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Three-dimensional measuring method of the material distribution of an all-solid-state lithium-ion battery (ASSLiB) cathode, by synchrotron radiation high-resolution X-ray computational tomography (nanotomography, nano-CT) and deep learning is proposed in this study. The cathode of the ASSLiB comprised materials with high X-ray absorption coefficients, such as LiCoO2 and LiNi0.5Co0.2Mn0.3O2. Such high absorption coefficients imparted difficulties in obtaining a high-resolution, high-contrast image and in identifying materials with conventional CT value method. The method proposed in this study was effective in acquiring a high-resolution image with fewer artifacts and measured the heavy materials at a high signal-to-noise ratio. We used deep learning with a customized U-net, enabling high accuracy and ultra-high-speed material identification. Using this method, constituent materials were successfully identified in three dimensions. This material identification technique showed great potential for application to other techniques such as focused ion beam–scanning electron microscopy.

Objective: In carotid artery stenting (CAS) for internal carotid artery stenosis, the stent is often selected according to the plaque properties and arterial tortuosity. In our institute, an open-cell stent is used as the first-line stent regardless of the characteristics of the lesion. This study was performed to examine the outcome of CAS with an open-cell stent as the real-world results., Methods: In total, 811 CAS procedures using open-cell stents were performed for internal carotid artery stenosis from April 2002 to December 2019. Of these patients, we excluded those with hyperacute conditions for which CAS was performed within 3 days of onset, those in whom acute mechanical thrombectomy was performed simultaneously with CAS, and those with stenosis due to arterial dissection. Thus, 734 patients were retrospectively analyzed. Perioperative and long-term outcomes and risk factors for perioperative infarction were investigated., Results: The periprocedural stroke rate and mortality rate were 3.7% (27/734) and 0.4% (3/734), respectively. Low-echoic plaque was a significant risk factor for periprocedural stroke in both univariate (P < 0.03) and multivariate (odds ratio, 2.69; 95% confidence interval, 1.14-6.66; P = 0.02) analyses. Cerebral infarction and high grade restenosis were observed in 15 (2.0%) and 17 (2.3%) patients during a median 50-month follow-up., Conclusions: CAS with open-cell stents showed good results in terms of both the postoperative stroke incidence and long-term severe restenosis rate. However, low-echoic plaque was a risk factor for perioperative stroke incidence, which should be considered when deciding on the indication for CAS with an open-cell stent., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background Aims: The administration of human cell-processed therapeutic products (hCTPs) is associated with a risk of tumorigenesis due to the transformed cellular contaminants. To mitigate this risk, these impurities should be detected using sensitive and validated assays. The digital soft agar colony formation (D-SAC) assay is an ultrasensitive in vitro test for detecting tumorigenic transformed cells in hCTPs., Methods: In this study, we first evaluated the colony formation efficiency (CFE) precision of tumorigenic reference cells in positive control samples according to a previously reported D-SAC assay protocol (Protocol I) from multiple laboratories. However, the CFE varied widely among laboratories. Thus, we improved and optimized the test protocol as Protocol II to reduce variability in the CFE of tumorigenic reference cells. Subsequently, the improved protocol was validated at multiple sites. Human mesenchymal stromal cells (hMSCs) were used as model cells, and positive control samples were prepared by spiking them with HeLa cells., Results: Based on the previously reported protocol, the CFE was estimated using an ultra-low concentration (0.0001%) of positive control samples in multiple plates. Next, we improved the protocol to reduce the CFE variability. Based on the CFE results, we estimated the sample size as the number of wells (Protocol II) and assessed the detectability of 0.0001% HeLa cells in hMSCs to validate the protocol at multiple sites. Using Protocol I yielded low CFEs (mean: 30%) and high variability between laboratories (reproducibility coefficient of variance [CV]: 72%). In contrast, Protocol II, which incorporated a relatively high concentration (0.002%) of HeLa cells in the positive control samples, resulted in higher CFE values (mean: 63%) and lower variability (reproducibility CV: 18%). Moreover, the sample sizes for testing were estimated as the number of wells per laboratory (314-570 wells) based on the laboratory-specific CFE (42-76%). Under these conditions, all laboratories achieved a detection limit of 0.0001% HeLa cells in hMSCs in a predetermined number of wells. Moreover, colony formation was not observed in the wells seeded with hMSCs alone., Conclusions: The D-SAC assay is a highly sensitive and robust test for detecting malignant cells as impurities in hCTPs. In addition, optimal assay conditions were established to test tumorigenic impurities in hCTPs with high sensitivity and an arbitrary false negative rate., Competing Interests: Declaration of Competing Interest KB, HA, EO and TY are employees of Sumitomo Pharma Co., Ltd.; MY is an employee of Astellas Pharma Inc.; MI, AK and OT are employees of Sumika Chemical Analysis Service Ltd.; TO and KZ are employees of Mediford Corporation; MT is an employee of Axcelead Drug Discovery Partners Inc.; TW is an employee of Takeda Pharmaceutical Company Limited.; TY is an employee of Daiichi Sankyo Company, Ltd. The original protocol of the D-SAC assay has been patented in Japan (Patent No. JP6421297B2 to SK and YS); however, no international application under the Patent Cooperation Treaty has been filed by the technology licensing agency in charge for unknown reasons., (Copyright © 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

A 50-year-old man presented with mild unconsciousness after a fall-induced head injury. Initial imaging revealed a left-sided acute subdural hematoma. After transportation to our hospital, his condition deteriorated, leading to the discovery of a new hemorrhage and an anterior falcine artery aneurysm upon further examination. The patient underwent successful decompressive craniectomy and endovascular occlusion. This case, the first reported of a traumatic anterior falcine artery aneurysm, suggests the initial injury caused both the hematoma and aneurysm. The aneurysm's specific location near the crista galli likely contributed to the formation of the traumatic aneurysm, and the compression of the left frontal lobe by the acute subdural hematoma caused the subsequent hemorrhage. This case highlights the importance of considering traumatic aneurysms in atypical postinjury hemorrhages and adds to the understanding of traumatic intracranial aneurysms' mechanisms., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: We aimed to clarify the risk factors for postoperative recurrence in patients with epidermal growth factor receptor (EGFR)-mutated stage I lung adenocarcinoma, using EGFR wild-type adenocarcinoma as a comparator, to select optimal candidates for adjuvant therapy with EGFR tyrosine kinase inhibitor (TKI)., Methods: Data of patients with pathologic stage I EGFR-mutated (n = 713) and wild-type (n = 673) adenocarcinoma who did not receive adjuvant therapy were retrospectively analyzed. The cumulative incidence of recurrence (CIR) was estimated using Gray's method, and multivariable Fine-Gray competing risk models identified independent risk factors associated with recurrence., Results: The CIR did not differ significantly between patients with EGFR-mutated and wild-type adenocarcinoma (P = .32). Multivariable analysis revealed that greater size (cm) of invasive tumor (hazard ratio 1.539; 95% CI, 1.077-2.201), lymphovascular invasion (hazard ratio 5.180; 95% CI, 2.208-12.15), pleural invasion (hazard ratio 3.388; 95% CI, 1.524-7.533), and high-grade histologic subtype (hazard ratio 4.295; 95% CI, 1.539-11.99) were independent risk factors for recurrence in patients with EGFR-mutated adenocarcinoma. The 5-year CIR was significantly higher among patients with these factors (tumor size greater than 2 cm, 15.9%; lymphovascular invasion, 26.9%; pleural invasion, 39.3%; and high-grade subtype, 44.4%) than among patients without them (4.4%, 2.2%, 3.9%, and 5%, respectively; P < .001). For patients with EGFR wild-type adenocarcinoma, independent risk factors for recurrence were invasive tumor size, lymphovascular invasion, and pleural invasion, but not histologic subtypes., Conclusions: Even for patients with EGFR-mutated stage I lung adenocarcinoma, recurrence risk is stratified. Adjuvant therapy may be considered if they have high-risk factors for recurrence., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

14-3-3 is a family of conserved proteins that consist of seven isoforms which are highly expressed in the brain, and 14-3-3 zeta(ζ) is one of the isoforms encoded by the YWHAZ gene. Previous studies demonstrated that 14-3-3ζ is deposited in the neurofibrillary tangles of Alzheimer's disease (AD) brains, and that 14-3-3ζ interacts with tau from the purified neurofibrillary tangles of AD brain extract. The present study examined the cerebrospinal fluid (CSF) 14-3-3ζ levels of 719 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI), including cognitively normal (CN) participants, patients with mild cognitive impairment (MCI) and patients with AD dementia, and aimed to identify whether CSF 14-3-3ζ is associated with tau pathology. CSF 14-3-3ζ levels were increased in AD, and particularly elevated among tau pathology positive individuals. CSF 14-3-3ζ levels were associated with CSF phosphorylated tau 181 (p-tau) (r = 0.741, P < 0.001) and plasma p-tau (r = 0.293, P < 0.001), which are fluid biomarkers of tau pathology, and could predict tau pathology positive status with high accuracy (area under the receiver operating characteristic curve [AUC], 0.891). CSF 14-3-3ζ levels were also correlated to synaptic biomarker CSF GAP-43 (r = 0.609, P < 0.001) and neuroinflammatory biomarker CSF sTREM-2 (r = 0.507, P < 0.001). High CSF 14-3-3ζ levels at baseline were associated with progressive decline of cognitive function and neuroimaging findings during follow up. In conclusion, this study suggests that CSF 14-3-3ζ is a potential biomarker of AD that may be useful in clinical practice., Competing Interests: Declaration of competing interest The authors declare that there are no known competing financial interests or personal relationships which could have been perceived as influencing the work presented in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Sleep consolidation into nighttime is considered the primary goal of sleep development in early infants. However, factors contributing to sleep consolidation into nighttime remain unclear., Aim: To clarify the influences of the light environment and nighttime co-sleeping on sleep consolidation into nighttime in early infants., Study Design: Cross-sectional study., Subjects and Methods: Sleep-wake time and light stimulation were measured in infants for 4 consecutive days using actigraphy. The infants' mothers were asked to complete a sleep events diary and a questionnaire about childcare, including "co-sleeping", defined as when the infant and mother slept on the same surface throughout the night., Outcome Measures: The data were analyzed with a focus on daytime and nighttime sleep parameters., Results: Daytime light stimulation reduced daytime "active sleep", tended to reduce daytime sleep, and increased daytime waking. Nighttime light stimulation reduced nighttime "quiet sleep" and nighttime sleep and increased nighttime waking. Co-sleeping reduced nighttime waking, and, as a result, nighttime sleep time and sleep efficiency increased. Co-sleeping reduced daytime sleep and tended to increase daytime waking. Consequently, co-sleeping tended to increase the ratio of nighttime sleep to daytime sleep., Conclusions: The present findings suggest that an appropriate light environment promotes daytime waking and nighttime sleep in early infants, but it does not contribute to sleep consolidation into nighttime by itself. On the other hand, co-sleeping may promote sleep consolidation into nighttime. Therefore, further methods for safe co-sleeping need to be established while avoiding risk factors for sudden unexpected death in infancy/sudden infant death syndrome., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The efficacy of adjuvant chemotherapy (ACT) in elderly patients with completely resected p-stage II-IIIA non-small-cell lung cancer (NSCLC) remains unclear because all previous randomized controlled trials on ACT have been conducted among patients aged <75 years. Thus, this study aimed to evaluate the effectiveness of ACT in elderly patients with completely resected NSCLC., Patients: We extracted the nationwide data of 812 patients aged ≥75 years who underwent lobectomy with mediastinal nodal dissection in 2010 and were diagnosed with p-stage II-IIIA NSCLC, from nationwide registry data accumulated in 2016., Methods: We classified the 812 patients into 2 groups based on the ACT administration status and analyzed the differences in their postoperative overall survival (OS)., Results: Overall, 295 patients received ACT (36.3%; group A), whereas 517 patients did not (63.70%; group N). Group A showed significantly better OS as a whole (hazard ratio [HR]: 0.650 [95% confidence interval {CI}: 0.526-0.804]), in the p-stage II subset (HR: 0.688 [95% CI: 0.513-0.925]), and p-stage IIIA subset (HR: 0.547 [95% CI: 0.402-0.743]) than group N. Even after propensity score matching, group A showed significantly better OS as a whole (HR: 0.626 [95% CI: 0.495-0.792]), in the p-stage II subset (HR: 0.690 [95% CI: 0.493-0.964]), and p-stage IIIA subset (HR: 0.554 [95% CI: 0.398-0.772]) than group N., Conclusion: ACT is recommended even in elderly patients with completely resected p-stage II-IIIA NSCLC. Hence, physicians should not avoid ACT in patients with completely resected NSCLC based solely on age., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The PACIFIC trial findings drastically changed the c-stage III non-small cell lung cancer (NSCLC) treatment strategy. However, it remains uncertain whether surgery is no longer needed for treatment. We aimed to evaluate the efficacy of surgery and explore the prognostic factors of better outcomes in surgery-treated patients than in PACIFIC regimen-treated patients., Patients and Methods: From 2010 to 2020, 107 patients with clinical N2-stage III NSCLC underwent lung resection in our institute. We analyzed and compared the yearly postoperative overall survival (OS) benchmarks of these patients to those of patients treated in the PACIFIC trial., Results: The 1-, 2-, 3-, 4-, and 5-year OS rates of patients were 87.7%, 73.9%, 64.9%, 58.2%, and 55.4%, respectively, all of which were superior to those of PACIFIC regimen-treated patients. However, patients with cT3/T4 tumors and skip, multistation, distant, and bulky N2 metastases, as well as those who underwent bronchoplasty, showed inferior results in several yearly benchmarks than in PACIFIC regimen-treated patients. Multivariate analyses conducted among factors mentioned above showed that cT3/T4 tumor was a worse prognostic factor for surgery-treated patients than for PACIFIC regimen-treated patients (hazard ratio [HR] 1.89, P = .036). Distant N2 metastasis was also a worse prognostic factor, although its effect was not statistically significant (HR 1.81, P = .082)., Conclusion: Surgery remains the mainstay of N2-positive c-stage III NSCLC treatment, and the PACIFIC regimen may be suitable only for patients with unresectable disease. However, surgery should be cautiously considered for patients with cT3/4 disease., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Several methods for chest drainage after pulmonary resection of malignant lung tumors exist, but consensus on the ideal method has not been reached., Methods: We conducted a multicenter prospective observational study. We enrolled 2200 patients who underwent lung resection for lung tumors. Of the 1470 patients who underwent anatomic resection, 347 showed air leak on the morning of postoperative day 1. They were assigned to 3 groups according to the chest drainage method on postoperative day 1., Results: Of 347 patients with postoperative air leaks, 107 (30.8%), 179 (51.6%), and 61 (17.6%) were assigned to water seal, continuous suction, and digital drainage, respectively. The median postoperative air leak duration was significantly longer with digital drainage (4.0 days) than with either water seal (2.5 days) or continuous suction (3.0 days; P = .009). Chest tubes were required for significantly more days on average with digital drainage (6.0 days) than with water seal (4.0 days) or continuous suction (4.0 days; P = .003). Prolongation of air leak duration was significantly more likely to occur in patients with body mass index <18.5 kg/m 2 (hazard ratio [HR], 1.6; 95% CI, 1.1-2.3), moderate or severe air leak on postoperative day 1 (HR, 2.0; 95% CI, 1.5-2.6), or digital drainage (HR, 1.4; 95% CI, 1.01-1.9)., Conclusions: Water seal was associated with significantly shorter duration of postoperative air leak and chest drainage compared with continuous suction and digital drainage., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

There are several patterns of epidemiological study in Japan. One is the international collaborative studies, such as Seven Countries Study, NI-HON-SAN Study, International Study of Salt and Blood Pressure (INTERSALT), International Study of Macro-and Micro-nutrients and Blood Pressure (INTERMAP), and Monitoring of Cardiovascular Disease (MONICA). The next one is the several cohort studies in Japanese unique surveys, such as Hisayama Study, Osaka-Akita Study, Tanno-Sobetsu Study, Suita Study, Ohazama Study, National Integrated Project for Prospective Observation of Noncommunicable Disease and Its Trends in the Aged (NIPPON DATA), Japan Collaborative Cohort (JACC), and Japan Public Health Center-Based Study (JPHC). Finally, some recent special meta-analysis in Japan are Japan Arteriosclerosis Longitudinal Study (JALS) and Evidence for Cardio-vascular Prevention from Observational Cohorts in Japan (EPOCH-JAPAN). The aim of this review is to introduce the history of epidemiologcal study, especially, cardiovascular epidemiology from the mid-20th century to in the early 21st century by dividing three patterns., Competing Interests: Declaration of competing interest We do not have any actual or potential conflict of interest including any financial, personal, or other relationships to disclose., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: To investigate if the pretreatment dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)-based radiomics machine learning predicts the pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer patients., Methods: Seventy-eight breast cancer patients who underwent DCE-MRI before NAC and confirmed as pCR or non-pCR were enrolled. Early enhancement mapping images of pretreatment DCE-MRI were created using subtraction formula as follows: Early enhancement mapping = (Signal 1 min - Signal pre )/Signal pre . Images of the whole tumors were manually segmented and radiomics features extracted. Five prediction models were built using five scenarios that included clinical information, subjective radiological findings, first order texture features, second order texture features, and their combinations. In texture analysis workflow, the corresponding variables were identified by mutual information for feature selection and random forest was used for model prediction. In five models, the area under the receiver operating characteristic curves (AUC) to predict the pCR and several metrics for model evaluation were analyzed., Results: The best diagnostic performance based on F-score was achieved when both first and second order texture features with clinical information and subjective radiological findings were used (AUC = 0.77). The second best diagnostic performance was achieved with an AUC of 0.76 for first order texture features followed by an AUC of 0.76 for first and second order texture features., Conclusions: Pretreatment DCE-MRI can improve the prediction of pCR in breast cancer patients when all texture features with clinical information and subjective radiological findings are input to build the prediction model., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: Studies on vulvar adenocarcinoma are lacking. Thus, we aimed to compare the characteristics and survival outcomes between vulvar adenocarcinoma and squamous cell carcinoma (SCC)., Methods: This was a preplanned sub-analysis of a previously organized nationwide retrospective observational study in Japan conducted between 2001 and 2010 (JGOG-1075S). Surgically treated women with stage I-IV vulvar invasive adenocarcinoma were compared to those with SCC. Multivariable analysis was performed to identify patient and tumor characteristics related to adenocarcinoma. Inverse probability of treatment weighting was used to balance the background differences, and a Cox proportional hazards regression model was fitted to estimate the effect of the histological type on survival., Results: Forty-eight women with adenocarcinoma were compared with 537 women with SCC. On multivariable analysis, women with adenocarcinoma were younger (median age, 64.5 vs. 70 years, adjusted odds ratio [OR] per age 0.975, 95% confidence interval [CI] 0.955-0.995, P = 0.016) and had higher positive surgical margin rates (31.2% vs. 18.4%, adjusted OR 2.376, 95% CI 1.188-4.754, P = 0.014) than those with SCC. However, according to the weighted model, the survival outcomes were comparable (hazard ratio for progression-free survival, 1.088, 95% CI 0.740-1.601, P = 0.667 and hazard ratio for overall survival, 1.008, 95% CI 0.646-1.573, P = 0.973). Similar associations were observed when the cohort was stratified by age (≤70 or >70 years), stage (I-II or III-IV), and surgical margin (negative or positive) (all, P > 0.05)., Conclusion: Vulvar adenocarcinoma is characterized by a younger age at diagnosis and higher positive surgical margin rates than SCC, but the survival outcomes are comparable., Competing Interests: Declaration of competing interest Honorarium, Chugai, Astra Zeneca (T.E.); research funding, Merck Sharp & Dorme (S.M.); honorarium, Chugai (K.M.)., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Elevated blood pressure is a major risk factor for cardiovascular (CV) disease. But the effects of sodium intake or excretion on CV mortality are uncertain. The present study aimed to investigate the association between 24 h urinary sodium excretion, as a marker of dietary salt intake, and CV or cancer mortality in a healthy Japanese population using 24 hurine collection., Methods: The baseline study was conducted in 1980. A total of 1291 participants aged 21 to 85 years, underwent health check-ups, which included blood chemistry measurements and the collection of 24 h urine samples. Enrolled 1291 participants were followed up for 27.5 years, in whom the final follow-up rate was 95.8%. Cox proportional hazards regression models were used to assess the association between 24 h urinary sodium excretion and CV or cancer mortality., Results: The mean 24 h urinary sodium excretion was 5.80 ± 2.28 g/day. There were 631 deaths: 153 (27%) from cancer, 142 (26%) from CV disease. In the Cox proportional hazard regression model after adjustment for confounding factors, systolic and diastolic blood pressures, and uric acid were positively associated with CV mortality, and the 24 h urinary sodium and potassium excretions were inversely associated with CV mortality (p < 0.05). On the other hand, there were no association between 24 h urinary sodium excretions and cancer mortality. We divided the urinary sodium excretions levels into quartiles. After adjustment for confounding factors, the hazard ratio of CV mortality in the highest quartile of 24 h urinary sodium excretion versus the lowest was 0.46 (p < 0.05). The cumulative survival rate for CV death was significantly decreased in the lowest quartile compared with the other higher groups., Conclusions: We found that impacts of 24 h sodium excretion on CV and cancer mortalities were much different in the general population., (Copyright © 2021. Published by Elsevier Ltd.)

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: Both homocysteine (Hcy) and asymmetric dimethylarginine (ADMA) induce endothelial dysfunction. However, the impact of both elevations on all-cause death is not known. We investigated the association between elevations of Hcy or ADMA and all-cause death in a general population., Methods: A total of 517 subjects (224 men, 293 women; mean age, 62.8 years) were recruited from a population-based survey in 1999 in Tanushimaru, and we measured fasting plasma Hcy and ADMA levels. We followed them up for over 20 years and examined the effect on mortality using Cox proportional hazard regression model., Results: The mean follow-up years were 17.7 (1.8-20.8). In this period, 182 subjects have died (35.2%). The correlation between Hcy and ADMA was high (r=0.194; p<0.001). With Cox regression analysis after adjustments for age and sex, elevated log transformed Hcy levels were significantly associated with all-cause death (p=0.028). When Hcy and ADMA levels were divided into quintiles, the hierarchical model showed the synergistic effect of Hcy and ADMA on all-cause death., Conclusions: This is the first report that we have measured Hcy and ADMA levels simultaneously in this community-dwelling Japanese, and we demonstrated that combined elevations of Hcy and ADMA had big impact on all-cause death in this epidemiological study., (Copyright © 2021. Published by Elsevier Ltd.)

The elaborate ornaments and weapons of sexual selection, such as the vast array of horns observed in scarab beetles, are some of the most striking outcomes of evolution. How these novel traits have arisen, develop, and respond to condition is governed by a complex suite of interactions that require coordination between the environment, whole-animal signals, cell-cell signals, and within-cell signals. Endocrine factors, developmental patterning genes, and sex-specific gene expression have been shown to regulate beetle horn size, shape, and location, yet no overarching mechanism of horn shape has been described. Recent advances in microscopy and computational analyses combined with a functional genetic approach have revealed that patterning genes combined with intricate epithelial folding and movement are responsible for the final shape of a beetle head horn., (Copyright © 2021. Published by Elsevier Ltd.)

Background: The current understanding of ventilator efficiency variables during ramp exercise testing in the normal Japanese population is insufficient, and the responses of tidal volume (VT) and minute ventilation (V̇E) to the ramp exercise test in the normal Japanese population are not known., Methods: A total of 529 healthy Japanese subjects aged 20-78 years underwent cardiopulmonary exercise testing using a cycle ergometer with ramp protocols. VT and V̇E at rest, at anaerobic threshold, and at peak exercise were determined. The slope of V̇E versus carbon dioxide (V̇CO 2 ) (V̇E vs. V̇CO 2 slope), minimum V̇E/V̇CO 2 , and oxygen uptake efficiency slope (OUES) were determined., Results: For males and females in their 20 s, peak VT (VTpeak) was 2192 ± 376 and 1509 ± 260 mL (p < 0.001), peak V̇E (V̇Epeak) was 80.6 ± 18.7 and 57.7 ± 13.9 L/min (sex differences p < 0.001), the V̇E vs. V̇CO 2 slope was 24.4 ± 3.2 and 25.7 ± 3.2 (p = 0.035), the minimum V̇E/V̇CO 2 was 24.2 ± 2.3 and 27.0 ± 2.8 (p < 0.001), and the OUES was 2452 ± 519 and 1991 ± 315 (p < 0.001), respectively. VTpeak and V̇Epeak decreased with age and increased with weight and height. The V̇E vs. V̇CO 2 slope and minimum V̇E/V̇CO 2 increased with age, while conversely, the OUES decreased with age., Conclusions: We have established the normal range of VT and V̇E responses, the V̇E vs. V̇CO 2 slope, the minimum V̇E/V̇CO 2 , and the OUES for a healthy Japanese population. Some of these parameters were influenced by weight, height, sex, and age. These results provide useful reference values for interpreting the results of cardiopulmonary exercise testing in cardiac patients., (Copyright © 2020 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

We evaluated cerebral gyri (CG) on phase difference enhanced imaging (PADRE) of corticobasal syndrome (CBS), progressive supranuclear palsy (PSP), and Parkinson's disease (PD) patients to determine whether it is possible to discriminate among them on an individual basis. Two radiologists reviewed appearance of the normal CG and that of CBS patients on PADRE, and deviations from the appearance of the normal CG were recorded. Next, based on the CG abnormalities, two other reviewers reviewed PADRE images from 12 CBS, 14 PSP, and 30 PD patients. In healthy subjects on the PADRE images, the signal intensity (SI) of the gray matter (GM) was homogeneously, slightly hyperintense to the subcortical white matter (SCWM), and the SI of the SCWM was homogeneously hypointense. In CBS patients, hypointense layer in superficial GM and disappearance of hypointense in SCWM. The frequency of the abnormal findings on PADRE in the blinded manner by two readers was 100% (12/12), 3% (1/30), and 29% (4/14 in Reader 1) or 36% (5/14 in Reader 2) in CBS PD, and PSP patients, respectively. Laterality of the PADRE findings was showed in 12 (100%) CBS patients and 3 (21%) PSP, but not in any PD patients. The previously reported typical findings in CBS on conventional magnetic resonance image (MRIs) were observed in only 42% (5/12) of CBS patients. In conclusion, the abnormal findings in CG on PADRE appears more useful than conventional MRI findings for discriminating CBS from PD on an individual basis., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Exertional dyspnea is a major symptom of heart failure. We investigated the tidal volume (TV)-the respiratory rate (RR) regulation according to the peak O 2 uptake (VO 2 ) during cardiopulmonary exercise testing (CPET) for clarifying exercise ventilatory pattern., Methods: We enrolled 1111 patients (66±13 years old, 68% men) who had undergone CPET at our hospital. We investigated the relationship between TV and RR and drew the TV/height-RR figure according to the %peak VO 2 ., Results: During exercise, TV was greater, illustrated as higher %peak VO 2 . However, RR was weakly correlated with %peak VO 2 . Adjusted with age, height, sex, each point of RR, and %peak VO 2 , TV during exercise highly correlated with age, height, each point of RR, and % peak VO 2 (R=0.726 to 0.821, p<0.01). In the figure, regardless of the %peak VO 2 , TV/height and RR values were linearly related at rest, as well as at the point of anaerobic threshold, respiratory compensation, and peak exercise point, with each of these lines converging onto a single area (area M). The TV-RR slope values at early phase were also lower at lower %peak VO 2 ., Conclusions: We identified three ventilatory regularities during exercise. First, TV increases as greater %peak VO 2 . Second, the line relating TV/height and RR at each reference point during the incremental exercise test converged onto area M. Finally, the TV-RR slope at the early exercise phase was lower in patients with a lower %peak VO 2 . These ventilatory regularities may assist in elucidating the excise ventilatory pattern and help the diagnosis of exertional dyspnea., (Copyright © 2020. Published by Elsevier Ltd.)

Background: The advantage of using bioresorbable-polymer drug-eluting stent (BP-DES) compared with second-generation durable-polymer drug-eluting stent (2G DP-DES) still remains controversial in clinical situations. The purpose of this study to evaluate the degree of re-endothelialization and the prevalence of high-grade yellow-colored plaque (YCP), which might concern arterial healing after BP-DES and 2G DP-DES implantation using a high-resolution coronary angioscopy (CAS)., Methods: In total, 104 DESs (52: 2G DP-DES and 52: BP-DES) were prospectively observed using CAS 12±1 months after coronary intervention. The grade of neointimal coverage (NIC) over the stent was scored on a 4-point scale from 0 (no coverage) to 3 (complete coverage). YCP grade was also scored on a 4-point scale as 0 (white) to 3 (intensive yellow). High-grade YCP was defined as maximum grade ≥2. Moreover, the prevalence of high-grade YCP and the incidence of thrombus were investigated., Results: BP-DES revealed better dominant NIC grade and less NIC heterogeneity than 2G DP-DES (p=0.0001 and p=0.015, respectively). The prevalence of high-grade YCP was lower for BP-DES than for 2G DP-DES (p=0.05). However, the incidence of thrombus was not significantly different (p=0.41). Multivariate analysis identified that low-density lipoprotein cholesterol levels [odds ratio (OR), 1.03; 95% Confidence Interval (CI): 1.01-1.06, p=0.01] and the usage of BP-DES [OR, 0.36; 95% CI: 0.14-0.91, p=0.03] as independent predictors of high-grade YCP., Conclusions: Compared with 2G DP-DES, BP-DES was less heterogeneous and well-covered NIC and less prevalence of the high-grade YCP implying optimal arterial healing., (Copyright © 2020 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: The prevalence of sarcopenia and its subtypes, such as sarcopenic obesity, osteosarcopenia, and osteosarcopenic obesity, is little known in patients with cardiovascular diseases (CVD)., Methods: Physical, motor functional, and nutritional assessments were performed for 230 community-dwelling (CD) adults who came to receive a physical check-up, and 160 patients with CVD who were admitted to our hospital. Sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia guidelines. The subtypes of sarcopenia were consecutively diagnosed according to increased body fat percentage and decreased bone density., Results: The CVD patients had malnutrition when compared to the CD adults. Impaired motor function of the CVD patients occurred in females as compared with males. The prevalence of sarcopenia, osteosarcopenia, and osteosarcopenic obesity was higher in the CVD patients than in the CD adults (16.9% vs. 4.4%, p<0.001; 8.8% vs. 2.6%, p=0.009; and 4.4% vs. 0.9%, p=0.036, respectively). The prevalence of sarcopenia in the participants positively correlated with the serum N-terminal prohormone of brain natriuretic peptide concentration. Sarcopenia in the CVD patients was present in a younger population as compared with sarcopenia in the CD adults. The prevalence odds ratio of sarcopenia in the CVD patients was higher in females (6.40, 95% CI: 2.38-17.25, p<0.001) than males (4.03, 95% CI: 1.02-15.90, p=0.047). Based on the data of this study, we determined a calculation formula to get an index alternative to skeletal muscle index, followed by an easy diagnosis of sarcopenia. The formula was composed of sex, weight, and calf circumference. The sensitivity and specificity for the diagnosis with the index were 80.8% and 95.6%, respectively., Conclusions: CVD may accelerate sarcopenia, osteosarcopenia, and osteosarcopenic obesity. Our calculation formula for the easy diagnosis of sarcopenia may help in an early diagnosis and prevent it before worsening the patient's prognosis., (Copyright © 2020 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background and Aim: The association of serum cholesterol levels with the occurrence of coronary heart disease (CHD) mortality during a follow-up of 50 years was rarely investigated previously. Thus, we took advantage of results at hand in 10 pooled cohorts of men aged 40-59 years from the Seven Countries Study (9063 individuals and 2057 CHD fatal events) and we assessed this., Methods and Results: Cox proportional hazards models were run with CHD fatal events (as dependent variable) and cholesterol levels (as independent variables) at years 0, 10, and 25 (in 5 cohorts). Cumulative events during subsequent decades (cumulative approach: CA) and separately in each subsequent decade (partitioned approach: PA) were analyzed. The ecological correlation of average baseline serum cholesterol levels with CHD mortality was very high (R = 0.97). Serum cholesterol and CHD mortality for 50 years were associated at the individual level, and the association estimated by the Cox's coefficients (and related hazards ratios) was initially strong in both CA and PA, but slightly declined during later decades. Hazards ratios (for a difference of 40 mg/dl) ranged from 1.39 to 1.20 for CA and from 1.39 to 0.80 for PA. Coefficients were larger for CA than for PA and the decline was more evident for the latter. Partitioned coefficient became negative and significant in the last decade (from year 40-50). Coefficients derived from cholesterol levels measured at year 10 of follow-up showed similar trends but their magnitude was smaller., Conclusion: Thus, the relationship of serum cholesterol levels with CHD mortality remained relatively stable during at least 40 years after a single cholesterol measurement at baseline in middle-aged men., (Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

We investigated the periods from symptom onset to the first visit to the psychiatric consultation and the factors that influence psychiatric help-seeking behavior in university students. Students who first visited the psychiatric department of university health care center were the study participants. We surveyed the elicited information such as age, sex, period from symptom onset to the first visit, main symptoms, General Health Questionnaire GHQ-12, and perception of stigma associated with receiving a psychiatric consultation. We analyzed the factors affecting the duration until a psychiatric consultation was made using logistic regression analysis, examining age, sex, contents of the problem, GHQ-12, and stigma as independent variables. Of the participants, 48.2 % did not consult with a psychiatrist for more than 6 months and 51 participants (36.7 %) took more than a year before a consultation. We divided the study participants into two groups: early examinees and delayed examinees. In order to investigate the factors affecting the two groups, logistic regression analysis was performed. Of the independent variables, one consultation content (physical symptoms; odds ratio (OR) = 9.21, 95 % CI (confidence interval) = 2.00-42.62, p = 0.004) and the GHQ-12 (OR = 1.17, 95 % CI = 1.05-1.31, p = 0.005) were significant factors. It became clear that physical symptoms significantly accelerated consultation with psychiatry. When various problems occurred, the decision to seek a psychiatry consultation required a long time. Health education focusing on the values of seeking an early consultation is required so that when students have mental health problems they will seek psychiatric services in a timely manner., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest to report., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: The greatest advantage of local anesthesia (LA) in endovascular treatment (EVT) of unruptured intracranial aneurysms (UIAs) is that direct neurologic evaluation can be performed during the procedure, unlike with general anesthesia. However, the usefulness of such direct evaluation has not been established. In this study, we attempted to assess the effects of direct neurologic evaluation by identifying the causes, management, and outcomes of clinical symptoms during the procedure and procedure-related events during EVT under LA., Methods: We retrospectively evaluated the medical and radiologic data of 1000 patients (1015 UIAs) who had undergone coil embolization under LA from 2008 to 2016., Results: Clinical symptoms were identified in 62 patients (6.2%) during the procedure. The symptoms improved during the procedure in 27 of these patients (44%) and after the procedure in another 28 (45%). One month after the procedure, 55 patients (89%) had good outcomes and 7 (11%) had poor outcomes. Procedure-related events occurred in 67 patients (6.7%); of these 67 events, 39 were symptomatic and 28 were asymptomatic. Thirty-five of the 39 symptomatic events (90%) [13 of 13 (100%) ruptures, 6 of 10 (60%) thrombus formations, and 16 of 16 (100%) thromboembolisms] were detected on the basis of clinical symptoms before angiographic changes were identified, and they were managed promptly. All 28 patients with asymptomatic events were managed safely without further complications before symptoms developed., Conclusions: We demonstrated that appropriate management of clinical symptoms and procedure-related events under LA led to favorable outcomes of EVT of UIAs., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Although endovascular coiling of unruptured aneurysms is widely accepted, the endovascular treatment of wide-neck bifurcation aneurysms remains one of the most challenging morphologies. Our purpose was to describe our experience with 24-month follow-up for the treatment of unruptured intracranial bifurcation aneurysms using the PulseRider (Cerenovus, New Brunswick, NJ)., Methods: This study is a single-center, single-arm registry performed under institutional review board control to evaluate efficacy and safety of the PulseRider. Patients with bifurcation aneurysms were identified and enrolled prospectively. Angiography immediately after treatment and at 6 months, and magnetic resonance imaging and magnetic resonance angiography at 12- and 24-month follow-up were retrospectively analyzed. A modified Rankin score was obtained prior to procedure, at discharge, and at 6-, 12- and 24-month follow-up visits., Results: Eight patients with a mean age of 66 years were treated with the PulseRider. All patients had bifurcation aneurysms (2 anterior communicating, 2 carotid terminus, and 4 basilar apex). The aneurysm diameters ranged from 4.6 to 13.6 mm (mean 7.4 mm) with dome/neck ratio ranging from 1.4 to 2.2 (mean 1.6). In all cases, the PulseRider was successfully deployed. Complete occlusion was demonstrated at 6-month follow-up on 6 of 8 (75%), near complete occlusion in 1 of 8 (12.5%), and residual aneurysm in 1 of 8 (12.5%) patients. There was no change or recurrence on magnetic resonance angiography, nor clinical complication after the procedure through 24-month follow-up., Conclusions: Our experience with 24-month follow-up demonstrated favorable efficacy in the treatment of intracranial wide-neck bifurcation aneurysms using the PulseRider., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Stent-assisted coil embolization (SAC) for treating anterior communicating artery (AcomA) aneurysms is safe and effective. Straightening of parent vessels by stent placement can lead to progressive thrombosis. We describe our experience with SAC for AcomA aneurysms and demonstrate the effect of straightening the parent vessels., Methods: A total of 26 patients with AcomA aneurysms were treated using SAC in our institute between July 2010 and December 2017. Follow-up digital subtraction angiography was performed 6 months after treatment, magnetic resonance angiography was performed every year, and outcomes were analyzed., Results: From all aneurysms (n = 24), 12 (50.0%) were neck remnant, and 12 (50.0%) were dome-filling types immediately after the procedure. At the 6-month digital subtraction angiography follow-up (n = 22), 13 (59.1%) aneurysms were complete obliteration, 8 (36.4%) were neck remnant, and 1 (4.5%) was dome filling. The median parent vessel angle was measured preoperatively at 98.1°, increased to 124.8° immediately after stent deployment, and further increased to 149.6° at the 6-month follow-up. Progressive thrombosis was observed in 13 of 22 (59.1%) aneurysms. The parent vessel angle change immediately after stent deployment in the progressive thrombosis group tended to be larger than that observed in the no thrombosis group; this change was significant at the 6-month follow-up. The median follow-up term was 18 months. No patients required retreatment., Conclusions: Good SAC outcomes were achieved for AcomA aneurysms, and hemodynamic changes related to straightening of the parent vessels is a consideration in SAC., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Pseudouridylation is a post-transcriptional isomerization reaction that converts a uridine to a pseudouridine (Ψ) within an RNA chain. Ψ has chemical properties that are distinct from that of uridine and any other known nucleotides. Experimental data accumulated thus far have indicated that Ψ is present in many different types of RNAs, including coding and noncoding RNAs. Ψ is particularly concentrated in rRNA and spliceosomal snRNAs, and plays an important role in protein translation and pre-mRNA splicing, respectively. Ψ has also been found in mRNA, but its function there remains essentially unknown. In this review, we discuss the mechanisms and functions of RNA pseudouridylation, focusing on rRNA, snRNA and mRNA. We also discuss the methods, which have been developed to detect Ψs in RNAs. This article is part of a Special Issue entitled: mRNA modifications in gene expression control edited by Dr. Soller Matthias and Dr. Fray Rupert., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Bone metastases from endometrial cancer are rare. To our knowledge, only 2 cases of solitary vertebral metastases from endometrial cancer presenting with osseous and/or neurologic symptoms before the diagnosis of the primary endometrial cancer have been reported; however, in both cases, the metastases were thoracic. Thus, cervical vertebral metastases are extremely rare., Case Description: We describe the case of a 55-year-old woman who presented with right C6 radicular and neck pain. Neurologic imaging showed destruction of the C6 vertebral body by an extradural mass with kyphotic changes in the cervical spine. Fluorodeoxyglucose positron emission tomography showed increased uptake in the enlarged body of the uterus as well as the C6 vertebral body. Additional pelvic magnetic resonance images and endometrial biopsy confirmed endometrial cancer. The patient underwent excision of the cervical tumor with anterior reconstruction and posterior fixation followed 1 month later by semiradical hysterectomy and bilateral salpingo-oophorectomy with pelvic and para-aortic lymph node dissection. The cervical and endometrial histopathologic findings were similar, and the final diagnosis made was cervical metastatic adenocarcinoma originating from an endometrial cancer., Conclusions: We describe an extremely rare case of a precocious solitary cervical metastasis from an endometrial cancer presenting as cervical radicular pain. In our review of published reports, we found that solitary spinal metastases are significantly associated with longer overall survival than are multiple lesions. Resection of the spinal lesion with rigid spinal reconstruction followed by radical hysterectomy may be beneficial in such patients., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Insects can dramatically change their outer morphology at molting. To prepare for this drastic transformation, insects generate new external organs as folded primordia under the old cuticle. At molting, these folded primordia are physically extended to form their final outer shape in a very short time. Beetle horns are a typical example. Horn primordia are derived from a flat head epithelial sheet, on which deep furrows are densely added to construct the complex folded structure. Because the 3D structure of the pupa horn is coded in the complex furrow pattern, it is indispensable to know how and where the furrows are set. Here, we studied the mechanism of furrow formation using dachsous (ds) gene knocked down beetles that have shorter and fatter adult horns. The global shape of the beetle horn primordia is mushroom like, with dense local furrows across its surface. Knockdown of ds by RNAi changed the global shape of the primordia, causing the stalk region become apparently thicker. The direction of cell division is biased in wildtype horns to make the stalk shape thin and tall. However, in ds knocked down beetles, it became random, resulting in the short and thick stalk shape. On the other hand, a fine and dense local furrow was not significantly affected by the ds knockdown. In developing wildtype horn primordia, we observed that, before the local furrow is formed, the apical constriction signal emerged at the position of the future furrow, suggesting the pre-pattern for the fine furrow pattern. According to the results, we propose that development of complex horn primordia can be roughly divided to two distinct processes, 1) development of global primordia shape by anisotropic cell division, and 2) local furrow formation via actin-myosin dependent apical constriction of specific cells., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Although surgical outcomes of acute type A aortic dissection (ATAAD) have improved, it is still a high-risk procedure for octogenarians. This study analyzed early and late outcomes of surgical repair of ATAAD among octogenarians., Methods: From 1990 through 2016, 1,260 consecutive patients with ATAAD were emergently admitted to Jichi Medical University Hospitals. Of them, 1,026 patients who underwent emergency surgery for ATAAD within 48 hours of symptom onset were included in this retrospective study. Of these, 112 were aged 80 years or more (mean, 83.1 ± 2.7) and formed the octogenarian group; and 914 were aged less than 80 years (mean, 62.0 ± 11.4) and formed the control group. Early and late outcomes were compared., Results: The inhospital mortality rate was 6.3% for the octogenarian group and 7.4% for the control group (p = 0.85). No significant difference was observed in the causes of hospital death. Although the overall postoperative complication rate was not different (24.1% versus 23.0%), pneumonia was more frequent among octogenarians (p = 0.03). Multivariate analysis of hospital mortality did not indicate age 80 years or more as a risk factor. Overall postoperative survival for the octogenarian group was 84.6%, 70.5%, and 57.1% at 1, 3, and 5 years, respectively. For the control group, the rates were 89.1%, 85.6%, and 82.1%, respectively. Pneumonia and decrepitude were the major causes of remote death for the octogenarian group., Conclusions: No significant difference in the hospital mortality rate or the complication rate was observed between the groups. Emergency surgery for ATAAD in octogenarians could be performed with the same low risk observed for younger patients., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The endovascular stent graft is a novel therapeutic technique that is used in the treatment of aortic aneurysms. However, the aortic arch is a still an area that requires endovascular repair. Since 2008, the authors have treated aortic arch aneurysms (AAA) in patients without an extraanatomical bypass using a fenestrated stent graft (FSG). This study aimed to evaluate the early outcomes of FSG treatment., Methods: The authors retrospectively investigated the early outcomes of 54 AAA cases that were performed in their department from January 2008 to May 2016. The early results were analyzed retrospectively., Results: The primary technical success rate was 100%. There were 2 operative deaths due to shower embolism and respiratory failure (2 of 54, 3.7%). Two patients suffered central nervous system injury (2 of 54, 3.7%) without remaining sequelae. At a mean follow-up period of 41.4 months, the survival rate was 75.0% and there were no aortic-related deaths. On follow-up, secondary intervention was necessary in 3 cases. The rate of freedom from secondary reintervention was 92.5%., Conclusions: Although further observation and prospective studies involving larger numbers of patients will be needed to validate this process, the outcomes of FSG treatment and our procedures were acceptable. This procedure has the potential to expand the indications for treatment in patients with AAA that are deemed to be suitable for this treatment., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Cognitive impairment is an important element affecting our well-being, and as such, early diagnosis is critical today. We investigated whether serum cystatin C and microalbuminuria are associated with cognitive impairment., Methods: A total of 1943 subjects (774 males, 1169 females, mean age 65.8 years) took part in the investigation, and underwent a health examination in Tanushimaru, Japan, in 2009. The participants' cognitive function was evaluated using of mini-mental state examination (MMSE). We measured the levels of serum cystatin C using latex nephelometric immunoassay. Spot urine samples were used to measure microalbuminuria levels. Multivariate linear regression analyses were used to assess the relationship between MMSE scores and the level of cystatin C or microalbuminuria. All statistical analyses were performed using the SAS system., Results: The mean values of log-transformed serum cystatin C levels and log-transformed microalbuminuria were 0.95 (range 0.41-7.11) mg/L and 10.7 (range 1.1-2600) mg/g·Cr, respectively. The means of MMSE score were 27.7 ± 2.5. In the multivariate linear regression analyses adjusted for age and sex, MMSE was significantly associated with systolic blood pressure (p = 0.024, inversely), cystatin C (p = 0.046, inversely) and microalbuminuria (p = 0.019, inversely), whereas estimated glomerular filtration rate (eGFR) had an insignificant association (p = 0.197). In the multiple stepwise linear regression analysis, age, history of stroke, systolic blood pressure, serum cystatin C were independently associated with MMSE levels., Conclusions: We demonstrated for the first time that cognitive function was significantly and inversely associated with cystatin C and microalbuminuria, in the relatively younger general population., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: An understanding of the trends in regard to coronary risk factors and electrocardiogram (ECG) findings has an important role in public health. We investigated the trends in coronary risk factors and main ECG findings in 1977, 1989, 1999, and 2009 in the Japanese cohort of the Seven Countries Study, in Tanushimaru, a typical farming town on Kyushu Island., Methods and Results: A total of 1397 subjects (231 in 1977, 332 in 1989, 389 in 1999, and 445 in 2009) were enrolled in this study, and all of them were males aged over 65 years. In coronary risk factors, total cholesterol levels, diastolic blood pressure, body mass index, and uric acid significantly increased during these 3 decades. The prevalence of smokers markedly decreased from 56.7% in 1977 to 16.8% in 2009. ECG changes during 3 decades were wider QRS interval, increased prevalence of major abnormality, reduced heart rate, shortened PR interval and corrected QT, and decreased prevalence of left ventricular hypertrophy. Age, smoking habits, major and minor abnormalities in ECG were associated with mortality in 1977-1987. Age, total cholesterol levels (inversely) and corrected QT were associated with mortality in 1989-1999. Age, smoking habits, heart rate, and systolic blood pressure were associated with mortality in 1999-2009., Conclusions: Predictors of mortality have changed with the times. Coronary risk factors such as smoking, increased heart rate, and elevated blood pressure have been recently associated with mortalities in elderly male Japanese general population., (Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: Tensioned collagen gels with dermal fibroblasts (DFs) as a dermis model are usually utilized in a static culture (SC) that lacks medium flowing. To make the model closer to its in vivo state, we created a device to perfuse the model with media flowing at a physiological velocity and examined the effects of medium flow (MF) on the cultures., Methods: We constructed a medium perfusion device for human DF-embedded stretched collagen gels (human dermis model), exposed the model to media that flows upwardly at ~1mL/day, and examined water retention of the gels, cells' growth ability, metabolic activity, expression profiles of nine extracellular matrix (ECM)-related genes. The obtained data were compared with those from the model in SC., Results: MF increases the gels' water retention and cells' growth potential but had little effect on their metabolic activities. MF robustly enhanced hyaluronan synthase 2 (HAS2) and matrix metalloprotease 1 (MMP1) gene expressions but not of the other genes (MMP2, HYAL1, HYAL2, HYAL3, COL1A1, COL3A1, and CD44). MF significantly increased the amounts of cellular hyaluronan and adenosine triphosphate., Conclusions: The MF at a physiological speed significantly influences the nature of ECMs and their resident fibroblasts and remodels ECMs by regulating hyaluronan metabolism., General Significance: Fibroblasts in tensioned collagen gels altered their phenotypes in a MF rate-dependent manner. Collagen gel culture with tension and MF could be utilized as an appropriate in vitro model of interstitial connective tissues to evaluate the pathophysiological significance of mechanosignals generated by fluid flow and cellular/extracellular tension., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Myocardial ischemia induces cardiac dysfunction, resulting in insufficient oxygen supply to peripheral tissues and mismatched energy production during exercise. To relieve the insufficient oxygen supply, heart rate (HR) response is augmented; however, beta-adrenergic receptor blockers (BB) restrict HR response. Although BB are essential drugs for angina pectoris, the effect of BB on exercise tolerance in patients with angina has not been studied. The aim of this study was to clarify the importance of HR augmentation to preserve exercise tolerance in patients with angina pectoris., Methods: Forty-two subjects who underwent cardiopulmonary exercise testing (CPX) to detect myocardial ischemia were enrolled. CPX was performed until exhaustion or onset of significant myocardial ischemia using a ramp protocol. Subjects were assigned to three groups (Group A: with ST depression during CPX with significant coronary stenosis and taking BB; Group B: with ST depression and not taking BB; Group C: without ST depression and not taking BB). HR response to exercise was evaluated during the following two periods: below and above ischemic threshold (IT). In Group C, it was evaluated during the first 2min and the last 2min of a ramp exercise., Results: No significant differences were observed among the three groups with regard to patients' basic characteristics. Below IT, there were no differences in oxygen pulse/watt (O 2 pulse increasing rate), HR/watt (ΔHR/ΔWR), and ΔV˙O 2 /ΔWR. Above IT, O 2 pulse increasing rate was greater in Group A than in Group B. ΔHR/ΔWR was smaller in Group A than in Group B. ΔV˙O 2 /ΔWR became smaller in Group A than in Group B. There was no difference in anaerobic threshold, and peak V˙O 2 was smaller in Group A than in Group B., Conclusions: Restriction of HR response by a BB is shown to be one of the important factors in diminished exercise tolerance., (Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: Preoperative endovascular embolization of intracranial meningiomas denatures the tumor tissue, reduces intraoperative blood loss, and facilitates surgical removal. However, as most meningiomas are surgically removed within a few days after embolization, the effect of long-term volume reduction of the tumor due to the endovascular embolization remains unknown., Methods: Five patients with intracranial meningioma underwent endovascular embolization between January 2006 and December 2014 and were followed without surgical resection for >14 days. The reduction in tumor and peritumoral edema volumes on sequential head magnetic resonance imaging, along with the clinical symptoms, were retrospectively reviewed., Results: All the tumors indicated a 10%-30% volume reduction 30 days after embolization, which continued thereafter; no meningioma regrowth was observed for >90 days in 2 of 5 cases. Moreover, the peritumoral edema volume was reduced by 30%-70% at 30 days after embolization, and no subsequent increase was observed for >60 days in 4 of 5 cases. The neurologic symptoms related to the tumor mass effect improved after embolization., Conclusions: Endovascular embolization of intracranial meningiomas with n-butyl cyanoacrylate reduced the tumor and peritumoral edema volumes by 10%-30% and 30%-70%, respectively, within 30 days. Volume and edema reduction effect of embolization may last longer than expected, beyond the timing when most meningiomas are resected after embolization. In this study, we described our preliminary results of the volume reduction of intracranial meningiomas that were embolized using n-butyl cyanoacrylate and monitored without any surgical resection for >14 days. We believe that our study makes a significant contribution to the literature because we showed that volume and edema reduction effect of embolization may last longer than expected, beyond the timing when most meningiomas are resected after embolization., (Copyright © 2017 Elsevier Inc. All rights reserved.)