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Exercise in long COVID is poorly studied. Nevertheless, exerciserehabilitation could improve cardiorespiratory, muscular and autonomic functions. We aimed to investigate improvement in physical and autonomic performances of long COVID patients ( n = 38) after a 4-week exercise rehabilitation program (3 sessions/week) compared to two control groups composed of coronary artery disease ( n = 38) and fibromyalgia patients ( n = 38), two populations for whom exercise benefits are well known. Efficacy of exercise training was assessed by a cardiopulmonary exercise test, a handgrip force test, and a supine heart rate variability recording at rest before and after the rehabilitation program. Cardiorespiratory and muscular parameters were enhanced after exercise rehabilitation in the three groups ( p < 0.001). No significant difference was observed for the autonomic variables. Through this comparative study with control groups, we confirm and reinforce the interest of caring for long COVID patients without post-exertional symptom exacerbation by exercise rehabilitation of both strength and endurance training, by personalizing the program to the patient and symptoms.

Purpose: Sotrovimab (VIR-7831), a human IgG1κ monoclonal antibody (mAb), binds to a conserved epitope on the SARS-CoV-2 spike protein receptor binding domain (RBD). The Fc region of VIR-7831 contains an LS modification to promote neonatal Fc receptor (FcRn)-mediated recycling and extend its serum half-life. Here, we aimed to evaluate the impact of the LS modification on tissue biodistribution, by comparing VIR-7831 to its non-LS-modified equivalent, VIR-7831-WT, in cynomolgus monkeys., Methods: 89 Zr-based PET/CT imaging of VIR-7831 and VIR-7831-WT was performed up to 14 days post injection. All major organs were analyzed for absolute concentration as well as tissue:blood ratios, with the focus on the respiratory tract, and a physiologically based pharmacokinetics (PBPK) model was used to evaluate the tissue biodistribution kinetics. Radiomics features were also extracted from the PET images and SUV values., Results: SUV mean uptake in the pulmonary bronchi for 89 Zr-VIR-7831 was statistically higher than for 89 Zr-VIR-7831-WT at days 6 (3.43 ± 0.55 and 2.59 ± 0.38, respectively) and 10 (2.66 ± 0.32 and 2.15 ± 0.18, respectively), while the reverse was observed in the liver at days 6 (5.14 ± 0.80 and 8.63 ± 0.89, respectively), 10 (4.52 ± 0.59 and 7.73 ± 0.66, respectively), and 14 (4.95 ± 0.65 and 7.94 ± 0.54, respectively). Though the calculated terminal half-life was 21.3 ± 3.0 days for VIR-7831 and 16.5 ± 1.1 days for VIR-7831-WT, no consistent differences were observed in the tissue:blood ratios between the antibodies except in the liver. While the lung:blood SUV mean uptake ratio for both mAbs was 0.25 on day 3, the PBPK model predicted the total lung tissue and the interstitial space to serum ratio to be 0.31 and 0.55, respectively. Radiomics analysis showed VIR-7831 had mean-centralized PET SUV distribution in the lung and liver, indicating more uniform uptake than VIR-7831-WT., Conclusion: The half-life extended VIR-7831 remained in circulation longer than VIR-7831-WT, consistent with enhanced FcRn binding, while the tissue:blood concentration ratios in most tissues for both drugs remained statistically indistinguishable throughout the course of the experiment. In the bronchiolar region, a higher concentration of 89 Zr-VIR-7831 was detected. The data also allow unparalleled insight into tissue distribution and elimination kinetics of mAbs that can guide future biologic drug discovery efforts, while the residualizing nature of the 89 Zr label sheds light on the sites of antibody catabolism., (© 2022. The Author(s).)

Purpose: While the physiological determinants of road running have been widely studied, there is a lack of research in trail-running racing performance. The aim of our study was to determine the physiological predictors of trail-running performance in races of different distances in similar terrain and weather conditions., Methods: Seventy-five trail runners participating in one of the races of the Ultra-Trail du Mont-Blanc were recruited. Previous to the race, each runner was evaluated with (1) an incremental treadmill test to determine maximal oxygen uptake, ventilatory thresholds, cost of running, and substrate utilization; (2) a power-force-velocity profile on a cycle ergometer; (3) maximal voluntary contractions of the knee extensors and plantar flexors; and (4) anthropometric characteristics. Neuromuscular fatigue was evaluated after the races. Twenty-four runners finished a SHORT (<55 km), 16 finished a MEDIUM (101 km), and 14 finished a LONG (>145 km) race. Correlations and multiple linear regressions were used to find the determinants of performance in each race distance., Results: Performance in SHORT was explained by maximal oxygen uptake and lipid utilization at 10 km/h (r2 = .825, P < .001). Performance in MEDIUM was determined by maximal oxygen uptake, maximal isometric strength, and body fat percentage (r2 = .917, P < .001). A linear model could not be applied in LONG, but performance was correlated to peak velocity during the incremental test., Conclusions: Performance in trail running is mainly predicted by aerobic capacity, while lipid utilization also influences performance in races <60 km and performance in approximately 100 km is influenced by muscle strength and body composition.

Type 1 diabetes mellitus (T1D) is a chronic disease with potentially severe complications, and β-cell deficiency underlies this disease. Despite active research, no therapy to date has been able to induce β-cell regeneration in humans. Here, we discover the β-cell regenerative effects of glucagon receptor antibody (anti-GcgR). Treatment with anti-GcgR in mouse models of β-cell deficiency leads to reversal of hyperglycemia, increase in plasma insulin levels, and restoration of β-cell mass. We demonstrate that both β-cell proliferation and α- to β-cell transdifferentiation contribute to anti-GcgR-induced β-cell regeneration. Interestingly, anti-GcgR-induced α-cell hyperplasia can be uncoupled from β-cell regeneration after antibody clearance from the body. Importantly, we are able to show that anti-GcgR-induced β-cell regeneration is also observed in non-human primates. Furthermore, anti-GcgR and anti-CD3 combination therapy reverses diabetes and increases β-cell mass in a mouse model of autoimmune diabetes., Competing Interests: Declaration of interests All authors are current or former employees of NGM Biopharmaceuticals and may hold stocks in the company. NGM Biopharmaceuticals has filed patent applications related to anti-GcgR antibodies and their utility for treatment of diabetes., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The COVID-19 pandemic led to the closure of most cardiac therapy centers. One of the solutions was to adapt the existing cardiac rehabilitation (CR) program in an institute to a remote approach offered by home-based telerehabilitation. The aim of this study was to measure the cardiorespiratory effects of telerehabilitation compared to conventional center-based CR., Methods: Patients were assigned to two 3-week CR programs: telerehabilitation and conventional center-based CR. The telerehabilitation group wore a connected watch to monitor heart rate (HR) and gave their perception of effort according to a modified Borg scale. The exercise training (four sessions/week) consisted of 1-h aerobic endurance and strength training session at the target HR zone determined by results based on cardiopulmonary exercise test (CPET) and perception of effort, respectively. The exercise protocol was the same for conventional CR participants except the duration of session that lasted 2 h instead of one. The week before and after the training program, peak oxygen uptake (VO 2 peak), oxygen uptake at first ventilatory threshold (VO 2 at VT 1 ), peak workload, percent of predicted maximum HR, and the absolute differences in HR and systolic blood pressure between maximum and recovery at 1 and 3 min were measured using a CPET. A two-way ANOVA with one repeated measure and one independent factor was performed., Results: Fifty-four patients (mean age: 61.5 ± 8.6 years, 10 women) equally split in the two groups were included in this experiment. A significant increase was observed in both groups on VO 2 peak (telerehabilitation: 8.1 ± 7.8% vs. conventional: 10.1 ± 9.7%, p < 0.001), VO 2 at VT 1 (telerehabilitation: 8.8 ± 4.4% vs. conventional: 7.3 ± 19.0%, p = 0.02) and peak workload (telerehabilitation: 16.6 ± 18.9% vs. conventional: 17.2 ± 7.0%, p < 0.001) after the 3-week telerehabilitation and conventional CR, respectively. No significant difference was noticed between both groups., Conclusion: A 3-week exercise program improved patients' cardiorespiratory fitness. Telerehabilitation was as effective and represents a safe alternative CR program during the COVID-19 period. In the future, this approach could facilitate the continuity of care for patients unable to participate in center-based CR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fanget, Bayle, Labeix, Roche and Hupin.)

Purpose: Fatigue has previously been investigated in trail running by comparing maximal isometric force before and after the race. Isometric contractions may not entirely reflect fatigue-induced changes, and therefore dynamic evaluation is warranted. The aim of the present study was to compare the magnitude of the decrement of maximal isometric force versus maximal power, force, and velocity after trail running races ranging from 40 to 170 km., Methods: Nineteen trail runners completed races shorter than 60 km, and 21 runners completed races longer than 100 km. Isometric maximal voluntary contractions (IMVCs) of knee extensors and plantar flexors and maximal 7-second sprints on a cycle ergometer were performed before and after the event., Results: Maximal power output (Pmax; -14% [11%], P < .001), theoretical maximum force (F0; -11% [14%], P < .001), and theoretical maximum velocity (-3% [8%], P = .037) decreased significantly after both races. All dynamic parameters but theoretical maximum velocity decreased more after races longer than 100 km than races shorter than 60 km (P < .05). Although the changes in IMVCs were significantly correlated (P < .05) with the changes in F0 and Pmax, reductions in IMVCs for knee extensors (-29% [16%], P < .001) and plantar flexors (-26% [13%], P < .001) were larger (P < .001) than the reduction in Pmax and F0., Conclusions: After a trail running race, reductions in isometric versus dynamic forces were correlated, yet they are not interchangeable because the losses in isometric force were 2 to 3 times greater than the reductions in Pmax and F0. This study also shows that the effect of race distance on fatigue measured in isometric mode is true when measured in dynamic mode.

Background: The force-velocity-power (FVP) profile is used to describe dynamic force production capacities, which is of great interest in training high performance athletes. However, FVP may serve a new additional tool for cardiac rehabilitation (CR) of coronary artery disease (CAD) patients. The aim of this study was to compare the FVP profile between two populations: CAD patients vs. healthy participants (HP)., Methods: Twenty-four CAD patients (55.8 ± 7.1 y) and 24 HP (52.4 ± 14.8 y) performed two sprints of 8 s on a Monark cycle ergometer with a resistance corresponding to 0.4 N/kg × body mass for men and 0.3 N/kg × body mass for women. The theoretical maximal force ( F 0 ) and velocity ( V 0 ), the slope of the force-velocity relationship ( S fv ) and the maximal mechanical power output ( P max ) were determined., Results: The P max (CAD: 6.86 ± 2.26 W.kg -1 vs. HP: 9.78 ± 4.08 W.kg -1 , p (CAD: 5.10 ± 0.82 m.s V vs. HP: 5.79 ± 0.97 m.s 0 (CAD: 5.10 ± 0.82 m.s -1 vs. HP: 5.79 ± 0.97 m.s -1 , p = 0.010), and F 0 (CAD: 1.35 ± 0.38 N.kg -1 vs. HP: 1.65 ± 0.51 N.kg -1 .m.s p = 0.039) were significantly higher in HP than in CAD. No significant difference appeared in S fv .m.s -1 .m.s -1 vs. HS: -0.28 ± 0.07 N.kg -1 .m.s -1 , p = 0.541)., Conclusion: The lower maximal power in CAD patients was related to both a lower V 0 and F 0 . Physical inactivity, sedentary time and high cardiovascular disease (CVD) risk may explain this difference of force production at both high and low velocities between the two groups., (Copyright © 2020 Fanget, Rossi, Samozino, Morin, Testa, Roche, Busso, Laukkanen and Hupin.)

Two experiments examined the effect of mindfulness meditation and relaxation on time perception using a temporal bisection task. In Experiment 1, the participants performed a temporal task before and after exercises of mindfulness meditation or relaxation. In Experiment 2, the procedure was similar than that used in Experiment 1, except that the participants were trained to mediate or relax every day over a period of several weeks. The results showed that mindfulness meditation exercises increased sensitivity to time and lengthened perceived time. However, this temporal improvement with meditation exercises was primarily observed in the experienced meditators. Our results also showed the experienced meditators were less anxious than the novice participants, and that the sensitivity to time increased when the level of anxiety decreased. Our results were explained by the practice of mindfulness technique that had developed individuals' abilities in devoting more attention resources to temporal information processing., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: Determining how individuals solve arithmetic problems is crucial for our understanding of human cognitive architecture. Elderly adults are supposed to use memory retrieval more often than younger ones. However, they might backup their retrieval by reconstructive strategies. In order to investigate this issue, we used the operand-recognition paradigm, which capitalizes on the fact that algorithmic procedures degrade the memory traces of the operands., Method: Twenty-three older adults (M = 70.4) and 23 younger adults (M = 20.0) solved easy, difficult, and medium-difficulty addition and comparison problems and were then presented with a recognition task of the operands., Results: When one-digit numbers with sums larger than 10 were involved (medium-difficulty problem), it was more difficult for younger adults to recognize the operands after addition than comparison. In contrast, in older adults, recognition times of the operands were the same after addition and comparison., Discussion: Older adults, in contrast with younger adults, are able to retrieve the results of addition problems of medium difficulty. Contrary to what was suggested, older participants do not seem to resort to backup strategies for such problems. Finally, older adults' reliance on the more efficient retrieval strategy allowed them to catch up to younger adults in terms of solution times.

The aim of the present study was to investigate whether children with Autism Spectrum Disorders (ASD) have a deficit in time perception. Twelve ASD children of normal intelligence and twelve typically developing children (TD) - matched on sex, chronological age, and mental age - performed four temporal bisection tasks that were adapted to the population. Two short (0.5 to 1 s and 1.25 to 2.5 s) and two long duration ranges (3.12 to 6.25 s and 7.81 to 16.62 s) were thus examined. The findings suggested that the perception of time in bisection is not impaired in ASD.

The authors used the operand-recognition paradigm (C. Thevenot, M. Fanget, & M. Fayol, 2007) in order to study the strategies used by adults to solve subtraction problems. This paradigm capitalizes on the fact that algorithmic procedures degrade the memory traces of the operands. Therefore, greater difficulty in recognizing them is expected when calculations have been solved by reconstructive strategies rather than by retrieval of number facts from long-term memory. The present results suggest that low- and high-skilled individuals differ in their strategy when they solve problems involving minuends from 11 to 18. Whereas high-skilled individuals retrieve the results of such subtractions from long-term memory, lower skilled individuals have to resort to reconstructive strategies. Moreover, the authors directly confront the results obtained with the operand-recognition paradigm and those obtained with the more classical method of verbal report collection and show clearly that this second method of investigation fails to reveal this differential pattern. The rationale behind the operand-recognition paradigm is then discussed., ((c) 2010 APA, all rights reserved).)

According to LeFevre, Sadesky, and Bisanz, averaging solution latencies in order to study individuals' arithmetic strategies can result in misleading conclusions. Therefore, in addition to classical chronometric data, they collected verbal reports and challenged the assumption that adults rely systematically on retrieval of arithmetic facts from memory to solve simple addition problems. However, Kirk and Ashcraft questioned the validity of such a methodology and concluded that a more appropriate method has to be found. Thus, we developed an operand recognition paradigm that does not rely on verbal reports or on solution latencies. In accordance with LeFevre et al., we show in a first experiment that adults resort to nonretrieval strategies to solve addition problems involving medium numbers. However, in a second experiment, we show that high-skilled individuals can solve the same problems using a retrieval strategy. The benefits of our paradigm to the study of arithmetic strategies are discussed.