Exercise training-induced changes in exerkine concentrations may be relevant to the metabolic control of type 2 diabetes mellitus patients:A systematic review and meta-analysis of randomized controlled trials

Background:This study investigates the effects of exercise training on exerkines in patients with type 2 diabetes mellitus to determine the optimal exercise prescription.Methods:A systematic search for relevant studies was performed in 3 databases.Randomized controlled trials investigating the effects of exercise training on at least one of the following exerkines were included:adiponectin,apelin,brain-derived neurotrophic factor,fetuin-A,fibroblast growth factor-21,follistatin,ghrelin,interleukin(IL)-6,IL-8,IL-10,IL-15,IL-18,leptin,myostatin,omentin,resistin,retinol-binding protein 4,tumor necrosis factor-α,and visfatin.Results:Forty randomized controlled trials were selected for data extraction(n=2160).Exercise training induces changes in adiponectin,fetuin-A,fibroblast growth factor-21,IL-6,IL-10,leptin,resistin,and tumor necrosis factor-a levels but has no significant effects on apelin,IL-18,and ghrelin compared to controls.Physical exercise training favored large and positive changes in pooled exerkines(i.e.,an overall effect size calculated from several exerkine s)(Hedge’s g=1.02,95%confidence interval(95%CI):0.76-1.28),which in turn were related to changes in glycated hemoglobin(mean difference(MD)=-0.81%,95%CI:-0.95%to-0.67%),fasting glucose(MD=-23.43 mg/dL,95%CI:-30.07 mg/dL to-16.80 mg/dL),waist circumference(MD=-3.04 cm,95%CI:-4.02 cm to-2.07 cm),and body mass(MD=-1.93 kg,95%CI:-2.00 kg to-1.86 kg).Slightly stronger effects were observed with aerobic,resistance,or high-intensity interval protocols at moderate-to vigorous-intensity and with programs longer than 24 weeks that comprise at least 3 sessions per week and more than 60 min per session.Conclusion:Exercise training represents an anti-inflammatory therapy and metabolism-improving strategy with minimal side effects for patients with type 2 diabetes mellitus.

Twenty-four-hour movement guidelines during middle adolescence and their association with glucose outcomes and type 2 diabetes mellitus in adulthood

Purpose:The aim of the present study was to determine the association between adherence to the 24-h movement guidelines during middle adolescence and glucose outcomes(glycated hemoglobin and fasting glucose)and type 2 diabetes mellitus(T2DM)in adulthood,14 and 22 years later.Methods:We analyzed data from apparently healthy adolescents aged 12-18 years who participated in WavesⅠandⅡ(1994-1996,n=14,738),WaveⅣ(2008-2009,n=8913),and Wave V(2016-2018,n=3457)of the National Longitudinal Study of Adolescent to Adult Health(Add Health)in the United States.Physical activity,screen time,and sleep duration were measured using questionnaires,and the 24-h guidelines were defined as:5 or more times moderate-to-vigorous physical activity per week,≤2 h per day of screen time,and 9-11 h of sleep for 12-13 years and 8-10 h for 14-17 years.Capillary and venous whole blood was collected and analyzed to determine glycated hemoglobin and fasting glucose for WavesⅣandⅤ,respectively.Results:Only 2.1%of the adolescents met all the 3 guidelines,and 37.8%met none of them.In both wavesⅣandⅤ,adolescents who met physical activity and screen time guidelines had lower odds of T2DM in adulthood than those who did not meet any of these guidelines(WaveⅣ;prevalence ratio(PR)=0.57,95%confidence interval(95%CI):0.21-0.89;Wave V:PR=0.43,95%CI:0.32-0.74).Only for Wave V did adolescents who met all 3 guidelines have lower odds of T2DM at follow-up compared with those who did not meet any of these guidelines(PR=0.47,95%CI:0.24-0.91).Also,for each increase in meeting one of the 24-h recommendations,the odds of T2DM decreased by 18%(PR=0.82,95%CI:0.61-0.99)and 15%(PR=0.85,95%CI:0.65-0.98)in adulthood for WavesⅣandⅤ,respectively.Conclusion:Promoting all 24-h movement guidelines in adolescence,especially physical activity and screen time,is important for lowering the potential risk of T2DM in adulthood.

Endoscopic anti-reflux therapy for gastroesophageal reflux disease

Gastroesophageal reflux disease has an increasing incidence and prevalence worldwide.A significant proportion of patients have a suboptimal response to proton pump inhibitors or are unwilling to take lifelong medication due to concerns about long-term adverse effects.Endoscopic anti-reflux therapies offer a minimally invasive option for patients unwilling to undergo surgical treatment or take lifelong medication.The best candidates are those with a good response to proton pump inhibitors and without a significant sliding hiatal hernia.Transoral incisionless fundoplication and nonablative radiofrequency are the techniques with the largest body of evidence and that have been tested in several randomized clinical trials.Band-assisted ligation techniques,anti-reflux mucosectomy,antireflux mucosal ablation,and new plication devices have yielded promising results in recent noncontrolled studies.Nonetheless,the role of endoscopic procedures remains controversial due to limited long-term and comparative data,and no consensus exists in current clinical guidelines.This review provides an updated summary focused on the patient selection,technical details,clinical success,and safety of current and future endoscopic anti-reflux techniques.

Cardiorespiratory fitness measured with cardiopulmonary exercise testing and mortality in patients with cardiovascular disease:A systematic review and meta-analysis

Background Cardiorespiratory fitness(CRF)is inversely associated with mortality in apparently healthy subjects and in some clinical populations,but evidence for the association between CRF and all-cause and/or cardiovascular disease(CVD)mortality in patients with established CVD is lacking.This study aimed to quantify this association.Methods We searched for prospective cohort studies that measured CRF with cardiopulmonary exercise testing in patients with CVD and that examined all-cause and CVD mortality with at least 6 months of follow-up.Pooled hazard ratios(HRs)were calculated using random-effect inverse-variance analyses.Results Data were obtained from 21 studies and included 159,352 patients diagnosed with CVD(38.1%female).Pooled HRs for all-cause and CVD mortality comparing the highest vs.lowest category of CRF were 0.42(95%confidence interval(95%CI):0.28–0.61)and 0.27(95%CI:0.16–0.48),respectively.Pooled HRs per 1 metabolic equivalent(1-MET)increment were significant for all-cause mortality(HR=0.81;95%CI:0.74–0.88)but not for CVD mortality(HR=0.75;95%CI:0.48–1.18).Coronary artery disease patients with high CRF had a lower risk of all-cause mortality(HR=0.32;95%CI:0.26–0.41)than did their unfit counterparts.Each 1-MET increase was associated with lower all-cause mortality risk among coronary artery disease patients(HR=0.83;95%CI:0.76–0.91)but not lower among those with heart failure(HR=0.69;95%CI:0.36–1.32).Conclusion A better CRF was associated with lower risk of all-cause mortality and CVD.This study supports the use of CRF as a powerful predictor of mortality in this population.

Olfactory proteotyping: towards the enlightenment of the neurodegeneration

Although phylogenetically ancient,the olfactory system has received less attention than other sensorial systems.However,olfactory dysfunction is considered an early prodromal event in neurodegenerative diseases(NDs)(Doty,2012;Attems et al.,2014),which may vary from severe smell loss(e.g.,Alzheimer’s and Parkinson’s diseases)to relatively moderate loss(e.g.,progressive supranuclear palsy)(Doty,2017).Recently,a cluster of neuropathological and functional discoveries has evidenced the relevant role of the olfactory bulb(OB)during the neurodegenerative process(Attems et al.,2014;Rey et al.,2018).For instance,the double-transgenic APP/PS1 mouse model of Alzheimer’s disease(AD)develops early proteomic disturbances accompanied by a specific modulation of the focal adhesion kinase(FAK)and mitogen-activated protein kinase(MAPK)dynamics at the level of the OB,demonstrating that olfactory molecular alterations occur prior toβ-amyloid plaque appearance and memory impairments in APP/PS1 transgenic mice(Lachen-Montes et al.,2016).

Prevalence of meeting 24-Hour Movement Guidelines from pre-school to adolescence: A systematic review and meta-analysis including 387,437 participants and 23 countries

Background:Meeting the 24-Hour Movement Guidelines(physical activity,screen time,and sleep duration) has been associated with positive health indicators.However,there are no previous meta-analyses that have examined the overall adherence to the 24-Hour Movement Guidelines from pre-school to adolescence across the world.Therefore,the main purpose of this systematic review and meta-analysis was to examine the overall(non)adherence to the 24-Hour Movement Guidelines among preschoolers,children,and adolescents worldwide.Methods:Four electronic databases(MEDLINE,Scopus,Web of Science,and Cochrane Database of Systematic Reviews) were searched for quantitative studies published in Spanish and English between January 2016 and May 2021.Studies that were conducted with apparently healthy participants and reported the overall(non)adherence to the 24-Hour Movement Guidelines in preschoolers and/or children and/or adolescents were included.Results:Sixty-three studies comprising 387,437 individuals(51% girls) aged 3-18 years from 23 countries were included.Overall,7.12%(95%confidence interval(95%CI):6.45%-7.78%) of youth met all three 24-Hour Movement Guidelines,and 19.21%(95%CI:16.73%-21.69%)met none of the 3 recommendations.Concerning sex,adherence to all recommendations was significantly lower in girls(3.75%,95%CI:3.23%-4.27%) than in boys(6.89%,95%CI:5.89%-7.89%)(p <0.001).However,there were no sex differences regarding adherence to any of the 3 individual recommendations(girls,15.66%,95%CI:8.40%-22.92%;boys,12.95%,95%CI:6.57%-19.33%).In terms of age group,adherence to the 3 recommendations was 11.26%(95%CI:8.68%-13.84%),10.31%(95%CI:7.49%-13.12%),and 2.68%(95%CI:1.78%-3.58%) in preschoolers,children,and adolescents,respectively.Conversely,8.81%(95%CI:5.97%-11.64%) of preschoolers,15.57%(95%CI:11.60%-19.54%) of children,and 28.59%(95%CI:22.42%-34.75%) of adolescents did not meet any of the recommendations.South America was the region with the lowest adherence(all:2.93%;none:31.72%).Overall adherence to the 24-Hour Movement Guidelines was positively related to country Human Development Index(β=-0.37,95%CI:-0.65 to-0.09;p=0.010).Conclusion:Most young people fail to meet the three 24-Hour Movement Guidelines,particularly adolescents,girls,and those who are from countries with a lower Human Development Index.Moreover,1 in 5 young people did not meet any of these recommendations.Therefore,these results highlight the need to develop age-and sex-specific strategies to promote these movement behaviors from the early stages of life.

Is device-measured vigorous physical activity associated with health-related outcomes in children and adolescents? A systematic review and meta-analysis

Objective:This study sought to analyze the prospective association between vigorous-intensity physical activity(VPA)and health-related outcomes in children and adolescents.Methods:Studies reporting associations between device-measured VPA and health-related factors in children and adolescents aged 318 years were identified through database searches(MEDLINE,EMBASE,and SPORTDiscus).Correlation coefficients were pooled if outcomes were reported by at least 3 studies,using DerSimonian-Laird random effects models.Results:Data from 23 studies including 13,674 participants were pooled using random effects models.Significant associations were found between VPA at baseline and overall adiposity(r=0.09,95%confidence interval(95%CI):0.15 to0.03;p=0.002;I^(2)=89.8%),cardiometabolic risk score(r=0.13,95%CI:0.24 to0.02,p=0.020;I^(2)=69.6%),cardiorespiratory fitness(r=0.25,95%CI:0.150.35;p<0.001;I^(2)=57.2%),and total body bone mineral density(r=0.16,95%CI:0.06 to 0.25;p=0.001;I^(2)=0%).Conclusion:VPA seems to be negatively related to adiposity and cardiometabolic risk score and positively related to cardiorespiratory fitness and total body bone mineral density among children and adolescents at follow-up.Therefore,our findings support the need to strengthen physical activity recommendations regarding VPA due to its health benefits in children and adolescents.

The effects of plyometric jump training on physical fitness attributes in basketball players:A meta-analysis`

Background:There is a growing body of experimental evidence examining the effects of plyometric jump training(PJT)on physical fitness attributes in basketball players;however,this evidence has not yet been comprehensively and systematically aggregated.Therefore,our objective was to meta-analyze the effects of PJT on physical fitness attributes in basketball players,in comparison to a control condition.Methods:A systematic literature search was conducted in the databases PubMed,Web of Science,and Scopus,up to July 2020.Peer-reviewed controlled trials with baseline and follow-up measurements investigating the effects of PJT on physical fitness attributes(muscle power,i.e.,jumping performance,linear sprint speed,change-of-direction speed,balance,and muscle strength)in basketball players,with no restrictions on their playing level,sex,or age.Hedge’s g effect sizes(ES)were calculated for physical fitness variables.Using a random-effects model,potential sources of heterogeneity were selected,including subgroup analyses(age,sex,body mass,and height)and single training factor analysis(program duration,training frequency,and total number of training sessions).Computation of metaregression was also performed.Results:Thirty-two studies were included,involving 818 total basketball players.Significant(p<0.05)small-to-large effects of PJT were evident on vertical jump power(ES=0.45),countermovement jump height with(ES=1.24)and without arm swing(ES=0.88),squat jump height(ES=0.80),drop jump height(ES=0.53),horizontal jump distance(ES=0.65),linear sprint time across distances≤10 m(ES=1.67)and>10 m(ES=0.92),change-of-direction performance time across distances≤40 m(ES=1.15)and>40 m(ES=1.02),dynamic(ES=1.16)and static balance(ES=1.48),and maximal strength(ES=0.57).The meta-regression revealed that training duration,training frequency,and total number of sessions completed did not predict the effects of PJT on physical fitness attributes.Subgroup analysis indicated greater improvements in older compared to younger players in horizontal jump distance(>17.15 years,ES=2.11;≤17.15 years,ES=0.10;p<0.001),linear sprint time>10 m(>16.3 years,ES=1.83;≤16.3 years,ES=0.36;p=0.010),and change-of-direction performance time≤40 m(>16.3 years,ES=1.65;≤16.3 years,ES=0.75;p=0.005).Greater increases in horizontal jump distance were apparent with>2 compared with≤2 weekly PJT sessions(ES=2.12 and ES=0.39,respectively;p<0.001).Conclusion:Data from 32 studies(28 of which demonstrate moderate-to-high methodological quality)indicate PJT improves muscle power,linear sprint speed,change-of-direction speed,balance,and muscle strength in basketball players independent of sex,age,or PJT program variables.However,the beneficial effects of PJT as measured by horizontal jump distance,linear sprint time>10 m,and change-of-direction performance time≤40 m,appear to be more evident among older basketball players.

LIBRA:an adaptative integrative tool for paired single-cell multi-omics data

Background:Single-cell multi-omics technologies allow a profound system-level biology understanding of cells and tissues.However,an integrative and possibly systems-based analysis capturing the different modalities is challenging.In response,bioinformatics and machine learning methodologies are being developed for multi-omics single-cell analysis.It is unclear whether current tools can address the dual aspect of modality integration and prediction across modalities without requiring extensive parameter fine-tuning.Methods:We designed LIBRA,a neural network based framework,to learn translation between paired multi-omics profiles so that a shared latent space is constructed.Additionally,we implemented a variation,aLIBRA,that allows automatic fine-tuning by identifying parameter combinations that optimize both the integrative and predictive tasks.All model parameters and evaluation metrics are made available to users with minimal user iteration.Furthermore,aLIBRA allows experienced users to implement custom configurations.The LIBRA toolbox is freely available as R and Python libraries at GitHub(TranslationalBioinformaticsUnit/LIBRA).Results:LIBRA was evaluated in eight multi-omic single-cell data-sets,including three combinations of omics.We observed that LIBRA is a state-of-the-art tool when evaluating the ability to increase cell-type(clustering)resolution in the integrated latent space.Furthermore,when assessing the predictive power across data modalities,such as predictive chromatin accessibility from gene expression,LIBRA outperforms existing tools.As expected,adaptive parameter optimization(aLIBRA)significantly boosted the performance of learning predictive models from paired data-sets.Conclusion:LIBRA is a versatile tool that performs competitively in both“integration”and“prediction”tasks based on single-cell multi-omics data.LIBRA is a data-driven robust platform that includes an adaptive learning scheme.

Diagnostic performance of serum interleukin-6 in pediatric acute appendicitis:a systematic review

Background Despite the radiological and analytical advances of the last decades,there is still a significant rate of diagnostic error in pediatric acute appendicitis.In recent years,multiple biomarkers have emerged as potential diagnostic tools.This study aimed to examine the diagnostic performance of serum interleukin-6 in pediatric acute appendicitis.Methods We conducted a systematic review of the literature that involved an extensive search in the main databases of medical bibliography(Medline,PubMed,Web of Science and SciELO).Two independent reviewers selected the relevant articles based on the previously defined inclusion and exclusion criteria.Methodological quality of the selected article was rated using the QUADAS2 index.Data extraction was performed by two independent reviewers.Results The research in the medical bibliography databases resulted in 68 articles.We removed 26 duplicates.Among the remaining 42 articles,we excluded 33 following the inclusion and exclusion criteria.Of the final 9 studies included in this review,8 provided measured serum interleukin-6 values,and all of them reported significant differences between groups,but inconsistent results regarding sensitivity and specificity.Conclusions The diagnostic performance of interleukine-6 alone for the diagnosis of acute appendicitis in children is limited.The sensitivity and specificity of interleukine-6 for the diagnosis of non-complicated acute appendicitis in the pediatric population are moderate but increased in complicated appendicitis.There seems to be a direct relationship between serum level of interleukin-6 and the hours of evolution of abdominal pain in children with acute appendicitis.The increasingly widespread use of non-operative management of acute appendicitis warrants further exploration of the classificatory potential of this marker between complicated and uncomplicated appendicitis.We consider that this may be an avenue of research to explore in the future.

Rebooting Synthetic Phage-Inducible Chromosomal Islands:One Method to Forge Them All

Phage-inducible chromosomal islands(PICIs)are a widespread family of mobile genetic elements,which have an important role in bacterial pathogenesis.These elements mobilize among bacterial species at extremely high frequencies,representing an attractive tool for the delivery of synthetic genes.However,tools for their genetic manipulation are limited and timing consuming.Here,we have adapted a synthetic biology approach for rapidly editing of PICIs in Saccharomyces cerevisiae based on their ability to excise and integrate into the bacterial chromosome of their cognate host species.As proof of concept,we engineered several PICIs from Staphylococcus aureus and Escherichia coli and validated this methodology for the study of the biology of these elements by generating multiple and simultaneous mutations in different PICI genes.For biotechnological purposes,we also synthetically constructed PICIs as Trojan horses to deliver different CRISPR-Cas9 systems designed to either cure plasmids or eliminate cells carrying the targeted genes.Our results demonstrate that the strategy developed here can be employed universally to study PICIs and enable new approaches for diagnosis and treatment of bacterial diseases.

The intracellular signalosome of PD-L1 in cancer cells

Programmed cell death-1 ligand-1(PD-L1)overexpression in cancer cells accelerates tumor progression.PD-L1 possesses two main pro-oncogenic functions.First,PD-L1 is a strong immunosuppressive molecule that inactivates tumor-specific T cells by binding to the inhibitory receptor PD-1.Second,PD-L1 function relies on the delivery of intrinsic intracellular signals that enhance cancer cell survival,regulate stress responses and confer resistance toward pro-apoptotic stimuli,such as interferons.Here,we review the current knowledge on intracellular signal transduction pathways regulated by PD-L1,describe its associated signalosome and discuss potential combinations of targeted therapies against the signalosome with PD-L1/PD-1 blockade therapies.

Discriminatory capacity of serum interleukin-6 between complicated and uncomplicated acute appendicitis in children:a prospective validation study

Background Serum interleukin-6(IL-6)has a moderate diagnostic performance in pediatric acute appendicitis(PAA).The evidence regarding its capacity to discern between complicated and uncomplicated PAA is scarce.Methods We designed a prospective observational study to validate serum IL-6 as a marker for diagnostic classification between complicated and uncomplicated PAA.This study included 205 patients divided into three groups:(1)patients who underwent major outpatient surgery(n=57);(2)patients with non-surgical abdominal pain(NSAP)in whom the diagnosis of PAA was excluded(n=53),and(3)patients with a confirmed diagnosis of PAA(n=95).The PAA patients were further classified as uncomplicated or complicated PAA.IL-6 concentration was determined in all patients at diagnosis.Comparative statistical analysis was performed using the Mann-Whitney U test,the Fisher exact test and the Kruskall Wallis test.The area under the receiver operating characteristic curves(AUC)were calculated.Results Median(interquartile range,IQR)serum IL-6 values were 2 pg/mL(2.0–3.4)in group 1,3.9 pg/mL(2.4–11.9)in group 2,and 23.9 pg/mL(11.1–61.0)in group 3(P<0.001).Among the participants in group 3,those with uncomplicated PAA had median(IQR)serum IL-6 values of 17.2 pg/mL(8.5–36.8),and those with complicated PAA had 60.25 pg/mL(27.1–169)serum IL-6(P<0.001).At the cut-off point of 19.55 pg/mL,the AUC for the discrimination between patients in group 2 vs.3 was 0.83[95%confidence interval(CI)0.76–0.90],with a sensitivity of 61.3%and a specificity of 86.8.The AUC for the discrimination between patients with uncomplicated and complicated PAA was 0.77(95%CI 0.68–0.86)and the cut-off point was 25.90 pg/mL,with a sensitivity and specificity of 84.6%and 65.6%,respectively.Conclusions Serum IL-6 has a good performance in discerning between complicated and uncomplicated PAA.A score including clinical and radiological variables may increase the diagnostic performance of this molecule.

85岁以上高龄老人的运动锻炼 高龄并不妨碍老年人从量身定制的运动中获益

当今社会正在逐步老龄化,年龄≥85岁的人群已成为人口增长最快的群体,预计到2050年,他们的人口数量将增加2倍以上。如何在高龄时保持机体的健康和功能,对医护人员和公众来说,是个日益严峻的挑战。