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1.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(7): 812-818, 2020 Jul 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-32879085

RESUMO

OBJECTIVES: To explore the method and significance of prenatal counseling in cardiac surgery for fetal congenital heart disease (CHD). METHODS: The prenatal counseling should be provided by experienced CHD experts. The preliminary clinical diagnosis based on relevant data was carried out, the prognosis risk for fetal CHD was graded, and the pathophysiological process and potential hazards of the disease were analyzed. The current condition of CHD in the treatment plan, the long-term quality of life, and the special requirements of parturition in place, period and mode were described. A reliable follow-up system of the fetuses was established, the diagnosis after delivery was verified, and surgical treatment was carried out timely. RESULTS: From January 2016 to December 2018, 225 parents with fetal CHD received prenatal counseling, including 60 fetuses (26.7%) with simple CHD and 165 (73.3%) with complex CHD, among which 59 cases (98.3%) and 93 cases (56.4%) decided to continue the pregnancy, respectively. During the follow-up, 118 fetuses were born, of which 66 infants received surgical treatment within 6 months after birth, 63 infants (95.5%) recovered and 3 infants (4.5%) died. The rest 52 infants continued to be followed up. CONCLUSIONS: The prenatal counseling for fetal CHD can provide the parents a comprehensive medical information about CHD, which is beneficial to making appropriate pregnancy decisions, and can turn the fetuses from unreasonable birth and passive treatment to selective birth and active treatment in CHD.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Cardiopatias Congênitas/cirurgia , Aconselhamento , Feminino , Feto , Humanos , Gravidez , Diagnóstico Pré-Natal , Qualidade de Vida , Ultrassonografia Pré-Natal
2.
Nature ; 586(7828): 203-205, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32968244
3.
Nat Commun ; 11(1): 4544, 2020 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-32917861

RESUMO

Stratification of enhancers by signal strength in ChIP-seq assays has resulted in the establishment of super-enhancers as a widespread and useful tool for identifying cell type-specific, highly expressed genes and associated pathways. We examine a distinct method of stratification that focuses on peak breadth, termed hyperacetylated chromatin domains (HCDs), which classifies broad regions exhibiting histone modifications associated with gene activation. We find that this analysis serves to identify genes that are both more highly expressed and more closely aligned to cell identity than super-enhancer analysis does using multiple data sets. Moreover, genetic manipulations of selected gene loci suggest that some enhancers located within HCDs work at least in part via a distinct mechanism involving the modulation of histone modifications across domains and that this activity can be imported into a heterologous gene locus. In addition, such genetic dissection reveals that the super-enhancer concept can obscure important functions of constituent elements.


Assuntos
Cromatina/metabolismo , Elementos Facilitadores Genéticos/genética , Loci Gênicos/genética , Ativação Transcricional , Acetilação , Animais , Linhagem Celular Tumoral , Imunoprecipitação da Cromatina , Sequenciamento de Cromatina por Imunoprecipitação , Conjuntos de Dados como Assunto , Embrião de Mamíferos , Eritroblastos , Feminino , Feto , Código das Histonas/genética , Histonas/genética , Histonas/metabolismo , Humanos , Camundongos , Regiões Promotoras Genéticas/genética , RNA-Seq
4.
Wiad Lek ; 73(7): 1434-1437, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32759433

RESUMO

OBJECTIVE: The aim:to study the content of trace elements (Fe, Cu, Zn, Co, Cr, Ni, Pb) in the placenta of pregnant healthy women and with signs of intrauterine infection of the fetus, features of transplacental transmission of infectious process from mother to fetus and to investigate the role of the placenta in trace element supply of the fetus. PATIENTS AND METHODS: Materials and methods. 43 pregnant women between the aged 16 to 40 years were monitored, including 12 with physiological pregnancy (group 1) and 31 with signs of STI (group 2). All pregnant women underwent standard comprehensive examination, evaluation of fetal cardiac output and non-stress testing using cardio-toсography (CTG) in the third trimester. The group of pregnant women with signs of fetal ulcers included women whose pregnancy was complicated by chronic fetoplacental dysfunction (FPD), infectious lesions of the fetoplacental complex, which were diagnosed on the basis of ultrasound signs of placenta, syndrome of infectious and surrounding infections. RESULTS: Results:The content of essential trace elements in the placenta of the main group was significantly lower than in the placenta of the control group. There was a decrease in the concentration of iron by 32%, zinc - by 46%, nickel - by 44%, copper more than tripled, chromium - 4 times. Deficiency of essential trace elements (iron, zinc, copper, chromium, nickel) and elevated lead content in the placenta leads to the formation of conditions for the development of placental dysfunction, the progression of which leads to fetal distress, developmental delay syndrome and antenatal fetal death. CONCLUSION: Conclusions:1. One of the links in the pathogenesis of intrauterine infection in the fetus is the imbalance of essential trace elements in the system «mother - placenta - fetus¼. 2. Pregnant women with signs of intrauterine infection are characterized by a deficiency of serum Fe, Cu, Zn, Ni and an increased content of Pb, Cr and Co compared with pregnant women with physiological pregnancy. 3. Umbilical cord blood of women with evidence of fetal fetal infection also has a reduced content of iron, copper, zinc and high levels of lead, cobalt and chromium. 4. Disruption of placental function in intrauterine infection of the fetus is caused by reduced content of iron, zinc, copper, nickel and lead accumulation.


Assuntos
Doenças Transmissíveis , Adolescente , Adulto , Feminino , Feto , Humanos , Placenta , Gravidez , Oligoelementos , Adulto Jovem , Zinco
5.
Ecotoxicol Environ Saf ; 202: 110911, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32800246

RESUMO

Applications of TiO2 nanoparticles (NPs) in food, personal care products and industries pose risks on human health, particularly on vulnerable populations including pregnant women and infants. Fetus, deficient in mature defense system, is more susceptible to NPs. Publications on the developmental toxicity of TiO2 NPs on the maternal-exposed progeny have emerged. This review presents the main exposure routes of TiO2 NPs during pregnancy, including skin penetration, ingestion and inhalation, followed by transport of TiO2 NPs to the placenta. Accumulation of TiO2 NPs in placenta may cause dysfunction in nutrient transfer. TiO2 NPs can be even transported to the fetus and generate toxicities, such as impairments of nervous and reproductive system, and failure in lung and cardiovascular development. The toxicities rely on the crystalline phase and concentrations, and the main mechanisms include the accumulation of excessive reactive oxygen species, DNA damage, and over-activation of signaling pathways such as MAPK which impairs neurotransmission. Finally, this review remarks on the significance for identifying TiO2 NPs dosage safe for both mother and fetus, and particular attention should be paid at TiO2 NPs concentrations safe for mother but toxic to fetus. Importantly, research on the epigenetic trans-generational inheritance of TiO2 NPs is urgently needed to provide insights for deciding the prospects of TiO2 NPs applications.


Assuntos
Nanopartículas Metálicas/toxicidade , Titânio/toxicidade , Animais , Feminino , Feto , Humanos , Nanopartículas/toxicidade , Organogênese , Placenta/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Testes de Toxicidade
6.
Adv Exp Med Biol ; 1252: 107-114, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32816269

RESUMO

Non-obstetric surgery is needed in 0.75-2% of pregnant women, and safety of anesthesia for mother and child are key points at this time. Some breast diseases need to be approached in a short time interval, and surgery must be performed during pregnancy . In these cases, the technique of anesthesia regarding local, regional or general anesthesia and type of anesthetic medicine are selected based on the extent of the procedure, gestational age, and condition of the mother and child. The ideal timing for any surgery during pregnancy is in the second trimester because the risk of fetal adverse effects as well as preterm labor are lower. However, surgery of breast cancer during pregnancy is performed in any trimester as guided by treatment guidelines and is not deferred based on anesthesia preferences. Various types of anesthesia for breast surgery during pregnancy , preoperative and postoperative considerations are discussed in this chapter.


Assuntos
Anestesia/efeitos adversos , Anestesia/métodos , Anestésicos , Mama/cirurgia , Complicações na Gravidez , Neoplasias da Mama/cirurgia , Feminino , Feto/efeitos dos fármacos , Humanos , Trabalho de Parto Prematuro/induzido quimicamente , Trabalho de Parto Prematuro/etiologia , Trabalho de Parto Prematuro/prevenção & controle , Gravidez , Complicações na Gravidez/induzido quimicamente , Complicações na Gravidez/etiologia , Complicações na Gravidez/prevenção & controle
7.
N Engl J Med ; 383(6): 537-545, 2020 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-32757522

RESUMO

BACKGROUND: In 2015 and 2016, Colombia had a widespread outbreak of Zika virus. Data from two national population-based surveillance systems for symptomatic Zika virus disease (ZVD) and birth defects provided complementary information on the effect of the Zika virus outbreak on pregnancies and infant outcomes. METHODS: We collected national surveillance data regarding cases of pregnant women with ZVD that were reported during the period from June 2015 through July 2016. The presence of Zika virus RNA was identified in a subgroup of these women on real-time reverse-transcriptase-polymerase-chain-reaction (rRT-PCR) assay. Brain or eye defects in infants and fetuses and other adverse pregnancy outcomes were identified among the women who had laboratory-confirmed ZVD and for whom data were available regarding pregnancy outcomes. We compared the nationwide prevalence of brain and eye defects during the outbreak with the prevalence both before and after the outbreak period. RESULTS: Of 18,117 pregnant women with ZVD, the presence of Zika virus was confirmed in 5926 (33%) on rRT-PCR. Of the 5673 pregnancies with laboratory-confirmed ZVD for which outcomes had been reported, 93 infants or fetuses (2%) had brain or eye defects. The incidence of brain or eye defects was higher among pregnancies in which the mother had an onset of ZVD symptoms in the first trimester than in those with an onset during the second or third trimester (3% vs. 1%). A total of 172 of 5673 pregnancies (3%) resulted in pregnancy loss; after the exclusion of pregnancies affected by birth defects, 409 of 5426 (8%) resulted in preterm birth and 333 of 5426 (6%) in low birth weight. The prevalence of brain or eye defects during the outbreak was 13 per 10,000 live births, as compared with a prevalence of 8 per 10,000 live births before the outbreak and 11 per 10,000 live births after the outbreak. CONCLUSIONS: In pregnant women with laboratory-confirmed ZVD, brain or eye defects in infants or fetuses were more common during the Zika virus outbreak than during the periods immediately before and after the outbreak. The frequency of such defects was increased among women with a symptom onset early in pregnancy. (Funded by the Colombian Instituto Nacional de Salud and the Centers for Disease Control and Prevention.).


Assuntos
Encéfalo/anormalidades , Surtos de Doenças , Anormalidades do Olho/epidemiologia , Complicações Infecciosas na Gravidez , Infecção por Zika virus/complicações , Zika virus/isolamento & purificação , Adolescente , Adulto , Colômbia/epidemiologia , Feminino , Doenças Fetais/epidemiologia , Feto/anormalidades , Geografia Médica , Humanos , Incidência , Recém-Nascido , Masculino , Microcefalia/epidemiologia , Distribuição de Poisson , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Resultado da Gravidez , Prevalência , RNA Viral/sangue , Reação em Cadeia da Polimerase em Tempo Real , Adulto Jovem , Zika virus/genética , Infecção por Zika virus/epidemiologia
8.
Placenta ; 100: 69-74, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32862058

RESUMO

INTRODUCTION: While the COVID-19 pandemic continues to have a significant global health impact, rates of maternal to infant vertical transmission remain low (<5%). Parenchymal changes of placentas from COVID-19 infected mothers have been reported by several groups, but the localization and relative abundance of SARS-CoV-2 viral proteins and cellular entry machinery has not been fully characterized within larger placental tissue cohorts. METHODS: An extended placental tissue cohort including samples from 15 COVID-19 positive maternal-fetal dyads (with n = 5 cases with evidence of fetal transmission) in comparison with 10 contemporary COVID-19 negative controls. Using comparative immunofluorescence, we examined the localization and relative tissue abundance of SARS-CoV2 spike glycoprotein (CoV2 SP) along with the co-localization of two SARS-CoV2 viral entry proteins angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). RESULTS/CONCLUSIONS: CoV2 SP was present within the villous placenta in COVID-19 positive pregnancies with and without evidence of fetal transmission. We further identified the predominance of ACE2 expression in comparison with TMPRSS2. Importantly, both CoV2 SP and ACE2 expression consistently localized primarily within the outer syncytiotrophoblast layer placental villi, a key physiologic interface between mother and fetus. Overall this study provides an important basis for the ongoing evaluation of SARS-CoV-2 physiology in pregnancy and highlights the importance of the placenta as a key source of primary human tissue for ongoing diagnostic and therapeutic research efforts to reduce the global burden of COVID-19.


Assuntos
Betacoronavirus/química , Vilosidades Coriônicas/química , Infecções por Coronavirus , Pandemias , Peptidil Dipeptidase A/análise , Pneumonia Viral , Serina Endopeptidases/análise , Glicoproteína da Espícula de Coronavírus/análise , Feminino , Feto , Imunofluorescência/métodos , Humanos , Transmissão Vertical de Doença Infecciosa , Placenta/química , Gravidez , Complicações Infecciosas na Gravidez/virologia , Receptores Virais/análise , Trofoblastos/química
9.
PLoS One ; 15(8): e0236982, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32745099

RESUMO

BACKGROUND: Continuous intrapartum fetal monitoring is challenging and its clinical benefits are debated. The project evaluated whether short-term-variation (STV) and other computerised fetal heart rate (FHR) parameters (baseline FHR, long-term-variation, accelerations and decelerations) predicted acidaemia at birth. The aims of the study were to assess the changes in FHR pattern during labour and determine the feasibility of undertaking a definitive trial by reporting the practicalities of using the monitoring device, participant recruitment, data collection and staff training. METHODS: 200 high-risk women carrying a term singleton, non-anomalous fetus, requiring continuous FHR monitoring in labour were consented to participate from the Jessop Wing maternity unit, Sheffield, UK. The trans-abdominal fetal ECG monitor was placed as per clinical protocol. During the monitoring session, clinicians were blinded to the computerised FHR parameters. We analysed the last hour of the FHR and its ability to predict umbilical arterial blood pH <7.20 using receiver operator characteristics (ROC) curves. RESULTS: Of 200 women, 137 cases were excluded as either the monitor did not work from the onset of labour (n = 30), clinical staff did not return or used the monitor on another patient (n = 37), umbilical cord blood not obtained (n = 25), FHR data not recorded within an hour of birth (n = 34) and other reasons (n = 11). In 63 cases included in the final analysis, the computer-derived FHR parameters did not show significant correlation with umbilical artery cord pH <7.20. Labour was associated with a significant increase in short and long term variation of FHR and number of deceleration (P<0.001). However, baseline FHR decreased significantly before delivery (P<0.001). CONCLUSIONS: The project encountered a number of challenges, with learning points crucial to informing the design of a large study to evaluate the potential place of intrapartum computerised FHR parameters, using abdominal fetal ECG monitor before its clinical utility and more widespread adoption can be ascertained.


Assuntos
Eletroencefalografia/instrumentação , Monitorização Fetal/métodos , Frequência Cardíaca Fetal/fisiologia , Acidose/fisiopatologia , Adulto , Cardiotocografia , Eletrocardiografia , Estudos de Viabilidade , Feminino , Sangue Fetal , Doenças Fetais/fisiopatologia , Feto/fisiopatologia , Humanos , Concentração de Íons de Hidrogênio , Trabalho de Parto , Gravidez
10.
J Obstet Gynaecol Res ; 46(10): 1951-1957, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32779309

RESUMO

The outbreak of the 2019 novel coronavirus disease (SARS-CoV-2) has resulted in a major epidemic threat worldwide. However, the effects of neoviruses on infected pregnant women and especially on their fetuses and newborns are not well understood. Most up-to-date evidences about how SARS-CoV-2 affected patients especially in pregnancy were collected by conducting a comprehensive search of medical literature electronic databases. Immune-related data of pregnant women, fetuses and newborns were further analysis. According to the limited literature, SARS-CoV-2 utilizes angiotensin converting enzyme 2 as its receptor and causes severe hypoxemia. Insufficiency of angiotensin converting enzyme 2 in pregnant women and the effects of hypoxia on the placental oxygen supply will cause severe perinatal complications. In addition, SARS-CoV-2 infection may disrupt maternal-fetal immune tolerance and cause immunological damage to embryos. Because of these reasons, pregnancy complications such as fetal demise or premature birth, preeclampsia, intrauterine growth restriction, respiratory dyspnea, nervous system dysplasia and immune system defects are likely to occur in pregnant women with COVID-19 or their newborns. Pregnant women infected with SARS-CoV-2 should be treated as a special group and given special attention. Fetuses and newborns of SARS-CoV-2-infected pregnant women should be given more protection to reduce the occurrence of adverse events. In this review, we intend to provide an overview of the physiological and immunological changes that induce the pregnancy complications. This article will benefit the treatment and prognosis of fetuses and newborns of SARS-CoV-2-infected pregnant women.


Assuntos
Betacoronavirus , Infecções por Coronavirus/transmissão , Feto/virologia , Transmissão Vertical de Doença Infecciosa , Pneumonia Viral/transmissão , Complicações Infecciosas na Gravidez/virologia , Feminino , Humanos , Recém-Nascido , Pandemias , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia
11.
Beijing Da Xue Xue Bao Yi Xue Ban ; 52(4): 719-725, 2020 Aug 18.
Artigo em Chinês | MEDLINE | ID: mdl-32773809

RESUMO

OBJECTIVE: To find out the status of folic acid supplementation among women, to evaluate the prevention effects on neural tube defects (NTDs), and to explore the factors impact on folic acid supplementation compliance. METHODS: Based on the routine data of 92 121 women in prenatal health care and birth defect surveillance system in Tongzhou District of Beijing from 2013 to 2018, we described the prevalence of periconceptional folic acid supplementation, pre-pregnancy folic acid supplementation and regularly folic acid supplementation (compliance supplementation). Trend χ2 tests were used to evaluate the change of folic acid supplementation prevalence. The prevalence difference among the women with folic acid supplementation and without supplementation were tested with Fisher's exact test. Factors asso-ciated with folic acid supplementation compliance rate were analyzed with univariate and multivariate Logistic regression model. RESULTS: The prevalence of periconceptional folic acid supplementation during the six years was 90.08% and it was increased from 2013 to 2018, but the rate of pre-pregnancy and regular supplementation was only 41.5% and declined from 2013 to 2018, especially 2013 to 2015. The prevalence of NTDs among the fetuses whose mothers took folic acid during periconceptional period was 5.5/10 000, while the prevalence for the fetuses whose mothers did not take folic acid was 19.7/10 000 (P < 0.001), the rates ratio was 27.9% (χ2=23.74, P < 0.001). The difference between the prevalence of NTDs among the fetuses whose mothers took folic acid only and multiple micronutrients was not statistically significant. After controlling the confounding factors, it was found that the compliant folic acid supplementation rates in women, whose household registrations were outside Beijing and whose education levels were junior high school or below, and who were younger than 25 years old, and who were multiparas and who were pre-pregnancy underweight or obese, were lower than those of the corresponding control groups (P < 0.05). CONCLUSION: The rate of folic acid supplementation among women in Tongzhou District of Beijing was relatively high, but their compliance was poor. Women who did not take folic acid during periconception seriously affected the prevention effect of NTDs. We should focus on women who are younger than 25 years old, lower educated, pre-pregnancy underweight or obese, multiparas and nonlocal household registers, in order to improve the periconceptional folic acid supplementation compliance and improve the effects of NTDs prevention.


Assuntos
Suplementos Nutricionais , Defeitos do Tubo Neural , Adulto , Pequim , Feminino , Feto , Ácido Fólico , Humanos , Defeitos do Tubo Neural/epidemiologia , Gravidez , Prevalência
12.
Science ; 369(6503): 530-537, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32732419

RESUMO

Microglia, immune cells of the central nervous system (CNS), are important for tissue development and maintenance and are implicated in CNS disease, but we lack understanding of human fetal microglia development. Single-cell gene expression and bulk chromatin profiles of microglia at 9 to 18 gestational weeks (GWs) of human fetal development were generated. Microglia were heterogeneous at all studied GWs. Microglia start to mature during this developmental period and increasingly resemble adult microglia with CNS-surveilling properties. Chromatin accessibility increases during development with associated transcriptional networks reflective of adult microglia. Thus, during early fetal development, microglia progress toward a more mature, immune-sensing competent phenotype, and this might render the developing human CNS vulnerable to environmental perturbations during early pregnancy.


Assuntos
Encéfalo/embriologia , Desenvolvimento Embrionário/imunologia , Feto/imunologia , Microglia/imunologia , Fagocitose/imunologia , Encéfalo/citologia , Separação Celular , Células Cultivadas , Desenvolvimento Embrionário/genética , Redes Reguladoras de Genes , Humanos , Fagocitose/genética , Transcriptoma
13.
Science ; 369(6501): 320-325, 2020 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-32675374

RESUMO

Restricted V(D)J recombination during fetal development was postulated to limit antibody repertoire breadth and prevent autoimmunity. However, newborn serum contains abundant autoantibodies, suggesting that B cell tolerance during gestation is not yet fully established. To investigate this apparent paradox, we evaluated the reactivities of more than 450 antibodies cloned from single B cells from human fetal liver, bone marrow, and spleen. We found that incomplete B cell tolerance in early human fetal life favored the accumulation of polyreactive B cells that bound both apoptotic cells and commensal bacteria from healthy adults. Thus, the restricted fetal preimmune repertoire contains potentially beneficial self-reactive innate-like B cell specificities that may facilitate the removal of apoptotic cells during development and shape gut microbiota assembly after birth.


Assuntos
Anticorpos/imunologia , Linfócitos B/imunologia , Feto/imunologia , Autoanticorpos/imunologia , Autoantígenos/imunologia , Autoimunidade , Bactérias/imunologia , Feminino , Humanos , Imunidade Inata , Especificidade de Órgãos , Gravidez , Recombinação V(D)J
14.
PLoS Negl Trop Dis ; 14(7): e0008413, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32628667

RESUMO

Global Zika virus (ZIKV) outbreaks and their link to microcephaly have raised major public health concerns. However, the mechanism of maternal-fetal transmission remains largely unknown. In this study, we determined the role of yolk sac (YS) microglial progenitors in a mouse model of ZIKV vertical transmission. We found that embryonic (E) days 6.5-E8.5 were a critical window for ZIKV infection that resulted in fetal demise and microcephaly, and YS microglial progenitors were susceptible to ZIKV infection. Ablation of YS microglial progenitors significantly reduced the viral load in both the YS and the embryonic brain. Taken together, these results support the hypothesis that YS microglial progenitors serve as "Trojan horses," contributing to ZIKV fetal brain dissemination and congenital brain defects.


Assuntos
Feto/patologia , Microcefalia/patologia , Microglia/virologia , Complicações Infecciosas na Gravidez/patologia , Infecção por Zika virus/patologia , Zika virus/isolamento & purificação , Animais , Encéfalo/virologia , Modelos Animais de Doenças , Feminino , Feto/virologia , Humanos , Transmissão Vertical de Doença Infecciosa , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microcefalia/embriologia , Microcefalia/virologia , Microglia/metabolismo , Gravidez , Complicações Infecciosas na Gravidez/virologia , Carga Viral , Zika virus/fisiologia , Infecção por Zika virus/transmissão , Infecção por Zika virus/virologia
15.
Nat Commun ; 11(1): 3406, 2020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32641768

RESUMO

Cancer stem cells are critical for cancer initiation, development, and treatment resistance. Our understanding of these processes, and how they relate to glioblastoma heterogeneity, is limited. To overcome these limitations, we performed single-cell RNA sequencing on 53586 adult glioblastoma cells and 22637 normal human fetal brain cells, and compared the lineage hierarchy of the developing human brain to the transcriptome of cancer cells. We find a conserved neural tri-lineage cancer hierarchy centered around glial progenitor-like cells. We also find that this progenitor population contains the majority of the cancer's cycling cells, and, using RNA velocity, is often the originator of the other cell types. Finally, we show that this hierarchal map can be used to identify therapeutic targets specific to progenitor cancer stem cells. Our analyses show that normal brain development reconciles glioblastoma development, suggests a possible origin for glioblastoma hierarchy, and helps to identify cancer stem cell-specific targets.


Assuntos
Neoplasias Encefálicas/genética , Encéfalo/metabolismo , Glioblastoma/genética , Células-Tronco Neoplásicas/metabolismo , Análise de Sequência de RNA/métodos , Transcriptoma/genética , Adulto , Animais , Antineoplásicos Alquilantes/farmacologia , Encéfalo/embriologia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Células Cultivadas , Feminino , Feto , Glioblastoma/patologia , Glioblastoma/terapia , Humanos , Camundongos Endogâmicos NOD , Camundongos SCID , Células-Tronco Neoplásicas/efeitos dos fármacos , Análise de Célula Única/métodos , Temozolomida/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
16.
PLoS Negl Trop Dis ; 14(7): e0008453, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32730341

RESUMO

BACKGROUND: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel tick-borne phlebovirus, which is listed in the most dangerous pathogens by the World Health Organization, and has 12-30% fatality rates. SFTSV antibodies were reported in minks that experienced abortion or reproductive failure. The aim of this study was to determine whether SFTSV infection causes an adverse pregnancy outcome in the fetus using a pregnant mouse model. METHODOLOGY/PRINCIPAL FINDINGS: We found SFTSV in the fetus after infection in pregnant mice, and some dams showed adverse pregnancy outcomes after infection with SFTSV including placental damage, fetal reabsorption, and fetal intrauterine growth restriction (IUGR). SFTSV had obvious tropism characteristics in the placenta, especially in the labyrinth. In early-gestation, pregnant mice infected with SFTSV had fetal IUGR and a high viral load in the fetus. The virus widely spread in infected fetuses, including the hindbrain, thymus, heart, spinal cord, and liver. CONCLUSIONS: Our study demonstrated that SFTSV was vertically transmitted to the fetus through the placental barrier of immunocompetent mice, and resulted in adverse pregnancy outcomes.


Assuntos
Infecções por Bunyaviridae/patologia , Feto/anormalidades , Feto/virologia , Phlebovirus , Alquilantes/toxicidade , Animais , Feminino , Hospedeiro Imunocomprometido , Camundongos , Camundongos Endogâmicos C57BL , Mitomicina/toxicidade , Gravidez
17.
PLoS One ; 15(7): e0235836, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32649730

RESUMO

Muscle ultrasound density (MUD) is a non-invasive parameter to indicate neuromuscular integrity in both children and adults. In healthy fetuses and infants, physiologic MUD values during development are still lacking. We therefore aimed to determine the physiologic, age-related MUD trend of biceps, quadriceps, tibialis anterior, hamstrings, gluteal and calf muscles, from pre- to the first year of postnatal life. To avoid a bias by pregnancy-related signal disturbances, we expressed fetal MUD as a ratio against bone ultrasound density. We used the full-term prenatal MUD ratio and the newborn postnatal MUD value as reference points, so that MUD development could be quantified from early pre- into postnatal life. Results: During the prenatal period, the total muscle group revealed a developmental MUD trend concerning a fetal increase in MUD-ratio from the 2nd trimester up to the end of the 3rd trimester [median increase: 27% (range 16-45), p < .001]. After birth, MUD-values increased up to the sixth month [median increase: 11% (range -7-27), p = 0.025] and stabilized thereafter. Additionally, there were also individual MUD characteristics per muscle group and developmental stage, such as relatively low MUD values of fetal hamstrings and high values of the paediatric gluteus muscles. These MUD trends are likely to concur with analogous developmentally, maturation-related alterations in the muscle water to peptide content ratios.


Assuntos
Feto/diagnóstico por imagem , Músculo Esquelético/diagnóstico por imagem , Animais , Animais Recém-Nascidos , Bovinos , Feminino , Humanos , Recém-Nascido , Doenças Neuromusculares/diagnóstico por imagem , Gravidez , Ultrassonografia , Ultrassonografia Pré-Natal
18.
Pediatrics ; 146(2)2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32661188

RESUMO

Cannabinoids, the psychoactive compounds in marijuana, are one of the most commonly used substances in the United States. In this review, we summarize the impact of marijuana on child and adolescent health and discuss the implications of marijuana use for pediatric practice. We review the changing epidemiology of cannabis use and provide an update on medical use, routes of administration, synthetic marijuana and other novel products, the effect of cannabis on the developing brain, other health and social consequences of use, and issues related to marijuana legalization.


Assuntos
Cannabis , Uso da Maconha , Adolescente , Comportamento do Adolescente/efeitos dos fármacos , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/embriologia , Encéfalo/crescimento & desenvolvimento , Canabidiol/farmacologia , Canabidiol/uso terapêutico , Canabinoides/efeitos adversos , Canabinoides/síntese química , Canabinoides/farmacologia , Cannabis/efeitos adversos , Cannabis/química , Cannabis/envenenamento , Criança , Comportamento Infantil/efeitos dos fármacos , Interações Medicamentosas , Endocanabinoides/fisiologia , Feminino , Feto/efeitos dos fármacos , Humanos , Drogas Ilícitas/efeitos adversos , Masculino , Abuso de Maconha/epidemiologia , Abuso de Maconha/terapia , Uso da Maconha/efeitos adversos , Uso da Maconha/epidemiologia , Uso da Maconha/legislação & jurisprudência , Uso da Maconha/psicologia , Meios de Comunicação de Massa , Maconha Medicinal/efeitos adversos , Maconha Medicinal/uso terapêutico , Leite Humano/química , Transtornos Neurocognitivos/induzido quimicamente , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Receptores de Canabinoides/efeitos dos fármacos , Receptores de Canabinoides/fisiologia , Uso de Tabaco/epidemiologia
19.
Science ; 369(6505): 787-793, 2020 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-32675289

RESUMO

Although Huntington's disease is a late-manifesting neurodegenerative disorder, both mouse studies and neuroimaging studies of presymptomatic mutation carriers suggest that Huntington's disease might affect neurodevelopment. To determine whether this is actually the case, we examined tissue from human fetuses (13 weeks gestation) that carried the Huntington's disease mutation. These tissues showed clear abnormalities in the developing cortex, including mislocalization of mutant huntingtin and junctional complex proteins, defects in neuroprogenitor cell polarity and differentiation, abnormal ciliogenesis, and changes in mitosis and cell cycle progression. We observed the same phenomena in Huntington's disease mouse embryos, where we linked these abnormalities to defects in interkinetic nuclear migration of progenitor cells. Huntington's disease thus has a neurodevelopmental component and is not solely a degenerative disease.


Assuntos
Proteína Huntingtina/metabolismo , Doença de Huntington/metabolismo , Sistema Nervoso/embriologia , Animais , Ciclo Celular , Endossomos/metabolismo , Feto , Humanos , Proteína Huntingtina/genética , Doença de Huntington/genética , Camundongos , Camundongos Mutantes , Mitose , Mutação , Células Neuroepiteliais/metabolismo , Junções Íntimas/metabolismo , Proteína da Zônula de Oclusão-1/metabolismo
20.
Immunohematology ; 36(2): 60-63, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32667819

RESUMO

CONCLUSIONS: Red blood cell alloimmunization to antigens other than D, such as C, c, E, e, and antigens in the Kell, MNS, and Duffy blood group systems, has emerged as an important cause of hemolytic disease of the fetus and newborn (HDFN). Antibody screening for these antibodies is not routinely practiced for all antenatal patients in developing countries, mainly because of financial constraints. Here we report a rare case of HDFN due to dual antibodies to Rh and Kidd blood group system antigens: anti-E and anti-Jka. This case report highlights the importance of routine and regular antenatal screening of all pregnant women for proper monitoring and follow-up.


Assuntos
Eritroblastose Fetal , Anticorpos , Antígenos de Grupos Sanguíneos , Eritrócitos , Feminino , Feto , Humanos , Recém-Nascido , Gravidez
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