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Even today, when the surgical outcome of congenital heart disease in the neonatal period has improved, the prognosis for heterotaxy syndrome and functional single ventricle complicated with total anomalous pulmonary venous connection (TAPVC), especially the infra-cardiac type, is catastrophic. We describe a strategy that combines percutaneous ductus venosus (DV) stent placement and occlusion after TAPVC repair to ensure survival from initial surgery to bidirectional cavopulmonary shunt (BCPS) procedure and facilitate subsequent treatment. Three consecutive patients with heterotaxy syndrome and functional single ventricle complicated by infra-cardiac TAPVC treated with our own strategy were retrospectively studied. In two infants, DV stent placement was performed on the day of birth. In one case at 11 days of age. The risk of pulmonary vein obstruction was reduced, and on-pump surgery, including TAPVC repair, was performed on a standby basis. Since the rapid increase in hepatic enzymes occurred on postoperative day 0 to 1 in all cases, percutaneous stent occlusion was performed until postoperative day 3. The procedure improved liver function. One patient died due to severe atrioventricular valve regurgitation, one case underwent BCPS, and one patient was waiting to undergo. DV stent placement can avoid TAPVC repair in the early neonatal period. After TAPVC repair, the portosystemic shunt remained, resulting in hepatic dysfunction, but this could be improved by stent and vertical vein occlusion. A series of stepwise treatments can be useful to help such critically ill infants survive the high-risk neonatal period and achieve good BCPS circulation.

Objective: Most cases of severe metabolic alkalosis have many causes that may result in renal failure and death. Therefore, these should be treated promptly for successful recovery. Patient: A 61-year-old man was hospitalized due to an acute kidney injury (creatinine level of 4.36 mg/dL) after a 3-month history of anorexia and recurrent vomiting. He had been treated for tuberculosis in the past. Results: Blood gas analysis revealed severe metabolic alkalosis with pH=7.66, HCO3=94 mmol/L, and pCO2=82.0 mmHg. Routine biochemical examination revealed severe hypokalemia (K 2.9 mEq/L) that was associated with prolonged QTc interval (0.52 seconds) on the electrocardiogram. Gastrofiberscopic examination also revealed severe stenosis and ulcerated scarring of the gastric pylorus and severe esophagitis. Intravenous hydration and correction of hypokalemia improved renal function and resolved metabolic alkalosis. An investigation that was repeated after 6 days revealed a creatinine level of 1.58 mg/dL, pH=7.47, HCO3=23.4 mmol/L, K=3.6 mEq/L, and QTc of 0.45 seconds. The patient underwent gastrectomy and adenocarcinoma was observed. Conclusion: We described a resolved case of severe metabolic alkalosis and acute kidney injury in a rural medical setting following conservative management.

Sudden cardiac events in young athletes are a major concern in the field of sports cardiology. Although coronary artery anomalies remain a major cause of cardiac events in young athletes, only a few cases have been diagnosed prior to critical events. Here, we present the case of a previously asymptomatic young male runner who experienced sudden cardiac arrest at the end of a marathon. The patient immediately received cardiopulmonary resuscitation from a bystander and was transported to an emergency hospital. As his electrocardiogram showed ventricular fibrillation, he was treated with electric shock, and his rhythm was successfully converted to a normal sinus rhythm. Following successful resuscitation, the patient was diagnosed with an anomalous origin of the right coronary artery from the left sinus of Valsalva with an intramural course. The patient underwent coronary artery bypass using the right internal thoracic artery. Fifteen years later, the coronary bypass was found to be blocked, but the patient was asymptomatic. However, an exercise electrocardiogram revealed ST-segment elevation in the inferior leads. The patient then underwent an unroofing procedure. He has remained asymptomatic without complications for two years after the second surgery.

We present our experience with transcatheter vascular occlusion using 0.035-inch hydrogel expandable coils, which has been reported only in a few cases in the pediatric cardiology fields.This study is a retrospective analysis of all patients who underwent transcatheter embolization with 0.035-inch hydrogel coils at the Department of Pediatrics, Okayama University Hospital, between October 2018 and September 2020.Twenty patients with a median age of 5.1 years (0.05-26.0 years) and a median weight of 13.8 kg (3.0-56.8 kg) were included. A total of fifty-four 0.035-inch hydrogel coils, including 35 Azur 35 and nineteen Azur CX 35 coils (Terumo, Tokyo, Japan), were successfully deployed in 22 target vessels. The target vessels consisted of 10 aortopulmonary collaterals, 8 veno-venous collaterals, and 4 pulmonary arteriovenous malformations. We achieved technical success in all the target vessels. In total, the mean target vessel diameter was 4.4 mm, the mean number of 0.035-inch hydrogel coils was 2.5 per vessel. The mean device to vessel ratio was 1.6 for the anchor coil and 1.2 for the additional coil. Post-implantation angiograms revealed that the primary occlusion rate was 18/22 (82%). There were no periprocedural complications.The 0.035-inch hydrogel expandable coils are effective and safe in patients with congenital heart disease and vascular anomalies. These occlusion devices could be valuable options for interventional pediatric cardiologists.

Health monitoring systems are used to assess building damage immediately after an earthquake and have become widely utilized in Japan. For example, the system developed by the authors has been installed in more than 60 buildings since 2014. Such systems mostly rely on accelerometers to estimate the building performance. Recently, Micro electro mechanical system (MEMS) accelerometers have been increasingly applied for such uses due to their economic advantages. However, MEMS accelerometers are known to have relatively low measurement accuracy for certain frequency band excitations compared to servo type accelerometers. Past research has been undertaken to test their measurement accuracy, however, few studies review their performance under long period and large amplitude seismic motions. Evaluation of measurement accuracy in such conditions is essential since the system is also installed in tall buildings and isolated buildings with relatively long natural periods. Therefore, this study evaluates the measurement accuracy of the MEMS accelerometer under long period and large amplitude vibration based on the results of shake table testing.

Introduction Stem cell therapies have been shown to improve cardiac function; however, therapeutic potential of cardiosphere-derived cells (CDCs) in dilated cardiomyopathy (DCM) and the underlying mechanisms of paracrine effectors include CDC-secreted exosomes (CDCex) mediating cardiac repair remain unknown. Purpose- We aimed to evaluate the safety and therapeutic efficacy of CDCs in swine model of DCM and translate the preclinical results into children with DCM. Methods As a preclinical study, female Yorkshire pigs (n=15) were treated by intracoronary administration of microspheres (1.0×104 particles) to develop diffuse cardiac dysfunction and animals were randomly assigned to receive placebo or 9.0×106 CDC injection pretreated by DMSO or exosome inhibitor (EI; GW4869). CDCex-derived microRNAs (miRs) profile was assessed and ventricular ejection fraction (EF) was evaluated before and 1 month after cell infusion. In safety lead-in clinical trial, 5 patients with DCM ( Results Compared with placebo control, DMSO-treated CDC infusion resulted in improved cardiac function with decrease in myocardial fibrosis (18.2±4.1% versus; 9.5±3.6%; P Conclusions Intracoronary delivery of CDCs is safe and improves cardiac function through CDCex-derived miRs secretion in swine model of DCM. The safety lead-in results in patients warrant further assessment of clinical benefits and highlight miR-146a as a major paracrine mediator of CDC's antifibrotic function for clinical therapeutics. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Research Project for Practical Application of Regenerative Medicine (16bk0104052h0001, 17bk0104052h0002, 18bk0104052h0003) by the Japan Agency for Medical Research and Development

Bovine jugular vein (BJV) and expanded polytetrafluoroethylene (ePTFE) conduits have been described as alternatives to the homograft for right ventricular outflow tract (RVOT) reconstruction. This study compared RVOT reconstructions using BJV and ePTFE conduits performed in a single institution. The valve functions and outcomes of patients aged

Background Almost all reports on cardiac regeneration therapy have referred to adults, and only a few have focused on transcoronary infusion of cardiac progenitor cells using the stop-flow technique in children. Methods Intracoronary autologous cardiosphere-derived cell (CDC) transfer was conducted at Okayama University as a phase 1 clinical trial for seven patients with hypoplastic left heart syndrome between January 2011 and December 2012, and as a phase 2 clinical trial for 34 patients with single-ventricle physiology between July 2013 and March 2015. Results A total of 41 patients with single-ventricle physiology underwent transcoronary infusion of CDC with the stop-flow technique. The median age was 33 months (range, 5-70 months) and the median weight was 10.1 kg (range, 4.1-16.0 kg). Transient adverse events occurred during the procedure, including ST-segment elevation or depression, hypotension, bradycardia, and coronary artery vasospasm. All patients completely recovered. There were no major procedure-related adverse events. In this study, transcoronary infusion of CDC using the stop-flow technique was successfully completed in all patients. Conclusion Transcoronary infusion of CDC using the stop-flow technique in children is a feasible and safe procedure.

Rationale: Patients with single ventricle physiology are at high risk of mortality resulting from ventricular dysfunction. The preliminary results of the phase 1 trial showed that cardiosphere-derived cells (CDCs) may be effective against congenital heart failure. Objective: To determine whether intracoronary delivery of autologous CDCs improves cardiac function in patients with single ventricle physiology. Methods and Results: We conducted a phase 2 randomized controlled study to assign in a 1:1 ratio 41 patients who had single ventricle physiology undergoing stage 2 or 3 palliation to receive intracoronary infusion of CDCs 4 to 9 weeks after surgery or staged reconstruction alone (study A). The primary outcome measure was to assess improvement in cardiac function at 3-month follow-up. Four months after palliation, controls had an alternative option to receive late CDC infusion on request (study B). Secondary outcomes included ventricular function, heart failure status, somatic growth, and health-related quality of life after a 12-month observation. At 3 months, the absolute changes in ventricular function were significantly greater in the CDC-treated group than in the controls (+6.4% [SD, 5.5] versus +1.3% [SD, 3.7]; P =0.003). In study B, a late CDC infusion in 17 controls increased the ventricular function at 3 months compared with that at baseline (38.8% [SD, 7.7] versus 34.8% [SD, 7.4]; P P P P P P =0.014) relative to baseline. Conclusions: Intracoronary infusion of CDCs after staged palliation favorably affected cardiac function by reverse remodeling in patients with single ventricle physiology. This impact may improve heart failure status, somatic growth, and quality of life in patients and reduce parenting stress for their families. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01829750.

Ultraviolet photodissociation (UVPD) spectra of calix[4]arene (C4A) complexes with alkali metal ions, M+•C4A (M = Na, K, Rb, and Cs), are measured in the 34000–37000 cm–1 region under cold (~10 K) conditions in the gas phase. The Na+•C4A and K+•C4A complexes show several sharp vibronic bands, while the UVPD spectra of the Rb+•C4A and Cs+•C4A complexes exhibit only broad features. The UVPD spectra are assigned with the aid of quantum chemical calculations. Most of the features in the UVPD spectra can be attributed to cone isomers, which are the most stable for all the M+•C4A complexes. In all the cone isomers, the M+ ion is encapsulated inside the cavity of C4A, and the structure is distorted to C2 symmetry from that of bare C4A (C4 symmetry). The cone isomers show a big difference in the electronic structure between the K+ and Rb+ complexes. The Rb+ and Cs+ complexes have an electronic structure similar to that of bare C4A. In the Na+ and K+ complexes, a pair of two benzene rings facing to each other has a short distance between them (< 6 Å). This results in substantial overlap of π clouds between them, and an electronic transition is localized on this pair. Only this localized electronic transition of the Na+ and K+ complexes shows sharp band features in the UVPD spectra. In the Na+•C4A complex, the UVPD spectroscopic result suggests the coexistence of other isomers having a partial cone and 1,3-alternate form. The energetics for isomerization reactions of C4A and Na+•C4A is examined theoretically. Estimated potential barriers between the stable conformers are less than 75 kJ/mol for Na+•C4A, suggesting that conformational conversion can occur at room temperature, before the Na+•C4A complex enters the cold ion trap. The existence of multiple conformations for Na+•C4A is attributed to higher stability of these conformers, both kinetically and thermodynamically, compared to the case of bare C4A and the other M+•C4A complexes., This work was supported by JSPS KAKENHI Grant Number 16H04098.

Background Various types of conduits are available for right ventricular outflow tract reconstruction (RVOTR). The bovine jugular vein graft (BJVG) and expanded polytetrafluoroethylene graft (ePTFEG) have been descrived as an alternative to the homograft for RVOTR. Purpose- This study summarized the results to evaluate the single-center operation of RVOTR using BJVG and ePTFEG. Methods The valve functions of 27 patients under 20 years old who underwent primary RVOTR with BJVG and 26 patients with ePTFEG at our university hospital between 2013 and 2018 were retrospectively investigated. The valve conditions were assessed using echocardiography and cardiac catheterization. Results The median age at the time of operation was 1.8 years old (range, 6 days to 7.8 years old) with BJVG and 2.2 years old (range, 8 months to 9.1 years old) with ePTFEG. The median follow-up time was 3.4 years (range, 2 months to 5.2 years) with BJVG and 2.1 years (range, 1 month to 5.1 years) with ePTFEG. The peak RVOT gradient of BJVG was lower than ePTFEG (10.6±7.7 mmHg versus 18.1±16.2 mmHg, P=0.035). There were no differences in branch pulmonary stenosis defined as peak gradient up to 36mmHg (40.7% versus 50.0%, P=0.50) and pulmonary regurgitation graded worse than moderate (18.5% versus 11.5%, P=0.48) with BJVG and ePTFEG, respectively. Aneurysmal dilatation of the conduit was seen 22.2% with BJVG but none of patients with ePTFEG (P=0.01). All of patients with aneurysmal dilated BJVG had branch pulmonary stenosis. There were no differences in catheter intervention for branch pulmonary stenosis (22.2% versus 30.8%, P=0.48) and conduit replacement (11.1% versus 7.7%, log rank P=0.67) with BJVG and ePTFEG, respectively. There were no deaths during the fllow-up period in both groups. Conclusions The outcomes of RVOTR with BJVG and ePTFEG were clinically satisfactory. Aneurysmal dilatation was seen with BJVG and branch pulmonary stenosis was the risk factor for aneurysmal dilatation.

Introduction Stem cell therapy has been shown to improve cardiac function. The mechanisms of therapeutic efficacy are considered the secretion of paracrine factors but the details are still unknown. Hypothesis Exosomes are extracellular vesicles containing bioactive substances such as proteins, messenger RNAs and micro RNAs. We hypothesized that exosomes may be the main paracrine factors to mediate therapeutic efficacy of cardiosphere-derived cells (CDCs). Methods Farm pigs (30 kg, n=10) were treated by intracoronary administration of 10,000 microspheres (100–300 μm) into three vessels. Two weeks later, 9.0×106 CDCs pretreated by exosome inhibitor (EI; 20μM of GW4869) or DMSO as controls were selectively infused into three coronary arteries. Evaluation of ejection fraction (EF) was performed before cell infusion and 1 month after protocol treatment. Results Pigs developed diffuse hypokinetic heart failure (baseline EF 37.1%±2.1%) and randomly assigned into two groups (CDCs with EI: n=5, CDCs with DMSO: n=5). No serious adverse events were found during the CDCs infusion. Significant improvement of EF was observed in CDCs with DMSO group (37.1%±2.1% to 42.5%±3.0%; P=0.01), whereas no change was found in CDCs with EI group (37.1%±2.4% to 36.2%±2.9%; P=0.58). Myocardial fibrosis stained by picrosirius red was significantly reduced in CDCs with DMSO group compared with CDCs with EI group (9.5±3.6% versus 17.3±5.3%; P Conclusions We confirmed the therapeutic efficacy of CDCs and these effects were mainly mediated by exosomes.

Although cardiosphere-derived cells (CDCs) improve cardiac function and outcomes in patients with single ventricle physiology, little is known about their safety and therapeutic benefit in children with dilated cardiomyopathy (DCM). We aimed to determine the safety and efficacy of CDCs in a porcine model of DCM and translate the preclinical results into this patient population. A swine model of DCM using intracoronary injection of microspheres created cardiac dysfunction. Forty pigs were randomized as preclinical validation of the delivery method and CDC doses, and CDC-secreted exosome (CDCex)-mediated cardiac repair was analyzed. A phase 1 safety cohort enrolled five pediatric patients with DCM and reduced ejection fraction to receive CDC infusion. The primary endpoint was to assess safety, and the secondary outcome measure was change in cardiac function. Improved cardiac function and reduced myocardial fibrosis were noted in animals treated with CDCs compared with placebo. These functional benefits were mediated via CDCex that were highly enriched with proangiogenic and cardioprotective microRNAs (miRNAs), whereas isolated CDCex did not recapitulate these reparative effects. One-year follow-up of safety lead-in stage was completed with favorable profile and preliminary efficacy outcomes. Increased CDCex-derived miR-146a-5p expression was associated with the reduction in myocardial fibrosis via suppression of proinflammatory cytokines and transcripts. Collectively, intracoronary CDC administration is safe and improves cardiac function through CDCex in a porcine model of DCM. The safety lead-in results in patients provide a translational framework for further studies of randomized trials and CDCex-derived miRNAs as potential paracrine mediators underlying this therapeutic strategy.

The cooling of ionic species in the gas phase greatly simplifies the UV spectrum, which is of special importance to study the electronic and geometric structures of large systems, such as bio-related molecules and host-guest complexes. Many efforts have been devoted to achieving the ion cooling with a cold quadrupole Paul ion trap (QIT), but one problem was insufficient cooling of ions (up to ~30 K) in the QIT. In this study, we construct a mass spectrometer for ultraviolet photodissociation (UVPD) spectroscopy of gas-phase cold ions. The instrument consists of an electrospray ion source, a QIT cooled with a He cryostat, and a time-of-flight mass spectrometer. Giving a great care for the cooling condition, we can achieve ~10 K for the vibrational temperature of ions in the QIT, which is estimated from UVPD spectra of the benzo-18-crown-6 (B18C6) complex with potassium ion, K+•B18C6. Using this setup, we measure a UVPD spectrum of cold calix[4]arene (C4A) complex with potassium ion, K+•C4A. The spectrum shows a very weak band and a strong one at 36018 and 36156 cm–1, respectively, accompanied by many sharp vibronic bands in the 36000–36600 cm–1 region. In the geometry optimization of the K+•C4A complex, we obtain three stable isomers: one endo and two exo forms. On the basis of the total energy and UV spectral patterns predicted by density functional theory calculations, we attribute the structure of the K+•C4A complex to the endo isomer (C2 symmetry), in which the K+ ion is located inside the cup of C4A. The vibronic bands of K+•C4A at 36018 and 36156 cm–1 are assigned to the S1(A)–S0(A) and S2(B)–S0(A) transitions of the endo isomer, respectively., This work is partly supported by the Japan Society for the Promotion of Science (JSPS) through the program “Strategic Young Researcher Overseas Visits Program for Accelerating Brain Circulation”.

Because of social background, such as repeated large earthquakes and cheating in design and construction, structural health monitoring (SHM) systems are getting strong attention. The SHM systems are in a practical phase. An SHM system consisting of small number of sensors has been introduced to 6 tall buildings in Shinjuku area. Including them, there are 2 major issues in the SHM systems consisting of small number of sensors. First, optimal system number of sensors and the location are not well-defined. In the practice, system placement is determined based on rough prediction and experience. Second, there are some uncertainties in estimation results by the SHM systems. Thus, the purpose of this research is to provide useful information for increasing reliability of SHM system and to improve estimation results based on uncertainty analysis of the SHM systems. The important damage index used here is the inter-story drift angle. The uncertainty considered here are number of sensors, earthquake motion characteristics, noise in data, error between numerical model and real building, nonlinearity of parameter. Then I have analyzed influence of each factor to estimation accuracy. The analysis conducted here will help to decide sensor system design considering valance of cost and accuracy. Because of constraint on the number of sensors, estimation results by the SHM system has tendency to provide smaller values. To overcome this problem, a compensation algorithm was discussed and presented. The usefulness of this compensation method was demonstrated for 40 story S and RC building models with nonlinear response.

We have developed a metabolic flux analysis method that is based on (13)C-labeling patterns of the intracellular metabolites directly measured by capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). The flux distribution of the central carbon metabolism in Escherichia coli was determined by this new approach and the results were compared with findings obtained by conventional GC-MS analysis based on isotopomer of the proteinogenic amino acids. There were some differences in estimation results between new approach using CE-TOFMS and conventional approach using GC-MS. These were thought to be attributable to variations in measured mass distributions between amino acids and the corresponding precursors and to differences in the sensitivity of the exchange coefficients to mass distributions. However, our CE-TOFMS method facilitates high-throughput flux analysis without requiring complicated sample preparation such as hydrolysis of proteins and derivatization of amino acids.

Analysis of cellular components at multiple levels of biological information can provide valuable functional insights. We performed multiple high-throughput measurements to study the response of Escherichia coli cells to genetic and environmental perturbations. Analysis of metabolic enzyme gene disruptants revealed unexpectedly small changes in messenger RNA and proteins for most disruptants. Overall, metabolite levels were also stable, reflecting the rerouting of fluxes in the metabolic network. In contrast, E. coli actively regulated enzyme levels to maintain a stable metabolic state in response to changes in growth rate. E. coli thus seems to use complementary strategies that result in a metabolic network robust against perturbations.

This report describes 3 year old girl with the unusual presentation of polyarticular juvenile idiopathic arthritis (JIA) with anti-cyclic citrullinated peptide (anti-CCP) antibodies and a positive rheumatoid factor (RF). She was initially treated with a nonsteroidal anti-inflammatory drug (NSAID; ibuprofen) followed by methotrexate (MTX, 10 mg/m2/week) and prednisolone (0.25 mg/kg/day), but these treatments were ineffective. Administration of tocilizumab, a humanized antihuman interleukin-6 receptor monoclonal antibody, promptly improved her clinical manifestations, and she has been in complete remission (DAS28