Controlled Release of Vancomycin and Tigecycline from an Orthopaedic Implant Coating Prevents Staphylococcus aureus Infection in an Open Fracture Animal Model.

Introduction:Treatment of open fractures routinely involves multiple surgeries and delayed definitive fracture fixation because of concern for infection. If implants were made less susceptible to infection, a one-stage procedure with intramedullary nailing would be more feasible, which would reduce morbidity and improve outcomes. Methods:In this study, a novel open fracture mouse model was developed using Staphylococcus aureus (S. aureus) and single-stage intramedullary fixation. The model was used to evaluate whether implants coated with a novel "smart" polymer coating containing vancomycin or tigecycline would be colonized by bacteria in an open fracture model infected with S. aureus. In vivo bioluminescence, ex vivo CFUs, and X-ray images were evaluated over a 42-day postoperative period. Results:We found evidence of a markedly decreased bacterial burden with the local release of vancomycin and tigecycline from the PEG-PPS polymer compared to polymer alone. Vancomycin was released in a controlled fashion and maintained local drug concentrations above the minimum inhibition concentration for S. aureus for greater than 7 days postoperatively. Bacteria were reduced 139-fold from implants containing vancomycin and undetected from the bone and soft tissue. Tigecycline coatings led to a 5991-fold reduction in bacteria isolated from bone and soft tissue and 15-fold reduction on the implants compared to polymer alone. Antibiotic coatings also prevented osteomyelitis and implant loosening as observed on X-ray. Conclusion:Vancomycin and tigecycline can be encapsulated in a polymer coating and released over time to maintain therapeutic levels during the perioperative period. Our results suggest that antibiotic coatings can be used to prevent implant infection and osteomyelitis in the setting of open fracture. This novel open fracture mouse model can be used as a powerful in vivo preclinical tool to evaluate and optimize the treatment of open fractures before further studies in humans

Transforming Nanomaterial Synthesis with Flow Chemistry

Microfluidic methods for the synthesis of nanomaterials allow the generation of high-quality products with outstanding structural, electronic and optical properties. At a fundamental level, this is engendered by the ability to control both heat and mass transfer in a rapid and precise manner, but also by the facile integration of in-line characterization tools and machine learning algorithms. Such integrated platforms provide for exquisite control over material properties during synthesis, accelerate the optimization of electronic and optical properties and bestow new insights into the optoelectronic properties of nanomaterials. Herein, we present a brief perspec-tive on the role that microfluidic technologies can play in nanomaterial synthesis, with a particular focus on recent studies that incorporate in-line optical characterization and machine learning. We also consider the importance and challenges associated with integrating additional functional components within experimental workflows and the upscaling of microfluidic platforms for production of industrial-scale quantities of nanomaterials

Anatomical Ablation of the Atrioventricular Node

\ua9 The Author(s) 2024. Background: Atrioventricular (AV) conduction ablation has been achieved by targeting the area of penetration of the conduction axis as defined by recording a His bundle potential. Ablation of the His bundle may reduce the possibility of a robust junctional escape rhythm. It was hypothesised that specific AV nodal ablation is feasible and safe. Methods: The anatomical position of the AV node in relation to the site of penetration of the conduction axis was identified as described in dissections and histological sections of human hearts. Radiofrequency (RF) ablation was accomplished based on the anatomical criteria. Results: Specific anatomical ablation of the AV node was attempted in 72 patients. Successful AV nodal ablation was accomplished in 63 patients (87.5%), following 60 minutes (IQR 50–70 minutes) of procedure time, 3.4 minutes (IQR 2.4–5.5 minutes) of fluoroscopy time, and delivery of 4 (IQR 3–6) RF lesions. Αn escape rhythm was present in 45 patients (71%), and the QRS complex was similar to that before ablation in all 45 patients. Atropine was administered in six patients after the 10-min waiting period and did not result in restoration of conduction. In nine patients, AV conduction could not be interrupted, and AV block was achieved with ablation of the His after delivery of 12 (IQR 8–15) RF lesions. No cases of sudden death were encountered, and all patients had persistent AV block during a median 10.5 months (IQR 5–14 months) of follow-up. Conclusion: Anatomical ablation of the AV node is feasible and safe, and results in an escape rhythm similar to that before ablation

ARIADNE - A novel optical LArTPC: technical design report and initial characterisation using a secondary beam from the CERN PS and cosmic muons

ARIADNE is a 1-ton (330 kg fiducial mass) dual-phase liquid argon (LAr) time projection chamber (TPC) featuring a novel optical readout. Four electron-multiplying charge-coupled device (EMCCD) cameras are mounted externally, and these capture the secondary scintillation light produced in the holes of a thick electron gas multiplier (THGEM). Track reconstruction using this novel readout approach is demonstrated. Optical readout has the potential to be a cost effective alternative to charge readout in future LArTPCs. In this paper, the technical design of the detector is detailed. Results of mixed particle detection using a secondary beam from the CERN PS (representing the first ever optical images of argon interactions in a dual-phase LArTPC at a beamline) and cosmic muon detection at the University of Liverpool are also presented.Comment: 58 pages, 40 figures. Changes from previous version based on pre-publication review: improved quality of various figures, improved clarity of some definitions and reduced longer sentences for better readability, fixed typos and formatting error

Culprit-Vessel Percutaneous Coronary Intervention Followed by Contralateral Angiography Versus Complete Angiography in Patients With St-Elevation Myocardial Infarction

In patients with ST-elevation myocardial infarction, delay in door-to-balloon time strongly increases mortality rates. To our knowledge, no randomized studies to date have focused on reducing delays within the catheterization laboratory. We performed a retrospective analysis of all patients who presented with ST-elevation myocardial infarction at our institution from July 2006 through June 2010, looking primarily at time differences between percutaneous coronary intervention in the culprit vessel on the basis of ECG criteria, followed by contralateral angiography (Group 1), versus complete coronary angiography followed by culprit-vessel percutaneous intervention (Group 2). There were 49 patients in Group 1 and 57 patients in Group 2. No major differences in baseline characteristics were observed between the groups, except a higher prevalence of diabetes mellitus in Group 2. There was a statistically significant difference between Groups 1 and 2 in door-to-balloon time (median and interquartile range, 75 min [61–89] vs 87 min [70–115], P=0.03, respectively) and access-to-balloon time (12 min [9–18] vs 21 min [11–33], P=0.0006, respectively). Five Group 1 patients (10%) with inferior myocardial infarction had a contralateral culprit vessel. There were no differences in mortality rate or ejection fraction at the median 1-year follow-up. Four patients in Group 1 and 3 patients in Group 2 were referred for coronary artery bypass grafting after percutaneous intervention. This study suggests that performing culprit-vessel percutaneous intervention on the basis of electrocardiographic criteria, followed by angiography in patients with anterior ST-elevation myocardial infarction, might be the preferred approach, given the door-to-balloon time that is saved

Advanced database mining integrating sequence and structure bioinformatics with microfluidics challenges enzyme engineering

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The fate and behavior of selected endocrine disrupting chemicals in full scale wastewater and sludge treatment unit processes

Endocrine disrupting chemicals are discharged into the environment mainly through wastewater treatment processes. There is a need for better understanding of the fate of these compounds in the unit processes of treatment plant to optimize their removal. The fate of oestrone, 17β-estradiol, 17α-ethinyestradiol and nonylphenol in the unit processes of full scale wastewater treatment plants in the UK, including activated sludge plant, oxidation ditch, biofilter and rotating biological contractor were investigated. The overall removal efficiencies of all the compounds ranged from 41 % to 100 %. The removals were predominantly during the secondary biological treatment with the rates of removal related to the nitrification rates and the sludge age. The removal efficiency of the treatment processes were in the order activated sludge > oxidation ditch > biofilter > rotating biological contractors. Activated sludge plant configured for biological nutrient removal showed better removal of the endocrine disrupting chemicals compared to conventional activated sludge plant effluents. Tertiary treatment was also significant in the removal process through solids removal. Overall mechanisms of removal were biodegradation and sorption unto sludge biomass. Phytoremediation was also significant in the removal processes. The endocrine disrupting chemicals persisted in the anaerobic sludge digestion process with percentage removals ranging fro 10-48 %. Sorption of the endocrine disrupting chemicals onto the sludge increased with increasing values for the partitioning coefficients and the organic carbon contents of the sludge

International Consensus Based Review and Recommendations for Minimum Reporting Standards in Research on Transcutaneous Vagus Nerve Stimulation (Version 2020).

Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation (tVNS) across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation(VNS) and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice

A Mouse Model of Post-Arthroplasty Staphylococcus aureus Joint Infection to Evaluate In Vivo the Efficacy of Antimicrobial Implant Coatings

Post-arthroplasty infections represent a devastating complication of total joint replacement surgery, resulting in multiple reoperations, prolonged antibiotic use, extended disability and worse clinical outcomes. As the number of arthroplasties in the U.S. will exceed 3.8 million surgeries per year by 2030, the number of post-arthroplasty infections is projected to increase to over 266,000 infections annually. The treatment of these infections will exhaust healthcare resources and dramatically increase medical costs.To evaluate novel preventative therapeutic strategies against post-arthroplasty infections, a mouse model was developed in which a bioluminescent Staphylococcus aureus strain was inoculated into a knee joint containing an orthopaedic implant and advanced in vivo imaging was used to measure the bacterial burden in real-time. Mice inoculated with 5x10(3) and 5x10(4) CFUs developed increased bacterial counts with marked swelling of the affected leg, consistent with an acute joint infection. In contrast, mice inoculated with 5x10(2) CFUs developed a low-grade infection, resembling a more chronic infection. Ex vivo bacterial counts highly correlated with in vivo bioluminescence signals and EGFP-neutrophil fluorescence of LysEGFP mice was used to measure the infection-induced inflammation. Furthermore, biofilm formation on the implants was visualized at 7 and 14 postoperative days by variable-pressure scanning electron microscopy (VP-SEM). Using this model, a minocycline/rifampin-impregnated bioresorbable polymer implant coating was effective in reducing the infection, decreasing inflammation and preventing biofilm formation.Taken together, this mouse model may represent an alternative pre-clinical screening tool to evaluate novel in vivo therapeutic strategies before studies in larger animals and in human subjects. Furthermore, the antibiotic-polymer implant coating evaluated in this study was clinically effective, suggesting the potential for this strategy as a therapeutic intervention to combat post-arthroplasty infections