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Background and purposeAcute leptomeningeal collateral flow is vital for maintaining perfusion to penumbral tissue in acute ischemic stroke caused by large-vessel occlusion. In this study, we aimed to investigate the clinically available indicators of leptomeningeal collateral variability in embolic large-vessel occlusion.Materials and methodsAmong prospectively registered consecutive patients with acute embolic anterior circulation large-vessel occlusion treated with thrombectomy, we analyzed 108 patients admitted from January 2015 to December 2019 who underwent evaluation of leptomeningeal collateral status on pretreatment CTA. Clinical characteristics, extent of leukoaraiosis on MR imaging, embolic stroke subtype, time of imaging, occlusive thrombus characteristics, presenting stroke severity, and clinical outcome were collected. The clinical indicators of good collateral status (>50% collateral filling of the occluded territory) were analyzed using multivariate logistic regression analysis.ResultsGood collateral status was present in 67 patients (62%) and associated with independent functional outcomes at 3 months. Reduced leukoaraiosis (total Fazekas score, 0-2) was positively related to good collateral status (OR, 9.57; 95% CI, 2.49-47.75), while the cardioembolic stroke mechanism was inversely related to good collateral status (OR, 0.17; 95% CI, 0.02-0.87). In 82 patients with cardioembolic stroke, shorter thrombus length (OR, 0.91 per millimeter increase; 95% CI, 0.82-0.99) and reduced leukoaraiosis (OR, 5.79; 95% CI, 1.40-29.61) were independently related to good collateral status.ConclusionsAmong patients with embolic large-vessel occlusion, reduced leukoaraiosis, noncardiac embolism mechanisms including embolisms of arterial or undetermined origin, and shorter thrombus length in cardioembolism are indicators of good collateral flow.

Negar Hassani Besheli,1 Juul Verbakel,1 Maryam Hosseini,1 Lea Andrée,1 Ben Joosten,2 X Frank Walboomers,1 Alessandra Cambi,2 Fang Yang,1 Sander CG Leeuwenburgh1 1Department of Dentistry – Regenerative Biomaterials, Radboud Institute for Molecular Life Sciences, Radboudumc, Nijmegen, The Netherlands; 2Department of Cell Biology, Radboud Institute for Molecular Life Sciences, Radboudumc, Nijmegen, The NetherlandsCorrespondence: Sander CG Leeuwenburgh, Tel +31 6 15 40 9006, Fax +31 2 43 61 4657, Email sander.leeuwenburgh@radboudumc.nlIntroduction: There has recently been a surge of interest in mesoporous bioactive glass nanoparticles (MBGNs) as multi-functional nanocarriers for application in bone-reconstructive and -regenerative surgery. Their excellent control over their structural and physicochemical properties renders these nanoparticles suitable for the intracellular delivery of therapeutic agents to combat degenerative bone diseases, such as bone infection, or bone cancer. Generally, the therapeutic efficacy of nanocarriers strongly depends on the efficacy of their cellular uptake, which is determined by numerous factors including cellular features and the physicochemical characteristics of nanocarriers, particularly surface charge. In this study, we have systematically investigated the effect of the surface charge of MBGNs doped with copper as a model therapeutic agent on cellular uptake by both macrophages and pre-osteoblast cells involved in bone healing and bone infections to guide the future design of MBGN-based nanocarriers.Methods: Cu-MBGNs with negative, neutral, and positive surface charges were synthesized and their cellular uptake efficiency was assessed. Additionally, the intracellular fate of internalized nanoparticles along with their ability to deliver therapeutic cargo was studied in detail.Results: The results showed that both cell types internalized Cu-MBGNs regardless of their surface charge, indicating that cellular uptake of nanoparticles is a complex process influenced by multiple factors. This similarity in cellular uptake was attributed to the formation of a protein corona surrounding the nanoparticles when exposed to protein-rich biological media, which masks the original nanoparticle surface. Once internalized, the nanoparticles were found to mainly colocalize with lysosomes, exposing them to a more compartmentalized and acidic environment. Furthermore, we verified that Cu-MBGNs released their ionic components (Si, Ca, and Cu ions) in both acidic and neutral environments, leading to the delivery of these therapeutic cargos intracellularly.Conclusion: The effective internalization of Cu-MBGNs and their ability to deliver cargos intracellularly highlight their potential as intracellular delivery nanocarriers for bone-regenerative and -healing applications.Graphical Abstract: Keywords: intracellular delivery, nanocarrier, bioactive glass, copper, surface charge

Purpose: Universities have recognized their rich endowments in research, academic skills and facilities, as uniquely suited to finding "green" solutions. Moreover, the campus setting itself presents as a microcosm of greater society through which to investigate and test innovations. Thus, the "living lab" was born, a means of coupling sufficient resources and active stakeholders in the pursuit of practical, sustainable solutions. Much of the work to date, however, remains piecemeal, small-scale and disparate. This study aims to propose that the work of such labs must ultimately be directed, coordinated and integrated under a "university sustainability office," if they are to be ultimately effective. Design/methodology/approach: The research approach is twofold. In the first instance, a literature review charting the history and progress of living labs is reported, with emphasis of the university context. Second, a case study appraisal of Deakin University's initiatives in adopting and promoting sustainability through the living lab framework is undertaken. Findings: A main finding of this paper is that current efforts remain piecemeal and peripheral. If the apparent ambiguity regarding commitment is to be overcome, Deakin University should adopt measures as adopted by peer leaders in the field. Specifically, the setting up of a centralizing sustainability function bestowed with the capacity to coordinate university-wide living lab efforts, and at such a scale that substantial benefits transferable to greater society is generated. Originality/value: This paper stands out among previous studies in the field through facilitating a transition to living lab for other universities, where findings facilitate that progress and consider how the lessons learnt might inform the further evolution of university living lab initiatives.