Association between maternal cardiometabolic markers and fetal growth in non-complicated pregnancies: a secondary analysis of the PRINCESA cohort.

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 ( ß ^ = 24.00 g; 95%CI: 12.9, 35.3), were heavier at the sixth month ( ß ^ =48.24 g; 95%CI: 7.2, 89.7) and had higher birth weight ( ß ^ = 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 ( ß ^ = - 42.4 g; 95%CI: - 82.7, - 2.1 and ß ^ = - 50.35 g; 95%CI: - 94.2, - 6.4), and a higher DBP trajectory was associated with lower birth weight ( ß ^ = - 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.

Effects of PM10 Airborne Particles from Different Regions of a Megacity on In Vitro Secretion of Cytokines by a Monocyte Line during Different Seasons.

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.

Metabolomic Phenotype of Hepatic Steatosis and Fibrosis in Mexican Children Living with Obesity.

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.

The pregnancy research on inflammation, nutrition, & city environment: systematic analyses study (PRINCESA) cohort, 2009-2015.

The Pregnancy Research on Inflammation, Nutrition, & City Environment: Systematic Analyses Study (PRINCESA) cohort was set up to evaluate associations between air pollution and birth outcomes among pregnant persons in Mexico City. Specifically, the study was designed to improve air pollution exposure assessment and elucidate biological mechanisms underlying associations between maternal exposures and adverse pregnancy outcomes. Pregnant persons (all women) (N = 935) between ages 18-45 who lived and/or worked in metropolitan Mexico City, Mexico, from 2009 to 2015 and liveborn singleton infants (N = 815) of participants who completed follow-up were enrolled in the cohort. We followed participants monthly from enrollment to delivery and the following categories of data were obtained: demographic, medical and obstetric history, geo-referenced data, repeated measures on daily activity patterns, reported food intake, anthropometric, clinical and obstetric data, 20 serum and 20 cervicovaginal cytokines, and lower reproductive tract infection. Repeated ultrasound measures of fetal parameters and infant birth data are also included in the study's database. In addition, PRINCESA investigators calculated air pollution exposure measures for six pollutants measured by the Mexico City Atmospheric Monitoring System (SIMAT). These estimates utilize participants' addresses to account for spatial variation in exposure (nearest monitor, inverse distance weighting, and kriging) and are available daily during pregnancy for participants. To date, associations between environmental and nutritional impacts on maternal and child health outcomes have been evaluated. PRINCESA has a comprehensive database of maternal and infant data and biological samples and offers collaboration opportunities to study associations between environmental and other factors, including nutrition and pregnancy outcomes.

An early prediction model for gestational diabetes mellitus based on metabolomic biomarkers.

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.

Associations between Air Pollution Exposure and Blood Pressure during Pregnancy among PRINCESA Cohort Participants.

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.

Longitudinal large-scale changes in maternal circulating microRNAs associated with gestation-related compartments, fetal sex, and growth during and post-pregnancy.

Circulating microRNAs (c-miRNAs) during pregnancy could provide information regarding the functional status of the mother and fetus. However, it remains unclear which pregnancy-related processes are actually reflected by changes c-miRNAs. Here, we used large-scale c-miRNA profiling of maternal plasma during and post-pregnancy, and compared it with that of non-pregnant women. Fetal growth measurements and fetal sex data were used to identify associated changes in these transcripts. Surprisingly, c-miRNA subpopulations with prominent expression in maternal/fetal compartments (placenta, amniotic fluid, umbilical cord plasma and breast milk) were found to be under-expressed in circulation throughout pregnancy relative to non-pregnant plasma profiles. Furthermore, we found a bias in global c-miRNA expression in association with fetal sex right from the first trimester, in addition to a specific c-miRNA signature of fetal growth. Our results demonstrate the existence of specific temporal changes in c-miRNA populations associated with specific pregnancy-related compartments and processes, including fetal sex, and growth.

Conversion of M1 Macrophages to Foam Cells: Transcriptome Differences Determined by Sex.

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.

Cervicovaginal Cytokines to Predict the Onset of Normal and Preterm Labor: a Pseudo-longitudinal Study.

Inflammatory processes associated with human parturition are still not completely understood, not only because the gap between inflammation and the onset of labor has been difficult to study but also because of the limited knowledge about the role of cervicovaginal fluid (CVF) cytokines during the sequence of labor. We aimed to determine whether CVF cytokines could predict the onset of normal and preterm labor. Chemokines and proinflammatory and anti-inflammatory cytokines in CVF were measured in a pseudo-longitudinal manner in healthy women between 12 and 41 weeks gestation with intact fetal membranes before and during the first stage of labor. Women were grouped into five stages, from the absence of uterine activity and cervical changes to regular uterine contractions with cervix dilation > 3 cm (active phase of labor). Of 144 women with spontaneous labor, 96 gave birth at term, 48 gave birth preterm, and both groups displayed similar cytokine concentrations. We found positive correlations between proinflammatory cytokines and the initial sequence of labor, using individual cytokines and score-based data by principal component analysis (IFN-γ, TNF-α, IL-1ß, IL-6) as dependent variables. The risk of labor onset increased as the concentrations of IL-6 increased (hazard ratio = 202.09, 95% confidence interval = 24.57-1662.49, P < 0.001). The IL-6 concentration predicted the onset of labor within 12 days of sampling (area under the time-dependent ROC curve = 0.785, 95% confidence interval = 0.693-0.877). Here, we showed that regardless of gestational age, the onset of labor could be predicted by the IL-6 concentration in the CVF, since the initial sequence of spontaneous labor displayed an inflammatory response expressed by the increase in proinflammatory cytokines.

Factores de riesgo para complicaciones graves de COVID-19, comparando tres olas epidemiológicas. Un enfoque desde la atención primaria en México / Risk factors for COVID-19 severe complications comparing three major epidemiological waves: An approach from primary health care in Mexico

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.(AU)

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.(AU)

[Risk factors for COVID-19 severe complications comparing three major epidemiological waves: An approach from primary health care in Mexico]. / Factores de riesgo para complicaciones graves de COVID-19, comparando tres olas epidemiológicas. Un enfoque desde la atención primaria en México.

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.

Asociación de la exposición a contaminantes atmosféricos con indicadores epidemiológicos de morbilidad y mortalidad por Covid-19 en el Valle de México.

OBJETIVO: Analizar la asociación de la concentración de con-taminantes 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.

Sex-differential RXRα gene methylation effects on mRNA and protein expression in umbilical cord of the offspring rat exposed to maternal obesity.

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.

Sera from women with different metabolic and menopause states differentially regulate cell viability and Akt activation in a breast cancer in-vitro model.

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-ß/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-ß 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.

End-point RT-PCR based on a conservation landscape for SARS-COV-2 detection.

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.

miR-21 differentially regulates IL-1ß and IL-10 expression in human decidual cells infected with streptococcus B.

Intrauterine infections caused by bacteria like group B streptococcus (GBS) and the subsequent activation of the maternal inflammatory response have been long suspected to be the underlying cause of preterm labor. The inflammatory network triggered by maternal decidua has been widely described and includes the secretion of pro- and anti-inflammatory cytokines as IL-1ß and IL-10; however, the mechanisms that regulate their secretion have not been completely elucidated. MicroRNAs (miRNAs) are critical modulators of the inflammatory response by regulating cytokine expression in several cell types. Here, we explored the role of miR-21 in the expression of IL-1ß and IL-10 in human decidual stromal cells (DSCs) exposed in vitro to GBS. We observed that IL1B and IL10 expression at the mRNA level was increased in DSCs after GBS infection. IL-10 but not IL-1ß secretion was detected in the culture supernatants. We found a higher miR-21 expression (22-fold) in infected DSCs as compared with non-infected cells. miR-21 functional analysis revealed that DSCs transfected with an antagomiR vs. miR-21 significantly increased the secretion of IL-1ß but decreased that of IL-10 in DSCs cells infected with GBS. Our results suggest that miR-21 participates in balancing the inflammatory response in infected decidua through at least IL-1ß and IL-10 regulation. This is the first study attributing a functional role of miR-21 in the regulation of key molecules involved in the inflammatory response in infected DSCs, providing new insights into the epigenetic control of human decidual inflammation.

Association of pre-pregnancy body mass index and rate of weight gain during pregnancy with maternal indicators of cardiometabolic risk.

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: [Formula: see text] = 33.08, p = 0.010; TG: [Formula: see text] = 31.29, p = <0.001) but the concentrations increased less than in women with normal pBMI (TC: [Formula: see text] = -14.18, p = 0.001; TG: [Formula: see text] = -5.42, p < 0.001). By the end of pregnancy, women with pre-gestational obesity had lower concentrations of lipids than women with normal pBMI. By contrast, women with pre-gestational obesity had higher glucose concentrations and higher BP levels than women with normal pBMI over pregnancy. CONCLUSIONS: pBMI is differentially associated with longitudinal trajectories of maternal biochemical markers of cardiometabolic risk. MGWG did not significantly affect the biochemical indicators or BP trajectories. Our results suggest that pBMI is more relevant to predicting adverse cardiometabolic markers trajectories during pregnancy than MGWG.

Metabolic flexibility during normal pregnancy allows appropriate adaptation during gestation independently of BMI.

BACKGROUND & AIMS: Overweight and obesity in reproductive-age women hasten the development of insulin resistance and increase risk for deterioration of pregnancy metabolism. These pregnancy-associated metabolic changes are similar to those of the metabolic syndrome. Thus, some metabolic flexibility must allow appropriate adaptation to the metabolic load that pregnancy imposes. We evaluated metabolic flexibility during uncomplicated pregnancy in women with pre-gestational normal weight or overweight. METHODS: In 20 women with singleton pregnancies, pre-pregnancy BMI was categorized as normal-weight (Nw) or overweight (Ow). The women were seen quarterly, and fasting and postprandial blood samples were collected at each visit. Indirect fasting and/postprandial calorimetry was performed to evaluate metabolic flexibility (Δrespiratory quotient (RQ) = RQpostprandial - RQfasting). RESULTS: In the first trimester, metabolic flexibility was lower in the Ow group compared to the Nw group (0.031 ± 0.0131 vs 0.077 ± 0.018, respectively) without a statistically significant difference (p = 0.053). In the second trimester, the Ow group was significantly more flexible than the Nw group (0.190 ± 0.016 vs 0.077 ± 0.015, respectively (p = 0.004)). For the third trimester, the Ow and Nw groups did not differ in metabolic flexibility (0.074 ± 0.013 vs 0.087 ± 0.021, respectively) (p = 0.40). The most influential variables for metabolic flexibility during pregnancy were lactate, leptin, ß-hydroxybutyrate, glycerol, aromatic amino acids, medium and long chain acylcarnitine's. CONCLUSIONS: Our findings indicate that metabolic flexibility changes throughout pregnancy, independently of pre-pregnancy BMI. These changes maintain metabolic homeostasis between the mother and foetus, allowing for appropriate adjustments during pregnancy.

Timing of Cervico-Vaginal Cytokine Collection during Pregnancy and Preterm Birth: A Comparative Analysis in the PRINCESA Cohort.

Preterm birth (PTB), defined as birth before 37 completed weeks of gestation, is a major cause of infant morbidity and mortality. Inflammation is an important component in the physiopathologic pathway leading to PTB but results from cross-sectional studies on associations between inflammation, as measured by cytokines, and PTB are inconsistent. Timing of cytokine measurement during pregnancy varies between studies and may contribute to inconsistent findings. We investigated the effects of timing on associations between 16 cervico-vaginal cytokines (Eotaxin, IL-10, IL-12p40, IL-17, IL-1RA, sIL-2rα, IL-1a, IL-1ß, IL-2, IL-6, IP-10, MCP-1, MIP-1α, MIP-1ß, TNFα, and VEGF) and PTB among 90 women throughout pregnancy. We used logistic regression to compare associations between concentrations of cervico-vaginal cytokines from periods in pregnancy and PTB. Trimester 1 cytokines had the strongest positive associations with PTB; for example, OR = 1.76 (95% confidence interval: 1.28, 2.42) for IL-6. Second and third trimester associations were weaker but largely positive. IL-1α was the only cytokine with a negative association (trimesters 2, 3 and overall pregnancy). Strong first trimester associations between cytokines and PTB suggest that measuring cytokines early in pregnancy may hold promise for early identification of PTB risk. Variations in cytokine measurement during pregnancy may contribute to inconsistencies among studies.

Saliva is a reliable and accessible source for the detection of SARS-CoV-2.

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.