Simultaneous visualisation of vasculature and surrounding tissue structures is essential for a better understanding of vascular pathologies. In this work, we describe a histochemical strategy for ...three-dimensional, multicolour imaging of vasculature and associated structures, using a carbocyanine dye-based technique, vessel painting. We developed a series of applications to allow the combination of vessel painting with other histochemical methods, including immunostaining and tissue clearing for confocal and two-photon microscopies. We also introduced a two-photon microscopy setup that incorporates an aberration correction system to correct aberrations caused by the mismatch of refractive indices between samples and immersion mediums, for higher-quality images of intact tissue structures. Finally, we demonstrate the practical utility of our approach by visualising fine pathological alterations to the renal glomeruli of IgA nephropathy model mice in unprecedented detail. The technical advancements should enhance the versatility of vessel painting, offering rapid and cost-effective methods for vascular pathologies.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract CD14 is present in macrophage, monocyte, and granulocyte cells and their cell membranes, and it is said to be responsible for intracellular transduction of endotoxin signals. Its soluble ...fraction is present in blood and is thought to be produced in association with infections. It is called the soluble CD14-subtype (sCD14-ST), and in the following text it is referred to by its generic name, presepsin. We have previously reported that presepsin is produced in association with infection and that it is specifically expressed in sepsis. In the present study we developed a new rapid diagnostic method by using a chemiluminescent enzyme immunoassay that allowed making automated measurements in a shorter time. The results of using this method to measure presepsin values in different pathological conditions were normal, 294.2 ± 121.4 pg/ml; local infection, 721.0 ± 611.3 pg/ml; systemic inflammatory response syndrome, 333.5 ± 130.6 pg/ml; sepsis, 817.9 ± 572.7 pg/ml; and severe sepsis, 1,992.9 ± 1509.2 pg/ml; the presepsin values were significantly higher in patients with local infection, sepsis, and severe sepsis than in patients who did not have infection as a complication. In a comparative study with other diagnostic markers of sepsis based on ROC curves, the area under the curve (AUC) of presepsin was 0.845, and greater than the AUC of procalcitonin (PCT, 0.652), C-reactive protein (CRP, 0.815), or interleukin 6 (IL-6, 0.672). In addition, a significant correlation was found between the APACHE II scores, an index of disease severity, and the presepsin values, suggesting that presepsin values can serve as a parameter that closely reflects the pathology.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
As a 2-year project of the Japanese Society of Nuclear Medicine working group activity, normal myocardial imaging databases were accumulated and summarized. Stress-rest with gated and non-gated image ...sets were accumulated for myocardial perfusion imaging and could be used for perfusion defect scoring and normal left ventricular (LV) function analysis. For single-photon emission computed tomography (SPECT) with multi-focal collimator design, databases of supine and prone positions and computed tomography (CT)-based attenuation correction were created. The CT-based correction provided similar perfusion patterns between genders. In phase analysis of gated myocardial perfusion SPECT, a new approach for analyzing dyssynchrony, normal ranges of parameters for phase bandwidth, standard deviation and entropy were determined in four software programs. Although the results were not interchangeable, dependency on gender, ejection fraction and volumes were common characteristics of these parameters. Standardization of
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I-MIBG sympathetic imaging was performed regarding heart-to-mediastinum ratio (HMR) using a calibration phantom method. The HMRs from any collimator types could be converted to the value with medium-energy comparable collimators. Appropriate quantification based on common normal databases and standard technology could play a pivotal role for clinical practice and researches.
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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
The procedural numbers and medical costs of percutaneous coronary intervention (PCI), mainly elective PCI, have been increasing in Japan. Owing to increased interest in the appropriateness of ...coronary revascularization, we conducted this medical economics-based evaluation of testing and diagnosis of stable coronary artery disease (CAD).
We reviewed patients’ medical insurance data to identify stable CAD patients who underwent coronary computed tomography angiography, cardiac single-photon emission computed tomography, coronary angiography, or fractional flow reserve. Subjects were divided into anatomical and functional evaluation groups according to the modality of testing, and background factors were matched by propensity score. The endpoints were major adverse cardiovascular events (MACE), life years (LYs), medical costs, and cost-effectiveness analysis (CEA). The observations were performed for 36 months. MACE, medical costs, and CEA of the functional group in the overall category were trending to be better than the anatomical group (MACE, P = .051; medical costs: 3,105 US$ vs 4,430 US$, P = .007; CEA: 2,431 US$/LY vs 2,902 US$/LY, P = .043).
The functional evaluation approach improved long-term clinical outcomes and reduced cumulative medical costs. As a result, the modality composition of functional myocardial ischemia evaluation was demonstrated to offer superior cost-effectiveness in stable CAD.
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EMUNI, FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OILJ, PNG, SAZU, SBCE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Objective Exercise therapy as part of cardiac rehabilitation is one of the most effective treatments for patients with chronic heart failure (HF). The anaerobic threshold (AT) determined by an ...exhaled gas analysis during cardiopulmonary exercise testing (CPX) is used to prescribe the appropriate level of exercise therapy. However, CPX using an exhaled gas analysis is not widely performed because of its cost, complexity, and the need for skilled staff. Therefore, a simpler and inexpensive method for determining AT without respiratory gas measurements is required in patients with HF. The present study elucidated the relationship between the AT determined by the CPX ventilatory method (CPX-AT) and the AT determined by cardiac acoustic biomarkers (CABs), which are measured by acoustic cardiography (CAB-AT), in HF patients. Methods Patients underwent symptom-limited ramp CPX twice using a cycle ergometer. The ATs determined from the exhaled gas analysis were identified by three independent physicians. CABs, including S1 and S2 intensities (peak-to-peak amplitudes), electromechanical activation time (EMAT) defined as the time interval from the Q wave onset on electrocardiography to the first heart sound (S1), heart rate (HR), and other parameters, were collected during CPX. Patients Forty patients with HF were included in this study. Results A significant correlation (R=0.70; p<0.001) was found between CPX-AT and CAB-AT, using the double product of S1 intensity and heart rate. CAB-AT using S1 intensity also showed a significant correlation with CPX-AT (R=0.71; p<0.001). Conclusion The present study suggests a possible new method for determining AT without respiratory gas measurements in patients with HF.
Background: Although direct oral anticoagulants (DOACs) are widely used in Japanese patients with atrial fibrillation (AF), large-scale investigations into their use, with suitable follow-up times ...and rates, are lacking. Methods and Results: The SAKURA AF Registry is a prospective multicenter registry created to investigate therapeutic outcomes of oral anticoagulant (OAC) use in Japanese AF patients. We conducted a study involving 3,237 enrollees from 63 institutions in the Tokyo area being treated with any of 4 DOACs (n=1,676) or warfarin (n=1,561) and followed-up for a median of 39.3 months (range 28.5–43.6 months). Analyses of 1- and 2-year follow-up data available for 3,157 (97.5%) and 2,952 (91.2%) patients, respectively, showed no significant differences in rates of stroke or systemic embolism (SE), major bleeding, and all-cause mortality for DOAC vs. warfarin users (1.2 vs. 1.8%/year, 0.5 vs. 1.2%/year, and 2.1 vs. 1.7%/year, respectively). Under propensity score matching, the incidence of stroke or SE (P=0.679) and all-cause death (P=0.864) remained equivalent, but the incidence of major bleeding was significantly lower (P=0.014) among DOAC than warfarin users. Conclusions: A high follow-up rate allowed us to obtain reliable data on the status of OAC use and therapeutic outcomes among AF patients in Japan. Warfarin and DOACs appear to yield equivalent 3-year stroke and all-cause mortality rates, but DOACs appear to reduce the risk of major bleeding.
There have been no reports on prognostic prediction and risk stratification based on stress phase bandwidth (SPBW), or a left ventricular (LV) mechanical dyssynchrony index, in patients with known or ...suspected stable coronary artery disease (CAD) at low or intermediate risk of major cardiac events (MCEs) using the J-ACCESS risk model. We retrospectively investigated 4,996 consecutive patients with known or suspected CAD who underwent rest
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Tl and stress
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Tc-tetrofosmin electrocardiogram (ECG)-gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) and followed up for 3 years to confirm their prognosis. MCE risk over 3 years was estimated using an equation based on that used in the J-ACCESS study. The composite endpoint was the onset of MCEs consisting of cardiac death, non-fatal myocardial infarction (MI), and severe heart failure requiring hospitalization. SPBW was calculated by phase analysis with the Heart Risk View-F software and its normal upper limit was set to 38°. Based on the estimated 3-year incidence of MCEs obtained from the J-ACCESS risk model, 4,123 of the 4,996 consecutive patients were classified as low (
n
= 2,653) or intermediate risk (
n
= 1,470) and they were analyzed for follow-up. During the follow-up, 153 patients experienced MCEs: cardiac death (
n
= 38), non-fatal MI (
n
= 45), and severe heart failure (
n
= 70). The results of the multivariate analysis showed age, estimated glomerular filtration rate (eGFR), stress LV ejection fraction, and stress SPBW to be independent predictors of MCEs. The actual 3-year MCE rate in patients at intermediate risk was significantly higher than in those at low risk (6.7% vs. 2.1%,
P
< 0.0001). However, the actual 3-year MCE rate in patients with abnormal SPBW (> 38°) was 4.0% and 9.2% in low- and intermediate-risk patients, respectively, which corresponded to intermediate and high risk. Kaplan–Meier analysis also showed significant risk stratification by normal SPBW values for both low- and intermediate-risk patients. LV mechanical dyssynchrony assessed with ECG-gated SPECT MPI is useful for risk stratification of known or suspected stable CAD patients at low or intermediate risk of MCEs and may help identify higher risk patients who could not be identified as being at risk based on J-ACCESS risk assessment.
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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
Inadequate sleep durations (short or long) are related to worsening of lipid/glucose metabolism, leading to atherosclerotic cardiovascular diseases (ASCVD). Few data exist on sex differences in this ...relationship that, to date, has been scarcely reported. This cross-sectional study included 6678 men and 4700 women at the Health Planning Center of Nihon University Hospital, located in the center of Tokyo, between September 2015 and October 2016. The prevalence of diabetes and dyslipidemia in the participants was 3.3% and 6.5%, respectively. Sleep duration was divided into five categories: < 5 h, 5–6 h, 6–7 h, 7–8 h, and ≥ 8 h. We examined the odds ratio (OR) and 95% confidence interval (CI) of lipid/glucose metabolism-related markers for the reference value defined in each guideline with 6–7 h as the reference of comparison. In men, a sleep duration of < 5 h was associated with ORs of 1.32 and 1.33 (95% CI, 1.01–1.73 and 1.02–1.74) for LDL-C level ≥ 120 mg/dL and non-HDL-C level of ≥ 150 mg/dL (defined as “borderline hyper” by the Japan Atherosclerosis Society Guidelines for Prevention of ASCVD 2017), respectively. Moreover, a sleep duration of < 5 h was associated with an OR of 1.77 (1.33–2.35) for fasting blood glucose of ≥ 100 mg/dL (defined as “high” by a specialized lifestyle checkup program in Japan). In women, sleep duration of < 5 h was associated with an OR of 1.70 (1.24–2.33) for HbA1c level of ≥ 5.6% (defined as “high” by a specialized life style checkup program in Japan). However, there was no association between sleep duration and serum lipid profile. Inadequate short sleep duration was as a potential risk factor of adverse lipid and/or glucose metabolism in both sexes. However, there were sex differences in associations between sleep duration and lipid/glucose metabolism in urban Japan. To further reduce risks of ASCVD, it is of particular importance to emphasize adequate sleep duration in both sexes.
Trial registration
UMIN (
http://www.umin.ac.jp/
) Study ID: UMIN000037643 retrospectively registered on August 9, 2019.
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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
Aspergillosis is a major fungal infection in humans and animals. Penguins (Order Spheniscidae) are particularly susceptible to aspergillosis, and aspergillosis in captive penguins is presently a ...major problem. We were faced with the challenge of combating aspergillosis in an aquarium. As a solution, we organized a multidisciplinary aspergillosis control team, including a medical and veterinary mycologist. Since Aspergillus, including Aspergillus fumigatus, is abundant in soil, we thought it necessary to minimize contact between captive penguins and soil to prevent aspergillosis. As a countermeasure, we stopped using a route for outdoor penguin marches where the soil was exposed. Additionally, after outdoor penguin marches, the feet of penguins were washed with seawater to avoid bringing soil into the rearing facility for penguins. Furthermore, since A. fumigatus was detected on several spots in the environment of the rearing facility by swab analysis, we cleaned and sanitized the rearing facility with 0.02% sodium hypochlorite and hot water. As a result of the above measures, there has been no incidence of aspergillosis in captive penguins since 2016. These results show that our preventive measures are working well. As shown here, we presented an example of how the multidisciplinary control team, which included a mycologist, successfully implemented preventive measures against aspergillosis. Due to changes in the rearing environment and the impact of global warming on penguins, it is expected that the role of mycologists in aspergillosis control will expand in the future.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK