There continues to be an unmet need for safe and effective pain medications. Opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) dominate the clinical landscape despite limited effectiveness and considerable side-effect profiles. Although significant advancements have identified myriad potential pain targets over the past several decades, the majority of new pain pharmacotherapies have failed to come to market. The discovery of nerve growth factor (NGF) and its interaction with tropomyosin receptor kinase A (trkA) have been well characterized as important mediators of pain initiation and maintenance, and pharmacotherapies targeting this pathway have the potential to be considered promising methods in the treatment of a variety of nociceptive and neuropathic pain conditions. Several methodologic approaches, including sequestration of free NGF, prevention of NGF binding and trkA activation, and inhibition of trkA function, have been investigated in the development of new pharmacotherapies. Among these, NGF-sequestering antibodies have exhibited the most promise in clinical trials. However, in 2010, reports of rapid joint destruction leading to joint replacement prompted the US Food and Drug Administration (FDA) to place a hold on all clinical trials involving anti-NGF antibodies. Although the FDA has since lifted this hold and a number of new trials are under way, the long-term efficacy and safety profile of anti-NGF antibodies are yet to be established.

A model constructed from Navier-Stokes equations and a two-mass vocal fold description is proposed in this study. The composite model not only has the capability to describe the aerodynamics in a vibratory glottis but also can be used to study the vocal fold vibration under the driving of the complex airflow in the glottis. Numerical simulations show that this model can predict self-oscillations of the coupled glottal aerodynamics and vocal fold system. The Coanda effect could occur in the vibratory glottis even though the vocal folds have left-right symmetric prephonatory shape and tissue properties. The Coanda effect causes the asymmetric flow in the glottis and the difference in the driving force on the left and right vocal folds. The different pressures applied to the left and right vocal folds induce their displacement asymmetry. By using various lung pressures (0.6-2.0 kPa) to drive the composite model, it was found that the asymmetry of the vocal fold displacement is increased from 1.87% to 11.2%. These simulation results provide numerical evidence for the presence of asymmetric flow in the vibratory glottis; moreover, they indicate that glottal aerodynamics is an important factor in inducing the asymmetric vibration of the vocal folds.

Results showed phonation threshold flow to be more sensitive to posterior glottal width changes than phonation threshold pressure. Therefore, phonation threshold flow could be a more effective indicator than phonation threshold pressure for those vocal diseases related to abduction.

Background-The histone deacetylase (HDAC) inhibitors valproic acid (VPA) and suberoyl bishydroxamic acid (SBHA) have recently been demonstrated to be strong Notch1 activators. Upregulation of the Notch1 pathway has been shown to limit growth and suppress hormonal secretion in neuroendocrine (NE) tumors. We hypothesized that HDAC inhibition would be an effective strategy to activate the Notch1 pathway and inhibit growth and hormonal secretion in pheochromocytoma cells.