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.     

Untargeted metabolomics reveals links between Tiger nut (Cyperus esculentus L.) and its geographical origin by metabolome changes associated with membrane lipids

Tiger nuts and tiger nut milk are well-known Valencian products, and step-by-step these tubers and the tuber-based beverage are becoming more and more relevant products in international markets. However, the increasing demand and success of Valencian tiger nuts did not allow protected designation of origin (PDO) tuber to supply the domestic and international markets. Therefore, the verification of the geographical origin is highly required. In this research, the main objective was to combine an advance analytical method and chemometrics tools in order to decipher the geographical origin of 45 tiger nut samples from (i) ‘Xufa de València’ PDO and (ii) African samples. The analytical method, based on solid-liquid extraction followed by ultra-high performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC-HRMS) metabolomics approach, highlighted sensitivity and wide linear dynamic range in order to simultaneously analyse polar and non-polar metabolites. After data processing, a pronounced sample clustering according to the geographical origin was clearly observed using unsupervised models, and supervised models revealed that tiger nuts lipidome was associated with the geographical origin. As a result, African samples highlighted an overexpression of phospholipids, such as phosphatidylethanolamine 34:1, and triacylgricerols crosslinked to environmental stress and alteration of membrane lipid compositions.     

A supplemental computer-assisted intervention programme to prevent early reading difficulties in Spanish learners: A stratified random control trial

Difficulties in implementing effective instruction for at-risk students arise from two challenges: the transfer of evidence-based knowledge and the lack of economic resources. Computer-assisted programmes offer a suitable solution, providing quality instruction using low-cost resources. Thirty-two first-grade students with early learning difficulties were identified and paired based on at least three of the pre-intervention reading measures (reading efficiency of monosyllabic and disyllabic items, words, pseudowords and text reading speed). Each pair was assigned to one of two different intervention programmes: a computer-assisted intervention programme (CAIP) focused on syllables or the programme provided by the Spanish State School Assistance Services (SSAS). Every week, the CAIP participants received in pairs four 15-min training sessions on syllable decoding plus one 30-min group comprehension session. The CAIP was delivered by trainee students. The SSAS programme typically consisted of a 1-hr individual or in small groups sessions per week delivered by trained practitioners. Both programmes were administered for 11 weeks. The CAIP intervention showed better results than the SSAS intervention for both decoding and comprehension, with moderate to large effect sizes.     

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.     

Revisiting the Hydraulics of the Aznalcóllar Mine Disaster

The Aznalcóllar tailings pond failure (1998) is regarded as one of the severe ecological mine disasters ever reported. The spill of the mine tailings affected more than 60 km of the Agrio and Guadiamar rivers and caused major environmental damage. Despite the event being well-documented with more than 400 scientific publications, including two special issues and two reviews, several hydraulic uncertainties and inconsistencies remain. This paper conducts a state-of-the-art review of the most relevant hydraulic aspects of the mine disaster. It addresses the pond and fluid characteristics, the break type, the breaking time, the flow propagation, the volume potentially stored and subsequently spilled, area dimensions affected by the spill, and the morphological changes generated in the river and riverbanks caused by the spill, and later on by the restoration activities. Several discrepancies and plenty of controversial data have been unearthed that may affect general understanding of the event. In addition, new data is introduced and analysed applying photointerpretation and digital terrain analysis techniques, aiming to derive in essential hydraulic parameters. The most important findings are that the spill could have had a volume about 11.5 hm³, affecting about 86.7 km of river length, twice the most referenced values in the literature, and that applied restoration activities have substantially modified the hydro-sedimentary processes of the affected system. Additionally, a first video observation-based classification reveals that the fluid behaved more like a highly concentrated sediment-laden flow than like a mud flow.

     

Determination of Flame Emissivity in Hydrocarbon Pool Fires Using Infrared Thermography

A methodology is proposed for the determination of flame emissivity in hydrocarbon pool fires using infrared thermography. Experiments on gasoline and diesel oil pool fires with diameters of 0.13, 0.18 and 0.5 m were carried out, determining the flame emissivity for these types of fires in transition regime and turbulent regime. Also analysed was the evolution of the flame emissivity depending on the pool diameter, and a new correlation for the estimation of the emissivity depending on the above mentioned diameter was obtained.     

Selective Sharing of Load Current Components Among Parallel Power Electronic Interfaces in Three-phase Four-wire Stand-alone Microgrid

This paper investigates selective sharing of load current components among the parallel operation of distributed generators (DGs) in three-phase four-wire stand-alone microgrids. The proposed control method is based on master-slave operation of DGs, and the goal of selective sharing of load current components is to have DGs located in close proximity of the load operating in slave mode, in order to inject their available energy and also compensate the non-active load current components, while the distant DGs might operate in master mode to share the remaining load autonomously. Droop control is employed due to impracticality of communication at remote nodes, and resistive line impedance compensation is adopted to decouple active and reactive power controllers and ensure proper active power sharing among master DGs, irrespective of the mitigation of non-active current components by the slave inverters. The sharing factors for each current component are determined by a higher level control. The Conservative Power Theory (CPT) decompositions provide decoupled power and current references for the inverters, resulting in a selective sharing strategy. The principles supporting the developed control strategy are discussed, and the effectiveness of the control is demonstrated through computational simulations using PSIM software.     

Altered Fatty Acid Metabolism-Related Gene Expression in Liver from Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease

Lipid accumulation in the human liver seems to be a crucial mechanism in the pathogenesis and the progression of non-alcoholic fatty liver disease (NAFLD). We aimed to evaluate gene expression of different fatty acid (FA) metabolism-related genes in morbidly obese (MO) women with NAFLD. Liver expression of key genes related to de novo FA synthesis (LXRα, SREBP1c, ACC1, FAS), FA uptake and transport (PPARγ, CD36, FABP4), FA oxidation (PPARα), and inflammation (IL6, TNFα, CRP, PPARδ) were assessed by RT-qPCR in 127 MO women with normal liver histology (NL, n = 13), simple steatosis (SS, n = 47) and non-alcoholic steatohepatitis (NASH, n = 67). Liver FAS mRNA expression was significantly higher in MO NAFLD women with both SS and NASH compared to those with NL (p = 0.003, p = 0.010, respectively). Hepatic IL6 and TNFα mRNA expression was higher in NASH than in SS subjects (p = 0.033, p = 0.050, respectively). Interestingly, LXRα, ACC1 and FAS expression had an inverse relation with the grade of steatosis. These results were confirmed by western blot analysis. In conclusion, our results indicate that lipogenesis seems to be downregulated in advanced stages of SS, suggesting that, in this type of extreme obesity, the deregulation of the lipogenic pathway might be associated with the severity of steatosis.