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Phytochemical investigation on the aerial parts of Lysionotus pauciflorus Maxim. (Gesneriaceae), a medicinal plant used in Guangxi Zhuang Autonomous Region, China, resulted in the isolation of 13 secondary metabolites including two methoxyflavones, six flavonoid glycosides, and five caffeoyl phenylethanoid glycosides. Among these, the chemical structures of previously undescribed metabolites (1-3) were elucidated to be nevadensin 7-O-β-D-glucopyranosyl-(1 → 2)-β-D-glucopyranoside (1), nevadensin 7-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside (2), and 2-(3,4-dihydroxyphenyl)ethyl-1-O-β-D-apiofuranosyl-(1 → 4)-α-L-rhamnopyranosyl-(1 → 3)-β-D-(6'-O-E-caffeoyl)glucopyranoside (3) by detailed spectroscopic and HPLC analyses. Inhibitory activity of isolated compounds against RSL3-induced ferroptosis on human hepatoma Hep3B cells were evaluated., (© 2024. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)

Phytochemical study on the flowers of Hypericum formosanum Maxim. (Hypericaceae) led to the isolation of formohyperins G-L (1-6), whose structures were assigned by detailed spectroscopic analysis. Formohyperins G-L (1-6) are new benzoylphloroglucinols substituted by a C 10 unit, a prenyl group, and a methyl group. Formohyperins G-J (1-4) possess a 6/6/6-tricyclic structure, while formohyperins K (5) and L (6) have a unique 6/6/5/4-tetracyclic structure consisting of cyclohexadienone, dihydropyrane, cyclopentane, and cyclobutane rings. The absolute configurations of 1-6 were deduced by analysis of the ECD spectra. Formohyperins G-J (1-4) and L (6) were found to show potent inhibitory activities against IL-1β release from LPS-treated murine microglial cells with EC 50 values of 5.0, 10.9, 6.3, 10.8, and 13.7 µM, respectively, without cytotoxicity. 6-O-Methylformohyperins G (1a) and I (3a) also exhibited the inhibitory activities with EC 50 values of 4.7 and 2.7 µM, respectively, although they were cytotoxic against microglial cells., (© 2024. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)

Large dissymmetry factor of the circularly polarized luminescence (g CPL ) was observed in ligand and coordination tuned chiral tetrakis europium (Eu(III)) complexes with ammonium cations. The g CPL value was estimated to be -1.54, which is the largest among chiral luminescent molecules. Through photophysical measurements, single crystal X-ray structural analyses and quantum chemical calculations, changes in the geometric and electronic structures were observed for a series of chiral tetrakis Eu(III) complexes which enhanced the g CPL value. The emission quantum yield and photosensitized energy transfer efficiencies of chiral Eu(III) complexes with ammonium cations were also larger than those of chiral Eu(III) complex with Cs + . Based on the systematic modifications and analyses for chiral tetrakis Eu(III) complex, effect of the ammonium cation on enhanced CPL brightness is reported., (© 2024 Wiley-VCH GmbH.)

Although many neuroimaging studies have evaluated changes in the prefrontal cortex during mindfulness-based interventions, most of these studies were cross-sectional studies of skilled participants or involved pre-post comparisons before and after a single session. While functional near-infrared spectroscopy is a useful tool to capture changes in the hemodynamic response of the prefrontal cortex during continuous mindfulness-based intervention, its ability to detect the accumulated effects of continuous mindfulness-based intervention is currently unclear. We investigated whether a 12-wk online mindfulness-based intervention changed the hemodynamic response of the prefrontal cortex during a verbal fluency task. Eighty-two healthy university students were randomly allocated to a 12-wk online mindfulness-based intervention group or a wait-list control group. The integral values of oxygenated hemoglobin measured using functional near-infrared spectroscopy before and after the intervention were compared to the values in the wait-list group. The intervention condition showed significantly greater functional near-infrared spectroscopy signal activation than the control condition; however, the effect sizes before and after the intervention were small. Thus, continuous mindfulness-based intervention could alter prefrontal cortex function, and functional near-infrared spectroscopy could be useful for measuring the accumulated effects of continuous mindfulness-based interventions. With a better understanding of the association between mindfulness and functional near-infrared spectroscopy signals, functional near-infrared spectroscopy can be used for biofeedback analyses., (© The Author(s) 2024. Published by Oxford University Press.)

There is a strong demand for efficient second harmonic generation (SHG) in ultra-intense short-pulse lasers. This paper demonstrates the generation of an unconverted fundamental (1ω)+second harmonics (2ω) mixed laser on the LFEX laser system. The experimental setup utilizes 0.5 mm-thick LBO crystal plates in a focusing beams implemented after an off-axis parabola, the design reduces the size and cost of the SHG system. The LFEX laser beams with four-beams combined energy of 222 J and a pulse duration of 1.5 ps, is successfully converted to 102 J of 2ω light and 100 J of unconverted 1ω light, 20 J is lost through surface reflections, and they are mixed at the focal point. Verification of successful SHG is confirmed through X-ray pinhole imaging and electron spectrometry. This novel technique is not limited to LFEX lasers and holds applicability for various ultra-intense lasers. Consequently, this accomplishment significantly contributes to expanding the capability for high-energy density laser-plasma experiments.

The frequency of cardiac amyloidosis potentially present in patients with atrial fibrillation (AF) remains unclear. The purpose of this study is to determine the frequency and clinical characteristics of cardiac amyloidosis latent in AF by performing cardiac magnetic resonance imaging (MRI) in patients scheduled for AF ablation. We retrospectively analyzed 193 consecutive patients who underwent CA and cardiac MRI for atrial fibrillation. The primary endpoint of the study was the frequency of histologically confirmed cardiac amyloidosis or suspected cardiac amyloidosis [positive imaging findings on cardiac MRI strongly suspecting cardiac amyloidosis (diffuse subendocardial late gadolinium enhancement or MRI-derived extracellular volume of > 0.40)]. Among the 193 patients, 8 were confirmed or suspected cases of cardiac amyloidosis, representing a frequency of 4% (8/193 patients). Multivariate analysis identified interventricular septal thickness at end-diastole (LVSd) as an independent and significant predictor of cardiac amyloidosis (OR: 1.72, 95% CI 1.12-2.87, p = 0.020).The optimal cut-off value for IVSd was determined to be > 12.9 mm based on the Youden index. At this cut-off, the sensitivity was 75.0% (95% CI 34.9-96.8%) and the specificity was 92.3% (95% CI 87.4-95.7%), allowing for the identification of patients with definite or suspected cardiac amyloidosis. The frequency of confirmed and suspected cases of cardiac amyloidosis among patients with an IVSd > 12.9 mm was 30% (6/20 patients). In addition, prevalence of biopsy-proven cardiac amyloidosis was 10% (2/20). The prevalence of cardiac amyloidosis in atrial fibrillation patients scheduled for ablation with cardiac hypertrophy is not negligible., Competing Interests: Declarations. Conflict of interest: All authors have no conflict of interest regarding this study., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Background: Epicardial connections from surrounding structures to the right pulmonary vein (PV) antrum impede PV isolation., Objective: This study aimed to evaluate the efficacy of an ablation approach targeting epicardial connections for right PV isolation., Methods: We prospectively enrolled 124 patients with atrial fibrillation undergoing initial PV isolation. We identified the activation breakthrough into the right PV antrum (BT-RPV) on the activation map created during high right atrial pacing before PV isolation. BT-RPV sites were targeted when right PV isolation was not achieved by wide antral circumferential ablation (WACA)., Results: BT-RPV was observed in 83 patients (67%). PV isolation was achieved by WACA in all 41 patients without BT-RPV. Among patients with BT-RPV, PV isolation was achieved by WACA in 48 patients when all BT-RPV sites were covered by the PV isolation line. Conversely, PV isolation was completed by WACA in only 5 of 35 patients when not all BT-RPV sites were covered. In patients where WACA failed, 35 sites were targeted for BT-RPV ablation. Initial BT-RPV ablation led to PV isolation at 20 sites, while the remaining 15 BT-RPV sites required repeat BT-RPV ablation. The ablated area of successful BT-RPV ablation was 0.9 (0.6-1.2) cm 2 , corresponding to the area activated within 15 (14-16) ms after BT-RPV emergence. Ablating the area activated within 14 ms of BT-RPV emergence was associated with successful PV isolation (sensitivity 91%; specificity 100%)., Conclusion: Ablation targeting BT-RPV sites is effective for right PV isolation. Extensive ablation is required to eliminate BT-RPV., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Mental health problems among workers cause enormous losses to companies in Japan. However, workers have been considered to have limited access to psychological support because of time constraints, which makes it difficult for them to engage in face-to-face psychological support interventions., Objective: This study aimed to present an intervention protocol that describes a randomized controlled trial to examine whether brief guided mindfulness meditation (MM) or self-compassion meditation (SCM) provided by a smartphone app is effective for mental health and work-related outcomes among workers., Methods: This is an open-label, 3-arm randomized controlled trial. The participants will be recruited through an open call on relevant websites with the following inclusion criteria: (1) employees who are working more than 20 hours per week, (2) between the ages of 18 and 54 years, (3) not on a leave of absence, (4) not business owners or students, and (5) not currently diagnosed with a mental disorder and have a Kessler Psychological Distress Scale-6 score below 13 points. We will include 200 participants and randomly assign them to an SCM course (n=67), an MM course (n=67), and a waitlist group (n=66). The intervention groups (SCM and MM) will be instructed to engage in daily guided self-help, self-compassion, and MMs lasting 6-12 minutes per day over 4 weeks. Primary outcomes will include psychological distress and job performance, and secondary outcomes will include somatic symptoms, cognitive flexibility, self-esteem, self-compassion, perceived stress, well-being, emotion regulation, work engagement, anger, psychological safety, and creativity. All procedures were approved by the ethics committee of the University of Tokyo (22-326). All participants will be informed of the study via the websites, and written informed consent will be collected via web-based forms., Results: The recruitment of participants began in December 2022, and the intervention began in January 2023. As of September 2023, a total of 375 participants have been enrolled. The intervention and data collection were completed in late October 2023., Conclusions: This study will contribute to the development of effective self-care intervention content that will improve mental health, work performance, and related outcomes and promote mindful and self-compassionate attitudes when faced with distress., Trial Registration: University Hospital Medical Information Network Clinical Trials Registry UMIN000049466; https://tinyurl.com/23x8m8nf., International Registered Report Identifier (irrid): DERR1-10.2196/53541., (©Takumu Kurosawa, Koichiro Adachi, Ryu Takizawa. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 15.07.2024.)

Purpose: The left atrial posterior wall (LAPW) can be a target for atrial fibrillation (AF) catheter ablation but is sometimes difficult to completely isolate due to the presence of endocardial-epicardial connections. We aimed to investigate the incidence and distribution of epicardial residual connections (epi-RCs) and the electrogram characteristics at epi-RC sites during an initial LAPW isolation., Methods: We retrospectively studied 102 AF patients who underwent LAPW mapping before and after a first-pass linear ablation along the superior and inferior LAPW (pre-ablation and post-ablation maps) using an ultra-high-resolution mapping system (Rhythmia, Boston Scientific)., Results: Epi-RCs were observed in 41 patients (40.2%) and were widely distributed in the middle LAPW area and surrounding it. The sites with epi-RCs had a higher bipolar voltage amplitude and greater number of fractionated components than those without (median, 1.09 mV vs. 0.83 mV and 3.9 vs. 3.4 on the pre-ablation map and 0.38 mV vs. 0.27 mV and 8.5 vs. 4.2 on the post-ablation map, respectively; P < 0.001). Receiver operating characteristic analyses demonstrated that the number of fractionated components on the post-ablation map had a larger area under the curve of 0.847 than the others, and the sensitivity and specificity for predicting epi-RCs were 95.4% and 62.1%, respectively, at an optimal cutoff of 5.0., Conclusions: Among the patients with epi-RCs after a first-pass LAPW linear ablation, areas with a greater number of fractionated components (> 5.0 on the post-ablation LAPW map) may have endocardial-epicardial connections and may be potential targets for touch-up ablation to eliminate the epi-RCs., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A 50-year-old woman underwent catheter ablation for atrial fibrillation. Preoperative computed tomography revealed a left-sided variant of the right top pulmonary vein (PV) and a persistent left superior vena cava. The right top PV was successfully isolated through a wide antral circumferential ablation line simultaneously with the right PVs., (© 2023 Wiley Periodicals LLC.)

Formohyperins A-F, previously undescribed meroterpenes, and grandone, a prenylated benzoylphloroglucinol being considered to be one of their biogenetic precursors, were isolated from the flowers of a Hypericaceous plant, Hypericum formosanum Maxim. Detailed spectroscopic analyses showed that formohyperins A-D were meroterpenes with an enolized 3-phenylpropane-1,3-dione moiety. Formohyperins E and F were elucidated as meroterpenes having a 4-benzoyl-5-hydroxycyclopent-4-ene-1,3-dione moiety. Formohyperins A-C and E were optically active, and their absolute configurations were deduced by comparison of the experimental and TDDFT calculated ECD spectra. In contrast, formohyperin D was concluded to be a racemate. Formohyperins A-F and grandone were found to show inhibitory activities against LPS-stimulated IL-1β production from murine microglial cells with EC 50 values of 13.2, 6.6, 8.5, 24.3, 4.1, 10.9, and 3.0 μM, respectively., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: The optimal slow pathway (SP) ablation site in cases with an inferiorly located His bundle (HIS) remains unclear., Methods and Results: In 45 patients with atrioventricular nodal reentrant tachycardia, the relationship between the HIS location and successful SP ablation site was assessed in electroanatomical maps. We assessed the location of the SP ablation site relative to the bottom of the coronary sinus ostium in the superior-to-inferior (SPSI), anterior-to-posterior (SPAP), and right-to-left (SPRL) directions. The HIS location was assessed in the same manner. The HIS location in the superior-to-inferior direction (HISSI), SPSI, SPAP, and SPRL were 17.7 ± 6.4, 1.7 ± 6.4, 13.6 ± 12.3, and -1.0 ± 13.0 mm, respectively. The HISSI was positively correlated with SPSI (R 2  = 0.62; P < .01) and SPAP (R 2  = 0.22; P < .01), whereas it was not correlated with SPRL (R 2  = 0.01; P = .65). The distance between the HIS and SP ablation site was 17.7 ± 6.4 mm and was not affected by the location of HIS. The ratio of the amplitudes of atrial and ventricular potential recorded at the SP ablation site did not differ between the high HIS group (HISSI ≥ 13 mm) and low HIS group (HISSI < 13 mm) (0.10 ± 0.06 vs. 0.10 ± 0.06; P = .38)., Conclusion: In cases with an inferiorly located HIS, SP ablation should be performed at a lower and more posterior site than in typical cases., (© 2024 Wiley Periodicals LLC.)

A counter-propagating laser-beam platform using a spherical plasma mirror was developed for the kilojoule-class petawatt LFEX laser. The temporal and spatial overlaps of the incoming and redirected beams were measured with an optical interferometer and an x-ray pinhole camera. The plasma mirror performance was evaluated by measuring fast electrons, ions, and neutrons generated in the counter-propagating laser interaction with a Cu-doped deuterated film on both sides. The reflectivity and peak intensity were estimated as ∼50% and ∼5 × 10 18 W/cm 2 , respectively. The platform could enable studies of counter-streaming charged particles in high-energy-density plasmas for fundamental and inertial confinement fusion research.

The shock ignition (SI) approach to inertial confinement fusion is a promising scheme for achieving energy production by nuclear fusion. SI relies on using a high intensity laser pulse (≈10 16 W/cm 2 , with a duration of several hundred ps) at the end of the fuel compression stage. However, during laser-plasma interaction (LPI), several parametric instabilities, such as stimulated Raman scattering and two plasmon decay, nonlinearly generate hot electrons (HEs). The whole behavior of HE under SI conditions, including their generation, transport, and final absorption, is still unclear and needs further experimental investigation. This paper focuses on the development of an experimental platform for SI-related experiments, which simultaneously makes use of multiple diagnostics to characterize LPI and HE generation, transport, and energy deposition. Such diagnostics include optical spectrometers, streaked optical shadowgraph, an x-ray pinhole camera, a two-dimensional x-ray imager, a Cu Kα line spectrometer, two hot-electron spectrometers, a hard x-ray (bremsstrahlung) detector, and a streaked optical pyrometer. Diagnostics successfully operated simultaneously in single-shot mode, revealing the features of HEs under SI-relevant conditions.

The sympathetic nervous system plays an important role in life-threatening ventricular arrhythmias (VAs). Bilateral cardiac sympathetic denervation (BCSD) is performed for refractory VAs. We sought to assess our institutional experience with BCSD in managing treatment-resistant monomorphic ventricular tachycardia (MMVT) in heart failure patients with a reduced ejection fraction (HFrEF).Four patients with HFrEF (EF 30.0 ± 8.2%, New York Heart Association [NYHA] class IV 1) underwent BCSD for MMVT (VT storm 3, repetitive VT requiring implantable cardioverter defibrillator [ICD] therapy 1) refractory to antiarrhythmic drugs, catheter ablation and ICD therapy. BCSD was effective for suppressing VT in 3 patients for whom deep sedation was effective for suppressing VT. One patient remained alive after 14 months of follow-up without episodes of VT. One patient died of acute myocardial infarction before discharge and 1 patient died from unknown cause at 3 days post-discharge. In contrast, BCSD was completely ineffective for suppressing VT in a patient with NYHA class IV for whom deep sedation and stellate ganglion block were ineffective. This patient died on the 10th post-CSD day, despite left ventricular assist device implantation. In all cases, BCSD was successfully performed without procedure-related complications.Despite the limited number of cases, our results showed that BCSD in patients with HFrEF suppressed refractory MMVT in acute-phase except for a patient with NYHA class IV; however, the prognoses were not good. BCSD may be a treatment option at an earlier stage of NYHA and a bridge to orthotopic heart transplantation, even if BCSD is effective for suppressing VAs.

Research on underrepresented groups in leadership has shown that women and ethnic minorities are preferred as leaders during a crisis. In the present study, we investigated factors that shape voter preferences for minority political leaders in the COVID-19 crisis. We examined participant perceptions of the severity of the COVID-19 crisis in health, social, and economic domains and self-reported political leaning, and their impact on preference for a female (vs male) or minority political leader. We collected survey data in autumn 2020 using online platforms in France, Japan, the United Kingdom, the United States, and a snowball sample in Germany (total N  = 1,259). Results showed that female leaders were generally more preferred by politically left- than right-leaning participants independent of severity perceptions of the social or economic crisis. In addition, we found that preference for female leaders amongst right-leaning participants increased when their current regional leader's actions were judged insufficient to manage the health crisis, an effect primarily driven by participants in Germany and the United Kingdom. Left-leaning political orientation also predicted the preference for minority leaders across countries. Moreover, a more severe perception of the social aspects of the crisis increased minority preference, as expected, but mostly in Germany and the United States. We discuss cross-country variation of our results. Overall, our findings affirm and expand prior research showing the importance of political leaning and changing leadership demands in a crisis and their impact on the preference for minority leaders., Competing Interests: 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., (© 2022 The Authors.)

Recent epidemiological studies reported cases of cholangiocarcinoma in workers exposed to 1,2-dichloropropane (1,2-DCP) in an offset proof printing factory in Japan. The present study investigated the effects of 1,2-DCP on the expression of histone family member X (H2AX) phosphorylated on Ser 139 (γ-H2AX), a marker of DNA double strand break, in human immortalized cholangiocytes MMNK-1 cells. Mono-cultures of MMNK-1 cells and co-cultures of MMNK-1 cells with THP-1 macrophages were exposed to 1,2-DCP at concentrations of 100 and 500 μM for 24 h. Expression of γ-H2AX was visualized by immunofluorescence staining. Exposure to 1,2-DCP had no effect on the expression of γ-H2AX in mono-cultured MMNK-1 cells, but significantly increased the number of nuclear foci stained by γ-H2AX in MMNK-1 cells co-cultured with THP-1 macrophages. Exposure to 1,2-DCP also significantly increased the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in co-cultured MMNK-1 cells. The results suggest that macrophages play a critical role by producing cytokines in 1,2-DCP-induced DNA double strand break in MMNK-1 cells., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The liverwort Marchantia polymorpha possesses oil bodies in idioblastic oil body cells scattered in its thallus. Oil bodies are subcellular organelles in which specific sesquiterpenes and bisbibenzyls are accumulated. Therefore, a specialized system for the biosynthesis and accumulation of these defense compounds specifically in oil bodies has been implied. A recent study on M. polymorpha genome sequencing revealed 10 genes that shared high similarities with fungal-type terpene synthases (TPSs). Eight of these fungal-type TPS-like genes in M. polymorpha (MpFTPSL1-6, -9 and -10) are located within a 376-kb stretch on chromosome 6 and share similarities of over 94% at the nucleotide level. Therefore, these genes have likely originated from recent gene duplication events. The expression of a subset of MpFTPSLs was induced under non-axenic growth on vermiculite, which increased the amounts of sesquiterpenes and number of oil bodies. The tdTomato fluorescent protein-based in-fusion reporter assay with MpFTPSL2 promoter revealed fluorescent signals specifically in oil body cells of the thallus, indicating that MpFTPSL2 functions in oil body cells. Recombinant MpFTPSL2 expression in Escherichia coli led to sesquiterpene synthesis from farnesyl pyrophosphate. Moreover, suppression of a subset of MpFTPSLs through RNA interference reduced sesquiterpene accumulation in thalli grown on vermiculite. Taken together, these results suggest that at least a subset of MpFTPSLs is involved in sesquiterpene synthesis in oil body cells., (� The Author(s) 2021. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

1,2-Dichloropropane (1,2-DCP), a synthetic chlorinated organic compound, was extensively used in the past in offset color proof-printing. In 2014, the International Agency for Research on Cancer (IARC) reclassified 1,2-DCP from its initial Group 3 to Group 1. Prior to the reclassification, cholangiocarcinoma was diagnosed in a group of workers exposed to 1,2 -DCP in an offset color proof-printing company in Japan. In comparison with other forms of cholangiocarcinoma, 1,2-DCP-induced cholangiocarcinoma was of early onset and accompanied by extensive pre-cancerous lesions in large bile ducts. However, the mechanism of 1,2-DCP-induced cholangiocarcinoma is poorly understood. Inflammatory cell proliferation was observed in various sites of the bile duct in the noncancerous hepatic tissues of the 1,2-DCP-induced cholangiocarcinoma. The aim of this study was to enhance our understanding of the mechanism of 1,2-DCP-related cholangiocarcinogenesis. We applied an in vitro system to investigate the effects of 1,2-DCP, using MMNK-1 cholangiocytes cultured alone or with THP-1 macrophages. The cultured cells were exposed to 1,2-DCP at 0, 0.1, 0.2, 0.4, and 0.8 mM for 24 h, and then assessed for cell proliferation, cell cytotoxicity, DNA damage, and ROS production. Exposure to 1,2-DCP increased proliferation of MMNK-1 cholangiocytes cultured alone, but not those cultured with macrophages. 1,2-DCP also increased LDH cytotoxicity, DNA damage, and ROS production in MMNK-1 cholangiocytes co-cultured with macrophages but not those cultured alone. 1,2-DCP increased TNFα and IL-1β protein expression in macrophages. The results highlight the role of macrophages in enhancing the effects of 1,2-DCP on cytotoxicity, ROS production, and DNA damage in cholangiocytes.

Objectives: We explored Japanese physicians' work-related stressors and identified those unique to this population, as well as clarified the influence of cultural and medical system diversity on these stressors to determine the content of future stress-reducing interventions for hospital physicians in Japan., Design: We conducted a semistructured, face-to-face interview-based qualitative study between August and October 2017. The collected data were analysed using the grounded theory approach., Setting: Hospitals around the Tokyo metropolitan area, Japan., Participants: Sixteen hospital physicians (mean age (SD)=33.9 (4.2) years; 11 men, 5 women). Seven worked in internal medicine and nine in surgery., Results: We found unique stressors related to the Japanese medical system and culture, such as continuous all-day work after night shifts, and a hierarchical organisational system called Ikyoku . The results also indicated that Japanese physicians shared several stressors with Western physicians, such as sleep deprivation, high pressure and the limits of medicine., Conclusions: Our study clarifies some sources of work-related stressors among hospital physicians in Japan. While the key components of Western interventions might be useful in a Japanese context, the original evidence obtained from this study highlights the necessity of initiating interventions addressing the unique stressors of Japanese physicians. To reduce physicians' stress and enhance their well-being, psychological interventions for hospital physicians must be introduced in Japan., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Chimney thoracic endovascular aneurysm repair (TEVAR) has advantages that include no requirements for special devices; however, problems have been identified such as gutter leaks. The aim of this study is to evaluate the short- and mid-term results of TEVAR with chimney technique including the safety, efficacy, and risk factors for occurrence of gutter endoleak in this technique., Methods: A retrospective single-center study was conducted on 55 consecutive patients who underwent first-time chimney TEVAR for arch aneurysms in the past 7 years. This consisted of 33 cases of single-chimney (SC) TEVAR and 22 cases of double-chimney (DC) TEVAR. The outcomes of these 55 cases of SC-TEVAR and DC-TEVAR were retrospectively examined. Risk factors for endoleaks in chimney TEVAR were also examined., Results: Operative mortalities of 3.0% and 4.5% were observed in SC-TEVAR and DC-TEVAR, respectively. Incidences of stroke were 12.1% in the SC-TEVAR and 4.5% in the DC-TEVAR, resulting in endoleaks in 16 patients (48.5%) in SC-TEVAR and 6 patients (27.3%) in DC-TEVAR. Only 1 of the 77 chimney grafts was occluded, with a patency rate of 98.7%. SC-TEVAR and small distance from the common carotid artery were the risk factors of type I endoleaks. Overall survival rates over a period of 1, 3, and 5 years were 82.3%, 78.0%, and 57.7%, respectively, in the SC-TEVAR group and 95.2%, 89.3%, and 76.5%, respectively, in the DC-TEVAR group. Freedom from aneurysm-related death over 1, 3, and 5 years was 82.3%, 69.0%, and 57.7%, respectively, in the SC-TEVAR group and 95.2%, 89.3%, and 89.3% in the DC-TEVAR group. Freedom from secondary intervention over 1, 3, and 5 years was 80.2%, 64.7%, and 47.2%, respectively, in the SC-TEVAR group and 95.0%, 74.0%, and 74.0%, respectively, in the DC-TEVAR group., Conclusions: The short- and mid-term results of chimney TEVAR were worse than expectation. Especially, the results of SC-TEVAR were not acceptable because of extremely high incidence of type I endoleak and high incidence of stroke., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Individuals who experience bullying victimization are at increased risk for future health and social problems. Despite this, studies show that not all bullying victims are in ill health, suggesting the importance of investigating protective factors that could counteract the adverse effects. The present study focused on investigating the moderating effects of emotional competence (EC) in the relationship between cyber-bullying victimization (CV) and mental health among adolescents., Methods: Responses from 6403 adolescents aged 12 to 18 (1925 male, 4478 female, M age  = 16.35, SD = 1.46) with no missing data were used for analysis. The cross-sectional data analyzed in the present study was a part of a large longitudinal online survey conducted by the University of Tokyo in Japan. Participants were recruited among adolescent users of a social networking service widely used in Japan for communication., Results: Results of regression analysis showed significant direct effects of CV on psychological distress/self-esteem, confirming the adverse effects of victimization. Results also suggested that high intrapersonal EC weakened the relationship between CV and psychological distress, whereas high interpersonal EC strengthened the relationship. There were no significant interactions between CV and EC in predicting self-esteem., Conclusions: Intrapersonal and interpersonal EC may play differential moderating roles in the relationship between CV and psychological distress, the former by buffering the effect and the latter by exacerbating it. Interventions targeting abilities to handle one's own emotions may help decrease distress among adolescents with CV experiences., Competing Interests: Declaration of competing interest None., (Copyright © 2020 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.)

Background: Percutaneous endovascular aortic repair (PEVAR) is widespread for the treatment of abdominal aortic aneurysm (AAA). The purpose of this study was to present outcomes of PEVAR using simultaneous angiography via microsheath., Methods: There were 100 punctures in 50 patients undergoing PEVAR for AAA. All cases used the ProGlide closure device (Abbot Vascular, Santa Clara, CA, USA) for PEVAR, and another puncture with microsheath placed on the common femoral artery for a second insertion point of the ProGlide. Basically, a single ProGlide was used for each puncture in the PEVAR. Hemostasis, stenosis, dissection, and distal embolization were confirmed in angiography via the adjunctive microsheath after removal of the delivery system. Since the PEVAR for AAA requires at least two punctures, this procedure was applied to both sites. Primary outcome was technical success and occurrence rates of access-related complications in PEVAR. Technical success was defined as complete hemostasis without surgical intervention and the need for conversion to general anesthesia., Results: Technical success was achieved in 98% (98/100) of the cases. Access-related complications on perioperative periods were identified in two cases. One case involved a tip of the microsheath being transected by the ProGlide that led to a distal embolization, which is why a cut down was required to retrieve the tip of the sheath. Another case required a cut down due to persistent hemorrhage from the puncture site of the microsheath. Although persistent hemorrhage was identified in five punctures (5.0%) via the adjunctive microsheath angiography, additional manual compression or ProGlide achieved complete hemostasis. Both stenosis and dissection following PEVAR were not identified in any case., Conclusions: A supporting angiography via microsheath in confirming the absence of hemorrhage, stenosis, dissection, and distal embolization may be worthwhile to selectively use for cases of PEVAR.

The Keio Twin Research Center (KoTReC) was established in 2009 at Keio University to combine two longitudinal cohort projects - the Keio Twin Study (KTS) for adolescence and adulthood and the Tokyo Twin Cohort Project (ToTCoP) for infancy and childhood. KoTReC also conducted a two-time panel study of self-control and psychopathology in twin adolescence in 2012 and 2013 and three independent anonymous cross-sectional twin surveys (ToTcross) before 2012 - the ToTCross, the Junior and Senior High School Survey and the High School Survey. This article introduces the recent research designs of KoTReC and its publications.

Recent studies have shown that microRNAs (miRNAs) play a role as regulators of neurodevelopment by modulating gene expression. Altered miRNA expression has been reported in various psychiatric disorders, including schizophrenia. However, the changes in the miRNA expression profile that occur during the initial stage of schizophrenia have not been fully investigated. To explore the global alterations in miRNA expression profiles that may be associated with the onset of schizophrenia, we first profiled miRNA expression in plasma from 17 patients with first-episode schizophrenia and 17 healthy controls using microarray analysis. Among the miRNAs that showed robust changes, the elevated expression of has-miR-223-3p (miR-223) was validated via quantitative reverse transcription-polymerase chain reaction (qRT-PCR) using another independent sample set of 21 schizophrenia patients and 21 controls. To identify the putative targets of miR-223, we conducted a genome-wide gene expression analysis in neuronally differentiated SK-N-SH cells with stable miR-223 overexpression and an in silico analysis. We found that the mRNA expression levels of four genes related to the cytoskeleton or cell migration were significantly downregulated in miR-223-overexpressing cells, possibly due to interactions with miR-223. The in silico analysis suggested the presence of miR-223 target sites in these four genes. Lastly, a luciferase assay confirmed that miR-223 directly interacted with the 3' untranslated regions (UTRs) of all four genes. Our results reveal an increase in miR-223 in plasma during both the first episode and the later stage of schizophrenia, which may affect the expression of cell migration-related genes targeted by miR-223.

Objective: Victimized adolescents have an increased risk of self-injurious thoughts and behaviors. However, poor understanding of causal and non-causal mechanisms underlying this observed risk limits the development of interventions to prevent premature death in adolescents. This study tested whether pre-existing family-wide and individual vulnerabilities account for victimized adolescents' increased risk of self-injurious thoughts and behaviors., Method: Participants were 2,232 British children followed from birth to 18 years of age as part of the Environmental Risk Longitudinal Twin Study. Adolescent victimization (maltreatment, neglect, sexual victimization, family violence, peer/sibling victimization, cyber victimization, and crime victimization) was assessed through interviews with participants and co-informant questionnaires at the 18-year assessment. Suicidal ideation, self-harm, and suicide attempt in adolescence were assessed through interviews with participants at 18 years., Results: Victimized adolescents had an increased risk of suicidal ideation (odds ratio [OR] 2.40, 95% CI 2.11-2.74), self-harm (OR 2.38, 95% CI 2.10-2.69), and suicide attempt (OR 3.14, 95% CI 2.54-3.88). Co-twin control and propensity score matching analyses showed that these associations were largely accounted for by pre-existing familial and individual vulnerabilities, respectively. Over and above their prior vulnerabilities, victimized adolescents still showed a modest increase in risk for suicidal ideation (OR 1.45, 95%CI 1.10-1.91) and self-harm (OR 1.50, 95% CI 1.18-1.91) but not for suicide attempt (OR 1.28, 95% CI 0.83-1.98)., Conclusion: Risk for self-injurious thoughts and behaviors in victimized adolescents is explained only in part by the experience of victimization. Pre-existing vulnerabilities account for a large proportion of the risk. Therefore, effective interventions to prevent premature death in victimized adolescents should not only target the experience of victimization but also address pre-existing vulnerabilities., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Long-term longitudinal studies are necessary to establish neuroimaging indicators which contribute to the detection of severity changes over time in patients with major depressive disorder (MDD)., Methods: One hundred sixty-five patients with MDD underwent clinical assessments and near-infrared spectroscopy (NIRS) examination at the initial evaluation (T0). After 1.5 years, 45 patients who visited for the follow-up evaluation (T1.5) were included in the analysis. The authors conducted analyses using the 17-item Hamilton Rating Scale for Depression (HAMD) scores and mean oxy-hemoglobin concentration ([oxy-Hb]) changes during a cognitive task in NIRS at T0 (T0&#95;HAMD, T0&#95;[oxy-Hb]) and at T1.5 (T1.5&#95;HAMD, T1.5&#95;[oxy-Hb]), and their intra-individual longitudinal changes (ΔHAMD = T1.5&#95;HAMD - T0&#95;HAMD, Δ[oxy-Hb] = T1.5&#95;[oxy-Hb] - T0&#95;[oxy-Hb])., Results: For severity-dependent regions, the Δ[oxy-Hb] in the right inferior frontal gyrus (IFG) was negatively correlated with the ΔHAMD. For severity-independent regions, the intra-class correlation coefficients between T0&#95; and T1.5&#95;[oxy-Hb] were moderate in the bilateral middle frontal gyri (MFG)., Limitations: The percentage of patients included in the follow-up examination was relatively small., Conclusions: Brain activation in the right IFG and the bilateral MFG as measured by NIRS may differentially indicate clinical severity and trait-related abnormalities in MDD., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Negative bias to sad emotional stimuli has repeatedly been identified as a cognitive feature of major depressive disorder, particularly in facial expression recognition. However, it is unknown how negative bias applies to facial expression recognition in individuals with depressive symptoms., Methods: A total of 58 university students' facial expression recognition and depression scores were measured using facial stimuli displaying the whole face, with 39 participants completing a 3-month follow-up assessment of depressive symptoms. We used an index that differentiates sensitivity to sadness from sensitivity to general facial expressions. Participants gave written informed consent after a complete description of the study., Results: The group with higher depressive symptoms showed a higher sensitivity to sadness than those with lower depressive symptoms, indicating a relationship between negative bias in facial expression recognition and nonclinical depressive symptoms. From a longitudinal point of view, negative bias to sad expressions at one time point was found to predict the change in depression scores at the 3-month follow-up., Limitations: Since the participants included only college students, the generalizability of our results to other populations is limited. The three-month interval may not be sufficient to determine the prognosis of depression, suggesting the need for further replications., Discussion: This study was the first to report the negative bias of facial expression recognition in individuals with nonclinical depressive symptoms. Given that negative bias predicts present and future depression, facial expression recognition has the potential to be used as a screening tool for early detection of depression., (Copyright © 2018. Published by Elsevier B.V.)

Background: The aim of this study was to evaluate endovascular treatment for enlarged Stanford type B chronic aneurysmal aortic dissection (CAAD). The conventional treatment for CAAD is open repair; however, the operative mortality is high in extensive prosthetic graft replacements., Methods: A retrospective single-center study was conducted on 74 consecutive patients who underwent endovascular treatment for CAAD in the past 8.5 years. In the partial exclusion (PE) group, entry sites in close proximity to the maximum diameter of CAAD were closed using a stent graft and reentry sites were left without closure. In the complete exclusion (CE) group, we attempted to close all entry and reentry sites., Results: A total of 43 patients (PE group) and 31 patients (CE group) were included with mean ages of 59 and 63 years, respectively. Operative mortalities of 2.3% and 0% were observed in the PE and CE groups, respectively. Complete tear closure was successful in 17 of 31 patients (54.8%) in the CE group. In the PE group, complete thrombosis of the false lumen was achieved in only one case (2.3%). Freedom rates from reentry closure were 90.2%, 86.9%, and 78.2% at 1, 3, and 5 years, respectively. The diameter of the true lumen/aorta changed from 16.9/62.9 mm to 30.2/53.6 mm and from 13.7/55.1 mm to 25.8/51.0 mm in the aortic arch and descending thoracic aorta, respectively. The freedom rates from secondary intervention in successful and unsuccessful CE cases were 92.9% and 69.1%, respectively, at 1 year and 92.9% and 53.7%, respectively, at 3 years., Conclusion: Endovascular treatment for CAAD had favorable early and midterm outcomes.

Being bullied is associated with mental health problems in childhood, with increasing evidence of persisting negative impacts, and increased mental health service use, into adulthood. There are also impacts of bullying victimisation on employment, income and being in poverty, but little is known about the long-term economic impacts. We therefore aimed to estimate the most important economic consequences at age 50 of being bullied in childhood: to our knowledge this is the first study that does so. Using 1958 British birth cohort data collected in 1965, 1969, 1991, 2003 and 2008 (study samples size 7323-9242), we find substantial and durable individual and societal economic impacts four decades after the childhood bullying occurred. Both men and women who were bullied in childhood were less likely to be in employment and had accumulated less wealth in the form of home-ownership or savings than participants who were not bullied. Individual earnings from paid employment were lower for women who were bullied in childhood. Frequent bullying in childhood was also associated with higher societal employment-related costs for men and higher health service costs for women. Our findings underline the importance of preventing bullying in childhood and, as the consequences are so long-lasting and pervasive, supporting people still experiencing the negative consequences in the decades that follow., (Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.)

Objective: The genetic and environmental influences on prefrontal function in childhood are underinvestigated due to the difficulty of measuring prefrontal function in young subjects, for which near-infrared spectroscopy (NIRS) is a suitable functional neuroimaging technique that facilitates the easy and noninvasive measurement of blood oxygenation in the superficial cerebral cortices., Method: Using a two-channel NIRS arrangement, we measured changes in bilateral prefrontal blood oxygenation during a category version of the verbal fluency task (VFT) in 27 monozygotic twin pairs and 12 same-sex dizygotic twin pairs ages 5-17 years. We also assessed the participant's full-scale intelligence quotient (FIQ) and retrieved parental socioeconomic status (SES). Classical structured equation modeling was used to estimate the heritability., Results: The heritability of VFT-related brain activation was estimated to be 44% and 37% in the right and left prefrontal regions, respectively. We also identified a significant genetic contribution (74%) to FIQ, but did not to VFT task performance. Parental SES was not correlated with FIQ, task performance, or task-related prefrontal activation., Conclusions: This finding provides further evidence that variance in prefrontal function has a genetic component since childhood and highlights brain function, as measured by NIRS, as a promising candidate for endophenotyping neurodevelopmental disorders., (© 2018 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

Background: Bleeding from the thoracic aorta is potentially fatal in patients with advanced esophageal cancer. Thoracic endovascular aortic repair (TEVAR) was recently applied for aortic invasion by esophageal cancer. However, only a few case reports have been published. This study was performed to clarify the effectiveness and safety of TEVAR for patients with advanced esophageal cancer., Methods: We retrospectively reviewed 18 patients who underwent TEVAR for esophageal cancer. We also performed a literature search and reviewed 21 similar cases., Results: From 2007 to 2016, 10 patients were treated on an emergent basis for aortic hemorrhage (salvage group) and 8 patients underwent urgent prophylactic surgery (prophylactic group). Hemostasis was achieved in all cases. One (10%) patient in the salvage group died of aspiration pneumonia on postoperative day 1, while all patients in the prophylactic group survived for >1 month. The median survival period in the salvage and prophylactic group was 3.25 and 11.10 months, respectively. The longest survivor was still alive 9 years after TEVAR and chemoradiotherapy. No fatal adverse events or negative impacts on subsequent treatment for esophageal cancer occurred., Conclusions: TEVAR is feasible, safe, and effective in preventing fatal aortic hemorrhage secondary to esophageal cancer invasion, although it is palliative in most cases. Because the outcomes of emergent TEVAR after bleeding tended to be worse in the salvage than in prophylactic group, prophylactic TEVAR may be considered a viable treatment option for patients with aortic invasion by advanced esophageal cancer.

Aim: Research efforts aiming at neuroimaging-aided differential diagnosis for psychiatric disorders have been progressing rapidly. A previous multisite study has developed a supplementary diagnostic system using functional near-infrared spectroscopy (fNIRS) that can be easily applied to clinical settings. However, few neuroimaging biomarkers have been developed for the psychosis spectrum with various clinical stages., Methods: We employed the fNIRS as a clinical examination device for 143 participants, comprising 47 ultra-high risk for psychosis (UHR) individuals, 30 patients with first-episode psychosis (FEP), 34 patients with chronic schizophrenia (ChSZ), and 33 healthy controls, who were independent of the previous study. A 12-month follow-up measurement was also carried out on 34 UHR individuals (72%), 21 patients with FEP (70%), and 33 controls. The fNIRS algorithm variables used for classification were the intensity and timing of prefrontal activation following the start of the cognitive task as used in the previous multisite study., Results: The discrimination rate by timing of activation was modest but it became acceptable after adjusting confounding factors. Discrimination by intensity of activation was not improved by similar adjustment. A total of 63.8%, 86.7%, and 81.3% patients were classified as UHR, FEP, and ChSZ, respectively; and 85.1%, 86.7%, and 71.9% of patients in these groups, respectively, were classified as being on the psychosis spectrum. In the follow-up measurement, 88.2% of individuals with UHR and 95.0% of patients with FEP were successfully classified into the psychosis spectrum group., Conclusion: The fNIRS for supplementary clinical examination could be validly applied to differentiating people with the psychosis spectrum in various clinical stages. The fNIRS is a candidate biological marker for aiding diagnosis of psychosis spectrum in routine clinical settings., (© 2017 The Authors. Psychiatry and Clinical Neurosciences © 2017 Japanese Society of Psychiatry and Neurology.)

Background: Adults who were victims of childhood maltreatment tend to have poorer health compared with adults who did not experience abuse. However, many are in good health. We tested whether safe, supportive, and nurturing relationships buffer women with a history of childhood maltreatment from poor health outcomes in later life., Methods: Participants included women from the Environmental Risk (E-Risk) Longitudinal Twin Study who were involved in an intimate relationship at some point by the time their twin children were 10 years old. Women were initially interviewed in 1999-2000 (mean age = 33 years) and 2, 5, and 7 years later. They reported on their physical and mental health, and their health-risk behaviours., Results: Compared with women who did not experience abuse in childhood, women with histories of maltreatment were at elevated risk for mental, physical, and health-risk behaviours, including major depressive disorder, sleep, and substance use problems. Cumulatively, safe, supportive, and nurturing relationships characterized by a lack of violence, emotional intimacy, and social support buffered women with a history of maltreatment from poor health outcomes., Conclusions: Our findings emphasize that negative social determinants of health - such as a childhood history of maltreatment - confer risk for psychopathology and other physical health problems. If, however, a woman's current social circumstances are sufficiently positive, they can promote good health, particularly in the face of past adversity.

Background: Research supports robust associations between childhood bullying victimization and mental health problems in childhood/adolescence and emerging evidence shows that the impact can persist into adulthood. We examined the impact of bullying victimization on mental health service use from childhood to midlife., Method: We performed secondary analysis using the National Child Development Study, the 1958 British Birth Cohort Study. We conducted analyses on 9242 participants with complete data on childhood bullying victimization and service use at midlife. We used multivariable logistic regression models to examine associations between childhood bullying victimization and mental health service use at the ages of 16, 23, 33, 42 and 50 years. We estimated incidence and persistence of mental health service use over time to the age of 50 years., Results: Compared with participants who were not bullied in childhood, those who were frequently bullied were more likely to use mental health services in childhood and adolescence [odds ratio (OR) 2.53, 95% confidence interval (CI) 1.88-3.40] and also in midlife (OR 1.30, 95% CI 1.10-1.55). Disparity in service use associated with childhood bullying victimization was accounted for by both incident service use through to age 33 years by a subgroup of participants, and by persistent use up to midlife., Conclusions: Childhood bullying victimization adds to the pressure on an already stretched health care system. Policy and practice efforts providing support for victims of bullying could help contain public sector costs. Given constrained budgets and the long-term mental health impact on victims of bullying, early prevention strategies could be effective at limiting both individual distress and later costs.

Multichannel near-infrared spectroscopy (NIRS) is a functional neuroimaging modality that enables easy-to-use and noninvasive measurement of changes in blood oxygenation levels. We developed a clinically-applicable method for estimating resting state functional connectivity (RSFC) with NIRS using a partial correlation analysis to reduce the influence of extraneural components. Using a multi-distance probe arrangement NIRS, we measured resting state brain activity for 8min in 17 healthy participants. Independent component analysis was used to extract shallow and deep signals from the original NIRS data. Pearson's correlation calculated from original signals was significantly higher than that calculated from deep signals, while partial correlation calculated from original signals was comparable to that calculated from deep (cerebral-tissue) signals alone. To further test the validity of our method, we also measured 8min of resting state brain activity using a whole-head NIRS arrangement consisting of 17 cortical regions in 80 healthy participants. Significant RSFC between neighboring, interhemispheric homologous, and some distant ipsilateral brain region pairs was revealed. Additionally, females exhibited higher RSFC between interhemispheric occipital region-pairs, in addition to higher connectivity between some ipsilateral pairs in the left hemisphere, when compared to males. The combined results of the two component experiments indicate that partial correlation analysis is effective in reducing the influence of extracerebral signals, and that NIRS is able to detect well-described resting state networks and sex-related differences in RSFC., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aim: Neurofeedback has been studied with the aim of controlling cerebral activity. Near-infrared spectroscopy is a non-invasive neuroimaging technique used for measuring hemoglobin concentration changes in cortical surface areas with high temporal resolution. Thus, near-infrared spectroscopy may be useful for neurofeedback, which requires real-time feedback of repeated brain activation measurements. However, no study has specifically targeted neurofeedback, using near-infrared spectroscopy, in the frontal pole cortex., Methods: We developed an original near-infrared spectroscopy neurofeedback system targeting the frontal pole cortex. Over a single day of testing, each healthy participant (n = 24) received either correct or incorrect (Sham) feedback from near-infrared spectroscopy signals, based on a crossover design., Results: Under correct feedback conditions, significant activation was observed in the frontal pole cortex (P = 0.000073). Additionally, self-evaluation of control and metacognitive beliefs were associated with near-infrared spectroscopy signals (P = 0.006)., Conclusion: The neurofeedback system developed in this study might be useful for developing control of frontal pole cortex activation., (© 2016 The Authors. Psychiatry and Clinical Neurosciences © 2016 Japanese Society of Psychiatry and Neurology.)

Mismatch negativity (MMN) or its magnetic counterpart (magnetic mismatch negativity; MMNm) is regarded as a promising biomarker for schizophrenia. Previous electroencephalographic studies of MMN have demonstrated a moderate-to-high heritability for MMN amplitudes. N -methyl-D-aspartate receptor-dependent glutamatergic neurotransmission is implicated in MMN generation. We hypothesized that the differences between identical twins in MMNm variables might be associated with differences in plasma levels of amino acids involved in glutamatergic neurotransmission. Thirty-three pairs of monozygotic (MZ) and 10 pairs of dizygotic (DZ) twins underwent MMNm recording. The MMNm in response to tone duration changes, tone frequency changes, and phonemic changes was recorded using 204-channel magnetoencephalography. Of these, 26 MZ and 7 DZ twin pairs underwent blood sampling for determination of plasma amino acid levels. MMNm peak strength showed relatively high correlations in both MZ and DZ twin pairs. The differences in MMNm latencies tended to correlate with the differences in plasma amino acid levels within MZ pairs, while no significant correlation was observed after the Bonferroni correction. We observed a familial trait in MMNm strength. The differences in MMN latency in MZ twins might be influenced by changes in glutamate levels and glutamate-glutamine cycling; however, the results need to be replicated.

OBJECTIVE To compare expression, activity, and fecal concentration of intestinal alkaline phosphatase (IAP) between healthy dogs and dogs with chronic enteropathy (CE). ANIMALS 9 healthy university-owned Beagles and 109 healthy client-owned dogs (controls) and 28 dogs with CE (cases). PROCEDURES Cases were defined as dogs with persistent (> 3 weeks) gastrointestinal signs that failed to respond to antimicrobials and anti-inflammatory doses of prednisolone or dietary trials, did not have mechanical gastrointestinal abnormalities as determined by abdominal radiography and ultrasonography, and had a diagnosis of lymphoplasmacytic enteritis or eosinophilic gastroenteritis on histologic examination of biopsy specimens. Duodenal and colonic mucosa biopsy specimens were obtained from the 9 university-owned Beagles and all cases for histologic examination and determination of IAP expression (by real-time quantitative PCR assay) and activity (by enzyme histochemical analysis). Fecal samples were obtained from all dogs for determination of fecal IAP concentration by a quantitative enzyme reaction assay. RESULTS For dogs evaluated, IAP expression and activity were localized at the luminal side of epithelial cells in the mucosa and intestinal crypts, although both were greater in the duodenum than in the colon. Active IAP was detected in the feces of all dogs. Intestinal alkaline phosphatase expression and activity were lower for cases than for controls, and fecal IAP concentration for dogs with moderate and severe CE was lower than that for dogs with mild CE. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that dogs with CE had impaired IAP expression and activity. Additional research is necessary to elucidate the role of IAP in the pathogenesis of CE.

Recent studies have suggested that functional abnormalities in Broca's area, which is important in language production (speech and thoughts before speech), play an important role in the pathophysiology of schizophrenia. While multi-modal approaches have proved useful in revealing the specific pathophysiology of psychosis, the association of functional abnormalities with gray matter volume (GMV) here in subjects with an ultra-high risk (UHR) of schizophrenia, those with first-episode schizophrenia (FES), and healthy controls has yet to be clarified. Therefore, the relationship between cortical activity measured using functional near-infrared spectroscopy (fNIRS) during a verbal fluency task, and GMV in the Broca's area assessed using a manual tracing in magnetic resonance imaging (MRI), which considers individual structural variation, was examined for 57 subjects (23 UHR/18 FES/16 controls). The UHR and FES group showed significantly reduced brain activity compared to control group in the left pars triangularis (PT) (P=.036, .003, respectively). Furthermore in the FES group, the reduced brain activity significantly positively correlated with the volume in the left PT (B=0.29, P=.027), while significant negative association was evident for all subjects (B=-0.18, P=.010). This correlation remained significant after adjusting for antipsychotics dosage, and voxel-wise analysis could not detect any significant correlation between impaired cortical activity and volume. The significant relationship between neural activity and GMV in the left PT may reflect a specific pathophysiology related to the onset of schizophrenia., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objectives: The aim was to evaluate the current results of aortic arch aneurysm repair using inner branched endografts performed in three high volume aortic endovascular centers and to compare them to the pioneering global experience with this technology., Methods: Included patients underwent repair of aortic arch aneurysms >55 mm in diameter using inner branched endograft technology between April 2013 and November 2014. All patients were deemed unfit for open surgery. Inner branches were designed to perfuse the brachiocephalic trunk and the left common carotid artery in all cases. A left subclavian artery (LSA) revascularization was performed prior to the arch endovascular repair. Data were collected retrospectively in an electronic database. Parameters included length of procedure, fluoroscopy time, contrast volume, technical success, presence of endoleaks, early and late complications, and mortality., Results: Twenty-seven patients were included in the study. Technical success was achieved in all cases. No patients died during the 30 day post-operative period. Early neurologic events included two major strokes (7.4%) and one minor stroke (3.7%). Transient spinal cord ischemia with full recovery was observed in two patients (7.4%). Four patients (14.8%) underwent early (<30 day) re-interventions; these were for an access complication, an ischemic limb and exploration of the left ventricle through a sternotomy in two patients. During follow up (median 12 months), one patient (3.7%) died from a remote thoraco-abdominal aneurysm rupture. There were three Type 2 endoleaks (11.1%). Two re-interventions (7.4%) were performed, one to treat a Type 2 endoleak and one to treat a septic false aneurysm. A significant decrease in overall mortality was observed when comparing patients from the early experience with patients from the current report., Conclusions: The early outcomes associated with this technology are favorable. Branched endografting of aortic arch aneurysms should be considered in patients unfit for open surgery., (Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Methamphetamine abuse and dependence, frequently accompanied by schizophrenia-like psychotic symptoms [methamphetamine-associated psychosis (MAP)], is a serious public health problem worldwide. Few studies, however, have characterized brain dysfunction associated with MAP, nor investigated similarities and differences in brain dysfunction between MAP and schizophrenia. We compared prefrontal cortical activity associated with stop-signal inhibitory task in 21 patients with MAP, 14 patients with schizophrenia and 21 age- and gender-matched healthy controls using a 52-channel near-infrared spectroscopy (NIRS) system. Both the MAP and the schizophrenia groups showed significantly reduced activation in the bilateral ventrolateral prefrontal cortex compared with controls; however, only the MAP group showed reduced activation in the frontopolar prefrontal cortex. The MAP group demonstrated significant positive correlations between task performance and hemodynamic responses in the bilateral ventrolateral, polar and left dorsolateral regions of the prefrontal cortex. The MAP and schizophrenia groups demonstrated a significant difference in the relationship of impulsivity to hemodynamic changes in the bilateral premotor cortex. These findings characterize similarities and differences in prefrontal cortical dysfunction between psychosis associated with methamphetamine and schizophrenia. The reduced hemodynamic changes in the bilateral ventrolateral prefrontal cortex suggest a common underlying pathophysiology of MAP and schizophrenia, whereas those in the frontopolar prefrontal cortex point to an impaired state that is either inherent or caused specifically by methamphetamine use., (© 2015 Society for the Study of Addiction.)

Background: Few biomarkers can be used easily and noninvasively to measure clinical condition and future outcome in patients with first-episode psychosis (FEP). To develop such biomarker using multichannel functional near-infrared spectroscopy (fNIRS), cortical function in the prefrontal cortex was longitudinally measured during a verbal fluency task., Methods: Sixty-nine fNIRS measurements and 77 clinical assessments were obtained from 31 patients with FEP at baseline, 6-month, and 12-month follow-ups. Sixty measurements were obtained from 30 healthy controls matched for age, sex, and premorbid IQ. We initially tested signal changes for 12 months, and then investigated the relationship between fNIRS signals and clinical assessments., Results: Signal changes from baseline to 12-month follow-up were not evident in any group. Patients with FEP had significant positive correlation coefficients between 6-month fNIRS signals and the 12-month Global Assessment of Functioning (GAF) score in the left middle frontal gyrus (FDR-corrected p=.0016-.0052, r=.65-.59). fNIRS signals at the 12-month follow-up were associated with 12-month GAF score in the bilateral superior and middle frontal gyri (FDR-corrected p=.00085-.018, r=.72-.55), and with the difference between baseline and 12-month GAF scores in the right superior frontal gyrus (FDR-corrected p=.000067-.00012, r=.80-.78). These associations were significant even after controlling for demographic variables. No association between baseline fNIRS signals and later GAF scores was found., Discussion: fNIRS measurement can potentially be used as a biomarker to aid sequential assessment of neuro-clinical conditions through the early stage of psychosis., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Although methylphenidate hydrochloride (MPH) is a first-line treatment for children with attention-deficit hyperactivity disorder (ADHD), the non-response rate is 30%. Our aim was to develop a supplementary neuroimaging biomarker for predicting the clinical effect of continuous MPH administration by using near-infrared spectroscopy (NIRS). After baseline assessment, we performed a double-blind, placebo-controlled, crossover trial with a single dose of MPH, followed by a prospective 4-to-8-week open trial with continuous MPH administration, and an ancillary 1-year follow-up. Twenty-two drug-naïve and eight previously treated children with ADHD (NAÏVE and NON-NAÏVE) were compared with 20 healthy controls (HCs) who underwent multiple NIRS measurements without intervention. We tested whether NIRS signals at the baseline assessment or ΔNIRS (single dose of MPH minus baseline assessment) predict the Clinical Global Impressions-Severity (CGI-S) score after 4-to-8-week or 1-year MPH administration. The secondary outcomes were the effect of MPH on NIRS signals after single-dose, 4-to-8-week, and 1-year administration. ΔNIRS significantly predicted CGI-S after 4-to-8-week MPH administration. The leave-one-out classification algorithm had 81% accuracy using the NIRS signal. ΔNIRS also significantly predicted CGI-S scores after 1 year of MPH administration. For secondary analyses, NAÏVE exhibited significantly lower prefrontal activation than HCs at the baseline assessment, whereas NON-NAÏVE and HCs showed similar activation. A single dose of MPH significantly increased activation compared with the placebo in NAÏVE. After 4-to-8-week administration, and even after MPH washout following 1-year administration, NAÏVE demonstrated normalized prefrontal activation. Supplementary NIRS measurements may serve as an objective biomarker for clinical decisions and monitoring concerning continuous MPH treatment in children with ADHD.