116 research outputs found

    Iron regulates contrasting toxicity of uropathogenic <i>Escherichia coli</i> in macrophages and epithelial cells

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    By far most urinary tract infections are caused by genetically diverse uropathogenic Escherichia coli (UPEC). Knowledge of the virulence mechanisms of UPEC is critical for drug development, but most studies focus on only a single strain of UPEC. In this study, we compared the virulence mechanisms of four antibiotic-resistant and highly pathogenic UPEC isolates in human blood monocyte-derived macrophages and a bladder epithelial cell (BEC) line: ST999, ST131, ST1981 and ST95. We found that while non-pathogenic E. coli strains are efficiently killed by macrophages in bactericidal single membrane vacuoles, the UPEC strains survive within double-membrane vacuoles. On side-by-side comparison, we found that whereas ST999 only carries Fe3+ importers, ST95 carries both Fe2+ and Fe3+ importers and the toxins haemolysin and colibactin. Moreover, we found that ST999 grows in the Fe3+ rich vacuoles of BECs and macrophages with concomitant increased expression of haem receptor chuA and the hydrogen peroxide sensor oxyR. In contrast, ST95 produces toxins in iron-depleted conditions similar to that of the urinary tract. Whereas ST95 also persist in the iron rich vacuoles of BECs, it produces colibactin in response to low Fe3+ contributing to macrophage death. Thus, iron regulates the contrasting toxicities of UPEC strains in macrophages and bladder epithelial cells due to low and high labile iron concentrations, respectively

    Increased incidence of hypertensive disorders of pregnancy in women with a history of spontaneous preterm birth:A longitudinal linked national cohort study

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    Objective: Determine the risk of hypertensive disorders of pregnancy (HD) in women with a history of spontaneous preterm birth (SPTB). Study design: Longitudinal linked national cohort study within the Dutch Perinatal Registry (1999–2009) on linked data among 349,291 women with a first and second singleton pregnancy in the Netherlands. Main outcome measures: The incidence of HD, small for gestational age (SGA) and placental abruption in the second pregnancy. Results: Out of 349,291 women with a singleton first pregnancy, 19,991 (5.7%) had a SPTB. The incidence of HD in the second pregnancy was 8.1% in women with a previous SPTB, as compared to 5.6% in women with a previous term birth (aOR 1.49 (CI 1.41–1.57)). Also after excluding HD, SGA and/or placental abruption in the first pregnancy, women with a history of SPTB had a higher risk of HD in their second pregnancy compared to women with a previous term birth (4.6% versus 2.7%, aOR 1.77 (CI 1.64–191)). Similarly, the incidence of SGA and placental abruption was higher in the second pregnancy in women with a history of SPTB compared to term birth in the first pregnancy. Conclusions: Women with a history of SPTB are at elevated risk of HD in the subsequent pregnancy. These results support shared pathophysiology between SPTB and HD

    Group Concept Mapping als startpunt van ontwerpgericht onderzoek in het primair onderwijs

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    In deze studie onderzoeken we de vraag of Trochim’s Group Concept Mapping (GCM) een bruikbare methode is om een gemeenschappelijk mentaal model (‘shared mental model’) op te stellen van een thema dat centraal staat in ontwerpgericht onderzoek. In een meervoudige gevalsstudie (n=3) die is uitgevoerd in het primair onderwijs zijn processen, producten en toepassing van GCM in drie onderzoeksprojecten onderzocht. Resultaten van analyses van transcripties van discussies (gericht op GCM-proces), concept maps (gericht op GCM-product) en gekozen probleemstelling (gericht op GCM-toepassing) laten zien dat de uit de GCM voortgekomen gemeenschappelijke mentale modellen bruikbaar waren voor probleemselectie en –analyse in de analysefase van de ontwerpgerichte onderzoeksprojecten

    Influence of timing of maternal antibiotic administration during caesarean section on infant microbial colonisation:a randomised controlled trial

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    OBJECTIVE: Revised guidelines for caesarean section (CS) advise maternal antibiotic administration prior to skin incision instead of after umbilical cord clamping, unintentionally exposing the infant to antibiotics antenatally. We aimed to investigate if timing of intrapartum antibiotics contributes to the impairment of microbiota colonisation in CS born infants. DESIGN: In this randomised controlled trial, women delivering via CS received antibiotics prior to skin incision (n=20) or after umbilical cord clamping (n=20). A third control group of vaginally delivering women (n=23) was included. Faecal microbiota was determined from all infants at 1, 7 and 28 days after birth and at 3 years by 16S rRNA gene sequencing and whole-metagenome shotgun sequencing. RESULTS: Compared with vaginally born infants, profound differences were found in microbial diversity and composition in both CS groups in the first month of life. A decreased abundance in species belonging to the genera Bacteroides and Bifidobacterium was found with a concurrent increase in members belonging to the phylum Proteobacteria. These differences could not be observed at 3 years of age. No statistically significant differences were observed in taxonomic and functional composition of the microbiome between both CS groups at any of the time points. CONCLUSION: We confirmed that microbiome colonisation is strongly affected by CS delivery. Our findings suggest that maternal antibiotic administration prior to CS does not result in a second hit on the compromised microbiome. Future, larger studies should confirm that antenatal antibiotic exposure in CS born infants does not aggravate colonisation impairment and impact long-term health

    Pregnant women's willingness to participate in a randomized trial comparing induction of labor at 39 weeks versus expectant management: A survey in the Netherlands

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    IntroductionA randomized controlled trial (RCT) in the United States, the ARRIVE trial, has indicated that induction of labor (IOL) in low-risk nulliparous women with a gestational age (GA) of 39 weeks compared to expectant management (EM) resulted in a significant lower rate of cesarean deliveries. The Dutch maternity care system is different compared to the United States with, among other factors, an overall significantly lower percentage of caesarean sections (CS). To investigate whether IOL has a favorable outcome in the Dutch maternity care system, a new trial is advised. In this questionnaire-based study we aim to evaluate whether Dutch low-risk pregnant women would be willing to participate in an RCT comparing IOL at 39 weeks to EM. Materials and methodsWe conducted an online survey in 2020 in the Netherlands. Respondent recruitment took place both in outpatient clinics at hospitals and midwife practices and via social media. Inclusion criteria were pregnant women with singleton gestation, GA ≤ 39 weeks, age 18 years or older and residency in the Netherlands. Exclusion criteria were multiple gestation, a history of a CS, planned IOL or CS in current pregnancy and GA > 39 weeks. A subgroup was formed of low risk (receiving primary care) nulliparous women with a gestational age between 34 and 39 weeks, comparable with the ARRIVE trial. ResultsThree hundred eighty respondents participated. Of all respondents (nulli- and multiparous), 47 (12.4%) would be willing to participate in the hypothetical RCT and 70 (18.4%) might be willing to participate. Amongst the 70 women in the subgroup 11 women (15.7%) would be willing to participate and 17 (24.3%) might be willing to participate. Discussion and conclusionCalculating sample size in a country with a low CS rate, in relation to 69.2% of women are not willing to participate in an RCT comparing IOL at 39 weeks with EM, would require >18.000 women to be counselled for participation. We believe such a study is a challenge in the Netherlands
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