Multiaxial pulsatile dynamics of the thoracic aorta and impact of thoracic endovascular repair

Purpose: The thoracic aorta is a highly mobile organ whose dynamics are altered by thoracic endovascular aorta repair (TEVAR). The aim of this study was to quantify cardiac pulsatility-induced multi-axial deformation of the thoracic aorta before and after descending aortic TEVAR. Methods: Eleven TEVAR patients (8 males and 3 females, age 57–89) underwent retrospective cardiac-gated CT angiography before and after TEVAR. 3D geometric models of the thoracic aorta were constructed, and lumen centerlines, inner and outer surface curves, and cross-sections were extracted to measure aortic arclength, centerline, inner surface, and outer surface longitudinal curvatures, as well as cross-sectional effective diameter and eccentricity for the ascending and stented aortic portions. Results: From pre- to post-TEVAR, arclength deformation was increased at the ascending aorta from 5.9 \ub1 3.1 % to 8.8 \ub1 4.4 % (P < 0.05), and decreased at the stented aorta from 7.5 \ub1 5.1 % to 2.7 \ub1 2.5 % (P < 0.05). Longitudinal curvature and diametric deformations were reduced at the stented aorta. Centerline curvature, inner surface curvature, and cross-sectional eccentricity deformations were increased at the distal ascending aorta. Conclusions: Deformations were reduced in the stented thoracic aorta after TEVAR, but increased in the ascending aorta near the aortic arch, possibly as a compensatory mechanism to maintain overall thoracic compliance in the presence of reduced deformation in the stiffened stented aorta

Influence of Thoracic Endovascular Aortic Repair on True Lumen Helical Morphology for Stanford Type B Dissections

Objective: Thoracic endovascular aortic repair (TEVAR) can change the morphology of the flow lumen in aortic dissections, which may affect aortic hemodynamics and function. This study characterizes how the helical morphology of the true lumen in type B aortic dissections is altered by TEVAR. Methods: Patients with type B aortic dissection who underwent computed tomography angiography before and after TEVAR were retrospectively reviewed. Images were used to construct three-dimensional stereolithographic surface models of the true lumen and whole aorta using custom software. Stereolithographic models were segmented and co-registered to determine helical morphology of the true lumen with respect to the whole aorta. The true lumen region covered by the endograft was defined based on fiducial markers before and after TEVAR. The helical angle, average helical twist, peak helical twist, and cross-sectional eccentricity, area, and circumference were quantified in this region for pre- and post-TEVAR geometries. Results: Sixteen patients (61.3 \ub1 8.0 years; 12.5% female) were treated successfully for type B dissection (5 acute and 11 chronic) with TEVAR and scans before and after TEVAR were retrospectively obtained (follow-up interval 52 \ub1 91 days). From before to after TEVAR, the true lumen helical angle (–70.0 \ub1 71.1 to –64.9 \ub1 75.4\ub0; P =.782), average helical twist (–4.1 \ub1 4.0 to –3.7 \ub1 3.8\ub0/cm; P =.674), and peak helical twist (–13.2 \ub1 15.2 to –15.4 \ub1 14.2\ub0/cm; P =.629) did not change. However, the true lumen helical radius (1.4 \ub1 0.5 to 1.0 \ub1 0.6 cm; P <.05) and eccentricity (0.9 \ub1 0.1 to 0.7 \ub1 0.1; P <.05) decreased, and the cross-sectional area (3.0 \ub1 1.1 to 5.0 \ub1 2.0 cm2; P <.05) and circumference (7.1 \ub1 1.0 to 8.0 \ub1 1.4 cm; P <.05) increased significantly from before to after TEVAR. The distinct bimodal distribution of chiral and achiral native dissections disappeared after TEVAR, and subgroup analyses showed that the true lumen circumference of acute dissections increased with TEVAR, although it did not for chronic dissections. Conclusions: The unchanged helical angle and average and peak helical twists as a result of TEVAR suggest that the angular positions of the true lumen are constrained and that the endografts were helically conformable in the angular direction. The decrease of helical radius indicated a straightening of the corkscrew shape of the true lumen, and in combination with more circular and expanded lumen cross-sections, TEVAR produced luminal morphology that theoretically allows for lower flow resistance through the endografted portion. The impact of TEVAR on dissection flow lumen morphology and the interaction between endografts and aortic tissue can provide insight for improving device design, implantation technique, and long-term clinical outcomes

Definition of Tubular Anatomic Structures from Arbitrary Stereo Lithographic Surface

An accurate description of anatomies and dynamics of vessels is crucial to understand their characteristics and improve surgical techniques, thus it is the basis, in addition to surgeon experience, on which stent design and operation procedures rely. The process of producing this description is user intensive, and recent improvement in image processing of medical3D imaging allows for a more automated workflow. However, there is a need to bridge the gap from a processed geometry to a robust mathematical computational grid. By sequentially segmenting a tubular anatomic structure, here defined by a stereo lithographic (STL) surface, an initial centerline is formed by connecting centroids of orthogonal cross-sectional contours along the length of the structure. Relying on the initial centerline, a set of non-overlapping 2D cross sectional contours are defined along the centerline, a centerline which is updated after the 2D contours are produced. After a second iteration of producing 2D contours and updating the centerline, a full description of the structure is created. Our method for describing vessel geometry shows good coherence to existing method. The main advantages of our method include the possibility of having arbitrary triangulated STL surface input, automated centerline definition, safety against intersecting cross-sectional contours and automatic clean-up of local kinks and wrinkles

Levy-Student Distributions for Halos in Accelerator Beams

We describe the transverse beam distribution in particle accelerators within the controlled, stochastic dynamical scheme of the Stochastic Mechanics (SM) which produces time reversal invariant diffusion processes. This leads to a linearized theory summarized in a Shchr\"odinger--like (\Sl) equation. The space charge effects have been introduced in a recent paper~\cite{prstab} by coupling this \Sl equation with the Maxwell equations. We analyze the space charge effects to understand how the dynamics produces the actual beam distributions, and in particular we show how the stationary, self--consistent solutions are related to the (external, and space--charge) potentials both when we suppose that the external field is harmonic (\emph{constant focusing}), and when we \emph{a priori} prescribe the shape of the stationary solution. We then proceed to discuss a few new ideas~\cite{epac04} by introducing the generalized Student distributions, namely non--Gaussian, L\'evy \emph{infinitely divisible} (but not \emph{stable}) distributions. We will discuss this idea from two different standpoints: (a) first by supposing that the stationary distribution of our (Wiener powered) SM model is a Student distribution; (b) by supposing that our model is based on a (non--Gaussian) L\'evy process whose increments are Student distributed. We show that in the case (a) the longer tails of the power decay of the Student laws, and in the case (b) the discontinuities of the L\'evy--Student process can well account for the rare escape of particles from the beam core, and hence for the formation of a halo in intense beams.Comment: revtex4, 18 pages, 12 figure

The adenovirus E4orf4 protein targets PP2A to the ACF chromatin-remodeling factor and induces cell death through regulation of SNF2h-containing complexes

The adenovirus E4 open-reading-frame 4 (E4orf4) protein regulates the progression of viral infection and when expressed individually it induces non-classical apoptosis in transformed cells. Here we show that E4orf4 associates with the ATP-dependent chromatin-remodeling factor ACF that consists of a sucrose non fermenting-2h (SNF2h) ATPase and an Acf1 regulatory subunit. Furthermore, E4orf4 targets protein phosphatase 2A (PP2A) to this complex and to chromatin. Obstruction of SNF2h activity inhibits E4orf4-induced cell death, whereas knockdown of Acf1 results in enhanced E4orf4-induced toxicity in both mammalian and yeast cells, and Acf1 overexpression inhibits E4orf4′s ability to downregulate early adenovirus gene expression in the context of viral infection. Knockdown of the Acf1 homolog, WSTF, inhibits E4orf4-induced cell death. Based on these results we suggest that the E4orf4–PP2A complex inhibits ACF and facilitates enhanced chromatin-remodeling activities of other SNF2h-containing complexes, such as WSTF–SNF2h. The resulting switch in chromatin remodeling determines life versus death decisions and contributes to E4orf4 functions during adenovirus infection

One year follow-up of patients with refractory angina pectoris treated with enhanced external counterpulsation

BACKGROUND: Enhanced external counterpulsation (EECP) is a non-invasive technique that has been shown to be effective in reducing both angina and myocardial ischemia in patients not responding to medical therapy and without revascularization alternatives. The aim of the present study was to assess the long-term outcome of EECP treatment at a Scandinavian centre, in relieving angina in patients with chronic refractory angina pectoris. METHODS: 55 patients were treated with EECP. Canadian cardiovascular society (CCS) class, antianginal medication and adverse clinical events were collected prior to EECP, at the end of the treatment, and at six and 12 months after EECP treatment. Clinical signs and symptoms were recorded. RESULTS: EECP treatment significantly improved the CCS class in 79 ± 6% of the patients with chronic angina pectoris (p < 0.001). The reduction in CCS angina class was seen in patients with CCS class III and IV and persisted 12 months after EECP treatment. There was no significant relief in angina in patients with CCS class II prior to EECP treatment. 73 ± 7% of the patients with a reduction in CCS class after EECP treatment improved one CCS class, and 22 ± 7% of the patients improved two CCS classes. The improvement of two CCS classes could progress over a six months period and tended to be more prominent in patients with CCS class IV. In accordance with the reduction in CCS classes there was a significant decrease in the weekly nitroglycerin usage (p < 0.05). CONCLUSION: The results from the present study show that EECP is a safe treatment for highly symptomatic patients with refractory angina. The beneficial effects were sustained during a 12-months follow-up period

The Cytosolic Tail of the Golgi Apyrase Ynd1 Mediates E4orf4-Induced Toxicity in Saccharomyces cerevisiae

The adenovirus E4 open reading frame 4 (E4orf4) protein contributes to regulation of the progression of virus infection. When expressed individually, E4orf4 was shown to induce non-classical transformed cell-specific apoptosis in mammalian cells. At least some of the mechanisms underlying E4orf4-induced toxicity are conserved from yeast to mammals, including the requirement for an interaction of E4orf4 with protein phosphatase 2A (PP2A). A genetic screen in yeast revealed that the Golgi apyrase Ynd1 associates with E4orf4 and contributes to E4orf4-induced toxicity, independently of Ynd1 apyrase activity. Ynd1 and PP2A were shown to contribute additively to E4orf4-induced toxicity in yeast, and to interact genetically and physically. A mammalian orthologue of Ynd1 was shown to bind E4orf4 in mammalian cells, confirming the evolutionary conservation of this interaction. Here, we use mutation analysis to identify the cytosolic tail of Ynd1 as the protein domain required for mediation of the E4orf4 toxic signal and for the interaction with E4orf4. We also show that E4orf4 associates with cellular membranes in yeast and is localized at their cytoplasmic face. However, E4orf4 is membrane-associated even in the absence of Ynd1, suggesting that additional membrane proteins may mediate E4orf4 localization. Based on our results and on a previous report describing a collection of Ynd1 protein partners, we propose that the Ynd1 cytoplasmic tail acts as a scaffold, interacting with a multi-protein complex, whose targeting by E4orf4 leads to cell death

Genome-Wide Search Reveals the Existence of a Limited Number of Thyroid Hormone Receptor Alpha Target Genes in Cerebellar Neurons

Thyroid hormone (T3) has a major influence on cerebellum post-natal development. The major phenotypic landmark of exposure to low levels of T3 during development (hypothyroidism) in the cerebellum is the retarded inward migration of the most numerous cell type, granular neurons. In order to identify the direct genetic regulation exerted by T3 on cerebellar neurons and their precursors, we used microarray RNA hybridization to perform a time course analysis of T3 induced gene expression in primary cultures of cerebellar neuronal cell. These experiments suggest that we identified a small set of genes which are directly regulated, both in vivo and in vitro, during cerebellum post-natal development. These modest changes suggest that T3 does not acts directly on granular neurons and mainly indirectly influences the cellular interactions taking place during development