[Application of computational fluid dynamics in the evaluation of left ventricular function in cardiomyopathies and coronary disease].

Computational fluid dynamics (CFD) is an emerging technology applied in the field of cardiovascular medicine, which can obtain hemodynamic data by simulating the blood flow in the patient's heart for cardiac function assessment and disease diagnosis. Left ventricular function plays a key role in the occurrence and development of cardiomyopathies and coronary disease. CFD can reconstruct the left ventricular anatomic structures of patients to clarify pathophysiologic mechanisms and analyze hemodynamic parameters to evaluate left ventricular function, verify surgical efficacy, and guide surgical strategy, which has a positive effect on achieving early diagnosis and reducing mortality from cardiomyopathies and coronary disease. At present, there are still technical limitations in the large-scale clinical application of CFD, and various solutions are being developed and tested, and further improvement and refinement are needed.

Methicillin-sensitive and methicillin-resistant Staphylococcus aureus strains and their toxin genes in the nostrils of dogs and workers at an animal shelter.

AIMS: Methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MSSA and MRSA, respectively) in the nostrils of dogs and workers at an animal shelter were cultured. Staphylococcal toxin genes were analysed to identify potential health concerns. METHODS AND RESULTS: Samples were obtained from 441 dogs and 9 workers. The respective isolation rates of S. aureus and MRSA were 49·0% (216/441) and 1·6% (7/441) for shelter dogs and 44·4% (4/9) and 33·3% (3/9) for workers, respectively. Isolation of S. aureus in summer (61·9%) and in adult dogs (59·2%) were significantly higher than those in winter (35·8%) and in juvenile dogs (33·3%) (P < 0·001), respectively. The predominant enterotoxin genotypes and combination profiles of S. aureus were (sea, seb, seg, sei, sem, sen, seo, seu) and (sea, sea-seb, and seg-sei-sem-sen-seo-seu), respectively, and 20% of isolates carried food poisoning-associated enterotoxins. The se profiles in shelter dogs were different from those in general pet dogs and their owners. MRSA isolates were identified as SCCmec IV and VII, and they shared se combination profiles of (sec-seg-sei-sel-sem-sen-seo-seu) and (seb-sek-seq). MRSA in this shelter had similar microbiological characteristics as those reported in CA-MRSA ST59 in humans. CONCLUSIONS: Human health-associated bacteria and food poisoning-related toxin genes were identified. Further evaluations of health concerns in animal shelters are necessary. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study to focus on se prevalence and MRSA characteristics in an animal shelter in Taiwan. The MRSA characteristics determined in this study were similar to those of CA-MRSA strains isolated from communities in the past, indicating potential health risks in cities.

Mechanical design and fabrication of the VHF-gun, the Berkeley normal-conducting continuous-wave high-brightness electron source.

A high repetition rate, MHz-class, high-brightness electron source is a key element in future high-repetition-rate x-ray free electron laser-based light sources. The VHF-gun, a novel low frequency radio-frequency gun, is the Lawrence Berkeley National Laboratory (LBNL) response to that need. The gun design is based on a normal conducting, single cell cavity resonating at 186 MHz in the VHF band and capable of continuous wave operation while still delivering the high accelerating fields at the cathode required for the high brightness performance. The VHF-gun was fabricated and successfully commissioned in the framework of the Advanced Photo-injector EXperiment, an injector built at LBNL to demonstrate the capability of the gun to deliver the required beam quality. The basis for the selection of the VHF-gun technology, novel design features, and fabrication techniques are described.

Pentoxifylline Decreases Dialysis Risk in Patients With Advanced Chronic Kidney Disease.

Few studies evaluated the effects of pentoxifylline on hard endpoints in patients with predialysis stage 5 chronic kidney disease (CKD). Thus, we tried to explore the effects of pentoxifylline and its interaction with renin-angiotensin-aldosterone system (RAAS) blockade on the development of endstage renal disease (ESRD) and mortality. This nationwide cohort study retrospectively included patients who had a serum creatinine level of >6 mg/dL and received erythropoiesis-stimulating agents (ESAs) between 2000 and 2010. We analyzed 7,366 pentoxifylline users and 7,366 propensity score-matched nonusers. Using Cox proportional hazard models, pentoxifylline reduced the risks of ESRD and the composite renal outcome but not that of mortality. In terms of the risks of developing ESRD, pentoxifylline alone exerted a comparable beneficial effect to combined therapy with an RAAS inhibitor and greater renoprotection than RAAS inhibitor monotherapy. This study suggests pentoxifylline is efficacious in slowing progression to ESRD in patients with predialysis stage 5 CKD.

Heterogeneity and phylogenetic relationships of community-associated methicillin-sensitive/resistant Staphylococcus aureus isolates in healthy dogs, cats and their owners.

AIMS: To investigate the distribution of staphylococcal enterotoxin genes (se) and the molecular features of community-associated methicillin-sensitive/resistant Staphylococcus aureus (CA-MSSA/MRSA) isolates in the nostrils of healthy pets and their owners. METHODS AND RESULTS: A total of 114 Staph. aureus isolates were identified from 1563 nasal swab samples, and CA-MRSA accounted for 20·2% (n = 23) of the total identified isolates. CA-MRSA isolates (91·3%, 21/23) harboured higher percentage of se than did CA-MSSA isolates (58·2%, 53/91) (P < 0·01), and the two highest se profiles of CA-MRSA were seb-sek-seq (42·9%, 9/21) and seb-sek-seq-sep (28·6%, 6/21). Of the MSSAs, 42·8% (39/91) were resistant to at least one antimicrobial drug and 8·8% (8/91) were multidrug resistant (MDR). We identified nine staphylocoagulase (SC) types (I-VIII and X) and three multilocus sequence types (ST59-MRSA-IV/V, ST-239-MRSA-V and ST241-MRSA-V). SC VII (23·4%, 22/94), a staphylococcal food poisoning isolate found mainly in Japan, and ST-59-MRSA-IV/V (85%, 17/20), a widespread CA-MRSA clone found mainly in Taiwan, both were the most predominant types. Phylogenetic analysis together with se and molecular characteristics obtained using pulsed-field gel electrophoresis showed that high levels of antimicrobial resistance and the se-carrying clone ST59-MRSA-IV/V-SC VII were all clustered in genogroup 5. CONCLUSIONS: The CA-MRSA clone of se-carrying-MDR-ST-59-IV/V-SC VII was identified predominantly in this study, and this clone might play a significant role in staphylococcal food poisoning in community settings. SIGNIFICANCE AND IMPACT OF THE STUDY: To our knowledge, this is the first study focussing on enterotoxin-carrying CA-MRSA/MSSA in pets and their owners, and the results support the future warnings in animal-human bond caused by CA-staphylococci in the commonwealth and the need to take cautions worldwide.

Serovar distribution and antimicrobial susceptibility of swine Salmonella isolates from clinically ill pigs in diagnostic submissions from Indiana in the United States.

AIMS: To determine serovar distribution and levels of antimicrobial susceptibility of Salmonella isolated from clinically ill pigs in diagnostic submissions. METHODS AND RESULTS: A total of 197 Salmonella isolates were obtained by the Indiana Animal Disease Diagnostic Laboratory from 2003 to 2005. Minimal inhibitory concentrations (MICs) were determined using the standard microbroth dilution method. The top four serovars identified were Salm. enterica serovar Typhimurium variant Copenhagen, Salm. Derby, Salm. Choleraesuis var. Kunzendorf and Salm. Typhimurium. All isolates were susceptible to the fluoroquinolones tested except that eight isolates were intermediate to difloxacin. The isolates showed a low prevalence of resistance to trimethoprim/sulphadiazine (Sxt), gentamicin (G), ceftiofur (Cf) and cephalothin (Cp) with low MIC(50) value of

A novel splicing mutation of the CYLD gene in a Taiwanese family with multiple familial trichoepithelioma.

Multiple familial trichoepithelioma (MFT) is an autosomal dominant disease characterized by numerous skin-coloured papules on the central face. Mutations in the CYLD gene, which is also the gene responsible for familial cylindromatosis, have been reported recently. Recent studies indicate that CYLD is a tumour-suppressor gene. The CYLD protein is a negative regulator of the activation of transcription factor nuclear factor-kappaB, and loss of CYLD contributes to oncogenesis. We report a novel splicing mutation (IVS12 + 1 G-->A) in the CYLD gene in a Taiwanese pedigree with MFT, and discuss new developments in treatment options.

Synthesis of 1-benzyl-3-(5'-hydroxymethyl-2'-furyl)indazole analogues as novel antiplatelet agents.

1-Benzyl-3-(5'-hydroxymethyl-2'-furyl)indazole (28, YC-1) was selected as the lead compound for systemic structural modification. After screening for antiplatelet activity, SARs of YC-1 analogues were established. Among these potent active derivatives, compounds 29, 30, 31, 44, and 45 functioned as potent activators of sGC and inhibitors of PDE5 with potency comparable to that of YC-1. In addition, compound 58 was found to be a selective and potent inhibitor of protease-activated receptor type 4 (PAR4)-dependent platelet activation.

Reverse micelles as life-mimicking systems.

In this review, we attempt to demonstrate that reverse micelles are simple artificial systems that mimic many life systems from cell division to the creation of an enzyme catalytic mechanism. For a membranous enzyme like placental alkaline phosphatase, the kinetic properties observed in reverse micelles might represent those found under physiological conditions. The reverse micellar system, consisting of a positively charged surfactant, mimics a detoxification enzyme glutathione transferase. We propose a novel island-in-oil-lake reverse micellar model for the glutathione transferase that can account for almost all the catalytic properties of this enzyme. Reverse micelles may provide an excellent model system in investigating the reaction mechanism of other detoxification enzymes.

Inhibition of octopus glutathione transferase by Meisenheimer complex analog, S-(2,4,6-trinitrophenyl) glutathione.

The tight binding of Meisenheimer intermediate with octopus digestive gland glutathione transferase was analyzed with 1,3,5-trinitrobenzene, which forms a trapped Meisenheimer complex with glutathione because there is no leaving group at the ipso carbon. By steady-state enzyme kinetic analysis, an inhibition constant of 1.89 +/- 0.17 microM was found for the transient formed, S-(2,4,6-trinitrophenyl) glutathione. The above inhibition constant is 407-fold smaller than the Km value for the substrate (2,4-dinitrochlorobenzene). Thus, S-(2,4,6-trinitrophenyl) glutathione is considered to be a transition-state analog. The tight binding of this inhibitor to the enzyme provides an explanation for the involvement of the biological binding effect on the rate enhancement in the glutathione transferase-catalyzed SNAr mechanism.

Sentinel surveillance for enterovirus 71, Taiwan, 1998.

Outbreaks of enterovirus 71 have been reported around the world since 1969. The most recent outbreak occurred in Taiwan during April-July 1998. This hand, foot, and mouth disease epidemic was detected by a sentinel surveillance system in April at the beginning of the outbreak, and the public was alerted.

Biotransformation of curcumin through reduction and glucuronidation in mice.

Curcumin, the yellow pigment in turmeric and curry, has antioxidative and anticarcinogenic activities. In this study, we investigated the pharmacokinetic properties of curcumin in mice. After i.p. administration of curcumin (0.1 g/kg) to mice, about 2.25 microg/ml of curcumin appeared in the plasma in the first 15 min. One hour after administration, the levels of curcumin in the intestines, spleen, liver, and kidneys were 177.04, 26.06, 26.90, and 7.51 microg/g, respectively. Only traces (0.41 microg/g) were observed in the brain at 1 h. To clarify the nature of the metabolites of curcumin, the plasma was analyzed by reversed-phase HPLC, and two putative conjugates were observed. Treatment of the plasma with beta-glucuronidase resulted in a decrease in the concentrations of these two putative conjugates and the concomitant appearance of tetrahydrocurcumin (THC) and curcumin, respectively. To investigate the nature of these glucuronide conjugates in vivo, the plasma was analyzed by electrospray. The chemical structures of these metabolites, determined by mass spectrometry/mass spectrometry analysis, suggested that curcumin was first biotransformed to dihydrocurcumin and THC and that these compounds subsequently were converted to monoglucuronide conjugates. Because THC is one of the major metabolites of curcumin, we studied its stability at different pH values. THC was very stable in 0.1 M phosphate buffers of various pH values. Moreover, THC was more stable than curcumin in 0.1 M phosphate buffer, pH 7.2 (37 degrees C). These results, together with previous findings, suggest that curcumin-glucuronoside, dihydrocurcumin-glucuronoside, THC-glucuronoside, and THC are major metabolites of curcumin in vivo.

Solvent kinetic isotope effects of human placental alkaline phosphatase in reverse micelles.

Human placental alkaline phosphatase was embedded in a reverse micellar system prepared by dissolving the surfactant sodium bis(2-ethylhexyl) sulphosuccinate (Aerosol-OT) in 2,2, 4-trimethylpentane. This microemulsion system provides a convenient instrumental tool to study the possible kinetic properties of the membranous enzyme in an immobilized form. The pL (pH/p2H) dependence of hydrolysis of 4-nitrophenyl phosphate has been examined over a pL range of 8.5-12.5 in both aqueous and reverse micellar systems. Profiles of log V versus pL were Ha-bell shaped in the acidic region but reached a plateau in the basic region in which two pKa values of 9.01-9.71 and 9.86-10.48, respectively, were observed in reverse micelles. However, only one pKa value of 9.78-10.27 in aqueous solution was detected. Profiles of log V/K versus pL were bell-shaped in the acidic region. However, they were wave-shaped in the basic region in which a residue of pKa 9.10-9.44 in aqueous solution and 8.07-8.78 in reverse micelles must be dehydronated for the reaction to reach an optimum. The V/K value shifted to a lower value upon dehydronation of a pKa value of 9.80-10.62 in aqueous solution and 11.23-12.17 in reverse micelles. Solvent kinetic isotope effects were measured at three pL values. At pL 9.5, the observed isotope effect was a product of equilibrium isotope effect and a kinetic isotope effect; at pL 10.4, the log V/K value was identical in water and deuterium. The deuterium kinetic isotope effect on V/K was 1.14 in an aqueous solution and 1.16 in reverse micelles. At pL 11.0 at which the log V values reached a plateau in either solvent system, the deuterium kinetic isotope effect on V was 2.08 in an aqueous solution and 0.62 in reverse micelles. Results from a proton inventory experiment suggested that a hydron transfer step is involved in the transition state of the catalytic reaction. The isotopic fractionation factor (pi) for deuterium for the transition state (piT) increased when the pH of the solution was raised. At pL 11.0, the piT was 1.07 in reverse micelles, which corresponds to the inverse-isotope effect of the reaction in this solvent system. Normal viscosity effects on kcat and kcat/Km were observed in aqueous solution, corresponding to a diffusional controlled physical step as the rate-limiting step. We propose that the rate-limiting step of the hydrolytic reaction changes from phosphate releasing in aqueous solution to a covalent phosphorylation or dephosphorylation step in reverse micelles.

Inhibitory effect of magnesium ion on the human placental alkaline phosphatase-catalyzed reaction in a reverse micellar system.

Human placental alkaline phosphatase is a membrane-anchored protein. Entrapping the enzyme into a reverse micellar vesicle mimics the in vivo conditions and allows examination of the properties of the enzyme. Placental alkaline phosphatase is enzymatically active in Aerosol-OT/isooctane reverse micelles. Substantially different kinetic behavior of the enzyme has been observed in aqueous or reverse micellar systems. In aqueous solution, Mg2+ is a nonessential activator of the enzyme. In the experiments described in the present report Mg2+ was found to be an inhibitor for the enzyme in reverse micelles. This inhibition is presumably due to a time-dependent conformational change of the enzyme molecule, which resulted in a curvature in the recorder tracings of the enzyme assays. The Mg2+-induced conformational change of the enzyme was completely prevented by phosphate and partially reserved by EDTA. High concentrations of Zn2+ also strongly inhibited enzyme activity in both aqueous and reverse micellar solvent systems, presumably by occupying the Mg2+ (M3) site of the enzyme. However, binding of Zn2+ at the M3 site did not cause conformational change of the enzyme and the enzyme assay tracing was linear. The M3 site of the enzyme is proposed to have a modulatory role in vivo using magnesium ion as the modulator.

Performance of a neodymium yttrium aluminum borate green laser pumped with a fiber-coupled laser diode.

Using a space-dependent rate-equation model and considering the effect of pump beam quality, the optimum pump condition for a fiber-coupled diode end-pumped neodymium yttrium aluminum borate laser has been determined. Under optimum pump conditions, greater than 10% optical-to-optical conversion efficiency was obtained when the laser was pumped by a fiber-coupled laser diode with good beam quality. The influence of pump beam quality on the conversion efficiency is also discussed.

Single-Mode Operation and Frequency Doubling of Fiber-Coupled Diode Butt-Coupling-Pumped Nd:YVO(4) Lasers.

We present a simple way to achieve single-frequency operation by using a fiber-coupled diode butt-coupling-pumped Nd:YVO(4) laser in a flat-flat cavity. Single-mode outputs of 620 and 260 mW for fundamental and second-harmonic wavelengths were obtained when the laser was pumped by an 1100-mW fiber-coupled laser diode. Experimental results show that thermal effects provide not only a stable resonator with a good overlap of laser mode and pump size but also enhance single-frequency performance.

Compact and Efficient 3.2-W Diode-Pumped Nd:YVO(4)/KTP Green Laser.

We demonstrate a simple way to achieve single-frequency operation by using fiber-coupled diode-pumped Nd:YVO(4)/KTP green lasers in a short standing-wave linear cavity. A single-mode output with 3.2-W green power was generated with a 12.6-W pump power corresponding to a conversion efficiency of 25.4%. The single-mode operation was obtained through the combined action of the anisotropic emission cross section of Nd:YVO(4) and the KTP crystal acting as a birefringent filter.

First EBV vaccine trial in humans using recombinant vaccinia virus expressing the major membrane antigen.

In the absence of a truly representative animal model, the question of whether EBV-related diseases can be prevented by a vaccine has been studied for the first time in humans. A live recombinant virus based on the licensed vaccinia strain Tien Tan, expressing under the 11K vaccinia promoter the major EBV membrane antigen BNLF-1 MA (gp 220-340), was constructed and tested in three different human populations: EBV-positive and vaccinia-virus-exposed adults; EBV-positive, non-vaccinia-virus-exposed juveniles; and EBV and vaccinia virus-naive infants. No significant titre variations for EBV were observed in the adults, but EBV-neutralising titres increased in the vaccinated juveniles, while antibodies to VCA of EBV remained unchanged. All nine vaccinated infants developed antibodies to MA (membrane antigen) with neutralising properties in vitro; three of these infants were infected by EBV via natural routes over a period of 16 months after vaccination and all ten unvaccinated control infants became infected. It has been shown for the first time that protection against and/or delay of EBV infection by the natural route is possible in humans and that live vaccinia vectors can be used and are efficacious.

Dissociation of pigeon-liver malic enzyme in reverse micelles.

Pigeon-liver malic enzyme has a tendency to aggregate at a large concentration of protein. The larger aggregates (hexamer and octamer) were demonstrated to be enzymically active with specific activity similar to that of the tetramer. When the enzyme was embedded in a reverse micellar system prepared by dissolving the surfactant sodium bis(2-ethylhexyl)-sulfosuccinate (AOT) in isooctane, the tetrameric enzyme dissociated into monomers. The dissociated monomers were also enzymically active but with diminished specific activity relative to the activity in aqueous media. The decreased enzyme activity in reverse micelles was due to interactions of surfactant with the enzyme molecules, suggesting that the cytosolic malic enzyme is located near the plasma membrane. When the dissociation was monitored by altering the degree of hydration of the system (represented by the ratio [H2O]/[AOT]), the detergent and organic solvent slightly affected KTD, the dissociation constant of tetramer to dimers (T <--> 2 D), but increased KDM, the dissociation constant of dimer to monomers (D <--> 2 M), by 1-2 orders of magnitude; this change caused a 2-3 orders of magnitude increase in the overall dissociation constant KTM (T <--> 4 M). The dissociation of the tetrameric malic enzyme to monomers was favored by approximately 16 kJ/mol in AOT/isooctane reverse micelles versus aqueous media. We propose water-shell and induced-fit models for the enzyme in AOT/isooctane reverse micelles at large and small [H2O]/[AOT] ratios to explain this data, respectively. The asymmetric quaternary structure of the enzyme [Lee, H. J. & Chang, G. G. (1990) FEBS Lett. 277, 175-179] was re-evaluated in terms of the subunit interactions and various interconvertible enzyme forms.