Search Results (84)

Sudden cardiac death represents an unexpected death for which a strong underlying genetic background has been described. The primary causes are identified in cardiomyopathies and channelopathies, which are heart diseases of the muscle and electrical system, respectively, without coronary artery disease, hypertension, valvular disease, and congenital heart malformations. Genetic variants, especially single nucleotide variants and short insertions/deletions impacting essential myocardial functions, have shown that cardiomyopathies display high heritability. However, genetic heterogeneity, incomplete penetrance, and variable expression may complicate the interpretation of genetic findings, thus delaying the management of seriously at-risk patients. Moreover, recent studies show that the diagnostic yield related to genetic cardiomyopathies ranges from 28 to 40%, raising the need for further research. In this regard, investigating the occurrence of structural variants, especially copy number variants, may be crucial. Based on these considerations, this review aims to provide an overview of copy number variants identified in cardiomyopathies and discuss them, considering diagnostic yield. This review will ultimately address the necessity of incorporating copy number variants into routine genetic testing for cardiomyopathies and channelopathies, a process increasingly enabled by advances in next-generation sequencing technologies. Full article

Concentrating photovoltaic-thermal (CPVT) collectors use reflective surfaces to focus sunlight onto a smaller receiver area, increasing thermal energy output while maintaining annual energy efficiency. Ray-tracing simulations are employed in this study using Tonatiuh to optimise the characteristics of the Double MaReCo (DM) collector, which is an improved version of the commercially available Solarus Power Collector (PC). Focused on enhancing electrical performance, the photovoltaic (PV) cell configurations are varied on the bottom side of the receiver, while the top-side PV cells remain constant. The study also analyses the influence of diodes and transparent gables on the annual solar irradiance received by the PV cells. From the analysis, it is observed that the specific annual irradiance received by the PV cells in the DM collector with transparent gables is nearly 64% more compared to that of the PC counterpart. It is also observed that the transparency of gables becomes significant only when the whole area of the receiver is covered by PV cells. With the goal of improving performance while lowering the cost and complexity of the DM collector, the study investigates various collector design characteristics that may shed more light on optimising the current model. Full article

Inherited arrhythmia syndromes include several different diseases, as well as Brugada syndrome (BrS), long QT syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and short QT syndrome (SQTS). They represent, together with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C), an important cause of sudden cardiac death in the young. Most arrhythmia syndromes are inherited in an autosomal dominant manner, and genetic studies are suggested.: to report the spectrum of genetic variations and clinical phenotype in an Italian cohort with confirmed inherited arrhythmia syndromes and arrhythmogenic cardiomyopathy using whole-exome sequencing (WES). Patients with confirmed inherited arrhythmia syndromes and hereditary cardiomyopathy were recruited at the Cardiology Unit, University Polyclinic Hospital of Foggia, Italy and were included in this study. Genomic DNA samples were extracted from peripheral blood and conducted for WES. The variants were annotated using BaseSpace Variant Interpreter Annotation Engine 3.15.0.0 (Illumina). Reported variants were investigated using ClinVar, VarSome Franklin and a literature review. They were categorised agreeing to the criteria of the American College of Medical Genetics and Genomics. Overall, 62 patients were enrolled. Most of them had a clinical diagnosis of BrS (n 48, 77%). The remaining patients included in the present study had diagnosis of confirmed LQT (n 7, 11%), AR-DCM (n 4, 6.5%), ARVD (n 2, 3%), and SQT (n 1, 1.6%). Using the WES technique, 22 variants in 15 genes associated with Brugada syndrome were identified in 21 patients (34%). Among these, the SCN5A gene had the highest number of variants (6 variants, 27%), followed by KCNJ5 and CASQ2 (2 variants). Only one variant was identified in the remaining genes. In 27 patients with a clinical diagnosis of BrS, no gene variant was detected. In patients with confirmed LQT, SQT, 10 variants in 9 genes were identified. Among patients with ARVD and AR-DCM, 6 variants in 5 genes were found. Variants found in our cohort were classified as pathogenic (6), likely pathogenic (3), of uncertain significance (26), and benign (1). Two additional gene variants were classified as risk factors. In this study, 13 novel genetic variations were recognized to be associated with inherited arrhythmogenic cardiomyopathies. Our understanding of inherited arrhythmia syndromes continues to progress. The era of next-generation sequencing has advanced quickly, given new genetic evidence including pathogenicity, background genetic noise, and increased discovery of variants of uncertain significance. Although NGS study has some limits in finding the full genetic data of probands, large-scale gene sequencing can promptly be applied in real clinical practices, especially in inherited and possibly fatal arrhythmia syndromes. Full article

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a highly arrhythmogenic syndrome triggered by stress, primarily linked to gain-of-function point mutations in the cardiac ryanodine receptor (RyR2). Flecainide, as an effective therapy for CPVT, is a known blocker of the surface-membrane Na⁺ channel, also affecting the intracellular RyR2 channel. The therapeutic relevance of the flecainide-RyR2 interaction remains controversial, as flecainide blocks only the RyR2 current flowing in the opposite direction to the physiological Ca²⁺ release from the sarcoplasmic reticulum (SR). However, it has been proposed that charge-compensating countercurrent from the cytosol to SR lumen plays a critical role, and its reduction may indeed suppress excessive diastolic SR Ca²⁺ release through RyR2 channels in CPVT. Monitoring single-channel properties, we examined whether flecainide can target intracellular pathways for charge-balancing currents carried by RyR2 and SR Cl⁻ channels under cell-like conditions. Particularly, the Tris⁺ countercurrent flowed through the RyR2 channel simultaneously with a dominant reverse Ca²⁺/Ba²⁺ current. We demonstrate that flecainide blocked the RyR2-mediated countercurrent without affecting channel activity. In contrast, the SR Cl⁻ channel was completely resistant to flecainide. Based on these findings, it is reasonable to propose that the primary intracellular target of flecainide in vivo is the RyR2-mediated countercurrent. Full article

Background: This work focused on the study of the indirect fortification of Mexican tortillas made from nixtamalized masa (NM) with nixtamalized commercial corn flour (NCC-F) fortified with Zn, Fe, vitamins and folic acid. Methods: The chemical proximate values (CPV), ash content, mineral composition by inductively coupled plasma, in vitro protein digestibility (PD), protein digestibility-corrected amino acid score (PDCAAS), the total starch content, the resistant starch (RS) content in nixtamalized corn tortillas (NC-T) and nixtamalized commercial corn flour tortillas (NCCF-T) and the contribution of tortillas prepared with a mixture of NM and NCC-F (75:25 and 50:50, NM:NCC-F) to the recommended dietary intake (RDI) of minerals and vitamins were determined. Results: No significant differences (p < 0.05) were found in CPV and RS content between NCCF-T and NC-T. Ca content was significantly higher (p < 0.05) in NC-T than in NCCF-T, while Fe, K, Zn, folic acid contents, PD and PDCAAS content was higher in NCCF-T compared to NC-T (p < 0.05). The tortillas made with a mixture of NM and NCC-F (50:50) provide 43.07% of the RDI of Ca for Mexican children and adults, while ~45% and >100% of the RDI of Mg for adults and children, respectively, are provided by these tortillas. Similarly, tortillas from the NM:NCC-F mixture (50:50) provide average values of 45, 71 and ~91% of the RDI of Fe, Zn and folic acid, respectively, for all age groups of the Mexican population. Conclusions: NCCF-T contribute significantly to the recommended daily intake (RDI) of micronutrients such as iron, zinc, magnesium and folic acid, while tortillas made from the traditional nixtamalized corn of the Mexican diet have a higher calcium content. Tortillas made from a mixture of NCC-F and traditional NM may be an effective way to address micronutrient deficiencies in the Mexican population. Full article

The effects of global warming are severely recognizable and, according to the OECD, 47% of the world’s population will soon live in regions with insufficient drinking water. Already, many countries depend on desalination for fresh water supply, but such facilities are often powered by fossil fuels. This paper presents an energy self-sufficient desalination system that runs entirely on solar power. Sunlight is harvested using parabolic trough collectors with an effective aperture area of 1.5 m × 0.98 m and a theoretical concentration ratio of 150 suns, in which a concentrator photovoltaic thermal (CPV-T) hybrid-absorber converts the radiation to electricity and heat. This co-generated energy runs a multi-effect distillation (MED) plant, whereby the waste heat of multi-junction concentrator solar cells is used in the desalination process. This concept also takes advantage of synergy effects of optical elements (i.e., mirrors), resulting in a cost reduction of solar co-generation compared to the state of the art, while at the same time increasing the overall efficiency to ~75% (consisting of an electrical efficiency of 26.8% with a concurrent thermal efficiency of 48.8%). Key components such as the parabolic trough hybrid absorber were built and characterized by real-world tests. Finally, results of system simulations, including fresh water output depending on different weather conditions, degree of autonomy, required energy storage for off-grid operation etc. are presented. Simulation results revealed that it is possible to desalinate around 2,000,000 L of seawater per year with a 260 m² plant and 75 m³ of thermal storage. Full article

Inherited cardiac channelopathies are major causes of sudden cardiac death (SCD) in young people. Genetic testing is focused on the identification of single-nucleotide variants (SNVs) by Next-Generation Sequencing (NGS). However, genetically elusive cases can carry copy number variants (CNVs), which need specific detection tools. We underlie the utility of identifying CNVs by investigating the literature data and internally analyzing cohorts with CNVs in KCNQ1, KCNH2, SCN5A, and RYR2. CNVs were reported in 119 patients from the literature and 21 from our cohort. Young patients with CNVs in KCNQ1 show a Long QT (LQT) phenotype > 480 ms and a higher frequency of syncope. None of them had SCD. All patients with CNV in KCNH2 had a positive phenotype for QT > 480 ms. CNVs in SCN5A were represented by the Brugada pattern, with major cardiac events mainly in males. Conversely, adult females show more supraventricular arrhythmias. RYR2-exon3 deletion showed a broader phenotype, including left ventricular non-compaction (LVNC) and catecholaminergic polymorphic ventricular tachycardia (CPVT). Pediatric patients showed atrial arrhythmias and paroxysmal atrial fibrillation. Relatively higher syncope and SCA were observed in young females. The detection of CNVs can be of greater yield in two groups: familial channelopathies and patients with suspected Jervell and Lange-Nielsen syndrome or CPVT. The limited number of reported individuals makes it mandatory for multicentric studies to give future conclusive results. Full article

Mutations in the ryanodine receptor (RyR2) gene have been linked to arrhythmia and possibly sudden cardiac death (SCD) during acute emotional stress, physical activities, or catecholamine perfusion. The most prevalent disorder is catecholaminergic polymorphic ventricular tachycardia (CPVT1). Four primary mechanisms have been proposed to describe CPVT1 with a RyR2 mutation: (a) gain-of-function, (b) destabilization of binding proteins, (c) store-overload-induced Ca²⁺ release (SOICR), and (d) loss of function. The goal of this study was to use computational models to understand these four mechanisms and how they might contribute to arrhythmia. To this end, we have developed a local control stochastic model of a ventricular cardiac myocyte and used it to investigate how the Ca²⁺ dynamics in the mutant RyR2 are responsible for the development of an arrhythmogenic episode under the condition of β-adrenergic (β-AR) stimulation or pauses afterward. Into the model, we have incorporated 20,000 distinct cardiac dyads consisting of stochastically gated L-type Ca²⁺ channels (LCCs) and ryanodine receptors (RyR2s) and the intervening dyadic cleft to analyze the alterations in Ca²⁺ dynamics. Recent experimental findings were incorporated into the model parameters to test these proposed mechanisms and their role in triggering arrhythmias. The model could not find any connection between SOICR and the destabilization of binding proteins as the arrhythmic mechanisms in the mutant myocyte. On the other hand, the model was able to observe loss-of-function and gain-of-function mutations resulting in EADs (Early Afterdepolarizations) and variations in action potential amplitudes and durations as the precursors to generate arrhythmia, respectively. These computational studies demonstrate how GOF and LOF mutations can lead to arrhythmia and cast doubt on the feasibility of SOICR as a mechanism of arrhythmia. Full article

Since the first description of catecholaminergic polymorphic ventricular tachycardia (CPVT) in the 1970s, new insights have progressively unraveled the understanding of this inherited arrhythmia syndrome. The identification of new distinct clinical entities related to RYR2, the gene encoding the cardiac ryanodine receptor, has allowed significant refinement in the diagnosis of previously labeled “atypical” CPVT cases. Among RYR2-ryanodinopathies, the characterization of calcium release deficiency syndrome (CRDS) is still in its infancy and represents a diagnostic challenge due to the need for functional studies which may confirm the loss-of-function nature of the RYR2 variant. The present review summarizes current evidence on CRDS. First, by providing an overview on RYR2 structure and function, we will elucidate the different pathophysiological underpinnings of CRDS and CPVT. Second, by retrieving in detail reported CRDS variants and their clinical phenotypes, we will provide, if any, genetic and clinical red flags that should raise suspicion for CRDS in daily clinical practice. Finally, we will discuss available therapies to provide clinicians with practical therapeutic options for CRDS management. Full article

A proton exchange membrane electrolyzer can effectively utilize the electricity generated by intermittent solar power. Different methods of generating electricity may have different efficiencies and hydrogen production rates. Two coupled systems, namely, PV/T- and CPV/T-coupling PEMEC, respectively, are presented and compared in this study. A maximum power point tracking algorithm for the photovoltaic system is employed, and simulations are conducted based on the solar irradiation intensity and ambient temperature of a specific location on a particular day. The simulation results indicate that the hydrogen production is relatively high between 11:00 and 16:00, with a peak between 12:00 and 13:00. The maximum hydrogen production rate is 99.11 g/s and 29.02 g/s for the CPV/T-PEM and PV/T-PEM systems. The maximum energy efficiency of hydrogen production in CPV/T-PEM and PV/T-PEM systems is 66.7% and 70.6%. Under conditions of high solar irradiation intensity and ambient temperature, the system demonstrates higher total efficiency and greater hydrogen production. The CPV/T-PEM system achieves a maximum hydrogen production rate of 2240.41 kg/d, with a standard coal saving rate of 15.5 tons/day and a CO₂ reduction rate of 38.0 tons/day. Compared to the PV/T-PEM system, the CPV/T-PEM system exhibits a higher hydrogen production rate. These findings provide valuable insights into the engineering application of photovoltaic/thermal-coupled hydrogen production technology and contribute to the advancement of this field. Full article

Background and objectives: Sudden cardiac death (SCD) is a natural and unexpected death of cardiac origin that occurs within 1 h from the onset of acute symptoms. The major leading causes of SCD are cardiomyopathies and channelopathies. In this review, we focus on channelopathies, inherited diseases caused by mutations affecting genes encoding membrane ion channels (sodium, potassium or calcium channels) or cellular structures that affect Ca²⁺ availability. The diagnosis of diseases such as long QT, Brugada syndrome, short QT and catecholaminergic polymorphic ventricular tachycardia (CPVT) is still challenging. Currently, genetic testing and next-generation sequencing allow us to identify many rare alterations. However, some non-coding variants, e.g., splice-site variants, are usually difficult to interpret and to classify. Methods: In our review, we searched for splice-site variants of genes involved in channelopathies, focusing on variants of unknown significance (VUSs) registered on ClinVar up to now. Results: The research led to a high number of splice-site VUSs of genes involved in channelopathies, suggesting the performance of deeper studies. Conclusions: In order to interpret the correlation between variants and pathologies, we discuss experimental studies, such as RNA sequencing and functional analysis of proteins. Unfortunately, as these in vitro analyses cannot always be performed, we draw attention to in silico studies as future perspectives in genetics. This review has the aim of discussing the potential methods of detection and interpretation of VUSs, bringing out the need for a future reclassification of variants with currently unknown significance. Full article

This paper addresses the potential of integrating a concentrating photovoltaic thermal (CPV/T) system with an absorption chiller for the purpose of space cooling in residential buildings in the United Arab Emirates (UAE). The proposed system consists of a low concentrating photovoltaic thermal (CPV/T) collector that utilizes mono-crystalline silicon photovoltaic (PV) cells integrated with a single-effect absorption chiller. The integrated system was modeled using the Transient System Simulation (TRNSYS v17) software. The obtained model was implemented in a case study represented by a villa situated in Abu Dhabi having a peak cooling load of 366 kW. The hybrid system was proposed to have a contribution of 60% renewable energy and 40% conventional nonrenewable energy. A feasibility study was carried out that demonstrated that the system could save approximately 670,700 kWh annually and reduce carbon dioxide emissions by 461 tons per year. The reduction in carbon dioxide emissions is equivalent of removing approximately 98 cars off the road. The payback period for the system was estimated to be 3.12 years. Full article

Brucellosis is a global problem, with the causative agent being the genus Brucella. B. canis can cause undulant fever in dogs, which is a zoonotic disease that can spread not only among dogs but also to humans. This poses a public health threat to society. In this study, a rapid and straightforward immune colloidal gold test strip was developed for the diagnosis of canine brucellosis through the detection of anti-LPS antibodies in serum samples. Rabbit anti-canine IgG conjugated with colloidal gold was employed as the colloidal gold-labeled antibody. The extracted high-purity R-LPS was employed as the capture antigen in the test line (T-line), while goat anti-rabbit IgG was utilized as the capture antibody in the control line (C-line). The colloidal gold strip exhibited high specificity in the detection of brucellosis, with no cross-reaction observed with the common clinical canine diseases caused by Canine coronavirus (CCV), Canine distemper virus (CDV), and Canine parvovirus (CPV). In comparison to the commercial iELISA kit, the sensitivity and specificity of the colloidal gold test strip were found to be 95.23% and 98.76%, respectively. The diagnostic coincidence rate was 98.47%. The findings of this study indicate that colloidal gold test strips may be employed as a straightforward, expeditious, sensitive, and specific diagnostic instrument for the identification of canine brucellosis, particularly in resource-limited regions. Full article

Concentrator photovoltaics (CPVs) have demonstrated high electrical efficiencies and technological potential, especially when deployed in CPV–thermal (CPV-T) hybrid absorbers, in which the cells’ waste heat can be used to power industrial processes. However, the high cost of tracking systems and the predominant use of expensive multi-junction PV cells have caused the market of solar co-generation technologies to stall. This paper describes the development and testing of a low-cost alternative CPV cell based on crystalline silicone (c-Si) for use in a novel injection-molded parabolic hybrid solar collector, generating both, photovoltaic electricity and thermal power. The study covers two different c-Si cell technologies, namely, passive emitter rear contact (PERC) and aluminum back surface field (Al-BSF). Simulation design and manufacturing are described with special attention to fingerprinting in order to achieve high current carrying capacities for concentrated sunlight. It was determined that Al-BSF cells offer higher efficiencies than PERC for the considered use case. Solar simulator tests showed that the highly doped 4 cm² cells (50 ohm/sq) reach efficiencies of 16.9% under 1 sun and 13.1% under 60 suns at 25 °C with a temperature coefficient of −0.069%(Abs)/K. Finally, options to further improve the cells are discussed and an outlook is given for deployment in a field-testing prototype. Full article

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a fatal rare inherited cardiac channelopathy. Affected patients are susceptible to develop deadly ventricular arrythmias after physical or emotional stress. The typical arrhythmia presents as bidirectional and/or polymorphic ventricular tachycardias. To illustrate the clinical challenges in properly diagnosing this disease, we report two cases of CPVT together with a brief literature review. Full article