Microvessels of the blood-brain barrier (BBB) regulate transport into the brain. The highly specialized brain microvascular endothelial cells, a major component of the BBB, express tight junctions and efflux transporters which regulate paracellular and transcellular permeability. However, most existing models of BBB microvessels fail to exhibit physiological barrier function. Here, using (iPSC)-derived human brain microvascular endothelial cells (dhBMECs) within templated type I collagen channels we mimic the cylindrical geometry, cell-extracellular matrix interactions, and shear flow typical of human brain post-capillary venules. We characterize the structure and barrier function in comparison to non-brain-specific microvessels, and show that dhBMEC microvessels recapitulate physiologically low solute permeability and quiescent endothelial cell behavior. Transcellular permeability is increased two-fold using a clinically relevant dose of a p-glycoprotein inhibitor tariquidar, while paracellular permeability is increased using a bolus dose of hyperosmolar agent mannitol. Lastly, we show that our human BBB microvessels are responsive to inflammatory cytokines via upregulation of surface adhesion molecules and increased leukocyte adhesion, but no changes in permeability. Human iPSC-derived blood-brain barrier microvessels support quantitative analysis of barrier function and endothelial cell dynamics in quiescence and in response to biologically- and clinicallyrelevant perturbations.

As the majority of therapeutic agents do not cross the blood–brain barrier (BBB), transient BBB opening (BBBO) is one strategy to enable delivery into the brain for effective treatment of CNS disease. Intra-arterial infusion of the hyperosmotic agent mannitol reversibly opens the BBB; however, widespread clinical use has been limited due to the variability in outcomes. The current model for mannitol-induced BBBO assumes a transient but homogeneous increase in permeability; however, the details are poorly understood. To elucidate the mechanism of hyperosmotic opening at the cellular level, we developed a tissue-engineered microvessel model using stem cell-derived human brain microvascular endothelial cells (BMECs) perturbed with clinically relevant mannitol doses. This model recapitulates physiological shear stress, barrier function, microvessel geometry, and cell-matrix interactions. Using live-cell imaging, we show that mannitol results in dose-dependent and spatially heterogeneous increases in paracellular permeability through the formation of transient focal leaks. Additionally, we find that the degree of BBB opening and subsequent recovery is modulated by treatment with basic fibroblast growth factor. These results show that tissue-engineered BBB models can provide insight into the mechanisms of BBBO and hence improve the reproducibility of hyperosmotic therapies for treatment of CNS disease.

Multi-agent teaming achieves better performance when there is communication among participating agents allowing them to coordinate their actions for maximizing shared utility. However, when collaborating a team of agents with different action and observation spaces, information sharing is not straightforward and requires customized communication protocols, depending on sender and receiver types. Without properly modeling such heterogeneity in agents, communication becomes less helpful and could even deteriorate the multi-agent cooperation performance. We propose heterogeneous graph attention networks, called HetNet, to learn efficient and diverse communication models for coordinating heterogeneous agents towards accomplishing tasks that are of collaborative nature. We propose a Multi-Agent Heterogeneous Actor-Critic (MAHAC) learning paradigm to obtain collaborative per-class policies and effective communication protocols for composite robot teams. Our proposed framework is evaluated against multiple baselines in a complex environment in which agents of different types must communicate and cooperate to satisfy the objectives. Experimental results show that HetNet outperforms the baselines in learning sophisticated multi-agent communication protocols by achieving ∼10% improvements in performance metrics.

Objective The COVID-19 pandemic has dramatically changed healthcare, forcing providers to adopt and implement telehealth technology to provide continuous care for their patients. Amid this rapid transition from in-person to remote visits, differences in telehealth utilization have arisen among neurosurgical subspecialties. In this study, we analyze the impact of telehealth on neurosurgical healthcare delivery during the COVID-19 pandemic at our institution and highlight differences in telehealth utilization across different neurosurgical subspecialties. Methods To quantify differences in telehealth utilization, we analyzed all outpatient neurosurgery visits at a single academic institution. Internal surveys were administered to neurosurgeons and to patients to determine both physician and patient satisfaction with telehealth visits. Patient Likelihood-to-Recommend Press Ganey scores were also evaluated. Results There was a decrease in outpatient visits during the COVID-19 pandemic in all neurosurgical subspecialties. Telehealth adoption was higher in spine, tumor, and interventional pain than in functional, peripheral nerve, or vascular neurosurgery. Neurosurgeons agreed that telehealth was an efficient (92%) and effective (85%) methodology; however, they noted it was more difficult to evaluate and bond with patients. The majority of patients were satisfied with their video visits and would recommend video visits over in-person visits. Conclusions During the COVID-19 pandemic, neurosurgical subspecialties varied in adoption of telehealth, which may be due to the specific nature of each subspecialty and their necessity to perform in-person evaluations. Telehealth visits will likely continue after the pandemic as they can improve clinical efficiency; overall both patients and physicians are satisfied with healthcare delivery over video.

BACKGROUND Vertebral artery injury is a devastating potential complication of C1–2 posterior fusion. Intraoperative navigation can reduce the risk of neurovascular complications and improve screw placement accuracy. However, the use of intraoperative computed tomography (CT) increases radiation exposure and operative time, and it is unable to image vascular structures. The Machine-vision Image Guided Surgery (MvIGS) system uses optical topographic imaging and machine vision software to rapidly register using preoperative imaging. The authors presented the first report of intraoperative navigation with MvIGS registered using a preoperative CT angiogram (CTA) during C1–2 posterior fusion. OBSERVATIONS MvIGS can register in seconds, minimizing operative time with no additional radiation exposure. Furthermore, surgeons can better adjust for abnormal vertebral artery anatomy and increase procedure safety. LESSONS CTA-guided navigation generated a three-dimensional reconstruction of cervical spine anatomy that assisted surgeons during the procedure. Although further study is needed, the use of intraoperative MvIGS may reduce the risk of vertebral artery injury during C1–2 posterior fusion.