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OBJECTIVE: To evaluate the accuracy of the modified Borg scale to estimate lung impairment, measured via FEV1 in children and adolescents with cystic fibrosis. METHODS: This cross-sectional prospective study was conducted with cystic fibrosis patients, 6-18 y old. With the modified Borg scale we evaluated their subjective perceptions of dyspnea before and after submaximal exercises, and its correlation with lung function (spirometry), 6-min walk test (6MWT), and nutritional status according to body mass index. RESULTS: Forty-one patients (mean +/- SD age range 11.1 +/- 4.1 y), were included in the study. The median (and interquartile range) modified Borg scale score after 6MWT was 2 (1-3). The mean percent-of-predicted FEV1 (FEV1%) was 97 +/- 32%. The Z score of the 6MWT distance (6MWTZ) for 61% of the patients was

BACKGROUND: Positive-expiratory-pressure (PEP) therapy uses positive airway pressure generated by a either a fixed-orifice resistor or a threshold resistor. We hypothesized that tubing diameter and length, and the diameter of the PEP bottle's air-escape orifice would impact the PEP pressure delivered to the airway and determine whether the PEP bottle acts as a threshold resistor or a fixed-orifice resistor. METHODS: We designed a model composed of a bottle partially filled with water, a compressed air source, a pneumotachometer, and a manometer, to evaluate the effects of various tubing diameters (range 2-25 mm inner diameter) and lengths (range 20-80 cm long). In the first set of experiments, the PEP bottle had an open top, so there was no pressure other than the atmospheric pressure against the air escaping from the immersed tubing. The distal tip of the tube was 10 cm below the surface of the water (ie, a water-column pressure of 10 cm H(2)O), and we tested flows of 1, 5, 10, 15, 20, and 25 L/min. In the second set of experiments we tested a PEP bottle, the top of which was closed except for an air-escape orifice (4, 6, 8, 9, or 10 mm). RESULTS: With tubing of 2-6 mm inner diameter, the length of the tubing and the flow significantly affected the PEP pressure (ie, the system was not a threshold resistor). With tubing >/= 8 mm inner diameter there were no significant PEP-pressure differences with any of the tubing lengths or flows tested, which indicates a threshold-resistor system. The 4-mm and 6-mm air-escape orifices significantly increased the PEP pressure, whereas the 8 mm air-escape orifice did not increase the PEP pressure. CONCLUSIONS: To obtain a threshold-resistor PEP bottle system (ie, the PEP pressure is generated only by the water-column pressure), the tubing must be >/= 8 mm inner diameter, and the air-escape orifice must be >/= 8 mm. [ABSTRACT FROM AUTHOR]

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 (SpO 2 ), and the Borg score for dyspnea and lower limb fatigue were monitored., Results: Twenty-three patients (10.7 ± 3.7 years) with a mean FEV 1 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 SpO 2 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 SpO 2 ), 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 SpO 2 ( r = 0.61). The Bland-Altman analysis showed a mean difference in final SpO 2 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., Competing Interests: The authors declare no conflict of interest., (© 2024 Chinese Medical Association. Pediatric Investigation published by John Wiley & Sons Australia, Ltd on behalf of Futang Research Center of Pediatric Development.)

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., (© 2024. The Author(s).)

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 CCl 4 -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 CCl 4 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

In pulmonary fibrosis, the proliferation of fibroblasts and their differentiation into myofibroblasts is often caused by tissue damage, such as oxidative damage caused by reactive oxygen species, which leads to progressive rupture and thus destruction of the alveolar architecture, resulting in cell proliferation and tissue remodeling. Bezafibrate (BZF) is an important member of the peroxisome proliferator-activated receptor (PPARs) family agonists, used in clinical practice as antihyperlipidemic. However, the antifibrotic effects of BZF are still poorly studied. The objective of this study was to evaluate the effects of BZF on pulmonary oxidative damage in lung fibroblast cells. MRC-5 cells were treated with hydrogen peroxide (H 2 O 2 ) to induce oxidative stress activation and BZF treatment was administered at the same moment as H 2 O 2 induction. The outcomes evaluated were cell proliferation and cell viability; oxidative stress markers such as reactive oxygen species (ROS), catalase (CAT) levels and thiobarbituric acid reactive substances (TBARS); col-1 and α-SMA mRNA expression and cellular elasticity through Young's modulus analysis evaluated by atomic force microscopy (AFM). The H 2 O 2 -induced oxidative damage decreased the cell viability and increased ROS levels and decreased CAT activity in MRC-5 cells. The expression of α-SMA and the cell stiffness increased in response to H 2 O 2 treatment. Treatment with BZF decreased the MRC-5 cell proliferation, ROS levels, reestablished CAT levels, decreased the mRNA expression of type I collagen protein (col-1) and α-smooth muscle actin (α-SMA), and cellular elasticity even with H 2 O 2 induction. Our results suggest that BZF has a potential protective effect on H2O2-induced oxidative stress. These results are based on an in vitro experiment, derived from a fetal lung cell line and may emerge as a possible new therapy for the treatment of pulmonary fibrosis., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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 SpO 2 , 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., Competing Interests: The authors have no conflicts of interest to disclose., (© 2023, Hong Kong Physiotherapy Association.)

Objective: To compare lung function between adolescents with and without substance use disorder (SUD)., Methods: This was an observational, cross-sectional exploratory study. The sample consisted of 16 adolescents with SUD and 24 age-matched healthy controls. The adolescents in the clinical group were recruited from a psychiatric inpatient unit for detoxification and rehabilitation; their primary diagnosis was SUD related to marijuana, cocaine, or polysubstance use. Questionnaires and pulmonary function tests were applied for clinical evaluation., Results: We found that FVC, FEV1, and their percentages of the predicted values were significantly lower in the adolescents with SUD than in those without. Those differences remained significant after adjustment for BMI and the effects of high levels of physical activity. The largest effect size (Cohen's d = 1.82) was found for FVC as a percentage of the predicted value (FVC%), which was, on average, 17.95% lower in the SUD group. In addition, the years of regular use of smoked substances (tobacco, marijuana, and crack cocaine) correlated negatively with the FVC%., Conclusions: This exploratory study is innovative in that it demonstrates the early consequences of smoked substance use for the lung health of adolescents with SUD.

Introduction: Exercise intolerance is common in chronic airway diseases (CAD), but its mechanisms are still poorly understood. The aim of this study was to evaluate exercise capacity and its association with lung function, ventilatory limitation, and ventilatory efficiency in children and adolescents with cystic fibrosis (CF) and asthma when compared to healthy controls., Methods: Cross-sectional study including patients with mild-to-moderate asthma, CF and healthy children and adolescents. Anthropometric data, lung function (spirometry) and exercise capacity (cardiopulmonary exercise testing) were evaluated. Primary outcomes were peak oxygen consumption (VO 2 peak), forced expiratory volume in 1 s (FEV 1 ), breathing reserve (BR), ventilatory equivalent for oxygen consumption (V E /VO 2 ) and for carbon dioxide production (V E /VCO 2 ), both at the ventilatory threshold (VT 1 ) and peak exercise., Results: Mean age of 147 patients included was 11.8 ± 3.0 years. There were differences between asthmatics and CF children when compared to their healthy peers for anthropometric and lung function measurements. Asthmatics showed lower VO 2 peak when compared to both healthy and CF subjects, although no differences were found between healthy and CF patients. A lower BR was found when CF patients were compared to both healthy and asthmatic. Both CF and asthmatic patients presented higher values for V E /VO 2 and V E /VCO 2 at VT 1 when compared to healthy individuals. For both V E /VO 2 and V E /VCO 2 at peak exercise CF patients presented higher values when compared to their healthy peers., Conclusion: Patients with CF achieved good exercise capacity despite low ventilatory efficiency, low BR, and reduced lung function. However, asthmatics reported reduced cardiorespiratory capacity and normal ventilatory efficiency at peak exercise. These results demonstrate differences in the mechanisms of ventilatory limitation to maximum exercise testing in children and adolescents with CAD., (© 2023 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Objective: To evaluate the impact of COVID-19 social distancing recommendations on nutritional status, pulmonary function, and morbidity in patients with cystic fibrosis (CF)., Methods: A retrospective cohort study including patients older than six years with a diagnosis of CF was performed. Demographic and clinical data, anthropometric measurements, pulmonary function, days of antibiotic use, and length of hospital stay were recorded. Variables were recorded at three time points relative to the baseline for implementation of social distancing measures: T-1 (14 months before implementation), T0 (baseline), and T1 (14 months after implementation). Delta (Δ) was calculated for each period: Δ1 (pre-pandemic T0-T-1) and Δ2 (pandemic T1-T0)., Results: The study included 25 patients, with a mean age of 11.7±4.3 years. The mean forced expiratory volume in the first second (FEV1) was 85.6±23.6%, and body mass index (BMI) was 17.5±3.0 kg/m2. When comparing the two periods (Δ1 and Δ2), there was a significant increase in the FEV1/forced vital capacity (FVC) ratio (p=0.013) and in the forced expiratory flow between 25 and 75% of vital capacity (FEF25-75%) (p=0.037) in the pandemic period. There was also a significant reduction (p=0.005) in the use of antibiotics in the pandemic period compared with the pre-pandemic period. The Δ1 and Δ2 values did not differ significantly for BMI, FEV1, or length of hospital stay., Conclusions: COVID-19 social distancing recommendations had a positive impact (decrease) on morbidity (use of antibiotics) and small airway obstruction (FEF25-75%) in patients with CF.

Background: Whereas pulmonary exacerbations and aerobic fitness play a key role in the prognosis of cystic fibrosis (CF), the use of ventilatory threshold data as markers of exacerbation risk has been scarcely addressed. This study sought to examine the association between aerobic fitness, assessed through ventilatory threshold variables recorded during cardiopulmonary exercise testing (CPET), and the risk of exacerbations in individuals with CF., Methods: Participants of this retrospective cohort study were subjects from 6 y of age. Over a 4-y period, the following data were recorded: lung function indicators, CPET variables, time to first exacerbation and antibiotic use, along with demographic, clinical, and anthropometric data., Results: The mean age of 20 subjects included was 16 ± 5.4 y. Univariate regression analysis revealed that lung function (FEV 1 : Cox hazard ratio [HR] 0.97, P = .03; and forced expiratory flow between 25-75% of vital capacity [FEF 25-75 ]: Cox HR 0.98, P = .036) and aerobic fitness (oxygen consumption [V̇ O 2 ] at ventilatory threshold: Cox HR 0.94, P = .01; and ventilatory equivalent for carbon dioxide [V̇ E /V̇ CO 2 ] at ventilatory threshold: Cox HR 1.13, P = .049) were associated with exacerbation risk, whereas in the multivariate model, only V̇ O 2 at the ventilatory threshold (%max) (Cox HR 0.92, P = .01) had a significant impact on this risk. Consistently, individuals experiencing exacerbation had significantly lower V̇ O 2 values (%max) at the ventilatory threshold ( P = .050) and higher ventilatory equivalent for oxygen consumption (V̇ E /V̇ O 2 ) ( P = .040) and V̇ E /V̇ O 2 ( P = .037) values at the ventilatory threshold. Time to exacerbation was significantly correlated with V̇ O 2 at the ventilatory threshold (r = 0.50, P = .02), V̇ E /V̇ O 2 (r = -0.48, P = .02), and V̇ E /V̇ CO 2 (r = -0.50, P = .02)., Conclusions: Our results suggest an association between CPET variables at the ventilatory threshold and exacerbations. Percentage V̇ O 2 at the ventilatory threshold could serve as a complementary variable to monitor exacerbations in people with CF., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2023 by Daedalus Enterprises.)

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, I 2  = 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, I 2  = 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, I 2  = 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., (© 2023 Wiley Periodicals LLC.)

Coumaric acid is a phenolic compound found in medicinal plants. Its use has been reported in the treatment of inflammatory diseases, prevention of alterations induced by oxidative stress, as well as acetaminophen-induced hepatotoxicity. Thus, this study evaluated coumaric acid as a potential treatment for liver fibrosis. Cell proliferation was assessed by the trypan blue exclusion technique and the cytotoxicity of coumaric acid was performed using an LDH assay. Mechanisms of cell apoptosis were evaluated by flow cytometry. The expression of genes associated with apoptosis, cell cycle control, and fibrosis was assessed by qPCR. The production of lipid droplets was quantified by oil red staining. The experiments performed showed that the treatment with coumaric acid was able to reduce cell proliferation without causing cell cytotoxicity or apoptosis. Coumaric acid was able to inhibit the expression of cyclin D1 and CDK's (CDK2, CDK4, and CDK6), increasing p53 and p21, which could lead to cell cycle arrest. Treatment with coumaric acid was also able to revert the activated phenotype of GRX cells to their quiescent state. Thus, our results suggest that coumaric acid has a potential therapeutic effect against liver fibrosis., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To analyze the lipid profile and cardiovascular risk of overweight and obese adolescents and correlate the findings with anthropometric measurements., Methods: This is a cross-sectional study on overweight and obese adolescents of both sexes (aged 14 to 18 years old). The collected variables were sex, weight, height, age, total cholesterol, triglycerides, High-density lipoprotein (HDL) and low-density lipoprotein (LDL). The Atherogenic Index of Plasma and Castelli Risk Indices I and II were calculated. These indices were classified into cutoff points to stratify cardiovascular risk. The anthropometric profile was evaluated by Z score according to Body Mass Index for age. Significance level was considered as p≤0.05., Results: A total of 146 adolescents participated in the study; the mean age was 16.4±1.1 years and most of them were girls (74.7%) and obese (52.7%). The prevalent dyslipidemias were high triglycerides (47.9%), LDL (26.7%), total cholesterol (37.7%), and low HDL (46.6%). Most adolescents presented increased atherogenic risk according to the Atherogenic Index of Plasma (55.5%); 15.1% presented high cardiovascular risk according to Castelli Risk Index I; and 13.7%, according to Castelli Risk Index II. Boys presented higher values of anthropometric measurements and Castelli Risk Indices I and II in relation to girls - who, conversely, presented higher values of HDL. There was a positive correlation of the Z score with Atherogenic Index of Plasma and a negative correlation with HDL., Conclusions: The adolescents of the study presented high prevalence of cardiovascular and atherogenic risk according to the evaluated indices. In addition, the increased cardiovascular risk was correlated with higher Body Mass Index.

Acute lung injury (ALI) is a disease of high prevalence and is characterized by the excessive production of inflammatory mediators in the lungs of people sick. Inflammation is the major characteristic of ALI and studies report that inhibition of inflammatory cytokines could be an alternative treatment. Statins such as Simvastatin (SV) are known to their use for cholesterol reduction but also for inflammatory and immunoregulatory processes. In this study, we evaluated the effects of SV on LPS-induced alveolar macrophages and in ALI mice model. Our study has demonstrated the protective effects of SV on LPS-activated alveolar macrophages RAW 264.7 and LPS-induced ALI in mice. SV treatment significantly inhibited the alveolar macrophages activation by decreasing the iNOS, IL-1β, and IL-6 gene expression in vitro and in vivo. The treatment also decreased the inflammatory cells migration and the cytokines gene expression. Our findings suggest that SV can act as an anti-inflammatory agent for acute lung injury., Competing Interests: Conflict of interest The authors have no financial relationships or conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., (© 2022 Wiley Periodicals LLC.)

The purpose of the study was to evaluate the association of field test outcomes with peak oxygen uptake (VO 2 peak) in patients with cystic fibrosis (CF) and to describe the main prediction equations available. Data searches were performed in five databases (Pubmed, Embase, LILACs, Scopus and Web of Science) and also in the reference lists of articles included. The following inclusion criteria were used: studies including individuals with CF, presenting both a field test and a cardiopulmonary exercise testing (CPET), and describing a predictive equation or coefficient of correlation/determination. Case studies, abstracts, letters of reply, editorials and duplicate publications were excluded. The methodological quality analysis was performed using the JBI Critical Appraisal Checklist for Analytical Cross-Sectional Studies scale. Protocol registration number: CRD42020148363. Ten studies were eligible. Five equations were found to predict VO 2 peak. Equations derived from the shuttle tests (ST) showed strong correlations with VO 2 peak ( r = 0.79 to 0.95). The six-minute walk test (6MWT) showed moderate associations with VO 2 peak in participants with moderate disease severity ( r = 0.53 to 0.65). Furthermore, patients with lower maximum heart rate on the three-minute step test tended to have a higher percent predicted VO 2 peak ( r = -0.40), and the one-minute sit-to-stand test demonstrated moderate correlations between VO 2 peak and the number of repetitions ( r = 0.52 to 0.66). In conclusion, field test outcomes correlate with oxygen consumption assessed through CPET, although only the ST seems to be valid as a predictor of VO 2 peak in patients with CF.

The present study aimed to evaluate the effects of treadmill maternal exercise on alterations induced by prenatal stress in neonatal mice. Female and male Balb/c mice were divided into five groups: control (CON), prenatal restraint stress (PNS), prenatal restraint stress and physical exercise before pregnancy (PNS + EX1), prenatal restraint stress and physical exercise during pregnancy (PNS + EX2), and prenatal restraint stress and physical exercise before and during pregnancy (PNS + EX3). Exercise was performed using a treadmill, at a speed of 10 m/min, for 60 min, 5 days a week. Maternal behavior was assessed on days 3, 4 and 5 postpartum (PPD). Placental gene expression of glucocorticoid receptor (GR), 11-β-hydroxysteroid dehydrogenase 2 (11β-HSD2), 5-hydroxytryptamine receptor 1A (5HT 1A R), and corticotropin releasing hormone receptor 1 (CRHR1) were analyzed. In neonatal mice, the gene expression of GR, mineralocorticoid receptor (MR), CRHR1, 5HTr1, oxytocin Receptor 1 (OXTr1), tropomyosin related kinase B (TRκB), brain-derived neurotrophic factor exon I (BDNF I), and BDNF IV was analyzed in the brain (PND0) and hippocampus (PND10). Maternal exercise improved (p < 0.05) maternal care. In the placenta, maternal exercise prevented (p < 0.01) the increase in GR expression caused by PNS. In the brain from PND0, exercise before pregnancy prevented (p = 0.002) the decreased CRHR1 expression promoted by PNS. In the hippocampus of PND10 males, PNS decreased (p = 0.0005) GR expression, and exercise before pregnancy prevented (p = 0.003) this effect. In PND10 females, maternal exercise prevented (p < 0.05) the PNS-induced increase in MR expression. PNS + EX2 males showed increased (p < 0.01) BDNF I gene expression and PNS + EX1 females demonstrated increased (p = 0.03) BDNF IV expression. In conclusion, maternal physical exercise may play a role in modulating maternal-fetal health and may contribute to preventing neurodevelopmental changes induced by prenatal stress., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background and Aims: The high consumption of ultra-processed products is a concern because it is positively associated with the incidence of chronic non-communicable diseases, as metabolic syndrome (MetS). The aim is to evaluate the effects of three different interventions to modify lifestyle on the consumption of ultra-processed foods in adults with MetS., Methods and Results: This was a randomized clinical trial, in which the participants were divided into three groups: Standard Intervention (SI), Group Intervention (GI) and Individual Intervention (II). The interventions were carried out over a three-month period and the data was collected in a 24-h food record, taken at the beginning and end of the intervention. The food they ate was classified into four groups according to the degree of processing (unprocessed or minimally processed foods, processed culinary ingredients, processed foods, and ultra-processed foods) in accordance with the NOVA food classification. Seventy adults took part in the study with a mean age of 51.2 ± 6.6 years old; most of whom were female (55.7%). The amount of ultra-processed food consumed by the three groups (SI, GI and II) was significantly reduced (46%, 34%, and 33%, respectively). The amount of processed food consumed only reduced in the II group. The Total Energy Value (TEV) consumed by the SI and II groups decreased., Conclusions: The interventions that were intended to alter lifestyles were able to reduce the amount of ultra-processed food consumed, which can have an impact on the prevention and treatment of MetS., Registration: registered in the Brazilian Registry of Clinical Trials, ReBEC, under number: RBR-9wz5fc., Competing Interests: Declaration of competing interest The authors state that there are no conflicts of interest in this work., (Copyright © 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

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., Competing Interests: The authors have no conflicts of interest to declare, and confirm that this study meets the ethical standards of the journal [42]., (Thieme. All rights reserved.)

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 FEV 1 ( 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 FEV 1 ( 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., Competing Interests: The authors have no conflict of interests to declare., (© 2021, Hong Kong Physiotherapy Association.)

Background: Evidence on resistance-training programs for cystic fibrosis (CF) is limited and the possible benefits of the addition of neuromuscular electrical stimulation (NMES) are unknown. This study aimed to evaluate the effects of a supervised resistance-training program, associated or not with NMES, on muscle strength, aerobic fitness, lung function and quality of life in children with CF presenting mild-to-moderate pulmonary impairment., Methods: This is a randomized controlled trial including CF patients aged between 6 and 17years. Subjects were randomly allocated to control (CON); exercise (EX); or exercise and NMES (EX + NMES) groups, and evaluated at baseline and at the end of an 8-week individualized exercise-program (3 days/week, 60min/session). NMES was applied in the quadriceps and the interscapular region, simultaneously to the exercises. CON group followed the CF team recommendations. The main outcome measures were lung function, cardiorespiratory fitness, functional capacity, quality of life and muscle strength., Results: Twenty-seven patients, aged 12.6 ± 3.0 years, were analyzed. No significant interactions were found for cardiorespiratory fitness. Functional capacity presented significant differences, indicating a better performance in both EX and EX + NMES. No significant changes between groups were seen for quality of life and lung function. As for muscle strength, EX and EX + NMES presented large effect sizes and significant differences, compared to CON, for quadriceps (p = 0.004, η 2 p  = 0.401), pectoral (p = 0.001, η 2 p  = 0.487), dorsal (p = 0.009, η 2 p  = 0.333) and handgrip (p = 0.028, η 2 p  = 0.278)., Conclusion: A resistance exercise-training program led to improvements in muscle strength and functional capacity in CF patients with mild-to-moderate pulmonary impairment. The addition of NMES to the training program resulted in no extra favorable effects., (Copyright © 2022. Published by Elsevier Ltd.)

Inflammatory markers represent important candidates responsible for the altered behavior and physiology observed after stressful experiences. In the maternal brain, the olfactory bulb (OB) is a key constituent of the neural circuit that mediates the reciprocal interaction between mother and infant. This study aimed to investigate the effects of stress during pregnancy on maternal behavior and inflammatory changes in the olfactory bulb of lactating mice. Female Balb/c mice were divided into two groups: control (CT) and restraint stress (RS). Maternal behavior was performed during the first 8 days of life of the offspring. On the 10th day after parturition, corticosterone, gene, and protein expression were assessed. Stress during pregnancy decreased the maternal index at postnatal day 4 and the nuclear factor-κB 1 (NFκB1) gene expression in the OB. Moreover, females from the RS group showed increased interleukin (IL-1β) protein expression. In contrast, stressed females exhibited a decreased tumor necrosis factor (TNF-α) protein expression in the OB. In conclusion, exposure to stress during pregnancy was able to induce specific postnatal effects on maternal behavior and balance of inflammatory mediators in the OB., (© 2021 International Society for Developmental Neuroscience.)

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., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

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 (FEV 1 ) was 91.3 ± 9.2%. EIB occurred in 54.2% of patients. In CPET, the peak oxygen uptake ( V O 2peak ) was 34.1 ± 7.8 mL kg -1  min -1 . A significant correlation between ventilatory reserve and FEV 1 ( r  = 0.57; p  = 0.003) was found. Similarly, there was a significant correlation between CPET and percent of FEV 1 fall in the EIB test for both V E / V O 2 ( r  = 0.47; p  = 0.02) and V E / V CO 2 ( r  = 0.46; p  = 0.02). Patients with FEV 1 <80% had lower ventilatory reserve ( p  = 0.009). In addition, resting heart rate correlated with V O 2peak (r=-0.40; p  = 0.04), V E / V O 2 ( r  = 0.46; p  = 0.02) and V E / V CO 2 ( 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.

Objective/background: Sleep disorders in cystic fibrosis may be present before daytime clinical manifestations, regardless of lung function impairment, affecting quality of life and disease progression. This study investigated the prevalence of obstructive sleep apnea in children and adolescents with cystic fibrosis and preserved lung function or mild impairment, and evaluated its association with clinical variables., Methods: A systematic review with meta-analysis of prevalence was conducted, including observational studies with polysomnographies in patients with cystic fibrosis who presented mean lung function values > 60% predicted. The methodological quality of the studies was analyzed, and a meta-analysis was performed to assess the prevalence of obstructive sleep apnea., Results: Of the 2318 studies identified, 7 were included in the systematic review and 6 in the meta-analysis of prevalence. The confounding factors and strategies identified were the items with greatest weakness in the methodological quality assessment. Most studies were cross-sectional, and sample size ranged from 9 to 67 individuals. The most frequent criterion for defining obstructive sleep apnea was apnea-hypopnea index (AHI) > 1 per hour. The prevalence found ranged from 32.3 to 100% and the pooled prevalence was 65% (I 2  = 53.4%), considering AHI>1, and 52% (I 2  = 89.4%) for AHI>2 per hour. It was not possible to verify the association between obstructive sleep apnea and clinical variables., Conclusions: A high prevalence of obstructive sleep apnea in children and adolescents with cystic fibrosis was found, regardless of age and lung function impairment, reinforcing the importance of investigating sleep-disordered breathing during clinical visits even when lung function is not yet compromised., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Studies have shown interest in nutraceuticals for the prevention of liver diseases. Methoxyeugenol, is a molecule found in foods, such as nutmeg (Myristica fragrans Houtt.) and Brazilian red propolis. These two sources of methoxyeugenol, propolis and nutmeg, are used in folk medicine for the treatment of hepatic and gastrointestinal disorders, although little is known about their effects on the prevention of liver fibrosis. Natural PPAR (Peroxisome proliferator-activated receptor) agonists would represent unique molecules for therapy, considering the lack of therapeutics to treat liver fibrosis in chronic liver disease. Thus, investigation on new alternatives are necessary, including the search for natural compounds from renewable and sustainable sources. Liver fibrosis is a pathological process characterized by an exacerbated cicatricial response in the hepatic tissue, which compromises liver function. Therefore, inhibition of HSC (hepatic stellate cell) activation and hepatocyte damage are considered major strategies for the development of new anti-fibrotic treatments., Aim of the Study: This study aimed to investigate the effects of methoxyeugenol treatment on HSC phenotype modulation in human and murine cells, hepatocyte damage prevention, and protective effects in vivo, in order to evaluate its therapeutic potential for liver fibrosis prevention., Methods: We investigated the effects of methoxyeugenol in (i) in vitro models using human and murine HSC and hepatocytes, and (ii) in vivo models of CCl 4 (carbon tetrachloride) -induced liver fibrosis in mice., Results: We herein report that methoxyeugenol decreases HSC activation through the activation of PPAR-ɣ, ultimately inducing a quiescent phenotype highlighted by an increase in lipid droplets, loss of contraction ability, and a decrease in the proliferative rate and mRNA expression of fibroblast markers. In addition, methoxyeugenol prevented hepatocytes from oxidative stress damage. Moreover, in mice submitted to chronic liver disease through CCl 4 administration, methoxyeugenol decreased the inflammatory profile, liver fibrosis, mRNA expression of fibrotic genes, and the inflammatory pathway signaled by NF-kB (Nuclear factor kappa B)., Conclusion: We propose methoxyeugenol as a novel and potential therapeutic approach to treat chronic liver disease and fibrosis., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Acute viral bronchiolitis (AVB) is associated with significant morbidity and no study has addressed the safety of airway clearance techniques (ACT) for non-hospitalized infants. This study aimed to evaluate the safety of the use of ACT combined with bronchodilator and hypertonic saline in non-hospitalized children with the first episode of AVB., Methods: A quasi-experimental study of infants aged 2-12 months, with a clinical diagnosis of AVB (mild to moderate), was performed. The Wang score, breathing frequency, oxygen saturation (SpO 2 ), heart rate (HR), and the presence of adverse events were evaluated before, 10 and 20 min after the application of a protocol including ACT (nasal irrigation, prolonged slow expiration, and provoked cough), bronchodilator and hypertonic saline inhalation. A total of 265 infants, mean age 6.86±3.01 months, were included., Results: A reduction (p<0.001) in the Wang score and in the breathing frequency as well as an increase in SpO 2 were found. There was also a transient HR increment at 10 min followed by a reduction at 20 min (p<0.05). The proportion of patients presenting with chest retraction and wheezing decreased (p<0.001) after treatment. Most of the children (88.3%) did not experience adverse events. A post-treatment increment (p<0.001) of patients classified as having normal values, as well as a decrease in those with mild and moderate AVB, was found for the Wang score levels., Conclusion: The use of ACT combined with bronchodilator and hypertonic saline was safe, immediately after treatment, for non-hospitalized children with mild to moderate AVB. No clinically important deterioration or adverse events were identified in the follow-up period., Competing Interests: Declarations of Competing interest The authors have no conflict of interest., (Copyright © 2021 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

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 (FEV 1 ) of 51.8 ± 28.1 (% of predicted) were included. Mean peak oxygen consumption (VO 2 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 VO 2 peak ≤ 30 mL• kg -1 • min -1 (P = .03) and a SpO 2 ≤ 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 VO 2 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., (© 2021 John Wiley & Sons Ltd.)

Objective: Chronic neurological disorders (CNDs) generally produce deleterious effects on the musculoskeletal system and can affect physical activity and increase sedentary behavior in children, hindering the execution of training programs and the attainment of a correct dose of exercise. The purpose of this systematic review was to analyze the effect of neuromuscular electrical stimulation (NMES) on skeletal muscle and then on biomechanics of movement, functional mobility, strength, spasticity, muscle architecture, and body composition of children and adolescents with CNDs and chronic diseases., Methods: The search was conducted in April 2020 in PubMed, MEDLINE, Scopus, the Cochrane Library, and Web of Science, without publication period restriction. Publications investigating the effect of NMES on children and adolescents with CNDs and other chronic diseases were independently selected by 2 researchers. One author independently extracted data from the studies selected, and a second author cross-checked., Results: Eighteen studies with 595 participants aged between 3 and 14 years were included. Quality assessment showed that 50% of the studies presented a low risk of bias. The pooled effect of NMES on gross motor functional measure, calculated as a standardized mean difference using a random effects model, was 0.41 (95% CI = 0.19-0.64)., Conclusion: The use of NMES programs for children diagnosed with cerebral palsy, spinal muscular atrophy, and obstetric injury of the brachial plexus was effective in improving muscle strength, biomechanics of movement, and functional mobility., Impact: NMES can be a useful tool to prevent the reduction of mobility that results from CNDs., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To assess the association of sleep disorders with the findings of heart rate variability (HRV) in children and adolescents with cystic fibrosis (CF)., Methods: Cross-sectional study including children and adolescents aged six to 18 years with a clinical diagnosis of CF. Sociodemographic and clinical data were collected. Sleep disorders were evaluated using baseline nocturnal polysomnography. The autonomic nervous system (ANS) was evaluated through resting HRV., Results: A total of 30 individuals (11.2 years) with a mean forced expiratory volume in the first second (FEV1) of 62.7% were included. The respiratory disturbance index presented a median of 2.6 and obstructive sleep apnea syndrome (OSAS) was identified in 30%. In the HRV analysis, a mean standard deviation of all inter-beat (RR) intervals (SDNN) of 60.8±45.9ms was found. There was a significant correlation between the HRV low-frequency/high-frequency (LF/HF) global modulation index and the minimum SpO2 during sleep in patients with FEV1<60% (r=0.71; p=0.02). The prevalence of sleep disorders and HRV abnormalities was higher in individuals with lesser pulmonary function (FEV1<60%)., Conclusions: The results indicate a weak correlation of sleep disorders (minimum SpO2) with HRV parameters (LH/HF) in children and adolescents with CF. When pulmonary function was reduced, a stronger correlation was found, highlighting the influence of disease severity. A high prevalence of ANS disorders, nocturnal hypoxemia, and presence of OSAS was also found.

Objective: Asthma is a chronic disease that may affect physical fitness, although its primary effects on exercise capacity, muscle strength, functionality and lifestyle, in children and adolescents, are still poorly understood. This study aimed to evaluate the differences in cardiorespiratory fitness, muscle strength, lifestyle, lung function, and functionality between asthmatics with exercise symptoms and healthy children. In addition, we have analyzed the association between clinical history and the presence of asthma., Study Design: Cross-sectional study including 71 patients with a diagnosis of asthma and 71 healthy children and adolescents (7-17 years of age). Anthropometric data, clinical history, disease control, lifestyle (KIDMED and physical activity questionnaires), lung function (spirometry), exercise-induced bronchoconstriction test, aerobic fitness (cardiopulmonary exercise test), muscle strength and functionality (timed up and go; timed up and down stairs) were evaluated., Results: Seventy-one patients with asthma (mean age 11.5 ± 2.7) and 71 healthy subjects (mean age 10.7 ± 2.5) were included. All asthmatic children had mild to moderate and stable asthma. EIB occurred in 56.3% of asthmatic children. Lung function was significantly (p < .05) lower in the asthmatic group when compared to healthy peers, as well as the cardiorespiratory fitness, muscle strength, lifestyle and functionality. Moreover, asthmatic children were more likely to have atopic dermatitis, allergic reactions, food allergies, and a family history of asthma when compared to healthy children., Conclusions: Children with mild-to-moderate asthma presenting exercise symptoms show a reduction in cardiorespiratory fitness, muscle strength, lung function, functionality, and lifestyle when compared to healthy peers. The study provides data for pediatricians to support exercise practice aiming to improve prognosis and quality of life in asthmatic children., (© 2021 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Background: Patients with cystic fibrosis (CF) present exercise intolerance and episodes of pulmonary exacerbations. This study aimed to evaluate the association of the distance covered on the modified shuttle test (MST), as well as other clinical variables (anthropometry, chronic colonization by Pseudomonas aeruginosa, lung function), with the risk of hospitalization for pulmonary exacerbation., Methods: Cohort study including CF patients older than 6 years, from two specialized CF centers. All patients underwent a MST and a lung function test at the time of inclusion. Demographic, anthropometric and clinical data were collected. Free time until the first hospitalization, total days of hospitalization and use of antibiotics during the two years of follow-up were recorded., Results: Sixty-seven patients with a mean (SD) age of 12.4 (5.2) years and forced expiratory volume in the first second (FEV 1 ) of 78.7% (22.4) were included. The mean distance covered (m) in the MST was 775.6 (255.7) (73.4 ± 19.5% of predicted). The distance achieved (MST) was considered as the main independent variable to predict the risk of hospitalization (Cox HR 0.97, p = 0.029). Patients who walked a distance of less than 80% of predicted in the MST showed an increase of 3.9 (95%CI 1.0-15.3) in the relative risk for hospitalization and significantly higher total number of days of hospitalization (p = 0.022)., Conclusion: There is an association between the distance covered in the MST and the risk of hospitalization in youths with CF. Patients with reduced exercise capacity presented a 3.9 times increase in the relative risk for hospitalization due to pulmonary exacerbation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors have no conflict of interests to declare., (Copyright © 2020. Published by Elsevier B.V.)

Maternal stress has been described as an important component in the offspring's cerebral development, altering the susceptibility to diseases in later life. Moreover, the postnatal period is essential for the development and integration of several peripheral and central systems related to the control of homeostasis. Thus, this study aimed to evaluate the effects of prenatal stress on the activation of cortical neurons, by performing experiments both under basal conditions and after KCl-induced depolarization. Female mice were divided in two groups: control and prenatal restraint stress. Cortical neurons from the offspring were obtained at gestational day 18. The effects of prenatal stress and KCl stimulations on cellular mortality, autophagy, gene expression, oxidative stress, and inflammation were evaluated. We found that neurons from PNS mice have decreased necrosis and autophagy after depolarization. Moreover, prenatal stress modulated the HPA axis, as observed by the increased GR and decreased 5HTr1 mRNA expression. The BDNF is an important factor for neuronal function and results demonstrated that KCl-induced depolarization increased the gene expression of BDNF I, BDNF IV, and TRκB. Furthermore, prenatal stress and KCl treatment induced significant alterations in oxidative and inflammatory markers. In conclusion, prenatal stress and stimulation with KCl may influence several markers related to neurodevelopment in cortical neurons from neonate mice, supporting the well-known long-term effects of maternal stress., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: The aim of the study was to evaluate the diagnostic performance of the item concerning physical activity of the Global Initiative for Asthma (GINA) asthma control questionnaire for detection of exercise-induced bronchoconstriction (EIB) in children and adolescents., Material and Methods: We divided participants (aged 6-18 years) with a diagnosis of asthma into two groups according to the GINA severity classification: mild/moderate asthma (MMA) and severe therapy-resistant asthma (STRA). We collected anthropometric, clinical and functional data (spirometry) and performed an EIB test. We used item 4 of the GINA questionnaire regarding exercise-induced symptoms to assess the diagnostic power of this instrument., Results: We included 40 patients (17 with MMA and 23 with STRA) with a mean age of 11.3 years and a mean FEV 1 z-score of -0.33, of who 13 (32.5%) were classified as having uncontrolled asthma. Of the patients with uncontrolled asthma, 7 (53.8%) exhibited a decrease in the FEV 1 after the EIB test. We found a higher frequency of EIB in participants with FEV 1 z-score values of less than -1.0 compared to those with a z-score of -1.0 or greater (P = .05). There were no significant differences in the frequency of EIB based on disease severity and control. We also found no association of item 4 (GINA) with EIB. The area under the ROC curve demonstrated that the discriminative power of the GINA questionnaire for the detection of EIB is inadequate (P = .41), with sensitivity of 42.1% and specificity of 57.1%., Conclusions: The item concerning physical activity in the GINA questionnaire has insufficient diagnostic power to detect EIB in children and adolescents with asthma., (Copyright © 2021 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: To evaluate the reproducibility of the modified shuttle test (MST) and to determine whether the test needs to be performed more than once to assess the exercise capacity of children and adolescents with cystic fibrosis (CF)., Methods: This was a longitudinal study including patients diagnosed with CF aged more than 6 years. The participants were followed for a period of 9 months and were evaluated at three different time points (visits 1, 2, and 3). Spirometric, anthropometric, clinical, and genetic data were collected, and two MSTs were performed at each visit., Results: Forty-eight clinically stable volunteers with a mean age of 10.1 ± 2.7 years were initially included. The reproducibility of the test was evaluated using the distance achieved (DA) as the main variable. There were no significant differences in the DA (visit 1, p = .23; visit 2, p = .24; visit 3, p = .85), baseline heart rate (HR) (visit 1, p = .35; visit 2, p = .20; visit 3, p = .98), and peak HR (visit 1, p = .16; visit 2, p = .94; visit 3, p = .23) between the tests performed at each visit. The test-retest reliability demonstrated a high intraclass correlation coefficient at all visits (visit 1, 2, and 3: 0.83, 0.90, and 0.80, respectively) and the variation in HR was the main factor associated with the DA in the MST over time., Conclusion: The MST was found to be a reproducible and reliable test. The data presented here support the use of a single MST to evaluate and monitor exercise capacity of patients with CF during clinic visits., (© 2021 Wiley Periodicals LLC.)

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 (VO 2 peak). Muscle strength (biceps and quadriceps) also correlated with the ventilatory equivalent for oxygen consumption (V E /VO 2 ) at anaerobic threshold (AT) and with the ventilatory equivalent for carbon dioxide production (V E /VCO 2 ) 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 VO 2 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., (© 2021 John Wiley & Sons Ltd.)

Background: Lower exercise tolerance is an important component of asthma and the possible effects of non-invasive ventilation on exercise capacity in individuals with severe therapy-resistant asthma (STRA) are unknown. This study aimed to evaluate the immediate effect of continuous positive airway pressure (CPAP) on exercise tolerance in children with STRA., Methods: We performed a controlled, randomized, crossover clinical trial including subjects aged 6 to 18 years old diagnosed with STRA. Clinical, anthropometric and lung function data were collected. The participants in the intervention group (IG) used CPAP (PEEP 10cmH 2 O and FiO 2 0.21) for a period of 40 min. Subjects in the control group (CG) used CPAP with minimum PEEP at 1 cmH 2 0 also for 40 min. Afterwards, subjects from both groups underwent cardiopulmonary exercise testing (CPET). After a 15-day washout period, on a subsequent visit, subjects participated in the opposite group to the initial one., Results: Thirteen subjects with a mean age of 12.30 ± 1.7 years were included. The variables of peak expiratory flow (PEF) and forced expiratory volume in the first second (FEV 1 ) before using CPAP and after performing CPET did not show significant differences. Regarding CPET results, there was no significant difference (P = 0.59) between groups at peak exercise for oxygen consumption-VO 2 (CG: 33.4 ± 6.3 and IG: 34.5 ± 5.9, mL kg -1  min -1 ). However, the IG (12.4 ± 2.1) presented a total test time (min) significantly (P = 0.01) longer than the CG (11.5 ± 1.3)., Conclusion: The results suggest that the use of CPAP before physical exercise increases exercise duration in children and adolescents with STRA.

Stressful events during the prenatal period have been related to hyperactive hypothalamic-pituitary-adrenal (HPA) axis responses as well as metabolic changes in adult life. Moreover, regular exercise may contribute to the improvement of the symptoms associated with stress and stress-related chronic diseases. Therefore, this study aims to investigate the effects of exercise, before the gestation period, on the metabolic changes induced by prenatal stress in adult mice. Female Balb/c mice were divided into three groups: control (CON), prenatal restraint stress (PNS) and exercise before the gestational period plus PNS (EX + PNS). When adults, the plasmatic biochemical analysis, oxidative stress, gene expression of metabolic-related receptors and sex differences were assessed in the offspring. Prenatal stress decreased neonatal and adult body weight when compared to the pregestational exercise group. Moreover, prenatal stress was associated with reduced body weight in adult males. PNS and EX + PNS females showed decreased hepatic catalase. Pregestational exercise prevented the stress-induced cholesterol increase in females but did not prevent the liver mRNA expression reduction on the peroxisome proliferator-activated receptors (PPARs) α and γ in PNS females. Conversely, PNS and EX + PNS males showed an increased PPARα mRNA expression. In conclusion, pregestational exercise prevented some effects of prenatal stress on metabolic markers in a sex-specific manner.

Background: Cystic fibrosis (CF) affects the autonomic nervous system (ANS) and exercise in healthy children modulates the interaction between sympathetic and parasympathetic activity. This study aimed to evaluate the effects of a short-term resistance exercise program on heart rate variability (HRV) in children and adolescents with CF. Methods: A randomized controlled trial was carried out in children diagnosed with CF aged 6-18 years. Individuals were divided into two groups: control (CON) and resistance-training (EX). Individuals in the EX group completed an individualized guided resistance program (5-RM-60-80%) for 8 weeks (3 sessions of 60 min/week). Upper and lower limbs exercises (seated bench press, seated lateral row, and leg press) were used. HRV was measured using a Suunto watch with subjects in lying position. Results: Nineteen subjects (13 boys) were included (CON = 11; and EX = 8). Mean age was 12.2 ± 3.3, FEV 1 (forced expiratory volume in the first second) z-score was 1.72 ± 1.54 and peak oxygen consumption (VO 2 peak) 42.7 ± 7.4 mL.Kg -1 .min -1 . Exercise induced significant changes in the frequency-domain variables, including a decrease in LF power ( p = 0.001, d = 0.98) and LF/HF ratio ( p = 0.020, d = 0.92), and an increase in HF power ( p = 0.001, d = -0.97), compared to the CON group. No significant changes were found for time-domain variables, although increases with a moderate effect size were seen for SDNN ( p = 0.152, d = -0.41) and RMSSD ( p = 0.059, d = -0.49) compared to the CON group. Conclusion: A short-term resistance exercise-training program was able to modulate HRV in children and adolescents with CF presenting mild to moderate lung function impairment and good physical condition. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT04293926., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Estévez-González, Donadio, Cobo-Vicente, Fernández-Luna, Sanz-Santiago, Villa Asensi, Iturriaga Ramirez, Fernández-del-Valle, Diez-Vega, Larumbe-Zabala and Pérez-Ruiz.)

Background: No studies have investigated the use and safety of high-frequency chest wall compression (HFCWC) for non-hospitalized infants with acute viral bronchiolitis (AVB). The aim of the present study was to evaluate the immediate effects and safety of HFCWC as compared to airway clearance techniques in children with AVB., Methods: In this randomized clinical trial in non-hospitalized infants (0-12 months old) with mild to moderate AVB, children were randomized into 2 groups: airway clearance techniques (20 min of prolonged slow expiration and provoked cough) or HFCWC (15 min). A single session was performed and children were evaluated at baseline and at 10 min and 20 min after treatments. Outcomes measures were the Wang severity score, [Formula: see text], sputum wet-weight, and the presence of adverse events., Results: A total of 91 infant subjects, mean age 7.9 ± 2.6 months, were included. Significant ( P = .004) between-group differences were found in the Wang score, which was 0.28 points lower in the airway clearance techniques group. There was a greater increase of infants classified as normal and a greater decrease of those classified as mild according to the Wang score when airway clearance techniques were used compared to the use of HFCWC ( P = .009). The sputum wet-weight was lower in subjects treated with the airway clearance techniques ( P < .001). Although [Formula: see text]improved in both groups, no differences were found between them. There was also no difference for adverse events, and the majority of children did not present any adverse events after 20 min., Conclusions: The use of HFCWC induced similar clinical effects as airway clearance techniques and was safe for non-hospitalized infants with AVB. Both techniques reduced respiratory symptoms and acutely improved [Formula: see text]. (ClinicalTrials.gov: NCT03835936.)., Competing Interests: Dr Donadio is supported in part by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior and Conselho Nacional de Desenvolvimento Científico e Tecnológico. The other authors have disclosed no conflicts of interests., (Copyright © 2021 by Daedalus Enterprises.)

Studies have shown that an adverse environment in utero influences fetal growth and development, leading to several neuroendocrine and behavioral changes in adult life. Nevertheless, the mechanisms involved in the long-term benefits of pregestational exercise are still poorly understood. Thus, this study aimed to evaluate the effects of physical exercise before the gestational period on memory behavior and gene expression in the hippocampus of adult mice submitted to prenatal stress. Female Balb/c mice were divided into three groups: control (CON), prenatal restraint stress (PNS), and exercise before the gestational period plus PNS (EX + PNS). When adults, male and female offspring were submitted to the object recognition test followed by the hippocampal evaluation of BDNF exons I and IV mRNA expression, as well as hypothalamic-pituitary-adrenal axis related genes. Pregestational exercise did not prevent the decreased recognition index, as well as GR and CRHR1 gene expression observed in PNS males. Conversely, prenatal stress did not influence female memory behavior. Moreover, exercise attenuated the effects of prenatal stress on female BDNF IV gene expression. The results indicate that pregestational exercise was able to prevent the effects of maternal stress on hippocampal BDNF IV gene expression in females, although no effects were seen on the stress-induced memory impairment in males., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Potassium 5-cyano-4-methyl-6-oxo-1,6-dihydropyridine-2-olate (CPBMF65) is a potent inhibitor of the uridine phosphorylase 1 (UPP1) enzyme. Its non-ionized analog has already demonstrated biological properties by reducing adverse effects caused by the chemotherapeutic 5-fluorouracil (5-FU). In addition, it has been demonstrated that uridine inhibits inflammation and fibrosis in bleomycin lung injury, decreasing collagen production. The purpose of this study was to investigate the in vitro and in vivo effects of CPBMF65 on activated hepatic stellate cells (HSC) and on carbon tetrachloride-induced liver fibrosis in mice. After incubation with CPBMF65, decreased cell proliferation and phenotype reversion were observed in vitro. In addition, CPBMF65 promoted a protective effect on tetrachloride-induced liver fibrosis in mice, demonstrated by its antifibrotic and anti-inflammatory actions. The results of the present study indicate that the UPP1 inhibitor (CPBMF65) may have potential as a novel therapeutic agent for the treatment of liver fibrosis., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To evaluate factors associated with the performance of children and adolescents with cystic fibrosis (CF) in the Modified Shuttle Test (MST) and compare it with healthy children and adolescents., Methods: This is a cross-sectional study, with children and adolescents divided into two groups: cystic fibrosis (CFG) and control (CG). Variables evaluated in the MST: walking distance, test level, heart rate variation (∆Hr), post-test mean arterial pressure (MAP Pt) and peripheral oxygen saturation variation (∆SPO2). Statistical analysis included Mann Whitney and Spearman coefficient tests, being significant p<0.05., Results: Sixty individuals aged 6-16 years old were evaluated. Anthropometric data was similar between groups. Differences between groups were shown for: baseline heart rate (BHr), peak heart rate (PHr), ∆Hr, recovery heart rate (RHr), post-test respiratory rate (PtBr), saturation variables, peripheral oxygen level (SpO2B) and level test. The ∆Hr and MAP Pt had a moderate positive correlation with distance and level test for both groups (respectively: r=0.6 / p<0.001; r=0.6 / p<0.001). In CFG, the level test had a significant association (r=0.4 - p=0.02) with %FEV1., Conclusions: Children with cystic fibrosis presented functional limitation in the Modified Shuttle Test, which was influenced by lung function.

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.