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Left ventricular pseudoaneurysm is a serious and rare disorder that usually develops after acute myocardial infarction. It can lead to potentially lethal mechanical complications, such as acute left ventricular free wall rupture. This report presents the case of a 64-year-old man with a left ventricular pseudoaneurysm and myocardial rupture that was managed by left ventricular restoration with aneurysmectomy and coronary artery bypass with 2 grafts.

The ARX mutations encompass a nearly continuous spectrum of neurodevelopmental disorders (NDDs), ranging from lissencephaly to Proud syndrome, as well as infantile spasms without brain malformations, and including both syndromic and non-syndromic intellectual disabilities (IDs). We describe worsening neuropsychiatric symptoms in the offspring of a Korean family with ID/developmental delay (DD) caused by a novel ARX p.Lys385Ter variant. Sequential genetic testing was performed to investigate the ID, DD, agenesis of the corpus callosum (ACC), and developmental epileptic encephalopathy (DEE) observed in the proband. A comprehensive trio clinical exome sequencing approach using a Celemics G-Mendeliome Clinical Exome Sequencing Panel was employed. Given the clinical manifestations observed in the proband, gene panel sequencing identified a heterozygous ARX variant, c.1153A>T/p.Lys385Ter (Reference transcript ID: NM_139058.3), as the most likely cause of ID, DD, ACC, and DEE in the proband. Sanger sequencing confirmed the segregation of the ARX variant, c.1153A>T/p.Lys385Ter, with the phenotype and established the maternally inherited dominant status of the heterozygous variant in the patient, as well as in her grandmother, mother, and aunt. Our case report adds to the understanding of the female phenotype in ARX-related disorders caused by loss-of-function variants in the ARX gene. Genetic counseling for ARX families should proceed with caution, as female carriers can exhibit a wide range of phenotypes, from normal cognitive development to ID/DD, ACC, and DEE.

Maturity-onset diabetes of the young (MODY; OMIM # 606391) comprises a cluster of inherited disorders within non-autoimmune diabetes mellitus (DM), typically emerging during adolescence or young adulthood. We report a novel in-frame deletion of HNF1B in a family with renal cysts and MODY, furthering our understanding of HNF1B-related phenotypes. We conducted sequential genetic testing to investigate the glucose intolerance, renal cysts, hepatic cysts, and agenesis of the dorsal pancreas observed in the proband. A comprehensive clinical exome sequencing approach using a Celemics G-Mendeliome Clinical Exome Sequencing Panel was employed. Considering the clinical manifestations observed in the proband, gene panel sequencing identified a heterozygous HNF1B variant, c.36_38delCCT/p.(Leu13del) (reference transcript ID: NM_000458.4), as the most likely cause of MODY in the proband. The patient’s clinical presentation was consistent with MODY caused by the HNF1B variant, showing signs of glucose intolerance, renal cysts, hepatic cysts, and agenesis of the dorsal pancreas. Sanger sequencing confirmed the same HNF1B variant and established the paternally inherited autosomal dominant status of the heterozygous variant in the patient, as well as in his father and sister. The presence of early-onset diabetes, renal cysts, a family history of the condition, and nephropathy appearing before or after the diagnosis of diabetes mellitus (DM) suggests a diagnosis of HNF1B-MODY5. Early diagnosis is crucial for preventing complications of DM, enabling family screening, providing pre-conceptional genetic counseling, and monitoring kidney function decline.

Progressive tissue remodeling after myocardial infarction (MI) promotes cardiac arrhythmias. This process is well studied in young animals, but little is known about pro-arrhythmic changes in aged animals. Senescent cells accumulate with age and accelerate age-associated diseases. Senescent cells interfere with cardiac function and outcome post-MI with age, but studies have not been performed in larger animals, and the mechanisms are unknown. Specifically, age-associated changes in timecourse of senescence and related changes in inflammation and fibrosis are not well understood. Additionally, the cellular and systemic role of senescence and its inflammatory milieu in influencing arrhythmogenesis with age is not clear, particularly in large animal models with cardiac electrophysiology more similar to humans than previously studied animal models. Here, we investigated the role of senescence in regulating inflammation, fibrosis, and arrhythmogenesis in young and aged infarcted rabbits. Aged rabbits exhibited increased peri-procedural mortality and arrhythmogenic electrophysiological remodeling at the infarct border zone (IBZ) compared to young rabbits. Studies of the aged infarct zone revealed persistent myofibroblast senescence and increased inflammatory signaling over a 12-week timecourse. Senescent IBZ myofibroblasts in aged rabbits appear to be coupled to myocytes, and our computational modeling showed that senescent myofibroblast-cardiomyocyte coupling prolongs action potential duration (APD) and facilitates conduction block permissive of arrhythmias. Aged infarcted human ventricles show levels of senescence consistent with aged rabbits, and senescent myofibroblasts also couple to IBZ myocytes. Our findings suggest that therapeutic interventions targeting senescent cells may mitigate arrhythmias post-MI with age.

Recent advances in human induced pluripotent stem cell (hiPSC)-derived cardiac microtissues provide a unique opportunity for cardiotoxic assessment of pharmaceutical and environmental compounds. Here, we developed a series of automated data processing algorithms to assess changes in action potential (AP) properties for cardiotoxicity testing in 3D engineered cardiac microtissues generated from hiPSC-derived cardiomyocytes (hiPSC-CMs). Purified hiPSC-CMs were mixed with 5-25% human cardiac fibroblasts (hCFs) under scaffold-free conditions and allowed to self-assemble into 3D spherical microtissues in 35-microwell agarose gels. Optical mapping was performed to quantify electrophysiological changes. To increase throughput, AP traces from 4x4 cardiac microtissues were simultaneously acquired with a voltage sensitive dye and a CMOS camera. Individual microtissues showing APs were identified using automated thresholding after Fourier transforming traces. An asymmetric least squares method was used to correct non-uniform background and baseline drift, and the fluorescence was normalized (ΔF/F0). Bilateral filtering was applied to preserve the sharpness of the AP upstroke. AP shape changes under selective ion channel block were characterized using AP metrics including stimulation delay, rise time of AP upstroke, APD30, APD50, APD80, APDmxr (maximum rate change of repolarization), and AP triangulation (APDtri = APDmxr-APD50). We also characterized changes in AP metrics under various ion channel block conditions with multi-class logistic regression and feature extraction using principal component analysis of human AP computer simulations. Simulation results were validated experimentally with selective pharmacological ion channel blockers. In conclusion, this simple and robust automated data analysis pipeline for evaluating key AP metrics provides an excellent in vitro cardiotoxicity testing platform for a wide range of environmental and pharmaceutical compounds.

Abstract The occurrence of tick‐borne infectious diseases, including zoonotic babesiosis, has become a serious concern in recent years. In this study, we detected Babesia spp. using polymerase chain reaction (PCR) amplification of the 18S rRNA of the parasites isolated from ixodid ticks collected from small mammals in the Republic of Korea (ROK). Sequence analysis of the PCR amplicon revealed the presence of B. duncani, B. venatorum, B. capreoli/divergens, and, the most prevalent, B. microti in the ticks. The molecular phylogenetic analysis showed that the four species‐specific18S rRNA sequences clustered in four distinct clades. This is the first study to provide molecular evidence for the presence of zoonotic Babesia spp. other than B. microti in ticks in the ROK.

Self-powered implantable devices have the potential to extend device operation, though current energy harvesters are both insufficient and inconvenient. Here the authors report on a commercial coin battery-sized high-performance inertia-driven triboelectric nanogenerator based on body motion and gravity that can be used to charge a lithium-ion battery and integrated into a cardiac pacemaker.

Abstract Cardiotoxicity of pharmaceutical drugs, industrial chemicals, and environmental toxicants can be severe, even life threatening, which necessitates a thorough evaluation of the human response to chemical compounds. Predicting risks for arrhythmia and sudden cardiac death accurately is critical for defining safety profiles. Currently available approaches have limitations including a focus on single select ion channels, the use of non-human species in vitro and in vivo, and limited direct physiological translation. We have advanced the robustness and reproducibility of in vitro platforms for assessing pro-arrhythmic cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes and human cardiac fibroblasts in 3-dimensional microtissues. Using automated algorithms and statistical analyses of eight comprehensive evaluation metrics of cardiac action potentials, we demonstrate that tissue-engineered human cardiac microtissues respond appropriately to physiological stimuli and effectively differentiate between high-risk and low-risk compounds exhibiting blockade of the hERG channel (E4031 and ranolazine, respectively). Further, we show that the environmental endocrine disrupting chemical bisphenol-A (BPA) causes acute and sensitive disruption of human action potentials in the nanomolar range. Thus, this novel human 3D in vitro pro-arrhythmic risk assessment platform addresses critical needs in cardiotoxicity testing for both environmental and pharmaceutical compounds and can be leveraged to establish safe human exposure levels.

Most cardiac arrhythmias at the whole heart level result from alteration of cell membrane ionic channels and intracellular calcium concentration ([Ca2+]i) cycling with emerging spatiotemporal behavior through tissue-level coupling. For example, dynamically induced spatial dispersion of action potential duration, QT prolongation, and alternans are clinical markers for arrhythmia susceptibility in regular and heart-failure patients that originate due to changes of the transmembrane voltage (Vm) and [Ca2+]i. We present an optical-mapping methodology that permits simultaneous measurements of the Vm - [Ca2+]i signals using a single-camera without cross-talk, allowing quantitative characterization of favorable/adverse cell and tissue dynamical effects occurring from remodeling and/or drugs in heart failure. We demonstrate theoretically and experimentally in six different species the existence of a family of excitation wavelengths, we termed semasbestic, that give no change in signal for one dye, and thus can be used to record signals from another dye, guaranteeing zero cross-talk.

Background: Hereditary hemolytic anemia (HHA) is defined as a group of heterogeneous and rare diseases caused by defects of red blood cell (RBC) metabolism and RBC membrane, which leads to lysis or premature clearance. The aim of this study was to investigate individuals with HHA for potential disease-causing variants in 33 genes reported to be associated with HHA. Methods: A total of 14 independent individuals or families diagnosed with suspected HHA, and in particular, RBC membranopathy, RBC enzymopathy, and hemoglobinopathy, were collected after routine peripheral blood smear testing. A custom designed panel, including the 33 genes, was performed using gene panel sequencing on the Ion Torrent PGM™ Dx System. The best candidate disease-causing variants were confirmed by Sanger sequencing. Results: Several variants of the HHA-associated genes were detected in 10 out of 14 suspected HHA individuals. After excluding those variants predicted to be benign, 10 pathogenic variants and 1 variant of uncertain significance (VUS) were confirmed in 10 individuals with suspected HHA. Of these variants, the p.Trp704Ter nonsense variant of EPB41 and missense p.Gly151Asp variant of SPTA1 were identified in two out of four hereditary elliptocytoses. The frameshift p.Leu884GlyfsTer27 variant of ANK1, nonsense p.Trp652Ter variant of the SPTB, and missense p.Arg490Trp variant of PKLR were detected in all four hereditary spherocytosis cases. Missense p.Glu27Lys, nonsense p.Lys18Ter variants, and splicing errors such as c.92 + 1G > T and c.315 + 1G > A within HBB were identified in four beta thalassemia cases. Conclusions: This study provides a snapshot of the genetic alterations in a cohort of Korean HHA individuals and demonstrates the clinical utility of using gene panels in HHA. Genetic results can provide precise clinical diagnosis and guidance regarding medical treatment and management for some individuals.

Objective Head elevation at an angle of 30° during cardiopulmonary resuscitation (CPR) was hemodynamically beneficial compared to supine position in a previous porcine cardiac arrest experimental study. However, survival benefit of head-up elevation during CPR has not been clarified. This study aimed to assess the effect of head-up tilt position during CPR on 24-hour survival in a porcine cardiac arrest experimental model. Methods This was a randomized experimental trial using female farm pigs (n=18, 42±3 kg) sedated, intubated, and paralyzed on a tilting surgical table. After surgical preparation, 15 minutes of untreated ventricular fibrillation was induced. Then, 6 minutes of basic life support was performed in a position randomly assigned to either head-up tilt at 30° or supine with a mechanical CPR device, LUCAS-2, and an impedance threshold device, followed by 20 minutes of advanced cardiac life support in the same position. Primary outcome was 24-hour survival, analyzed by Fisher exact test. Results In the 8 pigs from the head-up tilt position group, one showed return of spontaneous circulation (ROSC); all eight pigs expired within 24 hours. In the eight pigs from the supine position group, six had the ROSC; six pigs survived for 24 hours and two expired. The head-up position group showed lower 24-hour survival rate and lower ROSC rate than supine position group (P

Purpose Kawasaki disease (KD) is a common, acute systemic vasculitis in children. Acute phase reactants (APRs) have been used to assist diagnosis, and to predict outcome in children with KD. However, it remains unknown on levels of APRs depending on duration of fever. We aimed to compare APR levels of children with KD who visited with < 5 days duration of fever and with ≥ 5 days. Methods Children (≤ 15 years) with complete KD who visited the emergency department were enrolled from March 2012 through February 2018. The children were divided into the early (fever < 5 days) and late (fever ≥ 5 days) presenters. The baseline characteristics, APR levels, such as platelet count, and outcomes were compared between the 2 groups. Results A total of 145 children with complete KD were enrolled. Median age was 27.0 (interquartile range [IQR], 12.0-46.5) months, and boys accounted for 60.0%. The early presenters (63 [43.4%]) had a younger age (17.0 [IQR, 7.0-45.0] vs. 32.5 [IQR, 14.0-48.0] months; P = 0.006), shorter duration of fever (3.0 [IQR, 2.0-4.0] days vs. 6.0 [IQR, 5.0-7.0] days; P < 0.001), and a lower platelet count (336.7 ± 105.2 [× 103/μL] vs. 381.6 ± 121.8 [× 103/μL], P = 0.02) than the late presenters. The other APR levels, and frequency of resistance to intravenous immunoglobulin and coronary artery abnormalities showed no differences between the 2 groups. Conclusion Children with KD who visited with < 5 days duration of fever had a lower platelet count compared to those with ≥ 5 days. No differences were found in the other APR levels and the outcomes. It may be necessary to consider the differences in APR levels depending on duration of fever when treating children with KD.

We describe aortic arch endarterectomy performed concomitantly with on-pump cardiac surgery in 2 patients with grade V arch atherosclerosis. In both patients, transesophageal echocardiographic findings led to the diagnosis of severe arch atherosclerosis associated with a mobile atheromatous plaque in the aortic arch. The severe arch atherosclerosis was managed with endarterectomy under deep hypothermic circulatory arrest. In patients with severe grade V atherosclerosis in the aortic arch, performing endarterectomy simultaneously with primary cardiac surgery may be justified as a way to reduce the risk of peripheral embolism, including cerebrovascular accidents, with minimal additional surgical risk.

Exploring the ground state of two-dimensional (2D) magnetic systems enriches the fundamental understanding of magnetism and boosts the applications. The authors here show the suppression of magnetic order and 2D XY behavior in XXZ-type antiferromagnet NiPS3 when approaching the monolayer limit by Raman spectroscopy.

Abstract Background Open distal graft to proximal aortic arch anastomosis is central to a hemiarch replacement. Even if the ischemic tolerance time of several organs during circulatory arrest (CA) at normothermia is much longer than that of the brain, very little is known about the safety and clinical efficacy of moderate hypothermia for organ protection during the average duration of CA needed for aortic arch replacement. Hemiarch replacement using the standard techniques of deep hypothermia and antegrade perfusion has often ignored the effects of prolonged distal body CA. Maintenance of distal organ, especially the liver and kidney, perfusion reduces the risk of postoperative renal dysfunction and coagulopathy. Case presentation A 72-year-old female patient was referred to our institute due to chest discomfort. Radiologic investigations revealed a giant aneurysm of the ascending aorta extending but confined to the proximal aortic arch. We performed an alternative technique for hemiarch replacement using a dual inflow source. Conclusions Although this technique cannot apply to all aneurysmal aortic diseases, our basic technique involving the use of dual inflow may be well suited for standard hemiarch replacement that is confined to the proximal aortic arch, given the shortening of the bypass and ischemic times.

Objective For patients with acute myocardial infarction (AMI), symptoms assessed by emergency medical services (EMS) providers have a critical role in prehospital treatment decisions. The purpose of this study was to evaluate the diagnostic accuracy of EMS provider-assessed cardiac symptoms of AMI. Methods Patients transported by EMS to 4 study hospitals from 2008 to 2012 were included. Using EMS and administrative emergency department databases, patients were stratified according to the presence of EMS-assessed cardiac symptoms and emergency department diagnosis of AMI. Cardiac symptoms were defined as chest pain, dyspnea, palpitations, and syncope. Disproportionate stratified sampling was used, and medical records of sampled patients were reviewed to identify an actual diagnosis of AMI. Using inverse probability weighting, verification bias-corrected diagnostic performance was estimated. Results Overall, 92,353 patients were enrolled in the study. Of these, 13,971 (15.1%) complained of cardiac symptoms to EMS providers. A total of 775 patients were sampled for hospital record review. The sensitivity, specificity, positive predictive value, and negative predictive value of EMS provider-assessed cardiac symptoms for the final diagnosis of AMI was 73.3% (95% confidence interval [CI], 70.8 to 75.7), 85.3% (95% CI, 85.3 to 85.4), 3.9% (95% CI, 3.6 to 4.2), and 99.7% (95% CI, 99.7 to 99.8), respectively. Conclusion We found that EMS provider-assessed cardiac symptoms had moderate sensitivity and high specificity for diagnosis of AMI. EMS policymakers can use these data to evaluate the pertinence of specific prehospital treatment of AMI.

Abstract Background An aberrant right subclavian artery (ARSA) is a relatively prevalent vascular anomaly. What is the most appropriate treatment for thoracic aortic aneurysm combined a non-aneurysmal change ARSA? Case presentation A 52-year-old man was admitted to our institute due to a history of chronic cough, dysphagia and an abnormal chest radiographic finding. Because of his progressive symptoms and large fusiform thoracic aneurysm, we performed the hybrid repair for simultaneous relief of an ARSA causing dysphagia and thoracic aneurysm. Conclusion In case without aneurysm of ARSA, especially in conjunction with approximate thoracic aneurysm, our approach is suitable because the revascularization using the right carotid to subclavian artery re-routing prior to endograft deployment is justified in order to preserve circulation of posterior brain, spinal cord, internal mammary artery and upper limb and to prevent large retrograde type II endoleaks, as well as simplicity and durability.

Cardiac tissue engineering using hiPSC-derived cardiomyocytes is a promising avenue for cardiovascular regeneration, pharmaceutical drug development, cardiotoxicity evaluation, and disease modeling. Limitations to these applications still exist due in part to the need for more robust structural support, organization, and electromechanical function of engineered cardiac tissues. It is well accepted that heterotypic cellular interactions impact the phenotype of cardiomyocytes. The current study evaluates the functional effects of coculturing adult human cardiac fibroblasts (hCFs) in 3D engineered tissues on excitation and contraction with the goal of recapitulating healthy, nonarrhythmogenic myocardium in vitro. A small population (5% of total cell number) of hCFs in tissues improves tissue formation, material properties, and contractile function. However, two perturbations to the hCF population create disease-like phenotypes in engineered cardiac tissues. First, increasing the percentage of hCFs to 15% resulted in tissues with increased ectopic activity and spontaneous excitation rate. Second, hCFs undergo myofibroblast activation in traditional two-dimensional culture, and this altered phenotype ablated the functional benefits of hCFs when incorporated into engineered cardiac tissues. Taken together, the results of this study demonstrate that human cardiac fibroblast number and activation state modulate electromechanical function of hiPSC-cardiomyocytes and that a low percentage of quiescent hCFs are a valuable cell source to advance a healthy electromechanical response of engineered cardiac tissue for regenerative medicine applications.

Abstract In terms of advances in technology, especially electronic devices for human use, there are needs for miniaturization, low power, and flexibility. However, there are problems that can be caused by these changes in terms of battery life and size. In order to compensate for these problems, research on energy harvesting using environmental energy (mechanical energy, thermal energy, solar energy etc.) has attracted attention. Ferroelectric materials which have switchable dipole moment are promising for energy harvesting fields because of its special properties such as strong dipole moment, piezoelectricity, pyroelectricity. The strong dipole moment in ferroelectric materials can increase internal potential and output power of energy harvesters. In this review, we will provide an overview of the recent research on various energy harvesting fields using ferroelectrics. A brief introduction to energy harvesting and the properties of the ferroelectric material are described, and applications to energy harvesters to improve output power are described as well.

Purpose Peripheral intravenous cannulation (PIC) for children is technically difficult. We aimed to investigate factors associated with the primary success of PIC for children in the emergency department (ED). Methods This prospective observational study was conducted on children younger than 3 years who visited the ED from September 2014 to August 2015. The children undergoing primary success, defined as success at the first attempt, comprised the success group. Using a case report form, information about the children (age, sex, and weight), practitioners’ occupation (doctors, nurses, emergency medical technicians [EMTs]), treatment venue, insertion site of PIC, presence of guardians, and use of auxiliary devices were collected and compared between the success and failure groups. Multivariable logistic regression models were constructed to identify factors associated with the primary success. Results Of 439 children, 271 underwent the primary success (61.7%). The success group showed older age, heavier weight, and higher proportion of EMT. No differences were found in treatment venue, insertion site, and presence of the guardian. We found that patients’ age (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.003-1.1), and practitioners’ occupation (EMT; OR, 3.0; 95% CI, 1.9-4.7, compared with doctors) were the factors associated with the primary success. Conclusion Practitioners’ occupation (EMT) and children’s age (older) may be associated with the primary success of PIC. It may be helpful to have specialized personnel when performing PIC on children in the ED.

Abstract Background Since its introduction, the Revised Trauma Score (RTS) has been widely used to determine the prognosis of trauma patients. Recent studies have revealed a need to change the parameters of the RTS. We have designed a new trauma score (NTS) based on revised parameters, including the adoption of the actual Glasgow Coma Scale (GCS) score instead of a GCS code, the revision of the systolic blood pressure interval used for the code value and the incorporation of peripheral oxygen saturation (SpO2) instead of respiratory rate. The purpose of this study was to evaluate the predictive performance of the NTS for in-hospital mortality compared with the RTS and other trauma scores. Methods This was a prospective observational study using data from the trauma registry of a tertiary hospital. The subjects were selected from patients who arrived at the ED between July 1, 2014, and June 30, 2016, and, for external validation purposes, those who arrived at the ED between July 1, 2011, and June 30, 2013. Demographic data and physiological data were analyzed. NTS models were calculated using logistic regression for GCS score, SBP code values, and SpO2. The mortality predictive performance of NTS was compared with that of other trauma scores. Results A total of 3263 patients for derivation and 3106 patients for validation were included in the analysis. The NTS showed better discrimination than the RTS (AUC = 0.935 vs. 0.917, respectively, AUC difference = 0.018, p = 0.001; 95% CI, 0.0071–0.0293) and similar discrimination to that of mechanism, Glasgow Coma scale, age, and arterial pressure (MGAP) and the Glasgow Coma Scale, age, and systolic arterial pressure (GAP). In the validation cohort, the global properties of the NTS for mortality prediction were significantly better than those of the RTS (AUC = 0.919 vs. 0.906, respectively; AUC difference = 0.013, p = 0.013; 95% CI, 0.0009–0.0249) and similar to those of the MGAP and GAP. Conclusions The NTS predicts in-hospital mortality substantially better than the RTS.

Once fabricated, the gates of conventional electronic devices are spatially fixed. Here, the authors introduce tunnelling triboelectrification to create, modify and destroy on-demand ghost floating gates underneath 2D materials, with the spatial resolution of an atomic force microscope.

In a physiological setting, mitochondria increase oxidative phosphorylation during periods of stress to meet increased metabolic demand. This in part is mediated via enhanced mitochondrial Ca2+ uptake, an important regulator of cellular ATP homeostasis. In a pathophysiological setting pharmacological modulation of mitochondrial Ca2+ uptake or retention has been suggested as a therapeutic strategy to improve metabolic homeostasis or attenuate Ca2+-dependent arrhythmias in cardiac disease states. To explore the consequences of mitochondrial Ca2+ accumulation, we tested the effects of kaempferol, an activator of mitochondrial Ca2+ uniporter (MCU), CGP-37157, an inhibitor of mitochondrial Na+/Ca2+ exchanger, and MCU inhibitor Ru360 in rat ventricular myocytes (VMs) from control rats and rats with hypertrophy induced by thoracic aortic banding (TAB). In periodically paced VMs under β-adrenergic stimulation, treatment with kaempferol (10 μmol/L) or CGP-37157 (1 μmol/L) enhanced mitochondrial Ca2+ accumulation monitored by mitochondrial-targeted Ca2+ biosensor mtRCamp1h. Experiments with mitochondrial membrane potential-sensitive dye TMRM revealed this was accompanied by depolarization of the mitochondrial matrix. Using redox-sensitive OMM-HyPer and ERroGFP_iE biosensors, we found treatment with kaempferol or CGP-37157 increased the levels of reactive oxygen species (ROS) in mitochondria and the sarcoplasmic reticulum (SR), respectively. Confocal Ca2+ imaging showed that accelerated Ca2+ accumulation reduced Ca2+ transient amplitude and promoted generation of spontaneous Ca2+ waves in VMs paced under ISO, suggestive of abnormally high activity of the SR Ca2+ release channel ryanodine receptor (RyR). Western blot analyses showed increased RyR oxidation after treatment with kaempferol or CGP-37157 vs. controls. Furthermore, in freshly isolated TAB VMs, confocal Ca2+ imaging demonstrated that enhancement of mitochondrial Ca2+ accumulation further perturbed global Ca2+ handling, increasing the number of cells exhibiting spontaneous Ca2+ waves, shortening RyR refractoriness and decreasing SR Ca2+ content. In ex vivo optically mapped TAB hearts, kaempferol exacerbated proarrhythmic phenotype. On the contrary, incubation of cells with MCU inhibitor Ru360 (2 μmol/L, 30 min) normalized RyR oxidation state, improved intracellular Ca2+ homeostasis and reduced triggered activity in ex vivo TAB hearts. These findings suggest facilitation of mitochondrial Ca2+ uptake in cardiac disease can exacerbate proarrhythmic disturbances in Ca2+ homeostasis via ROS and enhanced activity of oxidized RyRs, while strategies to reduce mitochondrial Ca2+ accumulation can be protective.

This paper presents an advanced estimation method for obtaining the probability density functions of a damage parameter for valve leakage detection in a reciprocating pump. The estimation method is based on a comparison of model data which are simulated by using a mathematical model, and experimental data which are measured on the inside and outside of the reciprocating pump in operation. The mathematical model, which is simplified and extended on the basis of previous models, describes not only the normal state of the pump, but also its abnormal state caused by valve leakage. The pressure in the cylinder is expressed as a function of the crankshaft angle, and an additional volume flow rate due to the valve leakage is quantified by a damage parameter in the mathematical model. The change in the cylinder pressure profiles due to the suction valve leakage is noticeable in the compression and expansion modes of the pump. The damage parameter value over 300 cycles is calculated in two ways, considering advance or delay in the opening and closing angles of the discharge valves. The probability density functions of the damage parameter are compared for diagnosis and prognosis on the basis of the probabilistic features of valve leakage.

Objective Head injury in children is a common problem presenting to emergency departments, and cranial computed tomography scanning is the diagnostic standard for these patients. Several decision rules are used to determine whether computed tomography scans should be used; however, the use of computed tomography scans is often influenced by guardians’ preference toward the scans. The objective of this study was to identify changes in guardian preference for minor head injuries after receiving an explanation based on the institutional clinical practice guideline. Methods A survey was conducted between July 2010 and June 2012. Patients younger than 16 years with a Glasgow Coma Scale score of 15 after a head injury and their guardians were included. Pre- and post-explanation questionnaires were given to guardians to assess their preference for computed tomography scans and factors related to the degree of preference. Treating physicians explained the risks and benefits of cranial computed tomography scanning using the institutional clinical practice guideline. Guardian preference for a computed tomography scan was examined using a 100-mm visual analog scale. Results In total, 208 patients and their guardians were included in this survey. Guardian preference for computed tomography scans was significantly reduced after explanation (46.7 vs. 17.4, P

Lyme disease is a tick-borne zoonotic disease caused by Borrelia burgdorferi sensu lato (s. l.) via transmission cycles involving competent tick vectors and vertebrate reservoirs. Here, we determined the prevalence and distribution of Borrelia genospecies in 738 ticks of at least three species from wild rodents in nine regions of the Republic of Korea (ROK). Ticks were analyzed using nested PCR targeting partial flagellin B gene sequences, followed by sequence analysis. The prevalence of Borrelia infection was 33.6%, and the most common genospecies were B. afzelii (62.5%), B. valaisiana (31.9%), B. yangtzensis (2.4%), B. garinii (1.6%), and B. tanukii (1.6%). Borrelia afzelii was found in all regions except Jeju Island; this predominant genospecies was found in the northern and central sampling regions. Borrelia valaisiana, B. yangtzensis, and B. tanukii were found only in the southern regions with B. valaisiana being the most common, whereas B. yangtzensis and B. tanukii were only found on Jeju Island. Our study is the first to describe the nationwide prevalence of B. burgdorferi s. l. in ticks from wild rodents in the ROK. Continuous surveillance in ticks, animals, humans, and different regions is required to avoid disease distribution and possible transmission to humans in the ROK.

Despite of numerous evidences that elevated serum lactate levels were associated with unfavorable outcomes, there have been no study demonstrated an optimal cutoff of serum lactate in unselected patients. This study was aimed to evaluate the prognostic property of lactate, and to identify a cutoff of serum lactate level for predicting 30-day in-hospital mortality among unselected patients presenting to the emergency department (ED).We performed a retrospective observational study from January 2010 to December 2016. 61,151 patients were used for propensity score analysis after exclusion. 14,015 patients who underwent lactate test at ED arrival were enrolled for final analysis.The average treatment effect (ATE) of carrying out a lactate test on 30-day in-hospital mortality was 0.53% (adjusted odds ratio (OR) = 1.013, p = 0.19; 95% confidence interval (CI), 0.997-1.013). Adjusted OR of serum lactate calculated from multivariable analysis was 1.09 (p < 0.001; 95% CI, 1.07-1.10). The area under a ROC curve (AUC) of serum lactate was 0.711 (p < 0.001; 95% CI, 0.703-0.718). The sensitivity, specificity, and positive and negative predictive values for the cutoff > 2.6 mmol/L were 56.7%, 74.3%, 20.8%, and 93.5%, respectively. Mortality of the high-lactate group (> 2.6 mmol/L) was significantly higher than that of the low lactate group (≤ 2.6 mmol/L) (20.8% vs. 6.5%, difference = 14.3%, p < 0.01; 95% CI, 13.0% - 15.7%).A serum lactate level > 2.6 mmol/L predicted 30-day in-hospital mortality in unselected patients who arrived to the ED and were admitted to the hospital. Additionally, serum lactate test in the ED could be an effective screening method for identifying low risk patients.

Multicellular spheroids generated through cellular self-assembly provide cytoarchitectural complexities of native tissue including three-dimensionality, extensive cell-cell contacts, and appropriate cell-extracellular matrix interactions. They are increasingly suggested as building blocks for larger engineered tissues to achieve shapes, organization, heterogeneity, and other biomimetic complexities. Application of these tissue culture platforms is of particular importance in cardiac research as the myocardium is comprised of distinct but intermingled cell types. Here, we generated scaffold-free 3D cardiac microtissue spheroids comprised of cardiac myocytes (CMs) and/or cardiac fibroblasts (CFs) and used them as building blocks to form larger microtissues with different spatial distributions of CMs and CFs. Characterization of fusing homotypic and heterotypic spheroid pairs revealed an important influence of CFs on fusion kinetics, but most strikingly showed rapid fusion kinetics between heterotypic pairs consisting of one CF and one CM spheroid, indicating that CMs and CFs self-sort in vitro into the intermixed morphology found in the healthy myocardium. We then examined electrophysiological integration of fused homotypic and heterotypic microtissues by mapping action potential propagation. Heterocellular elongated microtissues which recapitulate the disproportionate CF spatial distribution seen in the infarcted myocardium showed that action potentials propagate through CF volumes albeit with significant delay. Complementary computational modeling revealed an important role of CF sodium currents and the spatial distribution of the CM-CF boundary in action potential conduction through CF volumes. Taken together, this study provides useful insights for the development of complex, heterocellular engineered 3D tissue constructs and their engraftment via tissue fusion and has implications for arrhythmogenesis in cardiac disease and repair.

INTRODUCTION:Despite relevant evidence that supplemental oxygen therapy can be harmful to patients with myocardial injury, the association between hyperoxia and the clinical outcome of such patients has not been evaluated. We assessed whether early hyperoxia negatively affects outcomes in hospitalized patients with myocardial injury. METHODS:This was a retrospective study conducted at a tertiary referral teaching hospital. Between January 2010 and December 2016, 2,376 consecutive emergency department patients with myocardial injury, defined as a peak troponin-I level ≥ 0.2 ng/mL, within the first 24 hours of presentation were included. The metrics used to define hyperoxia were the maximum average partial pressure of oxygen (PaO2MAX), average partial pressure of oxygen (PaO2AVG), and area under the curve during the first 24 hours (AUC24). The association between early hyperoxia within 24 hours after presentation and clinical outcomes was evaluated using multiple imputation and logistic regression analysis. The primary outcome was 28-day in-hospital mortality. The secondary outcomes were new-onset cardiovascular, coagulation, hepatic, renal, and respiratory dysfunctions (sequential organ failure sub-score ≥ 2). RESULTS:Compared with normoxic patients, the adjusted odds ratios (ORs) for PaO2MAX, PaO2AVG, and AUC24 were 1.55 (95% confidence interval (CI) 1.05-2.27; p = 0.026), 2.13 (95% CI 1.45-3.12; p = 0.001), and 1.73 (95% CI 1.15-2.61; p = 0.008), respectively, in patients with mild hyperoxia and 6.01 (95% CI 3.98-9.07; p < 0.001), 8.92 (95% CI 3.33-23.88; p < 0.001), and 7.32 (95% CI 2.72-19.70; p = 0.001), respectively, in patients with severe hyperoxia. The incidence of coagulation and hepatic dysfunction (sequential organ failure sub-score ≥ 2) was significantly higher in the mild and severe hyperoxia group. CONCLUSIONS:Hyperoxia during the first 24 hours of presentation is associated with an increased 28-day in-hospital mortality rate and risks of coagulation and hepatic dysfunction in patients with myocardial injury.

The triboelectric generator (TEG) is a strong candidate for low-power sensors utilized in the Internet of Things (IoT) technology. Within IoT technologies, advanced driver assistance system (ADAS) technology is included within autonomous driving technology. Development of an energy source for sensors necessary for operation becomes an important issue, since a lot of sensors are embedded in vehicles and require more electrical energy. Although saving energy and enhancing energy efficiency is one of the most important issues, the application approach to harvesting wasted energy without compromising the reliability of existing mechanical systems is still in very early stages. Here, we report of a new type of TEG, a suspension-type free-standing mode TEG (STEG) inspired from a shock absorber in a suspension system. We discovered that the optimum width of electrode output voltage was 131.9 V and current was 0.060 µA/cm2 in root mean square (RMS) value while the optimized output power was 4.90 μW/cm2 at 66 MΩ. In addition, output power was found to be proportional to frictional force due to the contact area between two frictional surfaces. It was found that the STEG was made of perfluoroalkoxy film and showed good mechanical durability with no degradation of output performance after sliding 11,000 times. In addition, we successfully demonstrated charging a capacitor of 330 μF in 6 min.

BACKGROUND:Remodeling of cardiac repolarizing currents, such as the downregulation of slowly activating K+ channels (IKs), could underlie ventricular fibrillation (VF) in heart failure (HF). We evaluated the role of Iks remodeling in VF susceptibility using a tachypacing HF model of transgenic rabbits with Long QT Type 1 (LQT1) syndrome. METHODS AND RESULTS:LQT1 and littermate control (LMC) rabbits underwent three weeks of tachypacing to induce cardiac myopathy (TICM). In vivo telemetry demonstrated steepening of the QT/RR slope in LQT1 with TICM (LQT1-TICM; pre: 0.26±0.04, post: 0.52±0.01, P

Conduction velocity (CV) restitution is a key property that characterizes any medium supporting traveling waves. It reflects not only the dynamics of the individual constituents but also the coupling mechanism that mediates their interaction. Recent studies have suggested that cardiac tissues, which have a non-monotonic CV-restitution property, can support alternans , a period-2 oscillatory response of periodically paced cardiac tissue. This study finds that single-hump, non-monotonic, CV-restitution curves are a common feature of in vitro cultures of rat cardiac cells. We also find that the Fenton–Karma model, one of the well-established mathematical models of cardiac tissue, supports a very similar non-monotonic CV restitution in a physiologically relevant parameter regime. Surprisingly, the mathematical model as well as the cell cultures support bistability and show cardiac memory that tends to work against the generation of an alternans. Bistability was realized by adopting two different stimulation protocols, ‘S1S2’, which produces a period-1 wave train, and ‘alternans-pacing’, which favors a concordant alternans. Thus, we conclude that the single-hump non-monotonicity in the CV-restitution curve is not sufficient to guarantee a cardiac alternans, since cardiac memory interferes and the way the system is paced matters.