Oxygen reduction reaction catalyzed by epsilon-MnO2: Influence of the crystalline structure on the reaction mechanism

The oxygen reduction reaction (ORR) was studied in KOH electrolyte on carbon supported epsilon-manganese dioxide (epsilon-MnO2/C). The epsilon-MnO2/C catalyst was prepared via thermal decomposition of manganese nitrate and carbon powder (Vulcan XC-72) mixtures. X-ray powder diffraction (XRD) measurements were performed in order to determine the crystalline structure of the resulting composite, while energy dispersive X-ray analysis (EDX) was used to evaluate the chemical composition of the synthesized material. The electrochemical studies were conducted using cyclic voltammetry (CV) and quasi-steady state polarization measurements carried out with an ultra thin layer rotating ring/disk electrode (RRDE) configuration. The electrocatalytic results obtained for 20% (w/w) Pt/C (E-TEK Inc., USA) and alpha-MnO2/C for the ORR, considered as one of the most active manganese oxide based catalyst for the ORR in alkaline media, were included for comparison. The RRDE results revealed that the ORR on the MnO2 catalysts proceeds preferentially through the complete 4e(-) reduction pathway via a 2 plus 2e(-) reduction process involving hydrogen peroxide as an intermediate. A benchmark close to the performance of 20% (w/w) Pt/C (E-TEK Inc., USA) was observed for the epsilon-MnO2/C material in the kinetic control region, superior to the performance of alpha-MnO2/C, but a higher amount of HO2- was obtained when epsilon-MnO2/C was used as catalyst. The higher production of hydrogen peroxide on epsilon-MnO2/C was related to the presence of structural defects, typical of this oxide, while the better catalytic performance in the kinetic control region compared to alpha-MnO2/C was related with the higher electrochemical activity for the proton insertion kinetics, which is a structure sensitive process. (C) 2012 Elsevier Ltd. All rights reserved.

Taxonomic and Functional Microbial Signatures of the Endemic Marine Sponge Arenosclera brasiliensis

The endemic marine sponge Arenosclera brasiliensis (Porifera, Demospongiae, Haplosclerida) is a known source of secondary metabolites such as arenosclerins A-C. In the present study, we established the composition of the A. brasiliensis microbiome and the metabolic pathways associated with this community. We used 454 shotgun pyrosequencing to generate approximately 640,000 high-quality sponge-derived sequences (similar to 150 Mb). Clustering analysis including sponge, seawater and twenty-three other metagenomes derived from marine animal microbiomes shows that A. brasiliensis contains a specific microbiome. Fourteen bacterial phyla (including Proteobacteria, Cyanobacteria, Actinobacteria, Bacteroidetes, Firmicutes and Cloroflexi) were consistently found in the A. brasiliensis metagenomes. The A. brasiliensis microbiome is enriched for Betaproteobacteria (e.g., Burkholderia) and Gammaproteobacteria (e.g., Pseudomonas and Alteromonas) compared with the surrounding planktonic microbial communities. Functional analysis based on Rapid Annotation using Subsystem Technology (RAST) indicated that the A. brasiliensis microbiome is enriched for sequences associated with membrane transport and one-carbon metabolism. In addition, there was an overrepresentation of sequences associated with aerobic and anaerobic metabolism as well as the synthesis and degradation of secondary metabolites. This study represents the first analysis of sponge-associated microbial communities via shotgun pyrosequencing, a strategy commonly applied in similar analyses in other marine invertebrate hosts, such as corals and algae. We demonstrate that A. brasiliensis has a unique microbiome that is distinct from that of the surrounding planktonic microbes and from other marine organisms, indicating a species-specific microbiome.

Morphological evidence of neurotoxicity in retina after methylmercury exposure

The visual system is particularly sensitive to methylmercury (MeHg) exposure and, therefore, provides a useful model for investigating the fundamental mechanisms that direct toxic effects. During a period of 70 days, adult of a freshwater fish species Hoplias malabaricus were fed with fish prey previously labeled with two different doses of methylmercury (0.075 and 0.75 mu g g(-1)) to determine the mercury distribution and morphological changes in the retina. Mercury deposits were found in the photoreceptor layer, in the inner plexiform layer and in the outer plexiform layer, demonstrating a dose-dependent bioaccumulation. The ultrastructure analysis of retina revealed a cellular deterioration in the photoreceptor layer, morphological changes in the inner and outer segments of rods, structural changes in the plasma membrane of rods and double cones, changes in the process of removal of membranous discs and a structural discontinuity. These results lead to the conclusion that methylmercury is able to cross the blood-retina barrier, accumulate in the cells and layers of retina and induce changes in photoreceptors of H. malabaricus even under subchronic exposure. (c) 2012 Elsevier Inc. All rights reserved.

Entwicklung eines Verfahrens zur Ultraspurenbestimmung der Platingruppenelemente in Umwelt- und geologischen Proben mit einem ICP-QMS unter Verwendung der Isotopenverdünnungsanalyse sowie geeigneter Separationstechniken

ZusammenfassungSchwerpunkt dieser Arbeit war die Verfahrensentwicklung zur Ultraspurenbestimmung der Platingruppenelemente (PGE) in Umwelt- und geologischen Proben unter Verwendung der massenspektrometrischen Isotopenverdünnungsanalyse mit anschließender Bestimmung an einem Quadrupol ICP-MS (ICP-QMSIVA). Geeignete Separationstechniken in der Probenaufbereitung, um die PGE von der Matrix der untersuchten Proben zu trennen, stellten eine richtige und präzise Bestimmung der Ultraspuren an einem Quadrupol ICP-MS sicher.Das Verfahren konnte anhand von geologischen Referenzmaterialien aus Kanada sichergestellt werden. Gerade die Wiederholungsbestimmungen der verschiedenen Referenzmaterialien unter Verwendung des ICP-QMSIVA Verfahrens sind beispiellos und in dieser Form noch nicht in der Literatur beschrieben. Durch systematische Messungen konnten Richtigkeit und Präzision des Verfahrens bestätigt werden und die Inhomogenität des Referenzmaterials UMT-1 bezüglich Pt bewiesen werden. Das in dieser Arbeit entwickelte Verfahren zur Ultraspurenbestimmung der PGE mit ICP-QMSIVA wurde im Rahmen des Projektes 'Production and certification of a road dust reference material for platinum, palladium and rhodium (PGEs) in automative catalytic converters (PACEPAC)' der Europäischen Union zur Zertifizierung von zwei Referenzmaterialien für Umweltproben eingesetzt. Hierbei wurde bei der Zertifizierung ('intercomparison round') eine sehr gute Übereinstimmung der Ergebnisse mit dem gewichteten Mittelwert der Ergebnisse für Pd und Pt mit den übrigen teilnehmenden Laboratorien festgestellt. Die mit der hier entwickelten Methode erhaltenen Ergebnisse wurden ohne Ausnahme für alle gemessenen Elemente zur Zertifizierung herangezogen. Damit leistete die vorliegende Arbeit einen erheblichen Beitrag zum erfolgreichen Abschluß dieses Projekts. Den Erwartungen hinsichtlich Richtigkeit und Reproduzierbarkeit des entwickelten Verfahrens wurde somit voll entsprochen. Erneut konnte die große Bedeutung der Isotopenverdünnungstechnik für die Zertifizierung von Referenzmaterialien aufgezeigt werden, da mit dieser Technik bei sachgerechtem Einsatz Ergebnisse hoher Richtigkeit erzielt werden. Durch vergleichende Messungen mit der NiS-Dokimasie und NAA, die in einer Kooperation mit dem Kernchemischen Institut der Universität Mainz durchgeführt wurden, und dem hier verwendeten Verfahren, konnten übereinstimmende Daten, hinsichtlich der Abnahme der Konzentrationen von Pd und Pt in Abhängigkeit von der Entfernung zu einer Autobahn, erzielt werden. Diese Arbeit und die Forschungsergebnisse, die mit der anerkannten NAA erzielt wurden, zeigen, daß die PGE durch Katalysatoren von Automobilen überwiegend metallisch emittiert werden. Der anthropogene Eintrag der PGE in die Umwelt kann mit dem ICP-QMSIVA Verfahren weiterhin sehr gut verfolgt werden.

Multidimensional item response theory models with general and specific latent traits for ordinal data

The aim of the thesis is to propose a Bayesian estimation through Markov chain Monte Carlo of multidimensional item response theory models for graded responses with complex structures and correlated traits. In particular, this work focuses on the multiunidimensional and the additive underlying latent structures, considering that the first one is widely used and represents a classical approach in multidimensional item response analysis, while the second one is able to reflect the complexity of real interactions between items and respondents. A simulation study is conducted to evaluate the parameter recovery for the proposed models under different conditions (sample size, test and subtest length, number of response categories, and correlation structure). The results show that the parameter recovery is particularly sensitive to the sample size, due to the model complexity and the high number of parameters to be estimated. For a sufficiently large sample size the parameters of the multiunidimensional and additive graded response models are well reproduced. The results are also affected by the trade-off between the number of items constituting the test and the number of item categories. An application of the proposed models on response data collected to investigate Romagna and San Marino residents' perceptions and attitudes towards the tourism industry is also presented.

Accuracy of liver stiffness measurement using fibroscan ® to predict the response to antiviral therapy in patients with chronic hepatitis c viral infection

Introduction: Antiviral therapy can prevent disease progression in patients with chronic hepatitis C . Transient Elastografy (TE; Fibroscan) is an accurate surrogate marker to liver fibrosis, by measuring liver stiffness (LS). LS decrease has been associated with sustained virologic response (SVR). Aim: to assess the changes of LS measurments in CHC patients during and one year after Interferon (IFN)-based antiviral therapy (IFN/ribavirin) or (telaprevir+IFN/ribavirin). Methods: consecutive 69 CHC patients (53.6% females, mean age 57.9 ± 11.4) who underwent antiviral therapy for at least 20 weeks were enrolled. LS was measured using FibroScan at baseline, after three months, at the end of treatment and one year after treatment discontinuation. Fibrosis was graded using METAVIR score. Results: twenty patients treated with triple therapy and 49 with IFN/ribavirin. Fifty patients had SVR and 19 were non-responders. SVR patients: F0-F1, F2 and F3 patients (39.1%, 7.2% and 17.4%; respectively) showed no significant LS decrease (P= 0.186, 0.068 and 0.075; respectively). Conversely, in F4 patients (36.2%) LS was significantly decreased (P=0.015) after one year of treatment completion. In all patients with no SVR, no significant decrease in LS was observed. Interestingly, all Patients with F4 fibrosis (even non-responders) showed an initial significant decrease in LS (P=0.024) at 3 months after the start of treatment. However, this decrease was not predictive of SVR; area under the ROC curve 0.369 (CI %: 0.145-0.592) P= 0.265. Conclusion: Our study showed that initial decrease in LSM, especially in patients with higher baseline fibrosis score is unlikely to predict an SVR. In addition no significant association was found between clinical or virological parameters and fibrosis improvement. Further studies are needed to delineate the most appropriate clinical scenarios for the LSM by Fibroscan in chronic hepatitis C and its role in monitoring the response to antiviral treatment.

Fast kinase domain-containing protein 3 is a mitochondrial protein essential for cellular respiration

Fas-activated serine/threonine phosphoprotein (FAST) is the founding member of the FAST kinase domain-containing protein (FASTKD) family that includes FASTKD1-5. FAST is a sensor of mitochondrial stress that modulates protein translation to promote the survival of cells exposed to adverse conditions. Mutations in FASTKD2 have been linked to a mitochondrial encephalomyopathy that is associated with reduced cytochrome c oxidase activity, an essential component of the mitochondrial electron transport chain. We have confirmed the mitochondrial localization of FASTKD2 and shown that all FASTKD family members are found in mitochondria. Although human and mouse FASTKD1-5 genes are expressed ubiquitously, some of them are most abundantly expressed in mitochondria-enriched tissues. We have found that RNA interference-mediated knockdown of FASTKD3 severely blunts basal and stress-induced mitochondrial oxygen consumption without disrupting the assembly of respiratory chain complexes. Tandem affinity purification reveals that FASTKD3 interacts with components of mitochondrial respiratory and translation machineries. Our results introduce FASTKD3 as an essential component of mitochondrial respiration that may modulate energy balance in cells exposed to adverse conditions by functionally coupling mitochondrial protein synthesis to respiration.

Anthracyclines during induction therapy in acute myeloid leukaemia: a systematic review and meta-analysis

This systematic review and meta-analysis compared the efficacy of different anthracyclines and anthracycline dosing schedules for induction therapy in acute myeloid leukaemia in children and adults younger than 60 years of age. Twenty-nine randomized controlled trials were eligible for inclusion in the review. Idarubicin (IDA), in comparison to daunorubicin (DNR), reduced remission failure rates (risk ratio (RR) 0·81; 95% confidence interval (CI), 0·66-0·99; P = 0·04), but did not alter rates of early death or overall mortality. Superiority of IDA for remission induction was limited to studies with a DNR/IDA dose ratio <5 (ratio <5: RR 0·65; 95% CI, 0·51-0·81; P < 0·001; ratio ≥5: RR 1·03; 95% CI, 0·91-1·16; P = 0·63). Higher-dose DNR, compared to lower-dose DNR, was associated with reduced rates for remission failure (RR 0·75; 95% CI, 0·60-0·94; P = 0·003) and overall mortality (RR 0·83; 95% CI, 0·75-0·93; P < 0·001), but not for early death. Comparisons of several other anthracycline derivates did not reveal significant differences in outcomes. Survival estimates in adults suggest that both high-dose DNR (90 mg/m(2) daily × 3 or 50 mg/m(2) daily × 5) and IDA (12 mg/m(2) daily × 3) can achieve 5-year survival rates of between 40 and 50 percent.

Ultrasonographic-guided ilioinguinal/iliohypogastric nerve block in pediatric anesthesia: what is the optimal volume?

Recently, our study group demonstrated the usefulness of ultrasonographic guidance in ilioinguinal/iliohypogastric nerve blocks in children. As a consequence, we designed a follow-up study to evaluate the optimal volume of local anesthetic for this regional anesthetic technique. Using a modified step-up-step-down approach, with 10 children in each study group, a starting dose of 0.2 mL/kg of 0.25% levobupivacaine was administered to perform an ilioinguinal/iliohypogastric nerve block under ultrasonographic guidance. After each group of 10 patients, the results were analyzed, and if all blocks were successful, the volume of local anesthetic was decreased by 50%, and a further 10 patients were enrolled into the study. Failure to achieve a 100% success rate within a group subjected patients to an automatic increase of half the previous volume reduction to be used in the subsequent group. Using 0.2 and 0.1 mL/kg of 0.25% levobupivacaine, the success rate was 100%. With a volume of 0.05 mL/kg of 0.25% levobupivacaine, 4 of 10 children received additional analgesia because of an inadequate block. Therefore, according to the protocol, the amount was increased to 0.075 mL/kg of 0.25% levobupivacaine, where the success rate was again 100%. We conclude that ultrasonographic guidance for ilioinguinal/iliohypogastric nerve blocks in children allowed a reduction of the volume of local anesthetic to 0.075 mL/kg.

Evidence for low-grade systemic proinflammatory activity in patients with posttraumatic stress disorder

Posttraumatic stress disorder (PTSD) may increase cardiovascular risk but the psychophysiological mechanisms involved are elusive. We hypothesized that proinflammatory activity is elevated in patients with PTSD as diagnosed by the Clinician Administered PTSD Scale (CAPS) interview. Plasma levels of proinflammatory C-reactive protein (CRP), interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha, and of anti-inflammatory IL-4 and IL-10 were measured in 14 otherwise healthy PTSD patients and in 14 age- and gender-matched healthy non-PTSD controls. Levels of TNF-alpha (p=0.038; effect size Cohen's d=0.58) and of IL-1beta (p=0.075, d=0.68) were higher in patients than in controls. CRP (d=0.10), IL-6 (d=0.18), IL-4 (d=0.42), and IL-10 (d=0.37) were not significantly different between groups. Controlling for traditional cardiovascular risk factors, mood, and time since trauma revealed lower IL-4 in patients than in controls (p=0.029) and rendered group differences in TNF-alpha and IL-1beta insignificant. In all subjects, TNF-alpha correlated with total (frequency and intensity) PTSD symptom cluster of re-experiencing (r=0.49, p=0.008), avoidance (r=0.37, p=0.050), and hyperarousal (r=0.42, p=0.026), and with PTSD total symptom score (r=0.37, p=0.054). Controlling for time since trauma attenuated these associations. The correlation between IL-1beta and total avoidance symptoms (r=0.42, p=0.028) became insignificant when controlling for anxiety and depression. IL-4 correlated with total hyperarousal symptoms (r=-0.38, p=0.047), and after controlling for systolic blood pressure and smoking status, with PTSD total symptom score (r=-0.41, p=0.035). PTSD patients showed a low-grade systemic proinflammatory state, which, moreover, was related to PTSD symptom levels suggesting one mechanism by which PTSD could contribute to atherosclerotic disease.

Maternal tobacco smoking and decreased leukocytes, including dendritic cells, in neonates

Maternal smoking in pregnancy is associated with respiratory diseases in the offspring, possibly due to prenatal influences on the developing immune system. We investigated whether maternal smoking in pregnancy was associated with cord blood leukocyte numbers, including precursor dendritic cells, adjusting for concomitant factors. In a prospective healthy birth cohort study, total leukocyte counts were reduced in neonates of smoking mothers [10.7 (8.4-13.0), n=14] compared with nonexposed infants [14.7 (13.7-15.7), n=74, p=0.002] [geometric mean cells x 10(3)/microL (95% confidence interval)]. All leukocyte subsets were decreased, most prominently segmented neutrophils [4.3 (2.8-5.7) versus 6.2 (5.5-6.8), p=0.021], lymphocytes [3.8 (2.9-4.8) versus 5.0 (4.5-5.6), p=0.036], and myeloid precursor dendritic cells [12.7 cells/microL (9.1-17.8) versus 18.3 (15.8-21.2), p=0.055]. These differences persisted after adjustment for possible confounders. Predictors of myeloid precursor dendritic cell numbers in multivariable models were maternal smoking (-5.1 cells/microL, p=0.042), age (-0.5 cells/microL/y, p=0.035), and, marginally, asthma (+8.1 cells/microL, p=0.075). The decrease of all leukocytes in neonates of smoking mothers could be clinically significant and suggests a decreased cell production, increased peripheral recruitment, or retention in bone marrow. Given the importance of dendritic cells in early immune responses, their decrease might reflect an impact of maternal smoking on the developing fetal immune system.