estimated to 38.2% (95% CI, 35.9 to 40.6%). Extrapolations of seroprevalence rates led to estimate, at 143,000 and at 300,000 (95% CI, 283,000 to 320,000), the number of people infected in s1 and in s2, respectively. In comparison, the surveillance-system estimated at 130,000 and 266,000 the number of people infected for the same periods. CONCLUSION: A rapid serosurvey in pregnant women can be helpful to assess the attack rate when large seroprevalence studies cannot be done. On the other hand, a population-based serosurvey is useful to refine the estimate when clinical diagnosis underestimates it. Our findings give valuable insights to assess the herd immunity along the course of epidemics.

Rheumatic manifestations associated with Chikungunya virus infection: A study of 307 patients with 32-month follow-up (RHUMATOCHIK study).

OBJECTIVES: In the wake of the Chikungunya epidemic which struck Reunion Island in 2005 and 2006, we conducted a prospective, multicentre study (RHUMATOCHIK) whose main objective was analyse the characteristics and progression of rheumatic manifestations in patients with post-Chikungunya joint pain. METHODS: A cohort of 307 consecutively included patients underwent rheumatological examinations for pain secondary to Chikungunya virus infection. The long-term evaluation was conducted by telephone survey 1 and 2 years after the onset of the viral infection. RESULTS: At inclusion, mean age was 54 years (24-87) and 83.1% of the patients were female. Chronic joint pain was associated with synovitis in 64.2% of the patients, affecting primarily the wrists, the proximal interphalangeal joints of the fingers, and the ankles. Attempts to detect the viral genome in joint fluid (10 patients) and synovial tissue (6 patients) using the RT-PCR technique were repeatedly unsuccessful. With a mean follow-up of 32 months, joint pain persisted in 83.1% of the patients. Functional impairment, however, was moderate, with a HAQ score of 0.44±0.5. CONCLUSION: Chikungunya virus infection is frequently the cause of joint manifestations that can persist for several months, or even several years. In some cases, the clinical symptoms closely resemble those usually associated with rheumatoid arthritis. Further studies are necessary to improve the therapeutic management of these patients.

Sexual dimorphism in the association between gestational diabetes mellitus and overweight in offspring at 5-7 years: The OBEGEST cohort study.

Evidence from literature is mixed regarding a possible association of maternal gestational diabetes mellitus (GDM) and overweight in the offspring. Sexual dimorphism, or sex disparities in the pathogenesis linking GDM exposure to overweight, could be at play. The objective of this study was to investigate the association between GDM and child overweight at 5-7 years. Six hundred pairs (1:1) of Reunionese liveborn singletons selected from a hospital-based birth registry, matched for sex, gestational age, and birth period, underwent a prospective in-home follow-up and were analyzed with respect to their exposure to GDM. The primary outcome was child overweight at 5-7 years, as defined by the International Obesity Task Force. The association between GDM exposure and child overweight was estimated by the odds ratio (OR) using conditional logistic regression models. For the subset of children exposed to GDM with available maternal glycemic data, we analyzed the relationship between maternal glycemic levels during pregnancy and child body mass index (BMI) at 5-7 years with a linear regression model. In light of the significant interaction between sex and GDM, all statistical analyses were then stratified by sex. After controlling for pre-pregnancy BMI and maternal sociodemographic characteristics, the risk of overweight increased with exposure to GDM for boys (adjusted OR: 2.34; 95% confidence interval = 1.26-4.34, P = 0.007) but not for girls (adjusted OR: 0.56; 95%CI = 0.28-1.10, P = 0.093). Consistent with this, the linear increase of boys' BMI at 5-7 years with maternal blood glucose levels during pregnancy, in the exposed group, displayed a dose-response relationship. Our findings indicate that exposure to GDM is a risk factor for childhood overweight in boys but not in girls, which adds to the growing body of evidence suggesting greater sensitivity of male offspring to intrauterine hyperglycemia.