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Adipocyte dysregulation is one mechanism linking overweight and breast cancer recurrence. Exercise and weight loss are associated with a decreased risk of breast cancer recurrence in breast cancer survivors with overweight or obesity, which may be mediated through reduced leptin levels, increased adiponectin levels, and an elevated adiponectin to leptin (A:L) ratio. The four-arm randomized controlled WISER Survivor trial examined the 12-month intervention effects of exercise, weight loss, and the combination of exercise and weight loss on adipokine levels among breast cancer survivors (n = 339) with overweight or obesity. Compared with Control, the Combination of Exercise and Weight Loss decreased leptin levels (-35.9%; 95% CI: -46.8%, -25.0%) and increased A:L ratio (11.6%; 95% CI: 5.6%, 17.6%) but did not change adiponectin levels (4.1%; 95% CI: -3.1%, 11.2%). Compared with Control, Weight Loss Alone decreased leptin levels (-35.6%; 95% CI: -46.6%, -24.5%) and increased A:L ratio (10.6%; 95% CI: 4.7%, 16.5%) but did not change adiponectin levels (0.9%; 95% CI: -6.0%, 7.9%). Compared with Control, Exercise Alone did not change leptin levels, adiponectin levels, or A:L ratio. In analyses that consolidated intervention groups, compared with Control, weight loss of ≥5% decreased leptin levels (p trend < 0.01) and increased A:L ratio (p trend < 0.01) but did not alter adiponectin levels (p trend = 0.53). Weight loss, with or without exercise, was associated with decreased leptin levels in breast cancer survivors with overweight or obesity. Improvements in the adipokine secretion profile (A:L ratio) were primarily driven by a weight loss-induced change in leptin levels.

Definitive haematopoietic stem and progenitor cells (HSPCs) generate erythroid, lymphoid and myeloid lineages. HSPCs are produced in the embryo via transdifferentiation of haemogenic endothelial cells in the aorta-gonad-mesonephros (AGM). HSPCs in the AGM are heterogeneous in differentiation and proliferative output, but how these intrinsic differences are acquired remains unanswered. Here we discovered that loss of microRNA (miR)-128 in zebrafish leads to an expansion of HSPCs in the AGM with different cell cycle states and a skew towards erythroid and lymphoid progenitors. Manipulating miR-128 in differentiating haemogenic endothelial cells, before their transition to HSPCs, recapitulated the lineage skewing in both zebrafish and human pluripotent stem cells. miR-128 promotes Wnt and Notch signalling in the AGM via post-transcriptional repression of the Wnt inhibitor csnk1a1 and the Notch ligand jag1b. De-repression of cskn1a1 resulted in replicative and erythroid-biased HSPCs, whereas de-repression of jag1b resulted in G2/M and lymphoid-biased HSPCs with long-term consequence on the respective blood lineages. We propose that HSPC heterogeneity arises in the AGM endothelium and is programmed in part by Wnt and Notch signalling.

Seagrass is an important marine habitat that provides benefits to society in the form of ecosystem services. Services include the provision of food via fisheries, the regulation of water quality and the ability to sequester and store carbon. In the UK, seagrass beds are in decline, increasing the risk of ecosystem service loss. Current efforts to protect, restore and create seagrass habitat, beyond spatial management measures, rely on grant funding and donations. Emerging carbon, biodiversity and wider ecosystem service markets offering potential revenue sources could facilitate the enhancement of seagrass habitat at scale. Participation in ecosystem service markets, requires that projects deliver on the ecosystem service benefits defined. As the benefits will have been paid for, there are risks associated with not delivering on ecosystem service benefits. It is important that the risk is clearly defined. In this study we further the marine natural capital and risk register approach and apply the method to a case study area to support the development of sustainable funding options for seagrass habitat enhancement in Plymouth Sound, UK. Habitat Suitability modelling is also used to map potential areas for seagrass habitat enhancement. We find that, in the Plymouth Sound area, the risk of loss of ecosystem services for subtidal seagrass habitats is, at present, high. This is primarily linked to the declining extent and condition of subtidal seagrass assets. Under current governance, all of Plymouth Sound’s subtidal seagrass are within a Marine Protected Area, though this conservation designation does not guarantee that the seagrass bed is protected from damaging activity. Under current environmental conditions there is opportunity for widespread seagrass restoration and creation. Risk to seagrass beds and any future private funding could be reduced by governance actions that enable effective direct protection of the seagrass assets and mitigate harmful pressures (e.g., reduction of water pollution). Emerging financial ‘products’ from seagrass ecosystem services that can support restoration and creation, require a high degree of integrity. The natural capital asset and risk register framework can provide information to underpin product development. With the development of revenue streams from ecosystem services there is a need for more intentional governance and site-based monitoring of these habitats as natural capital assets. Further research is needed to define any social or economic outcomes. Synthesis and Application By assessing the risk to the status of seagrass assets through this approach, it is possible to determine the complementary governance actions needed to underpin investment in seagrass habitat enhancement. The methods are transferable to other locations where data exists to define the asset status. These specific findings are relevant nationally where similar vectors of risk (pressures) are identified.

Excitotoxicity, a neuronal death process in neurological disorders such as stroke, is initiated by the overstimulation of ionotropic glutamate receptors. Although dysregulation of proteolytic signaling networks is critical for excitotoxicity, the identity of affected proteins and mechanisms by which they induce neuronal cell death remain unclear. To address this, we used quantitative N-terminomics to identify proteins modified by proteolysis in neurons undergoing excitotoxic cell death. We found that most proteolytically processed proteins in excitotoxic neurons are likely substrates of calpains, including key synaptic regulatory proteins such as CRMP2, doublecortin-like kinase I, Src tyrosine kinase and calmodulin-dependent protein kinase IIβ (CaMKIIβ). Critically, calpain-catalyzed proteolytic processing of these proteins generates stable truncated fragments with altered activities that potentially contribute to neuronal death by perturbing synaptic organization and function. Blocking calpain-mediated proteolysis of one of these proteins, Src, protected against neuronal loss in a rat model of neurotoxicity. Extrapolation of our N-terminomic results led to the discovery that CaMKIIα, an isoform of CaMKIIβ, undergoes differential processing in mouse brains under physiological conditions and during ischemic stroke. In summary, by identifying the neuronal proteins undergoing proteolysis during excitotoxicity, our findings offer new insights into excitotoxic neuronal death mechanisms and reveal potential neuroprotective targets for neurological disorders.

Background: Mindfulness interventions have been shown to ameliorate stress in support staff working with people with intellectual disabilities. This review aimed to explore what impact mindfulness interventions for staff have on their care and support behaviours, and on the experiences of people with intellectual disabilities receiving support. Method: A systematic search of PsycINFO, Web of Science, ASSIA, and PubMed identified nine studies meeting the inclusion criteria. Outcomes were collated and a quality assessment tool was used to inform the critical analysis of the studies. Results: Despite identified methodological issues, positive results were consistently reported. These included reduced use of restrictive practices by staff, increased positive interactions between staff and people with intellectual disabilities, and reduced aggression displayed by people with intellectual disabilities. Conclusions: Further research in this area is required; however, this review supports the benefits of mindfulness on staff behaviour and the quality of life of people with intellectual disabilities.

Abstract Malnutrition underlies almost half of all child deaths globally. Severe Acute Malnutrition (SAM) carries unacceptable mortality, particularly if accompanied by infection or medical complications, including enteropathy. We evaluated four interventions for malnutrition enteropathy in a multi-centre phase II multi-arm trial in Zambia and Zimbabwe and completed in 2021. The purpose of this trial was to identify therapies which could be taken forward into phase III trials. Children of either sex were eligible for inclusion if aged 6–59 months and hospitalised with SAM (using WHO definitions: WLZ

Abstract Endocrine therapy (ET) for breast cancer treatment is associated with cognitive complaints, but their etiology is poorly understood. To address this, we developed and implemented an ambulatory assessment protocol consisting of wearable activity monitors, brief surveys of affect, context, and perceived impairments, and ultra-brief performance-based measures of cognition. Newly diagnosed, ER/PR+, stage 0-III, female breast cancer patients, were recruited. Ambulatory assessments were conducted on smart phones and wearable activity monitors were used to monitor sleep and physical activity. Participants were asked to complete five 7-day measurement bursts (one before starting ET and one each month for 4 consecutive months while on ET). We observed a consent rate of 36%, 27 women completed the study. Of the women that withdrew, 91% dropped prior to the midpoint of follow up. There were no significant differences in demographics, clinical breast cancer characteristics, sleep or physical activity patterns, or measures of cognition between women who completed versus withdrew. Women who did not complete the study provided fewer valid days of baseline data. In conclusion, while some women may be overwhelmed with their cancer diagnosis, we did not identify any predictive characteristics of women whom did not complete the study. This novel method enables the prospective study of psychological changes associated with cancer treatment, capturing a wide array of information about behavior, experience, and cognition, thus providing a picture of the lived experiences of cancer patients before and during exposure to ET.

PURPOSE: Physical inactivity and obesity increase risk for breast cancer recurrence and cardiovascular death; inflammation is hypothesized to mediate these associations. METHODS: In a four-arm randomized controlled trial, 318 breast cancer survivors with overweight or obesity were randomized to exercise alone, weight loss alone, exercise plus weight loss, or control for 12 months. Inflammation outcomes included C-reactive protein (CRP), serum amyloid A (SAA), intracellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1). RESULTS: Compared with control, exercise alone increased ICAM-1 (9.3%; 95% confidence interval [CI] = 1.6-16.9) and VCAM-1 (8.6%; 95% CI = 2.6-14.5) but did not change CRP or SAA. Compared with control, weight loss alone reduced CRP (-35.2%; 95% CI = -49.9 to -20.7), and SAA (-25.6%; 95% CI = -39.8 to -11.9) but did not change ICAM-1 or VCAM-1. Compared with control, exercise plus weight loss reduced CRP (-44.1%; 95% CI = -57.1 to -31.1) and SAA (-26.6%; 95% CI = -40.5 to -12.6) but did not change ICAM-1 or VCAM-1. Among 194 participants with elevated CRP at baseline (e.g., >3 mg·L -1 ), compared with control, weight loss alone (0.17; 95% CI = 0.04-0.30) and exercise plus weight loss (0.31; 95% CI = 0.16-0.46) increased the probability of achieving normal CRP at month 12. In analyses that consolidated randomized groups, body weight and adiposity reductions, but not change in fitness level, correlated with decreased CRP, SAA, and ICAM-1 levels. CONCLUSIONS: In breast cancer survivors with overweight or obesity, weight loss or exercise plus weight loss reduced measures of inflammation that are associated with breast cancer recurrence and cardiovascular death.

We used data from 444 undergraduates and 375 adults recruited online to evaluate lay raters' perceptions of vignettes described as having high levels of narcissistic traits. Participants were presented with vignettes describing someone with grandiose narcissistic characteristics only (e.g., someone who is arrogant), followed by vignettes describing someone with both grandiose and vulnerable narcissistic features (e.g., feeling insecure). Our primary aims focused on determining the extent to which (a) lay raters viewed narcissistic grandiosity and vulnerability as interconnected and (b) how attitudes toward vignettes varied as a function of the vulnerable and grandiose characteristics in the vignette descriptions. We also examined associations between lay raters' self-rated personality (assessed using the Narcissistic Admiration and Rivalry Questionnaire and the Big Five Inventory-2) and their vignette perceptions. Lay raters rated the vignette described as having only grandiose features as being prone to experiencing vulnerability. Furthermore, lay raters had more favorable views of the vignette including descriptions of both grandiose and vulnerable features (versus grandiose features alone). Likability and sympathy ratings did not vary based on the name used for vignettes (i.e., using the name 'James' versus 'Mary'). Finally, lay raters' self-rated traits showed some interesting associations with their vignette perceptions, but generally associations were weak in magnitude. Collectively, our findings indicate that lay raters perceive grandiosity and vulnerability as overlapping, and co-occurring grandiosity and vulnerability (versus grandiosity alone) may represent a more sympathetic view of narcissism. Determining the extent to which these attitudes influence real-world interactions would be useful for extending our findings., Author(s): Mara Villalongo Andino [sup.1] , Matthew F. D. Brown [sup.2] , Taylor Sturgeon [sup.1] , Kasey Stanton [sup.3] Author Affiliations: (1) https://ror.org/02smfhw86, grid.438526.e, 0000 0001 0694 4940, Department of [...]

The exotic pet trade has resulted in substantial invasion and disease risks, owing to the release of pets into new environments. Scientists have conjectured that pet owners acquire and release species with undesirable traits because they are imperfectly informed about the traits of these animals. However, few studies have used social science methods to elicit pet owners’ preferences for exotic pets. In 2019 we administered a best-worst choice survey to 1,055 exotic pet owners in the United States (who own pet reptiles, amphibians, fish, or invertebrates) to examine how human preferences and incomplete information may contribute to the risks of the exotic pet trade. Respondents preferred colorful and patterned species. On average, respondents preferred medium-sized amphibians and reptiles, small fish, and large invertebrates, although they demonstrated heterogeneity in preferences with respect to the adult size of pets. Respondents also preferred amphibians and reptiles with medium life expectancies and fish and invertebrates with long life expectancies, although they again demonstrated heterogeneity in preferences with respect to pets’ life span. Respondents preferred docile animals, and were more likely to purchase lower-cost pets. We found some evidence that respondents’ decision to purchase exotic pets depended on whether these animals were native, rare, had unusual morphological features, and breed easily. Respondents’ decision to purchase specific taxa as exotic pets also depended on their age, education, and housing. Most respondents stated that they searched for information on pets’ diet, behavior, adult size, life span, costs of care such as equipment or veterinary costs, and whether the animal was captive bred before purchasing these animals. Excepting pets’ diets, fewer than half of respondents had been offered information on pets’ traits by sellers. On average, respondents rated the information they had been offered as average. Respondents typically obtained additional information about pets from online searches. Our results suggest that certification systems that provide critical information on exotic pets’ behaviors, adult size, longevity, fecundity, and husbandry needs should be implemented to prevent pet owners acquiring animals that they may subsequently abandon.

Abstract Background The use of medical 3D printing (focusing on anatomical modeling) has continued to grow since the Radiological Society of North America’s (RSNA) 3D Printing Special Interest Group (3DPSIG) released its initial guideline and appropriateness rating document in 2018. The 3DPSIG formed a focused writing group to provide updated appropriateness ratings for 3D printing anatomical models across a variety of congenital heart disease. Evidence-based- (where available) and expert-consensus-driven appropriateness ratings are provided for twenty-eight congenital heart lesion categories. Methods A structured literature search was conducted to identify all relevant articles using 3D printing technology associated with pediatric congenital heart disease indications. Each study was vetted by the authors and strength of evidence was assessed according to published appropriateness ratings. Results Evidence-based recommendations for when 3D printing is appropriate are provided for pediatric congenital heart lesions. Recommendations are provided in accordance with strength of evidence of publications corresponding to each cardiac clinical scenario combined with expert opinion from members of the 3DPSIG. Conclusions This consensus appropriateness ratings document, created by the members of the RSNA 3DPSIG, provides a reference for clinical standards of 3D printing for pediatric congenital heart disease clinical scenarios.

Abstract Background The Adolescents and Adults Living with Perinatal HIV (AALPHI) study is one of only three cohort studies worldwide evaluating the impact of HIV on young people living with perinatal HIV (PLHIV) relative to a comparable group of HIV negative young people in close relationship with an HIV positive individual, for example, their mother, sibling or partner. This project aimed to engage young people with the AALPHI study findings, help them take ownership, and decide how they would disseminate the key messages to both study participants and to the wider community. Methods In brief, 318 PLHIV and 100 HIV negative adolescents participated in AALPHI, where they each were interviewed twice, around two years apart. They were asked a wide range of psychosocial and risk behaviour questions and their cognitive function was assessed. We invited three AALPHI participants and seven members of the Youth Trials Board at the Children’s HIV Association (CHIVA) to attend up to four workshops. They were provided with the key AALPHI research findings and asked to develop them into a format that was accessible and understandable for young people. Some who had not participated before formed a group in the fourth dissemination workshop that confirmed the most important concepts and results. Results The young people decided to develop a film and a leaflet about the AALPHI findings and co-produced them with a film maker and graphic designer. Challenges included working with the film maker and the venue for the first three dissemination workshops was an office space which was not ideal. Conclusion Engaging young people in the dissemination of the AALPHI findings ensured the results were communicated in a way that was more likely to be relevant, accessible and useful to those affected by the study. This project demonstrates how young people in potentially stigmatised areas of care, such as HIV, can be involved in research dissemination.

BackgroundEpidemiological evidence suggests that inadequate sleep duration and insomnia may be associated with increased risk of metabolic syndrome (MetS). However, longitudinal data with repeated measures of sleep duration and insomnia and of MetS are limited. We examined the association of sleep duration and insomnia with MetS and its components using longitudinal data from the Women's Health Initiative (WHI).MethodsThe study included postmenopausal women (ages 50-79 years) diabetes-free at enrollment in the WHI, with baseline data on sleep duration (n = 5,159), insomnia (n = 5,063), MetS, and its components. Repeated measures of self-reported sleep duration and insomnia were available from years 1 or 3 of follow-up and of the MetS components from years 3, 6 and 9. Associations were assessed using logistic regression and generalized estimating equations models, and odds ratios and 95% confidence intervals (CI) adjusted for major risk factors were calculated.ResultsIn cross-sectional analysis, baseline sleep duration ≥ 9 h was positively associated with MetS (OR = 1.51; 95%CI 1.12-2.04), while sleep duration of 8-  88 cm and triglycerides ≥ 150 mg/dL (OR = 1.18; 95%CI 1.01-1.40 and OR = 1.23; 95%CI 1.05-1.46, respectively). Insomnia had a borderline positive association with MetS (OR = 1.14; 95%CI 0.99-1.31), and significant positive associations with waist circumference > 88 cm and glucose ≥ 100 mg/dL (OR = 1.18; 95%CI 1.03-1.34 and OR = 1.17; 95%CI 1.02-1.35, respectively). In the longitudinal analysis, change from restful sleep to insomnia over time was associated with increased odds of developing MetS (OR = 1.40; 95%CI 1.01-1.94), and of a triglyceride level ≥ 150 mg/dL (OR = 1.48; 95%CI 1.08-2.03).ConclusionsAmong postmenopausal women in the WHI, sleep duration and insomnia were associated with current and future risk of MetS and some of its components.

Introduction: Exposure to food marketing increases the risk of poor diet. Children's perception and interpretation of food marketing across digital media platforms is understudied. Children aged 9–11 years are uniquely susceptible to food marketing because children may watch content alone, and it is unclear whether embedded ads are decipherable by children (e.g., social media influencers) and if children are receptive to advertisements. Methods: The authors collected data from 21 child–parent dyads in 2022 to fill this gap. Children were interviewed about their food marketing exposure and media use and were asked to share their perspectives on food advertisements. Parents completed a survey for household digital devices, demographics, and perception of their child's food advertising knowledge. Results: This study found that all children generally recognized direct food advertisements, could describe them with varying levels of confidence, and shared examples. Despite self-identifying ads and understanding the intent of advertising, many children are still receptive to advertisements on the basis of engaging content (e.g., liking the ads as entertainment, watching ads even when given the chance to skip the ad) and the food items marketed (e.g., liking the taste of foods). Conclusions: These findings suggest that knowledge of advertisement exposure and intent of advertising are not sufficient to reduce receptiveness of unhealthy food ad exposure. Additional research on the potential impacts of embedded ads, such as through social media influencers, is needed to understand children's interaction with the current digital media landscape.

Abstract Introduction The American College of Sports Medicine provided guidelines for exercise prescriptions in cancer survivors for specific cancer‐ and treatment‐related health outcomes. However, there was insufficient evidence to generate exercise prescriptions for 10 health outcomes of cancer treatment. We sought to update the state of evidence. Methods We conducted a systematic review of these 10 understudied health outcomes (bone health, sleep, cardiovascular function, chemotherapy‐induced peripheral neuropathy (CIPN), cognitive function, falls and balance, nausea, pain, sexual function, and treatment tolerance) and provided an update of evidence. Results While the evidence base for each outcome has increased, there remains insufficient evidence to generate exercise prescriptions. Common limitations observed across outcomes included: variability in type and quality of outcome measurement tools, variability in definitions of the health outcomes, a lack of phase III trials, and a majority of trials investigating breast or prostate cancer survivors only. Conclusion We identified progress in the field of exercise oncology for several understudied cancer‐ and treatment‐related health outcomes. However, we were not able to generate exercise prescriptions due to continued insufficient evidence base. More work is needed to prescribe exercise as medicine for these understudied health outcomes, and our review highlights several strategies to aid in research acceleration within these areas of exercise oncology.

Abstract Background Chronic levels of inflammation are associated with higher risk of many chronic diseases. Physical activity (PA) lowers the risk of cancer, cardiovascular disease (CVD), diabetes and others. One mechanism for PA-induced protection may be through the immune system. We investigated the association between leisure-time PA and peripheral immune cell populations in a large nationally representative sample of the US general population. Methods A total of 17,093 participants [mean (SE) age of 41.6 (0.3) years] of the National Health and Nutrition Examination Survey 1999–2018 were included. Self-reported leisure-time PA was converted to metabolic equivalent of task hours per week (MET-hrs/wk). White blood cell (WBC) count, WBC ratios, and platelet count were derived. Multivariable linear regression analyses were used to estimate associations between leisure-time PA level and peripheral immune cell populations. Multivariable logistic regression analyses were used to estimate associations between leisure-time PA and metrics of WBC count and neutrophil-to-lymphocyte ratio (NLR) which may predict mortality. Results A higher leisure-time PA level was associated with a lower WBC count (> 14.0 vs. 14.0 vs. 8.1 × 109 cells/L; odds ratio [OR] = 0.76, 95% CI = 0.66–0.88) and high NLR (> 2.68; OR = 0.84, 95% CI = 0.72–0.99), which may predict CVD and all-cause mortality. The highest leisure-time PA level also linked to a lower probability of a high WBC count (≥ 8.3 × 109 cells/L; OR = 0.76, 95% CI = 0.66–0.88), which may predict cancer mortality. Conclusions We observed an inverse association between leisure-time PA level, WBC count, and NLR, particularly for neutrophil levels. These results suggest that participants at higher levels of leisure-time PA may have lower levels of inflammation, which may be important for future chronic disease outcomes.