Effects of a remotely supervised resistance training program on muscle strength and body composition in adults with cystic fibrosis: Randomized controlled trial.

INTRODUCTION: Among the limited studies on physical exercise interventions in adults with cystic fibrosis (CF), few have specifically addressed the improvement of peripheral muscle strength and body fat-free mass. The aim of this study was to examine the impacts of a remotely supervised, individualized 8-week resistance training program of moderate to high intensity on strength and body composition in these subjects. METHODS: This was a randomized controlled trial performed in adults with CF. The exercise group (EX) performed three 1-h resistance training sessions per week over 8 weeks. The control group (CON) followed the physical activity recommendations of their physician. The main outcomes were muscle strength and body composition, with secondary measures including pulmonary function and quality of life. Two-way repeated measures analysis was used. RESULTS: In 23 participants (age 32.13 ± 7.72 years), the intervention showed a significant beneficial effect on leg press strength, with a large effect size, both in absolute (p = 0.011; η p 2 $$ {\eta}_{\mathrm{p}}^2 $$ = 0.281) and relative (p = 0.007; η p 2 $$ {\eta}_{\mathrm{p}}^2 $$ = 0.310) terms. Large intervention effects were observed on total fat mass (p < 0.001; η p 2 $$ {\eta}_{\mathrm{p}}^2 $$ = 0.415), body adiposity index (p < 0.001; η p 2 $$ {\eta}_{\mathrm{p}}^2 $$ = 0.436), and fat mass index (p < 0.001; η p 2 $$ {\eta}_{\mathrm{p}}^2 $$ = 0.445), all showing reduction in the EX group. In addition, significant large size effects were detected on total fat-free mass (p = 0.046; η p 2 $$ {\eta}_{\mathrm{p}}^2 $$ = 0.177), trunk fat-free mass (p = 0.039; η p 2 $$ {\eta}_{\mathrm{p}}^2 $$ = 0.188), and fat-free mass index (p = 0.048; η p 2 $$ {\eta}_{\mathrm{p}}^2 $$ = 0.174), all favoring exercise. No significant effects were observed on pulmonary function and quality of life. CONCLUSIONS: An 8-week remotely supervised resistance training program, with moderate to high intensity, effectively improved lower limb muscle strength and body composition.

Effects and safety of hypertonic saline combined with airway clearance in non-hospitalized children with recurrent wheezing.

Background: The International Study of Wheezing in Infants defines recurrent wheezing as the presence of three or more medically documented episodes of wheezing within one year. To date, there is no evidence on the use of hypertonic saline (HS) combined with airway clearance techniques (ACT) for children with recurrent wheezing treated in an outpatient setting. Therefore, this is the first study to explore the use of such interventions in infants with recurrent wheezing. Objectives: To evaluate the effects and safety of a three-month protocol including HS and ACT for non-hospitalized infants with recurrent wheezing. Methods: Randomized, double-blind, controlled trial, including outpatient infants with recurrent wheezing. Children were randomized to either 3% HS or 0.9% saline groups and were treated with bronchodilator and nebulized with the respective solutions before ACT. The primary outcome was the Wang score. Secondary outcomes included the number of hospitalizations and respiratory crisis, need for rescue medication, and school absences. All variables were measured during the three previous months from inclusion and during intervention period. The study protocol was registered at ClinicalTrials.gov (NCT04331496) on March, 31, 2020. Results: Forty children were included. Regarding immediate effects, significant differences (p<0.001) were found for time, but not for group or interaction (group × time), in all outcome variables (increase in SpO2, decrease in heart and respiratory rate, wheezing episodes, retraction, and Wang score). Comparing the previous three months with the study period, there were significant differences in both groups for the severity of crisis (p<0.001) and medication steps (p=0.002). Conclusion: A three-month protocol including HS and ACT for outpatient infants with recurrent wheezing was safe and reduced morbidity. No differences were found between the use of HS and 0.9% saline.

Octyl gallate decrease lymphocyte activation and regulates neutrophil extracellular traps release.

BACKGROUND: Inflammation is a complex mechanism with an objective to destroy and eliminate the invading microorganisms. During acute inflammation, the neutrophils are the major cells involved in this process and, although they defend the organism, must die to not generate damage. The two major mechanisms that drive neutrophils to death are: apoptosis and a novel mechanism recently discovered denominated NETosis. This process is a "suicidal mechanism", in which the cells release "neutrophil extracellular traps" (NETs) during the inflammatory response. Octyl gallate (OG) is one of the gallic acid derivates, with several protective effects, such as antioxidant and anti-inflammatory in cancer models. Thus, this study aimed to investigate the action of OG on the proliferation of lymphocytes, neutrophils activation, and its effectiveness in an experimental sepsis model. METHODS: Lymphocytes and neutrophils were obtained from healthy donors. Cell viability, apoptosis, NETs release and antioxidant capacity of OG were observed. In addition, survival was evaluated in an experimental model of sepsis in C57BL/6 mice. RESULTS: Our study demonstrated, for the first time, that the OG can act as an inhibitor of reactive oxygen species (ROS) release, NETs formation in primary human neutrophils and, modulates the lipopolysaccharide (LPS) effect in neutrophil apoptosis. The OG also inhibited peripheral blood mononuclear cells (PBMCs) proliferation in vitro. Despite the positive results, we did not observe an increase in the survival of septic animals. CONCLUSIONS: The pharmacological potential of OG, modulating activation of neutrophils and lymphocytes, suggests the use as an adjuvant therapeutic strategy in inflammatory diseases.

Determinants of exercise capacity in children and adolescents with severe therapy-resistant asthma.

OBJECTIVE: To evaluate the exercise capacity of children and adolescents with severe therapy resistant asthma (STRA) aiming to identify its main determinants. METHODS: Cross-sectional study including individuals aged 6-18 years with a diagnosis of STRA. Clinical (age and gender), anthropometric (weight, height and body mass index) and disease control data were collected. Lung function (spirometry), cardiopulmonary exercise testing (CPET) and exercise-induced bronchoconstriction (EIB) test were performed. RESULTS: Twenty-four patients aged 11.5 ± 2.6 years were included. The mean forced expiratory volume in one second (FEV1) was 91.3 ± 9.2%. EIB occurred in 54.2% of patients. In CPET, the peak oxygen uptake (VO2peak) was 34.1 ± 7.8 mL kg-1 min-1. A significant correlation between ventilatory reserve and FEV1 (r = 0.57; p = 0.003) was found. Similarly, there was a significant correlation between CPET and percent of FEV1 fall in the EIB test for both VE/VO2 (r = 0.47; p = 0.02) and VE/VCO2 (r = 0.46; p = 0.02). Patients with FEV1<80% had lower ventilatory reserve (p = 0.009). In addition, resting heart rate correlated with VO2peak (r=-0.40; p = 0.04), VE/VO2 (r = 0.46; p = 0.02) and VE/VCO2 (r = 0.48; p = 0.01). CONCLUSIONS: Exercise capacity is impaired in approximately 30% of children and adolescents with STRA. The results indicate that different aspects of aerobic fitness are influenced by distinct determinants, including lung function and EIB.

Impact of maternal physical exercise on inflammatory and hypothalamic-pituitary-adrenal axis markers in the brain and lungs of prenatally stressed neonatal mice.

This study aimed to evaluate the effects of maternal exercise on alterations induced by prenatal stress in markers of the inflammatory process and the hypothalamic-pituitary-adrenal axis in the brain and lungs of neonatal mice. Female Balb/c mice were divided into three groups: control, prenatal restraint stress, prenatal restraint stress and physical exercise before and during the gestational period. On day 0 (PND0) and 10 (PND10), mice were euthanized for brain and lung analyses. The gene expression of GR, MR, IL-6, IL-10, and TNF in the brain and lungs and the protein expression of MMP-2 in the lungs were analyzed. Maternal exercise reduced IL-6 and IL-10 gene expression in the brain of PND0 mice. Prenatal stress and maternal exercise decreased GR, MR, IL-6, and TNF gene expression in the lungs of PND0 mice. In the hippocampus of PND10 females, exercise inhibited the effects of prenatal stress on the expression of MR, IL-6, and IL-10. In the lungs of PND10 females, exercise prevented the decrease in GR expression caused by prenatal stress. In the hippocampus and lungs of PND10 males, prenatal stress decreased GR gene expression. Our findings confirm the effects induced by prenatal stress and demonstrate that physical exercise before and during the gestational period may have a protective role on inflammatory changes.

Effects of Physical Training on Heart Rate Variability in Children and Adolescents with Chronic Diseases: A Systematic Review and Meta-analysis.

This study analyzed the effects of physical training programs on heart rate variability, as a measure of sympathovagal balance, in children and adolescents with chronic diseases. Relevant articles were systematically searched in Pubmed, Science Direct, Web of Science, Scopus, Google Scholar and Embase scientific databases. We performed a meta-analysis using an inverse variance heterogeneity model. Effect size calculation was based on the standardized mean differences between pre- and post-intervention assessments, assuring at least a single-group repeated-measures model for each extracted group. Ten studies (252 participants) were included, seven in obese subjects, two in type-1 diabetes, and one in cerebral palsy. When time-domain variables were analyzed, exercise was found to moderately increase RMSSD (SMD=0.478; 95%CI: 0.227 to 0.729; p<0.001), SDNN (SMD=0.367; 95%CI: 0.139 to 0.595; p=0.002) and pNN50 (SMD=0.817; 95%CI: 0.139 to 0.595; p=0.002). As for frequency-domain variables, exercise presented a moderate increasing effect on HF (SMD=0.512; 95%CI: 0.240 to 0.783; p<0.001), a negligible effect for LF (SMD=0.077; 95%CI: -0.259 to 0.412; p<0.001) and a non-significant reduction for LF/HF (SMD=-0.519; 95%CI: -1.162 to 0.124; p=0.114). In conclusion, physical training programs are able to modulate heart rate variability in children and adolescents with chronic diseases, affecting mainly the time-domain variables.

Heart rate variability, exercise capacity and levels of daily physical activity in children and adolescents with mild-to-moderate cystic fibrosis.

Background: Autonomic nervous system balance is altered in cystic fibrosis (CF), although its influence on physical fitness has been poorly explored. Objective: This study aimed to evaluate the association of heart rate variability (HRV) with exercise capacity and levels of daily physical activity in children and adolescents with mild-to-moderate CF. Methods: A cross-sectional study including individuals with CF aged 6-18 years, not under CFTR modulator therapy, was performed. Sociodemographic (age, sex) and clinical information (airway colonization, pancreatic insufficiency, and genotyping) were collected. In addition, exercise capacity (modified shuttle test - MST), lung function (spirometry), body composition (bioimpedance), levels of daily physical activity (5-day accelerometer), and HRV (both at rest and during the MST) were evaluated. Results: 30 individuals (20 females) aged 11 . 2 ± 3 . 7 years, mean FEV 1 62 . 8 ± 27 . 6 %, were included. A sympathovagal balance (LF/HF) increase ( p < 0 . 001 ) during the MST was shown, indicating a predominance of sympathetic modulation. The standard deviation of all RR intervals (SDNN) and the high frequency (HF) index during exercise correlated significantly with FEV1 ( r = 0 . 45 , p = 0 . 01 and r = 0 . 46 , p = 0 . 01 ; respectively). MST distance also correlated positively and significantly with SDNN ( r = 0 . 43 , p = 0 . 01 ), square root of the mean of the sums of squares of frequencies between RR intervals greater than 50 ms - RMSSD ( r = 0 . 53 , p < 0 . 01 ), low frequency - LF ( r = 0 . 48 , p < 0 . 01 ), HF ( r = 0 . 64 , p < 0 . 01 ), dispersion of points perpendicular to the short-term identity line - SD1 ( r = 0 . 40 , p = 0 . 02 ) and negatively with LF/HF ( r =- 0 . 57 , p < 0 . 01 ). Regarding daily physical activity, SDNN at rest ( r = 0 . 37 , p = 0 . 04 ) and exercise ( r = 0 . 41 , p = 0 . 02 ) showed positive correlations with time in moderate-to-vigorous activities. When normalizing the SDNN and classifying individuals as normal or altered, those presenting altered SDNN showed poorest FEV1 ( p = 0 . 001 ) and lower exercise capacity ( p = 0 . 027 ). Conclusion: HRV correlates with lung function, exercise capacity and levels of daily physical activity in children and adolescents with CF. The study highlights the influence of CF on autonomic function and suggests HRV measurement as an easy tool to be used in clinical settings as an alternative marker to monitor CF individuals.

Aerobic fitness is associated with extracellular DNA levels in the sputum of patients with cystic fibrosis.

AIMS: Patients with cystic fibrosis (CF) develop with progressive loss of lung function and aerobic fitness. However, the precise mechanisms of exercise intolerance are still controversial and appear to be influenced by several factors. This study aimed to evaluate the association of aerobic fitness with free DNA levels in the sputum of patients with CF. METHODS: This cross-sectional study included patients with CF older than 6 years, free from active exacerbations, but who were able to produce spontaneously expectorated sputum. Extracellular DNA in the sputum was quantified. Lung function (spirometry) and aerobic fitness (cardiopulmonary exercise testing [CPET]) were performed. In addition, demographic, anthropometric and clinical data were collected. RESULTS: Sixteen patients with a mean age of 19.4 ± 6.9 years and mean forced expiratory volume in the first second (FEV1 ) of 51.8 ± 28.1 (% of predicted) were included. Mean peak oxygen consumption (VO2 peak) was 32.8 ± 5.2 mL• kg-1 • min-1 , oxygen saturation at the end of the test was 90.6% ± 6.3% and mean extracellular DNA levels was 305.3 ± 153.6 µg/mL. Individuals with a VO2 peak ≤ 30 mL• kg-1 • min-1 (P = .03) and a SpO2 ≤ 90% at the end of the test (P = .03) had a greater amount of extracellular DNA in the sputum. The proportion of patients with reduced VO2 peak in the group of patients with the lowest concentration of DNA in the sputum (<243 µg/mL) was significantly lower (0% vs 100%; P = .04). CONCLUSION: There is an association between the presence of free DNA in sputum and aerobic fitness in patients with CF.

Peripheral muscle strength is associated with aerobic fitness and use of antibiotics in patients with cystic fibrosis.

AIMS: Individuals with cystic fibrosis (CF) may develop muscle abnormalities, although little is known on its clinical and functional impact. This study aimed to evaluate the association of peripheral muscle strength with aerobic fitness, habitual physical activity, lung function and the use of antibiotics (ATB) in patients with CF. METHODS: A cross-sectional study where individuals aged ≥6 years underwent peripheral muscle strength evaluation (biceps, quadriceps and hamstrings) and performed a cardiopulmonary exercise test. Demographic, anthropometric, genetic, lung function and total days of ATB use within 1 year of tests were also collected. RESULTS: Correlation was found for biceps (r = .45; P = .002) strength with the peak oxygen consumption (VO2 peak). Muscle strength (biceps and quadriceps) also correlated with the ventilatory equivalent for oxygen consumption (VE /VO2 ) at anaerobic threshold (AT) and with the ventilatory equivalent for carbon dioxide production (VE /VCO2 ) both at AT and peak exercise. Negative correlations were found for quadriceps (r = -.39) and hamstrings (r = -.42) with the total days of ATB use in the following year. Patients needing to use ATB presented lower biceps strength (P = .05) and individuals with VO2 peak lower than 37 mL·kg-1 ·min-1 presented lower muscle strength for both biceps (P = .01) and quadriceps (P = .02). CONCLUSIONS: The results have shown that peripheral muscle strength is associated with aerobic fitness and the use of antibiotics in patients with CF.

Anti-inflammatory effect of octyl gallate in alveolar macrophages cells and mice with acute lung injury.

Acute lung injury (ALI) is an inflammatory process, and has high incidence and mortality. ALI and the acute respiratory distress syndrome are two common complications worldwide that result in acute lung failure, sepsis, and death. Pro-inflammatory substances, such as cytokines and chemokines, are responsible for activating the body's defense mechanisms and usually mediate inflammatory processes. Therefore, the research of substances that decrease the uncontrolled response of organism is seen as potential for patients with ALI. Octyl gallate (OG) is a phenolic compound with therapeutic actions namely antimicrobial, antiviral, and antifungal. In this study, we evaluated its action on lipopolysaccharide (LPS)-activated alveolar macrophages RAW 264.7 cells and ALI in male mice. Our results demonstrated protective effects of OG in alveolar macrophages activated with LPS and mice with ALI. The OG treatment significantly decreased the inflammatory markers in both studies in vitro and in vivo. The data suggested that OG can act as an anti-inflammatory agent for ALI.

CPBMF65, a synthetic human uridine phosphorylase-1 inhibitor, reduces HepG2 cell proliferation through cell cycle arrest and senescence.

Hepatocellular carcinoma (HCC) is the most prevalent type of tumor among primary liver tumors and is the second highest cause of cancer-related deaths worldwide. Current therapies are controversial, and more research is needed to identify effective treatments. A new synthetic compound, potassium 5-cyano-4-methyl-6-oxo-1,6-dihydropyridine-2-olate (CPBMF65), is a potent inhibitor of the human uridine phosphorylase-1 (hUP1) enzyme, which controls the cell concentration of uridine (Urd). Urd is a natural pyrimidine nucleoside involved in cellular processes, such as RNA synthesis. In addition, it is considered a promising biochemical modulator, as it may reduce the toxicity caused by chemotherapeutics without impairing its anti-tumor activity. Thus, the objective of this study is to evaluate the effects of CPBMF65 on the proliferation of the human hepatocellular carcinoma cell line (HepG2). Cell proliferation, cytotoxicity, apoptosis, senescence, autophagy, intracellular Urd levels, cell cycle arrest, and drug resistance were analyzed. Results demonstrate that, after incubation with CPBMF65, HepG2 cell proliferation decreased, mainly through cell cycle arrest and senescence, increasing the levels of intracellular Urd and maintaining cell proliferation reduced during chronic treatment. In conclusion, results show, for the first time, the ability of a hUP1 inhibitor (CPBMF65) to reduce HepG2 cell proliferation through cell cycle arrest and senescence.

Maternal separation induces long-term oxidative stress alterations and increases anxiety-like behavior of male Balb/cJ mice.

Early life stress (ELS) exposure is a well-known risk factor for the development of psychiatric conditions, including anxiety disorder. Preclinical studies show that maternal separation (MS), a classical model of ELS, causes hypothalamic-pituitary-adrenal (HPA) axis alterations, a key contributor to the stress response modulation. Given that HPA axis activation has been shown to induce oxidative stress, it is possible to hypothesize that oxidative stress mediates the relationship between chronic ELS exposure and the development of several disorders. Here, we investigate the effects of MS in the oxidative status [plasma and brain reduced glutathione, catalase and thiobarbituric acid reactive substances (TBARS)], metabolism (glucose, triglycerides and cholesterol) and anxiety-like behaviors in adult Balb/cJ mice. In short, we found that MS increased anxiety-like behaviors in the open field, light/dark test but not in the elevated-plus maze. Animals also presented increased circulating cholesterol, increased TBARS in the plasma and decreased catalase in the hippocampus. Our findings suggest that MS induces long-term alterations in oxidative stress and increased anxiety-like behaviors.

Metabolic dysfunction in a rat model of early-life scarcity-adversity: Modulatory role of cafeteria diet.

NEW FINDINGS: What is the central question of this study? Early-life adversity is associated with increased risk for obesity and metabolic dysfunction. However, it is unclear whether obesity and metabolic dysfunction result from coping strategies to deal with adversity-related emotional dysregulation, a direct programming of systems regulating metabolic function, or a combination of both. What is the main finding and its importance? Early-life adversity increases vulnerability to later-life obesity and metabolic dysfunction, indicating that genetics and adult lifestyle are not the only determinants of obesity and related metabolic dysfunction. Moreover, consumption of cafeteria diet exacerbated metabolic dysfunction associated with early-life adversity, suggesting that poor dietary choices might have a bigger impact in the context of early-life adversity. ABSTRACT: Early-life adversity has become recognized as an important factor contributing to adult obesity and associated metabolic dysfunction. However, it is unclear whether obesity and metabolic dysfunction associated with early-life adversity result from coping strategies to deal with adversity-related emotional dysregulation, a direct programming of systems regulating metabolic function, or a combination. Interestingly, both early-life adversity and later-life dietary choices affect immune function, favouring pro-inflammatory mechanisms that are associated with obesity-related metabolic dysfunction. To investigate the unique and/or interactive effects of early-life adversity and later-life dietary choices for increased vulnerability to obesity and metabolic dysfunction, and specifically the role of the immune system in this vulnerability, we combined a naturalistic rat model of early-life scarcity-adversity with a rat model of obesity, the cafeteria diet. Our results indicate that early-life adversity alone induces insulin resistance, reduces pancreatic insulin secretion, plasma concentrations of triglycerides and cholesterol, and increases fasting glucose and tumour necrosis factor-α plasma concentrations. Importantly, animals exposed to adverse rearing were more vulnerable to metabolic dysregulation associated with the cafeteria diet, given that they consumed more energy, showed more severe hepatic steatosis and increased concentrations of the pro-inflammatory cytokine interleukin-1ß than normally reared animals fed the cafeteria diet. Together, our results suggest that early-life adversity negatively programmes physiological systems that regulate metabolic function and increases vulnerability to obesity and metabolic dysfunction in adulthood. These results highlight the intrinsic relationship between the quality of the early postnatal environment and later-life dietary choices on adult health outcomes.

Mesenchymal stem cells improves survival in LPS-induced acute lung injury acting through inhibition of NETs formation.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are syndromes of acute hypoxemic respiratory failure resulting from a variety of direct and indirect injuries to the gas exchange parenchyma of the lungs. During the ALI, we have an increase release of proinflammatory cytokines and high reactive oxygen species (ROS) formation. These factors are responsible for the release and activation of neutrophil-derived proteases and the formation of neutrophil extracellular traps (NETs). The excessive increase in the release of NETs cause damage to lung tissue. Recent studies have studies involving the administration of mesenchymal stem cells (MSCs) for the treatment of experimental ALI has shown promising results. In this way, the objective of our study is to evaluate the ability of MSCs, in a lipopolysaccharide (LPS)-induced ALI model, to reduce inflammation, oxidative damage, and consequently decrease the release of NETs. Mice were submitted lung injury induced by intratracheal instillation of LPS and subsequently treated or not with MSCs. Treatment with MSCs was able to modulate pulmonary inflammation, decrease oxidative damage, and reduce the release of NETs. These benefits from treatment are evident when we observe a significant increase in the survival curve in the treated animals. Our results demonstrate that MSCs treatment is effective for the treatment of ALI. For the first time, it is described that MSCs can reduce the formation of NETs and an experimental model of ALI. This finding is directly related to these cells modulate the inflammatory response and oxidative damage in the course of the pathology.

Inspiratory muscle function in asthmatic and healthy subjects: influence of age, nutrition and physical activity.

OBJECTIVE: To compare inspiratory muscle function (strength and endurance) between asthmatics and healthy controls, and the influence of age, nutritional status and physical activity on them. METHODS: This is a cross-sectional study. Asthmatic and healthy subjects, aged 6 to 18 years old, recruited from two public schools in Southern Brazil were included in the study. Asthmatic subjects were selected using the criteria presented by the International Study on Asthma and Allergies in Children and control subjects based on the absence of respiratory symptoms. Anthropometric data was measured, body mass index calculated and subjects classified as normal weight, overweight or obese. Physical activity levels, maximum inspiratory pressure (MIP) and inspiratory muscle endurance (IME) were also evaluated. RESULTS: A total of 314 participants were included, separated into control group (181) and asthmatics (133), with a total mean age of 11 years. When both groups were compared, there were no significant differences in both MIP and IME. However, when groups were analyzed subdivided in children and adolescents, IME was significantly reduced (p = 0.003) in asthmatic adolescents. Indeed, when groups were also stratified considering the nutritional status, IME showed a reduction in asthmatic adolescents with overweight (p = 0.042) and obesity (p = 0.041) when compared to healthy controls. No effects of physical activity levels between groups were found. CONCLUSIONS: Results demonstrate a reduction in the IME in asthmatic adolescents with overweight and obesity, indicating an association between asthma, nutritional status and respiratory muscle function.

Enhancing reporting through structure: a before and after study on the effectiveness of SPIRIT-based templates to improve the completeness of reporting of randomized controlled trial protocols.

BACKGROUND: Despite the improvements in the completeness of reporting of randomized trial protocols after the publication of the Standard Protocol Items: Recommendations for Interventional Trial (SPIRIT) guidelines, many items remain poorly reported. This study aimed to assess the effectiveness of using SPIRIT-tailored templates for trial protocols to improve the completeness of reporting of the protocols that master's students write as part of their master's theses. METHODS: Before and after experimental study performed at the University Master's Degree in Orthopaedic Manual Physiotherapy of the Universitat Internacional de Catalunya (Barcelona, Spain). While students in the post-intervention period were instructed to use a trial protocol template that was tailored to SPIRIT, students in the pre-intervention period did not use the template. PRIMARY OUTCOME: Difference between the pre- and post-intervention periods in the mean number of adequately reported items (0-10 scale). The outcomes were evaluated independently and in duplicate by two blinded assessors. Students and their supervisors were not aware that they were part of a research project. For the statistical analysis, we used a generalized linear regression model (dependent variable: number of adequately reported items in the protocol; independent variables: intervention period, call, language). RESULTS: Thirty-four trial protocols were included (17, pre-intervention; 17, post-intervention). Protocols produced during the post-intervention period (mean: 8.24; SD: 1.52) were more completely reported than those produced during the pre-intervention period (mean: 6.35; SD: 1.80); adjusted difference: 1.79 (95% CI: 0.58 to 3.00). CONCLUSIONS: SPIRIT-based templates could be used to improve the completeness of reporting of randomized trial protocols.

Feasibility of performing the 3-minute step test with remote supervision in children and adolescents with cystic fibrosis: A comparative study.

Importance: The 3-min step test is a simple option to monitor submaximal exercise capacity, although its use via remote video monitoring has not been investigated in children with cystic fibrosis (CF). Objective: This study aimed to assess the feasibility and reproducibility of performing the 3-min step test with remote supervision. Methods: A cross-sectional study including CF patients (6-18 years) from two CF services were performed. Demographic, anthropometric, clinical, and lung function data were collected and two 3-min step tests were performed: (i) in-person supervision, and (ii) remotely supervised by video monitoring. Before and after the tests, heart rate (HR), oxygen saturation (SpO2), and the Borg score for dyspnea and lower limb fatigue were monitored. Results: Twenty-three patients (10.7 ± 3.7 years) with a mean FEV1 of 89.5% ± 23.2% were included. There were no significant differences between tests, with mean differences (95% confidence intervals) in final HR of -3.3 (-8.9, 2.4), change in HR of -1.9 (-6.1, 2.1), final SpO2 of 0.3 (-0.4, 1.0), and final dyspnea of 0.1 (-0.8, 0.9). The intraclass correlation coefficient was 0.852 (final HR), 0.762 (final SpO2), and 0.775 (final lower limb fatigue). Significant and moderate correlations were found between tests for final HR (r = 0.75), change in HR (r = 0.61), and final SpO2 (r = 0.61). The Bland-Altman analysis showed a mean difference in final SpO2 between tests of 0.3% (limit of agreement -3.0%, 3.5%). Interpretation: Physiological responses between tests were similar, indicating it was feasible to perform the 3-min step test with remote supervision in CF children.

Baccharis anomala DC. extract reduces inflammation and attenuates hepatic fibrosis in vivo by decreasing NF-kB and extracellular matrix compounds.

Baccharis anomala DC. (BA) is a plant species found in the tropical regions of South America and is widely used for its hepatoprotective effects, as well as for the treatment of gastrointestinal diseases. Studies have recently reported its antioxidant and anti-inflammatory potential. BA extract can reverse the activated phenotype of hepatic stellate cells (HSC), which plays a central role in extracellular matrix (ECM) deposition in the development of liver fibrosis. Thus, this study aimed to evaluate the effects of the treatment with BA extract on liver fibrosis in a CCl4-induced liver fibrosis model in BALB/c mice. Methanolic extract was obtained from BA leaves, a gas chromatography/mass spectrometry (GC/MS) to detect the compounds present was performed, and then administered by intraperitoneal injection in Balb/C mice at a concentration of 50 and 100 mg/kg together with the administration of CCl4 for inducing liver fibrosis. After 10 weeks, blood analysis, histopathology, oxidative stress, as well as protein and gene expression in the hepatic tissue were performed. Treatment with BA extract was able to reduce profibrotic markers by reducing the expression of α-SMA and Col-1 proteins, as well as reducing the formation of free radicals and lipid peroxidation. (BA extract showed anti-inflammatory effects in the liver by suppressing NF-kB activation and reducing gene expression of signaling targets (IL-6 and iNOS). The data obtained showed that BA extract has antifibrotic and anti-inflammatory effects.

Impact of asthma on heart rate variability in children and adolescents: Systematic review and meta-analysis.

PURPOSE: Asthma is associated with abnormal autonomic function, and heart rate variability is considered a simple, accurate, and noninvasive tool for monitoring the autonomic system. Thus, the aim of this study was to investigate the impact of asthma on heart rate variability in children and adolescents. METHODS: This systematic review of observational studies and clinical trials evaluated heart rate variability in children and adolescents with asthma compared to healthy controls. The data were extracted independently by two reviewers. The quality of the selected articles was assessed using Agency for Health Care Research and Quality indicators. Random effects meta-analysis was performed for each outcome, with the effect size reported as standardized mean difference. RESULTS: Fifteen studies were included, of which five were classified as having high methodological quality. In the meta-analysis, long-term recording of the standard deviation of all normal-to-normal sinus R-R intervals differed significantly between groups (standardized mean difference [SMD] = -0.46 [95% confidence interval {CI}: -0.79 to -0.14], p < 0.005, I2 = 0%). Moreover, R-R intervals (long-term) were significantly shorter in asthmatic children than controls (SMD = -0.47 [95% CI: -0.68 to -0.25], p < 0.0001, I2 = 0). There were no significant differences between adjacent normal R-R intervals that exceed 50 ms (long-term) and the root mean square of successive differences between normal sinus R-R intervals (short-term). Regarding frequency-domain variables, long-term low frequency measurements differed significantly between groups (SMD = -0.34 [95% CI: -0.58 to -0.10], p < 0.005, I2 = 15%). There were no differences in high frequency measurements or in the ratio between low/high frequency powers (short- or long-term) between groups. CONCLUSION: The results confirm the impact of asthma on heart rate variability in children and adolescents, indicating lower heart rate variability and sympathetic modulation.