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A series of 6-min microgravity combustion experiments of opposed-flow flame spread over thermally thick PMMA has been conducted to extend data previously reported at high opposed flows to almost two decades lower in flow. The effect of flow velocity on flame spread shows a square-root power-law dependence rather than the linear dependence predicted by thermal theory. The experiments demonstrate that opposed-flow flame spread is viable to very low velocities and is more robust than expected from the two-dimensional numerical model, which predicts that, at very low velocities (< 5 cm/s), flame spread rates fall off more rapidly as flow is reduced. It is hypothesized that the enhanced flame spread observed in the experiments may be due to three- dimensional hydrodynamic effects, which are not included in the zero- gravity, two-dimensional hydrodynamic model. The effect of external irradiation was also studied and its effects were found to be more complex than the model predicted over the 0-2 W/cm² range. In the experiments, the flame compensated for the increased irradiation by stabilizing farther from the surface. A surface energy balance reveals that the imposed flux was at least partially offset by a reduced conductive flux from the increased standoff distance so that the effect on flame spread was weaker than anticipated. [ABSTRACT FROM AUTHOR]

Examines the functional role of paraventricular nucleus (PVN). Result of chemical stimulation of neurons within the PVN; Production of activation pattern for cardiovascular neurons by chemical activation of PVN neurons; Importance of PVN connections with the rostral ventrolateral medulla and spinal cord.

Given the hierarchical nature of bone and bone interfaces, osseointegration, namely the formation of a direct bone-implant contact, is best evaluated using a multiscale approach. However, a trade-off exists between field of view and spatial resolution, making it challenging to image large volumes with high resolution. In this study, we combine established electron microscopy techniques to probe bone-implant interfaces at the microscale and nanoscale with plasma focused ion beam-scanning electron microscopy (PFIB-SEM) tomography to evaluate osseointegration at the mesoscale. This characterization workflow is demonstrated for bone response to an additively manufactured Ti-6Al-4V implant which combines engineered porosity to facilitate bone ingrowth and surface functionalization via genistein, a phytoestrogen, to counteract bone loss in osteoporosis. SEM demonstrated new bone formation at the implant site, including in the internal implant pores. At the nanoscale, scanning transmission electron microscopy and energy-dispersive X-ray spectroscopy confirmed the gradual nature of the bone-implant interface. By leveraging mesoscale analysis with PFIB-SEM tomography that captures large volumes of bone-implant interface with nearly nanoscale resolution, the presence of mineral ellipsoids varying in size and orientation was revealed. In addition, a well-developed lacuno-canalicular network and mineralization fronts directed both towards the implant and away from it were highlighted., (© 2024. The Author(s).)

Opioid use after kidney transplant has been associated with an increased risk of death and graft loss. Several transplant centers have reported reductions in opioid use using multimodal analgesia and education. This study evaluated the impact of an opioid minimization protocol on inpatient opioid use and opioid prescribing on discharge. This was a single-center, retrospective study of adult kidney recipients transplanted from October 2021 to July 2022. Patients on chronic opioids prior to transplant were excluded. The protocol included an intra-operative ultrasound-guided lateral transversus abdominis plane (TAP) block combined with scheduled non-opioid analgesics and tramadol as needed. Acetaminophen 1000 mg and gabapentin 300 mg were given 1 hour prior to the procedure and continued three times daily after transplant. The gabapentin dose was reduced for patients with renal impairment. Additional analgesics including opioids could be added for uncontrolled pain. We hypothesized the protocol would decrease total inpatient morphine milligram equivalents (MMEs) and opioid prescribing on discharge. Fifty-nine post-protocol patients were compared to 52 pre-protocol patients. After the protocol, there was a significant decrease in total inpatient MMEs per day administered and no patient-controlled analgesia (PCA) devices were required. In alignment with the protocol, there was a significant increase in the use of TAP blocks, acetaminophen, gabapentin, and lidocaine patches. While opioid use was lowest in post-protocol patients who received TAP blocks, significant reductions in MMEs per day were still seen in those post-protocol who did not receive TAP blocks. Opioid prescribing at the time of discharge decreased significantly after protocol. No difference was seen in patient-reported pain scores, return to operating room, readmission within 30 days, or length of stay. The use of scheduled acetaminophen and gabapentin with or without a TAP block allowed the elimination of PCA devices and led to significant minimizations in both inpatient opioid use and opioid prescribing on discharge., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Bova et al.)

The additive manufacturing of titanium into porous geometries offers a means to generate low-stiffness endosseous implants with a greater surface area available for osseointegration. In this work, selective laser melting was used to produce gyroid-based scaffolds with a uniform pore size of 300 μm or functionally graded pore size from 600 μm to 300 μm. Initial in vitro assessment with Saos-2 cells showed favourable cell proliferation at pore sizes of 300 and 600 μm. Following implantation into rabbit tibiae, early histological observations at four weeks indicated some residual inflammation alongside neovessel infiltration into the scaffold interior and some early apposition of mineralized bone tissue. At twelve weeks, both scaffolds were filled with a mixture of adipocyte-rich marrow, micro-capillaries, and mineralized bone tissue. X-ray microcomputed tomography showed a higher bone volume fraction (BV/TV) and percentage of bone-implant contact (BIC) in the implants with 300 μm pores than in the functionally graded specimens. In functionally graded specimens, localized BV/TV measurement was observed to be higher in the innermost region containing smaller pores (estimated at 300-400 μm) than in larger pores at the implant exterior. The unit cell topology of the porous implant was also observed to guide the direction of bone ingrowth by conducting along the implant struts. These results suggest that in vivo experimentation is necessary alongside parametric optimization of functionally graded porous implants to predict short-term and long-term bone apposition., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kathryn Grandfield reports financial support was provided by Natural Sciences and Engineering Research Council of Canada. Kathryn Grandfield reports financial support was provided by Foshan Science and Technology Innovation Project. Anna Cecilia do Nascimento Pereira reports financial support was provided by State of Sao Paulo Research Foundation., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The prevention of bacterial colonization and the stimulation of osseointegration are two major requirements for bone-interfacing materials to reduce the incidence of complications and promote the restoration of the patient's health. The present investigation developed an effective, two-step functionalization of 3D printed scaffolds intended for bone-interfacing applications using a simple polydopamine (PDA) dip-coating method followed by the formation of silver nanoparticles (AgNPs) after a second coating step in silver nitrate. 3D printed polymeric substrates coated with a ∼20 nm PDA layer and 70 nm diameter AgNPs proved effective in hindering Staphylococcus aureus biofilm formation, with a 3000-8000-fold reduction in the number of bacterial colonies formed. The implementation of porous geometries significantly accelerated osteoblast-like cell growth. Microscopy characterization further elucidated homogeneity, features, and penetration of the coating inside the scaffold. A proof-of-concept coating on titanium substrates attests to the transferability of the method to other materials, broadening the range of applications both in and outside the medical sector. The antibacterial efficiency of the coating is likely to lead to a decrease in the number of bacterial infections developed after surgery in the presence of these coatings on prosthetics, thus translating to a reduction in revision surgeries and improved health outcomes.

(1) Background: The objective of this study was to evaluate the morphometry of peri-implant bone tissue in orchiectomized rats, treated with vitamin D isolated or associated with teriparatide. (2) Methods: 24 rats were divided into 4 groups: ORQ-orchiectomy, without drug treatment, ORQ+D-orchiectomy, treated with vitamin D, ORQTERI-orchiectomy, treated with teriparatide and ORQTERI+D-orchiectomy, treated with teriparatide + vitamin D. Each animal received an implant in the tibial metaphysis. Euthanasia occurred 60 days after implant surgery. Computed microtomography (micro-CT) was performed to evaluate the parameters of volume and percentage of bone volume (BV, BV/TV), trabecular thickness (Tb.Th), number and separation of trabeculae (Tb.N, Tb.Sp) and percentage of total porosity (Po-tot). Data were subjected to 1-way ANOVA and Tukey post-test, with a significance level of 5%. (3) Results: For the parameters BV, BV/TV, Tb.Th, the ORQTERI+D group showed the highest values in relation to the other groups and for Po-tot, the lowest values were for ORQTERI+D. For Tb.Sp and Tb.N, there was no statistically significant difference when comparing intragroup results ( p > 0.05). (4) Conclusions: It was possible to conclude that treatment with vitamin D associated with teriparatide increases bone volume and improves bone quality.

The US Food and Drug Administration (FDA) guidance describes how pharmacodynamic (PD) biomarkers can be used to address residual uncertainty and demonstrate no clinically meaningful differences between a proposed biosimilar and its reference product without relying on clinical efficacy end point(s). Pilot studies and modeling can inform dosing for such PD studies. To that end, we conducted a randomized, double-blinded, placebo-controlled, single-dose, parallel-arm clinical study in healthy participants to evaluate approaches to address information gaps, inform best practices for analysis of biomarker samples and study results, and apply emerging technologies in biomarker characterization. Seventy-two healthy participants (n = 8 per arm) received either placebo or 1 of 4 doses of the interleukin-5 inhibitors mepolizumab (3-24 mg) or reslizumab (0.1-0.8 mg/kg). A clinical study using doses lower than approved therapeutic doses was combined with modeling and simulation to evaluate the dose-response relationship of the biomarker eosinophils. There was no dose-response relationship for eosinophil counts due to variability, although the mepolizumab 24 mg and reslizumab 0.8 mg/kg doses showed clear effects. Published indirect-response models were used to explore eosinophil data across doses from this study and the unstudied therapeutic doses. Simulations were used to calculate typical PD metrics, such as baseline-adjusted area under the effect curve and maximum change from baseline. The simulation results demonstrate sensitivity of eosinophils as a PD biomarker and indicate doses lower than the approved doses would have PD responses overlapping with variability in the placebo arm. The simulation results further highlight the utility of model-based approaches in supporting use of PD biomarkers in biosimilar development., (Published 2022. This article is a U.S. Government work and is in the public domain in the USA.)

The osseointegration of metallic implants is reliant on a cascade of molecular interactions and the delivery of macromolecules to the implant environment that occurs before substantial bone formation. Early blood vessel formation is a requisite first step in the healing timeline for osteoid formation, where vascular development can be accelerated as a result of controlled hypoxic conditioning. In this study, alginate-derived xerogel films containing varied concentrations of disodium succinate salt which has been shown to induce pseudohypoxia (short-term hypoxic effects while maintaining an oxygenated environment) were developed. Xerogels were characterized for their morphology, succinate release over time and cellular response with osteoblast-mimicking Saos-2 and human umbilical vein endothelial cells (HUVEC). Scanning electron microscopy revealed a multiscale topography that may favour osseointegration and alamarBlue assays indicated no cytotoxic effects during in vitro proliferation of Saos-2 cells. pH measurements of eluted succinate reach 95 % of peak value after 7 h of immersion for all gels containing 10 mM of succinate or less, and 60 % within the first 40 min. In vitro exposure of HUVECs to succinate-conditioned media increased the net concentration of total proteins measured by bicinchoninic acid (BCA) assay and maintains stable vascular endothelial growth factor (VEGF) and extracellular platelet-derived growth factor (PDGF) for vessel formation through comparison of enzyme-linked immunosorbent assays (ELISAs) of the culture media and cell lysate. Tube formation assays also showed a sustained increase in tube diameter across the first 48 h of HUVEC culture when succinate concentrations of 1 and 10 μM in the xerogel. Overall, the succinate-alginate films serve as a prospective organic coating for bone-interfacing implant materials which may induce temporary pseudohypoxic conditions favourable for early angiogenesis and bone regeneration in vivo at succinate concentrations of 1 or 10 μM., 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 © 2022. Published by Elsevier B.V.)

Biominerals and biomaterials are part of our daily lives, from our skeleton and teeth to coral reefs and carbon-capturing single-cell organisms in the oceans, to engineered ceramics comprising our toothpaste and bone replacements. Many biominerals are hierarchically structured with remarkable material properties that arise from their unique combination of organic and inorganic components. Such structural hierarchy is often formed through a process of biomineralization. However, many fundamental questions remain regarding mineralization events in bones or teeth, and near biomaterials, partly due to the challenges in characterizing three-dimensional (3D) structure and chemical composition simultaneously at the nanometer scale. Atom probe tomography (APT) is a 3D characterization technique that combines both sub-nanometer spatial resolution and compositional sensitivity down to tens of parts per million. While APT is well-established in application to conventional engineering materials, recent years have seen its expansion into biomineralization research. Here, we focus our review on APT applications to biominerals, biomaterials and biointerfaces, providing a high-level summary of findings, as well as a primer on theory and best practices specific to the biomineralization community. We show that APT is a promising characterization tool, where its unique ability to quantify 3D chemical composition is not only complementary to other microscopy techniques but could become an integral part of biomaterial research. With the emerging trends of correlative and cryogenic workflow, notwithstanding the challenges outlined herein, APT has the potential to improve understanding of a broader range of biomaterials, while deriving innovative perspectives on clinical applications and strategies for biomaterial design. STATEMENT OF SIGNIFICANCE: Atom probe tomography (APT) is a three-dimensional characterization technique that can provide quantitative elemental and isotopic analysis with sub-nanometer resolution and compositional sensitivity down to tens of parts per million. These capabilities make it uniquely positioned for the analysis of biomineralized materials, both natural and synthetic. Here, we review the various applications of APT to the field of biomineralization, including applications in biominerals, biomaterials, biointerfaces and other biological materials, such as cells or proteins. A brief but comprehensive summary of the relevant technical concepts, limitations, and future perspectives to enable growth in this field are also included. Although APT is relatively new to the field of biomineralization, it has shown the potential to transform our basic understanding of biomineralization mechanisms and better inform biomaterials design., 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 © 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Purpose: Head and neck cancer survivors are increasing in prevalence, and 60-70% still experience at least one unmet emotional and/or physical need after treatment has ended. The purpose of this study was to determine the efficacy of a brief post-treatment psychoeducational intervention on perceived preparedness for coping with recovery using post-session evaluations., Methods: Between August 2013 and May 2018, a two-session, multidisciplinary "getting back on track" class was delivered to head and neck cancer patients approximately 2 months following radiation treatment at Princess Margaret Cancer Centre in Toronto, Canada. Three hundred and fifty attendees completed evaluations. Statistical analyses of the 310 patients surveyed measured change in level of preparedness to cope with recovery using the b-prepared scale. Qualitative analyses provided insight into potential benefits for future patients., Results: Almost two-thirds (58%) of patients reported an increase in level of preparedness in post-intervention surveys. Comparing self-reported level of preparedness among patients from before to after the class showed an increase in feeling prepared from 50 to 58%, and of those feeling very prepared, from 6 to 34%. The proportion of patients who reported feeling unprepared (11%) or neutral (33%) before the class decreased post-intervention, with 0% feeling unprepared and 7% feeling neutral. There were statistically significant differences in the ideal timing of the class, but overall attendees agreed that the class is an essential part of their recovery., Conclusion: Results confirm the efficacy of this brief psychoeducational intervention to improve preparedness in head and neck cancer survivors following radiation treatment., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Motive: External vibration excitation might be key to many novel non-surgical interventions for pathologies in the musculoskeletal system and in other parts of the human organism. Lack of understanding about vibration patterns, their controllability, and reproducibility are three limitations of ongoing research. This study establishes a bovine vibration model and animal model replacements for future research., Methods: We used biological samples (n=5) and one polyurethane sample of the bovine femur. Mechanical resonance was measured experimentally and analysed numerically by finite element method., Main Results: The experiments obtained 5 distinct mode shapes for the biological sample set, with standard deviation < 7.5%. Finite element analysis of the biological samples can replicate experimental mode shape deflection. The use of polyurethane changes resonance character but results are also good approximations of the biological samples., Conclusions: A model of the bovine femur with consistent resonance behaviour is presented with alternatives (polyurethane and finite element analysis) that can serve in reducing the number of necessary biological samples. Future work will be to adapt results to human anatomy. Of clinical interest will be to influence bone pathologies such as post-surgical non-union, or bone functionality as part of haematopoiesis and endocrine secretion., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The development of treatment strategies for improving secondary stability at the bone-implant interface is a challenge. Porous implants are one solution for improving long-term implant stability, but the osteoconduction process of implants into the bone can be slow. Strain-driven osteogenesis from the mechanostat theory offers insight into pathways for post-operative treatment but mechanisms to deliver strain to the bone-implant interface need refinement. In this work, the use of therapeutic ultrasound is simulated to induce resonance into a porous implant structure. Local strains through the scaffold are measured by varying systemic variables such as damping ratio, applied vibrational force, primary bone-implant stability, and input frequency. At the natural frequency of the system with applied forces of 0.5 N and a damping ratio of 0.5%, roughly half of the nodes in the simulated environment exceed the microstrain threshold of 1000 με required for new bone formation. A high degree of sensitivity was noted upon changing input frequency, with minor sensitivities arising from damping ratio and applied vibrational force. These findings suggest that the application of therapeutic resonance to improve osseointegration of the bone-implant interface may be viable for applications including dental implants or segmental bone defects., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The geometry of a metallic scaffold is important for the success of bone implants, where the introduction of porosity can reduce stress shielding effects and allow for bone tissue integration. In this work, porous scaffolds were designed to closely mimic the natural structure of trabecular bone using selective Voronoi tessellation with preferential seeding. A workflow to generate these structures is introduced, where voided regions of seeds in the starting volume create preferential texture during polyhedral expansion, resulting in modified strut orientation in the implant. Anisotropy was digitally characterized by mean-intercept length and star volume distribution measurements to determine similarity to trabecular orientation. This work demonstrates that selective Voronoi tessellation is an effective method to generate biomimetic porous scaffolds with increased anisotropy and tunable strut architecture in three dimensions as a suitable alternative to patient-derived bone geometries., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Recent advances in the field of metallic additive manufacturing have expanded production capabilities for bone implants to include porous lattice structures. While traditional models of de novo bone formation can be applied to fully dense implant materials, their applicability to the interior of porous materials has not been well-characterized. Unlike other reviews that focus on materials and mechanical properties of lattice structures, this review compiles biological performance from in vivo studies in pre-clinical models only. First, we introduce the most common lattice geometry designs employed in vivo and discuss some of their fabrication advantages and limitations. Then lattice geometry is correlated to quantitative (histomorphometric) and qualitative (histological) assessments of osseointegration. We group studies according to two common implant variables: pore size and percent porosity, and explore the extent of osseointegration using common measures, including bone-implant contact (BIC), bone area (BA), bone volume/total volume (BV/TV) and biomechanical stability, for various animal models and implantation times. Based on this, trends related to in vivo bone formation on the interior of lattice structures are presented. Common challenges with lattice structures are highlighted, including nonuniformity of bone growth through the entirety of the lattice structure due to occlusion effects and avascularity. This review paper identifies a lack of systematic in vivo studies on porous AM implants to target optimum geometric design, including pore shape, size, and percent porosity in controlled animal models and critical-sized defects. Further work focusing on surface modification strategies and systematic geometric studies to homogenize in vivo bone growth through the scaffold interior are recommended to increase implant stability in the early stages of osseointegration., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s). Published by Elsevier Ltd.)

Background and Objectives: A randomized clinical trial demonstrated that 10 kHz SCS (10kHz-SCS) therapy is superior to traditional low-frequency SCS (LF-SCS) at 12- and 24-month clinical follow-ups and led to Food and Drug Administration (FDA) approval of the therapy. The results of the study led our practices to trial 10kHz-SCS in patients who had not maintained pain relief with LF-SCS therapy. Here, we report a large set of data from two clinical sites to assess if 10kHz-SCS is an effective salvage modality when LF-SCS fails., Methods: We conducted a retrospective chart review of 120 patients across two clinical sites who had LF-SCS implants and were salvaged with 10kHz-SCS., Results: Data were analyzed from 105 patients between 28 and 90 years old (median 60) with chronic pain for 13.6 years. The mean duration of LF-SCS therapy was 4.66±3.9 years. The average Visual Analog Scale (VAS) decreased from 8.30±1.4 (median of 8) cm to 3.32±2.0 (median of 3) cm at 12 months and 3.36±2.0 (median of 3) cm at the most recent clinic visit (p<0.001) following salvage therapy. Pain relief of 50% or more was obtained in 85 out of 105 (81%) patients. Opioid usage decreased from 60.3±77.1 mg to 32.1±44.0 mg MSO4 equivalents (p = 0.001) at 12 months after salvage therapy., Conclusion: Eighty-one percent of patient cases reviewed, where LF-SCS had failed, achieved >50% pain relief with 10kHz-SCS, and almost all exhibited some clinical improvement. Therefore, 10kHz-SCS should be considered an appropriate option to rescue failed LF-SCS., Competing Interests: Drs Kapural and Sayed are paid consultants for Nevro Corp. This study was funded by an investigator initiated grant from Nevro to Drs Kapural and Sayed. Dr Leonardo Kapural reports research grants from Nevro, Biotronik, Saluda Medical, Gimer and Neuros, personal fees from Nalu, Abbott and Medtronic, during the conduct of the study;and personal fees from Nevro, outside the submitted work. Dr Dawood Sayed reports personal fees, consulting fees and sponsored research from Nevro, Abbott, Vertos,Medtronic, Flowonix, and Boston Scientific, and equity in SPR, PainTeq, and Vertos, outside the submitted work. The authors report no other potential conflicts of interest for this work., (© 2020 Kapural et al.)

Visualizing bone mineralization and collagen fibril organization at intermediate scales between the nanometer and the hundreds of microns range, is still an important challenge. Similarly, visualizing cellular components which locally affect the tissue structure requires a precision of a few tens of nanometers at maximum while spanning several tens of micrometers. In the last decade, gallium focused ion beam (FIB) equipped with a scanning electron microscope (SEM) proved to be an extremely valuable structural tool to meet those ends. In this study, we assess the capability of a recent plasma FIB-SEM technology which provides a potential increase in measurement speed over gallium FIB-SEM, thus paving the way to larger volume analysis. Nanometer-scale layers of demineralized and mineralized unstained human femoral lamellar bone were sequentially sectioned over volumes of 6-16,000 μm 3 . Analysis of mineralized tissue revealed prolate ellipsoidal mineral clusters measuring approximately 1.1 µm in length by 700 nm at their maximum diameter. Those features, suggested by others in high resolution studies, appear here as a ubiquitous motif in mineralized lamellar bone over thousands of microns cubed, suggesting a heterogeneous and yet regular pattern of mineral deposition past the single collagen fibril level. This large scale view retained sufficient resolution to visualize the collagen fibrils while also partly visualizing the lacuno-canalicular network in three-dimensions. These findings are strong evidence for suitability of PFIB as a bone analysis tool and the need to revisit bone mineralization over multi-length scales with mineralized tissue., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Post-operative therapy for joint replacement is often performed to optimize bone volume and bone-implant contact. Methods, such as pulsed therapeutic ultrasound, have been shown to be a valuable addition to regular physiotherapy to increase bone regeneration. To evaluate the efficacy of kilohertz-frequency (kHz) resonant stimuli to additively manufactured implant analogues, Saos-2 cells were seeded onto porous stainless steel scaffolds and flat substrates. Resonant frequency modes were mapped in the low kHz range, and cells were subjected to daily stimulus for 10 min at a frequency of 1.278 kHz. kHz-frequency excitation was found to increase normalized alkaline phosphatase production by almost twofold on metallic substrates relative to non-vibrated control scaffolds, while peak velocity influenced alkaline phosphatase production on porous scaffolds but not flat substrates. Total cell proliferation was downregulated by excitation, and all excited samples displayed larger variability. This work indicates that vibration within the range of 0.16-0.48 mm/s may reduce cell proliferation, but favour osteogenic gene expression. This study highlights the potential of using kHz-resonance therapy to mitigate early-onset pore occlusion to achieve uniform osseointegration through porous metallic scaffolds., 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 © 2020 Elsevier Ltd. All rights reserved.)

For the first time, an electrophoretic deposition (EPD) method has been developed for the deposition of polymethylmethacrylate (PMMA) and PMMA-alumina films for biomedical implant applications. The proposed biomimetic approach was based on the use of a bile salt, sodium cholate (NaCh), which served as a multifunctional solubilizing, charging, dispersing and film-forming agent. Investigations revealed PMMA-Ch - and PMMA-alumina interactions, which facilitated the deposition of PMMA and PMMA-alumina films. This approach allows for the use of a non-toxic water-ethanol solvent for PMMA. The proposed deposition strategy can also be used for co-deposition of PMMA with other functional materials. The PMMA and composite films were tested for biomedical implant applications. The PMMA-alumina films showed statistically improved metabolic results compared to both the bare stainless steel substrate and pure PMMA films. Alkaline phosphatase (ALP) activity affirmed the bioactivity and osteoconductive potential of PMMA and composite films. PMMA-alumina films showed greater ALP activity than both the PMMA-coated and uncoated stainless steel., 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 © 2019 Elsevier B.V. All rights reserved.)

This review provides a snapshot of the current ethical issues related to research with human brain organoids. The issues fall into the following main themes: research oversight; human biomaterials procurement and donor consent; translational delivery; animal research; and organoid consciousness and moral status. Each of these areas poses challenges for researchers, bioethicists, regulators, research institutions, and tissue banks. However, progress can be made if these parties build on past experiences with stem cell research, ethics, and policy, but adapted accordingly to new aspects of brain organoid research., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Modifications to the compositional, topographical and morphological aspects of bone implants can lead to improved osseointegration, thus increasing the success of bone implant procedures. This study investigates the creation of dual-scale topography on Ti-5Al-5Mo-5V-3Cr (Ti5553), an alloy not presently used in the biomedical field, and compares it to Ti-6Al-4V (Ti64), the most used Ti alloy for bone implants. Dual-scale surface topography was obtained by combining selective laser melting (SLM) and electrochemical anodization, which resulted in micro- and nanoscale surface features, respectively. Ti5553 and Ti64 samples were manufactured by SLM and showed comparable surface topography. Subsequent electrochemical anodization succeeded in forming titania nanotubes (TNTs) on both alloys, with larger nanotubes obtained with Ti5553 at all investigated anodization voltages. At an anodization voltage of 40 V, a minimum time of 20 min was necessary to have nanotube formation on the surface of either alloy, while only nanopores were evident for shorter times. Seeded Saos-2 cells showed ideal interactions with surface-modified structures, with filopodia extending to both surface microparticles characteristic of SLM and to the interior of TNTs. Attractiveness of Ti5553 lies in its lower elastic modulus (E = 72 GPa) compared to Ti64, which should mitigate stress-shielding phenomena in vivo. This, combined with the analogous results obtained in terms of dual-scale surface topography and cell-substrate interaction, could indicate Ti5553 as a promising alternative to the widely-employed Ti64 for bone implant device manufacturing.

As countries around the world struggle to provide oncology care and treatment to their populations, nurses, as the largest healthcare workforce, are faced with the challenge of obtaining, maintaining, and developing specialized oncology nursing knowledge and expertise. Strategies that can be deployed at a local level to support nurses with integrating new knowledge into practice are important in meeting and overcoming this challenge. This article describes a theory-based model for implementing oncology nursing best practices in the Middle Eastern country of Kuwait. 
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Background: Military aircrew with minimal coronary artery disease (MCAD) may be restricted from flying high-performance aircraft due to possible ischemia during high +Gz. An animal model is presented to provide ischemia data for a more informed decision., Methods: There were 18 swine that were placed on a high cholesterol/high fat diet for up to 57 wk. Five control swine were maintained on a standard swine diet. Also, nine male baboons had a constrictor placed around the left anterior descending coronary artery. Two baboons were sham-operated controls. The unanesthetized swine and baboons were infused with Tc-99m at the end of +Gz exposure and scanned for myocardial perfusion., Results: Five swine died unexpectedly before +Gz exposure with moderate-to-severe CAD. Dysrhythmias during +Gz were seen equally in both the control and experimental swine and in the baboons before and after stenosis, with or without propranolol. During +Gz, ECG ST-T wave changes suggesting ischemia were observed in the cholesterol swine but not the control swine, and in the baboons before and after stenosis, with or without propranolol. There was a positive relationship between a normal/abnormal ECG and a normal/abnormal myocardial perfusion scan in the swine and a weak relationship in the baboon before stenosis, but somewhat better after stenosis. Coronary histopathology showed normal vessels from the control swine and stenoses ranging from 0-95% from the cholesterol swine. Baboon stenosis averaged 37.6 +/- 15.0%., Conclusions: In the swine and the baboon extended high levels of +Gz, were associated with evidence of myocardial ischemia.

Unlabelled: Hetastarch is used for intravascular volume expansion in cardiac surgery. Studies show conflicting effects of intraoperative hetastarch administration on postoperative bleeding. Hetastarch was routinely used for volume expansion during cardiovascular surgeries at our institution until its use was discontinued intraoperatively. We performed a retrospective chart review on patients undergoing primary coronary artery bypass grafting, valve repair or replacement requiring cardiopulmonary bypass (n = 444), 234 of which received intraoperative hetastarch and 210 did not. There was no difference in demographics, cardiac surgery, or cardiopulmonary bypass duration between the two groups. Blood loss for 0-4 h postoperatively was 377 +/- 244 mL in the group not receiving hetastarch compared with 515 +/- 336 mL in the group that received hetastarch (P < 0.001). For 0-24 h postoperatively, blood loss was 923 +/- 473 mL versus 1,283 +/- 686 mL in the absence and presence of hetastarch, respectively (P < 0.001). Allogeneic transfusion requirements (cryoprecipitate, fresh frozen plasma, and platelets) were larger in the hetastarch group (all P < 0.001). Nearly all (99%) patients in the hetastarch group received less than the manufacturer's recommended dose (20 mL/kg) of hetastarch., Implications: Our large retrospective study suggests that intraoperative use of hetastarch in primary cardiac surgery with cardiopulmonary bypass may increase bleeding and transfusion requirements. A large prospective study is needed to determine if intraoperative administration of hetastarch should be avoided during cardiovascular surgery.

A study of job satisfaction of nursing assistants (NAs) was conducted in two nursing homes (one in a relatively poor urban neighborhood, the other in an affluent suburban neighborhood). When it comes to job content, NAs were more satisfied than dissatisfied. However, they are less satisfied with working conditions. The NAs of the suburban facility were less satisfied than those of the urban facility. Managers need to focus more on the work environment than on job content to develop a more satisfied work force.

The objective of our study was to determine the rates of bleeding complications and thromboembolic events in patients receiving oral anticoagulant therapy monitored with the prothrombin time (PT) ratio versus therapy monitored with the International Normalized Ratio (INR) using a retrospective time-series study design. Over 650 patients enrolled in a large anticoagulation clinic were studied during two time periods corresponding to the use of the PT ratio versus the INR to guide anticoagulant therapy, with over 400 patient-years of follow-up for each time period. The rate of bleeding complications using the PT ratio to guide therapy was 6.7% (1.2% major, 5.5% minor) per patient-year, compared with 2.9% (0% major, 2.9% minor) using the INR (p = 0.02). The rate of thromboembolic complications was 1.0% using the PT ratio, compared with 0.2% using the INR (p = NS). Therapy monitored with the INR required 19.8 visits per year, compared with 20.7 visits per year using the PT ratio. We conclude that the INR should be used to monitor oral anticoagulant therapy in an effort to reduce bleeding complications while maintaining an acceptable rate of thromboembolic events.

Two cases of pacemaker lead fracture associated with weight-lifting are presented. This is a rare association which has only recently been described in the literature. In both cases, the pacemaker lead was fractured between the clavicle and the first rib, suggesting crush injury. The chest X-ray, pacemaker telemetry with measurement of lead impedance, and pacemaker reprogramming were all helpful in management.

Ammonium ion repressed nitrogenase in cells fixing N2 gas. Immunological tests and electrophoresis in various gels show that components I (Fe-Mo-S protein) was completely repressed by ammonium, whereas component II (Fe-S protein) apoprotein was not markedly affected. Component II from ammonium-grown cells, however, was inactive since it did not cross react with component I to reduce C2H2 to C2H4. The inactive component II apoprotein is immunologically identical to its active counterpart from cells fixing N2. Identical protein patterns were also observed in various gel-electrophoresis systems. Oxygen-inactivated component II may be reactivated with FeSo4. This salt is preferable to ferrous ammonium sulphate which inactivated component I. Immunodiffusion under aerobic conditions shows that purified component I is composed of aggregated and non-aggregated forms which are antigenically distinct. The aggregate was dissociated by treatment with sodium dodecyl sulphate (SDS) into a single antigenic species which was further resolved into two subunits on SDS disc polyacrylamide gel electrophoresis.