Perioperative Stroke Following General Surgery

AbstractPerioperative stroke is rare; however, patients undergoing cardiovascular surgery are considered to be at high risk for perioperative stroke. Here, we outline a case where perioperative stroke occurred following total hip replacement surgery. The risk factors and possible causes of the stroke in this patient are discussed. In addition, we reiterate the appropriate management approaches needed to prevent perioperative stroke. Briefly, the importance of precise preoperative evaluation and of proper intraoperative and postoperative management should not be overlooked. Finally, it is important to realize that decreasing perioperative strokes and the disabilities associated with them will lower the financial burden on families and the community

Regulation of CLC-1 chloride channel biosynthesis by FKBP8 and Hsp90β.

Mutations in human CLC-1 chloride channel are associated with the skeletal muscle disorder myotonia congenita. The disease-causing mutant A531V manifests enhanced proteasomal degradation of CLC-1. We recently found that CLC-1 degradation is mediated by cullin 4 ubiquitin ligase complex. It is currently unclear how quality control and protein degradation systems coordinate with each other to process the biosynthesis of CLC-1. Herein we aim to ascertain the molecular nature of the protein quality control system for CLC-1. We identified three CLC-1-interacting proteins that are well-known heat shock protein 90 (Hsp90)-associated co-chaperones: FK506-binding protein 8 (FKBP8), activator of Hsp90 ATPase homolog 1 (Aha1), and Hsp70/Hsp90 organizing protein (HOP). These co-chaperones promote both the protein level and the functional expression of CLC-1 wild-type and A531V mutant. CLC-1 biosynthesis is also facilitated by the molecular chaperones Hsc70 and Hsp90β. The protein stability of CLC-1 is notably increased by FKBP8 and the Hsp90β inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) that substantially suppresses cullin 4 expression. We further confirmed that cullin 4 may interact with Hsp90β and FKBP8. Our data are consistent with the idea that FKBP8 and Hsp90β play an essential role in the late phase of CLC-1 quality control by dynamically coordinating protein folding and degradation

Impact of interleukin-28B polymorphism on HCV-1 infected patients treated with response-guided therapy

SummaryBackgroundSingle nucleotide polymorphisms (SNPs) of interleukin-28B (IL28B) were associated with sustained virological response (SVR) in hepatitis C virus genotype 1 (HCV-1) infected patients treated with a standard 48-week regimen of peginterferon and ribavirin combination. Whether IL28B SNP genotype would be the influential prognosticator for patients treated with response-guided therapy (RGT) is still not well understood.AimsTo investigate the impact of IL28B rs809917 genotype on HCV-1 infected patients treated with RGT.MethodsA total of 128 consecutive treatment-naïve HCV-1 infected patients between July 2006 and July 2011 were analyzed. For rapid virological response (RVR) patients, we allowed an abbreviated 24-week regimen regardless of baseline viral loads; otherwise, a 48-week regimen was implemented (for patients with early virological response). The IL28B rs8099917 SNP genotypes were determined accordingly.ResultsA total of 117 patients (91.4%) were of rs8099917 TT genotype and 11 (8.6%) were of GT/GG genotype. Eighty-two of the 128 (64.1%) patients achieved SVR, occurring in 54 of 67 RVR patients (80.6%) and 28 of 61 non-RVR patients (45.9%, p < 0.001). Compared to the GT/GG genotype, patients with the TT genotype had significantly higher SVR rates (67.5% vs. 27.3%; p = 0.008) and low relapse rates (28.2% vs. 70.0%; p = 0.006). The multivariate analysis showed that RVR (odds ratio, 4.51; 95% confidence interval, 1.87–10.90; p = 0.001) and rs8099917 TT genotype (odds ratio, 6.91; 95% confidence interval, 1.53–31.17; p = 0.012) were independent factors associated with SVR.ConclusionFor HCV-1 infected patients who were treated with RGT, the IL28B unfavorable genotype predicted a higher relapse rate; RVR and IL28B favorable genotype were independent factors associated with SVR in patients treated with RGT

LrrA, a novel leucine-rich repeat protein involved in cytoskeleton remodeling, is required for multicellular morphogenesis in Dictyostelium discoideum

AbstractCell sorting by differential cell adhesion and movement is a fundamental process in multicellular morphogenesis. We have identified a Dictyostelium discoideum gene encoding a novel protein, LrrA, which composes almost entirely leucine-rich repeats (LRRs) including a putative leucine zipper motif. Transcription of lrrA appeared to be developmentally regulated with robust expression during vegetative growth and early development. lrrA null cells generated by homologous recombination aggregated to form loose mounds, but subsequent morphogenesis was blocked without formation of the apical tip. The cells adhered poorly to a substratum and did not form tight cell–cell agglomerates in suspension; in addition, they were unable to polarize and exhibit chemotactic movement in the submerged aggregation and Dunn chamber chemotaxis assays. Fluorescence-conjugated phalloidin staining revealed that both vegetative and aggregation competent lrrA− cells contained numerous F-actin-enriched microspikes around the periphery of cells. Quantitative analysis of the fluorescence-stained F-actin showed that lrrA− cells exhibited a dramatically increase in F-actin as compared to the wild-type cells. When developed together with wild-type cells, lrrA− cells were unable to move to the apical tip and sorted preferentially to the rear and lower cup regions. These results indicate that LrrA involves in cytoskeleton remodeling, which is needed for normal chemotactic aggregation and efficient cell sorting during multicellular morphogenesis, particularly in the formation of apical tip

Reshaping of Truncated Pd Nanocubes: Energetic and Kinetic Analysis Integrating Transmission Electron Microscopy with Atomistic-Level and Coarse-Grained Modeling

Stability against reshaping of metallic fcc nanocrystals synthesized with tailored far-from-equilibrium shapes is key to maintaining optimal properties for applications such as catalysis. Yet Arrhenius analysis of experimental reshaping kinetics, and appropriate theory and simulation, is lacking. Thus, we use TEM to monitor the reshaping of Pd nanocubes of ∼25 nm side length between 410 °C (over ∼4.5 h) and 440 °C (over ∼0.25 h), extracting a high effective energy barrier of Eeff ≈ 4.6 eV. We also provide an analytic determination of the energy variation along the optimal pathway for reshaping that involves transfer of atoms across the nanocube surface from edges or corners to form new layers on side {100} facets. The effective barrier from this analysis is shown to increase strongly with the degree of truncation of edges and corners in the synthesized nanocube. Theory matches experiment for the appropriate degree of truncation. In addition, we perform simulations of a stochastic atomistic-level model incorporating a realistic description of diffusive hopping for undercoordinated surface atoms, thereby providing a visualization of the initial reshaping process

Kinetics, Energetics, and Size Dependence of the Transformation from Pt to Ordered PtSn Intermetallic Nanoparticles

The outstanding catalytic activity and chemical selectivity of intermetallic compounds make them excellent candidates for heterogeneous catalysis. However, the kinetics of their formation at the nanoscale is poorly understood or characterized, and precise control of their size, shape as well as composition during synthesis remains challenging. Here, using well-defined Pt nanoparticles (5 nm and 14 nm) encapsulated in mesoporous silica, we study the transformation kinetics from monometallic Pt to intermetallic PtSn at different temperatures by a series of time-evolution X-ray diffraction studies. Observations indicate an initial transformation stage mediated by Pt surface-controlled intermixing kinetics, followed by a second stage with distinct transformation kinetics corresponding to a Ginstling-Brounstein (G-B) type bulk diffusion mode. Moreover, the activation barrier for both surface intermixing and diffusion stages are obtained through the development of appropriate kinetic models for analysis of experimental data. Our density-functional-theory (DFT) calculations provide further insights into the atomistic-level processes and associated energetics underlying surface-controlled intermixing

Evaluation of Intrarenal Blood Flow by Doppler Ultrasonography Immediately after Extracorporeal Shock Wave Lithotripsy on Hydronephrotic Kidney

Extracorporeal shock wave lithotripsy (ESWL) is an effective and relatively noninvasive mode of treatment for urinary calculi. The aim of this study was to test whether therapeutic ESWL induces changes in renal parenchymatous blood flow and to evaluate shock wave side effects on the renal parenchyma. A total of 45 patients who underwent ESWL for ureteropelvic stone between January 2002 and July 2003 were included in this prospective study. Color Doppler sonography before and 30 minutes after ESWL showed no significant morphologic change. Resistive index (RI) was used to estimate renovascular resistance. The RI significantly increased in obstructed hydronephrotic kidneys. However, no significant change was observed in both treated and untreated kidneys before and after treatment. Hydronephrotic kidneys do not have a higher risk of post-ESWL renovascular resistance interference. The measurement of changes in RI with Doppler ultrasonography may provide useful information for clinical diagnosis of renal tubulointerstitial and vascular damage

The intrinsic parameter fluctuation on high-j/metal gate bulk FinFET devices

a b s t r a c t In this work, based on the experimentally calibrated 3D device simulation, we for the first time estimate the impact of intrinsic parameter fluctuation on the electrical characteristic of 16-nm-gate TiN/HfO 2 bulk FinFETs. The sources of intrinsic parameter fluctuation include the random discrete dopants, interface traps and work function differences, simultaneously. The full 3D simulated threshold voltage fluctuation, induced by the aforementioned random sources simultaneously, is 26.2 mV for the N-type bulk FinFET (and is 55.5 mV for the planar N-MOSFET). For the N-type bulk FinFET, the statistical sum of these fluctuations is 9.5% (and is 12.3% for the planar device) overestimation, compared with the full 3D simulation. One of the main reasons is the independence assumption on these random variables is destroyed owing to interactions to different extents among RDs, ITs and WKs. The coupled surface potentials cannot be simply estimated by using their statistical sum of individual random source. Under the same threshold voltage, compared with the result of the planar MOSFETs, more than 50% reduction on the threshold voltage fluctuation of the explored bulk FinFETs is observed owing to the benefit of 3D structural nature