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ABSTRACT Aim Nocturia impairs the quality of life in patients with type 2 diabetes mellitus. Although sodium glucose co‐transporter 2 inhibitors (SGLT2i) such as tofogliflozin increase urine volume, their impact on nocturia, in conjunction with dietary salt restriction, is less clear. Materials and Methods This multicenter, open‐label, randomized, parallel‐group trial included 80 subjects with type 2 diabetes and nocturia. The patients were divided into two groups: one receiving tofogliflozin, the shortest half‐life, without salt restriction, and the other receiving both tofogliflozin and dietary salt restriction. The primary endpoint was nocturia frequency at 12 weeks. The secondary outcomes included changes in daytime urination frequency, urine volume, and home blood pressure. Results At 12 weeks, there were no significant differences in nocturia changes between both groups. Nocturia frequency did not change in the tofogliflozin without salt restriction group from 1.5 ± 0.8 to 1.3 ± 1.1 times per night (P = 0.297), and significantly decreased from 1.6 ± 1.0 to 1.3 ± 0.7 times per night in the tofogliflozin and dietary salt restriction group (P = 0.049). There was a trend toward increased urine volume and frequency during the daytime in the group with salt restriction, indicating a time‐shift effect of the short half‐life tofogliflozin and salt restriction on urinary time. Conclusions The frequency of nocturia after tofogliflozin did not increase. Tofogliflozin reduced nocturia when combined with salt restriction. Furthermore, daytime urine volume and frequency showed an increasing trend, suggesting a shift in urine production to daytime hours due to the short half‐life of tofogliflozin. Dietary modifications can enhance the therapeutic benefits of tofogliflozin in managing nocturia in people with type 2 diabetes.

IntroductionEcological underpinnings of the invasion success of exotic plants may be found in their interactions with microbes, either through the enemy release hypothesis and the enhanced mutualism hypothesis. Whereas recent high-throughput sequencing techniques have significantly expanded our understanding of plant-associated microbiomes and their functional guilds, few studies to date have used these techniques to compare the microbiome associated with invasive plants between their native and exotic ranges.MethodsWe extracted fungal and bacterial DNA within leaf endosphere, root endosphere and soil of an invasive plant, Ardisia crenata, sampled from their native range Japan and exotic range Florida, USA. Using Illumina sequencing data, we compared microbial community compositions and diversity between the native and exotic ranges, and tested whether abundance of pathogenic or mutualistic microbes differ between the native or exotic ranges in accordance to the enemy release hypothesis or the enhanced mutualism hypothesis.ResultsFungal and bacterial community compositions differed among leaves, roots and soil, and between the native and exotic ranges. Despite a higher microbial diversity in the soil in the exotic range than in the native range, the microbial diversity within leaf and root was lower in the exotic range compared to the native range. In addition, leaves in the native range harbored a greater number of plant pathogenic fungi compared to those in the exotic range.DiscussionThese patterns suggest plant controls over what microbes become associated with leaves and roots. The higher abundance of leaf pathogenic fungi, including the pathogen which is known to cause specific disease in A. crenata in the exotic range than in the native range, support the enemy release hypothesis and highlighted potential importance of examining microbial communities both above- and below-ground.

Nocturia is a common disease in patients with type 2 diabetes mellitus that can reduce the quality of life. Sodium glucose co-transporter 2 (SGLT2) inhibitors increase the urine volume and are often discontinued when polyuria occurs, although tofogliflozin, which has a short half-life in the blood, may improve nocturia by managing hyperglycemia and hypertension, without aggravating nocturia. As excessive sodium intake worsens nocturia and increases urine volume, sodium restriction is also effective in managing nocturia. This multicenter, open-label, randomized parallel-group trial will examine 80 patients with type 2 diabetes who experienced nocturia. After the baseline examination, the patients are randomly stratified into two groups and receive tofogliflozin treatment with or without sodium restriction for 12 weeks. The primary outcome is nocturia frequency at 12 weeks. The secondary outcomes are the frequency of daytime urine, changes in urine volume, and changes in home blood pressure.

Abstract Background Borderline resectable pancreatic cancer (BRPC) is a category of pancreatic cancer that is anatomically widely spread, and curative resection is uncommon with upfront surgery. Intensity-modulated radiation therapy (IMRT) is a form of radiation therapy that delivers precise radiation to a tumor while minimizing the dose to surrounding normal tissues. Here, we conducted a phase 2 study to estimate the curability and efficacy of neoadjuvant chemoradiotherapy using IMRT (NACIMRT) for patients with BRPC with arterial abutment (BRPC-A). Methods A total of 49 BRPC-A patients were enrolled in this study and were treated at our hospital according to the study protocol between June 2013 and March 2021. The primary endpoint was microscopically margin-negative resection (R0) rates and we subsequently analyzed safety, histological effect of the treatment as well as survivals among patients with NACIMRT. Results Twenty-nine patients (59.2%) received pancreatectomy after NACIMRT. The R0 rate in resection patients was 93.1% and that in the whole cohort was 55.1%. No mortality was encountered. Local therapeutic effects as assessed by Evans classification showed good therapeutic effect (Grade 1, 3.4%; Grade 2a, 31.0%; Grade 2b, 48.3%; Grade 3, 3.4%; Grade 4, 3.4%). Median disease-free survival was 15.5 months. Median overall survival in the whole cohort was 35.1 months. The only independent prognostic pre-NACIMRT factor identified was serum carbohydrate antigen 19–9 (CA19-9) > 400 U/ml before NACIMRT. Conclusions NACIMRT showed preferable outcome without significant operative morbidity for BRPC-A patients. NACIMRT contributes to good local tumor control, but a high initial serum CA19-9 implies poor prognosis even after neoadjuvant treatment. Trial Registration UMIN-CTR Clinical Trial: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000011776 Registration number: UMIN000010113. Date of first registration: 01/03/2013,

Abstract We aimed to investigate if estimated hemoglobin A1c (eHbA1c) levels determined using a flash continuous glucose monitoring system could be an indicator of glycemic control status in hemodialysis patients with diabetes. Hemodialysis patients with type 2 diabetes were recruited. eHbA1c levels were measured using the FreeStyle Libre Flash Glucose Monitoring System®. A total of 18 hemodialysis patients with diabetes were included in the study. The eHbA1cGA – calculated based on glycated albumin level, and body mass index and serum hemoglobin concentration were also included in the formula – was higher than the eHbA1c in most patients. Furthermore, the eHbA1cGA – eHbA1c values were >2% in all patients with body mass index

Abstract Aims/Introduction The maximum value of home systolic blood pressure is correlated with damage to target organs, including diabetic nephropathy. However, the precise relationship between the development of diabetic nephropathy and maximum home systolic blood pressure has not been elucidated. Materials and Methods In this prospective 2‐year cohort subanalysis of the KAMOGAWA‐HBP study, the patient population was 477 Japanese patients with normoalbuminuria. We investigated the effects of mean and maximum home blood pressure on the development of diabetic nephropathy, which we defined as a urinary albumin excretion value ≥30 mg/g creatinine. Among the 477 patients, 67 developed diabetic nephropathy. Results In our multivariate logistic regression analyses, the maximum morning home systolic blood pressure was significantly positively associated with the development of diabetic nephropathy after adjusting for patient sex and age, smoking status, the diabetes mellitus duration, body mass index, creatinine, total cholesterol, hemoglobin A1c, and antihypertensive medication use (odds ratio 1.21, 95% confidence interval 1.03–1.42, P = 0.021). Conclusions Maximum home blood pressure can be identified at a glance, and its measurement would thus be helpful to healthcare providers who treat patients with diabetes and normoalbuminuria.

Introduction Trigger finger is one of the complications affecting the upper extremity in patients with diabetes. Diabetes is also a well-known risk factor that predisposes individuals to cardiovascular diseases (CVDs). This retrospective cohort study aimed to establish the association between trigger finger and the patients with incident CVD with type 2 diabetes.Materials and methods Trigger finger was diagnosed by palpating a thickened tendon during flexion or on the manifestation of a locking phenomenon during extension or flexion of either finger. The relationship between trigger finger and other clinical parameters or complications of diabetes was examined by a comparative analysis. Cox regression analysis was used to evaluate the association between trigger finger and incidence of CVD. We calculated the propensity scores using sex, body mass index, age, smoking status, duration of diabetes, estimated glomerular filtration rate, hypertension, dyslipidemia, and hemoglobin A1c as the number of patients with incident CVD during the follow-up period was low.Results Among the 399 patients with type 2 diabetes, 54 patients had trigger finger. Patients with trigger finger were significantly older in age and had been suffering from diabetes for a longer duration. They also displayed worse renal function and glycemic control, along with a higher incidence of hypertension, neuropathy and nephropathy. During the average 5.66±1.12 years of follow-up, a total of 18 incidents occurred. According to the Cox regression analysis, trigger finger was shown to be associated with enhanced risk of the incidence of CVD after adjustment for the covariates (adjusted HR=3.33 (95% CI 1.25 to 8.66), p=0.017).Conclusions Trigger finger is associated with the risk of incident CVD in patients with type 2 diabetes. Thus, clinicians must consider these factors at the time of diagnosis of such patients.

We report the pulsed laser deposition (PLD) of anatase TiO2, LaAlO3, and La0.7Ca0.3MnO3 epitaxial thin films by a fifth-harmonic Nd:Y3Al5O12 (Nd:YAG) laser. High-quality anatase Ti0.996Nb0.004O2 epitaxial thin films were deposited and showed transparent conducting properties, with a maximum mobility of 94 cm2V−1s−1 at 80 K. These results are consistent with those obtained for films deposited by excimer lasers. Furthermore, we report the deposition of droplet-free flat LaAlO3 and La0.7Ca0.3MnO3 films. The latter films exhibited an insulator-to-metal transition at ∼240 K, accompanied by a large magnetoresistive effect, in agreement with previous studies using excimer lasers. These results indicate that the fifth harmonic of a Nd:YAG laser may be a potential alternative to excimer lasers for PLD.

Anemia, which might contribute to pathogenesis of kidney dysfunction, is a common finding in patients with type 2 diabetes. The aim of this study was to investigate if hemoglobin concentration is associated with the degree of change in urinary albumin-creatinine ratio or the development of albuminuria in patients with type 2 diabetes.We measured hemoglobin concentration in 470 (296 men and 174 women) consecutive type 2 diabetic patients without albuminuria. We performed a follow-up study to assess the progression or development of albuminuria, the interval of which was 3.0 years. Then we evaluated relationships between hemoglobin concentration and albuminuria, using multivariate linear regression analyses and logistic regression analyses.Eighty four patients developed albuminuria during follow-up duration. In multivariate analyses, hemoglobin concentration was negatively associated with a change in urinary albumin-creatinine ratio in men (ß = -0.259, P = 0.0002) and women (ß = -0.194, P = 0.030). Moreover, multivariate adjusted odds ratio associated with 1 g/L in hemoglobin for the development of albuminuria was 0.93 (95% confidence interval; 0.89-0.96) in men and 0.94 (95% confidence interval; 0.88-0.99) in women, respectively. And, multivariate analyses revealed that adjusted odds ratios for the development of albuminuria were 4.78 (95% confidence interval; 1.65-13.91) in men and 4.62 (95% confidence interval; 1.34-16.68) in women with anemia (hemoglobin < 130 g/L for men and < 120 g/L for women), which were higher than those without anemia.Low hemoglobin concentration could be a predictor for the progression and development of albuminuria in patients with type 2 diabetes.

BACKGROUND/AIMS: The senescence marker protein-30 (SMP30) is a 34 kDa protein originally identified in rat liver that shows decreased levels with age. Several functional studies using SMP30 knockout (Smp30(Y/-) ) mice established that SMP30 functions as an antioxidant and protects against apoptosis. To address the potential role of SMP30 in nonalcoholic fatty liver disease (NAFLD) pathogenesis, we established Smp30(Y/-) mice on a Lepr(db/db) background (Lepr(db/db)Smp30(Y/-) mice). RESEARCH DESIGN/PRINCIPAL FINDINGS: Male Lepr(db/db)Smp30(Y/-) mice were fed a standard diet (340 kcal/100 g, fat 5.6%) for 16 weeks whereupon the lipid/lipoprotein profiles, hepatic expression of genes related to lipid metabolism and endoplasmic reticulum stress markers were analyzed by HPLC, quantitative RT-PCR and western blotting, respectively. Changes in the liver at a histological level were also investigated. The amount of SMP30 mRNA and protein in livers was decreased in Lepr(db/db)Smp30(Y/+) mice compared with Lepr(db/+)Smp30(Y/+) mice. Compared with Lepr(db/db)Smp30(Y/+) mice, 24 week old Lepr(db/db)Smp30(Y/-) mice showed: i) increased small dense LDL-cho and decreased HDL-cho levels; ii) fatty liver accompanied by numerous inflammatory cells and increased oxidative stress; iii) decreased mRNA expression of genes involved in fatty acid oxidation (PPARα) and lipoprotein uptake (LDLR and VLDLR) but increased CD36 levels; and iv) increased endoplasmic reticulum stress. CONCLUSION: Our data strongly suggest that SMP30 is closely associated with NAFLD pathogenesis, and might be a possible therapeutic target for NAFLD.