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We used a resonant-tunneling-diode (RTD) oscillator as the source of a terahertz-wave radar based on the principle of the swept-source optical coherence tomography (SS-OCT). Unlike similar reports in the terahertz range, we apply the stepwise frequency modulation to a subcarrier obtained by amplitude modulation instead of tuning the terahertz carrier frequency. Additionally, we replace the usual optical interference with electrical mixing and, by using a quadrature mixer, we can discriminate between negative and positive optical path differences, which doubles the measurement range without increasing the measurement time. To measure the distance to multiple targets simultaneously, the terahertz wave is modulated in amplitude at a series of frequencies; the signal returning from the target is detected and homodyne mixed with the original modulation signal. A series of voltages is obtained; by Fourier transformation the distance to each target is retrieved. Experimental results on one and two targets are shown.

A 7-year-old boy presented at our hospital with syncope. At birth, electrocardiography had shown a long QT interval with torsade de pointes (TdP). Congenital long QT syndrome (LQTS) had been diagnosed by genetic testing, and was successfully controlled with oral propranolol. At age 7, TdP had recurred with syncope. Electrocardiography revealed a prominent long QT interval with T-wave alternans. The propranolol dose was increased, but TdP remained uncontrolled. A cardioverter-defibrillator (ICD) was implanted epicardially, and TdP completely resolved with atrial pacing. We report this rare case of ICD implantation in a child with LQTS.

We introduce a new principle for distance measurement in the terahertz-wave range using a resonant-tunneling-diode (RTD) oscillator as a source at 511 GHz and relying on the frequency-modulated continuous-wave (FMCW) radar technique. Unlike the usual FMCW radar, where the sawtooth frequency modulation is applied to the carrier, we propose applying it to a subcarrier obtained by amplitude modulation; this is advantageous when the source cannot be controlled precisely in oscillation frequency, but can easily be modulated in amplitude, as is the case of the RTD oscillator. The detailed principle and a series of proof-of-concept experimental results are presented.

A IV-VI compound SnTe is proposed to be a topological crystalline insulator (TCI), and the band structures have been studied by using angle-resolved photoemission spectroscopy (ARPES). However, the topological surface states (TSSs) that hallmark the nontrivial topology disperse mostly in the unoccupied side where access via ARPES is limited. Here we investigate the (111) face of a SnTe film by using pump-probe ARPES. We find distinct energy sections in the unoccupied side that behave differently in terms of the excitation and recovery dynamics. From these different behaviors, the boundaries of these sections are attributed to the edges of the conduction and valence bands. High statistics data reveal that the TSSs are traversing the band gap, which evidences that SnTe belongs to a TCI. We also find that the bulk bands near the gap show splitting, which is attributed to the Rashba effect occurring in the dipolar surface region.

Influenza A viruses (IAVs) pose a serious global threat to humans and their livestock. This study aimed to determine the ideal irradiation by ultraviolet-light emitting diodes (UV-LEDs) for IAV disinfection. We irradiated the IAV H1N1 subtype with 4.8 mJ/cm2 UV using eight UV-LEDs [peak wavelengths (WL) = 365, 310, 300, 290, 280, 270, and 260 nm)] or a mercury low pressure (LP)-UV lamp (Peak WL = 254 nm). Inactivation was evaluated by the infection ratio of Madin–Darby canine kidney (MDCK) cells or chicken embryonated eggs. Irradiation by the 260 nm UV-LED showed the highest inactivation among all treatments. Because the irradiation-induced inactivation effects strongly correlated with damage to viral RNA, we calculated the correlation coefficient (RAE) between the irradiant spectrum and absorption of viral RNA. The RAE scores strongly correlated with the inactivation by the UV-LEDs and LP-UV lamp. To increase the RAE score, we combined three different peak WL UV-LEDs (hybrid UV-LED). The hybrid UV-LED (RAE = 86.3) significantly inactivated both H1N1 and H6N2 subtypes to a greater extent than 260 nm (RAE = 68.6) or 270 nm (RAE = 42.2) UV-LEDs. The RAE score is an important factor for increasing the virucidal effects of UV-LED irradiation.

Pulmonary artery aneurysms (PAA) can be complicated with pulmonary arterial hypertension (PAH), causing sudden death due to PA rupture and dissection. Because treatment with PAH-targeted drugs does not always prevent PAA progression, prophylactic surgical repair of the PAA seems a promising alternative. However, although it avoids rupture and dissection of the PAs, additional benefits have not been forthcoming. We therefore present two patients with co-existing PAH and a PAA who underwent surgical repair of the aneurysm. Following the surgery, their lung function and pulmonary hypertension improved. Optimal treatment of PAA remains uncertain, however, with no clear guidelines regarding the best therapeutic approach. This case series provides physicians with reasons to repair PAA surgically in patients with PAH.

Pulmonary arterial hypertension (PAH) is characterized by remodeling and narrowing of the pulmonary arteries, which lead to elevation of right ventricular pressure, heart failure, and death. Proliferation of pulmonary artery smooth muscle cells (PASMCs) is thought to be central to the pathogenesis of PAH, although the underlying mechanisms are still being explored. The protein p53 is involved in cell cycle coordination, DNA repair, apoptosis, and cellular senescence, but its role in pulmonary hypertension (PH) is not fully known. We developed a mouse model of hypoxia-induced pulmonary hypertension (PH) and found significant reduction of p53 expression in the lungs. Our in vitro experiments with metabolomic analyses and the Seahorse XF extracellular flux analyzer indicated that suppression of p53 expression in PASMCs led to upregulation of glycolysis and downregulation of mitochondrial respiration, suggesting a proliferative phenotype resembling that of cancer cells. It was previously shown that systemic genetic depletion of p53 in a murine PH model led to more severe lung manifestations. Lack of information about the role of cell-specific p53 signaling promoted us to investigate it in our mouse PH model with the inducible Cre-loxP system. We generated a mouse model with SMC-specific gain or loss of p53 function by crossing Myh11-Cre/ERT2 mice with floxed Mdm4 mice or floxed Trp53 mice. After these animals were exposed to hypoxia for 4 weeks, we conducted hemodynamic and echocardiographic studies. Surprisingly, the severity of PH was similar in both groups of mice and there were no differences between the genotypes. Our findings in these mice indicate that activation or suppression of p53 signaling in SMCs has a minor role in the pathogenesis of PH and suggest that p53 signaling in other cells (endothelial cells, immune cells, or fibroblasts) may be involved in the progression of this condition.

Background The usefulness of vascular function tests for management of patients with a history of coronary artery disease is not fully known. Methods and Results We measured flow‐mediated vasodilation (FMD) and brachial–ankle pulse wave velocity (baPWV) in 462 patients with coronary artery disease for assessment of the predictive value of FMD and baPWV for future cardiovascular events in a prospective multicenter observational study. The first primary outcome was coronary events, and the second primary outcome was a composite of coronary events, stroke, heart failure, and sudden death. During a median follow‐up period of 49.2 months, the first primary outcome occurred in 56 patients and the second primary outcome occurred in 66 patients. FMD above the cutoff value of 7.1%, derived from receiver‐operator curve analyses for the first and second primary outcomes, was significantly associated with lower risk of the first (hazard ratio, 0.27; 95% confidence interval, 0.06–0.74; P=0.008) and second (hazard ratio, 0.32; 95% confidence interval, 0.09–0.79; P=0.01) primary outcomes. baPWV above the cutoff value of 1731 cm/s was significantly associated with higher risk of the first (hazard ratio, 1.86; 95% confidence interval, 1.01–3.44; P=0.04) and second (hazard ratio, 2.19; 95% confidence interval, 1.23–3.90; P=0.008) primary outcomes. Among 4 groups stratified according to the combination of cutoff values of FMD and baPWV, stepwise increases in the calculated risk ratio for the first and second primary outcomes were observed. Conclusions In patients with coronary artery disease, both FMD and baPWV were significant predictors of cardiovascular events. The combination of FMD and baPWV provided further cardiovascular risk stratification. Clinical Trial Registration URL: www.umin.ac.jp. Unique identifier: UMIN000012950.

BackgroundA drug provocation test using a sodium channel blocker (SCB) can unmask a type 1 ECG pattern in patients with Brugada syndrome. However, the prognostic value of the results of an SCB challenge is limited in patients with non–type 1 ECG. We investigated the associations of future risk for ventricular fibrillation with SCB‐induced ECG changes and ventricular tachyarrhythmias (VTAs). Methods and ResultsWe administered intravenous pilsicainide to 245 consecutive patients with Brugada syndrome (181 patients with spontaneous type 1 ECG, 64 patients with non–type 1 ECG). ECG parameters before and after the test and occurrence of drug‐induced VTAs were evaluated. During a mean follow‐up period of 113±57 months, fatal VTA events occurred in 31 patients (sudden death: n=3, ventricular tachycardia/ventricular fibrillation: n=28). Symptomatic patients and spontaneous type 1 ECG were associated with future fatal arrhythmic events. Univariable analysis of ECG parameters after the test showed that long PQ and QRS intervals, high ST level, and SCB‐induced VTAs were associated with later VTA events during follow‐up. Multivariable analysis showed that symptomatic patients, high ST level (V1) ≥0.3 mV after the test, and SCB‐induced VTAs were independent predictors for future fatal arrhythmic events (hazard ratios: 3.28, 2.80, and 3.62, 95% confidence intervals: 1.54–7.47, 1.32–6.35, and 1.64–7.75, respectively; P

Intraosseous hemangiomas are rare, and although they have been described in the calvaria and vertebrae, those occurring in the zygomatic bone are extremely rare. We report the case of a 52-year-old man who presented with a painless hard swelling in the left zygomatic process. The computed tomography and magnetic resonance imaging findings showed an intraosseous mass located in the left zygomatic bone just inferolateral to the orbit. A pathologic analysis of the surgical specimen revealed a cavernous hemangioma. The surgical defect was reconstructed with an autogenous rib bone that was fixated with titanium miniplates. The literature is reviewed and computed tomography, magnetic resonance imaging, and angiographic findings are discussed with particular reference to a surgical resection and reconstruction.

IKEA, a Swedish furniture company, is considering entering the Brazilian market. This paper examines whether or not IKEA might be successful in the Brazilian market by reviewing the following issues: the growth of middle class, consumer spending, internet usage and eco-awareness. This study finds that the growing middle class in the country and the increasing average household disposable income is a promising sign that the ability of consumers to afford IKEA products is increasing. The growing online presence of Brazilian consumers is also a positive aspect of IKEA’s potential move into the market as it would enable consumers to browse and purchase product via the internet in accordance with current company practices. Brazilian consumers are currently involved in a trend that favours eco-friendly companies such as IKEA. The paper concludes that IKEA would be received favourably among customers within the market.

The number of nonprofit organizations (NPOs) has been growing worldwide in the last few decades. In Japan, the number of NPOs started skyrocketing in the late 1990s and now has reached almost 50,000, a significant increase from fewer than 10,000 in the early 2000s. Despite their increasing importance, the majority of NPOs are financially strained in Japan. To address this issue, this study analyzes data collected from interviews with management-level officials from 50 nonprofit organizations about their activities, management, and marketing in Nagoya, Japan.

Cystatin C is a cysteine protease inhibitor that is produced by nearly all human cells. The serum level of cystatin C is a stronger predictor of the renal outcome and the risk of cardiovascular events than the creatinine level. The resistive index (RI) on renal Doppler ultrasonography is a good indicator of vascular resistance as well as the renal outcomes in patients with chronic kidney disease (CKD). However, it is unclear whether serum cystatin C is associated with signs of vascular dysfunction, such as the renal RI. We measured the serum cystatin C levels in 101 CKD patients and investigated the relationships between cystatin C and markers of vascular dysfunction, including the renal RI, ankle-brachial pulse wave velocity (baPWV), intima-media thickness (IMT), and cardiac function. The renal RI was significantly correlated with the serum cystatin C level (p < 0.0001, r = 0.6920). The serum cystatin C level was found to be a significant determinant of the renal RI (p < 0.0001), but not the baPWV, in a multivariate regression analysis. The multivariate odds ratio of the serum cystatin C level for a renal RI of more than 0.66 was statistically significant (2.92, p = 0.0106). The area under the receiver-operating characteristic curve comparing the sensitivity and specificity of cystatin C for predicting an RI of more than 0.66 was 0.882 (cutoff value: 2.04 mg/L). In conclusion, the serum cystatin C level is an independent biomarker associated with the renal RI in patients with CKD.

As an innovative financial mechanism to explore additional funds for social development programs in developing countries, debt swaps for development, including debt-for-education swaps, became popular between the 1980s and 2000s. Their popularity, however, seems to have diminished since the beginning of the 2010s. This article describes debt swaps for development with a focus on debt-for-education swaps, explaining how they became popular, examining why they have lost momentum, and exploring whether debt-for-education swaps are a feasible option for funding social development programs. Despite recent economic recovery and growth worldwide, one of the key obstacles for achieving the United Nations’ Sustainable Development Goal 4—to ensure inclusive and equitable quality education and promote lifelong learning opportunities for all—remains inefficient funding for education programs in developing countries. Based on the findings, this article argues for the feasibility of debt-for-education swaps to seek funding with a number of conditions.

Green fluorescence imaging (e.g., flavoprotein autofluorescence imaging, FAI) can be used to measure neuronal activity and oxygen metabolism in living brains without expressing fluorescence proteins. It is useful for understanding the mechanism of various brain functions and their abnormalities in age-related brain diseases. However, hemoglobin in cerebral blood vessels absorbs green fluorescence, hampering accurate assessments of brain function in animal models with cerebral blood vessel dysfunctions and subsequent cerebral blood flow (CBF) alterations. In the present study, we developed a new method to correct FAI signals for hemoglobin-dependent green fluorescence reductions by simultaneous measurements of green fluorescence and intrinsic optical signals. Intrinsic optical imaging enabled evaluations of light absorption and scatters by hemoglobin, which could then be applied to corrections of green fluorescence intensities. Using this method, enhanced flavoprotein autofluorescence by sensory stimuli was successfully detected in the brains of awake mice, despite increases of CBF, and hemoglobin interference. Moreover, flavoprotein autofluorescence could be properly quantified in a resting state and during sensory stimulation by a CO2 inhalation challenge, which modified vascular responses without overtly affecting neuronal activities. The flavoprotein autofluorescence signal data obtained here were in good agreement with the previous findings from a condition with drug-induced blockade of cerebral vasodilation, justifying the current assaying methodology. Application of this technology to studies on animal models of brain diseases with possible changes of CBF, including age-related neurological disorders, would provide better understanding of the mechanisms of neurovascular coupling in pathological circumstances.

BACKGROUND:Pulmonary vascular remodeling of pulmonary arterial hypertension (PAH) is characterized by an inappropriate increase of vascular cells. The receptor for advanced glycation end products (RAGE) is a type I single-pass transmembrane protein belonging to the immunoglobulin superfamily and is involved in a broad range of hyperproliferative diseases. RAGE is also implicated in the etiology of PAH and is overexpressed in pulmonary artery smooth muscle cells (PASMCs) in patients with PAH. We examined the role of RAGE in the inappropriate increase of PASMCs in patients with PAH. METHODS AND RESULTS:PASMCs were obtained from 12 patients with PAH including 9 patients with idiopathic PAH (IPAH) and 3 patients with heritable PAH (HPAH) (2 patients with BMPR2 mutation and one patient with SMAD9 mutation) who underwent lung transplantation. Western blot analysis and immunofluorescence staining revealed that RAGE and S100A8 and A9, ligands of RAGE, were overexpressed in IPAH and HPAH-PASMCs in the absence of any external growth stimulus. PDGF-BB (10 ng/mL) up-regulated the expression of RAGE in IPAH and HPAH-PASMCs. PAH-PASMCs are hyperplastic in the absence of any external growth stimulus as assessed by 3H-thymidine incorporation. This result indicates overgrowth characterized by continued growth under a condition of no growth stimulation in PAH-PASMCs. PDGF-BB stimulation caused a higher growth rate of PAH-PASMCs than that of non-PAH-PASMCs. AS-1, an inhibitor of TIR domain-mediated RAGE signaling, significantly inhibited overgrowth characterized by continued growth under a condition of no growth stimulation in IPAH and HPAH-PASMCs (P

Distal digital replantation is frequently associated with arterial thrombosis and/or spasm, leading ischemia in the replanted tissue. This report introduced a rescue technique for ischemia after distal digital replantation without reanastomosis. Two males, 64 and 51 years old, underwent Ishikawa subzone II finger amputations. Microsurgical replantations with vein grafts were performed. Intraoperatively, heparin and urokinase through intra-arterial infusion were given for one week. At 40 to 48 hours after surgeries, the replanted digits developed ischemia; massaging digital arteries at the proximal phalanx regions with running warm water was immediately initiated and ischemia was improved. In both cases, the replanted tissues were rescued, though a partial necrosis requiring full-thickness skin grafting was found in one case. This massage was easily, safely, and effectively performed without complications and was applicable in cases with ischemia after distal digital replantation, especially where reanastomosis was unfeasible.

Our previous study examined an effect of remote ischemic preconditioning (RIPC) or intravenous nicorandil on reduction of periprocedural myocardial injury (pMI) following percutaneous coronary intervention (PCI) in patients with stable coronary artery disease (CAD). We further investigated the effect of RIPC or nicorandil on pMI in older patients.Patients with stable CAD who planned to undergo PCI were assigned to a 1:1:1 ratio to control, intravenous nicorandil, or upper-limb RIPC groups. This substudy analyzed patients aged >65 years (n = 282) from the principal cohort. The primary outcome was the incidence of pMI following PCI. We defined pMI as an elevated level of high-sensitive cardiac troponin T or creatine kinase myocardial band 12 or 24 hours after PCI.We found that pMI following PCI was significantly reduced in the nicorandil group compared with the control group (37.2% vs. 53.7%, multiplicity-adjusted p = 0.046), but not in the RIPC group compared with the control group (43.0% vs. 53.7%, multiplicity-adjusted p = 0.245). The adjusted odds ratios (95% confidence interval) for pMI in the RIPC and nicorandil groups versus the control group were 0.63 (0.34 to 1.16) and 0.51 (0.27 to 0.96), respectively.Intravenous nicorandil significantly reduces pMI following PCI in a subgroup of older patients with stable CAD. Phase 3 trials are required to validate our results.UMIN Clinical Trials Registry UMIN000005607.

PURPOSE:To investigate the surgical outcome of patients with osteophyte-associated dysphagia (OAD) using the functional outcome swallowing scale (FOSS). METHODS:A retrospective chart review of 10 surgical cases of OAD (9 male and 1 female patient; mean age of 65 years) from 1982 to 2017 was performed, and radiographic evaluations were conducted by video fluoroscopic swallow study (VFSS) and conventional radiography. All OAD cases were treated at a single institution, and osteophytes were surgically resected by the anterior approach under gentle retraction of the affected esophagus. FOSS (0 for normal, 5 for worst) was used for clinical evaluations, and surgical complications were recorded. RESULTS:VFSS evaluation of OAD showed that the affected osteophyte was located at C4/5 in four patients, followed by C3/4 in three patients. The mean FOSS showed significant improvement from 2.5 preoperatively to 0.3 postoperatively, and no major surgical complications were recorded. Comorbidities were diabetes mellitus in four patients, ossification of the posterior longitudinal ligament in three patients, and lumbar spinal stenosis (LSS) in three patients. CONCLUSION:Surgical treatment of OAD was promising, and all patients showed clinical recovery. Evaluation of dysphagia using FOSS was easy and reliable for OAD management, and FOSS 2 might be a good indication for surgical intervention.

Three-dimensional (3D) printing is a simple and versatile process for producing parts of complex geometries. Although the process possesses several manufacturing advantages, such as rapid prototyping, customization, and complexity, the optimization of the 3D printing procedure remains a challenge. Here we explore the influences of various processing conditions on the mechanical properties of melt extrusion- and solution extrusion-printed polylactide (PLA) products by adopting a robust experimental design model. In addition to the commercially available melt extrusion 3D printer, a novel solution-type 3D printer has been exploited especially for this study, which consists of a solution-type plunger-actuated feeding system, stepper motors and motion components, a power supply unit, a print bed, a user interface, and connectivity. The effects of various parameters were investigated by adopting a robust experimental design. We compared the parts printed using the melt extrusion and solution extrusion methods and found that, in the melt extrusion printing, the print speed and fill density were the principal parameters affecting product quality, while in the solution extrusion printing, oven temperature, fill density, and PLA/dichloromethane (DCM) ratio were the key parameters. By scanning electron microscopy, we found that the melt extrusion-printed parts exhibit a strip-like microstructure and the solution extrusion-printed parts show a fused surface morphology. Due to the addition of solvent, the solution-printed PLA material show a different thermal profile in the differential scanning calorimeter analysis, which in turn affects the mechanical behaviour of printed parts.

Purpose: This study examines the impact of the Association to Advance Collegiate Schools of Business (AACSB) accreditation on education quality. We discern the prospective influences of AACSB, focusing on shifts in teaching methods and content and assessment procedures. Design/methodology/approach: Using a case study approach, in-depth interviews are conducted with a Japanese-accredited business school's faculty members to understand their perceptions of the school's education-quality issues. The data were thematically analyzed. Findings: Respondents acknowledged that AACSB accreditation has positively influenced teaching, encouraging active learning and the case method. However, they also indicated that accreditation had a restrictive effect on assessment activities, pushing toward compliance rather than genuine learning evaluation. This dichotomy suggests a need for balancing standard adherence with the flexibility to maintain educational depth and assessment integrity. Research limitations/implications: Convenience sampling may introduce self-selection bias. Furthermore, the qualitative case study approach does not allow for statistical generalization. However, when combined with existing literature, the findings can be analytically generalized and transferred to other contexts. Originality/value: We provide insights regarding AACSB accreditation's impact on business education, encompassing shifts in teaching methods and content and faculty perceptions of assessment. This study enhances the scholarly understanding of business school accreditation and offers guidance to accredited or accreditation-seeking academic institutions.

Rather than relying solely on subjective pain evaluation using means such as the visual analogue scale (VAS), in clinical situations it is possible to observe evoked responses of the autonomic nervous system (ANS) as objective indicators. Few studies, however, have reported these relationships under finely controlled sedation. 16 healthy male participants were administrated in intravenous sedation with either propofol or midazolam randomly. We initially determined, using pharmacokinetic simulation, the effect-site concentration (Ce) of anaesthetic at loss of response to verbal command and eyelash reflex (Ce-LOR). Then subsequently adjusted Ce to 75%, 50%, and 25% of Ce-LOR to achieve deep, moderate, and light sedation. At awake control state and each sedation level, a noxious electrical stimulation was applied three times at the right forearm, an average pain intensity of the three stimuli was rated on a VAS (0-10). Changes in the peripheral perfusion index measured by oximetry were used as an indicator of ANS response. We analyzed the influence of sedation level on VAS and ANS responses compared to the awake control state. While ANS responses were similar in all conditions, VAS was statistically significantly lower in moderate (5.6±0.6, p

The klotho gene was identified as an "aging-suppressor" gene that accelerates arterial calcification when disrupted. Serum and vascular klotho levels are reduced in patients with chronic kidney disease, and the reduced levels are associated with arterial calcification. Intake of eicosapentaenoic acid (EPA), an n-3 fatty acid, reduces the risk of fatal coronary artery disease. However, the effects of EPA on arterial calcification have not been fully elucidated. The aim of this study was to determine the effect of EPA on arterial calcification in klotho mutant mice.Four-week-old klotho mutant mice and wild-type (WT) mice were given a diet containing 5% EPA (EPA food, klotho and WT: n = 12, each) or not containing EPA (control food, klotho and WT: n = 12, each) for 4 weeks. Calcium volume scores of thoracic and abdominal aortas assessed by computed tomography were significantly elevated in klotho mice after 4 weeks of control food, but they were not elevated in klotho mice after EPA food or in WT mice. Serum levels of EPA and resolvin E1, an active metabolite of EPA, in EPA food-fed mice were significantly increased compared to those in control food-fed mice. An oxidative stress PCR array followed by quantitative PCR revealed that NADPH oxidase-4 (NOX4), an enzyme that generates superoxide, gene expression was up-regulated in arterial smooth muscle cells (SMCs) of klotho mice. Activity of NOX was also significantly higher in SMCs of klotho mice than in those of WT mice. EPA decreased expression levels of the NOX4 gene and NOX activity. GPR120, a receptor of n-3 fatty acids, gene knockdown by siRNA canceled effects of EPA on NOX4 gene expression and NOX activity in arterial SMCs of klotho mice.EPA prevents arterial calcification together with reduction of NOX gene expression and activity via GPR120 in klotho mutant mice.

Stromal interaction molecule 1 (STIM1), an endo/sarcoplasmic reticulum Ca2+ sensor, has been shown to control a Ca2+-dependent signal that promotes cardiac hypertrophy. However, whether STIM1 has adaptive role that helps to protect against cardiac overload stress remains unknown. We hypothesized that STIM1 deficiency causes a maladaptive response to pressure overload stress. We investigated STIM1 heterozygous KO (STIM1+/-) mice hearts, in which STIM1 protein levels decreased to 27% of wild-type (WT) with no compensatory increase in STIM2. Under stress-free conditions, no significant differences were observed in electrocardiographic and echocardiographic parameters or blood pressure between STIM1+/-and WT mice. However, when STIM1+/-mice were subjected to transverse aortic constriction (TAC), STIM1+/-mice had a higher mortality rate than WT mice. The TAC-induced increase in the heart weight to body weight ratio (mean mg/g ± standard error of the mean) was significantly inhibited in STIM1+/-mice (WT sham, 4.12 ± 0.14; WT TAC, 6.23 ± 0.40; STIM1+/-sham, 4.53 ± 0.16; STIM1+/-TAC, 4.63 ± 0.08). Reverse transcription-polymerase chain reaction analysis of the left ventricles of TAC-treated STIM1+/-mice showed inhibited induction of cardiac fetal genes, including those encoding brain and atrial natriuretic proteins. Western blot analysis showed upregulated expression of transient receptor potential channel 1 (TRPC1) in TAC-treated WT mice, but suppressed expression in TAC-treated STIM1+/-mice. Taken together, the hearts of STIM1 haploinsufficient mice had a superficial resemblance to the WT phenotype under stress-free conditions; however, STIM1 haploinsufficient mice showed a maladaptive response to cardiac pressure overload.

This paper reconsiders active learning (AL) in the context of Japanese higher education. AL encourages students to actively engage with learning, enhancing their generic and employability skills. In Japan, AL has become increasingly popular but lacks a clear definition. AL proponents suggest that it is the use of instructional methods that encourage cooperative learning (CL) and problem/project-based (PBL) learning approaches, without established learning contents and goals. CL and/or PBL used alone may not enhance students’ learning. I argue that AL should be viewed as one approach contributing toward a pedagogical methodology, rather than a collection of methods. The term proactive learning may be a more precise descriptor of this approach. Using the word proactive may help Japanese university instructors to: (1) Avoid misunderstanding of AL as physical activity; (2) Divert their attention from specific methods to a broader methodology; and (3) Refocus on the ultimate purpose of using AL.

Purpose To determine whether articular chondrocytes derived from osteoarthritic knee joints could evoke alloreactive proliferation of peripheral blood mononuclear cells (PBMC) and inhibit mitogenic activity of polyclonally activated CD4 + major histocompatibility complex (MHC) class II–restricted T cells in vitro . Methods Osteoarthritic cartilages of 17 patients aged 61 to 85 years were harvested during total knee arthroplasty. Chondrocytes were cultured for experiments. PBMCs, CD4 + T cells, CD8 + T cells, and CD14 + monocytes from healthy subjects were also used. To investigate the allogeneic response and immunosuppressive properties of chondrocytes, assays for one-way mixed lymphocyte reaction (MLR), apoptosis, activated CD4 + T-cell proliferation, and cytotoxic CD8 + T-cells were performed. Chondrocyte cell-surface antigens were examined using flow cytometry. Results Chondrocytes failed to trigger an allogeneic PBMC reaction and did not induce apoptosis of allogeneic PBMCs in the MLR assay. Chondrocytes inhibited the proliferation of polyclonally activated CD4 + T cells via cell-cell contact and escaped the allogeneic cytotoxic reactivity of CD8 + T cells. Chondrocytes expressed MHC class I but not MHC class II molecules or B7-1/-2-positive co-stimulatory molecules. Conclusion Chondrocytes from osteoarthritic knees in older patients exhibited similar immunomodulatory properties in vitro to those in juveniles or adults.

Background: Anti-arrhythmic drugs (AADs) are often administered following catheter ablation (CA) for persistent atrial fibrillation (peAF) to maintain sinus rhythm (SR). It remains unclear whether AADs can be withdrawn in patients showing no recurrence after CA. Method: We administered hybrid therapy consisting of CA and AAD (bepridil) in 75 patients with peAF. Withdrawal of AADs was attempted in patients who had no recurrence of AF for ≥6 months. We followed them for 22±16 months. Results: Patients received 1.2±0.4 sessions of CA and a mean bepridil dose of 131±46 mg/day. After a 3-month “blanking period,” 62 (83%) patients maintained SR without recurrence of tachyarrhythmia for ≥6 months. AADs were discontinued in 41 patients who agreed to medication withdrawal. Ten of these (24%) experienced a relapse of tachycardia, and these patients had a higher incidence of residual inducibility of tachyarrhythmia at the end of the CA procedure (70% vs. 32%; P=0.03) and required a higher dose of bepridil to maintain SR (170±48 mg vs. 106±30 mg; P

Acute vasoreactivity testing for patients with pulmonary arterial hypertension (PAH) has been reported to be useful to identify patients with sustained beneficial response to oral calcium-channel blockers (CCBs), but there is a risk of exacerbation during the testing with oral CCBs. Therefore, we developed a testing method utilizing intravenous nicardipine, a short-acting CCB, and examined the safety and usefulness of acute vasoreactivity testing with nicardipine in PAH patients. Acute vasoreactivity testing with nicardipine was performed in 65 PAH patients. Nicardipine was administered by short-time continuous infusion (1 μg·kg−1·min−1 for 5 min and 2 μg·kg−1·min−1 for 5 min) followed by bolus injection (5 μg/kg). Hemodynamic responses were continuously measured using a right heart catheter. Acute responders were defined as patients who showed a decrease in mean pulmonary artery pressure of at least 10 mmHg to an absolute level below 40 mmHg with preserved or increased cardiac output. Two acute responders and sixty-three non-acute responders were identified. There was no hemodynamic instability requiring additional inotropic agents or death during the testing. Acute responders had good responses to long-term oral CCBs. The acute vasoreactivity testing with nicardipine might be safe and useful for identifying CCB responders in PAH patients. Keywords:: calcium-channel blocker, acute vasoreactivity testing, pulmonary arterial hypertension

Oxidative stress has been implicated in the pathogenesis of heart failure. Reactive oxygen species (ROS) are produced in the failing myocardium, and ROS cause hypertrophy, apoptosis/cell death and intracellular Ca2+ overload in cardiac myocytes. ROS also cause damage to lipid cell membranes in the process of lipid peroxidation. In this process, several aldehydes, including 4-hydroxy-2-nonenal (HNE), are generated and the amount of HNE is increased in the human failing myocardium. HNE exacerbates the formation of ROS, especially H2O2 and ·OH, in cardiomyocytes and subsequently ROS cause intracellular Ca2+ overload. Treatment with beta-blockers such as metoprolol, carvedilol and bisoprolol reduces the levels of oxidative stress, together with amelioration of heart failure. This reduction could be caused by several possible mechanisms. First, the beta-blocking effect is important, because catecholamines such as isoproterenol and norepinephrine induce oxidative stress in the myocardium. Second, anti-ischemic effects and negative chronotropic effects are also important. Furthermore, direct antioxidative effects of carvedilol contribute to the reduction of oxidative stress. Carvedilol inhibited HNE-induced intracellular Ca2+ overload. Beta-blocker therapy is a useful antioxidative therapy in patients with heart failure.

Background: Both nifekalant hydrochloride (NIF), a selective IKr blocker, and intravenous amiodarone (AMD), a multi-channel (including IKr blocking) blocker, have been reported to be efficacious for refractory arrhythmias. However, the optimal use of those antiarrhythmic drugs for refractory arrhythmia with severe heart failure has not been established. Intravenous AMD might be effective for arrhythmias refractory to NIF in patients with severe heart failure. Here, we report that intravenous amiodarone was effective in the treatment of nifekalant-resistant in a group of arrhythmia patients with severe heart failure. Methods: Eleven severe heart failure patients who had received intravenous AMD for treatment of NIF-resistant arrhythmias were included in this study, and retrospective analysis was performed. Clinical efficacy (terminative and preventive effects on arrhythmia) of intravenous AMD was evaluated. Results: All cases were emergent cases and had depressed left ventricular ejection fraction (30 ± 13%). Clinical arrhythmias were ventricular fibrillation (VF) in four patients, ventricular tachycardia (VT) in six patients, and atrial fibrillation (AF) in one patient. NIF was administered to all patients by intravenous injection. After administration of NIF, VT/VF/AF was terminated in seven of the 10 patients, but a preventive effect was not obtained in any of the patients (NIF-resistance). Intravenous AMD (maintenance dose: 484 ± 166 mg/day) was effective both in termination (80%) and in prevention (80%) of VT/VF events in those patients. It was also effective in termination (80%) and prevention (60%) of AF events refractory to NIF. During continuous AMD administration, no significant adverse effects or proarrhythmic effects were observed in any of the patients. Five patients died within one month, but there was no arrhythmic deaths. Conclusions: Intravenous AMD was effective in NIF-resistant lethal arrhythmias and was relatively safe in emergent cases with severe heart failure.

This work reports on an experimental study of the fast stretching of a cyclic olefin copolymer (COC) film. We measured the stress retardation of the polymer film during fast stretching and identified a relationship between stress and birefringence. This relationship indicates that the film obeys the stress optical rule (SOR) at the onset of stretching. At slower stretching speeds, the stress optical constant (SOC) settles at a certain value. With faster stretching speeds, SOC values approach the photo-elastic constant (PEC). Our study also investigated the effects of stretching temperatures and stretching modes for both uniaxial stretching and biaxial stretching. We applied techniques of thermal analysis to evaluate higher order structures after fast stretching.

Hiroshi Ito1, Hiroyoshi Kawaai1, Shinya Yamazaki1, Yosuke Suzuki21Division of Systemic Management, Department of Oral Function, 2Division of Radiology and Diagnosis, Department of Medical Sciences, Ohu University, Post Graduate School of Dentistry, Koriyama City, Fukushima Prefecture, JapanAbstract: From a retrospective evaluation of data on accidents and deaths during dental procedures, it has been shown that several patients who refused dental treatment died of asphyxia during dental procedures. We speculated that forcible maximum opening of the mouth by using a mouth prop triggers this asphyxia by affecting the upper airway. Therefore, we assessed the morphological changes of the upper airway following maximal opening of the mouth. In 13 healthy adult volunteers, the sagittal diameter of the upper airway on lateral cephalogram was measured between the two conditions; closed mouth and maximally open mouth. The dyspnea in each state was evaluated by a visual analog scale. In one subject, a computed tomograph (CT) was taken to assess the three-dimensional changes in the upper airway. A significant difference was detected in the mean sagittal diameter of the upper airway following use of the prop (closed mouth: 18.5 ± 3.8 mm, maximally open mouth: 10.4 ± 3.0 mm). All subjects indicated upper airway constriction and significant dyspnea when their mouth was maximally open. Although a CT scan indicated upper airway constriction when the mouth was maximally open, muscular compensation was admitted. Our results further indicate that the maximal opening of the mouth narrows the upper airway diameter and leads to dyspnea. The use of a prop for the patient who has communication problems or poor neuromuscular function can lead to asphyxia. When the prop is used for patient refusal in dentistry, the respiratory condition should be monitored strictly, and it should be kept in mind that the “sniffing position” is effective for avoiding upper airway constriction. Practitioners should therefore consider applying not only systematic desensitization, but also general anesthesia to the patient who refuses treatment, because the safety of general anesthesia has advanced, and general anesthesia may be safer than the use of a prop and restraints.Keywords: mouth prop, dental procedure, upper airway constriction, asphyxia, maximum opening of the mouth, risk management

This case report describes a patient with incessant atrial tachycardia (AT) who underwent catheter ablation. During electrophysiological study, the stable AT circuit spontaneously shifted to unstable AT due to intermittent frequent firing from the right inferior pulmonary vein (PV) after termination of cavo-tricuspid isthmus dependent atrial flutter. A macroreentrant AT circuit was observed after electrical isolation of right inferior PV potentials. These findings suggest that the presence of rapid activated firing is likely to be associated with the development of instability in the AT circuit. This may lead to a greater understanding of the physiology of atrial tachyarrhythmia as a simple clinical model.

Coronary computed tomography angiography (CCTA) in combination with first-pass CT myocardial perfusion imaging (MPI) has a better diagnostic performance than CCTA alone, compared with invasive coronary angiography as the reference standard. The aim of this study was to investigate the additional diagnostic value of first-pass CT-MPI without stress for detecting hemodynamic significance of coronary stenosis, compared with invasive fractional flow reserve (FFR). We recruited 53 patients with suspected coronary artery disease undergoing both CCTA and first-pass CT-MPI without stress and invasive FFR, and 75 vessels were analyzed. We used the same raw data for CCTA and CT-MPI. First-pass CT-MPI was reconstructed by examining the diastolic signal densities as a bull's eye map. Invasive FFR

The loss of dopaminergic (DA) neurons in the substantia nigra (SN) is a major pathophysiological feature of patients with Parkinson's disease (PD). As nigral DA neurons contain both neuromelanin (NM) and dopamine transporter (DAT), decreased intensities in both NM-sensitive MRI and DAT PET reflect decreased DA neuronal density. This study demonstrates that a more specific metric for the nigral DA neuronal density can be derived with multimodal MRI and PET. Participants were 11 clinically diagnosed PD patients and 10 age and gender matched healthy controls (HCs). Two quantities, the NM-related index (RNM) and the binding potential of the radiotracer [18F]FE-PE2I to DAT (BPND) in SN, were measured for each subject using MRI and PET, respectively. Principal component analysis (PCA) was applied to the multimodal data set to estimate principal components. One of the components, PCP, corresponds to a basis vector oriented in a direction where both BPND and RNM increase. The ability of BPND, RNM and PCP to discriminate between HC and PD groups was compared. Correlation analyses between the motor score of the unified Parkinson's disease rating scale and each metric were also performed. PCP, BPND and RNM for PD patients were significantly lower than those for HCs (F = 16.26, P

Hypertrophic obstructive cardiomyopathy (HOCM) is cardiac hypertrophy of ventricular myocardium with left ventricular outflow tract obstruction. We report a pregnancy with HOCM after defibrillator implantation surgery. The patient was a 33-year-old nulligravida and was categorized as New York Heart Association class II. Her brain natriuretic peptide (BNP) level was 724.6 pg/dL at preconception. She received careful pregnancy management. However, because frequent uterine contractions were observed at 25 weeks and 6 days of pregnancy, she was hospitalized, and magnesium sulfate was started as a tocolytic agent. At 27 weeks and 5 days of pregnancy, she had respiratory discomfort and orthopnea with a sudden decrease in peripheral oxygen saturation. Cardiac ultrasonography showed a worsened condition of HOCM and her BNP level was 1418.0 pg/mL. We performed an emergent cesarean section and she delivered a boy weighing 999 g. The Apgar score was 8 and 9 points at 1 and 5 minutes, respectively. The mother’s heart failure quickly improved after birth and she was discharged at 10 days postoperatively. Fluctuations in circulatory dynamics during pregnancy may sometimes exacerbate heart disease. Therefore, the risks should be fully explained and careful assessment of cardiac function should be performed during pregnancy in patients with severe HOCM.

This case report describes the treatment of atrial fibrillation (AF) in a patient with Brugada syndrome. We found the triggers of AF in the superior vena cava during electrophysiological study and the isolation of superior vena cava with catheter ablation successfully eliminated the recurrence of AF. This case suggests that abnormal myocardial repolarization due to Na+-channel abnormality is not always the etiology of AF in patients with Brugada syndrome. In case of the focal trigger related to the initiation of AF, catheter ablation can be an effective therapeutic strategy.

Establishment of a biological pacemaker is expected to solve the persisting problems of a mechanical pacemaker including the problems of battery life and electromagnetic interference. Enhancement of the funny current (If) flowing through hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and attenuation of the inward rectifier K+ current (IK1) flowing through inward rectifier potassium (Kir) channels are essential for generation of a biological pacemaker. Therefore, we generated HCN4-overexpressing mouse embryonic stem cells (mESCs) and induced cardiomyocytes that originally show poor IK1 currents, and we investigated whether the HCN4-overexpressing mESC-derived cardiomyocytes (mESC-CMs) function as a biological pacemaker in vitro.The rabbit Hcn4 gene was transfected into mESCs, and stable clones were selected. mESC-CMs were generated via embryoid bodies and purified under serum/glucose-free and lactate-supplemented conditions. Approximately 90% of the purified cells were troponin I-positive by immunostaining. In mESC-CMs, expression level of the Kcnj2 gene encoding Kir2.1, which is essential for generation of IK1 currents that are responsible for stabilizing the resting membrane potential, was lower than that in an adult mouse ventricle. HCN4-overexpressing mESC-CMs expressed about a 3-times higher level of the Hcn4 gene than did non-overexpressing mESC-CMs. Expression of the Cacna1h gene, which encodes T-type calcium channel and generates diastolic depolarization in the sinoatrial node, was also confirmed. Additionally, genes required for impulse conduction including Connexin40, Connexin43, and Connexin45 genes, which encode connexins forming gap junctions, and the Scn5a gene, which encodes sodium channels, are expressed in the cells. HCN4-overexpressing mESC-CMs showed significantly larger If currents and more rapid spontaneous beating than did non-overexpressing mESC-CMs. The beating rate of HCN4-overexpressing mESC-CMs responded to ivabradine, an If inhibitor, and to isoproterenol, a beta-adrenergic receptor agonist. Co-culture of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with aggregates composed of mESC-CMs resulted in synchronized contraction of the cells. The beating rate of hiPSC-CMs co-cultured with aggregates of HCN4-overexpressing mESC-CMs was significantly higher than that of non-treated hiPSC-CMs and that of hiPSC-CMs co-cultured with aggregates of non-overexpressing mESC-CMs.We generated HCN4-overexpresssing mESC-CMs expressing genes required for impulse conduction, showing rapid spontaneous beating, responding to an If inhibitor and beta-adrenergic receptor agonist, and having pacing ability in an in vitro co-culture system with other excitable cells. The results indicated that these cells could be applied to a biological pacemaker.

Nonalcoholic fatty liver disease is associated with a risk of coronary artery disease (e.g., diabetes mellitus, dyslipidemia, metabolic syndrome). We evaluated whether nonalcoholic hepatic steatosis is associated with high-risk plaques as assessed by multidetector computed tomography (CT).This retrospective study involved 414 participants suspected of having coronary artery disease. Nonalcoholic hepatic steatosis was defined as a liver-to-spleen fat ratio of

The number of nonprofit organizations (NPOs) has been growing worldwide in the last few decades. In Japan, the number of NPOs started skyrocketing in the late 1990s and now has reached almost 50,000, a significant increase from fewer than 10,000 in the early 2000s. Despite their increasing importance, the majority of NPOs are financially strained in Japan. To address this issue, this study analyzes data collected from interviews with management-level officials from 50 nonprofit organizations about their activities, management, and marketing in Nagoya, Japan. Keywords: Nonprofit marketing; nonprofit management; nonprofit strategy JEL Classifications: M; Y