Outcomes and characteristics of ertapenem-nonsusceptible Klebsiella pneumoniae bacteremia at a university hospital in Northern Taiwan: A matched case-control study

Background and purposeCarbapenem-resistant Klebsiella pneumoniae is an emerging problem worldwide. The object of this study was to investigate the risk factors, characteristics and outcomes of ertapenem-nonsusceptible K pneumoniae (ENSKp) bacteremia.MethodsWe conducted a 1:2 ratio matched case-control study. The controls were randomly selected among patients with ertapenem-susceptible K pneumoniae (ESKp) bacteremia and were matched with ENSKp cases for bacteremia.ResultsSeventy-five patients were included in this study (25 cases and 50 controls). Bivariate analysis showed that prior exposure to either β-Lactam/β-Lactam-lactamase inhibitors (p = 0.008) or 4th generation cephalosporins (p < 0.001), chronic obstructive pulmonary disease (COPD) (p = 0.001), acute renal failure (p = 0.021), chronic kidney disease without dialysis (p = 0.021), recent hospital stay (p = 0.016), intensive care unit stay (p = 0.002), mechanical ventilation (p = 0.003), central venous catheter placement (p = 0.016), Foley indwelling (p = 0.022), polymicrobial bacteremia (p = 0.003) and higher Pittsburgh bacteremia score (p < 0.001) were associated with ENSKp bacteremia. The multivariate analysis showed that prior exposure to 4th generation cephalosporins (odds ratio [OR], 28.05; 95% confidence interval [CI], 2.92–269.85; p = 0.004), COPD (OR, 21.38; 95% CI, 2.95–154.92; p = 0.002) and higher Pittsburgh bacteremia score (OR, 1.35; 95% CI, 1.10–1.66; p = 0.004) were independent factors for ENSKp bacteremia. ENSKp bacteremia had a higher 14-day mortality rate than ESKp bacteremia (44.0% vs. 22.0%; p = 0.049). The overall in-hospital mortality rates for these two groups were 60.0% and 40.0% respectively (p = 0.102).ConclusionENSKp bacteremia had a poor outcome and the risk factors were prior exposure of 4th generation cephalosporins, COPD and higher Pittsburgh bacteremia score. Antibiotic stewardship may be the solution for the preventive strategy

Antitumor Agents. 266. Design, Synthesis, and Biological Evaluation of Novel 2-(Furan-2-yl)naphthalen-1-ol Derivatives as Potent and Selective Antibreast Cancer Agents

In a continuing study, we explored how the individual rings in neo-tanshinlactone (1) influence its potent and selective in vitro anti-breast cancer activity. Accordingly, we discovered a novel class of anti-breast cancer agents, 2-(furan-2-yl) naphthalen-1-ol derivatives, based on an active C-ring opened model compound 5. Further optimization led to 18 and 21, which showed decreased cytotoxic potency, but better selectivity than neo-tanshinlactone analog 2. Interestingly, compound 20 showed broad cytotoxicity against human cancer cell lines

Two-Dimensional Fracture Mechanics Analysis Using a Single-Domain Boundary Element Method

This work calculates the stress intensity factors (SIFs) at the crack tips, predicts the crack initiation angles, and simulates the crack propagation path in the two-dimensional cracked anisotropic materials using the single-domain boundary element method (BEM) combined with maximum circumferential stress criterion. The BEM formulation, based on the relative displacements of the crack tip, is used to determine the mixed-mode SIFs and simulate the crack propagation behavior. Numerical examples of the application of the formulation for different crack inclination angles, crack lengths, degree of material anisotropy, and crack types are presented. Furthermore, the propagation path in Cracked Straight Through Brazilian Disc (CSTBD) specimen is numerically predicted and the results of numerical and experimental data compared with the actual laboratory observations. Good agreement is found between the two approaches. The proposed BEM formulation is therefore suitable to simulate the process of crack propagation. Additionally, the anisotropic rock slope failure initiated by the tensile crack can also be analyzed by the proposed crack propagation simulation technique

Direct evidence of ZnO morphology modification via the selective adsorption of ZnO-binding peptides

Biomolecule-mediated ZnO synthesis has great potential for the tailoring of ZnO morphology for specific application in biosensors, window materials for display and solar cells, dye-sensitized solar cells (DSSCs), biomedical materials, and photocatalysts due to its specificity and multi-functionality. In this contribution, the effect of a ZnO-binding peptide (ZnO-BP, G-12: GLHVMHKVAPPR) and its GGGC-tagged derivative (GT-16: GLHVMHKVAPPRGGGC) on the growth of ZnO crystals expressing morphologies dependent on the relative growth rates of (0001) and (10 (1) over bar0) planes of ZnO have been studied. The amount of peptide adsorbed was determined by a depletion method using oriented ZnO films grown by Atomic Layer Deposition (ALD), while the adsorption behavior of G-12 and GT-16 was investigated using XPS and a computational approach. Direct evidence was obtained to show that (i) both the ZnO-BP identified by phage display and its GGGC derivative (GT-16) are able to bind to ZnO and modify crystal growth in a molecule and concentration dependent fashion, (ii) plane selectivity for interaction with the (0001) versus the (10 (1) over bar0) crystal planes is greater for GT-16 than G-12; and (iii) specific peptide residues interact with the crystal surface albeit in the presence of charge compensating anions. To our knowledge, this is the first study to provide unambiguous and direct quantitative experimental evidence of the modification of ZnO morphology via (selective and nonselective) adsorption-growth inhibition mechanisms mediated by a ZnO-BP identified from phage display libraries

HDAC8 Inhibition Specifically Targets Inv(16) Acute Myeloid Leukemic Stem Cells by Restoring p53 Acetylation

SummaryAcute myeloid leukemia (AML) is driven and sustained by leukemia stem cells (LSCs) with unlimited self-renewal capacity and resistance to chemotherapy. Mutation in the TP53 tumor suppressor is relatively rare in de novo AML; however, p53 can be regulated through post-translational mechanisms. Here, we show that p53 activity is inhibited in inv(16)+ AML LSCs via interactions with the CBFβ-SMMHC (CM) fusion protein and histone deacetylase 8 (HDAC8). HDAC8 aberrantly deacetylates p53 and promotes LSC transformation and maintenance. HDAC8 deficiency or inhibition using HDAC8-selective inhibitors (HDAC8i) effectively restores p53 acetylation and activity. Importantly, HDAC8 inhibition induces apoptosis in inv(16)+ AML CD34+ cells, while sparing the normal hematopoietic stem cells. Furthermore, in vivo HDAC8i administration profoundly diminishes AML propagation and abrogates leukemia-initiating capacity of both murine and patient-derived LSCs. This study elucidates an HDAC8-mediated p53-inactivating mechanism promoting LSC activity and highlights HDAC8 inhibition as a promising approach to selectively target inv(16)+ LSCs

PSR J1926-0652: A Pulsar with Interesting Emission Properties Discovered at FAST

We describe PSR J1926-0652, a pulsar recently discovered with the Five-hundred-meter Aperture Spherical radio Telescope (FAST). Using sensitive single-pulse detections from FAST and long-term timing observations from the Parkes 64-m radio telescope, we probed phenomena on both long and short time scales. The FAST observations covered a wide frequency range from 270 to 800 MHz, enabling individual pulses to be studied in detail. The pulsar exhibits at least four profile components, short-term nulling lasting from 4 to 450 pulses, complex subpulse drifting behaviours and intermittency on scales of tens of minutes. While the average band spacing P3 is relatively constant across different bursts and components, significant variations in the separation of adjacent bands are seen, especially near the beginning and end of a burst. Band shapes and slopes are quite variable, especially for the trailing components and for the shorter bursts. We show that for each burst the last detectable pulse prior to emission ceasing has different properties compared to other pulses. These complexities pose challenges for the classic carousel-type models.Comment: 13pages with 12 figure

Energy-dependent solar neutrino flux depletion in the Exact Parity Model and implications for SNO, SuperKamiokande and BOREXINO

Energy-dependent solar neutrino flux reduction caused by the Mikheyev-Smirnov-Wolfenstein (MSW) effect is applied to the Exact Parity Model. Several scenarios are possible, depending on the region of parameter space chosen. The interplay between intergenerational MSW transitions and vacuum ``intragenerational'' ordinary-mirror neutrino oscillations is discussed. Expectations for the ratio of charged to neutral current event rates at the Sudbury Neutrino Observatory (SNO) are estimated. The implications of the various scenarios for the Boron neutrino energy spectrum and BOREXINO are briefly discussed. The consequences of MSW-induced solar neutrino depletion within the Exact Parity Model differ in interesting ways from the standard $\nu_e - \nu_{\mu, \tau}$ and $\nu_e - \nu_s$ cases. The physical causes of these differences are determined.Comment: 43 pages, 8 figures, RevTeX; to appear in Phys. Rev. D, accepted versio

Review of the literature examining the correlation among DNA microarray technologies

DNA microarray technologies are used in a variety of biological disciplines. The diversity of platforms and analytical methods employed has raised concerns over the reliability, reproducibility and correlation of data produced across the different approaches. Initial investigations (years 2000–2003) found discrepancies in the gene expression measures produced by different microarray technologies. Increasing knowledge and control of the factors that result in poor correlation among the technologies has led to much higher levels of correlation among more recent publications (years 2004 to present). Here, we review the studies examining the correlation among microarray technologies. We find that with improvements in the technology (optimization and standardization of methods, including data analysis) and annotation, analysis across platforms yields highly correlated and reproducible results. We suggest several key factors that should be controlled in comparing across technologies, and are good microarray practice in general. Environ. Mol. Mutagen. 48:380–394, 2007. © 2007 Wiley-Liss, Inc

Obliquity pacing of the western Pacific Intertropical Convergence Zone over the past 282,000 years

The Intertropical Convergence Zone (ITCZ) encompasses the heaviest rain belt on the Earth. Few direct long-term records, especially in the Pacific, limit our understanding of long-term natural variability for predicting future ITCZ migration. Here we present a tropical precipitation record from the Southern Hemisphere covering the past 282,000 years, inferred from a marine sedimentary sequence collected off the eastern coast of Papua New Guinea. Unlike the precession paradigm expressed in its East Asian counterpart, our record shows that the western Pacific ITCZ migration was influenced by combined precession and obliquity changes. The obliquity forcing could be primarily delivered by a cross-hemispherical thermal/pressure contrast, resulting from the asymmetric continental configuration between Asia and Australia in a coupled East Asian-Australian circulation system. Our finding suggests that the obliquity forcing may play a more important role in global hydroclimate cycles than previously thought