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1.
J Immunol ; 208(8): 1857-1872, 2022 04 15.
Article in English | MEDLINE | ID: mdl-35379748

ABSTRACT

Pregnant women are at increased risk of adverse outcomes, including preeclampsia and preterm birth, that may result from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Pregnancy imprints specific maternal immune responses that can modulate host susceptibility to microbial infection; therefore, recent studies have focused on the humoral response against SARS-CoV-2 in pregnant women. However, the pregnancy-specific cellular immune responses triggered by SARS-CoV-2 infection are poorly understood. In this study, we undertook an extensive in vitro investigation to determine the cellular immune responses to SARS-CoV-2 particles and proteins/peptides in pregnant women. First, we show that SARS-CoV-2 particles do not alter the pregnancy-specific oxidative burst of neutrophils and monocytes. Yet, SARS-CoV-2 particles/proteins shift monocyte activation from the classical to intermediate states in pregnant, but not in nonpregnant, women. Furthermore, SARS-CoV-2 proteins, but not particles or peptide pools, mildly enhance T cell activation during pregnancy. As expected, B cell phenotypes are heavily modulated by SARS-CoV-2 particles in all women; yet, pregnancy itself further modified such responses in these adaptive immune cells. Lastly, we report that pregnancy itself governs cytokine responses in the maternal circulation, of which IFN-ß and IL-8 were diminished upon SARS-CoV-2 challenge. Collectively, these findings highlight the differential in vitro responses to SARS-CoV-2 in pregnant and nonpregnant women and shed light on the immune mechanisms implicated in coronavirus disease 2019 during pregnancy.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Premature Birth , Female , Humans , Immunity, Cellular , Infant, Newborn , Pregnancy , Pregnancy Outcome , Pregnant Women , SARS-CoV-2
2.
JCI Insight ; 7(5)2022 03 08.
Article in English | MEDLINE | ID: mdl-35260533

ABSTRACT

Parturition is a well-orchestrated process characterized by increased uterine contractility, cervical ripening, and activation of the chorioamniotic membranes; yet, the transition from a quiescent to a contractile myometrium heralds the onset of labor. However, the cellular underpinnings of human parturition in the uterine tissues are still poorly understood. Herein, we performed a comprehensive study of the human myometrium during spontaneous term labor using single-cell RNA sequencing (scRNA-Seq). First, we established a single-cell atlas of the human myometrium and unraveled the cell type-specific transcriptomic activity modulated during labor. Major cell types included distinct subsets of smooth muscle cells, monocytes/macrophages, stromal cells, and endothelial cells, all of which communicated and participated in immune (e.g., inflammation) and nonimmune (e.g., contraction) processes associated with labor. Furthermore, integrating scRNA-Seq and microarray data with deconvolution of bulk gene expression highlighted the contribution of smooth muscle cells to labor-associated contractility and inflammatory processes. Last, myometrium-derived single-cell signatures can be quantified in the maternal whole-blood transcriptome throughout pregnancy and are enriched in women in labor, providing a potential means of noninvasively monitoring pregnancy and its complications. Together, our findings provide insights into the contributions of specific myometrial cell types to the biological processes that take place during term parturition.


Subject(s)
Labor, Obstetric , Myometrium , Endothelial Cells , Female , Humans , Labor, Obstetric/genetics , Labor, Obstetric/metabolism , Myometrium/metabolism , Parturition/genetics , Parturition/metabolism , Pregnancy , Transcriptome
3.
Am J Perinatol ; 2022 May 06.
Article in English | MEDLINE | ID: mdl-35253115

ABSTRACT

OBJECTIVES: The aim of the study is to estimate hospital charges (HC) and length of stay (LOS) for pregnancy and 6 weeks postpartum and to characterize the outliers who utilize a disproportionate share of health care resources. STUDY DESIGN: We performed a cross-sectional study of 500 subjects at a tertiary center between 2012 and 2014. Subjects were included who had inpatient status and an ICD-9 code for pregnancy; those with an ICD-9 code for ectopic pregnancy were excluded. Data were collected 266 days prior to the estimated date of delivery (EDD) and up to 42 days post-delivery. Medical diagnoses, obstetrical details, demographics, HC, and LOS were collected. Super-utilizers (SUs) were selected as patients with total HC exceeding $75,000, those who incurred $75,000 or less were assigned to the typical utilizer (TU) group. RESULTS: HC was positively skewed, with median's (interquartile range) of $151,143 (97,707-198,732) and $28,186 (19,292-38,943) among SUs and TUs, respectively. Despite the low proportion of SU patients (7%, n = 36), they accounted for 30% of charges. Similarly, SUs had longer LOS (16 vs. 3 days, p <0.05). They had earlier deliveries (34.5 vs. 38.5 weeks, p <0.05), higher cesarean section rates (69 vs. 35%, p <0.05), and more hysterectomies (8.3 vs. 0%, p <0.05). The most common complications in SUs were preterm labor (33.3 vs. 5.4%, p <0.05) and preterm premature rupture of membranes (25 vs. 3.9%, p< 0.05). The most common pre-existing condition in SUs was chronic hypertension (11.1 vs. 3%, p< 0.05). CONCLUSION: Although SUs comprise only 7% of the obstetrical population, they account for almost a third of the total HCs; in turn, SUs are at risk of adverse outcomes. Targeting this population can guide efforts to improve maternal health through prevention, research, and personalized care. SUs may have clustering at hospitals with higher levels of care and this topic warrants further investigation with state and national level data. KEY POINTS: · Just 7% of pregnant patients accounted for 30% of hospital charges.. · Super-utilizers had higher rates of preterm delivery, cesarean section, and hysterectomy.. · The most common pre-existing medical condition in super-utilizers was chronic hypertension..

4.
JAMA Netw Open ; 2(12): e1918007, 2019 12 02.
Article in English | MEDLINE | ID: mdl-31860106

ABSTRACT

Importance: Citation analysis is a bibliometric method that uses citation rates to evaluate research performance. This type of analysis can identify the articles that have shaped the modern history of obstetrics and gynecology (OBGYN). Objectives: To identify and characterize top-cited OBGYN articles in the Institute for Scientific Information Web of Science's Science Citation Index Expanded and to compare top-cited OBGYN articles published in specialty OBGYN journals with those published in nonspecialty journals. Design, Setting, and Participants: Cross-sectional bibliometric analysis of top-cited articles that were indexed in the Science Citation Index Expanded from 1980 to 2018. The Science Citation Index Expanded was queried using search terms from the American Board of Obstetrics and Gynecology's 2018 certifying examination topics list. The top 100 articles from all journals and the top 100 articles from OBGYN journals were evaluated for specific characteristics. Data were analyzed in March 2019. Main Outcomes and Measures: The articles were characterized by citation number, publication year, topic, study design, and authorship. After excluding articles that featured on both lists, top-cited articles were compared. Results: The query identified 3 767 874 articles, of which 278 846 (7.4%) were published in OBGYN journals. The top-cited article was published by Rossouw and colleagues in JAMA (2002). Top-cited articles published in nonspecialty journals were more frequently cited than those in OBGYN journals (median [interquartile range], 1738 [1490-2077] citations vs 666 [580-843] citations, respectively; P < .001) and were more likely to be randomized trials (25.0% vs 2.2%, respectively; difference, 22.8%; 95% CI, 13.5%-32.2%; P < .001). Whereas articles from nonspecialty journals focused on broad topics like osteoporosis, articles from OBGYN journal focused on topics like preeclampsia and endometriosis. Conclusions and Relevance: This study found substantial differences between top-cited OBGYN articles published in nonspecialty vs OBGYN journals. These differences may reflect the different goals of the journals, which work together to ensure optimal dissemination of impactful articles.


Subject(s)
Bibliometrics , Gynecology/statistics & numerical data , Journal Impact Factor , Obstetrics/statistics & numerical data , Periodicals as Topic/statistics & numerical data , Cross-Sectional Studies , Humans , Publishing
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