Sequence variants in oxytocin pathway genes and preterm birth: a candidate gene association study

Peer reviewe

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Correction: Interferon Regulatory Factor 6 Has a Protective Role in the Host Response to Endotoxic Shock.

[This corrects the article DOI: 10.1371/journal.pone.0152385.]

Interferon Regulatory Factor 6 Has a Protective Role in the Host Response to Endotoxic Shock.

Interferon Regulatory Factor (IRF) 6, a member of the IRF family, is essential for epidermal and orofacial embryonic development. Irf6 is strongly expressed in keratinocytes, in which it regulates epidermal proliferation, differentiation, and migration. A recent role for Irf6 in Toll-like receptor 2-dependent chemokine gene expression was also reported in an epithelial cell line. However, a function for Irf6 in innate immune cells was not previously reported. In the present study, we investigated the expression and function of Irf6 in bone marrow-derived neutrophils and macrophages. We show here, using a conditional knockout of Irf6 in lysosymeM expressing cells, that Irf6 is required for resistance to LPS-induced endotoxic shock. In addition, Irf6-deficient bone marrow-derived neutrophils exhibited increased chemotactic index and velocity compared with wild-type cells in vitro. TLR4-specific KC and IL6 secretions were upregulated in Irf6-deficient bone marrow-derived macrophages in vitro. These cells also exhibited an increased level of phosphorylated IkBa. Collectively, our findings suggest a role for Irf6 in the resistance to endotoxic shock due to NFk-B-mediated alteration of cytokine production

Transforming growth factor Beta 3 is required for excisional wound repair in vivo.

Wound healing is a complex process that relies on proper levels of cytokines and growth factors to successfully repair the tissue. Of particular interest are the members of the transforming growth factor family. There are three TGF-ß isoforms-TGF- ß 1, 2, and 3, each isoform showing a unique expression pattern, suggesting that they each play a distinct function during development and repair. Previous studies reported an exclusive role for TGF-ß 3 in orofacial development and a potent anti-scarring effect. However, the role of TGF- ß 3 in excisional wound healing and keratinocyte migration remains poorly understood. We tested the effect of TGF-ß 3 levels on excisional cutaneous wounds in the adult mouse by directly injecting recombinant TGF-ß 3 or neutralizing antibody against TGF-ß 3 (NAB) in the wounds. Our results demonstrate that TGF-ß 3 does not promote epithelialization. However, TGF-ß 3 is necessary for wound closure as wounds injected with neutralizing antibody against TGF-ß 3 showed increased epidermal volume and proliferation in conjunction with a delay in keratinocyte migration. Wild type keratinocytes treated with NAB and Tgfb3-deficient keratinocytes closed an in vitro scratch wound with no delay, suggesting that our in vivo observations likely result from a paracrine effect

Irf6 in innate immune cells is required for resistance to LPS-induced endotoxic shock.

<p>(A) qPCR for <i>Irf6</i> in bone marrow-derived macrophages from wild-type and cKO animals. Data are expressed as percentage of wild-type (n = 3; unpaired t-test, **** <i>P</i> < 0.0001). (B) Western blot analysis of protein extracts from WT (n = 2) and cKO macrophages (n = 2), and embryonic day (e) 17.5 skin (C) Survival of wild-type and cKO was assessed over a 7-day period following LPS-induced endotoxic shock (n = 37–39, Gehan-Breslow-Wilcoxon test, * <i>P</i> < 0.05).</p

<i>In vivo</i> cytokine levels and peritoneal migration of neutrophils are not significantly different between wild-type and cKO.

<p>Low (LPS 15 mg/kg, A, B) and high (LPS 400 mg/kg, C, D) levels of LPS were injected intraperitoneally in wild-type (WT) and cKO animals. (A, C) Serum cytokine levels were measured 8 h following injection and reported as fold ratio cKO over wild-type. (B, D) Number of neutrophils (PMN) were counted following intraperitoneal lavage. Data are means ± SEM, n = 6–13 animals per group.</p

Irf6 inhibits NFkB activation in bone marrow-derived macrophages <i>in vitro</i>.

<p>(A) Western blot analysis (one representative of 3 experiments) for pIkBa, IkBa and Bactin of wild-type (WT) and Irf6 cKO (cKO) macrophages (MΦ) unstimulated or stimulated with LPS for 30, 60 and 180 min. (B, C) Quantitative analysis of three independent Western blot analysis as presented in (A) expressed as fold change from the unstimulated (T0) control cells.</p