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Stillbirth rates have stalled or increased in some European countries during the last decade. We investigate to what extent time-trends and between-country differences in stillbirth rates are explained by the changing prevalence of advanced maternal age and teenage pregnancies or multiple births. We analysed data on stillbirths and live births by maternal age and multiplicity from 2010 to 2021 in 25 European countries using Kitagawa decomposition to separate rate differences into compositional and rate components. Rates significantly decreased in six countries, but increased in two. Changes in maternal age structure reduced national stillbirth rates by a maximum of 0.04 per 1000 in the Netherlands and increased rates by up to 0.85 in Cyprus. Changes in the prevalence of multiple births decreased rates by up to 0.19 in the Netherlands and increased rates by up to 0.01 across multiple countries. Maternal age differences explained between 0.11 of the below-European average stillbirth rate in Belgium and 0.13 of the above-average rate in Ireland. Excluding Cyprus, differences in multiple births explained between 0.05 of the below-average rate in Malta and 0.03 of the above-average rate in Ireland. For most countries, the increase in advanced-age pregnancies contributed to rising stillbirth rates over time, while reductions in multiples led to decreases in rates. However, large parts of the trends remain unexplained by those factors. By 2021, neither factor explained the differences between countries, due to increased compositional uniformity and declining stillbirth risk for advanced maternal age.

Emotional and behavioural difficulties including depression, anxiety, and hyperactivity are elevated in autistic children (AC). Family processes of a psychological nature are associated with these difficulties, but the direction of influence is uncertain. We searched seven bibliographic databases for prospective, quantitative studies on the impact of family processes across the parent, dyad, and family system levels on the later well-being of AC without intellectual disability, across a minimum of six months. Eligible studies were extracted following PRISMA guidelines and narratively synthesised. Sixteen of the 17 studies included for review reported significant associations between at least one family process and later well-being. Parenting stress and aspects of the parent–child relationship yielded most robust associations. Weaker support was found for parent mental health problems. Clinical and research implications are discussed.

Background Adolescent girls and young women (AGYW) in Zambia face an elevated risk of acquiring HIV. Long-acting injectable pre-exposure prophylaxis (LAI-PrEP) is an effective scientific method to prevent new HIV infections. However, awareness and acceptability of LAI-PrEP among AGYW remain limited. Thus, we aimed to assess awareness and acceptability of LAI-PrEP among female students. Methods This multi-center, institution-based cross-sectional study involved 760 female students from three universities in Lusaka, Zambia. Data were collected using a structured, self-administered questionnaire. Questions on acceptability and awareness were presented in a yes/no format. Data analysis was performed using STATA version 15.1. Results Of the 760 participants, less than half, 349 (45.9%), were aware of injectable PrEP, with lectures being the most common source of information. In terms of acceptability, 531 (69.9%) of respondents indicated they would be willing to take LAI-PrEP once available. Biomedical science students were significantly less likely to accept injectable PrEP (AOR = 0.10, CI: 0.01–0.94, p  = 0.044), as were those not at risk of HIV in the past three months (AOR = 0.41, CI: 0.21–0.81, p  = 0.011). Conversely, knowing a partner’s HIV status (AOR = 2.52, CI: 1.27–4.98, p  = 0.0001) and being at risk of HIV in the past three months (AOR = 3.4, CI: 1.78–7.81, p  = 0.011) were significantly associated with LAI-PrEP acceptability. Conclusion The study revealed a notable gap in awareness of LAI-PrEP among participants, with less than half being informed about its existence. Despite this low awareness, a significant majority expressed a willingness to accept LAI-PrEP if it were made available to them. This indicates a strong potential for adoption of LAI-PrEP, contingent upon improved education and awareness efforts.

Cardiomyocyte transplantation after heart attack improves contractile function in monkeys. Pluripotent stem cell–derived cardiomyocyte grafts can remuscularize substantial amounts of infarcted myocardium and beat in synchrony with the heart, but in some settings cause ventricular arrhythmias. It is unknown whether human cardiomyocytes can restore cardiac function in a physiologically relevant large animal model. Here we show that transplantation of ∼750 million cryopreserved human embryonic stem cell–derived cardiomyocytes (hESC-CMs) enhances cardiac function in macaque monkeys with large myocardial infarctions. One month after hESC-CM transplantation, global left ventricular ejection fraction improved 10.6 ± 0.9% vs. 2.5 ± 0.8% in controls, and by 3 months there was an additional 12.4% improvement in treated vs. a 3.5% decline in controls. Grafts averaged 11.6% of infarct size, formed electromechanical junctions with the host heart, and by 3 months contained ∼99% ventricular myocytes. A subset of animals experienced graft-associated ventricular arrhythmias, shown by electrical mapping to originate from a point-source acting as an ectopic pacemaker. Our data demonstrate that remuscularization of the infarcted macaque heart with human myocardium provides durable improvement in left ventricular function.

Cell autonomous cancer dependencies are now routinely identified using CRISPR loss-of-function viability screens. However, a bias exists that makes it difficult to assess the true essentiality of genes located in amplicons, since the entire amplified region can exhibit lethal scores. These false-positive hits can either be discarded from further analysis, which in cancer models can represent a significant number of hits, or methods can be developed to rescue the true-positives within amplified regions. We propose two methods to rescue true positive hits in amplified regions by correcting for this copy number artefact. The Local Drop Out (LDO) method uses the relative lethality scores within genomic regions to assess true essentiality and does not require additional orthogonal data (e.g. copy number value). LDO is meant to be used in screens covering a dense region of the genome (e.g. a whole chromosome or the whole genome). The General Additive Model (GAM) method models the screening data as a function of the known copy number values and removes the systematic effect from the measured lethality. GAM does not require the same density as LDO, but does require prior knowledge of the copy number values. Both methods have been developed with single sample experiments in mind so that the correction can be applied even in smaller screens. Here we demonstrate the efficacy of both methods at removing the copy number effect and rescuing hits from some of the amplified regions. We estimate a 70-80% decrease of false positive hits with either method in regions of high copy number compared to no correction.

Despite the desire of gynecologic oncology (GO) patients to speak openly about their sexual health experience with nurses, nurses often feel ill equipped to engage in these conversations. There are very few educational interventions available to GO nurses to improve sexual health communication with patients. The purpose of this narrative review is to identify and summarize existing educational interventions in this field. A literature search conducted in three databases, for the years 2010 through 2020, identified 11 papers. The results of the review indicate a mix of nurse training modalities and explore the potential for improving this communication. Existing training programs vary in terms of mode of delivery (online or in person), length, type of instructor, learning strategies and themes addressed. Overall, however, the results show a general lack of sexual health training for nurses caring for GO patients.

Dexamethasone (Dex), a synthetic glucocorticoid (GC), in feed has been shown to increase gut permeability via stress-mediated mechanisms, but the exact mode of action on gut barrier function is not fully understood. Stress has been reported to alter the profile and virulence of intestinal flora predisposing for opportunistic disease. This study aimed to evaluate the relationship between dietary Dex and recoverable intestinal microbial profile in broilers to better understand mode of action and refine future uses of the model. Three experiments were conducted that administered Dex-treated feed for one week in conjunction with the antibiotics BMD (bacitracin methylene disalicylate) or Baytril® (enrofloxacin) to evaluate if enteric microbial mechanisms were important in Dex-induced permeability. Serum fluorescein isothiocyanate-dextran (FITC-d) and bacterial translocation (BT) have been reported to increase after Dex treatment and were used to assess gut epithelial leakage. Shifts in bacterial profiles were also measured on selective agar. Combining Dex with BMD or Baytril resulted in increased (P < 0.05) serum FITC-d versus Dex-only. Additionally, Baytril did not reduce aerobic BT and bacterial profiles remained similar after Dex. These results suggest a minimal role of intestinal microbes in Dex-induced changes to intestinal barrier function.

Nat. Biotechnol. 36, 597–605 (2018); published online 2 July 2018; corrected after print 18 July 2018 In the version of this article initially published, NIH grant P51 OD010425 was omitted. The error has been corrected in the HTML and PDF versions of the article.

Malgré le désir de la clientèle gynéco-oncologique (GO) de parler ouvertement de son expérience de santé sexuelle avec les infirmières, ces dernières souvent ne se sentent pas assez outillées pour entamer ces conversations. Peu d'interventions éducationnelles existent afin d'améliorer la communication en santé sexuelle auprès des patientes pour les infirmières œuvrant aux soins GO. Cette revue narrative vise à synthétiser les différentes interventions éducationnelles disponibles dans ce contexte. Une recherche documentaire effectuée de 2010 à 2020 dans trois bases de données a permis de cibler 11 articles. Les résultats soulignent la variété des modalités de formations infirmières et leur potentiel d'améliorer cette communication. Qu'elles soient en ligne ou en présentiel, ces formations diffèrent entre autres au niveau de la durée, du type de formateur, des stratégies d'apprentissage et des thèmes abordés. Toutefois, les résultats soulignent le manque de formation en santé sexuelle dédiée aux infirmières œuvrant aux soins GO.

Pluripotent stem cell–derived cardiomyocyte grafts can remuscularize substantial amounts of infarcted myocardium and beat in synchrony with the heart, but in some settings cause ventricular arrhythmias. It is unknown whether human cardiomyocytes can restore cardiac function in a physiologically relevant large animal model. Here we show that transplantation of 750 million cryopreserved human embryonic stem cell–derived cardiomyocytes (hESC-CMs) enhances cardiac function in macaque monkeys with large myocardial infarctions. One month after hESC-CM transplantation, global left ventricular ejection fraction improved 10.6±0.9% vs. 2.5±0.8% in controls, and by 3 months there was an additional 12.4% improvement in treated vs. a 3.5% decline in controls. Grafts averaged 11.6% of infarct size, formed electromechanical junctions with the host heart and by 3 months contained 99% ventricular myocytes. A subset of animals experienced graft-associated ventricular arrhythmias, shown by electrical mapping to originate from a point-source acting as an ectopic pacemaker. Our data demonstrate that remuscularization of the infarcted macaque heart with human myocardium provides durable improvement in left ventricular function.