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Refrigeration systems have a broad range of applications, playing a critical role in human life. Especially, vaccine preservation in rural regions has become more critical than in the past during the COVID19 era. In this sense, meeting the cooling process's energy need with renewable energy is critical, as the grid cannot support it. Thus, solar energy has been extensively studied for use in refrigeration cycles. Compression, absorption, adsorption, desiccant, and ejector refrigeration cycles are frequently used in this configuration. This article discusses multiple studies showing various attributes' impact on a system's overall efficiency. Most previous reviews did not cover PV with refrigeration cycles. So, this paper surveys the literature on PV-powered cooling cycles. For better classification, PV technologies are categorized into three types: PV, PVT, and CPVT. With this regard, CPVTs still have a way to progress due to a lack of studies compared to PV. The works are divided into three main sections as Exergy Studies, Experimental Studies, and Simulation and Numerical Studies. This review paper categorizes and rates refrigeration-assisted solar systems based on exergy destruction, exergy efficiency, and COP of cooling cycles. The results showed that PV panels have the highest exergy destruction in most of the systems. It is concluded that using PV technologies has a great potential to supply cooling demand, especially in a hot climate condition. Moreover, the study's findings are anticipated to aid designers in scaling up photovoltaic-based cooling systems, resulting in more efficient and sustainable designs.

Heterozygous missense variants of the cardiac ryanodine receptor gene (RYR2) cause catecholaminergic polymorphic ventricular tachycardia (CPVT). These missense variants of RYR2 result in a gain of function of the ryanodine receptors, characterized by increased sensitivity to activation by calcium that results in an increased propensity to develop calcium waves and delayed afterdepolarizations. We have recently detected a nonsense variant in RYR2 in a young patient who suffered an unexplained cardiac arrest. To understand the mechanism by which this variant in RYR2, p.(Arg4790Ter), leads to ventricular arrhythmias, human induced pluripotent stem cells (hiPSCs) harboring the novel nonsense variant in RYR2 were generated and differentiated into cardiomyocytes (RYR2-hiPSC-CMs) and molecular and calcium handling properties were studied. RYR2-hiPSC-CMs displayed significant calcium handling abnormalities at baseline and following treatment with isoproterenol. Treatment with carvedilol and nebivolol resulted in a significant reduction in calcium handling abnormalities in the RYR2-hiPSC-CMs. Expression of the mutant RYR2 allele was confirmed at the mRNA level and partial silencing of the mutant allele resulted in a reduction in calcium handling abnormalities at baseline. The nonsense variant behaves similarly to other gain of function variants in RYR2. Carvedilol and nebivolol may be suitable treatments for patients with gain of function RYR2 variants.

Human induced pluripotent stem cells (hiPSCs) can be used to generate various cell types in the human body. Hence, hiPSC-derived cardiomyocytes (hiPSC-CMs) represent a significant cell source for disease modeling, drug testing, and regenerative medicine. The immaturity of hiPSC-CMs in two-dimensional (2D) culture limit their applications. Cardiac tissue engineering provides a new promise for both basic and clinical research. Advanced bioengineered cardiac in vitro models can create contractile structures that serve as exquisite in vitro heart microtissues for drug testing and disease modeling, thereby promoting the identification of better treatments for cardiovascular disorders. In this review, we will introduce recent advances of bioengineering technologies to produce in vitro cardiac tissues derived from hiPSCs.

Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is a rare electrical genetic disease characterized by ventricular polymorphic tachycardia and/or bidirectional ventricular tachycardia induced by the release of catecholamines caused by intense physical or emotional stress in structurally normal hearts. Mostly, it is caused by mutations in genes that are involved in calcium homeostasis, in particular in the gene encoding for cardiac ryanodine receptor (RyR2). Our observation is the first description of familial CPVT caused by mutation of the RyR2 gene, linked to the complete AV block.

The heat absorbed by the heat transfer fluid for cooling a concentrated photovoltaic thermal (CPVT) solar collector can be used for purposes such as residential heating and cooking. Because of the combined production of heat and power, these systems are proposed for individual or commercial use in rural areas. In this study, a hybrid system was proposed to increase the electrical efficiency of the system. Experiments were conducted in winter conditions. Two operational modes were compared, namely a CPVT system with HP (HP-CPVT) and without HP (CPVT). The evaporator of the heat pump was settled inside the triangular trough receiver. The effects of cooling the PV system with a heat pump in the bifacial CPVT system on the electrical and thermal energy efficiencies were investigated. The electricity and thermal energy efficiencies of the CPVT system were calculated as 12.54% and 38.37% in the HP-CPVT system, respectively, and 10.05% and 81.97% in the CPVT system, respectively. The electrical exergy efficiencies of the CPVT system with and without HP were 14.65% and 10.73%, respectively. The thermal exergy efficiencies of the CPVT system with and without HP were 82.47% and 85.63%, respectively. The thermal heat obtained from the HP-CPVT system can be used for heating needs. Thus, the bifacial HP-CPVT system was an example of the micro-CHP system.

The brief opening mode of the mitochondrial permeability transition pore (mPTP) serves as a calcium (Ca2+) release valve to prevent mitochondrial Ca2+ (mCa2+) overload. Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a stress-induced arrhythmic syndrome due to mutations in the Ca2+ release channel complex of ryanodine receptor 2 (RyR2). We hypothesize that inhibiting the mPTP opening in CPVT exacerbates the disease phenotype. By crossbreeding a CPVT model of CASQ2 knockout (KO) with a mouse missing CypD, an activator of mPTP, a double KO model (DKO) was generated. Echocardiography, cardiac histology, and live-cell imaging were employed to assess the severity of cardiac pathology. Western blot and RNAseq were performed to evaluate the contribution of various signaling pathways. Although exacerbated arrhythmias were reported, the DKO model did not exhibit pathological remodeling. Myocyte Ca2+ handling was similar to that of the CASQ2 KO mouse at a low pacing frequency. However, increased ROS production, activation of the CaMKII pathway, and hyperphosphorylation of RyR2 were detected in DKO. Transcriptome analysis identified altered gene expression profiles associated with electrical instability in DKO. Our study provides evidence that genetic inhibition of mPTP exacerbates RyR2 dysfunction in CPVT by increasing activation of the CaMKII pathway and subsequent hyperphosphorylation of RyR2.

Rationale: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare disease, manifested by syncope or sudden death in children or young adults under stress conditions. Mutations in the Ca 2+ release channel/RyR2 (type 2 ryanodine receptor) gene account for about 60% of the identified mutations. Recently, we found and described a mutation in RyR2 N-terminal domain, RyR2 R420Q . Objective: To determine the arrhythmogenic mechanisms of this mutation. Methods and Results: Ventricular tachycardias under stress conditions were observed in both patients with catecholaminergic polymorphic ventricular tachycardia and knock-in mice. During action potential recording (by patch-clamp in knock-in mouse cardiomyocytes and by microelectrodes in mutant human induced pluripotent stem cell-derived cardiomyocytes), we observed an increased occurrence of delayed afterdepolarizations under isoproterenol stimulation, associated with increased Ca 2+ waves during confocal Ca 2+ recording in both mouse and human RyR2 R420Q cardiomyocytes. In addition, Ca 2+ -induced Ca 2+ -release, as well as a rough indicator of fractional Ca 2+ release, were higher and Ca 2+ sparks longer in the RyR2 R420Q -expressing cells. At the ultrastructural nanodomain level, we observed smaller RyR2 clusters and widened junctional sarcoplasmic reticulum measured by gated stimulated emission depletion super-resolution and electron microscopy, respectively. The increase in junctional sarcoplasmic reticulum width might be due to the impairment of RyR2 R420Q binding to JPH2 (junctophilin-2), as there were less junctophilin-2 coimmunoprecipitated with RyR2 R420Q . At the single current level, the RyR2 R420Q channel dwells longer in the open state at low intracellular Ca 2+ ([Ca 2+ ] i ), but there is predominance of a subconductance state. The latter might be correlated with an enhanced interaction between the N terminus and the core solenoid, a RyR2 interdomain association that has not been previously implicated in the pathogenesis of arrhythmias and sudden cardiac death. Conclusions: The RyR2 R420Q catecholaminergic polymorphic ventricular tachycardia mutation modifies the interdomain interaction of the channel and weakens its association with JPH2. These defects may underlie both nanoscale disarrangement of the dyad and channel dysfunction.

The double MaReCo (symmetric reflector geometry) solar collector (DM-CPVT) has been designed and developed by MG Sustainable Engineering AB (MG) and the University of Gävle (HiG). Performance and overall electrical and thermal parameters of the collector have been studied and presented. The outdoor tests have been performed in both Sweden during the summer months of 2020 and Greece in September of 2020. The goal of the studied designs is to optimize the incoming solar radiation that can be collected without the need for tracking. This is possible due to the use of a symmetric reflector geometry with low concentration factor and lower collector depth. The use of a symmetric reflector geometry allows higher annual outputs worldwide. Furthermore, a low concentration factor is necessary to avoid tracking and a lower collector depth to reduce the shading, which is particularly important for the electrical production of these DM-CPVT design concepts. The testing facilities in both locations are also described in this paper. The information on the thermal performance of a collector is important for the prediction of the energy output of any solar system. The thermal properties assessment of the DM-CPVT collector followed the procedures of the ISO 9806:2017 standard and reported. The outdoor testing results have been validated with a deviation of 2.8% and 2.4% for both thermal and electrical peak efficiencies between the testing facilities, respectively. Regarding the Incidence Angle Modifier testing results, the deviation is negligible for all angles of incidence, which shows that outdoor testing procedures can be fairly accurate when tracking systems are not available.&nbsp

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Bioquímica. Fecha de Lectura: 19-11-2021, Esta tesis tiene embargado el acceso al texto completo hasta el 19-05-2023, Calcium transients between the Sarcoplasmic Reticulum (SR) and the cytoplasm are essential for coordinated contraction in cardiomyocytes. Loss of the SR protein Calsequestrin 2 (CASQ2) causes the recessive form of Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT2) by increasing the diastolic opening probability of the main SR calcium channel Ryanodine receptor 2 (RyR2), and by causing an unexplained decrease of its regulatory protein Triadin (TRDN). Here we studied the mechanisms of TRDN reduction in CASQ2-KO mice and show that ablation of CASQ2 activates histone-deacetylase HDAC6, which regulates several cellular processes. In CASQ2 deficient cardiomyocytes, HDAC6 reduces alpha-Tubulin acetylation, thus impairing microtubule stability and altering TRDN trafficking and co-localization with RyR2. Misplaced TRDN binds HSP70, forming Aggresomes that are degraded by autophagy. The study identifies a novel cascade of post-transcriptional events initiated by the loss of CASQ2 that leads to a major rearrangement of SR protein trafficking and stability in cardiomyocytes, El flujo de calcio que tiene lugar entre el Retículo Sarcoplasmático (SR) y el citoplasma es esencial para la contracción coordinada de los cardiomiocitos. La ausencia de la proteína del SR Calsecuestrina 2 (CASQ2) ocasiona la forma recesiva de la Taquicardia Ventricular Polimórfica Catecolaminérgica 2 (CPVT2), causando un incremento en la probabilidad de apertura “open probability” diastólica del principal canal de calcio del SR, el Receptor de Rianodina 2 (RyR2), y causando un descenso inexplicado de la proteína reguladora Triadina (TRDN). En este proyecto, se estudiaron los mecanismos responsables de la reducción de TRDN presentes en el modelo murino CASQ2-KO y se muestra como la ablación de CASQ2 activa la histona deacetilasa HDAC6, encargada de regular diversos procesos celulares. En los cardiomiocitos deficientes en CASQ2, HDAC6 reduce la acetilación de la α-tubulina, perjudicando la estabilidad de los microtúbulos y alterando tanto la movilización de la TRDN como su colocalización con RyR2. La TRDN mal posicionada se une a la HSP70 formando Agresomas que terminan siendo degradados mediante autofagia. Este estudio identifica una novedosa cascada de sucesos post-transcripcionales iniciados a causa de la pérdida de CASQ2, lo que desemboca en una reorganización importante tanto del tráfico proteico desde el SR como de la estabilidad proteica en los cardiomiocitos

Photovoltaic thermal (PVT) solar collectors can be an effective solution for system output improvement. Photovoltaic thermal collectors naturally have a more expensive receiver than simpler photovoltaic or thermal only collectors, therefore making concentration a more appealing solution to achieve cost reduction. However, concentrating systems need careful analysis on the design phase in order to optimize the annual output. In addition, for stationary (non-tracking) collectors, it is critical to determine the incidence angle modifier (IAM). For this reason, a reflector study was carried out to determine suitable reflector designs for a stationary concentrating PVT collector. The reflectors were simulated using a Monte Carlo raytracing software called Tonatiuh. The two selected reflectors designs were named “pure parabola” (PP) and “compound parabolic concentrator” (CPC). The concentration ratio of 1.2 and 1.6 were selected for each reflector designs, which means a total of 4 collector troughs. The next step involved the construction of the two selected C-PVT collector designs, which were built and subsequently tested by the authors. The IAM was assessed and discussed by simulation and outdoor testing in detail. The IAM results show similar decreases in longitudinal IAM for both the PP and the CPC CPVT collector for the 1.2 concentration factor. For the transversal IAM with 1.2 of concentration factor, the CPC over performs. For the 1.6 concentration prototype collectors, the results are fairly similar. Lastly, the annual output was also simulated and presented.

Background Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a severe genetic arrhythmogenic disorder characterized by adrenergically induced ventricular tachycardia manifesting as stress-induced syncope and sudden cardiac death. While CPVT is not associated with dilated cardiomyopathy (DCM) in most cases, the combination of both disease entities poses a major diagnostic and therapeutic challenge. Case summary We present the case of a young woman with CPVT. The clinical course since childhood was characterized by repetitive episodes of exercise-induced ventricular arrhythmias and a brady-tachy syndrome due to rapid paroxysmal atrial fibrillation and sinus bradycardia. Medical treatment included propranolol and flecainide until echocardiography showed a dilated left ventricle with severely depressed ejection fraction when the patient was 32 years old. Cardiac magnetic resonance imaging revealed non-specific late gadolinium enhancement. Myocardial inflammation, however, was excluded by subsequent endomyocardial biopsy. Genetic analysis confirmed a mutation in the cardiac ryanodine receptor but no pathogenetic variant associated with DCM. Guideline-directed medical therapy for HFrEF was limited due to symptomatic hypotension. Over the next months, the patient developed progressive heart failure symptoms that were finally managed by heart transplantation. Discussion Management in patients with CPVT and DCM is challenging, as Class I antiarrhythmic drugs are not recommended in structural heart disease and prophylactic internal cardioverter-defibrillator implantation without adjuvant antiarrhythmic therapy can be detrimental. Regular echocardiographic screening for DCM is recommendable in patients with CPVT. A multidisciplinary team of heart failure specialists, electrophysiologists, geneticists, and imaging specialists is needed to collaborate in the delivery of clinical care.

Cardiovascular disease-related deaths frequently arise from arrhythmias, but treatment options are limited due to perilous side effects of commonly used antiarrhythmic drugs. Cardiac rhythmicity strongly depends on cardiomyocyte Ca2+ handling and prevalent cardiac diseases are causally associated with perturbations in intracellular Ca2+ handling. Therefore, intracellular Ca2+ transporters are lead candidate structures for novel and safer antiarrhythmic therapies. Mitochondria and mitochondrial Ca2+ transport proteins are important regulators of cardiac Ca2+ handling. Here, the authors evaluated the potential of pharmacological activation of mitochondrial Ca2+ uptake for the treatment of cardiac arrhythmia. To this aim, the authors tested substances that enhance mitochondrial Ca2+ uptake for their ability to suppress arrhythmia in a murine model for ryanodine receptor 2 (RyR2)-mediated catecholaminergic polymorphic ventricular tachycardia (CPVT) in vitro and in vivo and in induced pluripotent stem cell-derived cardiomyocytes from a CPVT patient. In freshly isolated cardiomyocytes of RyR2R4496C/WT mice efsevin, a synthetic agonist of the voltage-dependent anion channel 2 (VDAC2) in the outer mitochondrial membrane, prevented the formation of diastolic Ca2+ waves and spontaneous action potentials. The antiarrhythmic effect of efsevin was abolished by blockade of the mitochondrial Ca2+ uniporter (MCU), but could be reproduced using the natural MCU activator kaempferol. Both mitochondrial Ca2+ uptake enhancers (MiCUps), efsevin and kaempferol, significantly reduced episodes of stress-induced ventricular tachycardia in RyR2R4496C/WT mice in vivo and abolished diastolic, arrhythmogenic Ca2+ events in human iPSC-derived cardiomyocytes. These results highlight an immediate potential of enhanced mitochondrial Ca2+ uptake to suppress arrhythmogenic events in experimental models of CPVT and establish MiCUps as promising pharmacological tools for the treatment and prevention of Ca2+-triggered arrhythmias such as CPVT.

Calmodulin (CaM) is a ubiquitous Ca2+‐sensing protein regulating many important cellular processes. Several CaM‐associated variants have been identified in a small group of patients with cardiac arrhythmias. The mechanism remains largely unknown, even though a number of ion channels, including the ryanodine receptors and the L‐type calcium channels have been shown to be functionally affected by the presence of mutant CaM. CaM is constitutively bound to the SK channel, which underlies the calcium‐gated I SK contributing to cardiac repolarization. The CaM binding to SK channels is essential for gating, correct assembly, and membrane expression. To elucidate the effect of nine different arrhythmogenic CaM variants on SK3 channel function, HEK293 cells stably expressing SK3 were transiently co‐transfected with CaMWT or variant and whole‐cell patch‐clamp recordings were performed with a calculated free Ca2+ concentration of 400 nmol/L. MDCK cells were transiently transfected with SK3 and/or CaMWT or variant to address SK3 and CaM localization by immunocytochemistry. The LQTS‐associated variants CaMD96V, CaMD130G, and CaMF142L reduced I SK,Ca compared with CaMWT (P

Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is a primary electrical disease characterized by a normal resting electrocardiogram and induction of malignant arrhythmias during adrenergic stress leading to syncope or sudden cardiac death (SCD). CPVT is caused by mutations in the cardiac ryanodine receptor (RyR2) or in the sarcoplasmic reticulum protein calsequestrin 2 genes (CASQ2). The RyR2 mutations are responsible for the autosomal dominant form of CPVT, while CASQ2 mutations are rare and account for the recessive form. These mutations cause a substantial inballance in the homeostasis of intracellular calcium resulting in polymorphic ventricular tachycardia through triggered activity. Beta blockers were for years the cornerstone of therapy in these patients. Sodium channel blockers, especially flecainide, have an additive role in those not responding in beta blockade. Implantation of defibrillators needs a meticulous evaluation since inappropriate shocks may lead to electrical storm. Finally, cardiac sympathetic denervation might also be an alternative therapeutic option. Early identification and risk stratification is of major importance in patients with CPVT. The aim of the present review is to present the arrhythmogenic mechanisms of the disease, the current therapies applied and potential future perspectives.

C and 2.2 L/min flow rate showed that the electrical yield can increase by 25%. On the other hand, by using insulation, the thermal yield increases up to 3% when working at a temperature of 23 &deg, vle University (Sweden) with the ability to measure ambient, cell and HTF temperature, flow rate and solar radiation. The experimental results were validated by means of an in-house developed CFD model. Based on the validated model, the effect of collector tilt angle, HTF, insulation (on the back side of the reflector), receiver material and front glass on the collector performance were considered. The impact of tilt angle is more pronounced on the thermal production than the electrical one. Furthermore, the HTF recirculation with an average temperature of 35.1 &deg, C above ambient., Photovoltaic (PV) panels and thermal collectors are commonly known as mature technologies to capture solar energy. The efficiency of PV cells decreases as operating cell temperature increases. Photovoltaic Thermal Collectors (PVT) offer a way to mitigate this performance reduction by coupling solar cells with a thermal absorber that can actively remove the excess heat from the solar cells to the Heat Transfer Fluid (HTF). In order for PVT collectors to effectively counter the negative effects of increased operating cell temperature, it is fundamental to have an adequate heat transfer from the cells to the HTF. This paper analyzes the operating temperature of the cells in a low concentrating PVT solar collector, by means of both experimental and Computational Fluid Dynamics (CFD) simulation results on the Solarus asymmetric Compound Parabolic Concentrator (CPC) PowerCollector (PC). The PC solar collector features a Compound Parabolic Concentrator (CPC) reflector geometry called the Maximum Reflector Concentration (MaReCo) geometry. This collector is suited for applications such as Domestic Hot Water (DHW). An experimental setup was installed in the outdoor testing laboratory at G&auml

Calmodulin (CaM) is a ubiquitous intracellular Ca2+ sensing protein that modifies gating of numerous ion channels. CaM has an extraordinarily high level of evolutionary conservation, which led to the fundamental assumption that mutation would be lethal. However, in 2012, complete exome sequencing of infants suffering from recurrent cardiac arrest revealed de novo mutations in the three human CALM genes. The correlation between mutations and pathophysiology suggests defects in CaM-dependent ion channel functions. Here, we review the current state of the field for all reported CaM mutations associated with cardiac arrhythmias, including knowledge of their biochemical and structural characteristics, and progress towards understanding how these mutations affect cardiac ion channel function.

Background Andersen–Tawil syndrome (ATS) is a rare arrhythmia disorder caused by a mutation in the KCNJ2 gene. Typical presentation includes a triad of cardiac arrhythmia, dysmorphia, and periodic paralysis. However, KCNJ2 mutations can mimic other disorders such as catecholaminergic polymorphic ventricular tachycardia (CPVT) making treatment challenging. Case summary A 9-year-old asymptomatic female patient presented with an irregular heart rate noted at a well-child visit. Physical examination revealed short stature and facial dysmorphism. An initial rhythm strip showed intermittent runs of non-sustained bidirectional ventricular tachycardia with a prolonged QT interval of 485 ms at rest. Exercise testing showed no significant increase in ectopy from baseline at higher heart rates. Cardiac imaging was normal, and the burden of ventricular ectopy was significantly reduced on a beta-blocker and Class IC antiarrhythmic combination. Genetic testing marked a D71N mutation in the KCNJ2 gene. Discussion Clinical distinction between ATS and CPVT is a challenge. Genetic testing in the above patient attributed a likely pathogenic variant for both ATS and CPVT to a single D71N mutation in the KCNJ2 gene. Further evaluation revealed no clinical CPVT, emphasizing the need for cautious interpretation of genetic results in inherited arrhythmia disorders.

The integration of renewable energy sources (geothermal, biomass, and solar) and desalination systems into novel polygeneration plants is investigated. Two main arrangements are considered: geothermal (GP) and biomass (BP) polygeneration. Both systems include concentrating photovoltaic/thermal solar collectors, a multieffect distillation system for seawater desalination, a single-effect LiBr-H2O absorption chiller, storage tanks, heat exchangers, balance-of-plant devices; a biomass auxiliary heater and geothermal wells are also included, in BP and GP, respectively. The systems can provide electricity and hot water, used for space heating, cooling, domestic hot water production, and drinkable desalted water. Both systems are simulated by means of a zero-dimensional dynamical simulation model. Thermoeconomic, exergy, and exergoeconomic analyses are also presented, aiming at defining the best values of the main design variables. Two case studies are discussed: city of Naples (BP) and Pantelleria island (GP), both characterized by solar and geothermal resources and scarcity of fossil fuels and freshwater.

Andersen - Tawil syndrome (ATS) is an autosomal - dominant or sporadic disorder characterized by ventricular arrhythmias, periodic paralysis, and distinctive facial and skeletal dysmorphism. Mutations in KCNJ2, which encodes the α-subunit of the potassium channel Kir2.1, were identified in patients with ATS. This genotype has been designated as type-1 ATS (ATS1). KCNJ2 mutations are detectable in up to 60 % of patients with ATS. Cardiac manifestations of ATS include frequent premature ventricular contractions (PVC), Q-U interval prolongation, prominent U-waves, and a special type of polymorphic ventricular tachycardia (PMVT) called bidirectional ventricular tachycardia (BiVT). The presence of frequent PVCs at rest are helpful in distinguishing ATS from typical catecholaminergic polymorphic ventricular tachycardia (CPVT). In typical CPVT, rapid PMVT and BiVT usually manifest during or after exercising. Additionally, CPVT or torsade de pointes in LQTS are faster, very symptomatic causing syncope or often deteriorate into VF resulting in sudden cardiac death. PVCs at rest are quite frequent in ATS1 patients, however, in LQTS patients, PVCs and asymptomatic VT are uncommon which also contributes to differentiating them. The article describes the new electrocardiographic criteria proposed for diagnosis of type-1 Andersen-Tawil syndrome. A differential diagnosis between Andersen-Tawil syndrome, the catecholamine polymorphic ventiruclar tachycardia and long QT syndrome is depicted. Special attention is paid on the repolarization abnormalities, QT interval and the pathologic U wave. In this article, we aim to provide five new electrocardiographic clues for the diagnosis of ATS1.

International audience; Exchanges of matrix contents are essential to the maintenance of mitochondria. Cardiac mitochondrial exchange matrix content in two ways: by direct contact with neighboring mitochondria and over longer distances. The latter mode is supported by thin tubular protrusions, called nanotunnels, that contact other mitochondria at relatively long distances. Here, we report that cardiac myocytes of heterozygous mice carrying a catecholaminergic polymorphic ventricular tachycardia-linked RyR2 mutation (A4860G) show a unique and unusual mitochondrial response: a significantly increased frequency of nanotunnel extensions. The mutation induces Ca2+ imbalance by depressing RyR2 channel activity during excitation-contraction coupling, resulting in random bursts of Ca2+ release probably due to Ca2+ overload in the sarcoplasmic reticulum. We took advantage of the increased nanotunnel frequency in RyR2(A4860G+/-) cardiomyocytes to investigate and accurately define the ultrastructure of these mitochondrial extensions and to reconstruct the overall 3D distribution of nanotunnels using electron tomography. Additionally, to define the effects of communication via nanotunnels, we evaluated the intermitochondrial exchanges of matrix-targeted soluble fluorescent proteins, mtDsRed and photoactivable mtPA-GFP, in isolated cardiomyocytes by confocal microscopy. A direct comparison between exchanges occurring at short and long distances directly demonstrates that communication via nanotunnels is slower.

OBJECTIVE: The aim of this study was to characterise disease penetrance, course of disease and use of antiarrhythmic medication and implantable cardioverter-defibrillator (ICD) therapy in a Danish nationwide cohort of patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) due to mutations in the ryanodine receptor-2 (RyR2) gene.METHODS: The study population was identified through the national hereditary heart disease database (Progeny). The study population was divided into three groups: probands, symptomatic and asymptomatic relatives.RESULTS: We identified 23 symptomatic probands, 18 symptomatic and 10 asymptomatic relatives with a RyR2 mutation. Twenty (87%) probands and 10 (36%) relatives had severe presenting symptoms (sudden cardiac death (SCD), aborted SCD (ASCD) or syncope).As compared with symptomatic relatives, probands had lower age at onset of symptoms (16 years (IQR, 10-33) vs 43 years (IQR, 25-54), pCONCLUSIONS: In a national cohort of RyR2 mutation-positive CPVT patients, SCD, ASCD and syncope were presenting events in the majority of probands and also occurred in 36% of relatives identified through family screening. Probands were younger at disease onset and more prone to fatal or near-fatal events than relatives.

Although β-blockers can be used to eliminate stress-induced ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT), this treatment is unsuccessful in ∼25% of cases. Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) generated from these patients have potential for use in investigating the phenomenon, but it remains unknown whether they can recapitulate patient-specific drug responses to β-blockers. This study assessed whether the inadequacy of β-blocker therapy in an individual can be observed in vitro using patient-derived CPVT iPSC-CMs. An individual with CPVT harboring a novel mutation in the type 2 cardiac ryanodine receptor (RyR2) was identified whose persistent ventricular arrhythmias during β-blockade with nadolol were abolished during flecainide treatment. iPSC-CMs generated from this patient and two control individuals expressed comparable levels of excitation-contraction genes, but assessment of the sarcoplasmic reticulum Ca2+ leak and load relationship revealed intracellular Ca2+ homeostasis was altered in the CPVT iPSC-CMs. β-adrenergic stimulation potentiated spontaneous Ca2+ waves and unduly frequent, large and prolonged Ca2+ sparks in CPVT compared with control iPSC-CMs, validating the disease phenotype. Pursuant to the patient's in vivo responses, nadolol treatment during β-adrenergic stimulation achieved negligible reduction of Ca2+ wave frequency and failed to rescue Ca2+ spark defects in CPVT iPSC-CMs. In contrast, flecainide reduced both frequency and amplitude of Ca2+ waves and restored the frequency, width and duration of Ca2+ sparks to baseline levels. By recapitulating the improved response of an individual with CPVT to flecainide compared with β-blocker therapy in vitro, these data provide new evidence that iPSC-CMs can capture basic components of patient-specific drug responses., Editors' choice: Clinically observed drug response differentials to β-blocker and flecainide treatment in catecholaminergic polymorphic ventricular tachycardia can be modeled in vitro using patient-derived iPSC-cardiomyocytes.

Aims Cardiac ryanodine receptor mutations are associated with catecholaminergic polymorphic ventricular tachycardia (CPVT), and some, including RyR2-P2328S, also predispose to atrial fibrillation. Recent work associates reduced atrial Nav1.5 currents in homozygous RyR2-P2328S (RyR2S/S) mice with slowed conduction and increased arrhythmogenicity. Yet clinically, and in murine models, the Nav1.5 blocker flecainide reduces ventricular arrhythmogenicity in CPVT. We aimed to determine whether, and how, flecainide influences atrial arrhythmogenicity in RyR2S/S mice and their wild-type (WT) littermates. Methods We explored effects of 1 μm flecainide on WT and RyR2S/S atria. Arrhythmic incidence, action potential (AP) conduction velocity (CV), atrial effective refractory period (AERP) and AP wavelength (λ = CV × AERP) were measured using multi-electrode array recordings in Langendorff-perfused hearts; Na+ currents (INa) were recorded using loose patch clamping of superfused atria. Results RyR2S/S showed more frequent atrial arrhythmias, slower CV, reduced INa and unchanged AERP compared to WT. Flecainide was anti-arrhythmic in RyR2S/S but pro-arrhythmic in WT. It increased INa in RyR2S/S atria, whereas it reduced INa as expected in WT. It increased AERP while sparing CV in RyR2S/S, but reduced CV while sparing AERP in WT. Thus, RyR2S/S hearts have low λ relative to WT; flecainide then increases λ in RyR2S/S but decreases λ in WT. Conclusions Flecainide (1 μm) rescues the RyR2-P2328S atrial arrhythmogenic phenotype by restoring compromised INa and λ, changes recently attributed to increased sarcoplasmic reticular Ca2+ release. This contrasts with the increased arrhythmic incidence and reduced INa and λ with flecainide in WT.

Alterations in cardiomyocyte Ca2+ handling initiate and sustain arrhythmias. Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), is an inherited arrhythmogenic disease due to a gain-of-function mutation of RyR2 Ca2+ channels, causing Ca2+ leak from the sarcoplasmic reticulum and abnormal membrane depolarization. How these events are linked to the onset of tissue-wide arrhythmias remains unclear. Ca2+ signaling was investigated in a multicellular model of cardiac tissue, by using a multispot multiphoton microscope that unmasked fast occurring Ca2+ dependent signals. The multicellular model allowed to visualize Ca2+ alternans and synchronized spontaneous Ca2+ releases in CPVT. Such synchronization, would be necessary to overcome the source-sink mismatch in the heart and generate ectopic foci of depolarization that serve as arrhythmia trigger. We thus used optogenetics to calculate the critical mass (

This thesis reports the results of many experimental tests conducted to gain a deeper insight on the two-phase heat transfer inside minichannels and to characterize the thermal performance of two refrigerants with low environmental impact: propane (R290) and R1234ze(E). Furthermore, some considerations on the application of the minichannel technology in refrigeration applications and solar concentrators are presented. As pressure drops greatly affect the heat transfer in two-phase flow, the experimental investigation on frictional pressure gradient during adiabatic flow of R134a, R1234ze(E) and propane (R290) at different mass velocities and at saturation temperatures between 30°C and 50°C has been conducted in two single copper minichannels with a circular cross section and hydraulic diameters of 0.96 mm and 2 mm. The experimental points are compared with several models available in the open literature. Heat transfer coefficients have been experimentally measured during the condensation at 40°C and during the vaporization at 31°C of R1234ze(E) and propane at different mass velocities inside a single circular cross section minichannel with an internal diameter of 0.96 mm. During the test runs, the refrigerant exchanges heat with a secondary fluid, that is distilled water, so the local heat flux is not constant along the measuring section and its accurate calculation becomes the main issue. An assessment of several predicting correlations has been presented for predicting the heat transfer coefficient both in condensation and in vaporization. The condensation process inside minichannels depends on the relative importance of shear stress, gravity and surface tension, especially in presence of corners in the cross section shape. Nevertheless, few studies concern the effect of inclination. In this work, the effect of the channel orientation has been experimentally analyzed and discussed during the condensation of R134a and R32 at 40°C saturation temperature inside a single square cross section minichannel with a hydraulic diameter equal to 1.23 mm. Several configurations of the test section from vertical upward flow to vertical downward flow have been examined. When considering the application of the minichannel technology in refrigeration, a general methodology to evaluate the potential heat transfer performance of refrigerants during in-tube condensation is a powerful tool to optimize the performance and the design of heat exchangers. The Performance Evaluation Criteria (PEC) named Penalty Factor for condensation (PF) and Total Temperature Penalization on the refrigerant side (TTP) are applied to rank several refrigerants starting from an experimental database collected in a single circular minichannel with internal diameter of 0.96 mm at the Two-Phase Heat Transfer Lab at the University of Padova. In electronics, the minichannel technology has proved to be reliable and effective in removing high heat fluxes through small heat transfer areas. This feature has suggested to use minichannel-based receivers for solar concentration systems. In this work, a parabolic trough linear solar concentrator is described and tested using two different minichannel-based receivers: a concentrating hybrid photovoltaic thermal (CPVT) receiver for the cogeneration of electrical energy and heat and a thermal receiver with a selective coating for the generation of heat in the medium temperature range. An optical modeling has been developed for the two cases in order to assess the optical efficiency and the flux distribution on the receiver. Tests with both the receivers have been performed using water in single-phase flow as working fluid in order to get a preliminary characterization of the whole system. The performance of the thermal receiver at medium temperature (up to 150°C) when two-phase heat transfer is realized inside the channels has been evaluated through a numerical model.