Dietary Patterns and Their Association with Body Composition and Cardiometabolic Markers in Children and Adolescents: Genobox Cohort

Diet is a key factor for obesity development; however, limited data are available on dietary cluster analysis in children with obesity. We aimed to assess the associations between dietary patterns and obesity and several cardiometabolic markers. Anthropometry, bioelectrical impedance, blood pressure and plasma biomarkers of oxidative stress, inflammation and endothelial damage were determined in 674 Caucasian children, aged 5–16, with normal or excess weight. Using a food frequency questionnaire and cluster analysis, two consistent dietary patterns were shown, labeled as health conscious (HC) and sweet and processed (SP). The HC pattern included a greater proportion of participants with overweight/obesity than the SP cluster (80.1% vs. 63.8%). However, children with obesity within the HC cluster, showed less abdominal fat, through waist to hip (0.93 vs. 0.94) and waist to height (0.61 vs. 0.63) indexes (p < 0.01). Univariate general models showed several additional di erences in cardiometabolic risk biomarkers in the global and stratified analyses, with a healthier profile being observed mainly in the HC cluster. However, multivariate models questioned these findings and pointed out the need for further studies in this field. Anyhow, our findings support the benefits of a healthy diet and highlight the importance of dietary patterns in the cardiometabolic risk assessment of children with overweight/obesity, beyond weight control.Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica (I+D+I), Instituto de Salud Carlos III-Health Research Funding (FONDOS FEDER) PI05/1968 PI11/01425 PI11/02042 PI11/02059 PI16/01301 PI16/01205 PI1600871CIBEROBN Network CB15/00131 CB15/00043Juan de la Cierva-Formacion from the Spanish Government FJCI-2017-34967 FJCI-2014-19795Vice-Rectorate of Research and Transfer of the University of Granada, Spai

Longitudinal associations between cardiovascular biomarkers and metabolic syndrome during puberty: the PUBMEP study

Puberty has been described as a life stage of considerable metabolic risk specially for those with obesity. The low-grade systemic inflammatory status associated with obesity could be one of the connections with metabolic syndrome (MetS). Thus, we aimed to assess the relationship between inflammatory and cardiovascular biomarkers and the development of MetS during puberty. Seventy-five children from the PUBMEP study (33 females), aged 4–18 years, were included. Cardiovascular and inflammatory biomarkers were measured in the prepubertal and pubertal stage, including high-sensitivity C-reactive protein (CRP), leptin, tumor necrosis factor-alpha (TNFα), interleukin 8 (IL8), monocyte chemoattractant protein 1 (MCP-1), total plasminogen activator inhibitor-1 (tPAI), resistin, adiponectin, myeloperoxidase (MPO), and soluble intercellular adhesion molecule-1 (sICAM-1). MetS was diagnosed at each measurement point. Mixed-effects and logistic regressions were performed. Those children with MetS in puberty presented higher prepubertal values of several cardiometabolic biomarkers in comparison to those without MetS (z-score body mass index (zBMI), waist circumference, insulin, HOMA-IR, leptin, and tPAI (p < 0.05)). For prepubertal children with obesity, the odds of developing MetS in puberty were significantly higher in those having high zBMI (OR = 4.27; CI: 1.39–22.59) or high concentrations of tPAI (OR = 1.19; CI: 1.06–1.43). Conclusion: Those with obesity with higher prepubertal tPAI plasma levels had 19% higher odds of having MetS at puberty highlighting the existence of association between MetS, obesity, and inflammation already in puberty. Thus, assessing cardiometabolic and inflammatory status in children with obesity already at prepuberty is key to avoiding future comorbidities.CRUE-CSIC agreementSpringer NaturePlan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica (I + D + I), Instituto de Salud Carlos III-Health Research PI11/01425 PI11/02042 PI11/02059 PI16/01301 PI16/01205 PI16/00871 PI20/00563CIBEROBN Network CB15/00131 CB15/00043Redes tematicas de investigacion cooperativa RETIC Red SAMID RD12/0026/001

Nutrición, inflamación y riesgo metabólico en niños y adolescentes europeos

El estudio de los factores de riesgo cardio-metabólicos es importante para intentar prevenir enfermedades futuras. Estos factores de riesgo aparecen cada vez a edades más tempranas como en la adolescencia, o incluso en la infancia, y parecen estar asociados con algunos estilos de vida como la alimentación. Se ha observado que la la inflamación crónica de bajo grado se relaciona con factores de riesgo cardio-metabólicos. Por lo tanto, el estudio del estado inflamatorio en niños y adolescentes es necesario para evaluar esta relación desde sus orígenes y, de esta manera, poder entender sus mecanismos de aparición. Es por ello que el objetivo general de esta Tesis Doctoral es evaluar la relación entre la inflamación, valorada mediante una serie de marcadores inflamatorios, la ingesta y las alteraciones cardio-metabólicas asociadas con la obesidad en niños y adolescentes europeos. Esta memoria se ha realizado por compendio de publicaciones, incluyendo seis artículos.La presente Tesis Doctoral se ha llevado a cabo teniendo en cuenta los resultados de dos grandes estudios europeos: el estudio IDEFICS (Identification and Prevention of Dietary- and Lifestyle- induced Health Effects in Children and Infants) y el estudio HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence). En el estudio IDEFICS se obtuvo información de más de 16.000 niños, con edades comprendidas entre 2 y 9 años, procedentes de ocho países europeos (Italia, Estonia, Chipre, Bélgica, Suecia, Alemania, Hungría y España). La medida incial se realizó durante el curso 2007-2008. Estos niños fueron re-evaluados dos años después del incio del estudio. Se seleccionaron sujetos de este estudio para valorar la asociación entre la dieta y la proteína C-reactiva de alta sensibilidad (PCR-hs), como marcador de inflamación. En el primer artículo se valoró la asociación entre los ácidos grasos, medidos en sangre total, y la inflamación. Los ácidos grasos son componentes de la dieta que se relacionan con el estado inflamatorio, especialmente en el caso de los ácidos grasos de cadena larga. Se observó que los acidos grasos omega-6 (suma de omega 6 y ácido linoleico) se asociaron con valores bajos de PCR-hs, en chicos, y con valores altos de PCR-hs en chicas (ácido araquidónico, suma de omega 6 altamente insaturados y relación acido araquidónico/linoleico). En el segundo artículo se observó una asociación clara entre la frecuencia de consumo de algunos alimentos y la PCR-hs. Específicamente, la elevada frecuencia de consumo de vegetales se relacionaba inversamente con la inflamación mientras que otros tipos de alimentos, como las bebidas azucaradas o la mayonesa, se relacionaban directamente con la inflamación.En el tercer artículo, tres tipos de patrones dietéticos fueron identificados y mantenidos a lo largo del seguimiento: el patrón ”saludable”, el patrón de “proteína animal y carbohidratos refinados” y el patrón “dulces y alimentos procesados”. En el análisis transversal, realizado al final del seguimiento, se observó que aquellos niños incluidos en el patrón ”dulces y alimentos procesados” mostraban una mayor probabilidad de tener la PCR-hs elevada, en comparación con aquellos asignados a un patrón ”saludable”. De igual manera, se observó que aquellos incluidos en un patrón de “dulces y alimentos procesados” mantenido en el tiempo, es decir, desde la valoración inicial hasta la medida de seguimiento, mostraban mayor probabilidad de tener valores más elevados de la PCR-hs, en comparación con los incluidos en un patrón saludable en las dos valoraciones. En el estudio HELENA, realizado entre 2006 y 2007, se valoraron más de 3.000 adolescentes de 10 ciudades europeas: Atenas, Heraklion, Dortmund, Gante, Lille, Pecs, Roma, Estocolmo, Viena y Zaragoza. Las edades de los adolescentes participantes estaban entre 12,5 y 17,5 años. Con datos de este estudio, se valoraron las asociaciones entre el riesgo cardio-metabólico y la inflamación en la adolescencia. La American Heart Asociation (AHA) ha propuesto un índice de salud cardiovascular ideal (ISCI) que incluye cuatro comportamientos y tres factores saludables. Los criterios relacionados con los comportamientos son: no haber fumado, ser físicamente activo, tener un IMC normal y tener una alimentación saludable, mientras que los factores saludables incluidos son valores normales de: tensión arterial, colesterol total y glucosa. Mediante el uso de este índice se valoró la relación entre la salud cardiovascular y la inflamación, la cual fue medida mediante un índice inflamatorio y, a su vez, mediante los biomarcadores que componían el citado índice individualmente: PCR, el factor C3 y C4 del complemento, leptina y el recuento de glóbulos blancos. En este cuarto artículo, se observó que puntuaciones superiores del índice de salud cardiovascular se relacionaban inversamente con los valores del índice inflamatorio y, además, con algunos de sus componentes individualmente. En el quinto artículo, se observó que la composición corporal juega un papel importante en la relación entre la resistencia a la insulina y la inflamación, medida con varios marcadores inflamatorios. La asociación entre la resistencia a la insulina y el factor C3 del complemento fue especialmente relevante para aquellos adolescentes con mayores niveles de adiposidad. Finalmente, en el último artículo, se valoró la asociación entre la salud metabólica y varios marcadores inflamatorios seleccionados, teniendo en cuenta la presencia o no de sobrepeso/obesidad. La existencia de sobrepeso/obesidad y un estatus metabólico alterado se asocia con marcadores inflamatorios, siendo la PCR, C3 y C4 los marcadores más relacionados con esta condición. C3 y C4 se asociaron consistentemente con la salud cardio-metabólica.En resumen, los resultados de esta Tesis Doctoral confirman la existencia de una asociación entre alimentación y PCR-hs desde la infancia y, a su vez, que los marcadores de riesgo cardio-metabólico están presentes desde la adolescencia y se asocian con distintos marcadores inflamatorios, en esta etapa de la vida. Estos resultados ponen de manifiesto la importancia del desarrollo de estrategias de prevención precoz, teniendo en cuenta la promoción de estilos de vida saludables, para evitar el desarrollo de los factores de riesgo cardio-metabólico y la aparición de un estado inflamatorio crónico de bajo grado, asociado a los mismos.<br /

Prospective physical fitness status and development of cardiometabolic risk in children according to body fat and lifestyle behaviours: The IDEFICS study

Ministerio de Ciencia e Innovacion, Grant/Award Number: FJCI-2017-34967; Sixth Framework Programme, Grant/Award Number: 016181 FOODThis work was done as part of the IDEFICS study (www.idefics.eu). We gratefully acknowledge the financial support of the European Community within the Sixth RTD Framework Programme Contract No. 016181 (FOOD).Background Elevated cardiometabolic risk (CMR) is an important factor for cardiovascular diseases later in life while physical fitness seems to decrease CMR. Objective Thus, the aim of the present study is to assess the association between muscular fitness (MF) and cardiorespiratory fitness (CRF) on CMR in European children, both cross-sectional and longitudinally. Methods A total of 289 children (49.5% males) from eight European countries, aged 6 to 9, with longitudinal information on blood pressure, triglycerides, total cholesterol, HDL-cholesterol, homoeostasis model assessment, body mass index, data on fitness level, objectively measured physical activity (PA), diet quality, and total screen time were included. A CMR score was calculated and dichotomized. MF and CRF were also dichotomized. Cross-sectional and longitudinal multilevel logistic regressions adjusting for lifestyle behaviours were performed. Results Reaching a high level of MF during childhood as well as remaining in that level over-time were associated with an 82% and 62% lower probability of high CMR at follow-up, respectively. Also, children who became top CRF over time, showed a 77% lower probability (P < 0.05) of being in the highest CMR quartile at follow-up, independently of sociodemographic and lifestyle indicators. Conclusions A high MF at early childhood and during childhood reduces the odds of having CMR. Same occurs with the improvement of CRF during childhood. These findings highlight the importance of enhancing fitness to avoid CMR already in children.Instituto de Salud Carlos III Spanish Government European Commission FJCI-2017-34967European Commission 016181 FOO

Chiral Bronsted Acid-Catalyzed Enantioselective alpha-Amidoalkylation Reactions: A Joint Experimental and Predictive Study,

Enamides with a free NH group have been evaluated as nucleophiles in chiral Bronsted acid-catalyzed enantioselective alpha-amidoalkylation reactions of bicyclic hydroxylactams for the generation of quaternary stereocenters. A quantitative structure-reactivity relationship (QSRR) method has been developed to find a useful tool to rationalize the enantioselectivity in this and related processes and to orient the catalyst choice. This correlative perturbation theory (PT)-QSRR approach has been used to predict the effect of the structure of the substrate, nucleophile, and catalyst, as well as the experimental conditions, on the enantioselectivity. In this way, trends to improve the experimental results could be found without engaging in a long-term empirical investigation.Ministerio de Economia y Competitividad (CTQ2013-41229-P), IKERBASQUE foundation, Gobierno Vasco (IT-623-13) and Universidad del Pais Vasco/Euskal Herriko Unibertsitatea UPV/EHU are gratefully acknowledged for their financial support. Technical and human support provided by Servicios Generales de Investigacion SGIker (UPV/EHU, MINECO, GV/EJ, ERDF and ESF) is also acknowledged

The Vitamin D Decrease in Children with Obesity Is Associated with the Development of Insulin Resistance during Puberty: The PUBMEP Study

This work was supported by the Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I + D + I), Instituto de Salud Carlos III-Health Research Funding (FONDOS FEDER) (PI11/01425, PI11/02042, PI11/02059, PI16/01301, PI16/01205, PI16/00871 and PI20/00563); CIBEROBN Network (CB15/00131, CB15/00043); Redes temáticas de investigación cooperativa RETIC (Red SAMID RD12/0026/0015). The authors also acknowledge Instituto de Salud Carlos III for personal funding: Contratos i-PFIS: doctorados IIS-empresa en ciencias y tecnologías de la salud de la convocatoria 2017 de la Acción Estratégica en Salud 2013–2016 (IFI17/00048). E.M.G.-G. holds a Juan de la Cierva-Formación grant (FJCI-2017-34967) from the Ministerio de Ciencia e Innovación (Spanish Government). L.V.P. acknowledges financial support of the Visiting Professor Program from the Coordination for the Improvement of Higher Education Personnel (CAPES—Grant 88881.337237/2019-01), Brazil.Obesity and cardiometabolic risk have been associated with vitamin D levels even in children. The objective of the present study was to evaluate the association between insulin resistance (IR), cardiometabolic risk factors, and vitamin D in children from prepubertal to pubertal stages. A total of 76 children from the PUBMEP study, aged 4-12 years at baseline, were included. Children were evaluated in prepubertal and pubertal stages. Anthropometric measurements and selected cardiometabolic risk biomarkers, such as plasma glucose, blood lipids, insulin, adiponectin, leptin, and blood pressure, and serum 25-hydroxyvitamin D (25(OH)D) were determined. Children were categorized by obesity degree and IR status combined before and after puberty. Paired t-test and multivariate linear regression analyses were conducted. During puberty, the increase in triacylglycerols, insulin, and HOMA-IR and the decrease in QUICKI were significantly associated with the reduction in 25(OH)D (B = -0.274, p = 0.032; B = -0.219, p = 0.019; B = -0.250, p = 0.013; B = 1.574, p = 0.013, respectively) after adjustment by BMI-z, sex, and pubertal stage. Otherwise, prepubertal non-IR children with overweight/obesity that became IR during puberty showed a significant decrease in 25(OH)D and HDL-c, and an increase in waist circumference and triacylglycerol concentrations (p < 0.05 for all) over time. These results suggest that changes in IR seem to be associated with an effect on 25(OH)D levels during puberty, especially in children with overweight.Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I + D + I)Instituto de Salud Carlos III-Health Research Funding (FONDOS FEDER) (PI11/01425, PI11/02042, PI11/02059, PI16/01301, PI16/01205, PI16/00871 and PI20/00563)CIBEROBN Network (CB15/00131, CB15/00043)Redes temáticas de investigación cooperativa RETIC (Red SAMID RD12/0026/0015)Instituto de Salud Carlos III (IFI17/00048)Juan de la Cierva-Formación grant (FJCI-2017-34967) Ministerio de Ciencia e Innovación (Spanish Government)Coordination for the Improvement of Higher Education Personnel (CAPES—Grant 88881.337237/2019-01), Brazi

Creación de contenido audiovisual online acerca del diagnóstico de patología pulpar y periapical, como apoyo a la docencia teórica de la asignatura PTD1

Memoria ID-036 Ayudas de la Universidad de Salamanca para la innovación docente, curso 2020-2021

Perturbation-Theory and Machine Learning (PTML). Model for High-Throughput Screening of Parham Reactions: Experimental and Theoretical Studies

Machine Learning (ML) algorithms are gaining importance in the processing of chemical information and modelling of chemical reactivity problems. In this work, we have developed a PTML model combining Perturbation-Theory (PT) and ML algorithms for predicting the yield of a given reaction. For this purpose, we have selected Parham cyclization, which is a general and powerful tool for the synthesis of heterocyclic and carbocyclic compounds. This reaction has both structural (substitution pattern on the substrate, internal electrophile, ring size, etc.) and operational variables (organolithium reagent, solvent, temperature, time, etc.), so predicting the effect of changes on substrate design (internal elelctrophile, halide, etc.) or reaction conditions on the yield is an important task that could help to optimize the reaction design. The PTML model developed uses PT operators to account for perturbations in experimental conditions and/or structural variables of all the molecules involved in a query reaction compared to a reaction of reference. Thus, a dataset of >100 reactions has been collected for different substrates and internal electrophiles, under different reaction conditions, with a wide range of yields (0 – 98%). The best PTML model found using General Linear Regression (GLR) has R = 0.88 in training and R = 0.83 in external validation series for 10000 pairs of query and reference reactions. The PTML model has a final R = 0.95 for all reactions using multiple reactions of reference. We also report a comparative study of linear vs. non-linear PTML models based on Artificial Neural Networks (ANN) algorithms. PTML-ANN models (LNN, MLP, RBF) with R ≈ 0.1 - 0.8 do not outperform the first PMTL model. This result confirms the validity of the linearity of the model. Next, we carried out an experimental and theoretical study of non-reported Parham reactions to illustrate the practical use of the PTML model. A 500000-point simulation and a Hammett analysis of the reactivity space of Parham reactions are also reportedMinisterio de Economía y Competitividad (CTQ2016-74881-P) / Ministerio de Economía y Competitividad (CTQ2013-41229-P) / Gobierno Vasco (IT1045-16

Modeling Antibacterial Activity with Machine Learning and Fusion of Chemical Structure Information with Microorganism Metabolic Networks

Predicting the activity of new chemical compounds over pathogenic microorganisms with different metabolic reaction networks (MRNs) is an important goal due to the different susceptibility to antibiotics. The ChEMBL database contains >160 000 outcomes of preclinical assays of antimicrobial activity for 55 931 compounds with >365 parameters of activity (MIC, IC50, etc.) and >90 bacteria strains of >25 bacterial species. In addition, the Leong and Barabàsi data set includes >40 MRNs of microorganisms. However, there are no models able to predict antibacterial activity for multiple assays considering both drug and MRN structures at the same time. In this work, we combined perturbation theory, machine learning, and information fusion techniques to develop the first PTMLIF model. The best linear model found presented values of specificity = 90.31/90.40 and sensitivity = 88.14/88.07 in training/validation series. We carried out a comparison to nonlinear artificial neural network (ANN) techniques and previous models from the literature. Next, we illustrated the practical use of the model with an experimental case of study. We reported for the first time the isolation and characterization of terpenes from the plant Cissus incisa. The antibacterial activity of the terpenes was experimentally determined. The more active compounds were phytol and α-amyrin, with MIC = 100 μg/mL for Vancomycin-resistant Enterococcus faecium and Acinetobacter baumannii resistant to carbapenems. These compounds are already known from other sources. However, they have been isolated and evaluated for the first time here against several strains of multidrug-resistant bacteria including World Health Organization (WHO) priority pathogens. Last, we used the model to predict the activity of these compounds versus other microorganisms with different MRNs in order to find other potential targets.Ministerio de Economía y Competitividad (CTQ2016-74881-P) // Gobierno Vasco (IT1045-16