LytR-CpsA-Psr proteins in Staphylococcus aureus display partial functional redundancy and the deletion of all three severely impairs septum placement and cell separation

Staphylococcus aureus contains three members of the LytR-CpsA-Psr (LCP) family of membrane proteins: MsrR, SA0908 and SA2103. The characterization of single-, double- and triple-deletion mutants revealed distinct phenotypes for each of the three proteins. MsrR was involved in cell separation and septum formation and influenced β-lactam resistance; SA0908 protected cells from autolysis; and SA2103, although displaying no apparent phenotype by itself, enhanced the properties of msrR and sa0908 mutants when deleted. The deletion of sa0908 and sa2103 also further attenuated the virulence of msrR mutants in a nematode-killing assay. The severely defective growth phenotype of the triple mutant revealed that LytR-CpsA-Psr proteins are essential for optimal cell division in S. aureus. Growth could be rescued to varying degrees by any one of the three proteins, indicating some functional redundancy within members of this protein family. However, differing phenotypic characteristics of all single and double mutants and complemented triple mutants indicated that each protein played a distinct role(s) and contributed differently to phenotypes influencing cell separation, autolysis, cell surface properties and virulenc

Longitudinal changes in intracardiac repolarization lability in patients with implantable cardioverter-defibrillator.

PMC3740232Background: While it is known that elevated baseline intracardiac repolarization lability is associated with the risk of fast ventricular tachycardia (FVT)/ventricular fibrillation (VF), the effect of its longitudinal changes on the risk of FVT/VF is unknown. Methods and Results: Near-field (NF) right ventricular (RV) intracardiac electrograms (EGMs) were recorded every 3-6 months at rest in 248 patients with structural heart disease [mean age 61.2 ± 13.3; 185(75%) male; 162(65.3%) ischemic cardiomyopathy] and implanted cardioverter-defibrillator (ICD) or cardiac resynchronization therapy defibrillator (CRT-D) [201 (81%) primary prevention]. Intracardiac beat-to-beat QT variability index (QTVINF) was measured on NF RV EGM. During the first study phase (median 18 months), participants made on average 2.4 visits. Then remote follow-up was continued for an additional median period of 3 years. Average QTVINF did not change during the first year after ICD implantation (-0.342 ± 0.603 at baseline vs. -0.262 ± 0.552 at 6 months vs. -0.334 ± 0.603 at 12 months); however, it decreased thereafter (-0.510 ± 0.603 at 18 months; P = 0.042). Adjusted population-averaged GEE model showed that the odds of developing FVT/VF increased by 75% for each 1 unit increase in QTVINF. (OR 1.75 [95%CI 1.05-2.92]; P = 0.031). However, individual patient-specific QTVINF trends (increasing, decreasing, flat) varied from patient to patient. For a given patient, the odds of developing FVT/VF were not associated with increasing or decreasing QTVINF over time [OR 1.27; (95%CI 0.05-30.10); P = 0.881]. Conclusion: While on average the odds of FVT/VF increased with an increase in QTVINF, patient-specific longitudinal trends in QTVINF did not affect the odds of FVT/VF.JH Libraries Open Access Fun

Diminished Left Ventricular Dyssynchrony and Impact of Resynchronization in Failing Hearts With Right Versus Left Bundle Branch Block

ObjectivesWe compared mechanical dyssynchrony and the impact of cardiac resynchronization therapy (CRT) in failing hearts with a pure right (RBBB) versus left bundle branch block (LBBB).BackgroundCardiac resynchronization therapy is effective for treating failing hearts with conduction delay and discoordinate contraction. Most data pertain to LBBB delays. With RBBB, the lateral wall contracts early so that biventricular (BiV) pre-excitation may not be needed. Furthermore, the magnitude of dyssynchrony and impact of CRT in pure RBBB versus LBBB remains largely unknown.MethodsDogs with tachypacing-induced heart failure combined with right or left bundle branch radiofrequency ablation were studied. Basal dyssynchrony and effects of single and BiV CRT on left ventricular (LV) function were assessed by pressure-volume catheter and tagged magnetic resonance imaging, respectively.ResultsLeft bundle branch block and RBBB induced similar QRS widening, and LV function (ejection fraction, maximum time derivative of LV pressure [dP/dtmax]) was similarly depressed in failing hearts with both conduction delays. Despite this, mechanical dyssynchrony was less in RBBB (circumferential uniformity ratio estimate [CURE] index: 0.80 ± 0.03 vs. 0.58 ± 0.09 for LBBB, p < 0.04; CURE 0→1 is dyssynchronous→synchronous). Cardiac resynchronization therapy had correspondingly less effect on hearts with RBBB than those with LBBB (i.e., 5.5 ± 1.1% vs. 29.5 ± 5.0% increase in dP/dtmax, p < 0.005), despite similar baselines. Furthermore, right ventricular-only pacing enhanced function and synchrony in RBBB as well or better than did BiV, whereas LV-only pacing worsened function.ConclusionsLess mechanical dyssynchrony is induced by RBBB than LBBB in failing hearts, and the corresponding impact of CRT on the former is reduced. Right ventricular-only pacing may be equally efficacious as BiV CRT in hearts with pure right bundle branch conduction delay

Confrontation and the Utility of Rules

There is a good reason why evidence scholars continue to be fascinated and perplexed, and some courts continue at least to be perplexed, by the types of evidence that tend to be lumped together misleadingly under the headings nonassertive conduct or implied assertions. Evidence of this sort highlights a paradox of the prevailing law of hearsay. I believe that this paradox cannot be resolved without fundamentally transforming the structure of that law. Thus, while I agree - within the current framework - with many of the insights so ably stated in this Symposium, I think evidence scholars must devote their efforts to construction of a better structure

Influence of Atrial Function and Mechanical Synchrony on LV Hemodynamic Status in Heart Failure Patients on Resynchronization Therapy

ObjectivesThe aim of this study was to evaluate atrial and ventricular function in patients undergoing cardiac resynchronization therapy (CRT).BackgroundRight atrial pacing (AP) in CRT induces delays in electrical and mechanical activation of the left atrium. The influence of atrial sensing (AS) versus AP on ventricular performance in CRT and the mechanisms underlying the differences between AS and AP in CRT have not been fully elucidated.MethodsFifty-five patients with heart failure undergoing CRT for 9 ± 12.5 months and 22 control subjects without heart failure were enrolled. Conventional and tissue Doppler echocardiography was performed to examine atrial and ventricular mechanics and hemodynamic status.ResultsThe optimal atrioventricular interval was shorter in AS compared with AP mode (126 ± 19 ms vs. 155 ± 20 ms, p < 0.0001). Left ventricular (LV) outflow tract time-velocity integral (22 ± 7 cm vs. 20 ± 7 cm, p < 0.001), diastolic filling period (468 ± 124 ms vs. 380 ± 93 ms, p < 0.001), and global strain (−32 ± 24% vs. −27 ± 22%, p = 0.001) were greater in AS compared with AP mode. Atrial strain was higher in AS compared with AP mode in the right atrium (−28.2 ± 8.6% vs. −22.6 ± 7.6%, p = 0.0007), interatrial septum (−17.1 ± 6.5% vs. −13.2 ± 5.4%, p = 0.002), and left atrium (−16.4 ± 11.0% vs. −13.6 ± 8.5%, p = 0.02). There was no difference in intraventricular dyssynchrony but significantly lower atrial dyssynchrony in AS compared with AP mode (31 ± 19 ms vs. 42 ± 24 ms, p = 0.0002).ConclusionsAS is associated with preserved atrial contractility and atrial synchrony, resulting in optimal LV diastolic filling, stroke volume, and LV systolic mechanics. This pacing mode maximizes LV performance and the hemodynamic benefit of CRT in patients with heart failure

The Century Survey Galactic Halo Project III: A Complete 4300 deg^2 Survey of Blue Horizontal Branch Stars in the Metal-Weak Thick Disk and Inner Halo

We present a complete spectroscopic survey of 2414 2MASS-selected blue horizontal branch (BHB) candidates selected over 4300 deg^2 of the sky. We identify 655 BHB stars in this non-kinematically selected sample. We calculate the luminosity function of field BHB stars and find evidence for very few hot BHB stars in the field. The BHB stars located at a distance from the Galactic plane |Z|<4 kpc trace what is clearly a metal-weak thick disk population, with a mean metallicity of [Fe/H]= -1.7, a rotation velocity gradient of dv_{rot}/d|Z|= -28+-3.4 km/s in the region |Z|<6 kpc, and a density scale height of h_Z= 1.26+-0.1 kpc. The BHB stars located at 5<|Z|<9 kpc are a predominantly inner-halo population, with a mean metallicity of [Fe/H]= -2.0 and a mean Galactic rotation of -4+-31 km/s. We infer the density of halo and thick disk BHB stars is 104+-37 kpc^-3 near the Sun, and the relative normalization of halo to thick-disk BHB stars is 4+-1% near the Sun.Comment: 12 pages in emulateapj format, accepted for publication in February A