Opioids Delay Healing of Spinal Fusion: A Rabbit Posterolateral Lumbar Fusion Model

Background Context Opioid use is prevalent in the management of pre- and postoperative pain in patients undergoing spinal fusion. There is evidence that opioids downregulate osteoblasts in vitro, and a previous study found that morphine delays the maturation and remodeling of callus in a rat femur fracture model. However, the effect of opioids on healing of spinal fusion has not been investigated before. Isolating the effect of opioid exposure in humans would be limited by the numerous confounding factors that affect fusion healing. Therefore, we have used a well-established rabbit model to study the process of spinal fusion healing that closely mimics humans. Purpose The objective of this work was to study the effect of systemic opioids on the process of healing of spinal fusion in a rabbit posterolateral spinal fusion model. Study Design/Setting This is a preclinical animal study. Materials and Methods Twenty-four adult New Zealand white rabbits were studied in two groups after approval from the Institutional Animal Care and Use Committee (IACUC). The opioid group (n=12) received 4 weeks\u27 preoperative and 6 weeks\u27 postoperative transdermal fentanyl. Serum fentanyl levels were measured just before surgery and 4 weeks postoperatively to ensure adequate levels. The control group (n=12) received only perioperative pain control as necessary. All animals underwent a bilateral L5–L6 posterolateral spinal fusion using iliac crest autograft. Animals were euthanized at the 6-week postoperative time point, and assessment of fusion was done by manual palpation, plain radiographs, microcomputed tomography (microCT), and histology. Results Twelve animals in the control group and 11 animals in the opioid group were available for analysis at the end of 6 weeks. The fusion scores on manual palpation, radiographs, and microCT were not statistically different. Three-dimensional microCT morphometry found that the fusion mass in the opioid group had a lower bone volume (p=.09), a lower trabecular number (p=.02), and a higher trabecular separation (p=.02) compared with the control group. Histologic analysis found areas of incorporation of autograft and unincorporated graft fragments in both groups. In the control group, there was remodeling of de novo woven bone to lamellar organization with incorporation of osteocytes, formation of mature marrow, and relative paucity of hypertrophied osteoblasts lining new bone. Sections from the opioid group showed formation of de novo woven bone, and hypertrophied osteoblasts were seen lining the new bone. There were no sections showing lamellar organization and development of mature marrow elements in the opioid group. Less dense trabeculae on microCT correlated with histologic findings of relatively immature fusion mass in the opioid group. Conclusions Systemic opioids led to an inferior quality fusion mass with delay in maturation and remodeling at 6 weeks in this rabbit spinal fusion model. These preliminary results lay the foundation for further research to investigate underlying cellular mechanisms, the temporal fusion process, and the dose-duration relationship of opioids responsible for our findings

Optical, Thermal and Topological Characterization of Quaternary Se65Ge15Te20-aSba Chalcogenide Glasses

Se-Te based chalcogenide glasses have been found suitable for optical memory devices due to their distinct amorphous-to-crystalline transformation. In the present work alloys of Se65Ge15Te20-aSba (a = 3, 6, 9, 12, 15, 18) glasses have been synthesized using melt quench technique. Author report investigations leading to optical, thermal and topological properties of these glasses by varying the concentrations of Te and Sb. Glass transition and crystallization kinetics of alloys have been investigated using differential thermal analysis at different heating rates (5, 10, 15, and 20 Kmin-1). The results so obtained verify the usefulness of above composition

A Design of Experiment Approach for Optimization and Characterization of Clarithromycin Ternary System Using Spray Drying

The aim of present work was to characterize Clarithromycin (CLT), Polyvinyl pyrrolidone K30 (PVP K30) and Hydroxypropyl β-cyclodextrin (HPB) ternary system so as to check the effect of complexation on solubility of CLT. Physical mixtures of a drug and polymers in several weight ratios (1:1, 1:2) were prepared to check the effect of individual polymers on solubility of CLT. Spray drying method was accustomed investigate the combined effect of PVP K30 and HPB on Drug release (DR), Dissolution efficiency (DE) and mean dissolution time (MDT) of CLT. For the preparation and optimization of ternary system the Design of experiment (DoE) was used . Drug polymer interactions were analyzed with Fourier transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC), X-ray diffraction (XRD) and particle size analysis. Results of solubility study suggested that there was significant increase in solubility of CLT with increase within the concentration of PVP K30 and HPB (*p<0.05). This may be thanks to the solubilizing effect of PVP K30 and sophisticated formation of CLT with HPB. Various combinations of PVP K30 and HPB prepared using DoE approach by spray drying method showed greater solubility of CLT than its physical mixtures (*p<0.05). Results of FTIR, DSC, XRD and particle size analysis revealed the interaction between CLT, PVP K30 and HPB. This suggested formation of amorphous ternary system with mean particle diameter within the range of 312±1.35 nm. Combine use of PVP K30 and HPB with DoE approach was an efficient tool for formulating ternary system of CLT. Keywords: Clarithromycin, Spray drying, polyvinyl pyrrolidone K30, Hydroxypropyl β-cyclodextrin, Design of experiments, Ternary system.&nbsp

The (h,k)-Server Problem on Bounded Depth Trees

We study the k-server problem in the resource augmentation setting, i.e., when the performance of the online algorithm with k servers is compared to the offline optimal solution with h ≤ k servers. The problem is very poorly understood beyond uniform metrics. For this special case, the classic k-server algorithms are roughly (1+1/ϵ)-competitive when k=(1+ϵ) h, for any ϵ > 0. Surprisingly, however, no o(h)-competitive algorithm is known even for HSTs of depth 2 and even whe

Outer bounds on the storage-repair bandwidth trade-off of exact-repair regenerating codes

In this paper, three outer bounds on the normalised storage-repair bandwidth trade-off of regenerating codes having parameter set {(n, k, d),(alpha, beta)} under the exact-repair (ER) setting are presented. The first outer bound, termed as the repair-matrix bound, is applicable for every parameter set (n, k, d), and in conjunction with a code construction known as improved layered codes, it characterises the normalised ER trade-off for the case (n, k = 3, d = n - 1). The bound shows that a non-vanishing gap exists between the ER and functional-repair (FR) trade-offs for every (n, k, d). The second bound, termed as the improved Mohajer-Tandon bound, is an improvement upon an existing bound due to Mohajer et al. and performs better in a region away from the minimum-storage-regenerating (MSR) point. However, in the vicinity of the MSR point, the repair-matrix bound outperforms the improved Mohajer-Tandon bound. The third bound is applicable to linear codes for the case k = d. In conjunction with the class of layered codes, the third outer bound characterises the normalised ER trade-off in the case of linear codes when k = d = n - 1

Tight bounds for Double Coverage against weak adversaries

We study the Double Coverage (DC) algorithm for the k-server problem in tree metrics in the (h,k)-setting, i.e., when DC with k servers is compared against an offline optimum algorithm with h ≤ k servers. It is well-known that in such metric spaces DC is k-competitive (and thus optimal) for h = k. We prove that even if k > h the competitive ratio of DC does not improve; in fact, it increases slightly as k grows, tending to h + 1. Specifically, we give matching upper and lower bounds of (k(h+1)) / (k+1) on the competitive ratio of DC on any tree metric

Freeze Extrusion Fabrication of 13-93 Bioactive Glass Scaffolds for Bone Repair

There is an increasing demand for synthetic scaffolds with the requisite biocompatibility, internal architecture, and mechanical properties for the bone repair and regeneration. In this work, scaffolds of a silicate bioactive glass (13-93) were prepared by a freeze extrusion fabrication (FEF) method and evaluated in vitro for potential applications in bone repair and regeneration. The process parameters for FEF production of scaffolds with the requisite microstructural characteristics, as well as the mechanical and cell culture response of the scaffolds were evaluated. After binder burnout and sintering (60 min at 700°C), the scaffolds consisted of a dense glass network with interpenetrating pores (porosity ≈ 50%; pore width = 100-500 μm). These scaffolds had a compressive strength of 140 ± 70 MPa, which is comparable to the strength of human cortical bone and far higher than the strengths of bioactive glass and ceramic scaffolds prepared by more conventional methods. The scaffolds also supported the proliferation of osteogenic MLO-A5 cells, indicating their biocompatibility. Potential application of these scaffolds in the repair and regeneration of load-bearing bones, such as segmental defects in long bones, is discussed

A chemical genetic approach reveals distinct EphB signaling mechanisms during brain development.

EphB receptor tyrosine kinases control multiple steps in nervous system development. However, it remains unclear whether EphBs regulate these different developmental processes directly or indirectly. In addition, given that EphBs signal through multiple mechanisms, it has been challenging to define which signaling functions of EphBs regulate particular developmental events. To address these issues, we engineered triple knock-in mice in which the kinase activity of three neuronally expressed EphBs can be rapidly, reversibly and specifically blocked. We found that the tyrosine kinase activity of EphBs was required for axon guidance in vivo. In contrast, EphB-mediated synaptogenesis occurred normally when the kinase activity of EphBs was inhibited, suggesting that EphBs mediate synapse development by an EphB tyrosine kinase-independent mechanism. Taken together, our data indicate that EphBs control axon guidance and synaptogenesis by distinct mechanisms and provide a new mouse model for dissecting EphB function in development and disease