Elevated ACKR2 expression is a common feature of inflammatory arthropathies

Objectives. Chemokines are essential contributors to leucocyte accumulation at sites of inflammatory pathology. Interfering with chemokine or chemokine receptor function therefore represents a plausible therapeutic option. However, our currently limited understanding of chemokine orchestration of inflammatory responses means that such therapies have not yet been fully developed. We have a particular interest in the family of atypical chemokine receptors that fine-tune, or resolve, chemokine-driven responses. In particular we are interested in atypical chemokine receptor 2 (ACKR2), which is a scavenging receptor for inflammatory CC-chemokines and that therefore helps to resolve in vivo inflammatory responses. The objective of the current study was to examine ACKR2 expression in common arthropathies. Methods. ACKR2 expression was measured by a combination of qPCR and immuno-histochemistry. In addition, circulating cytokine and chemokine levels in patient plasma were assessed using multiplexing approaches. Results. Expression of ACKR2 was elevated on peripheral blood cells as well as on leucocytes and stromal cells in synovial tissue. Expression on peripheral blood leucocytes correlated with, and could be regulated by, circulating cytokines with particularly strong associations being seen with IL-6 and hepatocyte growth factor. In addition, expression within the synovium was coincident with aggregates of lymphocytes, potentially atopic follicles and sites of high inflammatory chemokine expression. Similarly increased levels of ACKR2 have been reported in psoriasis and SSc. Conclusion. Our data clearly show increased ACKR2 in a variety of arthropathies and taking into account our, and others’, previous data we now propose that elevated ACKR2 expression is a common feature of inflammatory pathologies

Towards a circular economy: exploring factors to repair broken electrical and electronics products by users with pro-environmental inclination

User repair can prolong product lifespan and support in turn the transformative Circular Economy agenda. Current research concerning user motivations and propensity to repair differs as to the extent at which users’ environmental concerns influence repair propensity. Because of this, the focus of this study is on potential individuals with pro-environmental inclination, as a mean to identify the factors supporting and hindering repair. To this end, an in-depth survey exploring factors influencing repair propensity for electrical and electronic goods was executed. Findings from 208 respondents affiliated with pro-environmental communities identify innovativeness and frugality traits as significant factors influencing repair propensity. Qualitative analysis has shown the significance of financial considerations in deciding to repair or replace, and how access to helping relationships alleviate most of the barriers to repair, including lack of access to repair shops and lack of knowledge and skills. The findings of this study provide much needed insight into repair behaviour. Furthermore, the insights provided will aid researchers and policy makers to develop appropriate interventions to support repair

Molecular Subtypes and Personalized Therapy in Metastatic Colorectal Cancer

Development of colorectal cancer occurs via a number of key pathways, with the clinicopathological features of specific subgroups being driven by underlying molecular changes. Mutations in key genes within the network of signalling pathways have been identified; however, therapeutic strategies to target these aberrations remain limited. As understanding of the biology of colorectal cancer has improved, this has led to a move toward broader genomic testing, collaborative research and innovative, adaptive clinical trial design. Recent developments in therapy include the routine adoption of wider mutational spectrum testing prior to use of targeted therapies and the first promise of effective immunotherapy for colorectal cancer patients. This review details current biomarkers in colorectal cancer for molecular stratification and for treatment allocation purposes, including open and planned precision medicine trials. Advances in our understanding, therapeutic strategy and technology will also be outlined

The development and productivity of a measure for identifying low language abilities in children aged 24 – 36 months

Acknowledgements First, we would like to acknowledge the leadership, mentorship and unparalleled contribution to the field of child language research of Professor James Law, OBE, who led this study. Professor Law passed away in October 2021. We also acknowledge the contribution of Professor Sue Roulstone, Caitlin Holme and Rose Watson in aspects of the wider study which contributed to the successful data collection in this study. We would like to express sincere thanks to all the practitioners and parents who gave their time, expertise, and insights in the workshop and codesign activities. The team also wish to acknowledge the role of Sheena Carr and Renvia Mason and colleagues at Public Health England and The Department for Education for their feedback on the original report. Funding The project was funded by the UK’s Department for Education in conjunction with Public Health England.Peer reviewedPublisher PD

Universal language development screening : comparative performance of two questionnaires

Acknowledgments The authors would like to acknowledge other members of the “Early Identification” team: Professor Sue Roulstone and Caitlin Holme from the Bristol Speech and Language Therapy Research Unit, Rose Watson from Newcastle University, and Sheena Carr and Renvia Mason from Public Health England for their support throughout the project. Finally, we would like to thank the children and their families who attended the clinics and the health visitors and speech and language therapists who were involved in collecting data for the project.Peer reviewedPublisher PD

Reduced selenium concentrations and glutathione peroxidase activity in preeclamptic pregnancies

Preeclampsia is a pregnancy-specific condition affecting 2-7% of women and a leading cause of perinatal and maternal morbidity and mortality. Preeclampsia may also predispose the fetus to increased risks of adult cardiovascular disease. Selenium, acting through the selenoprotein glutathione peroxidases, has critical roles in regulating antioxidant status. Recent reports implicate poor maternal selenium status as a nutritional factor predisposing the mother to preeclampsia but the fetus and placenta have not been studied in tandem. Measurement of selenium concentrations, expression and activity levels of glutathione peroxidase and markers of oxidative stress were performed on maternal and umbilical venous blood samples or the placenta from 27 normal pregnant, 25 preeclamptic and 22 healthy age-matched non-pregnant women. The results of this study revealed highly significant reductions in serum selenium concentrations and plasma glutathione peroxidase activity in pregnancy per se compared to non-pregnant controls. Moreover, these levels were further decreased in the preeclamptic mothers and babies compared to normal pregnancies. Umbilical venous selenium was particularly low (42.1±11.8 and 29.0 ± 9.9 mug/L; mean ±s.d.; P<0.05). Both mother and baby had significantly increased levels of markers for oxidative stress in the preeclamptic group. The placental glutathione peroxidase activity and immunohistochemical staining were also reduced in the preeclampsia placentae. Oxidative stress associated with preeclampsia may be a consequence of reduced antioxidant defence pathways specifically involving glutathione peroxidases, perhaps linked to reduced selenium availability. Reduced glutathione peroxidases could be associated with increased generation of toxic lipid peroxides contributing to the endothelial dysfunction and hypertension of preeclampsia

Through An Equity Lens: Illuminating The Relationships Among Social Inequities, Stigma And Discrimination, And Patient Experiences of Emergency Health Care

People who experience the greatest social inequities often have poor experiences in emergency departments (EDs) so that they are deterred from seeking care, leave without care complete, receive inadequate care, and/or return repeatedly for unre- solved problems. However, efforts to measure and monitor experiences of care rarely capture the experiences of people facing the greatest inequities, experiences of discrimination, or relationships among these variables. This analysis examined how patients’ experiences, including self-reported ratings of care, experiences of discrimination, and repeat visits vary with social and economic circumstances. Every consecutive person presenting to three diverse EDs was invited if/when they were able to consent; 2424 provided demographic and contact information; and 1692 (70%) completed the survey. Latent class analysis (LCA) using sociodemographic variables: age, gender, financial strain, employment, housing stability, English as first language, born in Canada, and Indigenous identity, indicated a six-class solution. Classes differed significantly on having regular access to primary care, reasons for the visit, and acuity. Classes also differed on self-reported discrimination every day and during their ED visit, ratings of ED care, and number of ED visits within the past six months. ED care can be improved through attention to how intersecting forms of structural disadvantage and inequities affect patient experiences

2017 State of the Commonwealth Report

This is the third State of the Commonwealth Report produced by the Center for Economic Analysis and Policy at Old Dominion University. The report is sponsored, in part, by ODU\u27s Strome College of Business. While the report represents the work of many people connected in various ways to the university, it does not constitute an official viewpoint of Old Dominion, its president, John R. Broderick, or the Board of Visitors. This report maintains the goal of stimulating thought and discussion that ultimately will make the Commonwealth of Virginia an even better place to live, work, and do business. We are proud of Virginia\u27s many successes, but realize it is possible to improve our performance. To do so, we must have accurate and objective information about where we are and a sound understanding of the policy options open to us