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Vascular staplers are routinely used in laparoscopic liver resection, which has become a standard procedure in advanced medical facilities. Although previous reports have outlined the benefits of staple line reinforcement (SLR), its application in Glissonean pedicle transection during hepatic resection remains poorly studied. This study investigated surgical SLR as a tool to enhance staple line strength and improve perioperative hemostasis. Here, 10 patients who underwent laparoscopic liver resection using the Tri‐StapleTM2.0 Reinforced Reload were included. Patient characteristics, surgical details, and outcomes were assessed. The results demonstrated successful outcomes with no complications related to bile leakage or injuries during staple insertion. Overall, our findings suggest that SLR can be safely utilized in Glissonean pedicle transection during laparoscopic liver resections. Further studies are required to comprehensively evaluate its benefits compared with conventional surgical staplers. [ABSTRACT FROM AUTHOR]

This article examines the impact of working‐hour restrictions on the well‐being, performance, and education of medical residents in Japan. Despite Japan's plan to introduce new regulations for resident working hours by 2024, there is still an ongoing debate regarding their appropriateness. This review provides a comprehensive overview of the current regulations of resident working hours worldwide, with a specific focus on weekly hours. The varying regulations are highlighted, including the 80‐hour‐per‐week regulation in the United States and the 48‐h‐per‐week regulation in the European Union influencing other regions. The article also discusses the effectiveness of working‐hour restrictions on residents' mental health, with shorter working hours having potentially greater benefits. However, the impacts on medical safety and resident education are mixed, and further reduction in working hours must be carefully considered to avoid adverse effects. The planned changes to working‐hour limits for residents in Japan offer a unique opportunity to gain new evidence on the impact of such regulations, which will be of interest to policymakers and researchers worldwide. [ABSTRACT FROM AUTHOR]

A newly developed O‐glycosylated M‐hepatitis B surface antigen (HBsAgGi) measurement system can detect hepatitis B surface antigen (HBsAg) associated with infectious particles. We investigated the association of HBsAgGi levels with clinical parameters and a history of hepatocellular carcinoma (HCC) development in a cross‐sectional cohort analysis (Study 1) as well as the quantitative changes in HBsAgGi during nucleos(t)ide analogue (NA) therapy in a longitudinal cohort analysis (Study 2). A total of 124 patients with genotype C chronic HBV infection were analysed in Study 1 to evaluate correlations of HBsAgGi with conventional HBV markers and HCC history. Among those, 36 patients receiving NA therapy were enrolled in Study 2 for quantitative comparisons between pre‐treatment baseline and 48 weeks of NA therapy. In Study 1, serum HBsAgGi was significantly associated with HBsAg (r =.5857, p <.00001) and weakly but significantly correlated with HBV DNA (r =.2936, p =.001). Although HBsAgGi (p =.111) was comparable between HCC history (+) group and HCC history (−) group, the HBsAgGi/HBsAg ratio (p =.011) was significantly higher in HCC history (+) patients. In Study 2, HBsAgGi was significantly decreased after 48 weeks of NA therapy (p <.001). HBsAg findings were similar (p =.005) along with an HBV DNA reduction (p <.001). In the baseline hepatitis B e antigen (HBeAg) (+) subgroup, HBsAgGi decreased significantly between baseline and 48 weeks of NA (p =.005), while HBsAg was comparable (p =.051). Low HBsAg and high HBsAgGi were associated with a history of HCC development. HBsAgGi decreased significantly by 48‐week NA therapy. [ABSTRACT FROM AUTHOR]

Background and Aim: As the exact prevalence of portopulmonary hypertension (PoPH) and the etiology of chronic liver disease (CLD) remain unknown, the present study aimed to clarify these points in Japanese patients with CLD using symptom‐based questionnaire screening. Methods: Patients with CLD were asked to complete an eight‐item written questionnaire on pulmonary hypertension (PH) symptoms. If at least one item response was "yes," the patient was offered ultrasonic echocardiography (UCG). Patients identified as having an intermediate or high risk of PH by UCG were referred to a cardiologist for further evaluation, whereby a definitive diagnosis of PoPH was made using right heart catheterization (RHC) findings. Results: A total of 1111 patients with CLD completed the survey. Of the 566 symptomatic patients with at least one question answered as "yes," approximately half agreed to undergo UCG (n = 267). Compared with asymptomatic patients, symptomatic patients were significantly older, predominantly female, and more frequently exhibited cirrhosis. Based on UCG findings, 228, 12, and 8 patients had a low, intermediate, or high risk for PH, respectively. Intermediate‐/high‐risk patients showed significantly more advanced disease progression status than low‐risk patients. The frequencies of answer to the eight questions were comparable. Ultimately, three patients were diagnosed as having PoPH (1.1% of UCG cases), one with underlying hepatitis C virus (HCV) infection and two with primary biliary cholangitis (PBC). Conclusion: This symptom‐based PoPH screening study clarified the prevalence of PoPH in CLD patients according to a PH symptom questionnaire, UCG, and RHC. Patients with HCV and PBC may have a higher risk of PoPH. [ABSTRACT FROM AUTHOR]

Background: Hay fever is a common allergic disease, with an estimated worldwide prevalence of 14.4% and a variety of symptoms. This study assessed the minimal clinically important difference (MCID) of nasal symptom score (NSS), non‐nasal symptom score (NNSS), and total symptoms score (TSS) for app‐based hay‐fever monitoring. Methods: MCIDs were calculated based on the data from a previous large‐scale, crowdsourced, cross‐sectional study using AllerSearch, an in‐house smartphone application. MCIDs were determined with anchor‐based and distribution‐based methods. The face scale score of the Japanese Allergic Conjunctival Disease Standard Quality of Life Questionnaire Domain III and the daily stress level due to hay fever were used as anchors for determining MCIDs. The MCID estimates were summarized as MCID ranges. Results: A total of 7590 participants were included in the analysis (mean age: 35.3 years, 57.1% women). The anchor‐based method produced a range of MCID values (median, interquartile range) for NSS (2.0, 1.5–2.1), NNSS (1.0, 0.9–1.2), and TSS (2.9, 2.4–3.3). The distribution‐based method produced two MCIDs (based on half a standard deviation, based on a standard error of measurement) for NSS (2.0, 1.8), NNSS (1.3, 1.2), and TSS (3.0, 2.3). The final suggested MCID ranges for NSS, NNSS, and TSS were 1.8–2.1, 1.2–1.3, and 2.4–3.3, respectively. Conclusions: MCID ranges for app‐based hay‐fever symptom assessment were obtained from the data collected through a smartphone application, AllerSearch. These estimates may be useful for monitoring the subjective symptoms of Japanese patients with hay fever through mobile platforms. [ABSTRACT FROM AUTHOR]

Background: Crowned dens syndrome (CDS) is characterized by calcification around the odontoid process, accompanied by neck pain. Although CDS is supposedly rare, we regularly diagnose and manage this condition, indicating a perception gap between previous studies and our experience. The purpose of this study was to determine the annual incidence of CDS, time to diagnosis in CDS, as well as the features of CDS. Methods: The study design was a retrospective case series study conducted at eight teaching hospitals in Japan. We identified CDS cases from April 2013–March 2015. CDS was diagnosed when patients had acute onset of neck pain and CT showed calcification around the dens and when other diagnoses were unlikely. Results: Seventy‐two CDS cases were identified. Mean annual incidence was 4.6 ± 2.3 cases at each hospital. Among those with available data, 57 of 64 had limited rotation (89.1%). The diagnosis of CDS was made in general internal medicine or the emergency medicine department in 61 cases (84.7%). A total of 62 cases (86.1%) were diagnosed within 1 day of presentation, and the median time from initial presentation at the hospital to diagnosis was 0.0 days (25th–75th percentiles, 0.0–1.0). For treatment, NSAIDs were used in 56cases (77.8%) and acetaminophen in 20 cases (27.8%). Conclusion: CDS might be more common than has been reported to date. Time to diagnosis of CDS was within 1 day of visiting a teaching hospital. Cervical motion restriction is common in CDS and may be useful in establishing the diagnosis. [ABSTRACT FROM AUTHOR]

Background: The effect of duty hour (DH) restrictions on postgraduate residents' acquisition of clinical competencies is unclear. We evaluated the relationship between DHs and competency‐related knowledge acquisition using the General Medicine In‐training Examination (GM‐ITE). Methods: We conducted a multicenter, cross‐sectional study of community hospital residents among 2019 GM‐ITE examinees. Self‐reported average DHs per week were classified into five DH categories and the competency domains were classified into four areas: symptomatology and clinical reasoning (CR), physical examination and clinical procedure (PP), medical interview and professionalism (MP), and disease knowledge (DK). The association between these scores and DHs was examined using random‐intercept linear models with and without adjustment for confounding factors. Results: We included 4753 participants in the analyses. Of these, 31% were women, and 49.1% were in the postgraduate year (PGY) 2. Mean CR and MP scores were lower among residents in Category 1 (<50 h) than in residents in Category 3 (≥60 and <70 h; reference group). Mean DK scores were lower among residents in Categories 1 and 2 (≥50 and <60 h) than in the reference group. PGY‐2 residents in Categories 1 and 2 had lower CR scores than those in Category 3; however, PGY‐1 residents in Category 5 showed higher scores. Conclusions: The relationship between DHs and each competency area is not strictly linear. The acquisition of knowledge of physical examination and clinical procedures skills in particular may not be related to DHs. [ABSTRACT FROM AUTHOR]

Background: Burnout is a psychological syndrome consisting of emotional exhaustion, cynicism, and decreased professional efficacy. The Maslach Burnout Inventory (MBI) is widely used as the standard measure. However, the MBI is lengthy and not free to use, which makes it a less than ideal tool for regularly assessing burnout. The single question burnout measure (SMB) is a novel and simple measure of burnout, which is associated well with emotional exhaustion and has sufficient diagnostic performance for burnout. This study aimed to evaluate the concurrent and convergent validity of the Japanese version of the single‐item measure of burnout (SMB‐J) compared with the MBI. Methods: Ninety‐four medical residents volunteered to complete the MBI‐General Survey (MBI‐GS) and the SMB‐J. We assessed the concurrent (sensitivity and specificity) and convergent validity of the SMB‐J compared with the MBI‐GS. Results: The sensitivity for identifying burnout using the SMB‐J was 53.8%, and the specificity was 88.2%. The area under the receiver operating characteristic curve (AUC) was 0.71. MBI‐GS scores on the subscales of Emotional Exhaustion (r = 0.509, p < 0.0001) and Cynicism (r = 0.57, p < 0.0001) strongly correlated with the SMB‐J scores. Conclusions: We concluded that for identifying burnout among Japanese medical residents, the psychometric properties of the SMB‐J are comparable to those of the original version of the SMB. Although the SMB‐J has low sensitivity to detect burnout, it is more convenient to use than the MBI. [ABSTRACT FROM AUTHOR]

Aim: Accurate detection of the hepatic fibrosis stage is essential to estimate the outcome of patients with non‐alcoholic fatty liver disease (NAFLD). Many formulas, biomarkers, and imaging tests are being developed to predict advanced liver fibrosis without performing a liver biopsy. However, these tests do not have high efficiency in detecting early‐stage hepatic fibrosis. Therefore, we aimed to detect the presence of hepatic fibrosis (≥F1) merely by using only standard clinical markers. Methods: A total of 436 patients with NAFLD who underwent liver biopsy were retrospectively enrolled as the discovery cohort (316 patients) and the validation cohort (120 patients). Liver biopsy and laboratory data were matched to extract simple parameters for identifying ≥F1. Results: We developed a novel simplified ≥F1 detecting system, designated as 2‐Step PLT16‐AST44 method, where (1) PLT of 16 × 104/μl or less, or (2) PLT greater than 16 × 104/μl and AST greater than 44 U/L is determined as having ≥F1 fibrosis. The 2‐Step PLT16‐AST44 method had a sensitivity of 68%, a specificity of 90%, a positive predictive value (PPV) of 97%, a negative predictive value (NPV) of 40%, and an accuracy of 72% to detect ≥F1 fibrosis in the discovery cohort. Validation studies further supported these results. Despite its simplicity, the 2‐Step PLT16‐AST44 method's power to detect ≥F1 fibrosis in total NAFLD patients was comparable to hyaluronic acid, type 4 collagen 7S, FIB‐4, and APRI. Conclusions: We propose the 2‐Step PLT16‐AST44 method as a simple and beneficial early‐stage hepatic fibrosis detection system. [ABSTRACT FROM AUTHOR]

INTELLANCE‐J was a phase 1/2 study of a potent antibody‐drug conjugate targeting epidermal growth factor receptor (EGFR), depatuxizumab mafodotin (Depatux‐M), as a second‐ or first‐line therapy, alone or combined with chemotherapy or chemoradiotherapy in 53 Japanese patients with World Health Organization (WHO) grade III/IV glioma. In second‐line arms, patients with EGFR‐amplified recurrent WHO grade III/IV glioma received Depatux‐M plus chemotherapy (temozolomide) or Depatux‐M alone regardless of EGFR status. In first‐line arms, patients with newly diagnosed WHO grade III/IV glioma received Depatux‐M plus chemoradiotherapy. The study was halted following lack of survival benefit with first‐line Depatux‐M in the global trial INTELLANCE‐1. The primary endpoint was 6‐month progression‐free survival (PFS) in patients with EGFR‐amplified tumors receiving second‐line Depatux‐M plus chemotherapy. Common nonocular treatment‐emergent adverse events (TEAEs) with both second‐line and first‐line Depatux‐M included lymphopenia (42%, 33%, respectively), thrombocytopenia (39%, 47%), alanine aminotransferase increase (29%, 47%), and aspartate aminotransferase increase (24%, 60%); incidence of grade ≥3 TEAEs was 66% and 53%, respectively. Ocular side effects (OSEs) occurred in 93% of patients receiving second‐line Depatux‐M plus chemotherapy and all patients receiving second‐line Depatux‐M alone or first‐line Depatux‐M plus chemoradiotherapy. Most OSEs were manageable with dose modifications and concomitant medications. The 6‐month PFS estimate was 25.6% (95% confidence interval [CI] 11.4‒42.6), and median PFS was 2.1 months (95% CI 1.9‒3.9) with second‐line Depatux‐M plus chemotherapy in the EGFR‐amplified subgroup. This study showed acceptable safety profile of Depatux‐M alone or plus chemotherapy/chemoradiotherapy in Japanese patients with WHO grade III/IV glioma. The study was registered at ClinicalTrials.gov (NCT02590263). [ABSTRACT FROM AUTHOR]

This article is a response to a reader's comments on a study about distinguishing crowned dens syndrome (CDS) from acute meningitis. The authors acknowledge that there was no uniform indication for lumbar puncture in the study and that the decision to perform the procedure was at the discretion of the examining physician. They suggest that cervical rotation restriction, characterized by an inability to rotate the neck or pain with slow neck rotation, may be a characteristic finding of CDS. They hope that distinct clinical criteria for diagnosing CDS, including cervical rotation restriction, can be developed. The authors have stated that there are no conflicts of interest related to the article. [Extracted from the article]

We conducted a prospective multicenter trial to compare the usefulness of 11C‐methionine (MET) and 18F‐fluorodeoxyglucose (FDG) positron emission tomography (PET) for identifying tumor recurrence. Patients with clinically suspected tumor recurrence after radiotherapy underwent both 11C‐MET and 18F‐FDG PET. When a lesion showed a visually detected uptake of either tracer, it was surgically resected for histopathological analysis. Patients with a lesion negative to both tracers were revaluated by magnetic resonance imaging (MRI) at 3 months after the PET studies. The primary outcome measure was the sensitivity of each tracer in cases with histopathologically confirmed recurrence, as determined by the McNemar test. Sixty‐one cases were enrolled, and 56 cases could be evaluated. The 38 cases where the lesions showed uptake of either 11C‐MET or 18F‐FDG underwent surgery; 32 of these cases were confirmed to be subject to recurrence. Eighteen cases where the lesions showed uptake of neither tracer received follow‐up MRI; the lesion size increased in one of these cases. Among the cases with histologically confirmed recurrence, the sensitivities of 11C‐MET PET and 18F‐FDG PET were 0.97 (32/33, 95% confidence interval [CI]: 0.85‐0.99) and 0.48 (16/33, 95% CI: 0.33‐0.65), respectively, and the difference was statistically significant (P <.0001). The diagnostic accuracy of 11C‐MET PET was significantly better than that of 18F‐FDG PET (87.5% vs. 69.6%, P =.033). No examination‐related adverse events were observed. The results of the study demonstrated that 11C‐MET PET was superior to 18F‐FDG PET for discriminating between tumor recurrence and radiation‐induced necrosis. [ABSTRACT FROM AUTHOR]

Aims: Hepatocellular carcinoma (HCC) can still occur in hepatitis C virus (HCV) patients who have achieved a sustained virologic response (SVR), which remains an important clinical issue in the direct‐acting antivirals era. The current study investigated the clinical utility of the aMAP score (consisting of age, male, albumin–bilirubin, and platelets) for predicting HCC occurrence in HCV patients achieving an SVR by direct‐acting antivirals. Methods: A total of 1113 HCV patients without HCC history, all of whom achieved an SVR, were enrolled for clinical comparisons. Results: Hepatocellular carcinoma was recorded in 50 patients during a median follow‐up period of 3.7 years. The aMAP score was significantly higher in the HCC occurrence group than in the HCC‐free group (53 vs. 47, p < 0.001). According to risk stratification based on aMAP score, the cumulative incidence of HCC occurrence for the low‐, medium‐, and high‐risk groups was 0.14%, 4.49%, and 9.89%, respectively, at 1 year and 1.56%, 6.87%, and 16.17%, respectively, at 3 years (low vs. medium, low vs. high, and medium vs. high: all p < 0.01). Cox proportional hazard analysis confirmed aMAP ≥ 50 (hazard ratio [HR]: 2.78, p = 0.014), age≥ 70 years (HR: 2.41, p = 0.028), ALT ≥ 17 U/L (HR: 2.14, p < 0.001), and AFP ≥ 10 ng/mL (HR: 2.89, p = 0.005) as independent risk factors of HCC occurrence. Interestingly, all but one patient (99.5%) with aMAP less than 40 was HCC‐free following an SVR. Conclusion: The aMAP score could have clinical utility for predicting HCC occurrence in HCV patients achieving an SVR. [ABSTRACT FROM AUTHOR]

A limited understanding of intersubject and intrasubject variability hampers effective biomarker translation from in vitro/in vivo studies to clinical trials and clinical decision support. Specifically, variability of biomolecule concentration can play an important role in interpretation, power analysis, and sampling time designation. In the present study, a wide range of 749 plasma metabolites, 62 urine biogenic amines, and 1,263 plasma proteins were analyzed in 10 healthy male volunteers measured repeatedly during 12 hours under tightly controlled conditions. Three variability components in relative concentration data are determined using linear mixed models: between (intersubject), time (intrasubject), and noise (intrasubject). Biomolecules such as 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoate, platelet‐derived growth factor C, and cathepsin D with low noise potentially detect changing conditions within a person. If also the between component is low, biomolecules can easier differentiate conditions between persons, for example cathepsin D, CD27 antigen, and prolylglycine. Variability over time does not necessarily inhibit translatability, but requires choosing sampling times carefully. [ABSTRACT FROM AUTHOR]

Background: In patients with bronchial asthma and those with chronic obstructive pulmonary disease (COPD), inhalation therapy and rinsing of the mouth and the oropharynx by gargling ("RMOG") after inhalation are recommended. We performed a cross‐sectional audit aimed at investigating (a) the proportion of patients performing "RMOG" after inhalation and (b) storage place of patients' inhaler. Methods: Patients with bronchial asthma and those with COPD were asked by medical aids at outpatient visits whether they did "RMOG every time," "RMOG sometimes," or "no RMOG" after inhalation, and where they stored their inhaler. Results: During a six month study period up to September 2017, 330 consecutive patients with asthma and those with COPD were included in the study. Two hundred and thirty‐two (70.3%) of the 330 patients answered "RMOG every time" and 98 (29.7%) of them did "RMOG sometimes" and did "no RMOG." There was a difference in the proportion of patients performing RMOG after inhalation with patient age. With regard to the storage location of inhaler, we found the proportion of patients performing RMOG was higher in those who stored inhalers in a room with running water than in those who stored inhalers at other places. This difference was found in patients with both bronchial asthma and those with COPD. Conclusions: Further implementation of "patient education" on performing RMOG after inhalation for patients receiving inhaled medication is still necessary. Our results suggest that it is better to store inhalers in places where there is easy access to tap water used for RMOG. [ABSTRACT FROM AUTHOR]

Acute appendicitis is the most common general surgical problem encountered during pregnancy. Laparoscopic appendectomy (LA) is widely accepted as a minimally invasive procedure for acute appendicitis. However, LA during the third trimester is associated with problems, including technical difficulty, risk of preterm delivery, and fetal loss. We successfully managed three cases of LA during the third trimester between 2011 and 2016. None of the cases required conversion to an open procedure, and none of the patients had postoperative complications and/or fetal loss. We reviewed the literature using the PubMED database from 2007 to 2016 to acquire further evidence and identified 6 reports and 17 cases. The conversion rate was 11.8% (2 cases), the complication rate was 6.67% (1 case), and the preterm delivery rate was 20% (3 cases); no fetal loss was observed. Our study and literature review highlights the role of LA as a potentially feasible treatment approach for appendicitis during the third trimester. [ABSTRACT FROM AUTHOR]

ABSTRACT: Aim: Hangekobokuto, a kampo medicine, is considered effective against anxiety neurosis, amnesia, insomnia, and neurotic gastritis. The mechanism of action and verification of effect, however, remain to be confirmed. The aim of this study was therefore to confirm the effect of hangekobokuto for amelioration of aggressiveness and social behavior in a mouse stress model. Methods: Four‐week‐old male ddY mice were socially stressed by isolated rearing for 4 weeks. The control group was reared in a social group. Hangekobokuto was then given orally in drinking water to the isolation‐reared mice at a dose of 0% (purified water), 0.25% and 0.5% for 2 weeks. The socially reared control group was not given any treatment. Aggressiveness and social behavior were evaluated. Blood samples were obtained after the test, and serum corticosterone and interleukin (IL)‐6 were measured. The prefrontal region of the brain and the brainstem region were enucleated, and serotonin, dopamine and IL‐6 were measured. Results: Hangekobokuto dose‐dependently controlled the aggressive behavior induced by isolation stress, and the effect disappeared on 5HT1A receptor antagonist treatment. Blood corticosterone, increased by isolation stress, decreased with hangekobokuto treatment. Serotonin and dopamine in the prefrontal region, decreased by isolation stress, increased with hangekobokuto treatment. IL‐6 in the brainstem, increased by isolation stress, decreased dose dependently on hangekobokuto treatment. Conclusion: Hangekobokuto ameliorates aggressiveness induced by anxiety caused by stress. Furthermore, the mechanism of effect involves the serotonin system. [ABSTRACT FROM AUTHOR]

Abstract: This study was conducted to test our hypothesis that intramuscular fat (IMF) accumulation increases in pigs fed on a low lysine diet during the dark period than those fed on the same diet during the light period. Using barrows aged 6 weeks, we monitored whether serum glucose and insulin levels were affected by light conditions. Two diets with different levels of lysine, 0.78% (LL diet) and 1.37% (control diet) were prepared. Eight pigs were fed on the diet during the light period, while the remaining pigs were fed during the dark period. The pigs were fed either the LL diet or the control diet. Although IMF contents of Longissimus dorsi (LD) muscle were higher in the pigs fed on a LL diet (p < .05), the light conditions had no effect. Low dietary lysine caused reduction in serum glucose levels (p < .05) and serum insulin levels (p = .0613). However, they were also unaffected by the lighting conditions. To gain further insights, we determined the messenger RNA levels of insulin receptor, insulin receptor substrate 1, acetyl CoA carboxylase, and fatty acid synthase in LD and Rhomboideus muscles and in the liver. [ABSTRACT FROM AUTHOR]

Abstract: Background: Despite the presence of ganglion cells in the rectum, some patients have symptoms similar to those of Hirschsprung's disease. A consensus has yet to be established regarding the terminology for these diseases. We defined this group of diseases as “allied disorders of Hirschsprung's disease” and compiled these guidelines to facilitate accurate clinician diagnosis and provide appropriate treatment strategies for each disease. Methods: These guidelines were developed using the methodologies in the Medical Information Network Distribution System (MINDS). Of seven allied disorders, isolated hypoganglionosis; megacystis‐microcolon‐intestinal hypoperistalsis syndrome; and chronic idiopathic intestinal pseudo‐obstruction were selected as targets of clinical questions (CQ). In a comprehensive search of the Japanese‐ and English‐language articles in PubMed and Ichu‐Shi Web, 836 pieces of evidence related to the CQ were extracted from 288 articles; these pieces of evidence were summarized in an evidence table. Results: We herein outline the newly established Japanese clinical practice guidelines for allied disorders of Hirschsprung's disease. Given that the target diseases are rare and intractable, most evidence was drawn from case reports and case series. In the CQ, the diagnosis, medication, nutritional support, surgical therapy, and prognosis for each disease are given. We emphasize the importance of full‐thickness intestinal biopsy specimens for the histopathological evaluation of enteric ganglia. Considering the practicality of the guidelines, the recommendations for each CQ were created with protracted discussions among specialists. Conclusions: Clinical practice recommendations for allied disorders of Hirschprung's disease are given for each CQ, along with an assessment of the current evidence. We hope that the information will be helpful in daily practice and future studies. [ABSTRACT FROM AUTHOR]

Clinicians should be aware that gastrointestinal obstruction, especially due to achalasia, is one of the causes of aspiration pneumonia in young patients and consider performing additional CT scan imaging. Keywords: achalasia; aspiration pneumonia; dysphagia EN achalasia aspiration pneumonia dysphagia 195 196 2 05/05/22 20220501 NES 220501 In this case, a chest computed tomography scan of a young patient with pneumonia revealed esophageal obstruction, which led to the diagnosis of aspiration pneumonia due to achalasia. [Extracted from the article]

It remains challenging to develop alternatives, based on widely abundant elements, to highly active Pt catalysts for the hydrogen evolution reaction. Metal sulfide nanoparticles (NPs) are potential candidates for such catalysts because of their metallic features and intrinsic high surface area; however, their poor electrocatalytic activity, owing to the presence of surface ligands, is an obstacle to practical use. Here we report the selective synthesis of oleylamine (OAm)-stabilized Ni3S4 (Ni3S4/OAm) NPs. The insulating ligands were exchanged with S2− and loaded on electrodes by a layer-by-layer (LbL) assembly method with metal cation linkers. The enhanced catalytic properties were confirmed by electrochemical measurements. A LbL assembled film with Ni2+ as a linker (11 cycles) showed an overpotential of 555 mV@-4 mA cm−2 at pH 6.8 and a stable current density for 12 h. In addition, when this LbL assembly method was applied to a CdS/Cu(In,Ga)Se2 photocatalyst electrode, the resulting photoelectrode showed an enhanced photocurrent compared with that of the Ni3S4/OAm NPs-spin coated and bare photoelectrodes. These results indicate the versatility of LbL assembly for fabrication of ligand-free NP electrocatalyst films. [ABSTRACT FROM AUTHOR]

G-protein-coupled receptors ( GPCRs) are the largest family of integral membrane receptors with key roles in regulating signaling pathways targeted by therapeutics, but are difficult to study using existing proteomics technologies due to their complex biochemical features. To obtain a global view of GPCR-mediated signaling and to identify novel components of their pathways, we used a modified membrane yeast two-hybrid ( MYTH) approach and identified interacting partners for 48 selected full-length human ligand-unoccupied GPCRs in their native membrane environment. The resulting GPCR interactome connects 686 proteins by 987 unique interactions, including 299 membrane proteins involved in a diverse range of cellular functions. To demonstrate the biological relevance of the GPCR interactome, we validated novel interactions of the GPR37, serotonin 5- HT4d, and adenosine ADORA2A receptors. Our data represent the first large-scale interactome mapping for human GPCRs and provide a valuable resource for the analysis of signaling pathways involving this druggable family of integral membrane proteins. [ABSTRACT FROM AUTHOR]

Taste is a crucial factor of meat quality, and amino acids are important taste-active components in meat. Here, the effects of dietary lysine (Lys) content on taste-active components in meat, especially free glutamate (Glu), were investigated. Twenty-eight-day-old broilers ( Gallus gallus) were fed diets with graded Lys content of 90% or 100% of the recommended Lys requirement, (according to the National Research Council, ) for 10 days. Free amino acid content in meat and sensory scores of meat soup were estimated. Free Glu content, the main taste-active component of meat, was significantly increased by a reduction of dietary Lys. Compared with the Lys 100% group (control), free Glu concentrations of meat were increased by 35.7% in the Lys 90% group ( P < 0.05). In addition, free glycine, valine, isoleucine, leucine, histidine and threonine concentrations of meat were significantly increased in the Lys 90% group ( P < 0.05). Sensory evaluation of meat soup made from the Lys 100% and 90% groups indicated different meat tastes. Sensory scores of taste intensity, umami and kokumi tastes were significantly higher in the Lys 90% group. These results suggest that a reduction of dietary lysine increased free glutamate content in meat and improved its taste. [ABSTRACT FROM AUTHOR]

Pyridoxamine, a reactive carbonyl (RCO) scavenger, can ameliorate peritoneal deterioration in uremic peritoneal dialysis (PD) rats when given via dialysate. We examined the effects of scavenging circulating RCOs by oral pyridoxamine. Rats underwent nephrectomy and 3 weeks of twice daily PD either alone or with once daily oral pyridoxamine. PD solution was supplemented with methylglyoxal, a major glucose-derived RCO, to quench intraperitoneal pyridoxamine. Oral pyridoxamine achieved comparable blood and dialysate pyridoxamine concentrations, suppressed pentosidine accumulation in the blood but not in the mesenterium or dialysate, and reduced the increases in small solute transport and mesenteric vessel densities, with no effects on submesothelial matrix layer thickening or serum creatinine. Thus, reducing circulating RCOs by giving oral pyridoxamine with PD provides limited peritoneal protection. However, orally given pyridoxamine efficiently reaches the peritoneal cavity and would eliminate intraperitoneal RCOs. Oral pyridoxamine is more clinically favorable and may be as protective as intraperitoneal administration. [ABSTRACT FROM AUTHOR]

We compared interleukin-6 (IL-6) removal and induction between conventional polysulfone (Con) and TORAYLIGHT NV (NV) dialyzers in hemodialysis patients. Twenty patients on Con with high IL-6 concentrations (2.7-8.5 pg/mL) were randomized to Con or NV group. Dialyzer performance was determined in NV group while patients were on Con and after being switched onto NV. Erythropoiesis-stimulating agent (ESA) response index (ERI) was assessed every 4 months for one year. IL-6 clearance was comparable between Con and NV. IL-6 removal rates were comparable for the first 1 h, but were higher with NV for the entire session ( P = 0.03). Before-to-during-dialysis IL-6 concentration ratios were lower with NV on the venous side after the session ( P = 0.03). During the one-year study, hemoglobin was lower in Con group than in NV group at month 8 ( P = 0.046). ERI decreased in NV and increased in Con group, with a significant difference between the groups ( P = 0.002). NV and Con are comparable in removing IL-6 and both induce IL-6. However, the data suggest that NV induces less IL-6, which may reduce the risk of ESA hyporesponsiveness. [ABSTRACT FROM AUTHOR]

Introduction We studied the mortality risk of long term and new antipsychotic drug use in Alzheimer's disease (AD) patients in Japan to determine improved treatment protocols. Methods This 24-week prospective cohort study included 10,079 Japanese AD patients (female, 69%; average age, 81 years) under routine clinical care in 357 medical sites. The antipsychotic medication history was varied (63.7% were long-term users). Mortality rates and odds ratio were analyzed (initial 10 weeks and from 11–24 weeks). Results The antipsychotic exposed group with shorter treatment periods had a higher mortality risk compared to controls. The newly prescribed users (antipsychotic treatment started during the follow-up) showed increased mortality (9.4% during the 11–24 week period). Conclusions New use of antipsychotic drugs represents a distinct risk for mortality; those on long-term antipsychotic therapy seem to be at less risk. The warning issued 10 years earlier on antipsychotics use for AD patients should be reviewed. [ABSTRACT FROM AUTHOR]

The asymmetric synthesis of dragmacidin D ( 1) was completed in 10 steps. Its sole stereocenter was set by using direct asymmetric alkylation enabled by a C2-symmetric tetramine and lithium N-(trimethylsilyl)- tert-butylamide as the enolization reagent. A central Larock indole synthesis was employed in a convergent assembly of the heterocyclic subunits. The stereochemical evidence from this work strongly supports the predicted S configuration at the 6′′′ position, which is consistent with other members of the dragmacidin family of natural products. [ABSTRACT FROM AUTHOR]

Regulation of taste is important for improving meat quality and glutamate ( Glu) is one of the important taste-active components in meat. Here, the effects of dietary lysine ( Lys) content on taste-active components in meat, especially free Glu, were investigated. Fourteen-day-old broiler chicks ( Gallus gallus) were fed on diets containing 100% or 150% of the recommended Lys content for 10 days. Concentrations of free amino acids in plasma, muscle and liver were measured. The levels of messenger RNAs ( mRNAs) for enzymes related to Glu metabolism were determined in muscle and liver. The concentration of muscle metabolites was also determined. The free Glu content in muscle of chicks fed the Lys150% diet was increased by 44.0% compared with that in chicks fed the Lys100% diet ( P < 0.01). The mRNA level of lysine α-ketoglutarate reductase, which is involved in Lys degradation and Glu production, was significantly increased ( P < 0.05) in the Lys150% group. Metabolome analysis showed that the Lys degradation products, muscular saccharopine, pipecolic acid and α-aminoadipic acid, were increased in the Lys150% group. Our results suggest that free Glu content in muscle is regulated by Lys degradation. These results suggest that a short-term feeding of high- Lys diet could improve the taste of meat. [ABSTRACT FROM AUTHOR]

We have investigated the IR photoluminescence (PL) behavior of Cu-doped β-FeSi2 nanocrystals (β-NCs) embedded in Si layers. The diffusion rate of Cu atom was controlled by annealing. The most appropriate condition brought the largest intensities of both the intrinsic A band emission at 0.803 eV by 214% and the acceptor related C band emission at ∼0.75 eV by 582% in comparison with those of non-doped β-NCs. Rutherford backscattering spectrometry (RBS) revealed increase of Cu atoms in the Si layer with β-NCs with increasing the anneal duration. The C band enhancement surely is originated from increase of a density of state at acceptor levels relating to increase of Cu in β-lattice. Photocarrier injection PL measurements (PCI-PL) reveal that the enhancement of the A band emission may be attributed to a controlled migration process of holes with a repeated trap process due to Cu-doping into the Si phase. This dynamic condition leads to an increase of valence band offset at the β-NCs/Si heterointerfaces where the migration of holes from the β-NCs to Si is prevented, so that a radiative recombination rate can be enhanced. (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

Temozolomide ( TMZ) is an oral alkylating agent which is widely used in the treatment of glioblastoma ( GBM) and is composed of astrocytic and/or oligodendroglial tumors, and the evaluation of O6-methylguanine DNA methyltransferase ( MGMT) expression is important to predict the response to TMZ therapy. In this study, we conducted immunohistochemical analysis of 117 cases of Japanese GBM including 19 cases of GBM with oligodendroglioma component ( GBMO), using a scoring system for quantitative evaluation of staining intensity and proportion of MGMT, and performed survival analysis of these patients. Immunohistochemically, 55 cases (47%) were positive for MGMT with various intensities and proportions (total score ( TS) ≥ 2), while 62 cases (53%) were negative ( TS = 0). The distribution of MGMT expression pattern was not affected by any clinicopathological parameters such as the histological subtype ( GBM vs. GBMO), age and gender. The survival analysis of these patients revealed that the minimal expression of MGMT ( TS ≥ 2) was a significant unfavorable prognostic factor ( P < 0.001) as well as resectability ( P = 0.004). Moreover, multivariate analysis showed that minimal MGMT expression in GBM was the most potent independent predictor for progression free survival ( P < 0.001) and also overall patient survival ( P < 0.001). This is the first report employing the scoring system for both staining intensity and proportion to evaluate immunohistochemical MGMT expression in GBM. In addition, our results emphases the clinicopathological values of the immunohistochemical approach for MGMT expression in glioma patients as a routine laboratory examination. [ABSTRACT FROM AUTHOR]

Aims It remains debatable whether early intervention for psychosis is capable of meeting the needs of at-risk subjects. The aims of this study were to describe the actual impact of interventions on subjective difficulties and to explore the factors that may be associated with a poor outcome. Methods Participants were help-seeking outpatients at a university hospital who met the Criteria of Prodromal Syndromes. Changes in the symptoms, subjective experience and current insight were assessed using the Scales of Prodromal Symptoms, the Subjective Well-being under Neuroleptics, and the Scale to Assess Unawareness of Mental Disorder, respectively. Global functioning, social functioning and subjective quality of life were evaluated using the Global Assessment of Functioning Scale, the Social Functioning Scale, and the WHO- Quality of Life 26, respectively. These measures were assessed both at baseline and after 1 year. Results Forty-six patients agreed to participate. Of the 27 patients who completed the reassessment at the follow-up point, 13 patients (48%) showed little improvement in their positive/negative symptoms, subjective well-being or awareness of their symptoms. Additionally, less severe negative symptoms, more severe general symptoms and lower subjective well-being at baseline significantly predicted a deterioration of positive/negative symptoms after 1 year. Conclusion Our findings suggest that the current strategy for reducing psychosis risk based on positive symptoms should be reappraised. [ABSTRACT FROM AUTHOR]

We investigated the effects of a low crude protein ( CP) diet and a low CP diet supplemented with synthetic essential amino acids ( EAA) on the meat quality of broiler chickens. Twenty-one-day-old chickens were assigned to one of three diets: control, low CP ( LCP), or low CP supplemented with EAA ( ELCP). The chickens received these diets for 10 days. The shear force value ( SFV) and free glutamate content of the Pectoralis major muscle were measured as indicators of the meat toughness and taste. The collagen and crude fat content of the muscle and the cross-sectional area of myofibers were measured to evaluate the effects of the LCP and ELCP diets on meat toughness. The SFV of the ELCP group was 47% lower than that of the control group ( P < 0.01). However, the LCP diet did not affect the SFV. The collagen and crude fat content were not affected by the dietary treatment. The cross-sectional area was lower in the LCP and ELCP groups ( P < 0.05) than the control group. The free glutamate content of muscle was not affected by the dietary treatment. Thus, a low CP diet supplemented with EAA is an effective means of producing tender meat. [ABSTRACT FROM AUTHOR]

This paper deals with a novel wireless biosignal acquisition system employing ZigBee wireless technology, which consists mainly of two components, an intelligent electrode and a data acquisition host. The former is the main topic of this paper. It is placed on a subject's body to amplify biosignals such as EMG or ECG and streams its data at up to 2 ksps. One of the most remarkable features of the intelligent electrode is that it can change its own parameters, both digital and analog, online. The author describes its design first, then introduces a small, light, and low-cost implementation of the intelligent electrode called 'VAMPIRE-BAT.' He then presents some experimental results to confirm its usability and to estimate its practical performances. © 2013 Wiley Periodicals, Inc. Electron Comm Jpn, 96(5): 1-10, 2013; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/ecj.11489 5 [ABSTRACT FROM AUTHOR]

In the CNS, primary tumors with rhabdoid components are classified as atypical teratoid/rhabdoid tumor, rhabdoid meningioma or rhabdoid glioblastoma. The authors present a young adult patient with supratentorial rhabdoid tumor incidentally found after head trauma as a small pre-existing lesion in the parahippocampal gyrus. MRI demonstrated an area of hypointensity on T1-weighted images and hyperintensity on T2-weighted and fluid attenuated inversion recovery images. A serial MR scan revealed no change 3 months after the initial examination but drastic changes at 6 months. As the tumor and accompanying intratumoral hemorrhage enlarged rapidly, resection of the tumor was performed. Histopathology revealed that the main component of the tumor was typical rhabdoid cells with some necrotic areas. There were also pathological features consistent with oligoastrocytoma. The specimen had neither vascular proliferation usually seen in high-grade glioma nor the meningothelial pattern that suggests meningioma. Immunohistochemical findings revealed that cells were strongly positive for vimentin, epithelial membrane antigen and INI-1 antibody throughout the specimen. Further, monosomy 22 was detected by fluorescence in situ hybridization. The tumor was finally thought to be an unclassifiable primitive rhabdoid tumor with oligoastrocytoma that arose in the CNS. The patient died within 5 months of detection of the tumor, regardless of surgical resection, radiotherapy and chemotherapy. [ABSTRACT FROM AUTHOR]

Abstract: Background: Shakuyakukanzoto (SKT) has been shown to modulate nociception in streptozotocin-induced diabetic mice via selective activation of the descending noradrenergic systems. However, the active components of SKT that exert the analgesic effect remain unknown. Here, we administered Glycyrrhizae radix (G. radix), Paeoniae radix (P. radix), and the two active constituents of P. radix, paeoniflorin and albiflorin, to determine the components that stimulate spinal α2-adrenoceptors by promoting noradrenaline release. Methods: The two SKT components were separately administered to diabetic and non-diabetic mice. A tail-pressure test was used to determine the nociceptive threshold between 0 and 3h after oral dosing. The time-course profiles of the nociceptive threshold (g) and the area under the time response curve (AUC) were evaluated. Yohimbine, an α2-adrenoceptor antagonist, was intrathecally injected 15min after paeoniflorin administration. Results: P. radix and G. radix did not induce significant antinociception in non-diabetic mice. However, P. radix (250, 500mg/kg) dose-dependently and significantly increased the nociceptive threshold in diabetic mice between 0.5 and 2h after administration, whereas all the tested doses of G. radix did not increase the nociceptive threshold. Both paeoniflorin (30mg/kg) and albiflorin (10mg/kg) significantly elevated the nociceptive threshold between 0.5 and 3h and between 0.5 and 1h after administration, respectively. The antinociceptive effect of paeoniflorin (30mg/kg) was completely abolished by yohimbine. Conclusion: Our findings suggest that paeoniflorin is the key antinociceptive component in SKT that increases noradrenaline release and activates α2-adrenoceptors to modulate spinal nociceptive transmission in diabetic neuropathy. [Copyright &y& Elsevier]

Background and Purpose: We previously reported that pre-ischaemic i.v. miglitol reduces myocardial infarct size through the inhibition of glycogenolysis during ischaemia. Oral administration of miglitol has been reported to produce glucagon-like peptide 1 (GLP-1). We hypothesized that p.o. administration of miglitol, an absorbable antidiabetic drug, reduces myocardial infarct size by stimulating GLP-1 receptors and inhibiting glycogenolysis in the myocardium.Experimental Approach: The effects of p.o. and i.v. administration of miglitol on myocardial infarct size were compared in a rabbit model of ischaemia induced by 30 min of coronary occlusion and 48 h of reperfusion. The levels of phospho(p)-PI3kinase and p-Akt were measured in cardiac tissue by use of Western blot analysis.Results: Both p.o. and i.v. administration of miglitol reduced the infarct size, and this effect was greater after p.o. than after i.v. administration under similar plasma miglitol concentrations. The reduction in infarct size induced by p.o. miglitol but not that induced by i.v. miglitol was partially inhibited by treatment with exendin(9-39), a GLP-1 receptor blocker. Both p.o. and i.v. miglitol improved ejection fraction and ±dP/dt after myocardial infarction. Miglitol administered p.o. but not i.v. up-regulated the myocardial expression of phospho(p)-PI3kinase and p-Akt following myocardial infarction; an effect that was inhibited by exendin(9-39).Conclusions and Implications: Administration of miglitol p.o. reduces myocardial infarct size through stimulation of GLP-1 receptors and activation of PI3kinase-Akt pathway in addition to the inhibition of glycogenolysis. These findings may have clinical implications for the p.o. administration of miglitol for the treatment of patients with diabetes mellitus combined with coronary artery disease. [ABSTRACT FROM AUTHOR]

Aim: 'Successful aging' in individuals with schizophrenia has been attracting attention. We examined two forward-looking factors of successful aging among schizophrenia patients: 'attitude toward aging' and 'preparing behavior for old age'. Methods: Fifty-seven middle-aged and elderly schizophrenia patients with successful aging were identified using the Attitude toward Aging Scale, the Preparing Behavior for Old Age Scale, and assessments of their cognitive function, psychiatric symptoms, social functioning and quality of life. A multiple regression analysis was used to detect determinants of attitude toward aging/preparing behavior for old age at that time ('present': community dwelling). We also analyzed predictors of successful aging using demographic/clinical data assessed 3 years previously ('past': residential care). Results: The multiple regression analysis revealed that quality of life was a significant determinant: a higher quality of life was related to a more positive attitude toward aging and less active preparing behavior. The significant predictors of preparing behavior were quality of life and the length of the hospital stay: a longer hospital stay and a higher quality of life were related to less active preparing behavior. Conclusion: Quality of life and the length of the hospital stay significantly contributed to forward-looking factors of successful aging. Avoiding long hospitalization periods for patients with schizophrenia may lead to more active preparing behavior, but the improvement of quality of life may not be a sufficient condition. As schizophrenia patients have an optimistic attitude and insufficient preparing behavior, support to prepare such individuals for old age is required as part of community-based psychiatric care strategies. [ABSTRACT FROM AUTHOR]

A new autonomous implant sensor positioning measurement technique is discussed. The goal of this study is to develop ubiquitous medical systems with autonomous nano-medical sensors and robots. The key to achieving the goal is to establish autonomous positioning measurement for these implant objects without imposing a burden on patients. For this purpose, this study proposes autonomous positioning measurement with human voxel data. The technique combines two algorithms: autonomous distributed measurement of sensors with Sammon's map, which is a nonlinear mapping algorithm, and a voxel human model clustered with the propagation characteristics of human tissue. A simulation experiment shows that the proposed technique makes possible precise positioning measurement in a heterogeneous propagation environment in the human body. © 2011 Wiley Periodicals, Inc. Electron Comm Jpn, 94(6): 1-9, 2011; Published online in Wiley Online Library (). DOI 10.1002/ecj.10336 [ABSTRACT FROM AUTHOR]

The major taste active component, glutamate (Glu), improves the taste of meat. In this study, we investigated the effect of a short-term high-protein (HCP) diet on the intramuscular free Glu content to improve the taste of meat. Furthermore, we elucidated how the muscle free Glu content was controlled by the HCP diet. Chicks (14 days old) were fed the control diet or HCP diet for 10 days. Plasma and muscle free amino acid concentrations, and activity and messenger RNA (mRNA) expression of muscle enzymes related to Glu metabolism were determined. Muscle free Glu content was increased ( P < 0.01) by 51%. Activity and mRNA expression of glutaminase (GA), which is one of the major Glu-related enzymes, were significantly decreased ( P < 0.05) in the HCP group because of feedback inhibition. The mRNA expression of lysine α-ketoglutarate reductase (LKR), which is the enzyme involved in lysine (Lys) degradation and Glu production, was significantly increased ( P < 0.001) in the HCP group. These results suggest that short-term dietary HCP feeding is an effective treatment for improving the taste of meat. Furthermore, our results suggest that the free Glu content in muscle is regulated by GA and LKR. [ABSTRACT FROM AUTHOR]

Aims: To examine the emergence of attenuated psychotic experiences, self-disturbance or affective symptoms among younger subjects in the general population and to investigate the intergroup differences on each symptom between adolescents and post-adolescents. Methods: A total of 781 participants, 496 university students (mean age: 19.3 ± 1.1 years) and 285 high school students (mean age: 16.0 ± 0.3 years), were administered self-reported questionnaires. Psychotic prodromal symptoms were evaluated using the PRIME Screen-Revised (PS-R), a 12-item self-reported questionnaire. To measure the cognitive, emotional and physical symptoms associated with depression, the Zung Self-rating Depression Scale (ZSDS), a 20-item self-reported questionnaire, was administered. Results: There were no intergroup differences on the factor score of the PS-R, except the self-demarcation factor (post-adolescents > adolescents), whereas there were significant differences in the factor score of the ZSDS, except for the anxiety factor. Among the post-adolescents, the factors of the PS-R showed a moderate correlation to the cognitive factor on the ZSDS; among the adolescents, the PS-R factors showed a greater correlation to the anxiety factor on the ZSDS than other factors. There were no differences in the distribution of each item of the PS-R between the two groups. Conclusions: The disturbance of self results in difficulty to precisely objectify, especially among adolescents, which would induce more primitive reactions such as agitation, irritability or anxiety; probably, the self disturbance would become an explicit symptom from an implicit experience with advancing age of the subject. Although these data are only preliminary, they could explain the pathway of progression prior to the onset of psychosis, from disturbance within the self to exaggerated self-absorption. [ABSTRACT FROM AUTHOR]

Abstract: Here we describe the interaction of phosphorylated ∼40kDa protein with phosphorylated Akt which is a serine/threonine kinase resulting from increased blood glucose in rat cardiac muscle. Mass spectrometry analysis revealed that this protein was glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Furthermore, increase in Akt and GAPDH phosporylation and induction of their association were both observed after insulin stimulation in the H9c2 cell line derived from embryonic rat ventricle. Moreover, the activation of GAPDH was upregulated when the GAPDH phosphorylation was increased. Our data suggest that GAPDH phosphorylation and association with Akt by insulin treatment have some bearing on the enhancement of GAPDH activity. Structured summary: MINT-7891324, MINT-7891304, MINT-7891314: GAPDH (uniprotkb:P04797) physically interacts (MI:0915) with Akt (uniprotkb:P47196) by anti bait coimmunoprecipitation (MI:0006) [Copyright &y& Elsevier]

Titanium dioxide (TiO2) is thought to be a photocatalytic agent excited by UV light. Our aim was to investigate the photocatalytic antitumor effect of water-dispersed TiO2 nanoparticles on C6 rat glioma cells and to evaluate the treatment responses by the spheroid models. Water-dispersed TiO2 nanoparticles were constructed by the adsorption of chemical modified polyethylene glycol (PEG) on the TiO2 surface (TiO2/PEG). Each monolayer and spheroid of C6 cells was coincubated with various concentrations of TiO2/PEG and subsequently irradiated with UV light. Damage of the cells and spheroids was evaluated sequentially by staining with the fluorescent dyes. The cytotoxic effect was correlated with the concentration of TiO2/PEG and the energy dose of UV irradiation. More than 90% of cells were killed after 13.5 J cm−2 of UV irradiation in the presence of 500 μg mL−1 TiO2/PEG. The irradiated spheroids in the presence of TiO2/PEG showed growth suppression compared with control groups. In TiO2/PEG-treated spheroids, the number of Annexin V-FITC-stained cells gradually increased during the first 6 h, and subsequently propidium iodide-stained cells appeared. The results of this study suggest that newly developed photoexcited TiO2/PEG have antitumoral activity. Photodynamic therapy utilizing this material can be a clue to a novel therapeutic strategy for glioma. [ABSTRACT FROM AUTHOR]

Site-directed mutagenesis guided by evolutionary trace analysis revealed that substitution of V179 and W183 within a cluster of evolutionarily important residues on the surface of the fourth transmembrane domain of the β1-adrenergic receptor (β1AR) significantly reduced the propensity of the receptor to self-assemble into homodimers as assessed by bioluminescence resonance energy transfer in living cells. These results suggest that mutation of V179 and W183 result in conformational changes that reduce homodimerization either directly by interfering with the dimerization interface or indirectly by causing local misfolding that result in reduced self-assembly. However, the mutations did not cause a general misfolding of the β1AR as they did not prevent heterodimerization with the β2AR. The homodimerization-compromised mutants were significantly retained in the endoplasmic reticulum (ER) and could not be properly matured and trafficked to the cell surface. Lipophilic β-adrenergic ligands acted as pharmacological chaperones by restoring both dimerization and plasma membrane trafficking of the ER-retained dimerization-compromised β1AR mutants. These results clearly indicate that homodimerization occurs early in the biosynthetic process in the ER and that pharmacological chaperones can promote both dimerization and cell surface targeting, most likely by stabilizing receptor conformations compatible with the two processes. [ABSTRACT FROM AUTHOR]

Aim: To describe clinical practice and research activities for early psychiatric intervention in Japan, a country with a huge number of psychiatric beds and a history of long-stay, hospital-based psychiatry. Methods: The characteristics, methods and activities of early intervention studies and implementation at four leading institutions in Japan are described. Results: The Tokyo Youth Club (Tokyo), the Department of Neuropsychiatry of Toyama University Hospital (Toyama), the endai t-risk Mental State and irst pisode (SAFE) service (Sendai), and the Il Bosco of Toho University Omori Medical Center (Tokyo) have unique and active psychiatric programmes. Eachcentre has its own clinical research programme and treatment strategies. The Japanese Society for the Prevention of Psychiatric Disorders, founded in 1996, has made a steady contribution to psychiatric care by providing a forum for members to promote best practices for early intervention and by hosting annual meetings to discuss research and treatment. Conclusions: The Japanese psychiatry service is continuing its transition from hospital-based psychiatry to community-based psychiatry. Despite these difficult circumstances, the publication of data on the duration of untreated psychosis in Japan along with evidence that early detection determines outcome has encouraged new attempts to promote early psychiatric intervention. [ABSTRACT FROM AUTHOR]

In this paper the authors propose a data hiding method for JPEG images that has a degree of freedom in selecting the hiding position and does not require a reference image or knowledge of the hiding position during extraction. In conventional methods, the position for the transform coefficients which hide the data must be specified beforehand, and that position must be known during extraction. The proposed method does not require specifying the hiding position beforehand and offers some freedom in selecting the hiding position. Therefore, a hiding position that is appropriate can be selected for each image and block to be subjected to JPEG encoding. Given this, the proposed method can reduce image degradation and improve compression efficiency compared to the conventional methods. Moreover, because knowledge of the hiding position is not required during extraction, information management is thus simpler during extraction. The effectiveness of the proposed method is confirmed through simulations. © 2007 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 90(11): 21–30, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.20356 [ABSTRACT FROM AUTHOR]

The Dickkopf-1 ( DKK1) gene product is an extracellular Wnt inhibitor. Hypermethylation of the DKK1 promoter results in transcriptional silencing and may play an important role in cancer development. Here, we investigated hypermethylation of the DKK1 promoter in patients with acute myeloid leukaemia (AML), especially core-binding factor (CBF) leukaemia. The methylation status of DKK1 was analysed using methylation-specific polymerase chain reaction in 47 patients with AML. DKK1 methylation was found in 14 (29·8%) patients, and more frequently in those with CBF leukaemia (6 of 12 patients), than in those with acute promyelocytic leukaemia (APL) (0 of 6 patients) ( P = 0·03). In contrast, Wnt inhibitory factor-1 methylation was found in APL (4 of 6 patients) but not in CBF leukaemia (0 of 12 patients) ( P = 0·001). Multivariate analyses suggested that DKK1 methylation was a risk factor for poorer overall survival. Sequential analysis using four paired samples obtained at diagnosis and relapse suggested that DKK1 methylation was involved in the progression of leukaemia. Therefore, DKK1 methylation may be involved in leukaemogenesis, especially in CBF leukaemia, and may be a useful prognostic marker in AML. [ABSTRACT FROM AUTHOR]

Angiotensin (Ang) II participates in the pathogenesis of heart failure through induction of cardiac hypertrophy. Ang II-induced hypertrophic growth of cardiomyocytes is mediated by nuclear factor of activated T cells (NFAT), a Ca2+-responsive transcriptional factor. It is believed that phospholipase C (PLC)-mediated production of inositol-1,4,5-trisphosphate (IP3) is responsible for Ca2+ increase that is necessary for NFAT activation. However, we demonstrate that PLC-mediated production of diacylglycerol (DAG) but not IP3 is essential for Ang II-induced NFAT activation in rat cardiac myocytes. NFAT activation and hypertrophic responses by Ang II stimulation required the enhanced frequency of Ca2+ oscillation triggered by membrane depolarization through activation of DAG-sensitive TRPC channels, which leads to activation of L-type Ca2+ channel. Patch clamp recordings from single myocytes revealed that Ang II activated DAG-sensitive TRPC-like currents. Among DAG-activating TRPC channels (TRPC3, TRPC6, and TRPC7), the activities of TRPC3 and TRPC6 channels correlated with Ang II-induced NFAT activation and hypertrophic responses. These data suggest that DAG-induced Ca2+ signaling pathway through TRPC3 and TRPC6 is essential for Ang II-induced NFAT activation and cardiac hypertrophy. [ABSTRACT FROM AUTHOR]

1. In the present study, we investigated the effect of 3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone), a free radical scavenger, on myocardial infarct (MI) size and cardiac function in an in vivo model of MI in rabbits. We further investigated the contribution of hydroxyl radicals, superoxide and nitric oxide (NO) to its effects. 2. Anaesthetized open-chest Japanese white male rabbits were subjected to 30 min coronary occlusion and 48 h reperfusion. The control group ( n = 10) was injected with saline 10 min before reperfusion. The edaravone group ( n = 10) was injected with a bolus of 3 mg/kg edaravone 10 min before reperfusion. The edaravone +  NG-nitro-l-arginine methyl ester (l-NAME) group ( n = 5) was given 10 mg/kg, i.v.,l-NAME 10 min before the administration of 3 mg/kg edaravone. Thel-NAME group ( n = 5) was given 10 mg/kg, i.v.,l-NAME 20 min before reperfusion. Infarct size was measured using the triphenyl tetrazolium chloride method and is expressed as a percentage of area at risk. Cardiac function was assessed by echocardiography 14 days after infarction. 3. In another series of experiments, rabbits were subjected to 30 min coronary occlusion and 30 min reperfusion and myocardial interstitial 2,3-dihydroxybenzoic acid (DHBA) and 2,5-DHBA levels, indicators of hydroxyl radical, were measured using a microdialysis technique. 4. Infarct size in the edaravone group was significantly reduced compared with that in the control group (27.4 ± 6.8 vs 43.4 ± 6.8%, respectively; P < 0.05). The edaravone-induced reduction of infarct size was abolished by pretreatment withl-NAME. Myocardial interstitial levels of 2,3-DHBA and 2,5-DHBA increased 20 and 30 min after ischaemia and peaked at 10 min reperfusion in the control group. Edaravone significantly inhibited the increase in 2,3-DHBA and 2,5-DHBA levels seen during reperfusion. Dihydroethidium staining showing in situ detectoion of superoxide was less intense in ischaemic myocardium in the edaravone-treated group compared with the control group. Edaravone improved cardiac function and left ventricular remodelling 14 days after infarction. 5. In conclusion, edaravone significantly reduces MI size and improves cardiac function and LV remodelling by decreasing hydroxyl radicals and superoxide in the myocardium and increasing the production of NO during reperfusion in rabbits. [ABSTRACT FROM AUTHOR]

The article discusses on the factors that promotes the growth of weeds in the fields . Some of the contributors on the growth of weeds include the type of soil where the crop is planted, the sowing time, and the application of chemicals in the crops. From the factors mention the most significant influence in the growth of weeds is the sowing time. The seasonal change shows a strong influence with the growth of most weed species. The density of weeds in the fields depends on the sowing date.