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Abstract DNA polymerase theta (Polθ)-mediated end-joining (TMEJ) repairs DNA double-strand breaks and confers resistance to genotoxic agents. How Polθ is regulated at the molecular level to exert TMEJ remains poorly characterized. We find that Polθ interacts with and is PARylated by PARP1 in a HPF1-independent manner. PARP1 recruits Polθ to the vicinity of DNA damage via PARylation dependent liquid demixing, however, PARylated Polθ cannot perform TMEJ due to its inability to bind DNA. PARG-mediated de-PARylation of Polθ reactivates its DNA binding and end-joining activities. Consistent with this, PARG is essential for TMEJ and the temporal recruitment of PARG to DNA damage corresponds with TMEJ activation and dissipation of PARP1 and PAR. In conclusion, we show a two-step spatiotemporal mechanism of TMEJ regulation. First, PARP1 PARylates Polθ and facilitates its recruitment to DNA damage sites in an inactivated state. PARG subsequently activates TMEJ by removing repressive PAR marks on Polθ.

Background: This article is one of a series aiming to inform analytical methods to improve comparability of estimates of ethnic health disparities based on different sources. This article explores the quality of ethnicity data and identifies potential sources of bias when ethnicity information is collected in three key NHS data sources. Future research can build on these findings to explore analytical methods to mitigate biases. Methods: Thematic analysis of semi-structured qualitative interviews to explore potential sources of error and bias in the process of collecting ethnicity information across three NHS data sources: General Practice Extraction Service (GPES) Data for Pandemic Planning and Research (GDPPR), Hospital Episode Statistics (HES) and Improving Access to Psychological Therapies (IAPT). The study included feedback from 22 experts working on different aspects of health admin data collection for England (including staff from NHS Digital, IT system suppliers and relevant healthcare service providers). Results: Potential sources of error and bias were identified across data collection, data processing and quality assurance processes. Similar issues were identified for all three sources. Our analysis revealed three main themes which can result in bias and inaccuracies in ethnicity data recorded: data infrastructure challenges, human challenges, and institutional challenges. Conclusions: Findings highlighted that analysts using health admin data should be aware of the main sources of potential error and bias in health admin data, and be mindful that the main sources of error identified are more likely to affect the ethnicity data for ethnic minority groups. Where possible, analysts should describe and seek to account for this bias in their research.

Abstract Background The lifelong risks of cardiovascular disease following preeclampsia and gestational hypertension are well-established. However, it is unclear whether this evidence has been translated into clinical practice guidelines. Thus, this review aimed to assess the quality and content of Australian clinical practice guidelines regarding the risk of cardiovascular disease following gestational hypertension and preeclampsia. Methods We conducted a systematic search of MEDLINE (Ovid), EMBASE (Ovid), and CINAHL databases, as well as hospital, obstetric society, and medical college websites. Publications were included if: they were a clinical practice guideline; were published in the previous ten years; and included recommendations for the management of future cardiovascular disease risk following hypertensive disorders of pregnancy. Quality assessment was performed using Appraisal of Guidelines for Research and Evaluation Instrument Version Two (AGREE-II) and AGREE Recommendations Excellence Instrument (AGREE-REX). Results Eighteen guidelines were identified, and of these, less than half (n = 8) included recommendations for managing future cardiovascular risk following hypertensive disorders of pregnancy. Across these eight, four main counselling recommendations were found regarding (1) risk of future cardiovascular disease; (2) risk factor screening; (3) lifestyle interventions; and (4) prenatal counselling for future pregnancies. The quality and content of these recommendations varied significantly, and the majority of guidelines (87.5%) were assessed as low to moderate quality. Conclusions There are limited Australian clinical practice guidelines providing appropriate advice regarding future risk of cardiovascular disease following hypertensive disorders of pregnancy. The quality and content of these guidelines varied significantly. These findings highlight the need for improved translation from evidence-based research to enhance clinical care and guidance.

Abstract Background For decades, antenatal care in high-resource settings has involved 12–14 face-to-face visits across pregnancy. The COVID-19 pandemic forced many care providers to rapidly embrace telehealth to reduce face-to-face visits. Here we review recent advances in telehealth used to provide antenatal care. Main body We conducted a narrative review examining the impact of telehealth on obstetric care. Two broad types of telehealth are used in antenatal care. The first is real-time telehealth, where consultations are done virtually instead of face-to-face. The second is remote monitoring, where in-clinic physical examinations are replaced with at-home alternatives. These can include blood pressure monitoring, fetal heart rate monitoring, and emerging technologies such as tele-ultrasound. Large cohort studies conducted during the pandemic era have shown that telehealth appears not to have increased adverse clinical outcomes for mothers or babies. However, further studies may be required to confidently conclude rare outcomes are unchanged, such as maternal mortality, serious morbidity, or stillbirth. Health economic studies suggest telehealth has the potential to reduce the financial cost of care provision. Telehealth in antenatal care seems to be acceptable to both pregnant women and healthcare providers. Conclusion Adoption of telehealth technologies may improve the antenatal care experience for women and reduce healthcare expenditure without adversely impacting health outcomes for the mother or baby. More studies are warranted to confirm telehealth does not alter the risk of rare outcomes such as maternal or neonatal mortality.

Objective The lifelong risks of cardiovascular disease following hypertensive disorders of pregnancy are well described. Awareness of these risks and associated health-seeking behaviours among affected individuals remains unclear. We aimed to assess participants’ knowledge of their cardiovascular disease risk and relevant health-seeking behaviours following a pregnancy affected by preeclampsia or gestational hypertension.Methods We undertook a single-site, cross-sectional cohort study. The target population included individuals who birthed at a large tertiary referral centre in Melbourne, Australia, between 2016 and 2020, and were diagnosed with gestational hypertension or pre-eclampsia. Participants completed a survey assessing pregnancy details, medical comorbidities, knowledge of future risks and health-seeking behaviours post-pregnancy.Results 1526 individuals met inclusion criteria and 438 (28.6%) completed the survey. Of these, 62.6% (n=237) were unaware of their increased risk of cardiovascular disease following a hypertensive disorder of pregnancy. Participants who reported awareness of their increased risk were more likely to have annual blood pressure monitoring (54.6% vs 38.1%, p