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This article discusses the use of Zokumeito (ZMT), a traditional medicine, for the rapid recovery of consciousness and physical function in a patient with cerebral infarction. ZMT is a combination of various herbs and is not available as an extract, so the authors prescribed similar medicines that contained some of the same ingredients. The patient, a 91-year-old male, showed significant improvement in his condition after starting the treatment, including increased vocalizations, the ability to sit in a wheelchair, and eventually being able to eat and drink without assistance. The authors note that further research is needed to fully understand the effects of ZMT in stroke patients. [Extracted from the article]

Background and Aim: Little is known about genetic mutations in the regenerated mucosa (RM) after endoscopic resection (ER) of esophageal carcinoma. Thus, this study investigates the status of genetic variation in RM after ER of esophageal squamous cell carcinoma (ESCC). Methods: The study cohort included 19 patients with ESCC. We used an esophageal carcinoma panel to identify target sequences for squamous cell carcinoma (SCC), background mucosa (BM), and RM after ER of ESCC. We used OncoKB to check whether each mutation was a putative driver. Results: We identified 77 mutations of 32 genes in SCC, 133 mutations of 34 genes in BM, and 100 mutations of 29 genes in RM. Putative driver mutations were identified in 20 mutations in 14 cases in SCC, 16 mutations in 10 cases in BM, and 7 mutations in 11 cases in RM. The rate of putative driver mutations to total mutations was significantly lower in RM (26% in SCC vs 12% in BM vs 7% in RM, P = 0.009). Additionally, the rate of cases with TP53 putative driver mutations was significantly lower in RM (63% in SCC vs 37% in BM vs 16% in RM, P = 0.011). The percentage of putative driver mutations and the percentage of cases with a putative driver of TP53 were significantly lower in RM. Conclusion: Esophageal RM after ER of ESCC could have a lower risk of carcinogenesis. [ABSTRACT FROM AUTHOR]

Background: Patients with acute cholangitis (AC) have increased mortality when associated with bacteremia. This study aimed to evaluate the predictive ability of serum lactate (Lac) for positive bacteremia in patients with acute cholangitis. Methods: In this single‐center, retrospective study, 138 consecutive patients with AC were analyzed. Their blood samples were collected and Lac was measured. Results: A total of 50 patients showed grade I, 50 showed grade II, and 38 showed grade III severity according to the Tokyo Guidelines 2018. Positive bacteremia was observed in 71 patients, of which 15 showed grade I, 25 showed grade II, and 31 showed grade III severity. Logistic regression analysis showed that Lac was a significant predictor of bacteremia. The area under the curve of Lac and procalcitonin (PCT) for bacteremia were 0.737 and 0.780, respectively. The optimal cutoff values for bacteremia were 17 mg/dL and 2.8 ng/mL, with sensitivity of 69.0% and 68.3%, respectively. Sensitivity of Lac and PCT for bacteremia in grade I was 58.3% and 25.0%, respectively. Three patients died from AC, all of whom were positive for bacteremia and hyperlactatemia. Conclusion: Lac is useful for predicting bacteremia in patients with AC. [ABSTRACT FROM AUTHOR]

This article discusses the successful treatment of menopausal arthralgia using a combination of two traditional Japanese herbal formulas, unkeito and boiogito. Menopausal arthralgia, characterized by joint pain, is a common symptom of menopause, but there is no established treatment for it. The three cases presented in the article showed significant improvement in arthralgia symptoms after treatment with unkeito and boiogito. The authors suggest that these herbal formulas may be effective for menopausal arthralgia that does not respond to nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen. Further research is needed to evaluate the effectiveness of this treatment. [Extracted from the article]

Background: Behavioural and psychological symptoms of dementia (BPSD) are challenging to manage, leading to caregiver burden and often to subsequent transfer of patients to a nursing home or psychiatric hospital for treatment. Eliciting favourable positive emotions should be an important goal in the treatment of negative emotions associated with BPSD. To date, no data have indicated that antipsychotic medications can improve positive emotions. BPSD are known to be associated with anxiety in patients with dementia. The traditional Chinese medicine Jia Wei Gui Pi Tang is officially indicated and approved for anxiety treatment in Japan. Methods: Here, we performed a multicentre, randomised, observer‐blind control study of the effect of Jia Wei Gui Pi Tang on BPSD in Alzheimer's disease (AD) patients. Patients with AD or AD with cerebral vascular disease were randomly divided into the Jia Wei Gui Pi Tang treatment group and the control group that received no traditional Chinese medicine. BPSD were scored using the Neuropsychiatric Inventory Nursing Home Version (NPI‐NH) and by favourable positive emotions using the Delightful Emotional Index (DEI). Results: A total of 63 participants (18 male and 45 female; mean age: 83.3 ± 6.0 years) were included in the study. Changes in NPI‐NH scores differed significantly between the two groups (one‐way analysis of variance, P < 0.001). Within the treatment group, there was a significant improvement in the NPI‐NH score from 29.8 ± 17.3 at baseline to 13.2 ± 9.4 at the endpoint (paired t‐test, P < 0.001), whereas there was no statistically significant change in the control group. Changes in DEI scores differed significantly between the two groups. Within the treatment group, there was a significant improvement in the DEI score from 24.3 ± 23.0 at baseline to 32.5 ± 21.2 at the endpoint (paired t‐test, P = 0.001), whereas there was no statistically significant change in the control group. Conclusion: The traditional Chinese medicine Jia Wei Gui Pi Tang significantly improved both BPSD and positive emotions. [ABSTRACT FROM AUTHOR]

Aim: The prognosis of patients with acute liver failure has improved dramatically in the past three decades due to advances in medical critical care and use of liver transplantation (LT) in Western countries, where the etiology of acute liver failure is different from that in Japan. We analyzed patients with fulminant hepatitis (FH) and late‐onset hepatic failure (LOHF) admitted to our unit over a 32‐year period to clarify the nature of Japanese patients with FH and LOHF. Methods: A total of 137 Japanese patients with FH and LOHF between 1986 and 2017 were analyzed for etiologies, disease types, treatment protocols, and outcome. Results: Of 137 patients, 124 were FH (53 acute type and 71 subacute type) and 13 LOHF. The major etiology was due to viral infections in 48% of patients. A total of 23.4% of patients recovered without LT, 7.3% received LT, and 69.3% died without LT. The number of patients showed rise and fall without an evident decrease during the period. Patients with autoimmune hepatitis increased after the establishment of autoimmune hepatitis criteria in 1999 (p < 0.001), and that with indeterminate cause decreased (p < 0.01). The mean age was older in the last decade than in the first decade (p = 0.036). Spontaneous and overall survival rates were not different during the period. Conclusions: The prognosis of our patients with FH and LOHF has not improved, probably because of aging and the increasing proportion of etiologies with poor prognosis and difficult‐to‐treat patients without response to medications regardless of advancement of clinical management, including artificial liver support devices and LT. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the validity of pathological diagnosis of early CRC (E‐CRC) from the genetic background by comparing data of E‐CRC to colorectal adenoma (CRA) and The Cancer Genome Atlas (TCGA) on advanced CRC (AD‐CRC). Methods: TCGA data on AD‐CRC were studied in silico, whereas by next‐generation sequencer, DNA target sequences were performed for endoscopically obtained CRA and E‐CRC samples. Immunohistochemical staining of mismatch repair genes and methylation of MLH1 was also performed. The presence of oncogenic mutation according to OncoKB for the genes of the Wnt, MAPK, and cell‐cycle–signaling pathways was compared among CRA, E‐CRC, and AD‐CRC. Results: The study included 22 CRA and 30 E‐CRC lesions from the Chiba University Hospital and 212 AD‐CRC lesions from TCGA data. Regarding the number of lesions with driver mutations in the Wnt and cell‐cycle–signaling pathways, E‐CRC was comparable to AD‐CRC, but was significantly greater than CRA. CRA had significantly more lesions with a driver mutation for the Wnt signaling pathway only, versus E‐CRC. Conclusions: In conclusion, the definition of E‐CRC according to the Japanese criteria had a different genetic profile from CRA and was more similar to AD‐CRC. Based on the main pathway, it seemed reasonable to classify E‐CRC as adenocarcinoma. The pathological diagnosis of E‐CRC according to Japanese definition seemed to be valid from a genetic point of view. [ABSTRACT FROM AUTHOR]

Aim: The aims of the present study were: (i) to examine the association between schizophrenia (SCZ) and 47, XXY or 47, XXX in a large case–control sample; and (ii) to characterize the clinical features of patients with SCZ with these X chromosome aneuploidies. Methods: To identify 47, XXY and 47, XXX, array comparative genomic hybridization (aCGH) was performed in 3188 patients with SCZ and 3586 controls. We examined the association between 47, XXY and 47, XXX and SCZ in males and females separately using exact conditional tests to control for platform effects. Clinical data were retrospectively examined for patients with SCZ with X chromosome aneuploidies. Results: Of the analyzed samples, 3117 patients (97.8%) and 3519 controls (98.1%) passed our quality control. X chromosome aneuploidies were exclusively identified in patients: 47, XXY in seven patients (0.56%), 47, XXX in six patients (0.42%). Statistical analysis revealed a significant association between SCZ and 47, XXY (P = 0.028) and 47, XXX (P = 0.011). Phenotypic data were available from 12 patients. Treatment‐resistance to antipsychotics and manic symptoms were observed in six patients each (four with 47, XXY and two with 47, XXX for both), respectively. Statistical analysis revealed that treatment‐resistance to antipsychotics, mood stabilizer use, and manic symptoms were significantly more common in patients with 47, XXY than in male patients without pathogenic copy number variations. Conclusion: These findings indicate that both 47, XXY and 47, XXX are significantly associated with risk for SCZ. Patients with SCZ with 47, XXY may be characterized by treatment‐resistance and manic symptoms. [ABSTRACT FROM AUTHOR]

Background and Aim: The effectiveness of cold snare polypectomy (CSP) for superficial non‐ampullary duodenal epithelial tumors (SNADETs) regarding long‐term outcomes is not fully clarified. This study aimed to investigate long‐term outcomes of CSP for SNADETs. Methods: Patients diagnosed with sporadic SNADETs and treated with CSP at Chiba University Hospital between March 2015 and May 2018 were retrospectively analyzed. Long‐term outcomes, short‐term outcomes, and adverse events were investigated. Results: In total, 35 patients with 46 lesions were included. The en‐bloc resection rate was 97.8%. Thirty‐seven lesions (80.4%) were diagnosed as adenomatous. The R0 resection rate for adenomatous lesions was 70.3%. Follow‐up investigations more than 12 months after CSP were completed for 35 adenomatous lesions (94.6%). The median observation period after CSP was 48 months. One patient whose observation period was only 3 months died from chronic heart failure with cardiac sarcoidosis 6 months after CSP. No patient died from SNADETs. The relapse‐free survival rate at 12 months after CSP was 97.1%. One recurrence (2.7%) was observed 12 months after CSP. We removed the recurrence lesion with CSP and cold forceps polypectomy. No new recurrence occurred within the observation period. No perforation or post‐operative bleeding occurred for CSP. Conclusions: Cold snare polypectomy for diminutive and small SNADETs is a safe and useful procedure with a high en‐bloc resection rate and long‐term local control capability. [ABSTRACT FROM AUTHOR]

Background and Aim: It is unclear whether second‐generation narrow‐band imaging (NBI) improves colorectal adenoma detection in clinical practice. We aimed to evaluate the ability of NBI to detect adenomas in academic and community hospitals. Methods: This observational, multicenter study was conducted in four academic and four community hospitals between July 2018 and April 2019. We enrolled patients aged ≥ 20 years who underwent colonoscopy for screening, polyp surveillance, or diagnostic workup. The primary endpoint was the adenoma detection rate (ADR) between NBI (NBI group) and white‐light imaging colonoscopies (WLI group) after propensity score (PS) matching. Results: Of 1831 patients analyzed before PS matching, the NBI and WLI groups included 742 and 1089 patients, respectively. After PS matching, 711 pairs from both groups were analyzed. ADR and the mean number of adenomas per patient did not differ significantly between the NBI and WLI groups (43.5% vs 44.4%, P = 0.71; 0.90 ± 1.38 vs 0.91 ± 1.40, P = 0.95, respectively). Academic hospitals showed higher ADR in the NBI group (60.5% vs 53.8%), whereas community hospitals showed higher ADR in the WLI group (35.8% vs 40.5%). In the NBI group, ADR was significantly higher among NBI‐screening‐experienced endoscopists than among NBI‐screening‐inexperienced endoscopists (63.2% vs 39.2%, P < 0.001). The mean number of flat and depressed lesions detected per patient was significantly higher with NBI than with WLI (0.62 ± 1.34 vs 0.44 ± 1.01, P = 0.035). Conclusions: Second‐generation NBI could not surpass WLI in terms of ADR based on patient recruitment from both academic and community hospitals but improved the detection of easily overlooked flat and depressed lesions. [ABSTRACT FROM AUTHOR]

Somatic mutations including the background mucosa in patients with Lugol‐voiding lesions (LVLs) are still not well known. The aim of this study was to evaluate the somatic mutations of the background mucosa in patients with LVLs (Squamous cell carcinoma (SCC), intraepithelial neoplasia (IN), and hyperplasia). Twenty‐five patients with LVLs (9 with SCC, 6 with IN, and 10 with hyperplasia) were included. A targeted sequence was performed for LVLs and background mucosa using an esophageal cancer panel. Each mutation was checked whether it was oncogenic or not concerning OncoKB. In LVLs, TP53 was the most dominant mutation (80%). Furthermore, 72% of TP53 mutations was putative drivers. In background mucosa, NOTCH1 was the most dominant mutation (88%) and TP53 was the second most dominant mutation (48%). Furthermore, 73% of TP53 mutations and 8% of NOTCH1 mutations were putative drivers. Putative driver mutations of TP53 had significantly higher allele frequency (AF) in SCC than in IN and hyperplasia. Conversely, putative driver mutations of NOTCH1 did not have a significant accumulation of AF in the progression of carcinogenesis. Furthermore, in SCC, AF of TP53 mutations was significantly higher in LVLs than in background mucosa, but not in IN and hyperplasia. Regarding NOTCH1, a significant difference was not observed between LVLs and background mucosa in each group. The background mucosa in patients with LVLs already had putative driver mutations such as TP53 and NOTCH1. Of these two genes, TP53 mutation could be the main target gene of carcinogenesis in esophageal SCC. Clinical Trials registry: UMIN000034247. [ABSTRACT FROM AUTHOR]

Genomic defects with large effect size can help elucidate unknown pathologic architecture of mental disorders. We previously reported on a patient with schizophrenia and a balanced translocation between chromosomes 4 and 13 and found that the breakpoint within chromosome 4 is located near the LDB2 gene. We show here that Ldb2 knockout (KO) mice displayed multiple deficits relevant to mental disorders. In particular, Ldb2 KO mice exhibited deficits in the fear‐conditioning paradigm. Analysis of the amygdala suggested that dysregulation of synaptic activities controlled by the immediate early gene Arc is involved in the phenotypes. We show that LDB2 forms protein complexes with known transcription factors. Consistently, ChIP‐seq analyses indicated that LDB2 binds to > 10,000 genomic sites in human neurospheres. We found that many of those sites, including the promoter region of ARC, are occupied by EGR transcription factors. Our previous study showed an association of the EGR family genes with schizophrenia. Collectively, the findings suggest that dysregulation in the gene expression controlled by the LDB2‐EGR axis underlies a pathogenesis of subset of mental disorders. Synopsis: The LDB2 gene is mapped in the breakpoint of a balanced chromosomal translocation seen in a patient with schizophrenia. This study provides a role of LDB2 and transcriptional regulation exerted by the "LDB2‐EGR axis" in the pathogenesis of mental disorders. LDB2 forms protein complexes with known transcription regulators such as the LHX and SSBP family proteins.ChIP‐seq analysis identified more than 10,000 LDB2 binding sites, which contained consensus DNA binding sequence for the EGR family proteins at high proportion.Dysregulation of LDB2 induces modulation in synaptic function via synapse‐related genes such as ARC.A potential role of the "LDB‐EGR axis" in the pathogenesis of mental disorders is suggested. [ABSTRACT FROM AUTHOR]

Kraepelin expected that the neuropathological hallmark of schizophrenia would be identified when he proposed the concept of dementia praecox 120 years ago. Although a variety of neuropathological findings have been reported since then, a consensus regarding the pathology of schizophrenia has not been established. The discrepancies have mainly been ascribed to limitations in the disease definition of schizophrenia that accompanies etiological heterogeneity and to the incompleteness of the visualization methodology and technology for biochemical analyses. However, macroscopic structural changes in the schizophrenia brain, such as volumetric changes of brain regions, must entail structural changes to cells composing the brain. This paper overviews neuropathology of schizophrenia and also summarizes recent application of synchrotron radiation nanotomography (nano‐CT) to schizophrenia brain tissues. Geometric parameters of neurites determined from the 3‐D nano‐CT images of brain tissues indicated that the curvature of neurites in schizophrenia cases is significantly higher than that of controls. The schizophrenia case with the highest curvature carried a frameshift mutation in the glyoxalase 1 gene and exhibited treatment resistance. Controversies in the neuropathology of schizophrenia are mainly due to the difficulty in reproducing histological findings reported for schizophrenia. Nano‐CT visualization using synchrotron radiation and subsequent geometric analysis should shed light on this long‐standing question about the neuropathology of schizophrenia. [ABSTRACT FROM AUTHOR]

Background and Aim: Cold snare polypectomy (CSP) is a safe treatment for colorectal adenomas. However, the R0 resection rate is not sufficiently high because of inadequate resection of muscularis mucosa. We hypothesized that CSP in an underwater environment could improve this procedure by helping to safely achieve resection containing the muscularis mucosa. We have named this procedure underwater cold snare polypectomy (UCSP). We aimed to investigate the efficacy and safety of UCSP for colorectal adenomas. Methods: Between May 2017 and April 2018, patients diagnosed with colorectal adenomas <9 mm underwent UCSP. After follow‐up colonoscopy 3 weeks later, the patients post‐UCSP scars were biopsied. Outcomes were compared with those of a historical control group who underwent conventional CSP in our previous study using propensity score‐matching methods. Results: Overall, 224 lesions in 65 patients were prospectively resected by UCSP. Pathologically, 209 lesions were adenomas (4.5 ± 1.5 mm) including one intramucosal carcinoma. Only one pathological residual adenoma was identified, but there was no significant difference in the residual rate between the UCSP and CSP groups (both 1.0%). No complications were observed. R0 resection rate and rate of area containing the muscularis mucosa in the UCSP group were significantly higher than those in the CSP group (80.2% vs 32.7%, P < 0.001; 50.0% vs 35.3%, P = 0.015). Conclusion: Underwater cold snare polypectomy for diminutive and small colorectal adenomas was safe and effective from the perspective of pathological complete resection, which is likely facilitated by achieving an adequate depth of resection. [ABSTRACT FROM AUTHOR]

Background and Aim: Venous thromboembolism (VTE) is a common complication of inflammatory bowel disease (IBD). The aim of the present study was to identify predictors of VTE in hospitalized patients with IBD. Methods: Patients with IBD who were hospitalized from February 2015 to March 2016 at the Chiba University Hospital were included. VTE was detected using enhanced computed tomography, and VTE onset within 2 months after admission was assessed. Predictors of VTE onset were investigated with clinical factors during hospitalization. Availability of the Caprini risk assessment model and Padua prediction score at the time of admission was also assessed. Results: Seventy‐two patients with IBD were hospitalized, and central venous catheters were placed in 43 of the 72 patients. During the observation period, VTE occurred in six patients (8.3%); however, none died as a result of the condition. Cox proportional hazards regression analysis identified D‐dimer values on admission as a risk factor that was highly associated with VTE onset (hazard ratio = 1.590; 95% confidence interval, 1.132–2.233; P = 0.007) and significantly predicted the occurrence of VTE using the receiver operating characteristic curve (P = 0.005, area under the curve = 0.893). However, Caprini risk assessment model and Padua prediction scores were not useful tools for predicting VTE onset in patients with IBD. Conclusion: In hospitalized patients with IBD, D‐dimer values were highly associated with VTE onset. Therefore, measurement of D‐dimer values on admission is critical for the management of thromboembolic complications in patients with IBD. [ABSTRACT FROM AUTHOR]

Background: The clinical course of ulcerative colitis (UC) is characterized by repeated episodes of relapse and remission. We hypothesized that biomarkers that help distinguish refractory UC patients who are in remission using strong anti‐immunotherapy could contribute in preventing the overuse of corticosteroids for treatment. Here, we clarified novel autoantibodies for UC patients in remission as clinical indicators to distinguish between refractory and non‐refractory UC. Methods: Antigen proteins recognized by serum antibodies of patients with UC in remission were screened using the protein array method. To validate the results, AlphaLISA was used to analyze the serum antibody titers with candidate protein antigens. Serum samples from 101 healthy controls, 121 patients with UC, and 39 patients with Crohn's disease were analyzed. Results: Of 66 candidate protein antigens screened by ProtoArray™, six were selected for this study. The serum titers of anti‐poly ADP‐ribose glycohydrolase (PARG), anti‐transcription elongation factor A protein‐like 1, and anti‐proline‐rich 13 (PRR13) antibodies were significantly higher in patients with UC than in healthy controls. Anti‐PARG and anti‐PRR13 antibody titers were significantly higher in patients with refractory UC than in patients with non‐refractory UC. There were no significant differences in any antibody titer between the active and remission phases. Conclusions: The serum titers of anti‐PARG, anti‐transcription elongation factor A protein‐like 1, and anti‐PRR13 antibodies were elevated in patients with UC. Anti‐PARG and anti‐PRR13 antibody titers may be novel clinical indicators for detecting refractory UC in patients in remission. [ABSTRACT FROM AUTHOR]

The title of this gastrointestinal session is "Kampo treatment for functional dyspepsia: Focusing on I rikkunshito i ", and the discussion will focus on I rikkunshito i . I Rikkunshito i is one of the Kampo formulas with the most fully elucidated mechanism of action, and research on I rikkunshito i related to the appetite-promoting hormone ghrelin is actively discussed at international conferences every year. [Extracted from the article]

Aim The aim of this clinical trial was to obtain proof of concept for high-dose pyridoxamine as a novel treatment for schizophrenia with enhanced carbonyl stress. Methods Ten Japanese schizophrenia patients with high plasma pentosidine, which is a representative biomarker of enhanced carbonyl stress, were recruited in a 24-week, open trial in which high-dose pyridoxamine (ranging from 1200 to 2400 mg/day) was administered using a conventional antipsychotic regimen. Main outcomes were the total change in Positive and Negative Syndrome Scale score and the Brief Psychiatric Rating Scale score from baseline to end of treatment at week 24 (or at withdrawal). Results Decreased plasma pentosidine levels were observed in eight patients. Two patients showed marked improvement in their psychological symptoms. A patient who harbors a frameshift mutation in the Glyoxalase 1 gene also showed considerable reduction in psychosis accompanied with a moderate decrease in plasma pentosidine levels. A reduction of greater than 20% in the assessment scale of drug-induced Parkinsonism occurred in four patients. Although there was no severe suicide-related ideation or behavior, Wernicke's encephalopathy-like adverse drug reactions occurred in two patients and were completely suppressed by thiamine supplementation. Conclusion High-dose pyridoxamine add-on treatment was, in part, effective for a subpopulation of schizophrenia patients with enhanced carbonyl stress. Further randomized, placebo-controlled trials with careful monitoring will be required to validate the efficacy of high-dose pyridoxamine for these patients. [ABSTRACT FROM AUTHOR]

Background: Corticosteroid (CS) has been introduced in most acute liver failure (ALF) patients for the purpose of suppressing pro‐inflammatory cytokines in Japan where a shortage of donor livers exists, whereas CS use is evaluated to be no benefit in Western countries. In the present study, we aimed to clarify the association between infectious complications and CS use in ALF, and determine when to evaluate treatment response and consider the timing for switching to liver transplantation (LT). Methods: Corticosteroid was administered to patients in the early stage prospectively. Clinical and biochemical features of 110 adult patients were analyzed. Results: Corticosteroids were administered to 78 (71%) patients. The duration between start of CS and onset of infection was 17 ± 10 days. Multivariate analysis revealed that infection was associated with age >50 years (P = 0.034) and T‐BIL >15 mg/dl (P < 0.001), and not with CS use (P = 0.10). Accumulative incidence of infection was not different between patients with and without CS (P = 0.18). Conclusions: Corticosteroid use did not significantly increase the incidence of infection. Two weeks after introduction of CS is a critical point for evaluating treatment response, avoiding infectious complications and switching to LT. Highlight Aiming to clarify the association between infectious complications and corticosteroid use in acute liver failure, Yasui and colleagues showed that corticosteroid use did not significantly increase the incidence of infection and that two weeks after corticosteroid initiation was a critical point for evaluating treatment response and switching to liver transplantation. [ABSTRACT FROM AUTHOR]

Background: Autoimmune hepatitis (AIH) is one of major etiologies of acute liver failure (ALF), and the survival rate without liver transplantation (LT) of patients with fulminant AIH is especially poor worldwide. We investigated the clinicopathological features of infectious complications in autoimmune ALF retrospectively and tried to determine when to continue corticosteroid (CS) treatment or abandon it for LT. Methods: Twenty patients with autoimmune ALF, comprising five severe hepatitis, 13 fulminant hepatitis and two late onset hepatic failure, were analyzed. Results: Corticosteroids were administered to 19 patients. Seventeen infectious complications were observed in 12 patients. The median (range) duration between the introduction of CS and onset of infection was 15 (10–41) days. There were no significant differences in clinicobiochemical features between patients with and without infection. Of 20 patients, eight (40%) recovered without LT, four (20%) received LT and eight (40%) died without LT. Dead or transplanted patients had more advanced liver failure on admission than recovered ones (P < 0.01). Conclusions: Two‐week after the introduction of CS is a critical point for avoiding infectious complications. Therefore, we should have evaluated efficacy of CS and performed LT by then at the latest in case of failure to improve. Highlight Fujiwara and colleagues reveal that the critical point for switching to liver transplantation without infectious complications in autoimmune acute liver failure is two weeks after the start of corticosteroid treatment. It is crucial to evaluate corticosteroid efficacy and, if no improvement is seen, to perform liver transplantation by that time. [ABSTRACT FROM AUTHOR]

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Background Pulmonary vein isolation (PVI) has become an important option for treating patients with atrial fibrillation (AF). Periesophageal nerve (PEN) injury after PVI causes pyloric spasms and gastric hypomotility. This study aimed to clarify the impact of PVI on gastric motility and assess the prevalence of gastric hypomotility after PVI. Methods Thirty consecutive patients with AF underwent PVI under luminal esophageal temperature (LET) monitoring. The 13 C-acetate breath test was conducted before and after the procedure for all patients (PVI group). Gastric emptying was evaluated using the time to peak concentration of 13 CO 2 ( T max ). This test was also conducted in another 20 patients who underwent catheter ablation procedures other than PVI (control group). Results The number of patients with abnormal T max (≥75 min) increased from seven (23%) to 13 (43%) and from three (15%) to five (25%) after the procedure in the PVI group and control group, respectively. The mean T max was longer after PVI than before PVI (64±14 min vs. 57±15 min, p =0.006), whereas there was no significant difference before and after the procedure in the control group. However, no significant difference in Δ T max was observed between the two groups ( p =0.27). No patients suffered from symptomatic gastric hypomotility. Conclusions Asymptomatic gastric hypomotility occurred more often after PVI. However, the average impact of PVI on gastric motility was minimal. [ABSTRACT FROM AUTHOR]

Aim The outcome of acute liver failure (ALF) is influenced by its etiology, making etiological consideration of ALF important. However, specific etiology could not be identified in 30-40% of adult patients in a Japanese nationwide survey. We examined our patients with severe (SH) and fulminant hepatitis (FH) of indeterminate etiology for the better understanding of ALF. Methods We investigated 106 adult patients with SH or FH including 24 of indeterminate etiology between 2000 and 2013, retrospectively. Results Of 24 patients, 12 were men. Seventeen were SH and seven FH (three FH acute type and four FH subacute type). Eighty-three percent of patients were positive for antinuclear antibody. Seventeen recovered without liver transplantation (LT), two received LT and five died without LT. Histology of 15 patients showed a pattern of acute hepatitis (massive necrosis in four, submassive necrosis in one, severe acute hepatitis in two and acute hepatitis in eight). The involvement of immune-mediated liver injury was histologically suggested in some patients. Conclusion There was no large cluster of etiology in our patients with indeterminate cause. The causes of ALF of indeterminate etiology were the mixture of various minor or rare ones, if precise diagnosis of acute AIH was done. Outcome of our patients with indeterminate cause was not poor if they were treated as early as possible after the diagnosis of severe disease. Careful examination of unknown viral infection, drugs, toxins, undefined metabolic disorders and histology may help detect some of these etiologies. [ABSTRACT FROM AUTHOR]

ABSTRACT Case Patients with dysphagia frequently suffer from aspiration pneumonia, are frequently hospitalized, and are often deprived of the joys of eating. Although dysphagia is life-threatening, treatment for dysphagia is still limited. Recently, the effectiveness of hangekobokuto ( Banxia-houpo-tang in Chinese; HKT) for dysphagia has attracted attention. We treated two dysphagic patients with HKT and evaluated deglutition before and after HKT treatment on imaging. Outcome The first patient was a 69-year-old alcoholic liver-cirrhosis patient who was diagnosed with dysphagia after hospital admission, and the second patient was a 92-year-old aspiration pneumonia patient. After treating the chief complaint, HKT ( TJ-16) extract (7.5 g/day) was given and continued indefinitely. Deglutition before and after HKT commencement was evaluated on video endoscopy and video fluoroscopy, respectively. Deglutition after the treatment was monitored visually. Conclusion Deglutition improved after HKT treatment, as judged on endoscopy and fluoroscopy. [ABSTRACT FROM AUTHOR]

Aim Older age has been widely believed to be associated with a poor prognosis of acute liver failure. We aimed to evaluate the impact of older age on outcomes of Japanese patients with severe and fulminant hepatitis in an era of a highly aging society. Methods We investigated 105 consecutive adult patients with fulminant hepatitis ( FH) or severe hepatitis ( SH) admitted to our liver unit between 2000 and 2013, consisting of 14 elderly patients (≥65 years) and 91 younger ones (<65 years). Results In elderly patients, the proportion of women was greater ( P < 0.001), the levels of aspartate aminotransferase and lactate dehydrogenase on admission were lower ( P = 0.011 and P = 0.010, respectively), and the survival rate without liver transplantation was lower ( P = 0.024) than younger ones. Two of seven SH and all seven FH elderly patients died, whereas all 45 SH and 16 of 46 FH younger patients recovered. Seventy-one percent of elderly patients had underlying diseases with medications, and 57% had additional complications after the start of treatment for acute liver failure. Patients aged 70 years or more showed even poorer prognoses than younger ones and those aged 65-69 years ( P = 0.0052 and P = 0.036, respectively). Conclusion Older age was associated with a poor prognosis of patients with SH and FH. One of the reasons other than complications and loss of organ reserve by aging would be that elderly patients consulted us at a more advanced stage of illness than younger ones. [ABSTRACT FROM AUTHOR]

Background: There has existed important differences in the definition of acute liver failure (ALF) between Japanese criteria and those of other countries. The novel diagnostic criteria for ALF in Japanese patients were established by the Intractable Hepato‐Biliary Diseases Study Group of Japan, in order to correspond to those for ALF in Europe and the USA. We prospectively diagnosed our ALF patients based on this novel criteria, and discussed the etiology by a fixed point observation. Methods: We investigated the etiology of 54 adult inpatients and outpatients with ALF between 2010 and 2012. Results: Of 54 patients, 36 were ALF without coma, 17 ALF with coma and one late onset hepatic failure. The etiology was due to viral infections in 38.9%, autoimmune hepatitis in 11.1%, drug‐induced liver injury in 13.0%, etiologies without hepatitis in 29.6% (circulatory disturbance in 18.5%, infiltration of the liver by malignant cells in 7.4%, and metabolic diseases in 3.7%) and indeterminate causes in 7.4%. Conclusions: Circulatory disturbance was the most frequent etiology according to the novel criteria. Indeterminate etiology was less observed in our study than the nation‐wide survey with significance (P = 0.0014). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Appropriate biological treatment and psychosocial support are essential to achieve and maintain recovery for patients with schizophrenia. Despite extensive efforts to clarify the underlying disease mechanisms, the main cause and pathophysiology of schizophrenia remain unclear. This is due in large part to disease heterogeneity, which results in biochemical differences within a single disease entity. Other factors include variability across clinical symptoms and disease course, along with varied risk factors and treatment responses. Although schizophrenia's positive symptoms are largely managed through treatment with atypical antipsychotics, new classes of drugs are needed to address the unmet medical need for improving cognitive dysfunction and promoting recovery of negative symptoms in these patients. Accumulation of toxic reactive dicarbonyls, such as methylglyoxal, are typical indicators of carbonyl stress, and result in the modification of proteins and the formation of advanced glycation end products, such as pentosidine. In June 2010, we reported on idiopathic carbonyl stress in a subpopulation of schizophrenia patients, leading to a failure of metabolic systems with plasma pentosidine accumulation and serum pyridoxal depletion. Our findings suggest two markers, pentosidine and pyridoxal, as beneficial for distinguishing a specific subgroup of schizophrenics. We believe that this information, derived from in vitro and in vivo studies, is beneficial in the search for personalized and hopefully more effective treatment regimens in schizophrenia. Here, we define a subtype of schizophrenia based on carbonyl stress and the potential for using carbonyl stress as a biomarker in the challenge of overcoming heterogeneity in schizophrenia treatment. [ABSTRACT FROM AUTHOR]

Aim Acute liver failure ( ALF) is a worldwide problem despite its rare incidence because of its extremely high mortality. There are no beneficial therapies except for emergency liver transplantation for ALF. However, in Japan where the problem of a shortage of donor livers still remains, therapies other than transplantation must be further investigated for patients with ALF. Our aim was to elucidate the efficacy of high-dose corticosteroid ( CS) in decreasing liver enzyme levels in the early stage of ALF. Methods Thirty-one consecutive Japanese patients with viral ALF in the early stage were prospectively examined for their clinical and biochemical features and treatment responses during 2 weeks after the start of treatment. Nineteen were treated with high-dose methylprednisolone, and 12 having clinical and biochemical backgrounds with no significant difference were treated without CS. Results The aspartate aminotransferase : alanine aminotransferase ratio became lower in patients treated with CS than in controls ( P < 0.05). Fifteen of 19 patients in the CS group and eight of 12 in the control group recovered ( P = 0.36). Hepatitis B viral infection and advanced liver damage at the start of treatment were associated with poor prognosis ( P < 0.05). Complications during the therapy were not greater in the CS group than control ( P = 0.64). Conclusion The introduction of high-dose CS in the early stage of ALF was effective in suppressing the destruction of hepatocytes. CS-treated patients showed slightly higher survival rates and slightly more improved liver regeneration than controls, although the differences were not statistically significant. [ABSTRACT FROM AUTHOR]

Background and Aim Gastric ulcer healing is a complex process involving cell proliferation and tissue remodeling. Sonic hedgehog ( Shh) activates the Shh signaling pathway, which plays a key role in processes such as tissue repair. Shh and interleukin 1β ( IL1β) have been reported to influence the proliferation of gastric mucosa. We evaluated the relationships between the speed of gastric ulcer healing and the levels of expression of Shh and IL1β. Methods The study included 45 patients (mean age 71.9 ± 9.0 years; M/ F, 30/15) who underwent endoscopic submucosal dissection ( ESD) for gastric cancer, followed by standard dose of oral proton-pump inhibitor for 4 weeks. Subsequently, the size of ESD-induced artificial ulcers were measured to determine the speed of gastric ulcer healing, and regenerating mucosa around the ulcers and appropriately matched controls were collected from patients by endoscopic biopsy. Polymerase chain reaction (PCR) array analysis of genes in the Shh signaling pathway was performed, and quantitative reverse transcription (RT)-PCR was used to measure IL1β mRNA. Results The levels of Shh and IL1β mRNA were 3.0 ± 2.7-fold and 2.5 ± 2.5-fold higher, respectively, in regenerating mucosa of artificial ulcers than in appropriately matched controls, with the two being positively correlated (r = 0.9, P < 0.001). Shh (r = 0.8, P < 0.001) and IL1β (r = 0.7, P < 0.005) expression was each positively correlated with the speed of gastric ulcer healing, but multivariate analysis showed that Shh expression was the only significant parameter ( P = 0.045). Conclusions Expression of Shh was correlated with the speed of gastric ulcer healing, promoting the regeneration of gastric mucosa. [ABSTRACT FROM AUTHOR]

Aim: Periodic surveillance colonoscopy is required for patients with ulcerative colitis to detect colitis-associated dysplasia at an early stage. However, sometimes colonoscopy may damage the fragile mucosa of patients with ulcerative colitis. The aim of this study was to devise a new method of surveillance colonoscopy for patients with mild to moderate ulcerative colitis. Methods: The 'flicking method' of colonoscope insertion was recently developed by our team. It is a completely novel method that involves using the elastic force of the colonoscope to introduce it into the deeper regions while using colon mucosa patterns as a guide. The subjects were 66 hospital outpatients with ulcerative colitis who underwent colonoscopies during a 2-year period, from April 2006 to March 2008, with both the conventional insertion method and the flicking method. Results: Cecal intubation rate, insertion time, patient pain level, change in number of defecations pre- and post-colonoscopy, and change in severity pre- and post-colonoscopy were compared between the conventional and flicking methods. The flicking method was superior in all respects. Conclusions: The flicking method is a novel colonoscope insertion method that is regarded as particularly useful in cases when the intestinal mucosa is fragile, as is the case with ulcerative colitis patients. [ABSTRACT FROM AUTHOR]

Aim: Recently, the number of acute hepatitis A cases has decreased in Japan. However, six patients with acute liver failure caused by hepatitis A virus (HAV) have been admitted to Chiba University Hospital, Japan, in the last 18 months, between 2010 and June 2011. The aim of this study is to characterize the recent HAV genotypes from an urban hospital in Japan and to compare the clinical differences. Methods: Hepatitis A virus RNA was detected by strand-specific reverse transcription. Then, HAV VP1/2A regions were amplified by nested polymerase chain reaction (PCR). Sequences were directly determined and phylogenetic trees were constructed for determining HAV subgenotypes. Results: Analysis of these HAV genomes revealed that 4 and 2 belonged to subgenotypes IA and IIIA, respectively. Conclusions: Fujiwara et al. reported a frequency of HAV subgenotype IIIA of only 2.1% in Japan. We conclude that HAV subgenotype IIIA might be widespread in our country. [ABSTRACT FROM AUTHOR]

Background and Aim: We investigated the prognosis of patients with C-viral chronic liver disease (C-CLD) according to the efficacy of interferon (IFN) therapy in a long-term retrospective cohort study. Methods: Of 721 patients with C-CLD who underwent liver biopsy between January 1986 and December 2005, 577 were treated with IFN, and 221 of these patients achieved sustained virological response (SVR) with a follow-up period of 9.9 ± 5.3 years. Results: The annual rate of HCC development was 2.71%/year, 2.31%/year, and 0.24%/year in untreated, non-SVR, and SVR patients, respectively. Multivariate Cox proportional regression analysis showed that the risk of HCC development was significantly lower in SVR patients than in untreated or non-SVR patients; moreover, this risk was similar in non-SVR patients and untreated patients. The annual mortality rate in overall death was 3.19%/year, 1.98%/year, and 0.44%/year in untreated, non-SVR, and SVR patients, respectively. Multivariate Cox proportional hazards regression analysis showed that the SVR status reduced the risk ratio for overall death to 0.173, whereas the non-SVR status did not significantly reduce the risk ratio. Conclusions: The risk ratio of overall death and HCC development was significantly reduced in SVR patients, whereas no significant reduction was found in non-SVR patients in a long-term cohort study. [ABSTRACT FROM AUTHOR]

Objective: On the basis of the hypothesis that copy number mutations of the genes encoding myelin compact proteins are responsible for myelin disorders in humans, we have explored the possibility of copy number mutations in patients with Charcot-Marie-Tooth disease (CMT) whose responsible genes remain undefined. Methods: A family with 6 affected members in 3 consecutive generations, presenting with motor and sensory demyelinating polyneuropathy, was investigated. Characteristic clinical features in this pedigree include Adie pupils and substantial intrafamilial variability in the age at onset, electrophysiological findings, and clinical severity. Nucleotide sequence analyses of PMP22, MPZ, or GJB1 and gene dosage study of PMP22 did not reveal causative mutations. Hence, we applied a custom-designed array for comparative genomic hybridization (CGH) analysis to conduct a comprehensive screening of copy number mutations involving any of the known causative genes for CMT other than PMP22. Results: The array CGH analyses revealed increased gene dosage involving the whole MPZ, and the flanking genes of SDHC and C1orf192. The gene dosage is estimated to be 5 copies. This mutation showed complete cosegregation with the disease phenotype in this pedigree. Interpretation: The increased gene dosage of MPZ and increased expression level of MPZ mRNA emphasize the important role of the dosage of the MPZ protein in the functional integrity of peripheral nerve myelin in humans, and provide a new insight into the pathogenic mechanisms underlying CMT. ANN NEUROL 2012;71:84-92 [ABSTRACT FROM AUTHOR]

After the establishment of the international criteria of autoimmune hepatitis (AIH) in 1999 and the recognition of acute onset AIH, the diagnosis of patients with fulminant type of AIH came to be made. We diagnosed autoimmune fulminant liver failure based on the criteria, and discussed the etiology of fulminant hepatitis (FH) and late onset hepatic failure (LOHF), and the characteristics of autoimmune fulminant liver failure. We investigated the etiology of 95 consecutive adult patients with FH or LOHF admitted to our liver unit between 1990 and 2009. Clinical and biochemical features, therapies and outcomes were examined in patients with AIH after 2000. Of 95 patients, 85 were FH and 10 LOHF. The etiology was due to viral infections in 51.6% (hepatitis A virus in 7.4%, hepatitis B virus in 43.2% and hepatitis E virus in 1.1%), AIH in 15.8%, drug allergy-induced in 12.6%, and unknown causes in 20.0%. The rate of patients with AIH increased significantly between 2000 and 2009 compared to the rate between 1990 and 1999 ( P = 0.002). In recovered patients with AIH without transplantation after 2000, coma grade was lower, alanine aminotransferase level, prothrombin time activity and alfa-fetoprotein level were higher than in the others with statistical significance. AIH is not a rare cause of FH and LOHF, and the number of patients with unknown causes would surely decrease in concert with the precise diagnosis of AIH. [ABSTRACT FROM AUTHOR]

After hepatitis B virus (HBV) e antigen (HBeAg) seroconversion, HBV-DNA continues to replicate, and HBeAg-negative patients still face the risk of liver disease progression. We investigated the predictive factors for alanine aminotransferase (ALT) elevation, antiviral drug use, and hepatocellular carcinoma (HCC) occurrence in HBeAg-negative patients. Age, sex, ALT, platelet counts, HBV-DNA levels, genotype, antidiabetic drug use, body mass index, smoking, and alcohol consumption were analyzed for a total of 244 HBV carriers who were HBeAg-negative. Of 244 HBeAg-negative patients, 158 (64.8%) showed normal ALT levels at baseline. Multivariate Cox hazard regression analysis identified high HBV-DNA levels and high ALT at baseline as independent risk factors for ALT elevation in the patients with normal ALT at baseline. The threshold ALT and HBV-DNA levels were determined to be 31 IU/L and 5.3 logcopies/mL, respectively. Seventeen (7.0%) patients used antiviral drugs. Multivariate Cox hazard regression analysis identified high HBV-DNA levels (threshold, 5.7 log copies/mL), the use of antidiabetic drugs, and daily alcohol consumption at baseline as an independent risk factor for the use of antiviral drugs in HBeAg-negative patients. In 10 patients (4.1%), HCC was detected, and a low platelet count (threshold, 10.0 × 10/mm) was associated with the occurrence of HCC. This study identified predictors of future active liver disease in HBeAg-negative patients, i.e. ALT elevation, unavoidable use of antiviral drugs, and occurrence of HCC. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) genotype C and the basic core promoter (BCP) mutations were reported to be associated with the development of hepatocellular carcinoma (HCC). In this study the full sequences of HBV genomes were analyzed in order to find the other predictors of HCC development. We determined the full sequences of HBV genomes in 24 genotype C carriers who developed HCC (HCC group) at the beginning of follow-up and at the time of HCC diagnosis, and 20 patients who did not develop HCC (non-HCC group) served as a control. The number of nucleotide and amino acid substitutions in most regions was higher in the HCC group than in the non-HCC group, and the following substitutions and deletions were found more frequently in the HCC group than in the non-HCC group: G1317A and T1341C/A/G in the X promoter region were detected in 13 and six of the HCC cases, four and none of the non-HCC cases, respectively; and pre-S2 deletion was detected in eight HCC and none of the non-HCC cases. Compared with the wild type X promoter, the mutant type X promoters, M1 (G1317A), M2 (T1341C), and M4 (T1341G) showed increases in activity of 2.3, 3.8, and 1.4 times, respectively, in HepG2 cells. Substitutions and deletion of nucleotides of the HBV genome, especially the pre-S2 deletion and G1317A and T1341C/A/G mutations may be useful markers for predicting the development of HCC. ( Cancer Sci 2007; 98: 1921–1929) [ABSTRACT FROM AUTHOR]

A 23-year-old Japanese woman was brought to the emergency department about 6.5 h after taking liquid and later a half tablet purchased on the street. About 4.5 h prior to presentation, she displayed excited and disorganized behavior. On examination, she was not alert or oriented, with a Glasgow Coma Scale score of 13, did not answer any questions from doctors while smirking and looking around restlessly, and sometimes exhibited echolalia, imitating the speech of doctors. She was given intravenous infusion of fluid for 8 h, then discharged. Gas chromatography-mass spectrometry of urine revealed 5-methoxy-diisopropyltryptamine, 5-methoxy-N-methyltryptamine and an unidentified tryptamine. Identifying chemical products based solely on information of users is insufficient, and urinalysis is necessary in cases potentially involving designer drugs. [ABSTRACT FROM AUTHOR]

In gastric cancer, increasing numbers of genes have been reported to be silenced by aberrant methylation. However, global analysis of epigenetic inactivation in cancer cells has rarely been performed. For screening the genes upregulated by the demethylating agent 5-aza-2′-deoxycytidine (DAC), cDNA microarray analysis (AceGene®, containing 30,000 genes) was performed using gastric cancer cell lines (AGS, MKN74, MKN1, MKN45 and Kato3) treated with DAC. The candidate upregulated genes were confirmed by real-time PCR, and the methylation status of 5′CpG islands was determined by bisulfite DNA sequencing or methylation-specific PCR. Among the upregulated genes considered to have CpG island in their promoter regions, we selected 5 genes (BCL2L10, DKK1, DNAJD1, GAGED2 and NMU) that exhibited a greater than 3-fold increase in at least 2 cell lines. Of these, we could determine the methylation status of 5′CpG islands of BCL2L10, DKK1 and DNAJD1. 5′CpG of BCL2L10 and DNAJD1 was hypermethylated in 4 of 5 gastric cancer cell lines, whereas 5′CpG of DKK1 was hypermethylated in only 1 cell line. MSP analysis for BCL2L10 revealed that the CpG island was demethylated after DAC treatment. In addition, we observed that overexpression of BCL2L10 could promote apoptosis and growth-inhibitory effect in gastric cancer cell lines. In conclusion, some of the genes upregulated by DAC treatment may be transcriptionally repressed by promoter hypermethylation. These genes might be related to gastric carcinogenesis. In particular, the suppression of BCL2L10, which could induce apoptosis and inhibit proliferation of cancer cells, might be one of the underlying mechanisms for gastric carcinogenesis. © 2006 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Major law reforms in Japan established a new system of guardianship for adults that took effect from early 2000, coinciding with the introduction of Japan's new long-term care insurance scheme. The new legislation created a new form of advisership, alongside reforms to existing curatorship and guardianship, and introduced voluntary guardianship. Replacing the traditional system based on incompetence and quasi-incompetence, the new system is based on respecting the autonomy of a principal as far as possible, in common with developments in other countries. After setting the context of the reforms, this paper gives with an account of the reform process and then outlines the structure of the new provisions and reports on their early operation. In concluding, some observations are made on the application of the adult guardianship to consent to medical treatment on the part of patients with dementia, an issue that remains unresolved. [ABSTRACT FROM AUTHOR]

A prolonged severe hepatitis of unknown etiology was treated with Inchinko-to, a Chinese herbal medicine, and this case is herein described. Inchinko-to was given with ursodeoxycholic acid (UDCA) and glycyrrhizin. The improvement in the patient’s liver function seemed to be accelerated after the treatment, especially after stopping the administration of kanamycin sulfate which might possibly inhibit the conversion of geniposide, one of the constituents of Inchinko-to, to an active ingredient through the suppression of the bacterial growth in intestinal flora, suggesting the usefulness of Inchinko-to for treatment of severe hepatitis. [Copyright &y& Elsevier]

In the post-genome-sequencing era, full-length cDNA-sequence resources are extremely useful for functional analyses of genes. In addition, comprehensive gene profiling of human tissues at the mRNA level is also useful in understanding the molecular mechanisms of tissue-specific functions and disease pathogenesis. In this study, to obtain a wide variety of full-length cDNA clones derived from digestive tissues, numerous expressed sequence tags were generated from libraries enriched with full-length cDNAs. In total, 13 575 sequences were obtained from three cDNA libraries, which were constructed from tissues and cell lines of human liver, stomach, and pancreas. The integration of overlapping clones categorized the sequences into 5936 clusters (1666, 2746, and 2222 clusters in the liver, stomach, and pancreas, respectively). Of these, 1138 clones were scored as full-length cDNAs. Surprisingly, the redundant clones from all three tissues were assembled to show that only 101 genes (1.7% of the assembled 5936 genes) were shared. These results suggest that functional differences between tissues are probably related to their divergent gene expression profiles, and form a basis for understanding the molecular mechanisms underlying tissue-specific pathogenesis that are expressed in different organs. In addition, the full-length cDNAs obtained in this study should prove useful for future functional analyses of the genes expressed in digestive tissues. [Copyright &y& Elsevier]

Social dysfunctions are common in various psychiatric disorders, including depression, schizophrenia, and autism, and are long‐lasting and difficult to treat. The development of treatments for social impairment is critical for the treatment of several psychiatric disorders. “Amyloban 3399,” a product extracted from the mushroom Hericium erinaceus, markedly improves social dysfunctions in patients with treatment‐resistant schizophrenia and depression. However, the molecular mechanism(s) through which amyloban ameliorates social impairment remains unclear. To clarify this mechanism, in this study, we aimed to establish a mouse model of social defeat stress (SDS) and investigate the effects of amyloban on social deficits. Amyloban administration ameliorated social deficits and the dopamine system activity in SDS mice. These findings suggest that there is a possibility that amyloban may improve social deficits by suppressing the hyperactivation of the dopaminergic system. Amyloban may be an effective treatment for social dysfunctions associated with various psychiatric disorders. [ABSTRACT FROM AUTHOR]

Background and Aim Evidence regarding safety and efficacy of heparin-bridging therapy for colonoscopic polypectomy remains scarce. The aim of the present study was to evaluate the risk of post-polypectomy bleeding (PPB) in patients receiving heparin-bridging therapy. Methods We retrospectively reviewed the database of patients who underwent colonoscopic polypectomy with prophylactic clip closure between January 2007 and December 2014 at our institution. We evaluated patients receiving heparin-bridging therapy (HB group) compared with those who did not receive antithrombotic therapy (No-HB group). Results A total of 1421 polypectomies were carried out on 773 patients; 45 patients were in the HB group and 728 patients were in the No-HB group. The incidence of PPB per patient was significantly higher in the HB group (22.2% vs 1.9%, P < 0.0001), and multivariate analysis showed that heparin-bridging therapy was an independent risk factor for PPB (OR 9.80, 95% CI 4.23-22.3, P < 0.0001). In the HB group, the polyp size was not a risk factor for PPB (OR 0.67, 95% CI 0.19-2.26, P = 0.55); the incidence of PPB in lesions of <10 mm and ≥10 mm in size was 14.6% and 10.2% respectively. In contrast, that was a significant risk factor in the No-HB group (OR 4.71, 95% CI 1.41-21.3, P = 0.011). Activated partial thromboplastin time and international normalized ratio were in or under the therapeutic range in the HB group when PPB occurred. Conclusions Heparin-bridging therapy is associated with a high risk of PPB regardless of polyp size. [ABSTRACT FROM AUTHOR]

Background and Aim Proton pump inhibitors (PPI) are effective at healing artificial ulcers after endoscopic submucosal dissection (ESD) for gastric neoplasms; however, the efficacy of vonoprazan is not completely understood. The aim of the present study was to determine the healing effect of vonoprazan on artificial ulcers post-gastric ESD relative to PPI. Methods Thirty-five patients who underwent gastric ESD between April and November 2015 were treated with vonoprazan 20 mg/day for 4 weeks and subsequently underwent endoscopy for evaluation of ulcer size (V group). Ulcer contraction rate was determined by the following formula: ([ESD specimen size] - [ulcer size at 4 weeks after ESD])/(ESD specimen size) × 100%. We compared the results with those of a historical control group treated with esomeprazole 20 mg/day for 4 weeks after gastric ESD and subsequently measured their ulcer size (33 patients, E group) by propensity score-matching methods. Results Sixty-two subjects were enrolled after propensity score-matching. Ulcer contraction rate at 4 weeks after ESD in the V group was significantly higher than that of the E group (97.7 ± 3.2% vs 94.5 ± 6.7%, respectively, P = 0.025). Number of subjects with a scar-stage ulcer (100% contraction rate) tended to be higher in the V group relative to the E group (32% [10 of 31] vs 13% [4 of 31], respectively, P = 0.070, McNemar's chi-squared test). Conclusion Vonoprazan has a faster post-gastric ESD artificial ulcer contraction rate than esomeprazole. Vonoprazan may supersede PPI in treating post-ESD artificial ulcers of the stomach. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the case of a drug-naive patient with at-risk mental state (ARMS), who showed enhanced carbonyl stress.

A letter to the editor is presented in response to the article "Increased advanced glycation end-products (AGEs) assessed by skin autofluorescence in schizophrenia," by Y. Kouidrat and colleagues in the 2013 issue.

Presents a letter to the editor of the May 2002 issue of the 'Journal of Gastroenterology and Hepatology,' about subacute hepatic failure likely caused by benzbromarone.