| 1. |
- Cadenas-Sanchez, Cristina, et al.
(author)
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Differences in Brain Volume between Metabolically Healthy and Unhealthy Overweight and Obese Children : The Role of Fitness
- 2020
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In: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 9:4
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Journal article (peer-reviewed)abstract
- The aim of this study was to examine whether metabolically healthy overweight/obese children have greater global and regional gray matter volumes than their metabolically unhealthy peers. We further examined the association between gray matter volume and academic achievement, along with the role of cardiorespiratory fitness in these associations. A total of 97 overweight/obese children (10.0 +/- 1.2 years) participated. We classified children as metabolically healthy/unhealthy based on metabolic syndrome cut-offs. Global and regional brain volumes were assessed by magnetic resonance imaging. Academic achievement was assessed using the Woodcock-Munoz standardized test. Cardiorespiratory fitness was assessed by the 20 m shuttle run test. Metabolically healthy overweight/obese (MHO) children had greater regional gray matter volume compared to those who were metabolically unhealthy (MUO) (all p <= 0.001). A similar trend was observed for global gray matter volume (p = 0.06). Global gray matter volume was positively related to academic achievement (beta = 0.237, p = 0.036). However, all the associations were attenuated or disappeared after adjusting for cardiorespiratory fitness (p > 0.05). The findings of the present study support that metabolically healthy overweight/obese children have greater gray matter volume compared to those that are metabolically unhealthy, which is in turn related to better academic achievement. However, cardiorespiratory fitness seems to explain, at least partially, these findings.
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| 2. |
- Cadenas-Sanchez, Cristina, et al.
(author)
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Fitness, physical activity and academic achievement in overweight/obese children
- 2020
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In: Journal of Sports Sciences. - : TAYLOR & FRANCIS LTD. - 0264-0414 .- 1466-447X. ; 38:7, s. 731-740
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Journal article (peer-reviewed)abstract
- The aim of this study was to examine the associations of fitness and physical activity with academic achievement in children with overweight/obesity. A total of 106 (10.0 +/- 1.1y, 61 boys) children participated. The fitness components were assessed by field and laboratory-based tests. Physical activity was measured via accelerometry. The academic achievement was assessed by a standardised test and school-grades. Field-based cardiorespiratory fitness was associated with language skills (ss-standardised- ranging from 0.281 to 0.365, p amp;lt; 0.01). The field-based muscular strength was associated with grade point average, natural and social sciences, and foreign language (ss = 0.280-0.326, all p amp;lt;= 0.01). Speed-agility was associated with some language-related skills (ss = 0.325-0.393, all p amp;lt;= 0.01). The laboratory-based muscular strength also showed an association with mathematics skills (ss = 0.251-0.306, all p amp;lt;= 0.01). Physical activity did not show significant association with academic achievement (p amp;gt; 0.01). Overall, the significant associations observed for muscular strength and speed/agility were attenuated and disappeared in many cases after additional adjustments for body mass index and cardiorespiratory fitness, indicating that these associations are inter-dependent. Our study contributes by indicating that other fitness components apart from cardiorespiratory fitness, such as muscular strength and speed-agility, are positively associated with academic achievement. However, these associations appear to be dependent on body mass index and cardiorespiratory fitness.
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| 3. |
- Cruz, Raquel, et al.
(author)
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Novel genes and sex differences in COVID-19 severity
- 2022
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In: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 31:22, s. 3789-3806
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Journal article (peer-reviewed)abstract
- Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.
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| 4. |
- Henriksson, Hanna, 1977-, et al.
(author)
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Hip and wrist accelerometers showed consistent associations with fitness and fatness in children aged 8-12 years
- 2020
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In: Acta Paediatrica. - : WILEY. - 0803-5253 .- 1651-2227. ; 109:5, s. 995-1003
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Journal article (peer-reviewed)abstract
- Aim Physical activity (PA) has traditionally been measured wearing accelerometers on the hip, but they are increasingly being worn on the wrist. We compared hip and wrist accelerometers with regard to their acceptability and any associations between PA and fatness and fitness. Methods This cross-sectional study comprised 103 children aged 8-12 years (62% boys) who participated in the ActiveBrains trial by the University of Granada, Spain, in 2014-2016. The children wore both ActiGraph GT3X+ hip and wrist accelerometers round the clock for 7 days. The acceptability of both placements was evaluated by a questionnaire, while the childrens fat mass index, waist circumference and cardiorespiratory fitness (CRF) were assessed. Results Wearing wrist accelerometers caused less disturbance, mainly because hip accelerometers caused more issues during the night. The measurements from both placements showed that lower PA levels were associated with fatness and that higher PA levels were associated with better CRF. Conclusion Both placements showed consistent results with regard to measuring associations between PA levels and fatness and fitness. However, wearing them on the wrist caused less discomfort at night. Future studies are needed to confirm the best placement for accelerometers during PA studies.
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| 5. |
- Jiménez-Balado, Joan, et al.
(author)
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DNA methylation and stroke prognosis : an epigenome-wide association study
- 2024
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In: Clinical Epigenetics. - : BioMed Central (BMC). - 1868-7083. ; 16:1
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Journal article (peer-reviewed)abstract
- Background and aimsStroke is the leading cause of adult-onset disability. Although clinical factors influence stroke outcome, there is a significant variability among individuals that may be attributed to genetics and epigenetics, including DNA methylation (DNAm). We aimed to study the association between DNAm and stroke prognosis.Methods and resultsTo that aim, we conducted a two-phase study (discovery-replication and meta-analysis) in Caucasian patients with ischemic stroke from two independent centers (BasicMar [discovery, N = 316] and St. Pau [replication, N = 92]). Functional outcome was assessed using the modified Rankin Scale (mRS) at three months after stroke, being poor outcome defined as mRS > 2. DNAm was determined using the 450K and EPIC BeadChips in whole-blood samples collected within the first 24 h. We searched for differentially methylated positions (DMPs) in 370,344 CpGs, and candidates below p-value < 10–5 were subsequently tested in the replication cohort. We then meta-analyzed DMP results from both cohorts and used them to identify differentially methylated regions (DMRs).After doing the epigenome-wide association study, we found 29 DMPs at p-value < 10–5 and one of them was replicated: cg24391982, annotated to thrombospondin-2 (THBS2) gene (p-valuediscovery = 1.54·10–6; p-valuereplication = 9.17·10–4; p-valuemeta-analysis = 6.39·10–9). Besides, four DMRs were identified in patients with poor outcome annotated to zinc finger protein 57 homolog (ZFP57), Arachidonate 12-Lipoxygenase 12S Type (ALOX12), ABI Family Member 3 (ABI3) and Allantoicase (ALLC) genes (p-value < 1·10–9 in all cases).DiscussionPatients with poor outcome showed a DMP at THBS2 and four DMRs annotated to ZFP57, ALOX12, ABI3 and ALLC genes. This suggests an association between stroke outcome and DNAm, which may help identify new stroke recovery mechanisms.
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| 6. |
- Keller, Magdalena, et al.
(author)
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Inhibiting the glycerophosphodiesterase EDI3 in ER-HER2+breast cancer cells resistant to HER2-targeted therapy reduces viability and tumour growth
- 2023
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In: Journal of Experimental & Clinical Cancer Research. - : BioMed Central (BMC). - 1756-9966. ; 42
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Journal article (peer-reviewed)abstract
- Background: Intrinsic or acquired resistance to HER2-targeted therapy is often a problem when small molecule tyrosine kinase inhibitors or antibodies are used to treat patients with HER2 positive breast cancer. Therefore, the identification of new targets and therapies for this patient group is warranted. Activated choline metabolism, characterized by elevated levels of choline-containing compounds, has been previously reported in breast cancer. The glycerophosphodiesterase EDI3 (GPCPD1), which hydrolyses glycerophosphocholine to choline and glycerol-3-phosphate, directly influences choline and phospholipid metabolism, and has been linked to cancer-relevant phenotypes in vitro. While the importance of choline metabolism has been addressed in breast cancer, the role of EDI3 in this cancer type has not been explored.Methods: EDI3 mRNA and protein expression in human breast cancer tissue were investigated using publicly-available Affymetrix gene expression microarray datasets (n = 540) and with immunohistochemistry on a tissue microarray (n = 265), respectively. A panel of breast cancer cell lines of different molecular subtypes were used to investigate expression and activity of EDI3 in vitro. To determine whether EDI3 expression is regulated by HER2 signalling, the effect of pharmacological inhibition and siRNA silencing of HER2, as well as the influence of inhibiting key components of signalling cascades downstream of HER2 were studied. Finally, the influence of silencing and pharmacologically inhibiting EDI3 on viability was investigated in vitro and on tumour growth in vivo.Results: In the present study, we show that EDI3 expression is highest in ER-HER2 + human breast tumours, and both expression and activity were also highest in ER-HER2 + breast cancer cell lines. Silencing HER2 using siRNA, as well as inhibiting HER2 signalling with lapatinib decreased EDI3 expression. Pathways downstream of PI3K/Akt/mTOR and GSK3 beta, and transcription factors, including HIF1 alpha, CREB and STAT3 were identified as relevant in regulating EDI3 expression. Silencing EDI3 preferentially decreased cell viability in the ER-HER2 + cells. Furthermore, silencing or pharmacologically inhibiting EDI3 using dipyridamole in ER-HER2 + cells resistant to HER2-targeted therapy decreased cell viability in vitro and tumour growth in vivo.Conclusions: Our results indicate that EDI3 may be a potential novel therapeutic target in patients with HER2-targeted therapy-resistant ER-HER2 + breast cancer that should be further explored.
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| 7. |
- Lang, Justin J., et al.
(author)
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Top 10 International Priorities for Physical Fitness Research and Surveillance Among Children and Adolescents : A Twin-Panel Delphi Study
- 2023
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In: Sports Medicine. - New Zealand : Adis International Ltd.. - 0112-1642 .- 1179-2035. ; 53:2, s. 549-564
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Journal article (peer-reviewed)abstract
- Background The measurement of physical fitness has a history that dates back nearly 200 years. Recently, there has been an increase in international research and surveillance on physical fitness creating a need for setting international priorities that could help guide future efforts. Objective This study aimed to produce a list of the top 10 international priorities for research and surveillance on physical fitness among children and adolescents. Methods Using a twin-panel Delphi method, two independent panels consisting of 46 international experts were identified (panel 1 = 28, panel 2 = 18). The panel participants were asked to list up to five priorities for research or surveillance (round 1), and then rated the items from their own panel on a 5-point Likert scale of importance (round 2). In round 3, experts were asked to rate the priorities identified by the other panel. Results There was strong between-panel agreement (panel 1: r(s) = 0.76, p < 0.01; panel 2: r(s) = 0.77, p < 0.01) in the priorities identified. The list of the final top 10 priorities included (i) "conduct longitudinal studies to assess changes in fitness and associations with health". This was followed by (ii) "use fitness surveillance to inform decision making", and (iii) "implement regular and consistent international/national fitness surveys using common measures". Conclusions The priorities identified in this study provide guidance for future international collaborations and research efforts on the physical fitness of children and adolescents over the next decade and beyond.
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| 8. |
- Medina-Dols, Aina, et al.
(author)
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Role of PATJ in stroke prognosis by modulating endothelial to mesenchymal transition through the Hippo/Notch/PI3K axis
- 2024
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In: Cell Death Discovery. - : Springer Nature. - 2058-7716. ; 10
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Journal article (peer-reviewed)abstract
- Through GWAS studies we identified PATJ associated with functional outcome after ischemic stroke (IS). The aim of this study was to determine PATJ role in brain endothelial cells (ECs) in the context of stroke outcome. PATJ expression analyses in patient's blood revealed that: (i) the risk allele of rs76221407 induces higher expression of PATJ, (ii) PATJ is downregulated 24 h after IS, and (iii) its expression is significantly lower in those patients with functional independence, measured at 3 months with the modified Rankin scale ((mRS) <= 2), compared to those patients with marked disability (mRS = 4-5). In mice brains, PATJ was also downregulated in the injured hemisphere at 48 h after ischemia. Oxygen-glucose deprivation and hypoxia-dependent of Hypoxia Inducible Factor-1 alpha also caused PATJ depletion in ECs. To study the effects of PATJ downregulation, we generated PATJ-knockdown human microvascular ECs. Their transcriptomic profile evidenced a complex cell reprogramming involving Notch, TGF-ss, PI3K/Akt, and Hippo signaling that translates in morphological and functional changes compatible with endothelial to mesenchymal transition (EndMT). PATJ depletion caused loss of cell-cell adhesion, upregulation of metalloproteases, actin cytoskeleton remodeling, cytoplasmic accumulation of the signal transducer C-terminal transmembrane Mucin 1 (MUC1-C) and downregulation of Notch and Hippo signaling. The EndMT phenotype of PATJ-depleted cells was associated with the nuclear recruitment of MUC1-C, YAP/TAZ, beta-catenin, and ZEB1. Our results suggest that PATJ downregulation 24 h after IS promotes EndMT, an initial step prior to secondary activation of a pro-angiogenic program. This effect is associated with functional independence suggesting that activation of EndMT shortly after stroke onset is beneficial for stroke recovery.
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| 9. |
- Migueles, Jairo Hidalgo, et al.
(author)
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Calibration and Cross-Validation of Accelerometer Cut-Points to Classify Sedentary Time and Physical Activity from Hip and Non-Dominant and Dominant Wrists in Older Adults
- 2021
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In: Sensors. - : MDPI. - 1424-8220. ; 21:10
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Journal article (peer-reviewed)abstract
- Accelerometers accuracy for sedentary time (ST) and moderate-to-vigorous physical activity (MVPA) classification depends on accelerometer placement, data processing, activities, and sample characteristics. As intensities differ by age, this study sought to determine intensity cut-points at various wear locations people more than 70 years old. Data from 59 older adults were used for calibration and from 21 independent participants for cross-validation purposes. Participants wore accelerometers on their hip and wrists while performing activities and having their energy expenditure measured with portable calorimetry. ST and MVPA were defined as <= 1.5 metabolic equivalents (METs) and >= 3 METs (1 MET = 2.8 mL/kg/min), respectively. Receiver operator characteristic (ROC) analyses showed fair-to-good accuracy (area under the curve [AUC] = 0.62-0.89). ST cut-points were 7 mg (cross-validation: sensitivity = 0.88, specificity = 0.80) and 1 count/5 s (cross-validation: sensitivity = 0.91, specificity = 0.96) for the hip; 18 mg (cross-validation: sensitivity = 0.86, specificity = 0.86) and 102 counts/5 s (cross-validation: sensitivity = 0.91, specificity = 0.92) for the non-dominant wrist; and 22 mg and 175 counts/5 s (not cross-validated) for the dominant wrist. MVPA cut-points were 14 mg (cross-validation: sensitivity = 0.70, specificity = 0.99) and 54 count/5 s (cross-validation: sensitivity = 1.00, specificity = 0.96) for the hip; 60 mg (cross-validation: sensitivity = 0.83, specificity = 0.99) and 182 counts/5 s (cross-validation: sensitivity = 1.00, specificity = 0.89) for the non-dominant wrist; and 64 mg and 268 counts/5 s (not cross-validated) for the dominant wrist. These cut-points can classify ST and MVPA in older adults from hip- and wrist-worn accelerometers.
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| 10. |
- Migueles, Jairo H., et al.
(author)
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Effects of an Exercise Program on Cardiometabolic and Mental Health in Children With Overweight or Obesity A Secondary Analysis of a Randomized Clinical Trial
- 2023
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In: JAMA Network Open. - : AMER MEDICAL ASSOC. - 2574-3805. ; 6:7
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Journal article (peer-reviewed)abstract
- Importance Childhood obesity is a risk factor associated with type 2 diabetes, cardiovascular disease, and mental disorders later in life. Investigation of the parallel effects of a defined exercise program on cardiometabolic and mental health in children with overweight or obesity may provide new insights on the potential benefits of exercise on overall health. Objective To investigate the effects of a 20-week exercise program on cardiometabolic and mental health in children with overweight or obesity. Design, Setting, and Participants This secondary analysis of a parallel-group randomized clinical trial was conducted in Granada, Spain, from November 1, 2014, to June 30, 2016. Data analyses were performed between February 1, 2020, and July 14, 2022. Children with overweight or obesity aged 8 to 11 years were eligible, and the study was performed in an out-of-school context. Intervention The exercise program included 3 to 5 sessions/wk (90 min/session) of aerobic plus resistance training for 20 weeks. The wait-list control group continued with their usual routines. Main Outcomes and Measures Cardiometabolic outcomes as specified in the trial protocol included body composition (fat mass, fat-free mass, and visceral adipose tissue), physical fitness (cardiorespiratory, speed-agility, and muscular), and traditional risk factors (waist circumference, blood lipid levels, glucose levels, insulin levels, and blood pressure). Cardiometabolic risk score (z score) was calculated based on age and sex reference values for levels of triglycerides, inverted high-density lipoprotein cholesterol, and glucose, the mean of systolic and diastolic blood pressure, and waist circumference. An additional cardiometabolic risk score also included cardiorespiratory fitness. Mental health outcomes included an array of psychological well-being and ill-being indicators. Results The 92 participants included in the per-protocol analyses (36 girls [39%] and 56 boys [61%]) had a mean (SD) age of 10.0 (1.1) years. The exercise program reduced the cardiometabolic risk score byapproximately0.38 (95% CI, -0.74 to -0.02) SDs; decreased low-density lipoprotein cholesterol level by -7.00 (95% CI, -14.27 to 0.37) mg/dL (to convert to mmol/L, multiply by 0.0259), body mass index (calculated as weight in kilograms divided by height in meters squared) by -0.59 (95% CI, -1.06 to -0.12), fat mass index by -0.67 (95% CI, -1.01 to -0.33), and visceral adipose tissue by -31.44 (95% CI, -58.99 to -3.90) g; and improved cardiorespiratory fitness by 2.75 (95% CI, 0.22-5.28) laps in the exercise group compared with the control group. No effects were observed on mental health outcomes. Conclusions and Relevance In this secondary analysis of a randomized clinical trial, an aerobic plus resistance exercise program improved cardiometabolic health in children with overweight or obesity but had no effect on mental health.
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