Sedimentary supply of humic-like fluorescent dissolved organic matter and its implication for chemoautotrophic microbial activity in the Izu-Ogasawara Trench.

Microbial community structure in the hadal water is reported to be different from that in the upper abyssal water. However, the mechanism governing the difference has not been fully understood. In this study, we investigate the vertical distributions of humic-like fluorescent dissolved organic matter (FDOMH), chemoautotrophic production, apparent oxygen utilization (AOU), and N* in the Izu-Ogasawara Trench. In the upper abyssal waters (< 6000 m), FDOMH has a significantly positive correlation with AOU; FDOMH deviates from the relationship and increases with depth without involving the increment of AOU in the hadal waters. This suggests that FDOMH is transferred from the sediments to the hadal waters through pore water, while the FDOMH is produced in situ in the upper abyssal waters. Chemoautotrophic production and N* increases and decreases with depth in the hadal waters, respectively. This corroborates the effluxes of dissolved substances, including dissolved organic matter and electron donors from sediments, which fuels the heterotrophic/chemoautotrophic microbial communities in the hadal waters. A simple box model analysis reveals that the funnel-like trench topography facilitates the increase in dissolved substances with depth in the hadal waters, which might contribute to the unique microbiological community structure in these waters.

A randomized phase III trial comparing S-1 versus UFT as adjuvant chemotherapy for stage II/III rectal cancer (JFMC35-C1: ACTS-RC).

BACKGROUNDS: Preventing distant recurrence and achieving local control are important challenges in rectal cancer treatment, and use of adjuvant chemotherapy has been studied. However, no phase III study comparing adjuvant chemotherapy regimens for rectal cancer has demonstrated superiority of a specific regimen. We therefore conducted a phase III study to evaluate the superiority of S-1 to tegafur-uracil (UFT), a standard adjuvant chemotherapy regimen for curatively resected stage II/III rectal cancer in Japan, in the adjuvant setting for rectal cancer. PATIENTS AND METHODS: The ACTS-RC trial was an open-label, randomized, phase III superiority trial conducted at 222 sites in Japan. Patients aged 20-80 with stage II/III rectal cancer undergoing curative surgery without preoperative therapy were randomly assigned to receive UFT (500-600 mg/day on days 1-5, followed by 2 days rest) or S-1 (80-120 mg/day on days 1-28, followed by 14 days rest) for 1 year. The primary end point was relapse-free survival (RFS), and the secondary end points were overall survival and adverse events. RESULTS: In total, 961 patients were enrolled from April 2006 to March 2009. The primary analysis was conducted in 480 assigned to receive UFT and 479 assigned to receive S-1. Five-year RFS was 61.7% [95% confidence interval (CI) 57.1% to 65.9%] for UFT and 66.4% (95% CI 61.9% to 70.5%) for S-1 [P = 0.0165, hazard ratio (HR): 0.77, 95% CI 0.63-0.96]. Five-year survival was 80.2% (95% CI 76.3% to 83.5%) for UFT and 82.0% (95% CI 78.3% to 85.2%) for S-1. The main grade 3 or higher adverse events were increased alanine aminotransferase and diarrhea (each 2.3%) in the UFT arm and anorexia, diarrhea (each 2.6%), and fatigue (2.1%) in the S-1 arm. CONCLUSION: One-year S-1 treatment is superior to UFT with respect to RFS and has therefore become a standard adjuvant chemotherapy regimen for stage II/III rectal cancer following curative resection.

Differential activation of dopaminergic systems in rat brain basal ganglia by morphine and methamphetamine.

Typical abused drug-induced behavioral changes are ordinarily mediated by the mesolimbic dopaminergic system and even the phenotypes of behavior are different from each other. However, the mechanisms that underlie the behavioral changes induced by these abused drugs have not yet been elucidated. The present study was designed to investigate the mechanisms that underlie how abused drugs induce distinct behavioral changes using neurochemical as well as behavioral techniques in rats. Methamphetamine (2mg/kg) more potently increased dopamine release from the striatum more than that from the nucleus accumbens. In contrast, the administration of morphine (10mg/kg) produced a significant increase in the release of dopamine from the nucleus accumbens, but not the striatum, which is accompanied by a decrease in the release of GABA in the ventral tegmental area. These findings indicate that morphine and methamphetamine differentially regulate dopaminergic systems to produce behavioral changes, even though both drugs have abuse potential through activation of the mesolimbic dopaminergic system.

Impact of obesity on outcomes of paediatric acute pancreatitis based on a national administrative database.

BACKGROUND: Insufficient information is available on the relationship between obesity and outcome of paediatric patients with acute pancreatitis. OBJECTIVES: This study aimed to investigate the effect of obesity on outcomes of paediatric patients with acute pancreatitis based on a national administrative database. METHODS: A total of 500 cases in 416 paediatric patients with acute pancreatitis (aged 5-17 years) were referred from 260 hospitals between 2010 and 2012 in Japan. Patients were divided into two groups according to the presence of obesity: with obesity (n = 65) and without obesity (n = 435). Patient data were collected from the administrative database to compare the prevalence of severe acute pancreatitis, in-hospital mortality, length of stay (LOS) and medical costs between the groups. RESULTS: Both prevalence of severe acute pancreatitis and in-hospital mortality were significantly higher in paediatric patients with obesity than those without (36.9% vs. 16.3% and 3.1% vs. 0.0%; P < 0.001, respectively). Longer LOS and higher medical costs were also observed in paediatric patients with obesity (25.7 vs. 15.2 days, P < 0.001 and 14 169.5 vs. 7457.7 US dollars, P < 0.001, respectively). CONCLUSION: This study demonstrated that obesity significantly influenced the outcomes of paediatric acute pancreatitis.

Search for bosonic superweakly interacting massive dark matter particles with the XMASS-I detector.

Bosonic superweakly interacting massive particles (super-WIMPs) are a candidate for warm dark matter. With the absorption of such a boson by a xenon atom, these dark matter candidates would deposit an energy equivalent to their rest mass in the detector. This is the first direct detection experiment exploring the vector super-WIMPs in the mass range between 40 and 120 keV. With the use of 165.9 day of data, no significant excess above background was observed in the fiducial mass of 41 kg. The present limit for the vector super-WIMPs excludes the possibility that such particles constitute all of dark matter. The absence of a signal also provides the most stringent direct constraint on the coupling constant of pseudoscalar super-WIMPs to electrons. The unprecedented sensitivity was achieved exploiting the low background at a level 10(-4) kg-1 keVee-1 day-1 in the detector.

Japanese traditional medicine, Senn-kinn-naidaku-sann up-regulates Toll-like receptor 4 and reduces murine allergic rhinitis.

OBJECTIVE: To determine the mechanisms by which a traditional herbal medicine, Senkinnaidakusan (SKNS), controls Th2 responses, we examined the production of IL-12 by murine macrophages treated with SKNS. RESULTS: Treatment with SKNS significantly increased TLR4 mRNA in macrophages. Furthermore, pre-treatment with SKNS enhanced the production of IL-12 by macrophages stimulated with LPS. When SKNS was orally administered to C3H/HeN mice at the induction phase after OVA sensitization, the serum levels of OVA-specific immunoglobulin (Ig)E and IgG1 decreased, Interleukin (IL)-4 production by spleen T cells in response to OVA was significantly suppressed, while interferon (IFN)-gamma production was increased. After nasal challenge of OVA, eosinophilic infiltration in the nasal mucosa and the number of sneezes were significantly inhibited in SKNS-treated mice compared with control mice. Besides, expression of IL-5 in the nasal mucosa was also inhibited. Using another strain of mice, C3H/HeJ (TLR4 negative), there was no difference in OVA-specific Igs or splenic cytokine production between the SKNS treatment and non-treatment groups. The eosinophilic infiltration in the nasal mucosa, the number of sneezes and IL-5 expression in the nasal mucosa were also not effected even after SKNS treatment. CONCLUSION: These results suggest that oral administration of SKNS inhibits Th2 responses by enhancement of IL-12 release from macrophages via up-regulation of TLR4 expression.

Methylation levels of LINE-1 in primary lesion and matched metastatic lesions of colorectal cancer.

BACKGROUND: LINE-1 methylation level is a surrogate marker of global DNA methylation. LINE-1 methylation in primary colorectal cancers (CRCs) is highly variable and strongly associated with a poor prognosis. However, no study has examined LINE-1 methylation levels of metastatic CRCs in relation to prognosis or assessed the heterogeneity of LINE-1 methylation level within the primary CRCs. METHODS: Pyrosequencing was used to quantify LINE-1 methylation level in 42 liver metastases, 26 matched primary tumours, and 6 matched lymph node (LN) metastases. KRAS, BRAF, and PIK3CA mutation status and microsatellite instability (MSI) status were also examined. RESULTS: The distribution of LINE-1 methylation level in liver metastases was as follows: mean, 67.3; range, 37.1-90.1. Primary tumours showed LINE-1 methylation levels similar to those of matched liver and LN metastases. The difference in LINE-1 methylation level between superficial areas and invasive front areas was within 7.0 in all six cases evaluated. Prognostic impact of LINE-1 hypomethylation in liver metastases on overall survival was not observed. The concordance rate was 94% for KRAS, 100% for BRAF, 88% for PIK3CA, and 97% for MSI. CONCLUSION: Alteration of LINE-1 methylation level may occur in early CRC tumorigenesis, and the LINE-1 methylation level is relatively stable during CRC progression.

Factors associated with self-assessed masticatory ability among community-dwelling elderly Japanese.

UNLABELLED: Self-assessed masticatory ability has been shown to be significantly related to general health among elderly persons. OBJECTIVE: To identify oral factors associated with the self-assessed masticatory ability. BASIC RESEARCH DESIGN: Cross-sectional study. PARTICIPANTS: A total of 736 community-dwelling elderly persons. MAIN OUTCOME MEASURES: Data on background factors and the self-assessed masticatory ability were collected by questionnaire. An intraoral examination examined the pattern of posterior occluding pairs of natural teeth (POPs), the WHO Community Periodontal Index of Treatment Needs (CPI) and denture-related factors such as use of dentures, pain when using dentures and stability and retention of dentures. Chi-squared tests examined the relationships between the self-assessed masticatory ability and the background factors and oral conditions. Ordinal regression models were constructed with the self-assessed masticatory ability as the dependent variable and oral conditions as the principal independent variables, to adjust for the potential confounding variables. RESULTS: Self-assessed impairment of masticatory ability was associated with lost POPs (p < 0.001) and CPI (p = 0.012). In the participants with lost POPs, self-assessed impairment of masticatory ability was associated with not using dentures and pain when using dentures (p < 0.001). In the totally edentulous subjects, impairment of masticatory ability was not associated with stability and retention of dentures (p = 0.070). CONCLUSIONS: Factors affecting self-assessed masticatory ability include the pattern of POPs, periodontal status, denture use and pain when using dentures.

Perceived chewing ability and need for long-term care in the elderly: a 5-year follow-up study.

Increasing need for long-term care in older adults is expected with the ageing of Japan's population. The aim of the present study was to show the relationship between perceived chewing ability and long-term care needs for over 5 years in elderly persons. The chewing ability of 812 elderly persons living independently was evaluated at baseline using self-assessed masticatory ability, and it was classified into one of three categories: ability to chew all foods (good masticatory ability), ability to chew only slightly hard food (fair masticatory ability), and ability to only chew soft or pureed food (poor masticatory ability). Participants' care needs were then followed through Japan's long-term care insurance system for over 5 years. The log-rank test and Cox proportional hazard model were used to examine statistical differences in the frequency of care-needs certification between participants with good and fair or poor masticatory ability. Among participants aged 65-79 years, the frequency of care-needs certification was significantly higher in those with fair or poor masticatory ability than in those with good masticatory ability, and the relative hazard ratio was significantly higher in those with fair or poor masticatory ability than in those with good masticatory ability, after adjusting for age, gender, current employment status, educational background, social interaction, chronic medical conditions and dentition status. These relationships were not found among those aged 80-93 years. Impairment in perceived chewing ability may be associated with higher incidence of certification in Japan's long-term care insurance system among elderly persons aged 65-79.

Decoding the activity of grasping neurons recorded from the ventral premotor area F5 of the macaque monkey.

Many neurons in the monkey ventral premotor area F5 discharge selectively when the monkey grasps an object with a specific grip. Of these, the motor neurons are active only during grasping execution, whereas the visuomotor neurons also respond to object presentation. Here we assessed whether the activity of 90 task-related F5 neurons recorded from two macaque monkeys during the performance of a visually-guided grasping task can be used as input to pattern recognition algorithms aiming to decode different grips. The features exploited for the decoding were the mean firing rate and the mean interspike interval calculated over different time spans of the movement period (all neurons) or of the object presentation period (visuomotor neurons). A support vector machine (SVM) algorithm was applied to the neural activity recorded while the monkey grasped two sets of objects. The original set contained three objects that were grasped with different hand shapes, plus three others that were grasped with the same grip, whereas the six objects of the special set were grasped with six distinctive hand configurations. The algorithm predicted with accuracy greater than 95% all the distinct grips used to grasp the objects. The classification rate obtained using the first 25% of the movement period was 90%, whereas it was nearly perfect using the entire period. At least 16 neurons were needed for accurate performance, with a progressive increase in accuracy as more neurons were included. Classification errors revealed by confusion matrices were found to reflect similarities of hand grips used to grasp the objects. The use of visuomotor neurons' responses to object presentation yielded grip classification accuracy similar to that obtained from actual grasping execution. We suggest that F5 grasping-related activity might be used by neural prostheses to tailor hand shape to the specific object to be grasped even before movement onset.

Associations between self-assessed masticatory ability and higher brain function among the elderly.

Among the elderly, the quality of higher brain function is a contributing factor in performing activities of daily living. The aim of the study is to elucidate, epidemiologically, associations between mastication and higher brain function. A total of 208 community-dwelling elderly persons, aged 70-74 years, were enrolled. Self-assessed masticatory ability (masticatory ability) was classified into one of three categories: ability to chew all kinds of food, ability to chew only slightly hard food, or ability to chew only soft or pureed food. Brain function was assessed by four neuropsychological tests: Raven's Colored Progressive Matrices (RCPM) test, the Verbal Paired Associates 1 (VerPA) task and the Visual Paired Associates 1 task (from the Wechsler Memory Scale Revised Edition), and the Block Design subtest (from the Wechsler Adult Intelligence Scales-Third Edition). Correlations between masticatory ability and each test were examined using Spearman rank correlation coefficients. Multinominal logistic regression models were conducted with the neuropsychological tests as the dependent variables and masticatory ability as the principal independent variable to adjust for age, gender, educational background, social activity, drinking/smoking habits, chronic medical conditions and dental status. Significant correlations were found between the RCPM test, the VerPA task, the Block Design test and masticatory ability. In multinominal logistic regression models, poor masticatory ability was significantly and independently related to the categories under the mean-s.d. points compared with those of the mean ± s.d. ranges for RCPM test and the VerPA task. Significant associations may exist between mastication and higher brain function among the elderly.

Self-assessed masticatory ability and hospitalisation costs among the elderly living independently.

The escalating medical costs are a social problem in many countries. Masticatory ability is thought to be related to the general health conditions. The purpose of this study was to show relationships between self-assessed masticatory ability and medical costs among the elderly living independently in community. Data on background factors and self-assessed masticatory ability were collected from 702 Japanese elderly persons by questionnaires. An intra-oral examination was performed to examine the number of remaining teeth. Self-assessed masticatory ability was classified into one of three categories: ability to chew all kinds of food (Good), ability to chew only slightly hard food (Fair) or ability to chew only soft or pureed food (Poor). Data on the annual medical excluding dental costs were obtained from the Japanese National Health Insurance system. The Kruskal-Wallis test was used to examine differences in outpatient costs and hospitalisation costs among the three groups of self-assessed masticatory ability. Univariate unconditional logistic regression models and multivariate logistic regression models were used with medical costs as the dependent variable and self-assessed masticatory ability as the principal independent variable. A significant difference (P=0·039) in hospitalisation costs but not outpatient costs was found among the three groups of self-assessed masticatory ability. The multivariate logistic regression analysis showed that severely impaired masticatory ability (Poor) was significantly related to higher costs of hospitalisation. Self-assessed impairment of masticatory ability may be a significant and independent indicator of higher costs of hospitalisation among community-dwelling elderly persons.

[Huge right atrial myxoma].

Myxomas are account for approximately half of primary cardiac tumors, and 75% cases originate in left atrium. We report our experience of a right atrial myxoma. A 68-year-old woman was referred to us due to anorexia, general fatigue and facial edema. Echocardiogram, computed tomography (CT), magnetic resonance imaging (MRI), and catheter angiocardiogram revealed a huge tumor in right atrium. The tumor was resected completely with the attached right atrial free wall under cardiopulmonary bypass. Pathological examination showed myxomatous tissue. Postoperative course was uneventful. She discharged the hospital on the 37th day after the operation, and is now doing well without any symptoms.

Endoscopic submucosal dissection using a novel grasping type scissors forceps.

Endoscopic submucosal dissection (ESD) with a knife is a technically demanding procedure that is associated with a high complication rate. The shortcoming of this method is the difficulty in fixing the knife to the target lesion. This difficulty can lead to unexpected incision, resulting in major complications such as perforation and bleeding. To reduce the risk of complications related to ESD, we developed a new grasping type scissors forceps (GSF), which can grasp and incise the targeted tissue using an electrosurgical current. The ESD procedure using the GSF was carried out in an animal model (resected porcine stomachs in vitro). After marking the lesion and injecting a solution into the submucosa, the lesion was separated from the surrounding normal mucosa following complete incision around the lesion using the GSF. A piece of submucosal tissue was grasped and cut with the GSF using an electrosurgical current to achieve submucosal exfoliation. ESD using the GSF was carried out safely and easily without unintentional incision. ESD using GSF appears to be an easy, safe, and technically efficient method for resecting gastrointestinal neoplasms.

Altered postural regulation of foot skin oxygenation and blood flow in patients with type 2 diabetes mellitus.

AIMS: Although skin oxygenation is an important factor in the development and healing of foot ulcers, its regulation was not fully understood. We studied changes in foot skin oxygenation and blood flow during postural changes in patients with type 2 diabetes mellitus. METHODS: Skin oxygenation was measured using transcutaneous oxygen pressure (TcPO(2)) and skin blood flow by laser Doppler flowmetry in 40 patients with type 2 diabetes mellitus without evidence of peripheral arterial disease and 13 healthy control subjects. RESULTS: TcPO(2) in the supine position was significantly lower in patients with type 2 diabetes mellitus compared with control, although skin blood flow was not different. In the sitting position, TcPO(2) significantly increased in control and diabetic patients. The postural change-related increase in TcPO(2) was significantly enhanced in diabetic patients. On the other hand, skin blood blow significantly decreased in the sitting position from the supine position in control subjects but remained stable in diabetic patients. Orthostatic drop in systolic blood pressure correlated negatively with TcPO(2) in the supine position while correlated positively with %change in TcPO(2) and blood flow by postural changes. CONCLUSIONS: The present study demonstrated the dissociated regulation of skin oxygenation and blood flow in response to leg dependency. Impaired postural vasoconstriction was associated with altered regulation of skin oxygenation probably due to sympathetic vascular dysfunction in diabetic patients.

Enhanced head-twitch response to 5-HT-related agonists in thiamine-deficient mice.

While many studies suggest an involvement of brain serotonergic systems in neuro-psychiatric disorders such as schizophrenia and depression, their role in Wernicke-Korsakoff syndrome (WKS) remains unclear. Since dietary thiamine deficiency (TD) in mice is considered as a putative model of WKS, it was used in the present study to investigate the function of serotonergic neurons in this disorder. After 20 days of TD feeding, the intensity of tryptophan hydroxylase immunofluorescence was found to be significantly decreased in the dorsal and medial raphe nuclei. In addition, the head-twitch response (HTR) elicited by the intracerebroventricular administration of the 5-HT(2A) agonist 2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) was significantly increased in TD versus control mice, whereas the injection of ketanserin, a 5-HT(2A) receptor antagonist, prevented this enhancement. A single injection of thiamine HCl on the 19th day of TD feeding did not reduce the enhanced DOI-induced HTR. On the other hand, the administration of d-fenfluramine, a 5-HT releaser, did not enhance the HTR in TD mice. Together, our results indicate that TD causes a super-sensitivity of 5-HT(2A) receptors by reducing presynaptic 5-HT synthesis derived from degenerating neurons projecting from the raphe nucleus.

[Severe tracheal compression resulting from atherosclerotic aortic arch aneurysm; report of a case].

A 70-year-old woman presented with severe respiratory insufficiency similar to an asthma attack. Computed tomography (CT) revealed an atherosclerotic aneurysm (maximum diameter 106 mm) on the aortic arch which resulted in a severe tracheal compression. We performed an aortic arch replacement. After the operation, we tried to manage breathing without a respirator twice without success. We then performed a tracheotomy on the 12th day after operation. The patient could breathe independently on the 19th day after the first operation. Peri-and postoperative respiratory management was difficult but the patient was discharged on the 86th day after operation without further complication.

[De Bakey type I aortic dissection complicating systemic lupus erythematosus; report of a case].

We report a 43-year-old patient of De Bakey type I aortic dissection [DA (I)] with a 2-year-history of systemic lupus erythematosus (SLE). He had had no treatment for SLE before the onset of dissection. Computed tomography (CT) on admission revealed DA (I), and he underwent emergency operation. Since the aortic valve and the left main coronary artery were severely damaged, aortic root replacement was performed. Coronary buttons were prepared in Carrel method and coronary reconstruction was performed in Piehler modification. After surgery, he suffered from repetitive hemolytic anemia. Corticosteroid therapy and rinsed blood transfusion were very effective for anemia. The combination with SLE and DA (I) was rare and this report of successful aortic root replacement is the second literature among English and Japanese papers.