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Searching for positive selection signals across genomes has identified functional genetic variants responding to environmental change. In Native Americans of Mexico, we used the fixation index (Fst) and population branch statistic (PBS) to identify SNPs suggesting positive selection. The 103 most differentiated SNPs were tested for associations with metabolic traits, the most significant association was FADS2/rs174616 with body mass index (BMI). This variant lies within a linkage disequilibrium (LD) block independent of previously reported FADS selection signals and has not been clearly associated with metabolic phenotypes. We tested this variant in two independent cohorts with cardiometabolic data. In the Genetics of Atherosclerotic Disease (GEA) cohort, the derived allele (T) was associated with increased BMI, lower LDL-C levels and a decreased risk of subclinical atherosclerosis in women. Significant gene-diet interactions affected lipid, apolipoprotein and adiponectin levels with differences according to sex, involving mainly total and complex dietary carbohydrate%. In the Genotype-related Effects of PUFA trial, the derived allele was associated with lower Δ-6 desaturase activity and erythrocyte membrane dihomo-gamma-linolenic acid (DGLA) levels, and with increased Δ-5 desaturase activity and eicosapentaenoic acid levels. This variant interacted with dietary carbohydrate% affecting Δ-6 desaturase activity. Notably, the relationship of DGLA and other erythrocyte membrane LC-PUFA indices with HOMA-IR differed according to rs174616 genotype, which has implications regarding how these indices should be interpreted. In conclusion, this observational study identified rs174616 as a signal suggesting selection in an independent linkage disequilibrium block, was associated with cardiometabolic and erythrocyte measurements of LC-PUFA in two independent Mexican cohorts and showed significant gene-diet interactions.

Abstract The objective of this study was to evaluate the association of maternal cardiometabolic markers trajectories (glucose, triglycerides (TG), total cholesterol, systolic blood pressure (SBP) and diastolic blood pressure (DBP)) with estimated fetal weight trajectories and birth weight in Mexican pregnant women without medical complications. Cardiometabolic marker trajectories were characterized using group-based trajectory models. Mixed-effect and linear regression models were estimated to assess the association of maternal trajectories with estimated fetal weight and birth weight. The final sample comprised 606 mother–child dyads. Two trajectory groups of maternal cardiometabolic risk indicators during pregnancy were identified (high and low). Fetuses from women with higher values of TG had higher weight gain during pregnancy ( $$\hat{\beta }$$ β ^ = 24.00 g; 95%CI: 12.9, 35.3), were heavier at the sixth month ( $$\widehat{\beta }$$ β ^ =48.24 g; 95%CI: 7.2, 89.7) and had higher birth weight ( $$\widehat{\beta }$$ β ^ = 89.08 g; 95%CI: 20.8, 157.4) than fetuses in the low values trajectory. Fetuses from mothers with high SBP and DBP had less weight in the sixth month of pregnancy ( $$\widehat{\beta }$$ β ^ = − 42.4 g; 95%CI: − 82.7, − 2.1 and $$\widehat{\beta }$$ β ^ = − 50.35 g; 95%CI: − 94.2, − 6.4), and a higher DBP trajectory was associated with lower birth weight ( $$\widehat{\beta }$$ β ^ = − 101.48 g; 95%CI: − 176.5, − 26.4). In conclusion, a longitudinal exposition to high values of TG and BP was associated with potentially adverse effects on fetal growth. These findings support the potential modulation of children’s phenotype by maternal cardiometabolic conditions in pregnancies without medical complications.

Abstract Background Gestational diabetes mellitus (GDM) represents the main metabolic alteration during pregnancy. The available methods for diagnosing GDM identify women when the disease is established, and pancreatic beta-cell insufficiency has occurred.The present study aimed to generate an early prediction model (under 18 weeks of gestation) to identify those women who will later be diagnosed with GDM. Methods A cohort of 75 pregnant women was followed during gestation, of which 62 underwent normal term pregnancy and 13 were diagnosed with GDM. Targeted metabolomics was used to select serum biomarkers with predictive power to identify women who will later be diagnosed with GDM. Results Candidate metabolites were selected to generate an early identification model employing a criterion used when performing Random Forest decision tree analysis. A model composed of two short-chain acylcarnitines was generated: isovalerylcarnitine (C5) and tiglylcarnitine (C5:1). An analysis by ROC curves was performed to determine the classification performance of the acylcarnitines identified in the study, obtaining an area under the curve (AUC) of 0.934 (0.873–0.995, 95% CI). The model correctly classified all cases with GDM, while it misclassified ten controls as in the GDM group. An analysis was also carried out to establish the concentrations of the acylcarnitines for the identification of the GDM group, obtaining concentrations of C5 in a range of 0.015–0.25 μmol/L and of C5:1 with a range of 0.015–0.19 μmol/L. Conclusion Early pregnancy maternal metabolites can be used to screen and identify pregnant women who will later develop GDM. Regardless of their gestational body mass index, lipid metabolism is impaired even in the early stages of pregnancy in women who develop GDM.

Several epidemiological studies have demonstrated that particulate matter (PM) in air pollution can be involved in the genesis or aggravation of different cardiovascular, respiratory, perinatal, and cancer diseases. This study assessed the in vitro effects of PM10 on the secretion of cytokines by a human monocytic cell line (THP-1). We compared the chemotactic, pro-inflammatory, and anti-inflammatory cytokines induced by PM10 collected for two years during three different seasons in five different Mexico City locations. MIP-1α, IP-10, MCP-1, TNF-α, and VEGF were the main secretion products after stimulation with 80 μg/mL of PM10 for 24 h. The THP-1 cells showed a differential response to PM10 obtained in the different sites of Mexico City. The PM10 from the north and the central city areas induced a higher pro-inflammatory cytokine response than those from the south. Seasonal pro-inflammatory cytokine secretion always exceeded anti-inflammatory secretion. The rainy-season-derived particles caused the lowest pro-inflammatory effects. We concluded that toxicological assessment of airborne particles provides evidence supporting their potential role in the chronic exacerbation of local or systemic inflammatory responses that may worsen the evolution of some chronic diseases.

Objetivo. Analizar la asociación de la concentración de con­taminantes atmosféricos y los indicadores epidemiológicos de Covid-19 en la Zona Metropolitana del Valle de México (ZMVM). Material y métodos. Se diseñó un estudio epidemiológico ecológico. Se utilizaron modelos lineales tipo Poisson para variables de conteo y modelos lineales de efectos aleatorios en variables continuas para cuantificar la asociación entre los contaminantes atmosféricos y los indicadores de Covid-19. Los datos obtenidos fueron del 28 de febrero de 2020 al 30 de junio de 2021. La exposición a contaminantes se estratificó por estaciones climáticas. Resultados. Los contaminantes que tuvieron asociación significativa con indicadores de morbilidad y mortalidad fueron CO, NOX, O3 y PM10. En la estación seca fría el CO y el NOX tuvieron efecto sobre los casos diarios confirmados y las defunciones diarias. Las PM10 se asociaron con efecto en los indicadores de casos diarios confirmados, incidencia diaria, porcentaje de hospitalizados y la tasa de letalidad. Conclusiones. Los resultados sugieren una asociación entre el comportamiento epidemiológico de Covid-19 y la exposición a CO, NOX, O3 y PM10, en la que se encontró un mayor efecto en la estación seca-fría en la ZMVM.

Abstract End-point RT-PCR is a suitable alternative diagnostic technique since it is cheaper than RT-qPCR tests and can be implemented on a massive scale in low- and middle-income countries. In this work, a bioinformatic approach to guide the design of PCR primers was developed, and an alternative diagnostic test based on end-point PCR was designed. End-point PCR primers were designed through conservation analysis based on kmer frequency in SARS-CoV-2 and human respiratory pathogen genomes. Highly conserved regions were identified for primer design, and the resulting PCR primers were used to amplify 871 nasopharyngeal human samples with a previous RT-qPCR based SARS-CoV-2 diagnosis. The diagnostic test showed high accuracy in identifying SARS-CoV-2-positive samples including B.1.1.7, P.1, B.1.427/B.1.429 and B.1.617.2/ AY samples with a detection limit of 7.2 viral copies/µL. In addition, this test could discern SARS-CoV-2 infection from other viral infections with COVID-19-like symptomatology. The designed end-point PCR diagnostic test to detect SARS-CoV-2 is a suitable alternative to RT-qPCR. Since the proposed bioinformatic approach can be easily applied in thousands of viral genomes and over highly divergent strains, it can be used as a PCR design tool as new SARS-CoV-2 variants emerge. Therefore, this end-point PCR test could be employed in epidemiological surveillance to detect new SARS-CoV-2 variants as they emerge and propagate.

Abstract Background/objective Changes in metabolism and extensive hemodynamic adjustments occur during normal pregnancy. The presence of maternal obesity imposes an overload to these physiological adaptations that may result in increased risk for the development of cardiometabolic complications during and after pregnancy. The aim of this study is to describe total cholesterol (TC), triglycerides (TG), glucose, and arterial blood pressure (BP) trajectories and to analyze the association of these cardiometabolic risk indicators during pregnancy with pre-pregnancy body mass index (pBMI) and monthly gestational weight gain (MGWG). Subjects/methods A prospective cohort study of pregnant women was conducted in Mexico City. Monthly samples of blood were taken during clinical follow-up and biochemical and blood pressure were measured during each visit. Adjusted linear mixed-effect regression models were fit to describe the trajectories of these biomarkers during pregnancy and to analyze the association with pBMI and MGWG. Results Seven hundred and twenty women were included of which 16.6% had pre-gestational obesity, 33.2% had pre-gestational overweight, 45.8% had normal pBMI and 4.4% had pre-gestational underweight. Women with pre-gestational obesity had higher lipids concentrations in the beginning of pregnancy (TC: $$\hat \beta$$ β ̂ = 33.08, p = 0.010; TG: $$\hat \beta$$ β ̂ = 31.29, p =

Resumen: Objetivos: Describir la asociación entre las enfermedades crónicas no transmisibles y la edad, con la hospitalización, desenlaces clínicos graves y las defunciones por COVID-19 en los casos confirmados en población mexicana, comparando las tres primeras olas epidemiológicas de la pandemia en México. Diseño: Se realizó un análisis transversal utilizando el Sistema de Vigilancia Epidemiológica de Enfermedad Respiratoria Viral para COVID-19. Emplazamiento: Sistema de Vigilancia Epidemiológica de Enfermedad Respiratoria Viral en México (SISVER). Participantes: Población mexicana confirmada para SARS-CoV-2 registrada en el SISVER. Mediciones principales: Los desenlaces graves analizados fueron hospitalización, neumonía, necesidad de ventilación mecánica, ingreso a la UCI y defunción. Se evaluó la asociación (odds ratio [OR]) entre los desenlaces y las variables clínicas, comparando las tres olas epidemiológicas en México. Resultados: Una edad mayor de 65 años se asocia a un mayor porcentaje de hospitalización, neumonía, y notablemente, con el total de defunciones, independientemente del efecto de las comorbilidades crónicas. Existe interacción entre la edad en conjunto con la obesidad, la cual se asocia con la hospitalización y neumonía. Estos hallazgos fueron consistentes a lo largo de las tres olas epidemiológicas. Conclusión: La obesidad, EPOC y la diabetes en interacción con la edad se asocian con peores desenlaces clínicos, primordialmente con defunciones en los pacientes con COVID-19. Abstract: Objectives: To describe the association between chronic noncommunicable diseases and age with hospitalization, death and severe clinical outcomes for COVID-19 in confirmed cases within the mexican population, comparing the first three epidemiological waves of the pandemic in Mexico. Design: We performed an analysis using Mexico's Government Epidemiological Surveillance System database for COVID-19. Emplacement: Mexico's Epidemiological Surveillance System for Respiratory Diseases. Participants: Mexican population confirmed with SARS-CoV-2 registered on Mexico's Epidemiological Surveillance System for Respiratory Diseases. Primary measurements: The analysed severe outcomes were hospitalization, pneumonia, use of mechanical ventilation, intensive care unit admission and death. The association (odds ratio) between the outcomes and clinical variables was evaluated, comparing the three epidemiological waves in Mexico. Results: Age over 65 is associated with a higher ratio of hospitalization and pneumonia, independent of the effect of chronic comorbidities. There is an interaction between age and obesity, which is associated with hospitalization, pneumonia and highly associated with death. These findings were consistent throughout the three epidemiological waves. Conclusion: Obesity, COPD and diabetes in interaction with age, are associated with worse clinical outcomes and, more importantly, death in patients with COVID-19.

Background and Objectives: Metabolic-dysfunction-associated steatotic liver disease or MASLD is the main cause of chronic liver diseases in children, and it is estimated to affect 35% of children living with obesity. This study aimed to identify metabolic phenotypes associated with two advanced stages of MASLD (hepatic steatosis and hepatic steatosis plus fibrosis) in Mexican children with obesity. Materials and Methods: This is a cross-sectional analysis derived from a randomized clinical trial conducted in children and adolescents with obesity aged 8 to 16 years. Anthropometric and biochemical data were measured, and targeted metabolomic analyses were carried out using mass spectrometry. Liver steatosis and fibrosis were estimated using transient elastography (Fibroscan® Echosens, Paris, France). Three groups were studied: a non-MASLD group, an MASLD group, and a group for MASLD + fibrosis. A partial least squares discriminant analysis (PLS-DA) was performed to identify the discrimination between the study groups and to visualize the differences between their heatmaps; also, Variable Importance Projection (VIP) plots were graphed. A VIP score of >1.5 was considered to establish the importance of metabolites and biochemical parameters that characterized each group. Logistic regression models were constructed considering VIP scores of >1.5, and the receiver operating characteristic (ROC) curves were estimated to evaluate different combinations of variables. Results: The metabolic MASLD phenotype was associated with increased concentrations of ALT and decreased arginine, glycine, and acylcarnitine (AC) AC5:1, while MASLD + fibrosis, an advanced stage of MASLD, was associated with a phenotype characterized by increased concentrations of ALT, proline, and alanine and a decreased Matsuda Index. Conclusions: The metabolic MASLD phenotype changes as this metabolic dysfunction progresses. Understanding metabolic disturbances in MASLD would allow for early identification and the development of intervention strategies focused on limiting the progression of liver damage in children and adolescents.

Maternal obesity (MO) induces negative consequences in the offspring development. Adiposity phenotype is associated with maternal diet at early pregnancy and DNA methylation marks in the RXRα promotor at birth. Glucocorticoids play an important role in the regulation of metabolism through the activation of nuclear hormone receptors such as the RXRα protein. The aim of the study was to analyze steroid hormone changes at the end of pregnancy in the obese mother and RXRα gene methylation in the umbilical cord. For this purpose, in a well-established MO model, female Wistar rats were fed either standard chow (controls: C) or high-fat obesogenic diet (MO) before and during pregnancy to evaluate at 19 days of gestation (19 dG): 1) maternal concentration of circulating steroid hormones in MO and C groups, 2) maternal and fetal weights, 3) analysis of correlation between hormones concentration and maternal and fetal weights, 4) DNA methylation status of a single locus of RXRα gene near the early growth response (EGR-1) protein DNA binding site, and 5) RXRα mRNA and protein expressions in umbilical cords. Our results demonstrate that at 19 dG, MO body weight before and during pregnancy was higher than C; MO progesterone and corticosterone serum concentrations were higher and estradiol lower than C. There were not differences in fetal weight between male and female per group, therefore averaged data was used; MO fetal weight was lower than C. Positive correlations were found between progesterone and corticosterone with maternal weight, and estradiol with fetal weight, while negative correlation was observed between corticosterone and fetal weight. Additionally, male umbilical cords from MO were hypermethylated in RXRα gene compared to male C group, without differences in the female groups; mRNA and protein expression of RXRα were decreased in F1 male but not in female MO compared to C. In conclusion, MO results in dysregulation of circulating steroid hormones of the obese mothers and low fetal weight in the F1, modifying DNA methylation of RXRα gene as well as RXRα mRNA and protein expression in the umbilical cord in a sex-dependent manner.

High blood pressure (BP) is a risk factor for hypertensive disease during pregnancy. Exposure to multiple toxic air pollutants can affect BP in pregnancy but has been rarely studied. We evaluated trimester-specific associations between air pollution exposure and systolic (SBP) and diastolic BP (DBP). Ozone (O3), sulfur dioxide (SO2), carbon monoxide (CO), nitrogen dioxide (NO2), and particulate matter less than 10 and 2.5 μm in aerodynamic diameter (PM10, PM2.5) in the Pregnancy Research on Inflammation, Nutrition, & City Environment: Systematic Analyses (PRINCESA) study. Multipollutant generalized linear regression models with each pollutant and O3 were fit. Due to nonlinear pollution/BP associations, results are presented for “below the median” or “above the median”, where the beta estimate is the change in BP at a pollutant’s median versus BP at the pollutant’s minimum or maximum, respectively. Associations varied across trimesters and pollutants, and deleterious associations (higher blood pressure with higher pollution) were found only at pollutant values below the median: for SBP with NO2 in the second and third trimesters, and PM2.5 during the third trimester, and for DBP, PM2.5, and NO2 in the second and third trimesters. Findings suggest that minimizing prenatal exposure to air pollution may reduce the risks of changes in BP.

Objectives: The aim of this study was to investigate the feasibility of saliva sampling as a non-invasive and safer tool to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to compare its reproducibility and sensitivity with nasopharyngeal swab samples (NPS). The use of sample pools was also investigated. Methods: A total of 2107 paired samples were collected from asymptomatic healthcare and office workers in Mexico City. Sixty of these samples were also analyzed in two other independent laboratories for concordance analysis. Sample processing and analysis of virus genetic material were performed according to standard protocols described elsewhere. A pooling analysis was performed by analyzing the saliva pool and the individual pool components. Results: The concordance between NPS and saliva results was 95.2% (kappa 0.727, p = 0.0001) and 97.9% without considering inconclusive results (kappa 0.852, p = 0.0001). Saliva had a lower number of inconclusive results than NPS (0.9% vs 1.9%). Furthermore, saliva showed a significantly higher concentration of both total RNA and viral copies than NPS. Comparison of our results with those of the other two laboratories showed 100% and 97% concordance. Saliva samples are stable without the use of any preservative, and a positive SARS-CoV-2 sample can be detected 5, 10, and 15 days after collection when the sample is stored at 4 °C. Conclusions: The study results indicate that saliva is as effective as NPS for the identification of SARS-CoV-2-infected asymptomatic patients. Sample pooling facilitates the analysis of a larger number of samples, with the benefit of cost reduction.

Background: M1 macrophages involved in pro-inflammatory processes can be induced by low-density lipoproteins (LDL), giving rise to foam cells. In the atheroma plaque, it has been identified that males present more advanced lesions associated with infiltration. Therefore, our study aims to investigate sex-related changes in the transcriptome of M1 macrophages during the internalization process of LDL particles. Methods: Peripheral blood mononuclear cells (PBMCs) from healthy male and female subjects were separated using Hystopaque, and monocytes were isolated from PBMCs using a positive selection of CD14+ cells. Cells were stimulated with LDL 10 µg/mL, and the transcriptional profile of M1 macrophages performed during LDL internalization was determined using a Clariom D platform array. Results: Chromosome Y influences the immune system and inflammatory responses in males expressing 43% of transcripts in response to LDL treatment. Males and females share 15 transcripts, where most correspond to non-coding elements involved in oxidative stress and endothelial damage. Conclusions: During LDL internalization, male monocyte-derived M1 macrophages display more marked proinflammatory gene expression. In contrast, female M1 macrophages display a more significant number of markers associated with cell damage.

Obesity is associated with an increased incidence and aggressiveness of breast cancer and is estimated to increment the development of this tumor by 50 to 86%. These associations are driven, in part, by changes in the serum molecules. Epidemiological studies have reported that Metformin reduces the incidence of obesity-associated cancer, probably by regulating the metabolic state. In this study, we evaluated in a breast cancer in-vitro model the activation of the IR-β/Akt/p70S6K pathway by exposure to human sera with different metabolic and hormonal characteristics. Furthermore, we evaluated the effect of brief Metformin treatment on sera of obese postmenopausal women and its impact on Akt and NF-κB activation. We demonstrated that MCF-7 cells represent a robust cellular model to differentiate Akt pathway activation influenced by the stimulation with sera from obese women, resulting in increased cell viability rates compared to cells stimulated with sera from normal-weight women. In particular, stimulation with sera from postmenopausal obese women showed an increase in the phosphorylation of IR-β and Akt proteins. These effects were reversed after exposure of MCF-7 cells to sera from postmenopausal obese women with insulin resistance with Metformin treatment. Whereas sera from women without insulin resistance affected NF-κB regulation. We further demonstrated that sera from post-Metformin obese women induced an increase in p38 phosphorylation, independent of insulin resistance. Our results suggest a possible mechanism in which obesity-mediated serum molecules could enhance the development of luminal A-breast cancer by increasing Akt activation. Further, we provided evidence that the phenomenon was reversed by Metformin treatment in a subgroup of women.

Matrix metalloproteinases (MMP) are key players in the remodelling of the extracellular matrix under physiological and pathological conditions. Thermodynamic parameters of human recombinant metalloproteinases of the active (rMMP2, 3, 7, 8 and 9) and latent (rPro-MMP2, 3 and 9) forms were obtained by differential scanning calorimetry (DSC). Temperature by itself does not result in autocatalysis of recombinant MMP. The transitions observed by DSC correspond to structural domains of the monomeric protein. In this study, we show the domain organization of these proteins, where the thermal transition (Tm) of the main component is observed at 71.3 °C (ProMMP-2); 74.8 °C (ProMMP-8); 80.0 °C (ProMMP-3); 92.6 °C (ProMMP-9) and 98.3 °C (ProMMP-7). For MMP-3, this main Tm is related to the catalytic domain (CD). The isolated recombinant CD of MMP-3 unfolds as a single transition at Tm 83.4 °C, matching the more stable domain observed in the full-length active form of rMMP-3. The denaturation profile of rProMMP-3 shows the main transition at Tm 80 °C, a less stable domain before the propeptide domain (PD) cleavage. Our results indicate that the structural stability of MMP and particularly their CD are not substantially altered after cleavage of the PD. We propose that the thermodynamic parameters obtained by DSC are relevant for the functional study of MMP, particularly to reveal their contribution in complex biological samples in health and disease.

Metabolic disturbances and systemic pro-inflammatory changes have been reported in children with obesity. However, it is unclear the time-sequence of metabolic or inflammatory modifications during children obesity evolution. Our study aimed to quantify simultaneously metabolomic and inflammatory biomarkers in serum from children with different levels of adiposity. For this purpose, a cross-sectional study was used to perform targeted metabolomics and inflammatory cytokines measurements. Serum samples from children between six to ten years old were analyzed using either body mass index (BMI) or waist-to-height ratio (WHtR) classifications. One hundred and sixty-eight school-aged children were included. BMI classification in children with overweight or obesity showed altered concentrations of glucose and amino acids (glycine and tyrosine). Children classified by WHtR exhibited imbalances in amino acids (glycine, valine, and tyrosine) and lipids (triacyl glycerides and low-density lipoprotein) compared to control group. No differences in systemic inflammation biomarkers or in the prevalence of other results were found in these children. Abnormal arterial blood pressure was found in 32% of children with increased adiposity. In conclusion, obesity in school-aged children is characterized by significant metabolic modifications that are not accompanied by major disturbances in circulating concentrations of inflammatory biomarkers.

Understanding the regulatory mechanisms that affect obesogenic genes expression in newborns is essential for early prevention efforts, but they remain unclear. Our study aimed to explore whether the maternal p-BMI and GWG were associated with regulatory single-locus DNA methylation in selected obesogenic genes. For this purpose, DNA methylation was assayed by Methylation-Sensitive High Resolution Melting (MS-HRM) technique and Sanger allele-bisulfite sequencing in fifty samples of umbilical vein to evaluate glucosamine-6-phosphate deaminase 2 (GNPDA2), peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α), and leptin receptor (LEPR) genes. Correlations between DNA methylation levels and indicators of maternal nutritional status were carried out. Western blotting was used to evaluate protein expression in extracts of the same samples. Results indicated that GNPDA2 and PGC1α genes have the same level of DNA methylation in all samples; however, a differential DNA methylation of LEPR gene promoter was found, correlating it with GWG and this correlation is unaffected by maternal age or unhealthy habits. Furthermore, leptin receptor (Lep-Rb) was upregulated in samples that showed the lowest levels of DNA methylation. This study highlights the association between poor GWG and adjustments on obesogenic genes expression in newborn tissues with potential consequences for development of obesity in the future.

Structural equation modeling (SEM) can help understanding complex functional relationships among obesity, non-alcoholic fatty liver disease (NAFLD), family history of obesity, targeted metabolomics and pro-inflammatory markers. We tested two hypotheses: 1) If obesity precedes an excess of free fatty acids that increase oxidative stress and mitochondrial dysfunction, there would be an increase of serum acylcarnitines, amino acids and cytokines in obese subjects. Acylcarnitines would be related to non-alcoholic fatty disease that will induce insulin resistance. 2) If a positive family history of obesity and type 2 diabetes are the major determinants of the metabolomic profile, there would be higher concentration of amino acids and acylcarnitines in patients with this background that will induce obesity and NAFLD which in turn will induce insulin resistance.137 normoglycemic subjects, mean age (SD) of 30.61 (8.6) years divided in three groups: BMI30 with absence of NAFLD (G2), n = 24; and BMI>30 with NAFLD (G3), n = 31. Family history of obesity (any) was present in 53%. Both models were adjusted in SEM. Family history of obesity predicted obesity but could not predict acylcarnitines and amino acid concentrations (effect size

[This corrects the article DOI: 10.1371/journal.pone.0193138.].

Objective. To assess the effects of two groups of exercise routines on cardiovascular disease risk markers. Material and Methods. An intervention study was conducted with 319 Mexican school-aged children in which routines were implemented Monday through Friday for 12 weeks. Routine A was the reference group, with 20 min of less intense activity and routine B was the new group with 40 min of aerobic exercises. Body mass index (BMI), waist circumference, fat mass percentage (FM%), systolic and diastolic blood pressure, lipids, lipoproteins, glucose and insulin were measured before and after the intervention. Results. Routine A had an effect on diastolic pressure, while routine B had an effect on BMI, FM%, blood pressure and triglycerides. Routine B had a greater effect on blood pressure than routine A. The prevalence of obesity, high blood pressure and hypertriglyceridemia decreased in both groups. Conclusion. Aerobic exercise is an effective health promotion strategy to reduce some cardiovascular disease risk markers.Objetivo. Evaluar el efecto de dos rutinas grupales de ejercicio sobre marcadores de riesgo cardiovascular. Material y métodos. Intervención en 319 escolares mexicanos. Las rutinas fueron implementadas por 12 semanas (rutina A (referencia): 20 min con ejercicios menos intensos vs rutina B (nueva): 40 min con ejercicios aeróbicos). Se midieron al inicio y al final el índice de masa corporal (IMC), masa grasa (%MG), presión arterial sistólica y diastólica, lípidos, lipoproteínas, glucosa e insulina. Resultados. La rutina A tuvo efecto sobre la presión diastólica; la B tuvo efecto sobre el IMC, %MG, presión arterial y triglicéridos. La rutina B tuvo mayores efectos en la presión arterial que la rutina A. Las prevalencias de obesidad, hipertensión arterial e hipertrigliceridemia disminuyeron en ambos grupos. Conclusiones. El ejercicio aeróbico es una estrategia de promoción exitosa para reducir algunos marcadores de riesgo cardiovascular.

OBJETIVO: Evaluar el efecto de un programa de actividad física sobre los marcadores de riesgo cardiovascular en escolares mexicanos. MATERIAL Y MÉTODOS: Escolares de dos escuelas públicas de Querétaro (n= 360, 8-14 años) realizaron una rutina de actividad física durante 16 semanas (febrero a mayo de 2006). Se compararon mediciones antropométricas, de presión arterial y química sanguínea, antes y después de la intervención. RESULTADOS: La presión sistólica, los triacilglicéridos y el colesterol total disminuyeron de forma significativa en los escolares. La reducción de los lípidos fue mayor en los escolares con valores iniciales alterados. En niñas con riesgo cardiovascular inicial, el puntaje de conglomerado de riesgo disminuyó en grado considerable. No se observaron cambios en el IMC, circunferencia de cintura e insulina sé-rica. CONCLUSIONES: La aplicación de una rutina de ejercicio sencilla tiene efectos notorios sobre los indicadores de riesgo cardiovascular en escolares. Estos resultados pueden considerarse un modelo de intervención para paliar los efectos de la obesidad infantil.OBJECTIVE: To assess the effect of a physical activity intervention on cardiovascular risk factors in Mexican school-age children. MATERIAL AND METHODS: Children from two public schools in Queretaro (n=360, 8-14 years old) performed a 20-minute physical activity routine every school day during 16 weeks (February-May 2006). Anthropometric, blood pressure and biochemical assessment was done before and after implementation. RESULTS: Systolic blood pressure, triglyceride and total cholesterol levels decreased significantly. The decrease in lipid and lipoprotein levels was higher in children with high baseline levels. In high-risk girls, the cardiovascular risk cluster score decreased significantly. No change in BMI, waist circumference, or insulin was observed. CONCLUSION: A simple physical activity program modified several cardiovascular risk markers in school-age children. These results may be taken as a reference to develop better intervention programs directed toward preventing the effects of children obesity.

BACKGROUND:The activity of matrix degrading enzymes plays a leading role in the rupture of the fetal membranes under normal and pathological human labor, and matrix metalloproteinase-9 (MMP-9) it is considered a biomarker of this event. To gain further insight into local MMP-9 origin and activation, in this study we analyzed the contribution of human placental leukocytes to MMP-9 secretion and explored the local mechanisms of the pro-enzyme activation. METHODS:Placental blood leukocytes were obtained from women at term gestation without labor and maintained in culture up to 72 h. MMP-9 activity in the culture supernatants was determined by zymography and using a specific substrate. The presence of a potential pro-MMP-9 activator in the culture supernatants was monitored using a recombinant biotin-labeled human pro-MMP-9. To characterize the endogenous pro-MMP-9 activator, MMP-1, -3, -7 and -9 were measured by multiplex assay in the supernatants, and an inhibition assay of MMP-9 activation was performed using an anti-human MMP-3 and a specific MMP-3 inhibitor. Finally, production of MMP-9 and MMP-3 in placental leukocytes obtained from term pregnancies with and without labor was assessed by immunofluorescence. RESULTS:Placental leukocytes spontaneously secreted pro-MMP-9 after 24 h of culture, increasing significantly at 48 h (P≤0.05), when the active form of MMP-9 was detected. Culture supernatants activated the recombinant pro-MMP-9 showing that placental leukocytes secrete the activator. A significant increase in MMP-3 secretion by placental leukocytes was observed since 48 h in culture (P≤0.05) and up to 72 h (P≤0.001), when concentration reached its maximum value. Specific activity of MMP-9 decreased significantly (P≤0.005) when an anti-MMP-3 antibody or a specific MMP-3 inhibitor were added to the culture media. Placental leukocytes from term labor produced more MMP-9 and MMP-3 compared to term non-labor cells. CONCLUSIONS:In this work we confirm that placental leukocytes from human term pregnancies are able to secrete large amounts of MMP-9, and that the production of the enzyme it is enhanced by labor. We also demonstrate for the first time that endogenous MMP-3 plays a major role in MMP-9 activation process. These findings support the contribution of placental leukocytes to create the collagenolytic microenvironment that induces the rupture of the fetal membranes during human labor.

Background. Due to the higher prevalence of obesity and diabetes mellitus (DM), more pregnant women complicated with diabetes are in need of clinical care. Purpose. Compare the effect of including only low glycemic index (GI) carbohydrates (CHO) against all types of CHO on maternal glycemic control and on the maternal and newborn’s nutritional status of women with type 2 DM and gestational diabetes mellitus (GDM). Methods. Women (n=107, ≤29 weeks of gestation) were randomly assigned to one of two nutrition intervention groups: moderate energy and CHO restriction (Group 1: all types of CHO, Group 2: low GI foods). Results. No baseline differences in clinical data were observed. Capillary glucose concentrations throughout pregnancy were similar between groups. Fewer women in Group 2 exceeded weight gain recommendations. Higher risk of prematurity was observed in women in Group 2. No differences in glycemic control were observed between women with type 2 DM and those with GDM. Conclusions. Inclusion of low GI CHO as part of a comprehensive nutrition intervention is equally effective in improving glycemic control as compared to all types of CHO. This strategy had a positive effect in preventing excessive maternal weight gain but increased the risk of prematurity.

Chemotaxis has been studied by classical methods that measure chemotactic and random motility responses in vitro, but these methods do not evaluate the total number and phenotype of migrating leukocytes simultaneously. Our objective was to develop and validate a novel assay, combined Boyden-flow cytometry chemotaxis assay (CBFCA), for simultaneous quantification and phenotypification of migrating leukocytes. CBFCA exhibited several important advantages in comparison to the classic Boyden chemotaxis assay (CBCA): 1) improved precision (intra-assay coefficients of variation (CVs): CBFCA-4.7 and 4.8% vs. CBCA-30.1 and 17.3%; inter-observer CVs: CBFCA-3.6% vs. CBCA 30.1%); 2) increased recovery of cells, which increased assay to provide increased sensitivity; 3) high specificity for determining the phenotype of migrating/attracted leukocytes; and 4) reduced performance time (CBFCA 120 min vs. CBCA 265 min). Other advantages of CBFCA are: 5) robustness, 6) linearity, 7) eliminated requirement for albumin and, importantly, 8) enabled recovery of migrating leukocytes for subsequent studies. This latter feature is of great benefit in the study of migrating leukocyte subsets. We conclude that the CBFCA is a novel and improved technique for experiments focused on understanding leukocyte trafficking during the inflammatory response.