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Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a systemic inflammatory disorder categorized as small-vessel vasculitis. We herein report an elderly Japanese man with AAV (granulomatosis with polyangiitis affecting the eyes, nose, lungs, and kidneys) who also showed periaortitis at the diagnosis and developed cranial hypertrophic pachymeningitis (HP) during steroid maintenance therapy. His consciousness disturbance caused by HP improved after steroid pulse therapy, but he died of aspiration pneumonia. Autopsy findings showed giant cells in the thickened pachymeninges and obsolete inflammatory lesions in the aortic adventitia and renal tubulointerstitium. This is the first case of AAV complicated by periaortitis and cranial HP.

Objectives Using a strategy of placing a surgical drain after kidney transplantation, the duration of a lymphatic fluid leakage and prevalence of a symptomatic lymphocele were retrospectively analyzed. The risk factors for persistent lymphatic fluid leakage or asymptomatic lymphocele were evaluated using multivariate analysis to estimate the origin of the lymphatic fluid leakage. Materials and methods Patients with persistent lymphatic fluid leakage and symptomatic lymphocele were defined as those with lymphatic fluid drainage >50 mL for more than 15 days and those who required a percutaneous drainage of the lymphocele, respectively. Results Persistent lymphatic fluid leakage and symptomatic lymphocele were observed in 40 (16.4%) and 10 (4.1%) of a total of 244 patients, respectively. The maximum durations of lymphatic fluid drainage from the initial drain tube and the second drainage of the symptomatic lymphocele were 48 and 28 days, respectively. Anastomosis of the graft artery to the external iliac artery was an independent risk factor to predict persistent lymphatic fluid leakage or symptomatic lymphocele after kidney transplantation (odds = 2.597, P = .008). Conclusion The findings of the study suggest that the lymphatic fluid originates from the recipient's iliac lymph trunk rather than from the graft kidney.

The hysteresis of the capacitance–voltage (C–V) characteristics of an Al2O3/n-GaN metal–insulator–semiconductor structure was evaluated under light (white LED)-irradiation and dark conditions. The hysteresis was not observed under the dark condition but was observed under the light-irradiation condition. The GaN surface was completely depleted in negative bias under the dark condition. The C–V characteristics indicated that the hysteresis is caused by hole trapping under the LED irradiation condition and that the holes are generated in the n-GaN surface by LED irradiation and subsequently injected into the Al2O3 films. When the holes are generated in the depletion region of GaN for any reason, such as a short generation lifetime, they can be trapped in the Al2O3 films.

We herein report the first pediatric case (a 13-year-old girl) of relapsing eosinophilic granulomatosis with polyangiitis (EGPA) successfully treated with mepolizumab (anti-interleukin-5). She was classified as having EGPA based on the presence of asthma, eosinophilia, pulmonary infiltrates, and extravascular eosinophil infiltration confirmed by a biopsy. She achieved remission after initial oral prednisolone (PSL) therapy, but EGPA relapsed during PSL tapering. Subsequent combined therapy with PSL and tacrolimus did not improve the recurrent disease. Intravenous methylprednisolone pulse therapy was started, followed by oral PSL. During PSL tapering, mepolizumab was added to the treatment, which resulted in sustained remission and successful PSL tapering.

The prognostic significance of glomerular extracapillary hypercellularity (EXHC) in diabetic kidney disease (DKD) is unclear. The aim of this study was to investigate the clinicopathological features and outcomes of DKD patients with EXHC. We studied 70 cases of renal biopsy-confirmed type 2 DKD that were diagnosed between 2004 and 2014 and compared the clinicopathological features and outcomes of 22 patients with EXHC (EXHC group) with those of 48 patients without EXHC (control group). All of the patients were Japanese. We assessed the renal biopsy specimens based on the Renal Pathology Society classification system. Clinical and laboratory data were collected at the time of the renal biopsy, and renal outcomes were assessed based on progression to end-stage renal disease (ESRD) requiring renal replacement therapy. The median duration of the observation period was 3 years. In pathological features, nodular sclerosis (Kimmelstiel–Wilson lesions) was observed more frequently in the EXHC group than in the control group (63.6% vs. 35.4%, P = 0.027). There were no significant intergroup differences in clinical features or renal outcomes. Univariate and multivariate Cox regression analyses of all patients showed that a high level of proteinuria, a low initial eGFR, and severe interstitial inflammation were poor prognostic factors. EXHC is related to nodular sclerosis, which is a known risk factor for ESRD. Careful observation is needed during the follow-up of DKD patients with EXHC, although there were no significant differences in renal outcomes between the EXHC and control groups.

Background and Objectives BK polyomavirus (BKV) causes BKV-associated nephropathy and haemorrhagic cystitis, subsequent to BKV reactivation. Intravenous immunoglobulin products (IVIg), manufactured from the plasma of over ten thousand donors, may contain antibodies against BKV. However, the antibody titres and batch-to-batch variations in IVIg across the manufacturing year are unknown. This study aims to determine the BKV-neutralizing activity of IVIg from donated blood in Japan and its trend over the past several years. Materials and Methods A reliable measurement method was established to quantitatively determine neutralizing activity using the human lung (carcinoma) cell line, A549 and the Gardner strain of BKV. Six lots of IVIg and four lots of pooled plasma were used as the source material for this study. Results The mean neutralizing titre against BKV in pooled plasma was 3·4 ± 0·1 log10 and that in IVIg was 4·1 ± 0·1 log10. The titres of IVIg lots manufactured from 1999 to 2010 were stable. Conclusion IVIg derived from donated blood in Japan demonstrated high neutralizing activity against BKV, and its titre was maintained over the duration of 10 years, suggesting high prevalence of BKV among the donor population in Japan. Further studies are required to clarify the clinical implications of this neutralizing activity in IVIg.

One of the major interests of governments in the area of environmental protection is to reduce greenhouse gas (GHG) emissions and air pollutants’ emissions (HC, CO, NOx, PM, and SOx) from vehicles. This paper aims at evaluating the efficiency of green and diesel vehicles. Two hundred fifty vehicles were selected for comparison study. The results show that the efficiency of each type of vehicle hardly differed in 2008 and 2009, but the gap between green and diesel vehicles became significant in 2010–2012. The results also indicate that larger automotive companies and smaller green vehicles show higher efficiency in recent years, whereas the type of green vehicles and the origin of automotive companies are not significantly related to the efficiency score of green vehicles. These findings provide more information for understanding differences in green vehicles.

Background Influenza virus transmission may be prevented by infection control measures, including vaccination, wearing a mask, gargling with water, and hand washing. It is unclear, however, whether these measures affect influenza epidemics in school settings. Methods A prospective epidemiological survey in all public elementary schools in Matsumoto City, Japan, during the 2014/2015 season evaluated the number of diagnosed patients in each school and calculated the reproduction number of schoolchildren. At the end of the prospective survey, a cross-sectional survey evaluated the implementation of infection control measures in these schools. Both results were combined and associations among infection control measures including vaccination, mask wearing, hand washing, water gargling, and epidemic level were evaluated. Results Of the 13,217 schoolchildren in 29 schools, 2548 were diagnosed with seasonal influenza. A significant negative association was observed between vaccination coverage and reproduction number at each school, but not between other infection control measures and the reproduction number. A regression curve with exponential function was most predictive. At 0% vaccination, the reproduction number was estimated to be 1.39. Conclusion These findings provide evidence that high vaccination coverage was associated with reduced epidemic levels in schools and suggest the need for increased vaccination of schoolchildren.

Aim The neuropsychiatric test (NP test) is a clinically available modality to confirm minimal hepatic encephalopathy (MHE), but it takes at least 30 min for outpatients to complete. An easier primary screening tool of the NP test would be helpful to predict MHE in routine testing on the public. Methods We performed a prospective cohort study on 59 cirrhotic outpatients at Kobe University Hospital. Laboratory measurements, the NP test and the Chronic Liver Disease Questionnaire (CLDQ) were performed. As an indicator of MHE, cases with and without two abnormal subsets or more in the NP test were compared, and the independent risk factors were statistically examined. Predictive scoring systems of the risk of MHE were established using multivariate logistic regression. Results CLDQ worry (WO) was the best predictive factor of MHE diagnosed by the NP test (P = 0.006). The predictive model using CLDQ WO discriminated well between patients with and without MHE (area under the curve, 0.714; 95% confidence interval, 0.582–0.824). The predictive scores of MHE enable the patient-specific probability to be easily looked up. Conclusion CLDQ WO was shown to be an independent factor associated with the NP test to diagnose MHE in cirrhotic patients. The easy predictive scoring system of the risk of MHE using CLDQ WO could become a primary screening tool before performing the NP test in a social setting.

Aim: Transcatheter arterial chemoembolization (TACE) is thought to be a safe and effective treatment for hepatocellular carcinoma (HCC). However, in some HCC patients, it potentially shortens survival due to liver damage. We aimed to identify independent factors to predict overall survival of HCC after TACE. Methods: We included a total of 96 consecutive HCC patients who underwent TACE at Kobe University Hospital. Areas of skeletal muscle and fat tissue were measured by computed tomography (CT) scan before TACE. We divided the patients into two groups in terms of the presence or absence of 1-year mortality after TACE. Factors associated with 1-year mortality after TACE were assessed by multivariate analyses, and the optimal cut-off values were evaluated using a propensity score. Results: Multivariate analyses showed that visceral fat accumulation on CT was an independent factor associated with 1-year mortality after TACE (p = 0.033). There were no differences in skeletal muscle area and subcutaneous and intermuscular fat area between the two groups. Cut-off values for visceral fat area associated with 1-year mortality after TACE were defined as 33.3 cm 2 /m 2 for males and 24.4 cm 2 /m 2 for females. Conclusions: High visceral fat area was a prognostic factor associated with increased mortality rate in HCC patients undergoing TACE. Using this value, 1-year mortality risk after TACE would be better estimated before the day TACE was performed. * Corresponding author.

The purpose of antiviral therapy in chronic hepatitis B (CHB) is generally to achieve a decrease and ultimately disappearance of HBs antigen (HBsAg). Interferon (IFN) therapy of CHB appears to be less effective in Asian countries than in European countries, and the advantage of IFN and nucleotide(s) analog (NA) combination therapy has yet to be fully investigated. The present study focused on the factors associated with a decrease in HBs antigen following IFN monotherapy or IFN + NA combination therapy. A total of 35 patients with CHB who received IFN-based therapy (mean ± standard deviation age 36.7±8.5 years; 27 males and 8 females) were enrolled in this study. Of the 35 patients, 21 patients received pegylated IFN monotherapy and 14 patients received IFN and adefovir (ADV) combination therapy. We examined the factors associated with reductions in the HBsAg titer of >1.0 log IU/ml from the initial HBsAg titer to the end of treatment and to 24 weeks after treatment. Although 13 patients (37%) had a reduction in HBsAg of >1.0 IU/ml at the end of treatment, it was only maintained to 24 weeks after treatment in 7 patients (20%). The HBV core-related antigen (HBcrAg) titer before treatment was significantly higher in patients with a decrease in HBsAg at the end of treatment than in patients without a decrease in HBsAg (6.56±0.78 vs. 5.30±1.66 log IU/ml, P2 times from baseline occurred significantly more frequently in patients with a decrease in HBsAg (62 vs. 14%, P

Three recent studies from the United States and China reported the clinicopathological features and short-term prognosis in patients with membranous nephropathy (MN) and crescents in the absence of secondary MN, anti-glomerular basement membrane (GBM) antibodies, and anti-neutrophil cytoplasmic antibodies (ANCA). We compared clinicopathological and prognostic features in 16 MN patients with crescents (crescent group) and 38 MN patients without crescents (control group), in the absence of secondary MN, anti-GBM antibodies, and ANCA. Median follow-up periods in the crescent and control groups were 79 and 50 months, respectively. Decreased estimated glomerular filtration rates (

A 75-year-old man who had undergone partial gastrectomy was referred to our hospital due to worsening leg edema, loose stools and malnutrition. Double balloon enteroscopy followed by insertion of an indwelling ileus tube was performed to investigate the microbial flora and for washing inside the blind loop. Trophozoites of Giardia were detected in the sampled fluid from the blind loop and DNA analysis disclosed an assemblage of genotype A-II of Giardia duodenalis. Treatment with oral metronidazole was effective. This case emphasizes the importance of a correct diagnosis when treating patients with blind loop syndrome in the digestive tract.

Background and Aim Capsule endoscopy (CE) is now widely accepted as a first-line diagnostic modality for obscure gastrointestinal bleeding (OGIB), with a high diagnostic yield compared to other modalities. However, even after negative CE examination, re-bleeding is often known to occur. The aim of the present study was to identify predictive factors of re-bleeding after negative CE, and to clarify the clinical utility of double-balloon enteroscopy (DBE) after negative CE for OGIB. Methods Two hundred and sixty patients who underwent CE for OGIB between October 2007 and September 2012 were included, and followed up for at least 1 year after CE examination. Demographic and clinical parameters associated with re-bleeding after negative CE were investigated. Results A total of 154 patients (59.2%) had negative findings. Thirteen of those patients (8.4%) had one or more re-bleeding episodes during the follow-up period. In comparing patients with and without re-bleeding, Cox hazard regression analysis revealed that advanced age was a predictive factor for re-bleeding after negative CE (hazard ratio 1.05 [1.01–1.10], P = 0.03). Subsequent DBE for reasons other than re-bleeding was carried out in 51 patients (33.1%). Mucosal lesions (ulcer or multiple erosions) were subsequently detected in seven patients (13.7%), and endoscopic therapies were carried out in two patients (3.9%). Conclusions In patients of advanced age, more extensive follow up is needed, even if the CE result is negative. In addition, DBE subsequent to negative CE may be useful to detect lesions that were overlooked on CE.

Diseases associated with metabolic syndromes are of major concern in developed countries. Nonalcoholic steatohepatitis (NASH) is one of the manifestations of metabolic syndrome in the liver. Previous studies have shown that NASH is also caused by malnutrition. In the present study, a case of malnutrition-associated NASH in a 66-year-old female with anorexia nervosa is reported. The patient had a body mass index (BMI) of only 11.1 kg/m2 and serum alanine aminotransferase levels of 1,495 IU/l. Steatohepatitis with fibrosis was confirmed by percutaneous liver needle biopsy. Total parenteral nutrition was conducted at first, followed by the administration of Stronger Neo-Minophagen C (a glycyrrhizin-containing preparation), ursodeoxycholic acid and prednisolone. The abnormal elevation of aminotransferase levels of the patient was prolonged and total bilirubin levels increased. Pioglitazone (15 mg/day), which has been identified to be effective for nonalcoholic steatohepatitis, was then administered. This resulted in marked reductions in aminotransferase and bilirubin levels within three months. Histological improvement of the liver was also confirmed by percutaneous liver needle biopsy after one year. The observations in the present case suggest that pioglitazone may be useful for the treatment of malnutrition-associated NASH.

OBJECTIVE The supplementation of oral branched-chain amino acid (BCAA) granules is known to improve energy metabolism in cirrhotic patients, but not those with hepatocellular carcinoma (HCC). We aimed to clarify whether BCAA granules improve energy metabolism in HCC patients after radiofrequency ablation (RFA). METHODS We performed a prospective cohort study (UMIN000004624) involving 40 HCC patients who underwent RFA at Kobe University Hospital. Indirect calorimetry and urinary/blood biochemical examinations were performed before and seven days after RFA. Blood biochemical examinations were also conducted three months after RFA. The patients treated with and without BCAA supplementation were compared, and univariate factors were statistically examined. RESULTS The non-protein respiratory quotient (npRQ) and albumin levels before RFA were significantly lower in the BCAA group than in the control group (p=0.024 and 0.005). The npRQ ratio (seven days after/before RFA) was significantly higher in the BCAA group than in the control group (p=0.019). In addition, the albumin ratio (three months after/before RFA) was significantly higher in the BCAA group than in the control group (p=0.018). CONCLUSION Supplementation with BCAA granules improves energy metabolism in addition to the liver function after RFA. Improvements in the liver function may result in consistently adequate treatment for HCC recurrence after RFA.

The patient was a 15-year-old girl with severe acute hepatitis. A liver biopsy showed the typical findings of autoimmune hepatitis (AIH). Subsequently, two lineages of cytopenia were found in the patient's peripheral blood. Hemophagocytosis by macrophages was observed in the bone marrow. Virus-, drug- and lymphoma-associated hemophagocytic syndrome (HPS) was ruled out. Therefore, the patient was diagnosed with autoimmune-associated HPS (AAHS). Following the administration of combination therapy with prednisolone and cyclosporine A, both the AAHS and AIH improved. This is the first report of AAHS originating from AIH. The patient was followed up for five years after treatment, and no disease recurrence was detected.

AIM To elucidate the factors associated with residual gastroesophageal reflux disease (GERD) symptoms in patients receiving proton pump inhibitor (PPI) maintenance therapy in clinical practice. METHODS The study included 39 GERD patients receiving maintenance PPI therapy. Residual symptoms were assessed using the Frequency Scale for Symptoms of GERD (FSSG) questionnaire and the Gastrointestinal Symptom Rating Scale (GSRS). The relationships between the FSSG score and patient background factors, including the CYP2C19 genotype, were analyzed. RESULTS The FSSG scores ranged from 1 to 28 points (median score: 7.5 points), and 19 patients (48.7%) had a score of 8 points or more. The patients’ GSRS scores were significantly correlated with their FSSG scores (correlation coefficient = 0.47, P < 0.005). In erosive esophagitis patients, the FSSG scores of the CYP2C19 rapid metabolizers (RMs) were significantly higher than the scores of the poor metabolizers and intermediate metabolizers (total scores: 16.7 ± 8.6 vs 7.8 ± 5.4, P < 0.05; acid reflux-related symptom scores: 12 ± 1.9 vs 2.5 ± 0.8, P < 0.005). In contrast, the FSSG scores of the CYP2C19 RMs in the non-erosive reflux disease patients were significantly lower than those of the other patients (total scores: 5.5 ± 1.0 vs 11.8 ± 6.3, P < 0.05; dysmotility symptom-related scores: 1.0 ± 0.4 vs 6.0 ± 0.8, P < 0.01). CONCLUSION Approximately half of the GERD patients receiving maintenance PPI therapy had residual symptoms associated with a lower quality of life, and the CYP2C19 genotype appeared to be associated with these residual symptoms.

Evaluating hepatic insulin resistance (IR) is the key to making a sensitive an accurate diagnosis of glucose intolerance. However, there is currently no suitable method to perform this procedure. This study was conducted to investigate whether the fasting (13)C-glucose breath test (FGBT) is useful as a convenient and highly sensitive clinical test for evaluating hepatic IR. Healthy nonobese subjects and a disease group consisting of patients with mild glucose intolerance were administered 100 mg (13)C-glucose after an overnight fast. A series of breath samples was collected until 360 minutes after ingestion, and the (13)CO2-to-(12)CO2 ratio was measured using an infrared spectrometer and was plotted as a kinetic curve of (13)C excretion. The area under the curve until 360 minutes (AUC360) of the (13)C excretion kinetic curve of the FGBT reflects the efficiency of energy production in the liver. First, we assessed the correlations between the AUC360 (or the (13)C excretion rate at 120 minutes) and the HOMA-IR and HbA1c levels as standard measurements of IR and diabetes mellitus (DM). There were relatively strong correlation coefficients (r = -0.49 to -0.81, r(2) = 0.24-0.66, P < 0.01; n = 35 males, n = 33 females). Second, we compared the AUC360 of healthy subjects and that of the patients with mild glucose intolerance. The AUC360 of the healthy subjects was consistently higher than that of the patients with mild glucose intolerance. The presence of IR or DM in males and females was diagnosed using cutoff values. The FGBT is a novel glucose metabolism test that can be used conveniently and safely to evaluate the balance of glucose metabolism in the liver. This test has excellent sensitivity for diagnosing alterations in hepatic glucose metabolism, particularly hepatic IR.

We previously showed that fibrocytes, a hematopoietic stem cell source of fibroblasts/myofibroblasts, infiltrated the colonic mucosa of a murine colitis model.We investigated whether fibrocytes were involved in the pathogenesis of Crohn's disease.Human surgical intestinal specimens were stained with anti-leukocyte-specific protein 1 and anti-collagen type-I (ColI) antibodies. Circulating fibrocytes in the human peripheral blood were quantified by fluorescence-activated cell sorting with anti-CD45 and anti-ColI antibodies. Cultured human fibrocytes were prepared by culturing peripheral CD14(+) monocytes.In the specimens of patients with Crohn's disease, the fibrocyte/total leukocyte percentage was significantly increased in inflammatory lesions (22.2 %, p0.01) compared with that in non-affected areas of the intestine (2.5 %). Interestingly, the percentage in fibrotic lesions was similar (2.2 %, p = 0.87) to that in non-affected areas. The percentages of circulating fibrocytes/total leukocytes were significantly higher in patients with Crohn's disease than in healthy controls. Both CXC-chemokine receptor 4(+) and intercellular adhesion molecule 1(+) fibrocyte numbers were significantly increased in Crohn's disease, suggesting that circulating fibrocytes have a higher ability to infiltrate injured sites and traffic leukocytes. In cultured fibrocytes, lipopolysaccharide treatment remarkably upregulated tumor necrosis factor (TNF)-α mRNA (17.0 ± 5.7-fold) and ColI mRNA expression (12.8 ± 5.7-fold), indicating that fibrocytes stimulated by bacterial components directly augmented inflammation as well as fibrosis.Fibrocytes are recruited early in the inflammatory phase and likely differentiate into fibroblasts/myofibroblasts until the fibrosis phase. They may enhance inflammation by producing TNF-α and can directly augment fibrosis by producing ColI.

Background & Aims Precisely what type of cells mainly contributes to portal fibrosis, especially in chronic viral hepatitis, such as hepatic stellate cells (HSCs) in the parenchyma or myofibroblasts in the portal area, still remains unclear. It is necessary to clarify the characteristics of cells that contribute to portal fibrosis in order to determine the mechanism of portal fibrogenesis and to develop a therapeutic target for portal fibrosis. This study was undertaken to examine whether LRAT+/CRBP-1+ HSCs contribute to portal fibrosis on viral hepatitis. Methods Antibodies to lecithin:retinol acyltransferase (LRAT), cellular retinol-binding protein-1 (CRBP-1) and widely ascertained antibodies to HSCs (alpha-smooth muscle actin, neurotrophin-3) and endothelial cells (CD31) were used for immunohistochemical studies to assess the distribution of cells that contribute to the development of portal fibrosis with the aid of fluorescence microscopy. A quantitative analysis of LRAT+/CRBP-1+ HSCs was performed. Results The number of LRAT+/CRBP-1+ HSCs was increased in fibrotic liver in comparison with normal liver in the portal area and fibrous septa. The number of double positive cells was less than 20% of all cells/field in maximum. Conclusion This study provides evidence that functional HSCs coexpressing both LRAT and CRBP-1 that continue to maintain the ability to store vitamin A contribute in part to the development of portal fibrogenesis in addition to parenchymal fibrogenesis in patients with viral hepatitis.

Pregenomic RNA (pgRNA) is generated from covalently closed circular DNA (cccDNA) and plays important roles in viral genome amplification and replication. Hepatic pgRNA and cccDNA expression levels indicate viral persistence and replication activity. This study was aimed to measure hepatic pgRNA and cccDNA expression levels in various states of hepatitis B virus (HBV) infection. Thirty-eight hepatocellular carcinoma (HCC) patients, including 14 positive for hepatitis B surface antigen (HBsAg) and 24 negative for HBsAg but positive for anti-hepatitis B core (anti-HBc) antibody, were enrolled in this study. In HBsAg-negative but anti-HBc-positive group, HBV-DNA was detected in 20 of 24 (83%) noncancerous liver tissues for at least two genomic regions based on polymerase chain reaction (PCR) analysis. pgRNA and cccDNA expression levels in occult HBV-infected patients were significantly lower than those in HBsAg-positive patients (P<0.001). pgRNA and cccDNA in cancerous tissues were also detected without significant difference from those in noncancerous tissues. In conclusion, cccDNA and pgRNA are detected and represented HBV replication not only in noncancerous but also in cancerous liver tissues. In addition, the replication is shown in not only patients with HBsAg-positive but also occult HBV-infected patients, suggesting the contribution to HCC development.

Measures of seasonal influenza control are generally divided into two categories: pharmaceutical and non-pharmaceutical interventions. The effectiveness of these measures remains unclear, because of insufficient study sample size and/or differences in study settings. This observational epidemiological study involved all elementary schoolchildren in Matsumoto City, Japan, with seasonal influenza during the 2014/2015 season. Questionnaires, including experiences with influenza diagnosis and socio-demographic factors, were distributed to all 29 public elementary schools, involving 13,217 children, at the end of February 2015. Data were obtained from 10,524 children and analyzed with multivariate logistic regression analysis. The result showed that vaccination (odds ratio 0.866, 95% confidence interval 0.786–0.954) and wearing masks (0.859, 0.778–0.949) had significant protective association. Hand washing (1.447, 1.274–1.644) and gargling (1.319, 1.183–1.471), however, were not associated with protection. In the natural setting, hand washing and gargling showed a negative association, which may have been due to inappropriate infection control measures or aggregating infected and non-infected children to conduct those measures. These results may indicate a pathway for influenza transmission and explain why seasonal influenza control remains difficult in school settings. The overall effectiveness of vaccination and mask wearing was 9.9% and 8.6%, respectively. After dividing children into higher (grades 4–6) and lower (grade 1–3) grade groups, the effectiveness of vaccination became greater in the lower grade group, and the effectiveness of wearing masks became greater in the higher grade group. These results may provide valuable information about designing infection control measures that allocate resources among children., Highlights • An influenza survey was conducted in all 29 elementary schools in Matsumoto City. • Vaccination and wearing of masks were effective in infection control. • Effectiveness of protection methods differed between old and young schoolchildren. • Communal hand washing and water gargling was associated with the risk of influenza.

A significant proportion of Crohn's disease (CD) patients receiving infliximab (IFX) maintenance therapy show loss of responsiveness despite a good initial response. The factors other than immunomodulators that prevent IFX dose escalation have yet to be fully elucidated. This study was performed to identify clinical factors or concomitant therapies associated with sustained response to IFX.Seventy-four consecutive CD patients who had successful IFX induction therapy between 2002 and 2010 underwent IFX maintenance therapy. Patients showing loss of response to IFX were treated with IFX intensification therapy. Factors involved in the sustained response to IFX were investigated retrospectively.After a median follow-up of 85 weeks, loss of response to IFX was observed in 30 (40.5%) cases. On logistic regression analysis, concomitant use of enteral nutrition (EN) therapy (elemental and/or polymeric formulas) was identified as an independent factor associated with sustained response to IFX. Receiver operating characteristic curve analysis indicated a cutoff value of 600 kcal/day. We divided the patients into the 'EN group' (≥ 600 kcal/day) and 'control group' (600 kcal/day). The cumulative number of loss of response was significantly lower in the EN group (odds ratio: 0.23, P = 0.0043). Kaplan-Meier analysis confirmed the significantly lower rate of loss of response in the EN group (P = 0.013). Multivariate hazard ratio was 0.37 (P = 0.025). Type of EN formula did not affect the results.Concomitant use of EN ≥ 600 kcal/day is likely to yield a sustained response to IFX in CD patients.

For patients chronically infected with hepatitis C virus (HCV), mutations in the non-structural 5A (NS5A) gene are important predictive factors for the response to interferon (IFN) therapy. In the present study, factor analysis of the therapeutic response of patients following pegylated IFN and ribavirin combination therapy was assessed in a multicenter study. Chronic HCV-infected patients with genotype 1b and high viral load (n=96, mean age 56.5 years; 59 males, 68 females) treated with pegylated IFN-α-2b and ribavirin combination therapy were enrolled. This study was conducted at Kobe University Hospital and 25 affiliated hospitals in Hyogo prefecture. Sixty-five patients (68%) completed treatment with both pegylated IFN and ribavirin at >80% of the weight-based scheduled dosages. Patients who reduced or terminated therapy were frequently aged women (mean age 60.8 years; 11 males, 17 females). Overall, a sustained viral response (SVR) was achieved in 42 (44%) patients out of 96. Based on per-protocol-based (PPB) analysis, the SVR rate in patients with ≥6 amino acid (aa) mutations in the IFN resistance-determining region (IRRDR) (75%) or ≥1 aa mutation in the IFN sensitivity-determining region (ISDR) (61%) was significantly higher than that in patients with

Genome-wide association studies have revealed a link between autophagy-related (ATG) genes and susceptibility to Crohn’s disease. This suggests underlying involvement of autophagy impairment in the pathogenesis of Crohn’s disease. This study was performed to investigate the pathophysiological importance of autophagy impairment in intestinal epithelial cells exposed to TNF-α. Human colonic epithelial cells (HT-29) and rat small intestinal epithelial cells (IEC-18) were used. Formation of phosphatidylethanolamine-conjugated microtubule-associated protein light chain 3 (LC3-II) was monitored as a marker of autophagy. Autophagy was inhibited using 3-methyladenine or short interfering RNA targeting ATG5 and ATG16L1. TNF-α treatment elicited a significant dose-dependent increase in LC3-II protein levels, thus autophagy is induced in the presence of TNF-α. Combined autophagy inhibition and TNF-α treatment induced a marked increase in the number of detached cells and a decrease in activated integrin β1 protein levels. Trypan blue staining indicated 70–80 % of the detached cells were alive, suggesting that these cells became detached not because they were killed but because of dysfunction of cellular adhesion. This is the first study indicating that intestinal epithelial cells with impaired autophagy lose their adhesive capacity in the presence of TNF-α. These observations indicate that impairment of autophagy leads to disruption of the intestinal epithelial cell layers in TNF-α-rich environments.

A liver neoplasm was found in a 63-year-old man with alcoholic liver disease. Sonazoid-enhanced ultrasonography (US) showed that the neoplasm was isoechoic at the early vascular phase and hypoechoic at the post-vascular phase. Gadolinium ethoxybenzyl-diethylenetriamine-enhanced magnetic resonance imaging (MRI) showed that the neoplasm was hypointense at the hepatobiliary phase. We suspected that it was a malignant tumor. By needle biopsy, however, the neoplasm was diagnosed as an inflammatory pseudotumor (IPT). We encountered a rare case of hepatic IPT, the differential diagnosis of which was difficult to distinguish from malignant tumor. Here, we report new US and MRI findings of hepatic IPT.

Background There is, as yet, no gold standard for making the diagnosis of acute onset autoimmune hepatitis (A-AIH). Novel histological characteristics have been reported, but etiologies other than AIH could show similar histological pattern. We attempted to determine what clinical characteristics we should consider as A-AIH different from other etiologies, and to whom histological characteristics should be applied for the diagnosis. Methods Clinical, biochemical, immunological and pathological features of 46 patients (35 women, mean age 55.9 ± 14.2 years) with non-severe A-AIH admitted to a community hospital between 2001 and 2015 were analyzed. Results Immunoglobulin G level was normal in 28%, and anti-nuclear antibody titer was < × 80 in 28%. Liver histology of 49% showed acute form and 51% chronic one. Centrilobular necrosis/collapse and/or plasma cell accumulation, rosette formation were characteristic for A-AIH. High levels of alanine aminotranferase persisted in 21 patients who could be observed for equal to or more than 4 weeks before the start of treatment. Conclusions Long persistence of high levels of alanine aminotransferase would be one of clinical features for considering A-AIH along with conventional features. Histological diagnostic features should be applied for such patients. Guidelines for diagnosing A-AIH should be urgently drawn up.

A field measurements of the blood pressure change of elderly with the room air temperature change during the bathing were made in winter of Sapporo and Fukui. Average room air temperatures of the undressing room in Sapporo versus Fukui were 19.8 versus 12.6 degree-C. The temperature differences between the living and the undressing room in Sapporo versus Fukui were 2.7 versus 6.5 degree-C, respectively. It would appear that the insulation performance of houses in Sapporo is higher that in Fukui. Therefore, over the 5 degree of air temperature drop between the living and the undressing room brings about a terrible rise in their blood pressure at the probability of 80 percent or more.

Liver organoids were reconstructed by mouse-immortalized hepatocytes and nonparenchymal cells (sinusoidal endothelial cells and hepatic stellate cells) in a radial-flow bioreactor (RFB). A biodegradable apatite-fiber scaffold (AFS) was used as a scaffold packed in the RFB, which enables three-dimensional cell cultures. The organoids cocultured in the RFB showed a liver-like structure with high-density layers of hepatocytes and the formation of vessel-like structures. A liver organoid consisting of three cocultured cells was transplanted under the kidney capsule (kidney group) or into the omentum (omentum group) using BALB/c nude mice. Transplanted liver organoids survived in the kidney or omentum. The expression of mRNAs of albumin, connexin 26 and 32, hepatocyte nuclear factor 4α, and glucose-6-phosphatase was increased in both groups at 8 weeks after transplantation in comparison to the pretransplant status. Tyrosine aminotransferase appeared only in the omentum group. The results suggested that the functions of liver organoids differed depending on the transplanted site in the recipient animals.

Garnet-type Li7-xLa3Zr2-xTaxO12 (LLZT) is considered a good candidate for the solid electrolyte in all-solid-state lithium batteries because of its reasonably high conductivity around 10&minus, 3 S cm&minus, 1 at room temperature and stability against lithium (Li) metal with the lowest redox potential. In this study, we synthesized LLZT with a tantalum (Ta) content of 0.45 via a conventional solid-state reaction process and constructed a Li/LLZT/Li symmetric cell by attaching Li metal foils on the polished top and bottom surfaces of an LLZT pellet. We investigated the influence of heating temperatures and times on the interfacial charge-transfer resistance between LLZT and the Li metal electrode. In addition, the effect of the interface resistance on the stability for Li deposition and dissolution was examined using a galvanostatic cycling test. The lowest interfacial resistance of 25 &Omega, cm2 at room temperature was obtained by heating at 175 &deg, C (5 &deg, C lower than the melting point of Li) for three to five hours. We confirmed that the current density at which the short circuit occurs in the Li/LLZT/Li cell via the propagation of Li dendrite into LLZT increases with decreasing interfacial charge transfer resistance.

The play ground of an orangutang in Sapporo Maruyama Zoo was renovated. The design was evaluated by comparison with behaviors of the orangutang and visitors in before and after the renovation. Following results were found: 1) 30 types of the orangutang's “behavioral repertries” appeared by 15 kinds of environmental enrichments. 2) Affiliative behaviors between the orangutang and visitors were encouraged; The orangutang prefers to stay on the concrete flat surface beside the window and the visitors come close to there, their communication through the windows was frequently observed. 3) The observation period of visitors increased 2.5 times as long as before.

Objective The aim of this study was to elucidate the effect of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) activating angiotensin receptor blocker (ARB) telmisartan and the non-PPAR-gamma activating ARB valsartan and candesartan on mycophenolic acid (MPA) pharmacokinetics in renal transplant recipients. Methods Recipients (n = 10 each group) were randomly given either 40 mg of telmisartan, 80 mg of valsartan or 8 mg of candesartan cilexetil for at least 6 months, and no ARB. Blood was sampled a year after transplantation. Results Dose-adjusted maximum and trough plasma concentration of MPA co-administered with telmisartan were the lowest in all groups. The mean dose-adjusted area under the concentration curve from 0 to 12 h (AUC(0-12)) and AUC(0-6) of MPA co-administered with telmisartan were significantly lower than that without ARB (98 vs. 138 ng x h/mL/mg, P = 0.0353 and 63 vs. 96 ng x h/mL/mg, P = 0.0305). Coadministration of valsartan and candesartan did not alter MPA pharmacokinetics. The AUC ratio of MPA glucuronide (MPAG)/MPA co-administered with telmisartan was higher than that without ARBs, but not significantly (14.2 vs. 9.1). The mean maximum and minimum plasma concentrations of telmisartan (40 mg) after oral administration were 84 and 15 ng/mL, respectively, and that of valsartan (80 mg) 2220 and 441 ng/mL, respectively. Plasma concentrations of candesartan in most transplant patients were not observed 19 h after oral administration of candesartan cilexeil (8 mg). Conclusions The degree of drug interaction between MPA and telmisartan was significantly greater than that between MPA and valsartan or candesartan. Uridine diphosphate-glucuronosyltransferase (UGT) 1A9 has been identified as a PPAR-gamma target gene. UGT induction by telmisartan might stimulate MPA glucuronidation. A combination of telmisartan and mycophenolate mofetil might require periodic monitoring of MPA.

The objective of this study was to elucidate the effects of CYP3A5, ABCB1, NR1I2 and NR3C1 BclI gene polymorphisms on prednisolone exposure for 65 Japanese renal transplant recipients in the maintenance stage one year after transplantation. Prednisolone dosage ranged from 2.5 to 15.0 mg day(-1) based on individual immunosuppressive states. The dose-adjusted area under the plasma concentration-time curve (AUC(0-24)) and the maximal plasma concentration (C(max)) of prednisolone in recipients with the BclI G allele were significantly higher than in those with the CC genotype (p = 0.029 and 0.021, respectively), but there were no significant differences in the half-life and T(max) of prednisolone between the two groups. None of the CYP3A5, ABCB1 or NR1I2 allele variants had any significant influence on the dose-adjusted AUC(0-24) of prednisolone. The NR3C1 BclI polymorphism was important in the inter-individual variability of prednisolone pharmacokinetics. The transactivation of the CYP3A4 promoter by prednisolone via the glucocorticoid receptor might be especially responsive for intestinal CYP3A4.

Mycophenolic acid (MPA), converted from the prodrug mycophenolate mofetil (MMF), is generated by intestinal and hepatic esterases. The role of carboxylesterase (CES) in MMF hydrolysis was examined in vitro using human liver microsomes. V(max) and K(m) values of MMF hydrolysis in pooled human liver microsomes were 1368 +/- 44 nmol min(-1) mg(-1) protein and 1030 +/- 65 microM, respectively. Hydrolytic activity was inhibited by the CES inhibitors phenylmethylsulfonylfluoride, bis-p-nitorophenylphosphate and diisopropylfluorophosphate, with IC(50) values of 77.1, 3.59 and 0.0312 microM, respectively. Eighty Japanese renal transplant recipients that received repeated-doses of MMF, tacrolimus and prednisolone,were evaluated for MPA pharmacokinetics 28 days after transplantation to investigate the relationship between MPA pharmacokinetics and CES2 genetic polymorphisms. No significant differences in MPA pharmacokinetics were observed between CES2 A4595G, C8721T orA-1548G genotype groups. CES2 allelic variants also did not appear to affect plasma MPA concentrations between individuals. In conclusion, the study demonstrated that while CES1 and/or CES2 are involved in the hydrolysis of MMF to MPA, CES2 allelic variants appeared to make only a minor contribution to inter-personal differences in MPA pharmacokinetics.

The old-fashioned orangutan house in Sapporo Maruyama Zoo was renovated with a concept of “environmental enrichment” in 2008 spring. The concept was stretched for not only the orangutan but also visitors and a zookeeper as well. In the outside field for the orangutan, there are soils, many natural plants, and some play equipments such as ropes, beds, seat swings, and ponds. On the other hand, at the observation area for visitors, they can see the movement and the condition of the orangutan at close range through the full-height glazing. In summer solar shading strategies as Sudare and louvers can provide the cool spots for the orangutan, visitors, and a zookeeper as well.