A hexagonal-close-packed (hcp), hierarchical amorphous TiO2 nanocolumn array was fabricated by pulsed laser deposition (PLD) using a PS colloidal monolayer as a template under a high pressure (6.7 ...Pa) of background oxygen gas. The formation mechanism was investigated, and a model of multidirection glancing deposition was proposed to explain the formation process. This strategy can be extended to the fabrication of similar structures using different materials. Interestingly, this nanostructured array could be transferred to almost any substrate, avoiding restriction of substrate types in fabrication of nanocolumn arrays, which is helpful in the design and creation of nanodevices on various desired substrates. This hierarchical nanocolumn array exhibits excellent superamphiphilicity with both water and oil contact angles of 0°, without further UV irradiation. More importantly, the amorphous TiO2 nanocolumn array demonstrates better performance in photocatalytic activity than an anatase nanocolumn array due to its large surface area and special microstructures, suggesting that the surface area of the TiO2 is preferable to its crystal structure for enhancing photocatalytic activity. The combination of superamphiphilicity and photocatalytic activity gives the surface an excellent self-cleaning effect.
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IJS, KILJ, NUK, PNG, UL, UM
Background
Although various work-related adverse events affect workers’ mental health, the association between long working hours and mental disorders remains unclear. We investigated the ...characteristics of overtime work and work-related adverse events among all cases of compensated work-related suicide in Japan to empirically reveal the context of the serious consequences.
Methods
We analysed all 167 cases of mental disorders resulting in suicide that were compensated in fiscal year 2015–2016. Hierarchical clustering was applied to the overtime working history. Work-related adverse events were also evaluated as the qualitative aspects of their jobs.
Results
More than half of the cases committed suicide within a month of developing a mental disorder. The Administrative and professional or engineering workers had a higher suicide rate. The clustering analysis revealed chronic long working hours (19%), gradual increase (27%), or rapid increase (25%) in working hours before the onset of a mental disorder. A group of cases with less overwork experienced more interpersonal conflicts.
Conclusion
This is the first study to employ a clustering technique to objectively reveal the actual working patterns behind suicide. The patterns of working overtime before the onset of mental disorders varied considerably among the cases. Taking the transition of working overtime into account may provide clearer insight into the relationship between long working hours and workers’ mental health. These results highlight the need for countermeasures especially for causes of chronic overworking, drastic increases in working hours, and interpersonal conflicts to prevent work-related suicide.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background:Atrial fibrillation (AF) is a common cardiac arrhythmia, associated with increased cardiovascular morbidity and mortality including thromboembolic events. The aims of this study were to ...assess the prevalence of left atrial appendage (LAA) thrombi in Japanese non-valvular atrial fibrillation (NVAF) patients undergoing preprocedural transesophageal echocardiography (TEE) during anticoagulation therapy, and to compare the efficacy of warfarin and direct oral anticoagulants (DOAC).Methods and Results:This retrospective study reviewed records of 559 consecutive NVAF patients (445 men; age, 62±11 years) undergoing preprocedural TEE following at least 3 weeks of anticoagulation therapy. Of these, 275 patients had non-paroxysmal AF (49%). LAA thrombus was observed in 15 patients (2.7%). The prevalence of LAA thrombi was similar between the DOAC group (2.6%) and the warfarin group (2.8%, P=0.86). No patients with CHA2DS2-VASc score=0, or paroxysmal AF without prior stroke or transient ischemic attack, had LAA thrombi. On univariate analysis, non-paroxysmal AF, structural heart disease, antiplatelet therapy, larger left atrium, higher brain natriuretic peptide (BNP), reduced LAA flow, and higher CHA2DS2-VASc score were all associated with LAA thrombi. On multivariate analysis, BNP ≥173 pg/mL remained the only independent predictor of LAA thrombi.Conclusions:LAA thrombi were found in 2.7% of Japanese NVAF patients scheduled for procedures despite ongoing oral anticoagulation therapy. Incidence of thrombi was similar for patients on DOAC and on warfarin.
Scientists engaged in prostate cancer research have been conducting experiments using two‐dimensional cultures of prostate cancer cell lines for decades. However, these experiments fail to reproduce ...and reflect the clinical course of individual patients with prostate cancer, or the molecular and genetic characteristics of prostate cancer, the basic requirement for most of the preclinical studies on prostate cancer. The use of human prostate cancer tissues in experiments has enabled the collection and verification of clinically relevant data, including chemical reactions, changes in proteins, and specific gene expression. Tissue recombination models have been employed for studying prostate development, the initiation and progression of prostate cancer, and the tumor microenvironment. Notably, the epithelial–stromal interaction, which might play a critical role in prostate cancer pathogenesis, can be reproduced in this model. Patient‐derived xenograft models have been developed as powerful avatars comprising patient‐derived prostate cancer tissues implanted in immunocompromised mice and could serve as a precision medicine approach for each prostate cancer patient. Spheroid and organoid assays, representative of modern three‐dimensional cultures, can replicate the conditions in human prostate tumors and the prostate organ itself as a miniature model. Although an intact immune system against the tumor is missing from the models aimed at investigating immuno‐oncological reagents in various malignancies, all these experimental models can help researchers in developing new drugs and selecting appropriate treatment strategies for prostate cancer patients.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Breast fibroadenoma (FA) and phyllodes tumour (PT) often have variations of gene mediator complex subunit 12 (MED12) and mutations in the telomerase reverse transcriptase promoter region (TERTp). ...TERTp mutation is usually tested by Sanger sequencing. In this study, we compared Sanger sequencing and droplet-digital PCR (ddPCR) to measure TERTp mutations in FA and PT samples.
FA and PT samples were collected from 82 patients who underwent surgery at our institution from 2005 to 2016. MED12 mutations for all cases and TERTp mutations for 17 tumours were detected by Sanger sequencing. ddPCR was performed to analyse TERTp mutation in all cases.
A total of 75 samples were eligible for analysis. Sanger sequencing detected MED12 mutations in 19/44 FA (42%) and 21/31 PT (68%). Among 17 Sanger sequencing-tested samples, 2/17 (12%) were TERTp mutation-positive. In ddPCR analyses, a significantly greater percentage of PT (19/31, 61%) was TERTp mutation-positive than was FA (13/44, 30%; P = 0.0046). The mutation positivity of TERTp and MED12 did not correlate, in either FA or PT.
ddPCR was more sensitive for detecting TERTp mutation than Sanger sequencing, being able to elucidate tumorigenesis in FA and PT.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Autoimmune (AI) diseases can affect many organs; however, the prostate has not been considered to be a primary target of these systemic inflammatory processes. Here, we utilize medical record data, ...patient samples, and in vivo models to evaluate the impact of inflammation, as seen in AI diseases, on prostate tissue. Human and mouse tissues are used to examine whether systemic targeting of inflammation limits prostatic inflammation and hyperplasia. Evaluation of 112,152 medical records indicates that benign prostatic hyperplasia (BPH) prevalence is significantly higher among patients with AI diseases. Furthermore, treating these patients with tumor necrosis factor (TNF)-antagonists significantly decreases BPH incidence. Single-cell RNA-seq and in vitro assays suggest that macrophage-derived TNF stimulates BPH-derived fibroblast proliferation. TNF blockade significantly reduces epithelial hyperplasia, NFκB activation, and macrophage-mediated inflammation within prostate tissues. Together, these studies show that patients with AI diseases have a heightened susceptibility to BPH and that reducing inflammation with a therapeutic agent can suppress BPH.
Background: Recurrent ventricular tachycardia (VT) and fibrillation (VF), the so-called “electrical storm” (ES) occurs at various stages of acute myocardial infarction (AMI), but its incidence, ...background, and short-term prognosis remain unclear. Methods and Results: A retrospective observational study was performed using the registry database of the Tokyo CCU Network. The individual data of 6,003 patients with AMI during 2011–2012 was corrected. ES was defined as more than 3 episodes of sustained VT/VF during a 24-h period as first documented after hospitalization. ES occurred in 55 patients after admission (0.9%). The ES(+) group had more severe heart failure (Killip class >III), more extensive MI (peak-CK), greater inflammatory reaction (CRP), history of diabetes, and more frequent application of hemodialysis as compared with the ES(−) group (n=5,865). When the ES patients were divided into Early-ES (n=37: ES occurred ≤48 h after the onset of MI) and Late-ES (n=15 >48 h after onset of MI) groups, logistic regression analysis revealed that Early-ES was associated with severity of MI, whereas Late-ES was related to systemic disorders, including inflammation, renal dysfunction, or diabetes. Late-ES was an independent predictor of in-hospital death. Conclusions: In-hospital ES was a rare clinical manifestation of AMI. The features and background of the ES varied as time elapsed after admission for MI.
Background:Recent experimental studies have demonstrated that several microRNAs (miRNAs) expressed in atrial tissue promote a substrate of atrial fibrillation (AF). However, because it has not been ...fully elucidated whether these experimental data contribute to identifying circulating miRNAs as biomarkers for AF, we used a combined analysis of human serum and murine atrial samples with the aim of identifying these biomarkers for predicting AF.Methods and Results:Comprehensive analyses were performed to screen 733 miRNAs in serum from 10 AF patients and 5 controls, and 672 miRNAs in atrial tissue from 6 inducible atrial tachycardia model mice and 3 controls. We selected miRNAs for which expression was detected in both analyses, and their expression levels were changed in the human analyses, the murine analyses, or both. This screening identified 11 candidate miRNAs. Next, we quantified the selected miRNAs using a quantitative RT-PCR in 50 AF and 50 non-AF subjects. The individual assessment revealed that 4 miRNAs (miR-99a-5p, miR-192-5p, miR-214-3p, and miR-342-5p) were significantly upregulated in AF patients. A receiver-operating characteristics curve indicated that miR-214-3p and miR-342-5p had the highest accuracy. The combination of the 4 miRNAs modestly improved the predictive accuracy for AF (76% sensitivity, 80% specificity).Conclusions:Novel circulating miRNAs were upregulated in the serum of AF patients and might be potential biomarkers of AF.
Atherosclerotic cardiovascular disease (ACVD) is an inflammatory phenomenon that leads to structural abnormality in the vascular lumen due to the formation of atheroma by the deposition of lipid ...particles and inflammatory cytokines. There is a close interaction between innate immune cells (neutrophils, monocyte, macrophages, dendritic cells) and adaptive immune cells (T and B lymphocytes) in the initiation and progression of atherosclerosis. According to novel insights into the role of adaptive immunity in atherosclerosis, the activation of CD4+T cells in response to oxidized low-density lipoprotein-antigen initiates the formation and facilitates the propagation of atheroma, whereas CD8+T cells cause the rupture of a developed atheroma by their cytotoxic nature. Peripheral CD4+and CD8+T-cell counts were altered in patients with other cardiovascular risk factors. Furthermore, on evaluation of the feasibility of immune cells as a diagnostic tool, the blood CD4+(helper), CD8+(cytotoxic), and CD4+CD25+Foxp3+(regulatory) T cells and the ratio of CD4 to CD8 cells hold promise as biomarkers of coronary artery disease and their subtypes. T cells also could be a therapeutic target for cardiovascular diseases. The goal of this review was therefore to summarize the available information regarding immune disorders in ACVD with a special focus on the clinical implications of circulating T-cell subsets as biomarkers.
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