Search

Background: Lower limb artery disease (LEAD) is accompanied by multiple comorbidities; however, the effect of hyperpolypharmacy on patients with LEAD has not been established. This study investigated the associations between hyperpolypharmacy, medication class, and adverse clinical outcomes in patients with LEAD., Methods: This study used data from a prospective multicenter observational Japanese registry. A total of 366 patients who underwent endovascular treatment (EVT) for LEAD were enrolled in this study. The primary endpoints were major adverse cardiac events (MACE), including myocardial infarction, stroke, and all-cause death., Results: Of 366 patients with LEAD, 12 with missing medication information were excluded. Of the 354 remaining patients, 166 had hyperpolypharmacy (≥10 medications, 46.9 %), 162 had polypharmacy (5-9 medications, 45.8 %), and 26 had nonpolypharmacy (<5 medications, 7.3 %). Over a 4.7-year median follow-up period, patients in the hyperpolypharmacy group showed worse outcomes than those in the other two groups (log-rank test, p < 0.001). Multivariate analysis revealed that the total number of medications was significantly associated with an increased risk of MACE (hazard ratio per medication increase 1.07, 95 % confidence interval 1.02-1.13 p = 0.012). Although an increased number of non-cardiovascular medications was associated with an elevated risk of MACE, the increase in cardiovascular medications was not statistically significant (log-rank test, p = 0.002 and 0.35, respectively)., Conclusions: Hyperpolypharmacy due to non-cardiovascular medications was significantly associated with adverse outcomes in patients with LEAD who underwent EVT, suggesting the importance of medication reviews, including non-cardiovascular medications., Competing Interests: Declaration of competing interest Koichiro Kuwahara is a member of the editorial team of the Journal of Cardiology. The other authors declare no conflicts of interest., (Copyright © 2024. 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.

The R1 (1/T1) map divided by the T2* map (R1/T2* map) draws attention as a high-resolution myelin-related map. However, both R1 and R2* (1/T2*) values demonstrate anisotropy dependent on the white matter (WM) fiber orientation with respect to the static magnetic (B0) field. Therefore, this study primarily aimed to investigate the comprehensive impact of these angular-dependent anisotropies on the R1/T2* value. This study enrolled 10 healthy human volunteers (age = 25 ± 1.3) on the 3.0 T MRI system. For R1/T2* map calculation, whole brain R1 and T2* maps were repeatedly obtained in three head tilt positions by magnetization-prepared two rapid gradient echoes and multiple spoiled gradient echo sequences, respectively. Afterward, all maps were spatially normalized and registered to the Johns Hopkins University WM atlas. R1/T2*, R1, and R2* values were binned for fiber orientation related to the B0 field, which was estimated from diffusion-weighted echo-planar imaging data with 3° intervals, to investigate angular-dependent anisotropies in vivo. A larger change in the R1/T2* value in the global WM region as a function of fiber orientation with respect to the B0 field was observed compared to the R1 and R2* values alone. The minimum R1/T2* value at the near magic-angle range was 18.86% lower than the maximum value at the perpendicular angle range. Furthermore, R1/T2* values in the corpus callosum tract and the right and left cingulum cingulate gyrus tracts changed among the three head tilt positions due to fiber orientation changes. In conclusion, the R1/T2* value demonstrates distinctive and complicated angular-dependent anisotropy indicating the trends of both R1 and R2* values and may provide supplemental information for detecting slight changes in the microstructure of myelin and axons., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

A strategy for enhancing value creation from pyrolysis gas and oil, derived from plastic waste, through the generation of two additional outputs of solid carbon and hydrogen was investigated. Three types of hard-to-recycle plastic waste (marine plastic litter, household mixed plastics and cosmetic products packaging) were thermally treated in two stages: (i) decomposition of feedstock into gas and oil via pyrolysis at 600 °C; and (ii) thermolytic conversion of the pyrolysis gas and a fraction of oil into hydrogen and solid carbon at 1300 °C separately. The thermolysis of both pyrolysis gas and oil fractions predominantly resulted in the production of solid carbon (39-70 wt% per plastic feedstock and carbon content of 91.3-98.6 wt%) and H 2 -rich gas (H 2 yield of 5.9-10.8 wt% per plastic waste feedstock and H 2 content of 71.4-97.2 vol% per gas volume). The incorporation of pyrolysis oil into the thermolysis process could enhance the outputs of solid carbon and hydrogen. Characterizations of solid carbon and hydrogen obtained from pyrolysis gas and oil fractions were further conducted. The observed similar properties of H 2 and solid carbon from pyrolysis gas and oil supported the feasibility of introducing all the pyrolytic products together into the thermolysis process without condensation of oil. To enhance the value of these solid carbon derived from plastics for practical usage, we utilized the obtained solid carbon as a reinforcing agent for polymer composite foam development. The solid carbon reinforced composite foam displayed great abrasion resistance (wear loss: 240 mg), compression strength (0.347 MPa), and dynamic impact properties (energy returned: 124 J/m and energy absorbed: 57.3 J/m), emphasizing the viability of solid carbon as a nucleating agent and reinforcing filler in polymer foam for cushioning applications. Overall, the strategy of pyrolysis-thermolysis, which harnesses both pyrolysis gas and oil, unlocks additional value creation by producing two new outputs from plastic waste. Depending on the market prices for solid carbon and hydrogen, this can substantially change the economics of plastic waste management and create new revenue streams, incentivizing plastic waste collection and processing., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aims: Standard manual analysis of IVUS to study the impact of anti-atherosclerotic therapies on the coronary vessel wall is done by a core laboratory (CL), the ground truth (GT). Automatic segmentation of IVUS with a machine learning (ML) algorithm has the potential to replace manual readings with an unbiased and reproducible method. The aim is to determine if results from a CL can be replicated with ML methods., Methods: This is a post-hoc, comparative analysis of the IBIS-4 (Integrated Biomarkers and Imaging Study-4) study (NCT00962416). The GT baseline and 13-month follow-up measurements of lumen and vessel area and percent atheroma volume (PAV) after statin induction were repeated by the ML algorithm., Results: The primary endpoint was change in PAV. PAV as measured by GT was 43.95 % at baseline and 43.02 % at follow-up with a change of -0.90 % (p = 0.007) while the ML algorithm measured 43.69 % and 42.41 % for baseline and follow-up, respectively, with a change of -1.28 % (p < 0.001). Along the most diseased 10 mm segments, GT-PAV was 52.31 % at baseline and 49.42 % at follow-up, with a change of -2.94 % (p < 0.001). The same segments measured by the ML algorithm resulted in PAV of 51.55 % at baseline and 47.81 % at follow-up with a change of -3.74 % (p < 0.001)., Conclusions: PAV, the most used endpoint in clinical trials, analyzed by the CL is closely replicated by the ML algorithm. ML automatic segmentation of lumen, vessel and plaque effectively reproduces GT and may be used in future clinical trials as the standard., Competing Interests: Declaration of competing interest Héctor M. García-García reports the following Institutional grant support: Biotronik, Boston Scientific, Medtronic, Abbott, Neovasc, Shockwave, Phillips and Corflow; Speaker's fee from Boston Scientific and Amgen. Lorenz Räber reports institutional grant support: Abbott, Biotronik, Boston Scientific, Sanofi, Regeneron, Infraredx and consultation fees by Abbott, Amgen, AstraZeneca, Occlutec, Medtronic, Sanofi, Vifor. Marco Roffi reports institutional research grants from Terumo, Biotronik, Medtronic and Cordis/Cardinal Health., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Percutaneous coronary intervention (PCI) in addition to guideline-directed medical therapy reduces the risk of spontaneous myocardial infarction (MI), urgent revascularization, and improves angina status; however, PCI is associated with an increased risk of periprocedural myocardial injury and MI. Numerous studies have investigated the mechanisms, predictors, and therapeutic strategies for periprocedural MI. Various definitions of periprocedural MI have been proposed by academic groups and professional societies requiring different cardiac biomarker thresholds and ancillary criteria for myocardial ischemia. The frequency and clinical significance of periprocedural MI substantially varies according to the definitions applied. In daily practice, accurate diagnosis of clinically-relevant periprocedural MI is essential because it may have a substantial impact on subsequent patient management. In the clinical trial setting, only clinically relevant periprocedural MI definitions should be applied as a clinical endpoint in order to avoid obscuring meaningful outcomes. In this review, we aim to summarize the mechanisms, predictors, frequency, and prognostic impact of periprocedural MI in patients undergoing PCI and to provide the current perspective on this issue., Competing Interests: Declaration of competing interest None Disclosures None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: We investigated the prevalence of headache, migraine, and medication-overuse headache (MOH) among children and adolescents through a school-based online questionnaire. We also investigated the triggers for migraine among them and the effect of the COVID-19 pandemic on headache frequency., Methods: Children and adolescents aged 6-17 y.o. completed an online questionnaire. Migraine, MOH was defined as The International Classification of Headache Disorders Third edition. Factor and clustering analyses were performed for migraine triggers. The effect of the coronavirus disease 2019 (COVID-19) pandemic on headache frequency was also asked., Results: Of the 2489 respondents, the prevalence of headache, migraine, and MOH were 36.44%, 9.48%, and 0.44%, respectively. Up to 70% of the respondents with headaches complained of the disturbance to daily life, but about 30% consulted doctors. The migraine triggers were grouped into 5 factors by factor analysis. The sensitivities of the migraineurs against the factors were divided into 3 clusters. Cluster 1 had stronger sensitivity for several triggers. Cluster 2 was sensitive to weather, smartphones, and video games. Cluster 3 had less sensitivity for triggers. Cluster 2 less consulted doctors even though the burden of migraine was enormous. During the COVID-19 pandemic, 10.25% of respondents increased headache attacks, while 3.97% decreased., Conclusions: This is the first detailed study on headache prevalence in Japanese students from elementary school to high school in one region. The burden of headaches is large among children and adolescents, and the unmet needs of its clinical practice should be corrected., Competing Interests: Conflict of interest statement This research has never been presented at a conference. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background/purpose: Guidelines recommend intracoronary optical coherence tomography (OCT) to assess stent failure and guide percutaneous coronary intervention (PCI) but OCT may be useful for other indications in routine clinical practice., Methods/materials: We conducted an international registry of OCT cases at two large tertiary care centers to assess clinical indications and the potential impact on decision making of OCT in clinical routine. Clinical indications, OCT findings, and their impact on interventional or medical treatment strategy were retrospectively assessed., Results: OCT was performed in 810 coronary angiography cases (1928 OCT-pullbacks). OCT was used for diagnostic purposes in 67% (N = 542) and OCT-guided percutaneous coronary intervention in 50% (N = 404, 136 cases with prior diagnostic indication). Most frequent indications for diagnostic OCT were culprit lesion identification in suspected ACS (29%) and stent failure assessment (28%). OCT findings in the diagnostic setting influenced patient management in 74%. OCT-guided PCIs concerned ACS patients in 45%. Among the 55% with chronic coronary syndrome, long lesions >28 mm (19%), left main PCI (16%), and bifurcation PCI with side-branch-stenting (5%) were the leading indications for PCI-guidance. Post-procedural OCT findings led to corrective measures in 52% (26% malapposition, 14% underexpansion, 6% edge dissection, 3% intrastent mass, 3% geographic plaque miss)., Conclusions: OCT was most frequently performed to identify culprit lesions in suspected ACS, for stent failure assessment, and PCI-guidance. OCT may impact subsequent treatment strategies in two out of three patients., Competing Interests: Declaration of competing interest JH received a travel-grant from Bayer. GCMS reported receiving honoraria from Abbott outside the submitted work. SB reports a research grant to the institution from Medis Medical Imaging Systems. SS has received research grants to the institution from Edwards Lifesciences, Medtronic, Abbott Vascular and Boston Scientific, serves as consultant for BTG and Teleflex and has received speaker fees from BTG and Boston Scientific. PM serves as consultant for St Jude Medical / Abbott and Terumo. SW reports research and educational grants to the institution from Abbott, Amgen, Bayer, BMS, Boston Scientific, Biotronik, Cardinal Health, CSL Behring, Daiichi Sankyo, Edwards Lifesciences, Guerbet AG, Johnson&Johnson, Medtronic, Sanofi-Aventis, and Terumo. SW serves as unpaid member of the steering/executive group of trials funded by Abbott, Abiomed, Amgen, BMS, Boston Scientific, Biotronik, Cardiovalve, Edwards Lifesciences, MedAlliance, Medtronic, Polares, Sinomed, V-Wave, and Xeltis, but has not received personal payments by any pharmaceutical company or device manufacturer. SW is member of the steering/executive committee group of several investigated-initiated trials that receive funding by industry without impact on his personal remuneration. GS serves as consultant for St Jude Medical / Abbott and Terumo. LR received research grants to the institution by Abbott, Biotronik, BostonScientific, Medis, Infraredx, Sanofi, Regeneron and consultation/speaker fees by Abbott, Amgen, AstraZeneca, Canon, Sanofi, Vifor. All other author have nothing to disclose., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The prevalence of acute coronary syndromes (ACS) among young individuals is increasing, but the phenotypic characteristics, causes and clinical outcomes in this group have not been well described., Methods: Between 2009 and 2017, 8712 ACS patients underwent percutaneous coronary intervention (PCI) and were prospectively enrolled. We defined a young patient as female <50 years and male <45 years. The causes of ACS were defined by an adjudication committee. The primary endpoint was the patient-oriented composite endpoint (POCE) of all-cause mortality, myocardial infarction or any revascularization at 12 months., Results: Among 8712 ACS patients, 472 (5.4%) patients were young (26% female). The main cause of ACS in young patients was atherosclerosis (86.5%), followed by coronary artery embolism (9%), and spontaneous coronary artery dissection (SCAD) (4.5%). POCE occurred less frequently in young compared to old patients (8.5% vs. 16.7%, hazard ratio 0.48 (95% confidence interval 0.35-0.66), p < 0.001). The rates of the individual components of the POCE were lower in young including all-cause mortality (3.2% versus 9.5%, 0.32 (0.19-0.54), p < 0.001), myocardial infarction (1.9% versus 3.7%, 0.49 (0.25-0.95), p = 0.035) and any revascularization (5.1% versus 7.4%, 0.65 (0.43-0.97), p = 0.037). Young patients with SCAD had a higher rate of death as compared to those with atherosclerosis, mainly attributed to cardiac deaths., Conclusions: One out of 20 ACS patients undergoing PCI was young and the principal cause was atherosclerosis. Young carry a lower risk for future events compared to older ACS patients. The underlying cause leading to ACS should be considered in appropriate risk stratification of young patients., Clinical Trial Registration: Clinicaltrials.gov. NCT02241291., (Copyright © 2022. Published by Elsevier B.V.)

Background: R2* relaxometry analysis combined with quantitative susceptibility mapping (QSM), which has high sensitivity to iron deposition, can distinguish microstructural changes of the white matter (WM) and iron deposition, thereby providing a sensitive and biologically specific measure of the WM owing to the changes in myelin and its surrounding environment. This study aimed to explore the microstructural WM alterations associated with cognitive impairment in patients with Parkinson's disease (PD) using R2* relaxometry analysis combined with QSM., Materials and Methods: We enrolled 24 patients with PD and mild cognitive impairment (PD-MCI), 22 patients with PD and normal cognition (PD-CN), and 19 age- and sex-matched healthy controls (HC). All participants underwent Montreal Cognitive Assessment (MoCA) and brain magnetic resonance imaging, including structural three-dimensional T1-weighted images and multiple spoiled gradient echo sequence (mGRE). The R2* and susceptibility maps were estimated from the multiple magnitude images of mGRE. The susceptibility maps were used for verifying iron deposition in the WM. The voxel-based R2* of the entire WM and its correlation with cognitive performance were analyzed., Results: In the voxel-based group comparisons, the R2* in the PD-MCI group was lower in some WM regions, including the corpus callosum, than R2* in the PD-CN and HC groups. The mean susceptibility values in almost all brain regions were negative and close-to-zero values, indicating no detectable paramagnetic iron deposition in the WM of all subjects. There was a significant positive correlation between R2* and MoCA in some regions of the WM, mainly the corpus callosum and left hemisphere., Conclusion: R2* relaxometry analysis for WM microstructural changes provided further biologic insights on demyelination and changes in the surrounding environment, supported by the QSM results demonstrating no iron existence. This analysis highlighted the potential for the early evaluation of cognitive decline in patients with PD., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Segmentation of lumen and vessel contours in intravascular ultrasound (IVUS) pullbacks is an arduous and time-consuming task, which demands adequately trained human resources. In the present study, we propose a machine learning approach to automatically extract lumen and vessel boundaries from IVUS datasets. The proposed approach relies on the concatenation of a deep neural network to deliver a preliminary segmentation, followed by a Gaussian process (GP) regressor to construct the final lumen and vessel contours. A multi-frame convolutional neural network (MFCNN) exploits adjacency information present in longitudinally neighboring IVUS frames, while the GP regression method filters high-dimensional noise, delivering a consistent representation of the contours. Overall, 160 IVUS pullbacks (63 patients) from the IBIS-4 study (Integrated Biomarkers and Imaging Study-4, Trial NCT00962416), were used in the present work. The MFCNN algorithm was trained with 100 IVUS pullbacks (8427 manually segmented frames), was validated with 30 IVUS pullbacks (2583 manually segmented frames) and was blindly tested with 30 IVUS pullbacks (2425 manually segmented frames). Image and contour metrics were used to characterize model performance by comparing ground truth (GT) and machine learning (ML) contours. Median values (interquartile range, IQR) of the Jaccard index for lumen and vessel were 0.913, [0.882,0.935] and 0.940, [0.917,0.957], respectively. Median values (IQR) of the Hausdorff distance for lumen and vessel were 0.196mm, [0.146,0.275]mm and 0.163mm, [0.122,0.234]mm, respectively. Also, the mean value of lumen area predictions, and limits of agreement were -0.19mm 2 , [1.1,-1.5]mm 2 , while the mean value and limits of agreement of plaque burden were 0.0022, [0.082,-0.078]. The results obtained with the model developed in this work allow us to conclude that the proposed machine learning approach delivers accurate segmentations in terms of image metrics, contour metrics and clinically relevant variables, enabling its use in clinical routine by mitigating the costs involved in the manual management of IVUS datasets., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest with regards to the present work., (Copyright © 2021. Published by Elsevier B.V.)

Background: Forged composites of raw particulate unsintered hydroxyapatite/poly-L-lactide (F-u-HA/PLLA) implants are widely used in surgeries because they possess high mechanical strength, bioactivity, and radio-opacity. We previously reported that F-u-HA/PLLA implants were useful for treating lateral tibial condylar, lateral humeral condylar, and ankle fractures. The study aim was to investigate the efficacy of F-u-HA/PLLA cannulated screws and FiberLoop® for treating transverse patellar fractures., Methods: From April 2013 to February 2019, 15 patients with transverse patellar fractures were treated with F-u-HA/PLLA cannulated screws and FiberLoop® as follows: Open reduction and internal fixation (ORIF) were performed with two F-u-HA/PLLA cannulated screws and a temporary fixation Kirshner wire (K-wire). Three No. 2 FiberLoops® were inserted into these two screw holes and the K-wire hole for temporary fixation. All patients were allowed to full weight-bearing gaits using a knee brace. Knee range of motion exercise was initiated on postoperative day 1. Knee flexion was restricted to ≤90° for 1 month postoperatively. Radiograph was performed to evaluate fracture healing, screw breakage, reduction loss, and screw radio-opacity. Clinical outcomes and postoperative complications were assessed., Results: The average follow-up was 16.0 months. All fractures were successfully united. Screw breakage, reduction loss, osteolysis, and radiolucent zones around the screws were not observed at the final radiographic follow-up. All F-u-HA/PLLA screw shadows were observed during the follow-up. The average range of flexion and extension were 132.0° and -2.7°, respectively. No patients experienced deep infection episodes, late aseptic tissue reactions, or foreign body reactions postoperatively. No patients complained of pain at the final follow-up. All patients returned to their pre-injury work level and activities of daily living., Conclusion: Our results strongly suggest that ORIF with F-u-HA/PLLA screws and FiberLoop® could be an alternative treatment option for transverse patellar fractures., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest with the contents of this paper., (Copyright © 2020. Published by Elsevier Ltd.)

Purpose: We investigated whether optical coherence tomography (OCT)-guided bioresorbable vascular scaffolds (BVS) implantation can improve in-scaffold minimal lumen area (MLA) at 6-month compared with angiography guidance., Methods: The OPTICO BVS was a randomized, international multicenter, assessor blind, superiority trial comparing OCT- versus angiography-guided percutaneous coronary intervention (PCI) (1:1 allocation) in patients with coronary artery disease undergoing Absorb BVS 1.1 implantation. The primary endpoint was in-scaffold MLA at 6-month., Results: The trial was prematurely stopped on May 31, 2017 after enrollment of 38 of 270 planned patients (14%) following the retraction of the device in Europe. Patients were randomly assigned to OCT- (n = 19) or angiography-guided PCI (n = 19). Scaffold diameter (OCT 3.0 ± 0.3 mm vs. angiography 3.1 ± 0.3 mm, P = .333) and length (28.8 ± 13.6 mm vs. 23.8 ± 12.3 mm, P = .223) were comparable. There was no significant difference in in-scaffold MLA at 6 months (4.47mm 2 vs. 5.08mm 2 , P = .692). Scaffold expansion at 6-month was significantly higher in the OCT-guided PCI as compared with angiography-guided PCI (84.5% vs. 76.5%, P = .010). There was no significant difference in clinical outcomes., Conclusions: Although in-scaffold MLA at 6-month did not differ between groups, scaffold expansion was improved following OCT- as compared with angiography-guided PCI. The findings of this study must be interpreted in view of the premature termination with inclusion of 14% of the initially planned study sample., Competing Interests: Declaration of competing interest Y. Ueki reports personal fees from Infraredex, outside the submitted work. E. Barbato reports personal fees from Abbott Vascular, personal fees from Boston Scientific, personal fees from GE, outside the submitted work. S. Brugaletta reports other from Boston Scientific, other from iVascular, grants from Astrazeneca, outside the submitted work. J. Hill reports grants and personal fees from Shockwave Medical, grants and personal fees from Abbott Vascular, grants and personal fees from Boston Scientific, grants and personal fees from Abiomed, outside the submitted work. F. Burzotta reports personal fees from ABBOTT, personal fees from MEDTRONIC, personal fees from ABIOMED, outside the submitted work. S. Windecker reports grants from Abbott Vascular, during the conduct of the study; grants from Amgen, grants from Bayer, grants from BMS, grants from Boston Scientific, grants and personal fees from Biotronik, grants from CSL Behring, grants from Edwards Lifesciences, grants from Medtronik, grants from Polares, grants from Sinomed, outside the submitted work. L. Räber reports grants and personal fees from Abbott Vascular, during the conduct of the study; grants from Biotronik, grants from Boston Scientific, grants from HeartFlow, grants and personal fees from Sanofi, grants from Regeneron, personal fees from Amgen, personal fees from AstraZeneca, personal fees from CSL Behring, personal fees from Occlutech, non-financial support from Vifor, outside the submitted work. The other author has no conflicts of interest to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

A sophisticated and delicate balance between bone resorption by osteoclasts and bone formation by osteoblasts regulates bone metabolism. Optineurin (OPTN) is a gene involved in primary open-angle glaucoma and amyotrophic lateral sclerosis. Although its function has been widely studied in ophthalmology and neurology, recent reports have shown its possible involvement in bone metabolism through negative regulation of osteoclast differentiation. However, little is known about the role of OPTN in osteoblast function. Here, we demonstrated that OPTN controls not only osteoclast but also osteoblast differentiation. Different parameters involved in osteoblastogenesis and osteoclastogenesis were assessed in Optn -/- mice. The results showed that osteoblasts from Optn -/- mice had impaired alkaline phosphatase activity, defective mineralized nodules, and inability to support osteoclast differentiation. Moreover, OPTN could bind to signal transducer and activator of transcription 1 (STAT1) and regulate runt-related transcription factor 2 (RUNX2) nuclear localization by modulating STAT1 levels in osteoblasts. These data suggest that OPTN is involved in bone metabolism not only by regulating osteoclast function but also by regulating osteoblast function by mediating RUNX2 nuclear translocation via STAT1., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: This study sought to examine the utility of multimodality intravascular imaging and of the endothelial shear stress (ESS) distribution to predict atherosclerotic evolution., Background: There is robust evidence that intravascular ultrasound (IVUS)-derived plaque characteristics and ESS distribution can predict, with however limited accuracy, atherosclerotic evolution; nevertheless, it is yet unclear whether multimodality imaging and ESS mapping enable more accurate prediction of coronary plaque progression., Methods: A total of 44 patients admitted with a myocardial infarction that had successful revascularization and 3-vessel IVUS and optical coherence tomography (OCT) imaging at baseline and 13-month follow-up were included in the study. The IVUS data acquired at baseline in the nonculprit vessels were fused with x-ray angiography to reconstruct coronary anatomy and in the obtained models blood flow simulation was performed and the ESS was estimated. The baseline plaque characteristics and ESS distribution were used to identify predictors of disease progression: defined as a lumen reduction and an increase in plaque burden at follow-up., Results: Seventy-three vessels were included in the final analysis. Baseline ESS and the IVUS-derived but not the OCT-derived plaque characteristics were independently associated with a decrease in lumen area and an increase in plaque burden. Low ESS (odds ratio: 0.45; 95% confidence interval: 0.28 to 0.71; p < 0.001) and plaque burden (odds ratio: 0.73; 95% confidence interval: 0.54 to 0.97; p = 0.030) were the only independent predictors of disease progression at follow-up. The accuracy of the IVUS-derived plaque characteristics in predicting disease progression did not improve when ESS (AUC: 0.824 vs. 0.847; p = 0.127) or when OCT variables and ESS (AUC: 0.842; p = 0.611) were added into the model., Conclusions: ESS and OCT-derived variables did not improve the efficacy of IVUS in predicting disease progression. Further research is required to investigate whether multimodality imaging combined with ESS mapping will allow more reliable vulnerable plaque detection. (Comparison of Biomatrix Versus Gazelle in ST-Elevation Myocardial Infarction [STEMI] [COMFORTABLE]; NCT00962416)., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The ionization source based on glow discharge plasma using ambient air is driven by a pulsed direct-current voltage for soft plasma ionization (SPI). The novelty of this work is that molecular ions [M+13] + related to the analyte species (M), which may be formed by numerous oxidation, can be dominantly detected as a base peak with little or no fragmentation of them in an air plasma at a pressure of several kPa. The unique ion [M+13] + was assigned to the oxidation product, [M+O-3H] + , which was confirmed as a deuterated ion [M+O-3D] + ([M+10] + ) by using a deuterated solvent. The ionization reactions were suggested that the product ion [M+O-3H] + may arise from hydride abstraction reaction of M with O 2 +• , dehydrogenation reaction of [M-H] +• and subsequently oxidation reaction of [M-3H] + with O 3 . n-Alkane mixtures was also measured to evaluate the intermolecular interaction in this system. The limits of detection (LOD) were in the range of 0.126-1.68 ppmv and the relative standard deviation (RSD) for repeatability was approximately 10.0% at the lowest concentration. To our knowledge, this is the first report demonstrating that the spectrum pattern of saturated hydrocarbons could be directly determined without any complicated fragmentation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: The aim of this study was to compare the efficacy and safety of a thin-strut, biodegradable-polymer everolimus-eluting stent (BP-EES) (Synergy, Boston Scientific, Marlborough, Massachusetts) and a thin-strut, durable-polymer everolimus-eluting stent (DP-EES) (XIENCE, Abbott Vascular, Abbott Park, Illinois) in an all-comers population., Background: BP-EES have been shown to be noninferior to DP-EES in randomized trials in patients at low to moderate risk., Methods: Among 7,042 consecutive patients who underwent percutaneous coronary intervention between December 2012 and December 2016, 3,870 patients were exclusively treated with BP-EES (n = 1,343) or with DP-EES (n = 2,527). After propensity score matching, the final study population consisted of 1,041 matched patients. The primary endpoint was the device-oriented composite endpoint (cardiac death, target vessel myocardial infarction, and target lesion revascularization) at 12 months., Results: The device-oriented composite endpoint did not differ between the 2 groups (7.8% with BP-EES vs. 7.1% with DP-EES; hazard ratio: 1.12; 95% confidence interval: 0.81 to 1.53; p = 0.49). There were no differences in rates of cardiac death (3.0% vs. 3.0%; p = 1.00), target vessel myocardial infarction (3.6% vs. 3.1%; p = 0.53), and target lesion revascularization (3.0% vs. 2.5%; p = 0.41). The rate of acute stent thrombosis was significantly higher in the BP-EES group compared with the DP-EES group (1.2% vs. 0.3%; hazard ratio: 4.00; 95% confidence interval: 1.13 to 14.19; p = 0.032). At 12 months, the frequency of definite stent thrombosis did not differ (1.5% vs. 0.9%; hazard ratio: 1.67; 95% confidence interval: 0.73 to 3.82; p = 0.22)., Conclusions: In this consecutively enrolled percutaneous coronary intervention population reflecting routine clinical practice, no difference in the device-oriented composite endpoint between BP-EES and DP-EES was observed throughout 12 months. There was a higher rate of acute stent thrombosis with the BP-EES, a difference that disappeared at 1 year. (CARDIOBASE Bern PCI Registry; NCT02241291)., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Hydrogen chloride (HCl) non-thermal plasma was applied to introduce Cl active sites on biochar prepared from sorghum straw in this study. Surface modified biochar was then placed in flue gas with typical components to investigate its elemental mercury (Hg 0 ) capture ability. To elucidate the adsorption mechanism & binding properties, samples were characterized by N 2 adsorption, scanning electron microscopy with energy dispersive spectrometer (SEM-EDS) and X-ray absorption near edge structure (XANES) analysis of Hg L III -edge, Cl K-edge and S K-edge. Experimental results showed that HCl plasma modification successfully increased Cl active sites on biochar and greatly increased its mercury removal efficiency. Both HCl treatments (w/without plasma involvement) altered biochar's surface structure and layered structure generated. XANES spectra revealed that adsorbed-Hg on HCl-treated biochars mainly in the form of Hg + . Gaseous Hg 0 was believed to heterogeneously react with chlorinated sites through electron-transfer and formed Hg 2 Cl 2 compounds. With the presence of NO or SO 2 in the system, adsorbed mercury existed on biochar mainly as Hg + . SO 2 competed and inhibited the adsorption of Hg 0 ; while NO promoted Hg 0 removal capacity by increasing the active sites and enhancing the adsorption kinetics of adjacent Cl-containing sites., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: This study sought to validate European Society of Cardiology guideline-endorsed high-risk features of stent-related recurrent ischemic events for the prediction of ischemic and bleeding outcomes including a stratification according to the PRECISE-DAPT score estimated bleeding risk., Background: The 2017 European Society of Cardiology-focused update on dual-antiplatelet therapy endorsed high-risk features of stent-related recurrent ischemic events. Because patients with high ischemic risk also have an increased bleeding risk, appropriate risk stratification for ischemic and bleeding events is crucial., Methods: Between January 2009 and December 2015, a total of 10,236 consecutive patients undergoing clinically indicated percutaneous coronary intervention were prospectively included in the Bern PCI Registry. Guideline-endorsed high-risk features were retrospectively assessed. The primary ischemic endpoint was device-oriented composite endpoint (DOCE) (cardiac death, target-vessel myocardial infarction, and target lesion revascularization) at 1 year, and the primary bleeding endpoint was Bleeding Academic Research Consortium (BARC) 3-5 at 1 year., Results: A total of 5,323 (52.0%) patients had at least 1 high-risk feature. Among patients with high-risk features, DOCE (12.3% vs. 5.5%; p < 0.001) and BARC 3-5 bleeding (4.9% vs. 2.2%; p < 0.001) occurred more frequently compared with those without. There was a graded risk increase for DOCE (0: 5.5%; 1 to 2: 11.3%; and ≥3: 16.7%; p < 0.001) and BARC 3-5 bleeding (0: 2.2%; 1 to 2: 4.5%; and ≥3: 6.6%; p < 0.001) as the number of high-risk features increased. High-PRECISE-DAPT score (≥25) was associated with an increased risk of DOCE and BARC 3-5 bleeding, irrespective of number of high-risk features., Conclusions: The European Society of Cardiology guideline-endorsed high-risk features were associated with increased ischemic and bleeding risks following percutaneous coronary intervention in routine clinical practice. (CARDIOBASE Bern PCI Registry; NCT02241291)., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The adhesion and migration of leukocytes to arterial endothelial cells (ECs), one of the indicators of early atherogenesis, is believed to be correlated with the blood flow conditions and interactions between vascular cells including vascular smooth muscle cells (SMCs). In this study, we investigated the effect of fluid shear stress on the transendothelial migration of leukocytes in a coculture model (CM) composed of human umbilical ECs and SMCs, a layer of collagen type I, and a porous membrane. Following exposure to a fluid shear stress of 1.5 Pa for 24 h, human mononuclear leukocytes were seeded on the EC surface and cultured for 1 h. Leukocytes migrating across the EC layer were observed by confocal laser scanning microscopy. The number of migrating leukocytes in the statically cultured CM was significantly larger than that in the static EC monoculture model. The exposure to the shear stress significantly decreased the leukocyte migration induced by the coculture condition. In the static CM, fluorescence staining and Western blotting showed a higher expression of intercellular adhesion molecule-1 (ICAM-1) of ECs. These results indicate that SMC-derived bioactive soluble factors may stimulate the ICAM-1 expression of cocultured ECs, possibly leading to leukocyte migration into the subendothelial space., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: This study compared adenosine stress computed tomography myocardial perfusion (CTP) with single-photon emission computed tomography (SPECT) in the diagnosis of functionally significant coronary artery stenosis using fractional flow reserve (FFR) as reference standard., Methods: We included a total of 93 coronary arteries from 31 patients in whom at least one vessel with ≥50% stenosis was detected with computed tomography coronary angiography. All patients underwent both SPECT and adenosine stress CTP, followed by invasive coronary angiography (ICA) and FFR. Diagnostic accuracy between CTP and SPECT was compared according to positive findings of either ≥99% stenosis on ICA or FFR ≤0.8., Results: Among 78 vessels eligible for the quantitative analyses, significant coronary artery disease (CAD) was diagnosed in 22 vessels of 19 patients. Comparison of CTP vs. SPECT for sensitivity, specificity, positive predictive value (PPV), negative predictive value, and accuracy in detecting significant CAD were 59% vs. 18%, 96% vs. 93%, 87% vs. 50%, 86% vs. 74%, and 86% vs. 72%, respectively., Conclusions: CTP demonstrated a significant diagnostic advantage over SPECT in the identification of significant CAD, especially in terms of sensitivity and PPV. Adenosine stress CTP is useful for the noninvasive diagnosis of functionally significant CAD., (Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

This study presents two simple and rapid methods for the quantification of therapeutic mAbs based on LC. Two mAbs (bevacizumab and infliximab) in plasma samples were purified using magnetic beads immobilized with a commercially-available idiotype antibody for each mAb. Purified mAbs were separated with HT-RPLC and detected with their native fluorescence. Using immunoaffinity beads, each mAb was selectively purified and detected as a single peak in the chromatogram. The HT-RPLC achieved good separation for the mAbs with sharp peaks within 20 min. The calibration curves of the two mAbs ranged from 1 to 20 μg mL(-1) (bevacizumab) and 1-10 μg mL(-1) (infliximab), and they had strong correlation coefficients (r(2) > 0.998). The LOD of bevacizumab and infliximab was 0.07 and 0.15 μg mL(-1), and the LLOQ of bevacizumab and infliximab was 0.12 and 0.25 μg mL(-1), respectively. Thus, the sensitivities were sufficient for clinical analysis. Immunoaffinity purification with HT-RPLC produced a selective and accurate bioanalysis without an LC-MS/MS instrument. Both methods could become general-purpose analytical methods and complement the results obtained with conventional LBA., (Copyright © 2016 Elsevier B.V. All rights reserved.)

A fast, simple, and sensitive flow injection analysis method was developed for the measurement of semicarbazide-sensitive amine oxidase (SSAO) activity in human serum. Benzaldehyde, generated by the action of SSAO after incubation of serum with benzylamine, was derivatized with a novel aromatic aldehyde-specific reagent (1,2-diaminoanthraquinone) and the fluorescent product was measured by fluorescence detection at excitation and emission wavelengths of 390 and 570nm, respectively. Serum SSAO activity was defined as benzaldehyde (nmol) formed per milliliter serum per hour. The method was linear over SSAO activity of 0.2-150.0nmolmL(-1)h(-1) with a detection limit of 0.06nmolmL(-1)h(-1). The %RSD of intra-day and inter-day precision did not exceed 9.4% and the accuracy ranged from -6.5 to -0.6%. The method was applied for the determination of the serum SSAO activity in healthy controls (C, n=24) and diabetes mellitus patients (DM, n=18). It was demonstrated that the activity (mean±SE) of SSAO in diabetics sera was significantly higher than that in healthy subjects' ones (DM; 73.3±1.8nmolmL(-1)h(-1)vs C; 58.9±2.2nmolmL(-1)h(-1), P<0.01)., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Although dopamine plays an important role for motor control and modulates the frontal function via basal ganglia-thalamo-cortical loop, it is not known whether dopamine can affect the awareness of motor intention or not. To test this hypothesis, we applied Libet's clock paradigm to Parkinson's disease (PD) patients. Thirteen PD patients and 13 age-matched, healthy controls took part in the experiment which consisted of three judgment paradigms: W, M and S judgment. In W and M judgments, subjects were asked to press the key at self-willed timing. In W judgment, subjects reported the location of the clock's hand when they became aware of the intention (W-time). In M judgment, subjects reported the time when they became aware of the actual movement (M-time). In S judgment, subjects reported the time of the electrical stimulation given to their hand (S-time). W-time was significantly shorter in PD patients than in healthy control subjects while M-time and S-time were not different between the two groups. Delayed awareness of motor intention but not of action in PD patients might be related to dopamine depletion in those patients., (Copyright © 2015 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.)

A highly sensitive, selective and reproducible chromatographic method is described for determination of low-molecular mass unsaturated aliphatic aldehydes in human serum. The method combines fluorescent labeling using 4-(N,N-Dimethylaminosulfonyl)-7-hydrazino-2,1,3-benzoxadiazole with peroxyoxalate chemiluminescence. The derivatives were separated on a reversed-phase column C8 isocratically using a mixture of acetonitrile and 90mM imidazole-HNO3 buffer (pH 6.4, 1:1, % v/v). The calibration ranges were: 20-420nM for methylglyoxal, 16-320nM for acrolein, 15-360nM for crotonaldehyde and 20-320nM for trans-2-hexenal. The detection limits were ranged from 4.4 to 6.5nM (88-130fmol/injection), the recovery results were within the range of 87.4-103.8% and the intra and inter-day precision results were lower than 5.5%. The proposed validated method has been successfully applied to healthy, diabetic and rheumatic arthritis patients' sera with simple pretreatment method. In conclusion, this new method is suitable for routine analysis of large numbers of clinical samples for assessment of the oxidative stress state in patients., (Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.)

Vitamin K is a fat-soluble vitamin involved in blood coagulation and bone metabolism. The detection and monitoring of vitamin K homologues in rheumatoid arthritis (RA) patients is a challenging problem due to the smaller concentrations of vitamin K and the presence of several interfering medications. Therefore, this study aimed to develop a new highly sensitive and selective chemiluminescence (CL) method designated to quantify vitamin K homologues in plasma of RA patients including phylloquinone (PK, vitamin K(1)), menaquinone-4 (MK-4, vitamin K(2)) and menaquinone-7 (MK-7, vitamin K(2)). The method was based on the unique photochemical properties of vitamin K homologues that were exploited for selective luminol CL reaction. The correlation coefficients of 0.998 or more were obtained in the concentration ranges of 0.1-100 ng mL(-1) vitamin K homologues. The detection limits were 0.03-0.1 ng mL(-1) in human plasma for vitamin K homologues. The developed HPLC-CL system was successfully applied for selective determination of vitamin K homologues in plasma of RA patients. The developed method may provide a useful tool for monitoring vitamin K homologues in different clinical studies such as RA, osteoporosis and hepatocellular carcinoma in which vitamin K is intervented., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Cardiogenesis proceeds with concomitant changes in hemodynamics to accommodate the circulatory demands of developing organs and tissues. In adults, circulatory adaptation is critical for the homeostatic regulation of blood circulation. In these hemodynamics-dependent processes of morphogenesis and adaptation, a mechanotransduction pathway, which converts mechanical stimuli into biological outputs, plays an essential role, although its molecular nature is largely unknown. Here, we report that expression of zebrafish miR-143 is dependent on heartbeat. Knocking-down miR-143 results in de-repression of retinoic acid signaling, and produces abnormalities in the outflow tracts and ventricles. Our data uncover a novel epigenetic link between heartbeat and cardiac development, with miR-143 as an essential component of the mechanotransduction cascade., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

This is a study of a patient who manifests all of the features of a diffuse leiomyomatosis-Alport syndrome (DL-ATS), and her two-year-old son who has already been diagnosed with Alport syndrome. Fourteen years ago, the patient underwent a partial esophageal resection followed by a replacement with jejunum. Recently, she underwent a surgical resection of the esophagus due to esophageal dysfunction. Genetic analyses of COL4A5 and COL4A6 on the X-chromosome were efficiently performed using the genomic DNA of her son. We have identified a novel deletion of 194-kb in length, encompassing COL4A5-COL4A6 promoters as well as nearly the entire large intron 1 of COL4A5 and intron 2 of COL4A6. To uncover the relationship of the esophagus-specific occurrence of the tumor and the expression of those genes, immunohistochemical analyses of type IV collagen α chains were conducted in the non-affected individuals. The esophageal smooth muscle-specific expression of α5(IV) and α6(IV) chains in the gastrointestinal tract was observed. Moreover, CAG repeat analysis of the androgen receptor gene and an immunohistochemical analysis in the leiomyoma revealed clonal overgrowth of the cells which received X-inactivation on the non-affected allele. These results may suggest that the dominant effect was caused by the partial deletion of the esophageal smooth muscle-specific genes, COL4A5 and COL4A6., (Copyright © 2010 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.)

Background: There is a growing evidence that reactive oxygen species (ROS) may cause many pathologic conditions including chronic diseases, neurodegenerative disorders, cancer and aging. There are a number of methods to measure the total antioxidative activity of the serum. However, since the lifetime and oxidative activity of various types of ROS are all different, to measure simply the total antioxidative activity of the serum is not enough. Therefore, to aid the diagnosis and to improve the therapeutic strategy, it is important to develop a simple and reliable method of assaying antioxidative activity of the serum., Methods: A method that combines sequential injection analysis (SIA) and luminol chemiluminescence (CL) detection was employed for the measurement of antioxidative activities of human serum. We collected sera from healthy subjects (n=42) and patients with diabetes (n=39) and rheumatoid arthritis (n=25) and tested the sensitivity, reproducibility and reliability of our method., Results: Since the operation is automatically controlled by a personal computer, we obtained a satisfactory repeatability without the need of much manpower. The time required for obtaining the antioxidative activity against one ROS for one individual is less than 3min. Although the value of antioxidative activity varies from subject to subject, there were a certain relationship between the disease and the antioxidative values of each type of ROS. The results suggest that the measurement of antioxidative activity against different ROS may provide us with valuable information regarding the disease state., Conclusions: The evaluation of antioxidative activities against each ROS by the proposed method should be more informative to understand the antioxidative status of biological fluid., (Crown Copyright 2010. Published by Elsevier B.V. All rights reserved.)

Introduction: Cherubism is a human genetic disorder that causes bilateral symmetrical enlargement of the maxilla and the mandible in children. It is caused by mutations in SH3BP2. The exact pathogenesis of the disorder is an area of active research. Sh3bp2 knock-in mice were developed by introducing a Pro416Arg mutation (Pro418Arg in humans) in the mouse genome. The osteoclast phenotype of this mouse model was recently described., Methods: We examined the bone phenotype of the cherubism mouse model, the role of Sh3bp2 during bone formation, osteoblast differentiation, and osteoblast function., Results: We observed delays in early postnatal development of homozygous Sh3bp2(KI/KI) mice, which exhibited increased growth plate thickness and significantly decreased trabecular bone thickness and bone mineral density. Histomorphometric and microcomputed tomography analyses showed bone loss in the cranial and appendicular skeletons. Sh3bp2(KI/KI) mice also exhibited a significant decrease in osteoid formation that indicated a defect in osteoblast function. Calvarial osteoblast cell cultures had decreased alkaline phosphatase expression and mineralization, suggesting reduced differentiation potential. Gene expression of osteoblast differentiation markers such as collagen type I, alkaline phosphatase, and osteocalcin were decreased in osteoblast cultures from Sh3bp2(KI/KI) mice., Conclusions: These data suggest that Sh3bp2 regulates bone homeostasis through not only osteoclast-specific effects, but also through effects on osteoblast differentiation and function., (Copyright (c) 2010 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.)

Fluid shear stress (FSS) acting on the apical surface of endothelial cells (ECs) can be sensed by mechano-sensors in adhesive protein complexes found in focal adhesions and intercellular junctions. This sensing occurs via force transmission through cytoskeletal networks. This study quantitatively evaluated the force transmitted through cytoskeletons to the mechano-sensors by measuring the FSS-induced strain on SFs using live-cell imaging for actin stress fibers (SFs). FSS-induced bending of SFs caused the SFs to align perpendicular to the direction of the flow. In addition, the displacement vectors of the SFs were detected using image correlation and the FSS-induced axial strain of the SFs was calculated. The results indicated that FSS-induced strain on SFs spanned the range 0.01-0.1% at FSSs ranging from 2 to 10 Pa. Together with the tensile property of SFs reported in a previous study, the force exerted on SFs was estimated to range from several to several tens of pN., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Functional and morphological responses of endothelial cells (ECs) to fluid shear stress are thought to be mediated by several mechanosensitive molecules. However, how the force due to fluid shear stress applied to the apical surface of ECs is transmitted to the mechanosensors is poorly understood. In the present paper, we performed an analysis of an intracellular mechanical field by observation of the deformation behaviors of living ECs exposed to shear stress with a novel experimental method. Lateral images of human umbilical vein ECs before and after the onset of flow were obtained by confocal microscopy, and image correlation and finite element analysis were performed for quantitative analyses of subcellular strain due to shear stress. The shear strain of the cells changed from 1.06+/-1.09% (mean+/-SD) to 4.67+/-1.79% as the magnitude of the shear stress increased from 2 to 10 Pa. The nuclei of ECs also exhibited shear deformation, which was similar to that observed in cytoplasm, suggesting that nuclei transmit forces from apical to intracellular components, as well as cytoskeletons. The obtained strain-stress relation resulted in a mean shear modulus of 213 Pa for adherent ECs. These results provide a mechanical perspective on the investigation of flow-sensing mechanisms of ECs., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Objective: To test whether the normal aging itself may change the cortical plasticity in human., Methods: Motor-evoked potentials (MEPs) were measured from 48 right-handed healthy volunteers (age 21-79) before and after the paired associative stimulation (PAS), comprising a single electric stimulus to the right median nerve at wrist and subsequent transcranial magnetic stimulation (TMS) of the left primary motor cortex., Results: The magnitude of MEP increased by PAS in the young and middle but not in the elderly and its change was negatively correlated with the age., Conclusions: These results suggest that the human M1 shows age-dependent reduction of cortical plasticity., Significance: The reduction of the M1 plasticity may be caused by the attenuated responsiveness of intracortical circuits in the M1 and/or disrupted sensorimotor integration within basal ganglia-thalamocortical loop., (Copyright 2009 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

We present two cases of young adults with acute disseminated encephalomyelitis (ADEM) who developed severe conscious and motor disturbances. Despite their similar initial clinical course and MRI findings, their motor function outcomes were quite different. In both cases, fluid attenuated inversion recovery (FLAIR) sequenced MRI showed multiple symmetric hyperintense lesions in the internal capsule and the brainstem at the subacute stage. However, in case 1 the apparent diffusion coefficient (ADC) was pathologically decreased in the internal capsule, whereas the ADC for case 2 was normal. At the end of the examination period, severe motor disability (bedridden state) with brain atrophy apparent on MRI remained in case 1, whereas case 2 made an almost full recovery without brain atrophy. These two cases suggest that altered ADC in the internal capsules at the subacute stage may reflect a different pathogenesis between cytotoxic and vasogenic edema, and may be a valuable indicator for the prognosis of motor disturbance.

CueO is a multicopper oxidase (MCO) that is involved in the homeostasis of Cu in Escherichia coli and is the sole cuprous oxidase to have ever been found. Differing from other MCOs, the substrate-binding site of CueO is deeply buried under a methionine-rich helical region including alpha-helices 5, 6, and 7 that interfere with the access of organic substrates. We deleted the region Pro357-His406 and replaced it with a Gly-Gly linker. The crystal structures of a truncated mutant in the presence and in the absence of excess Cu(II) indicated that the scaffold of the CueO molecule and metal-binding sites were reserved in comparison with those of CueO. In addition, the high thermostability of the protein molecule and its spectroscopic and magnetic properties due to four Cu centers were also conserved after truncation. As for functions, the cuprous oxidase activity of the mutant was reduced to ca 10% that of recombinant CueO owing to the decrease in the affinity of the labile Cu site for Cu(I) ions, although activities for laccase substrates such as 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), p-phenylenediamine, and 2,6-dimethoxyphenol increased due to changes in the access of these organic substrates to the type I Cu site. The present engineering of CueO indicates that the methionine-rich alpha-helices function as a barrier to the access of bulky organic substrates, which provides CueO with specificity as a cuprous oxidase.