Development of a behaviour change intervention to encourage timely cancer symptom presentation among people living in deprived communities using the Behaviour Change Wheel

We are grateful to the National Awareness and Early Diagnosis Initiative (NAEDI) for funding this work. The NAEDI funding consortium, under the auspices of the National Cancer Research Institute (NCRI), consists of Cancer Research UK; Department of Health (England); Economic and Social Research Council; Health and Social Care R&D Division, Public Health Agency (Northern Ireland); National Institute for Social Care and Health Research (Wales); and the Scottish Government. We would like to thank ABACus project management team members Tim Banks and Maura Matthews from Tenovus Cancer Care for their ongoing support and involvement in the project. The authors would also like to acknowledge the support of the ABACus steering group (Danny Antebi, Tracey Deacon, Karen Gully, Jane Hanson, Sharon Hillier, Alex Murray, Richard Neal, Gill Richardson, Mark Rogers, and Sara Thomas). Compliance with Ethical StandardsPeer reviewedPublisher PD

Glucocorticoids regulate mitochondrial fatty acid oxidation in fetal cardiomyocytes

Abstract: The late gestational rise in glucocorticoids contributes to the structural and functional maturation of the perinatal heart. Here, we hypothesized that glucocorticoid action contributes to the metabolic switch in perinatal cardiomyocytes from carbohydrate to fatty acid oxidation. In primary mouse fetal cardiomyocytes, dexamethasone treatment induced expression of genes involved in fatty acid oxidation and increased mitochondrial oxidation of palmitate, dependent upon a glucocorticoid receptor (GR). Dexamethasone did not, however, induce mitophagy or alter the morphology of the mitochondrial network. In vivo, in neonatal mice, dexamethasone treatment induced cardiac expression of fatty acid oxidation genes. However, dexamethasone treatment of pregnant C57Bl/6 mice at embryonic day (E)13.5 or E16.5 failed to induce fatty acid oxidation genes in fetal hearts assessed 24 h later. Instead, at E17.5, fatty acid oxidation genes were downregulated by dexamethasone, as was GR itself. PGC-1α, required for glucocorticoid-induced maturation of primary mouse fetal cardiomyocytes in vitro, was also downregulated in fetal hearts at E17.5, 24 h after dexamethasone administration. Similarly, following a course of antenatal corticosteroids in a translational sheep model of preterm birth, both GR and PGC-1α were downregulated in heart. These data suggest that endogenous glucocorticoids support the perinatal switch to fatty acid oxidation in cardiomyocytes through changes in gene expression rather than gross changes in mitochondrial volume or mitochondrial turnover. Moreover, our data suggest that treatment with exogenous glucocorticoids may interfere with normal fetal heart maturation, possibly by downregulating GR. This has implications for clinical use of antenatal corticosteroids when preterm birth is considered a possibility. Key points: Glucocorticoids are steroid hormones that play a vital role in late pregnancy in maturing fetal organs, including the heart. In fetal cardiomyocytes in culture, glucocorticoids promote mitochondrial fatty acid oxidation, suggesting they facilitate the perinatal switch from carbohydrates to fatty acids as the predominant energy substrate. Administration of a synthetic glucocorticoid in late pregnancy in mice downregulates the glucocorticoid receptor and interferes with the normal increase in genes involved in fatty acid metabolism in the heart. In a sheep model of preterm birth, antenatal corticosteroids (synthetic glucocorticoid) downregulates the glucocorticoid receptor and the gene encoding PGC-1α, a master regulator of energy metabolism. These experiments suggest that administration of antenatal corticosteroids in anticipation of preterm delivery may interfere with fetal heart maturation by downregulating the ability to respond to glucocorticoids

Sequential multiple assignment randomised trial to develop an adaptive mobile health intervention to increase physical activity in people poststroke in the community setting in Ireland: TAPAS trial protocol

INTRODUCTION: Stroke is the second-leading cause of death and disability globally. Participation in physical activity (PA) is a cornerstone of secondary prevention in stroke care. Given the heterogeneous nature of stroke, PA interventions that are adaptive to individual performance are recommended. Mobile health (mHealth) has been identified as a potential approach to supporting PA poststroke. To this end, we aim to use a Sequential Multiple Assignment Randomised Trial (SMART) design to develop an adaptive, user-informed mHealth intervention to improve PA poststroke. METHODS AND ANALYSIS: The components included in the 12-week intervention are based on empirical evidence and behavioural change theory and will include treatments to increase participation in Structured Exercise and Lifestyle or a combination of both. 117 participants will be randomly assigned to one of the two treatment components. At 6 weeks postinitial randomisation, participants will be classified as responders or non-responders based on participants' change in step count. Non-responders to the initial treatment will be randomly assigned to a different treatment allocation. The primary outcome will be PA (steps/day), feasibility and secondary clinical and cost outcomes will also be included. A SMART design will be used to evaluate the optimum adaptive PA intervention among community-dwelling, ambulatory people poststroke. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Health Service Executive Mid-Western Ethics Committee (REC Ref: 026/2022). The findings will be submitted for publication and presented at relevant national and international academic conferences.</p

Transforming Auxetic Metamaterials into Superhydrophobic Surfaces

Superhydrophobic materials are often inspired by nature, whereas metamaterials are engineered to have properties not usually occurring naturally. In both, the key to their unique properties is structure. Here, it is shown that a negative Poisson's ratio (auxetic) mechanical metamaterial can transform into a unique superhydrophobic material. When stretched, its surface has the counterintuitive property that it also expands in the orthogonal lateral direction. The change in the solid surface fraction as strain is applied is modeled, and it is shown that it decreases as the space between solid elements of the auxetic lattice expands. This results in a unique dependence of the superhydrophobicity on strain. Experimental models are constructed to illustrate the relationship between different states of strain and superhydrophobicity as the lattice transitions from an auxetic to a conventional structure. The findings offer a new approach to designing superhydrophobic materials for self‐cleaning surfaces, droplet transportation, droplet encapsulation, and oil–water separation

Characteristics of patients in platform C19, a COVID-19 research database combining primary care electronic health record and patient reported information

Background Data to better understand and manage the COVID-19 pandemic is urgently needed. However, there are gaps in information stored within even the best routinely-collected electronic health records (EHR) including test results, remote consultations for suspected COVID-19, shielding, physical activity, mental health, and undiagnosed or untested COVID-19 patients. Observational and Pragmatic Research Institute (OPRI) Singapore and Optimum Patient Care (OPC) UK established Platform C19, a research database combining EHR data and bespoke patient questionnaire. We describe the demographics, clinical characteristics, patient behavior, and impact of the COVID-19 pandemic using data within Platform C19. Methods EHR data from Platform C19 were extracted from 14 practices across UK participating in the OPC COVID-19 Quality Improvement program on a continuous, monthly basis. Starting 7th August 2020, consenting patients aged 18–85 years were invited in waves to fill an online questionnaire. Descriptive statistics were summarized using all data available up to 22nd January 2021. Findings From 129,978 invitees, 31,033 responded. Respondents were predominantly female (59.6%), white (93.5%), and current or ex-smokers (52.6%). Testing for COVID-19 was received by 23.8% of respondents, of which 7.9% received positive results. COVID-19 symptoms lasted ≥4 weeks in 19.5% of COVID-19 positive respondents. Up to 39% respondents reported a negative impact on questions regarding their mental health. Most (67%-76%) respondents with asthma, Chronic Obstructive Pulmonary Disease (COPD), diabetes, heart, or kidney disease reported no change in the condition of their diseases. Interpretation Platform C19 will enable research on key questions relating to COVID-19 pandemic not possible using EHR data alone

Enhanced stress resilience training for UK surgical trainees; Effect and evolution evaluated

Introduction Core Surgical Training (CST) programs are associated with high burnout. This study aimed to assess the influence of Enhanced Stress Resilience Training (ESRT) over a 2-year period in a single UK Statutory Education Body. Method CSTs participated in 5-weeks of formal ESRT to address work stressors. The primary outcome measure was career progression related to curriculum metrics and National Training Number (NTN) appointment. Secondary measures related to burnout using validated psychological inventories. Results Of 42 CSTs, 13 engaged fully with ESRT (31.0%; male 8, female 5, median age 28 year.), 11 engaged partially, and 18 did not. ESRT engagement was associated with better NTN appointment (ESRT 8/13 (61.5%) vs. not 1/18 (5.6%), p = 0.025), less burnout [aMBI; mean 5.14 (SD ± 2.35) vs. 3.14 (±2.25), F 6.637, p = 0.002, η p 2 =0.167], less stress [PSS-10; 19.22 (±5.91) vs. 15.79 (±5.47), F 8.740, p < 0.001, η p 2 =0.200], but more mindfulness [CAMS-R; 19.22 (±5.91) vs. 20.57 (±2.93), F 3.201, p = 0.047, η p 2 =0.084]. On multivariable analysis, Improving Surgical Training (run-through CST) program (OR 5.2 (95% CI 1.42-28.41, p = 0.022), MRCS pass (OR 17.128 (95% CI 1.48-197.11, p = 0.023) and ESRT engagement (OR 13.249, 95% CI 2.08-84.58, p = 0.006) were independently associated with NTN success. Discussion ESRT was associated with less stress and burnout, better mindfulness, and most importantly 13-fold better career progression

Alcohol-related brain damage in humans

Chronic excessive alcohol intoxications evoke cumulative damage to tissues and organs. We examined prefrontal cortex (Brodmann’s area (BA) 9) from 20 human alcoholics and 20 age, gender, and postmortem delay matched control subjects. H & E staining and light microscopy of prefrontal cortex tissue revealed a reduction in the levels of cytoskeleton surrounding the nuclei of cortical and subcortical neurons, and a disruption of subcortical neuron patterning in alcoholic subjects. BA 9 tissue homogenisation and one dimensional polyacrylamide gel electrophoresis (PAGE) proteomics of cytosolic proteins identified dramatic reductions in the protein levels of spectrin β II, and α- and β-tubulins in alcoholics, and these were validated and quantitated by Western blotting. We detected a significant increase in α-tubulin acetylation in alcoholics, a non-significant increase in isoaspartate protein damage, but a significant increase in protein isoaspartyl methyltransferase protein levels, the enzyme that triggers isoaspartate damage repair in vivo. There was also a significant reduction in proteasome activity in alcoholics. One dimensional PAGE of membrane-enriched fractions detected a reduction in β-spectrin protein levels, and a significant increase in transmembranous α3 (catalytic) subunit of the Na+,K+-ATPase in alcoholic subjects. However, control subjects retained stable oligomeric forms of α-subunit that were diminished in alcoholics. In alcoholics, significant loss of cytosolic α- and β-tubulins were also seen in caudate nucleus, hippocampus and cerebellum, but to different levels, indicative of brain regional susceptibility to alcohol-related damage. Collectively, these protein changes provide a molecular basis for some of the neuronal and behavioural abnormalities attributed to alcoholics

Can big data solve a big problem? Reporting the obesity data landscape in line with the Foresight obesity system map.

BACKGROUND: Obesity research at a population level is multifaceted and complex. This has been characterised in the UK by the Foresight obesity systems map, identifying over 100 variables, across seven domain areas which are thought to influence energy balance, and subsequent obesity. Availability of data to consider the whole obesity system is traditionally lacking. However, in an era of big data, new possibilities are emerging. Understanding what data are available can be the first challenge, followed by an inconsistency in data reporting to enable adequate use in the obesity context. In this study we map data sources against the Foresight obesity system map domains and nodes and develop a framework to report big data for obesity research. Opportunities and challenges associated with this new data approach to whole systems obesity research are discussed. METHODS: Expert opinion from the ESRC Strategic Network for Obesity was harnessed in order to develop a data source reporting framework for obesity research. The framework was then tested on a range of data sources. In order to assess availability of data sources relevant to obesity research, a data mapping exercise against the Foresight obesity systems map domains and nodes was carried out. RESULTS: A reporting framework was developed to recommend the reporting of key information in line with these headings: Background; Elements; Exemplars; Content; Ownership; Aggregation; Sharing; Temporality (BEE-COAST). The new BEE-COAST framework was successfully applied to eight exemplar data sources from the UK. 80% coverage of the Foresight obesity systems map is possible using a wide range of big data sources. The remaining 20% were primarily biological measurements often captured by more traditional laboratory based research. CONCLUSIONS: Big data offer great potential across many domains of obesity research and need to be leveraged in conjunction with traditional data for societal benefit and health promotion

Defining optimal soybean seeding rates and associated risk across North America

Soybean [Glycine max (L.) Merr.] seeding rate research across North America is typically conducted in small geo-political regions where environmental effects on the seeding rate × yield relationship are minimized. Data from 211 individual field studies (∼21,000 data points, 2007–2017) were combined from across North America ranging in yield from 1,000– 7,500 kg ha−1. Cluster analysis was used to stratify each individual field study into similar environmental (soil × climate) clusters and into high (HYL), medium (MYL), and low (LYL) yield levels. Agronomically optimal seeding rates (AOSR) were calculated and Monte Carlo risk analysis was implemented. Within the two northern most clusters the AOSR was higher in the LYL followed by the MYL and then HYL. Within the farthest south cluster, a relatively small (±15,000 seeds ha−1) change in seeding rate from the MYL was required to reach the AOSR of the LYL and HYL, respectively. The increase in seeding rate to reach the LYL AOSR was relatively greater (5x) than the decrease to reach the HYL AOSR within the northern most cluster. Regardless, seeding rates below the AOSR presented substantial risk and potential yield loss, while seeding rates above provided slight risk reduction and yield increases. Specific to LYLs and MYLs, establishing and maintaining an adequate plant stand until harvest maximized yield regardless of the seeding rate, while maximizing seed number was important with lower seeding rates. These findings will help growers manage their soybean seed investment by adjusting seeding rates based upon the productivity of the environment.Fil: Gaspar, Adam P.. Dow Agrosciences Argentina Sociedad de Responsabilidad Limitada.; ArgentinaFil: Mourtzinis, Spyridon. University of Wisconsin; Estados UnidosFil: Kyle, Don. Dow Agrosciences Argentina Sociedad de Responsabilidad Limitada.; ArgentinaFil: Galdi, Eric. Dow Agrosciences Argentina Sociedad de Responsabilidad Limitada.; ArgentinaFil: Lindsey, Laura E.. Ohio State University; Estados UnidosFil: Hamman, William P.. Ohio State University; Estados UnidosFil: Matcham, Emma G. University of Wisconsin; Estados UnidosFil: Kandel, Hans J.. North Dakota State University; Estados UnidosFil: Schmitz, Peder. North Dakota State University; Estados UnidosFil: Stanley, Jordan D.. North Dakota State University; Estados UnidosFil: Schmidt, John P.. Dow Agrosciences Argentina Sociedad de Responsabilidad Limitada.; ArgentinaFil: Mueller, Daren S.. University of Iowa; Estados UnidosFil: Nafziger, Emerson D.. University of Illinois; Estados UnidosFil: Ross, Jeremy. University of Arkansas for Medical Sciences; Estados UnidosFil: Carter, Paul R.. Dow Agrosciences Argentina Sociedad de Responsabilidad Limitada.; ArgentinaFil: Varenhorst, Adam J.. University of South Dakota; Estados UnidosFil: Wise, Kiersten A.. University of Kentucky; Estados UnidosFil: Ciampitti, Ignacio Antonio. Kansas State University; Estados UnidosFil: Carciochi, Walter Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; Argentina. Kansas State University; Estados UnidosFil: Chilvers, Martin I.. Michigan State University; Estados UnidosFil: Hauswedell, Brady. University of South Dakota; Estados UnidosFil: Tenuta, Albert U.. University of Guelph; CanadáFil: Conley, Shawn P.. University of Wisconsin; Estados Unido

Translational targeting of inflammation and fibrosis in frozen shoulder: Molecular dissection of the T cell/IL-17A axis

Frozen shoulder is a common fibroproliferative disease characterized by the insidious onset of pain and restricted range of shoulder movement with a significant socioeconomic impact. The pathophysiological mechanisms responsible for chronic inflammation and matrix remodeling in this prevalent fibrotic disorder remain unclear; however, increasing evidence implicates dysregulated immunobiology. IL-17A is a key cytokine associated with inflammation and tissue remodeling in numerous musculoskeletal diseases, and thus, we sought to determine the role of IL-17A in the immunopathogenesis of frozen shoulder. We demonstrate an immune cell landscape that switches from a predominantly macrophage population in nondiseased tissue to a T cell-rich environment in disease. Furthermore, we observed a subpopulation of IL-17A-producing T cells capable of inducing profibrotic and inflammatory responses in diseased fibroblasts through enhanced expression of the signaling receptor IL-17RA, rendering diseased cells more sensitive to IL-17A. We further established that the effects of IL-17A on diseased fibroblasts was TRAF-6/NF-κB dependent and could be inhibited by treatment with an IKKβ inhibitor or anti-IL-17A antibody. Accordingly, targeting of the IL-17A pathway may provide future therapeutic approaches to the management of this common, debilitating disease. [Abstract copyright: Copyright © 2021 the Author(s). Published by PNAS.