Genotypes of the UCP1 gene polymorphisms and cardiometabolic diseases: A multifactorial study of association with disease probability.

Cardiometabolic diseases (CMDs) are complex disorders with a heterogenous phenotype, which are caused by multiple factors including genetic factors. Single nucleotide polymorphisms (SNPs) rs45539933 (p.Ala64Thr), rs10011540 (c.-112A>C), rs3811791 (c.-1766A>G), and rs1800592 (c.-3826A>G) in the UCP1 gene have been analyzed for association with CMDs in many studies providing controversial results. However, previous studies only considered individual UCP1 SNPs and did not evaluate them in an integrated manner, which is a more powerful approach to uncover genetic component of complex diseases. This study aimed to investigate associations between UCP1 genotype combinations and CMDs or CMD risk factors in the context of non-genetic factors. We performed multiple logistic regression analysis and proposed new methodology of testing different combinations of SNP genotypes. We found that probability of CMDs increased in presence of the three-SNP combination of genotypes with minor alleles of c.-3826A>G and p.Ala64Thr and wild allele of c.-112A>C, with increasing age, body mass index (BMI), body fat percentage (BF%) and may differ between sexes and between countries. The combination of genotypes with c.-3826A>G minor allele and wild homozygotes of c.-112A>C and p.Ala64Thr was associated with increased probability of diabetes. While combination of genotypes with minor alleles of all three SNPs reduced the CMD probability. The present results suggest that age, BMI, sex, and UCP1 three-SNP combinations of genotypes significantly contribute to CMD probability. Varying of c.-112A>C alleles in the genotype combination with minor alleles of c.-3826A>G and p.Ala64Thr markedly changes CMD probability.

The Effect of High-Intensity Interval Training on Mitochondrial-Associated Indices in Overweight and Obese Adults: A Systematic Review and Meta-Analysis.

BACKGROUND: Obesity is a significant health problem with an increasing incidence, causing a low-grade systemic inflammatory state and being implicated in various chronic diseases. Moreover, obesity has been shown to cause mitochondrial dysfunction through oxidative stress and inflammation, eventually affecting energy metabolism. However, high-intensity interval training (HIIT) can improve mitochondrial efficiency through exercise-induced mitochondrial adaptations. This systematic review and meta-analysis aims to examine the potential effects of HIIT on mitochondrial-associated indices in obese and overweight adults. METHODS: PubMed, Scopus, and Web of Science databases were searched. RESULTS: Twenty-eight eligible studies were included, involving 530 participants. HIIT was found to significantly improve the activity of citrate synthase (CS), cytochrome C (COX-IV), beta-hydroxyacyl CoA-dehydrogenase (ß-HAD), Complexes I-V as well as VO2max in overweight and obese individuals, whereas no significant changes were shown in PGC-1α and SIRT1. Interestingly, subgroup analyses revealed that CS, COX-IV, ß-HAD, and Complexes I-V activity exhibited a significant improvement only in the healthy subgroup. CONCLUSIONS: Overall, HIIT can be utilized to enhance mitochondrial-associated indices in overweight and obese individuals. However, this improvement may be health status dependent.

Effects of lifestyle physical activity and sedentary behaviour interventions on disease activity and patient- and clinician- important health outcomes in rheumatoid arthritis: a systematic review with meta-analysis.

BACKGROUND: Lifestyle physical activity (PA) is defined as any type of PA undertaken as part of daily life. It can include engagement in activities of daily living (i.e., household chores, gardening, walking to work), incidental PA, walking and/or reducing sedentary or sitting behaviours (SB). Regular PA is recommended for people with Rheumatoid Arthritis (RA) to reduce disease activity and systemic inflammation, as well as to improve patient- and clinician-important health outcomes. However, there is no summarised evidence of the effectiveness of interventions specifically targeting lifestyle PA and SB in this population. The aims of this systematic review with meta-analysis were to evaluate interventions targeting lifestyle PA and/or SB on 1) disease activity; 2) PA, SB and 3) patient- and clinician-important outcomes in people with RA. METHODS: Eight databases [Medline, Cochrane Library CENTRAL, Web of Science, PsychINFO, Cumulative Index to Nursing & Allied Health Literature, Scopus, Excerpta Medica database and Physiotherapy Evidence Database] were searched from inception-August 2022. Inclusion criteria required interventions to target lifestyle PA and/or SB, conducted in adults with RA, assessing patient- and/or clinician-important outcomes. RESULTS: Of 880 relevant articles, 16 interventions met the inclusion criteria. Meta-analyses showed statistically significant effects of interventions on disease activity (standardised mean difference = -0.12 (95% confidence interval = -0.23 to -0.01, I2 = 6%, z = 2.19, p = .03), moderate-to-vigorous PA, light/leisure PA, steps, functional ability, and fatigue. Whereas, no intervention effects were visualised for total PA, pain, anxiety or quality of life. CONCLUSIONS: Lifestyle PA interventions led to increased PA, reductions in SB and improvements in disease activity and other patient- and/or clinician-important health outcomes in people with RA. Future interventions should be less heterogenous in content, structure, focus and outcome measures used to aid understanding of the most effective intervention components for improving health. More SB interventions are needed to determine their effectiveness at producing clinical benefits.

The Effects of a Single Session of a Rhythmic Movement Program on Selected Biopsychological Parameters in PD Patients: A Methodological Approach.

The aim of the present study is to examine the acute effects of a specially designed musicokinetic (MSK) program for patients with Parkinson's disease (PD) on (a) anxiety levels, (b) select kinematic and kinetic parameters, and (c) frontal cortex hemodynamic responses, during gait initiation and steady-state walking. Methods: This is a blind cross-over randomized control trial (RCT) in which 13 volunteers with PD will attend a 45 min MSK program under the following conditions: (a) a synchronous learning format and (b) an asynchronous remote video-based format. Changes in gait biomechanics and frontal cortex hemodynamic responses will be examined using a 10-camera 3D motion analysis (Vicon T-series, Oxford, UK), and a functional near-infrared spectroscopy (f-NIRS-Portalite, Artinis NL) system, respectively, while anxiety levels will be evaluated using the Hamilton Anxiety Rating Scale. Expected results: Guided by the rules of music, where periodicity is distinct, our specially designed MSK program may eventually be beneficial in improving motor difficulties and, hence, reducing anxiety. The combined implementation of f-NIRS in parallel with 3D gait analysis has yet to be evaluated in Parkinsonian patients following a MSK intervention. It is expected that the aforementioned intervention, through better rhythmicity, may improve the automatization of motor control, gait kinematics, and kinetics-supported by decreased frontal cortex hemodynamic activity-which may be linked to reduced anxiety levels.

Caveolin-1 protein expression as a prognostic biomarker of gastrointestinal tumours: A systematic review and meta-analysis.

BACKGROUND: Gastrointestinal (GI) cancers remain a major threat worldwide, accounting for over 30% of cancer deaths. The identification of novel prognostic biomarkers remains a challenge despite significant advances in the field. The CAV1 gene, encoding the caveolin-1 protein, remains enigmatic in cancer and carcinogenesis, as it has been proposed to act as both a tumour promoter and a tumour suppressor. METHODS: To analyse the differential role of caveolin-1 expression in both tumour cells and stroma in relation to prognosis in GI tumours, we performed a systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines; PROSPERO registration number: CRD42022299148. RESULTS: Our analysis showed that high levels of caveolin-1 in tumour cells were associated with poor prognosis and inferior overall survival (OS) in oesophageal and pancreatic cancer and hepatocellular carcinoma (HCC), but not in gastric and colorectal cancer. Importantly, our study showed that higher stromal caveolin-1 expression was associated with significantly longer OS and disease-free survival in colorectal cancer. Analysis of stromal caveolin-1 expression in the remaining tumours showed a similar trend, although it did not reach statistical significance. CONCLUSIONS: The data suggest that caveolin-1 expression in the tumour cells of oesophageal, pancreatic cancer and HCC and in the stroma of colorectal cancer may be an important novel predictive biomarker for the clinical management of these diseases in a curative setting. However, the main conclusion of our analysis is that caveolin-1 expression should always be assessed separately in stroma and tumour cells.

Muscle Architecture Adaptations to Static Stretching Training: A Systematic Review with Meta-Analysis.

BACKGROUND: Long-term stretching of human skeletal muscles increases joint range of motion through altered stretch perception and decreased resistance to stretch. There is also some evidence that stretching induces changes in muscle morphology. However, research is limited and inconclusive. OBJECTIVE: To examine the effect of static stretching training on muscle architecture (i.e., fascicle length and fascicle angle, muscle thickness and cross-sectional area) in healthy participants. DESIGN: Systematic review and meta-analysis. METHODS: PubMed Central, Web of Science, Scopus, and SPORTDiscus were searched. Randomized controlled trials and controlled trials without randomization were included. No restrictions on language or date of publication were applied. Risk of bias was assessed using Cochrane RoB2 and ROBINS-I tools. Subgroup analyses and random-effects meta-regressions were also performed using total stretching volume and intensity as covariates. Quality of evidence was determined by GRADE analysis. RESULTS: From the 2946 records retrieved, 19 studies were included in the systematic review and meta-analysis (n = 467 participants). Risk of bias was low in 83.9% of all criteria. Confidence in cumulative evidence was high. Stretching training induces trivial increases in fascicle length at rest (SMD = 0.17; 95% CI 0.01-0.33; p = 0.042) and small increases in fascicle length during stretching (SMD = 0.39; 95% CI 0.05 to 0.74; p = 0.026). No increases were observed in fascicle angle or muscle thickness (p = 0.30 and p = 0.18, respectively). Subgroup analyses showed that fascicle length increased when high stretching volumes were used (p < 0.004), while no changes were found for low stretching volumes (p = 0.60; subgroup difference: p = 0.025). High stretching intensities induced fascicle length increases (p < 0.006), while low stretching intensities did not have an effect (p = 0.72; subgroup difference: p = 0.042). Also, high intensity stretching resulted in increased muscle thickness (p = 0.021). Meta-regression analyses showed that longitudinal fascicle growth was positively associated with stretching volume (p < 0.02) and intensity (p < 0.04). CONCLUSIONS: Static stretching training increases fascicle length at rest and during stretching in healthy participants. High, but not low, stretching volumes and intensities induce longitudinal fascicle growth, while high stretching intensities result in increased muscle thickness. REGISTRATION: PROSPERO, registration number: CRD42021289884.

Combined Effects of Diet and Physical Activity on Inflammatory Joint Disease: A Systematic Review and Meta-Analysis.

Research evidence suggests that, individually, diet and physical activity are effective interventions for reducing levels of inflammation in inflammatory joint diseases (IJD), however little is known about their combined use. This systematic review and meta-analysis aimed to examine the effects and/or associations of combined diet and physical activity interventions in IJD, specifically rheumatoid arthritis (RA) and the spondyloarthropathies (SpA) (PROSPERO registration number: CRD42022370993). Ten out of 11 eligible studies examined RA patients. We found that a combination of diet/nutrition and physical activity/exercise improved Health Assessment Questionnaire score (standardized mean difference = -1.36, confidence interval (CI) = (-2.43)-(-0.30), I2 = 90%, Z = 2.5, p = 0.01), while surprisingly they increased erythrocyte sedimentation rate (mean difference = 0.20, CI = 0.09-0.31, I2 = 0%, Z = 3.45, p < 0.01). No effects were found on C-reactive protein or weight (p > 0.05) of RA patients. We did not find studies in other IJDs that provided sufficient data for a meta-analysis. The narrative data synthesis provided limited evidence to address our research question. No firm conclusions can be made as to whether the combination of diet/nutrition and physical activity/exercise affects inflammatory load in IJDs. The results of this study can only be used as a means of highlighting the low-quality evidence in this field of investigation and the need for further and better-quality research.

Relationship between Short- and Mid-Term Glucose Variability and Blood Pressure Profile Parameters: A Scoping Review.

Background. Increased variability of glucose (GV) and blood pressure (BPV) is linked to a higher risk of macro- and microvascular complications and other hard endpoints. This scoping review aims to summarize the existing evidence regarding the association between the parameters of the blood pressure (BP) profile, especially BPV, with indices of short- and mid-term GV. Methods. A literature search was conducted in the MEDLINE/PubMed, Cochrane, Embase, Web of Science, and Wiley Online Library databases. Results. The main findings of this review are as follows: (i) 13 studies were included, mainly with small sample sizes; (ii) there was a considerable degree of heterogeneity in the characteristics of the study participants (age range, individuals with normoglycemia, type 1 or 2 diabetes, normal BP, or hypertension), as well as in the methodologies (mainly in terms of the duration of the data collection period) and variability indices examined (mean amplitude of glycemic excursions and coefficient of glucose variation most frequently reported); and (iii) the results were heterogeneous regarding the association between GV and the parameters of the BP profile. Conclusions. There is a significant lack of evidence on the association between GV and BPV. Future research implementing a standardized methodology should focus on the determinants, association, and clinical relevance of GV and BPV.

Effects of Exercise and Physical Activity Levels on Childhood Cancer: An Umbrella Review.

Patients and survivors of childhood cancer experience adverse effects related to the disease and its treatment. These adverse effects are associated with both physiological and psychological health. Exercise helps manage the side effects and improve the health outcomes. The objective of this umbrella review is to search the current literature in the context of exercise and physical activity as complementary interventions on pediatric cancer and to provide comprehensive information about the derived health outcomes. A literature search was conducted on the Cochrane, PubMed, and Embase databases for systematic reviews published up to January 2023. Moreover, a hand search of reference lists was performed. We included participants under 19 years of age at diagnosis of any type of childhood cancer, without restriction on the type or phase of treatment, who participated in exercise interventions. The results showed a beneficial impact on fatigue, muscle strength, aerobic capacity, activity and participation levels, psychosocial health, cardiovascular/cardiorespiratory fitness, physical function, bone mineral density, and brain volume and structure, with limited and not serious adverse effects. These findings documented that exercise interventions had a positive effect on many physiological and psychological health outcomes in pediatric cancer patients and survivors.

Endothelial progenitor cell mobilization based on exercise volume in patients with cardiovascular disease and healthy individuals: a systematic review and meta-analysis.

Endothelial progenitor cells (EPCs) play a vital role in protecting endothelial dysfunction and cardiovascular disease (CVD). Physical exercise stimulates the mobilization of EPCs, and along with vascular endothelial growth factor (VEGF), promotes EPC differentiation, and contributes to vasculogenesis. The present meta-analysis examines the exercise-induced EPC mobilization and has an impact on VEGF in patients with CVD and healthy individuals. Database research was conducted (PubMed, EMBASE, Cochrane Library of Controlled Trials) by using an appropriate algorithm to indicate the exercise-induced EPC mobilization studies. Eligibility criteria included EPC measurements following exercise in patients with CVD and healthy individuals. A continuous random effect model meta-analysis (PROSPERO-CRD42019128122) was used to calculate mean differences in EPCs (between baseline and post-exercise values or between an experimental and control group). A total of 1460 participants (36 studies) were identified. Data are presented as standard mean difference (Std.MD) and 95% confidence interval (95% CI). Aerobic training stimulates the mobilization of EPCs and increases VEGF in patients with CVD (EPCs: Std.MD: 1.23, 95% CI: 0.70-1.76; VEGF: Std.MD: 0.76, 95% CI:0.16-1.35) and healthy individuals (EPCs: Std.MD: 1.11, 95% CI:0.53-1.69; VEGF: Std.MD: 0.75, 95% CI: 0.01-1.48). Acute aerobic exercise (Std.MD: 1.40, 95% CI: 1.00-1.80) and resistance exercise (Std.MD: 0.46, 95%CI: 0.10-0.82) enhance EPC numbers in healthy individuals. Combined aerobic and resistance training increases EPC mobilization (Std.MD:1.84, 95% CI: 1.03-2.64) in patients with CVD. Adequate exercise volume (>60%VO2max >30 min; P = 0.00001) yields desirable results. Our meta-analysis supports the findings of the literature. Exercise volume is required to obtain clinically significant results. Continuous exercise training of high-to-moderate intensity with adequate duration as well as combined training with aerobic and resistance exercise stimulates EPC mobilization and increases VEGF in patients with CVD and healthy individuals.

Population Characteristics, Symptoms, and Risk Factors of Idiopathic Chilblains: A Systematic Review, Meta-Analysis, and Meta-Regression.

BACKGROUND: Chilblains/perniosis is a non-freezing cold injury causing painful inflammatory skin lesions. Its pathogenesis remains poorly understood because it is often studied as secondary to other underlying conditions. METHODS: We systematically investigated the population characteristics, symptoms, and predisposing factors of chilblains in healthy adults exposed to cool/cold environments. We screened PubMed, Embase, and Cochrane Library, and we adopted PRISMA reporting guidelines (PROSPERO: CRD42021245307). The risk of bias was assessed by two independent reviewers (RTI item bank). Random-effects model meta-analyses were performed to calculate the pooled prevalence of histopathological features. Mixed-effects meta-regressions were used to assess other sources of between-study heterogeneity. RESULTS: Thirteen studies (477 patients) were included. Chilblains affect more women than men, up to 12% of the body skin surface, and most frequently, the hands and fingers. Meta-analyses of nine studies (303 patients) showed a frequent presence of perivascular lymphocytic infiltrate (81%), basal epidermal-cell layer vacuolation (67%), papillary dermal edema (66%), and perieccrine lymphocytic infiltrate (57%). Meta-regressions (p ≤ 0.05) showed that smoking and frequent occupational exposure to water increase the likelihood of histopathological features. CONCLUSIONS: The population characteristics, symptoms, and predisposing factors of chilblains revealed in this analysis should be incorporated in medical care to improve the condition's diagnosis and management.

Indicators to assess physiological heat strain - Part 1: Systematic review.

In a series of three companion papers published in this Journal, we identify and validate the available thermal stress indicators (TSIs). In this first paper of the series, we conducted a systematic review (registration: INPLASY202090088) to identify all TSIs and provide reliable information regarding their use (funded by EU Horizon 2020; HEAT-SHIELD). Eight databases (PubMed, Agricultural and Environmental Science Collection, Web of Science, Scopus, Embase, Russian Science Citation Index, MEDLINE, and Google Scholar) were searched from database inception to 15 April 2020. No restrictions on language or study design were applied. Of the 879 publications identified, 232 records were considered for further analysis. This search identified 340 instruments and indicators developed between 200 BC and 2019 AD. Of these, 153 are nomograms, instruments, and/or require detailed non-meteorological information, while 187 can be mathematically calculated utilizing only meteorological data. Of these meteorology-based TSIs, 127 were developed for people who are physically active, and 61 of those are eligible for use in occupational settings. Information regarding the equation, operating range, interpretation categories, required input data, as well as a free software to calculate all 187 meteorology-based TSIs is provided. The information presented in this systematic review should be adopted by those interested in performing on-site monitoring and/or big data analytics for climate services to ensure appropriate use of the meteorology-based TSIs. Studies two and three in this series of companion papers present guidance on the application and validation of these TSIs, to guide end users of these indicators for more effective use.

Indicators to assess physiological heat strain - Part 2: Delphi exercise.

In a series of three companion papers published in this Journal, we identify and validate the available thermal stress indicators (TSIs). In this second paper of the series, we identified the criteria to consider when adopting a TSI to protect individuals who work in the heat, and we weighed their relative importance using a Delphi exercise with 20 experts. Two Delphi iterations were adequate to reach consensus within the expert panel (Cronbach's α = 0.86) for a set of 17 criteria with varying weights that should be considered when adopting a TSI to protect individuals who work in the heat. These criteria considered physiological parameters such as core/skin/mean body temperature, heart rate, and hydration status, as well as practicality, cost effectiveness, and health guidance issues. The 17 criteria were distributed across three occupational health-and-safety pillars: (i) contribution to improving occupational health (55% of total importance), (ii) mitigation of worker physiological strain (35.5% of total importance), and (iii) cost-effectiveness (9.5% of total importance). Three criteria [(i) relationship of a TSI with core temperature, (ii) having categories indicating the level of heat stress experienced by workers, and (iii) using its heat stress categories to provide recommendations for occupational safety and health] were considered significantly more important when selecting a TSI for protecting individuals who work in the heat, accumulating 37.2 percentage points. These 17 criteria allow the validation and comparison of TSIs that presently exist as well as those that may be developed in the coming years.

Indicators to assess physiological heat strain - Part 3: Multi-country field evaluation and consensus recommendations.

In a series of three companion papers published in this Journal, we identify and validate the available thermal stress indicators (TSIs). In this third paper, we conducted field experiments across nine countries to evaluate the efficacy of 61 meteorology-based TSIs for assessing the physiological strain experienced by individuals working in the heat. We monitored 372 experi-enced and acclimatized workers during 893 full work shifts. We continuously assessed core body temperature, mean skin temperature, and heart rate data together with pre/post urine specific gravity and color. The TSIs were evaluated against 17 published criteria covering physiological parameters, practicality, cost effectiveness, and health guidance issues. Simple meteorological parameters explained only a fraction of the variance in physiological heat strain (R2 = 0.016 to 0.427; p < 0.001), reflecting the importance of adopting more sophisticated TSIs. Nearly all TSIs correlated with mean skin temperature (98%), mean body temperature (97%), and heart rate (92%), while 66% of TSIs correlated with the magnitude of dehydration and 59% correlated with core body temperature (r = 0.031 to 0.602; p < 0.05). When evaluated against the 17 published criteria, the TSIs scored from 4.7 to 55.4% (max score = 100%). The indoor (55.4%) and outdoor (55.1%) Wet-Bulb Globe Temperature and the Universal Thermal Climate Index (51.7%) scored higher compared to other TSIs (4.7 to 42.0%). Therefore, these three TSIs have the highest potential to assess the physiological strain experienced by individuals working in the heat.

Rhythmic cueing, dance, resistance training, and Parkinson's disease: A systematic review and meta-analysis.

Objectives: The aim of the present systematic review and meta-analysis was to synthesize evidence associated with the functional and clinical effectiveness of rhythmic cueing, dance, or resistance training (RT) on motor and non-motor parameters in Parkinson's Disease patients, and to provide a comparative perspective not offered by existing systematic reviews. Methodology: Eligibility criteria for selecting studies retained no restrictions in methodological design and included interventions of rhythmic cueing, dance, RT, and measurements of motor and non-motor parameters. Animal studies, reviews, editorials, conferences, magazines, and gray literature articles were excluded. Two independent investigators searched Cochrane Library, Medline, PubMed, and SPORTDiscus from the date of their inception until 1 June 2021. The ROBINS-I tool was employed for the non-randomized controlled trials, and the updated for Risk of Bias 2 tool of Cochrane Library used for randomized controlled trials. For meta-analyses, the RevMan 5.4.13 software was used. For incompatible meta-analysis studies, a narrative data synthesis was conducted. Results: A total of 49 studies included in the systematic review involving 3767 PD participants. Meta-analyses revealed that rhythmic cueing training assists gait velocity (p = 0.01), stride length (p = 0.01), and motor symptoms (p = 0.03). Similarly, dance training benefits stride length (p = 0.05), lower extremity function-TUG (p = 0.01), and motor symptoms (p = 0.01), whilst RT improves lower extremity function-TUG (p = 0.01), quality of life (p = 0.01), knee flexion (p = 0.02), and leg press (p = 0.01). Subgroup analyses have shown non-significant differences in gait velocity (p = 0.26), stride length (p = 0.80), functional mobility-TUG (p = 0.74), motor symptoms-UPDRS-III (p = 0.46), and quality of life-PDQ39 (p = 0.44). Conclusion: Rhythmic cueing, dance, or RT positively affect the examined outcomes, with rhythmic cueing to be associated with three outcomes (Gait, Stride, and UPDRS-III), dance with three outcomes (TUG, Stride, and UPDRS-III), and RT with two outcomes (TUG and PDQ-39). Subgroup analyses confirmed the beneficial effects of these forms of exercise. Clinicians should entertain the idea of more holistic exercise protocols aiming at improving PD manifestations.International Prospective Register of systematic reviews (PROSPERO) (registration number: CRD42020212380).

Is There a "Window of Opportunity" for Flexibility Development in Youth? A Systematic Review with Meta-analysis.

BACKGROUND: Flexibility is an important component of physical fitness for competitive and recreational athletes. It is generally suggested that flexibility training should start from childhood (6-11 years of age) to optimize joint range of motion (ROM) increases; however, evidence is limited and inconsistent. OBJECTIVE: To examine whether there is a difference in the effect of stretching training on flexibility during childhood (6-11 years of age) and adolescence (12-18 years of age). DESIGN: Systematic review and meta-analysis. METHODS: We searched PubMed Central, Web of Science, Scopus, Embase, and SPORTDiscus, to conduct this systematic review. Randomized controlled trials and non-randomized controlled trials were eligible. No language and date of publication restrictions were applied. Risk of bias was assessed using Cochrane RoB2 and ROBINS-I tools. Meta-analyses were conducted via an inverse variance random-effects model. GRADE analysis was used to assess the methodological quality of the studies. RESULTS: From the 2713 records retrieved 28 studies were included in the meta-analysis (n = 1936 participants). Risk of bias was low in 56.9% of all criteria. Confidence in cumulative evidence was moderate. We found that stretching was effective in increasing ROM in both children (SMD = 1.09; 95% CI = 0.77-1.41; Z = 6.65; p < 0.001; I2 = 79%) and adolescents (SMD = 0.90; 95% CI = 0.70-1.10; Z = 8.88; p < 0.001; I2 = 81%), with no differences between children and adolescents in ROM improvements (p = 0.32; I2 = 0%). However, when stretching volume load was considered, children exhibited greater increases in ROM with higher than lower stretching volumes (SMD = 1.21; 95% CI = 0.82-1.60; Z = 6.09; p < 0.001; I2 = 82% and SMD = 0.62; 95% CI = 0.29-0.95; Z = 3.65; p < 0.001; I2 = 0%, respectively; subgroup difference: p = 0.02; I2 = 80.5%), while adolescents responded equally to higher and lower stretching volume loads (SMD = 0.90; 95% CI = 0.47-1.33; Z = 4.08; p < 0.001; I2 = 83%, and SMD = 0.90; 95% CI = 0.69-1.12; Z = 8.18; p < 0.001; I2 = 79%, respectively; subgroup difference: p = 0.98; I2 = 0%). CONCLUSIONS: Systematic stretching training increases ROM during both childhood and adolescence. However, larger ROM gains may be induced in childhood than in adolescence when higher stretching volume loads are applied, while adolescents respond equally to high and low stretching volume loads. REGISTRATION: INPLASY, registration number: INPLASY202190032; https://inplasy.com/inplasy-2021-9-0032/.

Effects of Exercise and Physical Activity Levels on Vaccination Efficacy: A Systematic Review and Meta-Analysis.

Objective: We examined whether different intensities of exercise and/or physical activity (PA) levels affected and/or associated with vaccination efficacy. Methods: A systematic review and meta-analysis was conducted and registered with PROSPERO (CRD42021230108). The PubMed, EMBASE, Cochrane Library (trials), SportDiscus, and CINAHL databases were searched up to January 2022. Results: In total, 38 eligible studies were included. Chronic exercise increased influenza antibodies (standardized mean difference (SMD) = 0.49, confidence interval (CI) = 0.25−0.73, Z = 3.95, I2 = 90%, p < 0.01), which was mainly driven by aerobic exercise (SMD = 0.39, CI = 0.19−0.58, Z = 3.96, I2 = 77%, p < 0.01) as opposed to combined (aerobic + resistance; p = 0.07) or other exercise types (i.e., taiji and qigong, unspecified; p > 0.05). PA levels positively affected antibodies in response to influenza vaccination (SMD = 0.18, CI = 0.02−0.34, Z = 2.21, I2 = 76%, p = 0.03), which was mainly driven by high PA levels compared to moderate PA levels (Chi2 = 10.35, I2 = 90.3%, p < 0.01). Physically active individuals developed influenza antibodies in response to vaccination in >4 weeks (SMD = 0.64, CI = 0.30−0.98, Z = 3.72, I2 = 83%, p < 0.01) as opposed to <4 weeks (p > 0.05; Chi2 = 13.40, I2 = 92.5%, p < 0.01) post vaccination. Conclusion: Chronic aerobic exercise or high PA levels increased influenza antibodies in humans more than vaccinated individuals with no participation in exercise/PA. The evidence regarding the effects of exercise/PA levels on antibodies in response to vaccines other than influenza is extremely limited.

Prevalence of uncoupling protein one genetic polymorphisms and their relationship with cardiovascular and metabolic health.

Contribution of UCP1 single nucleotide polymorphisms (SNPs) to susceptibility for cardiometabolic pathologies (CMP) and their involvement in specific risk factors for these conditions varies across populations. We tested whether UCP1 SNPs A-3826G, A-1766G, Ala64Thr and A-112C are associated with common CMP and their risk factors across Armenia, Greece, Poland, Russia and United Kingdom. This case-control study included genotyping of these SNPs, from 2,283 Caucasians. Results were extended via systematic review and meta-analysis. In Armenia, GA genotype and A allele of Ala64Thr displayed ~2-fold higher risk for CMP compared to GG genotype and G allele, respectively (p<0.05). In Greece, A allele of Ala64Thr decreased risk of CMP by 39%. Healthy individuals with A-3826G GG genotype and carriers of mutant allele of A-112C and Ala64Thr had higher body mass index compared to those carrying other alleles. In healthy Polish, higher waist-to-hip ratio (WHR) was observed in heterozygotes A-3826G compared to AA homozygotes. Heterozygosity of A-112C and Ala64Thr SNPs was related to lower WHR in CMP individuals compared to wild type homozygotes (p<0.05). Meta-analysis showed no statistically significant odds-ratios across our SNPs (p>0.05). Concluding, the studied SNPs could be associated with the most common CMP and their risk factors in some populations.

Impact of supervised aerobic exercise on clinical physiological and mental parameters of people living with HIV: a systematic review and meta-analyses of randomized controlled trials.

Background: The benefits derived from supervised aerobic exercise in people living with human immunofeficiency virus- HIV (PLWH) have not yet been clearly identified.Objective: To evaluate the impact of supervised aerobic exercise on immunological, cardiorespiratory, pulmonary, hemodynamic and mental parameters of PLWH.Methods: A systematic review was carried out in accordance to PRISMA guidelines. PubMed, Physiotherapy Evidence Database (PEDro) and Cochrane Central Register of Controlled Trials (CENTRAL) were screened up to August 2021, for the identification of English written randomized trials, with participants aged 18 years and older, at any stage of the disease, with or without co-morbidities. The risk of bias assessment was conducted according to the Cochrane Collaboration's tool for assessing risk of bias. Meta- analyses were conducted using continuous, inverse variance, random-effects model.Results: Ten studies were suitable for meta-analysis based on inclusion criteria. Supervised aerobic exercise appeared to have beneficial effects on depressive symptoms [mean difference (MD)= -4.18 (confidence interval (CI)= (-6.55)-(-1.81), Z = 3.46, p = 0.0005, I2=0%, n = 2], forced expiratory volume in 1 sec [MD = 0.70, CI = 0.39-1.00, Z = 4.41, p < 0.0001, I2=0%, n = 2], and on the maximum oxygen uptake [MD = 1.38, CI = -0.02-2.78, Z = 1.94, p = 0.05, I2=94%, n = 4] of PLWH. No exercise effect was found for CD4 T-cell count (p = 0.16, n = 5), systolic blood pressure (p = 0.91, n = 2) and diastolic blood pressure (p = 0.72, n = 2).Conclusions: Supervised continuous aerobic exercise may improve lung function, depressive symptomatology and aerobic capacity of PLWH, however, the small number of available studies and the high heterogeneity concerning VO2max demonstrate the need for more research in this area.

Effects of Alpha-lipoic Acid Supplementation on Human Diabetic Nephropathy: A Systematic Review and Meta-analysis.

BACKGROUND: Diabetic nephropathy (DN) is kidney dysfunction, which occurs due to elevated urine albumin excretion rate and reduced glomerular filtration rate. Studies on animals have shown that alpha-lipoic acid (ALA) supplementation can reduce the development of DN. OBJECTIVES: We performed a systematic review and meta-analysis to examine the effects of ALA supplementation on biological indices (albumin, creatinine, etc.) indicative of human DN. METHODS: The search procedure included PubMed Central, Embase, Cochrane Library (trials), and Web of Science (protocol registration: INPLASY202060095). RESULTS: We found that ALA supplementation decreased 24h urine albumin excretion rate in patients with diabetes (standardized mean difference=-2.27; confidence interval (CI)=(-4.09)-(-0.45); I2=98%; Z=2.44; p=0.01). A subgroup analysis revealed that the results of studies examining only ALA did not differ from those examined ALA in combination with additional medicines (Chisquared= 0.19; p=0.66; I2=0%), while neither ALA nor ALA plus medication had an effect on 24h urine albumin excretion rate (p>0.05). Also, ALA supplementation decreased urine albumin mg/l (mean difference (MD)=-12.95; CI=(-23.88)-(-2.02); I2=44%; Z=2.32; p=0.02) and urine albumin to creatinine ratio (MD=-26.96; CI=(-35.25)-(-18.67); I2=0%; Z=6.37; p<0.01) in patients with diabetes. When the studies examining ALA plus medication were excluded, it was found that ALA supplementation had no effect on urine albumin mg/l (p>0.05) but did significantly decrease urine albumin to creatinine ratio (MD=-25.88, CI=(34.40-(-17.36), I2=0%, Z=5.95, p<0.00001). CONCLUSION: The available evidence suggests that ALA supplementation does not improve biological indices that reflect DN in humans. Overall, we identified limited evidence, and therefore, the outcomes should be considered with caution.