Autologous chondrocyte implantation-derived synovial fluids display distinct responder and non-responder proteomic profiles

Hulme, Charlotte H. & Wilson, Emma L. - Equal contributorsBackground Autologous chondrocyte implantation (ACI) can be used in the treatment of focal cartilage injuries to prevent the onset of osteoarthritis (OA). However, we are yet to understand fully why some individuals do not respond well to this intervention. Identification of a reliable and accurate biomarker panel that can predict which patients are likely to respond well to ACI is needed in order to assign the patient to the most appropriate therapy. This study aimed to compare the baseline and mid-treatment proteomic profiles of synovial fluids (SFs) obtained from responders and non-responders to ACI. Methods SFs were derived from 14 ACI responders (mean Lysholm improvement of 33 (17–54)) and 13 non-responders (mean Lysholm decrease of 14 (4–46)) at the two stages of surgery (cartilage harvest and chondrocyte implantation). Label-free proteome profiling of dynamically compressed SFs was used to identify predictive markers of ACI success or failure and to investigate the biological pathways involved in the clinical response to ACI. Results Only 1 protein displayed a ≥2.0-fold differential abundance in the preclinical SF of ACI responders versus non-responders. However, there is a marked difference between these two groups with regard to their proteome shift in response to cartilage harvest, with 24 and 92 proteins showing ≥2.0-fold differential abundance between Stages I and II in responders and non-responders, respectively. Proteomic data has been uploaded to ProteomeXchange (identifier: PXD005220). We have validated two biologically relevant protein changes associated with this response, demonstrating that matrix metalloproteinase 1 was prominently elevated and S100 calcium binding protein A13 was reduced in response to cartilage harvest in non-responders. Conclusions The differential proteomic response to cartilage harvest noted in responders versus non-responders is completely novel. Our analyses suggest several pathways which appear to be altered in non-responders that are worthy of further investigation to elucidate the mechanisms of ACI failure. These protein changes highlight many putative biomarkers that may have potential for prediction of ACI treatment success

Encountering the Earth: political geological futures?

This chapter summarises some of the key ideas that have emerged in this volume, and seeks to do so by looking forward to future research. What kinds of research might follow on from the work in this book and elsewhere in the published literature? What themes are starting to emerge? The chapter initially reflects on the three sections that were selected for this volume and then suggests a number of other cross-cutting themes that span multiple disciplines and that will continue to develop as political geology moves forwards. These relate to geopolitics, the Anthropocene, histories and cartographies, technologies and the physical sciences more explicitly. Ultimately, the chapter aims to provoke debate and discussion about ways in which political geological studies can develop and influence policy, politics and philosophy

Identification of patient subgroups and risk factors for persistent arm/shoulder pain following breast cancer surgery

PURPOSE: In this prospective, longitudinal study, we extend our findings on persistent breast pain in patients (n=398) following breast cancer surgery and evaluate the prevalence and characteristics of persistent pain in the arm/shoulder In addition, differences in the severity of common symptoms and quality of life outcomes measured prior to surgery, among the arm pain classes, were evaluated. METHODS AND SAMPLE: Patients were recruited from Breast Care Centers located in a Comprehensive Cancer Center, two public hospitals, and four community practices. Patients were assessed prior to and monthly for six months following breast cancer surgery. RESULTS: Using growth mixture modeling, patients were classified into no (41.6%), mild (23.6%), and moderate (34.8%) arm pain classes based on ratings of worst arm/shoulder pain. Compared to the no pain class, patients in the moderate pain class were significantly younger, had a higher body mass index, and were more likely to report preoperative breast pain and swelling in the affected breast. In addition, patients in the moderate pain class reported higher levels of depression, anxiety, and sleep disturbance than the no pain class. CONCLUSIONS: Findings suggest that approximately 35% of women experience persistent levels of moderate arm/shoulder pain in the first six months following breast cancer surgery. Moderate arm/shoulder pain is associated with clinically meaningful decrements in functional status and quality of life