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Dryadaula epischista (Meyrick, 1936), initially described from a single male specimen in Japan, is herein redescribed based on newly collected specimens from the type locality. Furthermore, we describe Dryadaula orientalis Park & Yagi, sp. nov., a new species from Japan that closely resembles D. epischista. The adults and genitalia of the two species are illustrated. The genitalia of D. epischista from a specimen collected at the type locality are shown for the first time. DNA barcodes of the two Dryadaula species and the genetic distances of barcode regions among them and other congeners are provided.

Objective: This study explores safety, feasibility, and potential improvement in functional status after intravenous infusion of mesenchymal stem cells (MSCs) in chronic severe brain injury (BI) patients. Methods: An intravenous infusion of autologous MSCs in autoserum cultured under Good Manufacturing Practice was delivered to four chronic patients with BI. In addition to assessing feasibility and safety, neurological function was evaluated using the National Institutes of Health Stroke Scale, Fugl-Meyer Assessment, Barthel Index, and cognitive-related behavioral assessment. Imaging studies with 18F-FDG-PETCT and 11C-methionine-PETCT (METPET) were carried out to evaluate brain metabolic activity. Results: No serious adverse events were recorded. None of the patients developed CNS tumors, abnormal cell growth, or neurological deterioration. While this initial case series was not blinded, gradual functional improvement was observed after MSC infusion. Serial 11C-METPETs displayed a statistically significant increase in methionine uptake, primarily in the thalamus and pons. Conclusion: We emphasize that this study was unblinded and did not exclude placebo effects, the contribution of endogenous recovery, or observer bias; however, our observations support feasibility and safety. No adverse events were observed. The data suggests improved quality of life after infused MSCs; however, a blinded, larger-scale study will be necessary to fully address this possibility.

Background: Despite evidence regarding the benefits of transcranial direct current stimulation (tDCS) in patients with severe traumatic brain injury, few trials have examined the treatment safety. Therefore, we created a phase I trial in Japan to investigate the safety of tDCS after severe brain injury. Methods: We verified the safety of tDCS through constant left frontal anodal stimulation at 2 mA for 20 min for 5 consecutive days. Additionally, we added a variable stimuli period to explore the effects of stimulus intensity, location, and duration. We adapted a traditional 3 + 3 study design. We assessed the rate of adverse effects, including skin burns and clinical seizure. Changes in neurological symptoms were evaluated using the Glasgow Coma Scale, Coma Recovery Scale-Revised, and 4 states of consciousness (coma, unresponsive wakefulness syndrome, minimally conscious state, and severe disability). Results: Six patients completed the study. No obvious adverse events were observed during the constant stimulation period or the variable stimulation period (right frontal anodal stimulation, stimulation frequency 2–4 mA, 1 or 5 times per week for a period of 4 weeks). Regarding the Coma Recovery Scale-Revised, patients in 4 out of 6 instances (66.7 %) improved by more than 1 point. Conclusion: Our phase I safety study indicated that a single course of tDCS was safe in patients with severe traumatic brain injury. The next step is a phase II trial to investigate the preliminary efficacy and safety of tDCS at 2 mA (in comparison with sham stimulation).

Abstract Aims Data regarding prognostic events following catheter ablation (CA) for atrial fibrillation (AF) in patients with heart failure with preserved ejection fraction (HFpEF) are scarce. We conducted this study to compare the incidence of major adverse clinical events (MACE) following CA for AF between patients with HFpEF and those with systolic heart failure (HF). Methods and results This single‐centre observational study included 142 patients with HF who underwent CA for AF (median follow‐up: 4.0 [2.6, 6.3] years). The patients were grouped based on the presence of HFpEF (n = 84) and systolic HF (left ventricular ejection fraction

Background: We previously demonstrated the clinical events in patients who underwent catheter ablation (CA) for atrial fibrillation (AF). Data on the association between the period of atrial tachyarrhythmia (ATA) recurrence after CA and long-term major adverse clinical events (MACE) remain unclear. In this study, we evaluated this issue in patients with systolic impairment (left ventricular ejection fraction

Left ventricular (LV) diastolic dysfunction is increasingly common in heart failure with preserved ejection fraction (HFpEF), and new drug therapy is desired. We recently reported that dantrolene (DAN) attenuates pressure-overload induced hypertrophic signaling through stabilization of tetrameric structure of cardiac ryanodine receptor (RyR2). Because cardiac hypertrophy substantially affects LV diastolic properties, we investigated the effect of DAN on LV diastolic properties in mineralocorticoid-salt–induced hypertensive rat model exhibiting the HFpEF phenotype.Male Sprague-Dawley (SD) rats (8 weeks old) received an uninephrectomy (UNX), subcutaneous implantation of a 200 mg pellet of deoxycorticosterone acetate (DOCA), and 0.9% NaCl water (UNX + DOCA-salt). UNX, a control pellet, and water without NaCl served as controls (UNX control). The effect of oral administration of 100 mg/kg/d DAN was examined in UNX control and UNX + DOCA-salt groups (UNX + DAN and UNX + DOCA-salt + DAN).UNX + DOCA-salt treatment resulted in mild hypertension. Chronic administration of DAN to UNX + DOCA-salt rats (UNX + DOCA-salt + DAN) did not affect blood pressure. DAN treatment increased the mitral annular early relaxation velocity in the UNX + DOCA-salt group. The size of cardiomyocytes increased in the UNX + DOCA-salt group, whereas the increase was suppressed by DAN treatment. LV fibrotic area was significantly smaller in the UNX + DOCA-salt + DAN group than in the UNX + DOCA-salt group (2.0 ± 0.2% vs 4.0 ± 0.4%). The LV chamber stiffness significantly increased in the UNX + DOCA-salt group, whereas the increase was suppressed by DAN treatment. DAN treatment normalized the CaM-RyR2 interaction and inhibited aberrant Ca2+ release.DAN improved left ventricular diastolic properties with respect to both myocardial relaxation and chamber stiffness. DAN may be a new treatment option for HFpEF.

A new Symplocos trumpet leafminer, Coptotriche yanbarensis Kim & Yagi sp. nov., feeding on S. stellaris and S. okinawensis (Symplocaceae) is described from Okinawa Island, Japan. The new species is distinguishable from the Japanese Symplocos feeding described species, C. symplocosella Kobayashi & Hirowatari, 2016 by the forewing coloration, the shape of genitalia, and also DNA barcodes.

Objective: The study aimed to investigate predictive factors associated with outcome six months after mild to moderate aneurysmal subarachnoid hemorrhage (SAH). Methods: We divided 136 patients (51 men and 85 women) after SAH (Hunt & Kosnik [H&K] grade I to III) into groups with good and poor outcome according to scores on the modified Rankin Scale (mRS) at six months after SAH onset: good outcome (mRS score, 0–1; n = 105) and poor outcome (mRS score, 2–6; n = 31). At admission, we assessed age, sex, H&K grade, and Fisher grade, and one month after aneurysmal SAH, we evaluated aneurysm location, treatment modality (coil embolization, clipping, or no surgical treatment), proportion of patients who underwent shunt placement, proportion of patients with delayed cerebral ischemia, and scores on neuropsychological tests (Mini-Mental State Examination, Raven’s Colored Progressive Matrices, Kana-hiroi Test, Trail Making Test, and Rey-Osterrieth Complex Figure Test, immediate recall). Results: H&K grade was associated with outcome (χ2 = 6.220, P = 0.005), and a significantly higher proportion of the good outcome group had an H&K grade II (P = 0.025). The good outcome group had significantly better scores on the Mini-Mental State Examination (U = 1251, P = 0.045), Raven’s Colored Progressive Matrices (U = 1224, P = 0.036), and Trail Making Test parts A (U = 1238, P = 0.043) and B (U = 1247, P = 0.048). However, we found no significant intergroup differences in the other patient demographic and disease characteristics, including age, treatment modality, and delayed cerebral ischemia, or in the other neuropsychological assessments. Binary logistic regression analysis identified H&K grade I and II as predictive factors associated with good outcome. Conclusion: Besides severity at admission as indicated by H&K grade, neuropsychological tests explicitly performed one month after mild to moderate aneurysmal SAH may help nursing staff to predict patient outcome, including possible symptoms after discharge.

Abstract Background This study aimed to investigate the correlation between left atrial low‐voltage areas (LVAs) and an arrhythmogenic superior vena cava (SVC) and the impact on the efficacy of an empiric SVC isolation (SVCI) along with a pulmonary vein isolation (PVI) of non‐paroxysmal atrial fibrillation (non‐PAF) with or without LVAs. Methods We retrospectively enrolled 153 consecutive patients with non‐PAF who underwent a PVI alone (n = 51) or empiric PVI plus an SVCI (n = 102). Left atrial voltage maps were constructed during sinus rhythm to identify the LVAs (

BackgroundBrain injuries resulting from motor vehicle accidents and falls, as well as hypoxic insults and other conditions, are one of the leading causes of disability and death in the world. Current treatments are limited but include continuous rehabilitation, especially for chronic brain injury. Recent studies have demonstrated that the intravenous infusion of mesenchymal stem cells (MSCs) has therapeutic efficacy for several neurological diseases, including stroke and spinal cord injury. ObjectiveThe objective of our investigator-initiated clinical trial is to assess the safety and potential efficacy of the intravenous infusion of autoserum-expanded autologous MSCs for patients with chronic brain injury. MethodsThe (phase 2) trial will be a single-arm, open-label trial with the primary objective of confirming the safety and efficacy of autoserum-expanded autologous MSCs (STR-01; produced under good manufacturing practices) when administered to patients with chronic brain injury. The estimated number of enrolled participants is 6 to 20 patients with a modified Rankin Scale grade of 3 to 5. The assessment of safety and the proportion of cases in which the modified Rankin Scale grade improves by 1 point or more at 180 days after the injection of STR-01 will be performed after MSC infusion. ResultsWe received approval for our clinical trial from the Japanese Pharmaceuticals and Medical Devices Agency on December 12, 2017. The trial will be completed on June 11, 2023. The registration term is 5 years. The recruitment of the patients for this trial started on April 20, 2018, at Sapporo Medical University Hospital in Japan. ConclusionsOur phase 2 study will aim to address the safety and efficacy of the intravenous infusion of MSCs for patients with chronic brain injury. The use of STR-01 has been performed for patients with cerebral infarction and spinal cord injury, providing encouraging results. The potential therapeutic efficacy of the systemic administration of autoserum-expanded autologous MSCs for chronic brain injury should be evaluated, given its safety and promising results for stroke and spinal cord injury. Trial RegistrationJapan Medical Association Center for Clinical Trials JMA-IIA00333; https://tinyurl.com/nzkdfnbc International Registered Report Identifier (IRRID)DERR1-10.2196/37898

Purpose: The purpose of this study was to analyze the role of homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 (Herpud1) gene in the development of cardiomyocyte hypertrophy. Method: In order to examine the effect of suppressing Herpud1 expression, Herpud1 small interfering RNA (siRNA) was introduced into H9C2 cells, which are cell lines derived from rat myocardium, and the degree of Herpud1 protein expression and cell hypertrophy in the Herpud1 siRNA-transfected group and the control group was compared by immunostaining 48 h after Herrpud1 siRNA introduction. To examine whether hypertrophy induced by angiotensin II (Ang II) can be suppressed by the overexpression of Herpud1, the green fluorescent protein (GFP)-Herpud1 plasmid was introduced into H9C2 cells, and the degree of cell hypertrophy was examined in the GFP-Herpud1-and control groups for 48 h. Nuclear translocation of nuclear factor of activated T-cells, cytoplasmic 4 (NFATc4), a transcription factor for hypertrophic genes, was also examined. Results: [1] Herpud1 siRNA-transfected cells showed decreased Herpud1 protein expression and hypertrophy formation compared to control cells [2]; Overexpression of Herpud1 suppresses Ang II-induced cell hypertrophy; and [3] Overexpression of Herpud1 inhibits nuclear translocation of NFATc4. Discussion: It was suggested that Herpud1 might be an anti-hypertrophic gene in Ang II induced cardiomyocytes hypertrophy.

Abstract Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive neuronal cell loss. Recently, dysregulation of intracellular Ca2+ homeostasis has been suggested as a common proximal cause of neural dysfunction in AD. Here, we investigated (1) the pathogenic role of destabilization of ryanodine receptor (RyR2) in endoplasmic reticulum (ER) upon development of AD phenotypes in App NL-G-F mice, which harbor three familial AD mutations (Swedish, Beyreuther/Iberian, and Arctic), and (2) the therapeutic effect of enhanced calmodulin (CaM) binding to RyR2. In the neuronal cells from App NL-G-F mice, CaM dissociation from RyR2 was associated with AD-related phenotypes, i.e. Aβ accumulation, TAU phosphorylation, ER stress, neuronal cell loss, and cognitive dysfunction. Surprisingly, either genetic (by V3599K substitution in RyR2) or pharmacological (by dantrolene) enhancement of CaM binding to RyR2 reversed almost completely the aforementioned AD-related phenotypes, except for Aβ accumulation. Thus, destabilization of RyR2 due to CaM dissociation is most likely an early and fundamental pathogenic mechanism involved in the development of AD. The discovery that neuronal cell loss can be fully prevented simply by stabilizing RyR2 sheds new light on the treatment of AD.

Sialorrhea is a major cause of recurrent aspiration pneumonia in severe chronic brain injury. Previous reports have shown that transdermal scopolamine can decrease saliva production. We present four patients with severe chronic brain injury who experienced repeat aspiration pneumonia with sialorrhea. Longitudinal computed tomography examinations to assess the therapeutic effect were performed in all four cases before and after transdermal scopolamine. Transdermal scopolamine was applied as a patch (0.1 g/2.5 cm 2 ) behind the earlobe every 24 h after confirming the absence of glaucoma. Patches were formulated as an in-hospital preparation (scopolamine butylbromide 0.25 g and hydrophilic cream 4.75 g) under the approval of our institutional review board. Longitudinal computed tomography after transdermal scopolamine use showed a decrease in pleural effusions associated with continuous aspiration pneumonia in all four cases. The data from repeat computed tomography suggest that long-term transdermal scopolamine for reducing saliva production may be a reasonable option for appropriate palliative care in severe chronic brain injury patients.

Objectives: Renal scintigraphy is widely used to evaluate residual function of a transplanted kidney from the donor. Dynamic computed tomography (CT) imaging can evaluate both kidney morphology and regional renal function. The aim of this study was to develop an imaging protocol and a calculation method using dynamic CT for assessing the effective renal plasma flow (ERPF) by model analysis, and to evaluate the validity of the obtained ERPF values. Methods: Preoperative dynamic CT examination with a low radiation dose exposure system was performed for 25 renal transplant donors, and ERPF was calculated from the obtained images (CT-ERPF). To calculate CT-ERPF, we set the region of interest (ROI) in the renal cortex using automatic ROI-setting software developed in our laboratory. We compared the processing time with automatic and manual ROI settings. To evaluate the validity of CT-ERPF, we examined the correlation of age with CT-ERPF and compared with reported ERPF values. We also compared the uptake rates of technetium-99m-dimercaptosuccinic acid and CT-ERPF in terms of the right-to-left ratio. Results: There was good agreement of CT-ERPF assessed using automatic and manual ROIs. CT-ERPF was negatively correlated with age and showed values below the reference ERPF range in 21 cases. The right-to-left ratio of CT-ERPF showed a significant correlation with that of technetium-99m-dimercaptosuccinic acid. Conclusions: Using our method, CT-ERPF was a useful indicator for preoperative evaluation of donor’s renal function.

Objective: Patients with good recovery after aneurysmal subarachnoid hemorrhage (SAH) are commonly discharged about one month after the event. However, these patients often still show cognitive symptoms, such as fatigue, difficulty concentrating, and irritability. Understanding the early cognitive outcome of patients with SAH with good recovery is thought to be crucial for neurosurgical nursing staff. We analyzed patient data to clarify whether cognitive outcome depends on the location of the ruptured aneurysm 1 month after SAH. Methods: For 186 patients (72 men and 114 women; median age, 57 years; age range, 21–83 years) who had experienced SAH (Hunt & Kosnik grade I to III), we retrospectively analyzed data on the location of the ruptured aneurysm, Fisher grade at admission, treatment modality (coil embolization, clipping, or no surgical treatment), neuropsychological assessments 1 month after SAH, and modified Rankin Scale 6 months after SAH. Results: Crystallized intelligence (i.e., IQ, assessed using the Mini-Mental State Examination and Kohs Block Design Test) improved to almost normal levels in all patients, irrespective of the location of the ruptured aneurysm. In contrast, fluid intelligence (e.g., executive function and attention, assessed using the Frontal Assessment Battery; Trail Making Test, Part A; and the Japanese Kana-hiroi test) did not improve as much, specifically in patients with a ruptured aneurysm in the basilar artery. Conclusions: These results may help nursing staff to identify mild- to moderate-grade patients at greater risk of problems and to arrange appropriate support strategies for patients after discharge.

Background Catheter ablation can improve long‐term prognosis of patients with atrial fibrillation with systolic impairment. However, atrial tachyarrhythmia (ATA) recurrence increases during long‐term follow‐up. We aimed to investigate the impact of ATA recurrence on the development of long‐term adverse clinical events following catheter ablation for atrial fibrillation and to identify predictors for the development of adverse clinical events. Methods and Results This single‐center observational study included 75 patients with systolic impairment (left ventricular ejection fraction

Introduction: Our previous studies demonstrated that dantrolene, a ryanodine receptor stabilizer, prevents endoplasmic reticulum (ER) stress in the heart. ER stress is a strong mediator of impaired lipid metabolism in the liver, thereby contributing to fatty liver disease. In this study, we investigated the effects of dantrolene on fatty liver disease in mice and ER stress in hepatocytes. Methods and results: Eight weeks old C57BL/6 mice were fed high-fat diet (HFD) for 8 weeks with or without the oral administration of dantrolene (100 mg/kg/day). The livers of mice without dantrolene (HFD group) showed severe fatty liver, whereas the livers of the mice treated with dantrolene (HFD + DAN group) only showed slightly fatty liver. To address the preventive effects of dantrolene, primary hepatocytes were cultured with palmitate in the presence or absence of dantrolene. Dantrolene reduced lipid load and prevents palmitate-induced increase in cytoplasmic Ca2+ and ER stress. Based on these findings, we propose that dantrolene is a potential new therapeutic agent against fatty liver disease.

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart disease that causes heart failure and/or sudden cardiac death. Several desmosomal genes (DSC2, PKG, PKP2, DSP, and RyR2) are thought to be the causative gene involved in ARVC. Out of them, DSC2 mutations account for 2% of ARVC genetic abnormalities. This study aimed to clarify the effect of G790del mutation in DSC2 on the arrhythmogenic mechanism and cardiac function in a mouse model. Result: Neither the heterozygous +/G790del nor homozygous G790del/G790del mice showed structural and functional defects in the right ventricle (RV) or lethal arrhythmia. The homozygous G790del/G790del 6-month-old mice slightly showed left ventricular (LV) dysfunction. Cell shortening decreased with prolongation of intracellular Ca2+ transient in cardiomyocytes isolated from the homozygous G790del/G790del mice, and spontaneous Ca2+ transients were frequently observed in response to isoproterenol. Conclusions: G790del mutation in DSC2 was not relevant to the pathogenesis of ARVC, but showed a slight contractile dysfunction and Ca2+ dysregulation in the LV. Keywords: Desmocollin-2 (DSC2), Arrhythmogenic right ventricular cardiomyopathy (ARVC)

Background: Recently, we showed an age-related increase in augmentation pressure (AP) measured using Mobil-O-Graph (MOG) in normotensive Japanese individuals. However, AP might be a poor index of wave reflection due to the overlap between the forward wave and reflected wave. Methods: We enrolled untreated hypertensive patients and patients currently on antihypertensive treatment. For 70 patients (median age, 70.5 years; 34 men), M-mode echocardiography was performed for determination of left ventricular hypertrophy (LVH), while hemodynamic measurements were taken using MOG. We investigated the influence of central hemodynamic parameters on LVH. Results: Spearman correlation coefficients between various parameters [age, height, systolic blood pressure (SBP), mean BP, diastolic BP, central systolic BP (cSBP), and AP] were calculated for LV mass indexed to body surface area (LVMI; g/m2). In men, age (r = 0.600, p = 0.0002), height (r = −0.495, p = 0.003), SBP (r = 0.423, p = 0.013), cSBP (r = 0.454, p = 0.007), and AP (r = 0.661, p < 0.0001) were correlated to LVMI. In women, cSBP (r = 0.334, p = 0.044) and AP (r = 0.480, p = 0.003) were correlated to LVMI. In men, LVMI (R2 = 0.578, p = 0.0001) was significantly associated with AP (β = 1.32 ± 0.56, p = 0.027) in multivariate regression analysis. In women, no significant independent parameter for LVMI was observed. ROC curve analysis was performed to estimate the utility of AP for the detection of LVH (LVMI >115 g/m2) in men. Area under the ROC curve was 0.83 (95% CI: 0.68–0.99). The optimal cut-off point of 12.5 mmHg produced 79.0% sensitivity and 86.7% specificity. Conclusion: Higher AP showing >12.5 mmHg calculated by MOG was a significant independent predictor of LVH in male hypertensive patients.

This paper provides new taxonomic and biological data on a complex of gracillariid moths in the endemic genus Philodoria Walsingham, 1907 that are associated with Myrsine (Primulaceae) in the Hawaiian Islands, United States. Two new species, Philodoria kauaulaensis Kobayashi, Johns & Kawahara, sp. n. (host: Myrsine lanaiensis, M. lessertiana, and M. sandwicensis) and P. kolea Kobayashi, Johns & Kawahara, sp. n. (host: M. lessertiana) are described. Biological data are provided for two previously described species that also feed on Myrsine: P. auromagnifica Walsingham, 1907 and P. succedanea Walsingham, 1907. For the first time we detail and illustrate genital structures, immature stages, biology, and host plants of P. auromagnifica and P. succedanea. Philodoria kolea, P. auromagnifica, and P. succedanea occur in sympatry on the island of Hawaii (Big Island), but each species differs in behavioral characters: P. kolea utilizes leaves of seedlings and forms a serpentine mine, whereas the latter two utilize leaves of larger plants, and form linear or serpentine to blotch mines. More broadly, leaf mine forms and diagnostic characteristics of the Myrsine-feeding species complex of Philodoria (as currently known) are reviewed and illustrated.

Abstract Background Steroid therapy, a key therapy for inflammatory, allergic, and immunological disorders, is often associated with steroid myopathy as one of the side effects. Steroid therapy is considered the first-line therapy for myositis; however, there have been no reports strictly comparing the muscle mass in patients with myositis before and after steroid therapy. Thus, it is currently unclear whether steroid therapy for such patients affects muscle volume in addition to muscle strength. We aimed to determine the change in muscle mass after steroid therapy via cross-sectional computed tomography (CT) in patients with myositis. Methods Data from seven patients with myositis and eight controls, who were all treated with high doses of steroids, were assessed before and after steroid therapy. Clinical factors in patients with myositis included serum muscle enzyme levels and muscular strength. The cross-sectional area of skeletal muscle and the low muscle attenuation rate at the level of the caudal end of the third lumbar vertebra were obtained using CT and measured using an image analysis program for all patients. Data were subjected to statistical analysis using several well-established statistical tests. The Wilcoxon signed-rank test was used for comparing paired data for each patient. The Mann-Whitney U test was used to compare sets of data sampled from two groups. The Spearman’s rank correlation coefficient was used for determining the correlations between two variables. Statistical significance was set at p

During an ongoing DNA-barcoding campaign of the leaf-mining moths that feed on woody plants in Northeast Asia, four lineages of the genus Phyllocnistis (Gracillariidae, Phyllocnistinae) were discovered on dogwood (Cornus spp): P. cornella Ermolaev, 1987 on C. controversa Hemsl. (Japan: Hokkaido) and three new species – one feeding on C. controversa, C. florida L. and C. macrophylla Wall. in Japan (Honshu, Shikoku, Kyushu), a second species on C. macrophylla in China (Yunnan) and a third on Siberian dogwood Cornus alba L. in Russia (Siberia). All these species showed differences in morphology, in the barcode region of the cytochrome c oxidase I gene and in two nuclear genes (histone H3 and 28S ribosomal RNA). No correlation was found between the deep mitochondrial splits observed and the Wolbachia infection pattern. Based on both morphological and molecular evidence, the three recently discovered lineages are described here as new species: P. indistincta Kobayashi & Triberti, sp. n. (Japan), P. saepta Kirichenko, Ohshima & Huang, sp. n. (China) and P. verae Kirichenko, Triberti & Lopez-Vaamonde, sp. n. (Russia). In addition, the authors re-describe the adult morphology of P. cornella, provide the first record of this species from Japan and highlight the diagnostic characters that allow these Cornus-feeding Phyllocnistis species to be distinguished.

The systematic position of Tonza Walker, 1864 is re-evaluated, based on the characteristics of immature stages and DNA barcodes. Larvae and pupae of Tonza citrorrhoa Meyrick, 1905 are described and illustrated for the first time. Larvae of this species form a loose web among the leaves and branches of the host plant, Putranjiva matsumurae Koidz. (Putranjivaceae Endl.). The immature stages of Tonza exhibit four unique apomorphies including: in the larva, the prolegs on A5 and A6 absent, and the seta L2 on the A1–A8 very small; in the pupa, four minute knobs are positioned in the middle portion on abdominal segments V and VI; while its caudal processes possess a W-shaped spine with numerous minute spines. These characteristics clearly distinguish Tonza from other yponomeutoid families and hence, we propose a new family group name, Tonzidae Kobayashi & Sohn fam. nov., for the genus Tonza. Existing DNA barcode data suggest a relationship with Glyphipterigidae Stainton, 1854. The family level status of Tonzidae fam. nov. provides a hypothesis that needs to be tested with larger molecular data.

Background: HEM-9000AI (HEM) is an established device for measurement of radial augmentation index (rAIx) used by applanation tonometry in Japan. Mobil-O-Graph (MOG) is a cuff-based oscillometric device for assessment of central aortic AIx (cAIx) and the usefulness to Europeans has been reported. We compared the AIx between HEM and MOG in Japanese normotensive subjects. Methods: We enrolled 106 normotensive volunteers (47 male, 21 to 79 years). The left radial arterial waveform was recorded with the HEM. MOG were taken on the left arms, which arm circumferences (ACs) were measured to allow the correct choice of cuff (two sizes available; 20–24 and 24–32 cm). We performed multiple regressions for AIx and key variables in HEM and MOG. Results: The ACs in M and F were 25.7±1.9 (mean±SD) cm and 23.5±2.1cm, respectively. Both rAIx (70.5±15.3% vs 83.6±11.9%, p < 0.001) and cAIx (17.2±7.3% vs 29.7±9.8%, p < 0.001) in M were smaller than those in F. Multiple regression analysis revealed that cAIx in M (R2 = 0.5176) was significantly associated with age (β = 0.17, p = 0.004) and cuff size (p = 0.001). cAIx obtained using the smaller cuff was significantly increased compared to the larger cuff (25.1±5.9% vs 14.8±5.9%). In F, cAIx (R2 = 0.2245) tended to be associated with age (β = 0.16, p = 0.072) and was significantly associated with height (β = −0.62, p = 0.007) and heart rate (β = −0.26, p = 0.0029). Conclusions: The brachial cuff-based waveform recordings are useful for Japanese normotensive individuals. However, the mean AC is close to the bound of two cuff sizes and the measurement of lower cAx using the larger cuff is less sensitive.

Novel antioxidants have been synthesized and characterized by their chemical properties as antioxidants with high superoxide scavenging activity. (2R,3R)-diphenylethylenediamine is a spacer in antioxidants, and we synthesized targets 11a and 11b by conjugation with o-hydroquinone and p-hydroquinone at the two N-termini, respectively. Superoxide scavenging activities of the plant flavonoid-like 11a and 11b were compared with those of known antioxidants, and shown to increase in the following order: curcumin << ascorbic acid < Trolox < ()-epicatechin < 11a < quercetin ≤ 11b . Compound 11a also formed a solvated 11a–metal complex with metal ions. The 11a–Cu2+ complex was shown to have higher superoxide scavenging activity than that of 11a, 11b, Cu2+, and the 11a–Al3+ and 11a–La3+ complexes, whereas the 11a–Al3+ complex increased rather than decreased superoxide levels. The 11a–Al3+ complex did not abstract one electron from the SOMO of O2−. since the HOMO and LUMO phases of Al3+ do not exist in the center of the 11a–Al3+ complex. However, the SOMO of the 11a–Cu2+ complex distributed in the center of Cu2+ may abstract one electron from the SOMO of O2−.. These results suggest that 11a and 11b are powerful antioxidants.

Catecholamines induce intracellular reactive oxygen species (ROS), thus enhancing diastolic Ca2+ leakage through the ryanodine receptor during heart failure (HF). However, little is known regarding the effect of atrial natriuretic peptide (ANP) on ROS generation and Ca2+ handling in failing cardiomyocytes. The aim of the present study was to clarify the mechanism by which an exogenous ANP exerts cardioprotective effects during HF. Cardiomyocytes were isolated from the left ventricles of a canine tachycardia-induced HF model and sham-operated vehicle controls. The degree of mitochondrial oxidized DNA was evaluated by double immunohistochemical (IHC) staining using an anti-VDAC antibody for the mitochondria and an anti-8-hydroxy-2'-deoxyguanosine antibody for oxidized DNA. The effect of ANP on ROS was investigated using 2,7-dichlorofluorescin diacetate, diastolic Ca2+ sparks assessed by confocal microscopy using Fluo 4-AM, and the survival rate of myocytes after 48 h. The double IHC study revealed that isoproterenol (ISO) markedly increased oxidized DNA in the mitochondria in HF and that the ISO-induced DNA damage was markedly inhibited by the co-presence of ANP. ROS production and Ca2+ spark frequency (CaSF) were increased in HF compared to normal controls, and were further increased in the presence of ISO. Notably, ANP significantly suppressed both ISO-induced ROS and CaSF without changing sarcoplasmic reticulum Ca2+ content in HF (p

We synthesized (2,4-trifluoromethyl-7-N-bis(2,5,8,11-tetraoxatridecane-13-yl)-aminoquinoline) TFMAQ-diEg4, an emissive aminoquinoline derivative that incorporated two tetraethyleneglycol chains into an amino group. TFMAQ-diEg4 showed fluorescence and thermo-responsive properties accompanied by a lower critical solution temperature (LCST), due to the introduction of the oligoethylene glycol chain. This thermo-responsive LCST behavior occurred at the border of a cloud point. Below and above the cloud point, self-assemblies of 6-7-nm nanoparticles and ~2000-nm microparticles were observed, in vitro. In addition, TFMAQ-diEg4 showed a high solubility, over 20 mM for aqueous solution, in vivo, which not only prevented thrombosis but also allowed various examinations, such as single intravenous administration and intravenous drips. Intravenous administration of TFMAQ-diEg4, to tumor-bearing, mice led to the accumulation of the molecule in the tumor tissue, as observed by fluorescence imaging. A subset of mice was treated with local heat around their tumor tissue and an intravenous drip of TFMAQ-diEg4, which led to a high intensity of TFMAQ-diEg4 emission within the tumor tissue. Therefore, we revealed that TFMAQ-diEg4 was useful as a fluorescence probe with thermo-responsive properties.

Urea benzene derivatives (UBD) with amphiphilic side chains showed self-assembly behavior in aqueous solution to form nanoparticles ~100 nm in size. Subsequent thermal treatment led to additional self-assembly of the nanoparticles due to dehydration of the amphiphilic side chains, producing microparticles. This self-assembly process was accompanied by a lower critical solution temperature (LCST) behavior, as revealed by the abrupt decrease in solution transmittance. In this study, three UBD (UBD-1–3) with different lengths of the alkyl segment in the amphiphilic side chain (namely, hexyl, heptyl, and octyl, respectively) were prepared to investigate the self-assembly behavior in aqueous solution. UBD-1–3 formed identical nanoparticles, with sizes in the 10~80 nm range but with different LCST values in the order 3 < 2 < 1. These results suggest a relationship between the hydrophobicity and the self-assembly behavior of UBD.

OBJECTIVES:The purpose of this study was to investigate whether adding a low-dose β1-blocker to milrinone improves cardiac function in failing cardiomyocytes and the underlying cardioprotective mechanism. BACKGROUND:The molecular mechanism underlying how the combination of low-dose β1-blocker and milrinone affects intracellular Ca(2+) handling in heart failure remains unclear. METHODS:We investigated the effect of milrinone plus landiolol on intracellular Ca(2+) transient (CaT), cell shortening (CS), the frequency of diastolic Ca(2+) sparks (CaSF), and sarcoplasmic reticulum Ca(2+) concentration ({Ca(2+)}SR) in normal and failing canine cardiomyocytes and used immunoblotting to determine the phosphorylation level of ryanodine receptor (RyR2) and phospholamban (PLB). RESULTS:In failing cardiomyocytes, CaSF significantly increased, and peak CaT and CS markedly decreased compared with normal myocytes. Administration of milrinone alone slightly increased peak CaT and CS, while CaSF greatly increased with a slight increase in {Ca(2+)}SR. Co-administration of β1-blocker landiolol to failing cardiomyocytes at a dose that does not inhibit cardiomyocyte function significantly decreased CaSF with a further increase in {Ca(2+)}SR, and peak CaT and CS improved compared with milrinone alone. Landiolol suppressed the hyperphosphorylation of RyR2 (Ser2808) in failing cardiomyocytes but had no effect on levels of phosphorylated PLB (Ser16 and Thr17). Low-dose landiolol significantly inhibited the alternans of CaT and CS under a fixed pacing rate (0.5 Hz) in failing cardiomyocytes. CONCLUSION:A low-dose β1-blocker in combination with milrinone improved cardiac function in failing cardiomyocytes, apparently by inhibiting the phosphorylation of RyR2, not PLB, and subsequent diastolic Ca(2+) leak.

Dietary chitosan, a polymer of glucosamine, decrease the absorption of dietary fat and then reduce the abdominal fat deposition in broiler chickens. Chitosan is also digested and absorbed in the form of glucosamine by hens and broilers. Thus, in broiler chickens, dietary chitosan may decrease lipogenesis and triglyceride (TG) synthesis in the liver in addition to decrease fat absorption, consequently resulting in a reduction of body fat deposition. However, little research has been done to determine whether dietary glucosamine decreases hepatic TG synthesis and body fat deposition in broiler chickens. The present experiment was conducted to determine the effects of dietary chitosan or glucosamine HCl on fat absorption, hepatic TG contents and body fat deposition in broiler chickens. Broiler chickens at 14d old were fed on a control diet based on corn and soybean meal or diets containing 5% chitosan or glucosamine HCl for 3 weeks. Dietary chitosan and glucosamine HCl did not affect feed intake, body weight gain, feed efficiency and breast muscle weight. Dietary chitosan significantly (P

Chitosan, a polymer of glucosamine, decrease the absorption of dietary fat and then reduce the abdominal fat deposition in broiler chickens. Chitosan is digested by hens and broilers. Thus, chitosan may decrease lipogenesis and triglyceride (TG) synthesis in the liver. However, little research has been done to determine whether dietary chitosan regulate hepatic lipid metabolism in chickens. Administration of antithyroid agent such as propylthiouracil (PTU) induces excessive lipid deposition in livers of chickens. The present experiment was conducted to determine the effect of dietary chitosan on liver lipid concentrations in broiler chickens fed on PTU containing diets. Male broiler chickens at 14d old were fed on the basal diet based on corn and soybean meal or a PTU containing (0.03%) diets supplemented with or without 5% chitosan for 2 weeks. Administration of PTU increased (P