DNA methylation accelerated age as captured by epigenetic clocks influences breast cancer risk.

Introduction: Breast cancer continues to be the leading form of cancer among women in the United States. Additionally, disparities across the breast cancer continuum continue to increase for women of historically marginalized populations. The mechanism driving these trends are unclear, however, accelerated biological age may provide key insights into better understanding these disease patterns. Accelerated age measured by DNA methylation using epigenetic clocks is to date the most robust method for estimating accelerated age. Here we synthesize the existing evidence on epigenetic clocks measurement of DNA methylation based accelerated age and breast cancer outcomes. Methods: Our database searches were conducted from January 2022 to April 2022 and yielded a total of 2,908 articles for consideration. We implemented methods derived from guidance of the PROSPERO Scoping Review Protocol to assess articles in the PubMed database on epigenetic clocks and breast cancer risk. Results: Five articles were deemed appropriate for inclusion in this review. Ten epigenetic clocks were used across the five articles demonstrating statistically significant results for breast cancer risk. DNA methylation accelerated age varied by sample type. The studies did not consider social factors or epidemiological risk factors. The studies lacked representation of ancestrally diverse populations. Discussion: DNA methylation based accelerated age as captured by epigenetic clocks has a statistically significant associative relationship with breast cancer risk, however, important social factors that contribute to patterns of methylation were not comprehensively considered in the available literature. More research is needed on DNA methylation based accelerated age across the lifespan including during menopausal transition and in diverse populations. This review demonstrates that DNA methylation accelerated age may provide key insights for tackling increasing rates of U.S. breast cancer incidence and overall disease disparities experienced by women from minoritized backgrounds.

"From taboo to routine": a qualitative evaluation of a hospital-based advocacy intervention for domestic violence and abuse.

BACKGROUND: Health services are often the first point of professional contact for people who have experienced domestic violence and abuse. We report on the evaluation of a multi-site, hospital-based advocacy intervention for survivors of domestic violence and abuse. Independent Domestic Violence Advisors (IDVAs), who provide survivors with support around safety, criminal justice, and health and wellbeing, were located in five hospitals in England between 2012 and 2015 in emergency departments and maternity services. We present views about IDVAs' approaches to tackling domestic violence and abuse, how the IDVA service worked in practice, and factors that hindered and facilitated engagement with survivors. METHODS: We adopted a convenience sampling approach and invited participation from all who offered to take part within the study timeframe. Sixty-four healthcare professionals, IDVAs, IDVA service managers, and commissioners at all sites were interviewed. Interviews were analysed using a thematic approach: familiarising ourselves with the data through repeated readings and noting initial ideas; generating initial codes through double coding notable features of the data across the dataset; collating codes into potential themes; and reviewing themes to ensure they captured the essence of the data. RESULTS: Two key themes emerged. The first was Hospital-based IDVAs fulfil several crucial roles. This theme highlighted that healthcare professionals thought the hospital-based IDVA service was valuable because it enhanced their skills, knowledge, and confidence in asking about domestic violence and abuse. It enabled them to immediately refer and provide support to patients who might have otherwise been lost along a referral pathway. It also reached survivors who might otherwise have remained hidden. The second theme was Success hinges on a range of structural factors. This theme illustrated the importance of ongoing domestic violence and abuse training for staff, the IDVA having private and dedicated space, and the service being embedded in hospital infrastructure (e.g. featuring it in hospital-wide policies and enabling IDVAs access to medical records). CONCLUSION: Hospital-based IDVAs offer a unique and valued way to respond to domestic violence and abuse in a healthcare setting. Further work must now be done to explore how to implement the service sustainably.

Histone deacetylase inhibitors prevent H2O2 from inducing stress granule formation.

Reactive Oxygen Species (ROS) are generated as by-products of aerobic metabolism. The production of ROS increases during xenobiotic stress and under multiple pathological conditions. Although ROS are considered harmful historically, mounting evidence recently indicates a signaling function of ROS, preceding to and regulating transcriptional or post-transcriptional events, contributing to cell death or cell survival and adaptation. Among the cellular defense mechanisms activated by ROS is formation of stress granules (SGs). The stalled translational apparatus, together with mRNA, aggregates into microscopically detectable and molecularly dynamic granules. We found that with H2O2, the dose most potent for inducing SGs in HeLa cells is 400-600 µM. With 200 µM H2O2, 2 h treatment induced the highest percentage of cells containing SGs. Whether ROS signaling pathways regulate the formation of SGs was tested using pharmacological inhibitors. We probed the potential role of PI3K, MAPKs, PKC or histone deacetylation in SG formation. Using deferoxamine as a positive control, we found a lack of inhibitory effect of wortmannin, LY-294002, JNK-I, SB-202190, PD-98059, or H89 when the percentage of cells containing SGs was counted. About 35% inhibition was observed with HDAC6 inhibitor Tubastatin A, whereas general HDAC inhibitor Trichostatin A provided a complete inhibition of SG formation. Our data point to the need of investigating the role of HDACs in SG formation during oxidative stress.