Year 2020

    • Relationship between intensive care unit-acquired weakness, fatigability and fatigue: What role for the central nervous system?

      Authors: Robin Souron, Jérôme Morel, Laurent Gergelé, Pascal Infantino, Callum G Brownstein, Thomas Lapole,Guillaume Y Millet.

      Published: 01 December 2020 - J Crit Care.


      Purpose: To provide a comprehensive review of studies that have investigated fatigue in intensive care unit (ICU) survivors and questions the potential link between intensive care unit-acquired weakness (ICUAW), fatigability and fatigue. We also question whether the central nervous system (CNS) may be the link between these entities.

      Material and methods: A narrative review of the literature that investigated fatigue in ICU survivors and review of clinical trials enabling understanding of CNS alterations in response to ICU stays.

      Results: Fatigue is a pervasive and debilitating symptom in ICU survivors that can interfere with rehabilitation. Due to the complex pathophysiology of fatigue, more work is required to understand the roles of ICUAW and/or fatigability in fatigue to provide a more holistic understanding of this symptom. While muscle alterations have been well documented in ICU survivors, we believe that CNS alterations developing early during the ICU stay may play a role in fatigue.

      Conclusions: Fatigue should be considered and treated in ICU survivors. The causes of fatigue are likely to be specific to the individual. Understanding the role that ICUAW and fatigability may have in fatigue would allow to tailor individual treatment to prevent this persistent symptom and improve quality of life.

      Keywords: Central nervous system; Fatigability; Fatigue; Intensive care unit-acquired weakness.

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    • Reliability and agreement of a dynamic quadriceps incremental test for the assessment of neuromuscular function

      Authors: Giorgio Varesco, Nicolas Royer, Benjamin Singh, Audrey Parent, Léonard Féasson, Thomas Lapole, Guillaume Y Millet, Vianney Rozand.

      Published: 19 November 2020 - J Electromyogr Kinesiol.


      The quadriceps-intermittent-fatigue (QIF) test assesses knee extensors strength, endurance and performance fatigability in isometric condition. We aimed to assess reliability and agreement for this test in dynamic conditions and with the use of transcranial magnetic stimulation. On two separate sessions, 20 young adults (25 ± 4 yr, 10 women) performed stages of 100 knee extensors concentric contractions at 120°/s (60° range-of-motion) with 10% increments of the initial maximal concentric torque until exhaustion. Performance fatigability across the test was quantified as maximal isometric and concentric torque loss, and its mechanisms were investigated through the responses to transcranial magnetic and electrical stimulations. Reliability and agreement were assessed using ANOVAs, coefficients of variation (CVs) and intra-class correlation coefficients (ICCs) with 95% CI. Good inter-session reliability and high agreement were found for number of contractions [489 ± 75 vs. 503 ± 95; P = 0.20; ICC = 0.85 (0.66; 0.94); CV = 5% (3; 7)] and total work [11,285 ± 4,932 vs. 11,792 ± 5838 Nm.s; P = 0.20; ICC = 0.95 (0.87; 0.98); CV = 8% (5; 11)]. Poor reliability but high agreement were observed for isometric [-33 ± 6 vs. -31 ± 7%; P = 0.13; ICC = 0.47 (0.05; 0.75); CV = 6% (4;8)] and concentric [-20 ± 11% vs. -19 ± 9%; P = 0.82; ICC = 0.26 (-0.22; 0.63); CV = 9% (6; 12)] torque loss. The dynamic QIF test represents a promising tool for neuromuscular evaluation in isokinetic mode.

      Keywords: Evaluation; Fatigability; Isokinetic; Neuromuscular fatigue; Transcranial magnetic stimulation.

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    • Impact of Trail Running Races on Blood Viscosity and Its Determinants: Effects of Distance

      Authors: Mélanie Robert, Emeric Stauffer, Elie Nader, Sarah Skinner, Camille Boisson, Agnes Cibiel, LéonardFeasson, Céline Renoux, Paul Robach, Philippe Joly, Guillaume Y Millet, Philippe Connes.

      Published: 12 November 2020 - Int J Mol Sci.


      Blood rheology is a key determinant of tissue perfusion at rest and during exercise. The present study investigated the effects of race distance on hematological, blood rheological, and red blood cell (RBC) senescence parameters. Eleven runners participated in the Martigny-Combes à Chamonix 40 km race (MCC, elevation gain: 2300 m) and 12 others in the Ultra-Trail du Mont Blanc (UTMB, 171 km, elevation gain: 10,000 m). Blood samples were collected before and after the races. After the UTMB, the percentage of RBC phosphatidylserine (PS) exposure was not affected while RBC CD235a levels decreased and RBC-derived microparticles increased. In contrast, after the MCC, RBC PS exposure increased, while RBC CD235a and RBC-derived microparticles levels were not affected. The free hemoglobin and hemolysis rate did not change during the races. RBC aggregation and blood viscosity at moderate shear rates increased after the MCC. RBC deformability, blood viscosity at a high shear rate, and hematocrit decreased after the UTMB but not after the MCC. Our results indicate that blood rheology behavior is different between a 40 km and a 171 km mountain race. The low blood viscosity after the ultra-marathon might facilitate blood flow to the muscles and optimize aerobic performance.

      Keywords: blood viscosity; hemorheology; red blood cell senescence; ultra-marathon.

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    • Use of transcranial magnetic stimulation to assess relaxation rates in unfatigued and fatigued knee-extensor muscles

      Authors: Gianluca Vernillo, Arash Khassetarash, Guillaume Y Millet, John Temesi.

      Published: 02 November 2020 - Exp Brain Res.


      We examined whether transcranial magnetic stimulation (TMS) delivered to the motor cortex allows assessment of muscle relaxation rates in unfatigued and fatigued knee extensors (KE). We assessed the ability of this technique to measure time course of fatigue-induced changes in muscle relaxation rate and compared relaxation rate from resting twitches evoked by femoral nerve stimulation. Twelve healthy men performed maximal voluntary isometric contractions (MVC) twice before (PRE) and once at the end of a 2-min KE MVC and five more times within 8 min during recovery. Relative (intraclass correlation coefficient; ICC2,1) and absolute (repeatability coefficient) reliability and variability (coefficient of variation) were assessed. Time course of fatigue-induced changes in muscle relaxation rate was tested with generalized estimating equations. In unfatigued KE, peak relaxation rate coefficient of variation and repeatability coefficient were similar for both techniques. Mean (95% CI) ICC2,1 for peak relaxation rates were 0.933 (0.724-0.982) and 0.889 (0.603-0.968) for TMS and femoral nerve stimulation, respectively. TMS-induced normalized muscle relaxation rate was - 11.5 ± 2.5 s-1 at PRE, decreased to - 6.9 ± 1.2 s-1 (- 37 ± 17%, P < 0.001), and recovered by 2 min post-exercise. Normalized peak relaxation rate for resting twitch did not show a fatigue-induced change. During fatiguing KE exercise, the change in muscle relaxation rate as determined by the two techniques was different. TMS provides reliable values of muscle relaxation rates. Furthermore, it is sufficiently sensitive and more appropriate than the resting twitch evoked by femoral nerve stimulation to reveal fatigue-induced changes in KE.

      Keywords: Fatigue; Knee extensors; Muscle relaxation rate; Transcranial magnetic stimulation.

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    • Local vibration training improves the recovery of quadriceps strength in early rehabilitation after anterior cruciate ligament reconstruction: a feasibility randomized controlled trial

      Authors: Claire Coulondre, Robin Souron, Alexandre Rambaud, Etienne Dalmais, Loïc Espeit, Thomas Neri, Alban Pinaroli, Gilles Estour, Guillaume Y Millet, Thomas Rupp, Léonard Feasson, Pascal Edouard, Thomas Lapole.

      Published: 12 October 2020 - Ann Phys Rehabil Med.


      Background: After anterior cruciate ligament reconstruction (ACLR), quadriceps strength must be maximized as early as possible.

      Objectives: We tested whether local vibration training (LVT) during the early post-ACLR period (i.e., ∼10 weeks) could improve strength recovery.

      Methods: This was a multicentric, open, parallel-group, randomized controlled trial. Thirty individuals attending ACLR were randomized by use of a dedicated Web application to 2 groups: vibration (standardized rehabilitation plus LVT, n=16) or control (standardized rehabilitation alone, n=14). Experimenters, physiotherapists and participants were not blinded. Both groups received 24 sessions of standardized rehabilitation over ∼10 weeks. In addition, the vibration group received 1 hr of vibration applied to the relaxed quadriceps of the injured leg at the end of each rehabilitation session. The primary outcome - maximal isometric strength of both injured and non-injured legs (i.e., allowing for limb asymmetry measurement) - was evaluated before ACLR (PRE) and after the 10-week rehabilitation (POST).

      Results: Seven participants were lost to follow-up, so data for 23 participants were used in the complete-case analysis. For the injured leg, the mean (SD) decrease in maximal strength from PRE to POST was significantly lower for the vibration than control group (n=11, -16% [10] vs n=12, -30% [11]; p=0.0045, Cohen's d effect size = 1.33). Mean PRE-POST change in limb symmetry was lower for the vibration than control group (-19% [11] vs -29% [13]) but not significantly (p=0.051, Cohen's d effect size = 0.85).

      Conclusion: LVT improved strength recovery after ACLR. This feasibility study suggests that LVT applied to relaxed muscles is a promising modality of vibration therapy that could be implemented early in ACLR.

      Keywords: anterior cruciate ligament reconstruction; local vibration; rehabilitation; strength.

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    • Exercise and colorectal cancer: a systematic review and meta-analysis of exercise safety, feasibility and effectiveness

      Authors: Benjamin Singh, Sandra C Hayes, Rosalind R Spence, Megan L Steele, Guillaume Y Millet, Laurent Gergele

      Published: 24 September 2020 - Int J Behav Nutr Phys Act. 


      Background: This meta-analysis evaluated the safety, feasibility and effect of exercise among individuals with colorectal cancer.

      Methods: A database search (CINAHL, Ebscohost, MEDLINE, Pubmed, ProQuest Health and Medical Complete, ProQuest Nursing, Science Direct) for randomised, controlled, exercise trials involving individuals with colorectal cancer, published before January 1, 2020 was undertaken. Safety (adverse events), feasibility (withdrawal and adherence rates) and effect data (health outcomes including quality of life, QoL) were abstracted. Risk difference (RD) and standardised mean differences (SMD) were calculated to compare safety and effects between exercise and usual care (UC). Subgroup analyses were conducted to assess whether outcomes differed by exercise mode, duration, supervision and treatment. Risk of bias was assessed using the Physiotherapy Evidence Database tool.

      Results: For the 19 trials included, there was no difference in adverse event risk between exercise and UC (RD = 0.00; 95% CI:-0.01, 0.01, p = 0.92). Median withdrawal rate was 12% (0-22%) and adherence was 86% (42-91%). Significant effects of exercise compared to UC were observed for QoL, fatigue, aerobic fitness, upper-body strength, depression, sleep and reduced body fat (SMD = 0.21-0.66, p < 0.05). Subgroup analyses suggested larger benefits (p < 0.05) for QoL and fatigue for supervised interventions; for QoL, aerobic fitness and reduced body fat for ≥12-week interventions; and for aerobic fitness when interventions were during chemotherapy.

      Conclusion: Although reporting of safety and compliance data was lacking in most trials, findings support that exercise is safe and feasible in colorectal cancer. Further, participation in mixed-mode exercise, including unsupervised exercise, leads to improvements in various health-related outcomes.

      Keywords: Aerobic exercise; Cancer; Colon; Colorectal; Exercise oncology; Neoplasm; Rectal; Resistance exercise.

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    • Feasibility and Effects on the Gut Microbiota of a 12-Week High Intensity Interval Training plus Lifestyle Education Intervention on Inactive Adults with Celiac Disease

      Authors: Cassandra Warbeck, A Justine Dowd, Liam Kronlund, Candice Parmar, Julia T Daun, Kathryn Wytsma-Fisher, Guillaume Y Millet, Alana Schick, Raylene A Reimer, Tak Fung, Nicole Culos-Reed.

      Published: 22 September 2020 - Appl Physiol Nutr Metab. 


      This study assessed the feasibility and benefits of high intensity interval training (HIIT) plus lifestyle education among inactive adults with celiac disease. 41 participants were randomized to receive the intervention (HIIT+) for 12-weeks or waitlist control (WLC). Testing was completed at baseline, immediately post- and 3-months post-intervention. Generalized estimating equations were used to assess changes in the outcome variables over time between the groups. Mean percent of age-predicted maximum heart rate was 97.9% and average rating of perceived exertion (RPE) was 6.33 (out of 10) during HIIT intervals. Following the intervention, the HIIT+ group showed enrichment in relative abundance of Parabacteroides and Defluviitaleaceae_UCG¬_011 while WLC showed enrichment in relative abundance of Roseburia intestinalis, Klebsiella and Adlercreutzia. A unique set of taxa were differentially abundant between the groups at 3-months post-intervention. HIIT+ participants experienced a reduction in resting heart rate (-6.6 bpm) immediately post-intervention compared to WLC. Further research is needed to establish an optimal HIIT protocol that may improve VO2max and metabolic syndrome biomarkers. Findings from this pilot study provide preliminary evidence that a HIIT+ intervention is feasible for inactive adults with celiac disease and leads to favourable changes in resting HR alongside potentially beneficial shifts in gut microbiota. Trial registration number: number NCT03520244 Novelty • High intensity interval training leads to potentially beneficial changes in the gut microbiota of adults with celiac disease. • A high intensity interval training exercise intervention is feasible and well tolerated for patients with celiac disease.


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    • Multiple sclerosis-related fatigue: the role of impaired corticospinal responses and heightened exercise fatigability

      Authors: Kyla Coates, Saied Jalal Aboodarda, Renata L Krüger, Tristan Martin, Luanne M Metz, Scott Jarvis Dr, Guillaume Y Millet.

      Published: 02 September 2020 - J Neurophysiol.


      It is unclear whether motor fatigability and perceived fatigue share a common pathophysiology in people with multiple sclerosis (PwMS). This cross-sectional investigation explored the relationship between the mechanisms of motor fatigability from cycling and fatigue severity in PwMS. Thirteen highly fatigued (HF) and thirteen non-fatigued (LF) PwMS, and thirteen healthy controls (CON) completed a step-test until volitional exhaustion on an innovative cycle ergometer. Neuromuscular evaluations involving femoral nerve electrical stimulation and transcranial magnetic stimulation were performed every three minutes throughout cycling. One-way ANOVA at baseline and exhaustion uncovered evidence of consistently smaller motor evoked potential (MEP) amplitudes (P = .011) and prolonged MEP latencies (P = .041) in HF, as well as a greater decline in maximal voluntary contraction force (HF: 63 ± 13%; LF: 75 ± 13%; CON: 73 ± 11% of pre; P = .037), and potentiated twitch force (HF: 35 ± 13%; LF: 50 ± 16%; CON: 47 ± 17% of pre; P = .049) in HF at volitional exhaustion. Hierarchical regression determined that fatigue severity on the Fatigue Severity Scale was predicted by prolonged MEP latencies (change in R2 = .389), elevated peripheral muscle fatigability (change in R2 = .183), and depressive symptoms (change in R2 = .213). These findings indicate that MS-related fatigue is distinguished by disrupted corticospinal responsiveness which could suggest progressive pathology, but fatigability from whole-body exercise and depressive symptoms also influence perceptions of fatigue in PwMS.

      Keywords: Fatigue; Motor Evoked Potentials; Multiple Sclerosis; Neuromuscular Fatigue; Transcranial Magnetic Stimulation.

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    • Task failure during sustained low-intensity contraction is not associated with a critical amount of central fatigue

      Authors: Robin Souron, Anne-Cloé Voirin, Djahid Kennouche, Loïc Espeit, Guillaume Y Millet, Thomas Rupp, Thomas Lapole.

      Published: 01 September 2020 - Scand J Med Sci Sports.


      Fatigue-related mechanisms induced by low-intensity prolonged contraction in lower limb muscles are currently unknown. This study investigated central fatigue kinetics in the knee extensors during a low-intensity sustained isometric contraction. Eleven subjects sustained a 10% maximal voluntary contraction (MVC) until task failure (TF) with neuromuscular evaluation every 3 minutes. Testing encompassed transcranial magnetic stimulation to evaluate maximal voluntary activation (VATMS ), motor evoked potential (MEP), and silent period (SP), and peripheral nerve stimulation to assess M-wave. Rating of perceived exertion (RPE) was also recorded. MVC progressively decreased up to 50% of the time to TF (ie, 50%TTF ) and then plateaued, reaching ~50% at TF (P < .001). VATMS progressively decreased up to 90%TTF and then plateaued, the decrease reaching ~20% at TF (P < .001). SP was lengthened early (ie, from 20%TTF ) during the exercise and then plateaued (P < .01). No changes were reported for MEP evoked during MVC (P = .87), while MEP evoked during submaximal contractions decreased early (ie, from 20%TTF ) during the exercise and then plateaued (P < .01). RPE increased linearly during the exercise to be almost maximal at TF. M-waves were not altered (P = .88). These findings confirm that TF is due to the subjects reaching their maximal perceived effort rather than any particular central event or neuromuscular limitations since MVC at TF was far from 10% of its original value. It is suggested that strategies minimizing RPE (eg, motivational self-talk) should be employed to enhance endurance performance.

      Keywords: RPE; central fatigue; sustained contraction; task failure; transcranial magnetic stimulation; voluntary activation.

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    • Spinal contribution to neuromuscular recovery differs between elbow-flexor and knee-extensor muscles after a maximal sustained fatiguing task

      Authors: Gianluca Vernillo, John Temesi, Matthieu Martin, Renata L Krüger,Guillaume Y Millet.

      Published: 01 September 2020 - J Neurophysiol.


      Data from studies of elbow-flexor (EF) or knee-extensor (KE) muscles suggest that a fatigue-related decrease in motoneuron excitability only occurs in EF. It is unknown how motoneuron excitability changes after sustained fatiguing maximal voluntary isometric contractions (MVICs) in EF and KE in the same participants. In two sessions, eight healthy men performed a 2-min MVIC of EF or KE to induce fatigue with brief MVICs before and six times after the 2-min MVIC. Electromyographic responses elicited by corticospinal tract stimulation at the transmastoid [cervicomedullary motor-evoked potential (CMEP)] or thoracic [thoracic motor-evoked potential (TMEP)] level were recorded from EF and KE, respectively. To account for muscle excitability, CMEPs and TMEPs were normalized to maximal M-wave (Mmax) elicited by peripheral nerve stimulation during each brief MVIC. Immediately after the 2-min MVIC, biceps brachii and brachioradialis CMEP/Mmax were 88% (SD 11%) (P = 0.026) and 87% (SD 12%) (P = 0.029) of pre-MVIC (PRE) values, respectively, and remained lower than PRE after 5 s of recovery [91% (SD 8%), P = 0.036 and 87% (SD 13%), P = 0.046, respectively]. No subsequent time points differed from PRE (all P ≥ 0.253). TMEP/Mmax for rectus femoris and vastus lateralis were not different from PRE at any time during the recovery period (all P > 0.050). A different recovery pattern in motoneuron excitability occurred in EF as it recovered by 60 s whereas KE motoneurons were unaffected by the fatiguing task. The present findings may contribute to better understand muscle-specific neurophysiological differences in spinal excitability.

      NEW & NOTEWORTHY By comparing the changes in motoneuron excitability in elbow-flexor and knee-extensor muscles after sustained fatiguing maximal voluntary contractions, this study shows that motoneuron recovery behavior depends on the muscle performing the exercise. A different recovery pattern in motoneuron excitability occurs in elbow flexors as it recovered by 60 s whereas knee extensors were unaffected by fatigue. This finding can help to increase understanding of the effect of a fatigue and subsequent recovery on neural processes.

      Keywords: fatigue; inhibition; maximal voluntary contraction; motoneuron; spinal excitability.

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    • Optimal load for a torque-velocity relationship test during cycling

      Authors: Renata L Krüger, Arthur Peyrard, Hervé di Domenico, Thomas Rupp, Guillaume Y Millet, Pierre Samozino.

      Published: 20 August 2020 - Eur J Appl Physiol. 


      Purpose: Lower limbs' neuromuscular force capabilities can only be determined during single sprints if the test provides a good fit of the data in the torque-velocity (T-V) and power-velocity (P-V) relationships. This study compared the goodness of fit of single sprints performed against traditional (7.5% of the body mass) vs. optimal load (calculated based on the force production capacity and ergometer specificities), and examined if reducing the load in fatigued state enhances T-V and P-V relationship goodness of fit.

      Methods: Thirteen individuals performed sprints before (PRE) and after (POST) a fatiguing task against different loads: (1) TRAD: traditional, (2) OPT: optimal, and (3) LOW-OPT: optimal load reduced according to fatigue levels.

      Results: At PRE, OPT sprints presented a higher R2 of the T-V relationship (0.92 ± 0.06) and lower time to reach maximal power (Pmax) (48 ± 9%) when compared with TRAD sprints (0.89 ± 0.06 and 66 ± 22%, respectively, p < 0.01). At POST, the range of velocity spectrum was greater in the LOW-OPT (33 ± 4%) vs. TRAD (24 ± 3%) and OPT (26 ± 8%, p < 0.007). Similarly, the time to reach Pmax was lower in the LOW-OPT (46 ± 12%) vs. TRAD (76 ± 24%) and OPT (70 ± 24%, p < 0.006).

      Conclusion: Sprints performed against an OPT load and reducing the OPT load after fatigue improve the fit of data in the T-V and P-V curves. Sprints load assignment should consider force production capacities rather than body mass.

      Keywords: Braking load; Force–velocity test; Maximal power output; Neuromuscular fatigue.

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    • Dynamic Changes of Performance Fatigability and Muscular O2 Saturation in a 4-km Cycling Time Trial

      Authors: Rafael de Almeida Azevedo, Fabio Milioni, Juan M Murias, Romulo Bertuzzi, Guillaume Y Millet.

      Published: 18 August 2020 - Med Sci Sports Exerc.


      Exercise intensity variations throughout a cycling time trial (TT) might be influenced by subject's functional state.

      Purpose: The current study characterized the performance fatigability etiology, immediately after exercise cessation, and its relation to the dynamic changes in muscle O2 saturation at different TT phases.

      Methods: Twelve males performed three separated TTs of different distances, in a crossover counterbalanced design, until the end of the fast-start (FS, 827±135m), even-pace (EP, 3590±66m) or end-spurt (ES, 4000m) TT phases. Performance fatigability was characterized by using isometric maximal voluntary contractions (IMVC), while the maximal voluntary activation (VA) and contractile function of knee extensors [e.g. peak torque of potentiated twitches (TwPt)] were evaluated using electrically-evoked contractions performed before and immediately after each exercise bouts. Muscle O2 saturation (SmO2), power output (PO) and electromyographic (EMG) were also recorded.

      Results: Immediately after the FS phase, there were lower values for IMVC (-23%), VA (-8%) and TwPt (-43%) (all p<0.001) but no further changes were measured after EP (IMVC, -28%; VA, -8%; TwPt, -38%). After the ES phase, the IMVC (-34%) and TwPt (-59%) further decreased compared to the previous phases (p<0.05). There were lower SmO2 and higher EMG/PO values during FS and ES compared to EP phase.

      Conclusion: FS and EP phases had similar performance fatigability etiology, but ES showed further impairments in contractile function. This later finding might be due to the abrupt changes in SmO2 and EMG/PO because of the high exercise intensity during the end-spurt, which elicited maximal decline in contractile function at the finish line.

      Keywords:: Central fatigue; Exercise performance; NIRS; Oxygen availability; Peripheral fatigue.

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    • Chronic fatigue in myelodysplastic syndromes: Looking beyond anemia

      Authors: Callum G Brownstein, Elisabeth Daguenet, Denis Guyotat, Guillaume Y Millet.

      Published: 27 July 2020 - Crit Rev Oncol Hematol.


      Chronic fatigue is the most common and severe symptom in myelodysplastic syndromes (MDS) and has a strong negative association with health-related quality of life (HRQoL). Despite anemia being the most common objective manifestation of MDS, and the associated link between anemia and fatigue, evidence on treatments which temporarily mitigate anemia is equivocal regarding the effects on fatigue. Furthermore, previous work has found weak associations between anemia and chronic fatigue in MDS. As such, given that improving HRQoL is one of the primary treatment aims in MDS, further work is required to identify other potential contributors to chronic fatigue in these patients. In addition to anemia, MDS is associated with numerous other deviations in physiological homeostasis and has negative psychological consequences with links to chronic fatigue. Accordingly, the present review provides several potential aetiologic agents relevant to chronic fatigue in MDS which can be used to guide future research in this field.

      Keywords: Chronic fatigue; Exercise; Inflammation; Myelodyplastic syndromes; Oxidative stress; Physical deconditioning; Red blood cell transfusions.

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    • Would the Covid have killed this many people 50 years ago?

      Authors:  Millet GY

      Article originally published in French in Le Quotidien du Médecin

      Let's be clear: the goal of this article is not to give morality lessons, and even less to make sick people feel guilty. It is to simply describe a reality: the Covid-19 does not kill everyone. Setting aside the case of the elderly who are naturally more fragile, the virus is dangerous mainly for people suffering from chronic diseases and co-morbidities such as hypertension, obesity and type II diabetes, i.e. contemporary pathologies. It is so true that one could wonder whether the lockdown would have been necessary 50 years ago? Or if the virus would have killed so many people, despite the modern equipment of the intensive care units?

      Overweight and obesity have exploded in rich countries. What is most worrying is that it starts at a very young age. In France, the rate of overweight 5-19 year olds has doubled since 1975 and the curve is not flattening, leaving a bright future for Covid and other similar pandemics. In the United States, African-Americans are more affected (33% of Covid-related hospitalisations, although they represent only 13% of the population). Because of the more exposed jobs and greater precariousness but perhaps also the fact that they are more affected by obesity problems. These last two points being related to each other.  

      Overweight and associated pathologies increase while the level of physical activity follows a diametrically opposite curve. The causes are known (passive transport & leisure, sedentary jobs). Again, this starts at a very young age. Fifty years ago, the vast majority of children used to go to school walking or even cross-country skiing! How many of them do so nowadays? We may do more sport than before, but we are much, much less active. As a result, physical performance drops dramatically. Comparing the performances of fathers (or mothers) with those of their sons (or daughters) at the same age is always in favour of the former, regardless of the physical quality. Maximum oxygen uptake (an index of sport performance but also an index of health) has fallen by almost 0.5% per year between 1980 and 2000. This is dramatic and there is no doubt that it continues to decrease. Here again overweight plays a role but it is not the only reason.

      It is true that the human being continues to break sports records. But never before have we had such a large gap between this very small percentage of the population that does sport at an elite level (and whose performance continues to increase) and the 50% least active people whose physical level is getting lower every day. Doesn't that remind you of the growing gap between the extremes in terms of earnings?

      During the lockdown, the French government has allowed the population to get outside one hour a day for physical activity. Yet this daily exercise may have not been enough to compensate for the teleworking/Netflix sedentary behavior (raise your hand if you were doing the famous 10,000 steps a day?). The resulting physical deconditioning is likely to put a strain on the health care system. And perhaps even accentuate the chronic fatigue of the population which will itself potentially lead to an increase in absenteeism and a drop in productivity. A kind of double penalty.

      As I said in the introduction, this is not a matter of moralizing at an individual level. Nor to ask the children to go back to school on cross-country skis (well, there is no more snow anyway). It is a matter of vehemently proclaiming that a proactive policy (sports facilities, promotion of physical activity, funding of research programs in movement sciences, improving cyclability and walkability of cities, sport at school, support for associations and companies) must be put in place to increase the level of physical activity of the population, at all ages. Of course the priority is to stop the dismantling of the health system, but combating sedentary lifestyles and inactivity certainly remains one of the best ways to reduce the number of people visiting hospitals every day.

    • Neuromuscular responses to fatiguing locomotor exercise

      Authors: Callum G Brownstein, Guillaume Y Millet, Kevin Thomas

      Published: 06 July 2020 - Acta Physiol (Oxf).


      Over the last two decades, an abundance of research has explored the impact of fatiguing locomotor exercise on the neuromuscular system. Neurostimulation techniques have been implemented prior to and following locomotor exercise tasks of a wide variety of intensities, durations, and modes. These techniques have allowed for the assessment of alterations occurring within the central nervous system and the muscle, while techniques such as transcranial magnetic stimulation and spinal electrical stimulation have permitted further segmentalization of locomotor exercise-induced changes along the motor pathway. To this end, the present review provides a comprehensive synopsis of the literature pertaining to neuromuscular responses to locomotor exercise. Sections of the review were divided to discuss neuromuscular responses to maximal, severe, heavy and moderate intensity, high-intensity intermittent exercise, and differences in neuromuscular responses between exercise modalities. During maximal and severe intensity exercise, alterations in neuromuscular function reside primarily within the muscle. Although post-exercise reductions in voluntary activation following maximal and severe intensity exercise are generally modest, several studies have observed alterations occurring at the cortical and/or spinal level. During prolonged heavy and moderate intensity exercise, impairments in contractile function are attenuated with respect to severe intensity exercise, but are still widely observed. While reductions in voluntary activation are greater during heavy and moderate intensity exercise, the specific alterations occurring within the central nervous system remain unclear. Further work utilizing stimulation techniques during exercise and integrating new and emerging techniques such as high-density electromyography is warranted to provide further insight into neuromuscular responses to locomotor exercise.

      Keywords: cycling; fatigue; neuromuscular physiology; neurostimulation; running.

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    • Fatigue-induced changes in short-interval intracortical inhibition and the silent period using stimulus intensities evoking maximal versus submaximal responses

      Authors: Callum G Brownstein, Loïc Espeit, Nicolas Royer, Thomas Lapole, Guillaume Y Millet

      Published: 25 June 2020 - J Appl Physiol .


      During fatiguing exercise, previous studies have employed transcranial magnetic stimulation (TMS) paradigms eliciting either maximal or submaximal short-interval intracortical inhibition (SICI) and silent period (SP) durations. However, the effect of using either approach on the change in these variables with fatigue is unknown. This study examined the effects of using conditioning stimulus (CS, Experiment A) and single-pulse TMS intensities (Experiment B) which elicit maximal and submaximal SICI and SP duration (MaxSICI vs SubmaxSICI - Experiment A, MaxSP vs SubmaxSP - Experiment B) on the change in these measures with fatigue. In both experiments, participants performed a 10 min sustained isometric knee-extension contraction at a constant level of EMG, with measures taken using maximal and submaximal intensities at baseline and every 2.5 min throughout the task. Immediately following the 10 min contraction (i.e. without recovery), responses were also measured at the same absolute force level as with baseline. In Experiment A, no change in SICI was observed with either CS intensity throughout the EMG task (P>0.05). However, a 18% decrease in SICI (i.e. less inhibition) was observed at the same absolute force only when using the MaxSICI CS intensity (P<0.01), with no change in SubmaxSICI (P=0.72). In Experiment B, the magnitude of increase in SP with fatigue was similar for both stimulus intensities (stimulus × time interaction: P=0.44). These results suggest that using CS intensities eliciting maximum SICI are more sensitive in detecting fatigue-induced reductions in SICI, while increases in SP are detectable using TMS intensities evoking maximal or submaximal SPs.

      Keywords: Fatigue; Inhibition; Short-interval intracortical inhibition; Silent period; Transcranial magnetic stimulation.

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    • Biomechanics of graded running: Part II-Joint kinematics and kinetic

      Authors: Arash Khassetarash, Gianluca Vernillo, Aaron Martinez, Michael Baggaley, Marlene Giandolini, Nicolas Horvais, Guillaume Y Millet, William Brent Edwards.

      Published: 2 June 2020 - Scand J Med Sci Sports. 


      Compared to level running (LR), different strategies might be implemented by runners to cope with specific challenges of graded running at different speeds. The changes in joint kinetics and kinematics associated with graded running have been investigated, but their interactions with speed are unknown. Nineteen participants ran on an instrumented treadmill at five grades (0°, ±5° and ± 10°) and three speeds (2.50, 3.33 and 4.17 m/s), while 3D motion and forces were recorded. Three speed × five-grade repeated-measures ANOVA was used to analyze kinetic and kinematic variables. A speed × grade interaction was observed for hip range of motion (ROM). Downhill running (DR) at fastest speed did not reduce ROM at the hip, compared to LR. Compared to LR, it was observed that the hip joint was responsible for a greater contribution of energy generation while running at the fastest speed at +10°. Speed × grade interactions were also observed for the energy absorption, peak moment, and peak power at the knee. Contrary to LR, running faster during UR did not require higher peak power at the knee. Finally, DR at the fastest speed did not increase peak negative power at the knee compared to LR. This study demonstrates that ankle, knee, and hip joint kinetics depend on speed and grade of running, while the effect of grade on joint kinematics was not substantially modulated by speed.

      Keywords: downhill; joint power; joint work; slope; uphill.

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    • Feasibility of eccentric overloading and neuromuscular electrical stimulation to improve muscle strength and muscle mass after treatment for head and neck cancer

      Authors: Colin Lavigne, Rosie Twomey, Harold Lau, George Francis, S Nicole Culos-Reed, Guillaume Y Millet.

      Published: 24 May 2020 - J Cancer Surviv.


      PURPOSE: Treatment of head and neck cancer (HNC) results in severe weight loss, mainly due to the loss of lean body mass. Consequently, decreases in muscular strength and health-related quality of life (HRQL) occur. This study investigated the feasibility of a 12-week novel strength training (NST) and conventional strength training (CST) intervention delivered after HNC treatment.

      CONCLUSIONS: Both interventions were found to be feasible for HNC patients after treatment. Strength training significantly improved maximal muscle strength, muscle cross-sectional area, and PROs after HNC treatment. Future research should include fully powered trials and consider the use of eccentric overloading and NMES during HNC treatment.

      Keywords: Cancer rehabilitation; Electromyostimulation; Exercise oncology.

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    • Greater Short-Time Recovery of Peripheral Fatigue After Short- Compared With Long-Duration Time Trial

      Authors: Christian Froyd,Fernando G. Beltrami, Guillaume Y. Millet, Brian R. MacIntosh,Timothy D. Noakes.

      Published: 14 May 2020 - Front Physiol.


      The kinetics of recovery from neuromuscular fatigue resulting from exercise time trials (TTs) of different durations are not well-known. The aim of this study was to determine if TTs of three different durations would result in different short-term recovery in maximal voluntary contraction (MVC) and evoked peak forces. Twelve trained subjects performed repetitive concentric right knee extensions on an isokinetic dynamometer self-paced to last 3, 10, and 40 min (TTs). Neuromuscular function was assessed immediately (<2 s) and 1, 2, 4, and 8 min after completion of each TT using MVCs and electrical stimulation. Electrical stimulations consisted of single stimulus (SS), paired stimuli at 10 Hz (PS10), and paired stimuli at 100 Hz (PS100). Electrically evoked forces including the ratio of low- to high-frequency doublets were similar between trials at exercise cessation but subsequently increased more (P < 0.05) after the 3 min TT compared with either the 10 or 40 min TT when measured at 1 or 2 min of recovery. MVC force was not different between trials. The results demonstrate that recovery of peripheral fatigue including low-frequency fatigue depends on the duration and intensity of the preceding self-paced exercise. These differences in recovery probably indicate differences in the mechanisms of fatigue for these different TTs. Because recovery is faster after a 3 min TT than a 40 min TT, delayed assessment of fatigue will detect a difference in peripheral fatigue between trials that was not present at exercise cessation.

      Keywords: peripheral fatigue, recovery, maximal voluntary contraction, femoral nerve electrical stimulation, motor unit recruitment, electromyography, self-paced exercise.

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    • Biomechanics of graded running: Part I - Stride parameters, external forces, muscle activations

      Authors: Gianluca Vernillo, Aaron Martinez, Michael Baggaley, Arash Khassetarash, Marlene Giandolini, Nicolas Horvais, William Brent Edwards, Guillaume Y Millet.

      Published: 12 May 2020 - Scand J Med Sci Sports. 


      Biomechanical alterations with graded running have only been partially quantified, and the potential interactions with running speed remain unclear. We measured spatiotemporal parameters, ground reaction forces, and leg muscle activations (EMG) in nineteen adults (10F/9M) running on an instrumented treadmills at 2.50, 3.33, and 4.17 m·s-1 and 0, ±5°, and ±10°. Step frequency illustrated a significant speed × grade interaction (P < .001) and was highest (+3%) at the steepest grade (+10°) and fastest speed (4.17 m·s-1 ) when compared to level running (LR) at the same speed. Significant interaction was also observed for ground reaction forces (all P ≤ .047). Peak ground reaction forces in the normal direction increased with running speed during downhill running (DR) only (+9% at -10° and 4.17 m·s-1 ). Impulse in the normal direction decreased at fastest speed and steepest DR (-9%) and uphill running (UR) (-17%) grades. Average normal loading rate increased and decreased at fastest speed and steepest DR (+52%) and UR (-28%) grades, respectively. Negative parallel impulse increased and decreased at fastest speed and steepest DR (+166%) and UR (-90%), respectively. Positive parallel impulse decreased and increased at fastest speed and steepest DR (-75%) and UR (+111%), respectively. EMG showed comparable u-shaped curves across the grades investigated, although only a change in vastus lateralis and tibilias anterior activity was detectable at the steepest grades and fastest speed. Overall, running grade and speed significantly influences spatiotemporal parameters, ground reaction forces, and muscle activations.

      Keywords: EMG; downhill; grade; ground reaction forces; hill; locomotion; slope; uphill.

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