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Rugby players must develop excellent levels of conditioning during adolescence. However, this pivotal period of life is also characterized by a surge in biological growth, which further increases the energy and nutritional requirements of this population. This study examined within-individual differences in energy intake (EI) and energy balance (EB) of 46 young rugby players during a pre-season micro-cycle. Two clusters were identified with significantly different characteristics and EB states, suggesting that young rugby players adjust their EI to match their body composition goals. The first cluster is characterized by players with a low body fat% (12.87 ± 2.53). They had a positive EB (330 ± 517 kcal), suggesting a goal of increasing muscle mass. Conversely, the second cluster is characterized by a higher body fat% (23.1 ± 1.6, p < 0.005) and reported a negative, lower EB (−683 ± 425 kcal, p < 0.005), suggesting a goal focused on reducing fat mass. Although our study provides more optimistic results than previous ones regarding the high risk of inadequate EI in young rugby players, we emphasize the importance of rigorous nutritional support, especially for players aiming to lose weight, to avoid severe caloric restriction, as well as the downstream effects of such practices on their nutritional status, given the higher risk of macro- (e.g., CHO < 6 g/kg/d) and micronutrient (e.g., iron < 11 mg/d, calcium < 1300 mg/d, vitamin D < 5 mg/d) deficiencies.

Low energy availability (LEA) has been associated with several physiological consequences, but its impact on sleep has not been sufficiently investigated, especially in the context of young athletes. This study examined the potential association between energy availability (EA) status and objective sleep quality in 42 male rugby players (mean age: 16.2 ± 0.8 years) during a 7-day follow-up with fixed sleep schedules in the midst of an intensive training phase. Participants’ energy intake was weighed and recorded. Exercise expenditure was estimated using accelerometry. Portable polysomnography devices captured sleep on the last night of the follow-up. Mean EA was 29.3 ± 9.14 kcal·kg FFM−1·day−1, with 47.6% of athletes presenting LEA, 35.7% Reduced Energy Availability (REA), and 16.7% Optimal Energy Availability (OEA). Lower sleep efficiency (SE) and N3 stage proportion, along with higher wake after sleep onset (WASO), were found in participants with LEA compared to those with OEA (p = 0.04, p = 0.03 and p = 0.005, respectively, with large effect sizes). Segmented regression models of the EA-sleep outcomes (SE, sleep onset latency [SOL]), WASO and N3) relationships displayed two separate linear regions and produced a best fit with a breakpoint between 21–33 kcal·kg FFM−1·day−1. Below these thresholds, sleep quality declines considerably. It is imperative for athletic administrators, nutritionists, and coaches to conscientiously consider the potential impact of LEA on young athletes’ sleep, especially during periods of heavy training.

Wolfram syndrome (WS) is a rare neurodegenerative disease resulting in deafness, optic atrophy, diabetes, and neurological disorders. Currently, no treatment is available for patients. The mutated gene, WFS1, encodes an endoplasmic reticulum (ER) protein, Wolframin. We previously reported that Wolframin regulated the ER-mitochondria Ca2+ transfer and mitochondrial activity by protecting NCS1 from degradation in patients’ fibroblasts. We relied on a zebrafish model of WS, the wfs1abKO line, to analyze the functional and behavioral impact of NCS1 overexpression as a novel therapeutic strategy. The wfs1abKO line showed an increased locomotion in the visual motor and touch-escape responses. The absence of wfs1 did not impair the cellular unfolded protein response, in basal or tunicamycin-induced ER stress conditions. In contrast, metabolic analysis showed an increase in mitochondrial respiration in wfs1abKO larvae. Interestingly, overexpression of NCS1 using mRNA injection restored the alteration of mitochondrial respiration and hyperlocomotion. Taken together, these data validated the wfs1abKO zebrafish line as a pertinent experimental model of WS and confirmed the therapeutic potential of NCS1. The wfs1abKO line therefore appeared as an efficient model to identify novel therapeutic strategies, such as gene or pharmacological therapies targeting NCS1 that will correct or block WS symptoms.

Background and aimsStatin-associated muscle symptoms (SAMS) are frequently reported. Nevertheless, few data on objective measures of muscle function are available. Recent data suggesting an important nocebo effect with statin use could confound such effects. The objective was to assess if subjective and objective measures of muscle function improve after drug withdrawal in SAMS reporters.MethodsPatients (59 men, 33 women, 50.3±9.6 yrs.) in primary cardiovascular prevention composed three cohorts: statin users with (SAMS, n = 61) or without symptoms (No SAMS, n = 15), and controls (n = 16) (registered at clinicaltrials.gov, NCT01493648). Force (F), endurance (E) and power (P) of the leg extensors (ext) and flexors (fle) and handgrip strength (Fhg) were measured using isokinetic and handheld dynamometers, respectively. A 10-point visual analogue scale (VAS) was used to self-assess SAMS intensity. Measures were taken before and after two months of withdrawal.ResultsFollowing withdrawal, repeated-measures analyses show improvements for the entire cohort in Eext, Efle, Ffle, Pext and Pfle (range +7.2 to +13.3%, all p≤0.02). Post-hoc analyses show these changes to occur notably in SAMS (+8.8 to +16.6%), concurrent with a decrease in subjective perception of effects in SAMS (VAS, from 5.09 to 1.85). Fhg was also improved in SAMS (+4.0 to +6.2%) when compared to No SAMS (-1.7 to -4.2%) (all p = 0.02).ConclusionsWhether suffering from "true" SAMS or nocebo, those who reported SAMS had modest but relevant improvements in muscle function concurrent with a decrease in subjective symptoms intensity after drug withdrawal. Greater attention by clinicians to muscle function in frail statin users appears warranted.Trial registrationThis study is registered in clinicaltrials.gov (NCT01493648).

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting upper and lower motor neurons. As a consequence, ALS patients display a locomotor disorder related to muscle weakness and progressive paralysis. Pathological mechanisms that participate in ALS involve deficient unfolded protein response, mitochondrial dysfunction and oxidative stress, among others. Finding a therapeutic target to break the vicious circle is particularly challenging. Sigma-1 receptor (S1R) is an endoplasmic reticulum (ER) chaperone that may be one of those targets. We here address and decipher the efficiency of S1R activation on a key ALS gene, TDP43, in zebrafish vertebrate model. While expression of mutant TDP43 (TDP43G348C) led to locomotor defects, treatment with the reference S1R agonist PRE-084 rescued motor performances in a zebrafish model. Treatment with the agonist ameliorated maximal mitochondrial respiration in the TDP43 context. We observed that TDP43G348C exacerbated ER stress induced by tunicamycin, resulting in increased levels of ER stress chaperone BiP and pro-apoptotic factor CHOP. Importantly, PRE-084 treatment in the same condition further heightened BiP levels but also EIF2α/ATF4 and NRF2 signalling cascades, both known to promote antioxidant protection during ER stress. Moreover, we showed that increasing NRF2 levels directly or by sulforaphane treatment rescued locomotor defects of TDP43G348C zebrafish. For the first time, we here provide the proof of concept that PRE-084 prevents mutant TDP43 toxicity by boosting ER stress response and antioxidant cascade through NRF2 signalling.

Neurodevelopmental axonal pathfinding plays a central role in correct brain wiring and subsequent cognitive abilities. Within the growth cone, various intracellular effectors transduce axonal guidance signals by remodeling the cytoskeleton. Semaphorin-3E (Sema3E) is a guidance cue implicated in development of the fornix, a neuronal tract connecting the hippocampus to the hypothalamus. Microtubule-associated protein 6 (MAP6) has been shown to be involved in the Sema3E growth-promoting signaling pathway. In this study, we identified the collapsin response mediator protein 4 (CRMP4) as a MAP6 partner and a crucial effector in Sema3E growth-promoting activity. CRMP4-KO mice displayed abnormal fornix development reminiscent of that observed in Sema3E-KO mice. CRMP4 was shown to interact with the Sema3E tripartite receptor complex within detergent-resistant membrane (DRM) domains, and DRM domain integrity was required to transduce Sema3E signaling through the Akt/GSK3 pathway. Finally, we showed that the cytoskeleton-binding domain of CRMP4 is required for Sema3E’s growth-promoting activity, suggesting that CRMP4 plays a role at the interface between Sema3E receptors, located in DRM domains, and the cytoskeleton network. As the fornix is affected in many psychiatric diseases, such as schizophrenia, our results provide new insights to better understand the neurodevelopmental components of these diseases.

This study aimed to determine the short-term effect of two isocaloric diets differing in the ratio of protein–carbohydrate on melatonin levels, sleep, and subsequent dietary intake and physical activity in healthy young men. Twenty-four healthy men took part in a crossover design including two sessions of three days on isocaloric diets whether high-protein, low-carbohydrate (HPLC) or low-protein, high-carbohydrate (LPHC) followed by 24-h free living assessments. Sleep was measured by ambulatory polysomnography pre-post-intervention. Melatonin levels were assessed on the third night of each session on eight-point salivary sampling. Physical activity was monitored by accelerometry. On day 4, participants reported their 24-h ad-libitum dietary intake. LPHC resulted in better sleep quality and increased secretion of melatonin compared to HPLC. A significant difference was noted in sleep efficiency (p < 0.05) between the two sessions. This was mainly explained by a difference in sleep onset latency (p < 0.01) which was decreased during LPHC (PRE: 15.8 ± 7.8 min, POST: 11.4 ± 4.5 min, p < 0.001). Differences were also noted in sleep staging including time spent on REM (p < 0.05) and N1 (p < 0.05). More importantly, REM latency (PRE: 97.2 ± 19.9 min, POST 112.0 ± 20.7 min, p < 0.001) and cortical arousals (PRE: 7.2 ± 3.9 event/h, POST 8.5 ± 3.3 event/h) increased in response to HPLC diet but not LPHC. On day 4, 24-h ad-libitum energy intake was higher following HPLC compared to LPHC (+64 kcal, p < 0.05) and explained by increased snacking behavior (p < 0.01) especially from carbohydrates (p < 0.05). Increased carbohydrates intake was associated with increased cortical arousals.

• Vitamin D supplementation has no beneficial effect on self-reported SAMS intensity. • Vitamin D supplementation has no beneficial effect on self-reported HRQoL. • Vitamin D supplementation has no beneficial effect on objective muscle performance. Statins are the leading lipid-lowering drugs, reducing blood cholesterol by controlling its synthesis. Side effects are linked to the use of statins, in particular statin-associated muscle symptoms (SAMS). Some data suggest that vitamin D supplementation could reduce SAMS. The purpose of this study was to evaluate the potential benefits of vitamin D supplementation in a randomized controlled trial. Men (n = 23) and women (n = 15) (50.5 ± 7.7 years [mean ± SD]) in primary cardiovascular prevention, self-reporting or not SAMS, were recruited. Following 2 months of statin withdrawal, patients were randomized to supplementation (vitamin D or placebo). After 1 month of supplementation, statins were reintroduced. Before and 2 months after drug reintroduction, muscle damage (creatine kinase and myoglobin) was measured. Force (F), endurance (E) and power (P) of the leg extensors (ext) and flexors (fle) and handgrip strength (FHG) were also measured with isokinetic and handheld dynamometers, respectively. The Short Form 36 Health Survey (SF-36) questionnaire and a visual analog scale (VAS) were administrated to assess participants' self-reported health-related quality of life and SAMS intensity, respectively. Repeated-measures analysis was used to investigate the effects of time, supplementation, and their interaction, according to the presence of SAMS. Despite no change for objective measures, subjective measures worsened after reintroduction of statins, independent of supplementation (VAS, SF-36 mental component score, all p < 0.05). However, no interaction between time and supplementation according to the presence of SAMS was observed for any variables. Vitamin D supplementation does not appear to mitigate SAMS. [ABSTRACT FROM AUTHOR]

Statins use is linked to side effects, notably muscular ones, known as Statin-Associated Muscle Symptoms (SAMS). These can include a pain, an increased sensitivity to palpation, aches, and cramps. SAMS are a real problem in the clinical management of patients, as it is difficult to causally link these complaints with drug use, and they may lead to a reduction in statin intake, or even to the patient -discontinuing their use. The absence of objective markers and the -variety of possible clinical manifestations of these muscular -complaints impede a full understanding of the objective and -subjective impacts of these symptoms on the everyday life of sympto-matic patients. This article assess the current state of knowledge on the impact of SAMS on performance and health--related quality of life., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Rugby players must develop excellent levels of conditioning during adolescence. However, this pivotal period of life is also characterized by a surge in biological growth, which further increases the energy and nutritional requirements of this population. This study examined within-individual differences in energy intake (EI) and energy balance (EB) of 46 young rugby players during a pre-season micro-cycle. Two clusters were identified with significantly different characteristics and EB states, suggesting that young rugby players adjust their EI to match their body composition goals. The first cluster is characterized by players with a low body fat% (12.87 ± 2.53). They had a positive EB (330 ± 517 kcal), suggesting a goal of increasing muscle mass. Conversely, the second cluster is characterized by a higher body fat% (23.1 ± 1.6, p < 0.005) and reported a negative, lower EB (-683 ± 425 kcal, p < 0.005), suggesting a goal focused on reducing fat mass. Although our study provides more optimistic results than previous ones regarding the high risk of inadequate EI in young rugby players, we emphasize the importance of rigorous nutritional support, especially for players aiming to lose weight, to avoid severe caloric restriction, as well as the downstream effects of such practices on their nutritional status, given the higher risk of macro- (e.g., CHO < 6 g/kg/d) and micronutrient (e.g., iron < 11 mg/d, calcium < 1300 mg/d, vitamin D < 5 mg/d) deficiencies.

Despite some reported benefits, there is a low quality of evidence for resistance training (RT) improving metabolic health of individuals with overweight or obesity. We evaluated the impact of RT on body composition, cardiorespiratory fitness (CRF) and physical performance, lipid-lipoprotein profile, inflammation, and glucose-insulin homeostasis in 51 postmenopausal women versus 29 controls matched for age, obesity, and physical activity. Exercised women were further subdivided for comparison of RT effects into those presenting metabolically healthy obesity (MHO) and those with metabolically unhealthy obesity (MUHO) classified according to Karelis and Rabasa-Lhoret or an approach based on adipose tissue secretory dysfunction using the plasma adiponectin(A)/leptin (L) ratio. Participants followed a 4-month weekly RT program targeting major muscle groups (3 × 10 repetitions at 80% one repetition maximum (1-RM)). Percent fat marginally decreased and lean body mass increased (0.01 <  p  < 0.05) while CRF and muscular strength improved in all women, after RT (effect size (ES): 0.11-1.21 (trivial to large effects), p ˂ 0.01). Fasting plasma triacylglycerol and high-density lipoprotein-cholesterol levels slightly increased and decreased, respectively, in participants with MHO using the A/L ratio approach (ES: -0.47 to 1.07 (small to large effects), p ˂ 0.05). Circulating interleukin-6 soluble receptor decreased in both groups and soluble tumor necrosis factor receptor-1/soluble tumor necrosis factor receptor-2 in women with MUHO only, irrespective of definition (ES: -0.42 to -0.84 (small to large effects), p ˂ 0.05). Glucose-insulin homeostasis was unchanged regardless of group or definition. RT improved physical performance and body composition but had a lesser impact on cardiometabolic risk in women with obesity, irrespective of their metabolic phenotype., Competing Interests: The authors declare that they have no conflict of interest related to the present study. AT receives funding from Johnson & Johnson, Medtronic, and GI Windows for research unrelated to the present study. AT also acted as consultant for Novo Nordisk, Bausch Health, and Biotwin. The authors alone are responsible for the contents and writing of the paper.

Low energy availability (LEA) has been associated with several physiological consequences, but its impact on sleep has not been sufficiently investigated, especially in the context of young athletes. This study examined the potential association between energy availability (EA) status and objective sleep quality in 42 male rugby players (mean age: 16.2 ± 0.8 years) during a 7-day follow-up with fixed sleep schedules in the midst of an intensive training phase. Participants' energy intake was weighed and recorded. Exercise expenditure was estimated using accelerometry. Portable polysomnography devices captured sleep on the last night of the follow-up. Mean EA was 29.3 ± 9.14 kcal·kg FFM -1 ·day -1 , with 47.6% of athletes presenting LEA, 35.7% Reduced Energy Availability (REA), and 16.7% Optimal Energy Availability (OEA). Lower sleep efficiency (SE) and N3 stage proportion, along with higher wake after sleep onset (WASO), were found in participants with LEA compared to those with OEA ( p = 0.04, p = 0.03 and p = 0.005, respectively, with large effect sizes). Segmented regression models of the EA-sleep outcomes (SE, sleep onset latency [SOL]), WASO and N3) relationships displayed two separate linear regions and produced a best fit with a breakpoint between 21-33 kcal·kg FFM -1 ·day -1 . Below these thresholds, sleep quality declines considerably. It is imperative for athletic administrators, nutritionists, and coaches to conscientiously consider the potential impact of LEA on young athletes' sleep, especially during periods of heavy training.

Background and Aims: Statin-associated muscle symptoms (SAMS) are frequently reported. Nevertheless, few data on objective measures of muscle function are available. Recent data suggesting an important nocebo effect with statin use could confound such effects. The objective was to assess if subjective and objective measures of muscle function improve after drug withdrawal in SAMS reporters., Methods: Patients (59 men, 33 women, 50.3±9.6 yrs.) in primary cardiovascular prevention composed three cohorts: statin users with (SAMS, n = 61) or without symptoms (No SAMS, n = 15), and controls (n = 16) (registered at clinicaltrials.gov, NCT01493648). Force (F), endurance (E) and power (P) of the leg extensors (ext) and flexors (fle) and handgrip strength (Fhg) were measured using isokinetic and handheld dynamometers, respectively. A 10-point visual analogue scale (VAS) was used to self-assess SAMS intensity. Measures were taken before and after two months of withdrawal., Results: Following withdrawal, repeated-measures analyses show improvements for the entire cohort in Eext, Efle, Ffle, Pext and Pfle (range +7.2 to +13.3%, all p≤0.02). Post-hoc analyses show these changes to occur notably in SAMS (+8.8 to +16.6%), concurrent with a decrease in subjective perception of effects in SAMS (VAS, from 5.09 to 1.85). Fhg was also improved in SAMS (+4.0 to +6.2%) when compared to No SAMS (-1.7 to -4.2%) (all p = 0.02)., Conclusions: Whether suffering from "true" SAMS or nocebo, those who reported SAMS had modest but relevant improvements in muscle function concurrent with a decrease in subjective symptoms intensity after drug withdrawal. Greater attention by clinicians to muscle function in frail statin users appears warranted., Trial Registration: This study is registered in clinicaltrials.gov (NCT01493648)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Peyrel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study aimed to determine the short-term effect of two isocaloric diets differing in the ratio of protein−carbohydrate on melatonin levels, sleep, and subsequent dietary intake and physical activity in healthy young men. Twenty-four healthy men took part in a crossover design including two sessions of three days on isocaloric diets whether high-protein, low-carbohydrate (HPLC) or low-protein, high-carbohydrate (LPHC) followed by 24-h free living assessments. Sleep was measured by ambulatory polysomnography pre-post-intervention. Melatonin levels were assessed on the third night of each session on eight-point salivary sampling. Physical activity was monitored by accelerometry. On day 4, participants reported their 24-h ad-libitum dietary intake. LPHC resulted in better sleep quality and increased secretion of melatonin compared to HPLC. A significant difference was noted in sleep efficiency (p < 0.05) between the two sessions. This was mainly explained by a difference in sleep onset latency (p < 0.01) which was decreased during LPHC (PRE: 15.8 ± 7.8 min, POST: 11.4 ± 4.5 min, p < 0.001). Differences were also noted in sleep staging including time spent on REM (p < 0.05) and N1 (p < 0.05). More importantly, REM latency (PRE: 97.2 ± 19.9 min, POST 112.0 ± 20.7 min, p < 0.001) and cortical arousals (PRE: 7.2 ± 3.9 event/h, POST 8.5 ± 3.3 event/h) increased in response to HPLC diet but not LPHC. On day 4, 24-h ad-libitum energy intake was higher following HPLC compared to LPHC (+64 kcal, p < 0.05) and explained by increased snacking behavior (p < 0.01) especially from carbohydrates (p < 0.05). Increased carbohydrates intake was associated with increased cortical arousals.

Young athletes must contend with the constraints of elite sports on top of school commitments and the physiological processes associated with adolescence. This study assessed week and weekend sleep and schedule of activities in elite adolescent rugby players during the in-season competitive phase compared with age-matched non-athlete controls. 32 adolescents (GR: 16 elite rugby players, GC: 16 controls) from the same boarding school filled out a daily schedule of activities and a sleep diary, and wore a multichannel electroencephalogram for 14 days. They later filled out questionnaires on their sleep quality, sleepiness, and perceived stress. Both groups showed insufficient sleep duration during the week (<7 h). Only GC caught up on their sleep debt during the weekend (increased TIB, TST and time spent in REM sleep, all p  < 0.001). Weekend TIB, TST and, N3 sleep remained similar to that for weekdays in GR. However, GR experienced lower sleep quality (decreased SE, increased WASO, all p  < 0.01) and a decrease in REM sleep ( p  < 0.01). Schedules of activities showed an increase in time spent on overall activities during the weekend, mainly due to competition and sport-specific travel, which resulted in a decrease in sleep opportunity time compared with GC ( p  < 0.001). Δ sleep opportunity time (weekend-week) was associated with Δ TST (weekend-week), and Δ TST (weekend-week) was associated with sleepiness and perceived stress. Busy schedules during the competitive season decreased sleep opportunity time and prevented elite adolescent rugby players from catching up on their sleep at weekends. HIGHLIGHTS Adolescent rugby players have insufficient sleep during both week and weekend of the in-season competitive phaseCongested schedule prevented elite adolescent rugby players from catching up on their sleep at weekends.Sleep considerations are necessary when planning the weekend sporting schedules.