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DNA knots are deleterious for living cells if not removed. Several theoretical and simulation approaches address the question of how topoisomerases select the intermolecular passages that preferentially lead to unknotting rather than to the knotting of randomly fluctuating DNA molecules, but the formation of knots in vivo remains poorly understood. DNA knots form in vivo in non-replicating and replicating molecules, and supercoiling as well as intertwining are thought to play a crucial role in both the formation and resolution of DNA knots by topoisomerase IV. To confirm this idea, we used two-dimensional agarose gel electrophoresis run with different concentrations of chloroquine to demonstrate that non-replicating pBR322 plasmids grown in a topoisomerase I-defective E. coli strain (RS2λ) were more negatively supercoiled than in a wild-type strain (W3110) and, concurrently, showed significantly fewer knots. In this way, using wild-type and E. coli mutant strains, we confirmed that one of the biological functions of DNA supercoiling is to reduce the formation of DNA knots.

Background/Objectives: Choline and essential fatty acids (EFA) are vital for fetal brain development, supporting pregnancy, and maintaining hormonal balance. They also promote overall health. The childbearing years present a window of opportunity to increase the intake of these key nutrients and develop healthy dietary habits. The aims of this study were to evaluate the intake of choline and EFA in women of childbearing age (15–49 years old), identify their food sources and determine if supplements containing choline and EFA were available across the Estudio Latinoamericano de Nutrición y Salud (ELANS) countries. Methods: Survey data were collected for the ELANS, including participants from Argentina, Brazil, Chile, Colombia, Costa Rica, Ecuador, Peru, and Venezuela (n = 9218; 15–65 years old). Women of childbearing age were extracted from the largest database (n = 3704). Results: In general, choline intake was inadequate in all countries, while EFA intake was normal or above requirements. Chile had the lowest intake of choline, and Colombia had the highest. The results showed that some countries had more inadequate choline intake than others. Consuming a larger quantity of eggs helped reduce choline inadequacy, as did including eggs and fish in the diet. The intake of EFA, including ALA, EPA, and DHA, showed variability. The contributions of EPA and DHA were lower than that of ALA, and the results differed by age group. Conclusions: choline intake is inadequate, and EFA intake is variable among women of childbearing age in the ELANS study. More awareness and education are needed to achieve better intake of these nutrients.

To date, the need for biomaterials capable of improving the treatment of chronic skin wounds remains a clinical challenge. The aim of the present work is to formulate and characterize chitosan (Cs)/hydrolyzed collagen (HC) films as potential biomaterials with improved mechanical and hydration performances compared to single component formulations. Films were made by the solvent casting method, with or without glycerin and/or PEG1500 as plasticizers, resulting in a total of eight formulations. All films were characterized by their physico-chemical characteristics and their mechanical and hydration features. A full factorial design was also used to statistically assess the effect of HC concentration, type and concentration of plasticizers and their possible interactions on mechanical and swelling behaviors. Solid state characterization confirmed the hybrid nature of the films, with suggested electrostatic interactions between Cs and HC. Mechanical and swelling properties, along with the analysis of the experimental design, allowed the identification of formulations containing high HC concentration (2% w/v) and glycerin or glycerin/PEG1500 as more suitable candidates for skin wound treatment. Finally, viability assay of immortalized human keratinocytes (HaCaT) showed no statistical differences in cell survival compared to the complete culture medium, suggesting their potential as a promising tool for biomedical applications.

Topoisomerase I (TopoI) in Streptococcus pneumoniae, encoded by topA, is a suitable target for drug development. Seconeolitsine (SCN) is a new antibiotic that specifically blocks this enzyme. We obtained the topARA mutant, which encodes an enzyme less active than the wild type (topAWT) and more resistant to SCN inhibition. Likely due to the essentiality of TopoI, we were unable to replace the topAWT allele by the mutant topARA version. We compared the in vivo activity of TopoIRA and TopoIWT using regulated overexpression strains, whose genes were either under the control of a moderately (PZn) or a highly active promoter (PMal). Overproduction of TopoIRA impaired growth, increased SCN resistance and, in the presence of the gyrase inhibitor novobiocin (NOV), caused lower relaxation than TopoIWT. Differential transcriptomes were observed when the topAWT and topARA expression levels were increased about 5-fold. However, higher increases (10–15 times), produced a similar transcriptome, affecting about 52% of the genome, and correlating with a high DNA relaxation level with most responsive genes locating in topological domains. These results confirmed that TopoI is indeed the target of SCN in S. pneumoniae and show the important role of TopoI in global transcription, supporting its suitability as an antibiotic target.

The healing process of chronic wounds continues to be a current clinical challenge, worsened by the risk of microbial infections and bacterial resistance to the most frequent antibiotics. In this work, non-antibiotic nanohybrids based on chlorhexidine dihydrochloride and clay minerals have been developed in order to design advanced therapeutic systems aimed to enhance wound healing in chronic lesions. To prepare the nanohybrids, two methodologies have been compared: the intercalation solution procedure and the spray-drying technique, the latter as a one-step process able to reduce preparation times. Nanohybrids were then fully studied by solid state characterization techniques. Computational calculations were also performed to assess the interactions between the drug and the clays at the molecular level. In vitro human fibroblast biocompatibility and antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa were assessed to check biocompatibility and potential microbicidal effects of the obtained nanomaterials. The results demonstrated the effective organic/inorganic character of the nanohybrids with homogeneous drug distribution into the clayey structures, which had been confirmed by classical mechanics calculations. Good biocompatibility and microbicidal effects were also observed, especially for the spray-dried nanohybrids. It was suggested that it could be due to a greater contact area with target cells and bacterial suspensions.

Saltwater intrusion into groundwater systems is a problem worldwide and is induced mainly by human activities, such as groundwater overexploitation and climate change. The coastal Los Planes aquifer in the southern part of the Baja California Peninsula (Mexico) is affected by seawater intrusion due to more than 40 years of groundwater overexploitation. A dataset of 55 samples was compiled, including 18 samples from our campaigns between 2014 and 2016. Several methods exist to define the impact of seawater in a coastal aquifer, such as the “seawater fraction”, the “Chloro-Alkaline Indices”, the “Hydrochemical Facies Evolution Diagram”, and the “Saltwater Mixing Index”. These methods provide reasonable results for most of the coastal zone of the Los Planes aquifer. A slight increase in mineralization was observed from 2014 to 2016 compared with the situation in 2003. However, in its northwestern part, samples from hydrothermal wells were not recognized by these methods. Here, the aquifer is affected mainly by thermal water with elevated mineralization, introduced through the El Sargento fault, a main fault, which cuts through the study area in the north–south direction. By considering known hydrothermal manifestations in the interpretation, samples could be classified as a combination of four end-members: fresh groundwater, seawater, and the composition of two types of thermal water. One thermal endmember with very low mineralization coincides with the thermal water described from the Los Cabos Block, where meteoric water represents the source (found in the Sierra la Laguna). The second endmember is comparable to coastal thermal manifestations where seawater represents the main source. Therefore, the higher mineralization in the northwestern zone is the result of the mobilization of thermal groundwater and direct mixing with seawater, which is introduced locally at the coast due to overextraction. This finding is important for future management strategies of the aquifer.

For many years, convolutional neural networks dominated the field of computer vision, not least in the medical field, where problems such as image segmentation were addressed by such networks as the U-Net. The arrival of self-attention-based networks to the field of computer vision through ViTs seems to have changed the trend of using standard convolutions. Throughout this work, we apply different architectures such as U-Net, ViTs and ConvMixer, to compare their performance on a medical semantic segmentation problem. All the models have been trained from scratch on the DRIVE dataset and evaluated on their private counterparts to assess which of the models performed better in the segmentation problem. Our major contribution is showing that the best-performing model (ConvMixer) is the one that shares the approach from the ViT (processing images as patches) while maintaining the foundational blocks (convolutions) from the U-Net. This mixture does not only produce better results (DICE=0.83) than both ViTs (0.80/0.077 for UNETR/SWIN-Unet) and the U-Net (0.82) on their own but reduces considerably the number of parameters (2.97M against 104M/27M and 31M, respectively), showing that there is no need to systematically use large models for solving image problems where smaller architectures with the optimal pieces can get better results.

The DNA topoisomerases gyrase and topoisomerase I as well as the nucleoid-associated protein HU maintain supercoiling levels in Streptococcus pneumoniae, a main human pathogen. Here, we characterized, for the first time, a topoisomerase I regulator protein (StaR). In the presence of sub-inhibitory novobiocin concentrations, which inhibit gyrase activity, higher doubling times were observed in a strain lacking staR, and in two strains in which StaR was over-expressed either under the control of the ZnSO4-inducible PZn promoter (strain ΔstaRPZnstaR) or of the maltose-inducible PMal promoter (strain ΔstaRpLS1ROMstaR). These results suggest that StaR has a direct role in novobiocin susceptibility and that the StaR level needs to be maintained within a narrow range. Treatment of ΔstaRPZnstaR with inhibitory novobiocin concentrations resulted in a change of the negative DNA supercoiling density (σ) in vivo, which was higher in the absence of StaR (σ = −0.049) than when StaR was overproduced (σ = −0.045). We have located this protein in the nucleoid by using super-resolution confocal microscopy. Through in vitro activity assays, we demonstrated that StaR stimulates TopoI relaxation activity, while it has no effect on gyrase activity. Interaction between TopoI and StaR was detected both in vitro and in vivo by co-immunoprecipitation. No alteration of the transcriptome was associated with StaR amount variation. The results suggest that StaR is a new streptococcal nucleoid-associated protein that activates topoisomerase I activity by direct protein-protein interaction.

The acquisition of resistance to traditional chemotherapy and the chemoresistant metastatic relapse of minimal residual disease both play a key role in the treatment failure and poor prognosis of cancer. Understanding how cancer cells overcome chemotherapy-induced cell death is critical to improve patient survival rate. Here, we briefly describe the technical approach directed at obtaining chemoresistant cell lines and we will focus on the main defense mechanisms against common chemotherapy triggers by tumor cells. Such as, the alteration of drug influx/efflux, the enhancement of drug metabolic neutralization, the improvement of DNA-repair mechanisms, the inhibition of apoptosis-related cell death, and the role of p53 and reactive oxygen species (ROS) levels in chemoresistance. Furthermore, we will focus on cancer stem cells (CSCs), the cell population that subsists after chemotherapy, increasing drug resistance by different processes such as epithelial-mesenchymal transition (EMT), an enhanced DNA repair machinery, and the capacity to avoid apoptosis mediated by BCL2 family proteins, such as BCL-XL, and the flexibility of their metabolism. Finally, we will review the latest approaches aimed at decreasing CSCs. Nevertheless, the development of long-term therapies to manage and control CSCs populations within the tumors is still necessary.

Dietary protein intake is vital to life. Here we sought to characterize dietary sources of protein in eight Latin American countries. Survey data were collected for Estudio Latinoamericano de Nutrición y Salud (ELANS); participants were from Argentina, Brazil, Chile, Colombia, Costa Rica, Ecuador, Peru, and Venezuela (n = 9218, 15–65 years old). The primary aim of this analysis was to quantify per-person daily protein consumption by country and sociodemographic factors. Secondary aims: to quantify proportional intake of proteins by source, amount and processing, and to determine the adequacy of protein/essential amino acid intake. Younger groups (adolescents 15–19 years, adults 20–33 years) had the highest intake of proteins; middle-aged adults (34–49 years) had a lower intake, and older adults (50–65 years) had a strikingly lower intake. Protein consumption was higher in men than women. Animal proteins comprised nearly 70% of total daily protein intake in Argentina and Venezuela, contrasting with

TRPM8 is a non-selective cation channel expressed in primary sensory neurons and other tissues, including the prostate and urothelium. Its participation in different physiological and pathological processes such as thermoregulation, pain, itch, inflammation and cancer has been widely described, making it a promising target for therapeutic approaches. The detection and quantification of TRPM8 seems crucial for advancing the knowledge of the mechanisms underlying its role in these pathophysiological conditions. Antibody-based techniques are commonly used for protein detection and quantification, although their performance with many ion channels, including TRPM8, is suboptimal. Thus, the search for reliable antibodies is of utmost importance. In this study, we characterized the performance of six TRPM8 commercial antibodies in three immunodetection techniques: Western blot, immunocytochemistry and immunohistochemistry. Different outcomes were obtained for the tested antibodies; two of them proved to be successful in detecting TRPM8 in the three approaches while, in the conditions tested, the other four were acceptable only for specific techniques. Considering our results, we offer some insight into the usefulness of these antibodies for the detection of TRPM8 depending on the methodology of choice.

The impacts of climate change put pressure onto environmental and natural resources, which in turn increases the vulnerability of ecosystems and human communities. This makes social participation essential for biodiversity conservation. This article addresses the community perceptions of the adaptations made to climate change in the El Vizcaino Biosphere Reserve (REBIVI), in Baja California Sur (Mexico), one of the largest natural protected areas in Latin America. Workshops with local communities defined the Socio-ecological Assets for Conservation (SEACs) and prioritized the adaptation strategies and actions by multicriteria analysis. The conclusions point out that a combination of ecosystem-based adaptation (EbA) and communities-based adaptation (CbA) is the most appropriate pathway to affront the adverse impacts of climate change. Thus, a socioecological approach for land and biodiversity use planning has to be implemented if both human welfare and conservation are to be effectively promoted. The process is necessary and very important, as is the participation of the local residents in the implementation and monitoring of the adaptation actions.

The increase in cancer incidences shows that there is a need to better understand tumour heterogeneity to achieve efficient treatments. Interestingly, there are several common features among almost all types of cancers, with chronic inflammation induction and deaminase dysfunctions singled out. Deaminases are a family of enzymes with nucleotide-editing capacity, which are classified into two main groups: DNA-based and RNA-based. Remarkably, a close relationship between inflammation and the dysregulation of these molecules has been widely documented, which may explain the characteristic intratumor heterogeneity, both at DNA and transcriptional levels. Indeed, heterogeneity in cancer makes it difficult to establish a unique tumour progression model. Currently, there are three main cancer models—stochastic, hierarchic, and dynamic—although there is no consensus on which one better resembles cancer biology because they are usually overly simplified. Here, to accurately explain tumour progression, we propose interactions among chronic inflammation, deaminases dysregulation, intratumor genetic heterogeneity, cancer phenotypic plasticity, and even the previously proposed appearance of cancer stem-like cell populations in the edges of advanced solid tumour masses (instead of being the cells of origin of primary malignancies). The new tumour development model proposed in this study does not contradict previously accepted models and it may open up a window to interesting therapeutic approaches.

DNA topoisomerases are the enzymes that regulate DNA topology in all living cells. Since the discovery and purification of ω (omega), when the first were topoisomerase identified, the function of many topoisomerases has been examined. However, their ability to relax supercoiling and unlink the pre-catenanes of partially replicated molecules has received little attention. Here, we used two-dimensional agarose gel electrophoresis to test the function of three type II DNA topoisomerases in vitro: the prokaryotic DNA gyrase, topoisomerase IV and the human topoisomerase 2α. We examined the proficiency of these topoisomerases on a partially replicated bacterial plasmid: pBR-TerE@AatII, with an unidirectional replicating fork, stalled when approximately half of the plasmid had been replicated in vivo. DNA was isolated from two strains of Escherichia coli: DH5αF’ and parE10. These experiments allowed us to assess, for the first time, the efficiency of the topoisomerases examined to resolve supercoiling and pre-catenanes in partially replicated molecules and fully replicated catenanes formed in vivo. The results obtained revealed the preferential functions and also some redundancy in the abilities of these DNA topoisomerases in vitro.

Telomere length (TL) has been associated with aging and is determined by lifestyle. However, the mechanisms by which a dietary pattern such as the Mediterranean diet (MedDiet) affects TL homeostasis are still unknown. Our aim was to analyse the effect of an energy-restricted MedDiet with physical activity promotion (intervention group) versus an unrestricted-caloric MedDiet with no weight-loss advice (control group) on TL and 8-hydroxydeoxyguanosine (8-OHdG) plasma levels. In total, 80 non-diabetic participants with metabolic syndrome were randomly selected from the PREDIMED (PREvención con DIeta MEDiterránea)-Plus-Reus study. TL was measured by a hybridisation method and 8-OHdG levels by ELISA at baseline and after one year of intervention. Linear mixed models (LMM)—raw and after adjusting for potential confounders—were used to examine the associations between TL or 8-OHdG plasma levels by intervention group and/or time. A total of 69 subjects with available DNA samples were included in the analyses. A significant β-coefficient was found for time towards increasing values through the year of follow-up for TL (unadjusted β of 0.740 (95% CI: 0.529 to 0.951), and multivariable model β of 0.700 (95% CI: 0.477 to 0.922)). No significant βs were found, neither for the intervention group nor for the interaction between the intervention group and time. Regarding 8-OHdG plasma levels, no significant βs were found for the intervention group, time, and its interaction. Our results suggest that MedDiet could have an important role in preventing telomere shortening, but calorie restriction and exercise promotion did not provide an additional advantage concerning telomere length after one year of MedDiet intervention.

A comprehensive database was built to examine the spatial diversity patterns of polychaete species from the continental shelf in Southern Gulf of Mexico. Using Cluster and nMDS analysis we found the composition of polychaete species to be different between the terrigenous and carbonate regions of the Gulf. To test the relative importance of spatial and environmental components in the polychaetae community structure in the Southern Gulf of Mexico, we examined the spatial relationships between polychaetae assemblages and environmental variables over broad geographical scales. A distance-based redundancy analysis (dbRDA) and variation partitioning was used to quantify the relative importance of these explanatory variables on the spatial variations of species richness and composition. Variation partitioning is an important tool to investigate the importance of spatial structure to species distribution in communities, but it has not yet been used in marine ecosystems. The significance level of spatial and environmental components to the distribution of polychaete species showed that the combined effect of spatial processes and sediment characteristics explained a higher percentage of variance than those parameters could alone.

The increased prevalence of atrial fibrillation (AF) and heart failure (HF) highlights the need to better understand the mechanisms underlying these cardiovascular diseases (CVDs). In the present study, we aimed to evaluate the association between glycolysis-related metabolites and the risk of AF and HF in a Mediterranean population at high risk of CVD. We used two case–control studies nested within the PREDIMED trial. A total of 512 incident AF cases matched to 734 controls, and 334 incident HF cases matched to 508 controls, were included. Plasma metabolites were quantified by using hydrophilic interaction liquid chromatography coupled with high-resolution negative ion mode MS detection. Conditional logistic regression analyses were performed. The results showed no association between baseline plasma glycolysis intermediates and other related metabolites with AF. Only phosphoglycerate was associated with a higher risk of HF (OR for 1 SD increase: 1.28; 95% CI: 1.06, 1.53). The present findings do not support a role of the glycolysis pathway in the pathogenesis of AF. However, the increased risk of HF associated with phosphoglycerate requires further studies.

Geo-thermalism has been widely recognized on the Baja California Peninsula, especially during the last decade. The current research, carried out on Bahia Concepcion, evidences the existence of geothermal springs, which get recharged mainly by groundwater and seawater. The groundwater can be characterized as Na+-Cl− and Na+-HCO3− type, with a pH value close to neutrality. The slightly more acidic thermal sites presented temperatures between 32 °C and 59 °C at the surface. Based on the relationships of the Cl− and Br−, as well as the B/Cl−, and Br−/Cl− ratios, seawater was recognized as the main source of salinity. The spatial distribution is explained directly through marine intrusion, or via sprays and aerosols within the rainwater. Seawater ratios in thermal springs varied from 62% to 83%, corresponding mainly to shallow inflow, but seawater inputs into the deep thermal reservoir were also recognized. Temperatures in the geothermal deep reservoir were inferred from 114 to 209 °C, calculated through the SiO2 and Na+-K+ geothermometers. In addition to previously reported thermal sites at Bahía Concepción, and based on their elevated temperatures, two new sites were identified. Another five springs do not fulfill the commonly used definition, based on differential temperature, but show the typical hydrogeochemical signature of thermal water. A new approach to identify this low-temperature geothermal-influenced spring water by its hydrogeochemical composition is presented, for which the term “Masked Geothermal Waters” (MGW) is introduced. Our findings increase the area of the geothermal anomaly and, therefore, the potential of geothermal resources. The approach proposed in this research will also be useful to identify more MGW in other coastal areas.

One-year dietary quality change according to the preceding maximum weight in a lifestyle intervention program (PREDIMED-Plus trial, 55–75-year-old overweight or obese adults; n = 5695) was assessed. A validated food frequency questionnaire was used to assess dietary intake. A total of 3 groups were made according to the difference between baseline measured weight and lifetime maximum reported weight: (a) participants entering the study at their maximum weight, (b) moderate weight loss maintainers (WLM), and (c) large WLM. Data were analyzed by General Linear Model. All participants improved average lifestyle. Participants entering the study at their maximum weight were the most susceptible to improve significantly their dietary quality, assessed by adherence to Mediterranean diet, DII and both healthful and unhealthful provegetarian patterns. People at maximum weight are the most benefitted in the short term by a weight management program. Long term weight loss efforts may also reduce the effect of a weight management program.

Dietary polyphenol intake is associated with improvement of metabolic disturbances. The aims of the present study are to describe dietary polyphenol intake in a population with metabolic syndrome (MetS) and to examine the association between polyphenol intake and the components of MetS. This cross-sectional analysis involved 6633 men and women included in the PREDIMED (PREvención con DIeta MEDiterranea-Plus) study. The polyphenol content of foods was estimated from the Phenol-Explorer 3.6 database. The mean of total polyphenol intake was 846 ± 318 mg/day. Except for stilbenes, women had higher polyphenol intake than men. Total polyphenol intake was higher in older participants (>70 years of age) compared to their younger counterparts. Participants with body mass index (BMI) >35 kg/m2 reported lower total polyphenol, flavonoid, and stilbene intake than those with lower BMI. Total polyphenol intake was not associated with a better profile concerning MetS components, except for high-density lipoprotein cholesterol (HDL-c), although stilbenes, lignans, and other polyphenols showed an inverse association with blood pressure, fasting plasma glucose, and triglycerides. A direct association with HDL-c was found for all subclasses except lignans and phenolic acids. To conclude, in participants with MetS, higher intake of several polyphenol subclasses was associated with a better profile of MetS components, especially HDL-c.

Background: The interaction between obesity and genetic traits on high density lipoprotein (HDL) levels has been extensively studied. The variance of serum HDL has a strong genetic heritability, although the studied variant only explains a small part of this variation. The goal of this study was to investigate the associations between the apolipoprotein type 2 (APOA2) rs3813627 single nucleotide polymorphism (SNP) and anthropometric and biochemical variables, though body mass index (BMI). Methods: This study included 153 subjects (91 overweight/obese (BMI³25 kg/m2) and 62 non-obese individuals (BMI < 25 kg/m2)). The APOA2 rs3813627 SNP was selected and genotyped. Genotype analysis was performed to analyze the associations between APOA2 SNPs and anthropometric and biochemical variables through BMI. Results: The APOA2 rs3813627 TT genotype was associated with low HDL levels in comparison with the APOA2 rs3813627 GG and GT genotype in overweight/obese individuals, but not in the non-obese subjects (p < 0.05). The same trend was observed in the apolipoprotein type 1 (APOA1) protein levels (p < 0.05). Correlation analysis revealed a negative correlation between HDL and APOA1 levels and APOA2 rs3813627 SNP under recessive model (p < 0.05). The odds ratio for low HDL levels was 3.76 and 3.94 for low APOA1 levels. The mediation analysis of APOA2 rs3813627 SNP through BMI showed a full mediation on HDL and partial mediation on APOA1 levels (p < 0.05). Bioinformatic analysis showed that rs3813627 lies in the APOA2 promoter and overlaps motifs for several bound transcription factors. Conclusion: On the basis of these data, the APOA2 rs3813627 SNP is associated with low HDL and APOA1 levels susceptibility, and this effect was mediated by an increased BMI.

Indoor position estimation has become an attractive research topic due to growing interest in location-aware services. Nevertheless, satisfying solutions have not been found with the considerations of both accuracy and system complexity. From the perspective of lightweight mobile devices, they are extremely important characteristics, because both the processor power and energy availability are limited. Hence, an indoor localization system with high computational complexity can cause complete battery drain within a few hours. In our research, we use a data mining technique named boosting to develop a localization system based on multiple weighted decision trees to predict the device location, since it has high accuracy and low computational complexity. The localization system is built using a dataset from sensor fusion, which combines the strength of radio signals from different wireless local area network access points and device orientation information from a digital compass built-in mobile device, so that extra sensors are unnecessary. Experimental results indicate that the proposed system leads to substantial improvements on computational complexity over the widely-used traditional fingerprinting methods, and it has a better accuracy than they have.

Few studies have examined the association of a wide range of metabolites with total and subtypes of coffee consumption. The aim of this study was to investigate associations of plasma metabolites with total, caffeinated, and decaffeinated coffee consumption. We also assessed the ability of metabolites to discriminate between coffee consumption categories. This is a cross-sectional analysis of 1664 participants from the PREDIMED study. Metabolites were semiquantitatively profiled using a multiplatform approach. Consumption of total coffee, caffeinated coffee and decaffeinated coffee was assessed by using a validated food frequency questionnaire. We assessed associations between 387 metabolite levels with total, caffeinated, or decaffeinated coffee consumption (≥50 mL coffee/day) using elastic net regression analysis. Ten-fold cross-validation analyses were used to estimate the discriminative accuracy of metabolites for total and subtypes of coffee. We identified different sets of metabolites associated with total coffee, caffeinated and decaffeinated coffee consumption. These metabolites consisted of lipid species (e.g., sphingomyelin, phosphatidylethanolamine, and phosphatidylcholine) or were derived from glycolysis (alpha-glycerophosphate) and polyphenol metabolism (hippurate). Other metabolites included caffeine, 5-acetylamino-6-amino-3-methyluracil, cotinine, kynurenic acid, glycocholate, lactate, and allantoin. The area under the curve (AUC) was 0.60 (95% CI 0.56−0.64), 0.78 (95% CI 0.75−0.81) and 0.52 (95% CI 0.49−0.55), in the multimetabolite model, for total, caffeinated, and decaffeinated coffee consumption, respectively. Our comprehensive metabolic analysis did not result in a new, reliable potential set of metabolites for coffee consumption.

Magnesium (Mg) is an essential dietary element for humans involved in key biological processes. A growing body of evidence from epidemiological studies, randomized controlled trials (RCTs) and meta-analyses have indicated inverse associations between Mg intake and cardiovascular diseases (CVD). The present review aims to summarize recent scientific evidence on the topic, with a focus on data from epidemiological studies assessing the associations between Mg intake and major cardiovascular (CV) risk factors and CVD. We also aimed to review current literature on circulating Mg and CVD, as well as potential biological processes underlying these observations. We concluded that high Mg intake is associated with lower risk of major CV risk factors (mainly metabolic syndrome, diabetes and hypertension), stroke and total CVD. Higher levels of circulating Mg are associated with lower risk of CVD, mainly ischemic heart disease and coronary heart disease. Further, RCTs and prospective studies would help to clarify whether Mg intake and Mg circulating levels may also protect against other CVDs and CVD death.

Since Lotfi A. Zadeh introduced the concept of fuzzy sets in 1965, many authors have devoted their efforts to the study of these new sets, both from a theoretical and applied point of view. Fuzzy sets were later extended in order to get more adequate and flexible models of inference processes, where uncertainty, imprecision or vagueness is present. Type 2 fuzzy sets comprise one of such extensions. In this paper, we introduce and study an extension of the fuzzy numbers (type 1), the type 2 generalized fuzzy numbers and type 2 fuzzy numbers. Moreover, we also define a partial order on these sets, which extends into these sets the usual order on real numbers, which undoubtedly becomes a new option to be taken into account in the existing total preorders for ranking interval type 2 fuzzy numbers, which are a subset of type 2 generalized fuzzy numbers.

The present study examines the imprint of salt tectonics on carbonate depositional patterns of the Ionian zone platform edge to slope transition. The study area is part of an overturned rim syncline adjacent to a salt diapir. The Ionian zone is made up of three distinct stratigraphic sequences (pre-, syn- and post-rift sequences) represented by evaporites and shallow water carbonates at the base that pass gradually to a sequence consisting of pelagic limestones with shale intervals. In the study area, six cross sections were constructed, mainly covering the edge-to-slope overturned succession of Early Cretaceous to Eocene carbonates (post-rift stage) in the northern limb of the syncline. In the measured sections, abrupt changes in sediment texture resulted in the formation of distinct, thick-bedded carbonate layers, identified as packstones to grainstones–floatstones, with abundant fossil fragments, indicating deposition by debrites in a platform slope or slope-toe environment. Planar and ripple cross-lamination also suggest the involvement of turbidity currents in the depositional process. In the upper levels of the Lower Cretaceous carbonates, chert bodies with irregular shapes indicate soft sediment deformation due to instability of the slope triggered by salt intrusion. Internal unconformities identified in the field and in the available seismic data combined with the vertical to overturned dipping of the strata correspond to a basal megaflap configuration. Syn-sedimentary deformation resulted in the accumulation of debritic and turbiditic layers, while the compressional regime established in the area from the Late Cretaceous to Early Eocene enhanced the fracture porosity of carbonates, which could eventually affect the reservoir properties.

Latin American (LA) women have been exposed to demographic and epidemiologic changes that have transformed their lifestyle, with increasing sedentary and unhealthy eating behaviors. We aimed to identify characteristics of LA women to inform public policies that would benefit these women and their future children. The Latin American Study of Nutrition and Health (ELANS) is a multicenter cross-sectional study of representative samples in eight Latin American countries (n = 9218) with a standardized protocol to investigate dietary intake, anthropometric variables, physical activity, and socioeconomic characteristics. Here we included the subsample of all 3254 women of childbearing age (15 to

Professional development for teachers is fundamental in the configuration and functioning of smart schools. This paper aims to characterize professional development with the participation of compulsory secondary teachers in Spain and to detect key factors in the functioning and organization of schools associated with higher levels of ongoing teacher training. A cross-cutting non-experimental design was used to conduct a secondary analysis of data from PISA 2018 tests, including over 20,000 teachers and more than 1000 schools in Spain. Descriptive results show great variability in teachers’ commitment to their professional development; this variability is not associated with the grouping of teachers by school. The decision tree model completed with data mining tools shows that intensive professional teacher development in schools is associated with a better school climate and higher levels of innovation, cooperation, taking on shared goals and responsibilities, and leadership distributed among the education community. The conclusions highlight the importance of ongoing teacher training and how this improves educational quality in schools.

Chili pepper is produced by family farmers in central Chile incorporating modern technologies and maintaining traditional practices. Although chili pepper is deeply rooted in the local culture, the agricultural system supporting its production and the germplasm involved are poorly studied. This work focused on two main landraces lacking information about what features (agronomic, morphological and chemical) distinguish them and how distinct they are. It is also of high importance to deepen our understanding of the agricultural system and the aspects that may affect its sustainability. An integrated approach was applied for the evaluation of social characteristics of farmers, the growing system, morphological traits, and selected chemical components. Between landraces, flower and fruit morphology was clearly distinct. Total phenolic content, antioxidant capacity and total carotenoid content showed higher values in fruits of cacho de cabra than in chileno negro. Both landraces had a higher total phenolic content than other Capsicum cultivars in the world. Farmers ascribe distinct attributes for the landraces regarding agronomic performance, fruit quality and processing applications. Characteristics that may affect the sustainability of the agricultural system are small farm size, relatives working as employees, and low farmers’ educational attainment. The study landraces are distinct and represent unique genetic material produced in an agricultural system facing important challenges where farmers have adapted to socio-economic pressures, externalizing plant production, reducing harvest costs, and developing innovations in product and marketing.