Steroidogenic enzymes in the CP

Peripherally derived steroids affect steroid production in the brain via the blood–brain barrier. However, steroid concentrations are lower in the cerebrospinal fluid than those in the blood, indicating restricted influx of steroids because of their metabolization by choroid plexus (CP) epithelial cells. Here, we analyzed the gene expression of steroidogenic enzymes [cholesterol side-chain cleavage enzyme (P450scc), 17α-hydroxylase/C17-C20 lyase (P450c17), 3β-hydroxysteroid dehydrogenase (3β -HSD), 17β-hydroxysteroid dehydrogenase type 1 (17β -HSD1), aromatase (Cyp19a1), and 5α-reductase type 1 (5α -R1)]. These genes were expressed to a lesser extent in the CP than in the testis and to a similar extent in the cerebral cortex. However, P450scc levels were higher in the CP than in the cerebral cortex, whereas Cyp19a1 levels showed the opposite trend. We also evaluated the effects of orchiectomy and testosterone on the expression of these genes. P450c17 and 5α -R1 levels were unaffected by orchiectomy, whereas P450scc and 3β -HSD levels were increased and decreased, respectively. Cyp19a1 expression increased upon testosterone treatment, whereas that of 17β -HSD decreased upon orchiectomy or administration of testosterone. Immunohistochemistry analysis revealed that 17β -HSD was expressed in the cytoplasm of CP epithelial cells. These results indicate that CP epithelial cells synthesize and convert the certain types of steroids to contribute to the homeostasis of steroids in the brain

Shear Resistance Mechanisms on Steel Sheet Shear Walls with Burring Holes and Cross-Rails

Steel sheet shear walls with burring holes are employed in low and mid-rise buildings in seismically active regions. A configuration with burrs on the inside enables the thinner wall and omitting the machining of equipment holes. The effects of cross-rails which are generally designed to strengthen the bearing capacities of the studs, on 2.73~4.53m height shear walls were clarified by finite element analysis and experiments. Post-buckling behavior depends on tension fields restrained by the cross-rails. The formulas of the allowable strengths and the indexes of ultimate strengths were developed using the mechanisms

Shear Resistance Mechanisms on Steel Sheet Shear Walls with Burring Holes and Cross-Rails

Steel sheet shear walls with burring holes are employed in low and mid-rise buildings in seismically active regions. A configuration with burrs on the inside enables the thinner wall and omitting the machining of equipment holes. The effects of cross-rails which are generally designed to strengthen the bearing capacities of the studs, on 2.73~4.53m height shear walls were clarified by finite element analysis and experiments. Post-buckling behavior depends on tension fields restrained by the cross-rails. The formulas of the allowable strengths and the indexes of ultimate strengths were developed using the mechanisms

User Impressions of System Questions to Acquire Lexical Knowledge during Dialogues

We have been addressing the problem of acquiring attributes of unknown terms through dialogues and previously proposed an approach using the implicit confirmation process. It is crucial for dialogue systems to ask questions that do not diminish the user’s willingness to talk. In this paper, we conducted a user study to investigate user impression for several question types, including explicit and implicit, to acquire lexical knowledge. We clarified the order among the types and found that repeating the same question type annoys the user and degrades user impression even when the content of the questions is correct. We also propose a method for determining whether an estimated attribute is correct, which is included in an implicit question. The method exploits multiple-user responses to implicit questions about the attribute of the same unknown term. Experimental results revealed that the proposed method exhibited a higher precision rate for determining the correctly estimated attributes than when only single-user responses were considered

Diabetes-Related Ankyrin Repeat Protein (DARP/Ankrd23) Modifies Glucose Homeostasis by Modulating AMPK Activity in Skeletal Muscle.

Skeletal muscle is the major site for glucose disposal, the impairment of which closely associates with the glucose intolerance in diabetic patients. Diabetes-related ankyrin repeat protein (DARP/Ankrd23) is a member of muscle ankyrin repeat proteins, whose expression is enhanced in the skeletal muscle under diabetic conditions; however, its role in energy metabolism remains poorly understood. Here we report a novel role of DARP in the regulation of glucose homeostasis through modulating AMP-activated protein kinase (AMPK) activity. DARP is highly preferentially expressed in skeletal muscle, and its expression was substantially upregulated during myotube differentiation of C2C12 myoblasts. Interestingly, DARP-/- mice demonstrated better glucose tolerance despite similar body weight, while their insulin sensitivity did not differ from that in wildtype mice. We found that phosphorylation of AMPK, which mediates insulin-independent glucose uptake, in skeletal muscle was significantly enhanced in DARP-/- mice compared to that in wildtype mice. Gene silencing of DARP in C2C12 myotubes enhanced AMPK phosphorylation, whereas overexpression of DARP in C2C12 myoblasts reduced it. Moreover, DARP-silencing increased glucose uptake and oxidation in myotubes, which was abrogated by the treatment with AICAR, an AMPK activator. Of note, improved glucose tolerance in DARP-/- mice was abolished when mice were treated with AICAR. Mechanistically, gene silencing of DARP enhanced protein expression of LKB1 that is a major upstream kinase for AMPK in myotubes in vitro and the skeletal muscle in vivo. Together with the altered expression under diabetic conditions, our data strongly suggest that DARP plays an important role in the regulation of glucose homeostasis under physiological and pathological conditions, and thus DARP is a new therapeutic target for the treatment of diabetes mellitus

Serum IgG4 as a biomarker reflecting pathophysiology and post-operative recurrence in chronic rhinosinusitis

Background: Type 2 chronic rhinosinusitis (CRS), especially eosinophilic CRS (ECRS), is an intractable upper airway inflammatory disease. Establishment of serum biomarkers reflecting the pathophysiology of CRS is desirable in a clinical setting. As IgG4 production is regulated by type 2 cytokines, we sought to determine whether serum IgG4 levels can be used as a biomarker for CRS. Methods: Association between the serum IgG4 levels and clinicopathological factors was analyzed in 336 CRS patients. Receiver operating characteristics (ROC) analysis was performed to determine the cut-off value of serum IgG4 levels that can be used to predict the post-operative recurrence. Results: Serum IgG4 levels were significantly higher in patients with moderate to severe ECRS versus those with non to mild ECRS. The levels were also significantly higher in asthmatic patients and patients exhibiting recurrence after surgery compared to controls. ROC analysis determined that the best cut-off value for the serum IgG4 level to predict the post-operative recurrence was 95 mg/dL. The corresponding sensitivity and specificity were 39.7% and 80.5%, respectively. When we combined the two cut-off values for the serum IgG4 and periostin, patients with high serum levels of either IgG4 or periostin exhibited a high post-operative recurrence (OR: 3.95) as compared to patients having low serum levels of both IgG4 and periostin. Conclusions: The present results demonstrate that the serum IgG4 level is associated with disease severity and post-operative course in CRS. In particular, the combination of serum IgG4 and periostin could be a novel biomarker that predicts post-operative recurrence

Effects of Comprehensive Stroke Care Capabilities on In-Hospital Mortality of Patients with Ischemic and Hemorrhagic Stroke: J-ASPECT Study

Background: The effectiveness of comprehensive stroke center (CSC) capabilities on stroke mortality remains uncertain. We performed a nationwide study to examine whether CSC capabilities influenced in-hospital mortality of patients with ischemic and hemorrhagic stroke. Methods and Results: Of the 1,369 certified training institutions in Japan, 749 hospitals responded to a questionnaire survey regarding CSC capabilities that queried the availability of personnel, diagnostic techniques, specific expertise, infrastructure, and educational components recommended for CSCs. Among the institutions that responded, data on patients hospitalized for stroke between April 1, 2010 and March 31, 2011 were obtained from the Japanese Diagnosis Procedure Combination database. In-hospital mortality was analyzed using hierarchical logistic regression analysis adjusted for age, sex, level of consciousness on admission, comorbidities, and the number of fulfilled CSC items in each component and in total. Data from 265 institutions and 53,170 emergency-hospitalized patients were analyzed. Mortality rates were 7.8% for patients with ischemic stroke, 16.8% for patients with intracerebral hemorrhage (ICH), and 28.1% for patients with subarachnoid hemorrhage (SAH). Mortality adjusted for age, sex, and level of consciousness was significantly correlated with personnel, infrastructural, educational, and total CSC scores in patients with ischemic stroke. Mortality was significantly correlated with diagnostic, educational, and total CSC scores in patients with ICH and with specific expertise, infrastructural, educational, and total CSC scores in patients with SAH. Conclusions: CSC capabilities were associated with reduced in-hospital mortality rates, and relevant aspects of care were found to be dependent on stroke type

Consciousness Level and Off‐Hour Admission Affect Discharge Outcome of Acute Stroke Patients: A J‐ASPECT Study

Background-Poor outcomes have been reported for stroke patients admitted outside of regular working hours. However, few studies have adjusted for case severity. In this nationwide assessment, we examined relationships between hospital admission time and disabilities at discharge while considering case severity. Methods and Results-We analyzed 35 685 acute stroke patients admitted to 262 hospitals between April 2010 and May 2011 for ischemic stroke (IS), intracerebral hemorrhage (ICH), or subarachnoid hemorrhage (SAH). The proportion of disabilities/death at discharge as measured by the modified Rankin Scale (mRS) was quantified. We constructed 2 hierarchical logistic regression models to estimate the effect of admission time, one adjusted for age, sex, comorbidities, and number of beds; and the second adjusted for the effect of consciousness levels and the above variables at admission. The percentage of severe disabilities/death at discharge increased for patients admitted outside of regular hours (22.8%, 27.2%, and 28.2% for working-hour, off-hour, and nighttime; P<0.001). These tendencies were significant in the bivariate and multivariable models without adjusting for consciousness level. However, the effects of off-hour or nighttime admissions were negated when adjusted for consciousness levels at admission (adjusted OR, 1.00 and 0.99; 95% CI, 1.00 to 1.13 and 0.89 to 1.10; P=0.067 and 0.851 for off-hour and nighttime, respectively, versus working-hour). The same trend was observed when each stroke subtype was stratified. Conclusions-The well-known off-hour effect might be attributed to the severely ill patient population. Thus, sustained stroke care that is sufficient to treat severely ill patients during off-hours is important