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Alzheimer's disease is a progressive neurodegenerative disorder characterized by the abnormal processing of the Tau and the amyloid precursor proteins. The unusual aggregation of Tau is based on the formation of intermolecular β-sheets through two motifs: 275 VQIINK280 and 306 VQIVYK311 . Phenylthiazolyl-hydrazides (PTHs) are capable of inhibiting/disassembling Tau aggregates. However, the disaggregation mechanism of Tau oligomers by PTHs is still unknown. In this work, we studied the disruption of the oligomeric form of the Tau motif 306 VQIVYK311 by PTHs through molecular docking, molecular dynamics, and free energy calculations. We predicted hydrophobic interactions as the major driving forces for the stabilization of Tau oligomer, with V306 and I308 being the major contributors. Nonpolar component of the binding free energy is essential to stabilize Tau-PTH complexes. PTHs disrupted mainly the van der Waals interactions between the monomers, leading to oligomer destabilization. Destabilization of full Tau filament by PTHs and emodin was not observed in the sampled 20 ns; however, in all cases, the nonpolar component of the binding free energy is essential for the formation of Tau filament-PTH and Tau filament-emodin. These results provide useful clues for the design of more effective Tau-aggregation inhibitors.

En este articulo se pretende trasladar la experiencia, planteamientos y reflexiones de su autora desde el cargo de directora y coordinadora de los trabajos de redaccion de la LOTUS. El camino que ha llevado, de manera novedosa, a la adopcion de determinaciones concretas sobre criterios de ordenacion sostenible y planeamiento, que permiten la aplicacion al diseno de nuestros pueblos y ciudades de medidas correctoras contra las posibles situaciones de discriminacion, limitacion de uso y riesgos, que contravengan los principios basicos de igualdad de genero. Este avance logrado con la nueva Ley 11/2018, en la integracion de la perspectiva de genero en la ordenacion, debe verse complementado con otros importantes instrumentos que preve esta ley y que sirven para desarrollarla. El articulo concluye con una serie de reflexiones en cuanto a las previsiones que deben tenerse en cuenta por las administraciones para la correcta implantacion del desarrollo reglamentario en el que esta inmersa la comunidad autonoma de Extremadura.

Older adults with oropharyngeal dysphagia (OD) are unable to swallow pills safely, so some of them use liquid-formulated drugs mixed with thickeners to ensure safety. The aim of this study was to analyze the physical compatibility of a group of drugs with a thickener formulated with modified starch (Thick & Easy®). A secondary goal was to evaluate the amount of thickener needed to obtain the thickness levels 2, 3, and 4 defined by IDDSI framework for each drug. For this purpose, the rheological properties of the mixtures obtained were determined. Samples of each drug were prepared and 7, 10, and 12 g of thickener were added. Physical compatibility of the mixtures was observed; the apparent viscosity of the samples was measured using a rotational viscometer, and the results obtained were compared with the reference drug-free sample. We analyzed 45 medicinal products (38 active substances). Three drugs (almagate, ibuprofen, and macrogol) were found to be physically incompatible with the thickener and should not be mixed. Viscosity measurements indicated that clarithromycin and plantago ovata increased the viscosity of the mixture and required lower amount to achieve the target textures (110 cP, 590 cP, and 2620 cP for 7 g, 10 g, and 12 g in drug-free samples, respectively), whereas another subset reduced viscosity and required more thickener. This proved very relevant for acetylcysteine, amoxicillin, calcifediol, ferrous gluconate, fosfomycin, lactitol, lactulose, mepifiline, paracetamol, rivastigmine, sertraline, and tramadol. Measurements were below 1750 cP. Awareness of how each drug behaves when combined with thickeners is essential to avoid potential complications in OD.

[EN] In recent decades, concern about rabbit welfare and sustainability has increased. The housing system is a very important factor for animal welfare. However, information about how different available housing types for female rabbits affect their health status is scarce, but this is an important factor for their welfare. Hence, the objective of this study was to evaluate the health status of female rabbits in five common housing systems: three different single-housing systems with distinct available surfaces and heights; a single-housing system with a platform; a collective system. Female rabbits in the collective and platform cages had greater cortisol concentrations in hair than those in the single-housing system with no platform. Haptoglobin concentrations and kit mortality rates during lactation were greater for the collective-cage female rabbits. The collective group had more culled females and more lesions than in the other groups. The main reasons for culling in all the groups were reproduction problems and presence of abscesses, and the collective group of females was the most affected. In conclusion, it appears that keeping females together in collective systems negatively affects their health status and welfare, while single-housing systems imply lower kit mortality rates during lactation and cortisol concentrations, and fewer lesions in female rabbits., This study was supported by the INIA-INTERCUN Project (CUN2014-00001-00-00) and by Universidad CEU-Cardenal Herrera (INDI16/07, INDI17/07, INDI18/08). Grants for Sara Perez Fuentes, Asuncion Munoz Silvestre and Elena Moreno Grua from Universidad CEU-Cardenal Herrera, and also for Sara Perez Fuentes from Generalitat Valenciana and FSE (ACIF/2016/085), and for Elena Moreno Grua from Ministerio de Educacion, Cultura y Deporte (FPU17/02708) are also gratefully acknowledged.

Agradecimientos: A la Dirección General de Tráfico, por habernos facilitado la consulta y el uso del Registro Espanol ˜ de Accidentes de Tráfico con Víctimas, sin el cual la elaboración de este trabajo no hubiera sido posible., Objetivo: Cuantificar la magnitud de la asociación entre el tipo de vehículo y la probabilidad de ser el responsable de una colisión entre dos o más vehículos. Método: A partir del registro de accidentes de tráfico con víctimas de la Dirección General de Tráfico (2014 y 2015) se disenó˜ un estudio de casos y controles emparejado. Los casos fueron los conductores infractores implicados en las 27.630 colisiones entre dos o más vehículos, en las que solo uno de los conductores implicados había cometido algún error de conducción o infracción. Cada caso se emparejó con los conductores no infractores de los vehículos implicados en el mismo accidente; en total se dispuso de 31.219 controles. Aparte de la comisión de infracciones y del tipo de vehículo implicado, se obtuvo información para otras características del conductor (edad, sexo, etc.) y del vehículo (antigüedad). Se calcularon odds ratios (OR) para cuantificar la asociación entre cada tipo de vehículo y la odds de ser el causante de la colisión, crudas y ajustadas (ORa) (regresión logística condicionada) por el resto de las variables recogidas. Resultados: En comparación con los turismos, se obtuvo un menor riesgo de provocar la colisión para bicicletas (ORa: 0,30), ciclomotores (ORa: 0,52) y autobuses (ORa: 0,63), y un mayor riesgo para furgonetas (ORa: 1,19) y vehículos todoterreno (ORa: 1,33). Conclusión: Los vehículos de dos ruedas y los autobuses tienen un menor riesgo de provocar colisiones que los turismos. Esta asociación es independiente de algunas características del conductor, así como de la antigüedad del vehículo., Objective: To quantify the magnitude of the association between the type of vehicle and the probability of being responsible for a collision between two or more vehicles. Method: From the registry of road crashes with victims maintained by the Spanish Traffic General Directorate (2014 and 2015), a matched case-control study was designed. Cases were offending drivers involved in the 27,630 collisions between two or more vehicles in which only one of the drivers had committed a driving mistake or offence. Each case was matched with the non-offending drivers of the vehicles involved in the same crash: in all, 31,219 controls were included. Apart from the commission of offences and the type of vehicle involved, we got information about other characteristics of the driver (age, sex, etc.) and about the vehicle (age). Odds ratios (OR) were calculated in order to quantify the association between each type of vehicle and the odds of being responsible for the collision, crude and adjusted (by conditioned logistic regression) by the rest of collected variables. Results: In comparison with private cars, bicycles had a lower risk of causing a collision (adjusted OR: .30), and also mopeds (aOR: .52) and buses (aOR: .63). Vans (aOR: 1.19) and four-wheel vehicles (aOR: 1.33) increased the risk. Conclusion: Two-wheeled vehicles and buses had a lower risk of causing collisions than private cars. This association is independent of some of the characteristics of the driver, as well as the age of the vehicle.

La determinacion de las actividades acetilcolinesterasa (AChE) y butirilcolinesterasa (BuChE) es ampliamente utilizada en estudios de monitoreo biologico para evaluar la exposicion a compuestos anticolinesterasicos y sus efectos. No obstante, se ha observado una amplia variabilidad en los valores considerados como normales para estas actividades enzimaticas, lo que puede deberse a diversos factores. Uno de los que puede tener mas influencia es la falta de parametros preanaliticos y analiticos estandarizados. En este sentido, el objetivo de este trabajo fue conocer, con una metodologia consensuada, los intervalos de las actividades AChE y BuChE en individuos no expuestos ocupacionalmente a compuestos anticolinesterasicos en diferentes estados de la republica mexicana. Se observo que el 22 % de los laboratorios participantes reportaron valores de actividad AChE dentro del rango considerado como normal. Respecto a la actividad BuChE, el 67 % reporto valores dentro del rango para una poblacion no expuesta a compuestos anticolinesterasicos. Los resultados revelaron una importante variabilidad en los valores de las actividades AChE y BuChE, que muestran la necesidad de capacitacion continua entre los analistas y la homogeneizacion de las metodologias.

Brassinosteroids (BRs) are hormones found in a wide range of plant species, they are synthesized at low concentrations and are essential for normal growth and development. These phytohormones are recognized by the Leucine-rich-repeat ectodomain of the receptor-like-kinase BRI1 which leads to subsequent downstream signaling mediating plant growth/development. In spite of the advantages that BRs offer, their extraction from natural sources is highly expensive, which constitutes one of its major limitations. Thus, the design and synthesis of structural and/or functional analogues of BRs with higher activity and lower cost has a great practical significance in world agriculture. In this matter, in silico methods, such as molecular docking, are valuable tools for the prediction and design of new compounds with improved activity. In this work we performed molecular docking simulations of 20 synthetic steroids in order to identify active compounds. Contact based analysis, level of exposure of polar groups to the solvent and binding affinity were the parameters used to consider if a synthetic steroid was active. Our results suggested that 17 out of a total of 20 of the analyzed steroids can potentially activate BRI1 receptor.

Paraoxonase 1 (PON1) promotes antioxidant and antiatherogenic activity related to the hydrolysis of oxidized lipids of low-density lipoproteins. In rheumatoid arthritis (RA) patients, it has been reported that low PON1 activity is related to an impaired lipid profile, increasing cardiovascular risk (CVR). The goal of this study was to analyze the effect of common PON1 polymorphisms and haplotypes on enzymatic activity, PON1 serum levels (PON1s), and lipid parameters related to atherogenic profile in RA patients.A cross-sectional study was carried out on 250 Mexican patients with RA. The lipid profile was determined by colorimetric tests. The PON1 activity (CMPAase) was measured by spectrophotometry. The levels of PON1s were determined by ELISA, and the polymorphisms in the PON-1 gene (-108CT, L55M, and Q192R) were genotyped by the PCR-RFLP method. The haplotypes were estimated and statistical analysis was performed.The median of the CMPAase activity and PON1 levels was 13.91 U/mL and 24.75 ng/mL, respectively. The CMPAase activity was significantly lower in carriers of -108TT and 192QQ genotypes (β = - 4.09, P = 0.001 and β = - 3.73, P = 0.002, respectively); moreover, the PON1 levels were lower in 192Q allele carriers (P 0.01). The TLQ haplotype was associated with CMPAase activity 13.91 U/mL (OR = 2.29, P 0.001), as well as with levels of PON1s 24.75 ng/mL (OR = 1.65, P = 0.017). In this study, the CMPAase activity ( 13.91 U/mL) showed a positive association with lower levels of high-density lipoprotein cholesterol (HDL-c; 40/50 mg/dL), and with a triglycerides/HDL-c ratio 3%, and a total cholesterol/HDL-c ratio 4.5/5%, all representatives of an atherogenic risk lipid profile.PON1 polymorphisms modulate the CMPAase activity and PON1 levels in Mexican patients with RA. The CMPAase activity 13.91 U/mL is associated with an atherogenic lipid profile, independently of inflammation markers and treatment with anti-rheumatic drugs. Key Points •The haplotype TLQ is a marker for low PONase activity in rheumatoid arthritis. •The haplotype TLQ is a marker for low PON1 serum levels in rheumatoid arthritis. •The enzymatic PON1 activity represents the best marker for an atherogenic lipid profile in rheumatoid arthritis, in comparison with PON1 levels. •The haplotype TLQ is a marker of low PON1 activity, levels of PON1s, and atherogenic lipid profile, independent of treatment therapy in rheumatoid arthritis.

El presente estudio está orientado a determinar las actividades lúdicas que favorecen el aprendizaje en los niños y niñas del C.D.I de la Fundación Granitos de Paz, para lograr describir los tipos de juegos desarrollados en el salón de clase, además de identificar sus preferencias durante la permanencia en el centro educativo, de este modo precisar las actividades más integradas a la cotidianidad escolar. Está sustentado por autores estudiosos de la lúdica y desarrollo infantil: Piaget (1896-1980), Decroly (1871- 1932) & Montessori y otros (1870-1952). Es cualitativa de tipo participativa por la interrelación del proceso y las acciones en un determinado campo seleccionado por el investigador, con la contribución de los sujetos involucrados. Los resultados evidencian un interés por el aspecto socio afectivo como reflejo de su conocimiento en el marco del desarrollo cognitivo, es decir, se reconoce la relevancia del proceso actitudinal a partir de la relación educativa. Teniendo en cuenta la descripción del tipo de lúdica, se hace posible establecer la preferencia por las actividades que referencian los aspectos psicomotriz y cognitivo, en juegos de movimientos corporales unidos al conocimiento de las nociones básicas; de igual manera, muestran agrado por juegos relacionados con sus afectos, desarrollados en su entorno familiar, escolar y comunitario.

This current study attempted to examine the occurrence rates of Enterobacteriaceae in seafood samples collected from different fishmongers in the province of Constantine (Northeast Algeria) over a one-year period. Total and fecal coliforms were enumerated and selected Enterobacteriaceae colonies were identified. Escherichia coli (E. coli) and Salmonella isolates were serotyped, after which their antimicrobial susceptibility patterns were determined. Extended-spectrum beta-lactamases (ESBL) encoding genes, virulence genes (stx1, stx2 and eae) and plasmid-harboring were searched among E. coli isolates and their clonality was also assessed by pulsed-field gel electrophoresis (PFGE). Results showed that fecal coliform contamination levels are beyond the recommended limits. All strains of Salmonella (n = 2) isolated were of serovar infantis. One E. coli isolate from sardines belonged to serotype O127 and two others (one from sardines and one from shrimps) were identified as serotype O125. One E. coli isolate from sardines was characterized as enterohemorrhagic (EHEC) and six others as shiga toxin-producing (STEC) (three from sardines and three from shrimps). All tested strains were multidrug resistant, with five E. coli strains showing an ESBL phenotype and harboring the blaCTX-M-15 gene (four from sardines and one from shrimps). Plasmids of differents sizes were extracted from seven E. coli isolates (five from sardines and two from shrimps) with many strains carrying more than one plasmid. E. coli isolates belonged to two phylogenetic groups (B1 and, mainly, E) and scattered on eight distinct clones as defined by PFGE. Some strains are grouped within the same cluster regardless of their origin and characteristics, indicating a common source of contamination. These findings demonstrate that, in the study region, sardines and shrimp may play an important role in the dissemination of virulent and multi-drug resistant enterobacteria strains.

The synthesis of three libraries (1a-l, 1a’-l’ and 2a-l) of dimeric iminosugars through CuAAC reaction between three different alkynyl pyrrolidines and a set of diazides was carried out. The resulting crude dimers were screened in situ against two α-fucosidases (libraries 1a-l and 1a’-l’) and one β-galactosidase (2a-l). This method is pioneer in the search of divalent glycosidase inhibitors. It has allowed the rapid identification of dimer 1i as the best inhibitor of α-fucosidases from bovine kidney (Ki = 0.15 nM) and Homo sapiens (Ki = 60 nM), and dimer 2e as the best inhibitor of β-galactosidase from bovine liver (Ki = 5.8 μM). In order to evaluate a possible divalent effect in the inhibition, the synthesis and biological analysis of the reference monomers were also performed. Divalent effect was only detected in the inhibition of bovine liver β-galactosidase by dimer 2e.

Non-communicable diseases (NCDs) account for the five largest contributors to burden of disease in Mexico, with diabetes representing the greatest contributor. However, evidence supporting chronic disease programmes in Mexico is limited, especially in rural communities. Compañeros En Salud (CES) partnered with the Secretariat of Health of Chiapas, Mexico to implement a novel community-based NCD treatment programme. We describe the implementation of this programme and conducted a population-based, retrospective analysis, using a difference-in-differences regression approach to estimate the impact of the programme. Specifically, we examined changes in diabetes and hypertension control rates between 2014 and 2016, comparing CES intervention clinics (n = 9) to care-as-usual at non-CES clinics (n = 806), adjusting for differences in facility-level characteristics. In 2014, the percent of diabetes patients with this condition under control was 36.9% at non-CES facilities, compared with 41.3% at CES facilities (P0.05). For hypertension patients, these figures were 45.2% at non-CES facilities compared with 56.2% at CES facilities (P = 0.02). From 2014 to 2016, the percent of patients with diabetes under control declined by 9.2% at non-CES facilities, while improving by 11.3% at non-CES facilities where the Compañeros En Salud Programa de Enfermedades Crónicas intervention was implemented (P0.001). Among hypertension patients, those with the condition under control increased by 21.5% at non-CES facilities between 2014 and 2016, compared with 16.2% at CES facilities (P0.05). Introduction of the CES model of NCD care was associated with significantly greater improvements in diabetes management between 2014 and 2016, compared with care-as-usual. Hypertension control measures were already greater at CES facilities in 2014, a difference that was maintained through 2016. These findings highlight the successful implementation of a framework for providing NCD care in rural Mexico, where a rapidly increasing NCD disease burden exists.

El glufosinato de amonio (GLA) es un herbicida organofosforado que se utiliza para el control de malezas. La exposicion a GLA induce incrementos en la incidencia de partos prematuros, anormalidades y abortos en hembras prenadas, asi como un retraso en el desarrollo del cigoto de preimplantacion. Sin embargo, se desconoce si el GLA tiene como blanco de toxicidad a las celulas espermaticas durante la ultima fase de su desarrollo y de maduracion. Este estudio evaluo los efectos del GLA sobre la calidad de los espermatozoides y del ADN espermatico despues de la exposicion durante dos etapas cruciales, la de espermatida y la de maduracion epididimal. Ratones macho adultos de la cepa ICR fueron administrados diariamente con GLA [5, 7.5 y 10 mg/kg de peso corporal/v.o./5- o 15-dias de tratamiento (dt)], y sacrificados 24 h post-tratamiento. Los espermatozoides fueron obtenidos de la cola del epididimo-conducto deferente y despues fueron utilizados para evaluar la calidad espermatica y el dano al ADN. A los 5- o 15-dt, las dosis de 5, 7.5 y 10 mg/kg/d de GLA, disminuyeron significativamente los parametros de calidad espermatica. Asimismo, a los 5-dt, la dosis de 10 mg/kg/d incremento significativamente el %DFI (por sus siglas en ingles, “DNA Fragmentation Index”), mientras que a los 15-dt las dosis de 7.5 y 10 mg/kg/d incrementaron significativamente la media de %DFI y %HSD (por sus siglas en ingles, “High DNA stainability” o Alta fluorescencia del ADN). Estos datos sugieren que las espermatidas tempranas y los espermatozoides maduros son blancos de la exposicion a GLA.

A pesar del amplio uso de los Modelos de Distribucion de Especies (MDE: algoritmos que establecen relaciones estadisticas entre las presencias de una especie y las variables ambientales) en el estudio de la distribucion actual de los taxones y el impacto derivado del cambio climatico, su aplicabilidad y la validez de sus predicciones es todavia objeto de estudio. Esta tesis trata de reducir la incertidumbre de los MDE para mejorar su transferibilidad temporal y espacial mediante la incorporacion de la informacion aportada por la paleobotanica, por las imagenes de satelite y el estudio de la influencia de diferentes factores en el proceso de modelizacion. En primer lugar se revisa el potencial y las limitaciones del uso de los datos fosiles en los MDE y se proponen recomendaciones teniendo en cuenta las caracteristicas de los datos paleobotanicos en cuanto a representatividad, taxonomia y cronologia (Capitulo 2). Asimismo, se estudia la influencia de la complejidad de los modelos en la capacidad predictiva de los mismos y en su transferibilidad temporal mediante su proyeccion en el Holoceno Medio y su validacion con datos paleobotanicos (Capitulo 3). Posteriormente se evalua el efecto de los datos de entrada (division de los datos de presencia segun sub-habitats y bases de datos climaticas) en las predicciones de los modelos sobre poblaciones marginales y su aplicacion en el estudio del impacto del cambio climatico (Capitulo 4). Por ultimo se valida la capacidad predictiva de los MDE con imagenes de satelite, evaluando la influencia de las presencias y umbrales usados en el modelo y su uso en el estudio de la sensibilidad de especies frente al cambio climatico (Capitulo 5). Los resultados obtenidos en esta tesis doctoral indican que los parametros estudiados afectan de forma importante a la capacidad predictiva y a la idoneidad predicha por los modelos, influyendo en la precision y exactitud de los mismos. Por tanto, deben tenerse en cuenta a la hora de proyectar los modelos hacia diferentes periodos temporales y especialmente bajo escenarios futuros de cambio climatico. Ademas, se recomienda el uso de datos independientes (datos paleobotanicos o imagenes de satelite) para la validacion de los modelos y la seleccion de los parametros de modelizacion que mejor funcionen para cada estudio y especie.

El estudio analiza las competencias gerenciales, desde la perspectiva de la formación necesaria como fundamento para un desempeño autónomo, de autorrealización personal, para promover las competencias requeridas para abordar de manera pertinente el hecho educativo. La metodología fue descriptiva, documental-bibliográfica, destacando los principios curriculares de visión integral, diversidad humana, globalización, aprendizaje significativo, en armonía con la pertinencia de educar en un contexto diverso y cambiante. Se concluyó la relevancia de concebir al docente como mediador del proceso para el desarrollo humano, creativo, inventivo y descubridor. El docente debe ser un reflejo y más que maestro un continuo estudioso, presto a captar y comprender la percepción de la realidad desde la perspectiva de los estudiantes para así poder guiar y ser partícipe de su desarrollo humano, social, académico y espiritual. Para finalizar, las instituciones educativas, deben considerar como necesario desarrollar la aptitud natural de la inteligencia humana para ubicar todas sus informaciones en un contexto y en un conjunto, es decir, producir conocimiento pertinente. Asimismo, propiciar la comprensión, como medio y fin de la comunicación humana.

A detailed analysis of distribution shifts in Pinus hartwegii Lindl. is provided across time for Izta-Popo National Park (México). Combining satellite images, species distribution models, and connectivity analysis we disentangled the effect of climate change and anthropogenic land use on the habitat availability. Twenty-four Maxent habitat suitability models with varying complexity were combined with insights on vegetation and land cover change derived from two Landsat satellite images at 30-m resolution from 1993 and 2013. To evaluate effects of climate change on Izta-Popo’s P. hartwegii forest, projections for future climatic conditions (averaged for 2050 and 2070) were derived using two General Circulation Models under three Representative CO2 concentration pathways (RCPs). Calculated fragmentation and connectivity indexes (Equivalent Connected Area and Probability of Connectivity metrics) showed significant habitat loss and habitat fragmentation that weakens P. hartwegii dispersion flux and the strength of connections. Projections of future climate conditions showed a reduction of P. hartwegii habitat suitability as populations would have to migrate to higher altitudes. However, the impact of anthropogenic land use change documented over the 20 years masks the predicted impact of climate change in Izta-Popo National Park.

Saving represents one of the most important determinants of personal success and economic development. However, in developing economies, opportunities for structured and institutionalized savings are rare. The intention of the study is to generate evidence on the type of relationship existing between income levels and formal and informal saving habits of a group of people from three different cities in Mexico. From a non-probabilistic convenience sampling, the data of 260 participants were obtained. A logit model was estimated. The results show that there is a positive relationship between higher income levels and formal saving habits and an inverse relationship between higher income levels and informal saving practices. Although the size of the sample does not allow conclusions to be drawn to the level of generalization, it has allowed the generation of evidence that in future studies can be contrasted with a larger sample.

The increasing development of species distribution models (SDMs) using palaeodata has created new prospects to address questions of evolution, ecology and biogeography from wider perspectives. Palaeobotanical data provide information on the past distribution of taxa at a given time and place and its incorporation on modelling has contributed to advancing the SDM field. This has allowed, for example, to calibrate models under past climate conditions or to validate projected models calibrated on current species distributions. However, these data also bear certain shortcomings when used in SDMs that may hinder the resulting ecological outcomes and eventually lead to misleading conclusions. Palaeodata may not be equivalent to present data, but instead frequently exhibit limitations and biases regarding species representation, taxonomy and chronological control, and their inclusion in SDMs should be carefully assessed. The limitations of palaeobotanical data applied to SDM studies are infrequently discussed and often neglected in the modelling literature; thus, we argue for the more careful selection and control of these data. We encourage authors to use palaeobotanical data in their SDMs studies and for doing so, we propose some recommendations to improve the robustness, reliability and significance of palaeo-SDM analyses.

Purpose Median urinary iodine concentration (UIC) is used to describe the iodine status of a population. However, the link between UIC and iodine intake may vary during pregnancy. The aim of this study was to compare UIC during and after pregnancy, adjusting for factors that affect iodine intake. Methods Two repeated measures of UIC and data on maternal iodine intake estimated through questionnaires were collected during pregnancy and 1–4 years after pregnancy in a subsample of women (n = 598) from a mother and child cohort study in Spain. Random-effects interval regression was used to assess the changes in UIC according to pregnancy status. Results Median UIC was similar during (133 μg/L) and after pregnancy (139 μg/L). After adjusting for iodised salt, iodine supplement consumption, and socio-demographic related variables, UIC was 24.0% (95% CI 11.3, 38.2) higher after than during pregnancy. This difference was maintained in a subsample of women with exhaustive information on diet (n = 291): 26.2%, 95% CI 10.3, 44.4. Conclusions In an iodine sufficient area for the general population, iodine excretion was lower during than after pregnancy when factors affecting iodine intake were controlled for. Current recommendations of median UIC during pregnancy are based on the equivalence between iodine intake and UIC estimated from studies in non-pregnant populations, which might lead to overestimation of iodine deficiency during gestation. Further studies should evaluate the equivalence between iodine intake and its urinary excretion during pregnancy.

Parabens are used because of their antimicrobial effects, yet they have multiple adverse effects. The aim of this work was to evaluate the bactericidal activity and bacterial toxicity of the most common parabens: methylparaben, ethylparaben, propylparaben, isopropylparaben, butylparaben, isobutylparaben and phenylparaben. The bactericidal action was evaluated by means of the dilution-neutralization method against Escherichia coli and Staphylococcus aureus, and the biotest of inhibition of growth of E. coli was applied for the bacterial toxicity assay. Bactericidal concentrations were reached only for propylparaben, butylparaben and isobutylparaben. The toxicity study showed methylparaben to be the least toxic, whereas the most toxic one was phenylparaben. It can be concluded that the disinfectant activity of the parabens studied is insignificant against S. aureus and E. coli. Acute toxicity is very low, and the inhibitory effect is weak. Our results provide information about the risk–benefit balan...

The concentration and isotopic composition of lead in the blood of forty seven women of reproductive age (15-45y) exposed to multiple sources in two rural communities of the mining region of Taxco, Guerrero in southern Mexico were determined in order to identify specific contributing sources and their apportionment and to trace probable ingestion pathways. Our data indicate that >36% of the studied women have blood lead concentrations above 10μgdL-1 and up to 87% above 5μgdL-1. Tailings contain between 2128 and 5988mgkg-1 of lead and represent the most conspicuous source in the area. Lead contents in indoor dust are largely variable (21.7-987mgkg-1) but only 15% of samples are above the Mexican Regulatory Guideline for urban soils (400mgkg-1). By contrast, 85% of glazed containers (range: 0.026-68.6mgkg-1) used for cooking and food storage are above the maximum 2mgL-1 of soluble lead established in the Mexican Guideline. The isotopic composition indicates that lead in the blood of 95% of the studied women can be modeled in terms of a mixing system between local ores (and derivatives), glazed pottery and Morelos bedrock, end-members, with the two former being largely the most important contributors. Only one sample shows influence of indoor paints. Indoor dust is dominated by ores and derivatives but some samples show evidence of contribution from a less radiogenic source very likely represented by interior paints. This study supports the application of lead isotopic ratios to identify potential sources and their apportionment in humans exposed to multiple sources of lead from both, natural and anthropogenic origin.

Antiviral agents are increasingly considered an option for veterinary medicine. An understanding of their mechanism of activity is important to plan their administration either as monotherapy or in combination with other agents. Previous studies have shown that the broad spectrum antiviral agent favipiravir (T-705) and its derivatives T-1105 and T-1106 are efficient inhibitors of foot-and-mouth disease virus (FMDV) replication in cell culture and in vivo. However, no mechanism for their activity against FMDV has been proposed. In the present study we show that favipiravir (T-705) can act as a lethal mutagen for FMDV in cell culture. Evidence includes virus extinction associated with increase in mutation frequency in the mutant spectrum of 860 residues of the 3D (polymerase)-coding region, and a decrease of specific infectivity while the consensus nucleotide sequence of the region analyzed remained invariant. The mutational spectrum evoked by favipiravir differs from that observed with other viruses in that no predominant transition type is observed, indicating that a movement towards A,U- or G,C-rich regions of sequence space is not a prerequisite for virus extinction. We discuss prospects for the use of favipiravir to assist in the control of FMDV, and its possible broader use in veterinary medicine as an extension of its current status as antiviral agent for human influenza virus.

El propósito del estudio se centró en conocer cuál esquema de amortización de deuda genera mayor costo financiero entre los sistemas: Francés, Alemán y Americano así como la propuesta de García-Santillán, 2014) para el contexto latino. Al final se obtiene evidencia que nos lleva a pensar que el sistema Americano es el que genera mayor costo financiero a cargo del deudor que los otros esquemas. Además el sistema de amortización de deuda alemán es el que genera el más bajo costo financiero.

Lethal mutagenesis is an antiviral approach that consists of extinguishing a virus by an excess of mutations acquired during replication in the presence of a mutagenic agent, often a nucleotide analogue. One of its advantages is its broad-spectrum nature, which renders the strategy potentially effective against emergent RNA viral infections. Here we describe the synergistic lethal mutagenesis of hepatitis C virus (HCV) by a combination of favipiravir (T-705) and ribavirin. Synergy has been documented over a broad range of analogue concentrations using the Chou-Talalay method implemented in CompuSyn graphics software, with the average dose reduction index (DRI) being above 1 (68.02 101.6 for favipiravir and 5.83 6.07 for ribavirin) and the average combination indices (CI) being below 1 (0.52 0.28). Furthermore, analogue concentrations that individually did not extinguish high-fitness HCV in 10 serial infections extinguished high-fitness HCV in 1 to 2 passages when used in combination. Although both analogues displayed a preference for G ¡ A and C ¡ U transitions, deep sequencing analysis of mutant spectra indicated a different preference of the two analogues for the mutation sites, thus unveiling a new possible synergy mechanism in lethal mutagenesis. The prospects for synergy among mutagenic nucleotides as a strategy to confront emerging viral infections are discussed, C.P. is supported by the Miguel Servet program of the Instituto de Salud Carlos III (grant CP14/00121), cofinanced by the European Regional Development Fund (ERDF). The Centro de Investigación en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) is funded by the Instituto de Salud Carlos III. The work in Madrid, Spain, was supported by grant SAF2014-52400-R from the Ministerio de Economía y Competitividad, grants SAF2017-87846-R, BFU2017-91384-EXP, and PI18/00210 from the Ministerio de Ciencia, Innovación y Universidades, grant S2013/ABI-2906 from PLATESA from the Comunidad de Madrid/FEDER, and grant P2018/BAA-4370 from PLATESA2 from the Comunidad de Madrid/FEDER. The work in Barcelona, Spain, was also funded by the Instituto de Salud Carlos III; by grant PI16/00337, cofinanced by the European Regional Development Fund (ERDF); and by the Centro para el Desarrollo Tecnológico Industrial (CDTI), Spanish Ministry of Economics and Competitiveness (MINECO) (grant IDI-20151125). Institutional grants from the Fundación Ramón Areces and Banco Santander to CBMSO are also acknowledged.

10 pags., 8 figs., 2 tabs. -- Published as part of The Journal of Physical Chemistry virtual special issue “F. Javier Aoiz Festschrift”, Rotationally inelastic collisions of O2 with He in the 10−34 K thermal range are investigated by means of an experimental procedure based on supersonic gas jets probed by Raman spectroscopy. The procedure employs a kinetic master equation (MEQ) that describes the time evolution of the rotational populations of O2 along supersonic jets of O2 and He mixtures. The MEQ is expressed in terms of experimental quantities (number density and rotational populations) measured here, and state-to-state rate coefficients for the O2:He inelastic collisions calculated here, plus those for O2:O2 collisions from the literature. An agreement with the experiments is accomplished for temperatures between 10 and 34 K. Within this thermal range, the role of the fine structure due to electron spin in the collision dynamics of O2 is discussed., This work has been supported by the Spanish Ministerio de Economıá y Competitividad (MINECO), grants FIS2017- 84391-C2 and CONSOLIDER-ASTROMOL CSD2009-0038. F.G. thanks the Spanish Regional Government of Andalucıá for a postdoctoral grant (project P07-FQM-2600).

Alzheimer's disease is a progressive neurodegenerative disorder characterized by the abnormal processing of the Tau and the amyloid precursor proteins. The unusual aggregation of Tau is based on the formation of intermolecular β-sheets through two motifs

Liver-specific insulin resistance is associated with the development of the main challenges in metabolism, resulting in dyslipidemia, hyperinsulinemia and hyperglycemia. In vitro models developed for researching hepatic insulin resistance are limited and employed cell lines without similar characteristics to primary human hepatocytes. The Huh7 cell line has been established as a model with similar characteristics to primary human hepatocytes. In addition, it has been identified in the Huh7 cell line that infection with the hepatitis C virus induces insulin resistance. Therefore, we analyzed the induction of insulin resistance (IR) in the Huh7 cell line using an overdosage of insulin and treatment with metformin for its reversal, with the purpose of establishing an insulin resistance model useful for metabolic and pharmacological studies. Insulin-resistant Huh7 (Huh7-IR) showed a reduction in Glut2, glycogen levels, and glucose uptake stimulated by insulin or tyrosine phosphorylation from the β-fraction of insulin receptor post-insulin stimulation, with an increase of glucose production and lipid intracellular content. These biomarkers are frequently observed in insulin-resistant hepatic cells. Moreover, treatment of Huh7-IR with 0.5, 1 or 2 mM of metformin by 24 h decreased the biomarkers associated with an insulin-resistant state. These results suggest that Huh7-IR could be used as an in vitro system to research hepatic insulin resistance in metabolic and pharmacological studies.

Objectives: Key neurobiological factors contribute to vulnerability to nonsuicidal self-injury (NSSI) among adolescents and how they respond to treatment targeted to reduce such behaviors....

Background: The risk of cardiovascular disease in rheumatoid arthritis (RA) patients is 1.5 times higher compared to the general population. Some factors relationships to cardiovascular disease in RA are high clinic activity of the disease, the autoantibodies-positive, the disease duration and pharmacological treatment1, as well as single nucleotide polymorphisms. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism and is considered a drug-metabolizing enzyme; MTHFR 677C/T polymorphism was described leading to reduced enzyme activity, increasing serum concentration of homocysteine, an intermediate product of methotrexate metabolism. Paraoxonase 1 (PON1) is a multifunctional enzyme that can detoxify through its homocysteine thiolactonase activity, the polymorphism identified in the position PON1 -108C/T exerts effects on serum activity and expression levels. Objectives: We evaluate the association between the interaction MTHFR 677C/T and PON1 -108C/T polymorphisms and cardiovascular risk (CVR) in RA patients. Methods: A cross-sectional study was performed including 250 RA patients diagnosed according to ACR/EULAR 2010 criteria, attended in a public hospital from southern Mexico. MTHFR 677C/T and PON1 -108C/T genotypes were determined by PCR-RFLP method. The clinic and metabolic parameters were evaluated. CVR was defined using different diagnostic tools. Logistic regression models were used to evaluate the association between interaction polymorphisms and CVR. Results: We show high CVR in a variable prevalence according to diagnostics tools: TGs/HDL-c (64.8%), Castelli (50%) and Kannel (43%). Alleles frequency of 667C/T were 33% for C and 67% for T allele; PON1-108C/T 52% for C and 43% for T allele. In a multiple regression model adjusting by duration of disease, pharmacological therapy and DAS28-hsCRP score, carriers of the 667TT and -108CC genotypes had higher CVR according to TGs/HDL-c (>3%) (OR=4.68, p=0.019), Castelli (>3%) (OR=2.99, p=0.03) and Kannel index (>4.5% in woman and >5% in men) (OR=2.03, p=0.13). Conclusion: Our results demonstrate an interaction between MTHFR 677C/T and PON1 -108C/T polymorphisms on the CVR, associated to atherogenic indexes in RA patients from southern Mexico. References [1] Mackey RH, Kuller LH, Moreland LW. Cardiovascular disease risk in patients with rheumatic diseases. Clin Geriatr Med. 2017;33(1):105-117. doi: 10.1016/j.cger.2016.08.008. Disclosure of Interests: None declared

Breast cancer is the most common invasive neoplasia, and the second leading cause of death associated with cancer in women worldwide. Mammary tumorigenesis is severely linked to obesity, the potential connection is leptin. Leptin is a hormone secreted by adipocytes, which contributes to the progression of breast cancer. Cell migration, metalloproteases secretion, and invasion are cellular processes associated with various stages of metastasis. These processes are regulated by the kinases FAK and Src. In this study, we utilized the breast cancer cell lines MCF7 and MDA-MB-231 to determine the effect of leptin on FAK and Src kinases activation, cell migration, metalloproteases secretion, and invasion. By Western blot we found that leptin activates FAK and Src, and induces the localization of FAK to the focal adhesions. Specific inhibitors of FAK and Src showed that the effect exerted by leptin in cell migration, and invasion in breast cancer cells is dependent on these kinases. Moreover, by gelatin zymmography we established that leptin promotes the secretion of the extracellular matrix remodelers, MMP-2 and MMP-9, in a FAK and Src dependent manner. Our findings strongly suggest that leptin promotes the development of a more aggressive invasive phenotype in mammary cancer cells.

Anxiety about mathematics is a phenomenon that occurs regardless of age, gender, or area of professional study. This research provides an overview of this phenomenon in Mexico, as experienced by undergraduate students in economics, a science that requires significant use of mathematics. The study is cross-sectional and not experimental and makes use of the ANOVA technique. The results obtained from the application of the Abbreviated Version of the Mathematics Anxiety Rating Scale (AMARS) to 381 students nationwide provide evidence of the existence of this phenomenon in more than 50% of the sample and indicate differences in terms of gender, region of origin, and type of university.

La investigación que se presenta en este trabajo se ha realizado con alumnado de tercer curso del grado en maestro de educación infantil del Centro Universitario “Sagrada Familia” de Úbeda (Adscrito a la Universidad de Jaén). Se estudió la motivación que este alumnado presentaba antes, durante y después de realizar un BreakOut Edu para alumnos de 5 años. En este proceso, se fomentó la coordinación docente ya que implicaba a profesorado de distintas asignaturas del grado que actuaron como guías de apoyo al alumnado en todo momento, actuando de forma coordinada para que la actividad englobara contenidos de todas ellas. La metodología de investigación se basó en la puesta en práctica de esta actividad, encuestando después al alumnado participante. Los datos fueron analizados posteriormente con el programa Nvivo 11Pro para datos cualitativos. Los resultados muestran que este tipo de actuaciones aumenta en gran medida la motivación del alumnado y a su vez favorece la adquisición de contenidos.

Despite the fact that mathematics is present and necessary in any area of daily life, students have little interest in developing mathematical skills. Hence, the aim of the study is to check whether the variables motivation, usefulness, anxiety, confidence, and liking are determining in their attitude towards mathematics. The present research is quantitative, not experimental, transversal and confirmatory. The sample was of 362 students belonging to the Multidisciplinary Academic Area Middle Zone, in the city of Rioverde, San Luis Potosi. The participating students are from the Administration (154), Public Accounting and Finance (112) and Marketing (96). The data was collected through the test designed by Auzmendi (1992) the Attitude towards Mathematics Scale (EAM), which consists of 25 items. The results indicate that although it is true that students show a positive attitude (liking), they also admit that it causes them anxiety because they do not feel confident in their mathematical ability. It is necessary to add that the student does not feel any stimulus to have an interest in the subject.

Objective This study is a pragmatic randomized controlled trial, which compares the effectiveness of an adapted form of Dialectical Behavior Therapy for Adolescents (DBT-A) and treatment as usual plus group sessions (TAU + GS) to reduce suicidal risk for adolescents in a community health mental clinic. Method Thirty-five adolescents from a community outpatient clinic, with repetitive NSSI alone or with SA over the last 12 months and with current high suicide risk as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS), were enrolled. Participants were randomly assigned to undergo either DBT-A (n = 18) or TAU + GT (n = 17) treatments over a 16-week period. Primary outcomes were the difference between NSSI and SA recorded during the first 4 weeks and the final 4 weeks of treatment. Secondary outcomes included changes in Children's Global Assessment Scale (C-GAS), Suicidal Ideation Questionnaire (SIQ-JR), and Beck Depression Inventory-II (BDI-II). Results Dialectical Behavior Therapy for Adolescents was more effective than TAU + GS at reducing NSSI, use of antipsychotics, and improving C-GAS. No SAs were reported in the two groups at the end of the treatment. Both treatments were equally effective in decreasing SIQ-JR and BDI-II scores. Conclusions These findings support the feasibility and effectiveness of DBT-A for adolescents at high risk of suicide in community settings.

Effective control of COVID-19 requires antivirals directed against SARS-CoV-2. We assessed ten hepatitis C virus (HCV) protease-inhibitor drugs as potential SARS-CoV-2 antivirals. There is a striking structural similarity of the substrate binding clefts of SARS-CoV-2 main protease (Mpro) and HCV NS3/4A protease. Virtual docking experiments show that these HCV drugs can potentially bind into the Mpro binding cleft. We show that seven HCV drugs inhibit both SARS-CoV-2 Mpro protease activity and SARS-CoV-2 virus replication in Vero and/or human cells. However, their Mpro inhibiting activities did not correlate with their antiviral activities. This conundrum was resolved by demonstrating that four HCV protease inhibitor drugs, simeprevir, vaniprevir, paritaprevir, and grazoprevir inhibit the SARS CoV-2 papain-like protease (PLpro). HCV drugs that inhibit PLpro synergize with the viral polymerase inhibitor remdesivir to inhibit virus replication, increasing remdesivir’s antiviral activity as much as 10-fold, while those that only inhibit Mpro do not synergize with remdesivir., Graphical Abstract, Bafna et al. report that several available hepatitis C virus drugs inhibit the SARS-CoV-2 Mpro and/or PLpro proteases, and SARS-CoV-2 replication in cell culture. The four HCV drugs that inhibit PLpro enzyme activity also synergize with remdesivir to inhibit virus replication, increasing remdesivir and HCV drugs antiviral activity.