MRI assessment of pacing induced ventricular dyssynchrony in an isolated human heart

This study demonstrates the capabilities of MRI in the assessment of cardiac pacing induced ventricular dyssynchrony, and the findings support the need for employing more physiological pacing. A human donor heart deemed non‐viable for transplantation, was reanimated using an MR compatible, four‐chamber working perfusion system. The heart was imaged using a 1.5T MR scanner while being paced from the right ventricular apex (RVA) via an epicardial placed lead. Four‐chamber, short‐axis, and tagged short‐axis cines were acquired in order to track wall motion and intramyocardial strain during pacing. The results of this study revealed that the activation patterns of the left ventricle (LV) during RVA pacing demonstrated intraventricular dyssynchrony; as the left ventricular mechanical activation proceeded from the septum and anterior wall to the lateral wall, with the posterior wall being activated last. As such, the time difference to peak contraction between the septum and lateral wall was ～125 msec. Likewise, interventricular dyssynchrony was demonstrated from the four‐chamber cine as the time difference between the peak LV and RV free wall motion was 180 msec. With the ongoing development of MR safe and MR compatible pacing systems, we can expect MRI to be added to the list of imaging modalities used to optimize cardiac resynchronization therapy (CRT) and/or alternate site pacing. J. Magn. Reson. Imaging 2010; 31: 466–469. © 2010 Wiley‐Liss, Inc.     

Quantitative 3D elemental microtomography of Cyclotella meneghiniana at 400-nm resolution

X-ray fluorescence tomography promises to map elemental distributions in unstained and unfixed biological specimens in three dimensions at high resolution and sensitivity, offering unparalleled insight in medical, biological, and environmental sciences. X-ray fluorescence tomography of biological specimens has been viewed as impractical—and perhaps even impossible for routine application—due to the large time required for scanning tomography and significant radiation dose delivered to the specimen during the imaging process. Here, we demonstrate submicron resolution X-ray fluorescence tomography of a whole unstained biological specimen, quantifying three-dimensional distributions of the elements Si, P, S, Cl, K, Ca, Mn, Fe, Cu, and Zn in the freshwater diatom Cyclotella meneghiniana with 400-nm resolution, improving the spatial resolution by over an order of magnitude. The resulting maps faithfully reproduce cellular structure revealing unexpected patterns that may elucidate the role of metals in diatom biology and of diatoms in global element cycles. With anticipated improvements in data acquisition and detector sensitivity, such measurements could become routine in the near future.     

Obesity,Smoking, and Frontal Brain Dysfunction

Obesity, smoking, and conduct problems have all been associated with decrements in brain function. However, their additive and interactive effects have rarely been examined. To address the deficiency, we studied P300a and P300b electroencephalographic potentials in 218 women grouped by the presence versus absence of: (1) a BMI ≥ 30 kg/m²; (2) recent smoking; and (3) ≥ 2 childhood conduct problems. Analyses revealed smaller P300a and P300b amplitudes over the posterior scalp among recent smokers versus nonsmokers. No corresponding group differences were found in P300 latencies or frontal scalp amplitudes. The most interesting analysis result was an interaction between conduct problems and obesity limited to the frontally generated P300a component: its latency was significantly greater in women with both attributes than in those with either or neither attribute. An exploratory ANOVA, substituting the genotype of a GABRA2 SNP for conduct problems, also demonstrated an interaction with obesity affecting P300a latency. It is hypothesized that conduct problems, and a conduct‐problem‐associated GABRA2 genotype, decrease the age‐of‐onset and/or increase the lifetime duration of obesity. As a result, they may potentiate the adverse effects of obesity on frontal white matter and thereby increase P300a latency. Smoking may affect brain function by a different mechanism to reduce posterior scalp P300a and P300b amplitudes while preserving frontal scalp P300a latency and amplitude. (Am J Addict 2010;00:1–10)     

Physiological concentration of calcium inhibits elastase-induced cleavage of a functional recombinant fragment of surfactant protein D

Surfactant protein D (SP-D) plays an important role in lung host defence. SP-D levels have been shown to be depleted in cystic fibrosis (CF) patients. A recombinant fragment of the human SP-D (rfhSP-D) which consist of a hydrophobic neck and a CRD has been shown to be active in vivo and partially reverses the symptoms of the SP-D deficiency in the lungs when administered to SP-D knock-out mice. In this paper we studied the in vitro effect of different proteolytic enzymes commonly found in CF patients lungs, such as neutrophil elastase, cathepsin G and protease 3 as well as Pseudomonas elastase, on rfhSP-D. It was also shown that cleavage was inhibited by physiological concentration of calcium. When Western blot was compared with ELISA, we show that an anti-SP-D ELISA is a not a reliable assay of functional SP-D levels since non-functional fragments of SP-D are also detected. Thus, ELISA cannot be used as a reliable “diagnostic” tool for SP-D deficiency. Finally, we observe that SP-D is not cleaved in control patients but is degraded in about half the samples from cystic fibrosis patients, indicating that degradation of endogenous SP-D, by enzymes present in CF bronchioalveolar lavage fluid (BALF), may lead to deficiency of the protein as seen in CF and therefore rfhSP-D may be a useful future therapy.     

Correlation of transepidermal water loss with skin barrier properties in vitro: comparison of three evaporimeters

Aim: This study investigates the relationship between transepidermal water loss (TEWL) and skin permeability to tritiated water as a rapid assessment of the integrity of the barrier properties of skin as part of in vitro skin permeation studies.
Methods: TEWL values before and during the experimental period were measured using three evaporimeters (A, B, and C) representing different measuring principles and technologies. Single application of tritiated water was dosed on dermatomed human skin samples in a flow-through diffusion cell system. Radioactivity of the absorbed dose and the removable dose residues was counted to determine percent dose and flux rate. These data were further combined with TEWL values to analyze the correlation.
Results: Evaporimeter C, a closed chamber–condenser technology, had higher measurement capacity than other instruments, evaporimeter A, an open chamber, and evaporimeter B, a closed chamber ( P <0.001). The baseline TEWL value correlated with tritiated water flux ( r =0.34, P =0.04). The pattern of tritiated water expressed as percent dose permeated into receptor fluid was similar to that of TEWL values.
Conclusion: These data indicate that TEWL can be ascribed to be a measure of skin water barrier function. Further work should be conducted to interpret the significance of measuring TEWL by evaporimetry.     

Physiologic upper limit of pore size in the blood-tumor barrier of malignant solid tumors

Background  

The existence of large pores in the blood-tumor barrier (BTB) of malignant solid tumor microvasculature makes the blood-tumor barrier more permeable to macromolecules than the endothelial barrier of most normal tissue microvasculature. The BTB of malignant solid tumors growing outside the brain, in peripheral tissues, is more permeable than that of similar tumors growing inside the brain. This has been previously attributed to the larger anatomic sizes of the pores within the BTB of peripheral tumors. Since in the physiological state in vivo a fibrous glycocalyx layer coats the pores of the BTB, it is possible that the effective physiologic pore size in the BTB of brain tumors and peripheral tumors is similar. If this were the case, then the higher permeability of the BTB of peripheral tumor would be attributable to the presence of a greater number of pores in the BTB of peripheral tumors. In this study, we probed in vivo the upper limit of pore size in the BTB of rodent malignant gliomas grown inside the brain, the orthotopic site, as well as outside the brain in temporalis skeletal muscle, the ectopic site.     

Position representations lag behind targets in multiple object tracking

In the multiple object tracking (MOT) task, observers can typically keep track of up to four moving objects. Little is known however about the extent to which object motion is used by observers during MOT. For example, direction and speed might be used to anticipate future positions. We here ask to what extent position reports lag behind targets or instead correspond to extrapolated positions. Using a range of different motion trajectory patterns, observers tracked 1-4 targets among distracters and reported the final position of one of the targets. On average, reports corresponded to previous positions rather than the final position. This lag varied across conditions from around 10 to 70 ms of the object’s trajectory. Although some have suggested that extrapolation occurs during MOT, we find no evidence of anticipation of future positions of targets. The significant increase in lag with speed of the object is consistent with slow or intermittent updating of object positions during tracking.