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Our retrospective cohort study evaluates the diagnostic yield of weekly laboratory surveillance in outpatient management of hypertensive disorders of pregnancy (HDP) based on patient clinical status at the time of laboratory testing. The study included 459 patients and 1,082 laboratory episodes: 356 (32.9%) episodes were performed in the setting of concerning clinical findings and 726 (67.1%) when the patient was asymptomatic. Overall, the diagnostic yield for abnormal laboratory values (n=11) was 1.0% (95% CI 0.4-1.6%) of all assessments performed and 2.4% (95% CI 1.0-3.8%) among all patients in the cohort. The prevalence of abnormal test results was higher in patients with clinical findings (2.8%, 95% CI 1.1-4.5%) compared with those who were asymptomatic (0.1%, 95% CI 0-0.2%) ( P <.01). Clinical findings suggestive of worsening disease had a 91% sensitivity (95% CI 59-100%) and a 99% (95% CI 99-100%) negative predictive value for abnormal laboratory values. Directed screening based on signs and symptoms, rather than universal weekly screening, may be a potential strategy to lower costs and reduce multiple blood draws for patients with HDP, because there is a low diagnostic yield for this practice.
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Hipertensión Inducida en el Embarazo , Femenino , Humanos , Embarazo , Hipertensión Inducida en el Embarazo/diagnóstico , Hipertensión Inducida en el Embarazo/terapia , Hipertensión Inducida en el Embarazo/epidemiología , Laboratorios , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Espera Vigilante , Complicaciones Cardiovasculares del EmbarazoRESUMEN
OBJECTIVE: To compare frequency of perinatal death between pregnant patients who completed the mRNA coronavirus disease 2019 (COVID-19) vaccination series and unvaccinated patients. METHODS: This retrospective cohort study included 15,865 pregnant patients who delivered 16,132 newborns after 20 weeks of gestation within a large regional health system between January 1, 2021, and December 31, 2021. Patients who received two doses of mRNA vaccine (Pfizer-BioNTech [BNT162b2] or Moderna [mRNA-1273]) were included in the vaccinated group and were compared with unvaccinated patients. Exclusions included partial vaccination, viral-vector vaccine, major congenital anomalies, and higher-order multiple gestation. Our primary outcome was perinatal death, including stillbirth and neonatal death, which was evaluated by logistic regression. Unadjusted odds ratios and adjusted odds ratios (aORs) were reported, controlling for age, body mass index (BMI), diabetes, hypertension, smoking, twin gestation, and insurance status. Propensity score matching was also performed. RESULTS: A total of 15,865 patients were included in the final analysis: 2,069 in the vaccination group and 13,796 in the control group. Only 13.0% of the cohort was included in the vaccination group; however, the vaccination rate increased over the course of the study period as the vaccine became more widely available and accepted. Vaccinated patients were older, with higher rates of people of non-Black racial non-Hispanic ethnic backgrounds, people with private insurance, and those with higher BMIs. Vaccination was associated with a lower incidence of perinatal death (0.5% vaccinated group vs 0.8% unvaccinated group, aOR 0.20 0.05-0.88). Vaccination against COVID-19 was also associated with lower rates of preterm delivery (aOR 0.63, 0.48-0.82), neonates with very low birth weight (aOR 0.35, 0.15-0.84), and neonatal intensive care unit (NICU) admission (aOR 0.66, 0.52-0.85). The association between vaccination and lower rates of perinatal death was no longer significant after propensity score matching. CONCLUSION: In a large retrospective cohort study, receipt of the primary mRNA COVID-19 vaccination series was associated with a lower rate of several adverse pregnancy outcomes, including perinatal death, preterm delivery, neonates with very low birth weight, and NICU admission. Although the decreased rates of perinatal death did not remain significant after propensity score matching, there was evidence of directional benefit for vaccinated patients.
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Vacunas contra la COVID-19 , COVID-19 , Muerte Perinatal , Nacimiento Prematuro , Femenino , Humanos , Recién Nacido , Embarazo , Vacuna BNT162 , COVID-19/epidemiología , COVID-19/prevención & control , COVID-19/complicaciones , Vacunas contra la COVID-19/efectos adversos , Resultado del Embarazo/epidemiología , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/etiología , Estudios Retrospectivos , Vacunación/efectos adversosRESUMEN
For volatile organic compounds (VOCs) to be released from the plant cell into the atmosphere, they have to cross the plasma membrane, the cell wall, and the cuticle. However, how these hydrophobic compounds cross the hydrophilic cell wall is largely unknown. Using biochemical and reverse-genetic approaches combined with mathematical simulation, we show that cell-wall localized non-specific lipid transfer proteins (nsLTPs) facilitate VOC emission. Out of three highly expressed nsLTPs in petunia petals, which emit high levels of phenylpropanoid/benzenoid compounds, only PhnsLTP3 contributes to the VOC export across the cell wall to the cuticle. A decrease in PhnsLTP3 expression reduces volatile emission and leads to VOC redistribution with less VOCs reaching the cuticle without affecting their total pools. This intracellular build-up of VOCs lowers their biosynthesis by feedback downregulation of phenylalanine precursor supply to prevent self-intoxication. Overall, these results demonstrate that nsLTPs are intrinsic members of the VOC emission network, which facilitate VOC diffusion across the cell wall.
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Compuestos Orgánicos Volátiles , Compuestos Orgánicos Volátiles/metabolismo , Difusión , Fenilalanina , Pared Celular/metabolismo , LípidosRESUMEN
OBJECTIVE: The objective of our study is to determine if human immunodeficiency virus (HIV)-positive pregnant patients have a higher rate of group B streptococcus (GBS) rectovaginal colonization compared with HIV-negative pregnant patients. STUDY DESIGN: Our study is a multi-site retrospective study performed at Ochsner Louisiana State University-Health Shreveport and Monroe campuses including patients who delivered between December 2011and June 2019. Rates of GBS rectovaginal colonization between HIV-positive pregnant patients were compared with a control group of HIV-negative patients. The control group was age and race matched in a 2:1 fashion. The primary outcome was to investigate rates of GBS rectovaginal colonization. Secondary outcomes included GBS culture antibiotic sensitivities, presence of GBS urinary tract infection, GBS positivity based on HIV viral load, and GBS positivity based on new vs established diagnosis of HIV. Continuous data were analyzed using an unpaired t-test, and categorical data were analyzed using a Chi-squared test. The probability level of <0.05 was set as statistically significant. RESULTS: A total of 225 patients were included in the final analysis, 75 HIV-positive and 150 HIV-negative controls. Demographic differences were noted. HIV-positive patients were more likely to deliver preterm and were more likely to deliver via cesarean section. Our primary outcome showed no significant differences in incidence of GBS colonization between HIV-positive patients and control group (n = 31, 41.3% vs n = 46, 30.6%, p = 0.136). Antibiotic resistance patterns showed no significant difference between the two groups. There were no significant differences in GBS positivity based on HIV viral load. CONCLUSION: Our study does not show a statistically significant difference in the incidence of GBS colonization between HIV-positive patients and HIV-negative controls. KEY POINTS: · HIV-positive pregnant patients do not have an increased risk of GBS rectovaginal colonization.. · HIV-positive pregnant patients have similar rates of GBS colonization regardless of viral load.. · GBS antibiotic sensitivities are similar in HIV-positive and HIV-negative pregnant patients..
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Infecciones por VIH , Complicaciones Infecciosas del Embarazo , Infecciones Estreptocócicas , Recién Nacido , Embarazo , Humanos , Femenino , Complicaciones Infecciosas del Embarazo/diagnóstico , Estudios Retrospectivos , Cesárea , Antibacterianos/uso terapéutico , Streptococcus agalactiae , Infecciones Estreptocócicas/complicaciones , Infecciones Estreptocócicas/tratamiento farmacológico , Infecciones Estreptocócicas/epidemiología , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , VaginaRESUMEN
Vitamin D deficiency is a widespread health problem globally and vitamin D deficiency/ insufficiency in pregnancy is a risk factor for preeclampsia, a hypertensive disorder in human pregnancy. Vitamin D elicits its biological effects through binding to its receptor VDR. In the present study, we determined maternal vascular expression of VDR and hnRNPC1/C2, a native repressor of VDR, in subcutaneous adipose tissue from women with normal pregnancy and preeclampsia. Maternal antenatal and postnatal vitamin D levels were measured. We found that hnRNPC1/C2 expression was markedly increased, while VDR expression was markedly reduced, in maternal vessel endothelium and smooth muscle cells from women with preeclampsia compared to that from normal pregnant controls. Reduced VDR expression was relevant to low maternal antenatal and postnatal vitamin D levels in women with preeclampsia. Using human umbilical vein endothelial cells (HUVECs) as an endothelial model, we further investigated the role of hnRNPC1/C2-mediated VDR expression in endothelial cells, and tested effect of hnRNPC1/C2 inhibition on endothelial response to bioactive vitamin D, 1,25(OH)2D3. Our results showed that inhibition of hnRNPC1/C2 by hnRNPC1/C2 siRNA resulted in not only an increase in endothelial VDR expression, but further improved endothelial response to 1,25(OH)2D3. These findings indicate that aberrant hnRNPC1/C2 expression may contribute to reduced vascular expression of VDR in women with preeclampsia and suggest that hnRNPC1/C2 could be a target for improving vascular endothelial cell response to vitamin D.
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Preeclampsia , Deficiencia de Vitamina D , Endotelio Vascular/metabolismo , Femenino , Células Endoteliales de la Vena Umbilical Humana , Humanos , Preeclampsia/genética , Preeclampsia/metabolismo , Embarazo , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Vitamina D/metabolismo , VitaminasRESUMEN
Plant cuticles are a mixture of crystalline and amorphous waxes that restrict the exchange of molecules between the plant and the atmosphere. The multicomponent nature of cuticular waxes complicates the study of the relationship between the physical and transport properties. Here, a model cuticle based on the epicuticular waxes of Petunia hybrida flower petals was formulated to test the effect of wax composition on diffusion of water and volatile organic compounds (VOCs). The model cuticle was composed of an n-tetracosane (C24 H50 ), 1-docosanol (C22 H45 OH), and 3-methylbutyl dodecanoate (C17 H34 O2 ), reflecting the relative chain length, functional groups, molecular arrangements, and crystallinity of the natural waxes. Molecular dynamics simulations were performed to obtain diffusion coefficients for compounds moving through waxes of varying composition. Simulated VOC diffusivities of the model system were found to highly correlate with in vitro measurements in isolated petunia cuticles. VOC diffusivity increased up to 30-fold in completely amorphous waxes, indicating a significant effect of crystallinity on cuticular permeability. The crystallinity of the waxes was highly dependent on the elongation of the lattice length and decrease in gap width between crystalline unit cells. Diffusion of water and higher molecular weight VOCs were significantly affected by alterations in crystalline spacing and lengths, whereas the low molecular weight VOCs were less affected. Comparison of measured diffusion coefficients from atomistic simulations and emissions from petunia flowers indicates that the role of the plant cuticle in the VOC emission network is attributed to the differential control on mass transfer of individual VOCs by controlling the composition, amount, and dynamics of scent emission.
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Petunia , Compuestos Orgánicos Volátiles , Células Epidérmicas , Epidermis de la Planta/química , Hojas de la Planta/química , Compuestos Orgánicos Volátiles/análisis , Agua , Ceras/químicaAsunto(s)
COVID-19/epidemiología , Pandemias , Complicaciones Infecciosas del Embarazo/epidemiología , Atención Prenatal , SARS-CoV-2 , Adulto , COVID-19/etiología , COVID-19/prevención & control , Vacunas contra la COVID-19/administración & dosificación , Estudios de Cohortes , Femenino , Humanos , Embarazo , Complicaciones Infecciosas del Embarazo/etiología , Complicaciones Infecciosas del Embarazo/prevención & control , Resultado del Embarazo , Estudios Retrospectivos , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
OBJECTIVE: It was reported that fetal gender was associated with gestational-age related incidence of preeclampsia. However, there is no study to date to evaluate the association of fetal gender differences with all hypertensive disorders of pregnancy. The present study aimed to evaluate the association, if any, between fetal gender differences and the disposition to develop hypertensive disorders of pregnancy and the risk of developing severe features. METHODS: This was a single site retrospective cohort that included patients who were diagnosed with either gestational hypertension, preeclampsia without severe features, severe preeclampsia, superimposed preeclampsia, or superimposed preeclampsia with severe features. Patients were divided into two groups based on male versus female fetal gender. Our primary outcome was gestational age (GA) at diagnosis of hypertensive disorder. GA ranges evaluated were <28 weeks, 28-34 weeks, 34-37 weeks, and >37 weeks. Secondary outcomes were maternal morbidity (severe features at delivery, HELLP syndrome, placental abruption, eclampsia, maternal death, and maternal intensive care unit (ICU) admission), GA range at delivery, indication for delivery, and fetal outcomes. Continuous data were analyzed using an unpaired t-test and categorical data was analyzed using Chi-square test. A probability level was <.05 was set as statistically significant. RESULTS: A total of 597 patients were included, 275 with male fetus and 322 with female fetus. Demographic comparison between the two groups showed similar rates in patients complicated with chronic hypertension, but a higher incidence of antihypertensive medication used in the male fetus group, p < .05. All other demographics were similar between the two groups. There were no significant differences in maternal primary and secondary outcomes, including GA range at diagnosis and severe features at delivery, and fetal outcomes, including neonatal intensive care unit (NICU) admission, evaluated between the two groups. CONCLUSION: Our study did not find significant differences between fetal gender and GA at the diagnosis of hypertensive disorders of pregnancy or development of severe features in the study subjects.
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Eclampsia , Hipertensión Inducida en el Embarazo , Preeclampsia , Femenino , Humanos , Hipertensión Inducida en el Embarazo/epidemiología , Recién Nacido , Masculino , Placenta , Preeclampsia/diagnóstico , Preeclampsia/epidemiología , Embarazo , Estudios RetrospectivosRESUMEN
OBJECTIVE: To investigate differences in maternal and fetal outcomes among pregnant patients with chronic hypertension requiring antihypertensives for adequate control versus those who do not require antihypertensives. STUDY DESIGN: Single-site retrospective cohort study including pregnant patients with chronic hypertension from 2015-2018. Two groups included those who required antihypertensives versus those who did not. Primary outcome is composite morbidity: pregnancy loss after 20 weeks, IUGR, maternal death, maternal stroke or TIA, pulmonary edema, renal failure, hypertensive emergency, HELLP syndrome, placental abruption or delivery before 34 weeks. Secondary outcomes included development of severe features, indication for preterm labor less than 37 weeks, incidence of severe range blood pressures, and neonatal outcomes. Student t, chi square, and Kruskal-Wallis tests where appropriate. Logistic regression used to account for potential confounders. RESULTS: Study cohort included 117 on antihypertensives and 114 not on antihypertensives. Use of antihypertensives was associated with the composite primary outcome (Odds ratio [OR], 3.88; 95% confidence interval [CI], 1.66-9.78). Use of antihypertensive medications was also associated with increased risk of prenatal diagnosis of IUGR, delivery prior to 34 weeks, development of severe features, severe blood pressure during pregnancy, earlier mean gestational age at delivery, lower mean birth weight, and higher risk of NICU admission. Logistic regression analysis showed that the association between medication requirement and our composite primary outcome persisted even after adjustment for age, BMI, and presence of gestational diabetes. CONCLUSION: Our findings show an association between the requirement of antihypertensive medication use a significantly higher risk of composite primary outcome, prenatal diagnosis of IUGR, delivery prior to 34 weeks, and the development of severe features.
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Antihipertensivos , Hipertensión , Antihipertensivos/uso terapéutico , Femenino , Edad Gestacional , Humanos , Recién Nacido , Placenta , Embarazo , Estudios RetrospectivosRESUMEN
Photoautotrophic microorganisms are increasingly explored for the conversion of atmospheric carbon dioxide into biomass and valuable products. The Calvin-Benson-Bassham (CBB) cycle is the primary metabolic pathway for net CO2 fixation within oxygenic photosynthetic organisms. The cyanobacteria, Synechocystis sp. PCC 6803, is a model organism for the study of photosynthesis and a platform for many metabolic engineering efforts. The CBB cycle is regulated by complex mechanisms including enzymatic abundance, intracellular metabolite concentrations, energetic cofactors and post-translational enzymatic modifications that depend on the external conditions such as the intensity and quality of light. However, the extent to which each of these mechanisms play a role under different light intensities remains unclear. In this work, we conducted non-targeted proteomics in tandem with isotopically non-stationary metabolic flux analysis (INST-MFA) at four different light intensities to determine the extent to which fluxes within the CBB cycle are controlled by enzymatic abundance. The correlation between specific enzyme abundances and their corresponding reaction fluxes is examined, revealing several enzymes with uncorrelated enzyme abundance and their corresponding flux, suggesting flux regulation by mechanisms other than enzyme abundance. Additionally, the kinetics of 13C labeling of CBB cycle intermediates and estimated inactive pool sizes varied significantly as a function of light intensity suggesting the presence of metabolite channeling, an additional method of flux regulation. These results highlight the importance of the diverse methods of regulation of CBB enzyme activity as a function of light intensity, and highlights the importance of considering these effects in future kinetic models.
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Out of the three aromatic amino acids, the highest flux in plants is directed towards phenylalanine, which is utilized to synthesize proteins and thousands of phenolic metabolites contributing to plant fitness. Phenylalanine is produced predominantly in plastids via the shikimate pathway and subsequent arogenate pathway, both of which are subject to complex transcriptional and post-transcriptional regulation. Previously, it was shown that allosteric feedback inhibition of arogenate dehydratase (ADT), which catalyzes the final step of the arogenate pathway, restricts flux through phenylalanine biosynthesis. Here, we show that in petunia (Petunia hybrida) flowers, which typically produce high phenylalanine levels, ADT regulation is relaxed, but not eliminated. Moderate expression of a feedback-insensitive ADT increased flux towards phenylalanine, while high overexpression paradoxically reduced phenylalanine formation. This reduction could be partially, but not fully, recovered by bypassing other known metabolic flux control points in the aromatic amino acid network. Using comparative transcriptomics, reverse genetics, and metabolic flux analysis, we discovered that transcriptional regulation of the d-ribulose-5-phosphate 3-epimerase gene in the pentose phosphate pathway controls flux into the shikimate pathway. Taken together, our findings reveal that regulation within and upstream of the shikimate pathway shares control over phenylalanine biosynthesis in the plant cell.
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Hidroliasas/genética , Petunia/genética , Petunia/metabolismo , Fenilalanina/biosíntesis , Proteínas de Plantas/genética , Carbohidrato Epimerasas/genética , Carbohidrato Epimerasas/metabolismo , Flores/genética , Flores/metabolismo , Regulación de la Expresión Génica de las Plantas , Hidroliasas/metabolismo , Mutación , Fenilalanina/metabolismo , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente , Plastidios/genética , Plastidios/metabolismo , Metabolismo Secundario/genética , Ácido Shikímico/metabolismoRESUMEN
MiR-126-3p is a prototype of an endothelial miRNA and has protective effects on endothelial cells. However, little is known about the effects of miR-126-3p on placental trophoblasts. In the present study, we tested the hypothesis that aberrant miR-126-3p expression is present in preeclamptic placenta which contributes to increased inflammatory response in trophoblasts. Placentas were obtained immediately after delivery from normotensive and preeclamptic pregnancies. Villous tissue was either fixed with formalin or used for trophoblast isolation. Trophoblast miR-126-3p expression was assessed by in situ hybridization of formalin-fixed tissue sections and by RT-PCR in cultured syncytiotrophoblasts. Culture medium was collected for measurement of IL-6, TNFα, and 8-Isoprostane production by ELISA and total cellular protein was collected for evaluation of HIF1α expression by Western blot. Effects of overexpression of miR-126-3p in trophoblasts on cytokine production were tested by transfection of pre-mir-126, a precursor of miR-126, into primary isolated trophoblasts. We found that downregulation of miR-126-3p expression was associated with increased IL-6 and TNFα production in trophoblasts from preeclamptic placentas vs. normal placentas. Moreover, transient overexpression of miR-126-3p significantly reduced IL-6 and TNFα production in trophoblasts from both normal and preeclamptic placentas. We further found that increase in miR-126-3p expression not only suppressed hypoxia-induced increases in IL-6 and TNFα production, but also attenuated hypoxia-induced increases in HIF1α expression and 8-Isoprostane production in trophoblasts cultured under hypoxic condition. These results provide plausible evidence that downregulation of miR-126-3p expression reduces anti-inflammatory and anti-oxidative stress activities in placental trophoblasts in preeclampsia.
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Regulación hacia Abajo/inmunología , MicroARNs/metabolismo , Preeclampsia/inmunología , Trofoblastos/patología , Adulto , Hipoxia de la Célula/inmunología , Células Cultivadas , Dinoprost/análogos & derivados , Dinoprost/metabolismo , Femenino , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Interleucina-6/genética , MicroARNs/genética , Estrés Oxidativo/genética , Estrés Oxidativo/inmunología , Preeclampsia/patología , Embarazo , Trofoblastos/inmunología , Trofoblastos/metabolismo , Factor de Necrosis Tumoral alfa/genética , Adulto JovenRESUMEN
INTRODUCTION: N6-methyladenosine (m6A) has been recognized as one of the most abundant and functionally relevant modifications of RNAs and plays critical roles in biological and pathological processes. Placental trophoblast dysfunction significantly contributes to the pathogenesis of preeclampsia. The present study aimed to determine if altered m6A expression occurs in placental trophoblasts in preeclampsia. Expression of m6A methyltransferase (methyltransferase like 3 (METTL3)), m6A demethylases (fat mass and obesity-associated protein (FTO) and AlkB homolog 5 (ALKBH5)), and m6A reader protein, heterogeneous nuclear ribonucleoprotein C1/C2 (hnRNPC1/C2), were also examined. METHODS: A total of 43 placentas (20 normal term, 5 normotensive preterm, and 18 preeclamptic) were used in the study. Expression of m6A, METTL3, FTO, ALKBH5, and hnRNPC1/C2 were examined by immunostaining in villous tissue sections and/or by Western blot of total cellular protein in trophoblasts isolated from normotensive and preeclamptic placentas. Total RNA extracted from trophoblasts was used to measure m6A RNA methylation. Effects of METTL3 on m6A RNA methylation and hnRNPC1/C2 expression were assessed by transfection of METTL3 siRNA in trophoblasts from preeclamptic placentas. RESULTS: Expression of m6A and m6A RNA methylation were significantly increased in trophoblasts from preeclamptic vs. normotensive placentas, p < 0.05. Expression of METTL3 and hnRNPC1/C2, but not FTO and ALKBH5, was significantly upregulated in trophoblasts from preeclamptic vs. normotensive placentas, p < 0.01. Transfection of METTL3 siRNA significantly reduced the level of m6A RNA methylation and hnRNPC1/C2 expression in trophoblasts from preeclamptic placentas, p < 0.05. CONCLUSION: The finding of increased METTL3 expression and m6A RNA methylation associated with increased hnRNPC1/C2 expression provides a new posttranscriptional mechanism that aberrant m6A modification may contribute to trophoblast dysfunction in preeclampsia.
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Metiltransferasas/genética , Preeclampsia/genética , Procesamiento Postranscripcional del ARN/genética , Trofoblastos/metabolismo , Adenosina/metabolismo , Adulto , Estudios de Casos y Controles , Femenino , Regulación Enzimológica de la Expresión Génica , Humanos , Metilación , Metiltransferasas/metabolismo , Placenta/metabolismo , Placenta/patología , Preeclampsia/metabolismo , Preeclampsia/patología , Embarazo , ARN Mensajero/metabolismo , Trofoblastos/patología , Regulación hacia Arriba/genética , Adulto JovenRESUMEN
The plant cuticle is the final barrier for volatile organic compounds (VOCs) to cross for release to the atmosphere, yet its role in the emission process is poorly understood. Here, using a combination of reverse-genetic and chemical approaches, we demonstrate that the cuticle imposes substantial resistance to VOC mass transfer, acting as a sink/concentrator for VOCs and hence protecting cells from the potentially toxic internal accumulation of these hydrophobic compounds. Reduction in cuticle thickness has differential effects on individual VOCs depending on their volatility, and leads to their internal cellular redistribution, a shift in mass transfer resistance sources and altered VOC synthesis. These results reveal that the cuticle is not simply a passive diffusion barrier for VOCs to cross, but plays the aforementioned complex roles in the emission process as an integral member of the overall VOC network.
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Flores/química , Petunia/química , Compuestos Orgánicos Volátiles/química , Regulación hacia Abajo , Genes de Plantas/genética , Fenilalanina/química , Interferencia de ARN , SolventesRESUMEN
Adverse intrauterine environment has been considered a predisposing factor for fetal programming in preeclampsia. Using human umbilical vein endothelial cells (HUVECs), we specifically explored if aberrant histone methylation occurs in fetal endothelial cells in preeclampsia. Strikingly, we found that increased di-, and tri-methylation of histone H3 lysine 9 (H3K9me2 and H3K9me3) expression were associated with upregulation of methyltransferase G9a and downregulation of endothelial nitric oxide synthase and CuZn-SOD expression in preeclamptic HUVECs. We further demonstrated that hypoxia-induced hypermethylation of H3K9 and reduced CuZn-SOD expression mimicked what were seen in preeclamptic HUVECs and inhibition of G9a could attenuate these hypoxia-induced adverse events. Our study was the first to identify hypermethylation status in fetal endothelial cells in preeclampsia, which provides plausible evidence that increased oxidative stress in the intrauterine environment is likely a mechanism to induce aberrant histone modification in fetal endothelial cells which may have a significant impact on fetal programming in preeclampsia.
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Células Endoteliales/metabolismo , Células Endoteliales/patología , Feto/patología , Histonas/metabolismo , Lisina/metabolismo , Preeclampsia/metabolismo , Regulación hacia Arriba , Adulto , Hipoxia de la Célula , Regulación hacia Abajo , Femenino , Antígenos de Histocompatibilidad/metabolismo , N-Metiltransferasa de Histona-Lisina/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Metilación , Óxido Nítrico Sintasa de Tipo III/metabolismo , Estrés Oxidativo , Placenta/metabolismo , Embarazo , Superóxido Dismutasa/metabolismoRESUMEN
Coronavirus disease 2019 (COVID-19) is spreading rapidly around the world with devastating consequences on patients, healthcare workers, health systems, as well as economies. While, healthcare systems are globally operating at maximum capacity, healthcare workers and especially anesthesia providers are facing extreme pressures, something that is also leading to declining availability and increasing stress. In this regard, it is extremely concerning the fact that some regions worldwide have reported up to 20% of their cases to be healthcare workers. When considering that the global case fatality rate may be as much as 5.4%, these numbers are concerning and unacceptable. As this pandemic accelerates, access to personal protective equipment for health workers is a key concern since at present, healthcare workers are every country's most valuable resource in the fight against COVID-19. Governments and heath organizations should take care of their staff and support them in any way possible. This review aims to describe the current situation anesthesia providers are facing in the setting of COVID-19 and provide solutions and evidence on important concerns, including which guidance to follow, the level of equipment that is adequate, and the level of protection they need for every patient being administered an anesthetic.
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Anestesiología/métodos , Betacoronavirus , Infecciones por Coronavirus/prevención & control , Personal de Salud , Pandemias/prevención & control , Neumonía Viral/prevención & control , COVID-19 , Humanos , Equipo de Protección Personal , SARS-CoV-2RESUMEN
INTRODUCTION: Non-reassuring fetal tracing is the second leading cause of primary cesarean delivery in the United States. Prolonged fetal heart rate decelerations are non-reassuring fetal heart rate characteristics, which do not uniformly predict poor fetal outcome but can prompt obstetricians to proceed with cesarean delivery. The objective of this manuscript is to identify a strategy to reduce the primary cesarean section rate in patients with prolonged fetal heart rate decelerations in labor. METHODS: This is a retrospective cohort study over a 5-year period at an academic medical center, including patients undergoing primary cesarean section following labor induction, augmentation, or spontaneous labor who were noted to have prolonged fetal heart rate deceleration(s) in the 1 h prior to the time of delivery. Two groups were compared: "crash" cesarean sections versus "emergent" cesarean sections. The primary outcome was if fetal heart tones were rechecked in the operating room prior to cesarean section incision. Secondary outcomes included maternal-fetal monitoring versus Doppler fetal heart tones in the operating room, return to baseline noted in the operating room, fetal outcomes, fetal monitoring characteristics, and anesthesia type between crash versus emergent groups. RESULTS: Of 1969 term singleton cesarean sections, 119 patients met our inclusion criteria (emergent group n = 80) (crash group n = 39), which accounted for 13.9% of all primary cesarean sections during the study period. The emergent group had a significantly higher rate of reassessment of fetal heart tones in the operating room n = 61 (76.2%) versus the crash group n = 15 (38.4%) (p ≤ 0.0001). There were no statistically significant differences regarding fetal outcomes between the two groups. The crash group had a higher rate of category 1 fetal heart rate tracing prior to the prolonged deceleration, a longer median prolonged deceleration, and a deeper median nadir of the prolonged deceleration; these differences were statistically significant. The prolonged-to-delivery interval was significantly shorter in the crash group (median = 15 min) than tin he emergent group (median = 33 min) (p ≤ 0.0001). The crash group also had a higher rate of general anesthesia (n = 11, 28.2%) than the emergent group (n = 6, 7.5%) (p = 0.002). The crash group was specifically investigated. Of the 15 patients with fetal heart tones rechecked in the crash group, 7 had returned to baseline in the operating room, but underwent cesarean section without fetal monitoring. CONCLUSION: Our results indicate that the practice of placing patients on fetal monitor upon arrival to the operating room prior to performing crash cesarean delivery could reduce the rate of primary cesarean deliveries performed for prolonged decelerations in labor. When fetal heart tones have returned to baseline upon arrival in the operating room, the decision to proceed with cesarean delivery can be reconsidered. However, many clinical factors must be taken into consideration, and the decision to proceed is ultimately at the discretion of the obstetrics provider.
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Cesárea , Frecuencia Cardíaca Fetal , Desaceleración , Femenino , Humanos , Trabajo de Parto Inducido , Embarazo , Estudios RetrospectivosRESUMEN
In plants, phenylalanine biosynthesis occurs via two compartmentally separated pathways. Overexpression of petunia chorismate mutase 2 (PhCM2), which catalyzes the committed step of the cytosolic pathway, increased flux in cytosolic phenylalanine biosynthesis, but paradoxically decreased the overall levels of phenylalanine and phenylalanine-derived volatiles. Concomitantly, the levels of auxins, including indole-3-acetic acid and its precursor indole-3-pyruvic acid, were elevated. Biochemical and genetic analyses revealed the existence of metabolic crosstalk between the cytosolic phenylalanine biosynthesis and tryptophan-dependent auxin biosynthesis mediated by an aminotransferase that uses a cytosolic phenylalanine biosynthetic pathway intermediate, phenylpyruvate, as an amino acceptor for auxin formation.