Effects of a lifestyle intervention on cardiovascular risk factors in systemic lupus erythematosus patients: The study "Living well with lupus".

OBJECTIVE: The aim of the present study was to investigate the effects of a lifestyle intervention on cardiometabolic risk factors in patients with systemic lupus erythematosus with a high cardiovascular risk profile. METHODS: This trial was conducted in Sao Paulo, Brazil between August 2020 and March 2023. The patients were randomly assigned to lifestyle intervention or control. The intervention was a 6-month multifaced program focused on behavioral changes through personalized recommendations for increasing physical activity (structured and non-structured) and improving eating aspects. Cardiometabolic risk score (primary outcome), anthropometry and visceral fat, aerobic capacity, blood pressure, inflammatory and oxidative stress markers, and blood flow and endothelial function were assessed before and after the intervention. RESULTS: A total of 80 patients were randomized. Twelve and 6 patients dropped out due to personal reasons in the intervention and control groups, respectively. Average adherence rate for the intervention was 56.9%. Intention-to-treat analysis showed no significant difference between groups in the cardiometabolic risk score (intervention group - Pre: 1.7 ± 3.6; Post: -1.6 ± 4.0; control group - Pre: -1.9 ± 3.6; Post: -2.0 ± 3.8; estimated mean difference between groups at post: -0.4; 95% confidence intervals: -2.7; 1.9; p = 0.96). This finding was confirmed by exploratory, per-protocol analysis. No significant differences were observed between adherents vs. non-adherent participants. Secondary outcomes did not change between groups. CONCLUSION: This 6-month, individualized, lifestyle intervention did not improve cardiovascular risk factors in SLE patients with a high cardiovascular risk profile. TRIAL REGISTRATION: clinicaltrials.gov (NCT04431167).

A single session of aerobic exercise reduces systolic blood pressure at rest and in response to stress in women with rheumatoid arthritis and hypertension.

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease characterized by increased risk of cardiovascular disease and hypertension (HT). A single session of aerobic exercise may reduce blood pressure (BP) in different clinical groups; however, little is known about the acute effects of exercise on BP in RA patients. This is a randomized controlled crossover study that assessed the effects of a single session of aerobic exercise on resting BP, on BP responses to stressful stimuli, and on 24-h BP in women with RA and HT. Twenty women with RA and HT (53 ± 10 years) undertook sessions of 30-min treadmill exercise (50% VO2max) or control (no exercise) in a crossover fashion. Before and after the sessions, BP was measured at rest, and in response to the Stroop-Color Word Test (SCWT), the Cold Pressor Test (CPT), and an isometric handgrip test. After the sessions, participants were also fitted with an ambulatory BP monitor for the assessment of 24-h BP. A single session of exercise reduced resting systolic BP (SBP) (-5 ± 9 mmHg; p < 0.05), and reduced SBP response to the SCWT (-7 ± 14 mmHg; p < 0.05), and to the CPT (-5 ± 11 mmHg; p < 0.05). Exercise did not reduce resting diastolic BP (DBP), BP responses to the isometric handgrip test or 24-h BP. In conclusion, a single session of aerobic exercise reduced SBP at rest and in response to stressful stimuli in hypertensive women with RA. These results support the use of exercise as a strategy for controlling HT and, hence, reducing cardiovascular risk in women with RA.Clinical Trial Registration: This study registered at the Brazilian Clinical Trials ( https://ensaiosclinicos.gov.br/rg/RBR-867k9g ) at 12/13/2019.

Quality of life, fatigue, sleep quality, and mental health in systemic lupus erythematosus patients with a high cardiovascular risk profile.

Systemic lupus erythematosus (SLE) patients report worse health-related quality of life (HRQL), fatigue, anxiety, depression, and sleep quality, when compared to the general population and other chronic diseases. Furthermore, cardiometabolic diseases are highly prevalent in SLE and are also associated with these parameters. Thus, it is plausible to suggest that SLE patients with a high cardiovascular risk may report worse results for these parameters. The aim of the study is to describe HRQL, fatigue, anxiety and depression symptoms, and sleep quality in a sample of SLE patients with a high cardiovascular risk profile (i.e., BMI between 25 and 40 kg/m2 and/or dyslipidemia, hypertension, or diabetes). This was a cross-sectional study where patients were assessed for (i) demographic, anthropometric, and disease-related parameters, (ii) HRQL, (iii) fatigue, (iv) anxiety and depression symptoms, and (v) sleep quality. One-hundred patients completed the study; however, only 87 patients were assessed for sleep quality data. Patients averaged 41.7 ± 9 years, and most patients were classified as overweight/obese (87%). SF-36 scores for physical and mental components summary were 51.3 ± 9.6 and 54.2 ± 15.6, respectively, with "bodily pain" and "role emotional" presenting the lower scores. The total SLEQOL score was 105.1 ± 42.0, with lower scores reported for "self-image" and "mood." Fatigue score was 30.8 ± 8.9, and 78% and 93% reported severe symptoms of anxiety and depression, respectively. The average sleep effectiveness was 82.9 ± 6.6%. Sleep latency, total time in bed (TTiB), and total sleep time (TST) were 8.4 ± 8.9, 495.8 ± 79.7, and 409.7 ± 69.9 min, respectively. Patients reported an average of 17.8 ± 6.2 WE, with 4.5 ± 1.5 min duration and a WASO of 77.7 ± 36.6 min. Despite similar HRQL, fatigue, and sleep quality parameters to those reported by other SLE populations, SLE patients with a high cardiovascular risk had a higher prevalence of depression and anxiety. Understanding SLE patients' quality of life and psychological symptoms is of utmost importance to improve disease management. The findings of this study highlight the need for more intensive and global care regarding mental health when considering a high cardiovascular risk in SLE.

A randomized controlled trial of an intervention promoting physical activity and healthy eating recommendations in systemic lupus erythematosus: the protocol study "Living Well with Lupus".

There is a paucity of studies assessing multidisciplinary interventions focused on tackling physical inactivity/sedentary behavior and poor dietary habits in SLE. The Living well with Lupus (LWWL) is a randomized controlled trial to investigate whether a six-month lifestyle change intervention will improve cardiometabolic risk factors (primary outcome) among systemic lupus erythematosus (SLE) patients with low disease activity (SLEDAI score ≤ 4) and with high cardiovascular risk. As secondary goals, we will evaluate: (1) the intervention's safety, efficacy, and feasibility in promoting lifestyle changes, and (2) the effects of the intervention on secondary outcomes (i.e., clinical parameters, functional capacity, fatigue, psychological aspects, sleep quality and health-related quality of life). Patients will be randomly allocated to either a control (i.e., standard care) or a lifestyle intervention group using a simple randomization (1:1 ratio, blocks of 20). Mixed Model analyses will be conducted for comparing groups following an intention-to-treat approach. A per protocol analysis will also be conducted. This study has the potential to generate new, clinically relevant data able to refine the multidisciplinary management of SLE patients. Protocol version number: NCT04431167 (first version).

The utility of cardiopulmonary exercise testing in athletes and physically active individuals with or without persistent symptoms after COVID-19.

Introduction: Cardiopulmonary exercise testing (CPET) may capture potential impacts of COVID-19 during exercise. We described CPET data on athletes and physically active individuals with or without cardiorespiratory persistent symptoms. Methods: Participants' assessment included medical history and physical examination, cardiac troponin T, resting electrocardiogram, spirometry and CPET. Persistent symptoms were defined as fatigue, dyspnea, chest pain, dizziness, tachycardia, and exertional intolerance persisting >2 months after COVID-19 diagnosis. Results: A total of 46 participants were included; sixteen (34.8%) were asymptomatic and thirty participants (65.2%) reported persistent symptoms, with fatigue and dyspnea being the most reported ones (43.5 and 28.1%). There were a higher proportion of symptomatic participants with abnormal data for slope of pulmonary ventilation to carbon dioxide production (VE/VCO2 slope; p<0.001), end-tidal carbon dioxide pressure at rest (PETCO2 rest; p=0.007), PETCO2 max (p=0.009), and dysfunctional breathing (p=0.023) vs. asymptomatic ones. Rates of abnormalities in other CPET variables were comparable between asymptomatic and symptomatic participants. When assessing only elite and highly trained athletes, differences in the rate of abnormal findings between asymptomatic and symptomatic participants were no longer statistically significant, except for expiratory air flow-to-percent of tidal volume ratio (EFL/VT) (more frequent among asymptomatic participants) and dysfunctional breathing (p=0.008). Discussion: A considerable proportion of consecutive athletes and physically active individuals presented with abnormalities on CPET after COVID-19, even those who had had no persistent cardiorespiratory symptomatology. However, the lack of control parameters (e.g., pre-infection data) or reference values for athletic populations preclude stablishing the causality between COVID-19 infection and CPET abnormalities as well as the clinical significance of these findings.

Supplement-based nutritional strategies to tackle frailty: A multifactorial, double-blind, randomized placebo-controlled trial.

BACKGROUND: Sarcopenia plays a central role in the development of frailty syndrome. Nutrition and exercise are cornerstone strategies to mitigate the transition to frailty; however, there is a paucity of evidence for which dietary and exercise strategies are effective. OBJECTIVE: This large, multifactorial trial investigated the efficacy of different dietary strategies to enhance the adaptations to resistance training in pre-frail and frail elderly. METHODS: This was a single-site 16-week, double-blind, randomized, placebo-controlled trial conducted at the Clinical Hospital, School of Medicine - University of São Paulo, Sao Paulo, Brazil. Four integrated, sub-investigations were conducted to compare: 1) leucine vs. placebo; 2) whey vs. soy vs. placebo; 3) creatine vs. whey vs. creatine plus whey vs. placebo; 4) women vs. men in response to whey. Sub-investigations 1 to 3 were conducted in women, only. Two-hundred participants (154 women/46 men, mean age 72 ± 6 years) underwent a twice-a-week, resistance training program. The main outcomes were muscle function (assessed by dynamic and isometric strength and functional tests) and lean mass (assessed by DXA). Muscle cross-sectional area, health-related quality of life, bone and fat mass, and biochemical markers were also assessed. RESULTS: We observed that leucine supplementation was ineffective to improve muscle mass and function. Supplementation with whey and soy failed to enhance resistance-training effects. Similarly, supplementation with neither whey nor creatine potentiated the adaptations to resistance training. Finally, no sex-based differences were found in response to whey supplementation. Resistance exercise per se increased muscle mass and function in all sub-investigations. There were no adverse effects. CONCLUSION: Neither protein (whey and soy), leucine, nor creatine supplementation enhanced resistance training-induced adaptations in pre-frail and frail elderly, regardless of sex. These findings do not support the notion that some widely used supplement-based interventions can add to the already potent effects of resistance exercise to counteract frailty-related muscle wasting and dynapenia. CLINICAL TRIAL REGISTRY: NCT01890382; https://clinicaltrials.gov/ct2/show/NCT01890382. DATA SHARING: Data described in the manuscript will be made available upon request pending application.

Home-Based Exercise Training in Childhood-Onset Takayasu Arteritis: A Multicenter, Randomized, Controlled Trial.

Introduction: Childhood-onset Takayasu Arteritis (c-TA) is a rare, large-vessel vasculitis seen in children that could predisposing patients to a high risk of mortality. Exercise has the potential to improve overall health in several diseases, but evidence remains scant in c-TA. The main objective of this study was to investigate the safety and potential therapeutic effects of exercise in c-TA. Methods: This was a 12-week, multicenter, randomized, controlled trial, to test the effects of a home-based, exercise intervention vs. standard of care in c-TA patients in remission. The primary outcomes were arterial inflammation, assessed by [18F] FDG- PET/MRI and systemic inflammatory markers. Secondary outcomes included, physical activity levels, functionality, body composition, disease-related parameters, and quality of life. Results: Thirty-seven patients were assessed for eligibility, which represents the total number of c-TA patients being followed by the three specialized medical ambulatory services in Sao Paulo. After exclusions, fourteen c-TA patients (71.4% females) aged 12-25 years were randomly allocated into exercised (n=5) and non-exercised groups (n=9). Exercise did not exacerbate arterial inflammation. In fact, exercised patients had a reduction in the frequency of vessel segments with severe inflammation, whereas the non-exercised patients had an opposite response (P=0.007). Greater improvements in visceral fat, steps per day, functionality and physical component SF-36 were observed in the exercised patients (P ≤ 0.05). Conclusions: Exercise is safe and may improve visceral fat, physical activity levels, functionality, and physical component SF-36 in c-TA patients. Thus, exercise arises as a novel, evidence-based intervention to improve general health in c-TA. Clinical Trial Registration: https://www.clinicaltrials.gov/ct2/show/NCT03494062?term=NCT03494062&draw=2&rank=1, identifier NCT03494062.

High SARS-CoV-2 infection rate after resuming professional football in São Paulo, Brazil.

OBJECTIVE: To examine the SARS-CoV-2 infection rate in a cohort of 6500 professional athletes and staff during the 2020 football (soccer) season in São Paulo, Brazil. METHODS: This retrospective cohort study included 4269 players (87% male, age: 21.7±4.2 years) and 2231 staff (87% male, age: 42.6±11.9 years) from 122 teams (women: n=16) involved in eight leagues (women: n=2), which took place in São Paulo, Brazil. Between 4 July 2020 and 21 December 2020, swab samples were collected weekly (n=29 507) and tested for SARS-Cov-2 via reverse transcription-PCR by an accredited laboratory commissioned by the São Paulo Football Federation. We contacted the medical staff of each team with positive cases to collect information on disease severity. RESULTS: Among 662 PCR-confirmed cases, 501 were athletes and 161 were staff. The new infection rate was 11.7% and 7.2% for athletes and staff, respectively. Athletes were more susceptible to infection than staff (OR: 1.71, 95% CI: 1.42, 2.06, p<0.001), although with lower chance for moderate to severe disease (OR: 0.06, 95% CI: 0.01, 0.54, p=0.012). Six teams had ≥20 individuals testing positive for SARS-CoV-2, whereas 19 teams had ≥10 confirmed cases. Twenty-five mass outbreaks were identified (≥5 infections within a team in a 2-week period). The prevalence of SARS-CoV-2 infections was similar in athletes and staff as the general population in São Paulo. CONCLUSION: Despite weekly testing and other preventive measures, we found a high SARS-CoV-2 infection rate in athletes and staff after resuming football, which coincides with the high prevalence of infection in the community during the same period. These data may assist policy-makers and sports federations for determining if and when it is safe to resume competitions.

Poor physical activity levels and cardiorespiratory fitness among patients with childhood-onset takayasu arteritis in remission: a cross-sectional, multicenter study.

BACKGROUND: It is currently unknown whether patients with childhood-onset Takayasu disease (c-TA) are prone to physical inactivity and poor aerobic capacity. In this study, we assessed physical activity levels and cardiorespiratory fitness along with health-related quality of life (HRQL) and various traditional and non-traditional risk factors in patients with c-TA vs. healthy controls. METHODS: c-TA patients with non-active disease (n = 17) and age- and sex-matched healthy controls (n = 17) were enrolled in the study. We assessed physical activity levels, aerobic capacity, body composition, systemic inflammation, cardiometabolic markers, disease-related parameters, and HRQL. RESULTS: c-TA patients showed greater time spent in sedentary behavior (P = 0.010), and lower moderate-to-vigorous physical activity (P > 0.001) and lower step counts per day (P > 0.001). VO2peak (P < 0.001) and chronotropic response (P = 0.016) were significantly lower in patients with c-TA and they had worse HRQL in physical domain (P < 0.001), lower bone mineral content and density, and higher insulin levels vs. healthy controls (all P ≤ 0.05). CONCLUSIONS: c-TA patients exhibited reduced physical activity levels and aerobic capacity, worse cardiometabolic risk factors and HRQL parameter compared with healthy peers. Physical inactivity and aerobic deconditioning emerge as potentially novel risk factors for c-TA. The role of physical activity interventions in preventing poor outcomes and improving HRQL in c-TA remains to be explored.

Exercise Enhances the Effect of Bariatric Surgery in Markers of Cardiac Autonomic Function.

BACKGROUND: Bariatric surgery improves cardiovascular health, which might be partly ascribed to beneficial alterations in the autonomic nervous system. However, it is currently unknown whether benefits from surgery on cardiac autonomic regulation in post-bariatric patients can be further improved by adjuvant therapies, namely exercise. We investigated the effects of a 6-month exercise training program on cardiac autonomic responses in women undergoing bariatric surgery. METHODS: Sixty-two women eligible for bariatric surgery were randomly allocated to either standard of care (control) or an exercise training intervention. At baseline (PRE) and 3 (POST3) and 9 (POST9) months after surgery, we assessed chronotropic response to exercise (CR%; i.e., percentage change in heart rate from rest to peak exercise) and heart rate recovery (HRR30s, HRR60s, and HRR120s; i.e., decay of heart rate at 30, 60, and 120 s post exercise) after a maximal exercise test. RESULTS: Between-group absolute changes revealed higher CR% (Δ = 8.56%, CI95% 0.22-19.90, P = 0.04), HRR30s (Δ = 12.98 beat/min, CI95% 4.29-21.67, P = 0.01), HRR60s (Δ = 22.95 beat/min, CI95% 11.72-34.18, P = 0.01), and HRR120s (Δ = 34.54 beat/min, CI95% 19.91-49.17, P < 0.01) in the exercised vs. non-exercised group. CONCLUSIONS: Our findings demonstrate that exercise training enhanced the benefits of bariatric surgery on cardiac autonomic regulation. These results highlight the relevance of exercise training as a treatment for post-bariatric patients, ensuring optimal cardiovascular outcomes.

Increased sympathetic and haemodynamic responses to exercise and muscle metaboreflex activation in post-menopausal women with rheumatoid arthritis.

KEY POINTS: Rheumatoid arthritis (RA) patients present exacerbated blood pressure responses to exercise, but little is known regarding the underlying mechanisms involved.  This study assessed autonomic and haemodynamic responses to exercise and to the isolated activation of muscle metaboreflex in post-menopausal women with RA.  Participants with RA showed augmented pressor and sympathetic responses to exercise and to the activation of muscle metaboreflex. These responses were associated with multiple pro- and anti-inflammatory cytokines and with pain.  The results of the present study support the suggestion that an abnormal reflex control of circulation is an important mechanism underlying the exacerbated cardiovascular response to exercise and increased cardiovascular risk in RA. ABSTRACT: Studies have reported abnormal cardiovascular responses to exercise in rheumatoid arthritis (RA) patients, but little is known regarding the underlying mechanisms involved. This study assessed haemodynamic and sympathetic responses to exercise and to the isolated activation of muscle metaboreflex in women diagnosed with RA. Thirty-three post-menopausal women diagnosed with RA and 10 matched controls (CON) participated in this study. Mean arterial pressure (MAP), heart rate (HR) and muscle sympathetic nerve activity (MSNA frequency and incidence) were measured during a protocol of isometric knee extension exercise (3 min, 30% of maximal voluntary contraction), followed by post-exercise ischaemia (PEI). Participants with RA showed greater increases in MAP and MSNA during exercise and PEI than CON (ΔMAPexercise  = 16 ± 11 vs. 9 ± 6 mmHg, P = 0.03; ΔMAPPEI  = 15 ± 10 vs. 5 ± 5 mmHg, P = 0.001; ΔMSNAexercise  = 17 ± 14 vs. 7 ± 9 bursts min-1 , P = 0.04; ΔMSNAPEI  = 14 ± 10 vs. 6 ± 4 bursts min-1 , P = 0.04). Autonomic responses to exercise showed significant (P < 0.05) association with pro- (i.e. IFN-γ, IL-8, MCP-1 and TNFα) and anti-inflammatory (i.e. IL-1ra and IL-10) cytokines and with pain. In conclusion, post-menopausal women with RA showed augmented pressor and sympathetic responses to exercise and to the activation of muscle metaboreflex. These findings provide mechanistic insights that may explain the abnormal cardiovascular responses to exercise in RA.

A randomized controlled trial to reduce sedentary time in rheumatoid arthritis: protocol and rationale of the Take a STAND for Health study.

BACKGROUND: Patients with rheumatoid arthritis spend most of their daily hours in sedentary behavior (sitting), a predisposing factor to poor health-related outcomes and all-cause mortality. Interventions focused on reducing sedentary time could be of novel therapeutic relevance. However, studies addressing this topic remain scarce. We aim to investigate the feasibility and efficacy of a newly developed intervention focused on reducing sedentary time, and potential clinical, physiological, metabolic and molecular effects in rheumatoid arthritis. METHODS: The Take a STAND for Health study is a 4-month, parallel-group, randomized controlled trial, in which postmenopausal patients with rheumatoid arthritis will set individually tailored, progressive goals to replace their sedentary time with standing and light-intensity activities. Patients will be recruited from the Clinical Hospital (School of Medicine, University of Sao Paulo) and will be assessed at baseline and after a 4-month follow up. Outcomes will include objectively measured sedentary behavior (primary outcome) and physical activity levels, clinical parameters, anthropometric parameters and body composition; aerobic fitness, muscle function, blood pressure, cardiovascular autonomic function, vascular function and structure, health-related quality of life, and food intake. Blood and muscle samples will be collected for assessing potential mechanisms, through targeted and non-targeted approaches. DISCUSSION: Findings will be of scientific and clinical relevance with the potential to inform new prescriptions focused on reducing sedentary behavior, a modifiable risk factor that thus far has been overlooked in patients with rheumatoid arthritis. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03186924. Registered on 14 June 2017.

Ultra-processed food consumption associates with higher cardiovascular risk in rheumatoid arthritis.

To investigate the association between food consumption stratified by processing level and cardiovascular risk factors in rheumatoid arthritis. In this cross-sectional study, 56 patients (age: 62.5 ± 7.9 years, BMI: 28.4 ± 5.1 kg/m2) had food consumption evaluated according to the processing level (e.g., unprocessed or minimally processed foods, processed foods, and ultra-processed foods) and associated with cardiovascular risk factors. The most prevalent food processing level was unprocessed or minimally processed foods (42.6 ± 12.6% of total energy intake [TEI]), followed by processed (24.2 ± 11.9%TEI), ultra-processed (18.1 ± 11.8%TEI), and culinary ingredients (15.1 ± 6.4%TEI). Adjusted regression models showed that higher consumption of ultra-processed foods was positively associated with Framingham risk score (ß = 0.06, CI: 95% 0.001, 0.11, p = 0.045) and glycated hemoglobin (ß = 0.04, CI: 95% 0.01, 0.08, p = 0.021). In contrast, higher consumption of unprocessed or minimally processed foods was associated with lower 10-year risk of developing cardiovascular diseases (ß = -0.05, CI: 95% - 0.09, -0.003, p = 0.021) and LDL (ß = -1.09, CI: 95% - 1.94, -0.24, p = 0.013). Patients with rheumatoid arthritis consuming more ultra-processed foods showed worse metabolic profile, whereas those consuming more unprocessed or minimally processed foods had lower cardiovascular risks. A food pattern characterized by a high ultra-processed food consumption appears to emerge as a novel, modifiable risk factor for cardiovascular diseases in rheumatoid arthritis. Key-Points • Higher ultra-processed food consumption was associated with worse metabolic profile and increased cardiovascular risk, whereas higher unprocessed or minimally processed food consumption was associated with lower 10-year risk of developing cardiovascular diseases. • A food pattern characterized by a high ultra-processed food consumption appears to emerge as a novel, modifiable risk factor for cardiovascular diseases in rheumatoid arthritis.

"I put it in my head that the supplement would help me": Open-placebo improves exercise performance in female cyclists.

This study investigated the effect of open-placebo on cycling time-trial (TT) performance. Twenty-eight trained female cyclists completed a 1-km cycling TT following a control session or an open-placebo intervention. The intervention consisted of an individual presentation, provided by a medic, in which the concept of open-placebo was explained to the participant, before she ingested two red and white capsules containing flour; 15 min later, they performed the TT. In the control session, the participant sat quietly for 20 min. Heart rate and ratings of perceived exertion (RPE) were monitored throughout exercise, while blood lactate was determined pre- and post-exercise. Post-exercise questionnaires were employed to gain insight into the perceived influence of the supplement on performance. Open-placebo improved time-to-completion (P = 0.039, 103.6±5.0 vs. 104.4±5.1 s, -0.7±1.8 s, -0.7±1.7%) and mean power output (P = 0.01, 244.8±34.7 vs. 239.7±33.2, +5.1±9.5 W) during the TT. Individual data analysis showed that 11 individuals improved, 13 remained unchanged and 4 worsened their performance with open-placebo. Heart rate, RPE and blood lactate were not different between sessions (all P>0.05). Positive expectation did not appear necessary to induce performance improvements, suggesting unconscious processes occurred, although a lack of an improvement appeared to be associated with a lack of belief. Open-placebo improved 1-km cycling TT performance in trained female cyclists. Although the intervention was successful for some individuals, individual variation was high, and some athletes did not respond or even performed worse. Thus, open-placebo interventions should be carefully considered by coaches and practitioners, while further studies are warranted.

Exercise-induced anti-inflammatory effects in overweight/obese women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is characterized by exacerbated inflammation, which is implicated in cardiometabolic dysfunction. This study aimed to examine the potential effects of acute exercise on inflammatory responses in obese/overweight PCOS women and their controls. Participants underwent a single bout of moderate-intensity aerobic exercise (30 min at ∼65% of VO2peak). Blood and muscle samples were collected immediately before (PRE) and 60 min after the exercise session. Cytokines (i.e., IL-1ß, IL-6, IL-4, IL-10, TNF-α) were measured both in plasma and in skeletal muscle, and proteins related to inflammatory signaling (IKKα/ß and JNK) were assessed in skeletal muscle. At PRE, PCOS showed elevated muscle TNF-α (+62%, p = 0.0012) and plasma IL-1ß (+76%, p = 0.0010) compared to controls. In PCOS, exercise decreased plasma and muscle TNF-α (-14%, p = 0.0003 and -46%, p = 0.0003), as well as increased plasma and muscle IL-4 (+147%, p = 0.0018 and +62%, p = 0.0474) and plasma IL-10 (+38%, p = 0.0029). Additionally, IKKα/ß and JNK phosphorylation in skeletal muscle, which was higher in PCOS at PRE, was significantly reduced by exercise (-58%, p < 0.0001 and -46%, p < 0.0001, respectively), approaching control levels. Person's correlations between PRE values and delta changes (i.e., exercise effect) showed significant, negative associations for plasma IL-1ß (r = -0.92, p < 0.0001), TNF-α (r = -0.72, p = 0.0100) and IL-6 (r = -0.58, p = 0.05), and muscle TNF-α (r = -0.95, p < 0.0001), IKKα/ß (r = -0.75, p = 0.005), and JNK (r = -0.94, p < 0.0001) in PCOS. In conclusion, exercise can mitigate the inflammatory milieu in women with PCOS. The anti-inflammatory role of exercise could underlie its cardiometabolic protection in PCOS.

Feasibility, safety and efficacy of exercise training in immune-mediated necrotising myopathies: a quasi-experimental prospective study.

OBJECTIVES: To evaluate the feasibility, safety and efficacy of exercise training in patients with immune-mediated necrotising myopathies (IMNM). METHODS: Eight consecutive sedentary patients with IMNM (5 anti-signal recognition particle and 3 anti-hydroxy-methyl-glutaryl coenzyme A reductase) were engaged in this study. Disease status was based on International Myositis Assessment and Clinical Studies Group (IMACS) core set measures. Physical performance was evaluated by cardiopulmonary exercise test, repetition maximum (RM) protocol, handgrip dynamometry, sit-to-stand (STS) and timed up-and-go (TUG) tests. All these parameters were measured at baseline and after a 12-week, twice-a-week, supervised exercise training comprising aerobic and strength exercises. RESULTS: Patients (aged 61 years on average) were very disabled at the beginning of the disease (mean duration of 17.7 months), but after being aggressively treated with a treat-to-target approach, they presented only mild symptoms that were well-controlled with oral immunosuppression and low disease status scores by the time of the exercise intervention. No disease relapsing, worsening of the IMACS set scores or adverse events were observed throughout the training period. Patients also increased aerobic capacity (e.g. time to achieve anaerobic threshold and time to achieve exhaustion), muscle strength (e.g. 1RM bench press) and function (e.g. STS test). CONCLUSIONS: Supervised exercise training did not impair disease status and seemed to be feasible, safe and effective in patients with IMNM. Moreover, exercise training increased aerobic capacity, muscle strength and function, suggesting that this could be a novel potential coadjuvant therapy in IMNM.

Aerobic training modulates salience network and default mode network metabolism in subjects with mild cognitive impairment.

Aerobic training (AT) is a promising intervention to improve cognitive functioning. However, its modulatory effects on brain networks are not yet entirely understood. Sixty-five subjects with mild cognitive impairment performed a moderate intensity, 24-week AT program. Differences in resting regional brain glucose metabolism (rBGM) with FDG-PET were assessed before and after AT on a voxel-by-voxel basis. Structural equation modeling was used to create latent variables based on regions with significant rBGM changes and to test a hypothetical model about the inter-relationships between these changes. There were significant rBGM reductions in both anterior temporal lobes (ATL), left inferior frontal gyrus, left anterior cingulate cortex, right hippocampus, left meddle frontal gyrus and bilateral caudate nuclei. In contrast, there was an increase in rBGM in the right precuneus and left inferior frontal gyrus. Latent variables reflecting the salience network and ATL were created, while the precuneus represented the default mode network. In the model, salience network rBGM was decreased after AT. In contrast, rBGM in the default mode network increased as a final outcome. This result suggested improved salience network efficacy and increased control over other brain functional networks. The ATL network decreased its rBGM and connected to the salience network and default mode network with positive and negative correlations, respectively. The model fit values reached statistical significance, demonstrating that this model explained the variance in the measured data. In mild cognitive impairment subjects, AT modulated rBGM in salience network and default mode network nodes. Such changes were in the direction of the normally expected resting-state metabolic patterns of these networks.

Effects of a new intervention based on the Health at Every Size approach for the management of obesity: The "Health and Wellness in Obesity" study.

Health at Every Size® (HAES®) is a weight-neutral approach focused on promoting healthy behaviors in people with different body sizes. This study examined multiple physiological, attitudinal, nutritional, and behavioral effects of a newly developed, intensive, interdisciplinary HAES®-based intervention in obese women. This was a prospective, seven-month, randomized (2:1), controlled, mixed-method clinical trial. The intervention group (I-HAES®; n = 39) took part in an intensified HAES®-based intervention comprising a physical activity program, nutrition counseling sessions, and philosophical workshops. The control group (CTRL; n = 19) underwent a traditional HAES®-based intervention. Before and after the interventions, participants were assessed for physiological, psychological, and behavioral parameters (quantitative data) and took part in focus groups (qualitative data). Body weight, body mass index, and waist and hip circumferences did not significantly differ within or between groups (P > 0.05). I-HAES® showed increased peak oxygen uptake and improved performance in the timed-stand test (P = 0.004 and P = 0.004, between-group comparisons). No significant within- or between-group differences were observed for objectively measured physical activity levels, even though the majority of the I-HAES® participants indicated that they were engaged in or had plans to include physical activity in their routines. I-HAES® resulted in improvements in eating attitudes and practices. The I-HAES® group showed significantly improved all Body Attitude Questionnaire subscale and all Figure Rating Scale scores (P ≤ 0.05 for all parameters, within-group comparisons), whereas the CTRL group showed slight or no changes. Both groups had significant improvements in health-related quality of life parameters, although the I-HAES® group had superior gains in the "physical health," "psychological health," and "overall perception of quality of life and health" (P = 0.05, 0.03, and 0.02, respectively, between-group comparisons) domains. Finally, most of the quantitative improvements were explained by qualitative data. Our results show that this new intensified HAES®-based intervention improved participants' eating attitudes and practices, perception of body image, physical capacity, and health-related quality of life despite the lack of changes in body weight and physical activity levels, showing that our novel approach was superior to a traditional HAES®-based program.

Exercise Increases Insulin Sensitivity and Skeletal Muscle AMPK Expression in Systemic Lupus Erythematosus: A Randomized Controlled Trial.

Systemic lupus erythematosus (SLE) patients may show increased insulin resistance (IR) when compared with their healthy peers. Exercise training has been shown to improve insulin sensitivity in other insulin-resistant populations, but it has never been tested in SLE. Therefore, the aim of the present study was to assess the efficacy of a moderate-intensity exercise training program on insulin sensitivity and potential underlying mechanisms in SLE patients with mild/inactive disease. A 12-week, randomized controlled trial was conducted. Nineteen SLE patients were randomly assigned into two groups: trained (SLE-TR, n = 9) and non-trained (SLE-NT, n = 10). Before and after 12 weeks of the exercise training program, patients underwent a meal test (MT), from which surrogates of insulin sensitivity and beta-cell function were determined. Muscle biopsies were performed after the MT for the assessment of total and membrane GLUT4 and proteins related to insulin signaling [Akt and AMP-activated protein kinase (AMPK)]. SLE-TR showed, when compared with SLE-NT, significant decreases in fasting insulin [-39 vs. +14%, p = 0.009, effect size (ES) = -1.0] and in the insulin response to MT (-23 vs. +21%, p = 0.007, ES = -1.1), homeostasis model assessment IR (-30 vs. +15%, p = 0.005, ES = -1.1), a tendency toward decreased proinsulin response to MT (-19 vs. +6%, p = 0.07, ES = -0.9) and increased glucagon response to MT (+3 vs. -3%, p = 0.09, ES = 0.6), and significant increases in the Matsuda index (+66 vs. -31%, p = 0.004, ES = 0.9) and fasting glucagon (+4 vs. -8%, p = 0.03, ES = 0.7). No significant differences between SLT-TR and SLT-NT were observed in fasting glucose, glucose response to MT, and insulinogenic index (all p > 0.05). SLE-TR showed a significant increase in AMPK Thr 172 phosphorylation when compared to SLE-NT (+73 vs. -12%, p = 0.014, ES = 1.3), whereas no significant differences between groups were observed in Akt Ser 473 phosphorylation, total and membrane GLUT4 expression, and GLUT4 translocation (all p > 0.05). In conclusion, a 12-week moderate-intensity aerobic exercise training program improved insulin sensitivity in SLE patients with mild/inactive disease. This effect appears to be partially mediated by the increased insulin-stimulated skeletal muscle AMPK phosphorylation. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT01515163.