Investigaciones financiadas por la Unión Europea (OpenAire) - Europar Batasunak finantzatutako ikerketak (OpenAire)

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Open Access
Aldosterone impairs mitochondrial function in human cardiac fibroblasts via A-kinase anchor protein 12
(Springer, 2018) Ibarrola Ulzurrun, Jaime Francisco; Sádaba Sagredo, Rafael; Martínez Martínez, Ernesto; García Peña, Amaia; Gaínza Calleja, Alicia; Ciencias de la Salud; Osasun Zientziak
Aldosterone (Aldo) contributes to mitochondrial dysfunction and cardiac oxidative stress. Using a proteomic approach, A-kinase anchor protein (AKAP)-12 has been identified as a down-regulated protein by Aldo in human cardiac fibroblasts. We aim to characterize whether AKAP-12 down-regulation could be a deleterious mechanism which induces mitochondrial dysfunction and oxidative stress in cardiac cells. Aldo down-regulated AKAP-12 via its mineralocorticoid receptor, increased oxidative stress and induced mitochondrial dysfunction characterized by decreased mitochondrial-DNA and Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) expressions in human cardiac fibroblasts. CRISPR/Cas9-mediated knock-down of AKAP-12 produced similar deleterious effects in human cardiac fibroblasts. CRISPR/Cas9-mediated activation of AKAP-12 blunted Aldo effects on mitochondrial dysfunction and oxidative stress in human cardiac fibroblasts. In Aldo-salt-treated rats, cardiac AKAP-12, mitochondrial-DNA and PGC-1α expressions were decreased and paralleled increased oxidative stress. In myocardial biopsies from patients with aortic stenosis (AS, n = 26), AKAP-12, mitochondrial-DNA and PGC-1α expressions were decreased as compared to Controls (n = 13). Circulating Aldo levels inversely correlated with cardiac AKAP-12. PGC-1α positively associated with AKAP-12 and with mitochondrial-DNA. Aldo decreased AKAP-12 expression, impairing mitochondrial biogenesis and increasing cardiac oxidative stress. AKAP-12 down-regulation triggered by Aldo may represent an important event in the development of mitochondrial dysfunction and cardiac oxidative stress.
Open Access
Analysis of copy number alterations reveals the lncRNA ALAL-1 as a regulator of lung cancer immune evasion
(Rockefeller University Press, 2020) Athie, Alejandro; Marchese, Francesco P.; González, Jovanna; Lozano, Teresa; Raimondi, Ivan; Juvvuna, Prasanna Kumar; Abad, Amaya ; Marin-Béjar, Oskar; Serizay, Jacques; Martínez, Dannys; Ajona, Daniel; Pajares Villandiego, María Josefa; Sandoval, Juan; Montuenga, Luis M.; Kanduri, Chandrasekhar ; Lasarte, Juan José; Huarte, Maite ; Ciencias de la Salud; Osasun Zientziak
Cancer is characterized by genomic instability leading to deletion or amplification of oncogenes or tumor suppressors. However, most of the altered regions are devoid of known cancer drivers. Here, we identify lncRNAs frequently lost or amplified in cancer. Among them, we found amplified lncRNA associated with lung cancer-1 (ALAL-1) as frequently amplified in lung adenocarcinomas. ALAL-1 is also overexpressed in additional tumor types, such as lung squamous carcinoma. The RNA product of ALAL-1 is able to promote the proliferation and tumorigenicity of lung cancer cells. ALAL-1 is a TNFα− and NF-κB–induced cytoplasmic lncRNA that specifically interacts with SART3, regulating the subcellular localization of the protein deubiquitinase USP4 and, in turn, its function in the cell. Interestingly, ALAL-1 expression inversely correlates with the immune infiltration of lung squamous tumors, while tumors with ALAL-1 amplification show lower infiltration of several types of immune cells. We have thus unveiled a pro-oncogenic lncRNA that mediates cancer immune evasion, pointing to a new target for immune potentiation.
Open Access
Analysis of the association between polymorphisms in intergenic regions of Staphylococcus aureus genes involved in biofilm formation and periprosthetic joint infections
(2022) Morales Laverde, Liliana Andrea; Lasa Uzcudun, Íñigo; Solano Goñi, Cristina; Ciencias de la Salud; Osasun Zientziak
In this thesis, we have focused on studying variants found in IGRs adjacent to the most important genes involved in S. aureus biofilm formation; the icaADBCR locus, and the genes encoding the family of surface adhesins. For this purpose, we sequenced the whole genome of a collection of 71 S. aureus isolates from periprosthetic joint infections (PJI) and wound infections stored at the Clinical Bacteriological Laboratory of the Sahlgrenska University Hospital and at the Culture Collection University of Gothenburg (CCUG), respectively. In the first chapter, we explored the regulatory regions of the icaADBCR locus to identify patterns that might be associated with an increased capacity of the isolates to produce PIA/PNAG and form a biofilm. This study compared the regulatory regions of the icaADBCR locus in the genomes of PJI and wound isolates with those in the genome of the reference strain MW2. From these analyses, strains were grouped based on the SNPs found in the IGRs of the operon and also within the coding region of the transcriptional regulator IcaR. These regions showed high conservation rates, and no pattern associated with the origin of the isolates, either PJI or wounds, was detected. On the other hand, using transcriptional fusions between the regulatory region of the icaADBCR locus and the green fluorescent protein gene (gfp), we demonstrated that the expression of icaADBC genes was not affected by the presence of variations in IGRs. Notably, a SNP within the coding region of icaR, which results in an amino acid change in the transcriptional repressor IcaR V176E, led to a significant increase in the transcription of the icaADBC operon and the production of PIA/PNAG. Using a Galleria mellonella infection model, we were able to demonstrate a significant reduction in S. aureus virulence associated with the increase in PIA/PNAG production. In the second chapter, we focused on analyzing the association between SNPs in the promoter regions of genes encoding adhesion-related proteins with adhesins expression levels and therefore, the ability of the strain to adhere to medical devices. Genome analyses of PJI and wound isolates showed different profiles in the content of adhesin-encoding genes. Some of these, such as sasG and cna, were lineage-associated, and fifteen genes were present in the whole collection of strains. When the variability in the SNPs contained in regulatory regions that control the expression of each adhesin was investigated, different variation rates were found among the isolates. Following the same approach as in chapter I, based on transcriptional fusions between regulatory regions and the gfp gene, results showed that each genetic lineage contained a specific profile of adhesins expression under the same environmental condition. Moreover, we developed a biomaterial-associated murine infection model together with a metagenomic analysis to simultaneously compare the capacity of different S. aureus isolates to colonize medical implants. In summary, our results evidenced that SNPs in the IGRs flanking the genes encoding factors important for biofilm development may contribute to the generation of variability in the capacity of S. aureus to colonize medical implants. In particular, our results revealed that IGRs controlling the expression of the icaADBC locus and production of the PIA/PNAG exopolysaccharide are highly conserved and that very few silent SNPs can be detected between strains. On the contrary, SNPs in the IGRs of genes encoding surface adhesins provide a profile of proteins expression that is specific for each S. aureus clonal complex (CC). Altogether, these studies emphasize the importance of investigating the potential impact of SNPs inside IGRs on gene expression and specific bacterial traits, such as pathogen colonization success.
Open Access
Association between type 2 diabetes and depressive symptoms after a 1-year follow-up in an older adult mediterranean population
(Springer, 2024) Baenas, I.; Camacho-Barcia, L.; Granero, R.; Razquin, Cristina; Corella, Dolores; Gómez-Martínez, Carlos; Castañer, Olga; Martínez, J. Alfredo; Alonso Gómez, Ángel M.; Wärnberg, Julia; Vioque, Jesús; Romaguera, Dora; López Miranda, José; Estruch, Ramón; Tinahones, Francisco J.; Lapetra, José; Serra-Majem, Lluis; Cano Ibáñez, Noemí; Tur, Josep A.; Martín-Sánchez, Vicente; Pintó, Xavier; Gaforio, José J.; Matía-Martín, Pilar; Vidal, Josep; Vázquez, Clotilde; Daimiel, Lidia; Ros, Emilio; Jiménez-Murcia, S.; Dalsgaard, S.; García-Arellano, Ana; Babio, Nancy; Sorli, Jose V.; Lassale, Camille; García de la Hera, Manuela; Gómez-Gracia, Enrique; Zulet, María Ángeles; Konieczna, J.; Martín Peláez, Sandra; Tojal-Sierra, Lucas; Basterra Gortari, Francisco Javier; Las Heras-Delgado, Sara de; Portolés, Olga; Muñoz-Pérez, M. Á.; Arenas-Larriva, A. P.; Compañ-Gabucio, Laura María; Eguaras, S.; Shyam, S.; Fitó, Montserrat; Baños, R. M.; Salas-Salvadó, Jordi; Fernández-Aranda, Fernando; Ciencias de la Salud; Osasun Zientziak
Objectives: To examine the cross-sectional association between baseline depressive symptoms and the presence of type 2 diabetes (T2D), and its association with glycated hemoglobin (HbA1c) and other metabolic variables, and the prospective association of depressive symptoms and HbA1c after 1 year of follow-up. Methods: n = 6224 Mediterranean older adults with overweight/obesity and metabolic syndrome (48% females, mean age 64.9 ± 4.9 years) were evaluated in the framework of the PREDIMED-Plus study cohort. Depressive symptoms were assessed using the Beck Depression Inventory-II and HbA1c was used to measure metabolic control. Results: The presence of T2D increased the likelihood of higher levels of depressive symptoms (χ2 = 15.84, p = 0.001). Polynomial contrast revealed a positive linear relationship (χ2 = 13.49, p = 0.001), the higher the depressive symptoms levels, the higher the prevalence of T2D. Longitudinal analyses showed that the higher baseline depressive symptoms levels, the higher the likelihood of being within the HbA1c ≥ 7% at 1-year level (Wald-χ2 = 24.06, df = 3, p < .001, for the full adjusted model). Additionally, depressive levels at baseline and duration of T2D predicted higher HbA1c and body mass index, and lower physical activity and adherence to Mediterranean Diet at 1 year of follow-up. Conclusions: This study supports an association between T2D and the severity of depressive symptoms, suggesting a worse metabolic control from mild severity levels in the short–medium term, influenced by lifestyle habits related to diabetes care. Screening for depressive symptoms and a multidisciplinary integrative therapeutic approach should be ensured in patients with T2D.
Open Access
Augmented reality for intramuscular injection training: a cluster randomized controlled trial
(Elsevier, 2025-07-01) Soto Ruiz, María Nelia; Escalada Hernández, Paula; Bujanda Sainz de Murieta, Arantxa; Ballesteros Egüés, Tomás; Larráyoz Jiménez, Ana; San Martín Rodríguez, Leticia; Ciencias de la Salud; Osasun Zientziak; Institute of Smart Cities - ISC
Background: The acquisition of clinical skills, such as intramuscular injection, is crucial in nursing education, traditionally taught through theory and practice. Recent studies suggest that augmented reality (AR) enhances students' learning. Aim: To evaluate the effect of an augmented reality application (ARSim2care) for training intramuscular injections technique among undergraduate nursing students. Methods: A cluster randomized controlled trial was conducted. A total of 72 nursing students participated in the study (32 in the intervention group and 40 in the control group). Sociodemographic variables and dependent variables such as knowledge, skills, satisfaction and self-confidence with learning were measured. Results: The groups showed statistically significant differences in age. Knowledge acquisition in the intervention group was 0.56 points higher, this difference was statistically significant. No significant differences were found in technical skills, satisfaction and self-confidence although both groups showed positive results. Conclusions: The ARSim2care application enhanced nursing students' theoretical knowledge of intramuscular injections, although no significant improvements in technical skills were observed. Augmented reality shows potential as an educational tool; however, further research is required to evaluate its long-term effectiveness.
Open Access
Biofilm morphology and antibiotic susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) on poly-D,L-lactide-co-poly(ethylene glycol) (PDLLA-PEG) coated titanium
(Elsevier, 2024-10-05) Turner, Adam Benedict; Zermeño-Pérez, David; Mysior, Margaritha M.; Giraldo-Osorno, Paula Milena; García Martínez, Begoña; O'Gorman, Elizabeth; Oubihi, Shafik; Simpson, Jeremy C.; Lasa Uzcudun, Íñigo; Ó'Cróinín, Tadhg; Trobos, Margarita; Ciencias de la Salud; Osasun Zientziak
Biodegradable polymeric coatings are being explored as a preventive strategy for orthopaedic device-related infection. In this study, titanium surfaces (Ti) were coated with poly-D,L-lactide (PDLLA, (P)), polyethylene-glycol poly-D,L-lactide (PEGylated-PDLLA, (PP20)), or multi-layered PEGylated-PDLLA (M), with or without 1 % silver sulfadiazine. The aim was to evaluate their cytocompatibility, resistance to Staphylococcus aureus biofilm formation, and their potential to enhance the susceptibility of any biofilm formed to antibiotics. Using automated high-content screening confocal microscopy, biofilm formation of a clinical methicillin-resistant Staphylococcus aureus (MRSA) isolate expressing GFP was quantified, along with isogenic mutants that were unable to form polysaccharidic or proteinaceous biofilm matrices. The results showed that PEGylated-PDLLA coatings exhibited significant antibiofilm properties, with M showing the highest effect. This inhibitory effect was stronger in S. aureus biofilms with a matrix composed of proteins compared to those with an exopolysaccharide (PIA) biofilm matrix. Our data suggest that the antibiofilm effect may have been due to (i) inhibition of the initial attachment through microbial surface components recognising adhesive matrix molecules (MSCRAMMs), since PEG reduces protein surface adsorption via surface hydration layer and steric repulsion; and (ii) mechanical disaggregation and dispersal of microcolonies due to the bioresorbable/degradable nature of the polymers, which undergo hydration and hydrolysis over time. The disruption of biofilm morphology by the PDLLA-PEG co-polymers increased S. aureus susceptibility to antibiotics like rifampicin and fusidic acid. Adding 1 % AgSD provided additional early bactericidal effects on both biofilm and planktonic S. aureus. Additionally, the coatings were cytocompatible with immune cells, indicating their potential to enhance bacterial clearance and reduce bacterial colonisation of titanium-based orthopaedic biomaterials.
Open Access
Biofilm properties in relation to treatment outcome in patients with first-time periprosthetic hip or knee joint infection
(Elsevier, 2021) Malchau, Karin Svensson; Tillander, Jonatan; Zaborowska, Magdalena; Hoffman, Maria; Lasa Uzcudun, Íñigo; Thomsen, Peter; Malchau, Henrik; Rolfson, Ola; Trobos, Margarita; Ciencias de la Salud; Osasun Zientziak
Background: periprosthetic joint infections (PJI) are challenging complications following arthroplasty. Staphylococci are a frequent cause of PJI and known biofilm producers. Biofilm formation decreases antimicrobial susceptibility, thereby challenging favourable treatment outcomes. The aims of this study were to characterize the biofilm abilities and antimicrobial susceptibilities of staphylococci causing first-time PJI and correlate them to clinical outcome (infection resolution and recurrence). Methods: reoperations for PJI of the hip or knee between 1st January 2012 to 30th June 2015 performed at the Sahlgrenska University Hospital were identified in a local database. Medical records were reviewed and clinical parameters recorded for patients whose intraoperative bacterial isolates had been stored at the clinical laboratory. Staphylococcal strains isolated from reoperations due to first-time PJI were characterised by their ability to form biofilms using the microtiter plate test. Antimicrobial susceptibility of the strains was determined by minimum inhibitory concentration (MIC) when grown planktonically, and by minimum biofilm eradication concentration (MBEC) when grown as biofilms. MBEC determination was conducted using the Calgary biofilm device (CBD) and a custom-made antimicrobial susceptibility plate containing eight clinically relevant antimicrobial agents. Results: the study group included 49 patients (70 bacterial strains) from first-time PJI, whereof 24 (49%) patients had recurrent infection. Strong biofilm production was significantly associated with recurrent infection. Patients infected with strong biofilm producers had a five-fold increased risk for recurrent infection. Strains grown as biofilms were over 8000 times more resistant to antimicrobial agents compared to planktonic cultures. Biofilms were more susceptible to rifampicin compared to other antimicrobials in the assay. Increased biofilm susceptibility (MBEC > MIC) was observed for the majority of the bacterial strains and antimicrobial agents. Conclusions: Strong biofilm production was significantly associated with increased antimicrobial resistance and PJI recurrence. This underscores the importance of determining biofilm production and susceptibility as part of routine diagnostics in PJI. Strong staphylococcal biofilm production may have implications on therapeutic choices and suggest more extensive surgery. Furthermore, despite the increased biofilm resistance to rifampicin, results from this study support its use in staphylococcal PJI. The Translational Potential of this Article: Like for many biomaterial-associated infections, staphylococci are a common cause of PJI. Their ability to adhere to surfaces and produce biofilms on medical devices is proposed to play a role. However, clinical studies where biofilm properties are directly linked to patient outcome are scarce. This study demonstrates that the majority of staphylococci isolated from first-time PJI were biofilm producers with increased antimicrobial resistance. Patients suffering an infection caused by a staphylococcal strain with strong biofilm production ability had a five-fold greater risk of recurrent infection. This novel finding suggests the importance of evaluating biofilm production as a diagnostic procedure for the guidance of treatment decisions in PJI.
Open Access
The body mass index increases the genetic risk scores' ability to predict risk of hepatic damage in European adolescents: the HELENA study
(Wiley, 2023) Seral-Cortes, Miguel; Sabroso-Lasa, Sergio; González Gross, Marcela; Quesada-González, Carlos; Stehle, Peter; Gottrand, Frédéric; Marcos, Ascensión; Diaz, Ligia Esperanza; Manios, Yannis; Androutsos, Odysseas; Widhalm, Kurt; Molnár, Dénes; Huybrechts, Inge; Muntaner, Manon; Meirhaeghe, Aline; Salazar-Tortosa, Diego; Ruiz, Jonatan R.; Esteban, Luis Mariano; Labayen Goñi, Idoia; Moreno, Luis A.; Ciencias de la Salud; Osasun Zientziak
Background: Hepatic disorders are often complex and multifactorial, modulated by genetic and environmental determinants. During the last years, the hepatic disease has been progressively established from early stages in life. The use of genetic risk scores (GRS) to predict the genetic susceptibility to a particular phenotype among youth has gained interest in recent years. Moreover, the alanine aminotransferase (ALT) blood biomarker is often considered as hepatic screening tool, in combination with imaging techniques. The aim of the present study was to develop an ALT-specific GRS to help in the evaluation of hepatic damage risk in European adolescents. Methods: A total of 972 adolescents (51.3% females), aged 12.5¿17.5 years, from the Healthy Lifestyle in Europe by Nutrition in Adolescence study were included in the analyses. The sample incorporated adolescents in all body mass index (BMI) categories and was divided considering healthy/unhealthy ALT levels, using sex-specific cut-off points. From 1212 a priori ALT-related single nucleotide polymorphisms (SNPs) extracted from candidate gene selection, a first screening of 234 SNPs univariately associated was established, selecting seven significant SNPs (p <.05) in the multivariate model. An unweighted GRS (uGRS) was developed by summing the number of reference alleles, and a weighted GRS (wGRS), by multiplying each allele to its estimated coefficient. Results: The uGRS and wGRS were significantly associated with ALT (p <.001). The area under curve was obtained integrating BMI as clinical factor, improving the predictive ability for uGRS (.7039) and wGRS (.7035), using 10-fold internal cross-validation. Conclusions: Considering BMI status, both GRSs could contribute as complementary tools to help in the early diagnosis of hepatic damage risk in European adolescents.
Open Access
Breakfast energy intake and dietary quality and trajectories of cardiometabolic risk factors in older adults
(Elsevier, 2024-11-05) Pérez-Vega, Karla-Alejandra; Lassale, Camille; Zomeño, María Dolores; Castañer, Olga; Salas-Salvadó, Jordi; Basterra Gortari, Francisco Javier; Corella, Dolores; Estruch, Ramón; Ros, Emilio; Tinahones, Francisco J.; Blanchart, Gemma; Malcampo, Mireia; Muñoz-Aguayo, Daniel; Schröder, Helmut; Fitó, Montserrat; Hernáez, Álvaro; Ciencias de la Salud; Osasun Zientziak
Objectives: Not skipping breakfast is associated with a better overall diet quality and lower cardiometabolic risk. However, the impact of calorie intake and dietary quality of breakfast on cardiovascular health remains unexplored. We aimed to study the associations between breakfast energy intake and quality and time trajectories of cardiometabolic traits in high cardiovascular risk participants. Design: Prospective observational exploratory study with repeated measurements. Setting: Spanish older adults. Participants: 383 participants aged 55-75 with metabolic syndrome from PREDIMED-Plus, a clinical trial involving a weight-loss lifestyle intervention based on the Mediterranean diet. Measurements: Participants were followed for 36 months. Longitudinal averages of breakfast energy intake and quality were calculated. Three categories were defined for energy intake: 20-30% (reference), <20% (low), and >30% (high). Quality was estimated using the Meal Balance Index; categories were above (reference) or below the median score (low). Natural cubic spline mixed effects regressions described trajectories of cardiometabolic indicators (anthropometry, blood pressure, lipids, glucose, glycated hemoglobin, and kidney function) in breakfast groups. Inter-group differences in predicted values were estimated by linear regressions. Analyses were adjusted for age, sex, PREDIMED-Plus intervention group, education, smoking, physical activity, and total daily kilocalorie intake. Lipid profile analyses were further adjusted for baseline hypercholesterolemia, blood pressure analyses for baseline hypertension, and glucose/glycated hemoglobin analyses for baseline diabetes. Breakfast energy intake analyses were adjusted for breakfast quality, and vice versa. Results: At 36 months, compared to the reference, low- or high-energy breakfasts were associated with differences in body mass index (low: 0.61 kg/m² [95% confidence interval: 0.19; 1.02]; high: 1.18 kg/m² [0.71; 1.65]), waist circumference (low: 2.22 cm [0.96; 3.48]; high: 4.57 cm [3.13; 6.01]), triglycerides (low: 13.8 mg/dL [10.8; 16.8]; high: 28.1 cm [24.7; 31.6]), and HDL cholesterol (low: -2.13 mg/dL [-3.41; -0.85]; high: -4.56 mg/dL [-6.04; -3.09]). At 36 months, low-quality breakfast was associated with higher waist circumference (1.50 cm [0.53; 2.46]), and triglycerides (5.81 mg/dL [3.50; 8.12]) and less HDL cholesterol (-1.66 mg/dL [-2.63; -0.69]) and estimated glomerular filtration rate (-1.22 mL/min/1.73m2 [-2.02; -0.41]). Conclusions: Low- or high-energy and low-quality breakfasts were associated with higher adiposity and triglycerides, and lower HDL cholesterol in high-risk older adults. Low-quality breakfasts were also linked to poorer kidney function.
Open Access
Development of a genetic risk score to predict the risk of hypertension in european adolescents from the HELENA study
(Frontiers Media, 2023) Pérez-Gimeno, Gloria; Seral-Cortes, Miguel; Sabroso-Lasa, Sergio; Esteban, Luis Mariano; Lurbe, Empar; Béghin, Laurent; Gottrand, Frédéric; Meirhaeghe, Aline; Muntaner, Manon; Kafatos, Antonios; Molnár, Dénes; Leclercq, Catherine; Widhalm, Kurt; Kersting, Mathilde; Nova, Esther; Salazar-Tortosa, Diego; González Gross, Marcela; Breidenassel, Christina; Sinningen, Kathrin; Ruyter, Thaïs de; Labayen Goñi, Idoia; Rupérez, Azahara I.; Bueno-Lozano, Gloria; Moreno, Luis A.; Ciencias de la Salud; Osasun Zientziak; Institute on Innovation and Sustainable Development in Food Chain - ISFOOD
Introduction: From genome wide association study (GWAS) a large number of single nucleotide polymorphisms (SNPs) have previously been associated with blood pressure (BP) levels. A combination of SNPs, forming a genetic risk score (GRS) could be considered as a useful genetic tool to identify individuals at risk of developing hypertension from early stages in life. Therefore, the aim of our study was to build a GRS being able to predict the genetic predisposition to hypertension (HTN) in European adolescents. Methods: Data were extracted from the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) cross-sectional study. A total of 869 adolescents (53% female), aged 12.5–17.5, with complete genetic and BP information were included. The sample was divided into altered (≥130 mmHg for systolic and/or ≥80 mmHg for diastolic) or normal BP. Based on the literature, a total of 1.534 SNPs from 57 candidate genes related with BP were selected from the HELENA GWAS database. Results: From 1,534 SNPs available, An initial screening of SNPs univariately associated with HTN (p < 0.10) was established, to finally obtain a number of 16 SNPs significantly associated with HTN (p < 0.05) in the multivariate model. The unweighted GRS (uGRS) and weighted GRS (wGRS) were estimated. To validate the GRSs, the area under the curve (AUC) was explored using ten-fold internal cross-validation for uGRS (0.802) and wGRS (0.777). Further covariates of interest were added to the analyses, obtaining a higher predictive ability (AUC values of uGRS: 0.879; wGRS: 0.881 for BMI z-score). Furthermore, the differences between AUCs obtained with and without the addition of covariates were statistically significant (p < 0.05). Conclusions: Both GRSs, the uGRS and wGRS, could be useful to evaluate the predisposition to hypertension in European adolescents.
Open Access
Differences in specific abdominal fat depots between metabolically healthy and unhealthy children with overweight/obesity: the role of cardiorespiratory fitness
(Wiley, 2023) Cadenas-Sánchez, Cristina; Medrano Echeverría, María; Villanueva Larre, Arantxa; Cabeza Laguna, Rafael; Idoate, Fernando; Osés Recalde, Maddi; Rodríguez Vigil, Beatriz; Álvarez de Eulate, Natalia; Alberdi Aldasoro, Nerea; Ortega, Francisco B.; Labayen Goñi, Idoia; Ciencias de la Salud; Ingeniería Eléctrica, Electrónica y de Comunicación; Institute on Innovation and Sustainable Development in Food Chain - ISFOOD; Institute of Smart Cities - ISC; Osasun Zientziak; Ingeniaritza Elektrikoa, Elektronikoaren eta Telekomunikazio Ingeniaritzaren
Objectives: Fat depots localization has a critical role in the metabolic health status of adults. Nevertheless, whether that is also the case in children remains under- studied. Therefore, the aims of this study were: (i) to examine the differ-ences between metabolically healthy (MHO) and unhealthy (MUO) overweight/obesity phenotypes on specific abdominal fat depots, and (ii) to further explore whether cardiorespiratory fitness plays a major role in the differences between metabolic phenotypes among children with overweight/obesity. Methods: A total of 114 children with overweight/obesity (10.6 ±1.1 years, 62 girls) were included. Children were classified as MHO (n=68) or MUO. visceral (VAT), abdominal subcutaneous (ASAT), intermuscular abdominal (IMAAT), psoas, hepatic, pancreatic, and lumbar bone marrow adipose tissues were measured by magnetic resonance imaging. Cardiorespiratory fitness was assessed using the 20 m shuttle run test. Results: MHO children had lower VAT and ASAT contents and psoas fat fraction compared to MUO children (difference =12.4%– 25.8%, all p<0.035). MUO- unfit had more VAT and ASAT content than those MUO- fit and MHO- fit (difference =34.8%– 45.3%, all p<0.044). MUO- unfit shows also greater IMAAT fat fraction than those MUO- fit and MHO- fit peers (difference =16.4%– 13.9% respectively, all p≤0.001). In addition, MHO- unfit presented higher IMAAT fat fraction than MHO- fit (difference =13.4%, p<0.001). MUO- unfit presented higher psoas fat fraction than MHO- fit (difference =29.1%, p=0.008). Conclusions: VAT together with ASAT and psoas fat fraction, were lower in MHO than in MUO children. Further, we also observed that being fit, regardless of metabolic phenotype, has a protective role over the specific abdominal fat depots among children with overweight/obesity.
Open Access
Editorial: Evidence-based exercise enhances healthy aging
(Elsevier, 2024-12-31) Izquierdo Redín, Mikel; Fiatarone Singh, Maria; Ciencias de la Salud; Osasun Zientziak
As the global population continues to age, an urgent question arises: how can we improve the quality of life for older adults while reducing the burden of age-related diseases and disabilities? A growing body of evidence suggests that evidence-based exercise, used as both preventive and therapeutic medicine, may hold the key to extending healthy As the global population continues to age, an urgent question arises: howcanweimprovethequalityoflifeforolderadultswhilereducingthe burden of age-related diseases and disabilities? A growing body of evidence suggests that evidence-based exercise, used as both preventive and therapeutic medicine, may hold the key to extending healthy longevity, preventing chronic conditions, and preserving physical and cognitive function. The “Global consensus on optimal exercise recommendations for enhancing healthy longevity in older adults (ICFSR)” emphasizes the importance of integrating tailored exercise regimens into geriatric care, positioning exercise not only as preventive medicine but also as a therapeutic cornerstone in managing age-related decline. The updated consensus document introduces several advancements that distinguish it from the previous consensus published a few years ago. It emphasizes more personalized, evidence-based exercise prescriptions that align with individual health profiles and conditions, moving beyond genericactivityguidelines.
Open Access
Effects of an exercise program on cardiometabolic and mental health in children with overweight or obesity: a secondary analysis of a randomized clinical trial
(American Medical Association, 2023) Migueles, Jairo H.; Cadenas-Sánchez, Cristina; Lubans, David R.; Henriksson, Pontus; Torres-López, Lucía V.; Rodríguez Ayllon, María; Plaza Florido, Abel; Gil Cosano, José J.; Henriksson, Hanna; Escolano Margarit, María Victoria; Gómez Vida, José; Maldonado, José; Löf, Marie; Ruiz, Jonatan R.; Labayen Goñi, Idoia; Ortega, Francisco B.; Ciencias de la Salud; Osasun Zientziak; Institute on Innovation and Sustainable Development in Food Chain - ISFOOD
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 by approximately 0.38 (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. Trial Registration: ClinicalTrials.gov Identifier: NCT02295072.
Open Access
Effects of combined aerobic and resistance training on the inflammatory profile of children with overweight/obesity: a randomized clinical trial
(Wiley, 2024-07-31) Gil Cosano, José J.; Plaza Florido, Abel; Gracia-Marco, Luis; Migueles, Jairo H.; Cadenas-Sánchez, Cristina; Olvera-Rojas, Marcos; Ubago Guisado, Esther; Labayen Goñi, Idoia; Lucía, Alejandro; Ortega, Francisco B.; Ciencias de la Salud; Osasun Zientziak; Institute on Innovation and Sustainable Development in Food Chain - ISFOOD
Background: we assessed the effects of a 20-week combined (aerobic and resistance) exercise training programme on the inflammatory profile of prepubertal children with overweight or obesity. Methods: totally 109 participants (10.1±1.1 years, 41% girls) were randomly allocated to an exercise or control group. Adiponectin, C-reactive protein, epidermal growth factor, insulin-like growth factor-1, interleukin (IL)-1β, IL-6, leptin, tumour necrosis factor-α and vascular endothelial growth factor A (VEGFA) were analysed in plasma. Total white blood cell (WBC) count and immune subpopulations (eosinophils, basophils, neutrophils, lymphocytes and monocytes) were also determined. Results: no intervention effect was found for any of the analysed biomarkers (all p≥0.05). We observed a significant sex by intervention interaction for IL-1β (p= 0.03). When stratifying the sample by sex, the exercise programme induced a significant effect on IL-1β levels (mean Z-score difference, 0.66 [95% confidence interval 0.32-1.01]) in girls, but not in boys. A lower number of girls in the exercise group showed a meaningful reduction in IL-1β (i.e., ≥0.2 standard deviations) than in the control group (15% vs. 85%, p=0.01). Conclusions: this exercise programme failed to improve the inflammatory profile in prepubertal children with overweight/obesity. Future studies should explore the effect of longer exercise interventions and in combination with diet.
Open Access
Effects of different doses of high-speed resistance training on physical performance and quality of life in older women: a randomized controlled trial
(Dovepress, 2016) Ramírez Campillo, Rodrigo; Díaz, Daniela; Martínez Salazar, Cristian; Valdés Badilla, Pablo; Delgado Floody, Pedro; Méndez Rebolledo, Guillermo; Cañas Jamet, Rodrigo; Cristi Montero, Carlos; García Hermoso, Antonio; Celis Morales, Carlos; Moran, Jason; Buford, Thomas W.; Rodríguez Mañas, Leocadio; Alonso Martínez, Alicia; Izquierdo Redín, Mikel; Ciencias de la Salud; Osasun Zientziak
Objective: This study aimed to compare the effects of two frequencies of high-speed resistance training (HSRT) on physical performance and quality of life of older women. Methods: A total of 24 older women participated in a 12-week HSRT program composed of either two or three sessions/week (equated for volume and intensity). Women were randomized into three arms: a control group (CG, n=8), a resistance training group performing two sessions/week (RT2, n=8), and a resistance training group performing three sessions/week (RT3, n=8). The training program for both experimental groups included exercises that required high-speed concentric muscle actions. Results: No baseline differences were observed among groups. Compared with the CG, both training groups showed similar small to moderate improvements (P,0.05) in muscle strength, power, functional performance, balance, and quality of life. Conclusion: These results suggest that equated for volume and intensity, two and three training sessions/week of HSRT are equally effective for improving physical performance and quality of life of older women.
Open Access
Epigenetic clock indicates accelerated aging in glial cells of progressive multiple sclerosis patients
(Frontiers Media, 2022) Kular, Lara; Klose, Dennis; Urdánoz Casado, Amaya; Ewing, Ewoud; Planell, Nuria; Gómez-Cabrero, David; Needhamsen, Maria; Jagodic, Maja; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua
Background: Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease of the central nervous system (CNS) characterized by irreversible disability at later progressive stages. A growing body of evidence suggests that disease progression depends on age and inflammation within the CNS. We aimed to investigate epigenetic aging in bulk brain tissue and sorted nuclei from MS patients using DNA methylation-based epigenetic clocks. Methods: We applied Horvath’s multi-tissue and Shireby’s brain-specific Cortical clock on bulk brain tissue (n = 46), sorted neuronal (n = 54), and glial nuclei (n = 66) from post-mortem brain tissue of progressive MS patients and controls. Results: We found a significant increase in age acceleration residuals, corresponding to 3.6 years, in glial cells of MS patients compared to controls (P = 0.0024) using the Cortical clock, which held after adjustment for covariates (Padj = 0.0263). The 4.8-year age acceleration found in MS neurons (P = 0.0054) did not withstand adjustment for covariates and no significant difference in age acceleration residuals was observed in bulk brain tissue between MS patients and controls. Conclusion: While the findings warrant replication in larger cohorts, our study suggests that glial cells of progressive MS patients exhibit accelerated biological aging.
Open Access
Equivalency of four research-grade movement sensors to assess movement behaviors and its implications for population surveillance
(Springer Nature, 2022) Migueles, Jairo H.; Molina García, Pablo; Torres-López, Lucía V.; Cadenas-Sánchez, Cristina; Rowlands, Alex V.; Ebner-Priemer, Ulrich W.; Koch, Elena D.; Reif, Andreas; Ortega, Francisco B.; Osasun Zientziak; Institute on Innovation and Sustainable Development in Food Chain - ISFOOD; Ciencias de la Salud
The benefits of physical activity (PA) and sleep for health, accurate and objective population-based surveillance is important. Monitor-based surveillance has potential, but the main challenge is the need for replicable outcomes from different monitors. This study investigated the agreement of movement behavior outcomes assessed with four research-grade activity monitors (i.e., Movisens Move4, ActiGraph GT3X+, GENEActiv, and Axivity AX3) in adults. Twenty-three participants wore four monitors on the non-dominant wrist simultaneously for seven days. Open-source software (GGIR) was used to estimate the daily time in sedentary, light, moderate-to-vigorous PA (MVPA), and sleep (movement behaviors). The prevalence of participants meeting the PA and sleep recommendations were calculated from each monitor's data. Outcomes were deemed equivalent between monitors if the absolute standardized difference and its 95% confidence intervals (CI95%) fell within ± 0.2 standard deviations (SD) of the mean of the differences. The participants were mostly men (n = 14, 61%) and aged 36 (SD = 14) years. Pairwise confusion matrices showed that 83-87% of the daily time was equally classified into the movement categories by the different pairs of monitors. The between-monitor difference in MVPA ranged from 1 (CI95%:- 6, 7) to 8 (CI95%: 1, 15) min/day. Most of the PA and sleep metrics could be considered equivalent. The prevalence of participants meeting the PA and the sleep guidelines was 100% consistent across monitors (22 and 5 participants out of the 23, respectively). Our findings indicate that the various research-grade activity monitors investigated show high inter-instrument reliability with respect to sedentary, PA and sleep-related estimates when their raw data are processed in an identical manner. These findings may have important implications for advancement towards monitor-based PA and sleep surveillance systems.
Open Access
Fitness, physical activity and academic achievement in overweight/obese children
(Taylor & Francis, 2020) Cadenas-Sánchez, Cristina; Migueles, Jairo H.; Esteban Cornejo, Irene; Mora González, José; Henriksson, Pontus; Rodríguez Ayllon, María; Molina García, Pablo; Löf, Marie; Labayen Goñi, Idoia; Hillman, Charles H.; Catena, Andrés; Ortega, Francisco B.; Ciencias de la Salud; Osasun Zientziak
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 < 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 ≤ 0.01). Speed-agility was associated with some language-related skills (ß = 0.325–0.393, all p ≤ 0.01). The laboratory-based muscular strength also showed an association with mathematics skills (ß = 0.251–0.306, all p ≤ 0.01). Physical activity did not show significant association with academic achievement (p > 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.
Open Access
Fluorescent molecular beacons mimicking RNA secondary structures to study RNA chaperone activity
(Humana Press, 2020) Menéndez Gil, Pilar; Caballero Sánchez, Carlos; Solano Goñi, Cristina; Toledo Arana, Alejandro; Ciencias de la Salud; Osasun Zientziak; Universidad Pública de Navarra / Nafarroako Unibertsitate Publikoa
Molecular beacons (MBs) are oligonucleotide probes with a hairpin-like structure that are typically labelled at the 5′ and 3′ ends with a fluorophore and a quencher dye, respectively. The conformation of the MB acts as a switch for fluorescence emission. When the fluorophore is in close proximity to the quencher, fluorescence emission cannot be detected, meaning that the switch is in an OFF state. However, if the MB structure is modified, separating the fluorophore from the quencher, the switch turns ON allowing fluorescence emission. This property has been extensively used for a wide variety of applications including real-time PCR reactions, study of protein-DNA interactions, and identification of conformational changes in RNA structures. Here, we describe a protocol based on the MB technology to measure the RNA unfolding capacities of the CspA RNA chaperone from Staphylococcus aureus. This method, with slight variations, may also be applied for testing the activity of other RNA chaperones, RNA helicases, or ribonucleases.
Open Access
A food web approach reveals the vulnerability of biocontrol services by birds and bats to landscape modification at regional scale
(Nature Research, 2021) Herrera, José M.; Silva, Bruno; Jiménez Navarro, Gerardo; Barreiro, Silvia; Melguizo Ruiz, Nereida; Moreira, Francisco; Vasconcelos, Sasha; Morgado, Rui; Rodríguez Pérez, Javier; Ciencias de la Salud; Osasun Zientziak
Pest control services provided by naturally occurring species (the so-called biocontrol services) are widely recognized to provide key incentives for biodiversity conservation. This is particularly relevant for vertebrate-mediated biocontrol services as many vertebrate species are of conservation concern, with most of their decline associated to landscape modification for agricultural purposes. Yet, we still lack rigorous approaches evaluating landscape-level correlates of biocontrol potential by vertebrates over broad spatial extents to better inform land-use and management decisions. We performed a spatially-explicit interaction-based assessment of potential biocontrol services in Portugal, using 1853 pairwise trophic interactions between 78 flying vertebrate species (birds and bats) and 53 insect pests associated to two widespread and economically valuable crops in the Euro-Mediterranean region, olive groves (Olea europaea subsp. europaea) and vineyards (Vitis vinifera subsp. vinifera). The study area was framed using 1004 square cells, each 10 × 10 km in size. Potential biocontrol services were determined at all those 10 × 10 km grid-cells in which each crop was present as the proportion of the realized out of all potential pairwise interactions between vertebrates and pests. Landscape correlates of biocontrol potential were also explored. Our work suggests that both birds and bats can effectively provide biocontrol services in olive groves and vineyards as they prey many insect pest species associated to both crops. Moreover, it demonstrates that these potential services are impacted by landscape-scale features and that this impact is consistent when evaluated over broad spatial extents. Thus, biocontrol potential by vertebrates significantly increases with increasing amount of natural area, while decreases with increasing area devoted to target crops, particularly olive groves. Overall, our study highlights the suitability of our interaction-based approach to perform spatially-explicit assessments of potential biocontrol services by vertebrates at local spatial scales and suggest its utility for integrating biodiversity and ecosystem services in conservation planning over broad spatial extents.