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Copyright of Agro Productividad is the property of Colegio de Postgraduados and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: This study aimed to analyze the effect of a novel supervised exercise therapy (SET) program based on intermittent treadmill walking and circuit-based moderate-intensity functional training (MIFT) on walking performance and HRQoL in PAD patients., Design: All participants underwent a 12-week SET that involved 15 to 30 minutes of treadmill walking followed by a 15-minute moderate-intensity functional training (MIFT) continued by 12-week of follow-up. Maximum walking distance (MWD), pain-free walking distance (PFWD), gait speed and estimated peak oxygen uptake (peak VO2) were calculated through the 6-minute walk test (6-MWT) and HRQoL through the Short Form-36 (SF-36) and the Vascular Quality of Life Questionnaire-6 (VascuQol-6)., Results: There were statistically significant differences (p < 0.05) between baseline and post-intervention for walking performance outcomes [MWD (MD: 88.53 m), PFWD (MD: 62.89 m), gait speed (MD: 0.24 m·s-1) and peak VO2 (MD: 2.04 ml·kg-1·min-1)] and for HRQoL [physical functioning in SF-36 (MD: 6.93 points) and VascuQol-6 (MD: 1.46 points)]; while no differences were found between baseline and 12-week follow-up., Conclusion: Results seem to show that 12-week of novel SET based on intermittent walking and MIFT induced significant clinical improvements in key functional variables of PAD while cessation of exercise leads to significant negative clinical changes in subsequent weeks of follow-up., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Whether cardiac impairment can be fully discarded in McArdle disease-the paradigm of "exercise intolerance," caused by inherited deficiency of the skeletal muscle-specific glycogen phosphorylase isoform ("myophosphorylase")-remains to be determined., Methods: Eight patients with McArdle disease and seven age/sex-matched controls performed a 15-min moderate, constant-load cycle-ergometer exercise bout followed by a maximal ramp test. Electrocardiographic and two-dimensional transthoracic (for cardiac dimension's assessment) and speckle tracking (for left ventricular global longitudinal strain (GLS) assessments) echocardiographic evaluations were performed at baseline. Electrocardiographic and GLS assessments were also performed during constant-load exercise and immediately upon maximal exertion. Four human heart biopsies were obtained in individuals without McArdle disease, and in-depth histological/molecular analyses were performed in McArdle and wild-type mouse hearts., Results: Exercise intolerance was confirmed in patients ("second wind" during constant-load exercise, -55% peak power output vs controls). As opposed to controls, patients showed a decrease in GLS during constant-load exercise, especially upon second wind occurrence, but with no other between-group difference in cardiac structure/function. Human cardiac biopsies showed that all three glycogen phosphorylase-myophosphorylase, but also liver and especially brain-isoforms are expressed in the normal adult heart, thereby theoretically compensating for eventual myophosphorylase deficiency. No overall histological (including glycogen depots), cytoskeleton, metabolic, or mitochondrial (morphology/network/distribution) differences were found between McArdle and wild-type mouse hearts, except for lower levels of pyruvate kinase M2 and translocase of outer-membrane 20-kDa subunit in the former., Conclusions: This study provides preliminary evidence that cardiac structure and function seem to be preserved in patients with McArdle disease. However, the role for an impaired cardiac contractility associated with the second wind phenomenon should be further explored., (Copyright © 2024 by the American College of Sports Medicine.)

We explored the association between aerobic capacity (AC) and the skeletal muscle proteome of McArdle (n = 10) and wild-type (n = 8) mice, as models of intrinsically 'low' and 'normal' AC, respectively. AC was determined as total distance achieved in treadmill running until exhaustion. The quadriceps muscle proteome was studied using liquid chromatography with tandem mass spectrometry, with the Search Tool for the Retrieval of Interacting Genes/Proteins database used to generate protein-protein interaction (PPI) networks and enrichment analyses. AC was significantly associated (P-values ranging from 0.0002 to 0.049) with 73 (McArdle) and 61 (wild-type) proteins (r-values from -0.90 to 0.94). These proteins were connected in PPI networks that enriched biological processes involved in skeletal muscle structure/function in both groups (false discovery rate <0.05). In McArdle mice, the proteins associated with AC were involved in skeletal muscle fibre differentiation/development, lipid oxidation, mitochondrial function and calcium homeostasis, whereas in wild-type animals AC-associated proteins were related to cytoskeleton structure (intermediate filaments), cell cycle regulation and endocytic trafficking. Two proteins (WEE2, THYG) were associated with AC (negatively and positively, respectively) in both groups. Only 14 of the 132 proteins (∼11%) associated with AC in McArdle or wild-type mice were also associated with those previously reported to be modified by aerobic training in these mice, providing preliminary evidence for a large divergence in the muscle proteome signature linked to aerobic training or AC, irrespective of AC (intrinsically low or normal) levels. Our findings might help to gain insight into the molecular mechanisms underlying AC at the muscle tissue level., (© 2024 The Author(s). Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effectiveness of conservative, non-pharmacological interventions for chronic pain management in children and adolescents with juvenile idiopathic arthritis (JIA). A comprehensive search strategy was implemented across PubMed, PEDro, and Web of Science databases, utilizing predefined terms and strict inclusion and exclusion criteria. The initial search yielded 1,308 studies, which were subsequently narrowed to 65 relevant articles. Following a rigorous evaluation, 14 studies met the inclusion criteria for final review, with an average PEDro scale score of 6.1/10, indicating fair to good methodological quality. The included RCTs focused on various interventions, including physical exercise (five studies), hydrotherapy (three studies), orthoses (two studies), online cognitive behavior therapy for pain management (two studies), low-level laser therapy (one study), and video games (one study). A random-effects model meta-analysis was performed for interventions and outcome measures that were comparable across at least three RCTs. Physical exercise interventions met this criterion and were thus subjected to meta-analytic evaluation. The pooled analysis demonstrated a statistically significant beneficial effect of exercise interventions on chronic pain (mean difference (MD) = -1.37, 95% CI = -2.19 to -0.55, p < 0.01). Subgroup analyses further supported the efficacy of exercise compared to both other active interventions (MD = -1.37, 95% CI = -2.25 to -0.5, p < 0.01) and control conditions (MD = -1.69, 95% CI = -3.09 to -0.29, p = 0.02). These findings suggest that conservative, non-pharmacological interventions, particularly physical exercise, show promise as a component of a multidisciplinary pain management strategy for patients with JIA. While further high-quality research is needed to bolster the evidence base, our findings highlight the potential efficacy of integrating physical exercise interventions into comprehensive pain management strategies for this pediatric population., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Musso-Daury et al.)

Background: Recent trials of anti-amyloid-β (Aβ) monoclonal antibodies, including lecanemab and donanemab, in early Alzheimer disease (AD) showed that these drugs have limited clinical benefits and their use comes with a significant risk of serious adverse events. Thus, it seems crucial to explore complementary therapeutic approaches. Genome-wide association studies identified robust associations between AD and several AD risk genes related to immune response, including but not restricted to CD33 and TREM2. Here, we critically reviewed the current knowledge on candidate neuroinflammatory biomarkers and their role in characterizing the pathophysiology of AD., Main Body: Neuroinflammation is recognized to be a crucial and contributing component of AD pathogenesis. The fact that neuroinflammation is most likely present from earliest pre-stages of AD and co-occurs with the deposition of Aβ reinforces the need to precisely define the sequence and nature of neuroinflammatory events. Numerous clinical trials involving anti-inflammatory drugs previously yielded unfavorable outcomes in early and mild-to-moderate AD. Although the reasons behind these failures remain unclear, these may include the time and the target selected for intervention. Indeed, in our review, we observed a stage-dependent neuroinflammatory process in the AD brain. While the initial activation of glial cells counteracts early brain Aβ deposition, the downregulation in the functional state of microglia occurs at more advanced disease stages. To address this issue, personalized neuroinflammatory modulation therapy is required. The emergence of reliable blood-based neuroinflammatory biomarkers, particularly glial fibrillary acidic protein, a marker of reactive astrocytes, may facilitate the classification of AD patients based on the ATI(N) biomarker framework. This expands upon the traditional classification of Aβ ("A"), tau ("T"), and neurodegeneration ("N"), by incorporating a novel inflammatory component ("I")., Conclusions: The present review outlines the current knowledge on potential neuroinflammatory biomarkers and, importantly, emphasizes the role of longitudinal analyses, which are needed to accurately monitor the dynamics of cerebral inflammation. Such a precise information on time and place will be required before anti-inflammatory therapeutic interventions can be considered for clinical evaluation. We propose that an effective anti-neuroinflammatory therapy should specifically target microglia and astrocytes, while considering the individual ATI(N) status of patients., (© 2024. The Author(s).)

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-β (Aβ) ("A"), tau pathology ("T"), and neurodegeneration ("N"). Diagnostic cut-offs for Aβ 1-42 , the Aβ 1-42 /Aβ 1-40 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 Aβ 1-42 /Aβ 1-40 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., Competing Interests: Declaration of Competing Interest MM is a named inventor on patents related to blood biomarkers for neurodegenerative disease owned by the University of Rochester and Georgetown University. EE is the unique owner of 2E Science, a for-profit private scientific company. Neither EE nor 2E Science have any commercial interest or financial tie in relation with this article. MMM has served on scientific advisory boards and/or has consulted for Biogen, Eisai, LabCorp, Lilly, Merck, Roche, and Siemens Healthineers; received speaking honorariums from Novo Nordisk, PeerView Institute, and Roche. BPI is an employee at Chiesi Farmaceutici. He is listed among the inventors of a number of Chiesi Farmaceutici’s patents of anti-Alzheimer drugs. SL, FC, SL-O, JM-H, VT, CI, AG, JM, RN, and AS-L declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., Competing Interests: Declaration of Competing Interest EE is the unique owner of 2E Science, a for-profit private scientific company. Neither EE nor 2E Science have any commercial interest or financial tie in relation with this article. SL-O, GC, HM, SP-G, CSG, FC, RN, AL, AS-L, and SL declare that they have no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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 (Aβ), a peptide comprised of 40-42 amino acids, in extraneuronal plaques within the brain. Biochemical and histological studies have shown that overaccumulation of Aβ 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 Aβ 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 β-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, [ 11 C]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., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Neuromuscular electrical stimulation (NMES) in combination with blood flow restriction (BFR) enhances muscle hypertrophy and force-generating capacity. The present study aimed to investigate the acute effects of BFR and NMES, both in isolation and in combination, on muscle thickness (MT) and fatigue in the lower body of 20 young healthy subjects. Different stimuli were applied for 25 min, defined by the combination of BFR with high- and low-frequency NMES, and also isolated BFR or NMES. Changes in MT were then evaluated by ultrasound of the rectus femoris (RF) and vastus lateralis (VL) muscles at the end of the session (POST) and 15 min later (POST 15'). Lower limb fatigue was evaluated indirectly by strength performance. Results showed that RF MT was higher under the combined protocol (BFR + NMES) or isolated BFR than under NMES - regardless of the frequency - both at POST ( p  ≤ 0.018) and POST 15' ( p  ≤ 0.016). No significant changes in MT were observed under isolated NMES or BFR at POST 15' when compared with basal values ( p  ≥ 0.067). No significant differences were observed for VL MT between conditions ( p  = 0.322) or for fatigue between conditions ( p  ≥ 0.258). Our results indicate that a combination of BFR and NMES acutely increases MT in sedentary subjects. Also, although not significantly, BFR conditions had a greater tendency to induce fatigue than isolated NMES. Highlights The combination of blood flow restriction (BFR) and neuromuscular electrical stimulation (NMES) produces higher acute cell swelling than the isolated application of either NMES or BFR.BFR in isolation appears to produce greater cell swelling than NMES, regardless of the frequency used.BFR conditions had a greater tendency to induce fatigue than isolated NMES.

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., Competing Interests: Declaration of Competing Interest EE is the unique owner of 2E Science, a for-profit private scientific company. Neither EE nor 2E Science have any commercial interest or financial tie in relation with this article. BPI is an employee at Chiesi Farmaceutici. He is listed among the inventors of a number of Chiesi Farmaceutici’s patents of anti-Alzheimer drugs. SL, RG-D, SL-O, AG-D, HM, JM-H, AL, DC, VT, LL, MS, MC-C, JM, LL, MM, AS-L, and RN declare that they have no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

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 (VO 2 ) 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.

Introduction: During the last decade, physical activity (PA) (or "exercise") has been identified as one of the main modifiable factors that influence the development of Alzheimer's disease (AD) pathophysiology. We performed an umbrella review to summarize the evidence on the association between PA/exercise and the risk of developing AD risk, and the effect of exercise interventions on the progression of AD., Methods: A systematic search was performed in PubMed, SportDiscus, Cochrane Library and Web of Science (March 2022) to identify meta-analyses assessing the association between PA and the incidence of AD, and assessing the effect of exercise interventions on patients with AD., Results: Twenty-one studies were included. The results with strongest evidence revealed the positive effects of PA on AD risk. Specifically, meeting the WHO recommendations for PA was associated with a lower risk of AD. They also revealed positive effects of exercise on cognitive function, physical performance, and functional independence., Conclusions: There is strong evidence of a protective effect of regular PA against AD risk; however, the dose-response association remains unclear. Physical exercise seems to improve several dimensions in patients with AD, although research is warranted to elucidate the exercise characteristics that promote the greatest benefits., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Growing evidence suggests that, among the different molecular/cellular pathophysiological mechanisms associated with cancer, there are 14 hallmarks that play a major role, including: (i) sustaining proliferative signaling, (ii) evading growth suppressors, (iii) activating invasion and metastasis, (iv) enabling replicative immortality, (v) inducing angiogenesis, (vi) resisting cell death, (vii) reprogramming energy metabolism, (viii) evading immune destruction, (ix) genome instability and mutations, (x) tumor-promoting inflammation, (xi) unlocking phenotypic plasticity, (xii) nonmutational epigenetic reprogramming, (xiii) polymorphic microbiomes, and (xiv) senescent cells. These hallmarks are also associated with the development of breast cancer, which represents the most prevalent tumor type in the world. The present narrative review aims to describe, for the first time, the effects of physical activity/exercise on these hallmarks. In summary, an active lifestyle, and particularly regular physical exercise, provides beneficial effects on all major hallmarks associated with breast cancer, and might therefore help to counteract the progression of the disease or its associated burden.

Introduction: The World Health Organization has introduced the term 'intrinsic capacity' (IC) as a marker of healthy ageing. However, controversy exists on the definition and assessment of IC. We aimed to review the definitions and methods used for the assessment of IC in older adults. In addition, we proposed a new IC scoring method., Methods: A systematic search was performed in PubMed, Web of Science, Cochrane Library, Scopus and SPORTDiscus (up to February 10th, 2022) for studies assesing IC in older adults (>60 years)., Results: Thirty-three studies were included. There is overall consensus on the definition of IC as well as on its different dimensions, that is: locomotion, vitality, sensory, cognition and psychological. However, the methods for assessing each of these five dimensions differ substantially across studies and there is no consensus on the best method to compute an eventual global compound score to evaluate IC taking into account all its different dimensions., Conclusions: The IC represents a highly relevant clinical concept that has been unfortunately underutilized. We propose a standardization for the assessment of each dimension of IC, with a global 0 (worst) to 10 (highest) score., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Bovine leptospirosis is a bacterial disease that affects cattle herds, causing economic losses due to reproductive problems which require expensive treatments. The main source of transmission for cattle is still uncertain, but rodents and bats can play an important role in the transmission cycle by being maintenance hosts for the pathogenic species of the bacterium and spreading it through urine. In this study, we characterize possible risk areas for bovine leptospirosis exposure in the state of Veracruz, Mexico, based on the geographical distribution of flying (bats) and terrestrial (rodents and opossums) wild hosts of Leptospira sp. reported in Mexico, in addition to climate, geography, soil characteristics, land use and human activities (environmental variables). We used a generalized linear regression model to understand the association between the frequency of anti-Leptospira sp. antibodies (a proxy of exposure) in cattle herds exposed to Leptospira, the favourability of wild hosts of Leptospira as well as the environmental variables. The parameterized model explained 12.3% of the variance. The frequency of anti-Leptospira sp. antibodies exposure in cattle herds was associated with elevation, geographic longitude, pH of the soil surface and environmental favourability for the presence of rodents, opossums and bats. The variation in exposure was mainly explained by a longitudinal gradient (6.4% of the variance) and the favourability-based indices for wild hosts (9.6% of the variance). Describing the possible risks for exposure to Leptospira in an important and neglected livestock geographical region, we provide valuable information for the selection of areas for diagnosis and prevention of this relevant disease., (© 2021 Wiley-VCH GmbH.)

Peripheral arterial disease (PAD) is a prevalent cardiovascular disease. The main hallmarks of this condition are atherosclerosis and myopathy in the lower limbs, with progressive deterioration of the functional capacity and quality of life of affected individuals. There is evidence supporting physical exercise as an effective alternative for the treatment of PAD. In this context, unraveling the biological mechanisms by which exercise intervention might improve the clinical manifestation of PAD can help gain insight into the pathophysiology of this condition, as well as explore new treatment and preventive approaches. In this review, we thus describe the different mechanisms by which exercise could impact the different hallmarks of PAD. Physical exercise positively modulates pathways related to inflammation and the atherosclerotic process and can attenuate the progression of lower-limb myopathy, with subsequent improvements in patients' functional capacity and health-related quality of life. At the whole-body level, these improvements translate into a better functional status and wellbeing., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Aims: To assess the potential multi-domain benefits of exercise interventions on patients with Alzheimer's disease (AD), as well as to determine the specific effects of different exercise modalities (aerobic, strength, or combined training)., Methods: A systematic search was conducted in PubMed and Web of Science until March 2021 for randomized controlled trials assessing the effect of exercise interventions (compared with no exercise) on patients with AD. Outcomes included cognitive function (mini-mental state examination [MMSE] test), physical function (e.g., 6-minute walking test [6MWT]), functional independence (Barthel index), and neuropsychiatric symptoms (Neuropsychiatric Inventory [NPI]). A random-effects meta-analysis was conducted., Results: 28 studies (total n = 1337 participants, average age 79-90 years) were included in the systematic review, of which 21 could be meta-analyzed. Although considerable heterogeneity was found, exercise interventions induced several significant benefits, including in Barthel index (n = 147 patients, mean difference [MD]=8.36 points, 95% confidence interval [CI]=0.63-16.09), 6MWT (n = 369, MD=84 m, 95% CI=44-133)), and NPI (n = 263, MD=-4.4 points, 95% CI=-8.42 to -0.38). Benefits were also found in the MMSE test, albeit significance was only reached for aerobic exercise (n = 187, MD=2.31 points, 95% CI 0.45-4.27)., Conclusions: Exercise interventions appear to exert multi-domain benefits in patients with AD., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Alzheimer's disease (AD), the most common form of neurodegenerative dementia in adults worldwide, is a multifactorial and heterogeneous disorder characterized by the interaction of genetic and epigenetic factors and the dysregulation of numerous intracellular signaling and cellular/molecular pathways. The introduction of the systems biology framework is revolutionizing the study of complex diseases by allowing the identification and integration of cellular/molecular pathways and networks of interaction. Here, we reviewed the relationship between physical activity and the next pathophysiological processes involved in the risk of developing AD, based on some crucial molecular pathways and biological process dysregulated in AD: (1) Immune system and inflammation; (2) Endothelial function and cerebrovascular insufficiency; (3) Apoptosis and cell death; (4) Intercellular communication; (5) Metabolism, oxidative stress and neurotoxicity; (6) DNA damage and repair; (7) Cytoskeleton and membrane proteins; (8) Synaptic plasticity. Moreover, we highlighted the increasingly relevant role played by advanced neuroimaging technologies, including structural/functional magnetic resonance imaging, diffusion tensor imaging, and arterial spin labelling, in exploring the link between AD and physical exercise. Regular physical exercise seems to have a protective effect against AD by inhibiting different pathophysiological molecular pathways implicated in AD.

Importance: Vigorous exercise (particularly endurance sports) might increase the risk of atrial fibrillation (AF), but there is variability in the reported frequency of this condition among elite athletes. The underlying pathophysiologic source remains unclear., Objective: To determine AF incidence in a large cohort of elite athletes and its association with potential risk factors., Design, Setting, and Participants: Retrospective observational cohort of all Spanish athletes (N = 6813) referred to a single center was used to determine AF incidence from January 1, 1997, to December 31, 2017, and cross-sectional analysis was conducted to compare athletes with and without reported AF. The cohort covered most sports disciplines, and the studied athletes were on national teams and competed in major international events. Cardiologists responsible for echocardiographic assessment were not blinded to the condition (AF or no AF) of the athletes., Exposures: All participants underwent at least 1 cardiologic evaluation, including assessment at time of AF diagnosis in those with this condition., Main Outcomes and Measures: Diagnosis of AF based on resting and/or exercise electrocardiogram, and/or 24-hour Holter monitoring and echocardiography-assessed atrial dimensions., Results: A total of 6813 Spanish elite athletes (2385 [35.0%] women) were referred for cardiac evaluation during the study period. Mean (SD) age was 22 (7) years, and mean (SD) time of competition was 8 (5) years. Only 21 athletes (1 woman), participating in different types of sports, had AF (ie, paroxysmal [n = 18], persistent [n = 1], or long-standing persistent [n = 2]) during the 20-year study. In multivariate analysis, increasing values of age (odds ratio [OR], 1.07; 95% CI, 1.00-1.14), years of competition (OR, 1.14; 95% CI, 1.07-1.22), and left atrial anteroposterior diameter (OR, 1.21; 95% CI, 1.10-1.32) were associated with higher AF risk., Conclusions and Relevance: The incidence of AF is low among young Spanish elite athletes, even when considering only endurance athletes. Yet, potential contributors (particularly atrial remodeling) need to be monitored.

Objective: The demand for consultations and diagnostic studies for sleep apnea-hypopnea syndrome (SAHS) has increased, and this has led to considerable delays. We therefore need an updated evaluation of the diagnostic situation to serve as a management tool for specialists and health care administrations responsible for solving the problem. The objective of the present study was to carry out a descriptive analysis of the situation regarding the diagnosis of SAHS in Spanish hospitals., Methods: We undertook a descriptive cross-sectional observational study. Public and private hospitals listed in the Ministry of Health's 2005 catalog of health care institutions were contacted, and those that routinely evaluate patients for SAHS were included in the study. The person in charge of each hospital filled in a questionnaire concerning the availability of resources and waiting periods for diagnosis., Results: Of the 741 hospitals we contacted, 217 routinely evaluated patients for SAHS. In 88% of these, respiratory polygraphy (RP) (n=168) or polysomnography (PSG) (n=97) was available. The mean waiting period was 61 days for consultation and 224 days for RP. The mean number of RP systems was 0.99 per 100,000 inhabitants, while the recommended number is 3 per 100,000 inhabitants. The mean waiting period for PSG was 166 days. The mean number of PSG beds was 0.49 per 100,000 inhabitants, while the recommended number is 1 per 100,000., Conclusions: We observed a marked inadequacy of resources that has led to unacceptable waiting periods. While there has been a favorable change in the situation regarding SAHS diagnosis compared to previous studies, there is still room for improvement and it is urgent that healt hcare authorities allocate more resources to this public health problem.