Investigating the current knowledge and needs concerning a follow-up for long-term cardiovascular risks in Dutch women with a preeclampsia history:a qualitative study

Background There is increasing evidence that a history of preeclampsia is an important risk factor for future cardiovascular events. Awareness of this risk could provide opportunities for identification of women at risk, with opportunities for prevention and / or early intervention. A standardized follow-up has not yet been implemented in the north of the Netherlands. The objective of this qualitative study was to explore the opinions and wishes among women and physicians about the follow-up for women with a history of preeclampsia. Methods Semi-structured interviews with 15 women and 14 physicians (5 obstetricians, 4 general practitioners, 3 vascular medicine specialists and 2 cardiologists) were performed and addressed topics about knowledge on CVR, current - and future follow-up. Women were approached through the HELLP foundation and their physicians. Physicians were approached by email. The interviews were recorded, typed and coded using ATLAS.ti software. A theoretical-driven thematic analysis was performed. Results Women had some knowledge about the association between preeclampsia and the increased CVR, but missed information from their health care providers. Specialists were aware of the association, but the information and advice they provided to their patients was minimal and inconsistent according to themselves. Whereas some general practitioners regarded their own knowledge as limited. There was a clear desire among women for a more extensive follow-up with specific attention to both emotional and physical consequences of preeclampsia. Physicians indicated that they preferred to see a follow up program concerning the CVR at the general practitioner as part of the already existent cardiovascular risk management (CVRM) program. Conclusion Women and medical specialists consider it important to improve aftercare for women after a pregnancy complicated by preeclampsia. Introducing these women into the CVRM program at the general practitioner is regarded as a preferred first step. Further research is warranted to establish an evidence-based guideline for the follow-up of these women

Physical activity in non-frail and frail older adults

Introduction: Physical activity (PA) is important for healthy ageing. Better insight into objectively measured PA levels in older adults is needed, since most previous studies employed self-report measures for PA assessment, which are associated with overestimation of PA. Aim: This study aimed to provide insight in objectively measured indoor and outdoor PA of older adults, and in PA differences by frailty levels. Methods: Data were collected among non-frail (N = 74) and frail (N = 10) subjects, aged 65 to 89 years. PA, measured for seven days with accelerometers and GPS-devices, was categorized into three levels of intensity (sedentary, light, and moderate-to-vigorous PA). Results: Older adults spent most time in sedentary and light PA. Subjects spent 84.7%, 15.1% and 0.2% per day in sedentary, light and moderate-to-vigorous PA respectively. On average, older adults spent 9.8 (SD 23.7) minutes per week in moderate-to-vigorous activity, and 747.0 (SD 389.6) minutes per week in light activity. None of the subjects met the WHO recommendations of 150 weekly minutes of moderate-to-vigorous PA. Age-, sex- and health status-adjusted results revealed no differences in PA between non-frail and frail older adults. Subjects spent significantly more sedentary time at home, than not at home. Non-frail subjects spent significantly more time not at home during moderate-to-vigorous activities, than at home. Conclusions: Objective assessment of PA in older adults revealed that most PA was of light intensity, and time spent in moderate-to-vigorous PA was very low. None of the older adults met the World Health Organization recommendations for PA. These levels of MVPA are much lower than generally reported based on self-reported PA. Future studies should employ objective methods, and age specific thresholds for healthy PA levels in older adults are needed. These results emphasize the need for effective strategies for healthy PA levels for the growing proportion of older adults

Altered Levels of Decidual Immune Cell Subsets in Fetal Growth Restriction, Stillbirth, and Placental Pathology

Immune cells are critically involved in placental development and functioning, and inadequate regulation of the maternal immune system is associated with placental pathology and pregnancy complications. This study aimed to explore numbers of decidual immune cells in pregnancies complicated with fetal growth restriction (FGR) and stillbirth (SB), and in placentas with histopathological lesions: maternal vascular malperfusion (MVM), fetal vascular malperfusion (FVM), delayed villous maturation (DVM), chorioamnionitis (CA), and villitis of unknown etiology (VUE). Placental tissue from FGR (n = 250), SB (n = 64), and healthy pregnancies (n = 42) was included. Histopathological lesions were classified according to criteria developed by the Amsterdam Placental Workshop Group. Tissue slides were stained for CD68 (macrophages), CD206 (M2-like macrophages), CD3 (T cells), FOXP3 [regulatory T (Treg) cells], and CD56 [natural killer (NK) cells]. Cell numbers were analyzed in the decidua basalis using computerized morphometry. The Mann-Whitney U-test and Kruskal Wallis test with the Dunn's as post-hoc test were used for statistical analysis. Numbers of CD68+ macrophages were higher in FGR compared to healthy pregnancies (p &lt; 0.001), accompanied by lower CD206+/CD68+ ratios (p &lt; 0.01). In addition, in FGR higher numbers of FOXP3+ Treg cells were seen (p &lt; 0.01) with elevated FOXP3+/CD3+ ratios (p &lt; 0.01). Similarly, in SB elevated FOXP3+ Treg cells were found (p &lt; 0.05) with a higher FOXP3+/CD3+ ratio (p &lt; 0.01). Furthermore, a trend toward higher numbers of CD68+ macrophages was found (p &lt; 0.1) in SB. Numbers of CD3+ and FOXP3+ cells were higher in placentas with VUE compared to placentas without lesions (p &lt; 0.01 and p &lt; 0.001), accompanied by higher FOXP3+/CD3+ ratios (p &lt; 0.01). Elevated numbers of macrophages with a lower M2/total macrophage ratio in FGR suggest a role for a macrophage surplus in its pathogenesis and could specifically indicate involvement of inflammatory macrophages. Higher numbers of FOXP3+ Treg cells with higher Treg/total T cell ratios in VUE may be associated with impaired maternal-fetal tolerance and a compensatory response of Treg cells. The abundant presence of placental lesions in the FGR and SB cohorts might explain the increase of Treg/total T cell ratios in these groups. More functionality studies of the observed altered immune cell subsets are needed.</p

Exciton diffusion in two-dimensional metal-halide perovskites

Two-dimensional layered perovskites are attracting increasing attention as more robust analogues to the conventional three-dimensional metal-halide perovskites for both light harvesting and light emitting applications. However, the impact of the reduced dimensionality on the optoelectronic properties remains unclear, particularly regarding the spatial dynamics of the excitonic excited state within the two-dimensional plane. Here, we present direct measurements of exciton transport in single-crystalline layered perovskites. Using transient photoluminescence microscopy, we show that excitons undergo an initial fast diffusion through the crystalline plane, followed by a slower subdiffusive regime as excitons get trapped. Interestingly, the early intrinsic diffusivity depends sensitively on the choice of organic spacer. A clear correlation between lattice stiffness and diffusivity is found, suggesting exciton–phonon interactions to be dominant in the spatial dynamics of the excitons in perovskites, consistent with the formation of exciton–polarons. Our findings provide a clear design strategy to optimize exciton transport in these systemsThis work has been supported by the Spanish Ministry of Economy and Competitiveness through The “María de Maeztu” Program for Units of Excellence in R&D (MDM-2014-0377). M.S. acknowledges the financial support of a fellowship from “la Caixa” Foundation (ID 100010434). The fellowship code is LCF/BQ/IN17/11620040. M.S. has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No. 713673. F.P. acknowledges support from the Spanish Ministry for Science, Innovation, and Universities through the state program (PGC2018-097236-A-I00) and through the Ramón y Cajal program (RYC-2017-23253), as well as the Comunidad de Madrid Talent Program for Experienced Researchers (2016-T1/IND-1209). N.A., M.M. and R. D.B. acknowledges support from the Spanish Ministry of Economy, Industry and Competitiveness through Grant FIS2017-86007-C3-1-P (AEI/FEDER, EU). E.P. acknowledges support from the Spanish Ministry of Economy, Industry and Competitiveness through Grant FIS2016-80434-P (AEI/FEDER, EU), the Ramón y Cajal program (RYC-2011- 09345) and the Comunidad de Madrid through Grant S2018/ NMT-4511 (NMAT2D-CM). S.P. acknowledges financial support by the VILLUM FONDEN via the Centre of Excellence for Dirac Materials (Grant No. 11744

Placenta-on-a-Chip as an In Vitro Approach to Evaluate the Physiological and Structural Characteristics of the Human Placental Barrier upon Drug Exposure:A Systematic Review

Quantification of fetal drug exposure remains challenging since sampling from the placenta or fetus during pregnancy is too invasive. Currently existing in vivo (e.g., cord blood sampling) and ex vivo (e.g., placenta perfusion) models have inherent limitations. A placenta-on-a-chip model is a promising alternative. A systematic search was performed in PubMed on 2 February 2023, and Embase on 14 March 2023. Studies were included where placenta-on-a-chip was used to investigate placental physiology, placenta in different obstetric conditions, and/or fetal exposure to maternally administered drugs. Seventeen articles were included that used comparable approaches but different microfluidic devices and/or different cultured maternal and fetal cell lines. Of these studies, four quantified glucose transfer, four studies evaluated drug transport, three studies investigated nanoparticles, one study analyzed bacterial infection and five studies investigated preeclampsia. It was demonstrated that placenta-on-a-chip has the capacity to recapitulate the key characteristics of the human placental barrier. We aimed to identify knowledge gaps and provide the first steps towards an overview of current protocols for developing a placenta-on-a-chip, that facilitates comparison of results from different studies. Although models differ, they offer a promising approach for in vitro human placental and fetal drug studies under healthy and pathological conditions.</p

Distribution of decidual mast cells in fetal growth restriction and stillbirth at (near) term

Introduction: Placental pathology and pregnancy complications are associated with unfavorable regulation of the maternal immune system. Although much research has been performed towards the role of immune cells like macrophages and T cells in this context, little is known about the presence and function of mast cells (MC). MC can be sub classified in tryptase-positive (MCT) and tryptase- and chymase-positive (MCTC). This study investigates the presence of MC in the decidua of pregnancies complicated by fetal growth restriction (FGR) and stillbirth (SB). Methods: Placental tissue from FGR (n = 250), SB (n = 64) and healthy pregnancies (n = 42) was included. Histopathological lesions were classified according to the Amsterdam Placental Workshop Group criteria. Tissue sections were stained for tryptase and chymase. Decidual MC were counted manually, and the results were expressed as number of cells/mm2 decidual tissue. Results: A significant lower median number of MCTC was found in the decidua of FGR (0.40 per mm2; p < 0.001) and SB (0.51 per mm2; p < 0.05) compared to healthy controls (1.04 per mm2). No difference in MCT number (1.19 per mm2, 1.88 per mm2 and 1.37 per mm2 respectively) was seen between the groups. There was no difference in number of MCT and MCTC between placental pathological lesions. Discussion: Our findings suggest a shift in decidual MC balance towards MCT in pregnancy complications. No difference in numbers of MC subtypes was found to be related to histopathologic lesions

Practice variation in timing of antenatal corticosteroid administration in early-onset fetal growth restriction: A secondary analysis of the Dutch STRIDER study

INTRODUCTION: In early-onset fetal growth restriction the fetus fails to thrive in utero due to unmet fetal metabolic demands. This condition is linked to perinatal mortality and severe neonatal morbidity. Maternal administration of corticosteroids in high-risk pregnancies for preterm birth at a gestational age between 24 and 34 weeks has been shown to reduce perinatal mortality and morbidity. Practice variation exists in the timing of the administration of corticosteroids based on umbilical artery monitoring findings in early-onset fetal growth restriction. The aim of this study was to examine differences in neonatal outcomes when comparing different corticosteroid timing strategies. MATERIAL AND METHODS: This was a post-hoc analysis of the Dutch STRIDER trial. We examined neonatal outcomes when comparing institutional strategies of early (umbilical artery pulsatility index >95th centile) and late (umbilical artery shows absent or reversed end-diastolic flow) administration of corticosteroids. The primary outcomes were neonatal mortality and a composite of neonatal mortality and neonatal morbidity, defined as bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis or retinopathy of prematurity. We also analyzed predictors for adverse neonatal outcomes, including gestational age at delivery, birthweight, maternal hypertensive disorders, and time interval between corticosteroids and birth. RESULTS: A total of 120 patients matched our inclusion criteria. In 69 (57.5%) the early strategy was applied and in 51 (42.5%) patients the late strategy. Median gestational age at delivery was 28 4/7 (± 3, 3/7) weeks. Median birthweight was 708 (± 304) g. Composite primary outcome was found in 57 (47.5%) neonates. No significant differences were observed in the primary outcome between the two strategies (neonatal mortality adjusted odds ratio [OR] 1.22, 95% CI 0.44-3.38; composite primary outcome adjusted OR 1.05, 95% CI 0.42-2.64). Only gestational age at delivery was a significant predictor for improved neonatal outcome (adjusted OR 0.91, 95% CI 0.86-0.96). CONCLUSIONS: No significant differences in neonatal outcomes were observed when comparing early and late strategy of antenatal corticosteroid administration on neonatal outcomes in pregnancies complicated by early-onset fetal growth restriction. We found no apparent risk contribution of interval between corticosteroid administration and delivery in multivariate analysis. Gestational age at delivery was found to be an important predictor of neonatal outcome