Decision-making in obstetric emergencies. Individual differences and professional boundaries.

In affluent nations, variations in obstetric care, particularly during emergencies, perplexingly manifest in differing intervention and outcome rates. Although these variations mirror systemic disparities, they are also suggested to reflect the interplay of social and professional interactions between obstetricians/gynecologists and midwives, stemming from adherence to distinct professional paradigms and the influence of personal factors on decision-making and collaboration. This thesis sought to unpack these complexities by exploring individual differences and professional perspectives in decision-making during obstetric emergencies through a blend of interpretive and statistical approaches in a series of studies.Utilizing a narrative methodology with in-depth interviews and subsequent thematic analysis, Papers I and IV investigated the experiences of obstetricians/gynecologists (N=17) and midwives (N=27) during obstetric emergencies. Paper I used images of artwork as associative triggers in interviews, helping to illuminate decisionmakingprocesses, while Paper IV critically evaluated its thematic findings through the sociological lens of “boundary work”. Concurrently, Papers II and III employed psychometric instruments, including online questionnaires and the Five Factor Model personality test, to collect and analyze data from obstetricians/gynecologists and midwives (N = 472 for Paper II and N = 447 for Paper III). This involved investigating variables, such as Decision-Making styles, Negative Impact of Inductions, Healthcare Crisis Experience, and Job Satisfaction, alongside personality dimensions and complementary variables through various statistical tests.The studies revealed a diversity of findings: Paper I highlights that obstetricians/gynecologists navigate flexible decision-making environments, crystallizing into one of three distinct styles intertwining with their identities and practice narratives. Paper II unveils a specific personality profile among obstetricians/gynecologists and demonstrates correlations between personality traits, particularly Neuroticism, and distinct decision-making styles, while spotlightinggender and experience as significant influential factors. Paper III identifies divergent perspectives between the professions regarding labor inductions and job satisfaction, and highlights correlations among job satisfaction, views on labor inductions, and Neuroticism. Lastly, Paper IV underscores the multifaceted roles of midwives, who navigate, and sometimes resist, medical hierarchies to advocate for women’s physical and emotional well-being during childbirth, in a manner reshaping healthcare norms yet potentially sustaining historical tensions with obstetricians/gynecologists.This research highlights the intricate ways in which the personal and professional identities of obstetricians/gynecologists and midwives impact decision-making during obstetric emergencies. These insights invite a thoughtful reevaluation: How can training, support systems, and collaboration be recalibrated to encompass theseinfluential dynamics comprehensively? How can we as practitioners create work environments that not only acknowledge but also actively integrate varied personal perspectives and professional values and goals

A Crucial Role of Flagellin in the Induction of Airway Mucus Production by Pseudomonas aeruginosa

Pseudomonas aeruginosa is an opportunistic pathogen involved in nosocomial infections. Flagellin is a P. aeruginosa virulence factor involved in host response to this pathogen. We examined the role of flagellin in P. aeruginosa-induced mucus secretion. Using a mouse model of pulmonary infection we showed that PAK, a wild type strain of P. aeruginosa, induced airway mucus secretion and mucin muc5ac expression at higher levels than its flagellin-deficient mutant (ΔFliC). PAK induced expression of MUC5AC and MUC2 in both human airway epithelial NCI-H292 cell line and in primary epithelial cells. In contrast, ΔFliC infection had lower to no effect on MUC5AC and MUC2 expressions. A purified P. aeruginosa flagellin induced MUC5AC expression in parallel to IL-8 secretion in NCI-H292 cells. Accordingly, ΔFliC mutant stimulated IL-8 secretion at significantly lower levels compared to PAK. Incubation of NCI-H292 cells with exogenous IL-8 induced MUC5AC expression and pre-incubation of these cells with an anti-IL-8 antibody abrogated flagellin-mediated MUC5AC expression. Silencing of TLR5 and Naip, siRNA inhibited both flagellin-induced MUC5AC expression and IL-8 secretion. Finally, inhibition of ERK abolished the expression of both PAK- and flagellin-induced MUC5AC. We conclude that: (i) flagellin is crucial in P. aeruginosa-induced mucus hyper-secretion through TLR5 and Naip pathways; (ii) this process is mediated by ERK and amplified by IL-8. Our findings help understand the mechanisms involved in mucus secretion during pulmonary infectious disease induced by P. aeruginosa, such as in cystic fibrosis

Granulocyte-macrophage colony stimulatory factor enhances the pro-inflammatory response of interferon-γ-treated macrophages to pseudomonas aeruginosa infection

Pseudomonas aeruginosa is an opportunistic pathogen that can cause severe infections at compromised epithelial surfaces, such those found in burns, wounds, and in lungs damaged by mechanical ventilation or recurrent infections, particularly in cystic fibrosis (CF) patients. CF patients have been proposed to have a Th2 and Th17-biased immune response suggesting that the lack of Th1 and/or over exuberant Th17 responses could contribute to the establishment of chronic P. aeruginosa infection and deterioration of lung function. Accordingly, we have observed that interferon (IFN)-γ production by peripheral blood mononuclear cells from CF patients positively correlated with lung function, particularly in patients chronically infected with P. aeruginosa. In contrast, IL-17A levels tended to correlate negatively with lung function with this trend becoming significant in patients chronically infected with P. aeruginosa. These results are in agreement with IFN-γ and IL-17A playing protective and detrimental roles, respectively, in CF. In order to explore the protective effect of IFN-γ in CF, the effect of IFN-γ alone or in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), on the ability of human macrophages to control P. aeruginosa growth, resist the cytotoxicity induced by this bacterium or promote inflammation was investigated. Treatment of macrophages with IFN-γ, in the presence and absence of GM-CSF, failed to alter bacterial growth or macrophage survival upon P. aeruginosa infection, but changed the inflammatory potential of macrophages. IFN-γ caused up-regulation of monocyte chemoattractant protein-1 (MCP-1) and TNF-α and down-regulation of IL-10 expression by infected macrophages. GM-CSF in combination with IFN-γ promoted IL-6 production and further reduction of IL-10 synthesis. Comparison of TNF-α vs. IL-10 and IL-6 vs. IL-10 ratios revealed the following hierarchy in regard to the pro-inflammatory potential of human macrophages infected with P. aeruginosa: untreated < treated with GM-CSF < treated with IFN-γ < treated with GM-CSF and IFN-γ

Type I Interferon Signaling Regulates Ly6Chi Monocytes and Neutrophils during Acute Viral Pneumonia in Mice

Type I interferon (IFN-I) plays a critical role in the homeostasis of hematopoietic stem cells and influences neutrophil influx to the site of inflammation. IFN-I receptor knockout (Ifnar1−/−) mice develop significant defects in the infiltration of Ly6Chi monocytes in the lung after influenza infection (A/PR/8/34, H1N1). Ly6Chi monocytes of wild-type (WT) mice are the main producers of MCP-1 while the alternatively generated Ly6Cint monocytes of Ifnar1−/− mice mainly produce KC for neutrophil influx. As a consequence, Ifnar1−/− mice recruit more neutrophils after influenza infection than do WT mice. Treatment of IFNAR1 blocking antibody on the WT bone marrow (BM) cells in vitro failed to differentiate into Ly6Chi monocytes. By using BM chimeric mice (WT BM into Ifnar1−/− and vice versa), we confirmed that IFN-I signaling in hematopoietic cells is required for the generation of Ly6Chi monocytes. Of note, WT BM reconstituted Ifnar1−/− chimeric mice with increased numbers of Ly6Chi monocytes survived longer than influenza-infected Ifnar1−/− mice. In contrast, WT mice that received Ifnar1−/− BM cells with alternative Ly6Cint monocytes and increased numbers of neutrophils exhibited higher mortality rates than WT mice given WT BM cells. Collectively, these data suggest that IFN-I contributes to resistance of influenza infection by control of monocytes and neutrophils in the lung