Functional characterization of QT interval associated SCN5A enhancer variants identify combined additive effects.

Several empirical and theoretical studies suggest presence of multiple enhancers per gene that collectively regulate gene expression, and that common sequence variation impacting on the activities of these enhancers is a major source of inter-individual variability in gene expression. However, for vast majority of genes, enhancers and the underlying regulatory variation remains unknown. Even for the genes with well-characterized enhancers, the nature of the combined effects from multiple enhancers and their variants, when known, on gene expression regulation remains unexplored. Here, we have evaluated the combined effects from five SCN5A enhancers and their regulatory variants that are known to collectively correlate with SCN5A cardiac expression and underlie QT interval association in the general population. Using small deletions centered at the regulatory variants in episomal reporter assays in a mouse cardiomyocyte cell line we demonstrate that the variants and their flanking sequences play critical role in individual enhancer activities, likely being a transcription factor (TF) binding site. By performing oligonucleotide-based pulldown assays on predicted TFs we identify the TFs likely driving allele-specific enhancer activities. Using all 32 possible allelic synthetic constructs in reporter assays, representing the five biallelic enhancers in tandem in their genomic order, we demonstrate combined additive effects on overall enhancer activities. Using transient enhancer assays in developing zebrafish embryos we demonstrate the four out the five enhancer elements act as enhancers in vivo . Together, these studies extend the previous findings to uncover the TFs driving the enhancer activities of QT interval associated SCN5A regulatory variants, reveal the additive effects from allelic combinations of these regulatory variants, and prove their potential to act as enhancers in vivo .

Seroprevalence of Trypanosoma cruzi among children from Veracruz, Mexico: Epidemiological baseline for a control model based on Chagas disease active transmission / Seroprevalencia de Trypanosoma cruzi en niños de Veracruz, México: línea epidemiológica de base para un modelo de control fundamentado de la transmisión activa de la enfermedad de Chagas.

Introduction. In 2021, the Secretaría de Salud de México and the Pan American Health Organization launched an initiative to interrupt intra-domiciliary vector transmission of Trypanosoma cruzi based on the prevalence of Chagas disease in children. The Mexican State of Veracruz was leading this initiative. Objective. To estimate the seroprevalence of T. cruzi infection among children under 15 years of age from rural areas of Veracruz, México. Materials and methods. We identified eight localities of high priority from the Municipality of Tempoal, Veracruz, for baseline serology. Blood samples were collected on filter paper from 817 individuals between June and August 2017, for screening with a third-generation enzyme immunoassay. Reactive cases were confirmed by indirect hemagglutination, enzyme-linked immunosorbent assay, and indirect immunofluorescence tests on peripheral blood serum samples. We calculated seroprevalence and 95% confidence intervals (CI). Results. We confirmed Chagas disease cases in children under 15 years of age with a seroprevalence of 1,9% (95 % CI = 1,12-3,16) in the localities of Citlaltepetl, Cornizuelo, Cruz de Palma and Rancho Nuevo. Conclusions. These results indicate recent transmission of T. cruzi in these communities and allow to establish an epidemiological baseline for the design and implementation of a model focused on geographical areas with active transmission to advance toward the elimination of intra-domiciliary vector transmission of this parasite in Mexico.

Introducción. En el 2021, la Secretaría de Salud de México y la Organización Panamericana de la Salud lanzaron una iniciativa para interrumpir la transmisión vectorial intradomiciliaria de Trypanosoma cruzi, fundamentada en la prevalencia de la enfermedad de Chagas en la población infantil. El estado mexicano de Veracruz fue el pionero de esta iniciativa. Objetivo. Estimar la seroprevalencia de infección por T. cruzi en menores de 15 años de localidades rurales de Veracruz, México. Materiales y métodos. Se identificaron ocho localidades prioritarias para la serología basal del municipio de Tempoal, Veracruz. Entre junio y agosto de 2017, se recolectaron muestras de sangre en papel filtro de 817 individuos para su tamizaje mediante un inmunoensayo enzimático de tercera generación. Los casos reactivos del tamizaje se confirmaron mediante pruebas de hemaglutinación indirecta, ensayo de inmunoabsorción ligado a enzimas e inmunofluorescencia indirecta en muestras de suero. Se calculó la seroprevalencia y su intervalo de confianza (IC) del 95 %. Resultados. En las localidades de Citlaltépetl, Cornizuelo, Cruz de Palma y Rancho Nuevo se confirmaron casos de la enfermedad de Chagas en menores de 15 años con una seroprevalencia de 1,9 % (IC 95 % = 1,12-3,16). Conclusiones. Los resultados indican que estas comunidades presentan transmisión reciente de T. cruzi y permiten establecer una línea epidemiológica de base para el diseño e implementación de un modelo dirigido a aquellas áreas geográficas con transmisión activa. Se espera que dicho modelo contribuya a la eliminación de la transmisión vectorial intradomiciliaria del tripanosomátido en México.

MEDICAL-SURGICAL MANAGEMENT OF INTESTINAL INFECTION BY PROSTHENORCHIS ELEGANS IN NONHUMAN PRIMATES FROM COSTA RICA.

Parasitism is one of the most important diseases in nonhuman primates (NHP). Parasitism by Prosthenorchis elegans can be a threat to health and conservation of NHP in Costa Rica. Surgical management of intestinal acanthocephalan infection in two squirrel monkeys (Saimiri oerstedii) and one white-faced monkey (Cebus imitator) is described as an alternative to the lack of pharmacologic control options when there is a high burden of parasites present. A complete physical evaluation, including medical ultrasound techniques, allow for diagnosis of the parasite and its lesions. When animals present with a high burden of parasites, surgical management has shown to promote good health outcomes and increase the probability of survival.

Mixed quantum/classical calculations of rotationally inelastic scattering in the CO + CO system: a comparison with fully quantum results.

An updated version of the CO + CO potential energy surface from [R. Dawes, X. G. Wang and T. Carrington, J. Phys. Chem. A 2013, 117, 7612] is presented, that incorporates an improved treatment of the asymptotic behavior. It is found that this new surface is only slightly different from the other popular PES available for this system in the literature [G. W. M. Vissers, P. E. S. Wormer and A. Van Der Avoird, Phys. Chem. Chem. Phys. 2003, 5, 4767]. The differences are quantified by expanding both surfaces over a set of analytic functions and comparing the behavior of expansion coefficients along the molecule-molecule distance R. It is shown that all expansion coefficients behave similarly, except in the very high energy range at small R where the PES is repulsive. That difference has no effect on low collision-energy dynamics, which is explored via inelastic scattering calculations carried out using the MQCT program which implements the mixed quantum/classical theory for molecular energy exchange processes. The validity of MQCT predictions of state-to-state transition cross sections for CO + CO is also tested by comparison against full-quantum coupled-states calculations. In all cases MQCT gives reliable results, except at very low collision energy where the full-quantum calculations predict strong oscillations of state-to-state transition cross sections due to resonances. For strong transitions with large cross sections, the results of MQCT are reliable, especially at higher collision energy. For weaker transitions, and lower collision energies, the cross sections predicted by MQCT may be up to a factor of 2-3 different from those obtained by full-quantum calculations.

Rovibrational states calculations of the H2O-HCN heterodimer with the multiconfiguration time dependent Hartree method.

Water and hydrogen cyanide are two of the most common species in space and the atmosphere with the ability of binding to form dimers such as H2O-HCN. In the literature, while calculations characterizing various properties of the H2O-HCN cluster (equilibrium distance, vibrational frequencies and rotational constants) have been done in the past, extensive calculations of the rovibrational states of this system using a reliable quantum dynamical approach have yet to be reported. In this work, we intend to mend that by performing the first calculation of the rovibrational states of the H2O-HCN van der Waals complex on a recently developed potential energy surface. We use the block improved relaxation procedure implemented in the Heidelberg MultiConfiguration Time-Dependent Hartree (MCTDH) package to compute the states of the H2O-HCN isomer, from which we extract the transition frequencies and rotational constants of the complex. We further adapt an approach first suggested by Wang and Carrington-and supported here by analysis routines of the Heidelberg MCTDH package-to properly characterize the computed rovibrational states. The subsequent assignment of rovibrational states was done by theoretical analysis and visual inspection of the wavefunctions. Our simulations provide a Zero Point Energy (ZPE) and intermolecular vibrational frequencies in good agreement with past ab initio calculations. The transition frequencies and rotational constants obtained from our simulations match well with the available experimental data. This work has the broad aim to propose the MCTDH approach as a reliable option to compute and characterize rovibrational states of van der Waals complexes such as the current one.

A decade beyond the economic recession: A study of health-related lifestyles in urban and rural Spain (2006-2017).

The 2008 economic recession may have affected health-related indicators differently depending on the living environment. We analyze health-related indicators in Spain using data from four Spanish health surveys (2006, 2011, 2014, and 2017, 95 924 individuals aged ≥16 years). In 2006-2011, physical activity decreased among men and women, while in 2006-2017, physical activity only decreased among urban women. Daily vegetable intake, except in rural women, increased in 2006-2011 but decreased in 2006-2017 in all groups. Smoking decreased among urban women in 2006-2011 and 2006-2014 but only decreased among men, and even increased among rural women, in 2006-2017. In 2006-2017, obesity increased among men and urban women, good self-rated health status increased in all groups and flu vaccination declined. Blood pressure and cholesterol control decreased in urban women in 2006-2011 but increased in 2006-2017 in all groups, as well as mammographic and cytological control. Our findings highlight the differential impact of the economic recession on health-related lifestyles according to sex and place of residence, underscoring the need for targeted health policies to address evolving health disparities over time.

Ab initio quantum scattering calculations and a new potential energy surface for the HCl(X1Σ+)-O2(X3Σg-) system: Collision-induced line shape parameters for O2-perturbed R(0) 0-0 line in H35Cl.

The remote sensing of abundance and properties of HCl-the main atmospheric reservoir of Cl atoms that directly participate in ozone depletion-is important for monitoring the partitioning of chlorine between "ozone-depleting" and "reservoir" species. Such remote studies require knowledge of the shapes of molecular resonances of HCl, which are perturbed by collisions with the molecules of the surrounding air. In this work, we report the first fully quantum calculations of collisional perturbations of the shape of a pure rotational line in H35Cl perturbed by an air-relevant molecule [as the first model system we choose the R(0) line in HCl perturbed by O2]. The calculations are performed on our new highly accurate HCl(X1Σ+)-O2(X3Σg-) potential energy surface. In addition to pressure broadening and shift, we also determine their speed dependencies and the complex Dicke parameter. This gives important input to the community discussion on the physical meaning of the complex Dicke parameter and its relevance for atmospheric spectra (previously, the complex Dicke parameter for such systems was mainly determined from phenomenological fits to experimental spectra and the physical meaning of its value in that context is questionable). We also calculate the temperature dependence of the line shape parameters and obtain agreement with the available experimental data. We estimate the total combined uncertainties of our calculations at 2% relative root-mean-square error in the simulated line shape at 296 K. This result constitutes an important step toward computational population of spectroscopic databases with accurate ab initio line shape parameters for molecular systems of terrestrial atmospheric importance.

Cardiac muscle-restricted partial loss of Nos1ap expression has limited but significant impact on electrocardiographic features.

Genome-wide association studies have identified sequence polymorphisms in a functional enhancer of the NOS1AP gene as the most common genetic regulator of QT interval and human cardiac NOS1AP gene expression in the general population. Functional studies based on in vitro overexpression in murine cardiomyocytes and ex vivo knockdown in zebrafish embryonic hearts, by us and others, have also demonstrated that NOS1AP expression levels can alter cellular electrophysiology. Here, to explore the role of NOS1AP in cardiac electrophysiology at an organismal level, we generated and characterized constitutive and heart muscle-restricted Nos1ap knockout mice to assess whether NOS1AP disruption alters the QT interval in vivo. Constitutive loss of Nos1ap led to genetic background-dependent variable lethality at or right before birth. Heart muscle-restricted Nos1ap knockout, generated using cardiac-specific alpha-myosin heavy chain promoter-driven tamoxifen-inducible Cre, resulted in tissue-level Nos1ap expression reduced by half. This partial loss of expression had no detectable effect on the QT interval or other electrocardiographic and echocardiographic parameters, except for a small but significant reduction in the QRS interval. Given that challenges associated with defining the end of the T wave on murine electrocardiogram can limit identification of subtle effects on the QT interval and that common noncoding NOS1AP variants are also associated with the QRS interval, our findings support the role of NOS1AP in regulation of the cardiac electrical cycle.

Urban-rural differences in perceived environmental opportunities for physical activity: a 2002-2017 time-trend analysis in Europe.

Urban-rural disparities in resources, services and facilities not only impact daily living conditions but also contribute to inequalities in physical activity, which may be associated with variations in basic public resources between urban and rural areas. This study aims to examine the evolution of perceived opportunities for physical activity in European urban and rural environments from 2002 to 2017 and their association with an active lifestyle. Data from four waves (2002, 2005, 2013 and 2017) of cross-sectional Eurobarometer surveys were collected (n = 101 373), and multilevel binomial logistic regressions were conducted. Firstly, the time trend of perceived opportunities for physical activity between urban and rural environments was explored, and secondly, the effect of urban-rural perceived opportunities on achieving an active lifestyle over the years was estimated. The findings revealed that individuals residing in rural settings encountered less opportunities to be physically active. Conversely, urban settings experienced an increase in perceived opportunities. The significance of health promotion through perceived physical activity opportunities lies in the increased likelihood of being physically active, regardless of place of residence or individual socioeconomic factors [in the area: odds ratio (OR) = 1.40, 95% confidence interval (CI) = 1.34-1.47; provided by local sport clubs: OR = 1.29, 95% CI = 1.23-1.35]. Modifying environmental aspects, such as enhancing the quantity, quality and accessibility of physical activity opportunities in both rural and urban areas, may lead to improved physical activity and health promotion, particularly among individuals who are more physically inactive.

Association between Covid-19 sources of information, beliefs, and vaccination rates: an EU-wide survey.

BACKGROUND: Misinformation hampers vaccine uptake. The European Union (EU) employed a coordinated effort to curb misinformation during the Covid-19 pandemic. In this context, we investigated relationships between sources of information, vaccine safety/effectiveness, satisfaction with government vaccination strategy, and vaccination intent. METHODS: We used cross-sectional survey data (May 2021) from Flash Eurobarometer 494, a population-adjusted dataset comprised of a representative sample of those ≥15 years from 27 EU nations. We employed a latent class analysis to create clusters of information sources as the independent variable and beliefs in vaccine safety/efficacy, satisfaction with government vaccination strategy, and vaccine intent as four outcome variables. We first estimated the association between source clusters and each of the first three outcomes separately. Then, using these three as intermediate variables, we employed structural equation modeling to estimate the relationship between sources and vaccine intent. We adjusted for individual and country-level variables. RESULTS: Among 23 012 respondents, four clusters of information sources emerged: (1) national authorities/health professionals (n = 9602; 42%), (2) mostly health professionals (6184; 27%), (3) mixed (n = 1705; 17%) and (4) social media/family/friends (n = 5524; 24%). Using cluster (3) as the referent, we found decreasing odds of beliefs in vaccine safety/effectiveness, satisfaction and vaccine intent across clusters (1), (2) and (4), respectively. Demographics played a role. CONCLUSION: In the context of the Covid pandemic, these results provide the first EU-wide estimates of the association between sources of information about vaccine safety/effectiveness, satisfaction and vaccine intent. The coordinated approach promulgated by the EU to minimize misinformation provides a model for managing future pandemics.

Temperature Dependence of the Electronic Absorption Spectrum of NO2.

The nitrogen dioxide (NO2) radical is composed of the two most abundant elements in the atmosphere, where it can be formed in a variety of ways including combustion, detonation of energetic materials, and lightning. Relevant also to smog and ozone cycles, together these processes span a wide range of temperatures. Remarkably, high-resolution NO2 electronic absorption spectra have only been reported in a narrow range below about 300 K. Previously, we reported [ J. Phys. Chem. A 2021, 125, 5519-5533] the construction of quasi-diabatic potential energy surfaces (PESs) for the lowest four electronic states (X̃, Ã, B̃, and C̃) of NO2. In addition to three-dimensional PESs based on explicitly correlated MRCI(Q)-F12/VTZ-F12 ab initio data, the geometry dependence of each component of the dipoles and transition dipoles was also mapped into fitted surfaces. The multiconfigurational time-dependent Hartree (MCTDH) method was then used to compute the 0 K electronic absorption spectrum (from the ground rovibrational initial state) employing those energy and transition dipole surfaces. Here, in an extension of that work, we report an investigation into the effects of elevated temperature on the spectrum, considering the effects of the population of rotationally and vibrationally excited initial states. The calculations are complemented by new experimental measurements. Spectral contributions from hundreds of rotational states up to N = 20 and from 200 individually-characterized vibrational states were computed. A spectral simulation tool was developed that enables modeling the spectrum at various temperatures─by weighting individual spectral contributions via the partition function, or for pure excited initial states, which can be probed via transient absorption spectroscopy. We validate these results against experimental absorption spectroscopy data at high temperatures, as well as via a new measurement from the (1,0,1) initial vibrational state.

Prevalence Estimation, Antimicrobial Susceptibility, and Serotyping of Salmonella enterica Recovered from New World Non-Human Primates (Platyrrhini), Feed, and Environmental Surfaces from Wildlife Centers in Costa Rica.

Concern about zoonoses and wildlife has increased. Few studies described the role of wild mammals and environments in the epidemiology of Salmonella. Antimicrobial resistance is a growing problem associated with Salmonella that threatens global health, food security, the economy, and development in the 21st century. The aim of this study is to estimate the prevalence and identify antibiotic susceptibility profiles and serotypes of non-typhoidal Salmonella enterica recovered from non-human primate feces, feed offered, and surfaces in wildlife centers in Costa Rica. A total of 180 fecal samples, 133 environmental, and 43 feed samples from 10 wildlife centers were evaluated. We recovered Salmonella from 13.9% of feces samples, 11.3% of environmental, and 2.3% of feed samples. Non-susceptibility profiles included six isolates from feces (14.6%): four non-susceptible isolates (9.8%) to ciprofloxacin, one (2.4%) to nitrofurantoin, and one to both ciprofloxacin and nitrofurantoin (2.4%). Regarding the environmental samples, one profile was non-susceptible to ciprofloxacin (2.4%) and two to nitrofurantoin (4.8%). The serotypes identified included Typhimurium/I4,[5],12:i:-, S. Braenderup/Ohio, S. Newport, S. Anatum/Saintpaul, and S. Westhampton. The epidemiological surveillance of Salmonella and antimicrobial resistance can serve in the creation of strategies for the prevention of the disease and its dissemination throughout the One Health approach.

Rats conserve passive avoidance retention level throughout the light phase of diurnal cycle.

Emotions and memory formation are sensible to circadian rhythm. Here we study whether the time of day during the light phase of the diurnal cycle affects emotional memory in male Wistar rats using the passive avoidance (PA) test. Experiments were conducted at the beginning of Zeitgeber time (ZT) (ZT0.5-2), mid-time (ZT5-6.5), and end (ZT10.5-12) of the light period. Our results suggest that time of day has no impact on emotional response during acquisition trials, but slightly influences cognitive response during the 24-hour retention trial. Retention response was highest for ZT5-6.5, followed by ZT0.5-2, and lowest for ZT10.5-12.

DNA Methylation Remodeling after Bariatric Surgery Correlates with Clinical Parameters.

The altered functions of adipose tissue are one of the main issues in obesity. Bariatric surgery is associated with improvement of obesity associated comorbidities. Here DNA methylation remodeling in adipose tissue after bariatric surgery is examined. After six months postoperative, DNA methylation shows changes in 1155 CpG sites, 66 of these sites correlate with body mass index. Some sites also show correlation with LDL-C, HDL-C, total cholesterol, and triglycerides. CpG sites are located in genes that have not previously been linked to obesity or metabolic diseases. GNAS complex locus is one of those that presented CpG site with the greatest changes after surgery, and the most significant correlation with BMI and lipid profiles. These results show that epigenetic regulation may be involved in the alteration of adipose tissue functions in obesity.

Collisional excitation of C2H- by H2: New interaction potential and scattering calculations.

Interstellar anions play an important role in astrochemistry as being tracers of the physical and chemical conditions in cold molecular clouds and circumstellar gas. The local thermodynamic equilibrium is generally not fulfilled in media where anions are detected and radiative and collisional data are required to model the observed lines. The C2H- anion has not yet been detected in the interstellar medium; however, collisional data could be used for non-LTE models that would help in identifying the most intense lines. For this purpose, we have computed the first 4D potential energy surface (PES) of the C2H--H2 complex using an explicitly correlated coupled-cluster approach. The PES is characterized by a single deep minimum with a well-depth of 924.96 cm-1. From this interaction potential, we derived excitation cross sections and rate coefficients of C2H- induced by collisions with para- and ortho-H2. The results obtained for collisions with para-H2 are compared to previous calculations performed using a 2D-PES obtained from an average over H2 rotations.

Moderate Beer Consumption Is Associated with Good Physical and Mental Health Status and Increased Social Support.

There is little large-scale evidence on the effect of alcoholic beer consumption on physical, mental and, above all, socio-emotional health. Here, we conducted a secondary data analysis of the 2012 and 2017 National Health Surveys with 33,185 individuals aged 18 years and older to assess beer consumption in relation to self-perceived health, functional limitations, mental health, and social support. Logistic regression models assessed the association of alcohol consumption (abstainers, ex-drinkers, occasional drinkers, moderate beer drinkers, and heavy beer drinkers) with self-perceived health (poor or good), limitations of type (none, physical, mental, or both) and intensity (none, mild, or severe), mental health (poor, average, or good) and social support (poor, average, or good). Analyses were adjusted for sex, age, occupational social class, educational level, place of residence, survey, part-time physical activity, dietary information, smoking, and body mass index. Compared to abstainers, occasional and moderate beer drinkers were associated with better mental and self-perceived health and social support, and were less likely to report mild or severe physical limitations. In contrast, former drinkers were associated with worse indicators of self-perceived health, physical health, mental health, and social support than abstainers. Alcoholic beer consumption showed a J-shaped relationship with self-perceived, physical, mental, and social-emotional health, with better values at moderate levels.

Cryptic diversity in a gastrointestinal acanthocephalan of New World primates from Costa Rica.

Prosthenorchis elegans is a worm of the family Archiacanthocephala that infects non-human primates in the Americas, producing an intestinal pathology that may compromise the life of its hosts. Squirrel monkeys, Saimiri oerstedii citrinellus, were found with P. elegans in Costa Rica. Histopathological analysis revealed a severe pyogranulomatous response composed by macrophages, neutrophils, eosinophils, fibroblasts and lymphocytes. Morphological worm analyses revealed 36 hooks in the proboscis distributed in six rows; and total body, hook and lemnisci length were compatible to the original descriptions of P. elegans. In addition, phylogenetic, haplotype network and genetic distance analyses were done on cytochrome oxidase subunit 1, cox1, sequences obtained from the collected specimens. Sequences obtained herein clustered separately with high posterior probabilities in a Bayesian Inference tree and showed 8.12% nucleotide differences when compared to P. elegans from Colombia. This high divergence was confirmed in the TCS network that separated Colombian and Costa Rican sequences by 32 mutational steps, a genetic distance PCA which separated sequences from both geographical locations by 89.5% and an FST value of 0.655, indicating the presence of cryptic diversity in P. elegans. Additional studies from specimens collected from other definitive hosts and geographical locations are required to better understand the biodiversity of this species.

The Socioeconomic Paradox of Physical Activity and Sedentary Behavior in Europe.

BACKGROUND: A low socioeconomic status (SES) presents lower physical activity; however, the relationship between SES and sedentary behavior (SB) remains unclear. We aimed to assess this association of SES with physical activity (PA) and SB. METHODS: We employed representative self-reported data of the European Union from the cross-sectional survey Eurobarometer 2017, comprising a final sample of 13,708 citizens (18-64 y old), to assess the association of SES (education, occupation, and economic issues) with PA and sitting time quartiles, and to describe inequalities in vigorous, moderate, and walking activity and sitting time. RESULTS: Multinomial regressions revealed that people from higher SESs were more likely to report higher PA; nonetheless, higher educational attainment and occupations were also associated with higher sitting time but not with lower economic issues. The inequality, shown by Gini coefficients, describes a socioeconomic gradient in vigorous and moderate activity, from higher inequality in lower statuses to lower inequality in higher statuses. The Gini coefficients also indicated higher socioeconomic inequalities in PA than SB. CONCLUSIONS: Higher SESs showed paradoxically more PA and SB; however, sitting time presented smaller differences and a more homogeneous distribution across the population.

How socioeconomic status affects weight status through health-related lifestyles: a latent class analysis.

AIMS: Obesity levels have increased worldwide with serious public health concerns. However, weight status is related to socioeconomic status (SES), which may also influence health-related lifestyles. Here, we study the association between SES and obesity mediated by diet and physical activity. METHODS AND RESULTS: Using cross-sectional data from 2006, 2011, 2014, and 2017 Spanish health surveys (the final sample consisted of 61 768 adults aged between 18 and 64 years), we conducted a latent class analysis to estimate health-related lifestyle clusters (based on dietary patterns and physical activity) and mediation analyses to evaluate the association of SES and obesity through the clustering of health-related lifestyles. In both men and women, SES was inversely related to obesity (P < 0.001) and positively related to healthier lifestyle classes (P < 0.001). Obesity was inversely related to healthier lifestyle classes (P < 0.001). A small-although significant-proportion mediated by the clustering of lifestyles was found as follows: 4.9%, 95% CI (6.6%, 3.2%) in men and 2.3%, 95% CI (3.4%, 1.3%) in women for educational attainment, 5.3%, 95% CI (7.2%, 3.6%) in men and 2.0%, 95% CI (2.9%, 1.1%) in women for occupational social class, and 4.9%, 95% CI (6.5%, 3.1%) and 1.9%, 95% CI (2.9%, 1.1%) combining the above two SES indicators. CONCLUSIONS: SES is related to obesity through clustering health-related lifestyles, with greater emphasis on men. However, the complex relationship between SES and weight status also suggests other indicators that contribute to the social gradient of obesity.

DNA methylation and gene expression analysis in adipose tissue to identify new loci associated with T2D development in obesity.

BACKGROUND: Obesity is accompanied by excess adipose fat storage, which may lead to adipose dysfunction, insulin resistance, and type 2 diabetes (T2D). Currently, the tendency to develop T2D in obesity cannot be explained by genetic variation alone-epigenetic mechanisms, such as DNA methylation, might be involved. Here, we aimed to identify changes in DNA methylation and gene expression in visceral adipose tissue (VAT) that might underlie T2D susceptibility in patients with obesity. METHODS: We investigated DNA methylation and gene expression in VAT biopsies from 19 women with obesity, without (OND = 9) or with T2D (OD = 10). Differences in genome-scale methylation (differentially methylated CpGs [DMCs], false discovery rate < 0.05; and differentially methylated regions [DMRs], p value < 0.05) and gene expression (DEGs, p value <0.05) between groups were assessed. We searched for overlap between altered methylation and expression and the impact of altered DNA methylation on gene expression, using bootstrap Pearson correlation. The relationship of altered DNA methylation to T2D-related traits was also tested. RESULTS: We identified 11 120 DMCs and 96 DMRs distributed across all chromosomes, with the greatest density of epigenomic alterations at the MHC locus. These alterations were found in newly and previously T2D-related genes. Several of these findings were supported by validation and extended multi-ethnic analyses. Of 252 DEGs in the OD group, 68 genes contained DMCs (n = 88), of which 24 demonstrated a significant relationship between gene expression and methylation (p values <0.05). Of these, 16, including ATP11A, LPL and EHD2 also showed a significant correlation with fasting glucose and HbA1c levels. CONCLUSIONS: Our results revealed novel candidate genes related to T2D pathogenesis in obesity. These genes show perturbations in DNA methylation and expression profiles in patients with obesity and diabetes. Methylation profiles were able to discriminate OND from OD individuals; DNA methylation is thus a potential biomarker.