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1. DNA origami drives gene expression in a human cell culture system

Author

Chang Yong Oh, Haninder Kaur, Geetu Tuteja, and Eric R. Henderson

Subjects
DNA nanotechnology, DNA origami, Human cell line, Flow cytometry, Green fluorescent protein (GFP), Gene expression, Medicine, Science
Abstract

Abstract Self-assembling DNA nanoparticles have the potential to significantly advance the targeted delivery of molecular cargo owing to their chemical and architectural flexibility. Recently, it has been demonstrated that the genetic code embedded in DNA nanoparticles produced by the method of DNA origami or related techniques can be recognized and copied by RNA polymerase in vitro. Further, sculpted DNA nanoparticles can serve as a substrate for Cas9-mediated gene modification and gene expression in cell culture. In the present study, we further investigate the ability of DNA origami nanoparticles to be expressed in a human cell line with emphasis on the impact of single-stranded DNA (ssDNA) domains and the contributions of the architectural disposition of genetic control elements, namely promoter and enhancer sequences. Our findings suggest that while cells possess the remarkable capability to express genes within highly folded architectures, the presence and relative density and location of ssDNA domains appears to influence overall levels of gene expression. These results suggest that it may be possible to nuance folded DNA nanoparticle architecture to regulate the rate and/or level of gene expression. Considering the highly malleable architecture and chemistry of self-assembling DNA nanoparticles, these findings motivate further exploration of their potential as an economic nanotechnology platform for targeted gene editing, nucleic acid-based vaccines, and related biotherapeutic applications.

Published
2024
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2. Wind Energy Conversion by Plant-Inspired Designs.

Author

Michael A McCloskey, Curtis L Mosher, and Eric R Henderson

Subjects
Medicine, Science
Abstract

In 2008 the U.S. Department of Energy set a target of 20% wind energy by 2030. To date, induction-based turbines form the mainstay of this effort, but turbines are noisy, perceived as unattractive, a potential hazard to bats and birds, and their height hampers deployment in residential settings. Several groups have proposed that artificial plants containing piezoelectric elements may harvest wind energy sufficient to contribute to a carbon-neutral energy economy. Here we measured energy conversion by cottonwood-inspired piezoelectric leaves, and by a "vertical flapping stalk"-the most efficient piezo-leaf previously reported. We emulated cottonwood for its unusually ordered, periodic flutter, properties conducive to piezo excitation. Integrated over 0°-90° (azimuthal) of incident airflow, cottonwood mimics outperformed the vertical flapping stalk, but they produced << daW per conceptualized tree. In contrast, a modest-sized cottonwood tree may dissipate ~ 80 W via leaf motion alone. A major limitation of piezo-transduction is charge generation, which scales with capacitance (area). We thus tested a rudimentary, cattail-inspired leaf with stacked elements wired in parallel. Power increased systematically with capacitance as expected, but extrapolation to acre-sized assemblages predicts << daW. Although our results suggest that present piezoelectric materials will not harvest mid-range power from botanic mimics of convenient size, recent developments in electrostriction and triboelectric systems may offer more fertile ground to further explore this concept.

Published
2017
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3. In vitro transcription of self-assembling DNA nanoparticles

Author

Chang Yong Oh and Eric R. Henderson

Subjects
Medicine, Science
Abstract

Abstract Nucleic acid nanoparticles are playing an increasingly important role in biomolecular diagnostics and therapeutics as well as a variety of other areas. The unique attributes of self-assembling DNA nanoparticles provide a potentially valuable addition or alternative to the lipid-based nanoparticles that are currently used to ferry nucleic acids in living systems. To explore this possibility, we have assessed the ability of self-assembling DNA nanoparticles to be constructed from complete gene cassettes that are capable of gene expression in vitro. In the current report, we describe the somewhat counter-intuitive result that despite extensive crossovers (the stereochemical analogs of Holliday junctions) and variations in architecture, these DNA nanoparticles are amenable to gene expression as evidenced by T7 RNA polymerase-driven transcription of a reporter gene in vitro. These findings, coupled with the vastly malleable architecture and chemistry of self-assembling DNA nanoparticles, warrant further investigation of their utility in biomedical genetics.

Published
2023
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4. Pathologic Femur Fracture in an Immunocompetent Healthy Young Adult due to Acute Osteomyelitis

Author

Evan R. J. Goyette, Natalia Georgantzoglou, Darcy A. Kerr, Yvonne Cheung, Eric R. Henderson, and Konstantinos Linos

Subjects
Pathology, RB1-214
Abstract

An immunocompetent 33-year-old woman presented with a pathologic femur fracture after one month of progressively worsening right thigh pain. Open biopsy demonstrated acute suppurative osteomyelitis despite the lack of clinical risk factors. The polymicrobial infection was successfully treated with three operative procedures and culture-specific antibiotic agents. Acute osteomyelitis, while an uncommon cause of pathologic fracture, must always be on the differential diagnosis, even when no obvious predisposing factors are present. When investigating for an infectious etiology in cases such as our own, considering immunodeficiency syndromes alongside the more typical causes of osteomyelitis is encouraged.

Published
2023
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5. Intraoperative assessment of bone viability through improved analysis and visualization of dynamic contrast-enhanced fluorescence imaging: technique report

Author

Jonathan Thomas Elliott, PhD, Shudong Jiang, PhD, Eric R. Henderson, MD, Gerard P. Slobogean, MD, FRCSC, Nathan N. O'Hara, MHA, Cao Xu, PhD, Jing Xin, PhD, Xinyue Han, MEng, Melanie L. Christian, and Ida Leah Gitajn, MD

Subjects
Orthopedic surgery, RD701-811
Abstract

Abstract. Bone devitalization is believed to be a critical determinant of complications such as infection or nonunion. However, intraoperative assessment of bone devitalization, particularly in open fractures and infections, remains highly subjective resulting in variation in treatment. Optical imaging tools, particularly dynamic contrast-enhanced fluorescence imaging, can provide real-time, intraoperative assessment of bone and soft tissue perfusion, which informs the tissues' ability to heal and fight infection. We describe a novel technique to apply indocyanine green–based fluorescence imaging, using a device that is frequently used in the operating room to assess skin or flap perfusion in plastic surgery, to assess bone and deep tissue perfusion in three pertinent cases: (1) a chronic infection/nonunion after a Gustilo type 3A tibia fracture (patient 1), (2) an acute Gustilo type 3C tibia open fracture with extensive degloving/soft tissue stripping (patient 2), and (3) an atrophic nonunion of the humerus (patient 3). In all three cases, fluorescence imaging (both time-specific fluorescence and maximum fluorescence) and derived kinetic maps of time-to-peak, ingress slope, and egress slope demonstrated clear spatial variation in perfusion that corresponded to the patient pathogenesis. The impact of this information on patient outcome will need to be evaluated in future clinical trials; however, these cases demonstrate in principle that optical imaging information has the potential to inform surgical practice, reduce the variation in treatment, and improve outcomes observed in these challenging patients.

Published
2022
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6. Applications of artificial intelligence in orthopaedic surgery

Author

Faraz Farhadi, Matthew R. Barnes, Harun R. Sugito, Jessica M. Sin, Eric R. Henderson, and Joshua J. Levy

Subjects
artificial intelligence, Orthopaedics, Orthopaedic Surgery, machine learning, deep learning, Medical technology, R855-855.5
Abstract

The practice of medicine is rapidly transforming as a result of technological breakthroughs. Artificial intelligence (AI) systems are becoming more and more relevant in medicine and orthopaedic surgery as a result of the nearly exponential growth in computer processing power, cloud based computing, and development, and refining of medical-task specific software algorithms. Because of the extensive role of technologies such as medical imaging that bring high sensitivity, specificity, and positive/negative prognostic value to management of orthopaedic disorders, the field is particularly ripe for the application of machine-based integration of imaging studies, among other applications. Through this review, we seek to promote awareness in the orthopaedics community of the current accomplishments and projected uses of AI and ML as described in the literature. We summarize the current state of the art in the use of ML and AI in five key orthopaedic disciplines: joint reconstruction, spine, orthopaedic oncology, trauma, and sports medicine.

Published
2022
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7. Acceptability and Feasibility of Delivering Decision Aids to Veterans for Management of Knee Osteoarthritis – A Pilot Study

Author

Clifford A Reilly, Makenna L Rice, Dylan J Parker, Philip P Goodney, Jon D Lurie, Said A Ibrahim, and Eric R Henderson

Subjects
General Medicine, General Chemistry, Patient Related Outcome Measures
Abstract

Clifford A Reilly,1 Makenna L Rice,2 Dylan J Parker,2 Philip P Goodney,3– 6 Jon D Lurie,3,4 Said A Ibrahim,7,8 Eric R Henderson2,4,6 1Larner College of Medicine, University of Vermont, Burlington, VT, USA; 2Department of Orthopaedic Surgery, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA; 3The Dartmouth Institute for Health Policy and Clinical Practice, Dartmouth College, Hanover, NH, USA; 4Geisel School of Medicine, Dartmouth College, Hanover, NH, USA; 5Heart and Vascular Center, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA; 6White River Junction VA Medical Center, US Department of Veterans Affairs, White River Junction, VT, USA; 7Zucker School of Medicine, Hofstra University/Northwell Health, Hempstead, NY, USA; 8Department of Medicine, Long Island Jewish Medical Center, New Hyde Park, NY, USACorrespondence: Makenna L Rice, Department of Orthopaedic Surgery, Dartmouth Hitchcock Medical Center, 1 Medical Center Dr, Rubin 592, Lebanon, NH, 03756, USA, Tel +1 831 247-1106, Fax +1 603 653-3581, Email Makenna.L.Rice@hitchcock.orgIntroduction: Decision aids are effective tools in facilitating patient-centered care and patient involvement in the decision-making process. Given unique barriers to providing patient-centered care for Veterans, implementation of decision aids may improve overall quality of care. We aimed to assess the acceptability and feasibility of video-based and pamphlet-based decision aid use in Veterans with knee osteoarthritis.Materials and Methods: Veterans considering treatment for knee osteoarthritis received either an online video-based aid, pamphlet-based aid, or both before their surgical consult. At their visit, patients completed written pre-visit and post-visit questionnaires. The pre-visit questionnaire included questions about the patient’s demographics, decision-making preferences, experiences using the assigned decision aids, and the Hip-Knee Decision Quality Instrument. The post-visit questionnaire assessed the patient’s overall experience with the decision-making process and how use of the decision aid influenced their discussion with the physician.Results: All 16 patients who received the pamphlet-based aid reviewed the decision aid before their visit, compared to only five of the 12 patients who received the video-based aid. Thirteen of 20 patients indicated that they preferred to share treatment decision-making with their physician. Seventeen of 20 patients believed they would feel comfortable questioning the treatment recommendation of their surgeon after decision aid use. Most patients reported a positive experience using their decision aid, regardless of modality, and found it easily comprehensible and useful in visit preparation. A preference for a pamphlet-based aid was expressed by the majority of patients.Conclusion: Veterans considering treatment for knee osteoarthritis are well prepared to engage in a patient-centered care experience. Most patients preferred sharing the decision-making process with their physician and felt comfortable questioning them about treatment recommendations. Decision aids helped Veterans feel more informed about their treatment options and improved engagement and discussion with their physician. Pamphlet-based aids were utilized more reliably than video-based aids.Keywords: patient-centered care, shared decision-making, decision aid, knee osteoarthritis, military service

Published
2023

8. Early identification of life-threatening soft-tissue infection using dynamic fluorescence imaging: first-in-kind clinical study of first-pass kinetics

Author

Samuel S. Streeter, Gabrielle S. Ray, Logan M. Bateman, Kendra A. Hebert, Fallon E. Bushee, Scott W. Rodi, I. Leah Gitajn, Jaimo Ahn, Sunil Singhal, Neils D. Martin, Nicholas M. Bernthal, Christopher Lee, William T. Obremskey, Jonathan G. Shoenecker, Jonathan T. Elliott, and Eric R. Henderson

Subjects
Article
Abstract

Necrotizing soft-tissue infections (NSTIs) are aggressive and deadly. Immediate surgical debridement is standard-of-care, but patients often present with non-specific symptoms, thereby delaying treatment. Because NSTIs cause microvascular thrombosis, we hypothesized that perfusion imaging using indocyanine green (ICG) would show diminished fluorescence signal in NSTI-affected tissues, particularly compared to non-necrotizing, superficial infections. Through a first-in-kind clinical study, we performed first-pass ICG fluorescence perfusion imaging of patients with suspected NSTIs. Early results support our hypothesis that ICG signal voids occur in NSTI-affected tissues and that dynamic contrast-enhanced fluorescence parameters reveal tissue kinetics that may be related to disease progression and extent.

Published
2023

9. Proceduralist criteria for evaluating interface utility of novel imaging modalities in early phase clinical trials: evaluating the need for standardized criteria

Author

Eric R. Henderson, Jonathan T. Elliott, Shudong Jiang, Ida L. Gitajn, John Y. K. Lee, Summer L. Gibbs, Michael Bouvet, Anita Mahadevan-Jansen, Michael Daly, Samuel S. Streeter, Keith D. Paulsen, Brian W. Pogue, Kimberley S. Samkoe, and Sunil Singhal

Subjects
Article
Abstract

Accelerating innovation in the space of fluorescence imaging for surgical applications has increased interest in safely and expediently advancing these technologies to clinic through Food and Drug Administration-(FDA-) compliant trials. Conventional metrics for early phase trials include drug safety, tolerability, dosing, and pharmacokinetics. Most procedural imaging technologies rely on administration of an exogenous fluorophore and concurrent use of an imaging system; both of which must receive FDA approval to proceed to clinic. Because fluorophores are classified as medical imaging agents, criteria for establishing dose are different, and arguably more complicated, than therapeutic drugs. Since no therapeutic effect is desired, medical imaging agents are ideally administered at the lowest dose that achieves adequate target differentiation. Because procedural imaging modalities are intended to enhance and/or ease proceduralists’ identification or assessment of tissues, beneficial effects of these technologies may manifest in the form of qualitative endpoints such as: 1) confidence; 2) decision-making; and 3) satisfaction with the specified procedure. Due to the rapid expansion of medical imaging technologies, we believe that our field requires standardized criteria to evaluate existing and emerging technologies objectively so that both quantitative and qualitative aspects of their use may be measured and useful comparisons to assess their relative value may occur. Here, we present a 15-item consensus-based survey instrument to assess the utility of novel imaging technologies from the proceduralist’s standpoint.

Published
2023

10. Epidermal growth factor-targeted fluorescence is unaffected by standard neoadjuvant therapies in human sarcomas

Author

Eric R. Henderson, Paul M. Werth, Xiaochun Xu, Lesley Jarvis, Keith D. Paulsen, P. Jack Hoopes, Eben L. Rosenthal, Brian W. Pogue, and Kimberley S. Samkoe

Subjects
Article
Abstract

Curative surgery for other many cancers requires that the tumor be removed with a zone of normal tissue surrounding the tumor with ‘negative’ margins. Sarcomas, cancers of the bones, muscles, and fat, require WLE for cure. Unfortunately, ‘positive’ margins occur in 20–25% of sarcoma surgeries, associated with cancer recurrence and reduced survival. Our group successfully tested a small-molecule fluorophore (ABY-029) in sarcomas that targets the epidermal growth factor receptor. We sought to evaluate human sarcoma xenografts for epidermal growth factor receptor expression and binding of ABY-029 with and without exposure to standard presurgical chemotherapy and radiation. We inoculated groups of 24 NSG mice with five cell lines (120 mice total). Eight mice from each cell line received: 1) radiation alone; 2) chemotherapy alone; or 3) chemotherapy and radiation. We administered ABY-029 2–4 hours before surgery. Tumor and biopsy portions of background tissues were removed. All tissues were imaged on a LI-COR Odyssey and processed in pathology. There were no significant reductions in epidermal growth factor receptor expression or in ABY-029-mediated fluorescence in tumors exposed to chemotherapy, radiation, or both. fluorescence-guided surgery demonstrates strong promise to improve curative surgical cancer care, particularly for sarcomas where the positive margin rate is substantial. Fluorophore performance must be evaluated under circumstances that duplicate accurately the biological milieu relevant to a particular cancer. This work shows that human sarcoma xenografts subjected to standard therapies do not demonstrate a change in epidermal growth factor receptor expression or in epidermal growth factor receptor-targeted fluorescence, thereby indicating that epidermal growth factor receptor-targeted fluorescence-guided surgery should be feasible under normal therapeutic conditions in the clinic.

Published
2022

11. Reliability, Validity, and Responsiveness of the Western Ontario and McMaster Universities Osteoarthritis Index for Elderly Patients with a Femoral Neck Fracture

Author

Paul T.P.W. Burgers, Rudolf W Poolman, Theodorus MJ Van Bakel, Wim E Tuinebreijer, Stephanie M Zielinski, Mohit Bhandari, Peter Patka, Esther MM Van Lieshout, P J Devereaux, Gordon H Guyatt, Thomas A Einhorn, Lehana Thabane, Emil H Schemitsch, Kenneth J Koval, Frede Frihagen, Kevin Tetsworth, Ernesto Guerra-Farfan, Stephen D Walter, Sheila Sprague, Marilyn Swinton, Taryn Scott, Paula McKay, Kim Madden, Diane Heels-Ansdell, Lisa Buckingham, Aravin Duraikannan, Heather Silva, Martin J Heetveld, Robert D Zura, Victoria Avram, Ajay Manjoo, Dale Williams, John Antoniou, Tim Ramsay, Earl R Bogoch, Andrew Trenholm, Stephen Lyman, Madhu Mazumdar, Kevin J Bozic, Mark Luborsky, Stuart Goodman, Susan Muray, Rob Korley, Richard Buckley, Paul Duffy, Shannon Puloski, Kimberly Carcary, Melissa Lorenzo, Michael D McKee, Jeremy A Hall, Aaron Nauth, Daniel Whelan, Timothy R Daniels, James P Waddell, Henry Ahn, Milena R Vicente, Jennifer T Hidy, Melanie T MacNevin, Hans Kreder, Terry Axelrod, Richard Jenkinson, Markku Nousiainen, David Stephen, Veronica Wadey, Monica Kunz, Katrine Milner, Ria Cagaanan, Melanie MacNevin, Peter J O’Brien, Piotr A Blachut, Henry M Broekhuyse, Pierre Guy, Kelly A Lefaivre, Gerard P Slobogean, Raman Johal, Irene Leung, Chad Coles, Ross Leighton, C. Glen Richardson, Michael Biddulph, Michael Gross, Michael Dunbar, J. David Amirault, David Alexander, Catherine Coady, Mark Glazebrook, David Johnston, William Oxner, Gerald Reardon, Ivan Wong, Kelly Trask, Shelley MacDonald, Andrew Furey, Craig Stone, Minnie Parsons, Trevor Stone, Mauri Zomar, Robert McCormack, Kelly Apostle, Dory Boyer, Farhad Moola, Bertrand Perey, Darius Viskontas, Karyn Moon, Raely Moon, Yves Laflamme, Benoit Benoit, Pierre Ranger, Michel Malo, Julio Fernandes, Karine Tardif, Julie Fournier, Pascal André Vendittoli, Vincent Massé, Alain G Roy, Martin Lavigne, Daniel Lusignan, Craig Davis, Philip Stull, Stewart Weinerman, Peter Weingarten, Steven Lindenbaum, Michael Hewitt, Rebecca Danielwicz, Janell Baker, Michael Mont, Donald E Delanois, Bhaveen Kapadia, Kimona Issa, Marylou Mullen, Andrew Sems, Barb Foreman, Javad Parvizi, Tiffany Morrison, Courtland Lewis, Stephanie Caminiti, Paul Tornetta, William R Creevy, Michelle J Lespasio, Hope Carlisle, Andrew Marcantonio, Michael Kain, Lawrence Specht, John Tilzey, John Garfi, Samir Mehta, John L Esterhai, Jaimo Ahn, Derek Donegan, Annamarie Horan, Kelly McGinnis, James Roberson, Thomas Bradbury, Greg Erens, Kyle Webb, Brian Mullis, Karl Shively, Andrew Parr, Janos Ertl, Ripley Worman, Mark Webster, Judd Cummings, Valda Frizzell, Molly Moore, Clifford B Jones, James R Ringler, Debra L Sietsema, Jane E Walker, Enes Kanlic, Amr Abdelgawad, Juan Shunia, Charles DePaolo, Susan Sutherland, Rachel Alosky, Robert Zura, Maria Manson, Gregg Strathy, Kathleen Peter, Paul Johnson, Meaghan Morton, James Shaer, Tyson Schrickel, Barbara Hileman, Marina Hanes, Elisha Chance, E. Matthew Heinrich, David Dodgin, Michele LaBadie, David Zamorano, Martin Tynan, Ran Schwarzkopf, John A Scolaro, Ranjan Gupta, Samuel Bederman, Nitin Bhatia, Bang Hoang, Douglas Kiester, Neil Jones, Gregory Rafijah, Damon Alavekios, Jason Lee, Akshay Mehta, Steven Schroder, Tom Chao, Vincent Colin, Phuc (Phil) Dang, Stephen Keun Heng, Gregory Lopez, Samuel Galle, Sohrab Pahlavan, Duy L Phan, Minal Tapadia, Christopher Bui, Nickul Jain, Tyler Moore, Nathan Moroski, Deeba Pourmand, Erik N Kubiak, Jeremy Gililland, David Rothberg, Christopher Peters, Christopher Pelt, Ami R Stuart, Kirby Corbey, Franklin D Shuler, James Day, Tigran Garabekyan, Felix Cheung, Ali Oliashirazi, Jonathon Salava, Linda Morgan, Timothy Wilson-Byrne, Mary Beth Cordle, Leon H.G.J. Elmans, Joost A.A.M. van den Hout, Adrianus JP Joosten, Ad FA van Beurden, Stefan BT Bolder, Denise Eygendaal, Adrianus F.C.M. Moonen, Rutger CI van Geenen, Eric A Hoebink, Robert Wagenmakers, Wouter van Helden, Hans-Peter W van Jonbergen, Herbert Roerdink, Joost M Reuver, Alexander FW Barnaart, Elvira R Flikweert, Rover Krips, J. Bernard Mullers, Hans Schüller, Mark LM Falke, Frans J Kurek, Adrianus CH Slingerland, Jan P van Dijk, Wouter H van Helden, Hugo W Bolhuis, Pieter HJ Bullens, Mike Hogervorst, Karin E de Kroon, Rob H Jansen, Ferry Steenstra, Eric EJ Raven, W. Peter J Fontijne, Saskia C Wiersma, Bastiaan Boetes, Edgar JT ten Holder, Huub JL van der Heide, Jochem Nagels, Enrike H.M.J. van der Linden-van der Zwaag, Stefan B Keizer, Jan-Willem A Swen, Peter HC den Hollander, Bregje JW Thomassen, Willem Jan Kleyn Molekamp, Frank R.A.J. de Meulemeester, Arthur EB Kleipool, Robert Haverlag, Maarten P Simons, Eduard L.A.R. Mutsaerts, Rob Kooijman, Roelf R Postema, René J.T.M. Bleker, Harald IH Lampe, Lein Schuman, John Cheung, Frank van Bommel, W. Paul Winia, Daniel Haverkamp, Harm van der Vis, Peter A Nolte, Michel PJ van den Bekerom, Tjitte de Jong, Arthur van Noort, Diederik A Vergroesen, Bernard G Schutte, Harm M van der Vis, Lijkele Beimers, Jasper de Vries, Arthur W Zurcher, G.H. Rob Albers, Maarten Rademakers, Stefan Breugem, Ibo van der Haven, Pieter Jan Damen, Gythe H Bulstra, Martin M Campo, Mathijs P Somford, Daniël Haverkamp, Susan Liew, Harvinder Bedi, Ashley Carr, Andrew Chia, Steve Csongvay, Craig Donohue, Stephen Doig, Elton Edwards, Max Esser, Richard Freeman, Andrew Gong, Doug Li, Russell Miller, Lu Ton, Otis Wang, Ian Young, Adam Dowrick, Zoe Murdoch, Claire Sage, Richard Page, David Bainbridge, Richard Angliss, Ben Miller, Andrew Thomson, Graeme Brown, Simon Williams, Kevin Eng, David Bowyer, John Skelley, Chatar Goyal, Sally Beattie, Enrique Guerado, Encarnacion Cruz, Juan Ramon Cano, Miguel Angel Froufe, Lluis Marull Serra, Samer Al-dirra, Cristina Martinez, Francisco José Tarazona Santabalbina, Jordi Teixidor Serra, Jordi Tomas Hernandez, Marc Aguilar Garcia, Vicente Molero Garcia, Sergi Barrera, Miriam Garrido, Lars Nordsletten, John Clarke-Jenssen, Geir Hjorthaug, Anne Christine Brekke, Elise Berg Vesterhus, Ingunn Skaugrud, Pradeep Tripathi, Sandesh Katiyar, Preksha Shukla, Marc Swiontkowski, Gordon Guyatt, Kyle Jeray, Stephen Walter, Helena Viveiros, Victoria Truong, Kaitlin Koo, Qi Zhou, Deborah Maddock, Nicole Simunovic, Julie Agel, Amar Rangan, Birgit C Hanusch, Lucksy Kottam, Rachel Clarkson, Gregory J Della Rocca, Gerard Slobogean, Jeffrey Katz, Brenda Gillespie, Gail A Greendale, Curtis Hartman, Craig Rubin, James Waddell, H. Michael Lemke, Amber Oatt, Richard E Buckley, Robert Korley, Kelly Johnston, James Powell, David Sanders, Abdel Lawendy, Christina Tieszer, John Murnaghan, Diane Nam, Albert Yee, Daniel B Whelan, Lisa M Wild, Ryan M Khan, Cathy Coady, David Amirault, Glen Richardson, Gwen Dobbin, Ryan Bicknell, Jeff Yach, Davide Bardana, Gavin Wood, Mark Harrison, David Yen, Sue Lambert, Fiona Howells, Angela Ward, Paul Zalzal, Heather Brien, V Naumetz, Brad Weening, Eugene K Wai, Steve Papp, Wade T Gofton, Stephen P Kingwell, Garth Johnson, Joseph O’Neil, Darren M Roffey, Vivian Borsella, Todd M Oliver, Vicki Jones, Terrence J Endres, Samuel G Agnew, Kyle J Jeray, J. Scott Broderick, David R Goetz, Thomas B Pace, Thomas M Schaller, Scott E Porter, Stephanie L Tanner, Rebecca G Snider, Lauren A Nastoff, Shea A Bielby, Julie A Switzer, Peter A Cole, Sarah A Anderson, Paul M Lafferty, Mengnai Li, Thuan V Ly, Scott B Marston, Amy L Foley, Sandy Vang, David M Wright, Andrew J Marcantonio, Michael SH Kain, Richard Iorio, Lawrence M Specht, John F Tilzey, Margaret J Lobo, John S Garfi, Heather A Vallier, Andrea Dolenc, Chalitha Robinson, Michael J Prayson, Richard Laughlin, L. Joseph Rubino, Jedediah May, Geoffrey Ryan Rieser, Liz Dulaney-Cripe, Chris Gayton, John T Gorczyca, Jonathan M Gross, Catherine A Humphrey, Stephen Kates, Krista Noble, Allison W McIntyre, Kaili Pecorella, Craig A Davis, Stephen Lindenbaum, John Schwappach, Janell K Baker, Tori Rutherford, Heike Newman, Shane Lieberman, Erin Finn, Kristin Robbins, Meghan Hurley, Lindsey Lyle, Khalis Mitchell, Kieran Browner, Erica Whatley, Krystal Payton, Christina Reeves, Lisa K Cannada, David Karges, Leslie Hill, John Esterhai, Annamarie D Horan, Christine A Kaminski, Brynn N Kowalski, Jonathan P Keeve, Christopher G Anderson, Michael D McDonald, Jodi M Hoffman, Ivan Tarkin, Peter Siska, Gary Gruen, Andrew Evans, Dana J Farrell, James Irrgang, Arlene Luther, William W Cross, Joseph R Cass, Stephen A Sems, Michael E Torchia, Tyson Scrabeck, Mark Jenkins, Jules Dumais, Amanda W Romero, Carlos A Sagebien, Mark S Butler, James T Monica, Patricia Seuffert, Joseph R Hsu, James Ficke, Michael Charlton, Matthew Napierala, Mary Fan, Chadi Tannoury, Michael Archdeacon, Ryan Finnan, Toan Le, John Wyrick, Shelley Hess, Michael L Brennan, Robert Probe, Evelyn Kile, Kelli Mills, Lydia Clipper, Michelle Yu, Katie Erwin, Daniel Horwitz, Kent Strohecker, Teresa K Swenson, Andrew H Schmidt, Jerald R Westberg, Kamran Aurang, Gary Zohman, Brett Peterson, Roger B Huff, Joseph Baele, Timothy Weber, Matt Edison, Jessica McBeth, Janos P Ertl, J. Andrew Parr, Molly M Moore, Erin Tobias, Emily Thomas, Charles J DePaolo, Leslie E Shell, Lynne Hampton, Stephanie Shepard, Tracy Nanney, Claudine Cuento, Robert V Cantu, Eric R Henderson, Linda S Eickhoff, E. Mark Hammerberg, Philip Stahel, David Hak, Cyril Mauffrey, Douglas Gibula, Hannah Gissel, Corey Henderson, David P Zamorano, Martin C Tynan, Deanna Lawson, Brett D Crist, Yvonne M Murtha, Linda K Anderson, Colleen Linehan, Lindsey Pilling, Courtland G Lewis, Raymond J Sullivan, Elizabeth Roper, William Obremskey, Philip Kregor, Justin E Richards, Kenya Stringfellow, Michael P Dohm, Abby Zellar, Michiel JM Segers, Jacco AC Zijl, Bart Verhoeven, Anke B Smits, Jean Paul PM de Vries, Bram Fioole, Henk van der Hoeven, Evert BM Theunissen, Tammo S de Vries Reilingh, Lonneke Govaert, Philippe Wittich, Maurits de Brauw, Jan Wille, Peter M.N.Y.M. Go, Ewan D Ritchie, Ronald N Wessel, Eric R Hammacher, Gijs A Visser, Heyn Stockmann, Rob Silvis, Jaap P Snellen, Bram Rijbroek, Joris JG Scheepers, Erik GJ Vermeulen, Michiel PC Siroen, Ronald Vuylsteke, Hans LF Brom, Herman Rijna, Piet AR de Rijcke, Cees L Koppert, Steven E Buijk, Richard PR Groenendijk, Imro Dawson, Geert WM Tetteroo, Milko MM Bruijninckx, Pascal G Doornebosch, Eelco JR de Graaf, Maarten van der Elst, Carmen C van der Pol, Martijne van’t Riet, Tom M Karsten, Mark R de Vries, Laurents PS Stassen, Niels WL Schep, G Ben Schmidt, W H Hoffman, Frank H.W.M. van der Heijden, W. Jaap Willems, Cor P van der Hart, Kahn Turckan, Sebastiaan Festen, Frank de Nies, Nico JM Out, Jan Bosma, Albert van Kampen, Jan Biert, Arie B van Vugt, Michael JR Edwards, Taco J Blokhuis, Jan Paul M Frölke, Leo MG Geeraedts, Jean WM Gardeniers, Edward T.C.H. Tan, Lodewijk M.S.J. Poelhekke, Maarten C de Waal Malefijt, Bart Schreurs, Gert R Roukema, Hong A Josaputra, Paul Keller, Peter D de Rooij, Hans Kuiken, Han Boxma, Berry I Cleffken, Ronald Liem, Steven J Rhemrev, Coks HR Bosman, Alexander de Mol van Otterloo, Jochem Hoogendoorn, Alexander C de Vries, Sven AG Meylaerts, Michiel HJ Verhofstad, Joost Meijer, Teun van Egmond, Igor van der Brand, Martin G Eversdijk, Rolf Peters, Dennis Den Hartog, Oscar JF Van Waes, Pim Oprel, Martin Campo, Ronald Verhagen, G.H. Robert Albers, Rogier KJ Simmermacher, Jeroen van Mulken, Karlijn van Wessem, Steven M van Gaalen, Luke PH Leenen, Maarten W.G.A. Bronkhorst, Onno R Guicherit, J. Carel Goslings, Kees Jan Ponsen, Mahesh Bhatia, Vinod Arora, Vivek Tyagi, Ajay Gupta, Neeraj Jain, Farah Khan, Ateet Sharma, Amir Sanghavi, Mittal Trivedi, Anil Rai, null Subash, Kamal Rai, Vineet Yadav, Sanjay Singh, Amal Shankar Prasad, Vimlesh Mishra, D C Sundaresh, Angshuman Khanna, Joe Joseph Cherian, Davy J Olakkengil, Gaurav Sharma, Akhil Dadi, Naveen Palla, Utsav Ganguly, B. Sachidananda Rai, Janakiraman Rajakumar, Peter Hull, Sophie Lewis, Simone Evans, Rajesh Nanda, Rajanikanth Logishetty, Sanjeev Anand, Carol Bowler, Andrew Jennings, Graham Chuter, Glynis Rose, Gillian Horner, Callum Clark, Kate Eke, Mike Reed, Chris Herriott, Christine Dobb, Hamish Curry, Greg Etherington, Arvind Jain, Ash Moaveni, Matthias Russ, Geoff Donald, Patrick Weinrauch, Paul Pincus, Steven Yang, Brett Halliday, Trevor Gervais, Michael Holt, Annette Flynn, Marinis Pirpiris, David Love, Andrew Bucknill, Richard J Farrugia, Torben Ianssen, Asgeir Amundsen, Jan Egil Brattgjerd, Tor Borch, Berthe Bøe, Bernhard Flatøy, Sondre Hasselund, Knut Jørgen Haug, Kim Hemlock, Tor Magne Hoseth, Geir Jomaas, Thomas Kibsgård, Tarjei Lona, Gilbert Moatshe, Oliver Müller, Marius Molund, Tor Nicolaisen, Fredrik Nilsen, Jonas Rydinge, Morten Smedsrud, Are Stødle, Axel Trommer, Stein Ugland, Anders Karlsten, Guri Ekås, Hans-Christoph Pape, Matthias Knobe, Roman Pfeifer, Orthopedic Surgery and Sports Medicine, Graduate School, Other departments, Surgery, Other Research, Amsterdam Movement Sciences, Cardiothoracic Surgery, and Emergency Medicine

Subjects
Male, medicine.medical_specialty, WOMAC, Abstracting and Indexing, Osteoarthritis, Cronbach's alpha, Surveys and Questionnaires, medicine, Humans, Orthopedics and Sports Medicine, Clinical significance, Femoral neck, Aged, 80 and over, Ontario, business.industry, Reproducibility of Results, Construct validity, General Medicine, medicine.disease, RELIABILITY VALIDITY, Femoral Neck Fractures, Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10], Clinical trial, Reconstructive and regenerative medicine Radboud Institute for Molecular Life Sciences [Radboudumc 10], medicine.anatomical_structure, Physical therapy, Female, Surgery, business
Abstract

Item does not contain fulltext BACKGROUND: The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) has been extensively evaluated in groups of patients with osteoarthritis, yet not in patients with a femoral neck fracture. This study aimed to determine the reliability, construct validity, and responsiveness of the WOMAC compared with the Short Form-12 (SF-12) and the EuroQol 5D (EQ-5D) questionnaires for the assessment of elderly patients with a femoral neck fracture. METHODS: Reliability was tested by assessing the Cronbach alpha. Construct validity was determined with the Pearson correlation coefficient. Change scores were calculated from ten weeks to twelve months of follow-up. Standardized response means and floor and ceiling effects were determined. Analyses were performed to compare the results for patients less than eighty years old with those for patients eighty years of age or older. RESULTS: The mean WOMAC total score was 89 points before the fracture in the younger patients and increased from 70 points at ten weeks to 81 points at two years postoperatively. In the older age group, these scores were 86, 75, and 78 points. The mean WOMAC pain scores before the fracture and at ten weeks and two years postoperatively were 92, 76, and 87 points, respectively, in the younger age group and 92, 84, and 93 points in the older age group. Function scores were 89, 68, and 79 points for the younger age group and 84, 71, and 73 points for the older age group. The Cronbach alpha for pain, stiffness, function, and the total scale ranged from 0.83 to 0.98 for the younger age group and from 0.79 to 0.97 for the older age group. Construct validity was good, with 82% and 79% of predefined hypotheses confirmed in the younger and older age groups, respectively. Responsiveness was moderate. No floor effects were found. Moderate to large ceiling effects were found for pain and stiffness scales at ten weeks and twelve months in younger patients (18% to 36%) and in the older age group (38% to 53%). CONCLUSIONS: The WOMAC showed good reliability, construct validity, and responsiveness in both age groups of elderly patients with a femoral neck fracture who had been physically and mentally fit before the fracture. The instrument is suitable for use in future clinical studies in these populations. CLINICAL RELEVANCE: The results are based on two clinical trials. The questionnaires used concern pure, clinically relevant issues (ability to walk, climb stairs, etc.). Moreover, the results can be used for future research comparing clinical outcomes (or treatments) for populations with a femoral neck fracture.

Published
2015

14. An overhanging 3' terminus is a conserved feature of telomeres

Author

Eric R. Henderson and Elizabeth H. Blackburn

Subjects
Guanine, Base Sequence, Osmium Tetroxide, genetic processes, DNA, Single-Stranded, Cell Biology, DNA, Ribosomal, enzymes and coenzymes (carbohydrates), Tetrahymena, Animals, Myxomycetes, Molecular Biology, Research Article, Repetitive Sequences, Nucleic Acid
Abstract

The reactivity of single-stranded thymidines with osmium tetraoxide was used to demonstrate the existence of a terminal overhang of the G-rich strand of telomeres from two distantly related eucaryotes, the ciliated protozoan Tetrahymena spp. and the acellular slime mold Didymium spp. Conservation of a G-strand overhang at the molecular terminus of telomeres is consistent with our suggestion that an unusual DNA structure formed by the G-strand overhang is important for telomere function (E. Henderson, C. C. Hardin, S. K. Wolk, I. Tinoco Jr., and E. H. Blackburn, Cell 51:899-908, 1987).

Published
1989

16. Expandable Total Humeral Replacement in a Child with Osteosarcoma

Author

Eric R. Henderson, Jidi Gao, John Groundland, Odion Binitie, and G. Douglas Letson

Subjects
Orthopedic surgery, RD701-811
Abstract

Case. A right-handed 8-year-old female patient presented with a conventional, high-grade osteosarcoma involving her right humerus; through-shoulder amputation was recommended. After consultation, total humerus resection with expandable, total humeral endoprosthesis reconstruction was performed with a sleeve to encourage soft-tissue ingrowth. At three-year follow-up she has received one lengthening procedure and her functional scores are excellent. Conclusion. Total humeral resection and replacement in the pediatric population are rare and although early reports of expandable total humeral endoprosthesis outcomes demonstrate high failure rates, this patient’s success indicates that expandable total humeral replacement is a viable option.

Published
2015
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17. Dedifferentiated Peripheral Chondrosarcoma: A Review of Radiologic Characteristics

Author

Eric R. Henderson, Elisa Pala, Andrea Angelini, Eugenio Rimondi, and Pietro Ruggieri

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Introduction. Peripheral de-differentiated chondrosarcomas are among the rarest malignant mesenchymal tumors. This tumor’s descriptive radiographic characteristics are reported but objective quantification does not exist. This investigation surveyed imaging of peripheral de-differentiated chondrosarcomas to facilitate better recognition of these uncommon tumors. Methods. Database interrogation for peripheral de-differentiated chondrosarcomas was performed; 23 patients were identified and imaging for 18 was reviewed. A musculoskeletal radiologist reviewed all studies for mineralization characteristics; presence of pre-existing osteochondromas; preserved corticomedullary continuity; adjacent cortical obliteration; soft-tissue mass; tumor necrosis; and presence of a cartilage cap. Tumor luminance was measured with computer software. Results. Mineralization was present in 17 tumors. Pre-existing exostoses were evident in nine cases, corticomedullary continuity was preserved in three cases. There was no difference in mineralization or other characteristics based on tumor location. Mean tumor luminance was 94.9 candela/m2. Conclusions. The imaging characteristics described for central de-differentiated chondrosarcomas are similar to the peripheral form of this tumor. Peripheral mineralization with a bimorphic pattern on CT scan and the presence of a soft-tissue mass should be considered worrisome for a peripheral de-differentiated chondrosarcoma, particularly in the setting of multiple hereditary exostoses.

Published
2013
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