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Purpose To elucidate biological changes in Hunner lesions, which underlie the pathophysiology of Hunner-type interstitial cystitis, by characterizing their whole transcriptome and immunopathological profiles. Materials and methods Paired bladder mucosal biopsies, one sample each from the Hunner lesion and non-lesion area, were obtained from 25 patients with Hunner-type interstitial cystitis. The samples were subjected to whole-transcriptome profiling; immunohistochemical quantification of CD3, CD4, CD8, CD20, CD138, mast cell tryptase, cytokeratin, and HIF1α; and quantitative polymerase chain reaction for IFN-α, IFN-β, IFN-γ, TNF, TGF-β1, HIF1α, IL-2, IL-4, IL-6, IL-10, and IL-12A. The results were compared between the lesion and non-lesion areas. Results RNA sequencing identified 109 differentially expressed genes and 30 significantly enriched biological pathways in Hunner lesions. Up-regulated pathways (N=24) included "HIF1α signaling pathway", "PI3K-Akt signaling pathway", "RAS signaling pathway", and "MAPK signaling pathway." By contrast, down-regulated pathways (N=6) included "basal cell carcinoma" and "protein digestion and absorption". The mRNA levels of HIF1α, IFN-γ, and IL-2 and the HIF1α protein level were significantly higher in lesion areas. Otherwise, there were no significant differences between the lesion and non-lesion samples in terms of mRNA levels of inflammatory cytokines or histological features such as lymphoplasmacytic and mast cell infiltration, epithelial denudation, and CD4/CD8 T-lymphocyte ratio. Conclusions Our findings demonstrate significant overexpression of HIF1α and up-regulation of its related biological pathways in Hunner lesions. The results indicate that ischemia, in conjunction with inflammation, plays a pathophysiological role in this subtype of interstitial cystitis/bladder pain syndrome, particularly in Hunner lesions.

The incidence of acute cholecystitis has a seasonal peak in summer. However, the reason for such seasonality remains unclear. This retrospective cohort study was performed to examine the association between ambient temperature and acute cholecystitis.We identified admissions for acute cholecystitis from January 2011 to December 2017 from a nationwide inpatient database in Japan. We performed a Poisson regression analysis to investigate the association between ambient temperature and admission for acute cholecystitis with adjustment for relative humidity, national holidays, day of the week, and year. We accounted for clustering of the outcome within prefectures using a generalized estimating equation.We analyzed 601 665 admissions for acute cholecystitis. With an ambient temperature of 5.0 °C-9.9 °C as a reference, Poisson regression showed that the number of admissions increased significantly with increasing temperature (highest above 30 °C; relative risk, 1.35; 95% confidence interval, 1.34-1.37). An ambient temperature of5.0 °C was also associated with higher admission for acute cholecystitis than an ambient temperature of 5.0 °C-9.9 °C (relative risk, 1.23; 95% confidence interval, 1.21-1.25).The present nationwide Japanese inpatient database study showed that high temperature (≥10.0 °C) and low temperature (5.0 °C) were associated with increased admission for acute cholecystitis.

Background In Japan, six types of sodium–glucose cotransporter inhibitors (SGLT2Is) are currently in use. Here, we evaluated differences in renal composite outcomes between SGLT2Is with or without evidence of cardio vascular outcome trials (CVOTs). Methods We retrospectively surveyed 536 Japanese patients with type 2 diabetes mellitus with chronic kidney disease who received SGLT2Is for more than 1 year. Patients were classified as having received empagliflozin, canagliflozin, or dapagliflozin (n = 270, Evidence (+) group) or as having received ipragliflozin, tofogliflozin, or luseogliflozin (n = 266, Evidence (−) group). The propensity score matching method was performed. Result On matched cohort model including 205 cases in each group, there were no significant differences in the incidence of renal composite outcomes (n = 28 [14%] in the Evidence (+) group, n = 21 [10%] in the Evidence (−) group for the matched model; p = 0.29) between groups. Cox hazard analyses in the matched cohort model showed that the risk ratio for renal composite outcomes in the Evidence (−) group was 0.73 (95% confidence interval: 0.40–1.32), which was greater than the noninferiority margin of 1.22. Conclusion Three SGLT2Is with no CVOT’s evidence did not show noninferiority compared with other SGLT2Is with evidences.

[Purpose] Understanding the neuromuscular cooperativeness functions when an athlete is fatigued is essential in preventing sports injuries and examining post-injury return standards. This study aimed to investigate the kinds of changes in neuromuscular cooperativeness before and after fatigue loading. [Participants and Methods] Fifteen female university athletes were examined for chronological changes in neuromuscular cooperativeness. Muscle fatigue loading was performed using BIODEX (180°/s) during knee flexion and extension exercises on one side. Surface electromyography of the rectus femoris and biceps femoris was performed on both sides before and immediately, 5 min, 10 min, and 15 min after loading. The switching silent period and pre-motor time were calculated from the electromyographic waveforms to indicate neuromuscular cooperativeness. [Results] The switching silent periods in the loading side immediately and 5 min after loading were significantly prolonged compared with that before loading. [Conclusion] Muscle fatigue loading instantaneously prolonged the switching silent period and decreased the neuromuscular cooperativeness. Furthermore, recovery generally occurred within 10 minutes after loading.

OBJECTIVE: The aim was to compare short-term and long-term reproducibilities of in-office unattended blood pressure (BP), namely automated office blood pressure (AOBP), conventionally measured attended office BP, and self-measured home BP. METHODS: A multicentre, clinical study was conducted in Japan, and 287 Japanese outpatients on antihypertensive drug medication were followed-up for 1 year. RESULTS: The intensity of drug treatment was sustained consistently throughout the study period (defined daily doses, 1.62-1.68; P = 0.12). The mean SBP differences between baseline and 1 month later, as well as baseline and 1 year later, were less than 1.5 mmHg, whereas the standard deviations of the differences for home, AOBP, and attended office measurements for the 1-year interval were 7.7, 14.5, and 15.3 mmHg, respectively. The coefficients of variation were significantly smaller for home BP than for AOBP among all patients at both 1-month and 1-year intervals (P

Background: Crookes tube is utilized in junior high and high schools in Japan to study the character of electrons and current, and not for radiological education. There is no official guideline or regulation for these radiation source to the public. Therefore, most teachers have no information about the leakage of X-rays from Crookes tube. The peak energy of X-rays is approximately 20 keV, and it is impossible to measure using conventional survey meters.Materials and Methods: Each leakage dose of low energy X-rays from 38 Crookes tube in the education field, such as junior and senior high schools in Japan, was explored by the teachers in the school using radio-photoluminescence (RPL) dosimeters. Before and after the measurements, the dosimeters were sent by postal mails.Results and Discussion: At the exploration in this study, it was estimated that the 70 μm dose equivalent, Hp(0.07) of X-rays from 31 Crookes tubes were smaller than 100 μSv in 10 minutes, at the distance of 1 m, where the Crookes tube was usually observed. However, the highest dose was estimated as 0.69 mSv by an equipment with the full power. Furthermore, one Crookes tube exhibited 0.62 mSv with minimum output power of the induction coil. This relatively large dose was reduced by the shorter distance of discharge electrodes of the induction coil.Conclusion: The leakage dose of low energy X-rays from 38 Crookes tube was explored using RPL dosimeters. It was estimated that the Hp(0.07) of X-rays from 31 Crookes tubes were smaller than 100 μSv in 10 minutes at the distance of 1 m, while some equipment radiated a higher dose. With this study, the provisional guideline for the safety operation of Crookes tube is established.

Background Fibroblast growth factor (FGF)‐23 is increased first in the sequence of changes associated with chronic kidney disease (CKD)‐mineral and bone disorder. Thus, its measurement may serve as a predictive indicator of incident hyperphosphatemia. Objectives To investigate whether serum FGF‐23 concentration in normophosphatemic dogs with CKD is associated with the risk of the subsequent development of hyperphosphatemia and CKD progression. Animals Forty‐two normophosphatemic dogs with CKD. Methods Blood samples and medical records were retrospectively investigated. Hyperphosphatemia was defined as a serum phosphorous concentration >5.0 mg/dL. Progression was defined as a >1.5‐fold increase in serum creatinine concentration. The time periods and hazard ratios for these outcomes were assessed using Kaplan‐Meier analysis, log‐rank test, and univariate Cox regression analysis. The variables associated with the outcomes in the univariate analysis were included in the multivariate Cox regression model with backward selection. Results Serum FGF‐23 concentration >528 pg/mL was associated with a shorter time to development of hyperphosphatemia (P

Objective Although prophylactic clip closure after endoscopic mucosal resection may prevent delayed bleeding, information regarding colorectal endoscopic submucosal dissection (CR-ESD) is lacking. Therefore, this study evaluated the effect of prophylactic clip closure on delayed bleeding rate after CR-ESD. Materials and methods A total of 614 CR-ESD procedures performed in 561 patients were retrospectively reviewed. The primary outcome, which was delayed bleeding rate, was analyzed between the prophylactic clip closure and non-closure groups. Furthermore, the predictors of delayed bleeding were also evaluated. Results The patients were divided into the clip closure group (n = 275) and non-closure group (n = 339). Delayed bleeding rate was significantly lower in the closure group than in non-closure group (6 cases [2.2%] vs. 20 cases [5.9%], p = .026). The univariate logistic regression analyses revealed that delayed bleeding was significantly associated with laterally spreading tumor-granular-nodular mixed type (LST-G-Mix; odds ratio [OR], 3.77; 95% confidence interval [CI], 1.70-8.34; p = .001). By contrast, prophylactic clip closure was significantly associated with low delayed bleeding rate (OR, 0.36; 95%CI, 0.14-0.90; p = .029). The multivariate logistic regression analyses revealed LST-G-Mix as a significant independent delayed bleeding predictor (OR, 3.25; 95%CI, 1.45-7.32; p = .004), whereas, prophylactic clip closure was identified as a significant independent preventive factor of delayed bleeding (OR, 0.39; 95%CI, 0.15-1.00; p = .049). Conclusions Prophylactic clip closure after CR-ESD is associated with low delayed bleeding rate. LST-G-Mix promotes delayed bleeding, and performing prophylactic clip closure may be advisable.

We herein report the case of a 54-year-old Japanese man with hepatitis C virus (HCV)-related membranoproliferative glomerulonephritis (MPGN), which developed at the time of relapse of immune thrombocytopenic purpura (ITP) after rituximab therapy. Antiviral therapy for HCV led to the improvement of both MPGN and ITP. Rituximab therapy may have contributed to the exacerbation of HCV infection and induced the development of HCV-related MPGN and the relapse of ITP. Our case suggested that HCV treatment should be prioritized over rituximab therapy for HCV-positive patients with ITP and that antiviral therapy for HCV may be effective for treating ITP itself.

Aims/Introduction Large‐scale clinical trials have reported that, in patients with type 2 diabetes mellitus, sodium–glucose cotransporter 2 (SGLT2) inhibitor treatment affords favorable renal outcomes; the underlying mechanisms, however, remain unclear. Thus, this study investigated how SGLT2 inhibitor‐induced changes in the mean arterial pressure (MAP; denoted as ΔMAP) are associated with renal outcomes in type 2 diabetes mellitus patients with chronic kidney disease (CKD). Materials and Methods We retrospectively assessed the data of 624 Japanese type 2 diabetes mellitus patients with CKD who had been using SGLT2 inhibitors for >1 year. For propensity score matching (1:1 nearest neighbor match, with caliper value = 0.053, no replacement), patients were categorized into two groups based on the ΔMAP (>−4 mmHg [n = 329] and ≤−4.0 mmHg [n = 295]). Composite albuminuria progression or a ≥15% annual reduction in the estimated glomerular filtration rate was regarded as the end‐point. Results Per group, 173 propensity‐matched patients were compared. Patients with ΔMAP ≤−4 mmHg had a significantly lower incidence of composite renal outcomes than those with ΔMAP ≥−4 mmHg (5.8% [n = 10] vs 15.6% [n = 27], P = 0.003). Although the between‐group differences in the estimated glomerular filtration rates were non‐significant, patients with a ΔMAP ≤−4 mmHg had significantly larger reductions in the logarithmic urine albumin‐to‐creatinine ratio (P = 0.005). Conclusions The degree of blood pressure reduction after SGLT2 inhibitor treatment influenced renal composite outcomes in Japanese type 2 diabetes mellitus patients with CKD, confirming the importance of blood pressure management in type 2 diabetes mellitus patients with CKD, even when they are under SGLT2 inhibitor treatment., From the results of the propensity score matching method, the incidence of renal composite outcome was significantly lower in patients with changes in the mean arterial pressure ≤−4 mmHg than in those with changes in the mean arterial pressure >−4 mmHg (n = 10 [5.8%] and n = 27 [15.6%], respectively, P = 0.003). The reduction in mean arterial pressure after sodium–glucose cotransporter 2 inhibitor treatment influenced the renal composite outcome in Japanese patients with type 2 diabetes mellitus and chronic kidney disease.

In 2019, the Japanese Society of Hypertension guidelines for the management of hypertension (JSH) were revised. We previously reported the awareness of JSH among general practitioners in 2014, and in the current study, the same questionnaire was administered to determine their awareness of JSH 2019, and their responses were compared. We also sought to identify effective strategies to raise awareness of hypertension. The questionnaires included the same 12 questions as in 2014 and were mailed to members of two professional organizations from October to November 2019. Responses from 256 general practitioners in 2019 and 209 in 2014 were compared using the propensity score matching method to align the responders’ backgrounds. Component analysis was performed to classify responders into appropriate clusters. The matched cohort of all 202 responders was analyzed. In both 2014 and 2019, >80% of responders instructed patients to perform home blood pressure monitoring (JSH 2014: 81.7% and JSH 2019: 84.6% in the matched cohort), and >70% instructed patients with hypertension to restrict their salt intake (JSH 2014: 79.7% and JSH 2019: 74.7% in the matched cohort). Regarding the clinical blood pressure measurement method, more responders answered “one time outside the consulting room” in the JSH 2019 group (p = 0.042). Fewer general practitioners responded that differential diagnosis for primary aldosteronism was performed in the JSH 2019 group (p = 0.032); however, the frequency of checking the aldosterone-renin ratio increased in the JSH 2019 group (p = 0.055). We confirmed the change in general practitioners’ awareness of hypertension management. The categorized clusters may be useful for the development of effective strategies for higher-quality hypertension management in clinical practice.

Larger hip flexion range of motion with knee extension (hip flexion ROM) and passive stiffness of the hamstring is associated with greater production of isometric and concentric knee flexion torque at longer muscle lengths. Nevertheless, associations among hip flexion ROM, passive stiffness of hamstring, and eccentric knee flexion torque at a longer muscle length remain unclear. Therefore, we aimed to investigate the association among hip flexion ROM, passive stiffness of hamstring and eccentric knee flexion angle-torque relationship. Seventeen healthy male college students participated in this study, and all measurements were performed on both legs (34 legs). No participants had any previous hamstring strain injury. Hip flexion ROM, passive stiffness of hamstring, peak torque and peak torque angle during isokinetic eccentric knee flexion were measured. The correlation among the variables of interest were assessed. Passive stiffness of hamstring and eccentric peak knee flexion torque negatively correlated with the peak torque angle (r = −0.39). On the other hand, peak torque angle was not correlated with hip flexion ROM (r = 0.08). The present study revealed that higher passive stiffness of hamstring was associated with greater production of eccentric knee flexion torque at longer muscle lengths.

Objective: In 2020, coronavirus disease-2019 (COVID-19) became the cause of a pandemic. In response, the Japan Sports Agency issued warnings about secondary damage to health, such as the threat to physical and mental well-being due to the lack of exercise in this situation. In this study, we report on cross-sectional and longitudinal examinations of standing trunk flexion to evaluate how temporary long-term school closures affected musculoskeletal function in elementary school students. Patients and Methods: All children in one public elementary school in T-city during the school years 2019 and 2020 were included in this study. A digital forward flexion meter was used to measure standing trunk flexion. Results: In this study, 284 (284/289: 98.3%) and 266 (266/274: 97.1%) children in school years 2020 and 2019, respectively, were found to have valid data for cross-sectional analysis. The standing trunk flexion did not show significant differences between grades or sexes. In the longitudinal analysis, the results of the comparison of standing trunk flexion in children for two consecutive years revealed significant differences only between grades 3 and 4 (P

Introduction Intravesical Bacillus Calmette–Guerin immunotherapy is known to prevent recurrence of bladder cancer, but it can cause tuberculosis infections as an adverse event. Case presentation A 75‐year‐old man visited our hospital due to hematuria. The patient was diagnosed with bladder cancer and underwent transurethral resection of the bladder tumor. Postoperatively, the patient received Bacillus Calmette–Guerin immunotherapy. One year later, we performed transurethral surgery and prostate biopsy because of cystoscopic findings showing nodulous lesions in the bladder and an elevated serum prostate‐specific antigen level. The patient presented with high fever and malaise since the surgery. After careful examination, the patient was diagnosed with miliary tuberculosis caused by Mycobacterium bovis. The pathology of the bladder and prostate revealed acid‐fast bacilli collection by Ziehl–Neelsen staining. Conclusion The surgery exacerbated the local infection into a systemic infection. The risk of developing miliary tuberculosis should be considered at transurethral surgery or prostate biopsy in patients after intravesical Bacillus Calmette–Guerin immunotherapy.

We report a patient with sigmoid colon cancer who revealed a unique collision of hemorrhagic vascular adrenal cyst and adrenocortical adenoma with myelolipomatous changes. Two months before referral to our hospital, anticoagulant therapy was started for acute myocardial infarction. The components of the adrenocortical adenoma demonstrated a typical signal drop in opposed-phase magnetic resonance (MR) images although macroscopic fat was also depicted both on CT and MR images. The components of the vascular adrenal cyst demonstrated peripheral nodular enhancement with progressive enhancement on dynamic contrast-enhanced CT and a hemorrhagic change in the central region, which showed hyper intensity on T1-weighted images (T1WI) and hypo intensity on T2-weighted images (T2WI). Microscopically, the cyst was filled with foci of hemorrhage, fibrin, fibrosis, and hemosiderin. Furthermore, a white thrombus was found that corresponded to the central low signal intensity depicted on T2WI. Dilated vascular channels that were immunohistochemically positive for CD31 and CD34 were identified within the cyst. They were consistent with the pathological findings of hemorrhagic vascular adrenal cyst. Radiologists should be aware that the diagnosis of adrenal vascular cyst could be challenging since image findings may resemble hemangiomas, pheochromocytomas, and malignancy.

Purpose Renal function is frequently impaired in the patients with upper tract urothelial carcinoma. We aimed to evaluate the impact of renal function and its change after surgery on survival rates in patients with upper tract urothelial carcinoma after nephroureterectomy. Methods The study cohort comprised 755 patients with upper tract urothelial carcinoma who underwent nephroureterectomy between 1995 and 2016 at nine hospitals in Japan. Estimated glomerular filtration rate was calculated using the three-variable Japanese equation for glomerular filtration rate estimation from serum creatinine level and age. Outcomes were recurrence-free, cancer-specific and overall survivals. Univariate and multivariate Cox proportional hazards regression analyses were used. Results Median patients’ age was 72 years old. Pre- and post-surgical median estimated glomerular filtration rate were 55.5 and 42.9 ml/min/1.73 m2, respectively. Median estimated glomerular filtration rate decline after surgery, which represents function of the affected side kidney, was 13.1 ml/min/1.73 m2. The 5-year recurrence-free, cancer-specific and overall survivals were 68.3, 79.4 and 74.0%, respectively. Multivariate analysis indicated that lower preoperative estimated glomerular filtration rate and estimated glomerular filtration rate decline were associated with poorer recurrence-free, cancer-specific and overall survivals, but post-operative estimated glomerular filtration rate was not. Estimated glomerular filtration rate decline was more significant poor-prognosticator than preoperative estimated glomerular filtration rate. Proportions of the patients with estimated glomerular filtration rate Conclusions Lower preoperative renal function, especially of the affected side kidney, was significantly associated with poor prognosis after nephroureterectomy for upper tract urothelial carcinoma. Many patients with locally advanced disease have reduced renal function at diagnosis and even more after surgery.

Leguminous plants produce nodules for nitrogen fixation; however, nodule production incurs an energy cost. Therefore, as an adaptive strategy, leguminous plants halt root nodule development when sufficient amounts of nitrogen nutrients, such as nitrate, are present in the environment. Although legume NODULE INCEPTION (NIN)-LIKE PROTEIN (NLP) transcription factors have recently been identified, understanding how nodulation is controlled by nitrate, a fundamental question for nitrate-mediated transcriptional regulation of symbiotic genes, remains elusive. Here, we show that two Lotus japonicus NLPs, NITRATE UNRESPONSIVE SYMBIOSIS 1 (NRSYM1)/LjNLP4 and NRSYM2/LjNLP1, have overlapping functions in the nitrate-induced control of nodulation and act as master regulators for nitrate-dependent gene expression. We further identify candidate target genes of LjNLP4 by combining transcriptome analysis with a DNA affinity purification-seq approach. We then demonstrate that LjNLP4 and LjNIN, a key nodulation-specific regulator and paralog of LjNLP4, have different DNA-binding specificities. Moreover, LjNLP4–LjNIN dimerization underlies LjNLP4-mediated bifunctional transcriptional regulation. These data provide a basic principle for how nitrate controls nodulation through positive and negative regulation of symbiotic genes.

The new disease concept of multisystem inflammatory syndrome in children (MIS-C), which is a systemic inflammatory syndrome with multiple organ involvement after SARS-CoV2 infection, was established in 2020. MIS-C is common in Hispanic and black children in Europe and North America, with few reports in East Asians. A significant portion of patients with MIS-C develop Kawasaki disease (KD)-like symptoms. Therefore, differential diagnosis is challenging, especially in East Asia, where KD is most prevalent. No Japanese cases have been reported in the literatures so far. We report a case of MIS-C in Japan with KD-like symptoms. A 9-year-old Japanese boy, who was infected with SARS-CoV2 1 month previously along with his family, was admitted to our hospital owing to fever for 6 d and erythema mainly in the groyne and pubic area. He also had conjunctivitis, strawberry tongue and diarrhoea. His laboratory findings were as follows: WBC, 12,840/µL (lymphocytes, 4%); CRP, 22.6 mg/dL, pro-calcitonin, 1.8 ng/mL (normal

A birth cohort study was conducted in Khan Hoa Province, central Vietnam between 2009 and 2012 to determine the seroprevalence of hepatitis B virus (HBV) in pregnant women and their children, and associated risk factors. We enrolled 1987 pregnant women with their babies at the birth phase, and 12.6% (95% confidence interval [CI]: 11.1–14.0) of mothers were hepatitis B surface antigen (HBsAg)+. At 2-year follow-up phase, 1339 (67.4%) children were enrolled of whom 76.6% completed hepatitis B vaccines (HepB) and 1.9% (95% CI: 1.2–2.7) were HBsAg+. When mothers were hepatitis B e antigen (HBeAg)+, 28.3% of children have got infected even with complete HepB. HBV infection in mothers, hepatitis B surface antibody (anti-HBs antibody) below the seroprotective level in children, and mothers with pre-pregnancy low body mass index were associated with HBV infection in children. Meanwhile, HBV infection in children, older maternal age, no or incomplete doses of HepB, and boys were associated with anti-HBs antibody below the seroprotective level in children. Our birth cohort study determined a low rate of congenital HBV infection and associated risk factors in Vietnam, however further studies are needed to advance prevention including anti-viral therapy in pregnant women at high risk., Scientific Reports, 11, art. no. 8676; 2021

Nonalcoholic fatty liver disease (NAFLD) is often accompanied by metabolic disorders such as metabolic syndrome and type 2 diabetes (T2DM). Heat shock response (HSR) is one of the most important homeostatic abilities but is deteriorated by chronic metabolic insults. Heat shock (HS) with an appropriate mild electrical stimulation (MES) activates HSR and improves metabolic abnormalities including insulin resistance, hyperglycemia and inflammation in metabolic disorders. To analyze the effects of HS + MES treatment on NAFLD biomarkers, three cohorts including healthy men (two times/week, n = 10), patients with metabolic syndrome (four times/week, n = 40), and patients with T2DM (n = 100; four times/week (n = 40) and two, four, seven times/week (n = 20 each)) treated with HS + MES were retrospectively analyzed. The healthy subjects showed no significant alterations in NAFLD biomarkers after the treatment. In patients with metabolic syndrome, many of the NAFLD steatosis markers, including fatty liver index, NAFLD-liver fat score, liver/spleen ratio and hepatic steatosis index and NAFLD fibrosis marker, aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, were improved upon the treatment. In patients with T2DM, all investigated NAFLD steatosis markers were improved and NAFLD fibrosis markers such as the AST/ALT ratio, fibrosis-4 index and NAFLD-fibrosis score were improved upon the treatment. Thus, HS + MES, a physical intervention, may become a novel treatment strategy for NAFLD as well as metabolic disorders.

Intravenous lipoma of the inferior vena cava is an incidental finding on contrast-enhanced computed tomography in 0.5% of individuals. We report a case of multiple intravenous lipomas discovered during diagnosis of cholangitis in a 39-year-old woman. Imaging revealed three fatty masses that appeared connected by cordlike structures: one in the left renal vein with wide mural attachment and two in the inferior vena cava, the higher of which was mobile. We hypothesize that these originated as a single lipoma that subsequently divided into three distinct masses. Because mobile masses may cause pulmonary thromboembolism, surgery is recommended in these cases.

Aim: Sodium–glucose cotransporter 2 inhibitors (SGLT2is) provide renal protection in patients with type 2 diabetes mellitus (T2DM). The aim of this study was to elucidate the renal effects of long-...

Intrinsically stretchable electronics can form intimate interfaces with the human body, creating devices that could be used to monitor physiological signals without constraining movement. However, mechanical strain invariably leads to the degradation of the electronic properties of the devices. Here we show that strain-insensitive intrinsically stretchable transistor arrays can be created using an all-elastomer strain engineering approach, in which the patterned elastomer layers with tunable stiffnesses are incorporated into the transistor structure. By varying the cross-linking density of the elastomers, areas of increased local stiffness are introduced, reducing strain on the active regions of the devices. This approach can be readily incorporated into existing fabrication processes, and we use it to create arrays with a device density of 340 transistors cm–2 and a strain insensitivity of less than 5% performance variation when stretched to 100% strain. We also show that it can be used to fabricate strain-insensitive circuit elements, including NOR gates, ring oscillators and high-gain amplifiers for the stable monitoring of electrophysiological signals. An all-elastomer strain engineering approach, which uses patterned elastomer layers with tunable stiffnesses, can be used to create intrinsically stretchable transistor arrays with a device density of 340 transistors cm–2 and strain insensitivity of less than 5% performance variation when stretched to 100% strain.

It is desirable to estimate the degree of the decrease in pulmonary function before lung stereotactic body radiation therapy (SBRT) especially for patients with poor pulmonary function. The purpose of this study was to investigate whether decreases in pulmonary function after SBRT may be predicted from radiation dose–volume parameters. A total of 70 patients undergoing SBRT were evaluated for changes in pulmonary function. Of these, 67 had primary lung cancer and 3 had lung metastasis. Twenty-six (37%) patients had chronic obstructive pulmonary disease. Pulmonary function tests (PFTs) were performed shortly before and at 18–24 months after SBRT. Radiation pneumonitis was Grade 2 in 10 patients and Grade 3 in 1. Mean forced vital capacity (FVC) decreased from 2.67 to 2.51 L (P 5 Gy) and %V40Gy. Although the correlation was not significant, the %V20Gy value was the closest to the percent reduction in predicted FVC; %V20Gy of 10% tended to be associated with ~10% reduction in predicted FVC. Patients with poor pulmonary function did not necessarily show greater decreases in each PFT parameter. Decreases in FVC and FEV1 were within previously reported ranges. PTV was associated with decreases in FVC. The %V20Gy value was closest to the percentage decrease in predicted FVC.

The purpose of the present study was to investigate the effects of using a combination of static stretching and aerobic exercise on muscle tendon unit stiffness and muscle strength in the ankle plantar-flexor muscles. Fifteen healthy males (23.3 ± 2.7 years, 170.3 ± 6.5 cm, 64.9 ± 8.7 kg) received three different interventions, in random order. Intervention 1 received 10 min of aerobic exercise after five cycles of one minute of static stretching. Intervention 2 received 10 min of aerobic exercise before the static stretching. Intervention 3 received 5 min of aerobic exercise both before and after the static stretching. The range of motion of ankle dorsiflexion, stretch tolerance, muscle tendon unit stiffness, peak torque of ankle plantarflexion, and the amplitude of electromyography were measured. In all interventions, the range of motion and stretch tolerance significantly increased (

This study compared the cost of screening with outcomes and verified the utility of a screening program. This cross-sectional study included all elementary and junior high school students from Tsukuba city who underwent musculoskeletal screening in 2016; 19,583 students were included. Written marksheet type questionnaires were distributed that focused on reporting scoliosis, torticollis, flat foot, and pain, among other symptoms. Using information from the questionnaire, face-to-face screening was performed by a doctor on-campus and/or orthopedic surgeons. Students with abnormalities on screening were identified and referred for a hospital visit. The screening, questionnaire, reasons for and number of hospital visits, examination, treatment, and their individual costs were examined. Hospital visits were recommended to 532/19,583 (2.7%) students after musculoskeletal screening. Among them, 250 and 129 students visited other and our hospitals, respectively. Overall, 11 students required treatment. Costs associated with screening, hospital examination, and treatment totaled to ¥8,526,351; 129 students visited our institution, of whom 11 (8.5%) required treatment. Among them, 10/11 and 1/11 were treated using orthotic and operative treatments, respectively. If scoliosis surgery may be prevented by musculoskeletal screening and orthotic treatment, it is possible that the outcomes may justify the examination costs.

Recently, chronic hyponatremia, even mild, has shown to be associated with poor quality of life and high mortality. The mechanism by which hyponatremia contributes to those symptoms, however, remains to be elucidated. Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is a primary cause of hyponatremia. Appropriate animal models are crucial for investigating the pathophysiology of SIADH. A rat model of SIADH has been generally used and mouse models have been rarely used. In this study, we developed a mouse model of chronic SIADH in which stable and sustained hyponatremia occurred after 3-week continuous infusion of the vasopressin V2 receptor agonist 1-desamino-8-D-arginine vasopressin (dDAVP) and liquid diet feeding to produce chronic water loading. Weight gain in chronic SIADH mice at week 2 and 3 after starting dDAVP injection was similar to that of control mice, suggesting that the animals adapted to chronic hyponatremia and grew up normally. AQP2 expression in the kidney, which reflects the renal action of vasopressin, was decreased in dDAVP-infused water-loaded mice as compared with control mice that received the same dDAVP infusion but were fed pelleted chow. These results suggest that "vasopressin escape" occurred, which is an important process for limiting potentially fatal severe hyponatremia. Behavioral analyses using the contextual and cued fear conditioning test and T-maze test demonstrated cognitive impairment, especially working memory impairment, in chronic SIADH mice, which was partially restored after correcting hyponatremia. Our results suggest that vasopressin escape occurred in chronic SIADH mice and that chronic hyponatremia contributed to their memory impairment.

In Japan, since the introduction of newborn screening for congenital adrenal hyperplasia in 1989, most patients with 21-hydroxylase deficiency (21OHD) have been treated with glucocorticoid from the neonatal period (1, 2). Although early initiation of glucocorticoid therapy from the neonatal period remarkably improved the outcomes of final height, the average final height in 21OHD patients is below the standard height observed in normal healthy adults by approximately –1 standard deviation (SD) (3, 4), and optimization of glucocorticoid therapy remains challenging (5,6,7, 8). Glucocorticoids have a strong potential for reducing linear growth, whereas undertreatment with glucocorticoids leads to androgen excess, precipitating pubertal development (5,6,7). Recent studies have revealed that the final height positively correlates with height at two years of age (9), and the lowest possible hydrocortisone (HC) dose for maintenance treatment during the first two years of life considered crucial for maximizing the final height of 21OHD patients. For maintenance therapy, 15–25 mg/m2 HC therapy is widely accepted (10). In contrast to maintenance HC therapy, the optimal HC dose for initial treatment has not been established. The consensus statement on 21OHD by the Lawson Wilkins Pediatric Endocrine Society and the European Society for Pediatric Endocrinology (ESPE) suggests an HC dose of up to 25 mg/m2 for treatment initiation (11). Conversely, the Japanese Society for Pediatric Endocrinology (JSPE) recommended a considerably higher HC dose of HC (100–200 mg/m2) for the initial treatment (12), and in the revised guideline published in 2014, the recommended dose was lowered to 25–100 mg/m2, which is still higher than that recommended by the ESPE (13). A high initial HC dose may help normalize the elevated adrenal androgen levels during the neonatal and early infantile periods, followed by sufficient control by a lower maintenance dose. Our previous study has revealed that the height at two years of age in patients with 21OHD treated with a higher HC dose during initial therapy could be compared with those receiving lower HC doses (14). However, detailed differences between patients with 21OHD treated with higher and lower doses during initial HC therapy have not been assessed. In the present study, we aimed to evaluate the effects of initial HC treatments on clinical profiles during infancy and early childhood in patients with 21OHD.

SARS-CoV-2 infection elicits varying degrees of protective immunity conferred by neutralizing antibodies (nAbs). Here we report the persistence of nAb responses over 12 months after infection despite its decreasing trend noticed from 6 months. The study included sera from 358 individuals who had been infected with SARS-CoV-2 between January and May 2020. Samples were collected at 6 and 12 months after onset. The titers of IgG to the viral nucleocapsid protein (NP) and receptor-binding domain of the spike protein (RBD) were measured by CLEIA. The nAb titer was determined using lentivirus-based pseudovirus or authentic virus. Antibody titers of NP-IgG, RBD-IgG, and nAbs were higher in severe and moderate cases than in mild cases at 12 months after onset. While the nAb levels were likely to confer adequate protection against wild-type viral infection, the neutralization activity to recently circulating variants in some of the mild cases (∼30%) was undermined, implying the susceptibility of reinfection to the variants of concerns (VOCs). COVID-19 convalescent individuals have robust humoral immunity even at 12 months after infection albeit that the medical history and background of patients could affect the function and dynamics of antibody response to the VOCs.

Objective: The complexity of chromatin (i.e., irregular geometry and distribution) is one of the important factors considered in the cytological diagnosis of cancer. Fractal analysis with Kirsch edge detection is a known technique to detect irregular geometry and distribution in an image. We examined the outer cutoff value for the box-counting (BC) method for fractal analysis of the complexity of chromatin using Kirsch edge detection. Materials: The following images were used for the analysis: (1) image of the nucleus for Kirsch edge detection measuring 97 × 122 pix (10.7 × 13.4 μm) with a Feret diameter of chromatin mesh (n = 50) measuring 17.3 ± 1.8 pix (1.9 ± 0.5 μm) and chromatin network distance (n = 50) measuring 4.4 ± 1.6 pix (0.49 ± 0.18 μm), and (2) sample images for Kirsch edge detection with varying diameters (10.4, 15.9, and 18.1 μm) and network width of 0.4 μm. Methods: Three types of bias that can affect the outcomes of fractal analysis in cytological diagnosis were defined. (1) Nuclear position bias: images of 9 different positions generated by shifting the original position of the nucleus in the middle of a 256 × 256 pix (28.1 μm) square frame in 8 compass directions. (2) Nuclear rotation bias: images of 8 different rotations obtained by rotating the original position of the nucleus in 45° increments (0°, 45°, 90°, 135°, 180°, 225°, 270°, and 315°). (3) Nuclear size bias: images of varying size (diameter: 190 pix [10.4 μm], 290 pix [15.9 μm], and 330 pix [18.1 μm]) with the same mesh pattern (network width: 8 pix [0.4 μm]) within a 512 × 512 pix square. Different outer cutoff values for the BC method (256, 128, 64, 32, 16, and 8 pix) were applied for each bias to assess the fractal dimension and to compare the coefficient of variation (CV). Results: The BC method with the outer cutoff value of 32 pix resulted in the least variation of fractal dimension. Specifically, with the cutoff value of 32 pix, the CV of nuclear position bias, nuclear rotation bias, and nuclear size bias were p = 0.19). Our study suggests that the BC method with the outer cutoff value of 32 pix is suitable for the analysis of the complexity of chromatin with chromatin mesh.

We have synthesized inverse-perovskite-type oxysilicides and oxygermanides represented by R3SiO and R3GeO (R = Ca and Sr) and studied their characteristics in the search for nontoxic narrow band gap semiconductors. These compounds exhibit a sharp absorption edge around 0.9 eV and a luminescence peak in the same energy range. These results indicate that the obtained materials have a direct-band electronic structure, which was confirmed by hybrid DFT calculations. These materials, made from earth abundant and nontoxic elements and with a relatively light electron/hole effective mass, represent strong candidates for nontoxic optoelectronic devices in the infrared range.

The effects of different doses of orally administered sildenafil on pulmonary haemodynamics in dogs with pulmonary hypertension (PH) have not been documented in an invasive and quantitative manner. In this study, we examined the effects of oral sildenafil using a canine model of chronic embolic PH (CEPH). This CEPH model was created by repeatedly injecting microspheres through a catheter into the pulmonary artery under general anaesthesia at regular weekly intervals over several months. The CEPH dogs received 1, 2 or 4 mg/kg of sildenafil orally twice a day for seven days. Then, haemodynamic measurements including pulmonary artery pressure (PAP), systemic artery pressure (SAP), pulmonary artery wedge pressure (PAWP), right atrial pressure (RAP) and cardiac output (CO) were obtained after seven days of sildenafil administration via right heart catheterisation and oscillometric blood pressure measurements. Sildenafil was well tolerated in this study. Sildenafil administered at doses of 2 and 4 mg/kg significantly decreased systolic PAP compared with before administration. In addition, all doses of sildenafil significantly decreased the mean and diastolic PAP. Furthermore, 4 mg/kg of sildenafil significantly decreased PAP compared with 1 mg/kg. Sildenafil also significantly decreased pulmonary vascular resistance without notable changes in SAP or systemic vascular resistance. The PAWP, RAP and CO did not increase significantly at any doses. In conclusion, the oral administration of sildenafil to CEPH models decreased PAP in a dose-dependent manner.

Aims Neurogranin (NRGN) is a postsynaptic protein kinase substrate that binds calmodulin in the absence of calcium. Recent studies suggest that NRGN is involved in neuropsychiatric disorders, including schizophrenia, ADHD, and Alzheimer's disease. Previous behavioral studies of Nrgn knockout (Nrgn KO) mice identified hyperactivity, deficits in spatial learning, impaired sociability, and decreased prepulse inhibition, which suggest that these mice recapitulate some symptoms of neuropsychiatric disorders. To further validate Nrgn KO mice as a model of neuropsychiatric disorders, we assessed multiple domains of behavioral phenotypes in Nrgn KO mice using a comprehensive behavioral test battery including tests of homecage locomotor activity and nesting behavior. Methods Adult Nrgn KO mice (28‐54 weeks old) were subjected to a battery of comprehensive behavioral tests, which examined general health, nesting behavior, neurological characteristics, motor function, pain sensitivity, locomotor activity, anxiety‐like behavior, social behavior, sensorimotor gating, depression‐like behavior, and working memory. Results The Nrgn KO mice displayed a pronounced decrease in nesting behavior, impaired motor function, and elevated pain sensitivity. While the Nrgn KO mice showed increased locomotor activity in the open field test, these mice did not show hyperactivity in a familiar environment as measured in the homecage locomotor activity test. The Nrgn KO mice exhibited a decreased number of transitions in the light‐dark transition test and decreased stay time in the center of the open field test, which is consistent with previous reports of increased anxiety‐like behavior. Interestingly, however, these mice stayed on open arms significantly longer than wild‐type mice in the elevated plus maze. Consistent with previous studies, the mutant mice exhibited decreased prepulse inhibition, impaired working memory, and decreased sociability. Conclusions In the current study, we identified behavioral phenotypes of Nrgn KO mice that mimic some of the typical symptoms of neuropsychiatric diseases, including impaired executive function, motor dysfunction, and altered anxiety. Most behavioral phenotypes that had been previously identified, such as hyperlocomotor activity, impaired sociability, tendency for working memory deficiency, and altered sensorimotor gating, were reproduced in the present study. Collectively, the behavioral phenotypes of Nrgn KO mice detected in the present study indicate that Nrgn KO mice are a valuable animal model that recapitulates a variety of symptoms of neuropsychiatric disorders, such as schizophrenia, ADHD, and Alzheimer's disease., We found that Neurogranin knockout mice exhibit decreased nesting behavior, selective increases in locomotor activity in a novel environment, and paradoxically increased open arm exploration. Considering the behavioral phenotypes that had been previously identified, we propose that Neurogranin KO mice are a valuable animal model that recapitulates a variety of symptoms of neuropsychiatric disorders, such as schizophrenia, ADHD, and Alzheimer's disease.

Renal proteinuria is associated with promoted renal dysfunction and a shorter survival period in dogs with chronic kidney disease (CKD). Renin angiotensin- aldosterone system inhibitors are primarily used to treat renal proteinuria. In this retrospective, open-label study, we aimed to evaluate the anti-proteinuric and anti-hypertensive effects of telmisartan (angiotensin II receptor blocker) in dogs with proteinuric CKD. A total of 28 dogs with proteinuric CKD were included in the study, all dogs received telmisartan 1 mg/kg q24h, PO. The urine protein-to-creatinine ratio (UPC), urine albumin-to-creatinine ratio (UAC) and systolic blood pressure (SBP) decreased significantly after telmisartan administration (P 0.05). The median rate of change in UPC, UAC and SBP at Day 120 were - 65.1%, -75.9% and - 9.7%. Ten dogs (36.7%) achieved UPC 1.0 at Day 120, of which six dogs had UPC 0.5. A reduction of UPC to ≥50% was achieved in 10 dogs (36%) at Day 45 and 17 dogs (61%) at Day 120. Seventeen dogs (61%) had hypertension at baseline, of which 10 dogs (59%) had SBP 160 mmHg at Day 120. Two-way repeated measures analysis of variance did not attribute the observed changes in SBP, UPC or UAC to feeding with a renal diet. In conclusion, telmisartan therapy provides anti-proteinuric and anti-hypertensive effects in dogs with proteinuric CKD.

Somatic hotspot DICER1 mutations, which frequently coexist with germline inactivating mutation (i.e., DICER1 syndrome), have been identified in various types of benign and malignant conditions. Herein, we report an autopsy case of prostatic rhabdomyosarcoma (RMS) with a hotspot DICER1 c.5125G>A (p.D1709N) mutation. A 26 year-old man presented with a prostatic mass, hematuria, and urinary retention. He underwent total pelvic exenteration, colostomy, ileal conduit construction and partial urethrectomy. Five months postoperatively, he developed multiple metastases to the lungs, brain, iliopsoas muscles and bones. He died of respiratory failure, and autopsy was performed. Microscopically, the tumor was primarily composed of uniform primitive mesenchymal cells infiltrating to the prostate with cambium layer. Rhabdomyoblasts and anaplastic cells were focally observed. Immunohistochemically, tumor cells were positive for desmin, myogenin, PAX7, HMGA2. Multinodular goiter was detected at autopsy. Because the morphology is similar to pleuropulmonary blastoma and DICER1-mutant RMS of the female genital tract, we tested and identified a hotspot DICER1 mutation with Sanger sequencing. Recognizing DICER1-mutant tumor is important because of its frequent association with germline DICER1 inactivation and potential therapeutic implication. Further research is needed to clarify whether this case can be classified as embryonal RMS with anaplasia or 'DICER1-associated sarcoma'.

Objective: In 2016, Japan started conducting musculoskeletal examinations that included "limb status" of students as an essential item. Our institution implemented a unified musculoskeletal examination for all public elementary and junior high schools in T-city. In this study, we aimed to report the progress in the past 4 years. Patients and Methods: The Tsukuba Childhood Locomotive-Organ Screening Sheet (T-CLOSS), which is a questionnaire that includes some nationwide-recommended questions, was prepared and distributed to students. Results of the questionnaires were analyzed, and the orthopedic surgeon conducted examinations for the extracted items. From these questionnaires, the ratio of each item, rate of advisory for screening, and content of the advisory were investigated. Results: During 2016-2019, musculoskeletal examinations were conducted in every public schools, with nearly 20,000 students in T-city. The consultation advisory rate was 6.7% in 2019. Of the 524 students who received the third screening recommendation, the actual consultation rate was 248 (40.8%). After the third screening, the proportion of students requiring treatment and outpatient visits was 46.7% (n=248), which accounted for 1.2% of all elementary and junior high school students in the city. Conclusion: We reported the results of 4-year musculoskeletal examinations in a city. In our screening, we distributed a uniform questionnaire throughout the city, and orthopedic surgeons performed secondary examinations of identified students in all schools. This appears to be an advanced effort to prevent musculoskeletal impairment in students. We hope to conduct more sophisticated musculoskeletal examinations using our results, aiming at early detection, early treatment, and improvement of musculoskeletal function in elementary and junior high school students.

Prostate cancer is one of the most common malignancies, but a substantial portion remains latent throughout the patients’ lifetime. Analysis of temporal change in the latent prostate cancer pool would be beneficial for clinical decision-making, but longitudinal autopsy studies are rare. We conducted a hand-search of the Annual of Pathological Autopsy Cases in Japan from 1980 to 2016 for cases of latent prostate cancer. Of 570 997 males aged 30 or older, latent prostate cancer was detected in 12 562 patients (2.2%). Proportion of detected cases correlated strongly with ‘aging rate’, the percentage of population aged 65 or older (squared Pearson’s correlation coefficient r2 = 0.972, P value

Purpose To investigate preliminarily the effect of lactoferrin (LF)-fortified formula on sleep conditions in children. Study Design A preliminary, randomized, double-blind, placebo-controlled trial. Methods Healthy children between the ages of 12 and 32 months who attended nursery schools in Japan were divided into two groups and assigned a placebo or LF (48 mg/day)-fortified formula. Children's sleep conditions were investigated before and after the 13-week intervention using the Japanese Sleep Questionnaire for Preschoolers (JSQ-P). Results Altogether, 109 participants were randomized. Eight participants were eliminated due to lost to follow-up, withdrawal of consent, and ineligibility, with 101 participants (placebo, n = 48; LF, n = 53) included in the full analysis set (FAS) and used for analysis. Wake-up time, bedtime, and nighttime sleep were comparable between the two groups before and after intervention. The change in total JSQ-P T scores tended to improve in the LF group (placebo vs LF: 0.5 ± 6.5 vs -1.9 ± 6.1, p = 0.074), in particular, morning symptoms significantly improved (grumpy in the morning, hard to wake-up, and hard to get out of bed) (placebo vs LF: 0.8 ± 6.2 vs -1.9 ± 6.2, p = 0.028). A better trend was also observed in the LF group regarding restless legs syndrome (RLS)-motor (rubs feet at night and touches feet at night) (placebo vs LF: 2.3 ± 10.7 vs -0.6 ± 13.5, p = 0.083) and insufficient sleep (stays up more than one hour later the day before a holiday and wakes up more than one hour later on a holiday) (placebo vs LF: 0.1 ± 9.8 vs -1.7 ± 8.8, p = 0.095). No adverse drug reactions were found. Conclusion LF intake may improve sleep condition, especially morning symptoms in children above one year of age.

Introduction/Objectives The American College of Veterinary Internal Medicine (ACVIM) guidelines suggest that pimobendan should be initiated in dogs which meet all criteria of stage B2 myxomatous mitral valve disease (MMVD): murmur intensity ≥ 3/6, left atrial-to-aortic ratio ≥ 1.6, normalized left ventricular internal diameter in diastole ≥ 1.7, and vertebral heart size > 10.5. Recently, a new radiographic index for left atrial enlargement, vertebral left atrial size (VLAS), was proposed. The objective of the present study was to evaluate whether VLAS is useful in staging MMVD and if it can distinguish between ACVIM stages B1 and B2. Animals Ninety-seven client-owned dogs with MMVD were evaluated and classified as ACVIM stage B1, B2, or C-D. Materials and Methods The echocardiographs and radiographs of all the dogs were retrospectively evaluated to obtain left atrial-to-aortic ratio, normalized left ventricular internal diameter in diastole, and VLAS values. The data were analyzed to assess the correlation between these measurements and VLAS, and the optimal cutoff value of VLAS was determined. Results A VLAS cutoff value of 2.6 provided the greatest diagnostic accuracy for identification of dogs with ACVIM stage B2 MMVD (area under the curve, 0.96; sensitivity, 95%; specificity, 84%). A VLAS ≥2.5 exhibited the highest sensitivity (sensitivity, 100%; specificity, 78%), and a VLAS ≥ 3.1 exhibited the highest specificity (sensitivity, 47%; specificity, 100%). Conclusions VLAS is a helpful index for monitoring MMVD using radiography. A VLAS cutoff value of 2.5 could be used to identify dogs that may benefit from echocardiography to determine if they have reached ACVIM stage B2.

Some patients with schizophrenia have impaired hypothalamic-pituitary-adrenal axis function. However, there is a dearth of studies focusing on corticotropin-releasing hormone (CRH) levels in the brains of schizophrenia patients, which motivated us to examine whether cerebrospinal fluid (CSF) CRH concentrations are altered in these patients. We also examined the possible correlation of CSF CRH level with clinical variables such as schizophrenia symptoms and antipsychotic medication. The study population comprised 20 patients with a diagnosis of schizophrenia according to DSM-5 criteria and 25 healthy controls, who underwent lumbar puncture. Most of the patients were treated with antipsychotic drugs and their doses were converted to chlorpromazine (CP) equivalent values. CSF CRH concentrations were measured by an enzyme immunoassay. Symptom severity was assessed using the Positive and Negative Syndrome Scale (PANSS). There was a significantly lower CSF CRH concentration in the patients than in the controls (Mann-Whitney U test: p = 0.014). A significantly negative correlation of CSF CRH levels with PANSS negative scores was found in the patients (Spearman's: ρ = −0.58, p = 0.007). However, CSF CRH concentrations were not significantly correlated with the PANSS total (ρ = −0.035, p = 0.89), positive (ρ = 0.25, p = 0.30), or general psychopathology (ρ = 0.13, p = 0.59) scores. No significant correlation was found with CP equivalent values (ρ = 0.00, p = 1.00). In conclusion, we found that the patients with schizophrenia had lower CSF CRH concentrations compared to the controls and that the lower CSF CRH was associated with negative symptoms of the illness. Further studies in a larger sample and in drug-free patients are warranted.

To investigate whether surgery and stereotactic body radiotherapy (SBRT) yield comparable outcomes for clinical stage (c-stage) I non-small-cell lung cancer (NSCLC), propensity score-matching (PSM) analysis was conducted. This single-institutional retrospective study included patients who underwent surgery (n = 574) or SBRT (n = 182) between 2004 and 2014. PSM was performed based on tumor diameter, age, sex, performance status, forced expiratory volume, Charlson comorbidity index, and ground glass nodules (GGN) defined as cTis or cT1mi according to the 8th TNM classification. The median follow-up durations for the surgery and SBRT groups were 66 and 69 months, respectively. The multivariate analysis revealed that non-GGN was a significant factor for poorer overall survival (OS) and disease-free survival (DFS): hazard ratio (HR) 19.95% confidence interval (CI) 4.7–79, P

Aims/Introduction Sodium–glucose cotransporter 2 inhibitors (SGLT2i) improve renal outcome in patients with type 2 diabetes mellitus, but the mechanism is not fully understood. The aim of this retrospective study was to assess the association of achieved blood pressure with renal outcomes in Japanese type 2 diabetes mellitus patients with chronic kidney disease. Materials and Methods We assessed 624 Japanese type 2 diabetes mellitus patients with chronic kidney disease taking SGLT2i for >1 year. The patients were classified as those with post‐treatment mean arterial pressure (MAP) of ≥92 mmHg (n = 344) and those with MAP of, Incidence of renal composite outcome and changes in logarithmic value of the albumin‐to‐creatinine ratio and estimated glomerular filtration rate.