Anterior Cervical Infection: Presentation and Incidence of an Uncommon Postoperative Complication.

STUDY DESIGN: Retrospective multi-institutional case series. OBJECTIVE: The anterior cervical discectomy and fusion (ACDF) affords the surgeon the flexibility to treat a variety of cervical pathologies, with the majority being for degenerative and traumatic indications. Limited data in the literature describe the presentation and true incidence of postoperative surgical site infections. METHODS: A retrospective multicenter case series study was conducted involving 21 high-volume surgical centers from the AOSpine North America Clinical Research Network, selected for their excellence in spine care and clinical research infrastructure and experience. Medical records for 17 625 patients who received cervical spine surgery (levels from C2 to C7) between January 1, 2005, and December 31, 2011, inclusive, were reviewed to identify the occurrence of 21 predefined treatment complications. Patients who underwent an ACDF were identified in the database and reviewed for the occurrence of postoperative anterior cervical infections. RESULTS: A total of 8887 patients were identified from a retrospective database analysis of 21 centers providing data for postoperative anterior cervical infections (17/21, 81% response rate). A total of 6 postoperative infections after ACDF were identified for a mean rate of 0.07% (range 0% to 0.39%). The mean age of patients identified was 57.5 (SD = 11.6, 66.7% female). The mean body mass index was 22.02. Of the total infections, half were smokers (n = 3). Two patients presented with myelopathy, and 3 patients presented with radiculopathic-type complaints. The mean length of stay was 4.7 days. All patients were treated aggressively with surgery for management of this complication, with improvement in all patients. There were no mortalities. CONCLUSION: The incidence of postoperative infection in ACDF is exceedingly low. The management has historically been urgent irrigation and debridement of the surgical site. However, due to the rarity of this occurrence, guidance for management is limited to retrospective series

Misplaced Cervical Screws Requiring Reoperation.

STUDY DESIGN: A multicenter, retrospective case series. OBJECTIVE: In the past several years, screw fixation of the cervical spine has become commonplace. For the most part, this is a safe, low-risk procedure. While rare, screw backout or misplaced screws can lead to morbidity and increased costs. We report our experiences with this uncommon complication. METHODS: A multicenter, retrospective case series was undertaken at 23 institutions in the United States. Patients were included who underwent cervical spine surgery from January 1, 2005, to December 31, 2011, and had misplacement of screws requiring reoperation. Institutional review board approval was obtained at all participating institutions, and detailed records were sent to a central data center. RESULTS: A total of 12 903 patients met the inclusion criteria and were analyzed. There were 11 instances of screw backout requiring reoperation, for an incidence of 0.085%. There were 7 posterior procedures. Importantly, there were no changes in the health-related quality-of-life metrics due to this complication. There were no new neurologic deficits; a patient most often presented with pain, and misplacement was diagnosed on plain X-ray or computed tomography scan. The most common location for screw backout was C6 (36%). CONCLUSIONS: This study represents the largest series to tabulate the incidence of misplacement of screws following cervical spine surgery, which led to revision procedures. The data suggest this is a rare event, despite the widespread use of cervical fixation. Patients suffering this complication can require revision, but do not usually suffer neurologic sequelae. These patients have increased cost of care. Meticulous technique and thorough knowledge of the relevant anatomy are the best means of preventing this complication

Dynamics of the chiral phase transition from AdS/CFT duality

We use Lorentzian signature AdS/CFT duality to study a first order phase transition in strongly coupled gauge theories which is akin to the chiral phase transition in QCD. We discuss the relation between the latent heat and the energy (suitably defined) of the component of a D-brane which lies behind the horizon at the critical temperature. A numerical simulation of a dynamical phase transition in an expanding, cooling Quark-Gluon plasma produced in a relativistic collision is carried out.Comment: 30 pages, 5 figure

TRASER - Total Reflection Amplification of Spontaneous Emission of Radiation

Background and Objective: Light and lasers in medical therapy have made dramatic strides since their invention five decades ago. However, the manufacture of lasers can be complex and expensive which often makes treatments limited and costly. Further, no single laser will provide the correct parameters to treat all things. Hence, laser specialists often need multiple devices to practice their specialty. A new concept is described herein that has the potential to replace many lasers and light sources with a single ‘tunable ’ device. Study Design/Material and Methods: This device amplifies spontaneous emission of radiation by capturing and retaining photons through total internal reflection, hence the acronym Total Reflection Amplification of Spontaneous Emission of Radiation, or TRASER. Results: Specific peaks of light can be produced in a reproducible manner with high peak powers of variable pulse durations, a large spot size, and high repetition rate. Conclusion: Considering the characteristics and parameters of Traser technology, it is possible that this one device woul

Mechanical Metamaterials with Negative Compressibility Transitions

When tensioned, ordinary materials expand along the direction of the applied force. Here, we explore network concepts to design metamaterials exhibiting negative compressibility transitions, during which a material undergoes contraction when tensioned (or expansion when pressured). Continuous contraction of a material in the same direction of an applied tension, and in response to this tension, is inherently unstable. The conceptually similar effect we demonstrate can be achieved, however, through destabilisations of (meta)stable equilibria of the constituents. These destabilisations give rise to a stress-induced solid-solid phase transition associated with a twisted hysteresis curve for the stress-strain relationship. The strain-driven counterpart of negative compressibility transitions is a force amplification phenomenon, where an increase in deformation induces a discontinuous increase in response force. We suggest that the proposed materials could be useful for the design of actuators, force amplifiers, micro-mechanical controls, and protective devices.Comment: Supplementary information available at http://www.nature.com/nmat/journal/v11/n7/abs/nmat3331.htm

Genome-scale DNA methylation mapping of clinical samples at single-nucleotide resolution

August 1, 2010Bisulfite sequencing measures absolute levels of DNA methylation at single-nucleotide resolution, providing a robust platform for molecular diagnostics. Here, we optimize bisulfite sequencing for genome-scale analysis of clinical samples. Specifically, we outline how restriction digestion targets bisulfite sequencing to hotspots of epigenetic regulation; we show that 30ng of DNA are sufficient for genome-scale analysis; we demonstrate that our protocol works well on formalinfixed, paraffin-embedded (FFPE) samples; and we describe a statistical method for assessing significance of altered DNA methylation patterns.National Institutes of Health (U.S.) (Grant R01HG004401)National Institutes of Health (U.S.) (Grant U54HG03067)National Institutes of Health (U.S.) (Grant U01ES017155

Ab-Externo AAV-Mediated Gene Delivery to the Suprachoroidal Space Using a 250 Micron Flexible Microcatheter

The current method of delivering gene replacement to the posterior segment of the eye involves a three-port pars plana vitrectomy followed by injection of the agent through a 37-gauge cannula, which is potentially wrought with retinal complications. In this paper we investigate the safety and efficacy of delivering adeno-associated viral (AAV) vector to the suprachoroidal space using an ab externo approach that utilizes an illuminated microcatheter.6 New Zealand White rabbits and 2 Dutch Belted rabbits were used to evaluate the ab externo delivery method. sc-AAV5-smCBA-hGFP vector was delivered into the suprachoroidal space using an illuminated iTrackTM 250A microcatheter. Six weeks after surgery, the rabbits were sacrificed and their eyes evaluated for AAV transfection using immunofluorescent antibody staining of GFP.Immunostaining of sectioned and whole-mounted eyes demonstrated robust transfection in all treated eyes, with no fluorescence in untreated control eyes. Transfection occurred diffusely and involved both the choroid and the retina. No apparent adverse effects caused by either the viral vector or the procedure itself could be seen either clinically or histologically.The ab externo method of delivery using a microcatheter was successful in safely and effectively delivering a gene therapy agent to the suprachoroidal space. This method presents a less invasive alternative to the current method of virally vectored gene delivery

Chondrogenic and Gliogenic Subpopulations of Neural Crest Play Distinct Roles during the Assembly of Epibranchial Ganglia

In vertebrates, the sensory neurons of the epibranchial (EB) ganglia transmit somatosensory signals from the periphery to the CNS. These ganglia are formed during embryogenesis by the convergence and condensation of two distinct populations of precursors: placode-derived neuroblasts and neural crest- (NC) derived glial precursors. In addition to the gliogenic crest, chondrogenic NC migrates into the pharyngeal arches, which lie in close proximity to the EB placodes and ganglia. Here, we examine the respective roles of these two distinct NC-derived populations during development of the EB ganglia using zebrafish morphant and mutants that lack one or both of these NC populations. Our analyses of mutant and morphant zebrafish that exhibit deficiencies in chondrogenic NC at early stages reveal a distinct requirement for this NC subpopulation during early EB ganglion assembly and segmentation. Furthermore, restoration of wildtype chondrogenic NC in one of these mutants, prdm1a, is sufficient to restore ganglion formation, indicating a specific requirement of the chondrogenic NC for EB ganglia assembly. By contrast, analysis of the sox10 mutant, which lacks gliogenic NC, reveals that the initial assembly of ganglia is not affected. However, during later stages of development, EB ganglia are dispersed in the sox10 mutant, suggesting that glia are required to maintain normal EB ganglion morphology. These results highlight novel roles for two subpopulations of NC cells in the formation and maintenance of EB ganglia: chondrogenic NC promotes the early-stage formation of the developing EB ganglia while glial NC is required for the late-stage maintenance of ganglion morphology

In silico design and biological evaluation of a dual specificity kinase inhibitor targeting cell cycle progression and angiogenesis

Methodology: We have utilized a rational in silico-based approach to demonstrate the design and study of a novel compound that acts as a dual inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2) and cyclin-dependent kinase 1 (CDK1). This compound acts by simultaneously inhibiting pro-Angiogenic signal transduction and cell cycle progression in primary endothelial cells. JK-31 displays potent in vitro activity against recombinant VEGFR2 and CDK1/cyclin B proteins comparable to previously characterized inhibitors. Dual inhibition of the vascular endothelial growth factor A (VEGF-A)-mediated signaling response and CDK1-mediated mitotic entry elicits anti-Angiogenic activity both in an endothelial-fibroblast co-culture model and a murine ex vivo model of angiogenesis

Determinants of Glycan Receptor Specificity of H2N2 Influenza A Virus Hemagglutinin

The H2N2 subtype of influenza A virus was responsible for the Asian pandemic of 1957-58. However, unlike other subtypes that have caused pandemics such as H1N1 and H3N2, which continue to circulate among humans, H2N2 stopped circulating in the human population in 1968. Strains of H2 subtype still continue to circulate in birds and occasionally pigs and could be reintroduced into the human population through antigenic drift or shift. Such an event is a potential global health concern because of the waning population immunity to H2 hemagglutinin (HA). The first step in such a cross-species transmission and human adaptation of influenza A virus is the ability for its surface glycoprotein HA to bind to glycan receptors expressed in the human upper respiratory epithelia. Recent structural and biochemical studies have focused on understanding the glycan receptor binding specificity of the 1957-58 pandemic H2N2 HA. However, there has been considerable HA sequence divergence in the recent avian-adapted H2 strains from the pandemic H2N2 strain. Using a combination of structural modeling, quantitative glycan binding and human respiratory tissue binding methods, we systematically identify mutations in the HA from a recent avian-adapted H2N2 strain (A/Chicken/PA/2004) that make its quantitative glycan receptor binding affinity (defined using an apparent binding constant) comparable to that of a prototypic pandemic H2N2 (A/Albany/6/58) HA.National Institute of General Medical Sciences (U.S.) (GM57073)National Institute of General Medical Sciences (U.S.) (U54 GM62116)Singapore. Agency for Science, Technology and ResearchSingapore-MIT Alliance for Research and Technolog