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Oxysterols as promising small molecules for bone tissue engineering: Systematic review

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World Journal of Orthopedics 2020年第7期11卷 328-344页

作者： Ethan Cottrill Julianna Lazzari Zach Pennington Jeff Ehresman Andrew Schilling Naomi Dirckx nicholas theodore Daniel Sciubba Timothy Witham Department of Neurosurgery The Johns Hopkins University School of MedicineBaltimoreMD 21287United States

BACKGROUND Bone tissue engineering is an area of continued interest within orthopaedic surgery,as it promises to create implantable bone substitute materials that obviate the need for autologous bone ***,oxysterols–oxygenated derivatives of cholesterol-have been proposed as a novel class of osteoinductive small molecules for bone tissue ***,we present the first systematic review of the in vivo evidence describing the potential therapeutic utility of oxysterols for bone tissue *** To systematically review the available literature examining the effect of oxysterols on in vivo bone *** We conducted a systematic review of the literature following PRISMA *** the PubMed/MEDLINE,Embase,and Web of Science databases,we queried all publications in the English-language literature investigating the effect of oxysterols on in vivo bone *** were screened for eligibility using PICOS criteria and assessed for potential bias using an expanded version of the SYRCLE Risk of Bias assessment *** full-text articles examining the effect of oxysterols on in vivo bone formation were *** data included:Animal species,surgical/defect model,description of therapeutic and control treatments,and method for assessing bone *** outcome was fusion rate for spinal fusion models and percent bone regeneration for critical-sized defect *** were tabulated and described by both surgical/defect model and oxysterol ***,data from all included studies were aggregated to posit the mechanism by which oxysterols may mediate in vivo bone *** Our search identified 267 unique articles,of which 27 underwent full-text *** studies(all preclinical)met our inclusion/exclusion *** the 13 included studies,5 employed spinal fusion models,2 employed critical-sized alveolar defect models,and 6 employed critical-sized calvarial defect *** upon SYRCLE c

关键词： Oxysterol Bone tissue engineering Critical-sized defect Biomaterial Orthopaedic surgery Systematic review

Pedicle screw accuracy assessment in ExcelsiusGPS?robotic spine surgery:evaluation of deviation from pre-planned trajectory

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Chinese Neurosurgical Journal 2018年第3期4卷 118-123页

作者： Bowen Jiang A.Karim Ahmed Corinna C.Zygourakis Samuel Kalb Alex M.Zhu Jakub Godzik Camilo A.Molina Ari M.Blitz Ali Bydon Neil Crawford nicholas theodore Department of Neurosurgery The Johns Hopkins School of MedicineThe Johns Hopkins Hospital600 N.Wolfe StreetMeyer 7-113BaltimoreMD 21287USA Department of Neurosurgery Barrow Neurological InstituteSt.Joseph’s Hospital and Medical CenterPhoenixAZUSA Department of Neuroradiology Johns Hopkins School of MedicineThe Johns Hopkins Hospital600 N Wolfe StBaltimoreMD 21287USA Department of Neurosurgery Johns Hopkins University School of Medicine1800 Orleans StreetZayed Tower Mailstop 6007Baltimore 21287MDUSA Globus Medical Inc 2560 General Armistead AveAudubon 19403PAUSA

Background: The ExcelsiusGPS?(Globus Medical, Inc., Audubon, PA) is a next-generation spine surgery robotic system recently approved for use in the United States. The objective of the current study is to assess pedicle screw accuracy and clinical outcomes among two of the first operative cases utilizing the ExcelsiusGPS?robotic system and describe a novel metric to quantify screw deviation. Methods: Two patients who underwent lumbar fusion at a single institution with the ExcelsiusGPS?surgical robot were included. Pre-operative trajectory planning was performed from an intra-operative CT scan using the O-arm (Medtronic, Inc., Minneapolis, MN). After robotic-assisted screw implantation, a post-operative CT scan was obtained to confirm ideal screw placement and accuracy with the planned trajectory. A novel pedicle screw accuracy algorithm was devised to measure screw tip/tail deviation distance and angular offset on axial and sagittal planes. Screw accuracy was concurrently determined by a blinded neuroradiologist using the traditional Gertzbein-Robbins method. Clinical variables such as symptomatology, operative data, and post-operative follow-up were also collected. Results: Eight pedicle screws were placed in two L4-L5 fusion cases. Mean screw tip deviation was 2.1 mm (range 0.8-5.2 mm), mean tail deviation was 3.2 mm (range 0.9-5.4 mm), and mean angular offset was 2.4 degrees (range 0.7-3.8 degrees). All eight screws were accurately placed based on the Gertzbein-Robbins scale (88% Grade A and 12% Grade B). There were no cases of screw revision or new post-operative deficit. Both patients experienced improvement in Frankel grade and Karnofsky Performance Status (KPS) score by 6 weeks post-op. Conclusion: The ExcelsiusGPS? robot allows for precise execution of an intended pre-planned trajectory and accurate screw placement in the first patients to undergo robotic-assisted fusion with this technology.

关键词： Robotic spine surgery Robot-assisted surgery Excelsius GPS® Gertzbein-Robbins Pedicle screw accuracy

Investigational growth factors utilized in animal models of spinal fusion: Systematic review

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World Journal of Orthopedics 2019年第4期10卷 176-191页

作者： Ethan Cottrill A Karim Ahmed Noah Lessing Zachary Pennington Wataru Ishida Alexander Perdomo-Pantoja Sheng-fu Lo Elizabeth Howell Christina Holmes C Rory Goodwin nicholas theodore Daniel M Sciubba Timothy F Witham Department of Neurosurgery The Johns Hopkins Hospital Department of Neurosurgery Duke University Medical Center

BACKGROUND Over 400000 Americans annually undergo spinal fusion surgeries, yet up to 40%of these procedures result in pseudoarthrosis even with iliac crest autograft, the current "gold standard" treatment. Tissue engineering has the potential to solve this problem via the creation of bone grafts involving bone-promoting growth factors(e.g., bone morphogenetic protein 2). A broad assessment of experimental growth factors is important to inform future work and clinical potential in this area. To date, however, no study has systematically reviewed the investigational growth factors utilized in preclinical animal models of spinal *** To review all published studies assessing investigational growth factors for spinal fusion in animal models and identify promising agents for *** We conducted a systematic review of the literature using PubMed, Embase,Cochrane Library, and Web of Science databases with searches run on May 29 th,2018. The search query was designed to include all non-human, preclinical animal models of spinal fusion reported in the literature without a timespan limit. Extracted data for each model included surgical approach, level of fusion,animal species and breed, animal age and sex, and any other relevant characteristics. The dosages/sizes of all implant materials, spinal fusion rates,and follow-up time points were recorded. The data were analyzed and the results reported in tables and text. PRISMA guidelines were followed for this systematic *** Twenty-six articles were included in this study, comprising 14 experimental growth factors: AB204(n = 1); angiopoietin 1(n = 1); calcitonin(n = 3);erythropoietin(n = 1); basic fibroblast growth factor(n = 1); growth differentiation factor 5(n = 4), combined insulin-like growth factor 1 +transforming growth factor beta(n = 4); insulin(n = 1); NELL-1(n = 5); noggin(n= 1); P-15(n = 1); peptide B2 A(n = 2); and secreted phosphoprotein 24(n = 1).The fusion rates of the current gold sta

关键词： Spinal fusion Growth factor Pseudoarthrosis Systematic review

Excited electronic states and internal conversion in cyanocobalamin

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Chinese Chemical Letters 2015年第4期26卷 439-443页

作者： theodore E.Wiley Brenden C.Arruda nicholas A.Miller Michael Lenard Roseanne J.Sension Department of Chemistry University of Michigan

Cyanocobalamin （CNCbl） is a paradigm system for the study of excited electronic states and biological cofactors including the B12 vitamers, The photophysics of CNCbl has been thoroughly investigated using both ultrafast spectroscopy and time dependent density functional theory （TD-DFT）. Here we review the spectroscopic and theoretical investigations of CNCbl with emphasis on the nature of S1, the lowest excited electronic state, and extend the spectroscopic measurements to include the ultraviolet region of the spectrum. Ultrafast transient absorption measurements in the visible αβ band region and in the mid- infrared led to assignment of the S1 state to a ligand-to-metal charge transfer （LMCT） with lengthened axial bonds and a ~3 kcal/mol harrier for internal conversion to the ground state. The present measurements encompassing the y band region of the spectrum provide further support for the assignment of the S1 state. The experiments are in good agreement with the results of TD-DFT calculations which confirm the expected lengthening of the axial bonds in S1 and account for the observed barrier for internal conversion back to the ground state,

关键词： CyanocobalaminExcited electronic statesUltrafast spectroscopyTime dependent density functional theoryLigand-to-metal charge transfer

Stressor analysis approaches for endangered species assessments

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Natural Science 2013年第5期5卷 27-35页

作者： Johanna H. Salatas nicholas W. Gard theodore Wickwire Charles A. Menzie Exponent Bellevue Exponent Bellevue USA

The US Endangered Species Act is legislation with the power to limit human activities that may have deleterious effects on the viability of threatened and endangered species of fauna and flora. However, because most endangered species face multiple threats, it is often unclear whether limiting specific activities will improve the likelihood of long-term survival, particularly when the relative importance of different stressors is uncertain. Wildlife managers responsible for protecting these species face the challenge of determining the optimal allocation of limited funds and personnel among risk management and conservation priorities, in the absence of a good understanding of the relative importance of these stressors. We present an analytical framework that can serve as a technical basis for evaluating multiple risks to endangered species. Predictive and retrospective causal analysis applications are considered. The former address proposed projects where the potential exists for adverse interaction between the project and an endangered species. The latter involve existing projects or products for which a determination is being or has been made concerning the threats posed to an endangered species. The causal analysis method described herein is a well-established procedure that is widely used in other scientific fields and offers a practical and logical process through which threats to endangered species can be assessed and recovery actions prioritized.

关键词： Endangered Species Act Risk Management Conservation Priorities Multiple Stressor Analysis Causal Analysis

An Unsteady Two-Dimensional Complex Variable Boundary Element Method

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Applied Mathematics 2017年第6期8卷 878-891页

作者： Bryce D. Wilkins Joshua Greenberg Brittany Redmond Alan Baily nicholas Flowerday Adam Kratch theodore V. Hromadka Randy Boucher Howard D. McInvale Steve Horton Department of Mathematics United States Military Academy West Point NY USA

The Complex Variable Boundary Element Method (CVBEM) procedure is extended to modeling applications of the two-dimensional linear diffusion partial differential equation (PDE) on a rectangular domain. The methodology in this work is suitable for modeling diffusion problems with Dirichlet boundary conditions and an initial condition that is equal on the boundary to the boundary conditions. The underpinning of the modeling approach is to decompose the global initial-boundary value problem into a steady-state component and a transient component. The steady-state component is governed by the Laplace PDE and is modeled using the Complex Variable Boundary Element Method. The transient component is governed by the linear diffusion PDE and is modeled by a linear combination of basis functions that are the products of a two-dimensional Fourier sine series and an exponential function. The global approximation function is the sum of the approximate solutions from the two components. The boundary conditions of the steady-state problem are specified to match the boundary conditions from the global problem so that the CVBEM approximation function satisfies the global boundary conditions. Consequently, the boundary conditions of the transient problem are specified to be continuously zero. The initial condition of the transient component is specified as the difference between the initial condition of the global initial-boundary value problem and the CVBEM approximation of the steady-state solution. Therefore, when the approximate solutions from the two components are summed, the resulting global approximation function approximately satisfies the global initial condition. In this work, it will be demonstrated that the coupled global approximation function satisfies the governing diffusion PDE. Lastly, a procedure for developing streamlines at arbitrary model time is discussed.

关键词： Complex Variables Diffusion Equation Laplace Equation Complex Variable Boundary Element Method (CVBEM) Numerical Techniques for Partial Differential Equations