Objective To measure maternal gut microbiome biodiversity in pregnancy. Methods In phase 1, maternal fecal samples were collected by rectal swab in twenty healthy pregnant women (14–28 weeks gestation) to measure bacterial abundance. In phase 2, fecal samples were collected from 31 women at enrollment (< 20 weeks gestation, baseline) and at 36–39 weeks gestation (follow-up). We assessed cluster analysis to assess bacterial community profiles at the phylum level longitudinally through pregnancy. DNA was extracted from swabs, followed by PCR of the bacterial 16s rRNA gene and multiplex high-throughput sequencing (Ion Torrent). Results In phase 1, 16 of 20 samples yielded usable data. White women (n=10) had greater abundance of Firmicutes (23 ± 0.15 vs 16% ± 0.75, p =0.007) and Bacteroidetes (24 ± 0.14 vs 19% ± 0.68, p = 0.015) compared to non-White women (n=6). In the 11 paired specimens, Bacteroidetes increased in abundance from baseline to follow-up. Compared with women who gained below the median gestational weight gain (GWG) (<15.4 kg), those who gained above the median GWG had increased abundance of Bacteroidetes (p=0.02) and other phyla (p=0.04). Conclusion Maternal microbiome biodiversity changes as pregnancy progresses and correlates with GWG.
Wilms tumor (WT) blastema retains gene expression profiles characteristic of the multipotent nephron progenitor pool, or cap mesenchyme (CM), in the developing kidney. As a result, WT blastema and the CM are believed to represent contextual analogues of one another. Sine oculis homeobox 2 (SIX2) is a transcription factor expressed specifically in the CM, provides a critical mechanism for CM self-renewal, and remains persistently active in WT blastema, although its purpose in this childhood malignancy remains unclear. We hypothesized that SIX2, analogous to its function in development, confers a survival pathway to blastema, the putative WT stem cell. To test its functional significance in WT biology, wild-type SIX2 was overexpressed in the human WT cell line, WiT49. After validating this model, SIX2 effects on anchorage-independent growth, proliferation, invasiveness, canonical WNT pathway signaling, and gene expression of specific WNT pathway participants were evaluated. Relative to controls, WiT49 cells overexpressing SIX2 showed significantly enhanced anchorage-independent growth and early-passage proliferation representing surrogates of cell survival. Interestingly, overexpression of SIX2 generally repressed TCF/LEF-dependent canonical WNT signaling, which activates and coordinates both differentiation and stem pathways, but significantly heightened canonical WNT signaling through the survivin promoter, a mechanism that exclusively maintains the stem state. In summary, when overexpressed in a human WT cell line, SIX2 enhances cell survival and appears to shift the balance in WNT/β-catenin signaling away from a differentiation path and toward a stem cell survival path.
Antenatal counseling of women with previable PROM should include that one in seven women experience significant morbidity. Although expectant management was not associated with increased risk in this cohort, women with twins or those aged 35 years or older were at substantially increased risk.
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