Update on the Diagnostic Pitfalls of Autopsy and Post-Mortem Genetic Testing in Cardiomyopathies

Inherited cardiomyopathies are frequent causes of sudden cardiac death (SCD), especially in young patients. Despite at the autopsy they usually have distinctive microscopic and/or macroscopic diagnostic features, their phenotypes may be mild or ambiguous, possibly leading to misdiagnoses or missed diagnoses. In this review, the main differential diagnoses of hypertrophic cardiomyopathy (e.g., athlete’s heart, idiopathic left ventricular hypertrophy), arrhythmogenic cardiomyopathy (e.g., adipositas cordis, myocarditis) and dilated cardiomyopathy (e.g., acquired forms of dilated cardiomyopathy, left ventricular noncompaction) are discussed. Moreover, the diagnostic issues in SCD victims affected by phenotype-negative hypertrophic cardiomyopathy and the relationship between myocardial bridging and hypertrophic cardiomyopathy are analyzed. Finally, the applications/limits of virtopsy and post-mortem genetic testing in this field are discussed, with particular attention to the issues related to the assessment of the significance of the genetic variants.     

Sofosbuvir Selects for Drug-Resistant Amino Acid Variants in the Zika Virus RNA-Dependent RNA-Polymerase Complex In Vitro

The nucleotide analog sofosbuvir, licensed for the treatment of hepatitis C, recently revealed activity against the Zika virus (ZIKV) in vitro and in animal models. However, the ZIKV genetic barrier to sofosbuvir has not yet been characterized. In this study, in vitro selection experiments were performed in infected human hepatoma cell lines. Increasing drug pressure significantly delayed viral breakthrough (p = 0.029). A double mutant in the NS5 gene (V360L/V607I) emerged in 3 independent experiments at 40–80 µM sofosbuvir resulting in a 3.9 ± 0.9-fold half- maximal inhibitory concentration (IC₅₀) shift with respect to the wild type (WT) virus. A triple mutant (C269Y/V360L/V607I), detected in one experiment at 80 µM, conferred a 6.8-fold IC₅₀ shift with respect to the WT. Molecular dynamics simulations confirmed that the double mutant V360L/V607I impacts the binding mode of sofosbuvir, supporting its role in sofosbuvir resistance. Due to the distance from the catalytic site and to the lack of reliable structural data, the contribution of C269Y was not investigated in silico. By a combination of sequence analysis, phenotypic susceptibility testing, and molecular modeling, we characterized a double ZIKV NS5 mutant with decreased sofosbuvir susceptibility. These data add important information to the profile of sofosbuvir as a possible lead for anti-ZIKV drug development.     

Local acceptance of wind energy: Factors of success identified in French and German case studies

The objective of this paper is to identify and analyse factors that are important for winning acceptance of wind-energy parks on the local level. The developers of wind-energy parks need to know how to manage “social acceptance” at the different stages of planning, realisation and operation. Five case studies in France and Germany focused on factors of success in developing a wind-energy project on a given site and illuminated how policy frameworks influence local acceptance. Our hypothesis is that these factors fall into two categories: institutional conditions, such as economic incentives and regulations; and site-specific conditions (territorial factors), such as the local economy, the local geography, local actors, and the actual on-site planning process (project management).     

Selective partial oxidation of light paraffins with hydrogen peroxide on thin-layer supported Nafion-H catalysts

Thin-layer carbon supported Nafion-H catalysts were found to be active and highly selective (S>98%) for the partial oxidation of C₁-C₃ alkanes, in a three phase catalytic membrane reactor (3PCMR), under mild conditions and in the presence of H₂O₂. The influences of the catalyst teflon loading and H₂O₂ concentration on the reaction rate have been evaluated. A reaction pathway, based on the electrophilic hydroxylation of the C-H bond of alkanes with protonated hydrogen peroxide (H₃O ₂ ⁺ ), is discussed.     

Storage life of frozen salmonoids Effect of light and packaging conditions on carotenoid oxidation and lipid oxidation

Summary The combined effect of oxygen transmission of packaging material and of exposure to light with different spectral distribution on the oxidative degradation of carotenoids and lipids in frozen salmonoids has been characterized in a storage experiment with steaks of rainbow trout. The degradation of the carotenoid astaxanthin, as followed by HPLC analysis and tristimulus colorimetric measurement, was sensitive to the radiant flux density of UV light and less sensitive to the oxygen transmission rate of the packaging material, in agreement with previous findings for photooxidation of carotenoids in food model systems. This is in contrast to the lipid oxidation, which was found to be dependent on the accessability of oxygen rather than on exposure to UV light. Formation of peroxides in the product culminated after 3 months of storage (up to 8.4 mEq kg^–1 oil), and preceded the formation of thiobarbituric-acid-reactive substances. The product in packaging material with a high oxygen transmission rate (60 cm³ m^–2 bar^–1 per 24 h) reached a level of approximately 5 mol malonaldhyde/kg^–1 product, when stored exposed to standard fluorescent light or fluorescent light with a high UV component. Rancid taste was not detected by sensory evaluation for any of the products after 6 months of storage, whereas a bitter taste was noted for the product exposed to UV light.

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Die Haltbarkeit von Lachsforellen Einfluß von Licht und Verpackung auf die Carotenoid- und Fettoxydation

Zusammenfassung Der kombinierte Effekt von Sauerstoffdurchgang durch Verpackungsmaterial und der Lichteinwirkung verschiedener spektraler Verteilung auf den oxidativen Abbau der Carotinoide und Fette in gefrorenen Lachsforellen wurde in einem Lagerungsversuch untersucht. Der Abbau des Carotenoids Astaxanthin wurde mit HPLC undTristimulus-Calorimetrie beobachtet, und war empfindlich gegenüber UV-Licht und weniger empfindlich gegenüber der Sauerstoffdurchlässigkeit der Verpackung, was mit früheren Ergebnissen für Photooxidation der Carotinoide in Modellsystemen übereinstimmt. Dies widerspricht der Fettoxidation, die mehr von Sauerstoffzugang abhängig ist als von der Entwicklung des UV-Lichtes. Die Bildung von Peroxiden des Produktes kuliminierte nach 3monatiger Lagerung (bis 8,4 meq/kg Öl) und ging der Bildung von Thiobarbitursäure-aktiven Substanzen voraus. Das Produkt im Material mit hohem Sauerstoffdurchgang (60 cm³ m^–2 bar^–1 pro 24 h), das bei normalen fluorescierendem Licht oder bei fluorescierendem Licht mit hohem UV-Anteil aufbewahrt wurde, erreichte einen TBS-Wert von ungefähr 5 mol Malonaldehyd/kg Fleisch. Ein ranziger Geschmack wurde durch sensorische Bewertung nach 6monatiger Lagerung nicht erkannt, wohl aber ein bitterer Geschmack bei dem UV-Licht ausgesetzten Proben.

     

Attrition of spherical electrode carbon particles during batch fluidized combustion

Spherical electrode carbon particles prepared from carbon rods of dry cell batteries have been used to study the attrition behaviour in a bubbling fluidized bed combustor. Experiments have been conducted in a 40 mm I.D. and 1 m high fluidized bed combustor operated at 1 m/s superficial velocity. The bed was operated with nitrogen and with two different oxygen concentrations at 850°C to study the effect of combustion on attrition of these particles. The experimental technique used allowed the time resolution of attrited fines generation, providing detailed curves of attrition rates as a function of time. Attrition rate constants have been evaluated. Results show an enhancement of attrition due to combustion even for spherical, homogeneous and smooth particles.     

Innovative Membrane-Based Catalytic Process for Environmentally Friendly Synthesis of Oxygenates

Synthesis of liquid oxygenates from light alkanes (C₁--C₃) is achieved in a multifunctional three-phase catalytic membrane reactor (3PCMR) operating under mild conditions (T_R, 80-120 °C; P_R, 140 kPa). The features of superacid catalytic membranes mediated by the Meⁿ⁺/H₂O₂ Fenton system in activating C₁-C₃ alkanes are presented. The effect of operating conditions ([H₂O₂], [Meⁿ⁺]) on the catalyst activity is outlined. A general reaction pathway accounting for the activation of the CH bond of the alkane molecule on the superacid sites and the subsequent reaction of the activated alkane with primary reactive intermediates, generated from the Meⁿ⁺/H₂O₂ system, is proposed. The suitability of the 3PCMR in enabling simultaneous reaction and product separation is discussed.     

Characterisation of three different impellers using the LDV-technique

A characterisation of three commonly used impellers was made in this study by measuring local mean velocities and the fluctuations of these velocities with the LDV technique. The data was used to estimate volumetric flow, velocity fluctuations and turbulent intensity in the impeller region of the tank. The impellers investigated were a high flow impeller, a pitched blade turbine and a Rushton turbine. The cylindrical vessel used was made of Perspex, had a dished bottom (DIN 28013), was equipped with four baffles and had an inner diameter of 0.45 m. It was found that the bulk velocities could be scaled with the tip-speed of the impeller (ND). The flow rate at constant impeller speed increased in the order high flow impeller — Rushton turbine — pitched blade turbine. The corresponding order for the turbulence fluctuation is: high flow impeller — pitched blade turbine — Rushton turbine. The velocity profile of the flow out from the high flow impeller was furthermore, not as smooth as could be expected.     

Effect of the metal oxide loading on the activity of silica supported MoO3 and V2O5 catalysts in the selective partial oxidation of methane

Precipitated silica catalysts loaded with either MoO₃ (0.2–4.0 wt%) or V₂O₅ (0.2–5.3 wt%) have been studied in the selective partial oxidation of methane to formaldehyde with molecular oxygen at 520 °C. The functionality of the SiO₂ surface towards the formation of HCHO is significantly promoted by V₂O₅, while it is depressed by the MoO₃.