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The rare decay K_{L}→π^{0}νν[over ¯] was studied with the dataset taken at the J-PARC KOTO experiment in 2016, 2017, and 2018. With a single event sensitivity of (7.20±0.05_{stat}±0.66_{syst})×10^{-10}, three candidate events were observed in the signal region. After unveiling them, contaminations from K^{±} and scattered K_{L} decays were studied, and the total number of background events was estimated to be 1.22±0.26. We conclude that the number of observed events is statistically consistent with the background expectation. For this dataset, we set an upper limit of 4.9×10^{-9} on the branching fraction of K_{L}→π^{0}νν[over ¯] at the 90% confidence level.

As advanced synthetic technology has enabled drug candidate development with complex structure, resulting in low solubility and membrane permeability, the strategies to improve poorly absorbed drug bioavailability have attracted the attention of pharmaceutical companies. It has been demonstrated that nitric oxide (NO), a vital signaling molecule that plays an important role in various physiological systems, affects intestinal drug absorption. However, NO and its oxidants are directly toxic to the gastrointestinal tract, thereby limiting their potential clinical application as absorption enhancers. In this study, we show that sodium nitroprusside (SNP), an FDA-approved vasodilator, enhances the intestinal absorption of lipophilic drugs in the proximal parts of the small intestine in rats. The SNP pretreatment of the rat gastrointestinal sacs significantly increased griseofulvin and flurbiprofen permeation in the duodenum and jejunum but not in the ileum and colon. These SNP-related enhancement effects were attenuated by the co-pretreatment with dithiothreitol or c-PTIO, an NO scavenger. The permeation-enhancing effects were not observed in the case of antipyrine, theophylline, and propranolol in the duodenum and jejunum. Furthermore, the SNP treatment significantly increased acidic glycoprotein release from the mucosal layers specifically in the duodenum and jejunum but not in the ileum and colon. These results suggest that SNP increases lipophilic drug membrane permeability specifically in the proximal region of the small intestine through disruption of the mucosal layer.

Objective: To investigate the association between aortic stiffness and incident albuminuria and the decline in estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes.Research Design and Methods: We investigated 461 Japanese type 2 diabetic patients, comprising 199 women and 262 men, with a mean age of 59 ± 11 years. Patients were divided into two groups according to the median value of carotid-femoral pulse wave velocity (cf-PWV), which was used to evaluate aortic stiffness. The end point was defined as the transition from normo- to microalbuminuria or micro- to macroalbuminuria. The Cox proportional hazard model was used to calculate the hazard ratio (HR) and 95% CI. The correlation between cf-PWV and rate of change in eGFR was also determined by linear regression analysis.Results: The baseline mean (± SD) cf-PWV was 9.6 ± 2.4 m/s. During a median follow-up period of 5.9 years (range 0.3-8.6), progression of albuminuria was observed in 85 patients. The 5-year cumulative incidence of the end point in patients with cf-PWV below and above the median was 8.5 and 19.4%, respectively (P = 0.002, log-rank test). cf-PWV was significantly associated with incident albuminuria (HR 1.23, 95% CI 1.13-1.33, P < 0.001) by multivariate Cox regression analysis. A significant association between cf-PWV and annual change in eGFR was also suggested by multiple linear regression analysis (standardized estimate -0.095, P = 0.031).Conclusions: Aortic stiffness is associated with incident albuminuria and the rate of decline in glomerular filtration rate in type 2 diabetic patients. [ABSTRACT FROM AUTHOR]

Abstract: The interfacial resistance between the composite electrode and PEO-based solid polymer electrolyte was examined using two different symmetrical cells and AC impedance measurements in the temperature range of 30–60°C. Of the four major resistance components identified in our previous study, three components due to the resistances of the polymer electrolyte and the charge transfer resistance between LiFePO4-C and the electrolyte were assigned; however, one resistance component, in the medium frequency range has not yet been assigned. In this report, the medium frequency range resistance component was investigated using a symmetrical cell with composite electrodes composed of active and inactive materials (LiCoO2, LiMn2O4 and SiO2), solid polymer electrolyte, and carbon fiber as an electron conductor. The resistance was not affected by the carbon coating in LiFePO4-C and the conductive carbon additive (VGCF). An electron blocking cell was also prepared and the resistance was measured in the temperature range of 30–60°C to confirm the effect of the electrode thickness and the electrode composition. The resistance was not affected by the thickness, and decreased with decreasing PEO-LiTFSI electrolyte content in the composite electrode. However, no significant change in the activation energy was evident with the change in the electrode composition. [Copyright &y& Elsevier]

Abstract: The interface resistance between Li x FePO4 and poly(ethylene oxide) (PEO)–Li(CF3SO2)2N (LiTFSI) was examined by AC impedance measurement of a Li x FePO4/PEO–LiTFSI/Li x FePO4 cell in the temperature range of 30–60°C. Four types of resistance, R0, R1, R2 and R3 were proposed according to analysis of the cell impedance using an equivalent circuit. The sum of R0 and R1 in the high frequency range is consistent with the resistance of the PEO electrolyte. R2 in the middle frequency range is related to lithium ion transport to an active point for charge transfer inside the composite electrode, and R3 in the low frequency range is considered to be the charge transfer resistance. The activation energy for R2 was affected by the thickness and composition of the electrode, whereas that for R3 was not. [Copyright &y& Elsevier]

Abstract: LiFePO4/carbon composite electrode was prepared and applied to the dry polymer electrolyte. Enhanced low-temperature performance of LiFePO4 was achieved by modifying the interface between LiFePO4 and polymer electrolyte. The molecular weight of the polymer and the salt concentration as the Li/O ratio were optimized at 3×105 and 1/10, respectively. Impedance analysis revealed that a small resistive component occurred in the frequency range of the charge transfer process. The reversible capacity of the laminate cell was 140mAhg−1 (C/20) and 110mAhg−1 (C/2) at 40°C, which is comparable to the performance in the liquid electrolyte system. [Copyright &y& Elsevier]

Objective: To clarify the association of serum leptin levels with progression of diabetic kidney disease in patients with type 2 diabetes (T2D).Research Design and Methods: This was an observational cohort study of 668 patients with T2D. Patients were classified into three groups by sex-specific tertile of leptin levels. Outcome measurements were the rate of change in estimated glomerular filtration rate (eGFR) and progression to a more advanced stage of albuminuria.Results: Patients with low or high leptin levels had a steeper eGFR decline (-2.07 and -2.14 mL/min/1.73 m(2)/year) than those with midrange leptin levels (-0.82 mL/min/1.73 m(2)/year; P < 0.01), whereas patients with low leptin levels had an elevated risk of progression of albuminuria as compared with those with high leptin levels (hazard ratio 3.125 [95% CI 1.302-7.499]).Conclusions: Both low and high serum leptin levels were risk factors for kidney function decline. Meanwhile, lower serum leptin levels were associated with progression of albuminuria. [ABSTRACT FROM AUTHOR]

C16H21IN4, monoclinic, P21/n (no. 14), a = 10.433(1) Å, b = 13.846(1) Å, c = 12.162(1) Å, β = 97.294(2)°, V = 1742.7 Å3, Z = 4, Rgt(F) = 0.0352, wRref(F2) = 0.0935, T = 123 K.

Abstract: In this research an Electro Slag Remelting (ESR) process for metallothermic reduction of molybdenum trioxide by aluminum and silicon is described. The process uses fine MoO3 scrap as a raw material. After melting of nickel electrode, molybdenum is alloyed with nickel by direct reduction of MoO3 added to the slag. A mixture of aluminum and silicon can be used as reductant and the reduction is carried out in situ in the molten slag. Nickel–molybdenum ingots containing up to 33.7-wt% of molybdenum were produced by this process. The results show that Al–50%Si is a suitable compound for reduction of MoO3 and by using proper amount of reductants, flux and charge, high efficiency of reduction will be achieved; as the mean efficiency in these experiments was 92%. [Copyright &y& Elsevier]

Background: To report a case of tuberculum meningioma with recovery of glaucoma-like visual field defects after chiasmal decompression., Case Presentation: A 39-year-old woman presenting with headache was found to have bilateral arcuate retinal nerve fiber layer (RNFL) thinning on optical coherence tomography (OCT) with a corresponding arcuate scotomas consistent with glaucomatous change. However a suprasellar tumor compressing the anterior chiasm from below was found on magnetic resonance imaging of the brain. After resection of the mass, which was diagnosed as meningothelial meningioma by the pathological examination, the glaucoma-like visual field defects resolved despite the RNFL thinning on the OCT showing no improvement., Conclusions: Chiasmal compression may mimic glaucoma and produce arcuate scotoma rather than temporal visual field loss. There is a possibility that the development of chiasmal compression somehow converted preperimetric glaucoma into a more advanced form accompanied by visual field defects and that the glaucoma reverted to the preperimetric state after chiasmal decompression., (© 2024. The Author(s).)

Objective: To elucidate the association of glomerular filtration rate (GFR) at baseline with subsequent progression of albuminuria in individuals with type 2 diabetes., Research Design and Methods: This was a single-center retrospective cohort study of 6,618 Japanese adults with type 2 diabetes and urinary albumin-to-creatinine ratio of <300 mg/g, comprising 2,459 women and 4,159 men with a mean (± SD) age of 60 ± 12 years. The exposure was baseline estimated GFR (eGFR) (mL/min/1.73 m2), treated as a categorical variable and classified into five categories: ≥90, 75-90, 60-75, 45-60, and <45, as well as a continuous variable. The outcome was progression of albuminuria category (i.e., from normoalbuminuria to micro- or macroalbuminuria or from micro- to macroalbuminuria). Hazard ratios (HRs) for the outcome were estimated using the multivariable Cox proportional hazards model. In the analysis treating baseline eGFR as a continuous variable, the multivariable-adjusted restricted cubic spline model was used., Results: During the median follow-up period of 6.3 years, 1,190 individuals reached the outcome. When those with a baseline eGFR of 75-90 mL/min/1.73 m2 were considered the reference group, HRs (95% CIs) for the outcome in those with a baseline eGFR of ≥90, 60-75, 45-60, or <45 mL/min/1.73 m2 were 1.38 (1.14-1.66), 1.34 (1.14-1.58), 1.81 (1.50-2.20), or 2.37 (1.84-3.05), respectively. Furthermore, the inverse J-shaped curve was more clearly shown by the spline model., Conclusions: This study of Japanese adults with type 2 diabetes suggests that both high and low GFRs are implicated in the pathogenesis of albuminuria progression., (© 2022 by the American Diabetes Association.)

Background: Small cell bladder carcinoma (SCBC) is a rare and aggressive malignant tumor with no established treatment guidelines. Its treatment algorithm has been based on the small cell lung cancer (SCLC) guidelines. Metastatic SCBC has poor prognosis (even when treated with platinum-based chemotherapy, which is usually used for extensive-disease SCLC)., Case Presentation: Herein, we report a case of a 71-year-old man with SCBC who underwent radical cystectomy and received adjuvant chemotherapy with gemcitabine and cisplatin. However, recurrent tumors were found 6 months postoperatively. The patient was then treated with carboplatin, etoposide, and atezolizumab and achieved complete response. He continues receiving maintenance therapy with atezolizumab monotherapy without any evidence of recurrence over the 12 months follow up., Conclusion: To our knowledge, this is the first case of metastatic SCBC where carboplatin, etoposide, and atezolizumab achieved long-term complete response., (© 2022. The Author(s).)

This study aimed to develop a diagnostic software system to evaluate the enlarged extraocular muscles (EEM) in patients with Graves' ophthalmopathy (GO) by a deep neural network.This prospective observational study involved 371 participants (199 EEM patients with GO and 172 controls with normal extraocular muscles) whose extraocular muscles were examined with orbital coronal computed tomography. When at least one rectus muscle (right or left superior, inferior, medial, or lateral) in the patients was 4.0 mm or larger, it was classified as an EEM patient with GO. We used 222 images of the data from patients as the training data, 74 images as the validation test data, and 75 images as the test data to "train" the deep neural network to judge the thickness of the extraocular muscles on computed tomography. We then validated the performance of the network. In the test data, the area under the curve was 0.946 (95% confidence interval (CI) 0.894-0.998), and receiver operating characteristic analysis demonstrated 92.5% (95% CI 0.796-0.984) sensitivity and 88.6% (95% CI 0.733-0.968) specificity. The results suggest that the deep learning system with the deep neural network can detect EEM in patients with GO., (© 2022. The Author(s).)

Background: It is important to identify additional prognostic factors for diabetic kidney disease. Materials & methods: Baseline levels of ten cytokines (APRIL/TNFSF13, BAFF/TNFSF13B, chitinase 3-like 1, LIGHT/TNFSF14, TWEAK/TNFSF12, gp130/sIL-6Rβ, sCD163, sIL-6Rα, sTNF-R1, sTNF-R2) were measured in two cohorts of diabetic patients. In one cohort (n = 777), 156 individuals were randomly sampled after stratification and their plasma samples were analyzed; in the other cohort (n = 69), serum samples were analyzed in all the individuals. The levels of cytokines between rapid (estimated glomerular filtration rate decline >5 ml/min/1.73 m 2 /year) and non-rapid decliners were compared. Results: Multivariate analysis demonstrated significantly high levels of LIGHT/TNFSF14, TWEAK/TNFSF12 and sTNF-R2 in rapid decliners. Conclusion: These three cytokines can be potential biomarkers for the progression of diabetic kidney disease.

Laboratory animal medicine (LAM) is a corner stone of animal-based research and has been a veterinary specialty for over 60 y. Today 5 Colleges of LAM (American, European, Japanese, Korean, and Indian) that certify specialists (Diplomates) in LAM are members of the International Association of Colleges of LAM (IACLAM). Goals of IACLAM are to support the development of new Colleges of LAM, to harmonize expectations for the knowledge and skills of newly certified LAM Diplomate, and to harmonize the standards (best practices) for training and examination of candidates among the member Colleges. IACLAM recently conducted an in-depth review and comparison of oversight, training, credentialing, and examination standards in the 5 Colleges as part of an initiative to create a framework for harmonization and consistency for these activities across the 5 Colleges. The process has led to an agreement on recommendations for knowledge and skill requirements for a newly certified Diplomate, as described by each College in a detailed role delineation document (RDD). The RDD is based on task analyses of the work responsibilities of laboratory animal veterinary Diplomates. This agreement is an important step toward the goal of global harmonization of LAM Diplomate training. Further efforts are planned for areas such as training, research, publication, and examination. This paper describes the role and content of the RDD and lists the differences and similarities among the RDDs of 5 Colleges of LAM.

Aim/hypothesis: It remains unclear whether people with diabetes exhibiting non-albuminuric kidney insufficiency have higher risk of kidney function decline and mortality compared with those exhibiting preserved kidney function without albuminuria. Furthermore, information regarding the incidence of albuminuria in people with this unique phenotype is sparse. Here, we aimed to elucidate the risk of the kidney outcomes and all-cause mortality in people with diabetes exhibiting non-albuminuric kidney insufficiency., Methods: In this retrospective cohort study, 8320 Japanese adults with type 2 diabetes were classified into four groups based on the presence of albuminuria and kidney insufficiency at baseline, defined as urinary albumin/creatinine ratio of equal to or above 30 mg/g and eGFR of less than 60 ml min -1 1.73 m -2 , respectively. The primary composite kidney endpoint was a 50% decrease in eGFR from baseline or the initiation of kidney replacement therapy. The annual percentage change in eGFR slope and progression of albuminuria category were evaluated as the secondary and tertiary kidney endpoints, respectively. All-cause death was also set as the endpoint., Results: Compared with people exhibiting non-albuminuric preserved kidney function, those with non-albuminuric kidney insufficiency had the higher risk for the primary kidney endpoint (HR 4.1; 95% CI 2.5, 6.7; p < 0.001), steep percentage change in eGFR slope (-1.96%/year vs -1.36%/year, p < 0.001), incidence of albuminuria (HR 2.1; 1.7, 2.6; p < 0.001) and all-cause mortality (HR 1.5; 1.2, 2.0; p = 0.003). In the sensitivity analyses treating the incidence of albuminuria as a competing risk, people with non-albuminuric kidney insufficiency still had higher risk for the primary kidney endpoint and all-cause mortality than those with non-albuminuric preserved kidney function (subdistribution HR 2.8; 1.4, 5.6; p = 0.004; and 1.6; 1.1, 2.2; p = 0.014, respectively)., Conclusions/interpretation: People with type 2 diabetes exhibiting non-albuminuric kidney insufficiency had poorer kidney outcomes and life prognosis than those exhibiting non-albuminuric preserved kidney function., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Chronic kidney disease (CKD) is a well-known risk factor for postoperative complications in several surgical fields. However, although prevalent among diabetic candidates for vitrectomy, the effect of CKD on vitrectomy outcomes remains unclear. This study aimed at clarifying the relationship between CKD and the occurrence of vitrectomy-related complications in patients with proliferative diabetic retinopathy (PDR). The 6-month incidences of vitreous hemorrhage (VH) and neovascular glaucoma (NVG) following vitrectomy for PDR were compared among the following groups: stages 1-2 CKD (60 patients), stages 3-5 CKD (70 patients not on hemodialysis), and hemodialysis (HD; 30 patients). We also determined whether the deterioration of the estimated glomerular filtration rate (eGFR) was associated with post-vitrectomy events. The incidence of VH was significantly higher in the stages 3-5 CKD group (43%) than in the stages 1-2 CKD (10%) and HD (10%) groups. NVG was more common in the stages 3-5 CKD group (17%) than in the stages 1-2 CKD (2%) and HD (0%) groups. The reduced estimated glomerular filtration rate (eGFR) was the only significant variable associated with post-vitrectomy VH and NVG. Patients with PDR and CKD, particularly those with lower eGFR, might be at risk for post-vitrectomy VH and NVG.

Aims/introduction: For diabetes patients undergoing hemodialysis, vitreous hemorrhage seems to be a hemodialysis-induced hemorrhagic complication because of the effect of systemic anticoagulation. However, it is unclear whether hemodialysis is associated with vitreous hemorrhage in diabetes patients. We therefore carried out this cohort study to clarify the relationship between hemodialysis and vitreous hemorrhage in diabetes patients with proliferative diabetic retinopathy., Materials and Methods: This was a single-center, retrospective, cohort study. We compared the incidence of vitreous hemorrhage in non-vitrectomized proliferative diabetic retinopathy eyes between the hemodialysis group (145 eyes) and peritoneal dialysis group (36 eyes), which does not require the use of systemic anticoagulation (parallel-group study), and in hemodialysis patients in the 12-month period before and after the start of hemodialysis (before-after study). We also determined the risk factors for vitreous hemorrhage after the start of hemodialysis based on the patients' systemic and ophthalmic characteristics., Results: There was no significant difference in the first-year incidence of vitreous hemorrhage between the hemodialysis (23.4%) and peritoneal dialysis groups (22.2%, P = 1.000). The incidence of vitreous hemorrhage in the dialysis period (23.4%) was significantly lower than that in the predialysis period (35.2%, P = 0.008). Only application of panretinal photocoagulation within the 6 months immediately before hemodialysis was significantly associated with the incidence of vitreous hemorrhage after the start of hemodialysis (P < 0.001)., Conclusions: Hemodialysis therapy does not seem to be associated with a higher risk of vitreous hemorrhage in diabetes patients with proliferative diabetic retinopathy., (© 2019 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)