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1.
Scand J Immunol ; 92(2): e12914, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32533709

RESUMO

Immature immune system and immune tolerance induced by exposure to HBeAg in utero and/or shortly after infection in newborns were reportedly the causes of chronic HBV infection. To investigate the effect of maternal-derived HBeAg on neonatal T cell immunity, we analysed and compared T cell phenotypes and functions among neonates born to HBsAg+ /HBeAg+ mothers (HBeAg+ neonates), HBsAg+ /HBeAg- mothers (HBeAg- neonates) and healthy control mothers (HC neonates), using flow cytometry. The results showed that neonatal T cell phenotypes were similar regardless of HBeAg exposure. Upon anti-CD3 and anti-CD28 stimulation in HBeAg+ neonates, CD4+ T cell production of IFN-γ (P < .05) was significantly enhanced, while CD8+ T cells secreted significantly more IL-2 compared with those in HBeAg- and HC groups (P < .05). Moreover, similar levels of IFN-γ and IL-10 were observed in the culture supernatant after stimulation with rHBsAg, rHBcAg or rHBeAg among HBeAg+ , HBeAg- and HC neonates, whereas HBeAg+ neonates produced more TNF-α than HBeAg- neonates upon stimulation with rHBcAg. In conclusion, the results indicated that the HBsAg+ /HBeAg+ maternal environment did not influence the phenotypes of cord blood T cells but boosted neonatal non-specific Th1-type cytokine production.


Assuntos
Sangue Fetal/imunologia , Antígenos E da Hepatite B/imunologia , Complicações Infecciosas na Gravidez/imunologia , Efeitos Tardios da Exposição Pré-Natal/imunologia , Linfócitos T/imunologia , Citocinas/imunologia , Feminino , Hepatite B/imunologia , Humanos , Recém-Nascido , Transmissão Vertical de Doença Infecciosa , Gravidez
2.
PLoS One ; 15(5): e0232002, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32379777

RESUMO

BACKGROUND: In pregnant women with gestational diabetes, glyburide can be an alternative to insulin despite concerns about its transplacental transfer. However, transplacental transfer of glyburide is poorly quantified and the relationship between cord blood glyburide concentration and hypoglycemia has not been studied. Our objective was to quantify the transplacental transfer of glyburide at delivery and to study the association between the cord blood glyburide concentration and the risk of neonatal hypoglycemia in patients with gestational diabetes treated with glyburide. METHODS AND FINDINGS: INDAO was a multicenter, noninferiority, randomized trial conducted between May 2012 and November 2016 in 914 women with singleton pregnancies and gestational diabetes. An ancillary study was conducted in the 87 patients of the Bicêtre University Hospital Center. The sample consisted of 46 patients with utilizable assays at delivery. The relationships between glyburide concentration and the time since the last intake of glyburide and between fetal glyburide concentration and neonatal hypoglycemia were modeled with linear or logistic regressions using fractional polynomials. There was placental transfer of glyburide at a fetal to maternal ratio of 62% (95% CI [50; 74]). Umbilical cord blood glyburide concentration decreased steeply after the last maternal glyburide intake. After 24 hours, the mean umbilical cord blood concentration was less than 5 ng/mL. Neonatal hypoglycemia risk was increased with an odds ratio of hypoglycemia equal to 3.70 [1.40-9.77] for each 10 ng/mL increase in the cord blood glyburide concentration. However, no newborns were admitted to the NICU because of clinical signs of hypoglycemia or for treatment of hypoglycemia. CONCLUSION: Considering that neonatal glyburide exposure may be limited by stopping treatment a sufficient time before labor, there may still be a place for glyburide in the management of gestational diabetes.


Assuntos
Diabetes Gestacional/tratamento farmacológico , Glibureto/efeitos adversos , Hipoglicemia/etiologia , Hipoglicemiantes/uso terapêutico , Doenças do Recém-Nascido/etiologia , Administração Oral , Adulto , Relação Dose-Resposta a Droga , Feminino , Sangue Fetal/química , Sangue Fetal/metabolismo , Glibureto/análise , Glibureto/uso terapêutico , Humanos , Hipoglicemia/epidemiologia , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/análise , Recém-Nascido , Doenças do Recém-Nascido/epidemiologia , Modelos Lineares , Modelos Logísticos , Troca Materno-Fetal , Razão de Chances , Gravidez
4.
Am J Obstet Gynecol ; 223(1): 111.e1-111.e14, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32335053

RESUMO

BACKGROUND: The coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2, is a global public health emergency. Data on the effect of coronavirus disease 2019 in pregnancy are limited to small case series. OBJECTIVE: To evaluate the clinical characteristics and outcomes in pregnancy and the vertical transmission potential of severe acute respiratory syndrome coronavirus 2 infection. STUDY DESIGN: Clinical records were retrospectively reviewed for 116 pregnant women with coronavirus disease 2019 pneumonia from 25 hospitals in China between January 20, 2020, and March 24, 2020. Evidence of vertical transmission was assessed by testing for severe acute respiratory syndrome coronavirus 2 in amniotic fluid, cord blood, and neonatal pharyngeal swab samples. RESULTS: The median gestational age on admission was 38+0 (interquartile range, 36+0-39+1) weeks. The most common symptoms were fever (50.9%, 59/116) and cough (28.4%, 33/116); 23.3% (27/116) patients presented without symptoms. Abnormal radiologic findings were found in 96.3% (104/108) of cases. Of the 116 cases, there were 8 cases (6.9%) of severe pneumonia but no maternal deaths. One of 8 patients who presented in the first trimester and early second trimester had a missed spontaneous abortion. Of 99 patients, 21 (21.2%) who delivered had preterm birth, including 6 with preterm premature rupture of membranes. The rate of spontaneous preterm birth before 37 weeks' gestation was 6.1% (6/99). One case of severe neonatal asphyxia resulted in neonatal death. Furthermore, 86 of the 100 neonates tested for severe acute respiratory syndrome coronavirus 2 had negative results; of these, paired amniotic fluid and cord blood samples from 10 neonates used to test for severe acute respiratory syndrome coronavirus 2 had negative results. CONCLUSION: Severe acute respiratory syndrome coronavirus 2 infection during pregnancy is not associated with an increased risk of spontaneous abortion and spontaneous preterm birth. There is no evidence of vertical transmission of severe acute respiratory syndrome coronavirus 2 infection when the infection manifests during the third trimester of pregnancy.


Assuntos
Infecções por Coronavirus/patologia , Pneumonia Viral/patologia , Complicações Infecciosas na Gravidez/virologia , Aborto Espontâneo/virologia , Adulto , Líquido Amniótico/virologia , Betacoronavirus , China , Infecções por Coronavirus/complicações , Feminino , Sangue Fetal/virologia , Humanos , Recém-Nascido , Transmissão Vertical de Doença Infecciosa , Pandemias , Pneumonia Viral/complicações , Gravidez , Complicações Infecciosas na Gravidez/patologia , Resultado da Gravidez , Nascimento Prematuro/virologia
5.
Proc Natl Acad Sci U S A ; 117(16): 8845-8849, 2020 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-32253306

RESUMO

The genetic incorporation of noncanonical amino acids (ncAAs) into proteins has been realized in bacteria, yeast, and mammalian cells, and recently, in multicellular organisms including plants and animals. However, the addition of new building blocks to the genetic code of tissues from human origin has not yet been achieved. To this end, we report a self-replicating Epstein-Barr virus-based episomal vector for the long-term encoding of ncAAs in human hematopoietic stem cells and reconstitution of this genetically engineered hematopoietic system in mice.


Assuntos
Aminoácidos/genética , Diferenciação Celular/genética , Vetores Genéticos/genética , Células-Tronco Hematopoéticas/fisiologia , Engenharia de Proteínas/métodos , Animais , Sangue Fetal/citologia , Técnicas de Transferência de Genes , Código Genético , Células HEK293 , Transplante de Células-Tronco Hematopoéticas , Herpesvirus Humano 4/genética , Humanos , Camundongos , Camundongos Endogâmicos NOD , Plasmídeos/genética , Cultura Primária de Células/métodos , Transfecção/métodos , Quimeras de Transplante , Transplante Heterólogo/métodos
6.
Chemosphere ; 253: 126592, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32289600

RESUMO

Prenatal exposure to particulate matter (PM) in ambient air has been linked to changes in newborn mitochondrial DNA copy number (mtDNAcn), but the effects of exposure are inconsistent. We aimed to investigate the effect of weekly PM exposure during pregnancy on newborn mtDNAcn. The present study included 762 mother-infant pairs who were recruited in a birth cohort established between November 2013 and March 2015 in Wuhan, China. Mother's prenatal daily exposure to PM2.5 and PM10 was calculated using a spatial-temporal land use regression model. Relative mtDNAcn in cord blood leukocytes was determined by quantitative real-time polymerase chain reaction. Distributive lag regression models (DLMs) were applied to estimate the association between PM exposure and newborn mtDNAcn. In the adjusted models, prenatal PM2.5 exposure during 25-32 weeks and PM10 exposure during 25-31weeks were significantly associated with decreased cord blood mtDNAcn. PM2.5 exposure during the third trimester was related to decreased mtDNAcn (cumulative percent change: -8.55%, 95% CI: -13.32%, -3.51%). We also identified other exposure windows (17-22 and 11-22 weeks) in which PM exposure was positively associated with mtDNAcn. Overall, exposure to particulate air pollution during mid-to-late gestation is significantly associated with alterations in newborn mtDNAcn, potentially suggesting an enhanced sensitivity to PM exposure during this period.


Assuntos
Poluição do Ar/estatística & dados numéricos , Variações do Número de Cópias de DNA/fisiologia , DNA Mitocondrial/metabolismo , Exposição Materna/estatística & dados numéricos , Material Particulado/toxicidade , Poluentes Atmosféricos/farmacologia , China , DNA Mitocondrial/genética , Feminino , Sangue Fetal/efeitos dos fármacos , Humanos , Lactente , Recém-Nascido , Masculino , Mitocôndrias/efeitos dos fármacos , Mães , Gravidez , Primeiro Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Efeitos Tardios da Exposição Pré-Natal , Reação em Cadeia da Polimerase em Tempo Real
7.
J Clin Virol ; 127: 104356, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32302955

RESUMO

BACKGROUND: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is causing an outbreak of pneumonia in Wuhan, Hubei Province, China, and other international areas. OBJECTIVE: Here, we report the clinical characteristics of the newborns delivered by SARS-CoV-2 infected pregnant women. METHODS: We prospectively collected and analyzed the clinical features, laboratory data and outcomes of 7 newborns delivered by SARS-CoV-2 infected pregnant women in Zhongnan Hospital of Wuhan University during January 20 to January 29, 2020. RESULTS: 4 of the 7 newborns were late preterm with gestational age between 36 weeks and 37 weeks, and the other 3 were full-term infants. The average birth weight was 2096 ± 660 g. All newborns were born without asphyxia. 2 premature infants performed mild grunting after birth, but relieved rapidly with non-invasive continuous positive airway pressure (nCPAP) ventilation. 3 cases had chest X-ray, 1 was normal and 2 who were supported by nCPAP presented mild neonatal respiratory distress syndrome (NRDS). Samples of pharyngeal swab in 6 cases, amniotic fluid and umbilical cord blood in 4 cases were tested by qRT-PCR, and there was no positive result of SARS-CoV-2 nucleic acid in all cases. CONCLUSIONS: The current data show that the infection of SARS-CoV-2 in late pregnant women does not cause adverse outcomes in their newborns, however, it is necessary to separate newborns from mothers immediately to avoid the potential threats.


Assuntos
Infecções por Coronavirus/diagnóstico , Transmissão Vertical de Doença Infecciosa , Pneumonia Viral/diagnóstico , Complicações Infecciosas na Gravidez/virologia , Líquido Amniótico/virologia , Betacoronavirus , Peso ao Nascer , China/epidemiologia , Pressão Positiva Contínua nas Vias Aéreas , Infecções por Coronavirus/epidemiologia , Feminino , Sangue Fetal/virologia , Idade Gestacional , Humanos , Saúde do Lactente , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Pandemias , Pneumonia Viral/epidemiologia , Gravidez , Estudos Prospectivos , Medição de Risco , Tórax/diagnóstico por imagem , Tórax/virologia , Tomografia Computadorizada por Raios X
8.
Ecotoxicol Environ Saf ; 197: 110643, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32315786

RESUMO

Meteorological conditions during pregnancy can affect birth outcome, which has been linked to the H19/H19-differentially methylated region (DMR). However, the detailed mechanisms underlying this association are unclear. This was investigated in the present study to provide epidemiological evidence for elucidating the pathogenesis of adverse birth outcomes. A total of 550 mother-newborn pairs were recruited in Zhengzhou, China from January 2010 to January 2012. Meteorological data including temperature (T), relative humidity (RH), and sunshine duration (SSD) were obtained from the China Meteorological Data Sharing Service System. Bisulfite sequencing PCR was performed to determine the methylation levels of H19/H19-DMR using genomic DNA extracted from maternal peripheral and umbilical cord blood. The results showed that H19-DMR methylation status in cord blood was positively associated with that in maternal blood. Neonatal H19-DMR methylation was negatively associated with T and RH during the first trimester and positively associated with these variables during the third trimester. There was a positive correlation between neonatal H19-DMR methylation and SSD during the second trimester and a negative correlation during the third trimester. Similar associations were observed between maternal H19-DMR methylation and prenatal meteorological conditions. We also observed significant interaction effects of maternal H19/H19-DMR methylation and most prenatal meteorological factors on neonatal methylation, and found that changes in the methylation status of maternal H19-DMR were responsible for the effects of prenatal meteorological conditions on neonatal methylation. In summary, neonatal H19-DMR methylation was significantly associated with prenatal meteorological conditions, which was modified and mediated by maternal H19-DMR methylation changes. These findings provide insights into the relationship between meteorological factors during pregnancy and adverse birth outcomes or disease susceptibility in offspring, and can serve as a reference for environmental policy-making.


Assuntos
Metilação de DNA , Sangue Fetal/química , Exposição Materna/efeitos adversos , Conceitos Meteorológicos , RNA Longo não Codificante/genética , Adulto , China , DNA/sangue , Feminino , Impressão Genômica , Humanos , Recém-Nascido , Gravidez , Regiões Promotoras Genéticas , RNA Longo não Codificante/sangue , Adulto Jovem
9.
PLoS One ; 15(4): e0231239, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32294121

RESUMO

BACKGROUND: Chorioamnionitis has been linked to spontaneous preterm labor and complications such as neonatal sepsis. We hypothesized that microbial cell-free (cf) DNA would be detectable in maternal plasma in patients with chorioamnionitis and could be the basis for a non-invasive method to detect fetal exposure to microorganisms. OBJECTIVE: The purpose of this study was to determine whether next generation sequencing could detect microbial cfDNA in maternal plasma in patients with chorioamnionitis. STUDY DESIGN: Maternal plasma (n = 94) and umbilical cord plasma (n = 120) were collected during delivery at gestational age 28-41 weeks. cfDNA was extracted and sequenced. Umbilical cord plasma samples with evidence of contamination were excluded. The prevalence of microorganisms previously implicated in choriomanionitis, neonatal sepsis and intra-amniotic infections, as described in the literature, were examined to determine if there was enrichment of these microorganisms in this cohort. Specific microbial cfDNA associated with chorioamnionitis was first detected in umbilical cord plasma and confirmed in the matched maternal plasma samples (n = 77 matched pairs) among 14 cases of histologically confirmed chorioamnionitis and one case of clinical chorioamnionitis; 63 paired samples were used as controls. A correlation of rank of a given microorganism across maternal plasma and matched umbilical cord plasma was used to assess whether signals found in umbilical cord plasma were also present in maternal plasma. RESULTS: Microbial DNA sequences associated with clinical and/or histological chorioamnionitis were enriched in maternal plasma in cases with suspected chorioamnionitis when compared to controls (12/14 microorganisms, p = 0.02). Analysis of the microbial cfDNA in umbilical cord plasma among the 1,251 microorganisms detectable with this assay identified Streptococcus mitis, Ureaplasma spp., and Mycoplasma spp. in cases of suspected chorioamnionitis. This assay also detected cfDNA from Lactobacillus spp. in controls. Comparison between maternal plasma and umbilical cord plasma confirmed these signatures were also present in maternal plasma. Unbiased analysis of microorganisms with significantly correlated signal between matched maternal plasma and umbilical cord plasma identified the above listed 3 microorganisms, all of which have previously been implicated in patients with chorioamnionitis (Mycoplasma hominis p = 0.0001; Ureaplasma parvum p = 0.002; Streptococcus mitis p = 0.007). These data show that the pathogen signal relevant for chorioamnionitis can be identified in both maternal and umbilical cord plasma. CONCLUSION: This is the first report showing the detection of relevant microbial cell-free cfDNA in maternal plasma and umbilical cord plasma in patients with clinical and/or histological chorioamnionitis. These results may lead to the development of a specific assay to detect perinatal infections for targeted therapy to reduce early neonatal sepsis complications.


Assuntos
Ácidos Nucleicos Livres/sangue , Corioamnionite/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Análise de Sequência de DNA/métodos , Cordão Umbilical/microbiologia , Adulto , Corioamnionite/microbiologia , Estudos de Coortes , Feminino , Sangue Fetal/química , Sangue Fetal/metabolismo , Sangue Fetal/microbiologia , Idade Gestacional , Humanos , Recém-Nascido , Mycoplasma/genética , Mycoplasma/patogenicidade , Sepse Neonatal/sangue , Sepse Neonatal/diagnóstico , Sepse Neonatal/microbiologia , Gravidez , Streptococcus mitis/genética , Streptococcus mitis/patogenicidade , Cordão Umbilical/patologia , Ureaplasma/genética , Ureaplasma/patogenicidade , Adulto Jovem
10.
Ultrasound Obstet Gynecol ; 55(6): 835-837, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32249471

RESUMO

Imaging modalities play a crucial role in the management of suspected COVID-19 patients. Before reverse transcription polymerase chain reaction (RT-PCR) test results are positive, 60-93% of patients have positive chest computed tomographic (CT) findings consistent with COVID-19. We report a case of positive lung ultrasound findings consistent with COVID-19 in a woman with an initially negative RT-PCR result. The lung ultrasound-imaging findings were present between the negative and subsequent positive RT-PCR tests and correlated with CT findings. The point-of-care lung-ultrasound examination was easy to perform and, as such, could play an important role in the triage of women with suspected COVID-19. The neonatal swabs, cord blood and placental swab RT-PCR tests were negative for SARS-CoV-2, a finding consistent with the published literature suggesting no vertical transmission of this virus in pregnant women. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.


Assuntos
Infecções por Coronavirus/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Complicações Infecciosas na Gravidez/diagnóstico por imagem , Ultrassonografia/métodos , Adulto , Cesárea , Angiografia por Tomografia Computadorizada , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Diagnóstico Diferencial , Feminino , Sangue Fetal/virologia , Humanos , Leite Humano/virologia , Pandemias , Placenta/virologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Testes Imediatos , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/terapia , Embolia Pulmonar/diagnóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tomografia Computadorizada por Raios X
11.
Environ Pollut ; 261: 114195, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32114123

RESUMO

Adverse health effects of exposure to air pollution have been investigated in many previous studies. However, there is no study available on the association between maternal exposure to air pollution during pregnancy and cord blood lipid profile. This study, based on 150 mother-newborn pairs residing in Sabzevar, Iran (2018), evaluated the association of exposure to ambient air pollution as well as traffic indicators (total street length in different buffers around residential address and distance to major roads) during entire pregnancy with lipid levels cord blood lipid profile. Concentrations of PM10, PM2.5, and PM1 at maternal residential address were estimated using land use regression (LUR) models. We measured triglyceride (TAG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) levels and TC/HDL-C and TAG/HDL-C ratio in the cord blood samples to characterize their lipid profile. Multiple linear regression models were developed to estimate the association of exposure to air pollution and traffic indicators with cord blood lipid profile controlled for relevant covariates. Higher concentrations of PM2.5 and PM10 were associated with higher levels of TAG, TC, HDL-C, TC/HDL-C, and TAG/HDL-C in cord blood samples. Moreover, higher concentration of PM1 was associated with higher levels of TAG, TC and LDL-C. There was also a positive association between total street length in 100 m buffer around home and serum levels of TC, TAG, LDL-C and TC/HDL ratio (ß = 3.73, 95% confidence intervals (CI): 1.76, 5.71; ß = 2.75, 95% CI: 0.97, 4.53; ß = 1.87, 95% CI: 0.64, 3.09; ß = 0.06, 95% CI: 0.01, 0.11, respectively). However, the associations for total street length in larger buffers and distance to major roads were not statistically significant. Our findings support a relationship between exposure to air pollution during pregnancy and increase in cord blood lipid levels.


Assuntos
Poluentes Atmosféricos , Sangue Fetal , Lipídeos , Exposição Materna , Poluentes Atmosféricos/análise , Estudos Transversais , Feminino , Sangue Fetal/química , Humanos , Recém-Nascido , Irã (Geográfico) , Lipídeos/sangue , Gravidez
12.
Zhonghua Yu Fang Yi Xue Za Zhi ; 54(3): 289-293, 2020 Mar 06.
Artigo em Chinês | MEDLINE | ID: mdl-32187934

RESUMO

Objective: To understand the levels of Pb, Cd, As, Hg, Mn, and Se in maternal and umbilical cord blood, and to explore the transplacental transfer efficiency (TTE). Methods: From September 2010 to December 2013, a total of 773 pregnant women and their newborns (Laizhou Bay Birth Cohort) were recruited from a second grade hospital in the south bank of Laizhou Bay, Bohai, Shandong Province. According to different detection methods, the six measured elements are classified into three groups including the Hg measurement group (595 mother-newborn pairs), the Pb measurement group (534 mother-newborn pairs), and the Cd, As, Mn and Se measurement group (244 mother-newborn pairs). The demographic characteristics of pregnant women and their newborns were obtained by the questionnaire. The concentrations of elements in maternal and umbilical cord blood were detected and the TTE of each element (elemental concentration in cord blood/elemental concentration in maternal blood) was calculated. The correlation of elements between maternal and cord blood was analyzed using Spearman's rank correlation coefficient. Results: The mean±SD of maternal age, gestational week and newborn birth weight of 773 mother-infant pairs were (28.34±4.50) years, (39.47±1.39) weeks and (3 419.47±497.39) g respectively. The median concentrations of Pb, Cd, As, Hg, Mn and As in maternal and cord blood were 31.12 and 30.02, 1.19 and 0.47, 8.05 and 6.03, 0.69 and 1.26, 100.70 and 105.55, 127.25 and 115.00 µg/L, respectively. The TTE of Pb, Cd, As, Hg, Mn, and Se was 0.98, 0.41, 0.73, 1.73, 0.96 and 0.91, respectively. Pb, Cd, Hg, Mn, and Se showed a significant positive correlation between maternal blood and cord blood, with Spearman correlation coefficients of 0.397, 0.298, 0.698, 0.555, and 0.285 (all P values<0.001). Conclusion: Each element was commonly detected in maternal blood and cord blood. The TTE of Hg was the highest.


Assuntos
Cádmio/sangue , Sangue Fetal/química , Sangue Fetal/metabolismo , Chumbo/sangue , Manganês/sangue , Troca Materno-Fetal , Mercúrio/sangue , Selênio/sangue , Cordão Umbilical/química , Biomarcadores/análise , Biomarcadores/sangue , Feminino , Humanos , Recém-Nascido , Gravidez , Oligoelementos/análise , Oligoelementos/sangue , Cordão Umbilical/irrigação sanguínea
13.
PLoS One ; 15(3): e0230682, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32210456

RESUMO

Atherosclerosis is a chronic inflammatory disease and major cause of mortality worldwide. One of the crucial steps for atherosclerotic plaque development is oxidation of low-density lipoprotein (LDL). Through the oxidation, highly immunogenic epitopes are created and the immune system is activated. Association between atherosclerosis and periodontal diseases is well documented, and one of the main oral pathogens common in periodontitis is Aggregatibacter actinomycetemcomitans (Aa). Heat shock protein 60 (HSP60) is an important virulence factor for Aa bacteria and a strong activator of the immune system. Cross-reactivity of HSP60 and oxidized LDL (OxLDL) antibodies could be a potential mechanism in the progression of atherosclerosis and one possible link between atherosclerosis and periodontitis. Human plasma samples from neonates and mothers were analyzed to determine if antibody titer to Aa-HSP60 protein is already present in newborns. Further objectives were to characterize antibody response in Aa-HSP60 immunized mice and to determine possible antibody cross-reaction with oxidized LDL. We demonstrated that newborns already have IgM antibody levels to Aa-HSP60. We also showed that in mice, Aa-HSP60 immunization provoked IgG and IgM antibody response not only to Aa-HSP60 but also to malondialdehyde acetaldehyde-modified LDL (MAA-LDL). Competition assay revealed that the antibodies were specific to Aa-HSP60 and cross-reacted with MAA-LDL. Our results suggest a possibility of molecular mimicry between Aa-HSP60 and MAA-LDL, making it intriguing to speculate on the role of HSP60 protein in atherosclerosis that manifests at young age.


Assuntos
Aggregatibacter actinomycetemcomitans/metabolismo , Chaperonina 60/imunologia , Imunidade Humoral , Lipoproteínas LDL/imunologia , Aggregatibacter actinomycetemcomitans/imunologia , Animais , Reações Antígeno-Anticorpo , Chaperonina 60/genética , Chaperonina 60/metabolismo , Reações Cruzadas , Feminino , Sangue Fetal/metabolismo , Humanos , Imunoensaio , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia
14.
Arch Med Res ; 51(1): 54-62, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32086109

RESUMO

BACKGROUND: The umbilical cord blood bank at the Mexican Institute of Social Security (IMSS-CBB) was established in January 2005. This lead to the development of the UCB transplantation program. Herein, we describe the experience generated during these 13 years. STUDY DESIGN AND METHODS: Donor selection, as well as UCB collection, processing, and banking were performed under good manufacturing practices and standard operating procedures. UCB units were thawed, processed, and released for transplantation based on HLA and nucleated cell content. RESULTS: From January 2005-December 2017, 1,298 UCB units were banked; 164 of them were released for transplantation, and 118 UCB transplants were performed. Ninety-four transplants were performed in pediatric patients and 24 in adults. Sixty percent of them corresponded to patients with leukemia, 19% were patients with marrow failure, and the rest had immunodeficiency, hemoglobinopathy, metabolic disorders, or solid tumors. Engraftment was observed in 67 patients (57% of transplanted patients) and 64% of them were still alive when writing this article. In contrast, only 13 of the 51 (25%) non-engrafting patients were alive. At the time of writing this article, the disease-free survival rate was 37%, and the overall survival rate was 47%, with survival periods of 161-3,721 days. CONCLUSION: The IMSS UCB banking and transplantation program has had a significant impact for many IMSS patients. The hematopoietic transplantation program at our institution has benefited from the use of UCB as a source of transplantable cells.


Assuntos
Bancos de Sangue , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Sangue Fetal , Programas Nacionais de Saúde , Adolescente , Adulto , Idoso , Bancos de Sangue/métodos , Bancos de Sangue/estatística & dados numéricos , Bancos de Sangue/tendências , Transtornos da Insuficiência da Medula Óssea/epidemiologia , Transtornos da Insuficiência da Medula Óssea/terapia , Criança , Pré-Escolar , Transplante de Células-Tronco de Sangue do Cordão Umbilical/normas , Transplante de Células-Tronco de Sangue do Cordão Umbilical/estatística & dados numéricos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/tendências , Intervalo Livre de Doença , Feminino , Transplante de Células-Tronco Hematopoéticas/normas , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , História do Século XXI , Humanos , Lactente , Recém-Nascido , Leucemia/epidemiologia , Leucemia/terapia , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Programas Nacionais de Saúde/organização & administração , Programas Nacionais de Saúde/normas , Programas Nacionais de Saúde/tendências , Gravidez , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
15.
Chemosphere ; 244: 125499, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32050328

RESUMO

Thallium (Tl) is a highly toxic heavy metal that has been suggested to be responsible for oxidative stress and mitochondrial dysfunction. However, few studies have focused on the relationship of prenatal Tl exposure with children's neurobehavioural development. The purpose of our study was to investigate the association between prenatal Tl exposure and attention-deficit/hyperactivity disorder (ADHD) symptoms in 36-month-old children. We used data from 2851 mother-newborn pairs from the Ma'anshan Birth Cohort Study (MABC); serum Tl concentration was assessed in the first, second and third trimesters of pregnancy as well as in the umbilical cord blood. We assessed ADHD symptoms in the children using the Chinese version of the Conners abbreviated symptom questionnaire (C-ASQ). The adjusted odds ratio (OR) for the risk of ADHD symptoms was 2.00 [95% confidence interval (CI): 1.20, 3.32] and 2.08 (95% CI: 1.26, 3.43) for the third (60.25-75.21 ng/L) and fourth quartiles of serum Tl (>75.21 ng/L), respectively, in the second trimester of pregnancy, in comparison with the first quartile of serum Tl (<50.86 ng/L). The risk of ADHD symptoms was elevated among boys exposed to the fourth quartile of serum Tl in the second trimester of pregnancy (adjusted OR 2.08, 95% CI: 1.13, 3.83). Our results demonstrated that high levels of Tl exposure in the second trimester of pregnancy were related to a higher risk of ADHD symptoms in 36-month-old children, and the association of higher serum Tl exposure in the second trimester with ADHD symptoms was only found in boys.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/sangue , Efeitos Tardios da Exposição Pré-Natal/sangue , Tálio/sangue , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Pré-Escolar , Estudos de Coortes , Feminino , Sangue Fetal , Humanos , Recém-Nascido , Masculino , Mães , Gravidez , Segundo Trimestre da Gravidez/sangue , Terceiro Trimestre da Gravidez/sangue , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Fatores Sexuais , Tálio/toxicidade
16.
PLoS One ; 15(2): e0228630, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32027690

RESUMO

OBJECTIVE: The relevance between time-series fetal heart rate (FHR) pattern changes during labor and outcomes such as arterial blood gas data at delivery has not been studied. Using 3-tier and 5-tier classification systems, we studied the relationship between time-series FHR pattern changes before delivery and umbilical artery blood gas data at delivery. METHODS: The subjects were 1,909 low-risk women with vaginal delivery (age: 29.1 ± 4.4 years, parity: 1.7 ± 0.8). FHR patterns were classified by a skilled obstetrician based on each 10 min-segment of the last 60 min before delivery from continuous CTG records in an obstetric clinic. RESULTS: The relationship between each 10 min-segment FHR pattern classification from 60 minutes before delivery and umbilical artery blood pH and base excess (BE) values at delivery changed with time. In the 3-tier classification, mean pH of Category I group in each 10 min-segment was significantly higher than that of Category II group. For Category I groups in each 10-minute segment, its number decreased and its average pH increased as the delivery time approached. In the 5-tier classification, there was the same tendency. About each level group in 10 min-segment, the higher the level, the lower the blood gas values, and mean pH of higher level groups decreased as the delivery time approached. CONCLUSIONS: The relationship between classifications and outcomes was clear at any time from 60 min before delivery in 3- and 5-tier classifications, and the 5-tier classification was more relevant.


Assuntos
Sangue Fetal , Frequência Cardíaca Fetal , Adulto , Gasometria , Parto Obstétrico , Feminino , Monitorização Fetal/métodos , Humanos , Concentração de Íons de Hidrogênio , Trabalho de Parto , Gravidez , Fatores de Tempo , Artérias Umbilicais
17.
PLoS One ; 15(2): e0229079, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32069319

RESUMO

AIM: To analyse i) the association of physical fitness during early second trimester and late pregnancy with maternal and neonatal outcomes; and ii) to investigate whether physical fitness is associated with the type of birth (vaginal or caesarean section). METHODS: Pregnant women from the GESTAFIT Project (n = 159) participated in this longitudinal study. Maternal physical fitness including upper- and lower-body strength, cardiorespiratory fitness (CRF) and flexibility were measured through objective physical fitness tests at the 16th and 34th gestational weeks. Maternal and neonatal outcomes were collected from obstetric medical records. Umbilical arterial and venous blood gas pH and partial pressure of carbon dioxide (PCO2) and oxygen (PO2), were assessed. RESULTS: At the 16th week, greater upper-body muscle strength was associated with greater neonatal birth weight (r = 0.191, p<0.05). Maternal flexibility was associated with a more alkaline arterial pH (r = 0.220, p<0.05), higher arterial PO2 (r = 0.237, p<0.05) and lower arterial PCO2 (r = -0.331, p<0.01) in umbilical cord blood. Maternal CRF at the 16th gestational week was related to higher arterial umbilical cord PO2 (r = 0.267, p<0.05). The women who had caesarean sections had lower CRF (p<0.001) at the 16th gestational week and worse clustered overall physical fitness, both at the 16th (-0.227, p = 0.003, confidence interval (CI): -0.376, -0.078) and 34th gestational week (-0.223; p = 0.018; CI: -0.432, -0.015) compared with the women who had vaginal births. CONCLUSION: Increasing physical fitness during pregnancy may promote better neonatal outcomes and is associated with a decrease in the risk of caesarean section. This trial was registered at ClinicalTrials.gov (NCT02582567) on October 20, 2015.


Assuntos
Peso ao Nascer/fisiologia , Cesárea/estatística & dados numéricos , Recém-Nascido/fisiologia , Aptidão Física/fisiologia , Gravidez/fisiologia , Adulto , Dióxido de Carbono/análise , Feminino , Sangue Fetal/química , Humanos , Estudos Longitudinais , Oxigênio/análise , Pressão Parcial , Segundo Trimestre da Gravidez/fisiologia , Autorrelato
18.
Am J Trop Med Hyg ; 102(4): 876-879, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32043460

RESUMO

Zika virus (ZIKV) has recently been confirmed as endemic in Indonesia, but no congenital anomalies (CA) related to ZIKV infection have been reported. We performed molecular and serological testing for ZIKV and other flaviviruses on cord serum and urine samples collected in October 2016 to April 2017 during a prospective, cross-sectional study of neonates in Jakarta, Indonesia. Of a total of 429 neonates, 53 had CA, including 14 with microcephaly. These 53, and 113 neonate controls without evidence of CA, were tested by ZIKV-specific real-time reverse transcription polymerase chain reaction (RT-PCR), pan-flavivirus RT-PCR, anti-ZIKV and anti-DENV IgM ELISA, and plaque reduction neutralization test. There was no evidence of ZIKV infection among neonates in either the CA or non-CA cohorts, except in three cases with low titers of anti-ZIKV neutralizing antibodies. Further routine evaluation throughout Indonesia of pregnant women and their newborns for exposure to ZIKV should be a high priority for determining risk.


Assuntos
Anticorpos Antivirais/sangue , Anormalidades Congênitas/etiologia , Sangue Fetal/virologia , Infecção por Zika virus/sangue , Infecção por Zika virus/urina , Zika virus/isolamento & purificação , Adulto , Anormalidades Congênitas/sangue , Anormalidades Congênitas/urina , Anormalidades Congênitas/virologia , Feminino , Humanos , Imunoglobulina M/sangue , Imunoglobulina M/urina , Indonésia/epidemiologia , Recém-Nascido , Masculino , Gravidez , Complicações Infecciosas na Gravidez/sangue , Complicações Infecciosas na Gravidez/urina , Complicações Infecciosas na Gravidez/virologia , Adulto Jovem , Infecção por Zika virus/virologia
19.
N Engl J Med ; 382(6): 545-553, 2020 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-32023374

RESUMO

BACKGROUND: Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has shown remarkable clinical efficacy in B-cell cancers. However, CAR T cells can induce substantial toxic effects, and the manufacture of the cells is complex. Natural killer (NK) cells that have been modified to express an anti-CD19 CAR have the potential to overcome these limitations. METHODS: In this phase 1 and 2 trial, we administered HLA-mismatched anti-CD19 CAR-NK cells derived from cord blood to 11 patients with relapsed or refractory CD19-positive cancers (non-Hodgkin's lymphoma or chronic lymphocytic leukemia [CLL]). NK cells were transduced with a retroviral vector expressing genes that encode anti-CD19 CAR, interleukin-15, and inducible caspase 9 as a safety switch. The cells were expanded ex vivo and administered in a single infusion at one of three doses (1×105, 1×106, or 1×107 CAR-NK cells per kilogram of body weight) after lymphodepleting chemotherapy. RESULTS: The administration of CAR-NK cells was not associated with the development of cytokine release syndrome, neurotoxicity, or graft-versus-host disease, and there was no increase in the levels of inflammatory cytokines, including interleukin-6, over baseline. The maximum tolerated dose was not reached. Of the 11 patients who were treated, 8 (73%) had a response; of these patients, 7 (4 with lymphoma and 3 with CLL) had a complete remission, and 1 had remission of the Richter's transformation component but had persistent CLL. Responses were rapid and seen within 30 days after infusion at all dose levels. The infused CAR-NK cells expanded and persisted at low levels for at least 12 months. CONCLUSIONS: Among 11 patients with relapsed or refractory CD19-positive cancers, a majority had a response to treatment with CAR-NK cells without the development of major toxic effects. (Funded by the M.D. Anderson Cancer Center CLL and Lymphoma Moonshot and the National Institutes of Health; ClinicalTrials.gov number, NCT03056339.).


Assuntos
Antígenos CD19 , Células Matadoras Naturais/transplante , Leucemia Linfocítica Crônica de Células B/terapia , Linfoma não Hodgkin/terapia , Receptores de Antígenos Quiméricos/antagonistas & inibidores , Idoso , Aloenxertos , Terapia Baseada em Transplante de Células e Tecidos , Feminino , Sangue Fetal , Vetores Genéticos , Humanos , Células Matadoras Naturais/imunologia , Leucemia Linfocítica Crônica de Células B/imunologia , Linfoma não Hodgkin/imunologia , Masculino , Pessoa de Meia-Idade , Indução de Remissão/métodos , Retroviridae/genética , Condicionamento Pré-Transplante
20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 320-324, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32027296

RESUMO

Abstract  Currently, hematopoietic stem cell (HSC) transplantation is widely used in the therapy of hematological malignancies, non-malignant refractory anemia, genetic diseases and certain tumors with satisfactory therapeutic efficacy. HSC sources used for transplantation include bone marrow, mobilized peripheral blood and neonate umbilical cord blood. However, for many patients, sufficient number of human leukocyte antigen (HLA) -matched HSC cannot be found for transplantation, because the number of HSC in these tissues is small and HLA-identical donors are rare. Thus, in vitro generation of HSC has recently been focused. At present, the origin of HSC is hPSC, including hESC and hiPSC, which is worth to be the new origin of HSC transplantation. However, to generate functional hematopoietic stem cells which have efficient multi-lineage differentiation and in vivo engraftment potentials still is a big challenge to be confronted. In this review, the recent technical progress in HSC generation is summarizd, and the problems to be solved and new challenges to be confronted were discussed.


Assuntos
Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Medula Óssea , Sangue Fetal , Células-Tronco Hematopoéticas , Humanos
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