Aortic arch anomalies occur frequently in patients with TAD and therefore may represent a proclivity for this life threatening condition.
Mechanisms underlying Kv4 channel inactivation and recovery are presently unclear, although there is general consensus that the basic characteristics of these processes are not consistent with Shaker (Kv1) N- and P/C-type mechanisms. Kv4 channels also differ from Shaker in that they can undergo significant inactivation from pre-activated closed-states (closed-state inactivation, CSI), and that inactivation and recovery kinetics can be regulated by intracellular KChIP2 isoforms. To gain insight into the mechanisms regulating Kv4.3 CSI and recovery, we have analyzed the effects of increasing [K(+)](o) from 2 mM to 98 mM in the absence and in the presence of KChIP2b, the major KChIP2 isoform expressed in the mammalian ventricle. In the absence of KChIP2b, high [K(+)](o) promoted Kv4.3 inactivated closed-states and significantly slowed the kinetics of recovery from both macroscopic and closed-state inactivation. Coexpression of KChIP2b in 2 mM [K(+)](o) promoted non-inactivated closed-states and accelerated the kinetics of recovery from both macroscopic and CSI. In high [K(+)](o), KChIP2b eliminated or significantly reduced the slowing effects on recovery. Attenuation of CSI by the S4 charge-deletion mutant R302A, which produced significant stabilization of non-inactivated closed-states, effectively eliminated the opposing effects of high [K(+)](o) and KChIP2b on macroscopic recovery kinetics, confirming that these results were due to alterations of CSI. Elevated [K(+)](o) therefore slows Kv4.3 recovery by stabilizing inactivated closed-states, while KChIP2b accelerates recovery by destabilizing inactivated closed-states. Our results challenge underlying assumptions of presently popular Kv4 gating models and suggest that Kv4.3 possesses novel allosteric mechanisms, which are absent in Shaker, for coupling interactions between intracellular KChIP2b binding motifs and extracellular K(+)-sensitive regulatory sites.
Consistency and duplicability in Computed Tomography (CT) output is essential to quantitative imaging for lung cancer detection and monitoring. This study of CT-detected lung nodules investigated the reproducibility of volume-, density-, and texture-based features (outcome variables) over routine ranges of radiation dose, reconstruction kernel, and slice thickness. CT raw data of 23 nodules were reconstructed using 320 acquisition/reconstruction conditions (combinations of 4 doses, 10 kernels, and 8 thicknesses). Scans at 12.5%, 25%, and 50% of protocol dose were simulated; reduced-dose and full-dose data were reconstructed using conventional filtered back-projection and iterative-reconstruction kernels at a range of thicknesses (0.6–5.0 mm). Full-dose/B50f kernel reconstructions underwent expert segmentation for reference Region-Of-Interest (ROI) and nodule volume per thickness; each ROI was applied to 40 corresponding images (combinations of 4 doses and 10 kernels). Typical texture analysis metrics (including 5 histogram features, 13 Gray Level Co-occurrence Matrix, 5 Run Length Matrix, 2 Neighboring Gray-Level Dependence Matrix, and 3 Neighborhood Gray-Tone Difference Matrix) were computed per ROI. Reconstruction conditions resulting in no significant change in volume, density, or texture metrics were identified as “compatible pairs” for a given outcome variable. Our results indicate that as thickness increases, volumetric reproducibility decreases, while reproducibility of histogram- and texture-based features across different acquisition and reconstruction parameters improves. To achieve concomitant reproducibility of volumetric and radiomic results across studies, balanced standardization of the imaging acquisition parameters is required.
The interparietal bone, Os Incae, is formed in a persistent mendosal suture. This suture is a normal variant in the human skull, well-known in anatomy and radiology textbooks. We report 11 children with craniosynostosis in the presence of an interparietal bone, five from Children's Hospital at Montefiore and six children from Children's Hospital Boston. The true incidence of an interparietal bone in patients with craniosynostosis or craniofacial anomalies is not known; nor are there recognized sequelae of an interparietal bone (bathrocephaly). Hypotheses regarding mechanisms that may contribute to the formation of an interparietal bone are discussed.
• HRCT sagittal reconstruction is useful in the evaluation of obstructive lung disease. • Findings on sagittal reconstructions allow physicians to more accurately diagnose COPD. • Routine use of sagittal reconstructions increases the sensitivity for diagnosing COPD.
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