Health and wellbeing status of the long-lived individuals of the Spanish LONGECYL cross-sectional study.

BACKGROUND: The increase in life expectancy and long-lived individuals is a challenge for public health and provides an opportunity to understand the determinants of longevity. However, few studies have addressed the factors associated with the health status and quality of life in a long-lived individual population. We described the perceived health, clinical status, quality of life, and dependency for activities of daily living in a representative population in Castile and Leon, Spain. METHODS: A sample of 759 long-lived individuals aged 95 years and older was studied by the Health Sentinel Network of Castile and Leon (Spain) through a health examination and a structured questionnaire covering quality of life (EQ-5D-3), lifestyle habits, diet, working life and family health. A blood sample was taken for the study of biological and genetic markers. Chi Square and logistic regression OR with 95% confidence intervals were used to analyze the determinants of the long-lived individuals' health status. The significant level for the bivariate analysis was established at 0.05. RESULTS: Perceived health was good, very good or excellent in 64.2%, while only 46.0% had a quality-of-life index above 0.5 (ranging from 0 to 1) and 44.1% maintained acceptable independence for activities of daily living. Quality-of-life index was higher in the oldest, (OR 7.98 [2,32-27.41]) above 100 years compared to those under 98, and men had better values for independence than women (OR 2.43 [1.40-4.29]). Cardiovascular diseases were the most prevalent (85.5%), but neurological and mental diseases and vision problems had the highest impact on quality of life and independence. CONCLUSION: The long-lived individuals of Castile and Leon have a relatively well-preserved health status, although the perception of health is higher than that describing their quality of life and dependence. The quality of life was higher in the oldest age group and showed differences according to sex, with a better quality of life in men. Public health policies and programs should take in account the differences by sex and age as well as the prevention and control of the main conditions related with poor quality of life or dependence. Future research must include the interaction among genetic, socioeconomic, environmental, and other clinical factors in the quality of life and disability of long-lived individuals.

A critical appraisal of blood-based biomarkers for Alzheimer's disease.

Biomarkers that predict the clinical onset of Alzheimer's disease (AD) enable the identification of individuals in the early, preclinical stages of the disease. Detecting AD at this point may allow for more effective therapeutic interventions and optimized enrollment for clinical trials of novel drugs. The current biological diagnosis of AD is based on the AT(N) classification system with the measurement of brain deposition of amyloid-ß (Aß) ("A"), tau pathology ("T"), and neurodegeneration ("N"). Diagnostic cut-offs for Aß1-42, the Aß1-42/Aß1-40 ratio, tau and hyperphosphorylated-tau concentrations in cerebrospinal fluid have been defined and may support AD clinical diagnosis. Blood-based biomarkers of the AT(N) categories have been described in the AD continuum. Cross-sectional and longitudinal studies have shown that the combination of blood biomarkers tracking neuroaxonal injury (neurofilament light chain) and neuroinflammatory pathways (glial fibrillary acidic protein) enhance sensitivity and specificity of AD clinical diagnosis and improve the prediction of AD onset. However, no international accepted cut-offs have been identified for these blood biomarkers. A kit for blood Aß1-42/Aß1-40 is commercially available in the U.S.; however, it does not provide a diagnosis, but simply estimates the risk of developing AD. Although blood-based AD biomarkers have a great potential in the diagnostic work-up of AD, they are not ready for the routine clinical use.

Pumping up the Fight against Multiple Sclerosis: The Effects of High-Intensity Resistance Training on Functional Capacity, Muscle Mass, and Axonal Damage.

BACKGROUND: Resistance training (RT) has been recognized as a beneficial non-pharmacological intervention for multiple sclerosis (MS) patients, but its impact on neurodegeneration is not fully understood. This study aimed to investigate the effects of high-intensity RT on muscle mass, strength, functional capacity, and axonal damage in MS patients. METHODS: Eleven relapsing-remitting MS patients volunteered in this within-subject counterbalanced intervention study. Serum neurofilament light-chain (NfL) concentration, vastus lateralis thickness (VL), timed up-and-go test (TUG), sit-to-stand test (60STS), and maximal voluntary isometric contraction (MVIC) were measured before and after intervention. Participants performed 18 sessions of high-intensity RT (70-80% 1-RM) over 6 weeks. RESULTS: Significant (p < 0.05) differences were observed post-intervention for VL (ES = 2.15), TUG (ES = 1.98), 60STS (ES = 1.70), MVIC (ES = 1.78), and NfL (ES = 1.43). Although moderate correlations between changes in VL (R = 0.434), TUG (R = -0.536), and MVIC (R = 0.477) and changes in NfL were observed, only the correlation between VL and MVIC changes was significant (R = 0.684, p = 0.029). CONCLUSIONS: A 6-week RT program significantly increased muscle mass, functional capacity, and neuromuscular function while also decreasing serum NfL in MS patients. These results suggest the effectiveness of RT as a non-pharmacological approach to mitigate neurodegeneration while improving functional capacity in MS patients.

Physical exercise: a polypill against chronic kidney disease.

We are currently facing a pandemic of physical inactivity that might contribute to the growing prevalence of chronic kidney disease (CKD). Here, we summarize currently available evidence on the association between physical activity and CKD, and also review the effects of exercise intervention in affected patients. Physical activity/exercise might act as a polypill against CKD, preventing its development or even exerting beneficial effects once it is established (i.e. improvements in patients' physical fitness and cardiovascular risk, as well as in kidney function). Exercise benefits are also found at advanced CKD stages or in patients under hemodialysis. The biological mechanisms behind the clinical evidence are also discussed. An active lifestyle appears as a cornerstone in CKD prevention and management.

Lifestyle and cardiovascular risk in working young adults: insights from a nationwide Spanish cohort.

INTRODUCTION AND OBJECTIVES: This study aimed to describe the cardiovascular risk profile of working young adults from Spain and its association with lifestyle. METHODS: Participants (18-30 years) were recruited from a nationwide cohort of economically active adults insured by a large occupational risk prevention company, with data obtained from routine medical assessments. The participants were categorized as having an "unhealthy" cardiovascular risk profile based on the presence of prediabetes/diabetes, prehypertension/hypertension, or hypercholesterolemia, or a "healthy" profile if these conditions were completely absent. The association with lifestyle factors (weight, physical activity, sleeping characteristics, alcohol consumption, smoking) was assessed. RESULTS: A total of 78 421 young adults (27±2 years, 36% female) were evaluated at baseline. The "unhealthy" cardiovascular risk profile was prevalent (18%) and inversely associated (OR, 0.64; 95%CI, 0.57-0.80) with an optimal lifestyle (normal weight, regular physical activity, no drinking/smoking, and good sleep). The latter condition was found in only 3.5% of the participants. On the other hand, prospective analyses in 44 776 participants (median follow-up=2 [range 2-5] years) showed that 2.0% transitioned from a "healthy" to an "unhealthy" profile. Being physically active (OR, 0.95; 95%CI, 0.81-0.99) and having a normal weight (OR, 0.61; 95%CI, 0.51-0.70) were associated with a lower likelihood of this transition. No consistent associations were found for other lifestyle factors. CONCLUSIONS: The prevalence of cardiovascular risk factors is high in economically active young Spanish adults. An unhealthy cardiovascular risk profile is inversely associated with an optimal lifestyle, but the latter is highly infrequent in this population.

Impact of Physical Exercise on Melanoma Hallmarks: Current Status of Preclinical and Clinical Research.

In recent years, accumulating evidence from preclinical and clinical studies consistently indicated that physical activity/exercise plays a crucial role in reducing the incidence and recurrence of various malignancies, by exerting a beneficial modulation of cancer hallmarks. Moreover, physical activity is suggested to attenuate certain adverse effects of anticancer therapy, including the reduction of cardiovascular toxicity and symptoms related to depression and anxiety, among others, while preserving muscular strength. In the case of melanoma, the relationship with physical activity has been critically debated. Historically, several cohort studies and meta-analyses reported a positive association between physical activity/exercise and melanoma risk. This association was primarily attributed to outdoor activities that may expose the skin to UV radiation, a well-known risk factor for melanocyte transformation. However, more recent evidence does not support such association and recognizes physical activity/exercise role in both melanoma prevention and progression. Nevertheless, sun protection is recommended during outdoor training to minimize UV radiation exposure. This narrative review summarizes preclinical and clinical data about physical activity effects on melanoma hallmarks. Specifically, experimental evidence is reported concerning (i) invasion and metastasis, (ii) reprogramming of energy metabolism, (iii) angiogenesis, (iv) resistance to cell death, (v) evasion from immune destruction, and (vi) tumor-promoting inflammation.

Monitoring synaptic pathology in Alzheimer's disease through fluid and PET imaging biomarkers: a comprehensive review and future perspectives.

Alzheimer's disease (AD) is currently constrained by limited clinical treatment options. The initial pathophysiological event, which can be traced back to decades before the clinical symptoms become apparent, involves the excessive accumulation of amyloid-beta (Aß), a peptide comprised of 40-42 amino acids, in extraneuronal plaques within the brain. Biochemical and histological studies have shown that overaccumulation of Aß instigates an aberrant escalation in the phosphorylation and secretion of tau, a microtubule-binding axonal protein. The accumulation of hyperphosphorylated tau into intraneuronal neurofibrillary tangles is in turn correlated with microglial dysfunction and reactive astrocytosis, culminating in synaptic dysfunction and neurodegeneration. As neurodegeneration progresses, it gives rise to mild clinical symptoms of AD, which may eventually evolve into overt dementia. Synaptic loss in AD may develop even before tau alteration and in response to possible elevations in soluble oligomeric forms of Aß associated with early AD. These findings largely rely on post-mortem autopsy examinations, which typically involve a limited number of patients. Over the past decade, a range of fluid biomarkers such as neurogranin, α-synuclein, visinin-like protein 1 (VILIP-1), neuronal pentraxin 2, and ß-synuclein, along with positron emission tomography (PET) markers like synaptic vesicle glycoprotein 2A, have been developed. These advancements have facilitated the exploration of how synaptic markers in AD patients correlate with cognitive impairment. However, fluid biomarkers indicating synaptic loss have only been validated in cerebrospinal fluid (CSF), not in plasma, with the exception of VILIP-1. The most promising PET radiotracer, [11C]UCB-J, currently faces significant challenges hindering its widespread clinical use, primarily due to the necessity of a cyclotron. As such, additional research geared toward the exploration of synaptic pathology biomarkers is crucial. This will not only enable their extensive clinical application, but also refine the optimization process of AD pharmacological trials.

Digging into the intrinsic capacity concept: Can it be applied to Alzheimer's disease?

Historically, aging research has largely centered on disease pathology rather than promoting healthy aging. The World Health Organization's (WHO) policy framework (2015-2030) underscores the significance of fostering the contributions of older individuals to their families, communities, and economies. The WHO has introduced the concept of intrinsic capacity (IC) as a key metric for healthy aging, encompassing five primary domains: locomotion, vitality, sensory, cognitive, and psychological. Past AD research, constrained by methodological limitations, has focused on single outcome measures, sidelining the complexity of the disease. Our current scientific milieu, however, is primed to adopt the IC concept. This is due to three critical considerations: (I) the decline in IC is linked to neurocognitive disorders, including AD, (II) cognition, a key component of IC, is deeply affected in AD, and (III) the cognitive decline associated with AD involves multiple factors and pathophysiological pathways. Our study explores the application of the IC concept to AD patients, offering a comprehensive model that could revolutionize the disease's diagnosis and prognosis. There is a dearth of information on the biological characteristics of IC, which are a result of complex interactions within biological systems. Employing a systems biology approach, integrating omics technologies, could aid in unraveling these interactions and understanding IC from a holistic viewpoint. This comprehensive analysis of IC could be leveraged in clinical settings, equipping healthcare providers to assess AD patients' health status more effectively and devise personalized therapeutic interventions in accordance with the precision medicine paradigm. We aimed to determine whether the IC concept could be extended from older individuals to patients with AD, thereby presenting a model that could significantly enhance the diagnosis and prognosis of this disease.

Physical activity, chronic kidney disease, and cardiovascular risk: A study in half a million adults.

OBJECTIVE: There is a growing prevalence of chronic kidney disease (CKD), a condition associated with a higher cardiovascular disease (CVD) risk. We assessed the association between self-reported physical activity (PA) and CKD and also studied whether PA attenuates CKD-associated CVD risk. METHODS: A cohort of Spanish adults (18-64 years) participated in this nationwide study. Participants were categorized at baseline as being either inactive (performing no PA), regularly, or insufficiently active (meeting or not, respectively, international PA recommendations) and were followed for up to 5 years. The presence of CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2 ) and major CVD risk factors (diabetes, hypercholesterolemia, hypertension, obesity) was determined at baseline and at follow-up. RESULTS: 517 917 participants (44 ± 9 years, 67% male, CKD prevalence = 7%) were studied at baseline, with prospective analyses (median follow-up = 2 years, range = 2-5) in a subcohort of 264 581 individuals. Compared to physical inactivity, cross-sectional analyses at baseline showed that regular PA (odds ratio = 0.80; 95% confidence interval = 0.79-0.81), but not insufficient PA (1.02; 0.99-1.04) was associated with lower CKD prevalence. However, prospective analyses failed to confirm this association (p > 0.1). In turn, CKD was associated with a higher prevalence of hypertension (+3%) and diabetes (+5%) at baseline and with a greater incidence of hypertension at follow-up (+37%). Among those participants with CKD, regular PA was associated with a lower prevalence (-45% to -7%) and incidence (-38% to -4%) of all CVD risk factors. CONCLUSION: Although PA might not reduce incident CKD in the middle term (~2 years), it can attenuate the CVD risk linked to this condition.

Winners do what they fear: exercise and peripheral arterial disease-an umbrella review.

AIMS: This systematic review aims to evaluate and summarize findings from published meta-analyses on the effects of regular exercise in patients with peripheral arterial disease (PAD). The review will assess the impact of exercise on functional parameters, health-related quality of life, haemodynamic parameters, physical activity levels, adverse events, and mortality. METHODS AND RESULTS: A systematic search was performed in PubMed, Web of Science, Scopus, and Cochrane Library databases (up to May 2023) to identify meta-analyses including randomized controlled trials that examined the effects of regular exercise in patients with PAD. Sixteen studies, with a total of 198 meta-analyses, were identified. Results revealed with strong evidence that patients with PAD who exercised improved functional and health-related quality of life parameters. Specifically, supervised aerobic exercise (i.e. walking to moderate-maximum claudication pain) improves maximum walking distance [mean difference (MD): 177.94 m, 95% confidence interval (CI) 142.29-213.60; P < 0.00001; I2: 65%], pain-free walking distance (fixed MD: 68.78 m, 95% CI 54.35-83.21; P < 0.00001; I2: 67%), self-reported walking ability [i.e. distance score (MD: 9.22 points, 95% CI 5.74-12.70; P < 0.00001; I2: 0%), speed score (MD: 8.71 points, 95% CI 5.64-11.77; P < 0.00001, I2: 0%), stair-climbing score (MD: 8.02 points, 95% CI 4.84-11.21; P < 0.00001, I2: 0%), and combined score (MD: 8.76 points, 95% CI 2.78-14.74; P < 0.0001, I2: 0%)], aerobic capacity (fixed MD: 0.62 mL/kg/min, 95% CI 0.47-0.77, P < 0.00001, I2: 64%), and pain score (MD: 7.65, 95% CI 3.15-12.15; P = 0.0009; I2: 0%), while resistance exercise improves lower limb strength (standardized mean difference: 0.71, 95% CI 0.29-1.13, P = 0.0009; I2: 0%]. Regarding other outcomes, such as haemodynamic parameters, no significant evidence was found, while physical activity levels, adverse events, and mortality require further investigation. CONCLUSION: Synthesis of the currently available meta-analyses suggests that regular exercise may be beneficial for a broad range of functional tasks improving health-related quality of life in patients with PAD. Supervised aerobic exercise is the best type of exercise to improve walking-related outcomes and pain, while resistance exercise is more effective to improve lower limb strength.

Regular exercise is beneficial for a wide range of functional capacity-related outcomes that seem to improve health-related quality of life in patients with peripheral arterial disease (PAD). Supervised aerobic exercise (i.e. walking to moderate­maximum claudication pain) is the best type of exercise to improve walking-related outcomes and pain. Resistance exercise improves lower limb strength.

Integrative metabolomics science in Alzheimer's disease: Relevance and future perspectives.

Alzheimer's disease (AD) is determined by various pathophysiological mechanisms starting 10-25 years before the onset of clinical symptoms. As multiple functionally interconnected molecular/cellular pathways appear disrupted in AD, the exploitation of high-throughput unbiased omics sciences is critical to elucidating the precise pathogenesis of AD. Among different omics, metabolomics is a fast-growing discipline allowing for the simultaneous detection and quantification of hundreds/thousands of perturbed metabolites in tissues or biofluids, reproducing the fluctuations of multiple networks affected by a disease. Here, we seek to critically depict the main metabolomics methodologies with the aim of identifying new potential AD biomarkers and further elucidating AD pathophysiological mechanisms. From a systems biology perspective, as metabolic alterations can occur before the development of clinical signs, metabolomics - coupled with existing accessible biomarkers used for AD screening and diagnosis - can support early disease diagnosis and help develop individualized treatment plans. Presently, the majority of metabolomic analyses emphasized that lipid metabolism is the most consistently altered pathway in AD pathogenesis. The possibility that metabolomics may reveal crucial steps in AD pathogenesis is undermined by the difficulty in discriminating between the causal or epiphenomenal or compensatory nature of metabolic findings.

Obesity, cardiovascular risk, and lifestyle: cross-sectional and prospective analyses in a nationwide Spanish cohort.

AIMS: To assess whether overweight and obesity are independently associated with cardiometabolic health [as categorized based on the presence/absence of cardiovascular disease (CVD) risk factors (diabetes, hypercholesterolaemia, or hypertension)], and the role of lifestyle on this association. METHODS AND RESULTS: A nationwide cohort of Spanish adults (18-64 years) was studied using a cross-sectional design and prospective observational design. Lifestyle-related factors (physical activity, sleeping characteristics, alcohol drinking, and smoking) were registered, and participants were classified as having an 'unhealthy' or 'healthy' cardiometabolic status attending to the presence or absence, respectively, of ≥1 CVD risk factor. A number of 596 111 participants (44 ± 9 years, 67% male) were studied at baseline, with prospective analyses in a subcohort [n = 302 061; median follow-up, 2 years (range, 2 to 5)]. Compared to normal weight, overweight and obesity were associated with a higher prevalence [odds ratio, 1.67 (95% confidence interval, 1.61-1.67) and 2.70 (2.69-2.78), respectively] and incidence [1.62 (1.59-1.67) and 2.70 (2.63-2.78)] of an unhealthy cardiometabolic status. Meeting physical activity guidelines reduced the odds of an unhealthy cardiometabolic status at baseline [0.87 (0.85-0.88)] among individuals with overweight/obesity, as well as of transitioning from a healthy status to an unhealthy status during the follow-up [0.87 (0.84-0.94)]. No significant associations were found for the remainder of lifestyle factors. CONCLUSION: Overweight and obesity are independently associated with an unhealthy cardiometabolic status. Regular physical activity attenuates not only the prevalence but also the incidence of CVD risk factors.

This study (n = 596 111, with 302 061 participants followed for ∼2 years) indicates that overweigh and obesity are independently associated with the prevalence and incidence of major cardiovascular disease (CVD) risk factors (hypertension, diabetes, and hypercholesterolaemia). Individuals with metabolically healthy overweight/obesity are more likely to develop CVD risk factors in the short-to-middle term than their peers with normal weight even after accounting for lifestyle. Regular physical activity is the only lifestyle factor that seems to be inversely and independently associated with the prevalence and incidence of the studied CVD risk factors among individuals with overweight/obesity.

Aortic Diameters and Calcifications in Former World-Class Cyclists.

PURPOSE: Concerns on whether athletes--particularly older ones--are at an increased risk of pathological aortic dilation exist, and the prevalence of aortic calcifications in these individuals is unknown. We aimed to compare the dimensions, distensibility, and prevalence of calcifications in the thoracic aorta between former male professional cyclists (cases) and sex/age-matched controls. METHODS: We used a retrospective cohort design, where cases were former finishers of at least one Grand Tour (Tour de France, Giro d' Italia or Vuelta a España) and controls were untrained individuals with no previous sports history and free of cardiovascular risk. All participants underwent magnetic resonance and computer tomography assessments for the measurement of aortic dimensions and calcifications, respectively. RESULTS: Cases showed larger ( P < 0.05) dimensions than controls for aortic annulus, sinus, and arch, as well as for ascending and descending aorta. However, none of the participants presented with pathological aortic dilation (all diameters <40 mm). A slightly higher prevalence of calcifications in the ascending aorta was observed in cases (13% vs 0% in controls, P = 0.020). Subanalyses confirmed that cases who were still competing (masters category, n = 8) had larger aortic diameters ( P < 0.05) and a greater presence of calcifications in the ascending/descending aorta (38% vs 0% for both segments, P = 0.032) than those who had become inactive ( n = 15). No between-group differences were found for aortic distensibility. CONCLUSIONS: Former professional cyclists, particularly those who are still competing after retirement, show enlarged aortic diameters (albeit without exceeding upper limits of normality). Former professional cyclists also showed a slightly higher prevalence of calcifications in the ascending aorta than controls, although aortic distensibility was not compromised. The clinical relevance of these findings should be the subject of future studies.

Combined exercise intervention in a mouse model of high-risk neuroblastoma: effects on physical, immune, tumor and clinical outcomes.

Background: Exercise might exert anti-tumoral effects in adult cancers but this question remains open in pediatric tumors, which frequently show a different biology compared to adult malignancies. We studied the effects of an exercise intervention on physical function, immune variables and tumoral response in a preclinical model of a highly aggressive pediatric cancer, high-risk neuroblastoma (HR-NB). Methods: 6-8-week-old male mice with orthotopically-induced HR-NB were assigned to a control (N = 13) or exercise (5-week combined [aerobic+resistance]) group (N = 17). Outcomes included physical function (cardiorespiratory fitness [CRF] and muscle strength), as well as related muscle molecular indicators, blood and tumor immune cell and molecular variables, tumor progression, clinical severity, and survival. Results: Exercise attenuated CRF decline (p=0.029 for the group-by-time interaction effect), which was accompanied by higher muscle levels of oxidative capacity (citrate synthase and respiratory chain complexes III, IV and V) and an indicator of antioxidant defense (glutathione reductase) in the intervention arm (all p≤0.001), as well as by higher levels of apoptosis (caspase-3, p=0.029) and angiogenesis (vascular endothelial growth factor receptor-2, p=0.012). The proportion of 'hot-like' (i.e., with viable immune infiltrates in flow cytometry analyses) tumors tended to be higher (p=0.0789) in the exercise group (76.9%, vs. 33.3% in control mice). Exercise also promoted greater total immune (p=0.045) and myeloid cell (p=0.049) infiltration within the 'hot' tumors, with a higher proportion of two myeloid cell subsets (CD11C+ [dendritic] cells [p=0.049] and M2-like tumor-associated macrophages [p=0.028]), yet with no significant changes in lymphoid infiltrates or in cirulating immune cells or chemokines/cytokines. No training effect was found either for muscle strength or anabolic status, cancer progression (tumor weight and metastasis, tumor microenvironment), clinical severity, or survival. Conclusions: Combined exercise appears as an effective strategy for attenuating physical function decline in a mouse model of HR-NB, also exerting some potential immune benefits within the tumor, which seem overall different from those previously reported in adult cancers.

Effects of physical exercise on physical function in older adults in residential care: a systematic review and network meta-analysis of randomised controlled trials.

BACKGROUND: Physical exercise is effective at attenuating ageing-related physical decline in general, but evidence of its benefits for older adults in residential care, who often have functional dependency, multimorbidity, and polypharmacy, is inconclusive. We aimed to establish the effects of exercise interventions on the physical function of this population. METHODS: For this systematic review and network meta-analysis, we searched PubMed, Web of Science, Cochrane Library, Rehabilitation & Sports Medicine Source, and SPORTDiscus to identify randomised controlled trials assessing the effects of exercise interventions (vs usual care) on physical function (ie, functional independence, physical performance, and other related measures, such as muscle strength, balance, or flexibility) in adults aged 60 years or older living in residential care. Relevant studies published in English or Spanish up to Jan 12, 2023, were included in the systematic review. The quality of studies was assessed using the Tool for the Assessment of Study Quality and Reporting in Exercise (TESTEX) score. A network meta-analysis was performed for physical function-related outcomes reported in at least ten studies, with subanalyses for specific intervention (ie, exercise type, training volume, and study duration) and participant (eg, having cognitive impairment or dementia, pre-frail or frail status, and being functionally dependent) characteristics. The study protocol was registered on PROSPERO (CRD42021247809). FINDINGS: 147 studies (11 609 participants, with mean ages ranging from 67 years [SD 9] to 92 years [2]) were included in the systematic review, and were rated as having overall good quality (median TESTEX score 9 [range 3-14]). In the meta-analysis (including 105 studies, n=7759 participants), exercise interventions were associated with significantly improved overall physical function, with a standardised mean difference [SMD] of 0·13 (95% credible interval [CrI] 0·04-0·21), which was confirmed in all analysed subpopulations. The strongest association was observed with 110-225 min per week of exercise, and the greatest improvements were observed with 170 min per week (SMD 0·36 [95% CrI 0·20-0·52]). No significant differences were found between exercise types. Subanalyses showed significant improvements for almost all analysed physical function-related outcomes (Barthel index, five-times sit-to-stand test, 30-s sit-to-stand test, knee extension, hand grip strength, bicep curl strength, Short Physical Performance Battery, 6-min walking test, walking speed, Berg balance scale, and sit-and-reach test). Large heterogeneity was found between and within studies in terms of population and intervention characteristics. INTERPRETATION: Exercise interventions are associated with improved physical function in older adults in residential care, and should, therefore, be routinely promoted in long-term care facilities. FUNDING: None. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Healthcare Professionals' Knowledge about Pediatric Chronic Pain: A Systematic Review.

Pediatric chronic pain is a common public health problem with a high prevalence among children and adolescents. The aim of this study was to review the current knowledge of health professionals on pediatric chronic pain between 15-30% among children and adolescents. However, since this is an underdiagnosed condition, it is inadequately treated by health professionals. To this aim, a systematic review was carried out based on a search of the electronic literature databases (PubMed and Web of Science), resulting in 14 articles that met the inclusion criteria. The analysis of these articles seems to show a certain degree of heterogeneity in the surveyed professionals about the awareness of this concept, especially regarding its etiology, assessment, and management. In addition, the extent of knowledge of the health professionals seems to be insufficient regarding these aspects of pediatric chronic pain. Hence, the knowledge of the health professionals is unrelated to recent research that identifies central hyperexcitability as the primary factor affecting the onset, persistence, and management of pediatric chronic pain.

Exercise benefits in cardiovascular diseases: from mechanisms to clinical implementation.

There is a pandemic of physical inactivity that appears to parallel the widespread prevalence of cardiovascular disease (CVD). Yet, regular physical activity (PA) and exercise can play an important role not only in primary cardiovascular prevention but also in secondary prevention. This review discusses some of the main cardiovascular effects of PA/exercise and the mechanisms involved, including a healthier metabolic milieu with attenuation of systemic chronic inflammation, as well as adaptations at the vascular (antiatherogenic effects) and heart tissue (myocardial regeneration and cardioprotection) levels. The current evidence for safe implementation of PA and exercise in patients with CVD is also summarized.

Validation and Determination of Physical Activity Intensity GT3X+ Cut-Points in Children and Adolescents with Physical Disabilities: Preliminary Results in a Cerebral Palsy Population.

BACKGROUND: Children and adolescents with disabilities engage in low levels of moderate-to-vigorous intensity physical activity (MVPA), which may create the onset of a sedentary lifestyle. In light of this, MVPA levels must be quantified with a valid tool such as accelerometry. This study aimed to: (i) analyze the accuracy of Evenson cut-points by estimating MVPA and sedentary behavior (SB) in children and adolescents with disabilities; (ii) define new equations to estimate energy expenditure (EE) with the GT3X+ accelerometer in this population and particularly in those with cerebral palsy (CP); (iii) define specific GT3X+ cut-points to estimate MVPA in those with CP. METHODS: A total of 23 children and adolescents with disabilities (10 ± 3 years; 44%females) participated in the study. GT3X+-counts and oxygen uptake (VO2) were measured in four laboratory walking conditions. RESULTS: (i) Evenson cut-points were accurate; (ii) new equations were defined to effectively predict EE; (iii) specific GT3X+ cut-points (VM ≥ 702 counts·min-1; Y-Axis ≥ 360 counts·min-1) were defined for estimating MVPA levels in children and adolescents with CP. CONCLUSIONS: The use of specific cut-points for ActiGraph GT3X+ seems to be accurate to estimate MVPA levels in children and adolescents with disabilities and, particularly, in those with CP, at least in laboratory conditions.