Inflammatory Gene Regulatory Networks in Amnion Cells Following Cytokine Stimulation: Translational Systems Approach to Modeling Human Parturition

A majority of the studies examining the molecular regulation of human labor have been conducted using single gene approaches. While the technology to produce multi-dimensional datasets is readily available, the means for facile analysis of such data are limited. The objective of this study was to develop a systems approach to infer regulatory mechanisms governing global gene expression in cytokine-challenged cells in vitro, and to apply these methods to predict gene regulatory networks (GRNs) in intrauterine tissues during term parturition. To this end, microarray analysis was applied to human amnion mesenchymal cells (AMCs) stimulated with interleukin-1β, and differentially expressed transcripts were subjected to hierarchical clustering, temporal expression profiling, and motif enrichment analysis, from which a GRN was constructed. These methods were then applied to fetal membrane specimens collected in the absence or presence of spontaneous term labor. Analysis of cytokine-responsive genes in AMCs revealed a sterile immune response signature, with promoters enriched in response elements for several inflammation-associated transcription factors. In comparison to the fetal membrane dataset, there were 34 genes commonly upregulated, many of which were part of an acute inflammation gene expression signature. Binding motifs for nuclear factor-κB were prominent in the gene interaction and regulatory networks for both datasets; however, we found little evidence to support the utilization of pathogen-associated molecular pattern (PAMP) signaling. The tissue specimens were also enriched for transcripts governed by hypoxia-inducible factor. The approach presented here provides an uncomplicated means to infer global relationships among gene clusters involved in cellular responses to labor-associated signals

Care-seeking patterns for fatal non-communicable diseases among women of reproductive age in rural northwest Bangladesh

<p>Abstract</p> <p>Background</p> <p>Though non-communicable diseases contribute to an increasing share of the disease burden in South Asia, health systems in most rural communities are ill-equipped to deal with chronic illness. This analysis seeks to describe care-seeking behavior among women of reproductive age who died from fatal non-communicable diseases as recorded in northwest rural Bangladesh between 2001 and 2007.</p> <p>Methods</p> <p>This analysis utilized data from a large population-based cohort trial in northwest rural Bangladesh. To conduct verbal autopsies of women who died while under study surveillance, physicians interviewed family members to elicit the biomedical symptoms that the women experienced as well as a narrative of the events leading to deaths. We performed qualitative textual analysis of verbal autopsy narratives for 250 women of reproductive age who died from non-communicable diseases between 2001 and 2007.</p> <p>Results</p> <p>The majority of women (94%) sought at least one provider for their illnesses. Approximately 71% of women first visited non-certified providers such as village doctors and traditional healers, while 23% first sought care from medically certified providers. After the first point of care, women appeared to switch to medically certified practitioners when treatment from non-certified providers failed to resolve their illness.</p> <p>Conclusions</p> <p>This study suggests that treatment seeking patterns for non-communicable diseases are affected by many of the sociocultural factors that influence care seeking for pregnancy-related illnesses. Families in northwest rural Bangladesh typically delayed seeking treatment from medically certified providers for NCDs due to the cost of services, distance to facilities, established relationships with non-certified providers, and lack of recognition of the severity of illnesses. Most women did not realize initially that they were suffering from a chronic illness. Since women typically reached medically certified providers in advanced stages of disease, they were usually told that treatment was not possible or were referred to higher-level facilities that they could not afford to visit. Women suffering from non-communicable disease in these rural communities need feasible and practical treatment options. Further research and investment in adequate, appropriate care seeking and referral is needed for women of reproductive age suffering from fatal non-communicable diseases in resource-poor settings.</p