Building a biopsychosocial model of cancer-related fatigue: the BIOCARE FActory cohort study protocol.

BACKGROUND: Cancer-related fatigue (CRF) is the most common side effect of cancer and cancer treatment. CRF prevalence is up to 50% in breast cancer patients and can continue several years after cancer remission. This persistent subjective sense of exhaustion is multifactorial. Numerous parameters have been evidenced to be related to CRF across biological, physical, psychological, social and/or behavioral dimensions. Although CRF has been studied for many years, the majority of previous studies focused on only one dimension, i.e., physical function. Moreover, few studies investigated CRF longitudinally with repeated measures. These are the two main obstacles that limit the understanding of CRF mechanisms. The purpose of this study is to create a biopsychosocial model of CRF with simultaneous and longitudinal anthropometric, clinical, biological, physical, psychological and sociological parameters. METHODS: BIOCARE FActory is a multicentric prospective study that will consist of an 18-month follow-up of 200 women diagnosed with breast cancer. Four visits will be scheduled at diagnosis, after treatments, and 12 and 18 months after diagnosis. The same procedure will be followed for each visit. Each session will be composed of anthropometric data collection, a semi-structured interview, cognitive tests, postural control tests, neuromuscular fatigability tests and a cardiorespiratory fitness test. Clinical and biological data will be collected during medical follow-ups. Participants will also complete questionnaires to assess psychological aspects and quality of life and wear an actigraphy device. Using a structural equation modeling analysis (SEM), collected data will build a biopsychosocial model of CRF, including the physiological, biological, psychological, behavioral and social dimensions of CRF. DISCUSSION: This study aims to highlight the dynamics of CRF and its correlates from diagnosis to post treatment. SEM analysis could examine some relations between potential mechanisms and CRF. Thus, the biopsychosocial model will contribute to a better understanding of CRF and its underlying mechanisms from diagnosis to the aftermaths of cancer and its treatments. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov ( NCT04391543 ), May 2020.

Influence of Ergometer Design on Physiological Responses during Rowing.

The aim of this study was to compare the physiological responses and rowing efficiency on 2 different rowing ergometers: stationary vs. dynamic ergometers manufactured by Concept2. 11 oarswomen and oarsmen rowed 4 min at 60% and 70% of peak power output on both ergometers (randomized order). Power output, stroke rate, heart rate, oxygen uptake, carbon dioxide production, lactate accumulation and rating of perceived exertion were recorded at each stage on the 2 ergometers. Gross and net efficiencies were computed. Exercise intensity was associated with increases in all parameters. Rowing on dynamic ergometer was associated with higher heart rate, oxygen uptake, carbon dioxide production and stroke rate, concomitantly to lower blood lactate accumulation but also to lower gross and net efficiencies. The present study showed that rowing efficiency and blood lactate accumulation were lower on the Concept2 dynamic ergometer than on its stationary counterpart. If the use of the Concept2 dynamic ergometer may provide some advantages (reduced risk of injuries), its utilization requires a specific evaluation of physiological responses during an incremental exercise for an adapted management of training.

Lactate accumulation in response to supramaximal exercise in rowers.

The aim of this study was to test (a) three methods to estimate the quantity of lactate accumulated (QLaA ) in response to supramaximal exercise and (b) correlations between QLaA and the nonoxidative energy supply assessed by the accumulated oxygen deficit (AOD). Nine rowers performed a 3-min all-out test on a rowing ergometer to estimate AOD and lactate accumulation in response to exercise. Peak blood lactate concentration [(La)peak ] during recovery was assessed, allowing QLaA(m1) to be estimated by the method of Margaria et al. Application of a bicompartmental model of lactate distribution space to the blood lactate recovery curves allowed estimation of (a) the net amount of lactate released during recovery from the active muscles (NALR max ), and (b) QLaA according to two methods (QLaA(m2) and QLaA(m3)). (La)peak did not correlate with AOD. QLaA(m1), QLaA(m2) and QLaA(m3) correlated with AOD (r = 0.70, r = 0.85 and r = 0.92, respectively). These results confirm that (La)peak does not provide reliable information on nonoxidative energy supply during supramaximal exercise. The correlations between AOD and QLaA(m2) and QLaA(m3) support the concept of studying blood lactate recovery curves to estimate lactate accumulation and thus the contribution of nonoxidative pathway to energy supply during supramaximal exercise.

Effect of α-thalassaemia on exercise-induced oxidative stress in sickle cell trait.

AIM: Alpha-thalassaemia is known to reduce intra-erythrocyte HbS (sickle haemoglobin) concentration in sickle cell trait (SCT) subjects. Because HbS was shown to increase oxidative stress, the purpose of this study was to assess the effects of the coexistence of α-thalassaemia and SCT on oxidative stress markers and nitric oxide (NO) metabolism after an acute physical exercise. METHODS: Forty subjects (age: 23.5 ± 2.21 years), SCT carriers (HbAS) or healthy subjects (HbAA), with (-αT) or without (-NαT) an associated α-thalassaemia took part in the study. Plasma markers of oxidative stress [advanced oxidation protein products (AOPP), protein carbonyl, malondialdehyde (MDA) and nitrotyrosine], anti-oxidant defences and NO metabolism (NOx) were measured at rest (T(rest)), immediately following an incremental maximal exercise test (T(ex)) and during recovery (T(1h), T(2h) and T(24h)). RESULTS: Malondialdehyde expressed as the percentage of changes from baseline was significantly higher in the HbAS-NαT compared with HbAS-αT during recovery (+36.3 ± 14.1% vs. -1.8 ± 13.2% at T(1h), P = 0.02; +36.6 ± 13.4% vs. -11.4 ± 12.5% at T(2h), P = 0.004 and +24.1 ± 12.3% vs. -14.4 ± 11.5% at T(24h), P = 0.02 in HbAS-NαT vs. HbAS-αT). Compared with HbAS-NαT, HbAS-αT had a higher NOx change from baseline at T(ex) (-23.4 ± 20.6% vs. +57.7 ± 19.3%, respectively; P = 0.005) and lower nitrotyrosine change from baseline at T(1h) (+7.2 ± 22.2% vs. +93.5%±29.3%, respectively; P = 0.04). CONCLUSION: All these data suggest that the presence of α-thalassaemia may blunt the higher level of oxidative stress and the impaired bioavailability of NO observed in the SCT carriers.

Twelve weeks of endurance training increases FFA mobilization and reesterification in postmenopausal women.

We examined the effects of exercise intensity and training on rates of lipolysis, plasma free fatty acid (FFA) appearance (R(a)), disappearance (R(d)), reesterification (R(s)), and oxidation (R(oxP)) in postmenopausal (PM) women. Ten sedentary but healthy women (55 ± 0.6 yr) completed 12 wk of supervised endurance exercise training on a cycle ergometer [5 days/wk, 1 h/day, 65% peak oxygen consumption (Vo(2peak))]. Flux rates were determined by continuous infusion of [1-(13)C]palmitate and [1,1,2,3,3-(2)H(5)]glycerol during 90 min of rest and 60 min of cycle ergometer exercise during one pretraining exercise trial [65% Vo(2peak) (PRE)] and two posttraining exercise trials [at power outputs that elicited 65% pretraining Vo(2peak) (absolute training; ABT) and 65% posttraining Vo(2peak) (relative training; RLT)]. Initial body weights (68.2 ± 4.5 kg) were maintained over the course of study. Training increased Vo(2peak) by 16.3 ± 3.9% (P < 0.05) (Zarins ZA, Wallis GA, Faghihnia N, Johnson ML, Fattor JA, Horning MA and Brooks GA. Metabolism 58: 9: 1338-1346, 2009). Glycerol R(a) and R(d) were elevated in the RLT trial (P < 0.05), but not the ABT trial after training. Rates of plasma FFA R(a), R(d), and R(oxP) were elevated during the ABT compared with PRE trial (P < 0.05). FFA R(s) accounted for most (50-70%) of R(d) during exercise; training reduced FFA R(s) during ABT, but not RLT compared with PRE. We conclude that, despite the large age-related decrease in metabolic scope in PM women, endurance training increases the capacities for FFA mobilization and oxidation during exercises of a given power output. However, after menopause, total lipid oxidation capacity remains low, with reesterification accounting for most of FFA R(d).

Blood lactate and heat stress during training in rowers.

The purpose of the present study was to test the hypothesis that large increases in blood lactate concentration ([La] (b)) and/or body temperature may occur during an endurance training on a rowing ergometer and disrupt training. The influence of an increase in air convection on the capacity to perform a prolonged exercise was also explored. Ten trained oarsmen were asked to undergo twice, in control (C) and increased air ventilation (AV) conditions, two 30-min trainings on a rowing ergometer at a work rate corresponding to 2.5 mmol . L (-1) of [La] (b) determined during a previous incremental exercise (P (2.5)). Four subjects did not complete the training session in C despite a steady state in [La] (b) in two of them. In these four subjects, the end of the exercise was associated with the highest measured rectal temperatures (T (re), 39.4 +/- 0.1 degrees C) and rate of perceived exertion (RPE, 17.8 +/- 0.3). Regarding the six other subjects, their heart rate, oxygen uptake, RPE, T (re) and water loss values were lower (p < 0.05) in AV than in C. [La] (b) displayed the same profile in C and AV. This study suggests that i) high body temperature may constitute a significant factor of perceived exertion and disrupt indoor training session, and ii) capacity to perform an endurance training on a rowing ergometer was improved by increasing air convection.

Effects of training on lactate kinetics parameters and their influence on short high-intensity exercise performance.

The purpose of the present study was to relate the training-induced alterations in lactate kinetics parameters to the concomitant changes in time to exhaustion (T(lim)) at a work rate corresponding to maximal oxygen uptake (Pa(peak)). Eight subjects performed before and after training i) an incremental exercise up to exhaustion to determine Pa(peak), ii) a 5-min 90 % Pa(peak) exercise followed by a 90-min passive recovery to determine an individual blood lactate recovery curve fitted to the bi-exponential time function: La(t) = La(0) + A1(1 - e -gamma1 x t) + A2(1 - e -gamma2 x t), and iii) a time to exhaustion at Pa peak to determine T lim. A biopsy of the vastus lateralis muscle was made before and after training. The training programme consisted in pedalling on a cycle ergometer 2 h a day, 6 days a week, for 4 weeks. Training-induced increases (p < 0.05) in Pa(peak), muscle capillary density, citrate synthase activity, gamma2 that denotes the lactate removal ability (from 0.0547 +/- 0.0038 to 0.0822 +/- 0.0071 min (-1)) and T(lim) (from 299 +/- 23 to 486 +/- 63 s), decreases (p < 0.05) in activities of lactate dehydrogenase (LDH) and muscle type of LDH, the phosphofructokinase/citrate synthase activities ratio and the estimated net amount of lactate released (NALR) during exercise recovery (from 66.5 +/- 8.6 to 47.2 +/- 11.1 mmol) were also observed. The improvement of T (lim) with training was related to the increase in gamma2 (r = 0.74, p = 0.0367) and to the decrease in NALR (r = 0.77, p = 0.0250). These results suggest that the post-training greater ability to remove lactate from the organism and reduced muscle lactate accumulation during exercise account for the concomitant improvement of the time to exhaustion during high-intensity exercise performed at the same relative work rate.

Rowing performance and estimated training load.

We related the rowing performance and the associated physiological parameters to the training load as estimated by a questionnaire addressing the mean habitual weekly energy expenditure (MHWEE) of twenty-one international and national level oarsmen. The questionnaire also addressed the energy expenditure during training (EET) sessions classified as low- (EE1), moderate- (EE2), and high-intensity (EE3). To evaluate the physiological capability of the oarsmen, they performed incremental exercise to determine their maximal oxygen uptake (V.O(2max)) and the V.O(2) relative to V.O(2max) corresponding to the 4 mmol.l(-1) blood lactate concentration (V.O(2)4 %). The mean work rate sustained during a 2000-m all-out event on a rowing ergometer was considered as the rowing performance. On average, the rowers spent 16.4 +/- 1.0 h.wk(-1) in training with 56 +/- 3 % of the time spent on the water. EET represented 43.5 +/- 1.7 % of MHWEE. Rowing performance and V.O(2max) were both related to MHWEE and EET. Also, rowing performance was related to EE1, EE2, and EE3. In contrast, V.O(2)4 % was not related to the estimated energy expenditures. These results suggest that rowing performance and V.O(2max) are related to training load while V.O(2)4 % was not in the present group of highly trained oarsmen.

Peak power output predicts rowing ergometer performance in elite male rowers.

The aim of the present study was to test the hypothesis that peak power output (Ppeak) sustained during maximal incremental testing would be an overall index of rowing ergometer performance over 2000 m (P2000), and to study the influence of selected physiological variables on Ppeak. A group of 54 highly trained rowers (31 heavyweight [HW] and 23 lightweight [LW] rowers) was studied. Body mass, maximal oxygen uptake ((.-)VO(2max)), oxygen consumption corresponding to a blood lactate of 4 mmol. l (-1) expressed in percentage of (.-)VO(2max) (V.O (2)La4 %), and rowing gross efficiency (RGE) were also determined during the incremental test. In the whole group Ppeak was the best predictor of P2000 (r = 0.92, p < 0.0001). Body mass (r = 0.65, p < 0.0001), V.O (2max) (r = 0.84, p < 0.0001), (.-)VO 2)La4 % (r = 0.49, p < 0.0001) and RGE (r = 0.35, p < 0.01) were significantly correlated with P2000 as well. To take the influence of body mass into account, (.-)VO(2max) was related to kg (0.57). Ppeak was significantly related to body mass (r = 0.56, p < 0.0001), (.-)VO(2max) x kg (-0.57) (r = 0.63, p < 0.0001), (.-)VO(2)La4 % (r = 0.45, p < 0.001) and RGE (r = 0.34, p < 0.05). Multiple regression analysis indicated that the above parameters taken together explained 82.8 % of Ppeak variation in the whole group. It was also demonstrated that Ppeak was the best predictor of P2000 when LW and HW groups were considered separately. It was concluded that, by integrating the main physiological factors of performance, Ppeak is an overall index of physiological rowing capacity and rowing efficiency in heterogeneous as well as in homogeneous groups. It presents the further advantage of being easily measured in the field.

Laboratory blood lactate profile is suited to on water training monitoring in highly trained rowers.

AIM: This study validated the laboratory testing used to monitor on water training. The purpose was to test that reference heart rates (HR) determined during an incremental test elicit comparable blood lactate levels ([La](b)) during a 30 min on water rowing. METHODS: Blood lactate profile were determined during incremental graded exercise in 14 national and international level oarsmen. The HR corresponding to [La](b) of 2 and 3 mmol x l(-1) were determined (HRLa2 and HRLa3 respectively). The rowers then performed a 30 min training session in a boat. Training intensity, as assessed by HR monitors, had to range between HRLa2 and HRLa3. Field [La](b) (Laf) and HR (HRf) were measured at the end of the training session. RESULTS: Laf was 2.13+/-0.49 mmol x l(-1) (range: 1.43-3.07) and did not differ significantly from 2 mmol x l(-1). HRf (162+/-7.4 beats x min(-1)) ranged from HRLa2 (159+/-9.5 beats x min(-1)) to HRLa3 (171+/-9 beats x min(-1)). HRf was not significantly different from HRLa2. CONCLUSIONS: It was concluded that the HR determined during the laboratory testing are valid for monitoring on water training in highly trained rowers.

Differences in lactate exchange and removal abilities in athletes specialised in different track running events (100 to 1500 m).

The purpose of this study was to investigate whether track running specialisation could be associated with differences in the ability to exchange and remove lactate. Thirty-four male high-level runners were divided into two groups according to their specialty (100 - 400 m/800 - 1500 m). All performed a 1-min 25.2 km x h -1 event, followed by a 90-min passive recovery to obtain individual blood lactate recovery curves which were fitted to a bi-exponential time function: [La](t) = [La](0) + A 1 (1-e -gamma1t) + A 2 (1-e -gamma2t). The velocity constant gamma 1 which denotes the ability to exchange lactate between the previously worked muscles and blood was higher (p < 0.001) in middle-distance runners than in sprint runners. The velocity constant gamma 2 which reflects the overall ability to remove lactate did not differ significantly between the two groups. gamma 1 was positively correlated with the best performance over 800 m achieved by 16 athletes during the outdoor track season following the protocol (r = 0.55, p < 0.05). In conclusion, the lactate exchange ability seems to play a role on the athlete's capacity to sustain exercise close to 2-min-duration and specifically to run 800 m.

Time to exhaustion at VO(2)max is related to the lactate exchange and removal abilities.

The aim of the present study was to investigate the relationships between lactate exchange and removal abilities and the capacity to prolong exercise, as assessed by the time to exhaustion (Tlim) at a work rate corresponding to VO(2)max (Pa max ). The individual blood lactate recovery curves obtained for 13 untrained subjects after 5 min 90 % Pa max exercise were fitted to the biexponential time function: La(t) = La(0) + A(1) (1-e (-gamma(1) x t) + A(2) (1-e (-gamma(2) x t), where t is time into the recovery, La(0) is the arterialized lactate concentration measured at the end of the exercise, gamma(1) and gamma(2) are velocity constants denoting the lactate exchange and removal abilities, respectively. Tlim was positively related to gamma(1) and gamma(2) (r = 0.60, p < 0.05 and r = 0.56, p < 0.05, respectively) but was negatively related to La(0) (r = 0.75, p < 0.01). gamma()1 was positively related to the capillary density (r = 0.69, p < 0.01) and to the number of capillaries per type I fiber area (r = 0.62, p < 0.05). It was concluded that 1) high lactate exchange and removal abilities would allow continuing a high-intensity exercise for a longer duration, and 2) a high capillary density may explain the associated high lactate exchange ability.

Leg strength and stiffness as ability factors in 100 m sprint running.

BACKGROUND: The purpose of this study was to determine the importance of leg strength and stiffness relative to i) 100 m sprint performance, ii) mean speed on the three phases of the 100 m race (30-60-100 m) and iii) the speed differences between these phases. METHODS: Nineteen regional to national level male sprinters competed in a 100 m race. Video analysis was used to determine mean velocity parameters. Two subgroups were created since some of the runners decreased their velocity during the third phase (G1), whereas others maintained or accelerated it (G2). Leg strength (concentric half-squats - counter movement jump) and stiffness (hopping) were determined. Simple (r) and multiple regressions (R) were used. RESULTS: The mean performance over 100 m was 11.43 sec (10.72-12.87 sec). The concentric half-squats were related to 100 m (r=0.74, p<0.001) and to the mean speed of each phase (R=0.75, p<0.01). The counter movement jump was related to 100 m (r=0.57, p<0.05) and was the predictor of the first phase (r=0.66, p<0.01). The hopping test was the predictor of the two last phases (R=0.66, p<0.05). Athletes who had the greatest leg stiffness (G1) produced the highest acceleration between the first and the second phases, and presented a deceleration between the second and the third ones. CONCLUSIONS: The concentric half-squats test was the best predictor in the 100 m sprint. Leg stiffness plays a major role in the second phase.

Blood lactate exchange and removal abilities after relative high-intensity exercise: effects of training in normoxia and hypoxia.

The effects of 4 weeks of endurance training in conditions of normoxia or hypoxia on muscle characteristics and blood lactate responses after a 5-min constant-load exercise (CLE) at 90% of the power corresponding to the maximal oxygen uptake were examined at sea-level in 13 sedentary subjects. Five subjects trained in normobaric hypoxia (HT group, fraction of oxygen in inspired gas = 13.2%), and eight subjects trained in normoxia at the same relative work rates (NT group). The blood lactate recovery curves from the CLE were fitted to a biexponential time function: La(t) = La(0) + A1(1 - e- gamma 1.t) + A2(1 - e- gamma 2.t), where the velocity constants gamma 1 and gamma 2 denote the lactate exchange and removal abilities, respectively, A1 and A2 are concentration parameters that describe the amplitudes of concentration variations in the space represented by the arterial blood, La(t) is the lactate concentration at time t, and La(0) is the lactate concentration at the beginning of recovery from CLE. Before training, the two groups displayed the same muscle characteristics, blood lactate kinetics after CLE, and gamma 1 and gamma 2 values. Training modified their muscle characteristics, blood lactate kinetics and the parameters of the fits in the same direction, and proportions among the HT and the NT subjects. Endurance training increased significantly the capillary density (by 31%), citrate synthase activity (by 48%) and H isozyme proportion of lactate dehydrogenase (by 24%), and gamma 1 (by 68%) and gamma 2 (by 47%) values. It was concluded that (1) endurance training improves the lactate exchange and removal abilities estimated during recovery from exercises performed at the same relative work rate, and (2) training in normobaric hypoxia results in similar effects on lactate exchange and removal abilities to training in normoxia performed at the same relative work rates. These results, which were obtained non-invasively in vivo in humans during recovery from CLE, are comparable to those obtained in vitro or by invasive methods during exercise and subsequent recovery.

Lactate exchange and removal abilities in rowing performance.

The relationships between individual performance and lactate exchange and removal abilities were studies in 12 male rowers all subjected to three measurements on a rowing ergometer. An incremental exercise carried out to determine the maximal oxygen uptake (VO2max) and the corresponding maximal aerobic power (Pamax), a 2500-m all-out test where the mean work rate (P2500) represented the individual performance, and a 6-min 90% Pamax exercise designed to assess the lactate kinetics during the following 90 min passive recovery were performed. The lactate recovery curves were fitted to the bi-exponential time function: La(t) = La(O) + A1(1-e-gamma 1.t) + A2(1-e-gamma 2.t). The velocity constants gamma 1 and gamma 2 denote the lactate exchange and removal abilities, respectively. The mean value of P2500 sustained by the rowers was 376 +/- 41W (106 +/- 5% of Pamax (P2500%). P2500 was positively correlated with gamma 2 (P < 0.05). gamma 1 and gamma 2 explained 67% of the P2500 variance. P2500% was also correlated with gamma 2 (P < 0.01). These results suggest that a better performance on the rowing ergometer is associated with improved lactate exchange and removal abilities. Furthermore, the ability to row at high relative work rates was correlated with an increased lactate removal ability. Training-induced adaptations could explain the high gamma 1 and gamma 2 displayed by the present rowers.