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Higher Education Institutes (HEIs) have been met with an unprecedented demand on their student counselling and wellbeing services in recent years with the impacts of COVID-19 and high rates of mental health concerns amongst student populations. Online mental health programs offer one solution by providing students with quick and easy access to effective therapeutic content. The Focused Minds Program is an evidence-based eight-module online self-guided cognitive behavioural intervention that targets the transdiagnostic risk factor of perfectionism and has been shown to decrease depression, anxiety, and disordered eating. The program was implemented at a UK university between 2021 and 2023. Recruitment occurred via departmental emails, academic staff, and the university's counselling staff and website. Participants were provided with access to the intervention for 6-weeks and completed weekly surveys of psychosocial measures. The trial's implementation was assessed using the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework: reach (uptake via the recruitment channels), effectiveness (outcomes on psychometric measures of mental wellbeing), adoption (staff and organisational support), implementation (intervention engagement and attrition), and maintenance (continued implementation across the trial period). Key barriers to successful implementation, as well as proposed solutions, are discussed to guide future online mental health interventions provided in HEIs., (© 2024 The Author(s). Stress and Health published by John Wiley & Sons Ltd.)

Background: The Insomnia Severity Index (ISI) is a widely used measure of insomnia severity. Various ISI research findings suggest different factor solutions and meaningful within-individual change (MWIC) to detect treatment response in patients with insomnia. This study examined an ISI factor solution and psychometric indices to define MWIC in a robust patient sample from clinical trial settings., Methods: We endeavored to improve upon previous validation of ISI by examining structural components of confirmatory factor analysis (CFA) models using two large, placebo-controlled clinical trials of lemborexant for insomnia. Using the best-fitting two-factor solution, we evaluated anchor-based, distribution-based and receiver operating characteristic (ROC) curve methods to derive an estimate of the MWIC., Results: The model structure for the 7-item scale proposed in other research did not fit the observed data from our two lemborexant clinical trials (N = 1956) as well as a two-factor solution based on 6 items did. Using triangulation of anchor-based, distribution-based, and ROC methods, we determined that a 5-point reduction using 6 items best represented a clinically meaningful improvement in individuals with insomnia in our patient sample., Conclusions: A 6-item two-factor scale had better psychometric properties than the 7-item scale in this patient sample. On the 6-item scale, a reduction of 5 points in the ISI total score represented the MWIC. Generalizability of the proposed MWIC may be limited to patient populations with similar demographic and clinical characteristics., (© 2024. The Author(s).)

Background: Cognitive impairment associated with schizophrenia (CIAS) represents a distinct, persistent, and core group of schizophrenia symptoms. Cognitive symptoms have been shown to have an impact on quality of life. There are several published CIAS measures, but none based on direct patient self-report. It is important to capture the patient's perspective to supplement performancebased outcome measures of cognition to provide a complete picture of the patient's experience. This paper describes additional validation work on the Patient-Reported Experience of Cognitive Impairment in Schizophrenia (PRECIS) instrument., Methods: Data from two large, international, pharmaceutical clinical trials in medically and psychiatrically stable English-speaking patients with schizophrenia and 88 healthy controls were analyzed. An exploratory factor analysis (EFA) was conducted in one trial (n = 215), using the original 35-item PRECIS. The factor structure suggested by EFA was further evaluated using item response theory (IRT; Samejima's graded response model), and tested using confirmatory factor analysis (CFA). Both EFA and CFA results were tested in a second trial with similar inclusion/exclusion characteristics (n = 410). Additional statistical properties were evaluated in healthy controls., Results: EFA suggested that the best solution after item reduction suggested a factor structure of 6 factors based on 26 items (memory, communication, self-control, executive function, attention, sharpness of thought), supporting a total score, with an additional 2-item bother score (28 items in all). IRT analysis indicated the items were well-ordered within each domain. The CFA demonstrated excellent model fit, accounting for 69% of the variance. The statistical properties of the 28-item version of the PRECIS were confirmed in the second trial. Evidence for internal consistency and test-retest reliability was robust. Known-groups validity was supported by comparison of healthy controls with patients with schizophrenia. Correlations indicated moderate associations between PRECIS and functioning instruments like the Schizophrenia Cognition Rating Scale (SCoRS), but weak correlations with performance-based outcomes like MATRICS Consensus Cognitive Battery (MCCB)., Discussion: Using two clinical trial samples, we identified a robust factor structure for the PRECIS and were able to replicate it in the second sample. Evaluation of the meaningful score difference (MSD) should be repeated in future studies, as these samples did not show enough change for it to be evaluated., Conclusions: This analysis provides strong evidence for the reliability and validity of the PRECIS, a 28-item, patient-reported instrument to assess cognitive impairment associated with schizophrenia. The correlation with functioning and the weak correlation with performance on cognitive tasks suggests that patient reports of cognitive impairment measure a unique aspect of patient experience., (© 2024. The Author(s).)

Objective: Increasing effectiveness and sustainability of universal school-based eating disorder prevention is needed. This study adapted two existing selective prevention programmes for universal delivery, investigating feasibility, acceptability, and preliminary effects when delivered by trained teachers to classes of mixed-gender adolescents., Method: A three-arm controlled pilot study with Year 9 students (N = 288; M age  = 13.61 SD age  = .50). Three schools in south Wales and south-west England were allocated to mindfulness-based intervention (MBI), dissonance-based intervention (DBI), or classes-as-usual (CAU) control. Self-reported eating disorder risk factors were collected at baseline, 6-week post-intervention, and 2-month follow-up. Focus groups were conducted post-intervention., Results: Delivery and evaluation were feasible, allowing for flexibility in scheduling, with good retention. Student and teacher ratings indicated moderate acceptability of both interventions, with recommendations for refinement. Mixed model analyses, controlling for baseline, showed significant effects of condition across post-intervention and follow-up for body esteem (DBI > CAU; Cohen's d = .34) and positive affect (MBI > CAU, d = .58). For girls only, both MBI and DBI improved body satisfaction and internalization, and the MBI additionally resulted in improved weight and shape concerns, negative affect, and life disengagement (d's = .39-1.12), across post-intervention and follow-up., Discussion: Selective eating disorder prevention programmes based on cognitive dissonance and mindfulness can be delivered universally in schools, by teachers, allowing for appropriate flexibility necessary for real world implementation. Moderate acceptability indicates areas for improving content and delivery; positive effects on key outcomes are encouraging. These findings provide support for further robust evaluation., Public Significance: Existing universal eating disorder prevention is limited by small effects and reliance on highly trained facilitators. This study is the first to adapt mindfulness- and dissonance-based interventions for delivery by teachers, to adolescents of all genders in a classroom setting. Delivery was largely feasible and acceptable, and both interventions showed significant effects across key risk factors for eating disorders, with larger effect sizes than found previously. This underpins further robust evaluation., (© 2023 The Authors. International Journal of Eating Disorders published by Wiley Periodicals LLC.)

Background: Digital mindfulness-based interventions (MBIs) are a promising approach to deliver accessible and scalable mindfulness training and have been shown to improve a range of health outcomes. However, the success of digital MBIs is reliant on adequate engagement, which remains a crucial challenge. Understanding people's experiences of using digital MBIs and identifying the core factors that facilitate or act as barriers to engagement is essential to inform intervention development and maximize engagement and outcomes., Objective: This study aims to systematically map the literature on people's experiences of using digital MBIs that target psychosocial variables (eg, anxiety, depression, distress, and well-being) and identify key barriers to and facilitators of engagement., Methods: We conducted a scoping review to synthesize empirical qualitative research on people's experiences of using digital MBIs. We adopted a streamlined approach to ensure that the evidence could be incorporated into the early stages of intervention development. The search strategy identified articles with at least one keyword related to mindfulness, digital, user experience, and psychosocial variables in their title or abstract. Inclusion criteria specified that articles must have a qualitative component, report on participants' experiences of using a digital MBI designed to improve psychosocial variables, and have a sample age range that at least partially overlapped with 16 to 35 years. Qualitative data on user experience were charted and analyzed using inductive thematic synthesis to generate understandings that go beyond the content of the original studies. We used the Quality of Reporting Tool to critically appraise the included sources of evidence., Results: The search identified 530 studies, 22 (4.2%) of which met the inclusion criteria. Overall, the samples were approximately 78% female and 79% White; participants were aged between 16 and 69 years; and the most used measures in intervention studies were mindfulness, psychological flexibility, and variables related to mental health (including depression, anxiety, stress, and well-being). All studies were judged to be adequately reported. We identified 3 themes characterizing barriers to and facilitators of engagement: responses to own practice (ie, negative reactions to one's own practice are common and can deplete motivation), making mindfulness a habit (ie, creating a consistent training routine is essential yet challenging), and leaning on others (ie, those engaging depend on someone else for support)., Conclusions: The themes identified in this review provide crucial insights as to why people frequently stop engaging with digital MBIs. Researchers and developers should consider using person-based coparticipatory methods to improve acceptability of and engagement with digital MBIs, increase their effectiveness, and support their translation to real-world use. Such strategies must be grounded in relevant literature and meet the priorities and needs of the individuals who will use the interventions., (©Emma Louise Osborne, Ben Ainsworth, Nic Hooper, Melissa Jayne Atkinson. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 28.09.2023.)

Recent epidemiologic studies support an association between chronic low-dose radiation exposure and the development of cardiovascular disease (CVD). The molecular mechanisms underlying the adverse effect of chronic low dose exposure are not fully understood. To address this issue, we have investigated changes in the heart proteome of ApoE deficient (ApoE -/- ) C57Bl/6 female mice chronically irradiated for 300 days at a very low dose rate (1 mGy/day) or at a low dose rate (20 mGy/day), resulting in cumulative whole-body doses of 0.3 Gy or 6.0 Gy, respectively. The heart proteomes were compared to those of age-matched sham-irradiated ApoE -/- mice using label-free quantitative proteomics. Radiation-induced proteome changes were further validated using immunoblotting, enzyme activity assays, immunohistochemistry or targeted transcriptomics. The analyses showed persistent alterations in the cardiac proteome at both dose rates; however, the effect was more pronounced following higher dose rates. The altered proteins were involved in cardiac energy metabolism, ECM remodelling, oxidative stress, and ageing signalling pathways. The changes in PPARα, SIRT, AMPK, and mTOR signalling pathways were found at both dose rates and in a dose-dependent manner, whereas more changes in glycolysis and ECM remodelling were detected at the lower dose rate. These data provide strong evidence for the possible risk of cardiac injury following chronic low dose irradiation and show that several affected pathways following chronic irradiation overlap with those of ageing-associated heart pathology., Competing Interests: The authors declare no conflict of interest.

Background: No short patient-reported outcome (PRO) instruments assess overall health status across different obstructive lung diseases. Thus, the wording of the introduction to the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) was modified to permit use in asthma and/or COPD. This tool is called the Chronic Airways Assessment Test (CAAT)., Methods: The psychometric properties of the CAAT were evaluated using baseline data from the NOVELTY study (NCT02760329) in patients with physician-assigned asthma, asthma + COPD or COPD. Analyses included exploratory/confirmatory factor analyses, differential item functioning and analysis of construct validity. Responses to the CAAT and CAT were compared in patients with asthma + COPD and those with COPD., Results: CAAT items were internally consistent (Cronbach's alpha: > 0.7) within each diagnostic group (n = 510). Models for structural and measurement invariance were strong. Tests of differential item functioning showed small differences between asthma and COPD in individual items, but these were not consistent in direction and had minimal overall impact on the total score. The CAAT and CAT were highly consistent when assessed in all NOVELTY patients who completed both (N = 277, Pearson's correlation coefficient: 0.90). Like the CAT itself, CAAT scores correlated moderately (0.4-0.7) to strongly (> 0.7) with other PRO measures and weakly (< 0.4) with spirometry measures., Conclusions: CAAT scores appear to reflect the same health impairment across asthma and COPD, making the CAAT an appropriate PRO instrument for patients with asthma and/or COPD. Its brevity makes it suitable for use in clinical studies and routine clinical practice., Trial Registration: NCT02760329., (© 2023. The Author(s).)

Background: Pain has been identified as a core outcome for individuals with autosomal dominant polycystic kidney disease (ADPKD), but no disease-specific pain assessment has been developed using current development methodology for patient-reported outcomes (PRO) instruments. We developed and validated an ADPKD-specific pain questionnaire: the ADPKD Pain and Discomfort Scale (ADPKD-PDS)., Methods: Conceptual underpinnings were drawn from literature review, concept elicitation, expert consultation, and measurement performance. In the qualitative analysis phase, concepts were elicited from focus groups of adults with ADPKD, and the resulting draft instrument was refined using cognitive debriefing interviews with individuals with ADPKD. For quantitative analysis, adults with ADPKD completed the draft instrument and other PRO tools in an online survey, and a follow-up survey was conducted 3-4 weeks later. Survey responses were analyzed for item-level descriptive statistics, latent model fit statistics, item discrimination, item- and domain-level psychometric statistics, test-retest reliability, responsiveness to change, and convergent validity., Results: In the qualitative phase, 46 focus groups were conducted in 18 countries with 293 participants. Focus groups described three conceptually distinct types of ADPKD-related pain and discomfort (dull kidney pain, sharp kidney pain, and fullness/discomfort). In the quantitative phase, 298 adults with ADPKD completed the online survey, and 108 participants completed the follow-up survey. After iterative refinement of the instrument, latent variable measurement models showed very good fit (comparative fit and nonnormed fit indices both 0.99), as did item- and domain-level psychometric characteristics. The final ADPKD-PDS contains 20 items assessing pain severity and interference with activities over a 7-day recall period., Conclusions: The ADPKD-PDS is the first validated tool for systematically assessing pain and discomfort in ADPKD., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of American Society of Nephrology.)

Objective: Evidence suggests mindfulness may reduce risk factors for disordered eating. However, mechanisms of change in this relationship are unclear. This longitudinal study tested whether emotion regulation mediates the prospective associations between mindfulness and two proximal risk factors for disordered eating: weight and shape concerns, and negative affect., Method: This study is a secondary analysis of data collected within an eating disorder prevention trial. Adolescent girls (N = 374, M age  = 15.70, SD = 0.77) completed self-report measures of mindfulness, emotion regulation, weight and shape concerns, and negative affect at baseline, 2 months following baseline, and 7 months following baseline. Path analyses were computed to test hypothesized indirect effects using confidence intervals based on 5000 bootstrap samples., Results: Higher baseline mindfulness predicted lower weight and shape concerns and negative affect at 7 months via a mediator of better emotion regulation at 2 months. This effect remained while controlling for earlier measurements of the mediator and outcome in the model of negative affect but not weight and shape concerns., Discussion: Emotion regulation may be an important mechanism explaining how mindfulness influences negative affect. Efforts should be made to intervene on mindfulness and emotion regulation in prevention and early intervention programmes for eating disorders and other psychiatric conditions., Public Significance: Research has shown that mindfulness can help to reduce some of the risk of developing an eating disorder. This study explored whether mindfulness reduces some of this risk by helping people to better manage their emotions. Understanding this process can help us to develop better mindfulness-based strategies to support people who are at risk of developing an eating disorder., (© 2022 The Authors. International Journal of Eating Disorders published by Wiley Periodicals LLC.)

This study investigated a novel technique to improve body image among women who have undergone bariatric surgery-namely, by having them focus on their body functionality (everything the body can do, rather than how it looks). Participants were 103 women (M age  = 46.61) who had undergone bariatric surgery 5-7 months prior to the study. They were randomized to the 1-week online intervention, comprising three functionality-focused writing exercises (Expand Your Horizon; Alleva et al., 2015), or to a wait-list control group. Body appreciation, appearance and functionality satisfaction, body awareness, self-objectification, self-esteem, and self-kindness were assessed at pretest, posttest, and at 1-week and 3-month follow-up. Multilevel modeling analyses showed that, compared to the control, the intervention group experienced improved body appreciation at posttest, and these improvements persisted at both follow-ups. These findings were nonsignificant when intent-to-treat analyses were performed. Both available case and intent-to-treat analyses showed that all participants experienced improvements in facets of body image across time. Qualitative analyses of participants' responses to the intervention writing exercises provided more insight. Via coding reliability thematic analysis, we identified 11 themes that together provide evidence that intervention participants experienced facets of a more positive body image, while also facing challenges to their body image and well-being. Together, findings suggest that focusing on body functionality may contribute to improved body image among women who have undergone bariatric surgery, but effects may be nuanced compared to prior functionality research among general samples of women. The study was registered retrospectively (ClinicalTrials.gov; identifier NCT04883268)., (Copyright © 2022 Association for Behavioral and Cognitive Therapies. Published by Elsevier Ltd. All rights reserved.)

Objective: Eating disorders (EDs) often emerge in late adolescence. Schools are ideal settings for prevention programs; however, cost and time limit implementation. Microinterventions may overcome these challenges. This study adapted two microinterventions (cognitive dissonance, self-compassion) and assessed feasibility and acceptability among mid-adolescents to provide proof-of-concept for further investigation., Method: Feedback from staff (n = 5) and student (n = 15) focus groups contributed iteratively to the adaptation of intervention materials. Students in Grade 10 and 11 (N = 101, M age  = 15.80, SD = 0.68) were then randomly allocated by class to a 20-min video-based cognitive-dissonance or self-compassion intervention, accessed on their school devices. ED risk and protective factors were assessed at baseline, immediate postintervention (state outcomes), and 1-week follow-up (trait outcomes). Acceptability items were included at both timepoints., Results: Implementation was deemed feasible. Girls generally reported greater acceptability than boys. Among girls, the self-compassion intervention demonstrated greater acceptability. Among boys, some aspects of acceptability (e.g., lesson endorsement, utilization of techniques) were rated higher in the cognitive dissonance group whereas other aspects (e.g., understanding, interest) were greater in the self-compassion group. All groups exhibited favorable changes in most state outcomes, however trait outcome change was varied., Discussion: Microinterventions provide a feasible way of implementing prevention strategies in a time-poor educational context. Future large-scale evaluation is warranted to determine efficacy, following modifications based on current findings., Public Significance: This study shows promising feasibility and acceptability of two brief, self-guided video-based lessons (microinterventions) for adolescents in school classrooms, that use psychological techniques to target appearance pressures as a key risk factor for eating disorders. Such interventions are easier to implement in school settings than longer, facilitator-led interventions, to encourage greater uptake and ongoing use. Findings support further research to evaluate effectiveness, to ultimately provide accessible and gender-inclusive tools for busy schools., (© 2022 The Authors. International Journal of Eating Disorders published by Wiley Periodicals LLC.)

Poor student well-being at UK universities is overstretching institutional support services, highlighting a need for effective new resources. Despite extensive literature on mental health and well-being interventions, students' engagement with support remains unexplored. The study aimed to understand students' experience of engagement with well-being support, identify their well-being needs and form concrete recommendations for future intervention design and delivery. The Person-Based Approach to intervention design was followed to centralise users' experience, in turn maximising acceptability and effectiveness of resources. An online survey (N = 52) was followed by three focus groups (N = 14). Survey data were analysed descriptively, and reflexive thematic analysis was performed on qualitative data. Mixed-methods data integration produced four key student priorities for well-being resources - ease of access, inclusive and preventative approach, sense of community and a safe space, and applying skills to real-life contexts. Five actionable guiding principles for intervention design were produced through consultation with expert stakeholders. This work helps understand why and how students engage with support at university. The resulting recommendations can inform future intervention development, leading to more acceptable, engaging and effective student well-being resources., (© 2022 The Authors. Stress and Health published by John Wiley & Sons Ltd.)

Here we present a method to detect and quantify long non-coding RNAs, in particular those related to telomeres. By coupling the specificity of a peptide nucleic acid (PNA) probe with flow cytometry we have quantified cellular levels of TERRA and TERC lncRNAs in culture cell lines and PBMCs. This easy-to-use method appointed RNA-Flow allows reliable lncRNA quantification with broad applications in basic research and clinical diagnostics. In addition, the staining protocol presented here was proven useful for the detection and quantification of such lncRNAs on unfixed cells using confocal microscopy., (© 2022. The Author(s).)

Objective: We aimed to assess the reliability and validity of single-item global ratings (GR) of satisfaction with epilepsy surgery., Methods: We recruited 240 patients from four centers in Canada and Sweden who underwent epilepsy surgery ≥1 year earlier. Participants completed a validated questionnaire on satisfaction with epilepsy surgery (the ESSQ-19), plus a single-item GR of satisfaction with epilepsy surgery twice, 4-6 weeks apart. They also completed validated questionnaires on quality of life, depression, health state utilities, epilepsy severity and disability, medical treatment satisfaction and social desirability. Test-retest reliability of the GR was assessed with the intra-class correlation coefficient (ICC). Construct and criterion validity were examined with polyserial correlations between the GR measure of satisfaction and validated questionnaires and with the ESSQ-19 summary score. Non-parametric rank tests evaluated levels of satisfaction, and ROC analysis assessed the ability of GRs to distinguish among clinically different patient groups., Results: Median age and time since surgery were 42 years (IQR 32-54) and 5 years (IQR 2-8), respectively. The GR demonstrated good to excellent test-retest reliability (ICC = 0.76; 95% CI 0.67-0.84) and criterion validity (0.85; 95% CI 0.81-0.89), and moderate correlations in the expected direction with instruments assessing quality of life (0.59; 95% CI 0.51-0.63), health utilities (0.55; 95% CI 0.45-0.65), disability (-0.51; 95% CI -0.41, -0.61), depression (-0.48; 95% CI -0.38, -0.58), and epilepsy severity (-0.48; 95% CI -0.38, -0.58). As expected, correlations were lower for social desirability (0.40; 95% CI 0.28-0.52) and medical treatment satisfaction (0.33; 95% CI 0.21-0.45). The GR distinguished participants who were seizure-free (AUC 0.75; 95% CI 0.67-0.82), depressed (AUC 0.75; 95% CI 0.67-0.83), and self-rated as having more severe epilepsy (AUC 0.78; 95% CI 0.71-0.85) and being more disabled (AUC 0.82; 95% CI 0.74-0.90)., Significance: The GR of epilepsy surgery satisfaction showed good measurement properties, distinguished among clinically different patient groups, and appears well-suited for use in clinical practice and research., (© 2022 International League Against Epilepsy.)

Background and Purpose: Increased levels of the chaperone protein GRP78 have been implicated in poorer outcomes of cancer therapy. We have therefore explored the functional connection between the expression of GRP78 and the development of radioresistance and metastatic behavior in HNSCC., Material and Methods: The association between gene expression of GRP78 and survival in HNSCC patients was examined using the TCGA database. The influence of ionizing radiation on the GRP78 levels in HNSCC cell lines, their secreted extracellular vesicles (EV) and non-irradiated EV-recipient cells was investigated by Western Blot and FACS. The consequences of chemical inhibition or experimental overexpression of GRP78 on radioresistance and migration of HNSCC cells were analyzed by clonogenic survival and gap closure assays., Results: Elevated levels of GRP78 RNA in HNSCC correlated with poorer overall survival. Radiation increased GRP78 protein expression on the surface of HNSCC cell lines. Experimental overexpression of GRP78 increased both radioresistance and migratory potential. Chemical inhibition of GRP78 impaired cell migration. EVs were identified as a potential source of increased GRP78 content as elevated levels of surface GRP78 were found in EVs released by irradiated cells. These vesicles transferred GRP78 to non-irradiated recipient cells during co-cultivation., Conclusions: We have identified the chaperone protein GRP78 as a potential driver of increased radioresistance and motility in HNSCC. The uptake of GRP78-rich EVs originating from irradiated cells may contribute to a poorer prognosis through bystander effects mediated by the transfer of GRP78 to non-irradiated cells. Therefore, we consider the chaperone protein GRP78 to be an attractive target for improving radiotherapy strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer GM declared a shared parent affiliation with the authors MA and MP to the handling editor at the time of review., (Copyright © 2022 Schneider, Winkler, Kell, Pfaffl, Atkinson and Moertl.)

Glioblastoma stem-like cells (GSLCs) in glioblastoma limit effective treatment and promote therapeutic resistance and tumor recurrence. Using a combined radiation and drug-screening platform, we tested the combination of a histone deacetylase inhibitor (HDACi) and MAPK/ERK kinase inhibitor (MEKi) with radiation to predict the efficacy against GSLCs. To mimic a stem-like phenotype, glioblastoma-derived spheres were used and treated with a combination of HDACi (MS-275) and MEKi (TAK-733 or trametinib) with 4 Gy irradiation. The sphere-forming ability after the combined radiochemotherapy was investigated using a sphere formation assay, while the expression levels of the GSLC markers (CD44, Nestin and SOX2) after treatment were analyzed using Western blotting and flow cytometry. The combined radiochemotherapy treatment inhibited the sphere formation in both glioblastoma-derived spheres, decreased the expression of the GSLC markers in a cell-line dependent manner and increased the dead cell population. Finally, we showed that the combined treatment with radiation was more effective at reducing the GSLC markers compared to the standard treatment of temozolomide and radiation. These results suggest that combining HDAC and MEK inhibition with radiation may offer a new strategy to improve the treatment of glioblastoma.

Background: Negative body image predicts many adverse outcomes. The current study prospectively examined patterns of body esteem development in early adolescence and identified predictors of developmental subtypes. Methods: 328 girls and 429 boys reported annually across a 4-year period (Mage at baseline = 11.14, SD = 0.35) on body esteem, appearance ideal internalization, perceived sociocultural pressures, appearance comparisons, appearance-related teasing, self-esteem, positive and negative affect, and dietary restraint. We performed latent class growth analyses to identify the most common trajectories of body esteem development and examine risk and protective factors for body image development. Results: Three developmental subgroups were identified: (a) high body esteem (39.1%); (b) moderate body esteem (46.1%); and (c) low body esteem (14.8%). Body esteem was stable within the low trajectory and there were minor fluctuations in the high and moderate trajectories. Greater appearance-related teasing, lower self-esteem, less positive affect, and higher dietary restraint predicted the low trajectory, whereas higher self-esteem and lower dietary restraint best predicted the high trajectory. Conclusions: Low body esteem appears to be largely stable from age 11 years. Prevention programming may be enhanced by incorporating components to address transdiagnostic resilience factors such as self-esteem and positive affect.

Radiation-induced cardiovascular disease is associated with metabolic remodeling in the heart, mainly due to the inactivation of the transcription factor peroxisome proliferator-activated receptor alpha (PPARα), thereby inhibiting lipid metabolic enzymes. The objective of the present study was to investigate the potential protective effect of fenofibrate, a known agonist of PPARα on radiation-induced cardiac toxicity. To this end, we compared, for the first time, the cardiac proteome of fenofibrate- and placebo-treated mice 20 weeks after local heart irradiation (16 Gy) using label-free proteomics. The observations were further validated using immunoblotting, enzyme activity assays, and ELISA. The analysis showed that fenofibrate restored signalling pathways that were negatively affected by irradiation, including lipid metabolism, mitochondrial respiratory chain, redox response, tissue homeostasis, endothelial NO signalling and the inflammatory status. The results presented here indicate that PPARα activation by fenofibrate attenuates the cardiac proteome alterations induced by irradiation. These findings suggest a potential benefit of fenofibrate administration in the prevention of cardiovascular diseases, following radiation exposure.

Objective: The 19-item Epilepsy Surgery Satisfaction Questionnaire (ESSQ-19) is a validated and reliable post hoc means of assessing patient satisfaction with epilepsy surgery. Prediction models building on these data can be used to counsel patients., Methods: The ESSQ-19 was derived and validated on 229 patients recruited from Canada and Sweden. We isolated 201 (88%) patients with complete clinical data for this analysis. These patients were adults (≥18 years old) who underwent epilepsy surgery 1 year or more prior to answering the questionnaire. We extracted each patient's ESSQ-19 score (scale is 0-100; 100 represents complete satisfaction) and relevant clinical variables that were standardized prior to the analysis. We used machine learning (linear kernel support vector regression [SVR]) to predict satisfaction and assessed performance using the R 2 calculated following threefold cross-validation. Model parameters were ranked to infer the importance of each clinical variable to overall satisfaction with epilepsy surgery., Results: Median age was 41 years (interquartile range [IQR] = 32-53), and 116 (57%) were female. Median ESSQ-19 global score was 68 (IQR = 59-75), and median time from surgery was 5.4 years (IQR = 2.0-8.9). Linear kernel SVR performed well following threefold cross-validation, with an R 2 of .44 (95% confidence interval = .36-.52). Increasing satisfaction was associated with postoperative self-perceived quality of life, seizure freedom, and reductions in antiseizure medications. Self-perceived epilepsy disability, age, and increasing frequency of seizures that impair awareness were associated with reduced satisfaction., Significance: Machine learning applied postoperatively to the ESSQ-19 can be used to predict surgical satisfaction. This algorithm, once externally validated, can be used in clinical settings by fixing immutable clinical characteristics and adjusting hypothesized postoperative variables, to counsel patients at an individual level on how satisfied they will be with differing surgical outcomes., (© 2021 International League Against Epilepsy.)

Reliable data on the effects of chronic prenatal exposure to low dose (LD) of ionizing radiation in humans are missing. There are concerns about adverse long-term effects that may persist throughout postnatal life of the offspring. Due to their slow cell cycle kinetics and life-long residence time in the organism, mesenchymal stem cells (MSCs) are more susceptible to low level genotoxic stress caused by extrinsic multiple LD events. The aim of this study was to investigate the effect of chronic, prenatal LD gamma irradiation to the biology of MSCs later in life. C3H mice were exposed in utero to chronic prenatal irradiation of 10 mGy/day over a period of 3 weeks. Two years later, MSCs were isolated from the bone marrow and analyzed in vitro for their radiosensitivity, for cellular senescence and for DNA double-strand break recognition after a second acute gamma-irradiation. In addition to these cellular assays, changes in protein expression were measured using HPLC-MS/MS and dysregulated molecular signaling pathways identified using bioinformatics. We observed radiation-induced proteomic changes in MSCs from the offspring of in utero irradiated mice (leading to ~ 9.4% of all detected proteins being either up- or downregulated) as compared to non-irradiated controls. The proteomic changes map to regulation pathways involved in the extracellular matrix, the response to oxidative stress, and the Wnt signaling pathway. In addition, chronic prenatal LD irradiation lead to an increased rate of in vitro radiation-induced senescence later in life and to an increased number of residual DNA double-strand breaks after 4 Gy irradiation, indicating a remarkable interaction of in vivo radiation in combination with a second acute dose of in vitro radiation. This study provides the first insight into a molecular mechanism of persistent MSC damage response by ionizing radiation exposure during prenatal time and will help to predict therapeutic safety and efficacy with respect to a clinical application of stem cells., (© 2021. The Author(s).)

Background and Purpose: Cardiotoxicity is a well-known adverse effect of radiation therapy. Measurable abnormalities in the heart function indicate advanced and often irreversible heart damage. Therefore, early detection of cardiac toxicity is necessary to delay and alleviate the development of the disease. The present study investigated long-term serum proteome alterations following local heart irradiation using a mouse model with the aim to detect biomarkers of radiation-induced cardiac toxicity. Materials and Methods: Serum samples from C57BL/6J mice were collected 20 weeks after local heart irradiation with 8 or 16 Gy X-ray; the controls were sham-irradiated. The samples were analyzed by quantitative proteomics based on data-independent acquisition mass spectrometry. The proteomics data were further investigated using bioinformatics and ELISA. Results: The analysis showed radiation-induced changes in the level of several serum proteins involved in the acute phase response, inflammation, and cholesterol metabolism. We found significantly enhanced expression of proinflammatory cytokines (TNF-α, TGF-β, IL-1, and IL-6) in the serum of the irradiated mice. The level of free fatty acids, total cholesterol, low-density lipoprotein (LDL), and oxidized LDL was increased, whereas that of high-density lipoprotein was decreased by irradiation. Conclusions: This study provides information on systemic effects of heart irradiation. It elucidates a radiation fingerprint in the serum that may be used to elucidate adverse cardiac effects after radiation therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Azimzadeh, von Toerne, Subramanian, Sievert, Multhoff, Atkinson and Tapio.)

Assessing the impact of body image on engagement in a range of life domains is important; however, there is a lack of validated measures for adolescents. The current research developed the Body Image Life Disengagement Questionnaire (BILD-Q) and validated it among four samples of British adolescents. Study 1 (N = 1707; 11-13 years) indicated a 9-item unidimensional scale based on Exploratory Factory Analysis. In Study 2 (N = 1403; 11-13 years), Confirmatory Factor Analysis (CFA) showed an acceptable fit overall, but better among girls than boys. Further exploration with CFA in Study 3 (N = 2034; 13-14 years) showed a good to excellent fit overall, and acceptable among both boys and girls. The scale showed good internal consistency and test-retest reliability, and gender invariance indicated the scale can be used comparatively. In Study 4 (N = 288; 13-14 years), convergent validity was supported via expected relationships with body image and related constructs. Concurrent and predictive incremental validity were also evidenced via explaining significant unique variance in well-being. These studies provide support for the BILD-Q as a reliable and valid measure of broader impacts of body image among adolescents, which may benefit intervention evaluation and policy change efforts., Competing Interests: Declaration of Competing Interest PD is an independent research consultant to the Dove Self-Esteem Project global education initiative. The authors declare no other potential conflicts of interest in relation to this work., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: Weight stigma is prevalent across multiple life domains, and negatively affects both psychological and physical health. Yet, research into weight stigma reduction techniques is limited, and rarely results in reduced antipathy toward higher-weight individuals. The current pre-registered study investigated a novel weight stigma reduction intervention. We tested whether a writing exercise focusing on body functionality (i.e., everything the body can do, rather than how it looks) of another person leads to reductions in weight stigma., Method: Participants were 98 women (Mage = 23.17, Range = 16-63) who viewed a photograph of a higher-weight woman, "Anne," and were randomised to complete a writing exercise either describing what "Anne's" body could do (experimental group) or describing her home (active control group). Facets of weight stigma were assessed at pretest and posttest., Results: At posttest, the experimental group evidenced higher fat acceptance and social closeness to "Anne" compared with the active control group. However, no group differences were found in attribution complexity, responsibility, and likeability of "Anne"., Conclusions: A brief body functionality intervention effectively reduced some, but not all, facets of weight stigma in women. This study provides evidence that functionality-focused interventions may hold promise as a means to reduce weight stigma., Competing Interests: The authors have declared that no competing interests exist.

Objective: Brief self-guided activities designed for focused and immediate benefits, termed microinterventions, have the potential to aid reach and engagement in mental health interventions; however further validation is needed. This study evaluated effects of two microinterventions for responding to appearance-ideal media on risk and protective factors for disordered eating., Method: Undergraduate women (N = 202, M age = 19.90, SD = 2.75) were allocated quasi-randomly to one of three 15-min video-based microinterventions (mindfulness, cognitive dissonance, educational control) in the lab and assessed on state outcomes at baseline and immediate posttest. One week later, trait factors were assessed and participants underwent an appearance-ideal media exposure task., Results: Both mindfulness and dissonance groups reported significant immediate benefits to state appearance-ideal internalization, perceived sociocultural pressures and related distress, and mood, compared to educational control (Glass's Δ effect sizes = .40-.94), but not state weight or appearance satisfaction. At 1-week follow-up, mindfulness and dissonance groups demonstrated improved trait appearance-ideal internalization (Δ = .40 and .42), weight and shape concerns (Δ = .27 [ns] and .44), and body appreciation (Δ = .39 and .46) compared to the educational control. There were no effects on trait perceived pressures, negative affect, or body image psychological flexibility, and no differential changes in state outcomes from premedia to postmedia exposure., Discussion: Microinterventions using mindfulness and dissonance techniques show promise for improving some risk and potential protective factors for disordered eating in the immediate and short-term. Further research is required to substantiate their place within the spectrum of eating disorder prevention, early intervention and treatment techniques., (© 2021 Wiley Periodicals LLC.)

Purpose: Body dissatisfaction is common during adolescence and predicts poor psychological and physical health. Interventions have traditionally overrelied on delivery by external providers (e.g., researchers and psychologists), preventing scalability. This study evaluated the acceptability and effectiveness of a school-based body image intervention delivered by schoolteachers., Methods: Six British schools participated in a pragmatic cluster randomized controlled trial. Girls and boys aged 11-13 years received the five-session intervention delivered by their teachers (n = 848) or lessons-as-usual control (n = 647) and were assessed at baseline, postintervention, and 2-, 6-, 12-, 24- and 36-month follow-up. The primary outcome was body image (body esteem), secondary outcomes included risk factors for body image (internalization of appearance ideals, sociocultural pressures, social comparisons, appearance-related teasing, and conversations), and tertiary outcomes included psychosocial well-being (negative affect, self-esteem, dietary restraint, and life engagement)., Results: Compared with the control group, intervention students demonstrated improvements in the primary outcome of body esteem at postintervention (Cohen's d = .15), 2-month (d = .26), and 6-month follow-up (d = .15). For girls, there was also a significant reduction in experienced appearance-related teasing at 6-month (d = .24) and 12-month (d = .30) follow-up. No other significant intervention effects were observed. The intervention was acceptable to students., Conclusions: These findings present the longest sustained improvements in a cognitive-affective body image outcome observed among girls and boys during a teacher-led universal body image program to date. Intervention refinement and improved teacher training may further improve outcomes. Task-shifting intervention delivery to community providers to scale up interventions is a promising strategy., (Copyright © 2020 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background: The Respiratory Symptoms Questionnaire (RSQ) is a novel, four-item patient-reported diagnosis-agnostic tool designed to assess the frequency of respiratory symptoms and their impact on activity, without specifying a particular diagnosis. Our objective was to examine its validity in patients with asthma and/or chronic obstructive pulmonary disease (COPD)., Methods: Baseline data were randomly sampled from patients who completed the RSQ in the NOVELTY study (ClinicalTrials.gov: NCT02760329). The total sample (n=1530) comprised three randomly selected samples (n=510 each) from each physician-assigned diagnostic group (asthma, asthma+COPD and COPD). The internal consistency and structural validity of the RSQ were evaluated using exploratory and confirmatory factor analyses; psychometric performance was observed using Classical Test Theory and Item Response Theory analyses., Results: For the total sample, the mean±sd RSQ score was 5.6±4.3 (range 0-16). Irrespective of diagnosis, the internal consistency of items was uniformly adequate (Cronbach's α=0.76-0.80). All items had high factor loadings and structural characteristics of the measure were invariant across groups. Using the total sample, RSQ items informatively covered the θ score range of -2.0 to 2.8, with discrimination coefficients for individual items being high to very high (1.7-2.6). Strong convergent correlations were observed between the RSQ and the St George's Respiratory Questionnaire (0.77, p<0.001)., Conclusions: The RSQ is a valid, brief, patient-reported tool for assessing respiratory symptoms in patients across the whole spectrum of asthma and/or COPD, rather than using different questionnaires for each diagnosis. It can be used for monitoring respiratory symptoms in clinical practice, clinical trials and real-world studies., Competing Interests: Conflict of interest: N. Karlsson is an employee of AstraZeneca. Conflict of interest: M.J. Atkinson reports payment as an independent consultant to Evidera for activities contracted by AstraZeneca associated with the psychometric evaluation of the Respiratory Symptoms Questionnaire; he has provided analytic direction and unbiased interpretation of the RSQ findings. Conflict of interest: H. Müllerová is an employee of AstraZeneca. Conflict of interest: M. Alacqua is an employee of AstraZeneca. Conflict of interest: C. Keen is an employee of AstraZeneca. Conflict of interest: R. Hughes is an employee of AstraZeneca. Conflict of interest: C. Janson reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis and Teva Pharmaceuticals, outside the submitted work. Conflict of interest: B. Make reports grants (with funds provided to, and controlled by, National Jewish Health) from AstraZeneca, GlaxoSmithKline, National Heart, Lung, and Blood Institute, Pearl Research and Sunovion; personal fees from Takeda and Third Pole; nonfinancial support from AstraZeneca, Circassia, GlaxoSmithKline, Phillips, Shire, Spiration, Sunovion and Third Pole; and other support from Academy Continued Health Care Learning, American College of Chest Physicians, AstraZeneca, Boehringer Ingelheim, Catamount Medical, Circassia, Eastern Pulmonary Society, Eastern VA Medical Center, GlaxoSmithKline, Hybrid Communications, Medscape, Mount Sinai Medical Center, National Jewish Health, Novartis, Phillips, Projects in Knowledge, Science 24/7, Shire, Sunovion, Theravance, Ultimate Medical Academy, Verona, WebMD and Wolters Kluwer Health, all outside the submitted work. Conflict of interest: D. Price received funding for the conduct of this study from AstraZeneca and discloses board membership with Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, Mundipharma, Mylan, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, Teva Pharmaceuticals and Thermofisher; consultancy agreements with Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Mundipharma, Mylan, Novartis, Pfizer, Teva Pharmaceuticals and Theravance; grants and unrestricted funding for investigator-initiated studies (conducted through Observational and Pragmatic Research Institute Pte Ltd) from AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, Mundipharma, Mylan, Novartis, Pfizer, Regeneron Pharmaceuticals, Respiratory Effectiveness Group, Sanofi Genzyme, Teva Pharmaceuticals, Theravance and the UK National Health Service; payment for lectures/speaking engagements from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Kyorin, Mundipharma, Mylan, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme and Teva Pharmaceuticals; payment for the development of educational materials from Mundipharma and Novartis; payment for travel/accommodation/meeting expenses from AstraZeneca, Boehringer Ingelheim, Mundipharma, Mylan, Novartis and Thermofisher; funding for patient enrolment or completion of research from Novartis; stock/stock options from AKL Research and Development Ltd, which produces phytopharmaceuticals; owns 74% of the social enterprise Optimum Patient Care Ltd (Australia and UK) and 74% of Observational and Pragmatic Research Institute Pte Ltd (Singapore); 5% shareholding in Timestamp, which develops adherence monitoring technology; is peer reviewer for grant committees of the Efficacy and Mechanism Evaluation programme and Health Technology Assessment; and was an expert witness for GlaxoSmithKline. Conflict of interest: H.K. Reddel reports that this study is funded by AstraZeneca. She received reimbursement from AstraZeneca for time spent working on the study but not for manuscript preparation. She also reports advisory boards for AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis and Sanofi-Genzyme; data and safety monitoring boards for AstraZeneca, GlaxoSmithKline, Merck and Novartis; honoraria from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline and Teva Pharmaceuticals for independent medical educational presentations; and independent research funding from AstraZeneca, GlaxoSmithKline and Novartis, all outside the submitted work., (Copyright ©ERS 2021.)

As high-throughput approaches in biological and biomedical research are transforming the life sciences into information-driven disciplines, modern analytics platforms for big data have started to address the needs for efficient and systematic data analysis and interpretation. We observe that radiobiology is following this general trend, with -omics information providing unparalleled depth into the biomolecular mechanisms of radiation response-defined as systems radiobiology. We outline the design of computational frameworks and discuss the analysis of big data in low-dose ionizing radiation (LDIR) responses of the mammalian brain. Following successful examples and best practices of approaches for the analysis of big data in life sciences and health care, we present the needs and requirements for radiation research. Our goal is to raise awareness for the radiobiology community about the new technological possibilities that can capture complex information and execute data analytics on a large scale. The production of large data sets from genome-wide experiments (quantity) and the complexity of radiation research with multidimensional experimental designs (quality) will necessitate the adoption of latest information technologies. The main objective was to translate research results into applied clinical and epidemiological practice and understand the responses of biological tissues to LDIR to define new radiation protection policies. We envisage a future where multidisciplinary teams include data scientists, artificial intelligence experts, DevOps engineers, and of course radiation experts to fulfill the augmented needs of the radiobiology community, accelerate research, and devise new strategies.

Clinical tissue archives represent an invaluable source of biological information. Formalin-fixed, paraffin-embedded (FFPE) tissue can be used for retrospective investigation of biomarkers of diseases and prognosis.Recently, the number of studies using proteome profiling of samples from clinical archives has markedly increased. However, the application of conventional quantitative proteomics technologies remains a challenge mainly due to the harsh fixation process resulting in protein cross-linking and protein degradation. In the present chapter, we demonstrate a protocol for label-free proteomic analysis of FFPE tissue prepared from human cardiac autopsies. The data presented here highlight the applicability and suitability of FFPE heart tissue for understanding the molecular mechanism of cardiac injury using a proteomics approach.

Purpose: The MSc Radiation Biology course is a highly interdisciplinary degree program placing radiation biology at the interface between biology, medicine, and physics, as well as their associated technologies. The goal was to establish an internationally acknowledged program with diverse and heterogeneous student cohorts, who benefit from each other academically as well as culturally. We have completed a Five-Year evaluation of the program to assess our qualification profile and the further direction we want to take., Materials and Methods: We evaluated the student cohort's data from the last 5 years regarding gender, age, and nationality as well as the highest degree before applying and career path after graduation., Results: Data shows a great diversity regarding nationalty as well as undergraduate background. Cohort sizes could be increased and future prospects mainly aimed to a PhD. Measures after regular quality meetings and students' feedback led to improving the curriculum and workload, teacher's training, and changes to examination regulations., Conclusions: After 5 years, statistics show that our expectations have been met exceedingly. All graduates had excellent career opportunities reflecting the necessity of this MSc and its topics. We are continuously working on improving the program and adapting the curriculum to the requirements in radiation sciences. The future vision includes an expansion of the program as well as undergraduate education opportunities in this field.

Extracellular vesicles (EVs) are freely circulating nano/micrometer-sized membrane-bound vesicles released by various cell types. Their cargo consists of proteins, lipids, metabolites, and different types of RNA molecules reflecting the origin of the secreting cell type or tissue. Since the EV cargo is constantly changing in response to pathological status or different environmental stressors, it has been extensively studied in the quest for biomarkers, especially in the cancer research. Mass spectrometry (MS)-based proteome analysis is a powerful tool to elucidate the protein cargo in EVs. This chapter describes and characterizes three MS-compatible lysis methods, namely by using urea, guanidium hydrochloride, and radioimmunoprecipitation buffer for isolating proteins from EVs.

The miR-221 expression is dependent on the oncogenic RAS-RAF-MEK pathway activation and influences epithelial-to-mesenchymal transition (EMT). The Cancer Genome Atlas (TCGA) database analysis showed high gene significance for ZEB1 with EMT module analysis and miR-221 overexpression within the triple-negative breast cancer (TNBC) and HER2+ subgroups when compared to luminal A/B subgroups. EMT marker expression analysis after MEK1 (TAK-733) inhibitor treatment and irradiation was combined with miR-221 and ZEB1 expression analysis. The interaction of miR-221 overexpression with irradiation and its influence on migration, proliferation, colony formation and subsequent EMT target activation were investigated. The results revealed that MEK1 inhibitor treatment combined with irradiation could decrease the migratory potential of breast cancer cells including reduction of miR-221 and corresponding downstream ZEB1 (EMT) marker expression. The clonogenic survival assays revealed that miR-221 overexpressing SKBR3 cells were more radioresistant when compared to the control. Remarkably, the effect of miR-221 overexpression on migration in highly proliferative and highly HER2-positive SKBR3 cells remained constant even upon 8 Gy irradiation. Further, in naturally miR-221-overexpressing MDA-MB-231 cells, the proliferation and migration significantly decrease after miR-221 knockdown. This leads to the assumption that radiation alone is not reducing migration capacity of miR-221-overexpressing cells and that additional factors play an important role in this context. The miR-221/ZEB1 activity is efficiently targeted upon MEK1 inhibitor (TAK-733) treatment and when combined with irradiation treatment, significant reduction in migration of breast cancer cells was shown.

This study investigated death reflection as a novel strategy to improve body image among women. Young adult women (N = 158; M age = 21.35) completed a death reflection exercise, a death-related active control exercise (to ensure that effects were due to the manner in which women reflected on their death, rather than due to thoughts about death in general), or a non-death-related active control exercise. Participants completed measures of body image at posttest and 1-week follow-up. The women in the death reflection group, compared to the non-death-related control group, experienced higher body weight satisfaction at posttest. Among women higher in beauty orientation, those in the death reflection group experienced higher body shape satisfaction compared to women in the death-related control group. Effects were medium-to-large in magnitude. No group differences were observed for overall appearance satisfaction, appearance importance, broad conceptualisation of beauty, and endorsement of cultural appearance ideals. These findings provide preliminary support for death reflection as a technique to improve some facets of women's body image. Yet, future research is needed to test whether these effects are replicable and can be extended to other facets of body image., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: No validated tools exist to assess satisfaction with epilepsy surgery. We aimed to develop and validate a new measure of patient satisfaction with epilepsy surgery, the 19-item Epilepsy Surgery Satisfaction Questionnaire (ESSQ-19)., Methods: An initial 31-item measure was developed based on literature review, patient focus groups, thematic analysis, and Delphi panels. The questionnaire was administered twice, 4-6 weeks apart, to 229 adults (≥18 years old) who underwent epilepsy surgery ≥1 year earlier, at three centers in Canada and one in Sweden. Participants also completed seven validated questionnaires to assess construct validity. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) assessed the factorial structure of the questionnaire. Cronbach alpha and intraclass correlation coefficients (ICCs) assessed the internal consistency and test-retest reliability of the ESSQ-19. Spearman and polyserial correlations assessed construct validity., Results: Median age of participants and time since surgery were 42 years (interquartile range [IQR] = 32-54) and 5 years (IQR = 2-8.75), respectively. EFA and CFA yielded 18 items that segregated into four domains (mean score [SD]), namely, seizure control (76.4 [25]), psychosocial functioning (67.3 [26]), surgical complications (84 [22]), and recovery from surgery (73 [24]), one global satisfaction item, and a summary global score (74 [21]). The domain and summary scores demonstrated good to excellent internal reliability (Cronbach ⍺ range = .84-.95) and test-retest reliability (ICC range = 0.71-0.85). Construct validity was supported by predicted correlations with other instruments., Significance: The ESSQ-19 is a new, valid, and reliable measure of patient satisfaction with epilepsy surgery that can be used in clinical and research settings., (© 2020 International League Against Epilepsy.)

Radiation-induced inflammation leading to the permeability of the endothelial barrier may increase the risk of cardiovascular disease. The aim of this study was to investigate potential mechanisms in vitro at the level of the proteome in human coronary artery endothelial cells (HCECest2) that were exposed to radiation doses of 0, 0.25, 0.5, 2.0 and 10 Gy (60Co-γ). Proteomics analysis was performed using mass spectrometry in a label-free data-independent acquisition mode. The data were validated using bioinformatics and immunoblotting. The low- and moderate-dose-irradiated samples (0.25 Gy, 0.5 Gy) showed only scarce proteome changes. In contrast, an activation of DNA-damage repair, inflammation, and oxidative stress pathways was seen after the high-dose treatments (2 and 10 Gy). The level of the DNA damage response protein DDB2 was enhanced early at the 10 Gy dose. The expression of proteins belonging to the inflammatory response or cGAS-STING pathway (STING, STAT1, ICAM1, ISG15) increased in a dose-dependent manner, showing the strongest effects at 10 Gy after one week. This study suggests a connection between the radiation-induced DNA damage and the induction of inflammation which supports the inhibition of the cGAS-STING pathway in the prevention of radiation-induced cardiovascular disease.

Since early April 2020, there has been intense debate over proposed clinical use of ionizing radiation to treat life-threatening pneumonia in Coronavirus Disease 2019 (COVID-19) patients. At least twelve relevant papers appeared by 20 May 2020. The radiation dose proposed for clinical trials are a single dose (0.1-1 Gy) or two doses (a few mGy followed by 0.1-0.25 Gy involving a putative adaptive response, or 1-1.5 Gy in two fractions 2-3 days apart). The scientific rationale for such proposed so-called low dose radiotherapy (LDRT) is twofold (note that only doses below 0.1 Gy are considered as low doses in the field of radiation protection, but here we follow the term as conventionally used in the field of radiation oncology). Firstly, the potentially positive observations in human case series and biological studies in rodent models on viral or bacterial pneumonia that were conducted in the pre-antibiotic era. Secondly, the potential anti-inflammatory properties of LDRT, which have been seen when LDRT is applied locally to subacute degenerative joint diseases, mainly in Germany. However, the human and animal studies cited as supportive evidence have significant limitations, and whether LDRT produces anti-inflammatory effects in the inflamed lung or exacerbates ongoing COVID-19 damage remains unclear. Therefore, we conclude that the available scientific evidence does not justify clinical trials of LDRT for COVID-19 pneumonia, with unknown benefit and known mortality risks from radiogenic cancer and circulatory disease. Despite the significant uncertainties in these proposals, some clinical trials are ongoing and planned. This paper gives an overview of current situations surrounding LDRT for COVID-19 pneumonia.

Epidemiological studies on workers employed at the Mayak plutonium enrichment plant have demonstrated an association between external gamma ray exposure and an elevated risk of ischemic heart disease (IHD). In a previous study using fresh-frozen post mortem samples of the cardiac left ventricle of Mayak workers and non-irradiated controls, we observed radiation-induced alterations in the heart proteome, mainly downregulation of mitochondrial and structural proteins. As the control group available at that time was younger than the irradiated group, we could not exclude age as a confounding factor. To address this issue, we have now expanded our study to investigate additional samples using archival formalin-fixed paraffin-embedded (FFPE) tissue. Importantly, the control group studied here is older than the occupationally exposed (>500 mGy) group. Label-free quantitative proteomics analysis showed that proteins involved in the lipid metabolism, sirtuin signaling, mitochondrial function, cytoskeletal organization, and antioxidant defense were the most affected. A histopathological analysis elucidated large foci of fibrotic tissue, myocardial lipomatosis and lymphocytic infiltrations in the irradiated samples. These data highlight the suitability of FFPE material for proteomics analysis. The study confirms the previous results emphasizing the role of adverse metabolic changes in the radiation-associated IHD. Most importantly, it excludes age at the time of death as a confounding factor.

Mesenchymal stem cells (MSCs) are multilineage adult stem cells with considerable potential for cell-based regenerative therapies. In vitro expansion changes their epigenetic and cellular properties, with a poorly understood impact on DNA damage response (DDR) and genome stability. We report here results of a transcriptome-based pathway analysis of in vitro-expanded human bone marrow-derived mesenchymal stem cell (hBM-MSCs), supplemented with cellular assays focusing on DNA double-strand break (DSB) repair. Gene pathways affected by in vitro aging were mapped using gene ontology, KEGG, and GSEA, and were found to involve DNA repair, homologous recombination (HR), cell cycle control, and chromosomal replication. Assays for the recognition (γ-H2AX + 53BP1 foci) and repair (pBRCA1 + γ-H2AX foci) of X-ray-induced DNA DSBs in hBM-MSCs show that over a period of 8 weeks of in vitro aging (i.e., about 10 doubling times), cells exhibit a reduced DDR and a higher fraction of residual DNA damage. Furthermore, a distinct subpopulation of cells with impaired DNA DSB recognition was observed. Several genes that participate in DNA repair by HR (e.g., Rad51, Rad54, BRCA1) show a 2.3- to fourfold reduction of their mRNA expression by qRT-PCR. We conclude that the in vitro expansion of hMSCs can lead to aging-related impairment of the recognition and repair of DNA breaks., (© 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.)