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Directive 2002/32/EC of the European Parliament and of the Council of 7 May 2002 on undesirable substances in animal feed lists a range of substances from botanical origin (weed seeds) and additionally some chemical compounds directly originating from specific weeds. In order to examine the actual status of enforcement and of the present occurrence of these botanical substances, a survey was carried out. A questionnaire was sent to 103 laboratories, including official control labs from all member states of the European Union. The results, indicating the frequency of occurrence as far as reported, are compared to the publications of the EU Rapid Alert System for Food and Feed (RASFF). A total of 44 questionnaires was returned (42.7%) from 22 member states. Ten member states predominantly from north-western Europe appeared to have an active monitoring of botanical undesirable substances. The questionnaire results did not indicate that the other member states enforce this part of Directive 2002/32/EC. Reports on the frequency of occurrence include: a few to 25-50% of the samples contain traces of ergot (8 member states), a few to 24% contain at least some traces of thorn apple (6 member states), zero to 17% contain some castor oil plant seeds (3 member states), zero to a few samples contain Crotalaria seeds (3 member states), and zero to 6% contain traces of Sareptian mustard (4 member states). One member state conducted extra surveillance since several cases of animal intoxications have been reported. In some cases a coincidence with undesirable botanical substances was found.

The article discusses a study on second victims who are healthcare professionals (HCPs) involved in an unexpected adverse event such as a medical error or a patient-related injury and have become victimized and traumatized by the event. Topics discussed include the Danish Act on Patient Safety, feelings of guilt, anger, frustration, and fear of continued practice among HCPs, and the benefits of second-victim support programmes for medical staffs and patients.

Objective: To study the effects of lifestyle intervention on gestational weight gain (GWG) and obstetric outcomes.Research Design and Methods: The LiP (Lifestyle in Pregnancy) study was a randomized controlled trial in 360 obese women allocated in early pregnancy to lifestyle intervention or control. The intervention program included dietary guidance, free membership in fitness centers, physical training, and personal coaching.Results: A total of 360 obese pregnant women were included, and 304 (84%) were followed up until delivery. The intervention group had a significantly lower median (range) GWG compared with the control group of 7.0 (4.7-10.6) vs. 8.6 kg (5.7-11.5; P = 0.01). The Institute of Medicine (IOM) recommendations on GWG were exceeded in 35.4% of women in the intervention group compared with 46.6% in the control group (P = 0.058). Overall, the obstetric outcomes between the two groups were not significantly different.Conclusions: Lifestyle intervention in pregnancy resulted in limited GWG in obese pregnant women. Overall obstetric outcomes were similar in the two groups. Lifestyle intervention resulted in a higher adherence to the IOM weight gain recommendations; however, a significant number of women still exceeded the upper threshold. [ABSTRACT FROM AUTHOR]

A 6-year prospective observational cohort study of 4341 women in London compared the incidence of cesarean delivery with maternal body mass index. [ABSTRACT FROM AUTHOR]

The official control of animal proteins in feed is focused on the prevention of Bovine Spongiform Encephalopathy (mad cow disease). The current legislation of the European Union is planned to avoid the feeding of animal by-products to the same species as its origin (ban of cannibalism, or species-to-species ban). With respect to the official control, the circumscription of the term species in legislation should be defined, and species-specific markers should be available. Markers will include primer sets, antibodies, near-infrared profiles or visual characteristics. The method of classical light microscopy is currently the only accepted method in the framework of the official detection of animal proteins. Besides the necessary development of complementary methods, either as stand alone methods or in combination, the visual characteristics used for a microscopic examination of meat and bone meal particles should be fully explored. Multivariate analysis of a range of characteristics of lacunae in bone fragments revealed that discrimination is possible between mammalian and avian bone fragments. Translation to features for every day practical use should be carried out very carefully, and only comprehensively collected information on a range of features will give a first indication of the source. Characteristics of hairs and feather filaments can be used to identify the origin of animal particles. An in situ identification method has been developed for antibody conjugation with troponin I in muscle fibers on a microscopic slide. A proof of principle is presented. Interlaboratory transferability and validation have still to be achieved. The development and testing of light microscopy markers in the framework of the SAFEED-PAP project revealed that a fine tuning of existing microscopic characteristics appears to be possible.

Background: Increased prevalence of antimicrobial resistance coupled with a lack of new antibiotics against Gram-negative bacteria emphasize the imperative for novel therapeutic strategies. Colistin-resistant Pseudomonas aeruginosa constitutes a challenge, where conventional treatment options lack efficacy, in particular for biofilm-associated infections. Previously, synergy of colistin with other antibiotics was explored as an avenue for the treatment of colistin-resistant infections, and recently we reported our efforts towards colistin analogs capable of combating planktonic colistin-resistant strains., Aims: The aim of the present study was to investigate whether analogs of polymyxin B with improved potency in wild-type and moderate resistant Gram-negative pathogens would retain similarly increased activity in highly colistin-resistant clinical P. aeruginosa isolates (in planktonic and biofilm growth) when applied alone and in combination with rifampicin., Materials and Methods: In this in vitro study, we tested three analogs of polymyxin B prepared by solid-phase peptide synthesis. Antimicrobial susceptibility testing was performed by measurement of minimum inhibitory concentrations via the broth microdilution method. Interactions between two antimicrobials was quantified in a checkerboard broth microdilution assay by calculating the fractional inhibitory concentration index for each combination. For testing of antibiofilm activity a previously described model with alginate beads encapsulating a biofilm culture was applied. The minimum biofilm eradication concentrations (MBECs) were evaluated, and the fractional biofilm eradication concentration indices were calculated. Three recently identified colistin analogs (CEP932, CEP936 and CEP938) were tested against three isogenic pairs of colistin-susceptible and colistin-resistant P. aeruginosa clinical isolates as well as the reference strain PAO1., Results: For bacteria in planktonic growth CEP938 retained almost full potency in all three resistant isolates, while exhibiting similar activity as colistin in susceptible isolates. Against biofilms CEP938 was slightly more potent against PAO1 as compared to colistin, while also retaining activity against a biofilm of the colistin-resistant strain 41,782/98. Next, synergy between CEP938 and the antibiotic rifampicin was explored. Interestingly, CEP938 did not exhibit synergy with rifampicin in planktonic cultures. Importantly, for colistin-resistant biofilms the CEP938-rifampicin combination demonstrated activity superior to that found for the colistin-rifampicin combination., Conclusions: The present study showed in vitro efficacy of CEP938 against both colistin-susceptible and colistin-resistant P. aeruginosa biofilms as well as an ability of CEP938 to synergize with rifampicin in biofilm eradication., Competing Interests: The authors declare that they do not have any competing interests., (© 2024 The Authors.)

Introduction: Obstetric violence, or mistreatment of women in obstetric care, can have severe consequences such as fear of future childbirth, post-traumatic stress disorder, and depression., Material and Methods: The primary objective was to estimate the prevalence of obstetric violence in high-income countries. The secondary objective was to extract the main domains of obstetric violence perceived by women from qualitative studies. Following prospective registration (PROSPERO CRD42023468570), PubMed, Web of Science, Scopus, CINAHL, Embase, and Cochrane Library were searched with no restrictions. Included studies were cross-sectional, cohort, mixed methods, and qualitative studies based on populations from high-income countries. The review was conducted by two independent reviewers. Risk of bias was assessed. Rates of obstetric violence were pooled using random effects model, computing 95% confidence intervals (CI) and assessing heterogeneity using I 2 statistic. Funnel plots and Egger's test were used to detect potential reporting biases and small-study effects., Results: Of the 1821 records screened, 25 studies were included: 14 quantitative and 2 mixed methods studies, comprising 60 987 women, and 9 qualitative studies were included, comprising an additional 4356 women. 81.25% of quantitative studies, including the quantitative component of the mixed methods studies, were considered satisfactory or better regarding risk of bias. The prevalence of obstetric violence was overall 45.3% (95% CI 27.5-63.0; I 2  = 100.0%). The prevalence of specific forms of mistreatment was also estimated. Lack of access to analgesia was 17.3% (95% CI 6.9-27.7; I 2  = 99.7%). Ignored requests for help was 19.2% (95% CI 11.7-26.6; I 2  = 99.0%). Shouting and scolding 19.7% (95% CI 13.0-26.4; I 2  = 98.7%). The use of fundal pressure during the second stage of labor (Kristeller maneuver) was 30.3% (95% CI 22.1-38.5; I 2  = 97.6%). There was no funnel asymmetry. Lack of information and/or consent were the most frequent domains extracted from the qualitative articles and the qualitative component of the mixed methods studies., Conclusions: The results demonstrate that obstetric violence is a prevalent problem that women in high-income countries experience. Lack of information and/or consent were the domains most frequently described in the qualitative studies and the qualitative component of the mixed methods studies., (© 2024 The Author(s). Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Cancer curing immune responses against heterogeneous solid cancers require that a coordinated immune activation is initiated in the antigen avid but immunosuppressive tumor microenvironment (TME). The plastic TME, and the poor systemic tolerability of immune activating drugs are, however, fundamental barriers to generating curative anticancer immune responses. Here, we introduce the CarboCell technology to overcome these barriers by forming an intratumoral sustained drug release depot that provides high payloads of immune stimulatory drugs selectively within the TME. The CarboCell thereby induces a hot spot for immune cell training and polarization and further drives and maintains the tumor-draining lymph nodes in an anticancer and immune activated state. Mechanistically, this transforms cancerous tissues, consequently generating systemic anticancer immunoreactivity. CarboCell can be injected through standard thin-needle technologies and has inherent imaging contrast which secure accurate intratumoral positioning. In particular, here we report the therapeutic performance for a dual-drug CarboCell providing sustained release of a Toll-like receptor 7/8 agonist and a transforming growth factor-β inhibitor in preclinical tumor models in female mice., (© 2024. The Author(s).)

Objective: To predict birth weight at various potential gestational ages of delivery based on data routinely available at the first antenatal visit., Design: Individual participant data meta-analysis., Data Sources: Individual participant data of four cohorts (237 228 pregnancies) from the International Prediction of Pregnancy Complications (IPPIC) network dataset., Eligibility Criteria for Selecting Studies: Studies in the IPPIC network were identified by searching major databases for studies reporting risk factors for adverse pregnancy outcomes, such as pre-eclampsia, fetal growth restriction, and stillbirth, from database inception to August 2019. Data of four IPPIC cohorts (237 228 pregnancies) from the US (National Institute of Child Health and Human Development, 2018; 233 483 pregnancies), UK (Allen et al, 2017; 1045 pregnancies), Norway (STORK Groruddalen research programme, 2010; 823 pregnancies), and Australia (Rumbold et al, 2006; 1877 pregnancies) were included in the development of the model., Results: The IPPIC birth weight model was developed with random intercept regression models with backward elimination for variable selection. Internal-external cross validation was performed to assess the study specific and pooled performance of the model, reported as calibration slope, calibration-in-the-large, and observed versus expected average birth weight ratio. Meta-analysis showed that the apparent performance of the model had good calibration (calibration slope 0.99, 95% confidence interval (CI) 0.88 to 1.10; calibration-in-the-large 44.5 g, -18.4 to 107.3) with an observed versus expected average birth weight ratio of 1.02 (95% CI 0.97 to 1.07). The proportion of variation in birth weight explained by the model (R 2 ) was 46.9% (range 32.7-56.1% in each cohort). On internal-external cross validation, the model showed good calibration and predictive performance when validated in three cohorts with a calibration slope of 0.90 (Allen cohort), 1.04 (STORK Groruddalen cohort), and 1.07 (Rumbold cohort), calibration-in-the-large of -22.3 g (Allen cohort), -33.42 (Rumbold cohort), and 86.4 g (STORK Groruddalen cohort), and observed versus expected ratio of 0.99 (Rumbold cohort), 1.00 (Allen cohort), and 1.03 (STORK Groruddalen cohort); respective pooled estimates were 1.00 (95% CI 0.78 to 1.23; calibration slope), 9.7 g (-154.3 to 173.8; calibration-in-the-large), and 1.00 (0.94 to 1.07; observed v expected ratio). The model predictions were more accurate (smaller mean square error) in the lower end of predicted birth weight, which is important in informing clinical decision making., Conclusions: The IPPIC birth weight model allowed birth weight predictions for a range of possible gestational ages. The model explained about 50% of individual variation in birth weights, was well calibrated (especially in babies at high risk of fetal growth restriction and its complications), and showed promising performance in four different populations included in the individual participant data meta-analysis. Further research to examine the generalisability of performance in other countries, settings, and subgroups is required., Trial Registration: PROSPERO CRD42019135045., Competing Interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the National Institute for Health and Care Research Health Technology Assessment UK programme for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Dendritic cells (DCs) are central for the initiation and regulation of appropriate immune responses. While several studies suggest important regulatory roles of sialoglycans in DC biology, our understanding is still inadequate primarily due to a lack of appropriate models. Previous approaches based on enzymatic- or metabolic-glycoengineering and primary cell isolation from genetically modified mice have limitations related to specificity, stability, and species differences. This study addresses these challenges by introducing a workflow to genetically glycoengineer the human DC precursor cell line MUTZ-3, described to differentiate and maturate into fully functional dendritic cells, using CRISPR-Cas9, thereby providing and validating the first isogenic cell model for investigating glycan alteration on human DC differentiation, maturation, and activity. By knocking out (KO) the ST6GAL1 gene, we generated isogenic cells devoid of ST6GAL1-mediated α(2,6)-linked sialylation, allowing for a comprehensive investigation into its impact on DC function. Glycan profiling using lectin binding assay and functional studies revealed that ST6GAL1 KO increased the expression of important antigen presenting and co-stimulatory surface receptors and a specifically increased activation of allogenic human CD4 + T cells. Additionally, ST6GAL1 KO induces significant changes in surface marker expression and cytokine response to TNFα-induced maturation, and it affects migration and the endocytic capacity. These results indicate that genetic glycoengineering of the isogenic MUTZ-3 cellular model offers a valuable tool to study how specific glycan structures influence human DC biology, contributing to our understanding of glycoimmunology., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aim: We investigated associations between body mass index (BMI) z-scores for children aged 0-2 years and the BMI z-scores, body fat percentage and metabolic risk factors at 3 years of age., Methods: This was a secondary analysis of the Lifestyle in Pregnancy and Offspring randomised controlled trial, carried out at two university hospitals in Denmark. It comprised 149 mothers with BMI ≥30 kg/m 2 who did or did not receive a lifestyle intervention during pregnancy and a reference group of 97 mothers with normal-weight, with follow-up of their 3-year-old offspring. The children in these three groups were pooled for the data analyses, due to similar characteristics between groups. The BMI z-scores were calculated at 5 weeks, 5 months and 1, 2 and 3 years, using Danish reference groups. Their anthropometrics and metabolic outcomes were examined at 3 years of age., Results: BMI z-scores at 5 months to 2 years were associated with BMI z-scores and body fat percentage at 3 years of age and BMI z-scores were not associated with metabolic risk factors at 3 years., Conclusion: BMI z-scores from 5 weeks of age were associated with adverse anthropometric outcomes but not with metabolic risk factors at 3 years of age., (© 2024 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

In view of the increased prevalence of antimicrobial resistance among human pathogens, antibiotics against multidrug-resistant (MDR) bacteria are in urgent demand. In particular, the rapidly emerging resistance to last-resort antibiotic colistin, used for severe Gram-negative MDR infections, is critical. Here, a series of polymyxins containing unnatural amino acids were explored, and some analogues exhibited excellent antibacterial activity against Escherichia coli , Klebsiella pneumoniae , Acinetobacter baumannii , and Pseudomonas aeruginosa . Hydrophobicity of the compounds within this series (as measured by retention in reversed-phase analytical HPLC) exhibited a discernible correlation with their antimicrobial activity. This trend was particularly pronounced for colistin-resistant pathogens. The most active compounds demonstrated competitive activity against a panel of Gram-negative pathogens, while exhibiting low in vitro cytotoxicity. Importantly, most of these hits also retained (or even had increased) potency against colistin-susceptible strains. These findings infer that fine-tuning hydrophobicity may enable the design of polymyxin analogues with favorable activity profiles.

Objective: To investigate associations between maternal testosterone status and offspring birth anthropometrics., Design: Population-based prospective cohort study., Setting: University Hospital., Population: 1486 mother-child dyads from Odense Child Cohort., Methods: Maternal blood samples were collected at gestational weeks 27-30 and free testosterone (FT) levels were calculated using the Vermeulen equation from total testosterone (TT) analysed by mass spectrometry and sex hormone binding globulin. Associations between FT or TT levels and birth anthropometrics were analysed with multiple linear regression models according to offspring sex with adjustment for maternal age, parity, smoking and educational level. Analyses were repeated with polycystic ovary syndrome as exposure for offspring birth anthropometrics., Main Outcome Measures: Offspring birth weight (BW), birth length, abdominal and head circumferences., Results: Maternal mean (SD) age was 30.2 (4.5) years and pre-pregnancy body mass index was 23.5 (5.3) kg/m 2 . In boys (n = 787), higher FT was associated with lower birth weight (adjusted doubling constant = -65.53, P = 0.010), shorter birth length (adjusted doubling constant = -0.43, P < 0.001), and lower abdominal circumference (adjusted doubling constant = -0.39, P < 0.001); Higher TT was associated with lower abdominal circumference (adjusted doubling constant = -0.25, P = 0.028). In girls, no associations were found between maternal FT or TT and offspring anthropometrics., Conclusions: Higher maternal free testosterone exposure was linked to reduced birth weight, length and abdominal circumference in boys, whereas girls were not susceptible to maternal testosterone exposure., (© 2023 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Preeclampsia is a worldwide contributor to maternal and fetal morbidity and mortality. Women with preeclampsia are in a hyper-coagulable state with increased risk of thromboembolic disease later in life compared with normal pregnant women. The contact system (CAS) in plasma can mediate thrombin generation and is an important contributor to thrombus growth, but the activation of CAS during pregnancy complicated by preeclampsia is not yet elucidated, and CAS may play a role in the pathophysiology of preeclampsia. Therefore, the aim of the study is to address thrombin generation, and in particular, the capacity of the CAS-mediated pathway in patients with preeclampsia compared with pregnant controls. One hundred and seventeen women with preeclampsia and matched controls were included. The project was registered at www.clinicaltrials.gov as NCT04825145. CAS and tissue factor induced thrombin generation, proteins C and S, antithrombin, and histidine-rich glycoprotein (HRG) were assessed. Women with preeclampsia had significantly increased CAS and tissue factor-induced endogenous thrombin potential (ETP), and HRG compared with controls, P  = 0.022, P  = 0.024, and P  = 0.02, respectively. The concentrations of protein C and antithrombin were significantly reduced in the preeclampsia group, P  = 0.024 and P  < 0.0001, respectively. No significant difference in the concentration of protein S was detected, P  = 0.06. This study demonstrates a significant increased CAS-induced ETP and an overall decrease of important regulators of coagulation in women with preeclampsia compared with controls. These aspects can contribute to the hyper-coagulable state characterizing preeclampsia., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The emergence of the COVID-19 pandemic and the derived changes in maternity care have created stress and anxiety among pregnant women in different parts of the world. In times of stress and crisis, spirituality, including spiritual and religious practices, may increase., Objective: To describe if the COVID-19 pandemic influenced pregnant women's considerations and practises of existential meaning-making and to investigate such considerations and practices during the early pandemic in a large nationwide sample., Methods: We used survey data from a nationwide cross-sectional study sent to all registered pregnant women in Denmark during April and May 2020. We used questions from four core items on prayer and meditation practices., Results: A total of 30,995 women were invited, of whom 16,380 participated (53%). Among respondents, we found that 44% considered themselves believers, 29% confirmed a specific form of prayer, and 18% confirmed a specific form of meditation. In addition, most respondents (88%) reported that the COVID-19 pandemic had not influenced their responses., Conclusion: In a nationwide Danish cohort of pregnant women, existential meaning-making considerations and practices were not changed due to the COVID-19 pandemic. Nearly one in two study participants described themselves as believers, and many practised prayer and/or meditation., Competing Interests: Declaration of Competing Interest None of the authors have financial or other conflicts of interests related to the subject of this study., (Copyright © 2023. Published by Elsevier Ltd.)

Background: In cancer care, the promotion and implementation of shared decision-making in clinical practice guidelines (CPG) and consensus statements may have potential differences by gender., Objective: To systematically analyse recommendations concerning shared decision-making in CPGs and consensus statements for the most frequent cancers exclusively among males (prostate) and females (endometrial)., Search Strategy: We prospectively registered the protocol at PROSPERO (ID: RD42021241127). MEDLINE, EMBASE, Web of Science, Scopus and online sources (8 guideline databases and 65 professional society websites) were searched independently by two reviewers, without language restrictions., Inclusion Criteria: CPGs and consensus statements about the diagnosis or treatment of prostate and endometrial cancers were included from January 2015 to August 2021., Data Extraction and Synthesis: Quality assessment deployed a previously developed 31-item tool and differences between the two cancers analysed., Main Results: A total of 176 documents met inclusion criteria, 97 for prostate cancer (84 CPGs and 13 consensus statements) and 79 for endometrial cancer (67 CPGs and 12 consensus statements). Shared decision-making was recommended more often in prostate cancer guidelines compared to endometrial cancer (46/97 vs. 13/79, 47.4% vs. 16.5%; p < .001). Compared to prostate cancer guidelines (mean 2.14 items, standard deviation 3.45), compliance with the shared-decision-making 31-item tool was lower for endometrial cancer guidelines (mean 0.48 items, standard deviation 1.29) (p < .001). Regarding advice on the implementation of shared decision-making, it was only reported in 3 (3.8%) endometrial cancer guidelines and in 16 (16.5%) prostate cancer guidelines (p < .001)., Discussion and Conclusions: We observed a significant gender bias as shared decision-making was systematically more often recommended in the prostate compared to endometrial cancer guidelines. These findings should encourage new CPGs and consensus statements to consider shared decision-making for improving cancer care regardless of the gender affected., Patient or Public Contribution: The findings may inform future recommendations for professional associations and governments to update and develop high-quality clinical guidelines to consider patients' preferences and shared decision-making in cancer care., (© 2023 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Introduction: Phthalates freely cross the placenta and have the potential to influence pregnancy outcomes, with evidence of an increased incidence of preterm birth, low birth weight, pregnancy loss, and gestational diabetes. There is no regulation of phthalate concentrations in medications, which is often found in enteric coatings. Ingestion of phthalate containing medication during pregnancy may result in materno-fetal harm., Areas Covered: Phthalate subtypes, sources of phthalate exposure, mechanisms of phthalate toxicity, associations between phthalate exposure and incidence of preterm birth, low birth weight, fetal growth, gestational diabetes, and placental development., Expert Opinion: There is robust evidence to link exposure to phthalates in medical products including preterm birth, gestational diabetes, pregnancy-induced hypertension, and miscarriage. Nevertheless, future studies need to address standardization to avoid the heterogeneity of current studies. In future, the use of naturally occurring biopolymers may be safer, and the role of vitamin D as an immune modulator also has promise.

Introduction: We identified risk factors and outcomes associated with SARS-CoV-2 infection in pregnancy in a universally tested population according to disease severity and validated information on SARS-CoV-2 during pregnancy in national health registers in Denmark., Material and Methods: Cohort study using data from national registers and medical records including all pregnancies between March 1, 2020 and February 28, 2021. We compared women with a validated positive SARS-CoV-2 test during pregnancy with non-infected pregnant women. Risk factors and pregnancy outcomes were assessed by Poisson and Cox regression models and stratified according to disease severity defined by hospital admission status and admission reason (COVID-19 symptoms or other). Using medical record data on actual period of pregnancy, we calculated predictive values of the SARS-CoV-2 diagnosis in pregnancy in the registers., Results: SARS-CoV-2 infection was detected in 1819 (1.6%) of 111 185 pregnancies. Asthma was associated with infection (relative risk [RR] 1.63, 95% confidence interval [CI] 1.28-2.07). Risk factors for severe COVID-19 disease requiring hospital admission were high body mass index (median ratio 1.06, 95% CI 1.04-1.09), asthma (RR 7.47, 95% CI 3.51-15.90) and gestational age at the time of infection (gestational age 28-36 vs < 22: RR 3.53, 95% CI 1.75-7.10). SARS-CoV-2-infected women more frequently had hypertensive disorders in pregnancy (adjusted hazard ratio [aHR] 1.31, 95% CI 1.04-1.64), early pregnancy loss (aHR 1.37, 95% CI 1.00-1.88), preterm delivery before gestational age 28 (aHR 2.31, 95% CI 1.01-5.26), iatrogenically preterm delivery before gestational age 37 (aHR 1.49, 95% CI 1.01-2.19) and small-for-gestational age children (aHR 1.28, 95% CI 1.05-1.54). The associations were stronger among women admitted to hospital for any reason. The validity of the SARS-CoV-2 diagnosis in relation to pregnancy in the registers compared with medical records showed a negative predictive value of 99.9 (95% CI 99.9-100.0) and a positive predictive value of 82.1 (95% CI 80.4-83.7)., Conclusions: Women infected with SARS-CoV-2 during pregnancy were at increased risk of hypertensive disorders in pregnancy, early pregnancy loss, preterm delivery and having children small for gestational age. The validity of Danish national registers was acceptable for identification of SARS-CoV-2 infection during pregnancy., (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Objective: Pregnant women with type-1 diabetes have an increased risk of preeclampsia with kidney injury and cardiovascular complications. Urine excretion of plasmin and soluble membrane attack complex (sC5b-9) is elevated in severe preeclampsia. We hypothesized a coupling between these events and that active plasmin promotes intratubular complement activation and membrane deposition., Methods: Stored urine and plasma samples from pregnant women with type-1 diabetes (n = 88) collected at gestational weeks 12, 20, 28, 32, 36 and 38 were used. In the cohort, 14 women developed preeclampsia and were compared with 16 nonpreeclampsia controls., Results: Urine C3dg and sC5b-9-associated C9 neoantigen/creatinine ratios increased and were significantly higher in women who developed preeclampsia. Plasma concentrations did not change with gestation. Urine plasmin(ogen) correlated to urine C3dg (r = 0.51, P < 0.001) and C9 neoantigen (r = 0.68, P < 0.001); urine albumin correlated to C3dg (r = 0.44, P < 0.001) and C9 (r = 0.59, P < 0.001). Membrane-associated C3dg and C9 neoantigen was detected in urinary extracellular vesicles from patients but not controls at 36 weeks. Receiver operating characteristic curves showed that C3dg and C9 neoantigen were inferior to albumin as predictive biomarkers for preeclampsia., Conclusion: In preeclampsia, urinary excretion of activated complement relates significantly to albuminuria and to plasmin(ogen) but not to activation in plasma. Intratubular complement activation in preeclampsia is a postfiltration event tightly related to proteinuria/plasminogenuria and a possible mechanistic link to cellular damage and kidney injury., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: We aimed to describe the aim, data collection and content from a survey completed among pregnant women during the first peak of the COVID-19 pandemic in Denmark., Methods: The declaration of the COVID-19 pandemic in early 2020 challenged pregnant women's mental well-being due to a concern for their unborn child and their need for healthcare services through pregnancy and birth. To explore how the COVID-19 pandemic and the intensified measures such as the lockdown of Denmark impacted pregnant women's well-being and mental health, we conducted a questionnaire survey in the spring of 2020 when the COVID-19 pandemic was at its first peak, and the consequences for pregnant women and the unborn child were very uncertain. All women residing in Denmark and registered with an ongoing pregnancy on 24 April 2020 were invited to participate. The questionnaire included background information, variables on COVID-19 symptoms and validated batteries of questions on loneliness, anxiety, stress, quality of life, meditation and prayers. Additional questions were included to examine concerns related to pregnancy and childbirth during the pandemic., Cohort Characteristics: Almost 18,000 women answered the questionnaire, which represents 60% of all invited women who experienced a national lockdown for the first time. Their median age was 30 years, and they were more likely to be multiparous., Conclusions: Data from the COVIDPregDK Study will enable us to gain valuable knowledge on how the pandemic, the intensified measures from the health authorities and the national lockdown affected pregnant women's mental health and their concerns during the COVID-19 pandemic.

Background: Listeria monocytogenes is a commonly found organism in processed and prepared food and the disease of listeriosis is associated with a high morbidity and mortality. Compared with the general population, the risk of being diagnosed with listeriosis increases during pregnancy. Listeriosis can lead to miscarriage, spontaneous preterm labour and preterm birth, stillbirth and congenital neonatal infections., Objectives: We conducted a universal review of listeriosis in pregnancy and in the newborn., Search Strategy: The EMBASE, PubMed, Cinahl and Web of Science databases were searched for systematic reviews indexed before 1 December 2020., Selection Criteria: Any systematic reviews evaluating the prevalence, treatment, diagnosis and effects of listeriosis during pregnancy and up to 4 weeks postnatally were included., Data Collection and Analysis: Eligibility assessment, data extraction and quality assessment by the Methodological Quality Assessment of Systematic Reviews (AMSTAR-2) were performed in duplicate., Main Results: We identified 397 citations of which nine systematic reviews comprising 330 studies and 487 patients' reviews were included. Most systematic reviews (seven of nine) were of moderate to high quality. Prevention in pregnant women was based on adherence to strict dietary recommendations, such as reheating leftovers until steamed and avoiding unpasteurised dairy products. Listeriosis infections were likely to occur in the third trimester (66%) rather than in the first trimester (3%) of pregnancy. Symptoms are mostly fever and other flu-like symptoms, such as fatigue. Diagnosis was primarily made by culture of the pathogen. Intravenous amoxicillin or ampicillin were first-line treatment., Conclusions: Listeriosis, a rare but serious infectious disease in pregnancy, can cause devastating consequences for the fetus and newborn. Appropriate preventative treatment should be initiated during early pregnancy to avoid complications., Tweetable Abstract: Listeria is commonly found in processed and prepared food. Prevention is the best way to avoid listeriosis during pregnancy., (© 2022 John Wiley & Sons Ltd.)

Objective: Hypertension before and during early pregnancy has been associated with an increased risk of gestational diabetes mellitus (GDM) in retrospective analyses. We aimed to investigate the prospective blood pressure trackings in a population-based cohort of pregnant women, who were stratified according to their metabolic status in early third trimester., Methods: We recorded blood pressure longitudinally during pregnancy in 1230 women from the Odense Child Cohort, Denmark. Fasting glucose and insulin were measured at gestational weeks 28-30. Metabolic status was evaluated according to the WHO 2013 threshold for GDM (GDM-WHO: fasting plasma glucose ≥5.1 mmol/l), insulin and homeostatic model assessment of insulin resistance (HOMA-IR). Relationships between metabolic status in third trimester and blood pressure trajectories were evaluated with adjusted linear mixed models. Trajectory was defined as blood pressure records in pregnancy per 4 weeks interval., Results: Prevalence of GDM-WHO was 40% (498/1230). GDM-WHO was associated with 1.46 (0.22-2.70) mmHg higher SBP and 1.04 (0.07-2.01) mmHg higher DBP trajectories in the overall cohort. The associations were driven by differences in the overweight group, with 3.14 (1.05-5.25) mmHg higher SBP and 1.94 (0.42-3.47) mmHg higher DBP per 4 weeks in women with GDM-WHO compared with women without GDM-WHO. GDM-WHO was not associated with blood pressure in women with normal weight. Blood pressure trajectories were elevated across quartiles of insulin resistance., Conclusion: GDM-WHO is associated with higher blood pressure in pregnancy, and there appears to be a stronger effect in overweight women., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The pathophysiology of preeclampsia is not fully understood. Disturbances in the contact system are associated with preeclampsia. Few studies have investigated the association between preeclampsia and alterations in the contact system in plasma. This study aims to elucidate whether this basic biological system is affected in preeclampsia using new methods focusing on the dynamic interactions and total capacity of the contact system in blood., Design: Cross-sectional study matching women with preeclampsia and controls without preeclampsia regarding age, pregestational body mass index, and gestational age at onset of the disease., Setting: Two Danish University hospitals., Sample: A cohort of 117 women with preeclampsia and 117 controls., Methods: The turnover and capacity of the contact system were determined with new methods. Paired t -test, Wilcoxon signed-pairs signed rank test, Mann-Whitney or Chi 2 -test were applied, as appropriate., Main Outcome Measurements: Kallikrein generation (peak kallikrein concentration and endogenous kallikrein potential), coagulation factor XII, prekallikrein, H-kininogen, cleaved H-kininogen, and complement C1 esterase inhibitor., Results: The endogenous kallikrein potential, peak kallikrein concentration, prekallikrein and cleaved H-kininogen were significantly lower in women with preeclampsia compared to the controls, p ≤ 0.005, whereas the concentration of coagulation factor XII, H-kininogen and complement C1 esterase inhibitor was not significantly different, p > 0.05., Conclusion: This study demonstrates significant reduction in kallikrein generating capacity, prekallikrein and cleaved H-kininogen indicating that the contact system is affected in preeclampsia suggesting a link to the pathophysiology of the disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Godtfredsen, Gram, Pham, Dolleris, Jørgensen, Sidelmann and Palarasah.)

Objective: Health-care professionals (HCPs) who are involved in an unanticipated adverse patient event, a medical error or a patient-related injury can become second victims. Being a second victim can lead to various symptoms, affecting the well-being of HCPs and possible turnover intentions or absenteeism. An increasing number of hospitals have implemented a second-victim support programme. To achieve unique insights into what works and what does not work in second-victim support programmes, HCPs' perceptions are needed. The aim of this study was to translate the Second Victim Experience and Support Tool (SVEST) into Danish and test the psychometric properties of the Danish version (D-SVEST)., Methods: The SVEST self-administered questionnaire was translated into Danish following the World Health Organization's guidelines. Assessments of the content validity, construct validity and internal consistency were performed based on 171 participants., Results: The study demonstrated that the D-SVEST is content valid and fits the a priori defined structure. Yet, four items revealed unacceptable factor loadings (<0.4) and item-rest correlations <0.3. All Cronbach's alpha estimates for these five dimensions exceeded 0.70. The dimensions on colleague and institutional support did not contribute to the validity., Conclusions: In conclusion, the D-SVEST is considered relevant and valid for measuring second-victim experiences and the adequacy of support resources. However, we recommend a modification of items 9 and 25 to enhance the measurement scale in a Danish context. The D-SVEST can be used by health-care management at Danish hospitals.

Aims: Due to new evidence on fluoride neurotoxicity during early life, this study examined maternal exposure to fluoride through tea consumption in a low-fluoride region and measured fluoride releases from commercially available teas (tea bags and loose teas) to determine the need to limit fluoride exposure., Methods: Maternal urine fluoride (MUF) concentrations were measured in spot urine samples ( N =118) from first-trimester pregnant women and in prepared tea infusions made with deionised water from 33 brand teas and 57 loose-tea products, as determined by the direct method of using a fluoride-selective electrode., Results: The fluoride concentration in the local drinking water supplies ranged from 0.10 to 0.18 mg/L, and the creatinine-adjusted MUF ranged from 0.09 to 1.57 mg/L. Seventeen per cent of the women were daily tea drinkers, and their MUFs were higher than those with no consumption ( p =0.002). The fluoride concentration from tea bags ranged from 0.34 to 2.67 mg/L, while loose teas showed 0.72-4.50 mg/L (black), 0.56-1.58 mg/L (oolong), 1.28-1.50 mg/L (green), and 0.33-1.17 mg/L (white tea)., Conclusions: Fluoride exposure among pregnant women increases with tea consumption, with likely risks of developmental neurotoxicity to their children. As the fluoride release from tea varies widely, the fluoride concentration should be indicated on tea packages in order to allow consumers to make informed decisions on minimising their fluoride exposure.

Background: Healthcare professionals involved in adverse events may suffer severe physical and emotional distress in the aftermath. Adequate support is critical to an overall culture of safety for any healthcare institution. This study evaluates a formalised peer support program, 'the Buddy Study', in two Danish university hospital departments. The program consists of a 2-h seminar about second victims and self-selected buddies to provide peer support after adverse events., Methods: The study design involved a cross-sectional survey comprised of two close-ended questionnaires evaluating the Buddy Study seminar (Q1) and the Buddy Study program (Q2), along with two open-ended questions and three individual interviews for more elaborate answers., Results: Out of the 250 HCPs employed in both departments, 191 midwives, physicians, and nursing assistants completed Q1 and 156 completed Q2. The seminars were evaluated positively; 91.6% were satisfied with the overall content of the seminar, and 69.1% agreed that insight into how other people may react to adverse events has helped them contain their own reactions or emotions. Assessments of having the Buddy Study program in the department or using or being used as a buddy were more diverse, yet overall positive. Three benefits of the program were identified: the program i) has encouraged an open and compassionate culture; ii) has caused attentiveness to the wellbeing of colleagues; and iii) the self-selected buddy relationship has created a safe space for sharing. Additionally, three challenges or shortcomings were identified: i) although peer support is valuable, it should not stand alone; ii) informal peer support is already in place, hence making a formalised system redundant; and iii) the buddy system requires continuous maintenance and visibility., Conclusions: The overall evaluation of the Buddy Study program was positive, suggesting that this type of formalised peer support may contribute to a rapid and accessible second-victim support program in healthcare institutions. A key principle for the Buddy Study program is that relationships are crucial, and all buddy relationships are based on self-selection. This seems to offer a safe space for health care professionals to share emotional vulnerability and professional insecurity after an adverse event., (© 2022. The Author(s).)

Bacteriophages are obligate intracellular viruses that parasitize bacteria, making use of the host biosynthetic machinery. Bacterial vaginosis (BV) causes serious adverse sequelae, such as sexually transmitted infections, seroconversion to HIV positivity, and preterm birth. The aetiology of BV is multifactorial, and the vaginal microbiota, the response to antibiotics, and the phenotypic outcomes differ between cases. The choice of antibiotics to treat BV depends on the clinician's personal experience, which contributes to the poor outcome of BV treatment and high recurrence rate. In this review, we classify BV into two subtypes based on whether or not the BV case is sexually associated (potentially phage-related). An appropriate antibiotic can be selected on the basis of this BV-typing to optimise the short- and long-term effects of treatment. Not all Lactobacillus spp. are helpful or protective and some may sequestrate metronidazole, which mitigates its therapeutic efficacy. Phages, used therapeutically, could contribute to eubiosis by sparing beneficial species of Lactobacilli . However, Lactobacilli have an important role in maintaining vaginal eubiosis, so conventional wisdom has been that treatment of BV may benefit from metronidazole that conserves lactobacilli rather than clindamycin, which destroys lactobacilli. Furthermore, if the quality and quantity of vaginal lactobacilli are compromised by phage colonisation, as in the sexually transmitted subtype, eradication of lactobacilli with clindamycin followed by replacement by probiotics may be better therapeutically than metronidazole and reduce recurrence rates. Accordingly, the subtype of BV may provide a more scientific approach to antibiotic selection, which is absent in current clinical guidelines. We provide support for the role of bacteriophages in the aetiology, recurrence or failure to cure BV following treatment, through parasitic colonisation of lactobacilli that may be sexually transmitted and may be enhanced by other risk factors like smoking, a factor associated with BV., Competing Interests: The authors declare that they have no competing interests.No competing interests were disclosed.No competing interests were disclosed., (Copyright: © 2022 Lamont RF et al.)

Quantification of cytokines in cancerous tissue is important for understanding basic tumor biology and for deciphering anti-cancer mechanisms in drug development. Cytokine measurements on protein-level are often done by immunoassays such as enzyme-linked immunosorbent assay (ELISAs) and multiplex assays. However, immunoassays are prone to interference due to the presence of perturbing factors. The sum of these factors is known as the matrix effect, which results in a deviation of the measured cytokine concentration from the actual concentration. In this study, we demonstrated that matrix effects are present in tumor lysates from 11 different syngeneic murine tumors and that it can greatly affect cytokine measurements in ELISAs and multiplex assays. Dilution of tumor lysates and careful selection of lysis buffer components may decrease matrix effects. However, matrix effects are still present, and care should be taken when analyzing cytokine measurements of tumor lysates., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: Preeclampsia (PE) is a serious complication of pregnancy. The fibrinolytic system play crucial roles regarding placentation and evolution of PE., Aim: To study comprehensively components of the fibrinolytic system and fibrin lysability in women with PE., Design and Methods: 117 women with PE and matched controls were included. Tissue type plasminogen activator (t-PA), plasminogen, PAI-1, plasmin inhibitor (PI), D-dimer, the fibrinolytic potential of dextran sulphate euglobulin fraction (DEF), PAI-2, polymere PAI-2, fibrin clot lysability, thrombin activatable fibrinolysis inhibitor (TAFI) and fibrinogen were assessed., Results: Women with PE had significantly increased concentrations of t-PA and PAI-1, whereas the plasma concentration of PAI-2 was significantly lower compared to controls, p < 0.0001. Polymere PAI-2 was detected in both groups. DEF, TAFI and fibrinogen were not different between the groups. D-dimer was significantly increased and plasminogen/PI together with fibrin clot lysability time decreased in the PE-group, p  =  0.0004 p  =  0.04, p  =  0.03, p < 0.0001 respectively., Conclusion: This study demonstrates that PE is associated with an affected t-PA/PAI-1 system, decreased PAI-2 and increased fibrin lysability. Furthermore, PAI-2 has the potential to polymerize during pregnancy.

Introduction: Assessing the risk factors for and consequences of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy is essential to guide clinical care. Previous studies on SARS-CoV-2 infection in pregnancy have been among hospitalized patients, which may have exaggerated risk estimates of severe outcomes because all cases of SARS-CoV-2 infection in the pregnant population were not included. The objectives of this study were to identify risk factors for and outcomes after SARS-CoV-2 infection in pregnancy independent of severity of infection in a universally tested population, and to identify risk factors for and outcomes after severe infection requiring hospital admission., Material and Methods: This was a prospective population-based cohort study in Denmark using data from the Danish National Patient Register and Danish Microbiology Database and prospectively registered data from medical records. We included all pregnancies between March 1 and October 31, 2020 and compared women with a positive SARS-CoV-2 test during pregnancy to non-infected pregnant women. Cases of SARS-CoV-2 infection in pregnancy were both identified prospectively and through register linkage to ensure that all cases were identified and that cases were pregnant during infection. Main outcome measures were pregnancy, delivery, maternal, and neonatal outcomes. Severe infection was defined as hospital admission due to coronavirus disease 2019 (COVID-19) symptoms., Results: Among 82 682 pregnancies, 418 women had SARS-CoV-2 infection during pregnancy, corresponding to an incidence of 5.1 per 1000 pregnancies, 23 (5.5%) of which required hospital admission due to COVID-19. Risk factors for infection were asthma (odds ratio [OR] 2.19, 95% CI 1.41-3.41) and being foreign born (OR 2.12, 95% CI 1.70-2.64). Risk factors for hospital admission due to COVID-19 included obesity (OR 2.74, 95% CI 1.00-7.51), smoking (OR 4.69, 95% CI 1.58-13.90), infection after gestational age (GA) 22 weeks (GA 22-27 weeks: OR 3.77, 95% CI 1.16-12.29; GA 28-36 weeks: OR 4.76, 95% CI 1.60-14.12), and having asthma (OR 4.53, 95% CI 1.39-14.79). We found no difference in any obstetrical or neonatal outcomes., Conclusions: Only 1 in 20 women with SARS-CoV-2 infection during pregnancy required admission to hospital due to COVID-19. Risk factors for admission comprised obesity, smoking, asthma, and infection after GA 22 weeks. Severe adverse outcomes of SARS-CoV-2 infection in pregnancy were rare., (© 2021 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Here we apply hyperspectral bright field imaging to collect computed tomographic images with excellent energy resolution (~ 1 keV), applying it for the first time to map the distribution of stain in a fixed biological sample through its characteristic K-edge. Conventionally, because the photons detected at each pixel are distributed across as many as 200 energy channels, energy-selective images are characterised by low count-rates and poor signal-to-noise ratio. This means high X-ray exposures, long scan times and high doses are required to image unique spectral markers. Here, we achieve high quality energy-dispersive tomograms from low dose, noisy datasets using a dedicated iterative reconstruction algorithm. This exploits the spatial smoothness and inter-channel structural correlation in the spectral domain using two carefully chosen regularisation terms. For a multi-phase phantom, a reduction in scan time of 36 times is demonstrated. Spectral analysis methods including K-edge subtraction and absorption step-size fitting are evaluated for an ex vivo, single (iodine)-stained biological sample, where low chemical concentration and inhomogeneous distribution can affect soft tissue segmentation and visualisation. The reconstruction algorithms are available through the open-source Core Imaging Library. Taken together, these tools offer new capabilities for visualisation and elemental mapping, with promising applications for multiply-stained biological specimens., (© 2021. The Author(s).)