PULSED DOPPLER FROM THE SUPRASTERNAL NOTCH SYSTEMATICALLY UNDERESTIMATES MEAN BLOOD FLOW VELOCITY IN THE ASCENDING AORTA COMPARED TO PHASE CONTRAST MRI

Background Continuous pulsed-wave Doppler readings of flow velocity in the ascending aorta from the suprasternal position (sCD) are widely used in estimating stroke volume, particularly during physiological challenge maneuvers such as head-up tilt testing. Stroke volume is derived from velocity time integrals and vessel area. We compared the sCD against an established gold standard. Methods In 12 healthy women and men, we obtained 2D cross sectional, velocity encoded phase contrast MRI of the ascending aorta (2DMRI) and sCD to measure mean blood flow velocity (Vmean) at the ascending aorta. We compared sCD insonation depth to the distance between Doppler probe and sinotubular junction measured by MRI. Within an aortic 4D-Flow dataset, allowing flow measurements in every anatomical point along the ascending aorta, Vmean was determined at the sCD measurement point for comparison. Results sCD significantly underestimated Vmean compared with 2DMRI at the sinotubular junction (Vmean 2DMRI – Vmean sCD = 24.42 cm/s ± 12.55 cm/s, p = <0.001). Moreover, sCD sampled flow velocities 21.8 mm ± 7mm (p = <0.001) or 26% off the sinotubular junction. Yet, depth and velocity differences between sCD and 2DMRI were not correlated with each other (Pearson r = -0.147; p = 0.648). When we applied 4DMRI to assess flow velocity at the sCD measurement site, the Vmean difference between methodologies was reduced to 9.1 cm/s ± 12.38 cm/s (p = 0.035). Conclusion sCD profoundly underestimates Vmean in the ascending aorta compared to 4DMRI. The methodology has important limitations in accessing the ideal position for aortic flow measurements and precise information regarding the position of data acquisition for vessel area quantification cannot be ascertained. Overall, sCD is of limited utility in measuring absolute stroke volum

Chemical Sensing Using Fiber Cavity Ring-Down Spectroscopy

Waveguide-based cavity ring-down spectroscopy (CRD) can be used for quantitative measurements of chemical concentrations in small amounts of liquid, in gases or in films. The change in ring-down time can be correlated to analyte concentration when using fiber optic sensing elements that change their attenuation in dependence of either sample absorption or refractive index. Two types of fiber cavities, i.e., fiber loops and fiber strands containing reflective elements, are distinguished. Both types of cavities were coupled to a variety of chemical sensor elements, which are discussed and compared

A Mechanism for the Inhibition of Neural Progenitor Cell Proliferation by Cocaine

Investigating the mechanism of cocaine's effect on fetal brain development, Chun-Ting Lee and colleagues find that down-regulation of cyclin A by a cocaine metabolite inhibits neural proliferation

Post-translational modifications of voltage-gated sodium channels in chronic pain syndromes.

In the peripheral sensory nervous system the neuronal expression of voltage-gated sodium channels (Navs) is very important for the transmission of nociceptive information since they give rise to the upstroke of the action potential (AP). Navs are composed of nine different isoforms with distinct biophysical properties. Studying the mutations associated with the increase or absence of pain sensitivity in humans, as well as other expression studies, have highlighted Nav1.7, Nav1.8, and Nav1.9 as being the most important contributors to the control of nociceptive neuronal electrogenesis. Modulating their expression and/or function can impact the shape of the AP and consequently modify nociceptive transmission, a process that is observed in persistent pain conditions. Post-translational modification (PTM) of Navs is a well-known process that modifies their expression and function. In chronic pain syndromes, the release of inflammatory molecules into the direct environment of dorsal root ganglia (DRG) sensory neurons leads to an abnormal activation of enzymes that induce Navs PTM. The addition of small molecules, i.e., peptides, phosphoryl groups, ubiquitin moieties and/or carbohydrates, can modify the function of Navs in two different ways: via direct physical interference with Nav gating, or via the control of Nav trafficking. Both mechanisms have a profound impact on neuronal excitability. In this review we will discuss the role of Protein Kinase A, B, and C, Mitogen Activated Protein Kinases and Ca++/Calmodulin-dependent Kinase II in peripheral chronic pain syndromes. We will also discuss more recent findings that the ubiquitination of Nav1.7 by Nedd4-2 and the effect of methylglyoxal on Nav1.8 are also implicated in the development of experimental neuropathic pain. We will address the potential roles of other PTMs in chronic pain and highlight the need for further investigation of PTMs of Navs in order to develop new pharmacological tools to alleviate pain