Rajeev Gupta

Objective: Chronic nerve compression injuries occur when peripheral nerves are subjected to sustained mechanical forces, with increasing evidence implicating Schwann cells as key mediators. Integrins, a family of transmembrane adhesion molecules that are capable of intracellular signaling, have been implicated in a variety of biological processes such as myelination and nerve regeneration. In this study, we seek to define the physical stimuli mediating demyelination and to determine whether integrin plays a role in the demyelinating response. Methods: We used a previously described in vitro model of CNC injury where myelinating neuron-Schwann cell cocultures were subjected to independent manipulations of hydrostatic pressure, hypoxia, and glucose deprivation in a custom bioreactor. We assessed whether demyelination increased in response to applied manipulation and determined whether integrin-associated signaling cascades are upregulated. Results: Biophysical stimulation of neural tissue induced demyelination and Schwann cell proliferation without neuronal or glial cytotoxicity or apoptosis. Although glucose deprivation and hypoxia independently had minor effects on myelin stability, together they potentiated the demyelinating effects of hydrostatic compression, and in combination, significantly destabilized myelin. Biophysical stimuli transiently increased phosphorylation of the integrin-associated tyrosine kinase Src within Schwann cells. Silencing this integrin signaling cascade blocked Src activation and prevented pressure-induced demyelination. Colocalization analysis indicated that Src is localized within Schwann cells. Interpretation: These results indicate that myelin is sensitive to CNC injury and support the novel concept that myelinating cocultures respond directly to mechanical loading via activating an integrin signaling cascade. © 2012 American Neurological Association.

BACKGROUND: The numbers of people requiring total arthroplasty is expected to increase substantially over the next two decades. However, increasing costs and new payment models in the USA have created a sustainability gap. Ad hoc interventions have reported marginal cost reduction, but it has become clear that sustainability lies only in complete restructuring of care delivery. The Perioperative Surgical Home model, a patient-centered and physician-led multidisciplinary system of coordinated care, was implemented at UC Irvine Health in 2012 for patients undergoing primary elective total knee arthroplasty or total hip arthroplasty. This observational study examines the costs associated with this initiative. METHODS: The direct cost of materials and services for a random index sample following the Total Joint-PSH pathway was used to calculate per diem cost. Cost of orthopedic implants was calculated based on audit-verified direct cost data. Operating room and post-anesthesia care unit time-based costs were calculated for each case and analyzed for variation. Benchmark cost data were obtained from literature search. Data are presented as mean ± SD where possible. RESULTS: Total per diem cost was $10,042 ± 1,305 for TKA and $9,952 ± 1,294 for THA. Literature-reported benchmark per diem cost was $17,588 for TKA and $16,267 for THA. Implant cost was $7,482 ± 4,050 for TKA and $9869 ± 1,549 for THA. Total hospital cost was $17,894 ± 4,270 for TKA and $20,281 ± 2,057 for THA. In-room to incision time cost was $1,263 ± 100 for TKA and $1,341 ± 145 for THA. Surgery time cost was $1,558 ± 290 for TKA and $1,930 ± 374 for THA. Post-anesthesia care unit time cost was $507 ± 187 for TKA and $557 ± 302 for THA. CONCLUSIONS: Direct hospital costs were driven substantially below USA benchmark levels using the Total Joint-PSH pathway. The incremental benefit of each step in the coordinated care pathway is manifested as a lower average length of stay. We identified excessive variation in the cost of implants and post-anesthesia care.

© 2016. The American Astronomical Society. All rights reserved.We present DES14X3taz, a new hydrogen-poor superluminous supernova discovered by the Dark Energy Survey supernova program, with additional photometric data provided by the Survey Using DECam for Superluminous Supernovae. Spectra obtained using Optical System for Imaging and low-Intermediate-Resolution Integrated Spectroscopy on the Gran Telescopio CANARIAS show DES14X3taz is an SLSN-I at z = 0.608. Multi-color photometry reveals a double-peaked light curve: a blue and relatively bright initial peak that fades rapidly prior to the slower rise of the main light curve. Our multi-color photometry allows us, for the first time, to show that the initial peak cools from 22,000 to 8000 K over 15 rest-frame days, and is faster and brighter than any published core-collapse supernova, reaching 30% of the bolometric luminosity of the main peak. No physical 56Ni-powered model can fit this initial peak. We show that a shock-cooling model followed by a magnetar driving the second phase of the light curve can adequately explain the entire light curve of DES14X3taz. Models involving the shock-cooling of extended circumstellar material at a distance of ≃400 R⊙ are preferred over the cooling of shock-heated surface layers of a stellar envelope. We compare DES14X3taz to the few double-peaked SLSN-I events in the literature. Although the rise times and characteristics of these initial peaks differ, there exists the tantalizing possibility that they can be explained by one physical interpretation.