Rehabilitation Improves Persistent Symptoms of COVID-19: A Nonrandomized, Controlled, Open Study in Brazil.

OBJECTIVE: This study aimed to investigate the effects of an 8-wk face-to-face rehabilitation program on subjects with persistent symptoms of COVID-19 compared with a remote monitoring group. DESIGN: This is clinical, nonrandomized, controlled, and open study. The face-to-face supervised rehabilitation lasted eight consecutive weeks, twice a week. The remote monitoring group received health guidance. The allocation was carried out by preference because of the emergency period without vaccination during the pandemic. Fatigue, dyspnea (Pulmonary Functional Status and Dyspnea Questionnaire), and exercise capacity (Incremental Shuttle Walk Test) were the primary outcome measures. Lung function, functional status (Post-COVID-19 Functional Status), symptoms of anxiety and depression (Hospital Anxiety and Depression Scale), attention (d2-R), memory (Rey's Auditory-Verbal Learning Test), handgrip strength, and knee extensor strength were secondary outcome measures. RESULTS: Thirty-seven subjects (24.3% hospitalized) completed the baseline and final assessment, rehabilitation ( n = 22, 40.8 [SD, 10.0] yrs, 54.5% female), or remote guidance ( n = 15, 45.4 [SD, 10.5] yrs, 40% female). Both groups showed improved fatigue and exercise capacity. Exercise rehabilitation improved dyspnea, anxiety, attention, and short-term memory. CONCLUSIONS: Rehabilitation is essential for dyspnea in subjects with persistent symptoms of COVID-19 while fatigue naturally reverses.

The striatum drives the ergogenic effects of caffeine.

Caffeine is one of the main ergogenic resources used in exercise and sports. Previously, we reported the ergogenic mechanism of caffeine through neuronal A2AR antagonism in the central nervous system [1]. We now demonstrate that the striatum rules the ergogenic effects of caffeine through neuroplasticity changes. Thirty-four Swiss (8-10 weeks, 47 ± 1.5 g) and twenty-four C57BL/6J (8-10 weeks, 23.9 ± 0.4 g) adult male mice were studied behaviorly and electrophysiologically using caffeine and energy metabolism was studied in SH-SY5Y cells. Systemic (15 mg/kg, i.p.) or striatal (bilateral, 15 µg) caffeine was psychostimulant in the open field (p < 0.05) and increased grip efficiency (p < 0.05). Caffeine also shifted long-term depression (LTD) to potentiation (LTP) in striatal slices and increased the mitochondrial mass (p < 0.05) and membrane potential (p < 0.05) in SH-SY5Y dopaminergic cells. Our results demonstrate the role of the striatum in the ergogenic effects of caffeine, with changes in neuroplasticity and mitochondrial metabolism.

Post-viral fatigue in COVID-19: A review of symptom assessment methods, mental, cognitive, and physical impairment.

Coronavirus 2 is responsible for Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), and the main sequela is persistent fatigue. Post-viral fatigue is common and affects patients with mild, asymptomatic coronavirus disease-2019 (COVID-19). However, the exact mechanisms involved in developing post-COVID-19 fatigue remain unclear. Furthermore, physical and cognitive impairments in these individuals have been widely described. Therefore, this review aims to summarize and propose tools from a multifaceted perspective to assess COVID-19 infection. Herein, we point out the instruments that can be used to assess fatigue in long-term COVID-19: fatigue in a subjective manner or fatigability in an objective manner. For physical and mental fatigue, structured questionnaires were used to assess perceived symptoms, and physical and cognitive performance assessment tests were used to measure fatigability using reduced performance.

Deletion of CD73 increases exercise power in mice.

Ecto-5'-nucleotidase or CD73 is the main source of extracellular adenosine involved in the activation of adenosine A2A receptors, responsible for the ergogenic effects of caffeine. We now investigated the role of CD73 in exercise by comparing female wild-type (WT) and CD73 knockout (KO) mice in a treadmill-graded test to evaluate running power, oxygen uptake (V̇O2), and respiratory exchange ratio (RER) - the gold standards characterizing physical performance. Spontaneous locomotion in the open field and submaximal running power and V̇O2 in the treadmill were similar between CD73-KO and WT mice; V̇O2max also demonstrated equivalent aerobic power, but CD73-KO mice displayed a 43.7 ± 4.2% larger critical power (large effect size, P < 0.05) and 3.8 ± 0.4% increase of maximum RER (small effect size, P < 0.05). Thus, KO of CD73 was ergogenic; i.e., it increased physical performance.

Neuronal adenosine A2A receptors signal ergogenic effects of caffeine.

Caffeine is one of the most used ergogenic aid for physical exercise and sports. However, its mechanism of action is still controversial. The adenosinergic hypothesis is promising due to the pharmacology of caffeine, a nonselective antagonist of adenosine A1 and A2A receptors. We now investigated A2AR as a possible ergogenic mechanism through pharmacological and genetic inactivation. Forty-two adult females (20.0 ± 0.2 g) and 40 male mice (23.9 ± 0.4 g) from a global and forebrain A2AR knockout (KO) colony ran an incremental exercise test with indirect calorimetry (V̇O2 and RER). We administered caffeine (15 mg/kg, i.p., nonselective) and SCH 58261 (1 mg/kg, i.p., selective A2AR antagonist) 15 min before the open field and exercise tests. We also evaluated the estrous cycle and infrared temperature immediately at the end of the exercise test. Caffeine and SCH 58621 were psychostimulant. Moreover, Caffeine and SCH 58621 were ergogenic, that is, they increased V̇O2max, running power, and critical power, showing that A2AR antagonism is ergogenic. Furthermore, the ergogenic effects of caffeine were abrogated in global and forebrain A2AR KO mice, showing that the antagonism of A2AR in forebrain neurons is responsible for the ergogenic action of caffeine. Furthermore, caffeine modified the exercising metabolism in an A2AR-dependent manner, and A2AR was paramount for exercise thermoregulation.

Functional Recovery Occurs Even After Partial Remyelination of Axon-Meshed Median and Ulnar Nerves in Mice.

Upper limb nerve injuries are common, and their treatment poses a challenge for physicians and surgeons. Experimental models help in minimum exploration of the functional characteristics of peripheral nerve injuries of forelimbs. This study was conducted to characterize the functional recovery (1, 3, 7, 10, 14, and 21 days) after median and ulnar nerve crush in mice and analyze the histological and biochemical markers of nerve regeneration (after 21 days). Sensory-functional impairments appeared after 1 day. The peripheral nerve morphology, the nerve structure, and the density of myelin proteins [myelin protein zero (P0) and peripheral myelin protein 22 (PMP22)] were analyzed after 21 days. Cold allodynia and fine motor coordination recovery occurred on the 10th day, and grip strength recovery was observed on the 14th day after injury. After 21 days, there was partial myelin sheath recovery. PMP22 recovery was complete, whereas P0 recovery was not. Results suggest that there is complete functional recovery even with partial remyelination of median and ulnar nerves in mice.

The exercise sex gap and the impact of the estrous cycle on exercise performance in mice.

Exercise physiology is different in males and females. Females are poorly studied due to the complexity of the estrous cycle and this bias has created an exercise sex gap. Here, we evaluated the impact of sexual dimorphism and of the estrous cycle on muscle strength and running power of C57BL/6 mice. Like men, male mice were stronger and more powerful than females. Exercise-induced increase of O2 consumption ([Formula: see text]O2) and CO2 production ([Formula: see text]CO2) were equal between sexes, indicating that running economy was higher in males. Thermoregulation was also more efficient in males. In females, proestrus increased exercise [Formula: see text]O2 and [Formula: see text]CO2 at low running speeds (30-35% female [Formula: see text]O2max) and estrus worsened thermoregulation. These differences translated into different absolute and relative workloads on the treadmill, even at equal submaximal [Formula: see text]O2 and belt speeds. In summary, our results demonstrate the better muscle strength, running power and economy, and exercise-induced thermoregulation of males compared to females. Proestrus and estrus still undermined the running economy and exercise-induced thermoregulation of females, respectively. These results demonstrate an important exercise sex gap in mice.

The dose-dependent antioxidant effects of physical exercise in the hippocampus of mice.

Exercise increases both the consumption of oxygen and the production of reactive species in biological tissues, and this is counterbalanced by antioxidant adaptations to regular physical training. When the intensity of exercise fluctuates between mild and moderate, it improves the status of reduction-oxidation balance in the brain and induces neuroplasticity. However, intense exercise can oxidize the brain and impair neurological function. The effect of the frequency of exercise, which is an important factor in physical training, is still unknown. The effect of periodic exercise on biomarkers of oxidative stress in the hippocampus of mice was evaluated in this study. Mice were made to run on a treadmill for 8 weeks, two, three, or five times per week, and their hippocampi and quadriceps femoris muscles were then dissected. Biomarkers of oxidative damage were negatively correlated with the frequency of exercise and mitochondrial muscular activity, while the sulfhydryl contents were positively correlated with exercise frequency. A logistic analysis revealed a dose-dependent effect of exercise on these biomarkers. In summary, these results suggested that manipulating the frequency of physical exercise could induce antioxidant-related adaptations in the hippocampi of adult mice.

The IBB forelimb scale as a tool to assess functional recovery after peripheral nerve injury in mice.

BACKGROUND: This study was conducted to test whether the IBB Forelimb Scale (Irvine et al., 2010) which was originally developed for rats with spinal cord injury, is also capable of measuring the functional performance of Swiss mice with lesions of the median and ulnar nerves inflicted via crushing with standardized strength. NEW METHOD: This test was performed at days 1, 3, 7, 10, 14 and 21 after surgery and each animal gives a score of 9, where 0 represented the worst functionality and 9 represented the habitual behavior. RESULTS: The control animals usually exhibited movements in the task that were scored as 9 during the experimental period. The lesion group began with a score of 2 on the 1st and 3rd post-operative days. On the 7th and 10th postoperative days, respectively, they scored 7, and on the 14th post-operative day, they achieved a score of 8. Only on the 21st post-operative day, did they exhibit habitual skillful behaviors. COMPARISON WITH EXISTING METHOD(S): IBB Forelimb Scale is effective for determining how the animals perform the movements in detail, which is not readily revealed by other methods. Furthermore, this test show similar recovery periods with grasping test, staircase test and seems to be more sensitive than paw print analysis for this type of lesion. CONCLUSIONS: Our data demonstrate that IBB scale was capable of measuring gradual improvements in motor forelimb functions in this model and may be a new and effective assessment tool for peripheral nerve injury.

Cigarette smoke inhibits brain mitochondrial adaptations of exercised mice.

Physical exercise and smoking are environmental factors that generally cause opposite health-promoting adaptations. Both physical exercise and smoking converge on mitochondrial adaptations in various tissues, including the pro-oxidant nervous system. Here, we analyzed the impact of cigarette smoking on exercise-induced brain mitochondrial adaptations in the hippocampus and pre-frontal cortex of adult mice. The animals were exposed to chronic cigarette smoke followed by 8 weeks of moderate-intensity physical exercise that increased mitochondrial activity in the hippocampus and pre-frontal cortex in the non-smoker mice. However, mice previously exposed to cigarette smoke did not present these exercise-induced mitochondrial adaptations. Our results suggest that smoking can inhibit some brain health-promoting changes induced by physical exercise.