Influencia de la obesidad sobre los marcadores de metabolismo óseo y el riesgo de fractura

La osteoporosis se define como una enfermedad esquelética progresiva sistémica, caracterizada por baja masa ósea y un aumento de la fragilidad, que condiciona un aumento del riesgo de fractura. Por otro lado, la obesidad, supone la enfermedad metabólica más prevalente del mundo desarrollado. La relación entre obesidad y metabolismo óseo es controvertida, ya que, en las últimas décadas se ha puesto en duda el papel protector de la obesidad sobre el desarrollo de la osteoporosis debido a que sobre el hueso influyen gran cantidad de factores mecánicos, hormonales e inflamatorios. Nuestro objetivo es 1) Evaluar las diferencias en los parámetros bioquímicos de metabolismo óseo entre mujeres postmenopáusicas con y sin obesidad. 2) Comparar el riesgo de fractura a cinco años entre mujeres postmenopáusicas con y sin obesidad. Se diseñó un estudio de tipo observacional prospectivo longitudinal de cohortes de mujeres postmenopáusicas con obesidad (IMC (Índice de Masa Corporal)>30kg/m2)) y sin obesidad (IMC<30kg/m2). Se incluyeron en el estudio 250 pacientes, de las cuales 124 eran mujeres postmenopáusicas sin obesidad pertenecientes al área Oeste de Valladolid y 126 mujeres con obesidad delárea Este de salud. Se analizaron un grupo de variables de tipo epidemiológico, bioquímico (-CrossLaps, péptido aminoterminal del procolágeno tipo I (P1NP)); 25OH Vitamina D y hormona paratiroidea (PTH), antropométrico y datos de fractura a los 5 años del estudio inicial (desde 2014 a 2019). Se observó que las mujeres con obesidad mostraron niveles más bajos de Vitamina D (O: Obesidad :17,27 (7,85), NoO: 24,51 (9,60); p<0,01) junto con un aumento de PTH (O: 53,24 (38,44-65,96), NoO: 35,24 (25,36-42,40); p<0,01). El marcador de formación ósea (P1NP) se encontró elevado en mujeres sin obesidad, aunque, siendo únicamente significativo en las mujeres con edades menores de 53 hasta los 56 años (<53 años: O:46,11 (29,91-55,81), NoO: 65,49 (50,64-85,55); p<0,01; y de 53 a 56 años: O: 43,40 (32,86-46,40), NoO: 56,04 (44,78-70,01); p<0,01). El marcador de resorción ósea (-CrossLaps) se encontró aumentado en mujeres con obesidad siendo significativo en mayores de 59 años (O: 0,39 (0,14), NoO: 0,24 (0,09); p<0,05). Se realizó un análisis de regresión lineal en el que se encontró una relación inversa entre el IMC y la Vitamina D (<53 años: R=-0,33; p≤0,01) y entre el marcador de formación ósea P1NP y el IMC (<53 años: R=-0,37; p≤ 0,01). Se obtuvo una relación positiva entre los niveles de PTH y el IMC (<53 años: R=0,55; p≤ 0,01). No se observaron diferencias en el riesgo de fractura a 5 años en función del IMC. Las diferencias en el metabolismo óseo fueron un descenso de formación ósea (P1NP) a edades más tempranas y un aumento de resorción ósea (-crosslaps) en las mujeres con obesidad mayores de 59 años. Las mujeres con obesidad presentaron niveles inferiores de Vitamina D independientemente de la edad junto con aumento o de la PTH. La obesidad no supuso un incremento en el riesgo de fractura a 5 años.Grado en Medicin

A ‘click chemistry’ approach to the straightforward synthesis of new 4-aryl-1,2,3-triazolocarbanucleosides

The synthesis and biological evaluation as antiviral agents of a series of racemic 4-aryl-1,2,3- triazolyl carbanucleosides of type (±)-10/(±)-11 related to the broad spectrum antiviral agent ribavirin 1 are described. These compounds were produced using a “click chemistry” strategy starting from readily available protected alcohol 13b. The synthetic approach made use of olefinbased organic reactions for the stereoselective construction of the appropriately functionalized cyclopentane ring moiety followed by copper (I) catalyzed Huisgen 1,3-dipolar cycloaddition of azides and alkynes for the regioselective construction of the heterocyclic triazole moietyThe authors thank the Xunta de Galicia for financial support of this work under Project PGIDT02BTF20305PR. M.D.G. thanks the Xunta de Galicia for financial support under “Programa Isidro Parga Pondal”S

Machine learning techniques to discover genes with potential prognosis role in Alzheimer’s disease using different biological sources

Alzheimer’s disease is a complex progressive neurodegenerative brain disorder, being its prevalence ex pected to rise over the next decades. Unconventional strategies for elucidating the genetic mechanisms are necessary due to its polygenic nature. In this work, the input information sources are five: a public DNA microarray that measures expression levels of control and patient samples, repositories of known genes associated to Alzheimer’s disease, additional data, Gene Ontology and finally, a literature review or expert knowledge to validate the results. As methodology to identify genes highly related to this disease, we present the integration of three machine learning techniques: particularly, we have used decision trees, quantitative association rules and hierarchical cluster to analyze Alzheimer’s disease gene expres sion profiles to identify genes highly linked to this neurodegenerative disease, through changes in their expression levels between control and patient samples. We propose an ensemble of decision trees and quantitative association rules to find the most suitable configurations of the multi-objective evolutionary algorithm GarNet, in order to overcome the complex parametrization intrinsic to this type of algorithms. To fulfill this goal, GarNet has been executed using multiple configuration settings and the well-known C4.5 has been used to find the minimum accuracy to be satisfied. Then, GarNet is rerun to identify de pendencies between genes and their expression levels, so we are able to distinguish between healthy individuals and Alzheimer’s patients using the configurations that overcome the minimum threshold of accuracy defined by C4.5 algorithm. Finally, a hierarchical cluster analysis has been used to validate the obtained gene-Alzheimer’s Disease associations provided by GarNet. The results have shown that the ob tained rules were able to successfully characterize the underlying information, grouping relevant genes for Alzheimer Disease. The genes reported by our approach provided two well defined groups that per fectly divided the samples between healthy and Alzheimer’s Disease patients. To prove the relevance of the obtained results, a statistical test and gene expression fold-change were used. Furthermore, this rel evance has been summarized in a volcano plot, showing two clearly separated and significant groups of genes that are up or down-regulated in Alzheimer’s Disease patients. A biological knowledge integration phase was performed based on the information fusion of systematic literature review, enrichment Gene Ontology terms for the described genes found in the hippocampus of patients. Finally, a validation phase with additional data and a permutation test is carried out, being the results consistent with previous studies.Ministerio de Ciencia y Tecnología TIN2011-28956-C02-02Ministerio de Ciencia y Tecnología TIN2014-55894-C2-1-RJunta de Andalucía P11-TIC-752

Influence of obesity on bone turnover markers and fracture risk in postmenopausal women

Producción CientíficaBackground and aims: The relationship between obesity and bone metabolism is controversial. In recent decades, the protective role of obesity in the development of osteoporosis is questioned. The aims of this study are the following: to evaluate the differences in bone turnover markers between postmenopausal women with and without obesity and to compare the risk of fracture at five years between these groups. Methods: An observational longitudinal prospective cohort study of postmenopausal women with obesity (O) (body mass index (BMI) > 30 kg/m2) and non-obesity (NoO) (BMI < 30 kg/m2) is designed. 250 postmenopausal women are included in the study (NoO: 124 (49.6%) and O: 126 (50.4%)). It measures epidemiological variables, dietary variables (calcium intake, vitamin D intake, smoking, alcohol consumption, and physical activity), biochemicals (β-crosslap, type I procollagen amino-terminal peptide (P1NP), 25OH-vitamin D, and parathyroid hormone (PTH)), anthropometric variables, and fracture data five years after the start of the study. The mean age is 56.17 (3.91) years. Women with obesity showed lower levels of vitamin D (O: 17.27 (7.85) ng/mL, NoO: 24.51 (9.60) ng/mL; p < 0.01), and higher levels of PTH (O: 53.24 (38.44–65.96) pg/mL, NoO: 35.24 (25.36–42.40) pg/mL; p < 0.01). Regarding the bone formation marker (P1NP), it was found to be high in women without obesity, O: 45.46 (34.39–55.16) ng/mL, NoO: 56.74 (45.34–70.74) ng/mL; p < 0.01; the bone resorption marker (β-crosslap) was found to be high in women with obesity, being significant in those older than 59 years (O: 0.39 (0.14) ng/mL, NoO 0.24 (0.09) ng/mL; p < 0.05). No differences are observed in the risk of fracture at 5 years based on BMI (OR = 0.90 (95%CI 0.30–2.72); p = 0.85). Conclusions: Postmenopausal women with obesity showed lower levels of bone formation markers; older women with obesity showed higher markers of bone resorption

Benthic foraminifera as bioindicators of anthropogenic impacts in two north African lagoons: a comparison with ostracod assemblages

Numerous investigations have used the foraminiferal assemblages or species as bioindicators. This paper tests the responses of these microorganisms to different environmental changes (heavy metal pollution, treatment stations, artificial inlets, agricultural and urban sewages) and compares them to those observed previously on ostracod assemblages. Foraminifera are more tolerant to these changes, while ostracods present a more specialized response.Numerosas investigaciones han utilizado a las asociaciones o especies de foraminíferos como bioindicadores. Este trabajo investiga la respuesta de estos microorganismos ante diferentes cambios ambientales (contaminación por metales pesados, estaciones de tratamiento de residuos, pasajes artificiales, desechos urbanos e industriales) y la compara con la observada previamente en las asociaciones de ostrácodos. Los foraminíferos son más tolerantes a estos cambios, en tanto que la respuesta de los ostrácodos es más especializada

Hair cortisol concentrations in a Spanish sample of healthy adults

Hair cortisol concentration (HCC), as a novel promising method to retrospectively measure hypothalamic-pituitary-adrenal (HPA) axis activation, is being increasingly studied. We tested the relationships between HCC and a range of possible confounding variables in a Spanish sample of healthy adults and pregnant women. In this sample of healthy Spaniards, results suggested an association between HCC and physical exercise and educational level. In pregnant women, the prevalence of HCC was higher than in non-pregnant woman, and was related to educational level. This study emphasises the need to determine the relationship between HCC and confounders such as sociodemographic and lifestyle variables in the general population and specific groups formed by individuals such as pregnant women.This research is part of a doctoral thesis. It has been economically supported by the "PSI2015-63494-P" I+D Project of the Spanish Ministry of Economy and Competitiveness (MINECO) and FEDE

Biological Activity of Extracts from Aromatic Plants as Control Agents against Spoilage Molds Isolated from Sheep Cheese

[EN] The aim of this work was to assess the antifungal and antioxidant activity of essential oils and ethanolic extracts from distilled solid by-products from aromatic plants (Artemisia dracunculus, Hyssopus officinalis, Lavandula stoechas, Origanum vulgare and Satureja montana) against 14 fungi strains isolated from sheep cheese and identified at species level using DNA barcoding based on β-tubulin sequence analysis. In addition, capacity of fungi to produce ochratoxin A, patulin, cyclopiazonic acid and sterigmatocystin was analyzed. Of the isolates, 85.7% belonged to Penicillium (P. commune/biforme, P. crustosum) and 14.3% to Aspergillus (A. puulaauensis and A. jensenii), the first time that these Aspergillus species have been found in sheep’s cheese. All P. commune isolates were producers of cyclopiazonic acid, and the two Aspergillus strains produced sterigmatocystin, but the others did not produce any tested mycotoxin. Among the essential oils tested, oregano, savory and tarragon had a significant antifungal activity against all the isolated strains, but no ethanolic extract showed antifungal activity. By contrast, ethanolic extracts showed great potential as antioxidants. The identification of new molds in cheese will help the dairy industry to know more about those molds affecting the sector, and the use of aromatic plants in the control of fungal spoilage could be a suitable alternative to chemical preservatives used in the agri-food industrySIThis research was financially supported by the Spanish National Institute for Agricultural Research and Experimentation (INIA, http://inia.es) by the project RTA2015-00018-C03-0

8-Amide and 8-carbamate substitution patterns as modulators of 7-hydroxy-4-methylcoumarin's antidepressant profile: Synthesis, biological evaluation and docking studies

Psychiatric and neurological disorders affect millions of people worldwide. Currently available treatments may help to improve symptoms, but they cannot cure the diseases. Therefore, there is an urgent need for potent and safe therapeutic solutions. 8-Amide and 8-carbamatecoumarins were synthetized and evaluated as human monoamine oxidase A and B (hMAO-A and hMAO-B) inhibitors. Comparison between both scaffolds has been established, and we hypothesized that the introduction of different substituents can modulate hMAO activity and selectivity. N-(7-Hydroxy-4-methylcoumarin-8-yl)-4-methylbenzamide (9) and ethyl N-(7-hydroxy-4-methylcoumarin-8-yl)carbamate (20) proved to be the most active and selective hMAO-A inhibitors (IC50 = 15.0 nM and IC50 = 22.0 nM, respectively), being compound 9 an irreversible hMAO-A inhibitor twenty-four times more active in vitro than moclobemide, a drug used in the treatment of depression and anxiety. Based on PAMPA assay results, both compounds proved to be good candidates to cross the blood-brain barrier. In addition, these compounds showed non-significant cytotoxicity on neuronal viability assays. Also, the best compound proved to have a t1/2 of 6.84 min, an intrinsic clearance of 195.63 μL min−1 mg−1 protein, and to be chemically stable at pH 3.0, 7.4 and 10.0. Docking studies were performed to better understand the binding affinities and selectivity profiles for both hMAO isoforms. Finally, theoretical drug-like properties calculations corroborate the potential of both scaffolds on the search for new therapeutic solutions for psychiatric disorders as depressionThis research was funded by Consellería de Cultura, Educación e Ordenación Universitaria (EM2014/016), Ministerio de Ciencia e Innovación (PID2020-116076RJ-I00/AEI/10.13039/501100011033) and Fundação para a Ciência e Tecnologia (PTDC/ASP-PES/28397/2017, CEECIND/02423/2018, UIDB/00081/2020, LA/P/0056/2020 and EXPL/BIA-BQM/0492/2021). Financial support from the Xunta de Galicia (Centro de investigación de Galicia accreditation 2019–2022) and the European Union (European Regional Development Fund - ERDF), is also gratefully acknowledged. M.I.R.-F. acknowledges the economic support from the Spanish Ministry of Science, Innovation and Universities; Spanish Research Agency; and European Regional Development Funds (grant PID2021-122650OB-I00) and from CSIC (PIE-202080E118)S

Storm Gloria: sea state evolution based on in situ measurements and modeled data and its impact on extreme values

Storm Gloria, generated on January 17th, 2020 in the Eastern North Atlantic, crossed the Iberian Peninsula and impacted the Western Mediterranean during the following days. The event produced relevant damages on the coast and the infrastructures at the Catalan-Balearic Sea, due to extraordinary wind and wave fields, concomitant with anomalously intense rain and ocean currents. Puertos del Estado (the Spanish holding of harbors) has developed and operates a complex monitoring and forecasting system (PORTUS System), in collaboration with the Spanish Met Office (AEMET). The present work shows how Gloria was correctly forecasted by this system, alerts were properly issued (with special focus to the ports), and the buoys were able to monitor the sea state conditions during the event, measuring several new records of significant wave height and exceptional high mean wave periods. The paper describes, in detail, the dynamic evolution of the atmospheric conditions, and the sea state during the storm. It is by means of the study of both in situ and modeled PORTUS data, in combination with the AEMET weather forecast system results. The analysis also serves to place this storm in a historical context, showing the exceptional nature of the event, and to identify the specific reasons why its impact was particularly severe. The work also demonstrates the relevance of the PORTUS System to warn, in advance, the main Spanish Ports. It prevents accidents that could result in fatal casualties. To do so, the wave forecast warning performance is analyzed, making special focus on the skill score for the different horizons. Furthermore, it is demonstrated how a storm of this nature results in the need of changes on the extreme wave analysis for the area. It impacts all sorts of design activities at the coastline. The paper studies both how this storm fits into existing extreme analysis and how these should be modified in the light of this particular single event. This work is the first of a series of papers to be published on this issue. They analyze, in detail, other aspects of the event, including evolution of sea level and description of coastal damages