A real-time XAS PEEM study of the growth of cobalt iron oxide on Ru(0001).

The growth of mixed cobalt-iron oxides on Ru(0001) by high-temperature oxygen-assisted molecular beam epitaxy has been monitored in real time and real space by x-ray absorption photoemission microscopy. The initial composition is a mixed Fe-Co(II) oxide wetting layer, reflecting the ratio of the deposited materials. However, as subsequent growth of three dimensional spinel islands nucleating on this wetting layer takes place, the composition of the oxide in the wetting layer changes as iron is transferred into the spinel islands. The composition of the islands themselves also changes during growth.

Monotherapy with the once-weekly GLP-1 analogue dulaglutide for 12 weeks in patients with Type 2 diabetes: dose-dependent effects on glycaemic control in a randomized, double-blind, placebo-controlled study.

AIMS: Evaluate dose-dependent effects of once-weekly dulaglutide, a glucagon-like peptide-1 analogue, on glycaemic control in patients with Type 2 diabetes treated with lifestyle measures with or without previous metformin. METHODS: This 12-week, double-blind, placebo-controlled, dose-response trial randomized 167 patients who were anti-hyperglycaemic medication-naïve or had discontinued metformin monotherapy [mean baseline HbA(1c) 59 ± 8 to 61 ± 8 mmol/mol (7.6 ± 0.7 to 7.8 ± 0.8%)] to once-weekly injections of placebo or dulaglutide (0.1, 0.5, 1.0 or 1.5 mg). RESULTS: A significant dose-dependent reduction in HbA(1c) (least squares mean ± SE) was observed across doses (P < 0.001). HbA(1c) reductions in the 0.5, 1.0 and 1.5 mg dulaglutide groups were greater than in the placebo group [-10 ± 1, -11 ± 1 and -11 ± 1 vs. 0 ± 1 mmol/mol (-0.9 ± 0.1, -1.0 ± 0.1 and -1.0 ± 0.1 vs. 0.0 ± 0.1%), respectively, all P < 0.001]. Dose-dependent reductions in fasting plasma glucose were also observed [least squares mean difference (95% CI) ranging from -0.43 (-1.06 to 0.19) mmol/l for dulaglutide 0.1 mg to -1.87 (-2.56 to -1.19) mmol/l for dulaglutide 1.5 mg, P < 0.001]. Dose-dependent weight loss was demonstrated across doses (P = 0.009), but none of the groups were different from placebo. The most common adverse events were nausea and diarrhoea. CONCLUSIONS: The observed dulaglutide dose-dependent reduction in HbA(1c) and its acceptable safety profile support further clinical development for treatment of Type 2 diabetes.

Strontium hexaferrite platelets: a comprehensive soft X-ray absorption and Mössbauer spectroscopy study.

Platelets of strontium hexaferrite (SrFe12O19, SFO), up to several micrometers in width, and tens of nanometers thick have been synthesized by a hydrothermal method. They have been studied by a combination of structural and magnetic techniques, with emphasis on Mössbauer spectroscopy and X-ray absorption based-measurements including spectroscopy and microscopy on the iron-L edges and the oxygen-K edge, allowing us to establish the differences and similarities between our synthesized nanostructures and commercial powders. The Mössbauer spectra reveal a greater contribution of iron tetrahedral sites in platelets in comparison to pure bulk material. For reference, high-resolution absorption and dichroic spectra have also been measured both from the platelets and from pure bulk material. The O-K edge has been reproduced by density functional theory calculations. Out-of-plane domains were observed with 180° domain walls less than 20 nm width, in good agreement with micromagnetic simulations.

The dipeptidyl peptidase-4 inhibitor PHX1149 improves blood glucose control in patients with type 2 diabetes mellitus.

AIM: To determine the efficacy and tolerability of PHX1149, a novel dipeptidyl peptidase-4 (DPP4) inhibitor, in patients with type 2 diabetes. METHODS: This is a multicentre, randomized, double-blind, placebo-controlled, 4-week study in patients with type 2 diabetes with suboptimal metabolic control. Patients with a baseline haemoglobin A(1c) (HbA(1c)) of 7.3 to 11.0% were randomized 1 : 1 : 1 : 1 to receive once-daily oral therapy with either PHX1149 (100, 200 or 400 mg) or placebo; patients were on a constant background therapy of either metformin alone or metformin plus a glitazone. RESULTS: Treatment with 100, 200 or 400 mg of PHX1149 significantly decreased postprandial glucose area under the curve AUC(0-2 h) by approximately 20% (+0.11 +/- 0.50, -2.08 +/- 0.51, -1.73 +/- 0.49 and -1.88 +/- 0.48 mmol/l x h, respectively, for placebo and 100, 200 and 400 mg (p = 0.002, 0.008 and 0.004 vs. placebo). Postprandial AUC(0-2 h) of intact glucagon-like peptide-1, the principal mediator of the biological effects of DPP4 inhibitors, was increased by 3.90 +/- 2.83, 11.63 +/- 2.86, 16.42 +/- 2.72 and 15.75 +/- 2.71 pmol/l x h, respectively, for placebo and 100, 200 and 400 mg (p = 0.053, 0.001 and 0.002 vs. placebo). Mean HbA(1c) was lower in all dose groups; the placebo-corrected change in the groups receiving 400 mg PHX1149 was -0.28% (p = 0.02). DPP4 inhibition on day 28 was 53, 73 and 78% at 24 h postdose in the groups receiving 100, 200 and 400 mg PHX1149, respectively. There were no differences in adverse events between PHX1149-treated and placebo subjects. CONCLUSIONS: Addition of the DPP4 inhibitor PHX1149 to a stable regimen of metformin or metformin plus a glitazone in patients with type 2 diabetes was well tolerated and improved blood glucose control.

Doubling immunochemistry laboratory testing efficiency with the cobas e 801 module while maintaining consistency in analytical performance.

OBJECTIVES: The new immunochemistry cobas e 801 module (Roche Diagnostics) was developed to meet increasing demands on routine laboratories to further improve testing efficiency, while maintaining high quality and reliable data. DESIGN AND METHODS: During a non-interventional multicenter evaluation study, the overall performance, functionality and reliability of the new module was investigated under routine-like conditions. It was tested as a dedicated immunochemistry system at four sites and as a consolidator combined with clinical chemistry at three sites. RESULTS: We report on testing efficiency and analytical performance of the new module. Evaluation of sample workloads with site-specific routine request patterns demonstrated increased speed and almost doubled throughput (maximal 300 tests per h), thus revealing that one cobas e 801 module can replace two cobas e 602 modules while saving up to 44% floor space. Result stability was demonstrated by QC analysis per assay throughout the study. Precision testing over 21 days yielded excellent results within and between labs, and, method comparison performed versus the cobas e 602 module routine results showed high consistency of results for all assays under study. In a practicability assessment related to performance and handling, 99% of graded features met (44%) or even exceeded (55%) laboratory expectations, with enhanced reagent management and loading during operation being highlighted. CONCLUSION: By nearly doubling immunochemistry testing efficiency on the same footprint as a cobas e 602 module, the new module has a great potential to further consolidate and enhance laboratory testing while maintaining high quality analytical performance with Roche platforms.

P21Cip1/WAF1 downregulation is required for efficient PCNA ubiquitination after UV irradiation.

p21(Cip1/WAF1) is a known inhibitor of the short-gap filling activity of proliferating cell nuclear antigen (PCNA) during DNA repair. In agreement, p21 degradation after UV irradiation promotes PCNA-dependent repair. Recent reports have identified ubiquitination of PCNA as a relevant feature for PCNA-dependent DNA repair. Here, we show that PCNA ubiquitination in human cells is notably augmented after UV irradiation and other genotoxic treatments such as hydroxyurea, aphidicolin and methylmethane sulfonate. Intriguingly, those DNA damaging agents also promoted downregulation of p21. While ubiquitination of PCNA was not affected by deficient nucleotide excision repair (NER) and was observed in both proliferating and arrested cells, stable p21 expression caused a significant reduction in UV-induced ubiquitinated PCNA. Surprisingly, the negative regulation of PCNA ubiquitination by p21 does not depend on the direct interaction with PCNA but requires the cyclin dependent kinase binding domain of p21. Taken together, our data suggest that p21 downregulation plays a role in efficient PCNA ubiquitination after UV irradiation.

The Meropenem Yearly Susceptibility Test Information Collection antimicrobial susceptibility program in Spain: a 5-year analysis.

The Meropenem Yearly Susceptibility Test Information Collection program is a global study providing in vitro surveillance data on antimicrobial susceptibility in centers prescribing meropenem. This study summarizes data on the activity of meropenem and 5 comparators against 4022 clinical isolates from 7 centers in Spain (1999-2003). Those bacteria intrinsically resistant to meropenem were excluded. Among Enterobacteriaceae, 100% of Enterobacter spp., Citrobacter spp., and Serratia spp. were susceptible to meropenem. Escherichia coli and Klebsiella pneumoniae susceptibilities to carbapenems were 100% and > or =98%, respectively. Extended-spectrum beta-lactamase-producing Enterobacteriaceae were 3.8% of isolates, and all of them were susceptible to meropenem. Ciprofloxacin resistance in E. coli was around 20%. Meropenem and piperacillin/tazobactam were the most active agents against Pseudomonas aeruginosa. Acinetobacter baumannii were 61-90% susceptible to carbapenems, but only 6-21% susceptible to ciprofloxacin. In this period, around 100% of oxacillin-susceptible staphylococci were susceptible to meropenem. There was no significant decrease in susceptibility to the carbapenems throughout the 5-year period. The clinical use of meropenem in 7 Spanish centers did not increase bacterial resistance to this agent in the microorganisms evaluated.

Early diagnosis of candidiasis in non-neutropenic critically ill patients.

OBJECTIVE: To determine a method for the early diagnosis of candidiasis in non-neutropenic critically ill patients in order to reduce mortality. METHODS: A prospective study in non-neutropenic critically patients in whom Candida spp. were detected, was made in an intensive care unit (ICU) during an 8-year period from 3389 patients admitted. A diagnostic and therapeutic protocol was designed. Invasive candidiasis was defined according to dissemination and multifocality. RESULTS: Candida spp. were found in 145 cases (4.3%): 120 (83%) were considered as invasive candidiasis and 25 as colonisation (17%). The hospital mortality was 46% (67/145). A post-mortem study was carried out in 54% (36/67) of hospital deaths. Candida albicans was the most frequently isolated species (87%), followed by Candida glabrata (18%). There were 24 candidemias and three cases of endophtalmitis. Digestive and respiratory samples and non-C. albicans yeasts were risk factors for invasive candidiasis. The mortality rate was related statistically to invasive candidiasis and inversely to the appropriate antifungal treatment. CONCLUSIONS: Invasive candidiasis is related to digestive and respiratory samples and to the presence of non-C. albicans species. A simpler definition of invasive candidiasis in non-neutropenic critically ill patients will permit more rapid and accurate specific antifungal therapy.

Hybrid carbon nanotube networks as efficient hole extraction layers for organic photovoltaics.

Transparent, highly percolated networks of regioregular poly(3-hexylthiophene) (rr-P3HT)-wrapped semiconducting single-walled carbon nanotubes (s-SWNTs) are deposited, and the charge transfer processes of these nanohybrids are studied using spectroscopic and electrical measurements. The data disclose hole doping of s-SWNTs by the polymer, challenging the prevalent electron-doping hypothesis. Through controlled fabrication, high- to low-density nanohybrid networks are achieved, with low-density hybrid carbon nanotube networks tested as hole transport layers (HTLs) for bulk heterojunction (BHJ) organic photovoltaics (OPV). OPVs incorporating these rr-P3HT/s-SWNT networks as the HTL demonstrate the best large area (70 mm(2)) carbon nanotube incorporated organic solar cells to date with a power conversion efficiency of 7.6%. This signifies the strong capability of nanohybrids as an efficient hole extraction layer, and we believe that dense nanohybrid networks have the potential to replace expensive and material scarce inorganic transparent electrodes in large area electronics toward the realization of low-cost flexible electronics.

Quantification of thrombus hounsfield units on noncontrast CT predicts stroke subtype and early recanalization after intravenous recombinant tissue plasminogen activator.

BACKGROUND AND PURPOSE: Little is known about the factors that determine recanalization after intravenous thrombolysis. We assessed the value of thrombus Hounsfield unit quantification as a predictive marker of stroke subtype and MCA recanalization after intravenous rtPA treatment. MATERIALS AND METHODS: NCCT scans and CTA were performed on patients with MCA acute stroke within 4.5 hours of symptom onset. Demographics, stroke severity, vessel hyperattenuation, occlusion site, thrombus length, and time to thrombolysis were recorded. Stroke origin was categorized as LAA, cardioembolic, or indeterminate according to TOAST criteria. Two blinded neuroradiologists calculated the Hounsfield unit values for the thrombus and contralateral MCA segment. We used ROC curves to determine the rHU cutoff point to discriminate patients with successful recanalization from those without. We assessed the accuracy (sensitivity, specificity, and positive and negative predictive values) of rHU in the prediction of recanalization. RESULTS: Of 87 consecutive patients, 45 received intravenous rtPA and only 15 (33.3%) patients had acute recanalization. rHU values and stroke mechanism were the highest predictive factors of recanalization. The Matthews correlation coefficient was highest for rHU (0.901). The sensitivity, specificity, and positive and negative predictive values for lack of recanalization after intravenous rtPA for rHU ≤ 1.382 were 100%, 86.67%, 93.75%, and 100%, respectively. LAA thrombi had lower rHU than cardioembolic and indeterminate stroke thrombi (P = .004). CONCLUSIONS: The Hounsfield unit thrombus measurement ratio can predict recanalization with intravenous rtPA and may have clinical utility for endovascular treatment decision making.

Acute damage to the posterior limb of the internal capsule on diffusion tensor tractography as an early imaging predictor of motor outcome after stroke.

BACKGROUND AND PURPOSE: Early prediction of motor outcome is of interest in stroke management. We aimed to determine whether lesion location at DTT is predictive of motor outcome after acute stroke and whether this information improves the predictive accuracy of the clinical scores. MATERIALS AND METHODS: We evaluated 60 consecutive patients within 12 hours of middle cerebral artery stroke onset. We used DTT to evaluate CST involvement in the motor cortex and premotor cortex, centrum semiovale, corona radiata, and PLIC and in combinations of these regions at admission, at day 3, and at day 30. Severity of limb weakness was assessed by using the motor subindex scores of the National Institutes of Health Stroke Scale (5a, 5b, 6a, 6b). We calculated volumes of infarct and fractional anisotropy values in the CST of the pons. RESULTS: Acute damage to the PLIC was the best predictor associated with poor motor outcome, axonal damage, and clinical severity at admission (P < .001). There was no significant correlation between acute infarct volume and motor outcome at day 90 (P = .176, r = 0.485). The sensitivity, specificity, and positive and negative predictive values of acute CST involvement at the level of the PLIC for motor outcome at day 90 were 73.7%, 100%, 100%, and 89.1%, respectively. In the acute stage, DTT predicted motor outcome at day 90 better than the clinical scores (R(2) = 75.50, F = 80.09, P < .001). CONCLUSIONS: In the acute setting, DTT is promising for stroke mapping to predict motor outcome. Acute CST damage at the level of the PLIC is a significant predictor of unfavorable motor outcome.

Behavioural and biochemical responses to morphine associated with its motivational properties are altered in adenosine A(2A) receptor knockout mice.

BACKGROUND AND PURPOSE: The purinergic system through the A(2A) adenosine receptor regulates addiction induced by different drugs of abuse. The aim of the present study was to investigate the specific role of A(2A) adenosine receptors (A(2A)Rs) in the behavioural and neurochemical responses to morphine associated with its motivational properties. EXPERIMENTAL APPROACH: Mice lacking A(2A)Rs (A(2A) knockout (KO) mice) and wild-type littermates were used to evaluate behavioural responses induced by morphine. Antinociception was assessed using the tail-immersion and the hot-plate tests. Place-conditioning paradigms were used to evaluate the rewarding effects of morphine and the dysphoric responses of morphine withdrawal. Microdialysis studies were carried out to evaluate changes in the extracellular levels of dopamine in the nucleus accumbens of A(2A) KO mice after morphine administration. KEY RESULTS: The acute administration of morphine induced a similar enhancement of locomotor activity and antinociceptive responses in both genotypes. However, the rewarding effects induced by morphine were completely blocked in A(2A) KO mice. Also, naloxone did not induce place aversion in animals lacking the A(2A)Rs. CONCLUSIONS AND IMPLICATIONS: Our findings demonstrate that the rewarding and aversive effects associated with morphine abstinence were abolished in A(2A) KO mice, supporting a differential role of the A(2A) adenosine receptor in the somatic and motivational effects of morphine addiction. This study provides evidence for the role of A(2A)Rs as general modulators of the motivational properties of drugs of abuse. Pharmacological manipulation of these receptors may represent a new target in the management of drug addiction.

Molecular fingerprinting of Salmonella typhimurium by IS200-typing as a tool for epidemiological and evolutionary studies.

The aim of this work was to develop and evaluate a molecular typing strategy for Salmonella based on hybridization of chromosomal DNA with two different probes derived from insertion sequence IS200. Probe IS200-TT was specifically constructed for this study as a trimer of a 112 pb TaqI-TaqI fragment of IS200. Among several restriction enzymes evaluated, two were selected: EcoRI, which cuts the insertion sequence in two pieces, each one complementary to one of the probes used, and PstI, a restriction enzyme with no recognition site into IS200. With several combinations of these restrictions enzymes and probes, 43 Salmonella typhimurium strains were analyzed for copy number and location of IS200, as well as reproducibility and stability of the patterns. IS200 types have been shown to be stable, both in strains isolated from different patients implicated in the same salmonellosis outbreak and in strains isolated from the same patient at different times or from different specimens. The discriminatory power of the method has been 0.91 to 0.94. As a comparison, S. typhimurium strains were also ribotyped. Discriminatory power of the ribotypes oscillated between 0.44 and 0.55, depending on the enzyme used, and achieved a 0.78 value when the information obtained with two restriction enzymes was combined. Moreover, IS200 typing was able to differentiate among a group of S. typhimurium strains which were identical by ribotype and enzymatic electrophoretic mobility. These results enable us to conclude that, for the stability, reproducibility and discriminatory power of the patterns generated, IS200 probes can be a very useful tool in the molecular typing of S. typhimurium.

[ Exsanguination, extreme hemodilution and autologous retransfusion in cardiopulmonary bypass]. / exsanguinación, hemodilución extrema y retransfusión autológa en derivación cardiopulmonar

In ten dogs and seven patients undergoing open heart surgery, 94% of circulatory volume was replaced by electrolitic solutions; extracted blood was stored temporarily at 5degreesC. Usage of blood was avoided for replacement of extracorporeal fluid circuit and blood lost during surgery. After cardiopulmonar bypass, storage blood was transfused. In both experimental and clinical conditions neither renal, electrolitic nor blood alterations were observed.

The utility of serology in diagnosing candidosis in non-neutropenic critically ill patients.

This study was carried out to evaluate the utility of serological tests in the diagnosis of candidal infections in non-neutropenic critically ill patients. A prospective study was carried out in a 10-bed general intensive care unit; all patients with at least one organic sample with Candida spp. were included. A therapeutic-diagnostic algorithm was designed, and patients were treated or not, according to a classification. Blood samples were taken, and serological tests included: antigenaemia detection using two different commercial latex kits (Cand-Tec and Pastorex) and antibody detection by indirect haemagglutination (IHA) and indirect germ tube immunofluorescence (IFA). A total of 56% of antibody tests (IHA 45% and IFA 64%) and 26% of antigen tests (Cand-Tec 36% and Pastorex 17%) were positive. The sensitivity and specificity of these tests with respect to systemic candidosis were 37% and 78%, respectively, for antibodies, and 0% and 90% for antigens. There was statistical significance for mortality and low levels of antibodies; Candida glabrata was detected by IFA and Candida tropicalis by Cand-Tec. Serological tests may help to define the prognosis of these patients and to support the detection of specific Candida species.

Some toxinological aspects of Aurelia aurita (Linné) from the mexican caribbean

Aurelia aurita is scyphozoan, abundant in the Mexican Caribbean during summer. Although usually innocuous, there is evidence of it causing harm to humans. This work investigates the biological activities of crude and fractionated extracts of A. aurita. Live specimens were collected between July and September 1999 from the Mexican Caribbean. The tentacular margin was dissected immediately and frozen at -50ºC. A nematocyst suspension was prepared, discharged, and the supernatants lyophilized. Hemolytic assay was performed with lyophilized crude extract on bovine, sheep, and human red blood cells. Erythrocyte sensitivity to the toxin was ranked in descending order: human, sheep, and bovine. Toxic activity on Artemia nauplii was evaluated using the same crude extract for different exposure periods (3, 5, and 10 hours); only 48 and 72 hour old Artemia nauplii showed 50 per cent mortality. Partial toxin purification was completed by sequential liquid chromatography using three gels (Sephadex G-200, DEAE Sephadex A-50, and Sephadex G-100). Intramuscular neuroactivity was detected in the crab Ocypode quadrata for two partially purified fractions. These fractions were found to have molecular weight components of 66 and 45 kDa, respectively.