Improving material properties of a poloxamer P407 hydrogel-based hydroxyapatite bone substitute material by adding silica-A comparative in vivo study.

The structure and handling properties of a P407 hydrogel-based bone substitute material (BSM) might be affected by different poloxamer P407 and silicon dioxide (SiO2) concentrations. The study aimed to compare the mechanical properties and biological parameters (bone remodeling, BSM degradation) of a hydroxyapatite: silica (HA)-based BSM with various P407 hydrogels in vitro and in an in vivo rat model. Rheological analyses for mechanical properties were performed on one BSM with an SiO2-enriched hydrogel (SPH25) as well on two BSMs with unaltered hydrogels in different gel concentrations (PH25 and PH30). Furthermore, the solubility of all BSMs were tested. In addition, 30 male Wistar rats underwent surgical creation of a well-defined bone defect in the tibia. Defects were filled randomly with PH30 (n = 15) or SPH25 (n = 15). Animals were sacrificed after 12 (n = 5 each), 21 (n = 5 each), and 63 days (n = 5 each). Histological evaluation and histomorphometrical quantification of new bone formation (NB;%), residual BSM (rBSM;%), and soft tissue (ST;%) was conducted. Rheological tests showed an increased viscosity and lower solubility of SPH when compared with the other hydrogels. Histomorphometric analyses in cancellous bone showed a decrease of ST in PH30 (p = .003) and an increase of NB (PH30: p = .001; SPH: p = .014) over time. A comparison of both BSMs revealed no significant differences. The addition of SiO2 to a P407 hydrogel-based hydroxyapatite BSM improves its mechanical stability (viscosity, solubility) while showing similar in vivo healing properties compared to PH30. Additionally, the SiO2-enrichment allows a reduction of poloxamer ratio in the hydrogel without impairing the material properties.

Improving the Bias of Comparator Methods in Analytical Performance Assessments Through Recalibration.

BACKGROUND: In analytical performance studies, the choice of comparator method plays an important role, as studies have shown that there exist relevant systematic differences (bias) between laboratory analyzers. The feasibility of retrospective recalibration of measurement results through comparison with methods or materials of higher metrological order to minimize bias was therefore assessed. METHOD: Existing data from performance studies of continuous and blood glucose monitoring systems were retrospectively analyzed. Comparison with a higher-order method was performed for two different data sets. In both cases, subject samples were measured, and a subset was also measured on a higher-order method. Recalibration based on higher-order materials (standard reference material [SRM]) was conducted for two different data sets containing results from SRM and subject samples. Linear regression analysis was performed for each device separately. Resulting equations were applied to the respective complete data set of subject samples. Bias between devices in a data set across all subject samples was assessed before and after recalibration. RESULTS: Bias between devices was reduced from -3.6% to +0.6% in one data set and from +11.0% to +0.3% in the other by recalibration based on higher-order method. Using higher-order materials, bias was also reduced by recalibration, but mixed results were found: Bias was reduced from -3.1% to -0.1% in one data set and from -4.3% to -2.7% in the other. CONCLUSIONS: Recalibration did lead to a decrease in bias and thus can reduce the impact of the choice of comparator method. The procedure should be verified in a prospectively designed setting.

Zinc(II) Complex Containing Oxazole Ring: Synthesis, Crystal Structure, Characterization, DFT Calculations, and Hirshfeld Surface Analysis.

A new complex of Zn(II), with 5-chloro-2-methylbenzoxazole ligand (L), has been synthesized by the reaction of zinc dichloride with the ligand (L= C8H6ClNO) in ethanol solution: dichloridobis(5-chloro-2-methyl-1,3-benzoxazole)-zinc(II), C16H12Cl4N2O2Zn. The synthesized complex has been fully characterized by elemental analysis, molar conductivity, FT­IR, UV­Vis, and single-crystal X-ray diffraction (XRD).  The XRD analysis reveals that the complex has a 1:2 metal-to-ligand ratio. The zinc(II) complex has a distorted tetrahedral geometry with two coordinated nitrogen atoms from the ligand. Density Functional Theory (DFT) calculations were performed at the B3LYP level of theory using the LANL2DZ basis set for metal complex and the 6-31G(d) basis set for non-metal elements to determine the optimum geometry structure of the complex, and the calculated HOMO and LUMO orbital energies were presented. A natural bond orbital (NBO) analysis was carried out on the molecules to analyze the atomic charge distribution before and after the complexation of the ligand.  The Hirshfeld surface mapped over dnorm, shape index, and curvature exhibited strong H...Cl/Cl...H and H...H intermolecular interactions as the principal contributors to crystal packing.

Sustainable Surface Modification of Polyetheretherketone (PEEK) Implants by Hydroxyapatite/Silica Coating-An In Vivo Animal Study.

Polyetheretherketone (PEEK) has the potential to overcome some of the disadvantages of titanium interbody implants in anterior cervical and discectomy and fusion (ACDF). However, PEEK shows an inferior biological behavior regarding osseointegration and bioactivity. Therefore, the aim of the study was to create a bioactive surface coating on PEEK implants with a unique nanopore structure enabling the generation of a long-lasting interfacial composite layer between coating material and implant. Seventy-two PEEK implants-each thirty-six pure PEEK implants (PI) and thirty-six PEEK implants with a sprayed coating consisting of nanocrystalline hydroxyapatite (ncHA) embedded in a silica matrix and interfacial composite layer (SPI)-were inserted in the femoral condyles of adult rats using a split-side model. After 2, 4 and 8 weeks, the femur bones were harvested. Half of the femur bones were used in histological and histomorphometrical analyses. Additionally, pull-out tests were performed in the second half. Postoperative healing was uneventful for all animals, and no postoperative complications were observed. Considerable crestal and medullary bone remodeling could be found around all implants, with faster bone formation around the SPI and fewer regions with fibrous tissue barriers between implant and bone. Histomorphometrical analyses showed a higher bone to implant contact (BIC) in SPI after 4 and 8 weeks (p < 0.05). Pull-out tests revealed higher pull-out forces in SPI at all time points (p < 0.01). The presented findings demonstrate that a combination of a bioactive coating and the permanent chemical and structural modified interfacial composite layer can improve bone formation at the implant surface by creating a sustainable bone-implant interface. This might be a promising way to overcome the bioinert surface property of PEEK-based implants.

Personalized medicine for reconstruction of critical-size bone defects - a translational approach with customizable vascularized bone tissue.

Tissue engineering principles allow the generation of functional tissues for biomedical applications. Reconstruction of large-scale bone defects with tissue-engineered bone has still not entered the clinical routine. In the present study, a bone substitute in combination with mesenchymal stem cells (MSC) and endothelial progenitor cells (EPC) with or without growth factors BMP-2 and VEGF-A was prevascularized by an arteriovenous (AV) loop and transplanted into a critical-size tibia defect in the sheep model. With 3D imaging and immunohistochemistry, we could show that this approach is a feasible and simple alternative to the current clinical therapeutic option. This study serves as proof of concept for using large-scale transplantable, vascularized, and customizable bone, generated in a living organism for the reconstruction of load-bearing bone defects, individually tailored to the patient's needs. With this approach in personalized medicine for the reconstruction of critical-size bone defects, regeneration of parts of the human body will become possible in the near future.

Subdural Displacement of an Epidural Catheter With Spinal Cord Compression in a Patient With Chronic Cancer Pain: A Case Report.

Here we present the case of a 76-year-old woman with pancreatic cancer receiving epidural analgesia for chronic cancer pain treatment. Attempts of running the epidural catheter sequentially resulted in unexpected and extensive sensory block together with sympathicolysis but insufficient pain control. Finally, after 3 failed attempts of epidural catheter placements with insufficient pain control and uncommon neurological signs, a magnetic resonance imaging (MRI) scan of the spine was ordered. The MRI showed subdural catheter displacement with extensive liquid accumulation in the subdural space and consequent significant spinal cord compression. Findings normalized after removing the subdural catheter.

Sevoflurane Promotes Bactericidal Properties of Macrophages through Enhanced Inducible Nitric Oxide Synthase Expression in Male Mice.

BACKGROUND: Sevoflurane with its antiinflammatory properties has shown to decrease mortality in animal models of sepsis. However, the underlying mechanism of its beneficial effect in this inflammatory scenario remains poorly understood. Macrophages play an important role in the early stage of sepsis as they are tasked with eliminating invading microbes and also attracting other immune cells by the release of proinflammatory cytokines such as interleukin-1ß, interleukin-6, and tumor necrosis factor-α. Thus, the authors hypothesized that sevoflurane mitigates the proinflammatory response of macrophages, while maintaining their bactericidal properties. METHODS: Murine bone marrow-derived macrophages were stimulated in vitro with lipopolysaccharide in the presence and absence of 2% sevoflurane. Expression of cytokines and inducible NO synthase as well as uptake of fluorescently labeled Escherichia coli (E. coli) were measured. The in vivo endotoxemia model consisted of an intraperitoneal lipopolysaccharide injection after anesthesia with either ketamine and xylazine or 4% sevoflurane. Male mice (n = 6 per group) were observed for a total of 20 h. During the last 30 min fluorescently labeled E. coli were intraperitoneally injected. Peritoneal cells were extracted by peritoneal lavage and inducible NO synthase expression as well as E. coli uptake by peritoneal macrophages was determined using flow cytometry. RESULTS: In vitro, sevoflurane enhanced lipopolysaccharide-induced inducible NO synthase expression after 8 h by 466% and increased macrophage uptake of fluorescently labeled E. coli by 70% compared with vehicle-treated controls. Inhibiting inducible NO synthase expression pharmacologically abolished this increase in bacteria uptake. In vivo, inducible NO synthase expression was increased by 669% and phagocytosis of E. coli by 49% compared with the control group. CONCLUSIONS: Sevoflurane enhances phagocytosis of bacteria by lipopolysaccharide-challenged macrophages in vitro and in vivo via an inducible NO synthase-dependent mechanism. Thus, sevoflurane potentiates bactericidal and antiinflammatory host-defense mechanisms in endotoxemia.

Effect of Promotion via Social Media on Access of Articles in an Academic Medical Journal: A Randomized Controlled Trial.

PURPOSE: To study the effect of a planned social media promotion strategy on access of online articles in an established academic medical journal. METHOD: This was a single-masked, randomized controlled trial using articles published in Mayo Clinic Proceedings, a large-circulation general/internal medicine journal. Articles published during the months of October, November, and December 2015 (n = 68) were randomized to social media promotion (SoMe) using Twitter, Facebook, and LinkedIn or to no social media promotion (NoSoMe), for 30 days (beginning with the date of online article publication). Journal website visits and full-text article downloads were compared for 0-30 and 31-60 days following online publication between SoMe versus NoSoMe using a Wilcoxon rank-sum test. RESULTS: Website access of articles from 0 to 30 days was significantly higher in the SoMe group (n = 34) compared with the NoSoMe group (n = 34): 1,070 median downloads versus 265, P < .001. Similarly, full-text article downloads from 0-30 days were significantly higher in the SoMe group: 1,042 median downloads versus 142, P < .001. Compared with the NoSoMe articles, articles randomized to SoMe received a greater number of website visits via Twitter (90 vs 1), Facebook (526 vs 2.5), and LinkedIn (31.5 vs 0)-all P < .001. CONCLUSIONS: Articles randomized to SoMe were more widely accessed compared with those without social media promotion. These findings show a possible role, benefit, and need for further study of a carefully planned social media promotion strategy in an academic medical journal.

The implant surface and its role in affecting the dynamic processes of bone remodeling by means of distance osteogenesis: A comparative in vivo study.

PURPOSE: This study aimed to evaluate whether different surface modifications affect the dynamics of bone remodeling at the implant and the adjacent local bone. MATERIALS AND METHODS: Seventy-two dental implants with different surfaces (smooth and rough control [smCtrl; rCtrl], smooth and rough + O2-plasma spray [smPlas; rPlas], smooth and rough + nanocrystalline SiO2-hydroxyapatite coating [ncSiO2HA] + O2-plasma spray [smNB-C; rNB-C]; each n = 12) were bilaterally inserted into the femora of 36 New Zealand white rabbits. Intravital fluorochrome labeling was performed to visualize the dynamics of bone formation. The objectives were quantification of bone-to-implant contact (BIC [%]) at 2 and 4 weeks and the dynamic bone formation (dbf [%]) at the implants' adjacent local bone within 1, 2, and 3 weeks. RESULTS: After 2 weeks, BIC was significantly higher for both smNB-C (BIC: 59% ± 2% SEM) and rNB-C (BIC: 66% ± 3% SEM) compared with controls (BIC: 42% ± 1% SEM; P < .005). After 4 weeks, BIC for rNB-C (65% ± 2%) was superior to all test groups (BIC: 39% ± 2% SEM; P = .012). Regarding dbf (%), neither within 1 (P = .88), 2 (P = .48), nor after 3 weeks (P = .36) did any differences occur among the groups, even in accordance to the implant level. CONCLUSION: Although distance osteogenesis seems crucial for the development of secondary stability and thus of osseointegration, it apparently does not get affected by a bioactive ncSiO2HA surface coating. Changing the surfaces' release kinetics and composition may increase distance osteogenesis.

2018 ACC/HRS/NASCI/SCAI/SCCT Expert Consensus Document on Optimal Use of Ionizing Radiation in Cardiovascular Imaging-Best Practices for Safety and Effectiveness, Part 2: Radiological Equipment Operation, Dose-Sparing Methodologies, Patient and Medical Personnel Protection.

The stimulus to create this document was the recognition that ionizing radiation-guided cardiovascular procedures are being performed with increasing frequency, leading to greater patient radiation exposure and, potentially, to greater exposure to clinical personnel. While the clinical benefit of these procedures is substantial, there is concern about the implications of medical radiation exposure. ACC leadership concluded that it is important to provide practitioners with an educational resource that assembles and interprets the current radiation knowledge base relevant to cardiovascular procedures. By applying this knowledge base, cardiovascular practitioners will be able to select procedures optimally, and minimize radiation exposure to patients and to clinical personnel. "Optimal Use of Ionizing Radiation in Cardiovascular Imaging - Best Practices for Safety and Effectiveness" is a comprehensive overview of ionizing radiation use in cardiovascular procedures and is published online. To provide the most value to our members, we divided the print version of this document into 2 focused parts. "Part I: Radiation Physics and Radiation Biology" addresses radiation physics, dosimetry and detrimental biologic effects. "Part II: Radiologic Equipment Operation, Dose-Sparing Methodologies, Patient and Medical Personnel Protection" covers the basics of operation and radiation delivery for the 3 cardiovascular imaging modalities (x-ray fluoroscopy, x-ray computed tomography, and nuclear scintigraphy). For each modality, it includes the determinants of radiation exposure and techniques to minimize exposure to both patients and to medical personnel.

2018 ACC/HRS/NASCI/SCAI/SCCT Expert Consensus Document on Optimal Use of Ionizing Radiation in Cardiovascular Imaging-Best Practices for Safety and Effectiveness, Part 1: Radiation Physics and Radiation Biology: A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways Developed in Collaboration With Mended Hearts.

The stimulus to create this document was the recognition that ionizing radiation-guided cardiovascular procedures are being performed with increasing frequency, leading to greater patient radiation exposure and, potentially, to greater exposure for clinical personnel. Although the clinical benefit of these procedures is substantial, there is concern about the implications of medical radiation exposure. The American College of Cardiology leadership concluded that it is important to provide practitioners with an educational resource that assembles and interprets the current radiation knowledge base relevant to cardiovascular procedures. By applying this knowledge base, cardiovascular practitioners will be able to select procedures optimally, and minimize radiation exposure to patients and to clinical personnel. Optimal Use of Ionizing Radiation in Cardiovascular Imaging: Best Practices for Safety and Effectiveness is a comprehensive overview of ionizing radiation use in cardiovascular procedures and is published online. To provide the most value to our members, we divided the print version of this document into 2 focused parts. Part I: Radiation Physics and Radiation Biology addresses the issue of medical radiation exposure, the basics of radiation physics and dosimetry, and the basics of radiation biology and radiation-induced adverse effects. Part II: Radiological Equipment Operation, Dose-Sparing Methodologies, Patient and Medical Personnel Protection covers the basics of operation and radiation delivery for the 3 cardiovascular imaging modalities (x-ray fluoroscopy, x-ray computed tomography, and nuclear scintigraphy) and will be published in the next issue of the Journal.