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Abstract: Adsorption of serum proteins to the liposomal surface plays a critical role in liposome clearance from the blood. The aim of this study was to investigate the role of liposome-adsorbed serum proteins in the interaction of liposomes with hepatocytes. We analyzed the serum proteins adsorbing to the surface of differently composed small unilamellar liposomes during incubation with human or rat serum, and found that one protein, with a molecular weight of around 55 kDa, adsorbed in a large amount to negatively charged liposomes containing phosphatidylserine (PS) or phosphatidylglycerol (PG). The binding was dependent on the liposomal charge density. The ∼55-kDa protein was identified as β2-glycoprotein I (β2GPI) by Western blotting. Despite the high affinity of β2GPI for strongly negatively charged liposomes, in vitro uptake and binding experiments with isolated rat hepatocytes, Kupffer cells or liver endothelial cells, and with HepG2 cells showed no enhancing effect of this protein on the association of negatively charged liposomes with any of these cells. On the contrary, an inhibitory effect was observed. We conclude that despite abundant adsorption to negatively charged liposomes, β2GP1 inhibits, rather than enhances, liposome uptake by liver cells. [Copyright &y& Elsevier]

Introduction: The introduction of-or the transition to-a new electronic health record system (EHR) places an unrecognized burden on health care providers in our ever-changing health care environment of increased mandates, increased overhead, and reduced reimbursement to practice medicine., Purpose: The purpose of this study was to track the non-reimbursed time investment required for 6 providers from an independent spine surgery practice after a hospital system independently decided to transition to a new EHR system., Results: Between the 6 providers of the practice, 266 hours of required classroom time, in-person training, and video and phone call teaching sessions had to be completed to become "proficient" so that clinical utilization of the system for in-patient care was certified by the hospital trainers and the EHR company., Conclusions: The burdens associated with the introduction of mandatory EHRs are putting tremendous pressure on providers from a time commitment perspective. This detracts from patient care during that time and deserves to be compensated for by the EHR companies that extract billions of dollars from both federal and private insurers' health care budgets., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The accurate and safe positioning of cervical pedicle screws is crucial. While augmented reality (AR) use in spine surgery has previously demonstrated clinical utility in the thoracolumbar spine, its technical feasibility in the cervical spine remains less explored., Purpose: The objective of this study was to assess the precision and safety of AR-assisted pedicle screw placement in the cervical spine., Study Design: In this experimental study, 5 cadaveric cervical spine models were instrumented from C3 to C7 by 5 different spine surgeons. The navigation accuracy and clinical screw accuracy were evaluated., Methods: Postprocedural CT scans were evaluated for clinical accuracy by 2 independent neuroradiologists using the Gertzbein-Robbins scale. Technical precision was assessed by calculating the angular trajectory (°) and linear screw tip (mm) deviations in the axial and sagittal planes from the virtual pedicle screw position as recorded by the AR-guided platform during the procedure compared to the actual pedicle screw position derived from postprocedural imaging., Results: A total of forty-one pedicle screws were placed in 5 cervical cadavers, with each of the 5 surgeons navigating at least 7 screws. Gertzbein-Robbins grade of A or B was achieved in 100% of cases. The mean values for tip and trajectory errors in the axial and sagittal planes between the virtual versus actual position of the screws was less than 3 mm and 30°, respectively (p<.05). None of the cervical screws violated the cortex by more than 2 mm or displaced neurovascular structures., Conclusions: AR-assisted cervical pedicle screw placement in cadavers demonstrated clinical accuracy comparable to existing literature values for image-guided navigation methods for the cervical spine., Clinical Significance: This study provides technical and clinical accuracy data that supports clinical trialing of AR-assisted subaxial cervical pedicle screw placement., Competing Interests: Declarations of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Biomaterial-associated infection (BAI) is considered a unique infection due to the presence of a biomaterial yielding frustrated immune-cells, ineffective in clearing local micro-organisms. The involvement of surface-adherent/surface-adapted micro-organisms in BAI, logically points to biomaterial surface-modifications for BAI-control. Biomaterial surface-modification is most suitable for prevention before adhering bacteria have grown into a mature biofilm, while BAI-treatment is virtually impossible through surface-modification. Hundreds of different surface-modifications have been proposed for BAI-control but few have passed clinical trials due to the statistical near-impossibility of benefit-demonstration. Yet, no biomaterial surface-modification forwarded, is clinically embraced. Collectively, this leads us to conclude that surface-modification is a dead-end road. Accepting that BAI is, like most human infections, due to surface-adherent biofilms (though not always to a foreign material), and regarding BAI as a common infection, opens a more-generally-applicable and therewith easier-to-validate road. Pre-clinical models have shown that stimuli-responsive nano-antimicrobials and antibiotic-loaded nanocarriers exhibit prolonged blood-circulation times and can respond to a biofilm's micro-environment to penetrate and accumulate within biofilms, prompt ROS-generation and synergistic killing with antibiotics of antibiotic-resistant pathogens without inducing further antimicrobial-resistance. Moreover, they can boost frustrated immune-cells around a biomaterial reducing the importance of this unique BAI-feature. Time to start exploring the nano-road for BAI-control., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Necrotizing enterocolitis (NEC) is a life-threatening inflammatory disease. Its onset might be triggered by Toll-Like Receptor 4 (TLR4) activation via bacterial lipopolysaccharide (LPS). We hypothesize that a deficiency of intestinal alkaline phosphatase (IAP), an enzyme secreted by enterocytes that dephosphorylates LPS, may contribute to NEC development., Methods: In this prospective pilot study, we analyzed intestinal resection specimens from surgical NEC patients, and from patients undergoing Roux-Y reconstruction for hepatobiliary disease as controls. We assessed IAP activity via enzymatic stainings and assays and explored IAP and TLR4 co-localization through immunofluorescence., Results: The study population consisted of five NEC patients (two Bell's stage IIb and three-stage IIIb, median (IQR) gestational age 25 (24-28) weeks, postmenstrual age at diagnosis 28 (26-31) weeks) and 11 controls (unknown age). There was significantly lower IAP staining in NEC resection specimens [49 (41-50) U/g of protein] compared to controls [115 (76-144), P  = 0.03]. LPS-dephosphorylating activity was also lower in NEC patients [0.06 (0-0.1)] than in controls [0.3 (0.2-0.5), P  = 0.003]. Furthermore, we observed colocalization of IAP and TLR4 in NEC resection specimens., Conclusion: This study suggests a significantly lower IAP level in resection specimens of NEC patients compared to controls. This lower IAP activity suggests a potential role of IAP as a protective agent in the gut, which needs further confirmation in larger cohorts., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Martins, Hulscher, Timmer, Kooi and Poelstra.)