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Physiology of sedentary behavior.
Pinto, AJ, Bergouignan, A, Dempsey, PC, Roschel, H, Owen, N, Gualano, B, Dunstan, DW
Physiological reviews. 2023;(4):2561-2622
Abstract
Sedentary behaviors (SB) are characterized by low energy expenditure while in a sitting or reclining posture. Evidence relevant to understanding the physiology of SB can be derived from studies employing several experimental models: bed rest, immobilization, reduced step count, and reducing/interrupting prolonged SB. We examine the relevant physiological evidence relating to body weight and energy balance, intermediary metabolism, cardiovascular and respiratory systems, the musculoskeletal system, the central nervous system, and immunity and inflammatory responses. Excessive and prolonged SB can lead to insulin resistance, vascular dysfunction, shift in substrate use toward carbohydrate oxidation, shift in muscle fiber from oxidative to glycolytic type, reduced cardiorespiratory fitness, loss of muscle mass and strength and bone mass, and increased total body fat mass and visceral fat depot, blood lipid concentrations, and inflammation. Despite marked differences across individual studies, longer term interventions aimed at reducing/interrupting SB have resulted in small, albeit marginally clinically meaningful, benefits on body weight, waist circumference, percent body fat, fasting glucose, insulin, HbA1c and HDL concentrations, systolic blood pressure, and vascular function in adults and older adults. There is more limited evidence for other health-related outcomes and physiological systems and for children and adolescents. Future research should focus on the investigation of molecular and cellular mechanisms underpinning adaptations to increasing and reducing/interrupting SB and the necessary changes in SB and physical activity to impact physiological systems and overall health in diverse population groups.
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Physical Activity: A Strategy to Improve Antibody Response to a SARS-CoV-2 Vaccine Booster Dose in Patients With Autoimmune Rheumatic Diseases.
Gualano, B, Sieczkowska, SM, Lemes, ÍR, da Silva, RP, Pinto, AJ, Mazzolani, BC, Smaira, FI, Aikawa, NE, Kupa, LVK, Pasoto, SG, et al
Journal of physical activity & health. 2023;(4):311-316
Abstract
BACKGROUND Physical activity associates with improved immunogenicity following a 2-dose schedule of CoronaVac (Sinovac's inactivated SARS-CoV-2 vaccine) in patients with autoimmune rheumatic diseases (ARD). This study evaluates whether physical activity impacts vaccine-induced antibody responses to a booster dose in this population. METHODS This was a phase-4 trial conducted in São Paulo, Brazil. Patients with ARD underwent a 3-dose schedule of CoronaVac. One month after the booster, we assessed seroconversion rates of anti-SARS-CoV-2 S1/S2 IgG, geometric mean titers of anti-S1/S2 IgG, frequency of positive neutralizing antibodies, and neutralizing activity. Physical activity was assessed through questionnaire. RESULTS Physically active (n = 362) and inactive (n = 278) patients were comparable for most characteristics; however, physically active patients were younger (P < .01) and had a lower frequency of chronic inflammatory arthritis (P < .01). Adjusted models showed that physically active patients had ∼2 times odds of seroconversion rates (OR: 2.09; 95% confidence interval, 1.22 to 3.61), ∼22% greater geometric mean titers of anti-S1/S2 IgG (22.09%; 95% confidence interval, 3.91 to 65.60), and ∼7% greater neutralizing activity (6.76%; 95% confidence interval, 2.80 to 10.72) than inactive patients. CONCLUSIONS Patients with ARD who are physically active have greater odds of experiencing better immunogenicity to a booster dose of CoronaVac. These results support the recommendation of physical activity to improve vaccination responses, particularly for immunocompromised individuals.
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Association between physical activity and immunogenicity of an inactivated virus vaccine against SARS-CoV-2 in patients with autoimmune rheumatic diseases.
Gualano, B, Lemes, IR, Silva, RP, Pinto, AJ, Mazzolani, BC, Smaira, FI, Sieczkowska, SM, Aikawa, NE, Pasoto, SG, Medeiros-Ribeiro, AC, et al
Brain, behavior, and immunity. 2022;:49-56
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Abstract
OBJECTIVES To investigate whether physical activity is associated with enhanced immunogenicity of a SARS-CoV-2 inactivated vaccine (Coronavac) in patients with autoimmune rheumatic diseases (ARD) (n = 898) and in non-ARD (n = 197) individuals without pre-existing immunogenicity to SARS-CoV-2. METHODS This was a prospective cohort study within an open-label, single-arm, phase 4 vaccination trial. Immunogenicity was assessed after vaccination by measuring seroconversion rates of total anti-SARS-CoV-2 S1/S2 IgG (SC), geometric mean titers of anti-S1/S2 IgG (GMT), factor-increase in GMT (FI-GMT), frequency of neutralizing antibody (NAb), and median neutralizing activity. Physical activity (active being defined as ≥ 150 min/week) and sedentary behavior (>8h/day) were assessed by questionnaire. RESULTS Physically active ARD patients (n = 494) were younger and less frequently used prednisone/biologics than inactive patients (n = 404). After controlling for covariates, active patients exhibited greater SC (OR: 1.4 [95%CI: 1.1-2.0]), GMT (32% [95%CI: 8.8-60) and FI-GMT (33% [95%CI: 9.6-63%]) vs. inactive. Cluster analysis (physical activity/sedentary status) revealed greater GMT (43.0% [95% CI: 11.0-84.0%) and FI-GMT (48.0% [95%CI: 14.0-92.0%]) in active/non-sedentary vs. inactive/sedentary ARD patients. A dose-response was observed, with greater benefits for the group of patients performing ≥ 350 min/week of physical activity (OR: 1.6 [95%CI: 1.1-2.4]; 41% [95%CI: 10-80%]; 35% [95%CI: 4.3-74], for SC, GMT, and FI-GMT, respectively) vs. the least active group (≤30 min/week). Greater SC (OR: 9.9 [95%CI: 1.1-89.0]) and GMT (26% [95%CI: 2.2-56.0%]) were observed in active vs. inactive non-ARD. CONCLUSIONS A physically active lifestyle may enhance SARS-CoV-2 vaccine immunogenicity, a finding of particular clinical relevance for immunocompromised patients. TRIAL REGISTRATION Clinicaltrials.gov #NCT04754698.
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Effect of a single high dose of vitamin D3 on cytokines, chemokines, and growth factor in patients with moderate to severe COVID-19.
Fernandes, AL, Murai, IH, Reis, BZ, Sales, LP, Santos, MD, Pinto, AJ, Goessler, KF, Duran, CSC, Silva, CBR, Franco, AS, et al
The American journal of clinical nutrition. 2022;(3):790-798
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Abstract
BACKGROUND The modulating effect of vitamin D on cytokine concentrations in severe coronavirus disease 2019 (COVID-19) remains unknown. OBJECTIVES We aimed to investigate the effect of a single high dose of vitamin D3 on cytokines, chemokines, and growth factor in hospitalized patients with moderate to severe COVID-19. METHODS This is a post hoc, ancillary, and exploratory analysis from a multicenter, double-blind, placebo-controlled, randomized clinical trial. Patients with moderate to severe COVID-19 were recruited from 2 hospitals in São Paulo, Brazil. Of 240 randomly assigned patients, 200 were assessed in this study and randomly assigned to receive a single oral dose of 200,000 IU vitamin D3 (n = 101) or placebo (n = 99). The primary outcome was hospital length of stay, which has been published in our previous study. The prespecified secondary outcomes were serum concentrations of IL-1β, IL-6, IL-10, TNF-α, and 25-hydroxyvitamin D. The post hoc exploratory secondary outcomes were IL-4, IL-12p70, IL-17A, IFN-γ, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-8, IFN-inducible protein-10 (IP-10), macrophage inflammatory protein-1β (MIP-1β), monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), and leukocyte count. Generalized estimating equations for repeated measures, with Bonferroni's adjustment, were used for testing all outcomes. RESULTS The study included 200 patients with a mean ± SD age of 55.5 ± 14.3 y and BMI of 32.2 ± 7.1 kg/m2, of which 109 (54.5%) were male. GM-CSF concentrations showed a significant group-by-time interaction effect (P = 0.04), although the between-group difference at postintervention after Bonferroni's adjustment was not significant. No significant effects were observed for the other outcomes. CONCLUSIONS The findings do not support the use of a single dose of 200,000 IU vitamin D3, compared with placebo, for the improvement of cytokines, chemokines, and growth factor in hospitalized patients with moderate to severe COVID-19.This trial was registered at clinicaltrials.gov as NCT04449718.
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Physical activity and antibody persistence 6 months after the second dose of CoronaVac in immunocompromised patients.
Gualano, B, Lemes, ÍR, da Silva, RP, Pinto, AJ, Mazzolani, BC, Smaira, FI, Sieczkowska, SM, Aikawa, NE, Pasoto, S, Medeiros-Ribeiro, AC, et al
Scandinavian journal of medicine & science in sports. 2022;(10):1510-1515
Abstract
This prospective cohort study within an open-label, single-arm, phase 4 vaccination trial (clinicaltrials.gov #NCT04754698) aimed to investigate the association between physical activity and persistent anti-SARS-CoV-2 antibodies 6 months after two-dose schedule of CoronaVac in autoimmune rheumatic diseases (ARD) patients (n = 748). Persistent immunogenicity 6 months after the full-course vaccination was assessed using seroconversion rates of total anti-SARS-CoV-2 S1/S2 IgG, geometric mean titers of anti-S1/S2 IgG (GMT), and frequency of positive neutralizing antibodies (NAb). Physical activity was assessed trough questionnaire. Adjusted point estimates from logistic regression models indicated that physically active patients had greater odds of seroconversion rates (OR: 1.5 [95%CI: 1.1 to 2.1]) and NAb positivity (OR: 1.5 [95%CI: 1.0 to 2.1]), and approximately 43% greater GMT (42.8% [95%CI: 11.9 to 82.2]) than inactive ones. In conclusion, among immunocompromised patients, being physically active was associated with an increment in antibody persistence through 6 months after a full-course of an inactivated SARS-CoV-2 vaccine.
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Sex Differences in Physical Activity Among Individuals With Type 2 Diabetes Across the Life Span: A Systematic Review and Meta-analysis.
Whipple, MO, Pinto, AJ, Abushamat, LA, Bergouignan, A, Chapman, K, Huebschmann, AG, Masters, KS, Nadeau, KJ, Scalzo, RL, Schauer, IE, et al
Diabetes care. 2022;(9):2163-2177
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Abstract
BACKGROUND Physical activity (PA) is a cornerstone of type 2 diabetes mellitus (T2DM) treatment. Sex differences in PA behavior or barriers/facilitators to PA among individuals with T2DM are unclear. PURPOSE To summarize the evidence related to sex differences in participation in PA and barriers/facilitators to PA among individuals with T2DM across the life span. DATA SOURCES Systematic searches (CRD42021254246) were conducted with Ovid MEDLINE, Embase, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Allied and Complementary Medicine Database (AMED), APA PsychInfo, and SPORTDiscus. STUDY SELECTION We included studies with assessment of PA, sedentary behaviors (SB), or barriers/facilitators to PA among individuals with T2DM by sex or gender. DATA EXTRACTION Participant characteristics, meeting PA guidelines, participation in PA and SB, and barriers/facilitators to PA were extracted by two independent reviewers. DATA SYNTHESIS A total of 53 articles (65,344 participants) were included in the systematic review and 21 articles in the meta-analysis. Sex differences were not observed in meeting of PA guidelines among adolescents (odds ratio 0.70 [95% CI 0.31, 1.59]), but males were more likely than females to meet PA guidelines among adults (1.65 [1.36, 2.01]) and older adults (1.63 [1.27, 2.09]). Males performed more moderate-to-vigorous PA (MVPA) than females across all age-groups. Common barriers to PA were lack of time (men) and lack of social support and motivation (women). LIMITATIONS Limitations include heterogeneity of measures used to assess PA and lack of stratification of data by sex. CONCLUSIONS Sex differences in meeting PA guidelines were not observed among adolescents but were apparent among adults and older adults with T2DM. Females consistently engaged in less MVPA than males across the life span.
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Effect of an exercise bout before the booster dose of an inactivated SARS-CoV-2 vaccine on immunogenicity in immunocompromised patients.
Gualano, B, Saad, CGS, Sieczkowska, SM, Lemes, ÍR, da Silva, RP, Pinto, AJ, Mazzolani, BC, Smaira, FI, Gil, S, Oliveira-Junior, G, et al
Journal of applied physiology (Bethesda, Md. : 1985). 2022;(3):682-688
Abstract
This randomized controlled study aimed to investigate whether a single bout of exercise before the homologous booster dose of a SARS-CoV-2 inactivated vaccine could enhance immunogenicity in patients with spondyloarthritis. We selected 60 consecutive patients with spondyloarthritis (SpA). Patients assigned to the intervention group performed an exercise bout comprising three exercises. Then, they remained at rest for 1 h before vaccination. The control group remained at rest before vaccination. Immunogenicity was assessed before (Pre) and 1 mo after (Post) the booster using seropositivity rates of total anti-SARS-CoV-2 S1/S2 IgG, geometric mean titers of anti-S1/S2 IgG (GMT), frequency of neutralizing antibodies (NAb) positivity, and NAb activity. At Pre, 16 patients from the exercise group and 16 patients from the control group exhibited seropositivity for IgG (59% vs. 57.1%), and 1 mo after the booster dose, seropositivity occurred in 96% versus 100% of the cases. Only 10 patients from the exercise group and 12 patients from the control group showed positive NAb serology at Pre (37% vs. 42.8%). One month following the booster, NAb positivity was 96% versus 93%. GMT was comparable between groups at Pre. At Post, GMT increased similarly in both groups. Likewise, NAb activity was similar between groups at Pre and increased similarly in both of them as a result of the booster (47.5% vs. 39.9%). In conclusion, a single bout of exercise did not enhance immunogenicity to a homologous booster dose of an inactivated SARS-CoV-2 vaccine among patients with spondyloarthritis.NEW & NOTEWORTHY We tested the role of exercise as an adjuvant to a booster of a COVID-19 vaccine. Immunocompromised patients were immunized after an acute bout of exercise or not. Patients exhibited an excellent immunogenicity in response to the booster dose. Exercise did not add to the vaccine effects on IgG or neutralizing antibodies.
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Health at Every Size®-Based Interventions May Improve Cardiometabolic Risk and Quality of Life Even in the Absence of Weight Loss: An Ancillary, Exploratory Analysis of the Health and Wellness in Obesity Study.
Dimitrov Ulian, M, Pinto, AJ, de Morais Sato, P, Benatti, FB, Lopes de Campos-Ferraz, P, Coelho, D, Roble, OJ, Sabatini, F, Perez, I, Aburad, L, et al
Frontiers in nutrition. 2022;:598920
Abstract
We examined whether weight loss following HAES®-based interventions associates with changes in cardiometabolic risk factors and quality of life of women with obesity. This was an exploratory, ancillary analysis of a 7-month, mixed-method, randomized controlled trial. Fifty-five women (age: 33.0 ± 7.2; BMI: 30-39.9 kg/m2) were included in this study. Body weight, cardiovascular risk factors, clustered cardiometabolic risk, and quality of life were assessed before (Pre) and after HAES®-based interventions (Post). Delta scores (Post-Pre) were calculated for each outcome and used in linear regression models. After adjusting by potential confounders, weight loss was associated with improvements in waist circumference (β = 0.83, p <0.001), fasting glycemia (β = 0.45, p = 0.036), total cholesterol (β = 1.48, p = 0.024), LDL (β = 1.33, p = 0.012), clustered cardiometabolic risk (β = 0.18, p = 0.006), and quality of life (β = -1.05, p = 0.007). All participants but one who reduced body weight (n = 11) improved clustered cardiometabolic risk and quality of life. Of relevance, 34% and 73% of the participants who maintained or gained weight improved clustered cardiometabolic risk and quality of life, respectively, although the magnitude of improvements was lower than that among those who lose weight. Improvements in cardiovascular risk factors and quality of life following HAES®-based interventions associated with weight loss as expected. However, most of the participants who maintained or even gained weight experienced benefits to some extent. This suggests that weight-neutral, lifestyle-modification interventions may improve wellness and health-related outcomes, even in the absence of weight loss.
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The Acute Effects of Prolonged Uninterrupted Sitting on Vascular Function: A Systematic Review and Meta-analysis.
Taylor, FC, Pinto, AJ, Maniar, N, Dunstan, DW, Green, DJ
Medicine and science in sports and exercise. 2022;(1):67-76
Abstract
OBJECTIVE This study aimed to determine the dose-response relationship between prolonged sitting and vascular function in healthy individuals and those with metabolic disturbances and to investigate the acute effects, on vascular function, of interventions that target interrupting prolonged sitting. DESIGN This is a systematic review with meta-analysis. DATA SOURCES Ovid Embase, Ovid Medline, PubMed, and CINAHL were searched from inception to 4 December 2020. ELIGIBILITY CRITERIA Randomized crossover trials, quasi-randomized trials, and parallel group trials where vascular function (flow-mediated dilation [FMD]) was assessed before and after an acute period of sedentary behavior was used in this study. RESULTS Prolonged sitting resulted in a significant decrease in the standardized mean change (SMC) for lower-limb FMD at the 120-min (SMC = -0.85, 95% confidence interval [CI] = -1.32 to -0.38) and 180-min (SMC = -1.18, 95% CI = -1.69 to -0.66) time points. A similar pattern was observed for lower-limb shear rate. No significant changes were observed for any outcomes in the upper limb. Subgroup analysis indicated that prolonged sitting decreased lower-limb FMD in healthy adults (SMC = -1.33, 95% CI = -1.89 to -0.78) who had higher a priori vascular endothelial function, but not in those with metabolic and vascular dysfunction (SMC = -0.51, 95% CI = -1.18 to 0.15). Interrupting sitting with active interruptions increased the standardized mean difference for FMD, relative to prolonged sitting, but it was not statistically significant (0.13, 95% CI = -0.20 to 0.45). CONCLUSIONS Lower-limb vascular function is progressively impaired as a consequence of prolonged sitting, up to 180 min. A similar trend was not observed in upper-limb vascular function. Subgroup analysis indicated that prolonged sitting negatively affects healthy populations, a finding not observed in those with metabolic disturbances. Regularly interrupting sitting with activity may be beneficial for those with metabolic disturbances.
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Effect of a Single High Dose of Vitamin D3 on Hospital Length of Stay in Patients With Moderate to Severe COVID-19: A Randomized Clinical Trial.
Murai, IH, Fernandes, AL, Sales, LP, Pinto, AJ, Goessler, KF, Duran, CSC, Silva, CBR, Franco, AS, Macedo, MB, Dalmolin, HHH, et al
JAMA. 2021;(11):1053-1060
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IMPORTANCE The efficacy of vitamin D3 supplementation in coronavirus disease 2019 (COVID-19) remains unclear. OBJECTIVE To investigate the effect of a single high dose of vitamin D3 on hospital length of stay in patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTS This was a multicenter, double-blind, randomized, placebo-controlled trial conducted in 2 sites in Sao Paulo, Brazil. The study included 240 hospitalized patients with COVID-19 who were moderately to severely ill at the time of enrollment from June 2, 2020, to August 27, 2020. The final follow-up was on October 7, 2020. INTERVENTIONS Patients were randomly assigned to receive a single oral dose of 200 000 IU of vitamin D3 (n = 120) or placebo (n = 120). MAIN OUTCOMES AND MEASURES The primary outcome was length of stay, defined as the time from the date of randomization to hospital discharge. Prespecified secondary outcomes included mortality during hospitalization; the number of patients admitted to the intensive care unit; the number of patients who required mechanical ventilation and the duration of mechanical ventilation; and serum levels of 25-hydroxyvitamin D, total calcium, creatinine, and C-reactive protein. RESULTS Of 240 randomized patients, 237 were included in the primary analysis (mean [SD] age, 56.2 [14.4] years; 104 [43.9%] women; mean [SD] baseline 25-hydroxyvitamin D level, 20.9 [9.2] ng/mL). Median (interquartile range) length of stay was not significantly different between the vitamin D3 (7.0 [4.0-10.0] days) and placebo groups (7.0 [5.0-13.0] days) (log-rank P = .59; unadjusted hazard ratio for hospital discharge, 1.07 [95% CI, 0.82-1.39]; P = .62). The difference between the vitamin D3 group and the placebo group was not significant for in-hospital mortality (7.6% vs 5.1%; difference, 2.5% [95% CI, -4.1% to 9.2%]; P = .43), admission to the intensive care unit (16.0% vs 21.2%; difference, -5.2% [95% CI, -15.1% to 4.7%]; P = .30), or need for mechanical ventilation (7.6% vs 14.4%; difference, -6.8% [95% CI, -15.1% to 1.2%]; P = .09). Mean serum levels of 25-hydroxyvitamin D significantly increased after a single dose of vitamin D3 vs placebo (44.4 ng/mL vs 19.8 ng/mL; difference, 24.1 ng/mL [95% CI, 19.5-28.7]; P < .001). There were no adverse events, but an episode of vomiting was associated with the intervention. CONCLUSIONS AND RELEVANCE Among hospitalized patients with COVID-19, a single high dose of vitamin D3, compared with placebo, did not significantly reduce hospital length of stay. The findings do not support the use of a high dose of vitamin D3 for treatment of moderate to severe COVID-19. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT04449718.