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Immune checkpoint inhibitor (ICI)-induced myocarditis is a potentially life-threatening adverse event. We herein report a rare case of sick sinus syndrome (SSS) co-occurring with ICI-associated myocarditis. A 71-year-old woman with lung cancer undergoing pembrolizumab monotherapy was admitted owing to a fever, worsening kidney function, and sinus bradycardia. She was diagnosed with multi-organ immune-related adverse events, including myocarditis. Pulse steroid therapy was initiated immediately under the support of a temporary pacemaker, which resulted in the resolution of SSS in a few days. Biopsy specimens of the endomyocardium showed active myocarditis. Thus, we should be aware that SSS can co-occur with ICI-induced myocarditis.

We report a case of a patient presenting with arrhythmogenic cardiomyopathy, myofibrillar myopathy, and multiorgan tumors. A 41-year-old woman with a history of hypertrophic cardiomyopathy, diagnosed at 6 years of age, developed scoliosis after puberty. Following spinal surgery to address the scoliosis, she developed recurrent severe arrhythmia and heart failure. She developed hypoventilation at age 29 years. Proximal dominant weakness and mild elevation of serum creatine kinase indicated possible myopathy. Myofibrillar myopathy was diagnosed by muscle biopsy at age 30 year. Acute abdomen was repeatedly reported from age 33 years, eventually leading to a diagnosis of gastric polyp and erosive ulcer. A urinary bladder tumor was found at age 35 years, and breast cancer was diagnosed at age 40 years. Whole exome sequencing detected a heterozygous missense mutation in Filamin C. Recent evidences suggest that filamins are associated with tumors, and this case further highlights the clinical spectrum of filaminopathy.

Pazopanib, a multi-targeted tyrosine kinase inhibitor, is associated with cardiovascular adverse events, such as hypertension, cardiac dysfunction, and thromboembolism. However, symptomatic pazopanib-related bradycardia is uncommon. We herein report a case of symptomatic bradycardia of 35 beats per minute in a patient with solitary fibrous tumor/hemangiopericytoma (SFT/HPC) treated with pazopanib for 1 month. His heart rate recovered to a normal range soon after pazopanib cessation. He restarted pazopanib at a reduced dose, which was continued without SFT/HPC progression or bradycardia recurrence. This case highlights the possibility of bradycardia induced by pazopanib and the importance of monitoring the patient's heart rate.

単発または2連発の心室期外収縮により房室結節内で機能的縦解離したslow pathway(S路)を逆伝導し、fast pathway(F路)を下行する非通常型房室結節リエントリー頻拍が再現性をもって惹起されたと考えられた2例を報告した。症例1は50歳代女性、単発の心室期外収縮によりQRS直前に陰性P波を伴う房室結節リエントリー頻拍が惹起されたが、頻拍の第1拍は洞性P波でも、また洞性P波と陰性P波との心房融合でも惹起された。症例2は50歳代男性で、心室期外収縮2連発によりQRS直前に陰性P波を伴う非通常型房室結節リエントリー頻拍が惹起された。症例2も頻拍の第1拍は洞性P波でも頻拍は惹起されたことから、洞性刺激がリエントリー回路に進入する前にS路からF路への回帰が生じたと考えられた。症例2は頻拍QRSの立ち上がり部分にデルタ波を思わせる盛り上がりがあるように見えることから、bystander WPWとの鑑別診断についても述べ、考察した。

Purpose : Limited data exist about clinically relevant bleeding events related to antiplatelet therapy after percutaneous coronary intervention (PCI) in cancer patients. We investigated the risk factors for clinically relevant bleeding events in patients with cancer after PCI with stent implantation. Patients and Methods : Patients with solid cancer subjected to first PCI were divided into active (n = 45) and non-active cancer groups (n = 44). The active group included non-operable patients on treatment or with metastasis ; the non-active included those already subjected to or for whom radical surgery was planned within 3 months after the index PCI. Results : During a median follow-up of 2.2 years, 11 bleeding events occurred, with only one occurring in the non-active cancer group. Half of them occurred during the dual-antiplatelet therapy (DAPT) period, and the rest occurred during single-antiplatelet therapy (SAPT) period. Kaplan-Meier analysis showed significantly more bleeding events in the active cancer group (p = 0.010). Multivariate Cox regression hazard analysis revealed cancer activity as a significant independent risk factor for bleeding (p = 0.023) ; but not for three-point major adverse cardiovascular events. Conclusion : Clinically relevant bleeding risk after PCI was significantly lower in non-active cancer. Active cancer group had clinically relevant bleeding during both DAPT and SAPT periods. J. Med. Invest. 68 : 29-37, February, 2021.

A 54-year-old woman had been resuscitated after ventricular fibrillation and her electrocardiogram showed a QT prolongation (QTc=510 ms), and genetic screening revealed a missense variant, R1644C, in the SCN5A gene. She was therefore diagnosed with congenital long-QT syndrome (LQTS) type 3. However, the patient had left ventricular dysfunction, and based on the findings of cardiac magnetic resonance imaging, positron emission tomography and pathological examinations, she was diagnosed with cardiac sarcoidosis. Although both are rare diseases, their overlapping presence in this case may have led to an increased cardiovascular risk compared with either alone. Thus, not only genetic but comprehensive clinical examinations are important for making a correct diagnosis.

An increasing number of patients with cancer are being treated with immune checkpoint inhibitors. Consequently, the incidence of immune checkpoint inhibitor-related myocarditis has been increasing. Nonetheless, the diagnostic criteria for the immune checkpoint inhibitor-related myocarditis have not been sufficiently established. Therefore, the real-world incidence or prevalence of immune checkpoint inhibitor-related myocardial damage remains unknown. This was a single-center cohort study that included 100 patients admitted for immune checkpoint inhibitor therapy for any type of cancer. The patients underwent monthly measurement of cardiac troponin I and N-terminal pro-brain natriuretic peptide levels with electrocardiography. Additionally, echocardiography was performed every 3 months. Our protocol was continued until 6 months after the initiation of immune checkpoint inhibitors. We defined immune checkpoint inhibitor-related myocardial damage as an increase in cardiac troponin I levels by >0.026 ng/mL and/or a decrease in the left ventricular ejection fraction by >10% to

Adverse cardiovascular events have been reported in patients with multiple myeloma. We present a case of coronary spastic angina during combination therapy with bortezomib, lenalidomide, and dexamethasone for multiple myeloma. A 70-year-old man, newly diagnosed with multiple myeloma, was admitted to our hospital at his fifth therapy cycle due to exertional chest pain. Coronary angiography revealed diffuse spasm in the left coronary artery, which normalized after intracoronary injection of nitroglycerin. Calcium channel blockers were effective in treating his coronary spastic angina and the patient resumed treatment for multiple myeloma. This case highlights the importance of being aware of the possibility of coronary spastic angina when combination therapy with bortezomib, lenalidomide, and dexamethasone is initiated.

The sterilization of a small vial using electron cyclotron resonance (ECR) plasma was investigated. The ECR plasma was generated throughout the inside of the small vial, which was sealed with nonwoven fabric, by using magnetic configuration in which the ECR point was located inside the small vial. Moreover, it was demonstrated that the temperature of the small vial was finely controlled by the pulse width and pulse frequency of the pulsed microwave power. A biological indicator (BI), Geobacillus Stearothermophilus, containing 1 × 105 spores present inside the small vial was successfully inactivated in a total treatment time of about 14 min while maintaining treatment temperature of less than 65 °C.

Hematopoietic stem cell transplantation (HSCT) is occasionally associated with cardiac dysfunction during long-term follow-up. Global longitudinal strain (GLS) has emerged as an early predictor of cardiotoxicity associated with cancer therapy; however, the serial changes in GLS before and after HSCT have not been elucidated. To clarify the association between HSCT and GLS, we investigated serial changes in GLS before and after HSCT. We evaluated cardiac function before and 1, 3, and 6 months after HSCT in 38 consecutive HSCT patients enrolled in this study. Overall, GLS and left ventricular (LV) ejection fraction (EF) temporally decreased 1 month post-HSCT. LVEF completely recovered to baseline at 3 months after HSCT, whereas GLS partially recovered 6 months after HSCT. Except for five patients who died within 6 months, GLS values in the low EF group (LVEF ≤ 55% at 6 months post-HSCT, n = 6) were significantly and consistently lower than those in the normal EF group (LVEF > 55% at 6 months post-HSCT, n = 27) at any time during follow-up. These findings suggest that GLS before HSCT might be associated with a decrease in LVEF after HSCT in patients with hematologic malignancies. Further prospective and long-term data will be important for understanding the management of HSCT-associated cardiac dysfunction.

Background The effect of incidental pulmonary embolism (PE) on long-term prognosis in cancer patients is unclear. This study assessed the characteristics of cancer and venous thromboembolism (VTE) and the effect of incidental PE identified by oncologists on long-term survival of patients with cancer.Methods and Results:This single-center, retrospective, cohort study used hospital-based cancer registry data from the Osaka International Cancer Institute linked with electronic medical records and administrative data from Japan's Diagnosis Procedure Combination Per-diem Payment System. Overall, 15,689 cancer patients underwent contrast-enhanced thoracic computed tomography during 2010-2018. After excluding patients with missing data, symptomatic patients, or patients with suspected PE, 174 with incidental PE (PE+ group) and 13,197 with no PE (PE- group) were identified. The total incidence of incidental PE was 1.3%. No deaths from thrombotic events were identified in the PE+ group. Both groups were adjusted for cancer- and VTE-related characteristics using inverse probability weighting. After adjusting for immortal time bias in the PE+ group, Kaplan-Meier analysis revealed that all-cause mortality was higher in the PE+ group (hazard ratio, 2.26; 95% confidence interval, 1.53-3.33). A Cox proportional hazard model revealed that metastatic cancer and a history of curative treatment were significant prognostic factors, whereas central PE and residual proximal deep vein thrombosis were not. Conclusions Incidental PE in cancer patients indicates poorer prognosis. Cancer-related but not thrombosis-related factors determine prognosis.

Coronary emboli from malignant tumors rarely cause acute myocardial infarction. We report the case of a patient with tumor embolism from an upper tract urothelial carcinoma that caused acute myocardial infarction via a patent foramen ovale. Coronary blood flow was restored by embolus aspiration without stenting. Clinicians must consider malignant tumor embolism as a possible cause of acute myocardial infarction.

Background: Prevalence of cancer is a high risk factor for bleeding events related with antiplatelet therapy after percutaneous coronary intervention (PCI) in cancer patients. However, the long-term bleeding event rates have not been elucidated previously. Further risk stratification was not sufficiently assessed among cancer patients. This study aimed to evaluate the risk factors for clinically relevant bleeding events in cancer patients after PCI with stent implantation.Methods: Among 236 patients who received PCI between 2013 and 2018, 89 cancer patients with first PCI with stent implantation, without prior dual-antiplatelet therapy (DAPT), were analyzed. They were divided into the active cancer (n=44) and non-active cancer (n=45) groups. The active cancer group included non-operable patients currently on treatment or those with metastasis. The non-active cancer group included patients who had already undergone radical surgery or had planned radical surgery within 3 months after the index PCI. The primary endpoint was bleeding events, characterized as Bleeding Academic Research Consortium (BARC) types 2, 3, and 5. The secondary endpoint was 3-point major adverse cardiovascular events (3P-MACE) determined as the composite of cardiac death, nonfatal myocardial infarction, and nonfatal stroke.Results: During the median follow-up period of 2.2 years, there were 11 patients with bleeding events, with only 1 patient in the non-active cancer group. Of the other 10 patients, 5 experienced bleeding during the dual-antiplatelet therapy (DAPT) period, while the remaining 5 experienced bleeding during the single-antiplatelet therapy (SAPT) period. The Kaplan-Meier analysis showed that the active cancer group had a significantly greater number of bleeding events of BARC types 2, 3, and 5 (log-rank, P=0.010). Multivariate Cox regression hazards model analysis revealed that cancer activity was an independent significant risk factor (HR, 9.03; 95% CI, 1.33–176.69; P=0.023). During the 2.5-years [IQR: 0.7–3.0] follow-up period, there was no significant difference in the 3P-MACE between the active and non-active cancer patients.Conclusions: The non-active cancer group presented with significantly lower clinically relevant bleeding after PCI than the active cancer patients. However, the bleeding risk was high in the active cancer groups during both the DAPT and SAPT periods.

A 69-year-old man had experienced right chest pain for several months. Chest computed tomography (CT) showed a right upper lobe lung tumor and swelling of multiple mediastinal and right hilar lymph node. Three punctures to 4R lymph nodes and two punctures to 11i lymph nodes were performed, using endobronchial ultrasonography. Thirty days after punctures, he was admitted with appetite loss and general fatigue. Chest CT supposed the evidence of mediastinitis and pericarditis. Despite the antibiotics, cardiac tamponade developed on the third hospital day. Pericardial fenestration and pericardial drainage were performed. Gram-positive cocci were identified and Gemella sanguinis was eventually identified as the microbial identification system. Like the former reports, the necessity of surgical procedure for late onset of mediastinitis and pericarditis. caused by EBUS-TBNA was suggested.

Diversification of transcriptomic and epigenomic states may occur during the expansion of colorectal cancers. Certain cancer cells lose their epithelial characters and gain mesenchymal properties, known as epithelial-mesenchymal transition (EMT), and they aggressively migrate into the non-tumorigenic extracellular matrix. In this study, we isolated a subpopulation with accelerated baseline motility (MG cells) and an immotile one (non-MG cells) from a colon cancer cell line (HCT116). Gene expression signatures of the MG cells indicated that this subpopulation was likely an EMT hybrid. The MG cells substantially lost their migratory properties after treatment with a methyltransferase inhibitor, 5-azacytidine, suggesting a role of DNA methylation in this process. Global transcriptome assays of both types of cells with or without 5-azacytidine treatment identified 640 genes, whose expression might be methylation-dependently down-regulated in the MG cells. Global methylation analysis revealed that 35 out of the 640 genes were hyper-methylated in the MG cells. Among them, we focused on the anti-oncogene ZNF350, which encodes a zinc-finger and BRCA1-interacting protein. Notably, ZNF350 knockdown accelerated migration of the non-MG cells, while overexpression of ZNF350 in the MG cells significantly impaired their migration. Finally, pyrosequence analysis together with dual luciferase assays of serially truncated fragments of the ZNF350 promoter (-268 to +49 bp) indicated that three hyper-methylated sites were possibly responsible for the basal promoter activity of ZNF350. Taken together, our results suggest that hyper-methylation of the ZNF350 proximal promoter may be one of the crucial determinants for acquiring increased migratory capabilities in colon cancer cells.

The sterilization of a small vial using electron cyclotron resonance (ECR) plasma was investigated. The ECR plasma was generated throughout the inside of the small vial, which was sealed with nonwoven fabric, by using magnetic configuration in which the ECR point was located inside the small vial. Moreover, it was demonstrated that the temperature of the small vial was finely controlled by the pulse width and pulse frequency of the pulsed microwave power. A biological indicator (BI), Geobacillus Stearothermophilus, containing 1 × 105 spores present inside the small vial was successfully inactivated in a total treatment time of about 14 min while maintaining treatment temperature of less than 65 °C.

Transcribed-ultraconserved regions (T-UCRs), which contain conserved sequences with 100% identity across human, rat and mouse species, are a novel category of functional RNAs. The human transformer 2β gene (TRA2B) encodes a UCR that spans exon 2 (276 bp) and its neighboring introns. Among five spliced RNA variants (TRA2β1-5) transcribed from the TRA2B gene, only TRA2β4 contains the conserved exon 2. TRA2β4 is overexpressed in colon cancer cells and accelerates cell growth by blocking the transcription of CDKN1A. However, the mechanisms underlying the overexpression of TRA2β4 in colon cancer cells are unknown. Using biotinylated RNA pull-down assays followed by liquid chromatography-mass spectrometric analysis, we identified nucleolin as a TRA2β4-binding protein. Knockdown of nucleolin reduced the nuclear retention of TRA2β4 and accelerated its degradation in the cytoplasm, whereas nucleolin overexpression increased TRA2β4 levels and its mitogenic activity. Nucleolin directly bound to TRA2β4 exon 2 via the glycine/arginine-rich (GAR) domain. Overexpression of GAR-deficient nucleolin failed to increase TRA2β4 expression and growth of colon cancer cells. RNA fluorescence in situ hybridization showed that TRA2β4 co-localized with nucleolin in nuclei but not with the mutant lacking GAR. Our results suggest that specific interactions between nucleolin and UCR-containing TRA2β4 may be associated with abnormal growth of colon cancer cells.

Lamin A/C proteins, major components of the nuclear lamina, are encoded by the LMNA gene. These proteins have multiple cellular functions, including DNA transcription and replication, chromatin organization, regulation of the cell cycle, and apoptosis. Mutations in LMNA are associated with a variety of diseases called laminopathies. LMNA has implications in cancer; however, its mechanisms of dysregulation in cancer cells are not yet fully understood. In this study, among the LMNA transcript variants, we focused on a transcriptional variant 6 (termed LMNA-V6), which contains unique 3 exons upstream of exon 1 of LMNA. The promoter region of LMNA-V6 formed multiple G-quadruplexes and increased its transcriptional activity. Moreover, LMNA-V6 negatively regulated other LMNA mRNA variants, lamin A and lamin C, via direct interaction with their promoter. Knockdown of LMNA-V6 decreased the proliferation of colon cancer cells, whereas overexpression of the unique 3 exons of LMNA-V6 increased cell growth. Furthermore, microarray gene expression profiling showed that alteration of LMNA-V6 levels influenced the expression of p53 in colon cancer cells. Taken together, the results suggest that LMNA-V6 may be a novel functional RNA whose expression is regulated through multiple G-quadruplexes in colon cancer cells.

Venous thromboembolism occurs in prothrombotic states, such as malignancy. To prevent fatal pulmonary thromboembolism, an indwelling inferior vena cava (IVC) filter is considered in addition to anticoagulation therapy. We herein report a case of fracture of a retrievable IVC filter in a malignant lymphoma patient. One of the filter arms was fractured and fixed to the IVC wall after one year. Since dislocation of the fractured arm was assessed correctly using three-dimensional computed tomography, we were able to retrieve the main body of the IVC filter successfully. Indications and management of IVC filter fracture should be discussed.

Objectives The purpose of this study was to assess osimertinib-associated cardiac adverse events (AEs) in a real-world setting, using a retrospective single-center cohort study in Japan. Background Cases of osimertinib-associated cardiac AEs have been reported but remain poorly understood. Methods A total of 123 cases of advanced non–small cell lung cancer (NSCLC) with confirmed EGFR mutations who received osimertinib monotherapy from 2014 to 2019 at the Osaka International Cancer Institute (Osaka, Japan) were evaluated. Cardiac AEs were defined according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Changes in left ventricular ejection fraction (LVEF) and rates of cancer therapeutics-related cardiac dysfunction (CTRCD), defined as a ≥10 % absolute decline in LVEF from baseline to a value of, Central Illustration

The human TRA2B gene consists of 10 exons and 9 introns and produces 5 splice isoforms (TRA2β1 to TRA2β5). TRA2B exon 2 encodes multiple premature termination codons. TRA2β1 lacks exon 2 and is translated into a functional transformer 2β (Tra2β) protein, whereas TRA2β4 contains 10 exons and works as a functional RNA. Overexpressed Tra2β and ectopic expression of TRA2β4 may be oncogenic. We found that heterogeneous nuclear ribonucleoprotein (hnRNP)A1 and hnRNPU interacted with TRA2β4 exon 2. Minigene assays revealed that hnRNPA1 facilitated inclusion of exon 2, whereas hnRNPU promoted its skipping. However, knockdown of hnRNPA1 or hnRNPU reduced both TRA2β1 and TRA2β4 levels, and overexpression of these hnRNPs increased levels of both isoforms, suggesting that hnRNPA1 and hnRNPU mainly regulate the transcription of TRA2B. In fact, hnRNPA1 and hnRNPU positively regulated the promoter activity of TRA2B. Circular dichroism analyses, electrophoretic mobility shift assays and chromatin immunoprecipitation assays demonstrated the presence of G-quadruplex (G4) formation in the promoter of TRA2B. Formation of G4 suppressed TRA2B transcription, whereas hnRNPA1, but not hnRNPU, interacted with the G4 to facilitate transcription. Our results suggest that hnRNPA1 may modulate TRA2B transcription through its regulation of G4 formation in its promoter in colon cancer cells.

Geranylgeranylacetone (GGA) is a chaperon inducer that protects various types of cell and tissue against stress. We examined whether GGA modulated energy intake and expenditure under stressful conditions. After mice were untreated or treated orally with GGA (0.16 g per kg body weight per day) for 10 days, they were subjected to 2-h restraint stress once or once a day for 5 consecutive days. GGA administration did not affect corticosterone response to the stress. Restraint stress rapidly decreased plasma leptin levels in control mice. GGA significantly increased circulating leptin levels without changing food intake and prevented the stress-induced decline of circulating leptin. However GGA-treated mice significantly reduced food intake during the repeated stress, compared with control mice. GGA prevented the stress-induced decline of leptin mRNA and its protein levels in epidydimal adipose tissues. We also found that GGA decreased ghrelin mRNA expression in gastric mucosa before the stress, whereas GGA-treated mice recovered the ghrelin mRNA expression to the baseline level after the repeated stress. Leptin and ghrelin are now recognized as regulators of anxiety and depressive mood. Our results suggest that GGA may regulate food intake and relief stress-induced mood disturbance through regulating leptin and ghrelin secretions. J. Med. Invest. 65:103-109, February, 2018.

Transcribed-ultraconserved regions (T-UCRs), which contain conserved sequences with 100% identity across human, rat and mouse species, are a novel category of functional RNAs. The human

Genome integrity can be threatened by various endogenous or exogenous events. To counteract these stressors, the DNA damage response network contributes to the prevention and/or repair of genomic DNA damage and serves an essential function in cellular survival. DNA binding proteins are involved in this network. Recently, several RNA-binding proteins (RBPs) that are recruited to DNA damage sites have been shown to be direct players in the prevention or repair of DNA damage. In addition, non-coding RNAs, themselves, are involved in the RNA-mediated DNA repair system. Furthermore, RNA modification such as m6A methylation might also contribute to the ultraviolet-responsive DNA damage response. Accumulating evidence suggests that RNA metabolism is more deeply involved in diverse cellular functions than previously expected, and is also intricately associated with the maintenance of genome integrity. In this review, we highlight the roles of RBPs in the maintenance of genome integrity.

Adverse parenting is associated with an increased risk for the development of mood and behavioral disorders. In this study, we assessed the perceived parental bonding of 232 medical students using the parental bonding instrument (PBI) and extracted 22 students who reported their parents' rearing attitudes as affectionless control (LOW; low care, high overprotection). Using the 28-item general health questionnaire, the Zung self-rating depression scale (Zung-SDS), the hospital anxiety and depression scale (HADS), and the Spielberger state-trait-anxiety-inventory (STAI), physical and mental state of the LOW students were compared with those of 30 students who reported their parental bonding as optimal (OPT; high care and low overprotection). These questionnaire measurements demonstrated significantly higher anxiety and depressive mood in the LOW students versus the OPT students. Compared with the OPT students, the LOW students also exhibited a significantly reduced salivary cortisol awakening response (CAR) without changes across the rest of the diurnal salivary cortisol profile. Among glucocorticoid-related genes examined (GR, ADRB2, IκBα, IL10, IL1R2, IL1RN, MR, MC2R, TGFB1, TGFB2 and FASLG), real-time reverse transcription-PCR showed that the LOW students significantly increased expression of a dominant negative glucocorticoid receptor β (GRβ) mRNA and decreased β2-adrenergic receptor (ADRB2) mRNA levels in circulating leukocytes. These results suggest that negative perception of parents' child-rearing attitudes may be associated with anxiety and depressive mood and altered glucocorticoid signaling even in healthy young adults.

Organic-inorganic hybrid microtubes were prepared that consisted of polysaccharide inner layers and hydroxyapatite (HAp) outer layers. Poly(methyl methacrylate) (PMMA) fibers containing small amounts of polyethyleneimine (PEI) were used as templates for the layer-by-layer (LbL) assembly of chondroitin sulfate C and chitosan. HAp layers were then deposited on polysaccharide layer-coated fibers using biomimetic processes. PMMA-PEI fiber templates were removed by immersing the samples in chloroform. Examination of the resulting materials using various physical characterizations such as scanning electron microscopy, FT-IR spectroscopy, X-ray photoelectron spectroscopy, and X-ray diffraction studies supported the successful formation of the hybrid microtubes as designed. The results also showed that incorporation of PEI into PMMA fiber matrices was effective in inducing HAp deposition. The present procedure can be applied to the preparation of various hybrid microtubes consisting of biocompatible organic inner layers formed using LbL assemblies and HAp outer layers. Some of these hybrids have potential applications in regenerative medicine or tissue engineering.

Inequality in socioeconomic status (SES) is associated with an increased risk for the development of mental health problems. Here, we examined the association between socioeconomic status (SSS) and psychological distress, and measured gene expression signatures in peripheral blood leukocytes responsible for this association, in 129 healthy adults (27 males and 102 females, aged 44.0 ± 13.0 years) working in a private hospital in Japan. Depressive mood was assessed by Zung Self-rating Depression Scale (SDS). A multiple regression analysis adjusted for gender and age showed that subjective SSS was independently and negatively associated with SDS score. We next focused on 9 subjects who exhibited low SSS scores and 11 subjects with high SSS scores. Microarray analysis revealed that levels of 522 mRNAs were differentially expressed in periheral leukocytes between low and high-SSS groups. The differentially expressed genes were preferentially involved in cellular movement or inflammatory responses. Among them, mRNA levels of pro-platelet basic protein (PPBP) and solute carrier family 1 (glutamine transporter), member 7 (SLC1A7) were negatively correlated with SSS scores. Our results re-confirmed the association between negative perception of SES and depressive mood in healthy adults, and suggest a possible involvement of PPBP and SLC1A7 in the association.

Aims The prognostic impact of chronic total coronary occlusion (CTO) on implantable cardioverterdefibrillator (ICD) recipients remains unclear. Methods and Results Eighty-four consecutive patients with ischemic heart disease who received ICD therapy for primary or secondary prevention were analyzed. We investigated all-cause mortality and major adverse cardiac events (MACEs) including cardiac death, appropriate device therapy, hospitalization for heart failure, and ventricular assist device implantation. Of the study patients (mean age 70 ± 8 years; 86% men), 34 (40%) had CTO. There were no significant differences in age, left ventricular ejection fraction (LVEF), NYHA functional class III or IV status, and proportion who underwent secondary prevention between patients with CTO (CTO group) and without CTO (non-CTO group). During a median follow-up of 3.8 years (interquartile range 2.7 to 5.4 years), the CTO group tended to have a higher MACE rate (log-rank P=0.054) than the non-CTO group. Within the CTO group, there was no difference in the MACE rate between patients with and without viable myocardium. In patients with ICD for secondary prevention (n=47), 16 patients (34%) with CTO had a higher MACE rate than patients without CTO (logrank P

撹拌槽内の層流による混合パターン形成は，撹拌翼の先端から伸びる流脈線によって規定され，混合パターンの輪郭は，時間とともに流脈線形状に近づくことが知られている．そのため，流脈線の正確な形状把握は，混合機構の解析に重要な手がかりを与える．良混合を生み出すカオス的な流れ場では，流体軌跡は特定の方向に指数関数的に広がる傾向がある．そのため，実験で可視化された流脈は，その方向に急速に面状に広がり，線としての流脈の可視化が困難となるため，流脈線に基づく混合解析を妨げる大きな要因となっていた．本研究では，撹拌槽内のような3次元流れ場においても，鮮明な流脈“線”を可視化することのできる新しい実験手法を開発した．その特徴は，流脈となる可視化液中に特殊な界面活性剤を添加することにより，流脈の広がりを抑制したことにある．これにより，撹拌翼の羽根先端から伸びる鮮明な流脈線の可視化が可能になった．本手法で形成された流脈線は，長時間にわたって線の形状を安定に保つだけでなく，分子拡散効果による流脈液からの着色成分の漏出も少ないことがわかった．

Homeodomain-interacting protein kinase 2 (HIPK2) is a serine/threonine kinase that phosphorylates and activates the apoptotic program through interaction with diverse downstream targets including tumor suppressor p53. HIPK2 is activated by genotoxic stimuli and modulates cell fate following DNA damage. The DNA damage response (DDR) is triggered by DNA lesions or chromatin alterations. The DDR regulates DNA repair, cell cycle checkpoint activation, and apoptosis to restore genome integrity and cellular homeostasis. Maintenance of the DDR is essential to prevent development of diseases caused by genomic instability, including cancer, defects of development, and neurodegenerative disorders. Recent studies reveal a novel HIPK2-mediated pathway for DDR through interaction with chromatin remodeling factor homeodomain protein 1γ. In this review, we will highlight the molecular mechanisms of HIPK2 and show its functions as a crucial DDR regulator.

The characteristics of surface sterilization using electron cyclotron resonance (ECR) plasma were investigated. High-energy electrons and oxygen radicals were observed in the ECR zone using electric probe and optical emission spectroscopic methods. A biological indicator (BI), Geobacillus stearothermophilus, containing 1 × 106 spores was sterilized in 120 s by exposure to oxygen discharges while maintaining a temperature of approximately 55 °C at the BI installation position. Oxygen radicals and high-energy electrons were found to be the sterilizing species in the ECR region. It was demonstrated that the ECR plasma could be produced in narrow tubes with an inner diameter of 5 mm. Moreover, sterilization tests confirmed that the spores present inside the narrow tube were successfully inactivated by ECR plasma irradiation.