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.     

Coagulation process in Manchega sheep milk from Spain: A path analysis approach

Characteristics of sheep milk are of great interest for the dairy industry, as almost the totality of production is intended for cheesemaking. However, the existing relationships between these variables are complex. This study assessed composition, hygienic quality, coagulation properties, and curd yield of 1,200 individual Manchega sheep milk samples. The aim was to compare the effect of composition and hygienic quality on coagulation and curdling, and to evaluate the relationship between curd yields and the coagulation process and the effect of other features by using path analysis methodologies. Outcomes proved path analysis to be a useful and effective tool to assess these relationships through direct and indirect paths within the same model. Results showed that the factors that had a direct influence on milk coagulation were lactose concentration, casein content, and initial pH of milk. Contrastingly, somatic cells did not seem to have any effect (direct or indirect) on the coagulation process. Factors that directly affected curd yield were fat content, lactose concentration, casein content, and curd moisture. However, technological parameters showed little effect over curd yield.     

Identification of potential technologies for 1,4-Butanediol production using prospecting methodology

1,4-Butanediol (1,4-BDO) is a four-carbon diol used for industrial applications such as organic solvents, and the production of adhesives, fibers and polyurethanes. 1,4-BDO currently is produced through several petrochemical routes: hydrogenation of maleic anhydride, isomerization of propylene oxide, acetoxylation of butadiene, and the reaction between formaldehyde and acetylene. The current trends in 1,4-BDO production involve the utilization of renewable sources such as biomass. In this context, the present study aimed to identify promising technologies of 1,4-BDO production through prospecting methodology based on the analyses of patents and scientific article, describing the most relevant aspects of those emerging technologies. An increasing amount of 1,4-BDO production focused on biotechnological routes has been reported, with the US heavily involved in the development of new technologies. This study tracked three promising technologies which have potential for application in a biorefinery context because those processes involve (i) production of 1,4-BDO from sugars, classified herein as the biotechnological route; (ii) production of intermediates from sugar fermentation followed by catalytic conversion into 1,4-BDO, classified herein as the hybrid route, and (iii) furan/furfural conversion into 1,4-BDO. © 2020 Society of Chemical Industry     

Rare Titin (TTN) Variants in Diseases Associated with Sudden Cardiac Death

A leading cause of death in western countries is sudden cardiac death, and can be associated with genetic disease. Next-generation sequencing has allowed thorough analysis of genes associated with this entity, including, most recently, titin. We aimed to identify potentially pathogenic genetic variants in titin. A total of 1126 samples were analyzed using a custom sequencing panel including major genes related to sudden cardiac death. Our cohort was divided into three groups: 432 cases from patients with cardiomyopathies, 130 cases from patients with channelopathies, and 564 post-mortem samples from individuals showing anatomical healthy hearts and non-conclusive causes of death after comprehensive autopsy. None of the patients included had definite pathogenic variants in the genes analyzed by our custom cardio-panel. Retrospective analysis comparing the in-house database and available public databases also was performed. We identified 554 rare variants in titin, 282 of which were novel. Seven were previously reported as pathogenic. Of these 554 variants, 493 were missense variants, 233 of which were novel. Of all variants identified, 399 were unique and 155 were identified at least twice. No definite pathogenic variants were identified in any of genes analyzed. We identified rare, mostly novel, titin variants that seem to play a potentially pathogenic role in sudden cardiac death. Additional studies should be performed to clarify the role of these variants in sudden cardiac death.     

MicroRNA Profiling of B Cell Subsets from Systemic Lupus Erythematosus Patients Reveals Promising Novel Biomarkers

MicroRNAs control the differentiation and function of B cells, which are considered key elements in the pathogenesis of systemic lupus erythematosus (SLE). However, a common micro(mi)RNA signature has not emerged since published data includes patients of variable ethnic background, type of disease, and organ involvement, as well as heterogeneous cell populations. Here, we aimed at identifying a miRNA signature of purified B cells from renal and non-renal severe SLE patients of Latin American background, a population known to express severe disease. Genome-wide miRNA expression analyses were performed on naive and memory B cells and revealed two categories of miRNA signatures. The first signature represents B cell subset-specific miRNAs deregulated in SLE: 11 and six miRNAs discriminating naive and memory B cells of SLE patients from healthy controls (HC), respectively. Whether the miRNA was up or down-regulated in memory B cells as compared with naive B cells in HC, this difference was abolished in SLE patients, and vice versa. The second signature identifies six miRNAs associated with specific pathologic features affecting renal outcome, providing a further understanding for SLE pathogenesis. Overall, the present work provided promising biomarkers in molecular diagnostics for disease severity as well as potential new targets for therapeutic intervention in SLE.     

Bewirtschaftungsmaßnahmen zur Reduzierung der Nitratbelastung im Einzugsgebiet der Quellfassung Schleinitz

Grundwasser - Im Untersuchungsgebiet Schleinitz führte eine Grünlandumnutzung einer ehemaligen Ackerfläche über einen Zeitraum von annähernd 6 Jahren zu einer...     

A pseudo-transient heat transfer simulation of a continuous casting process,employing the element-free Galerkin method

The present work has been conducted in order to develop a novel solution for the heat transfer problem during the continuous casting of steel billets and blooms, by using the element-free Galerkin method under a pseudo-transient moving cross-section slice approach. The transport laws, non-linear aspects and boundary conditions of the initial value problem have been specified. A detailed explanation concerning the characteristics inherent to the application of the element-free Galerkin method to this problem has also been provided. The feasibility and suitability of this novel approach has been verified by comparison with the numerical techniques proposed and the results reported by other researchers as well as an analytical solution of a simple 1-D alloy solidification problem. The results have revealed that this technique could be used successfully in the pseudo transient moving cross-section solution of the heat transfer problem involved in the continuous casting of blooms and square billets.     

Aggregation Behavior,Antibacterial Activity and Biocompatibility of Catanionic Assemblies Based on Amino Acid-Derived Surfactants

The surface activity, aggregates morphology, size and charge characteristics of binary catanionic mixtures containing a cationic amino acid-derived surfactant N(π), N(τ)-bis(methyl)-L-Histidine tetradecyl amide (DMHNHC₁₄) and an anionic surfactant (the lysine-based surfactant N^α-lauroyl-N^εacetyl lysine (C₁₂C₃L) or sodium myristate) were investigated for the first time. The cationic surfactant has an acid proton which shows a strong pK_a shift irrespective of aggregation. The resulting catanionic mixtures exhibited high surface activity and low critical aggregation concentration as compared with the pure constituents. Catanionic vesicles based on DMHNHC₁₄/sodium myristate showed a monodisperse population of medium-size aggregates and good storage stability. According to Small-Angle X-Ray Scattering (SAXS), the characteristics of the bilayers did not depend strongly on the system composition for the positively charged vesicles. Negatively charged vesicles (cationic surfactant:myristate ratio below 1:2) had similar bilayer composition but tended to aggregate. The DMHNHC₁₄-rich vesicles exhibited good antibacterial activity against Gram-positive bacteria and their bactericidal effectivity declined with the decrease of the cationic surfactant content in the mixtures. The hemolytic activity and cytotoxicity of these catanionic formulations against non-tumoral (3T3, HaCaT) and tumoral (HeLa, A431) cell lines also improved by increasing the ratio of cationic surfactant in the mixture. These results indicate that the biological activity of these systems is mainly governed by the cationic charge density, which can be modulated by changing the cationic/anionic surfactant ratio in the mixtures. Remarkably, the incorporation of cholesterol in those catanionic vesicles reduces their cytotoxicity and increases the safety of future biomedical applications of these systems.