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BackgroundEpigenetic changes link medical, social, and environmental factors with cardiovascular and kidney disease and, more recently, with cancer. The mechanistic link between metabolic health and epigenetic changes is only starting to be investigated. In our in vitro and in vivo studies, we performed a broad analysis of the link between hyperinsulinemia and chromatin acetylation; our top "hit" was chromatin opening at H3K9ac.MethodsBuilding on our published preclinical studies, here, we performed a detailed analysis of the link between insulin resistance, chromatin acetylation, and inflammation using an initial test set of 28 women and validation sets of 245, 22, and 53 women.ResultsChIP-seq identified chromatin acetylation and opening at the genes coding for TNFα and IL6 in insulin-resistant women. Pathway analysis identified inflammatory response genes, NFκB/TNFα-signaling, reactome cytokine signaling, innate immunity, and senescence. Consistent with this finding, flow cytometry identified increased senescent circulating peripheral T-cells. DNA methylation analysis identified evidence of accelerated aging in insulin-resistant vs. metabolically healthy women.ConclusionsThis study shows that insulin-resistant women have increased chromatin acetylation/opening, inflammation, and, perhaps, accelerated aging. Given the role that inflammation plays in cancer initiation and progression, these studies provide a potential mechanistic link between insulin resistance and cancer.

Trastuzumab therapy in HER2+ breast cancer patients has mixed success owing to acquired resistance to therapy. A detailed understanding of downstream molecular cascades resulting from trastuzumab resistance is yet to emerge. In this study, we investigate the cellular mechanisms underlying acquired resistance using trastuzumab-sensitive and -resistant cancer cells (BT474 and BT474R) treated with endogenous ligands EGF and HRG across time. We probe early receptor organization through microscopy and signaling events through multiomics measurements and assess the bioenergetic state through mitochondrial measurements. Integrative analyses of our measurements reveal significant alterations in EGF-treated BT474 HER2 membrane dynamics and robust downstream activation of PI3K/AKT/mTORC1 signaling. EGF-treated BT474R shows a sustained interferon-independent activation of the IRF1/STAT1 cascade, potentially contributing to trastuzumab resistance. Both cell lines exhibit temporally divergent metabolic demands and HIF1A-mediated stress responses. BT474R demonstrates inherently increased mitochondrial activity. HRG treatment in BT474R leads to a pronounced reduction in AR expression, affecting downstream lipid metabolism with implications for treatment response. Our results provide novel insights into mechanistic changes underlying ligand treatment in BT474 and BT474R and emphasize the pivotal role of endogenous ligands. These results can serve as a framework for furthering the understanding of trastuzumab resistance, with therapeutic implications for women with acquired resistance.

The high cost of using the niobium (Nb) barrier for manufacturing magnesium diboride (MgB2) mono-and multi-filamentary wires for large-scale applications has become one of the barriers to replacing current commercial niobium-titanium superconductors. The potential of replacing the Nb barrier with a low-cost iron (Fe) barrier for multifilament MgB2 superconducting wires is investigated in this manuscript. Therefore, MgB2 wires with Fe barrier sintered with different temperatures are studied (from 650 °C to 900 °C for 1 h) to investigate the non-superconducting reaction phase of Fe-B. Their superconducting performance including engineering critical current density (Je) and n-value are tested at 4.2 K in various external magnetic fields. The best sample sintered at 650 °C for 1 h has achieved a Je value of 3.64 × 104 A cm−2 and an n-value of 61 in 2 T magnetic field due to the reduced formation of Fe2B, better grain connectivity and homogenous microstructure. For microstructural analysis, the focused ion beam (FIB) is utilised for the first time to acquire three-dimensional microstructures and elemental mappings of the interface between the Fe barrier and MgB2 core of different wires. The results have shown that if the sintering temperature can be controlled properly, the Je and n-value of the wire are still acceptable for magnet applications. The formation of Fe2B is identified along the edge of MgB2, as the temperature increases, the content of Fe2B also increases which causes the degradation in the performance of wires.

Karolin ME Nettelrodt,1 Ivonne Tomsic,1 Maike Stolz,2 Christian Krauth,2 Iris F Chaberny,3,4 Thomas von Lengerke1 1Department of Medical Psychology, Center of Public Health, Hannover Medical School, Hannover, Germany; 2Institute of Epidemiology, Social Medicine and Health Systems Research, Center of Public Health, Hannover Medical School, Hannover, Germany; 3Institute of Hygiene, Hospital Epidemiology and Environmental Medicine, Leipzig University Hospital, Leipzig, Germany; 4Christian-Albrecht University of Kiel and University Medical Center Schleswig-Holstein, Institute of Hospital Epidemiology and Environmental Hygiene, Kiel, GermanyCorrespondence: Thomas von Lengerke, Hannover Medical School, Center of Public Health, Department of Medical Psychology (OE 5430), Carl-Neuberg-Str. 1, Hannover, 30625, Germany, Tel +49 511 532 4445, Fax +49 511 532 4214, Email lengerke.thomas@mh-hannover.dePurpose: Psychosocial determinants influence healthcare workers’ compliance with surgical site infection (SSI) preventive interventions. In order to design needs-based interventions promoting compliance, such determinants must first be assessed using valid and reliable questionnaire scales. To compare professional groups without bias, the scales must also be measurement-equivalent. We examine the validity/reliability and measurement equivalence of four scales using data from physicians and nurses from outside the university sector. Additionally, we explore associations with self-reported SSI preventive compliance.Participants and Methods: N = 90 physicians and N = 193 nurses (response rate: 31.5%) from nine general/visceral or orthopedic/trauma surgery departments in six non-university hospitals in Germany participated. A written questionnaire was used to assess the compliance with SSI preventive interventions and the determinants of compliance based on the Capability-Opportunity-Motivation-Behavior-Model. Psychometric testing involved single- and multiple-group confirmatory factor analyses, and explorative analyses used t-tests and multiple linear regression.Results: The scales assessing individual determinants of compliance (capability, motivation, and planning) were found to be reliable (each Cronbach’s α ≥ 0.85) and valid (each Root-Mean-Square-Error of Approximation ≤ 0.065, each Comparative-Fit-Index = 0.95) and revealed measurement equivalence for physicians and nurses. The scale assessing external determinants (opportunity) did not demonstrate validity, reliability, or measurement equivalence. Group differences were found neither in compliance (p = 0.627) nor determinants (p = 0.192; p = 0.866; p = 0.964). Capability (β = 0.301) and planning (β = 0.201) showed associations with compliance for nurses only.Conclusion: The scales assessing motivation, capability, and planning regarding SSI preventive compliance provided reliable and valid scores for physicians and nurses in surgery. Measurement equivalence allows group comparisons of scale means to be interpreted without bias.Keywords: infection prevention and control, surgical site infections, compliance, nurses, physicians, capability-opportunity-motivation-behavior (COM-B) model, measurement equivalence

Children with intellectual disability experience significant challenges in accessing and receiving high-quality healthcare leading to poorer health outcomes and negative patient experiences. Families of these children often report a need for healthcare staff to better understand, communicate, and collaborate for better care while staff acknowledge a lack of training. To address this, we utilised an action research framework with a pre- and post-survey to evaluate an integrated continuing professional development and quality improvement program combining strategies from education, behavioural psychology and quality improvement that was delivered in two departments within a tertiary children's Hospital in Metropolitan Sydney in 2019-2020. Parents reported noticeable changes in the clinical practice of staff, and staff acknowledged and attributed their shift in behaviour to raising awareness and discussions around necessary adaptations. The program demonstrates a novel method for knowledge translation to practice and systems improvements.

BackgroundA recent cross-sectional study showed that both comorbidities and mortality in patients with adrenal incidentaloma (AI) are tied to sex. However, few longitudinal studies evaluated the development of arterial hypertension, hyperglycemia, dyslipidemia and bone impairment in patients with AI. The aim of this study is to analyze the impact of sex in the development of these comorbidities during long-term follow-up.MethodsWe retrospectively evaluated 189 patients (120 females, 69 males) with AI, from four referral centers in Italy and Croatia. Clinical characteristics, comorbidities and cortisol after 1-mg dexamethasone suppression test (1-mg DST) were assessed at baseline and at last follow-up visit (LFUV). Median follow-up was 52 (Interquartile Range 25-86) months.ResultsThe rates of arterial hypertension and hyperglycemia increased over time both in females (65.8% at baseline versus 77.8% at LFUV, p=0.002; 23.7% at baseline versus 39.6% at LFUV, p

Stories are one way that experiences, ideas and culture are shared with children in educational settings. Commercially published books are the standard means in schools for sharing stories. Qualitative content analysis was carried out on 30 personal narrative-based children's picture books. While the range of stories told in books is vast, our research focuses on refugee stories for children in light of the contemporary political and public focus on refugees and the forced movement of people around the world. Scholars have identified that books about refugees for children can be useful to explore the topic of refugees, but also caution that they can perpetuate simplistic and stereotypical understandings about forced movement in the world. In our research we examine personal narratives and propose that educators should use stories and books written and illustrated by children as a means to bring refugee children's voices into formal educational spaces. We argue that this is a respectful approach that counters a deficit model of refugee children; it highlights refugee children's authentic voices and stories told on their own terms. Additionally, it offers a counter-narrative to dominant refugee stories in the public sphere and presents understandings of forced migration and its legacies from children's perspectives. We suggest that to effectively examine refugee experiences through literature, educators should use a number of texts to begin conversations in classrooms, and stories by children who have experienced forced migration should be featured.

Over 90% of breast cancer is cured; yet there remain highly aggressive breast cancers that develop rapidly and are extremely difficult to treat, much less prevent. Breast cancers that rapidly develop between breast image screening are called "interval cancers." The efforts of our team focus on identifying multiscale integrated strategies to identify biologically aggressive precancerous breast lesions. Our goal is to identify spatiotemporal changes that occur prior to development of interval breast cancers. To accomplish this requires integration of new technology. Our team has the ability to perform single cell in situ transcriptional profiling, noncontrast biological imaging, mathematical analysis, and nanoscale evaluation of receptor organization and signaling. These technological innovations allow us to start to identify multidimensional spatial and temporal relationships that drive the transition from biologically aggressive precancer to biologically aggressive interval breast cancer. This article is categorized under: Cancer > Computational Models Cancer > Molecular and Cellular Physiology Cancer > Genetics/Genomics/Epigenetics.

In the age of COVID, art teachers face the unprecedented situation of teaching at distance a subject that involves hands-on activities with tangible tools and materials. Therefore, we have implemented e-studio workshops where the mentor and participants are not in the same room, but they interact as if they were. By using audio-video conferencing to link them together, it was possible to maintain two-way communication. This alternative option retains all the elements of live interaction. Since, unlike drawing in a real physical environment, the image on the screen that participants are asked to draw is the same for everyone, there are no views from different angles as in real space. This changes the relationship with the model and requires technical adaptations, which are presented in this article. The goals of the project included bringing distance learning closer to workshop providers, finding the optimal way to develop drawing skills at a distance, finding software that allows quality corrections, adapting the way knowledge is delivered to people with different needs, and enabling social interaction between participants and the mentor. Such an approach opened up new perspectives on the experience of drawing from a model and on the nature of drawing instruction.

During puberty, a woman's breasts are vulnerable to environmental damage ("window of vulnerability"). Early exposure to environmental carcinogens, endocrine disruptors, and unhealthy foods (refined sugar, processed fats, food additives) are hypothesized to promote molecular damage that increases breast cancer risk. However, prospective human studies are difficult to perform and effective interventions to prevent these early exposures are lacking. It is difficult to prevent environmental exposures during puberty. Specifically, young women are repeatedly exposed to media messaging that promotes unhealthy foods. Young women living in disadvantaged neighborhoods experience additional challenges including a lack of access to healthy food and exposure to contaminated air, water, and soil. The purpose of this review is to gather information on potential exposures during puberty. In future directions, this information will be used to help elementary/middle-school girls to identify and quantitate environmental exposures and develop cost-effective strategies to reduce exposures.