BACKGROUND
Preterm birth (PTB) is a leading cause of neonatal morbidity and mortality and is not uncommonly associated with chorioamnionitis. We recently have demonstrated that the placenta harbors a unique microbiome with similar flora to the oral community. We also have shown an association of these placental microbiota with PTB, history of antenatal infection, and excess maternal weight gain. On the basis of these previous observations, we hypothesized that the placental membranes would retain a microbiome community that would vary in association with preterm birth and chorioamnionitis.
OBJECTIVE
In the current study, we aimed to examine the differences in the placental membrane microbiome in association with PTB in both the presence and absence of chorioamnionitis and/ or funisitis using state-of-the-science whole-genome shotgun metagenomics.
STUDY DESIGN
This was a cross-sectional analysis with 6 nested spontaneous birth cohorts (n = 9–15 subjects/cohort): Term gestations without chorioamnionitis, term with chorioamnionitis, preterm without chorioamnionitis, preterm with mild chorioamnionitis, preterm with severe chorioamnionitis, and preterm with chorioamnionitis and funisitis. Histologic analysis was performed with Redline's criteria, and inflammatory cytokines were analyzed in the cord blood. DNA from placental membranes was extracted from sterile swabs collected at delivery, and whole-genome shotgun sequencing was performed on the Illumina HiSeq platform. Filtered microbial DNA sequences were annotated and analyzed with MG-RAST (ie, Metagenomic Rapid Annotations using Subsystems Technology) and R.
RESULTS
Subjects were assigned to cohorts on the basis of gestational age at delivery and independent scoring of histologic chorioamnionitis. We found that preterm subjects with severe chorioamnionitis and funisitis had increases in cord blood inflammatory cytokines. Of interest, although the placental membrane microbiome was altered in association with severity of histologic chorioamnionitis (permutational multivariate analysis of variance P = .005), there was no observable impact with either beta-methasone or antibiotic treatment. In preterm subjects with chorioamnionitis, we found a high abundance of both urogenital and oral commensal bacteria. These alterations in the microbiome were accompanied by significant variation (P < .05) in microbial metabolic pathways important in the glucose-fed pentose phosphate pathway (term subjects), or glycerophopholipid metabolism, and the biosynthesis of the siderophore group nonribosomal peptides (preterm subjects).
CONCLUSION
Consistent with ours and others previous findings, women who experienced spontaneous PTB harbor placental microbiota that further differed by severity of chorioamnionitis. Integrative meta-genomic analysis revealed significant variation in distinct bacterial metabolic pathways, which we speculate may contribute to risk of preterm birth with and without severe chorioamnionitis.
Targeted delivery at 34 weeks and team-managed diagnosis, treatment, and care of patients with placenta accreta were associated with improved maternal, but not neonatal outcomes.
We give a new and short proof of the characterization of monodromic nilpotent critical points. We also calculate the first generalized Lyapunov constants in order to solve the stability problem. We apply the results to several families of planar systems obtaining necessary and sufficient conditions for having a center. Our method also allows us to generate limit cycles from the origin.
The design of experiments (DoE) methodology is a technique that has been applied for many years in industry to improve quality. In this study, a summary of 77 cases of practical DoE application in the field of engineering is presented. All of the cases were published in important scientific journals between 2001 and 2005. The type of design that is applied, the size of the experiment, the number of factors that influence the response variable, and the sector of application of the design are analyzed. In addition, the increasing use of these designs over time is demonstrated. Copyright
Very low birth weight preterm newborns are susceptible to the development of debilitating inflammatory diseases, many of which are associated with chorioamnionitis. To define the effects of chorioamnionitis on the fetal immune system, IL-1β was administered intra-amniotically at ∼80% gestation in rhesus monkeys. IL-1β caused histological chorioamnionitis as well as lung inflammation (infiltration of neutrophils or monocytes in the fetal airways). There were large increases of multiple pro-inflammatory cytokine mRNAs in the lungs 24 h post-administration, which remained elevated relative to controls at 72 h. Intra-amniotic IL-1β also induced sustained expression of the surfactant proteins in the lungs. Importantly, IL-1β significantly altered the balance between inflammatory and regulatory T cells (Treg cells). Twenty-four h after IL-1β injection, the frequency of CD3+CD4+FOXP3+ T cells was decreased in lymphoid organs. In contrast, IL-17A–producing cells (CD3+CD4+, CD3+CD4−, and CD3−CD4− subsets) were increased in lymphoid organs. The frequency of IFN-γ-expressing cells did not change. In this model of a single exposure to an inflammatory trigger, CD3+CD4+FOXP3+ cells rebounded quickly and their frequency was increased at 72 h compared to controls. IL-17 expression was also transient. Interestingly, the T cell profile alteration was confined to the lymphoid organs and not to circulating fetal T cells. Together, these results suggest the chorioamnionitis-induced IL-1/IL-17 axis is involved in the severe inflammation that can develop in preterm newborns. Boosting Treg cells and/or controlling IL-17 may provide a means to ameliorate these abnormalities.
The recurrence rate of BPPV is 27%, and relapse largely occurs in the first 6 months. When BPPV recurrence is suspected, every canal on both sides must be investigated because it is the BPPV syndrome that recurs, rather than BPPV affecting a particular side or canal. Complex cases of BPPV have a greater risk of recurrence.
It is well known that the normal form theory can be applied to solve the center-focus problem for monodromic planar nilpotent singularities. In this paper we see how this theory can also be applied to generate limit cycles from this type of singularities.
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