| 1. |
- Cadenas-Sanchez, Cristina, et al.
(författare)
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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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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 9:4
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Tidskriftsartikel (refereegranskat)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.
(författare)
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Fitness, physical activity and academic achievement in overweight/obese children
- 2020
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Ingår i: Journal of Sports Sciences. - : TAYLOR & FRANCIS LTD. - 0264-0414 .- 1466-447X. ; 38:7, s. 731-740
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Tidskriftsartikel (refereegranskat)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. |
- Cadenas-Sanchez, Cristina, et al.
(författare)
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Physical fitness reference standards for preschool children : The PREFIT project.
- 2019
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Ingår i: Journal of Science and Medicine in Sport. - : Elsevier. - 1440-2440 .- 1878-1861. ; 22:4, s. 430-437
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Reference values are necessary for classifying children, for health screening, and for early prevention as many non-communicable diseases aggravate during growth and development. While physical fitness reference standards are available in children aged 6 and older, such information is lacking in preschool children. Therefore, the purposes of this study were (1) to provide sex-and age-specific physical fitness reference standards for Spanish preschool children; and (2) to study sex differences across this age period and to characterise fitness performance throughout the preschool period.DESIGN: Cross-sectional.METHODS: A total of 3179 preschool children (1678 boys) aged 2.8-6.4 years old from Spain were included in the present study. Physical fitness was measured using the PREFIT battery.RESULTS: Age- and sex-specific percentiles for the physical fitness components are provided. Boys performed better than girls in the cardiorespiratory fitness, muscular strength, and speed-agility tests over the whole preschool period studied and for the different percentiles. In contrast, girls performed slightly better than boys in the balance test. Older children had better performance in all fitness tests than their younger counterparts.CONCLUSIONS: Our study provides age- and sex-specific physical fitness reference standards in preschool children allowing interpretation of fitness assessment. Sexual dimorphism in fitness tests exists already at preschool age, and these differences become larger with age. These findings will help health, sport, and school professionals to identify preschool children with a high/very low fitness level, to examine changes in fitness over time, and to analyse those changes obtained due to intervention effects.
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| 4. |
- Cruz, Raquel, et al.
(författare)
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Novel genes and sex differences in COVID-19 severity
- 2022
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 31:22, s. 3789-3806
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Tidskriftsartikel (refereegranskat)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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| 5. |
- Esteban-Cornejo, Irene, et al.
(författare)
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Early life programming of attention capacity in adolescents : The HELENA study
- 2018
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Ingår i: Maternal and Child Nutrition. - : Wiley. - 1740-8695 .- 1740-8709. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The study aims to examine the individual and combined association of early life factors (birth weight, birth length, and any and exclusive breastfeeding) with attention capacity in adolescents. The study included 421 European adolescents (243 girls), aged 12.5-17.5 years, who participated in the Healthy Lifestyle in Europe by Nutrition in Adolescence Study. Body weight and length at birth of adolescents were collected from parental records. The duration of any and exclusive breastfeeding were self-reported. The d2 Test of Attention was administered to assess attention capacity. The main results showed that birth weight, birth length, breastfeeding, and exclusive breastfeeding were related to attention capacity in boys (β ranging from 0.144 to 0.196; all p < .05) after adjustment for age, centre, gestational age, maternal education, family affluence scale, and body mass index. Among boys, differences in attention capacity were found according to tertiles of birth weight and birth length (p < .05), as well as borderline significant differences across groups of any and exclusive breastfeeding (p = 0.055 and p = 0.108, respectively) after adjusting for potential confounders. In addition, boys with 3 early life risk factors (low birth weight, low birth length, and <3 months of breastfeeding) had significantly lower scores in attention capacity compared with boys with 0 risk factors (percentile score - 15.88; p = 0.009). In conclusion, early life factors, both separately and combined, may influence attention capacity in male European adolescents. Importantly, the combination of the 3 early life risk factors, low birth weight, low birth length, and <3 months of breastfeeding, even in normal ranges, may provide the highest reduction in attention capacity.
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| 6. |
- Esteban-Cornejo, Irene, et al.
(författare)
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Fitness, cortical thickness and surface area in overweight/obese children: The mediating role of body composition and relationship with intelligence
- 2019
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Ingår i: NeuroImage. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 1053-8119 .- 1095-9572. ; 186, s. 771-781
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Tidskriftsartikel (refereegranskat)abstract
- Cortical thickness and surface area are thought to be genetically unrelated and shaped by independent neurobiological events suggesting that they should be considered separately in morphometric analyses. Although the developmental trajectories of cortical thickness and surface area may differ across brain regions and ages, there is no consensus regarding the relationships of physical fitness with cortical thickness and surface area as well as for its subsequent influence on intelligence. Thus, this study examines: (i) the associations of physical fitness components (i.e., cardiorespiratory fitness, speed-agility and muscular fitness) with overall and regional cortical thickness and surface area; (ii) whether body composition indicators (i.e., body mass index, fat-free mass index and fat mass index) mediate these associations; and (iii) the association of physical fitness and cortical thickness with intelligence in overweight/obese children. A total of 101 overweight/obese children aged 8-11 years were recruited in Granada, Spain. The physical fitness components were assessed following the ALPHA health-related fitness test battery. T1-weighted images were acquired with a 3.0 Tesla Siemens Magnetom Tim Trio system. We used FreeSurfer software version 5.3.0 to assess cortical thickness (mm) and surface area (mm(2)). The main results showed that cardiorespiratory fitness and speed-agility were related to overall cortical thickness (beta = 0.321 and beta = 0.302, respectively; both P amp;lt; 0.05), and in turn, cortical thickness was associated with higher intelligence (beta = 0.198, P amp;lt; 0.05). Muscular fitness was not related to overall cortical thickness. None of the three physical fitness components were related to surface area (p amp;gt; 0.05). The associations of cardiorespiratory fitness and speed-agility with overall cortical thickness were mediated by fat mass index (56.86% amp; 62.28%, respectively). In conclusion, cardiorespiratory fitness and speed-agility, but not muscular fitness, are associated with overall cortical thickness, and in turn, thicker brain cortex is associated with higher intelligence in overweight/obese children. Yet, none of the three physical fitness components were related to surface area. Importantly, adiposity may hinder the benefits of cardiorespiratory fitness and speed-agility on cortical thickness. Understanding individual differences in brain morphology may have important implications for educators and policy makers who aim to determine policies and interventions to maximize academic learning and occupational success later in life.
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| 7. |
- Hellwig, Birte, et al.
(författare)
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Epsin Family Member 3 and Ribosome-Related Genes Are Associated with Late Metastasis in Estrogen Receptor-Positive Breast Cancer and Long-Term Survival in Non-Small Cell Lung Cancer Using a Genome-Wide Identification and Validation Strategy
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: In breast cancer, gene signatures that predict the risk of metastasis after surgical tumor resection are mainly indicative of early events. The purpose of this study was to identify genes linked to metastatic recurrence more than three years after surgery.Methods: Affymetrix HG U133A and Plus 2.0 array datasets with information on metastasis-free, disease-free or overall survival were accessed via public repositories. Time restricted Cox regression models were used to identify genes associated with metastasis during or after the first three years post-surgery (early-and late-type genes). A sequential validation study design, with two non-adjuvantly treated discovery cohorts (n = 409) and one validation cohort (n = 169) was applied and identified genes were further evaluated in tamoxifen-treated breast cancer patients (n = 923), as well as in patients with non-small cell lung (n = 1779), colon (n = 893) and ovarian (n = 922) cancer.Results: Ten late-and 243 early-type genes were identified in adjuvantly untreated breast cancer. Adjustment to clinicopathological factors and an established proliferation-related signature markedly reduced the number of early-type genes to 16, whereas nine late-type genes still remained significant. These nine genes were associated with metastasis-free survival (MFS) also in a non-time restricted model, but not in the early period alone, stressing that their prognostic impact was primarily based on MFS more than three years after surgery. Four of the ten late-type genes, the ribosome-related factors EIF4B, RPL5, RPL3, and the tumor angiogenesis modifier EPN3 were significantly associated with MFS in the late period also in a meta-analysis of tamoxifen-treated breast cancer cohorts. In contrast, only one late-type gene (EPN3) showed consistent survival associations in more than one cohort in the other cancer types, being associated with worse outcome in two non-small cell lung cancer cohorts. No late-type gene was validated in ovarian and colon cancer.Conclusions: Ribosome-related genes were associated with decreased risk of late metastasis in both adjuvantly untreated and tamoxifen-treated breast cancer patients. In contrast, high expression of epsin (EPN3) was associated with increased risk of late metastasis. This is of clinical relevance considering the well-understood role of epsins in tumor angiogenesis and the ongoing development of epsin antagonizing therapies.
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| 8. |
- Henriksson, Hanna, 1977-, et al.
(författare)
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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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Ingår i: Acta Paediatrica. - : WILEY. - 0803-5253 .- 1651-2227. ; 109:5, s. 995-1003
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Tidskriftsartikel (refereegranskat)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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| 9. |
- Henriksson, Hanna, et al.
(författare)
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Longitudinal Physical Activity, Body Composition, and Physical Fitness in Preschoolers
- 2017
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Ingår i: Medicine & Science in Sports & Exercise. - : LIPPINCOTT WILLIAMS & WILKINS. - 0195-9131 .- 1530-0315. ; 49:10, s. 2078-2085
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: This study aimed to investigate longitudinal associations of objectively measured physical activity (PA) and sedentary behavior (SB) with body composition and physical fitness at a 12-month follow-up in healthy Swedish 4-yr-old children. Methods: The data from the population-based MINISTOP trial were collected between 2014 and 2016, and this study included the 138 children who were in the control group. PA and SB were assessed using the wrist-worn ActiGraph (wGT3x-BT) accelerometer during seven 24-h periods and, subsequently, defined as SB, light-intensity PA, moderate-intensity PA, vigorous-intensity PA (VPA), and moderate-to-vigorous PA (MVPA). Body composition was measured using air-displacement plethysmography and physical fitness (cardiorespiratory fitness, lower and upper muscular strength as well as motor fitness) by the PREFIT fitness battery. Linear regression and isotemporal substitution models were applied. Results: Greater VPA and MVPA at the age of 4.5 yr were associated with higher fat-free mass index (FFMI) at 5.5 yr (P amp;lt; 0.001 and P = 0.044, respectively). Furthermore, greater VPA and MVPA at the age of 4.5 yr were associated with higher scores for cardiorespiratory fitness, lower body muscular strength, and motor fitness at 12-month follow-up (P = 0.001 to P = 0.031). Substituting 5 min.d(-1) of SB, light-intensity PA, or moderate-intensity PA for VPA at the age of 4.5 yr were associated with higher FFMI, and with greater upper and lower muscular strength at 12-month follow-up (P amp;lt; 0.001 to P = 0.046). Conclusion: Higher VPA and MVPA at the age of 4.5 yr were significantly associated with higher FFMI and better physical fitness at 12-month follow-up. Our results indicate that promoting high-intensity PA at young ages may have long-term beneficial effects on childhood body composition and physical fitness, in particular muscular strength.
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| 10. |
- Henriksson, Pontus, et al.
(författare)
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Associations of Fat Mass and Fat-Free Mass with Physical Fitness in 4-Year-Old Children: Results from the MINISTOP Trial
- 2016
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 8:8, s. 473-
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Tidskriftsartikel (refereegranskat)abstract
- Physical fitness is a powerful marker of health in youth. Studies in adolescents and adults suggest that higher fat mass is related to worse physical fitness. However, there is limited knowledge whether fat mass and fat-free mass are associated with physical fitness already in preschoolers. Baseline data from the MINISTOP (Mobile-based INtervention Intended to STop Obesity in Preschoolers) trial was utilized for this cross-sectional analysis. Body composition was assessed using air-displacement plethysmography. Fat mass index [fat mass (kg)/height(2) (m)] and fat-free mass index [fat-free mass (kg)/height(2) (m)] were used to provide height-adjusted measures of body composition. Physical fitness was measured using the PREFIT (FITness testing in PREschool children) battery, which assesses cardiorespiratory fitness, upper-body and lower-body muscular strength as well as motor fitness. In total, this study included 303 children (168 boys and 135 girls), who were on average 4.48 +/- 0.15 years old. Higher fat mass index was associated with worse cardiorespiratory fitness (standardized beta = -0.17, p = 0.002), lower-body muscular strength (beta = -0.17, p = 0.003) and motor fitness (beta = -0.21, p amp;lt; 0.001) in regression analyses adjusted for age, sex and mutually adjusted for fat-mass index and fat-free mass index. Conversely, higher fat-free mass index was associated with better cardiorespiratory fitness (beta = 0.18, p = 0.002), upper-body muscular strength (beta = 0.39, p amp;lt; 0.001), lower-body muscular strength (beta = 0.22, p amp;lt; 0.001) and motor fitness (beta = 0.17, p = 0.004). Thus, fat mass and fat-free mass in preschoolers appear to have joint but opposite associations with physical fitness, an important marker for current and future health.
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| 11. |
- Henriksson, Pontus, 1982-, et al.
(författare)
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Physical fitness in relation to later body composition in pre-school children
- 2019
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Ingår i: Journal of Science and Medicine in Sport. - : Elsevier. - 1440-2440 .- 1878-1861. ; 22:5, s. 574-579
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesAlthough physical fitness is considered a marker of health in youth, little is known whether physical fitness in pre-school age is related to later body composition. Thus, this study investigated (i) associations of physical fitness at 4.5 years of age with body composition 12 months later and (ii) whether improvements in physical fitness during the 12-month follow-up were associated with changes in body composition.DesignThis study included 142 children, measured at 4.5 and 5.5 years, from the control group of the MINISTOP trial.MethodsPhysical fitness (cardiorespiratory fitness, lower- and upper-body muscular strength and motor fitness) was measured using the PREFIT test battery. Body composition was assessed using air-displacement plethysmography.ResultsIn adjusted regression analyses, greater cardiorespiratory fitness, lower-body muscular strength and motor fitness at 4.5 years were associated with a lower fat mass index at 5.5 years (standardized β= −0.182 to −0.229, p ≤ 0.028). Conversely, greater cardiorespiratory fitness, lower- and upper-body muscular strength as well as motor fitness at 4.5 years of age were associated with a higher fat-free mass index (standardized β = 0.255–0.447, p ≤ 0.001). Furthermore, improvements in cardiorespiratory fitness, lower-body muscular strength and motor fitness during the 12-month follow-up period were associated with decreases in fat mass index and/or % fat mass.ConclusionsIn conclusion, the results of this study provide evidence of the importance of physical fitness early in life. Nevertheless, further studies are needed in order to clarify the influence of physical fitness in the pre-school age with later health outcomes.
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| 12. |
- Jiménez-Balado, Joan, et al.
(författare)
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DNA methylation and stroke prognosis : an epigenome-wide association study
- 2024
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Ingår i: Clinical Epigenetics. - : BioMed Central (BMC). - 1868-7083. ; 16:1
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Tidskriftsartikel (refereegranskat)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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| 13. |
- Keller, Magdalena, et al.
(författare)
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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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Ingår i: Journal of Experimental & Clinical Cancer Research. - : BioMed Central (BMC). - 1756-9966. ; 42
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Tidskriftsartikel (refereegranskat)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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| 14. |
- Lang, Justin J., et al.
(författare)
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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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Ingår i: Sports Medicine. - New Zealand : Adis International Ltd.. - 0112-1642 .- 1179-2035. ; 53:2, s. 549-564
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Tidskriftsartikel (refereegranskat)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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| 15. |
- Leist, Marcel, et al.
(författare)
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Adverse outcome pathways : opportunities, limitations and open questions
- 2017
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Ingår i: Archives of Toxicology. - : Springer Science and Business Media LLC. - 0340-5761 .- 1432-0738. ; 91:11, s. 3477-3505
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Tidskriftsartikel (refereegranskat)abstract
- Adverse outcome pathways (AOPs) are a recent toxicological construct that connects, in a formalized, transparent and quality-controlled way, mechanistic information to apical endpoints for regulatory purposes. AOP links a molecular initiating event (MIE) to the adverse outcome (AO) via key events (KE), in a way specified by key event erelationships (KER). Although this approach to formalize mechanistic toxicological information only started in 2010, over 200 AOPs have already been established. At this stage, new requirements arise, such as the need for harmonization and re-assessment, for continuous updating, as well as for alerting about pitfalls, misuses and limits of applicability. In this review, the history of the AOP concept and its most prominent strengths are discussed, including the advantages of a formalized approach, the systematic collection of weight of evidence, the linkage of mechanisms to apical end points, the examination of the plausibility of epidemiological data, the identification of critical knowledge gaps and the design of mechanistic test methods. To prepare the ground for a broadened and appropriate use of AOPs, some widespread misconceptions are explained. Moreover, potential weaknesses and shortcomings of the current AOP rule set are addressed (1) to facilitate the discussion on its further evolution and (2) to better define appropriate vs. less suitable application areas. Exemplary toxicological studies are presented to discuss the linearity assumptions of AOP, the management of event modifiers and compensatory mechanisms, and whether a separation of toxicodynamics from toxicokinetics including metabolism is possible in the framework of pathway plasticity. Suggestions on how to compromise between different needs of AOP stakeholders have been added. A clear definition of open questions and limitations is provided to encourage further progress in the field.
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| 16. |
- Lohr, Miriam, et al.
(författare)
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The prognostic relevance of tumour-infiltrating plasma cells and immunoglobulin kappa C indicates an important role of the humoral immune response in non-small cell lung cancer
- 2013
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Ingår i: Cancer Letters. - : Elsevier BV. - 0304-3835 .- 1872-7980. ; 333:2, s. 222-228
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Tidskriftsartikel (refereegranskat)abstract
- A prognostic impact of immunoglobulin kappa C (IGKC) expression has been described in cancer. We analysed the influence of B-cell and plasma cell markers, as well as IGKC expression, in non-small lung cancer (NSCLC) using immunohistochemistry on a tissue microarray. IGKC protein expression was independently associated with longer survival, with particular impact in the adenocarcinoma subgroup. Moreover, a correlation was seen with CD138+ cells, but not with CD20. CD138 expression revealed a comparable association with survival. In conclusion, IGKC expression in stroma–infiltrating plasma cells is a prognostic marker in NSCLC, supporting emerging treatment concepts that exploit the humoral immune response.
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| 17. |
- Medina-Dols, Aina, et al.
(författare)
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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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Ingår i: Cell Death Discovery. - : Springer Nature. - 2058-7716. ; 10
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Tidskriftsartikel (refereegranskat)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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| 18. |
- Migueles, Jairo H., et al.
(författare)
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Accelerometer Data Collection and Processing Criteria to Assess Physical Activity and Other Outcomes: A Systematic Review and Practical Considerations
- 2017
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Ingår i: Sports Medicine. - : ADIS INT LTD. - 0112-1642 .- 1179-2035. ; 47:9, s. 1821-1845
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Forskningsöversikt (refereegranskat)abstract
- Background Accelerometers are widely used to measure sedentary time, physical activity, physical activity energy expenditure (PAEE), and sleep-related behaviors, with the ActiGraph being the most frequently used brand by researchers. However, data collection and processing criteria have evolved in a myriad of ways out of the need to answer unique research questions; as a result there is no consensus. Objectives The purpose of this review was to: (1) compile and classify existing studies assessing sedentary time, physical activity, energy expenditure, or sleep using the ActiGraph GT3X/+ through data collection and processing criteria to improve data comparability and (2) review data collection and processing criteria when using GT3X/+ and provide age-specific practical considerations based on the validation/calibration studies identified. Methods Two independent researchers conducted the search in PubMed and Web of Science. We included all original studies in which the GT3X/+ was used in laboratory, controlled, or free-living conditions published from 1 January 2010 to the 31 December 2015. Results The present systematic review provides key information about the following data collection and processing criteria: placement, sampling frequency, filter, epoch length, non-wear-time, what constitutes a valid day and a valid week, cut-points for sedentary time and physical activity intensity classification, and algorithms to estimate PAEE and sleep-related behaviors. The information is organized by age group, since criteria are usually age-specific. Conclusion This review will help researchers and practitioners to make better decisions before (i.e., device placement and sampling frequency) and after (i.e., data processing criteria) data collection using the GT3X/? accelerometer, in order to obtain more valid and comparable data.
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| 19. |
- Migueles, Jairo H., et al.
(författare)
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Accelerometer Data Processing and Energy Expenditure Estimation in Preschoolers
- 2019
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Ingår i: Medicine & Science in Sports & Exercise. - : LIPPINCOTT WILLIAMS & WILKINS. - 0195-9131 .- 1530-0315. ; 51:3, s. 590-598
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To assess the capacity of different acceleration metrics from wrist accelerations to estimate total energy expenditure (TEE) and activity energy expenditure (AEE) using doubly labeled water in preschool children. Methods Thirty-nine preschoolers (5.5 0.1 yr) were included. Total energy expenditure was measured using doubly labeled water during 14 d, and AEE was then calculated using a predicted basal metabolic rate. Participants wore a wGT3X-BT accelerometer on their nondominant wrist for 5 d. We derived the following metrics from raw accelerations: raw ActiGraph activity counts using the normal filter and the low-frequency extension; and alternate summary metrics, such as the Euclidian norm minus 1g (ENMO), Euclidian norm of the high-pass-filtered accelerations (HFEN), the bandpass-filtered accelerations, the HFEN plus Euclidean norm of low-pass filtered accelerations minus 1g (HFEN+) and the mean amplitude deviation. Results Alternate summary metrics explained a larger proportion of the variance in TEE and AEE than ActiGraphs activity counts (counts, 7-8 and 25% of TEE and AEE; alternate summary metrics, 13%-16% and 35%-39% of TEE and AEE). Adjustments for body weight and height resulted in an explanation of 51% of AEE by ENMO. All of the metrics adjusted for fat mass and fat-free mass explained up to 84% and 67% of TEE and AEE, respectively. Conclusions ENMO and the other alternate summary metrics explained more of the variance in TEE and AEE than the ActiGraphs activity counts in 5-yr-old children, suggesting further exploration of these variables in studies on physical activity and energy expenditure in preschoolers. Our results need confirmation in other populations with wider age groups and varying body compositions.
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| 20. |
- Migueles, Jairo Hidalgo, et al.
(författare)
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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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Ingår i: Sensors. - : MDPI. - 1424-8220. ; 21:10
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Tidskriftsartikel (refereegranskat)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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| 21. |
- Migueles, Jairo H., et al.
(författare)
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Comparability of accelerometer signal aggregation metrics across placements and dominant wrist cut points for the assessment of physical activity in adults
- 2019
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Large epidemiological studies that use accelerometers for physical behavior and sleep assessment differ in the location of the accelerometer attachment and the signal aggregation metric chosen. This study aimed to assess the comparability of acceleration metrics between commonly-used body-attachment locations for 24 hours, waking and sleeping hours, and to test comparability of PA cut points between dominant and non-dominant wrist. Forty-five young adults (23 women, 18-41 years) were included and GT3X + accelerometers (ActiGraph, Pensacola, FL, USA) were placed on their right hip, dominant, and non-dominant wrist for 7 days. We derived Euclidean Norm Minus One g (ENMO), Low-pass filtered ENMO (LFENMO), Mean Amplitude Deviation (MAD) and ActiGraph activity counts over 5-second epochs from the raw accelerations. Metric values were compared using a correlation analysis, and by plotting the differences by time of the day. Cut points for the dominant wrist were derived using Lins concordance correlation coefficient optimization in a grid of possible thresholds, using the nondominant wrist estimates as reference. They were cross-validated in a separate sample (N = 36, 10 women, 22-30 years). Shared variances between pairs of acceleration metrics varied across sites and metric pairs (range in r(2) : 0.19-0.97, all p amp;lt; 0.01), suggesting that some sites and metrics are associated, and others are not. We observed higher metric values in dominant vs. non-dominant wrist, thus, we developed cut points for dominant wrist based on ENMO to classify sedentary time (amp;lt;50 mg), light PA (50-110 mg), moderate PA (110-440 mg) and vigorous PA (amp;gt;= 440 mg). Our findings suggest differences between dominant and non-dominant wrist, and we proposed new cut points to attenuate these differences. ENMO and LFENMO were the most similar metrics, and they showed good comparability with MAD. However, counts were not comparable with ENMO, LFENMO and MAD.
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| 22. |
- Migueles, Jairo H., et al.
(författare)
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Comparability of published cut-points for the assessment of physical activity: Implications for data harmonization
- 2019
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Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : WILEY. - 0905-7188 .- 1600-0838. ; 29:4, s. 566-574
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to compare estimations of sedentary time (SED) and time spent in physical activity (PA) intensities in children with overweight/obesity across different age-appropriate cut-points based on different body-worn attachment sites and acceleration metrics. A total of 104 overweight/obese children (10.1 +/- 1.1 years old, 43 girls) concurrently wore ActiGraph GT3X+ accelerometers on their right hip and non-dominant wrist for 7 days (24 hours). Euclidean norm -1 g (ENMO) and activity counts from both vertical axis (VACounts) and vector magnitude (VMCounts) were derived. We calculated estimates of SED and light, moderate, vigorous, and moderate-to-vigorous (MVPA) intensity PA using different published cut-points for children. The prevalence of children meeting the recommended 60 min/d of MVPA was calculated. The time spent in SED and the different PA intensities largely differed across cut-points based on different attachment sites and acceleration metrics (ie, SED = 11-252 min/d; light PA = 10-217 min/d; moderate PA = 1-48 min/d; vigorous PA = 1-35 min/d; MVPA = 4-66 min/d). Consequently, the prevalence of children meeting the recommended 60 min/d of MVPA varied from 8% to 96% of the study sample. The present study provides a comprehensive comparison between available cut-points for different attachment and acceleration metrics in children. Furthermore, our data clearly show that it is not possible (and probably will never be) to know the prevalence of meeting the PA guidelines based on accelerometer data since apparent differences range from almost zero to nearly everyone meeting the guidelines.
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| 23. |
- Migueles, Jairo H., et al.
(författare)
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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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Ingår i: JAMA Network Open. - : AMER MEDICAL ASSOC. - 2574-3805. ; 6:7
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Tidskriftsartikel (refereegranskat)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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| 24. |
- Migueles, Jairo H., et al.
(författare)
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Step-Based Metrics and Overall Physical Activity in Children With Overweight or Obesity: Cross-Sectional Study
- 2020
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Ingår i: JMIR mhealth and uhealth. - : JMIR PUBLICATIONS, INC. - 2291-5222. ; 8:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Best-practice early interventions to increase physical activity (PA) in children with overweight and obesity should be both feasible and evidence based. Walking is a basic human movement pattern that is practical, cost-effective, and does not require complex movement skills. However, there is still a need to investigate how much walking-as a proportion of total PA level-is performed by children who are overweight and obese in order to determine its utility as a public health strategy. Objective: This study aimed to (1) investigate the proportion of overall PA indicators that are explained by step-based metrics and (2) study step accumulation patterns relative to achievement of public health recommendations in children who are overweight and obese. Methods: A total of 105 overweight and obese children (mean 10.1 years of age [SD 1.1]; 43 girls) wore hip-worn accelerometers for 7 days. PA volumes were derived using the daily average of counts per 15 seconds, categorized using standard cut points for light-moderate-vigorous PA (LMVPA) and moderate-to-vigorous PA (MVPA). Derived step-based metrics included volume (steps/day), time in cadence bands, and peak 1-minute, 30-minute, and 60-minute cadences. Results: Steps per day explained 66%, 40%, and 74% of variance for counts per 15 seconds, LMVPA, and MVPA, respectively. The variance explained was increased up to 80%, 92%, and 77% by including specific cadence bands and peak cadences. Children meeting the World Health Organization recommendation of 60 minutes per day of MVPA spent less time at zero cadence and more time in cadence bands representing sporadic movement to brisk walking (ie, 20-119 steps/min) than their less-active peers. Conclusions: Step-based metrics, including steps per day and various cadence-based metrics, seem to capture a large proportion of PA for children who are overweight and obese. Given the availability of pedometers, step-based metrics could be useful in discriminating between those children who do or do not achieve MVPA recommendations.
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| 25. |
- Mora-Gonzalez, Jose, et al.
(författare)
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Physical Fitness, Physical Activity, and the Executive Function in Children with Overweight and Obesity
- 2019
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Ingår i: Journal of Pediatrics. - : MOSBY-ELSEVIER. - 0022-3476 .- 1097-6833. ; 208, s. 50-
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Tidskriftsartikel (refereegranskat)abstract
- Objective To examine the associations of physical fitness and physical activity with executive function in children with overweight and obesity. Study design A cross-sectional study involving 100 children with overweight and obesity (10.1 +/- 1.1 years old; 58.0% boys). We assessed physical fitness components (ie, muscular strength, speed-agility, and cardiorespiratory fitness) using the ALPHA battery, and physical activity and sedentary time by accelerometry. Cognitive flexibility was measured by the Design Fluency Test and Trail Making Test, inhibition by the Stroop test, and planning ability by the Zoo Map Test. Results Handgrip strength was positively associated with planning ability (P = .025). Speed-agility was positively related to cognitive flexibility and inhibition (P amp;lt; .05). Cardiorespiratory fitness and an overall fitness Z-score were positively associated with indicators of cognitive flexibility (P amp;lt; .05). No associations were found for physical activity and sedentary time with executive function (P amp;gt;= .05). Conclusions Muscular strength, speed agility, and cardiorespiratory fitness are associated with executive function in children with overweight and obesity. Cognitive flexibility seems to be more robustly associated with all fitness components, whereas planning ability and inhibition might depend on the component analyzed. The positive associations found in the present study in children with overweight and obesity call for more exercise-based randomized controlled trials in this population.
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| 26. |
- Ortega, Francisco B., et al.
(författare)
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Effects of an Exercise Program on Brain Health Outcomes for Children With Overweight or Obesity The ActiveBrains Randomized Clinical Trial
- 2022
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Ingår i: JAMA Network Open. - : American Medical Association. - 2574-3805. ; 5:8
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Pediatric overweight and obesity are highly prevalent across the world, with implications for poorer cognitive and brain health. Exercise might potentially attenuate these adverse consequences. OBJECTIVES To investigate the effects of an exercise program on brain health indicators, including intelligence, executive function, academic performance, and brain outcomes, among children with overweight or obesity and to explore potential mediators and moderators of the main effects of exercise. DESIGN, SETTING, AND PARTICIPANTS All preexercise and postexercise data for this 20-week randomized clinical trial of 109 children aged 8 to 11 years with overweight or obesity were collected from November 21, 2014, to June 30, 2016, with neuroimaging data processing and analyses conducted between June 1, 2017, and December 20, 2021. All 109 children were included in the intention-to-treat analyses; 90 children (82.6%) completed the postexercise evaluation and attended 70% or more of the recommended exercise sessions and were included in per-protocol analyses. INTERVENTIONS All participants received lifestyle recommendations. The control group continued their usual routines, whereas the exercise group attended a minimum of 3 supervised 90-minute sessions per week in an out-of-school setting. MAIN OUTCOMES AND MEASURES Intelligence, executive function (cognitive flexibility, inhibition, and working memory), and academic performance were assessed with standardized tests, and hippocampal volume was measured with magnetic resonance imaging. RESULTS The 109 participants included 45 girls (41.3%); participants had a mean (SD) body mass index of 26.8 (3.6) and a mean (SD) age of 10.0 (1.1) years at baseline. In per-protocol analyses, the exercise intervention improved crystallized intelligence, with the exercise group improving from before exercise to after exercise (mean z score, 0.62 [95% CI, 0.44-0.80]) compared with the control group (mean z score, -0.10 [95% CI, -0.28 to 0.09]; difference between groups, 0.72 SDs [95% CI, 0.46-0.97]; P < .001). Total intelligence also improved significantly more in the exercise group (mean z score, 0.69 [95% CI, 0.48-0.89]) than in the control group (mean z score, 0.07 [95% CI, -0.14 to 0.28]; difference between groups, 0.62 SDs [95% CI, 0.31-0.91]; P < .001). Exercise also positively affected a composite score of cognitive flexibility (mean z score: exercise group, 0.25 [95% CI, 0.05-0.44]; control group, -0.17 [95% CI, -0.39 to 0.04]; difference between groups, 0.42 SDs [95% CI, 0.13-0.71]; P = .005). These main effects were consistent in intention-to-treat analyses and after multiple-testing correction. There was a positive, small-magnitude effect of exercise on total academic performance (mean z score: exercise group, 0.31 [95% CI, 0.18-0.44]; control group, 0.10 [95% CI, -0.04 to 0.24]; difference between groups, 0.21 SDs [95% CI, 0.01-0.40]; P = .03), which was partially mediated by cognitive flexibility. Inhibition, working memory, hippocampal volume, and other brain magnetic resonance imaging outcomes studied were not affected by the exercise program. The intervention increased cardiorespiratory fitness performance as indicated by longer treadmill time to exhaustion (mean z score: exercise group, 0.54 [95% CI, 0.27-0.82]; control group, 0.13 [95% CI, -0.16 to 0.41]; difference between groups, 0.42 SDs [95% CI, 0.01-0.82]; P = .04), and these changes in fitness mediated some of the effects (small percentage of mediation [approximately 10%-20%]). The effects of exercise were overall consistent across the moderators tested, except for larger improvements in intelligence among boys compared with girls. CONCLUSIONS AND RELEVANCE In this randomized clinical trial, exercise positively affected intelligence and cognitive flexibility during development among children with overweight or obesity. However, the structural and functional brain changes responsible for these improvements were not identified.
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| 27. |
- Rodriguez-Ayllon, Maria, et al.
(författare)
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Role of Physical Activity and Sedentary Behavior in the Mental Health of Preschoolers, Children and Adolescents: A Systematic Review and Meta-Analysis
- 2019
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Ingår i: Sports Medicine. - : ADIS INT LTD. - 0112-1642 .- 1179-2035. ; 49:9, s. 1383-1410
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Forskningsöversikt (refereegranskat)abstract
- Background Evidence suggests that participation in physical activity may support young peoples current and future mental health. Although previous reviews have examined the relationship between physical activity and a range of mental health outcomes in children and adolescents, due to the large increase in published studies there is a need for an update and quantitative synthesis of effects. Objectives The objectives of this study were to determine the effect of physical activity interventions on mental health outcomes by conducting a systematic review and meta-analysis, and to systematically synthesize the observational evidence (both longitudinal and cross-sectional studies) regarding the associations between physical activity and sedentary behavior and mental health in preschoolers (2-5 years of age), children (6-11 years of age) and adolescents (12-18 years of age). Methods A systematic search of the PubMed and Web of Science electronic databases was performed from January 2013 to April 2018, by two independent researchers. Meta-analyses were performed to examine the effect of physical activity on mental health outcomes in randomized controlled trials (RCTs) and non-RCTs (i.e. quasi-experimental studies). A narrative synthesis of observational studies was conducted. Studies were included if they included physical activity or sedentary behavior data and at least one psychological ill-being (i.e. depression, anxiety, stress or negative affect) or psychological well-being (i.e. self-esteem, self-concept, self-efficacy, self-image, positive affect, optimism, happiness and satisfaction with life) outcome in preschoolers, children or adolescents. Results A total of 114 original articles met all the eligibility criteria and were included in the review (4 RCTs, 14 non-RCTs, 28 prospective longitudinal studies and 68 cross-sectional studies). Of the 18 intervention studies, 12 (3 RCTs and 9 non-RCTs) were included in the meta-analysis. There was a small but significant overall effect of physical activity on mental health in children and adolescents aged 6-18 years (effect size 0.173, 95% confidence interval 0.106-0.239, p amp;lt; 0.001, percentage of total variability attributed to between-study heterogeneity [I-2] = 11.3%). When the analyses were performed separately for children and adolescents, the results were significant for adolescents but not for children. Longitudinal and cross-sectional studies demonstrated significant associations between physical activity and lower levels of psychological ill-being (i.e. depression, stress, negative affect, and total psychological distress) and greater psychological well-being (i.e. self-image, satisfaction with life and happiness, and psychological well-being). Furthermore, significant associations were found between greater amounts of sedentary behavior and both increased psychological ill-being (i.e. depression) and lower psychological well-being (i.e. satisfaction with life and happiness) in children and adolescents. Evidence on preschoolers was nearly non-existent. Conclusions Findings from the meta-analysis suggest that physical activity interventions can improve adolescents mental health, but additional studies are needed to confirm the effects of physical activity on childrens mental health. Findings from observational studies suggest that promoting physical activity and decreasing sedentary behavior might protect mental health in children and adolescents. PROSPERO Registration Number: CRD42017060373.
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| 28. |
- Schmidt, Marcus, et al.
(författare)
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A comprehensive analysis of human gene expression profiles identifies stromal immunoglobulin kappa C as a compatible prognostic marker in human solid tumors
- 2012
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 18:9, s. 2695-2703
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE:Although the central role of the immune system for tumor prognosis is generally accepted a single robust marker is not yet available.EXPERIMENTAL DESIGN:Based on ROC (receiver operating characteristic) analyses robust markers were identified from a 60 gene B-cell derived metagene and analyzed in gene expression profiles of 1810 breast cancer, 1056 non-small cell lung cancer, 513 colorectal and 426 ovarian cancer patients. Protein and RNA levels were examined in paraffin embedded tissue of 330 breast cancer patients. The cell types were identified using immunohistochemical co-staining and confocal fluorescence microscopy.RESULTS:We identified immunoglobulin kappa C (IGKC) which as a single marker is similarly predictive and prognostic as the entire B-cell metagene. IGKC was consistently associated with metastasis free survival across different molecular subtypes in node-negative breast cancer (n=965) and predicted response to anthracycline-based neoadjuvant chemotherapy (n=845) [P less than 0.001]. In addition, IGKC gene expression was prognostic in non-small cell lung cancer and colorectal cancer. No association was observed in ovarian cancer. IGKC protein expression was significantly associated with survival in paraffin embedded tissues of 330 breast cancer patients. Tumor infiltrating plasma cells were identified as the source of IGKC expressionCONCLUSION:Our findings provide IGKC as a novel diagnostic marker for risk stratification in human cancer and support concepts to exploit the humoral immune response for anti-cancer therapy. It could be validated in several independent cohorts and performed similarly well in RNA from fresh frozen as well as from paraffin tissue and on protein level by immunostaining.
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| 29. |
- Torres-Lopez, Lucia V, et al.
(författare)
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Associations of Sleep-Related Outcomes with Behavioral and Emotional Functioning in Children with Overweight/Obesity
- 2022
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Ingår i: The Journal of Pediatrics. - : Elsevier. - 0022-3476 .- 1097-6833. ; 246, s. 170-178.e2
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Tidskriftsartikel (refereegranskat)abstract
- Objective To evaluate the associations of parent-reported sleep-disordered breathing (SDB) and device-assessed sleep behaviors with behavioral and emotional functioning in pediatric patients with overweight/obesity. Study design A total of 109 children with overweight/obesity (mean age, 10.0 +/- 1.1 years) were included in this cross-sectional study. We used the Spanish version of the Pediatric Sleep Questionnaire (PSQ) to assess SDB and its subscales (ie, snoring, daytime sleepiness, and inattention/hyperactivity). Device-assessed sleep behaviors (ie, wake time, sleep onset time, total time in bed, total sleep time, and waking after sleep onset) were estimated using wrist-worn accelerometers. We used the Behavior Assessment System for Children, second edition to assess behavioral and emotional functioning (ie, clinical scale: aggressiveness, hyperactivity, behavior problems, attention problems, atypicality, depression, anxiety, retreat, and somatization; adaptive scale: adaptability, social skills, and leadership). Results SDB was positively associated with all clinical scale variables (all beta > 0.197, P <=.041) and with lower adaptability and leadership (all beta < -0.226, P < .021). Specifically, the PSQ subscale relating to daytime sleepiness was associated with higher attention problems, depression, anxiety, and retreat (all beta > 0.196, P .045) and lower adaptability (beta = -0.246, P = .011). The inattention/hyperactivity subscale was significantly associated with the entire clinical and adaptive scales (all beta > vertical bar 0.192 vertical bar, P <= .046) except for somatization. The snoring subscale and device-assessed sleep behaviors were not related to any behavioral or emotional functioning variables. Conclusions Our study suggests that SDB symptoms, but not device-assessed sleep behaviors, are associated with behavioral and emotional functioning in children with overweight/obesity. Specifically, daytime sleepiness, a potential SDB symptom, was related to higher attention problems, depression, anxiety, and retreat and lower adaptability.
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| 30. |
- Torres-Lopez, Lucia V, et al.
(författare)
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Does sleep-disordered breathing add to impairments in academic performance and brain structure usually observed in children with overweight/obesity?
- 2022
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Ingår i: European Journal of Pediatrics. - : Springer. - 0340-6199 .- 1432-1076. ; 181, s. 2055-2065
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Tidskriftsartikel (refereegranskat)abstract
- Approximately 4-11% of children suffer from sleep-disordered breathing (SDB), and children with obesity are at increased risk. Both obesity and SDB have been separately associated with poorer brain health, yet whether SDB severity affects brain health in children with obesity remains unanswered. This study aimed to examine associations of SDB severity with academic performance and brain structure (i.e., total brain and gray and white matter volumes and gray matter volume in the hippocampus) in children with overweight/obesity. One hundred nine children aged 8-12 years with overweight/obesity were included. SDB severity and its subscales (i.e., snoring, daytime sleepiness, and inattention/hyperactivity) were evaluated via the Pediatric Sleep Questionnaire (PSQ), and academic performance was evaluated with the Woodcock-Munoz standardized test and school grades. Brain structure was assessed by magnetic resonance imaging. SDB severity was not associated with academic performance measured by the standardized test (all vertical bar beta vertical bar> 0.160, P > 0.076), yet it was associated with the school grade point average (beta = -0.226, P = 0.007) and natural and social science grades (beta = -0.269, P = 0.024). Intention/hyperactivity seemed to drive these associations. No associations were found between SDB severity and the remaining school grades (all beta < -0.188, P > 0.065) or brain volumes (all P > 0.05). Conclusion: Our study shows that SDB severity was associated with lower school grades, yet it was not associated with the standardized measurement of academic performance or with brain volumes in children with overweight/obesity. SDB severity may add to academic problems in children beyond the effects contributed by overweight/obesity status alone.
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| 31. |
- Torres-Lopez, Lucia V., et al.
(författare)
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Effects of exercise on sleep in children with overweight/obesity: a randomized clinical trial
- 2023
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Ingår i: Obesity. - : WILEY. - 1930-7381 .- 1930-739X.
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveThe objective of this study was to examine the chronic effects of a 20-week exercise training program on device-assessed sleep and sleep-disordered breathing; and to determine whether participating in a session of the exercise program had effects on device-assessed sleep the subsequent night in children with overweight/obesity.MethodsA randomized clinical trial was conducted from November 2014 to June 2016. A total of 109 children (age 8-11 years) with overweight/obesity were randomized into an exercise training or control group. The exercise program included aerobic and resistance training 3 to 5 days/week. The control group participants continued their usual lifestyle. Device-assessed sleep outcomes were measured using wrist-worn actigraphy at baseline, in the middle of the exercise program (10th week), and at postintervention for seven consecutive days (24 h/day), and sleep-disordered breathing was measured via the Pediatric Sleep Questionnaire.ResultsThe exercise training program had a statistically significant effect on wake after sleep onset time (-10.8 min/day, -0.5 SDs, p = 0.040). No other chronic or acute effects (i.e., the subsequent night of attending a session of the exercise training program) were observed on the remaining sleep outcomes.ConclusionsA 20-week exercise training program reduced wake after sleep onset time in children with overweight/obesity. Future randomized trials that include a sample of children with poor sleep health at baseline are needed to better appreciate the role of exercise in sleep health.
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| 32. |
- Zhang, C., et al.
(författare)
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LIPG-promoted lipid storage mediates adaptation to oxidative stress in breast cancer
- 2019
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 145:4, s. 901-915
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Tidskriftsartikel (refereegranskat)abstract
- Endothelial lipase (LIPG) is a cell surface associated lipase that displays phospholipase A1 activity towards phosphatidylcholine present in high‐density lipoproteins (HDL). LIPG was recently reported to be expressed in breast cancer and to support proliferation, tumourigenicity and metastasis. Here we show that severe oxidative stress leading to AMPK activation triggers LIPG upregulation, resulting in intracellular lipid droplet accumulation in breast cancer cells, which supports survival. Neutralizing oxidative stress abrogated LIPG upregulation and the concomitant lipid storage. In human breast cancer, high LIPG expression was observed in a limited subset of tumours and was significantly associated with shorter metastasis‐free survival in node‐negative, untreated patients. Moreover, expression of PLIN2 and TXNRD1 in these tumours indicated a link to lipid storage and oxidative stress. Altogether, our findings reveal a previously unrecognized role for LIPG in enabling oxidative stress‐induced lipid droplet accumulation in tumour cells that protects against oxidative stress, and thus supports tumour progression.
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| 33. |
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