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.     

Evaluation of the effect of processing on cocoa polyphenols: antiradical activity,anthocyanins and procyanidins profiling from raw beans to chocolate

The content and composition of anthocyanins and procyanidins in fermented cocoa beans (from different geographic origins: Ecuador, Cameroon, Ivory Coast, Ghana and Nigeria), roasted nibs, cocoa mass and chocolate were determined, beside the determination of the total antiradical capacity. Concerning geographic origin, cocoa beans and processed products from Ecuador showed the highest levels of anthocyanins, followed by Nigeria and Cameroon. Generally, as cocoa beans were further processed, the levels of anthocyanins and flavan‐3‐ols decreased. The largest observed losses of phenolics occurred during roasting. A progressive decreasing trend in polyphenol concentration was observed in the other processed samples as well. Despite the original content of polyphenols in raw cocoa beans, technological processes imply a significant impact on cocoa quality, confirming the need of specific optimisation to obtain high value chocolate.     

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.     

Characterization of the Residence Time Distribution in Spray Dryers

In this work it is presented a study on the residence time distribution (RTD) of particles in a co-current pilot-plant spray dryer operated with a rotary atomization system. A nuclear technique is applied to investigate the RTD responses of spray dryers. The methodology is based on the injection of a radioisotope tracer in the feed stream followed by the monitoring of its concentration at the outlet stream. The experiments were performed during the drying of aqueous suspensions of gadolinium oxide. The RTD responses obtained experimentally presented good reproducibility, indicating that the technique applied is well suited to investigating fluid-dynamics of spray dryers. In addition to the experimental investigation, a mathematical model was used to describe the RTD experimental curves.     

A high-speed gateable image pipeline

We present the performance of a high-speed gateable vacuum image pipeline, which permits individual images to be delayed and selected from continuous non-repetitive image stream. This device is composed of a vacuum tube equipped with a photocathode at one end, a phosphor screen at the other end, and a system of metal grids in between. Photoelectrons produced by the images focused on the photocathode, are guided by a uniform magnetic field, parallel to the tube axis. By changing the grid potentials, the drift time of the photoelectrons inside the tube can be varied from 0.35 to 1.5 μs. An image can then be selected by an external trigger with a time resolution in the range of 4–30 ns, depending on the delay time. The selected photoelectrons are finally accelerated onto the phosphor screen, set at 10 kV, where they reproduce the desired image. With a magnetic field of 0.1 T, a spatial resolution of 33 lp/mm was obtained. The high spatial and time resolution make this device an interesting tool for high-energy physics and astrophysics experiments, and for high-speed photography.     

Prevalence of adrenal carcinoma among incidentally discovered adrenal masses. A retrospective study from 1989 to 1994. Gruppo Piemontese Incidentalomi Surrenalici

BACKGROUND: The incidental discovery of an adrenal mass poses the problem of distinguishing between the frequent benign masses and the infrequent malignant ones that require surgery. Univocal guidelines to approach this problem are unavailable. OBJECTIVE: To perform a survey of the clinical management of incidentally discovered adrenal masses (ie, adrenal incidentalomas). DESIGN: A multicentric retrospective analysis of hospital medical records of adrenal incidentalomas diagnosed during a 5-year period; the medical records were scrutinized for demographic data and clinical details by means of a specifically tailored questionnaire. SETTING: The major surgical and medical centers of Piedmont, a northern Italian region with approximately 4 million inhabitants. The recruitment pattern of these centers was unselected. PATIENTS: The definition of adrenal incidentaloma was limited to patients with a physical examination and a clinical history unindicative of adrenal disease. Exclusion criteria also included hypertension of suspected endocrine origin and a history of neoplasms known to metastasize frequently in the adrenal glands. Two hundred twenty-four medical records were collected, and 210 were analyzed (14 excluded a posteriori). RESULTS: Most patients were in their 50s and 60s, and women were predominantly affected. The frequency of adrenocortical cancer was 13% among patients operated on. The tumor diameter was highly correlated with the risk of cancer; a cutoff at 5 cm had a sensitivity of 93% with a specificity of 64% in discriminating between benign and malignant cortical lesions. CONCLUSIONS: The occurrence of adrenocortical carcinoma among adrenal incidentalomas is not rare. The evaluation of the mass size is a simple and effective method for selecting patients at risk for cancer. The indication for surgery of masses larger than 5 cm, or of masses of any diameter that have suspicious imaging characteristics, limits unnecessary operations and costs.     

Building kernels from binary strings for image matching.

In the statistical learning framework, the use of appropriate kernels may be the key for substantial improvement in solving a given problem. In essence, a kernel is a similarity measure between input points satisfying some mathematical requirements and possibly capturing the domain knowledge. In this paper, we focus on kernels for images: we represent the image information content with binary strings and discuss various bitwise manipulations obtained using logical operators and convolution with nonbinary stencils. In the theoretical contribution of our work, we show that histogram intersection is a Mercer's kernel and we determine the modifications under which a similarity measure based on the notion of Hausdorff distance is also a Mercer's kernel. In both cases, we determine explicitly the mapping from input to feature space. The presented experimental results support the relevance of our analysis for developing effective trainable systems.     

An ecological-transactional understanding of community violence: Theoretical perspectives.

Community violence has emerged as a major risk factor for the development of mental health problems in children and adolescents. If mental health providers are to meet the needs of children and communities dealing with community violence, then they will need to integrate principles from various subdisciplines in psychology (e.g., developmental psychology, school psychology, developmental psychopathology) as well as disciplines outside of psychology (e.g., sociology, public health, medicine) to understand fully the developmental impact of exposure to community violence. The development of such a model is necessary to identify the pathways, risk, and protective factors on which prevention and intervention programs can be built. The goal of this article is to present an ecological-transactional model of community violence as a conceptual framework for understanding the existing literature and for guiding future research on community violence exposure and child development. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Effect of Particle Size on Monometallic and Bimetallic (Au,Pd)/C on the Liquid Phase Oxidation of Glycerol

The influence of metal particle size of monometallic and bimetallic supported catalysts (Au, Pd, Au–Pd)/C was studied using as a model reaction the liquid phase oxidation of glycerol. By tuning the metal particle size from 2 to 16 nm a progressive decrease of activity and simultaneously an increase in the selectivity to sodium glycerate was observed. Moreover, the influence of the temperature was studied and it was found that by increasing the temperature, only with a large particle size the formed glycerate was retained and not over-oxidized to tartronate.