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Water conformation around hydrophobic side chains of four amino acids (glycine, L-alanine, Laminobutyric acid, and L-norvaline) was investigated via changes in complex dielectric constant in the terahertz (THz) region. Each of these amino acids has the same hydrophilic backbone, with successive additions of hydrophobic straight methylene groups (-CH2-) to the side chain. Changes in the degree of hydration (number of dynamically retarded water molecules relative to bulk water) and the structural conformation of the water hydrogen bond (HB) network related to the number of methylene groups were quantitatively measured. Since dielectric responses in the THz region represent water relaxations and water HB vibrations at a sub-picosecond and picosecond timescale, these measurements characterized the water relaxations and HB vibrations perturbed by the methylene apolar groups. We found each successive straight -CH2 - group on the side chain restrained approximately two hydrophobic hydration water molecules. Additionally, the number of non-hydrogenbonded (NHB) water molecules increased slightly around these hydrophobic side chains. The latter result seems to contradict the iceberg model proposed by Frank and Evans, where water molecules are said to be more ordered around apolar surfaces. Furthermore, we compared the water-hydrophilic interactions of the hydrophilic amino acid backbone with those with the water-hydrophobic interactions around the side chains. As the hydrophobicity of the side chain increased, the ordering of the surrounding water HB network was altered from that surrounding the hydrophilic amino acid backbone, thereby diminishing the fraction of NHB water and ordering the surrounding tetrahedral water HB network. [ABSTRACT FROM AUTHOR]

Extreme temperatures are a major threat to the survival of ectotherms such as amphibians. The tree frogs belonging to the genus Buergeria have accomplished a latitudinal distribution and a wide range of thermal adaptations. In particular, Buergeria japonica , referred to as the "hot spring frog", has been reported to tolerate extremely high temperatures. However, it is unclear how the heat tolerance and metamorphic strategies of this species vary among populations at different temperatures. We therefore conducted long-term heat tolerance experiments on multiple populations of B. japonica tadpoles and their congenic species to determine their survivability and development speed. We observed heat tolerance differences between B. japonica/Buergeria choui and Buergeria buergeri. Buergeria japonica exhibited the highest tolerance among all species, and the Seranma hot spring population showed the highest survival rate and accelerated development speed. However, at temperatures higher than 35°C, they could not survive until the completion of metamorphosis, contrary to previous field observations. Our behavioral experiment showed attenuation of the high temperature preference of B. japonica tadpoles associated with developmental stages, suggesting that they can tolerate extreme temperatures for a limited time window during their development until metamorphosis.

Dopamine-secreting paragangliomas is known to be rare. The average annual incidence rate was reported 0.8 per 100,000 person-years. Approximately 1 to 2% of paragangliomas occur in the chest. We describe a patient with a large dopamine-secreting cardiac paraganglioma, right adrenal tumor and carotid body tumor. A 26-year-old man with progressive exertional dyspnea was referred to our hospital for further management of multiple paragangliomas. Positron emission tomography (PET) and PET-computed tomography (CT) detected those three legions. The diameter of cardiac paraganglioma was over 45 mm and was biggest among three tumors. Firstly, therefore, we planned cardiac paraganglioma resection. Through left lateral thoracotomy in the 4th intercostal space via, cardiac paraganglioma was resected under cardiopulmonary bypass and beating heart. Postoperative course was uneventful. Tumor cells were positive for synaptophysin and chromogranin A. Free metanephrines in the serum and urinary fractionated metanephrines normalized after cardiac surgery while the other two tumors remained untreated.

Background: Convolutional neural networks (CNNs) have emerged as a novel method for evaluating heart failure (HF) in adult electrocardiograms (ECGs). However, such CNNs are not applicable to pediatric HF, where abnormal anatomy of congenital heart defects plays an important role. ECG-based CNNs reflecting neurohormonal activation (NHA) may be a useful marker of pediatric HF. This study aimed to develop and validate an ECG-derived marker of pediatric HF that reflects the risk of future cardiovascular events., Methods: Based on 21,378 ECGs from 8324 children, a CNN was trained using B-type natriuretic peptide (BNP) and the occurrence of major adverse cardiovascular events (MACEs). The output of the model, or the electrical heart failure indicator (EHFI), was compared with the BNP regarding its ability to predict MACEs in 813 ECGs from 295 children., Results: EHFI achieved a better area under the curve than BNP in predicting MACEs within 180 days (0.826 versus 0.691, p = 0.03). On Cox univariable analyses, both EHFI and BNP were significantly associated with MACE (log10 EHFI: hazard ratio [HR] = 16.5, p < 0.005 and log10 BNP: HR = 4.4, p < 0.005). The time-dependent average precisions of EHFI in predicting MACEs were 32.4%-67.9% and 1.6-7.5-fold higher than those of BNP in the early period. Additionally, the MACE rate increased monotonically with EHFI, whereas the rate peaked at approximately 100 pg/mL of BNP and decreased in the higher range., Conclusions: ECG-derived CNN is a novel marker of HF with different prognostic potential from BNP. CNN-based ECG analysis may provide a new guide for assessing pediatric HF., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Since hydrothermal treatments can enhance resistant starch (RS) content in rice and provide health benefits when consumed, a less laborious and non-destructive method to determine RS content is needed. Terahertz (THz) spectroscopy is hypothesized as a suitable method to quantify RS content in rice after hydrothermal treatment with its sensitivity for the intermolecular forces increase in the formation of RS. In this study, we first used the traditional in vitro hydrolysis method to determine the content of RS in rice. Then, the potential of starch absorbance peaks to quantify RS content after three commonly used hydrothermal methods, soaking, mild heat-moisture treatment, and parboiling, was investigated. The second derivative intensities of the peak at 9.0, 10.5, 12.1, and 13.1 THz were confirmed as being correlated with RS content and showed the high accuracy to predict RS content in samples (R 2  > 0.96). Our results indicate the RS content of hydrothermally treated rice can be accurately quantified using these peaks., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Our study aimed to elucidate the role of different shunts and provide novel insights into optimal treatment approaches for complete transposition of the great arteries (TGA), which is characterized by unique and complicated circulatory dynamics. We constructed a computational cardiovascular TGA model and manipulated cardiovascular parameters, such as atrial septal defect (ASD) and patent ductus arteriosus (PDA) sizes, to quantify their effects on oxygenation and hemodynamics. In addition, ASD flow patterns were investigated as innovative indications for balloon atrial septostomy (BAS). Our model of TGA with an intact ventricular septum (TGA-IVS) showed that a large ASD can achieve sufficient mixing for survival without PDA, and the presence of PDA is detrimental to oxygen delivery. A treatment strategy for TGA-IVS that enlarges the ASD as much as possible by BAS and PDA closure would be desirable. In TGA with a ventricular septal defect (TGA-VSD), the VSD allows for higher oxygenation and reduces the detrimental effects of PDA on systemic circulation. In TGA-VSD, both strategies of enlarging the ASD by BAS with a closed PDA and adjusting the PDA in response to pulmonary vascular resistance (PVR) reduction without BAS may be effective. The simulated ASD flow patterns showed that the sharp peak left-to-right flow pattern in systole (σ-wave) reflected the hemodynamically significant ASD size, independent of PDA, VSD, and PVR. The ASD flow pattern visualized by Doppler echocardiography provides clinical insights into the significance of an ASD and indications for BAS, which are not readily apparent through morphological assessment. NEW & NOTEWORTHY Complete transposition of the great arteries (TGA) represents complex and unique circulation that is dependent on blood mixing through multiple interacting shunts. Consequently, the role of each shunt and the treatment strategy remain unclear. We developed a mathematical model of TGA circulation, revealing the significant influence of atrial septal defect (ASD) on oxygenation and hemodynamics. The blood flow pattern through the ASD reflects its hemodynamic impact and helps determine treatment strategies.

Survivors' adaptation to a suicide loss is likely influenced by their attitudes toward suicide and their respective sociocultural contexts. Our study aimed to compare suicide attitudes and their association with depressive symptoms and sense of community safety in Japanese and American suicide loss survivors. A total of 193 Japanese survivors and 232 American survivors completed online surveys. The results show that Japanese survivors tended not to consider suicide as an illness or to recognize that others understood their experience but were more likely than American survivors to consider suicide as justifiable. Regression analyses indicated that taking suicide as a right was associated with depressive symptoms. Further, their sense of being understood by others was positively correlated with perceived community safety in both samples, but justifying suicide and considering it to be an illness was positively related to perceived community safety only among Japanese survivors., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Invasive fungal infections (IFIs) represent a potentially fatal complication in patients who undergo allogeneic hematopoietic stem cell transplantation (HSCT) if the initiation of therapy is delayed. Some guidelines recommend antifungal prophylaxis or preemptive therapy for these patients depending on the risk of IFIs following allogeneic HSCT. This retrospective study aimed to identify the group of patients who safely undergo allogeneic HSCT with low-dose fluconazole (FLCZ) prophylaxis (100 mg/day)., Methods: We retrospectively reviewed 107 patients who underwent their first allogeneic HSCT at Nagoya City University Hospital from January 1, 2010, to December 31, 2019. We analyzed the efficacy of low-dose FLCZ prophylaxis and investigated the relationship between major risk factors and antifungal prophylaxis failure (APF) within 100 days post-transplant., Results: Of the 107 patients, 70 received low-dose FLCZ prophylaxis, showing a cumulative incidence of APF of 37.1% and a proven/probable IFI rate of 4.3%. There were no fungal infection-related deaths, including Aspergillus infections, in the FLCZ prophylaxis group. In a multivariable analysis, cord blood transplantation (CBT) (subdistribution hazard ratio (SHR), 3.55; 95% confidence interval (CI), 1.44-8.77; p = 0.006) and abnormal findings on lung CT before transplantation (SHR, 2.24; 95% CI, 1.02-4.92; p = 0.044) were independent risk factors for APF in the FLCZ prophylaxis group., Conclusion: Low-dose FLCZ prophylaxis is a useful and safe option for patients receiving allogeneic HSCT, except in those undergoing CBT or having any fungal risk features including history of fungal infections, positive fungal markers, and abnormal findings on lung CT before transplantation., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: There is a paucity of data regarding shorter life expectancy after aortic valve replacement (AVR) in patients with severe aortic stenosis (AS)., Methods: Among 3815 patients with severe AS enrolled in the CURRENT AS (Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe Aortic Stenosis) registry, there were 1469 patients (initial AVR: n = 647; conservative strategy: n = 822) with low surgical risk, 1642 patients (initial AVR: n = 433; conservative strategy: n = 1209) with intermediate surgical risk, and 704 patients (initial AVR: n = 117; conservative strategy: n = 587) with high surgical risk. Among 1163 patients who actually underwent surgical AVR as the initial strategy, patients were divided into 4 groups according to age <65 years (n = 185), 65 to 74 (n = 394), 75 to 80 (n = 345), and >80 (n = 239). The expected survival of the general Japanese population was obtained from the Statistics Bureau of Japan. The surgical risk was estimated using The Society of Thoracic Surgery (STS) score., Results: The median follow-up was 3.7 years. The cumulative incidences of all-cause death were significantly lower in the initial AVR strategy than in the initial conservative strategy across the 3 STS groups. Shorter life expectancy after surgical AVR was seen especially in younger patients. The observed mortality in low-risk patients was comparable to the expected mortality across all the age-groups, while intermediate-risk patients aged <75 years, and high-risk patients across all age-groups had higher mortality compared with the expected mortality., Conclusions: The risk stratification according to age and STS score might be useful to estimate shorter life expectancy after AVR, and these findings have implications for decision making in the choice of surgical or transcatheter AVR., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

To investigate the potential of Fourier-transform terahertz (FT-THz) spectroscopy to follow crystalline structure changes in rice starch after heat-moisture treatment (HMT), we measured the crystallinity by X-ray diffraction (XRD) spectra and found its correlation with THz spectra. According to A-type crystal structure and Vh-type crystalline structure of amylose-lipid complex (ALC) in rice starch, crystallinity is divided into A-type and Vh-type. The intensity of second derivative spectra peak at 9.0 THz was highly correlated with both A-type and Vh-type crystallinity. Additionally, other three peaks at 10.5 THz, 12.2 THz, and 13.1 THz were also sensitive to Vh-type crystalline structure. These results indicate that after HMT, the crystallinity of ALC (Vh-type) and A-type starch can be quantified using THz peaks., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

The mitochondrial genome (mt-genome) is one of the promising molecular markers for phylogenetics and population genetics. Recently, various mt-genomes have been determined rapidly by using massively parallel sequencers. However, the control region (CR, also called D-loop) in mt-genomes remain difficult to precisely determine due to the presence of repeat regions. Here, using Nanopore sequencing, we succeeded in rapid and collective determination of complete mt-genome of the hot-spring frog, Buergeria japonica, and found that its mt-genome size was 22,274 bp including CR (6,929 bp) with two types of tandem repeat motifs forming repeat regions. Comparison of assembly strategies revealed that the long- and short-read data combined together enabled efficient determination of the CR, but the short-read data alone did not. The B. japonica CR was longer than that of a congenic species inhabiting cooler climate areas, Buergeria buergeri, because of the long repeat regions in the former. During the thermal adaptation of B. japonica, the longer repeat regions in its CR may have accumulated within a period after divergence from B. buergeri., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Asaeda et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

A baby with complete atrioventricular block was born with a birth weight of 1403 g. Isoproterenol was ineffective and emergency pacing was required. Since transcutaneous pacing was ineffective and transvenous pacing was untenable due to small body size, transesophageal pacing was performed for 3.5 hours until permanent pacemaker implantation. There were no complications. This is the first report of continuous transesophageal pacing in a very-low-birth-weight infant.

Toward a comprehensive understanding of the mechanism of glycerol as a moisturizer, studies on the hydrogen-bond (HB) structure of hydration water, which is known to be disordered by glycerol, are insufficient. To this aim, we evaluated the HB configurations based on the HOH bending and OH stretching spectra of the hydration water from those of glycerol/water mixtures by subtracting the contributions of bulk water and glycerol using dielectric relaxation spectroscopy. Analysis of the HOH bending band showed that hydration water-donating HBs lose the intermolecular bending coupling with increasing glycerol by replacing the water-water HBs with water-glycerol HBs. The OH stretching band provided more detailed insight into the HB configuration, indicating that the double-donor double-acceptor and double-donor single-acceptor configurations in bulk water change to a predominantly double-donor single-acceptor configuration in hydration water around glycerol. The formation of more donor HBs than acceptor HBs may be due to the steric constrains by glycerol and/or differences in the partial charge on the oxygen atom between water and glycerol.

Although fish and its related products are good sources of protein and unsaturated fatty acids, like omega-3 in the human diet, their shelf-life is limited by biochemical and microbial changes. In this study, a front-face fluorescence spectroscopy technique was used to acquire Excitation-emission matrices (EEM) to monitor Japanese dace (Tribolodon hakonensis) fish freshness degradation during storage. EEM of Japanese dace fish parts (intact eyeball and surface-containing scales), excitation from 220 to 585 nm and emissions from 250 to 600 nm, were measured at different times during storage. To simplify the acquired complex spectra datasets from each fish part, the variables were reduced to those that were only significant/important (those with higher positive or negative correlation) for K value prediction, and as an index of freshness. Partial least square regression (PLSR) results demonstrated that combining the fluorescence EEM of the eyeball and surface-containing scales the best monitoring of fish freshness; excitation at 280 and 350 nm for both the eyeball and surface-containing scales, with 2.84 and 0.96 as RMSE and R 2 , respectively. These findings demonstrate that multiple excitation fluorescence approaches can be convenient for the freshness evaluation of fish., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

While bulk water and hydration water coexist in cells to support the expression of biological macromolecules, how the dynamics of water molecules, which have long been only a minor role in molecular biology research, relate to changes in cellular states such as cell death has hardly been explored so far due to the lack of evaluation techniques. In this study, we developed a high-precision measurement system that can discriminate bulk water content changes of ±0.02% (0.2 mg/cm 3 ) with single-cell-level spatial resolution based on a near-field CMOS dielectric sensor operating at 65 GHz. We applied this system to evaluate the temporal changes in the bulk water content during the cell death process of keratinocytes, called corneoptosis, using isolated SG1 (first layer of stratum granulosum) cells in vitro. A significant irreversible increase in the bulk water content was observed approximately 1 h before membrane disruption during corneoptosis, which starts with cytoplasmic high Ca 2+ signal. These findings suggest that the calcium flux may have a role in triggering the increase in the bulk water content in SG1 cells. Thus, our near-field CMOS dielectric sensor provides a valuable tool to dissect the involvement of water molecules in the various events that occur in the cell.

Background: The clinical significance of concomitant mitral regurgitation (MR) has not been well addressed in patients with severe aortic stenosis (AS)., Methods and results: We analyzed 3,815 patients from a retrospective multicenter registry of severe AS in Japan (CURRENT AS registry). We compared the clinical outcomes between patients with moderate/severe MR and with none/mild MR according to the initial treatment strategy (initial aortic valve replacement [AVR] or conservative strategy). The primary outcome measure was a composite of aortic valve-related death or heart failure hospitalization. At baseline, moderate/severe MR was present in 227/1,197 (19%) patients with initial AVR strategy and in 536/2,618 (20%) patients with a conservative strategy. The crude cumulative 5-year incidence of the primary outcome measure was significantly higher in patients with moderate/severe MR than in those with none/mild MR, regardless of the initial treatment strategy (25.2% vs. 14.4%, P<0.001 in the initial AVR strategy, and 63.3% vs. 40.7%, P<0.001 in the conservative strategy). After adjusting confounders, moderate/severe MR was not independently associated with higher risk for the primary outcome measure in the initial AVR strategy (hazard ratio [HR] 1.11, 95% confidence interval [CI] 0.67-1.83, P=0.69), and in the conservative strategy (HR 1.13, 95% CI 0.93-1.37, P=0.22)., Conclusions: Concomitant moderate/severe MR was not independently associated with higher risk for the primary outcome measure regardless of the initial treatment strategy.

Objective: Existing cross-sectional observational studies indicate that patients with multiple myeloma experience negative physical and psychological symptoms and low health-related quality of life. The study aim was to determine symptom prevalence, health-related quality of life and symptoms associated with health-related quality of life in patients with newly diagnosed multiple myeloma., Methods: This multicenter longitudinal cohort study was conducted in four hospitals in Japan. Patients with newly diagnosed multiple myeloma were asked to report their symptom intensity and health-related quality of life using validated questionnaires at three points: at diagnosis (T1), 1 month (T2) and 12 months after diagnosis (T3). Symptoms associated with health-related quality of life were explored using a mixed-effects model., Results: A total of 106 patients completed the assessment at T1. The symptoms more than 30% of patients reported were pain, disturbed sleep and distress at T1, pain, dry mouth, disturbed sleep and fatigue at T2, fatigue, numbness of tingling and pain and numbness or tingling at T3. Pain and depression were significantly associated with health-related quality of life negatively., Conclusions: The finding suggests that more than 30% of multiple myeloma patients suffered from pain and various symptoms and they received suboptimal palliative care within a year after starting initial chemotherapy. Pain and depression should be the main targets of interventions to improve health-related quality of life in this population., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Objective: We sought to evaluate contractile function in single-ventricle patients before and after imposition of Fontan physiology., Methods: Single right ventricle (SRV; n = 38) and single left ventricle (SLV; n = 11) patients underwent cardiac magnetic resonance imaging pre and post Fontan operation. Global radial strain (GRS), global circumferential strain (GCS), and global longitudinal strain were measured along with ejection fraction (EF) and atrioventricular valve regurgitation (AVVR)., Results: Age at cardiac magnetic resonance imaging before the Fontan operation was 3.1 ± 1.3 years and after the Fontan procedure was 5.8 ± 2.7 years. There were no significant EF differences between SRV and SLV patients before and after the Fontan procedure, and EF did not deteriorate significantly after the Fontan operation. GRS was significantly lower for SRV patients than for SLV patients before (24.3% vs 32.1%; P = .048) and after (21.8% vs 29.7%; P = .045) the Fontan procedure. GRS and GCS of the SRV patients deteriorated significantly after the Fontan operation (GRS, P = .01; GCS, P = .009). Strains showed positive correlations before and after the Fontan operation with positive correlations among each strain. Within all patients, strains correlated positively with EF. Strains and EF negatively correlated with AVVR (GRS P = .03, r = -0.22; GCS P = .03, r = -0.23; EF P < .001, r = -0.37)., Conclusions: Strains were lower for SRV than for SLV patients before and after the Fontan operation and deteriorated after the Fontan operation. Our study suggests that strain measures might detect ventricular deterioration earlier than EF. Because strains before and after the Fontan operation were positively correlated, and negatively correlated with AVVR, the early institution of myocardial protective therapy including AVVR management, especially for SRV patients, might have benefit., (Copyright © 2021 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

The stratum corneum (SC), the outermost epidermal layer, consists of nonviable anuclear keratinocytes, called corneocytes, which function as a protective barrier. The exact modes of cell death executed by keratinocytes of the upper stratum granulosum (SG1 cells) remain largely unknown. Here, using intravital imaging combined with intracellular Ca 2+ - and pH-responsive fluorescent probes, we aimed to dissect the SG1 death process in vivo. We found that SG1 cell death was preceded by prolonged (∼60 min) Ca 2+ elevation and rapid induction of intracellular acidification. Once such intracellular ionic changes were initiated, they became sustained, irreversibly committing the SG1 cells to corneocyte conversion. Time-lapse imaging of isolated murine SG1 cells revealed that intracellular acidification was essential for the degradation of keratohyalin granules and nuclear DNA, phenomena specific to SC corneocyte formation. Furthermore, intravital imaging showed that the number of SG1 cells exhibiting Ca 2+ elevation and the timing of intracellular acidification were both tightly regulated by the transient receptor potential cation channel V3. The functional activity of this protein was confirmed in isolated SG1 cells using whole-cell patch-clamp analysis. These findings provide a theoretical framework for improved understanding of the unique molecular mechanisms underlying keratinocyte-specific death mode, namely corneoptosis., Competing Interests: The authors declare no competing interest.

In this study, the growth of Escherichia coli was monitored using a complementary metal-oxide-semiconductor (CMOS) near-field sensor array. Each of the 1488 integrated elements, arranged in a 3 mm square, has a resonator that oscillates at 65 GHz. The effective capacitance of the resonator is altered by changes in the dielectric properties of the sensor surface, which shifts the resonance frequency. Growth curves of E. coli at different initial concentrations (OD 600  = 0.01, 0.03, and 0.05) were monitored. A suspension with initial turbidity of OD 600  = 0.05 was cultured in a medium, and the sensor successfully distinguished between viable E. coli and heat-treated dead E. coli in 20 min. Moreover, the apparent suppression of growth was observed in the presence of 500 μg/mL streptomycin. As the sensor is composed of arrayed elements, and the area of sensitivity distribution of the element is larger than the size of one bacteria, the variation in the output value of each element may reflect the number and movement of bacteria. This study revealed that the presence of viable E. coli could be rapidly confirmed by using the change in permittivity caused by the displacement of media by E. coli near the sensor surface., (Copyright © 2020 Elsevier B.V. All rights reserved.)

This study investigated the broadband terahertz and low-frequency Raman spectroscopy of liquid water (H 2 O, D 2 O, and H 2 18 O) over 2 decades of frequency to address long-standing challenges regarding the interpretation of the intermolecular stretching mode at around 5 THz. We experimentally demonstrated that the intermolecular stretching mode of liquid water obtained via terahertz spectroscopy is significantly redshifted and broadened compared with that via Raman. This result was rationalized by the enhanced dynamical collectivity probed by terahertz spectroscopy, although both have a common origin in the kinetic motion. Their temperature and isotope dependences emphasize the significance of oscillation mass in determining the intermolecular stretching lineshape, while quantum effects cannot be overlooked in both terahertz and low-frequency Raman spectra.

The biological functions of proteins depend on harmonization with hydration water surrounding them. Indeed, the dynamical transition of proteins, such as thermal denaturation, is dependent on the changes in the mobility of hydration water. However, the role of hydration water during dynamical transition is yet to be fully understood due to technical limitations in precisely characterizing the amount of hydration water. A state-of-the-art CMOS dielectric sensor consisting of 65 GHz LC resonators addressed this issue by utilizing the feature that oscillation frequency sensitively shifts in response to the complex dielectric constant at 65 GHz with extremely high precision. This study aimed to establish an analytical algorithm to derive the hydration number from the measured frequency shift and to demonstrate the transition of hydration number upon the thermal denaturation of human serum albumin. The determined hydration number in the native state drew a "global" hydration picture beyond the first solvation shell, with substantially reduced uncertainty of the hydration number (about ±1%). This allowed the detection of a rapid increase in the hydration number at about 55 °C during the heating process, which was in excellent phase with the irreversible rupture of the α-helical structure into solvent-exposed extended chains, whereas the hydration number did not trace the forward path in the subsequent cooling process. Our result indicates that the weakening of water hydrogen bonds trigger the unfolding of the protein structure first, followed by the changes in the number of hydration water as a consequence of thermal denaturation.

Background: The sociocultural context shapes attitudes toward suicide. Japanese literary works such as the Hagakure and the Bunraku Sonezaki-Shinju depict suicide as beautiful and honorable. Although suicide acceptance is likely to affect suicide rates and prevention efforts in Japan, studies in this area are limited. Aims: This study aimed to explore suicide acceptance and related factors among Japanese participants. Method: Using an Internet research company, questionnaires were distributed that measured acceptance of suicide, suicide stigma, mental health, an opinion on suicide prevention efforts, and demographic variables. Data from 2,051 participants were analyzed using t tests, analysis of variance (ANOVA), and hierarchical regression analysis. Results: We found a two-factor model (comprising beautification and justification factors) for the suicide acceptance scale and confirmed the scale's validity and reliability. The results showed significant differences in suicide acceptance by gender, age, educational level, employment status, and bereavement experience. A hierarchical regression analysis model revealed that suicide beautification was negatively related to positive opinion on suicide prevention efforts. Limitations: This study only focused on Japanese participants; therefore, further studies and cross-cultural comparisons are needed. Conclusion: The results revealed that suicide beautification was negatively associated with positive opinion on suicide prevention efforts after controlling for other variables.

To investigate the potential of terahertz spectroscopy to monitor and quantify starch in plants, terahertz spectra (3.0-13.5 THz) of mung bean plants 1-7 days after germination were examined and compared to those of starch and its constituent saccharides (standard reagents). Day 1 seedlings showed similar spectral features with standard starch, and absorption peaks gradually disappeared in the subsequent 6 day growth period. To interpret this result and identify useful peaks for starch quantification, standard starch and day 1 seedlings were hydrolyzed by α-amylase in vitro. Since both standard starch and seedlings showed that absorption peak at 9.0 THz disappeared after amylase hydrolysis, this peak is sensitive to changes in starch. Additionally, intensity of this peak was correlated with starch content as quantified by chemical analysis (r = 0.98). Our results indicate terahertz spectra of seedlings can provide an identifiable peak that is attributed to starch and not affected by the constituent saccharides., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: Liver fibrosis and cirrhosis are one of the critical complications in Fontan patients. However, there are no well-established non-invasive and quantitative techniques for evaluating liver abnormalities in Fontan patients. Intravoxel incoherent motion diffusion-weighted imaging with MRI is a non-invasive and quantitative method to evaluate capillary network perfusion and molecular diffusion. The objective of this study is to assess the feasibility of intravoxel incoherent motion imaging in evaluating liver abnormalities in Fontan children., Materials and Methods: Five consecutive Fontan patients and four age-matched healthy volunteers were included. Fontan patients were 12.8 ± 1.5 years old at the time of MRI scan. Intravoxel incoherent motion imaging parameters (D, D*, and f values) within the right hepatic lobe were compared. Laboratory test, ultrasonography, and cardiac MRI were also conducted in the Fontan patients. Results of cardiac catheterization conducted within one year of the intravoxel incoherent motion imaging were also examined., Results: In Fontan patients, laboratory test and liver ultrasonography showed almost normal liver condition. Cardiac catheter and MRI showed good Fontan circulation. Cardiac index was 2.61 ± 0.23 L/min/m2. Intravoxel incoherent motion imaging parameters D, D*, and f values were lower in Fontan patients compared with controls (D: 1.1 ± 0.0 versus 1.3 ± 0.2 × 10-3 mm2/second (p = 0.04), D*: 30.8 ± 24.8 versus 113.2 ± 25.6 × 10-3 mm2/second (p < 0.01), and f: 13.2 ± 3.1 versus 22.4 ± 2.4% (p < 0.01), respectively)., Conclusions: Intravoxel incoherent motion imaging is feasible for evaluating liver abnormalities in children with Fontan circulation.

Objective: Heterotaxy syndrome is associated with complex cardiac malformations and cardiac conduction system abnormalities. Those with right atrial isomerism (RAI) have dual sinus nodes and dual atrioventricular nodes predisposing them to supraventricular tachycardia (SVT). Those with left atrial isomerism (LAI) lack a normal sinus node and are at risk of sinus node dysfunction (SND) and atrioventricular block (AV block). We report the occurrence and risk factors associated with arrhythmias in heterotaxy syndrome., Methods: A retrospective review of all heterotaxy syndrome patients born and treated at our institution between 2000 and 2014 was performed., Results: A total of 40 patients were identified; 16/40 (40%) with LAI and 24/40 (60%) with RAI. There were 12 deaths during follow-up [LAI 3/16 (19%), RAI 9/24 (38%); p = 0.30]. Twenty-one patients had arrhythmias during a mean follow-up period of 5.4 years; 14/16 (87%) in LAI and 7/24 (29%) in RAI (p < 0.001). Freedom from arrhythmia at 1,3,5 years of age was 75.0%, 37.9%, 22.7% in LAI, and 83.3%, 77.5%, 69.6% in RAI, respectively(p = 0.00261). LAI had a three-fold increase in developing arrhythmias. Left atrial isomerism was the only factor identified to be associated with arrhythmia occurrence., Conclusions: Arrhythmias were commonly seen in heterotaxy syndrome particularly in left isomerism with more than half of the patients having arrhythmias by 3 years of age. Atrial situs was the only risk factor identified to be associated with arrhythmias, and close follow-up is warranted in these patients.

Aims: Tricuspid regurgitation (TR) has been reported to be associated with worse survival in various heart diseases, but there are few data in aortic stenosis (AS)., Methods and Results: In the Contemporary Outcomes after Surgery and Medical Treatment in Patients with Severe Aortic Stenosis (CURRENT AS) Registry enrolling 3815 consecutive patients with severe AS, there were 628 patients with moderate or severe TR (TR group) and 3187 patients with no or mild TR (no TR group). The study patients were subdivided into the initial aortic valve replacement (AVR) stratum (n = 1197) and the conservative stratum (n = 2618) according to treatment strategy. The primary outcome measure was a composite of aortic valve-related death or hospitalization due to heart failure. The 5-year freedom rate from the primary outcome measure was significantly lower in the TR group than in the no TR group (49.1% vs. 67.3%, P < 0.001). Even after adjusting for confounders, the excess risk of TR relative to no TR for the primary outcome measure remained significant [hazard ratio (HR): 1.25, 95% confidence interval (CI): 1.06-1.48; P = 0.008]. The trend for the excess adjusted risk in the TR group was consistent in the initial AVR and the conservative strata (HR 1.55, 95% CI: 0.97-2.48; P = 0.07; HR 1.22, 95% CI: 1.02-1.46; P = 0.03, respectively). In the initial AVR stratum, the 5-year freedom rate from the primary outcome measure was not different between the two groups with (n = 56) or without (n = 91) concomitant tricuspid annuloplasty (61.5% vs. 72.1%, P = 0.48)., Conclusion: The presence of clinically significant TR concomitant with severe AS is associated with a poor long-term outcome, regardless of the initial treatment strategy., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

Aim: Liver fibrosis caused by congestive hepatopathy has emerged as an important complication after Fontan procedure. We evaluated the utility of the hepatic vein (HV) waveform using Doppler ultrasound for identification of liver fibrosis in Fontan patients., Methods: We investigated the HV waveforms in 41 Fontan patients and assessed correlations with clinical parameters, liver fibrosis markers, and hemodynamic data., Results: Based on our preliminary analysis of 64 adult patients with chronic liver disease who underwent liver biopsy, we classified HV waveforms into five types with reference to the degree of flattening (from type 1, normal triphasic waveform; to type 5, a monophasic waveform indicating cirrhosis), and confirmed a significant correlation between waveform pattern and fibrosis stage. Notably, we detected HV waveforms in all of the Fontan patients and classified them into five types. The HV waveform pattern positively correlated with γ-glutamyl transferase and hyaluronic acid levels, and negatively correlated with albumin level and platelet count, but did not correlate with central venous pressure or brain natriuretic peptide level, suggesting that HV waveform could reflect pathophysiological changes in the liver without being affected by hepatic congestion. The highest area under the receiver operating characteristic curve of the HV waveform for detecting advanced liver fibrosis, as defined by ultrasonic findings and clinical features, was 0.829 (81.8% sensitivity, 73.3% specificity), which was higher than that of other non-invasive fibrosis markers., Conclusions: Hepatic vein waveforms change in accordance with liver fibrosis progression in Fontan patients, and can be a useful indicator of liver fibrosis after the Fontan procedure., (© 2018 The Japan Society of Hepatology.)

The Debye relaxation function is widely used to describe the large dielectric dispersion of ambient water around 20 GHz. However, from a theoretical point of view, this function is supposed to give incorrect predictions at high frequencies owing to the inappropriate assumption that inertial effects and intermolecular interactions do not affect the relaxation dynamics. Our ultrabroadband spectroscopy investigation of liquid water ranging from 500 MHz to 400 THz did demonstrate that the Debye function is inaccurate far above the microwave region. As an alternative, we tried a stochastic frequency modulation (SFM) model assuming instantaneous modification of the line shapes by the correlation with the surrounding system. The SFM relaxation model reproduced the experimental dielectric spectra up to 400 THz, showing that the hydrogen-bond dynamics are associated with the inertial effect that causes the non-exponential relaxation behaviour in a very short time (typically 25 fs). Within the framework of this relaxation model, the hindered translation modes are able to be approximated as fast modulation (homogeneous) line shapes because the interaction time with frequency modulation is too short. Compared with them, the libation mode is found to have a relatively slow modulation (inhomogeneous) origin, where disturbance of water hydrogen bonds induced by the hindered translations leads to fluctuations in the libration frequency.

Background: There is no large-scale study comparing postoperative mortality after aortic valve replacement (AVR) for asymptomatic severe aortic stenosis (AS) between initial treatment with AVR vs. eventual AVR after conservative management., Methods and results: We analyzed data from a multicenter registry enrolling 3,815 consecutive patients with severe AS. Of 1,808 asymptomatic patients, 286 patients initially underwent AVR (initial AVR group), and 377 patients were initially managed conservatively and eventually underwent AVR (AVR after watchful waiting group). Mortality after AVR was compared between the 2 groups. Subgroup analysis according to peak aortic jet velocity (Vmax) at diagnosis was also conducted. There was no significant difference between the 2 groups in 5-year overall survival (OS; 86.0% vs. 84.1%, P=0.34) or cardiovascular death-free survival (DFS; 91.3% vs. 91.1%, P=0.61), but on subgroup analysis of patients with Vmax ≥4.5 m/s at diagnosis, the initial AVR group was superior to the AVR after watchful waiting group in both 5-year OS (88.4% vs. 70.6%, P=0.003) and cardiovascular DFS (91.9% vs. 81.7%, P=0.023)., Conclusions: Asymptomatic severe AS patients who underwent AVR after watchful waiting had a postoperative survival rate similar to those who initially underwent AVR. In a subgroup of patients with Vmax ≥4.5 m/s at diagnosis, however, the AVR after watchful waiting group had worse postoperative survival rate than the initial AVR group.

Many cellular events are thought to be controlled by the temporal upregulation of multiple RNAs; the timing of the upregulation of these RNAs is not always the same. In this study, we first show that our light-directed intracellular RNA delivery method induced high concentrations of RNA in a short period. This effect was beneficial for the temporal control of cellular events by functional RNAs. Next, we stimulated the short-term upregulation of two different RNAs at different time points. Cytosolic delivery of a first RNA was induced by red light; thereafter, cytosolic delivery of a second RNA was induced by near-infrared light. The time difference between the introduction of the first and second RNA can be short (0.5-4 h) or long (>8 h). This strategy shows the potential for future applications of the deliberate control of time-dependent RNA concentration to guide various cellular functions by multiple RNAs.

Clostridium difficile infections (CDI) have recently increased worldwide. Some CDI progress to fulminant and recurrent CDI and are associated with high mortality and morbidity. CD produces toxins A and B, which cause intestinal mucosal damage, although toxin B exhibits greater cytotoxicity. Pepsin-treated lactoferrin (PLF) is the decomposed product of lactoferrin (LF), a multifunctional glycoprotein with anti-inflammatory properties. Here, we investigate the effects of LF and PLF in toxin B-stimulated rat intestinal epithelial (IEC-6) cells. Different toxin B concentrations were added to IEC-6 cells with or without LF or PLF. Mitochondrial function and cell cytotoxicity were assessed by measuring WST-1 and LDH levels, respectively. WST-1 levels were higher in IEC-6 cells treated with toxin B and LF or PLF than in the toxin B-only control (P < 0.05). Compared with the toxin B-only control, LDH levels significantly decreased after toxin B and LF or PLF addition (P < 0.05). Wound restitution measurement using microscopy demonstrated significantly greater levels of wound restitution in cells treated with toxin B and LF or PLF than in those treated with toxin B alone after 12 h (P < 0.001). Furthermore, changes in IEC-6 cell tight junctions (TJs) were evaluated by immunofluorescence microscopy and zonula occludens-1 (ZO-1) protein expression. When LF or PLF were added to IEC-6 cells, TJ structures were maintained, and ZO-1 and occludin expression was upregulated. Taken together, these results demonstrate that LF and PLF prevent the cytotoxicity of toxin B and might have the potential to control CDI.

Whether urea can serve as a kosmotrope or chaotrope has long been a topic of debate. In this study, broad-band THz spectroscopy (0.2-12 THz) of aqueous solutions of urea was used to characterize the hydration state and the hydrogen bond structure of water around urea. Three low-frequency vibration modes of urea were found around 2, 4, and above 12 THz. After eliminating the contribution of these modes, the "urea-vibration-free" complex dielectric constant was decomposed into the relaxation modes of bulk water and the oscillation modes of water. When hydration water is defined to be reorientationally retarded relative to bulk, our analysis revealed that the hydration number is 1.9 independent of urea concentrations up to 5 M, and this number is in close agreement with that of water constrained by strong acceptor hydrogen bonds of urea oxygen. Regarding the hydrogen bond structure, it was found that the tetrahedral-like water structure is mostly preserved (though the hydrogen bond lifetime is significantly shortened) but the population of non-hydrogen-bonded water molecules fragmented from the network is markedly increased, presumably due to urea's NH 2 inversion. These experimental results point to the coexistence of apparently two contradictory aspects of urea: dynamical retardation (the kosmotropic aspect) by the -CO group and slight structural disturbance (the chaotropic aspect) by the -NH 2 group.

We report the successful minimally invasive placement of a pericardial implantable cardioverter-defibrillator (ICD) in a 16-kg child. A transvenous ICD dual coil was advanced through a small subxiphoid incision and screwed into the oblique sinus pericardium under fluoroscopic guidance. An additional sense-pace lead was sutured onto the right ventricular apex, and the generator was placed in the upper abdominal wall through the same incision. Threshold testing demonstrated successful defibrillation at 15 J. After implantation, the patient had two episodes of appropriate shock for ventricular fibrillation. The ICD system continues to show stable impedance at 6 months of follow-up.

A total of 56 Japanese and 59 American survivor of suicide support group facilitators were asked to rank the mutual aid objectives of their groups following Shulman's scheme in terms of their frequency and importance. Both American and Japanese facilitators showed an emphasis on personal adaptation goals (such as helping bereaved feel less isolated in their grief or encouraging bereaved to share their coping with loss experiences) over collective goals (such as raising monies for more research on mental illness or trying to combat societal suicide stigma in their local communities). Differences were also noted with American facilitators evaluating helping with problem solving, sharing different ways of coping, viewing personal issues as societal problems, and advocating for promoting social change as significantly higher than the Japanese did. We believe some of these contrasts reflect differences in American and Japanese cultural values.

Background: There is discordance regarding the effect of symptom status before aortic valve replacement (AVR) on long-term outcome after AVR in severe aortic stenosis (AS).Methods and Results:The CURRENT AS registry is a multicenter retrospective registry enrolling 3,815 consecutive patients with severe AS. Among 1,196 patients managed with the initial AVR strategy, long-term clinical outcomes were compared between the symptomatic patients (n=905), and asymptomatic patients (n=291). Median follow-up interval was 1337 days with a 91% follow-up rate at 2 years. AVR was performed in 886 patients (98%) in the symptomatic group and in 287 patients (99%) in the asymptomatic group. Symptomatic patients were older and more often had comorbidities than asymptomatic patients with similar echocardiographic AS severity. The cumulative 5-year incidences of all-cause death and heart failure (HF) hospitalization were significantly higher in symptomatic patients than in asymptomatic patients (25.6% vs. 15.4%, P=0.001, and 14.2% vs. 3.8%, P<0.001, respectively). On landmark analysis at 30 days after AVR, the differences in mortality and HF hospitalization between the 2 groups were mainly observed beyond 30 days., Conclusions: When managed with the initial AVR strategy, the long-term outcomes of symptomatic severe AS were worse than those of asymptomatic severe AS. Early AVR strategy might be recommended in some selected asymptomatic severe AS patients with reasonable operative risk.

Modification of the water hydrogen bond network imposed by disaccharides is known to serve as a bioprotective agent in living organisms, though its comprehensive understanding is still yet to be reached. In this study, aiming to characterize the dynamical slowing down and destructuring effect of disaccharides, we performed broadband dielectric spectroscopy, ranging from 0.5 GHz to 12 THz, of sucrose and trehalose aqueous solutions. The destructuring effect was examined in two ways (the hydrogen bond fragmentation and disordering) and our result showed that both sucrose and trehalose exhibit an obvious destructuring effect with a similar strength, by fragmenting hydrogen bonds and distorting the tetrahedral-like structure of water. This observation strongly supports a chaotropic (structure-breaking) aspect of disaccharides on the water structure. At the same time, hydration water was found to exhibit slower dynamics and a greater reorientational cooperativity than bulk water because of the strengthened hydrogen bonds. These results lead to the conclusion that strong disaccharide-water hydrogen bonds structurally incompatible with native water-water bonds lead to the rigid but destructured hydrogen bond network around disaccharides. Another important finding in this study is that the greater dynamical slowing down of trehalose was found compared with that of sucrose, at variance with the destructuring effect where no solute dependent difference was observed. This discovery suggests that the exceptionally greater bioprotective impact especially of trehalose among disaccharides is mainly associated with the dynamical slowing down (rather than the destructuring effect).