Parkinson’s disease(PD)is a progressive age-related neurodegenerative disorder clinically defined by motor symptoms and pathologically by the loss of dopaminergic(DA)neurons in the substantia nigra pars compacta.Thes...Parkinson’s disease(PD)is a progressive age-related neurodegenerative disorder clinically defined by motor symptoms and pathologically by the loss of dopaminergic(DA)neurons in the substantia nigra pars compacta.These neurons are characterized by the presence of the cytoplasmic pigment neuromelanin(NM),and their degeneration is closely associated with the accumulation ofα-synuclein(α-syn)into intraneuronal inclusions known as Lewy bodies(LBs),which represent a neuropathological hallmark of PD.展开更多
After injury,bone tissue initiates a reparative response to restore its structure and function.The failure to initiate or delay this response could result in fracture nonunion.The molecular mechanisms underlying the o...After injury,bone tissue initiates a reparative response to restore its structure and function.The failure to initiate or delay this response could result in fracture nonunion.The molecular mechanisms underlying the occurrence of fracture nonunion are not yet established.We propose that hypoxia-triggered signaling pathways,mediated by reactive oxygen species(ROS)homeostasis,control Bmp2 expression and fracture healing initiation.The excessive ROS leads to oxidative stress and,ultimately,fracture nonunion.In this study,we silenced Apex1,the final ROS signaling transducer that mediates the activation of key transcription factors by their cysteines oxidoreduction,evaluating its role during endochondral ossification and fracture repair.Silencing Apex1 in limb bud mesenchyme results in transient metaphyseal dysplasia derived from impaired chondrocyte differentiation.During bone regeneration,Apex1 silencing induces a fracture nonunion phenotype,characterized by delayed fracture repair initiation,impaired periosteal response,and reduced chondrocyte and osteoblast differentiation.This compromised chondrocyte differentiation hampers callus vascularization and healing progression.Our findings highlight a critical mechanism where hypoxia-driven ROS signaling in mesenchymal progenitors through APEX1 is essential for fracture healing initiation.展开更多
Endochondral ossification is a physiological process involving a sequential formation of cartilage and bone tissues.Classically,cartilage and bone formation have been considered independent processes at cellular level...Endochondral ossification is a physiological process involving a sequential formation of cartilage and bone tissues.Classically,cartilage and bone formation have been considered independent processes at cellular level.However,the recently described multiple cell differentiation dynamics suggest that some bone cells are indeed the progeny of cartilage cells,or chondrocyte-derived osteoblasts.We hypothesized that the cartilage-to-bone phenotype transition is triggered by specific molecular events.First,the process was assessed in mouse bone tissue,and then,it was mimicked using in vivo cell implantation and in vitro serial differentiation protocols.Data indicates that cartilage cells transition to bone cell phenotype during postnatal physiological bone formation.This process can be reproduced using cartilage precursor cells coupled to specific implantation procedures or differentiation protocols.Gene expression profiling reveals that NOTCH,BMP and MAPK signaling pathways are relevant at the phenotype-switch,while the transcription factors Mesp1,Alx1,Grhl3 and Hmx3 are the feasible driver genes for chondrocyte-derived osteoblasts formation.Altogether,this report shows that endochondral ossification can be modeled using primary cell cultures and data indicate that this process is regulated by specific molecular events,previously described at skeleton morphogenesis during embryo development,and from now on also linkable to postnatal bone development and regeneration processes.展开更多
Purpose:The purpose of this study was to examine the associations between adherence to the 24-Hour Movement Guidelines and all-cause and cause-specific mortality in a large Spanish prospective cohort.Methods:We analyz...Purpose:The purpose of this study was to examine the associations between adherence to the 24-Hour Movement Guidelines and all-cause and cause-specific mortality in a large Spanish prospective cohort.Methods:We analyzed data from 14,288 participants of the Seguimiento Universidad de Navarra(SUN)Project,followed for a mean of 12.8 years(mean baseline age=38.3 years;60.1%women).Data were collected at baseline and through biennial follow-up questionnaires(up to 10 waves,depending on year of entry).The participants self-reported 24-h movement behaviors at baseline and were categorized based on the number of guidelines met(0-3).Behaviors were assessed at baseline only;changes in adherence during follow-up were not accounted for.Cox proportional hazards models were used to estimate hazard ratios(HRs)for all-cause and cause-specific mortality,adjusting for sociodemographic,lifestyle,and clinical covariates.Results:Meeting a greater number of 24-Hour Movement Guidelines at baseline was associated with a progressively lower risk of all-cause mortality.Compared with those meeting none,the multivariable-adjusted HRs were 0.52(95%confidence interval(95%CI):0.33-0.82)for meeting 1 guideline,0.47(95%CI:0.30-0.73)for meeting 2 guidelines,and 0.44(95%CI:0.28-0.71)for meeting all 3 guidelines.Only adherence to the physical activity guidelines was independently associated with a significantly lower mortality risk(HR=0.70;95%CI:0.55-0.89).A reduced risk was also observed for cancer and other-cause mortality among those meeting 2 or more guidelines.Conclusion:Adherence to the 24-Hour Movement Guidelines at baseline,particularly physical activity,was associated with a lower risk of mortality.Promoting an integrated approach to movement behaviors may be an effective strategy for improving population health and longevity.展开更多
Sirtuin 2 is a member of the sirtuin family nicotinamide adenine dinucleotide(NAD~+)-dependent deacetylases, known for its regulatory role in different processes, including inflammation. In this context, sirtuin 2 has...Sirtuin 2 is a member of the sirtuin family nicotinamide adenine dinucleotide(NAD~+)-dependent deacetylases, known for its regulatory role in different processes, including inflammation. In this context, sirtuin 2 has been involved in the modulation of key inflammatory signaling pathways and transcription factors by deacetylating specific targets, such as nuclear factor κB and nucleotide-binding oligomerization domain-leucine-rich-repeat and pyrin domain-containing protein 3(NLRP3). However, whether sirtuin 2-mediated pathways induce a pro-or an anti-inflammatory response remains controversial. Sirtuin 2 has been implicated in promoting inflammation in conditions such as asthma and neurodegenerative diseases, suggesting that its inhibition in these conditions could be a potential therapeutic strategy. Conversely, arthritis and type 2 diabetes mellitus studies suggest that sirtuin 2 is essential at the peripheral level and, thus, its inhibition in these pathologies would not be recommended. Overall, the precise role of sirtuin 2 in inflammation appears to be context-dependent, and further investigation is needed to determine the specific molecular mechanisms and downstream targets through which sirtuin 2 influences inflammatory processes in various tissues and pathological conditions. The present review explores the involvement of sirtuin 2 in the inflammation associated with different pathologies to elucidate whether its pharmacological modulation could serve as an effective strategy for treating this prevalent symptom across various diseases.展开更多
Data-driven drug repositioning using olfactory omics profiles-challenges and perspectives in neurodegeneration:Neurodegenerative diseases are characterized by progressive degeneration and loss of neuronal function in ...Data-driven drug repositioning using olfactory omics profiles-challenges and perspectives in neurodegeneration:Neurodegenerative diseases are characterized by progressive degeneration and loss of neuronal function in the central nervous system.These diseases are often characterized as proteinopathies,which are disorders primarily driven by the aggregation or misfolding of specific amyloid proteins within cells,leading to their dysfunction and eventual death.Despite the gain-of-function hypothesis related to the aggregation of these proteins,recently,an alternative hypothesis regarding the loss-of-function of the soluble monomeric proteins during the process of aggregation into amyloids is gaining currency.This last event is called proteinopenia and refers to conditions characterized by a deficiency or decrease in the levels of specific soluble proteins in the body(Ezzat et al.,2023).It has been demonstrated that levels of soluble proteins involved in neurodegenerative diseases are decreased.展开更多
Neuroinflammation is associated with Parkinson’s disease:Reactive gliosis and neuroinflammation are hallmarks of Parkinson’s disease(PD),a multisystem neurodegenerative disorder characterized by a progressive loss o...Neuroinflammation is associated with Parkinson’s disease:Reactive gliosis and neuroinflammation are hallmarks of Parkinson’s disease(PD),a multisystem neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons.Neuroinflammation has long been considered a mere consequence of neuronal loss,but whether it promotes PD or is a key player in disease progression remains to be determined.Human leukocyte antigen.展开更多
1.Introduction Adherence to 24-hour movement guidelines—which encompass regular physical activity,adequate sleep,and limited sedentary time1—significantly influences long-term health outcomes during adolescence and ...1.Introduction Adherence to 24-hour movement guidelines—which encompass regular physical activity,adequate sleep,and limited sedentary time1—significantly influences long-term health outcomes during adolescence and contributes holistically to overall health.2 However,its prospective relationship with midlife mortality remains unknown to date.Our aim was to determine the association between adherence to 24-hour movement guidelines during adolescence and premature mortality 26-27 years later.This aim was based on existing evidence3 suggesting a potential link between meeting these guidelines and reduced mortality risk among adults in an 11-year follow-up.展开更多
Background:A shift from self-reports to wearable sensors for global physical activity(PA)surveillance has been recommended.The conventional use of a generic cut-point to assess moderate-to-vigorous PA(MVPA)is problema...Background:A shift from self-reports to wearable sensors for global physical activity(PA)surveillance has been recommended.The conventional use of a generic cut-point to assess moderate-to-vigorous PA(MVPA)is problematic as these cut-points are often derived from non-representative samples under non-ecological laboratory conditions.This study aimed to develop age-and sex-(age-sex)specific cut-points for MVPA based on population-standardized values as a feasible approach to assess the adherence to PA guidelines and to investigate its associations with all-cause mortality.Methods:A total of 7601 participants(20-85+years)were drawn from the 2003-2004 and 2005-2006 National Health and Nutrition Examination Surveys(NHANES).Minutes per week of MVPA were assessed with a hip-worn accelerometer.Counts per minute(CPM)were used to define an age-sex specific target intensity,representing the intensity each person should be able to reach based on their age and sex.Age-sex specific MVPA cut-points were defined as any activity above 40%of the target intensity.These population-and free-living-based age-sex specific cut-points overcome many of the limitations of the standard generic cut-point approach.For comparison,we also calculated MVPA with a generic cut-point of 1952 CPM.Both approaches were compared for assessing adherence to PA guidelines and association of MVPA with allcause mortality(ascertained through December 2015).Results:Both approaches indicated that 37%of the sample met the 150+min/week guideline.The generic cut-point approach showed a trend to inactivity with age,which was less pronounced using the age-sex specific cut-points.Overall mortality rates were comparable using generic cutpoint(hazard ratio(HR)=0.61,95%confidence interval(95%CI):0.50-0.73)or age-sex specific cut-points(HR=0.57,95%CI:0.50-0.66)for the entire sample.The generic cut-point method revealed an age-and sex-related gap in the benefits of achieving 150+min/week of MVPA,with older adults showing an 18%greater reduction in mortality rates than younger adults,and a larger difference in women than in men.This disparity disappeared when using age-sex specific cut-points.Conclusion:Our findings underscore the value of age-sex specific cut-points for global PA surveillance.MVPA defined with age-sex specific thresholds was associated with all-cause mortality and the dose-response was similar for all ages and sexes.This aligns with the single recommendation of accumulating 150+min/week MVPA for all adults,irrespective of age and sex.This study serves as a proof of concept to develop this methodology for PA surveillance over more advanced open-source acceleration metrics and other national and international cohorts.展开更多
Background:Mammalian cells possess molecular clocks,the adequate functioning of which is decisive for metabolic health.Exercise is known to modulate these clocks,potentially having distinct effects on metabolism depen...Background:Mammalian cells possess molecular clocks,the adequate functioning of which is decisive for metabolic health.Exercise is known to modulate these clocks,potentially having distinct effects on metabolism depending on the time of day.This study aimed to investigate the impact of morning vs.evening moderate-intensity aerobic exercise on glucose regulation and energy metabolism in healthy men and women.It also aimed to elucidate molecular mechanisms within skeletal muscle.Methods:Using a randomized crossover design,healthy men(n=18)and women(n=17)performed a 60-min bout of moderate-intensity aerobic exercise in the morning and evening.Glucose regulation was continuously monitored starting 24 h prior to the exercise day and continuing until 48 h post-exercise for each experimental condition.Energy expenditure and substrate oxidation were measured by indirect calorimetry during exercise and at rest before and after exercise for 30 min.Skeletal muscle biopsies were collected immediately before and after exercise to assess mitochondrial function,transcriptome,and mitochondrial proteome.Results:Results indicated similar systemic glucose,energy expenditure,and substrate oxidation during and after exercise in both sexes.Notably,transcriptional analysis,mitochondrial function,and mitochondrial proteomics revealed marked sexual dimorphism and time of day variations.Conclusion:The sexual dimorphism and time of day variations observed in the skeletal muscle in response to exercise may translate into observable systemic effects with higher exercise-intensity or chronic exercise interventions.This study provides a foundational molecular framework for precise exercise prescription in the clinical setting.展开更多
Alzheimer's disease is the most common cause of dementia globally with an increasing incidence over the years,bringing a heavy burden to individuals and society due to the lack of an effective treatment.In this co...Alzheimer's disease is the most common cause of dementia globally with an increasing incidence over the years,bringing a heavy burden to individuals and society due to the lack of an effective treatment.In this context,sirtuin 2,the sirtuin with the highest expression in the brain,has emerged as a potential therapeutic target for neurodegenerative diseases.This review summarizes and discusses the complex roles of sirtuin 2 in different molecular mechanisms involved in Alzheimer's disease such as amyloid and tau pathology,microtubule stability,neuroinflammation,myelin formation,autophagy,and oxidative stress.The role of sirtuin 2 in all these processes highlights its potential implication in the etiology and development of Alzheimer's disease.However,its presence in different cell types and its enormous variety of substrates leads to apparently contra dictory conclusions when it comes to understanding its specific functions.Further studies in sirtuin 2 research with selective sirtuin2 modulators targeting specific sirtuin 2 substrates are necessary to clarify its specific functions under different conditions and to validate it as a novel pharmacological target.This will contribute to the development of new treatment strategies,not only for Alzheimer's disease but also for other neurodegenerative diseases.展开更多
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 studie...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.展开更多
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)(D...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).展开更多
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 cardiov...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.展开更多
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 t...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.展开更多
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...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.展开更多
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 betwee...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.展开更多
Dysphagia is commonly associated with malnutrition and an increased choking risk.To overcome these complications,food designed for people with dysphagia should have an appropriate texture and a high nutritional value....Dysphagia is commonly associated with malnutrition and an increased choking risk.To overcome these complications,food designed for people with dysphagia should have an appropriate texture and a high nutritional value.In this study,six formulations of a strawberry dessert enriched in protein(calcium caseinate)and fiber(wheat dextrin or inulin)were developed using different hydrocolloids(xanthan gum,carboxymethyl cellulose or modified starch)to provide desirable texture and stability.Nutritional value was calculated and total phenolic content and antioxidant activity of the samples were analyzed.Back-extrusion test,rheological measurements and sensory analysis were performed in refrigerated and frozen samples to characterize their textural and viscoelastic properties.The high content in protein(14.7 g/100 g)and fiber(7.9-8.7 g/100 g)made possible to use the claims“high protein”and“high fiber”.Phytochemicals supplied by strawberries contributed to the antioxidant properties of the dessert.Loss tangent ranged 0.28-0.35 for all the formulations,indicating a weak gel behavior,which could be considered safe to swallow.The formulations with dextrin in combination with carboxymethyl cellulose or xanthan gum seemed to be less susceptible to structural changes during frozen storage.This work provides insights for the development of a nutrient-dense dessert that meets the requirements of people with dysphagia.展开更多
Humans and animals use the classic five senses-sight,hearing,touch,smell,and taste-to detect and monitor their environment,with the sense of position and movement often referred to as the sixth sense.The perception of...Humans and animals use the classic five senses-sight,hearing,touch,smell,and taste-to detect and monitor their environment,with the sense of position and movement often referred to as the sixth sense.The perception of external signals through the senses is essential to an organism's survival,transmitting signals to the central nervous system(CNS)and prompting physiological changes in other biological systems.In addition to the direct effects of sense-induced mediators in the brain.展开更多
Unipolar depressive disorder(UDD)affects more than 264 million people worldwide and was projected well before the severe acute respiratory syndrome coronavirus 2 pandemic to be the leading cause of disability-adjusted...Unipolar depressive disorder(UDD)affects more than 264 million people worldwide and was projected well before the severe acute respiratory syndrome coronavirus 2 pandemic to be the leading cause of disability-adjusted life years lost in 2030.It is imperative for leading economies to implement preventive strategies targeted towards UDD,given consistent policies are currently lacking.Recently established similarities between the aetiological hypotheses of depression and cardiometabolic diseases are shifting paradigms within this field.It is believed that dietary practices could potentially reduce the incidence of depression;similar to their effects on metabolism.Thus,the aim of this review was to compile current evidence on healthy dietary patterns as suitable contributors towards primary prevention strategies against UDD.Most of the well-known biological mechanisms behind depression have been positively associated with healthful diets and dietary patterns to varying degrees.Interestingly,a common factor of UDD is the production and overall effects of inflammatory cytokines,such as interleukin-6,tumor necrosis factor-α,and Creactive protein.These compounds have been associated with depressive symptoms,disturbances in neuroendocrine function,leaky gut,monoamine activity and brain function,while also being key factors in the development of cardiometabolic diseases.The Mediterranean diet(MD)in particular,is well supported by first-level evidence regarding its preventive qualities against metabolic and cardiovascular diseases and thus considered a model for healthy eating by various organizations.In one of the few clinical trials investigating these associations,the PREDIMED trial,individuals with diabetes assigned to a MD supplemented with mixed tree nuts experienced a 41%relative risk reduction for developing depression.Lastly,there is a need to include health related quality of life as an indicator of physical and mental well-being,considering its putative associations with depression and suicide risk.Going forward,focusing on clinical trials,using precise nutritional assessments,and identifying nutritional biomarkers which may be related to depression are needed to fully support the implementation of dietary recommendations in the field of psychiatry.展开更多
基金This work was supported by PID2022-138285OB-I00financiado por MCIN/AEI/10.13039/501100011033/FEDER,UE to AGO and MCTAsociación de Amigos fellowship grant to MGG.
文摘Parkinson’s disease(PD)is a progressive age-related neurodegenerative disorder clinically defined by motor symptoms and pathologically by the loss of dopaminergic(DA)neurons in the substantia nigra pars compacta.These neurons are characterized by the presence of the cytoplasmic pigment neuromelanin(NM),and their degeneration is closely associated with the accumulation ofα-synuclein(α-syn)into intraneuronal inclusions known as Lewy bodies(LBs),which represent a neuropathological hallmark of PD.
基金supported by funds of the Ministerio de Ciencia, Innovación y Universidadesco-financed by European Regional Development Fund-FEDER “A way to make Europe” (Project Ref:PID2023-153309OB-I00) supported by MCIN/AEl/ 10.13039/501100011033/ FEDER, UE+10 种基金Ministerio de Ciencia, Innovación y Universidades through Instituto de Salud Carlos Ⅲ and European Regional Development Funds “A way to make Europe” (PI17/00136, PI20/00076)European Union Horizon 2020 program (grant agreement #874889, HEALIKICK) to F. Granero-MoltóNext Generation EU, Plan de Recuperación, Transformación y Resiliencia RICORS TERAV ISCIII (RD21/0017/0009)H2020-MSCA-RISE-2019 (grant agreement #872648, MEPHOS) to F. Próspersupported by a fellowship from “Asociación de Amigos de la Universidad de Navarra”supported by a fellowship CIMA AC from “Fundación para la Investigación Médica Aplicada”funded by grants PID2022-104776RB-100 and CB16/11/00399 (CIBER CV) from MCIN/AEI/10.13039/501100011033La Caixa Research Health Foundation (Ref. HR23-00084)supported by a fellowship of “Asociación de Amigos de la Universidad de Navarra” and “Obra Social La Caixa”the research leading to these results has received funding from “la Caixa” Banking Foundationsupported by a Sara Borrell grant (CD22/00027) from the Instituto Carlos Ⅲ and Next Generation EU。
文摘After injury,bone tissue initiates a reparative response to restore its structure and function.The failure to initiate or delay this response could result in fracture nonunion.The molecular mechanisms underlying the occurrence of fracture nonunion are not yet established.We propose that hypoxia-triggered signaling pathways,mediated by reactive oxygen species(ROS)homeostasis,control Bmp2 expression and fracture healing initiation.The excessive ROS leads to oxidative stress and,ultimately,fracture nonunion.In this study,we silenced Apex1,the final ROS signaling transducer that mediates the activation of key transcription factors by their cysteines oxidoreduction,evaluating its role during endochondral ossification and fracture repair.Silencing Apex1 in limb bud mesenchyme results in transient metaphyseal dysplasia derived from impaired chondrocyte differentiation.During bone regeneration,Apex1 silencing induces a fracture nonunion phenotype,characterized by delayed fracture repair initiation,impaired periosteal response,and reduced chondrocyte and osteoblast differentiation.This compromised chondrocyte differentiation hampers callus vascularization and healing progression.Our findings highlight a critical mechanism where hypoxia-driven ROS signaling in mesenchymal progenitors through APEX1 is essential for fracture healing initiation.
基金funded by Grants PID2021-127191OB-I00,RTI2018-101708-A-I00,PRE2018-084542 and PRE2022-102680 funded by MCIN/AEI/10.13039/501100011033 and by“ERDF A way of making Europe”Grant RYC2018-025502-I is funded by MCIN/AEI/10.13039/501100011033 and by“ESF Investing in your future”+1 种基金Grant MDM-20170720 Maria de Maeztu Units of Excellence Program funded by the Spanish State Research Agencysupported by Instituto de Salud CarlosⅢ,Infrastructure of Precision Medicine associated with Science and Technology(IMPaCT)of the Strategic Action in Health(iDATA-MP)。
文摘Endochondral ossification is a physiological process involving a sequential formation of cartilage and bone tissues.Classically,cartilage and bone formation have been considered independent processes at cellular level.However,the recently described multiple cell differentiation dynamics suggest that some bone cells are indeed the progeny of cartilage cells,or chondrocyte-derived osteoblasts.We hypothesized that the cartilage-to-bone phenotype transition is triggered by specific molecular events.First,the process was assessed in mouse bone tissue,and then,it was mimicked using in vivo cell implantation and in vitro serial differentiation protocols.Data indicates that cartilage cells transition to bone cell phenotype during postnatal physiological bone formation.This process can be reproduced using cartilage precursor cells coupled to specific implantation procedures or differentiation protocols.Gene expression profiling reveals that NOTCH,BMP and MAPK signaling pathways are relevant at the phenotype-switch,while the transcription factors Mesp1,Alx1,Grhl3 and Hmx3 are the feasible driver genes for chondrocyte-derived osteoblasts formation.Altogether,this report shows that endochondral ossification can be modeled using primary cell cultures and data indicate that this process is regulated by specific molecular events,previously described at skeleton morphogenesis during embryo development,and from now on also linkable to postnatal bone development and regeneration processes.
文摘Purpose:The purpose of this study was to examine the associations between adherence to the 24-Hour Movement Guidelines and all-cause and cause-specific mortality in a large Spanish prospective cohort.Methods:We analyzed data from 14,288 participants of the Seguimiento Universidad de Navarra(SUN)Project,followed for a mean of 12.8 years(mean baseline age=38.3 years;60.1%women).Data were collected at baseline and through biennial follow-up questionnaires(up to 10 waves,depending on year of entry).The participants self-reported 24-h movement behaviors at baseline and were categorized based on the number of guidelines met(0-3).Behaviors were assessed at baseline only;changes in adherence during follow-up were not accounted for.Cox proportional hazards models were used to estimate hazard ratios(HRs)for all-cause and cause-specific mortality,adjusting for sociodemographic,lifestyle,and clinical covariates.Results:Meeting a greater number of 24-Hour Movement Guidelines at baseline was associated with a progressively lower risk of all-cause mortality.Compared with those meeting none,the multivariable-adjusted HRs were 0.52(95%confidence interval(95%CI):0.33-0.82)for meeting 1 guideline,0.47(95%CI:0.30-0.73)for meeting 2 guidelines,and 0.44(95%CI:0.28-0.71)for meeting all 3 guidelines.Only adherence to the physical activity guidelines was independently associated with a significantly lower mortality risk(HR=0.70;95%CI:0.55-0.89).A reduced risk was also observed for cancer and other-cause mortality among those meeting 2 or more guidelines.Conclusion:Adherence to the 24-Hour Movement Guidelines at baseline,particularly physical activity,was associated with a lower risk of mortality.Promoting an integrated approach to movement behaviors may be an effective strategy for improving population health and longevity.
基金funded by FEDER/Ministerio de Ciencia,Innovación y Universidades Agencia Estatal de Investigación/Project(PID2020-119729GB-100,REF/AEI/10.13039/501100011033)(to EP)a predoctoral fellowship from the Spanish Ministry of Universities(FPU)and Amigos de la Universidad de Navarra(to NSS)“Programa MRR Investigo 2023”(to MGB and MMD)。
文摘Sirtuin 2 is a member of the sirtuin family nicotinamide adenine dinucleotide(NAD~+)-dependent deacetylases, known for its regulatory role in different processes, including inflammation. In this context, sirtuin 2 has been involved in the modulation of key inflammatory signaling pathways and transcription factors by deacetylating specific targets, such as nuclear factor κB and nucleotide-binding oligomerization domain-leucine-rich-repeat and pyrin domain-containing protein 3(NLRP3). However, whether sirtuin 2-mediated pathways induce a pro-or an anti-inflammatory response remains controversial. Sirtuin 2 has been implicated in promoting inflammation in conditions such as asthma and neurodegenerative diseases, suggesting that its inhibition in these conditions could be a potential therapeutic strategy. Conversely, arthritis and type 2 diabetes mellitus studies suggest that sirtuin 2 is essential at the peripheral level and, thus, its inhibition in these pathologies would not be recommended. Overall, the precise role of sirtuin 2 in inflammation appears to be context-dependent, and further investigation is needed to determine the specific molecular mechanisms and downstream targets through which sirtuin 2 influences inflammatory processes in various tissues and pathological conditions. The present review explores the involvement of sirtuin 2 in the inflammation associated with different pathologies to elucidate whether its pharmacological modulation could serve as an effective strategy for treating this prevalent symptom across various diseases.
基金funded by grants from the Spanish Ministry of Science,Innovation and Universities(Ref.PID2019-110356RB-I00/AEI/10.13039/501100011033)to JFI and ESthe Department of Economic and Business Development from Government of Navarra(Ref.0011-1411-2023-000028 to ES)+2 种基金supported by a predoctoral fellowship from the Public University of Navarra(UPNA)supported by a postdoctoral fellowship from Miguel Servet Foundation-Navarrabiomedsupported by“Programa MRR Investigo 2023”in the framework of the European Union recovery and resilience facility。
文摘Data-driven drug repositioning using olfactory omics profiles-challenges and perspectives in neurodegeneration:Neurodegenerative diseases are characterized by progressive degeneration and loss of neuronal function in the central nervous system.These diseases are often characterized as proteinopathies,which are disorders primarily driven by the aggregation or misfolding of specific amyloid proteins within cells,leading to their dysfunction and eventual death.Despite the gain-of-function hypothesis related to the aggregation of these proteins,recently,an alternative hypothesis regarding the loss-of-function of the soluble monomeric proteins during the process of aggregation into amyloids is gaining currency.This last event is called proteinopenia and refers to conditions characterized by a deficiency or decrease in the levels of specific soluble proteins in the body(Ezzat et al.,2023).It has been demonstrated that levels of soluble proteins involved in neurodegenerative diseases are decreased.
基金supported by the Spanish Government(ISCIII-FEDER)PI20/01063by Navarra Government(PC 060-061 and PC 192-193)Fundación Gangoiti(to MSA).LA was funded by FPU19/03255.
文摘Neuroinflammation is associated with Parkinson’s disease:Reactive gliosis and neuroinflammation are hallmarks of Parkinson’s disease(PD),a multisystem neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons.Neuroinflammation has long been considered a mere consequence of neuronal loss,but whether it promotes PD or is a key player in disease progression remains to be determined.Human leukocyte antigen.
文摘1.Introduction Adherence to 24-hour movement guidelines—which encompass regular physical activity,adequate sleep,and limited sedentary time1—significantly influences long-term health outcomes during adolescence and contributes holistically to overall health.2 However,its prospective relationship with midlife mortality remains unknown to date.Our aim was to determine the association between adherence to 24-hour movement guidelines during adolescence and premature mortality 26-27 years later.This aim was based on existing evidence3 suggesting a potential link between meeting these guidelines and reduced mortality risk among adults in an 11-year follow-up.
基金supported in part by the intramural research programs at the National Institute on Aging and National Cancer Institute(USA)supported by the Spanish Ministry of Science,Innovation and Universities under Beatriz Galindo's 2022 fellowship program(BG22/00075).
文摘Background:A shift from self-reports to wearable sensors for global physical activity(PA)surveillance has been recommended.The conventional use of a generic cut-point to assess moderate-to-vigorous PA(MVPA)is problematic as these cut-points are often derived from non-representative samples under non-ecological laboratory conditions.This study aimed to develop age-and sex-(age-sex)specific cut-points for MVPA based on population-standardized values as a feasible approach to assess the adherence to PA guidelines and to investigate its associations with all-cause mortality.Methods:A total of 7601 participants(20-85+years)were drawn from the 2003-2004 and 2005-2006 National Health and Nutrition Examination Surveys(NHANES).Minutes per week of MVPA were assessed with a hip-worn accelerometer.Counts per minute(CPM)were used to define an age-sex specific target intensity,representing the intensity each person should be able to reach based on their age and sex.Age-sex specific MVPA cut-points were defined as any activity above 40%of the target intensity.These population-and free-living-based age-sex specific cut-points overcome many of the limitations of the standard generic cut-point approach.For comparison,we also calculated MVPA with a generic cut-point of 1952 CPM.Both approaches were compared for assessing adherence to PA guidelines and association of MVPA with allcause mortality(ascertained through December 2015).Results:Both approaches indicated that 37%of the sample met the 150+min/week guideline.The generic cut-point approach showed a trend to inactivity with age,which was less pronounced using the age-sex specific cut-points.Overall mortality rates were comparable using generic cutpoint(hazard ratio(HR)=0.61,95%confidence interval(95%CI):0.50-0.73)or age-sex specific cut-points(HR=0.57,95%CI:0.50-0.66)for the entire sample.The generic cut-point method revealed an age-and sex-related gap in the benefits of achieving 150+min/week of MVPA,with older adults showing an 18%greater reduction in mortality rates than younger adults,and a larger difference in women than in men.This disparity disappeared when using age-sex specific cut-points.Conclusion:Our findings underscore the value of age-sex specific cut-points for global PA surveillance.MVPA defined with age-sex specific thresholds was associated with all-cause mortality and the dose-response was similar for all ages and sexes.This aligns with the single recommendation of accumulating 150+min/week MVPA for all adults,irrespective of age and sex.This study serves as a proof of concept to develop this methodology for PA surveillance over more advanced open-source acceleration metrics and other national and international cohorts.
基金funded by the Spanish Ministry of Culture and Sport,Consejo Superior de Deportes,Plan de Recuperación,Transformación y Resiliencia,Unión Europea,Next Generation EUAyudas Europeas a Proyectos de Investigaci on Aplicada a la Actividad Física Beneficiosa para la Salud y la Medicina Deportiva(EXP_77437)+9 种基金by the Spanish Ministry of Science and Innovation(PID2022-141506OB-I00)the European Regional Development Funds(ERDF)by the University of Granada Plan Propio de Investigación-Excellence actions:Unit of Excellence on Exercise Nutrition and Health(UCEENS)supported by the Spanish Ministry of Education,Culture and Sport(FPU19/03745 and FPU20/05530,respectively)supported by the Juan de la Cierva Formación Grant FJC2020-044453-I funded by Ministerio de Ciencia e Innovaci on/Agencia Estatal de Investigaci on MCIN/AEI/10.13039/501100011033European Union Next Generation,Plan de Recuperación,Transformación y Resilencia(EU/PRTR)“Ramón y Cajal fellowship 2013-2017”funded by MCIN/AEI/10.13039/501100011033 and“El Fondo Social Europeo invierte en tu futuro”partially supported by the Grant PID2020-114054RA-I001001100482funded by MCIN/AEI/10.13039/501100011033supported by a grant from the MCIN/AEI/10.13039/501100011033,Spain,and the ERDF(PID2021-126788OB-I00).
文摘Background:Mammalian cells possess molecular clocks,the adequate functioning of which is decisive for metabolic health.Exercise is known to modulate these clocks,potentially having distinct effects on metabolism depending on the time of day.This study aimed to investigate the impact of morning vs.evening moderate-intensity aerobic exercise on glucose regulation and energy metabolism in healthy men and women.It also aimed to elucidate molecular mechanisms within skeletal muscle.Methods:Using a randomized crossover design,healthy men(n=18)and women(n=17)performed a 60-min bout of moderate-intensity aerobic exercise in the morning and evening.Glucose regulation was continuously monitored starting 24 h prior to the exercise day and continuing until 48 h post-exercise for each experimental condition.Energy expenditure and substrate oxidation were measured by indirect calorimetry during exercise and at rest before and after exercise for 30 min.Skeletal muscle biopsies were collected immediately before and after exercise to assess mitochondrial function,transcriptome,and mitochondrial proteome.Results:Results indicated similar systemic glucose,energy expenditure,and substrate oxidation during and after exercise in both sexes.Notably,transcriptional analysis,mitochondrial function,and mitochondrial proteomics revealed marked sexual dimorphism and time of day variations.Conclusion:The sexual dimorphism and time of day variations observed in the skeletal muscle in response to exercise may translate into observable systemic effects with higher exercise-intensity or chronic exercise interventions.This study provides a foundational molecular framework for precise exercise prescription in the clinical setting.
基金funded by FEDER/Ministerio de CienciaInnovacion y Universidades Agencia Estatal de Investigacion(MCIN/AEI 10.13039/501100011033)Grant(SAF2017-87595-R and PID2020-119729G8-100)(to EP)"Amigos de Ia Universidad de Navarra"and the Spanish Ministry of Universities for a fellowship(FPU)to NSS。
文摘Alzheimer's disease is the most common cause of dementia globally with an increasing incidence over the years,bringing a heavy burden to individuals and society due to the lack of an effective treatment.In this context,sirtuin 2,the sirtuin with the highest expression in the brain,has emerged as a potential therapeutic target for neurodegenerative diseases.This review summarizes and discusses the complex roles of sirtuin 2 in different molecular mechanisms involved in Alzheimer's disease such as amyloid and tau pathology,microtubule stability,neuroinflammation,myelin formation,autophagy,and oxidative stress.The role of sirtuin 2 in all these processes highlights its potential implication in the etiology and development of Alzheimer's disease.However,its presence in different cell types and its enormous variety of substrates leads to apparently contra dictory conclusions when it comes to understanding its specific functions.Further studies in sirtuin 2 research with selective sirtuin2 modulators targeting specific sirtuin 2 substrates are necessary to clarify its specific functions under different conditions and to validate it as a novel pharmacological target.This will contribute to the development of new treatment strategies,not only for Alzheimer's disease but also for other neurodegenerative diseases.
文摘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.
基金funded by grants from the Spanish Ministry of Economy and Competitiveness(MINECO)(No.SAF2014-59340-R)Department of Economic Development from Government of Navarra(No.PC023-PC024,PC025,PC081-82 and PI059)and Obra Social la Caixa to ES+1 种基金The Proteomics Unit of Navarrabiomed is a member of Proteored,PRB3-ISCIIIsupported by grant PT17/0019 to JFI,of the PE I+D+i 2013-2016,funded by ISCIII and ERDF
文摘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).
基金AGH is a Miguel Servet Fellow at the Instituto de Salud Carlos III(CP18/0150)RRV is funded in part by a Postdoctoral Fellowship(Resolution ID 420/2019)from the Universidad Pública de Navarra.
文摘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.
基金the financial support of the Ministry of Economy and Infrastructures and European Communitysupported by the Ministry of Economy and Infrastructures of Extremadura (PD 18015)funded by FEDER,FSE and Govern of Extremadura,grant numbers GR18102 and TA18027.
文摘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.
文摘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.
文摘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.
基金Gobierno de Navarra(Proyectos Estratégicos para Navarra 2020)the FEDER program for the financial support of project NUTRI+。
文摘Dysphagia is commonly associated with malnutrition and an increased choking risk.To overcome these complications,food designed for people with dysphagia should have an appropriate texture and a high nutritional value.In this study,six formulations of a strawberry dessert enriched in protein(calcium caseinate)and fiber(wheat dextrin or inulin)were developed using different hydrocolloids(xanthan gum,carboxymethyl cellulose or modified starch)to provide desirable texture and stability.Nutritional value was calculated and total phenolic content and antioxidant activity of the samples were analyzed.Back-extrusion test,rheological measurements and sensory analysis were performed in refrigerated and frozen samples to characterize their textural and viscoelastic properties.The high content in protein(14.7 g/100 g)and fiber(7.9-8.7 g/100 g)made possible to use the claims“high protein”and“high fiber”.Phytochemicals supplied by strawberries contributed to the antioxidant properties of the dessert.Loss tangent ranged 0.28-0.35 for all the formulations,indicating a weak gel behavior,which could be considered safe to swallow.The formulations with dextrin in combination with carboxymethyl cellulose or xanthan gum seemed to be less susceptible to structural changes during frozen storage.This work provides insights for the development of a nutrient-dense dessert that meets the requirements of people with dysphagia.
基金supported by a grant from the Department of Economic and Business Development from the Government of Navarra(INNOLFACT project,Ref.0011-1411-2023-000094)。
文摘Humans and animals use the classic five senses-sight,hearing,touch,smell,and taste-to detect and monitor their environment,with the sense of position and movement often referred to as the sixth sense.The perception of external signals through the senses is essential to an organism's survival,transmitting signals to the central nervous system(CNS)and prompting physiological changes in other biological systems.In addition to the direct effects of sense-induced mediators in the brain.
文摘Unipolar depressive disorder(UDD)affects more than 264 million people worldwide and was projected well before the severe acute respiratory syndrome coronavirus 2 pandemic to be the leading cause of disability-adjusted life years lost in 2030.It is imperative for leading economies to implement preventive strategies targeted towards UDD,given consistent policies are currently lacking.Recently established similarities between the aetiological hypotheses of depression and cardiometabolic diseases are shifting paradigms within this field.It is believed that dietary practices could potentially reduce the incidence of depression;similar to their effects on metabolism.Thus,the aim of this review was to compile current evidence on healthy dietary patterns as suitable contributors towards primary prevention strategies against UDD.Most of the well-known biological mechanisms behind depression have been positively associated with healthful diets and dietary patterns to varying degrees.Interestingly,a common factor of UDD is the production and overall effects of inflammatory cytokines,such as interleukin-6,tumor necrosis factor-α,and Creactive protein.These compounds have been associated with depressive symptoms,disturbances in neuroendocrine function,leaky gut,monoamine activity and brain function,while also being key factors in the development of cardiometabolic diseases.The Mediterranean diet(MD)in particular,is well supported by first-level evidence regarding its preventive qualities against metabolic and cardiovascular diseases and thus considered a model for healthy eating by various organizations.In one of the few clinical trials investigating these associations,the PREDIMED trial,individuals with diabetes assigned to a MD supplemented with mixed tree nuts experienced a 41%relative risk reduction for developing depression.Lastly,there is a need to include health related quality of life as an indicator of physical and mental well-being,considering its putative associations with depression and suicide risk.Going forward,focusing on clinical trials,using precise nutritional assessments,and identifying nutritional biomarkers which may be related to depression are needed to fully support the implementation of dietary recommendations in the field of psychiatry.
