We examined the community ecology of vaginal microbial samples taken from pregnant women with previous preterm birth experience to investigate whether targeted pathogenic and commensal bacteria are related to risk of preterm birth in the current pregnancy. We found a significant correlation between the community structure of selected bacteria and birth outcome, but the correlation differed among self-reported racial/ethnic groups. Using a community ordination analysis, we observed infrequent co-occurrence of Mycoplasma and bacteria vaginosis associated bacteria 3 (BVAB3) among black and Hispanic participants. In addition, we found that the vaginal bacteria responded differently in different racial/ethnic groups to modifications of maternal behavioral (ie, douching and smoking) and biological traits (ie, body mass index [BMI]). Even after accounting for these maternal behaviors and traits, the selected vaginal bacteria was significantly associated with preterm birth among black and Hispanic participants. By contrast, white participants did not exhibit significant correlation between microbial community and birth outcome. Findings from this study affirm the necessity of considering women’s race/ethnicity when evaluating the correlation between vaginal bacteria and preterm birth. The study also illustrates the importance of studying the vaginal microbiota from an ecological perspective, and demonstrates the power of ecological community analysis to improve understanding of infectious disease.
Citation to related publication:
Selected Vaginal Bacteria and Risk of Preterm Birth: An Ecological Perspective
OBJECTIVE—Genital tract infection accounts for ~ 25–40% of all pre-term births. We sought to
assess the relationship between preterm birth and selected vaginal bacterial taxa associated with
preterm birth either directly or through their association with bacterial vaginosis (BV).
STUDY DESIGN—Vaginal fluid for Gram stain was collected between 17 and 22 weeks
gestation as part of a randomized trial of ultrasound-indicated cerclage for preterm birth
prevention in women at high risk for recurrent spontaneous preterm birth. Bacterial DNA was
extracted from the Gram stain slides and analyzed using quantitative PCR.
RESULTS—Among the 499 participants, Mycoplasma was positively correlated with increased
risk of preterm (RR = 1.83; 95% CI: 1.52,2.22) as was Mobiluncus (RR=1.36; 95% CI: 1.07, 1.73)
and Atopobium (RR=1.44; 95% CI: 1.1, 1.87). However, there were strong interactions between
race/ethnic group and the presence of these and other individual taxa on risk of preterm birth. By
contrast, BVAB3 was consistently associated with a reduction in risk of preterm birth for all
racial/ethnic groups (0.55; 95%CI: 0.39, 0.78).
CONCLUSIONS—BV is characterized by a reduction of Lactobacillus, and lactic acid
producing bacteria and the presence of Mobiluncus; we found these factors and presence of
Mycoplasma to be associated with increased risk of preterm birth. By contrast, the presence of a
recently identified organism sufficient to cause BV, BVAB3, decreased risk of preterm birth.
These findings give insight into why treating BV has mixed impact on risk of preterm birth.
Citation to related publication:
Mycoplasma, Bacterial Vaginosis Associated Bacteria BVAB3, Race, and Risk of Preterm Birth in a High Risk Cohort
Introduction: Diagnostic testing is common in the emergency department. The value of some testing is questionable. The purpose of this study was to assess how varying levels of benefit, risk, and costs influenced an individual’s desire to have diagnostic testing.
Methods: A survey through Amazon Mechanical Turk presented hypothetical clinical situations: low risk chest pain and minor traumatic brain injury. Each scenario included three given variables (benefit, risk, and cost), that was independently randomly varied over four possible values (0.1%, 1%, 5%, 10% for benefit and risk and $0, $100, $500, and $1000 for the individual’s personal cost for receiving the test). Benefit was defined as the probability of finding the target disease (traumatic intracranial hemorrhage or acute coronary syndrome).
Results: A total of 1000 unique respondents completed the survey. Increasing benefit from 0.1% to 10%, the percent of respondents who accepted a diagnostic test went from 28.4% to 53.1%. [OR: 3.42 (2.57-4.54)] As risk increased from 0.1% to 10%, this number decreased from 52.5% to 28.5%. [OR: 0.33 (0.25-0.44)] Increasing cost from $0 to $1000 had the greatest change of those accepting the test from 61.1% to 21.4%, respectively. [OR: 0.15 (0.11-0.2)]
Conclusions: The desire for testing was strongly sensitive to the benefits, risks and costs. Many participants wanted a test when there was no added cost, regardless of benefit or risk levels, but far fewer elected to receive the test as cost increased incrementally. This suggests that out of pocket costs may deter patients from undergoing diagnostic testing with low potential benefit.
Transcriptional accessibility of chromatin is central to guiding CD4+ T cell function through regulation of lineage specific gene expression. Myst1 is a histone acetyltransferase responsible for acetylation of the protein tail of histone 4 at lysine residue 16 (H416ac), resulting in increased transcriptional accessibility and activation of gene transcription. Previous studies have described a role for Myst1 in governing lymphocyte development in the thymus, however the role of Myst1 and H4K16ac in guiding activation of peripheral CD4+ T cells has not been studied. Activation of human and murine CD4+ T cells resulted in upregulation of Myst1 expression, and deletion of Myst1 resulted in changes in proliferative responses to both polyclonal stimulus and exogenous cytokines. Myst1-deficient T cells also exhibited modulations in lineage commitment, with decreased function in TH1/TH2 skewing conditions and increased function in response to TH17-promoting conditions. Regulation of Myst1 function in CD4+ T cells appears governed at least in part by STAT5, as Myst1 expression is regulated by STAT5 expression and DNA binding, and modulations in H4K16ac in Myst1-deficient CD4+ T cells is observable at sites in the promoter regions of lineage specific genes following skewing to the TH1 or TH2 lineage in vitro. Taken together, these results indicate an important role for the STAT5-Myst1 epigenetic axis in governing the activation and effector function of CD4+ T cells.