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Abstract Renal denervation is a promising new non-pharmacological treatment for resistant hypertension. However, there is a lack of data from Asian patients. The REQUIRE trial investigated the blood pressure-lowering efficacy of renal denervation in treated patients with resistant hypertension from Japan and South Korea. Adults with resistant hypertension (seated office blood pressure ≥150/90 mmHg and 24-hour ambulatory systolic blood pressure ≥140 mmHg) with suitable renal artery anatomy were randomized to ultrasound renal denervation or a sham procedure. The primary endpoint was change from baseline in 24-hour ambulatory systolic blood pressure at 3 months. A total of 143 patients were included (72 renal denervation, 71 sham control). Reduction from baseline in 24-hour ambulatory systolic blood pressure at 3 months was not significantly different between the renal denervation (−6.6 mmHg) and sham control (−6.5 mmHg) groups (difference: −0.1, 95% confidence interval −5.5, 5.3; p = 0.971). Reductions from baseline in home and office systolic blood pressure (differences: –1.8 mmHg [p = 0.488] and −2.0 mmHg [p = 0.511], respectively), and medication load, did not differ significantly between the two groups. The procedure-/device-related major adverse events was not seen. This study did not show a significant difference in ambulatory blood pressure reductions between renal denervation and a sham procedure in treated patients with resistant hypertension. Although blood pressure reduction after renal denervation was similar to other sham-controlled studies, the sham group in this study showed much greater reduction. This unexpected blood pressure reduction in the sham control group highlights study design issues that will be addressed in a new trial. Clinical trial registration NCT02918305 (http://www.clinicaltrials.gov).

Although variation among habitats in the ratio of gametophytes to sporophytes has been reported in various gigartinacean species, factors controlling the phase ratio remain poorly understood. Over 18 months, we examined the phase ratio of Chondrus ocellatus at three sites: a sheltered intertidal site, Hiruga A; an exposed intertidal site, Hiruga B; and a subtidal site, Shikimi. The mean proportion of gametophytes at Hiruga A (73.1%) was significantly higher than that at Shikimi (51.2%) and Hiruga B (44.7%). Due to a significantly higher water retention ability of the gametophytes, it was expected that the gametophytes would exhibit higher desiccation tolerance. After dehydration treatments, however, neither the photosynthetic rate of vegetative blades nor the survival rate of spores was significantly different between the phases. Measurements of blade strength indicated that the sporophytic blades were less stiff and more flexible, and a culture experiment revealed that the sporophytic germlings showed a significantly higher growth rate. Flexible blades and fast-growing germlings are considered advantageous for colonizing wave-swept intertidal habitats, so these properties may have caused the different fluctuation pattern of phase ratio among the sites. The present data demonstrate that biomechanical and physiological differences between the two phases of C. ocellatus make one phase advantageous in certain environmental conditions, and that these differences likely cause an unequal ratio of isomorphic phases.

Genetic engineering of eggplant using fruit-specific EEF48 promoter-driven bacterial PSY gene, crtB, confers β-carotene accumulation in fruit. Eggplant (Solanum melongena L.) is globally cultivated especially in Asia and is an important source of nutrients in the diets of low-income consumers in developing countries. Since fruits of eggplant have low provitamin A carotenoid content, it is expected to develop eggplant with high carotenoid content for combatting vitamin A deficiency. To achieve this, the present study implemented a metabolic engineering strategy to modify the carotenoid biosynthetic pathway in eggplant. Expression analysis of carotenogenic genes in eggplant tissues showed that the expression of the endogenous phytoene synthase (PSY) was low in fruit and callus. Orange-colored calluses were generated from ectopic expression of crtB gene, which encodes bacterial PSY, in eggplant cells. The orange calluses accumulated > 20 μg g−1 FW of β-carotene, which was approximately 150-fold higher than that of the untransformed calluses. These observations suggest that the PSY expression is the rate-limiting step for β-carotene production in callus and fruit. Since the orange calluses did not regenerate plants, we chose eggplant EEF48 gene, which is presumably expressed in fruit. We amplified its promoter region by TAIL-PCR and showed that the EEF48 promoter is indeed active in eggplant fruit. Subsequently, transgenic eggplant lines having EEF48 promoter-driven crtB were produced. Among the transgenic lines produced, one line set fruit containing 1.50 μg g−1 FW of β-carotene, which was 30-fold higher than that of the untransformed fruits (0.05 μg g−1 FW). The self-pollinated progenies showed a 3:1 segregation ratio for the presence and absence of the transgene, which was linked to the β-carotene accumulation in fruit. These results provide a strategy for improvement of carotenoid content in eggplant fruit.

Purpose:Drug-coated balloons (DCBs) are commonly used for endovascular treatment of femoropopliteal lesions. Here, we employed intravascular ultrasound (IVUS) to investigate the predictors of restenosis after DCB treatment.Methods:This retrospective and single-center study was performed to examine 1-year primary patency after DCB treatment and to identify the risk factors for restenosis by analyzing clinical characteristics, angiographic findings, and IVUS measurements. We included 111 consecutive patients undergoing DCB treatment for de novo femoropopliteal lesions at our hospital from July 2018 to March 2020.Results:The primary patency rate was found to be 80.0% at 1 year. The Cox proportional hazard multivariate analysis revealed that restenosis was independently associated with chronic total occlusion (CTO; p < 0.001), circumferential calcification (p = 0.023), and smaller postprocedural minimum lumen area (MLA; p = 0.036). Furthermore, receiver operating characteristic curve analysis showed that the cutoff value of postprocedural MLA to prevent restenosis was 12.7 mm2, with an area under the curve of 0.774 (p< 0.001). The multivariate analysis indicated that patients with a postprocedural MLA below 12.7 mm2(n = 44) had a significantly smaller distal reference vessel size (p 2(n = 67).Conclusions:Restenosis after DCB treatment was shown to correlate with CTO, circumferential calcification, and postprocedural MLA as evaluated by IVUS. Moreover, smaller vessel sizes might represent a particular challenge to the DCB strategy due to the difficulty of restoring a sufficient postprocedural lumen area by balloon dilatation.

The 2016 Kumamoto earthquake occurred on April 16, 2016, and induced the complex distribution of surface ruptures and fault displacements, which revealed the difficulty of evaluating off-fault displacement hazards. The evaluation of off-fault displacements is necessary for the site investigation of an important facility, such as nuclear installations, but is difficult because off-fault displacements are thought to occur on unmapped or small-scale structures. A probabilistic fault displacement hazard analysis (PFDHA) assesses an off-fault displacement hazard as well as an on-fault one. Several PFDHA models have been developed from fault displacement datasets parsed by global-specific and Japanese-various faulting types. We developed a procedure to assess off-fault displacement hazards based on probabilistic and numerical simulation approaches. In the probabilistic approach, we constructed strike-slip and reverse-slip PFDHA models from a dataset of Japanese fault displacements. The off-fault components in PFDHA had a probability of non-zero off-fault displacement and an attenuation relationship. In the case of evaluating the site of an important facility, detailed field surveys were performed to collect numerous site-specific information. There is little site-specific data of off-fault displacements in Japan. The trench surveys were performed at off-fault displacement sites from the 2016 Kumamoto earthquake. The two trench sites were selected based on a linear low-coherence zone derived from the InSAR analysis, which emphasizes small-scale displacements. The excavation survey result at one site suggests a shorter recurrence interval than that of the active fault long-term evaluation. We also performed a probabilistic fault hazard analysis (PFDHA) of the trench sites by using the global strike-slip model and Japanese PFDHA models with and without the site-specific data. For the PFDHA results without site-specific data, the difference in the annual rates of exceedance between the global strike-slip and Japanese models increased with increasing fault displacements. This is because of the reduced decrease in the attenuation relationship of Japanese models. The differences in the annual rates of exceedance constrained with the site-specific data are independent of fault displacements due to variation in the probability of non-zero off-fault displacement between the global strike-slip and Japanese PFDHA models. These results suggest that the off-fault PFDHA models have high variability. In the case of PFDHA evaluation with several models, the individual PFDHA components are carefully selected by considering the individual effects. The site-specific short recurrence interval revealed by the trench survey leads to higher annual rates of exceedance.

There are limited data regarding the use of antithrombotic therapy in patients with atrial fibrillation (AF) who underwent percutaneous coronary intervention (PCI) with drug-eluting stents (DES). In this prospective interventional study, we evaluated the feasibility of short-term dual-antiplatelet therapy (DAPT) after DES implantation in AF patients treated with oral anticoagulation (OAC). The antithrombotic regimen in the present study was 1-month DAPT, followed by single-antiplatelet therapy with OAC. A total of 285 consecutive patients were enrolled between 2015 and 2017. The mean CHA2DS2-VASc score was 3.91 ± 1.51. The duration of DAPT was 28.5 ± 11.5 days. At 1-year follow-up, serious bleeding complications, defined as Bleeding Academic Research Consortium type ≥ 2, were observed in 27 patients (9.5%). Multivariate analysis showed that previous history of bleeding episodes (P = 0.009) and continuation of aspirin (P = 0.003) were independent predictors for the serious bleeding complications. High ORBIT (P = 0.008) and PRECISE-DAPT (P = 0.002) scores were associated with the bleeding complications, and the cut-off values were 5.00 and 49.0, respectively. No definite stent thrombosis occurred in any of the patients. Short-term DAPT is feasible in AF patients treated with OAC after undergoing PCI with DES. The previous history of bleeding episodes and long-term aspirin use were associated with their 1-year serious bleeding events.

Purpose: To investigate the efficacy of scoring balloons for immediate success of percutaneous transluminal angioplasty (PTA) in femoropopliteal lesions. Materials and Methods: Between 2013 and 2019, 398 consecutive patients with de novo femoropopliteal lesions were treated using PTA in our hospital. The procedure success rate was compared among patients undergoing PTA with vs without scoring balloons after 1:1 propensity score matching on hemodialysis, TransAtlantic Inter-Society Consensus II classification, Peripheral Arterial Calcium Scoring System (PACSS) grade, lesion length, and use of intravascular ultrasound. Propensity matching produced 84 patients (mean age 73.4±8.3; 65 men) treated with scoring balloons and 84 patients (mean age 75.6±8.7; 56 men) treated with plain balloons. Kaplan-Meier analysis investigated patency after the procedure in both groups; estimates are given with the 95% confidence interval (CI). Results: Residual stenosis

Although variation among habitats in the ratio of gametophytes to sporophytes has been reported in various gigartinacean species, factors controlling the phase ratio remain poorly understood. Over 18 months, we examined the phase ratio of Chondrus ocellatus at three sites: a sheltered intertidal site, Hiruga A; an exposed intertidal site, Hiruga B; and a subtidal site, Shikimi. The mean proportion of gametophytes at Hiruga A (73.1%) was significantly higher than that at Shikimi (51.2%) and Hiruga B (44.7%). Due to a significantly higher water retention ability of the gametophytes, it was expected that the gametophytes would exhibit higher desiccation tolerance. After dehydration treatments, however, neither the photosynthetic rate of vegetative blades nor the survival rate of spores was significantly different between the phases. Measurements of blade strength indicated that the sporophytic blades were less stiff and more flexible, and a culture experiment revealed that the sporophytic germlings showed a significantly higher growth rate. Flexible blades and fast-growing germlings are considered advantageous for colonizing wave-swept intertidal habitats, so these properties may have caused the different fluctuation pattern of phase ratio among the sites. The present data demonstrate that biomechanical and physiological differences between the two phases of C. ocellatus make one phase advantageous in certain environmental conditions, and that these differences likely cause an unequal ratio of isomorphic phases.

Increasing the urine flow rate (UFR) reduces the toxic effect of contrast media. Use of the RenalGuard system enables the achievement of a high UFR by maintaining intravascular volume and prevents the development of contrast-induced acute kidney injury (CI-AKI). However, the efficacy and safety of RenalGuard system have not yet been evaluated in Japan. This multicenter prospective study evaluated the efficacy and safety of the RenalGuard therapy in preventing CI-AKI development in 60 Japanese patients with renal dysfunction [estimated glomerular filtration rate (eGFR)