Search

Aims/Introduction: Glucagon, a peptide hormone produced from proglucagon, is involved in the pathophysiology of diabetes. Plasma glucagon levels are currently measured by sandwich enzyme‐linked immunosorbent assay (ELISA), but the currently used sandwich ELISA cross‐reacts with proglucagon‐derived peptides, thereby providing incorrect results in subjects with elevated plasma proglucagon‐derived peptide levels. We aimed to develop a more broadly reliable ELISA for measuring plasma glucagon levels. Materials and Methods: A new sandwich ELISA was developed using newly generated monoclonal antibodies against glucagon. After its validation, plasma glucagon levels were measured with the new ELISA and the currently used ELISA in subjects who underwent laparoscopic sleeve gastrectomy (LSG) and in outpatients with suspected glucose intolerance. The ELISA results were compared with those from liquid chromatography‐high resolution mass (LC‐HRMS) analysis, which we previously established as the most accurate measuring system. Results: The new ELISA has high specificity (<1% cross‐reactivities) and high sensitivity (a lower range of 0.31 pmol/L). Plasma glucagon values in the subjects who underwent laparoscopic sleeve gastrectomy and some outpatients with suspected glucose intolerance differed between the new ELISA and the currently used ELISA. These subjects also showed markedly high plasma glicentin levels. Despite the elevated plasma glicentin levels, the new ELISA showed better positive correlation with LC‐HRMS than did the currently used ELISA. Conclusions: The new ELISA enables more accurate measurement of plasma glucagon than the currently used ELISA, even in subjects with elevated proglucagon‐derived peptide levels. It should be clinically useful in elucidating the pathophysiology of individual diabetic patients. [ABSTRACT FROM AUTHOR]

Aims: We investigated the changes in bladder and urethral function after cerebral infarction (CI) and the influence of tramadol on these functions. Methods: Twenty‐eight female Sprague Dawley rats were divided into normal and CI groups. In the awake condition, metabolic cage study and blood pressure were evaluated. Under urethane anesthesia, the intravenous effect of tramadol (0.01–1 mg/kg), which has both µ‐opioid receptor stimulation and inhibition of norepinephrine and serotonin reuptake, on continuous cystometry, and simultaneous measurements of bladder and urethral perfusion pressure (UPP) were recorded. Infarcted lesions were examined by staining with triphenyltetrazolium chloride, a marker of mitochondrial enzyme activity. Results: CI rats showed impaired sympathetic activity with Horner's syndrome and lower blood pressure. In metabolic cage study, urinary frequency during the dark phase was increased in CI rats. On bladder activity, in CI rats, the baseline pressure threshold for inducing bladder contractions was significantly lower (p < 0.01), and the intercontraction interval was prolonged after tramadol administration. On urethral activity, the baseline UPP was significantly lower in CI rats than in normal rats and it did not change after tramadol administration. Residual urine rate was significantly increased in normal rats, but not in CI rats. CI rats showed brain infarction including the cortex and hypothalamus, which is a center of the autonomic nervous system. Conclusions: CI‐induced ischemic brain damage results in impairment of both bladder and urethral functions, in addition to decreased sympathetic activity. Bladder overactivity after CI can be improved by tramadol; however, urethral activity cannot be improved by it. [ABSTRACT FROM AUTHOR]

Since the coronavirus disease 2019 (COVID-19) pandemic started, various medications and vaccinations have been developed. In COVID-19 pathogenesis, IFN lambdas may be exacerbating factors in relation to neutrophil chemotaxis and the complement/coagulation cascade.15 IFN 3 surged and then dropped suddenly before the development of severe disease requiring oxygen support.7 Therefore, IFN 3 may be useful in making decisions regarding appropriate patient placement. Although some scoring systems have been published to estimate the risk of severe disease in patients with COVID-19,4-6 an objective and simple index that predicts disease progression as early as possible (before critical illness) is needed. However, compared with a large study12 of hospitalized patients with COVID-19 in Japan, the patient backgrounds and rates of severe disease were similar, and we believe that this study reflects the general population in Japan to some extent. [Extracted from the article]

With increase in the number of photovoltaic system installations, the prospect of voltage deviation from the acceptable range in a distribution system is increasing. Voltage distribution can be controlled using step voltage regulators (SVRs) and static var compensators (SVCs); however, for their coordination, it is necessary to stringently adjust the set value for each distribution line. In this study, a method of applying model predictive control to the coordination between an SVR and an SVC is investigated. In this paper, we first describe the proposed method and subsequently present the results of the performance comparison of the proposed and conventional methods to validate the effectiveness of the proposed method. © 2022 Institute of Electrical Engineers of Japan. Published by Wiley Periodicals LLC. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Diabetes is associated with poor clinical outcomes of coronavirus disease 2019 (COVID‐19). However, the impact of newly diagnosed diabetes on prognosis has not been clarified. The objective of this study was to show the features and outcome of COVID‐19 patients with newly diagnosed diabetes in Japan. Materials and Methods: We retrospectively analyzed 62 patients with diabetes hospitalized for COVID‐19 between 1 April and 18 August 2021 at the National Center for Global Health and Medicine in Tokyo, Japan. We evaluated the worst severity of COVID‐19 and plasma blood glucose levels in patients with newly diagnosed diabetes or pre‐existing diabetes. Results: This study included 62 confirmed COVID‐19 patients with diabetes, including 19 (30.6%) patients with newly diagnosed diabetes and 43 (69.4%) patients with pre‐existing diabetes. Patients with newly diagnosed diabetes significantly progressed to a critical condition more frequently during hospitalization than patients with pre‐existing diabetes (52.6% vs 20.9%, P = 0.018). In addition, patients with newly diagnosed diabetes had significantly higher average plasma blood glucose levels for the first 3 days after admission than those with pre‐existing diabetes. Conclusions: Our study suggests that the proportion of COVID‐19 patients who are newly diagnosed with diabetes is high, and they have an increased risk of developing severe disease than those with pre‐existing diabetes. It might be advisable that at the point of COVID‐19 diagnosis, blood glucose and glycated hemoglobin levels be assessed in all patients. [ABSTRACT FROM AUTHOR]

Background: We evaluated the significance of perinatal plasma natriuretic peptide (NP) levels in neonates with congenital heart defects (CHDs) or arrhythmias and determined whether measurement of perinatal plasma NP levels and echocardiographic assessment in utero could predict heart failure after birth. Methods: The study was conducted between 2012 and 2016 to evaluate the correlation of perinatal atrial NP (ANP) and brain NP (BNP) levels at birth with the modified Ross score after birth and the cardiovascular profile (CVP) score before birth. Results: A total of 122 singletons with CHDs or arrhythmias and 27 controls were analyzed. Neonatal blood sampling was performed at a median of 0.7 h (range, 0.1–1.5) after birth. The neonatal plasma ANP and BNP levels shortly after birth were significantly higher than those in the umbilical artery (UA) plasma. The ANP and BNP levels in UA and neonatal blood were correlated with the modified Ross score. The neonatal plasma ANP and BNP levels and the modified Ross scores were inversely correlated with the CVP score in neonates with CHDs or arrhythmias. The area under the receiver operating characteristic curve of UA ANP levels for predicting neonatal heart failure was highest among those for the CVP score, perinatal plasma ANP and BNP levels, and their combinations. Conclusions: The plasma ANP and BNP levels increased markedly shortly after birth. Assessment of the UA plasma ANP level at birth and the CVP score in utero may be utilized to predict neonatal heart failure. [ABSTRACT FROM AUTHOR]

Natural lacquer has been used as a coating material for daily necessities for thousands of years. In the archeology and conservation science, identifying them provides useful information for the lacquer culture research and restoration work. In this study, an eared cup excavated in China was investigated by multiple analytical methods. The surface structure of ancient lacquerware has a multilayered structure. The type of lacquer was identified by pyrolysis gas chromatography/mass spectrometry (PyGC/MS). The layered structure and pigments were investigated by scanning electron microscopy/energy-dispersive X-ray spectrometry (SEM/EDX), which clearly showed elemental maps of the cross-section of the lacquer layers. Laser Raman spectroscopy (LRS) was used to distinguish between the types of carbon compound in the black layers. Additionally, the age of the eared cup was measured by radiocarbon dating. By combining these complementary results, we were able to derive a reliable interpretation of ancient lacquer processing techniques. This demonstrates the importance of properly combining multiple methods for analyzing the microscopic and complex structures of lacquerware. [ABSTRACT FROM AUTHOR]

Unveiling the details of the mechanisms of a chemical reaction is a difficult task as reaction mechanisms are strongly coupled with reaction conditions. Here, catalysts informatics combined with high‐throughput experimental data is implemented to understand the oxidative coupling of methane (OCM) reaction. In particular, pairwise correlation and data visualization are performed to reveal the relation between reaction conditions and selectivity/conversion. In addition, machine learning is used to fill the gap between experimental data points; thus, a more detailed understanding of the OCM reaction against reaction conditions can be achieved. Therefore, catalysts informatics is proposed for understanding the details of the reaction mechanism, thereby aiding reaction design. [ABSTRACT FROM AUTHOR]

Background: In order to tackle the COVID‐19 pandemic, a COVID‐19 convalescent plasma (CCP) procurement program was initiated in Japan in April 2020. The program was a collaboration between a government‐managed national hospital, an infectious disease research institute, and a blood banking organization. Each party assumed different responsibilities: recruitment, SARS‐CoV‐2 antibody profiling, and plasmapheresis; conduction of screening tests; and SARS‐CoV‐2 blood testing, respectively. Methods: We adopted a two‐point screening approach before the collected CCP was labeled as a CCP product for investigational use, for which we mainly tested anti‐SARS‐CoV‐2 antibody eligibility and blood product eligibility. Anti‐SARS‐CoV‐2 spike protein titer was measured using enzyme‐linked immunosorbent assay, and the IC50 value was denoted as the neutralizing activity. Blood donor eligibility was extended beyond the normal blood donation guidelines to include a broader range of participants. After both eligibility criteria were confirmed, participants were asked to revisit the hospital for blood donation, which is a unique aspect of the Japanese CCP program, as most donations are taking place in normal blood donation venues in other countries. Some donors were re‐scheduled for repeat plasma donations. As public interest in anti‐SARS‐CoV‐2 antibodies increased, test results were given to the participants. Results: As of September 17, 2020, our collection of CCP products was sufficient to treat more than 100 patients. As a result, projects for administration and distribution are also being conducted. Conclusions: We successfully implemented a CCP procurement scheme with the goal to expand to other parts of the country to improve treatment options for COVID‐19. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of direct hemoperfusion using a polymyxin B‐immobilized polystyrene column (PMX‐DHP) in severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐positive pneumonia patients. Methods: This study was a case series conducted at a designated infectious diseases hospital. Twelve SARS‐CoV‐2‐positive patients with partial pressure of arterial oxygen/percentage of inspired oxygen (P/F) ratio < 300 were treated with PMX‐DHP on two consecutive days each during hospitalization. We defined day 1 as the first day when PMX‐DHP was performed. PMX‐DHP efficacy was assessed on days 7 and 14 after the first treatment based on eight categories. Subsequently, improvement in P/F ratio and urinary biomarkers on days 4 and 8, malfunctions, and ventilator and extracorporeal membrane oxygenation avoidance rates were also evaluated. Results: On day 14 after the first treatment, disease severity decreased in 58.3% of the patients. P/F ratio increased while urine β2‐microglobulin decreased on days 4 and 8. Cytokine measurement pre‐ and post‐PMX‐DHP revealed decreased levels of interleukin‐6 and the factors involved in vascular endothelial injury, including vascular endothelial growth factor. Twenty‐two PMX‐DHPs were performed, of which seven and five PMX‐DHPs led to increased inlet pressure and membrane coagulation, respectively. When the membranes coagulated, the circuitry needed to be reconfigured. Circuit problems were usually observed when D‐dimer and fibrin degradation product levels were high before PMX‐DHP. Conclusions: Future studies are expected to determine the therapeutic effect of PMX‐DHP on COVID‐19. Because of the relatively high risk of circuit coagulation, coagulation capacity should be assessed beforehand. [ABSTRACT FROM AUTHOR]

The combination of deep learning and high‐throughput experiments is proposed for the direct design of heterogeneous catalysts in the oxidative coupling of methane (OCM) reaction. Deep learning predicts 20 active catalysts from high‐throughput 12,708 OCM experimental data where 19 of the predicted 20 catalysts have not been previously reported. The predicted 20 catalysts are then evaluated through high‐throughput experiments where a highly active unreported catalyst Ti−Na2WO4/TiO2 is discovered. Ti−Na2WO4/TiO2 results in a high C2 yield of 18.8 % where the maximum C2 yield is reported to be approximately 20 % within the 12,708 OCM data. Furthermore, the experimental conditions predicted for Ti−Na2WO4/TiO2 are also reproduced by high‐throughput experiment. Thus, deep learning demonstrates that both catalysts and experimental conditions can be simultaneously explored for designing catalysts. More importantly, deep learning assisted catalysts search is found to dramatically increase the chances of finding active catalysts where 9 out of 20 predicted catalysts result in a C2 yield over 15 %. Therefore, the combination of deep learning with high‐throughput experiments is proposed to be an effective strategy for the direct design of catalysts. [ABSTRACT FROM AUTHOR]

To confirm changes in urethral activity with age, both intravesical pressure and urethral perfusion pressure (UPP) were recorded and external urethral sphincter electromyography (EUS‐EMG) was performed. A total of 33 female Sprague Dawley rats aged 3 months (young rats), 12 months (middle‐aged rats), and 24 months (aged rats) were used. Bladder activity was evaluated using continuous cystometry. Urethral activity was evaluated by simultaneously recording intravesical pressure and UPP in isovolumetric conditions under urethane anesthesia in each group. Additionally, EUS‐EMG activity was monitored under the same conditions. In continuous cystometry, the amplitude of bladder contractions was not different among the three groups; nevertheless, residual urine volume was significantly increased in middle‐aged and aged rats, as compared in young rats. With respect to UPP, the change in UPP was significantly smaller in aged rats (60%) and middle‐aged rats (64%) than in young rats. Furthermore, the mean amplitude of high‐frequency oscillations of the EUS was significantly lower in aged (61%) and middle‐aged rats (70%) than in young rats. EUS‐EMG revealed EUS bursting activity during voiding with clear active and silent phases in young rats but unclear active and silent phases in aged rats. Masson's trichrome staining of the urethra showed EUS atrophy in aged rats compared to young and middle‐aged rats. The results indicate that aging induces two urethral dysfunctions in the urethral smooth muscle and EUS, which may lead to dyscoordination between the urinary bladder and urethra. [ABSTRACT FROM AUTHOR]

Thalidomide and its analogues are known as immunomodulatory drugs (IMiDs) that possess direct antimyeloma effects, in addition to other secondary effects, including antiangiogenic, antiinflammatory, and immunomodulatory effects. Although the involvement of natural killer (NK) cells in the antitumor effects of IMiDs has been reported, it is unclear whether IMiDs inhibit cancer cell metastasis by regulating the antitumor function of NK cells. In this study, we examined the protective effects of thalidomide against cancer metastasis by focusing on its immunomodulatory effects through NK cells. Using experimental lung metastasis models, we found that pharmacological effects of thalidomide on host cells, but not its direct anticancer tumor effects, are responsible for the inhibition of lung metastases. To exert the antimetastatic effects of thalidomide, both γ‐interferon (IFN‐γ) production and direct cytotoxicity of NK cells were essential, without notable contribution from T cells. In thalidomide‐treated mice, there was a significant increase in the terminally differentiated mature CD27lo NK cells in the peripheral tissues and NK cells in thalidomide‐treated mice showed significantly higher cytotoxicity and IFN‐γ production. The NK cell expression of T‐bet was upregulated by thalidomide treatment and the downregulation of glycogen synthase kinase‐3β expression was observed in thalidomide‐treated NK cells. Collectively, our study suggests that thalidomide induces the functional maturation of peripheral NK cells through alteration of T‐bet expression to inhibit lung metastasis of cancer cells. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells are innate lymphocytes that rapidly respond to cancer cells without prior sensitization or restriction to the cognate antigen in comparison with tumor antigen‐specific T cells. Recent advances in understanding NK‐cell biology have elucidated the molecular mechanisms underlying the differentiation and maturation of NK cells, in addition to the control of their effector functions by investigating the receptors and ligands involved in the recognition of cancer cells by NK cells. Such clarification of NK‐cell recognition of cancer cells also revealed the mechanism by which cancer cells potentially evade NK–cell‐dependent immune surveillance. Furthermore, the recent clinical results of T–cell‐targeted cancer immunotherapy have increased the expectations for new immunotherapies by targeting NK cells. However, the potential use of NK cells in cancer immunotherapy is not fully understood. In this review, we discuss the current evidence and future potential of pharmacological targeting of NK cells in cancer immunotherapy. [ABSTRACT FROM AUTHOR]

This paper describes the development of three‐dimensional (3D) human recognition system of flying drone system for emergency rescue and investigation. In this system, deep neural network and its application for 3D object recognition are key techniques for human detection from a free viewpoint. Some appearance based characteristics are captured as movie frames, and the system uses deep neural networks to automatically classify concerned object. The proposed system performs well that many kinds of views of personnel can be recognized from bird's eye view. Experimental results show that the system can effectively recognize human objects with high accuracy. [ABSTRACT FROM AUTHOR]

Sample pretreatment is key to obtaining good data in matrix‐assisted laser desorption/ionization mass spectrometry imaging (MALDI‐MSI). Although sublimation is one of the best methods for obtaining homogenously fine organic matrix crystals, its sensitivity can be low due to the lack of a solvent extraction effect. We investigated the effect of incorporating a thin film of metal formed by zirconium (Zr) sputtering into the sublimation process for MALDI matrix deposition for improving the detection sensitivity in mouse liver tissue sections treated with olanzapine. The matrix‐enhanced surface‐assisted laser desorption/ionization (ME‐SALDI) method, where a matrix was formed by sputtering Zr to form a thin nanoparticle layer before depositing MALDI organic matrix comprising α‐cyano‐4‐hydroxycinnamic acid (CHCA) by sublimation, resulted in a significant improvement in sensitivity, with the ion intensity of olanzapine being about 1800 times that observed using the MALDI method, comprising CHCA sublimation alone. When Zr sputtering was performed after CHCA deposition, however, no such enhancement in sensitivity was observed. The enhanced sensitivity due to Zr sputtering was also observed when the CHCA solution was applied by spraying, being about twice as high as that observed by CHCA spraying alone. In addition, the detection sensitivity of these various pretreatment methods was similar for endogenous glutathione. Given that sample preparation using the ME‐SALDI‐MSI method, which combines Zr sputtering with the sublimation method for depositing an organic matrix, does not involve a solvent, delocalization problems such as migration of analytes observed after matrix spraying and washing with aqueous solutions as sample pretreatment are not expected. Therefore, ME‐Zr‐SALDI‐MSI is a novel sample pretreatment method that can improve the sensitivity of analytes while maintaining high spatial resolution in MALDI‐MSI. [ABSTRACT FROM AUTHOR]

Summary: Betalains are plant pigments primarily produced by plants of the order Caryophyllales. Because betalain possesses anti‐inflammatory and anticancer activities, it may be useful as a pharmaceutical agent and dietary supplement. Recent studies have identified the genes involved in the betalain biosynthesis of betanin. Amaranthin and celosianin II are abundant in the quinoa (Chenopodium quinoa Willd.) hypocotyl, and amaranthin comprises glucuronic acid bound to betanin; therefore, this suggests the existence of a glucuronyltransferase involved in the synthesis of amaranthin in the quinoa hypocotyl. To identify the gene involved in amaranthin biosynthesis, we performed a BLAST analysis and phylogenetic tree analysis based on sequences homologous to flavonoid glycosyltransferase, followed by expression analysis on the quinoa hypocotyl to obtain three candidate proteins. Production of amaranthin in a transient Nicotiana benthamiana expression system was evaluated for these candidates and one was identified as having the ability to produce amaranthin. The gene encoding this protein was quinoa amaranthin synthetase 1 (CqAmaSy1). We also created a transgenic tobacco bright yellow‐2 (BY‐2) cell line wherein four betalain biosynthesis genes were introduced to facilitate amaranthin production. This transgenic cell line produced 13.67 ± 4.13 μm (mean ± SEM) amaranthin and 26.60 ± 1.53 μm betanin, whereas the production of isoamaranthin and isobetanin could not be detected. Tests confirmed the ability of amaranthin and betanin to slightly suppress cancer cell viability. Furthermore, amaranthin was shown to significantly inhibit HIV‐1 protease activity, whereas betanin did not. [ABSTRACT FROM AUTHOR]

Aim: To validate a novel digital health monitoring system to measure the volume of voided urine. Methods: Micturition volume was calculated using our novel digital self‐health monitoring system of urine excretion (s‐HMSU) in 18 participants (16 women and 2 men; average age, 40.8 years), without a history of voiding symptoms. Participants completed a self‐reported questionnaire regarding their medical history and water intake during the period of observation, as well as the Core Lower Urinary Tract Symptom Score (CLSS) questionnaire. To assess the reliability of the voided volumes measured using the s‐HMSU, the intraclass correlation coefficient (ICC) was calculated between the volume and the change in body weight before and after micturition. Results: The CLSS questionnaire confirmed the absence of urinary system diseases in all participants. The medical history was also negative with the exception of hypertension in one participant. The ICC (1,1) between the measured volume of urine excretion using the s‐HMSU and the change in body weight was 0.972 (95% confidence interval, 0.957‐0.982). Conclusions: The s‐HMSU system provides a reliable measure of voiding volume and is appropriate for home use. It has the potential to facilitate large‐scale clinical research to examine the relationship between medical diseases and voiding dysfunction. [ABSTRACT FROM AUTHOR]

Catalysis research is on the verge of experiencing a paradigm shift regarding how catalysts are designed and characterized due to the rise of catalyst informatics. The details of catalyst informatics are reviewed where the following three key concepts are proposed: catalyst data, catalyst data to catalyst design via data science, and catalyst platform. Additionally, progress and opportunities within catalyst informatics are explored and introduced. If the field of catalyst informatics grows in the appropriate manner, the methods and approaches taken for catalyst design would be fundamentally altered, leading towards great advancement within catalysis research. Data in, catalyst out: The emergence of catalyst informatics is introduced with an exploration of three key concepts: catalyst data, catalyst data to design via data science, and platform. The core idea of catalyst informatics is to design catalysts from catalyst data via data science. The current state of catalyst informatics is also reviewed in an effort to address issues and offer potential solutions to obstacles faced by the community. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is ongoing and spreading worldwide after cases of COVID-19 were reported in Wuhan, China in December 2019.1 Older age, diabetes, hypertension, and smoking have been reported as aggravating factors,2 and human immunodeficiency virus (HIV) infection is considered to be a potentially aggravating factor. There are very few reports of COVID-19 in untreated HIV patients3-5 HIV patients are known to be susceptible to respiratory viruses and to have more severe symptoms, but the clinical course and prognosis of COVID-19 in HIV patients are not known yet. COVID-19 pneumonia in untreated HIV patients requires careful follow-up for IRIS with ART. [Extracted from the article]

Objective: Diagnosing fetal heart failure remains challenging because it is difficult to know how well the fetal myocardium will perform as loading conditions change. In adult cardiology, natriuretic peptides (NPs) are established markers of heart failure. However, the number of studies investigating NP levels in fetuses is quite limited. The aim of this study was to evaluate the significance of plasma NP levels in the assessment of heart failure in fetuses with a congenital heart defect (CHD) and/or arrhythmia.Methods: This was a prospective observational study conducted at a tertiary pediatric cardiac center. A total of 129 singletons with CHD and/or arrhythmia and 127 controls were analyzed between 2012 and 2015. Umbilical cord plasma atrial NP, brain NP and N-terminal pro-brain NP levels at birth were compared with ultrasonography findings indicating fetal heart failure, such as cardiovascular profile (CVP) score and morphological characteristics.Results: Fetuses with CHD and/or arrhythmia had higher NP levels than did controls (P < 0.01). NP levels of fetuses with CHD and/or arrhythmia were correlated inversely with CVP score (P for trend < 0.01). No differences in NP levels were found in fetuses with CHD and/or arrhythmia and a CVP score of ≥ 8 in comparison to controls. Multivariate analysis showed that a CVP score of ≤ 5, tachy- or bradyarrhythmia at birth, preterm birth and umbilical artery pH < 7.15 were associated independently with high NP levels (P < 0.01). Among fetuses with a CVP score of ≤ 7, abnormal venous Doppler sonography findings were significantly more common and more severe in fetuses with tachy- or bradyarrhythmia than in those with CHD, and those with tachy- or bradyarrhythmia had higher NP levels than did those with CHD (P = 0.01). Fetuses with right-heart defect and moderate or severe tricuspid valve regurgitation had significantly higher NP levels than did fetuses with other types of CHD (P < 0.01).Conclusions: Plasma NP levels in fetuses with CHD and/or arrhythmia are correlated with the severity of fetal heart failure. Elevated NP levels are attributed mainly to an increase in central venous pressure secondary to arrhythmia or atrioventricular valve regurgitation due to CHD, rather than to the morphological abnormality itself. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Estimation of activation energies within heterogeneous catalytic reactions is performed using machine learning and catalysts dataset. In particular, descriptors for determining activation energy are revealed within the 788 activation energy dataset. With the implementation of machine learning and chosen descriptors, activation energy can be instantly predicted with over 90% accuracy during cross‐validation. Thus, rapid estimation of activation energies within heterogeneous catalytic reactions can be made achievable via machine learning, leading toward the acceleration of catalysts design and characterization. © 2018 Wiley Periodicals, Inc. Estimation of activation energies within heterogeneous catalytic reactions is performed using machine learning and catalysts dataset. With the implementation of machine learning and chosen descriptors, activation energy can be instantly predicted with over 90% accuracy during cross validation. [ABSTRACT FROM AUTHOR]

Accumulating evidence indicates the importance of natural killer (NK) cells in controlling tumor growth and metastasis. NK cell subsets display diversities in their function and tissue distribution and Mac‐1hi CD27lo NK cells are the predominant population of lung‐resident NK cells. Although the lung is a major organ where primary tumor develops and cancer cells metastasize, there is no clear evidence whether circulating NK cells and/or tissue‐resident NK cells control tumor growth in the lung. In the present study, we examined an antitumor function of lung‐resident NK cells to control pulmonary tumor growth. In an orthotopic lung tumor model, NK cells controlled pulmonary tumor growth, and mature circulating NK cell subsets were increased in tumor‐bearing lungs through a C‐X‐C motif chemokine receptor 3 (CXCR3)‐dependent mechanism. Although such increase in migratory NK cell subsets can be blocked by anti‐CXCR3 treatment, there was no difference in pulmonary tumor growth in anti‐CXCR3‐treated mice compared with control mice. In addition to pulmonary tumor growth, lung‐resident NK cells, but not migratory NK cells, play a dominant role in controlling metastatic growth of cancer cells in lung. These results strongly indicate an importance of lung‐resident NK cells for controlling pulmonary tumor growth. [ABSTRACT FROM AUTHOR]

Abstract: Catalysts for oxidative coupling of methane (OCM) are explored using data science and 1868 OCM catalysts from literature data. Machine learning reveals the descriptors responsible for determining the C2 yield produced during the OCM reaction. Trained machine predicts 56 undiscovered catalysts with corresponding conditions for OCM reactions achieving a C2 yield over 30 %. First principle calculations are implemented to evaluate the predicted catalysts where the activation of CH4, CH3, and O2 are confirmed with the predicted catalysts for the OCM reaction. Thus, machine learning is proven to be an effective approach for discovering hidden catalysts and should accelerate the catalyst design process in general. [ABSTRACT FROM AUTHOR]

Aims: We examined the efficacy of tramadol on the urethral reflex during sneezing, as well as the role of µ‐opioid receptors in the spinal cord, in rats. Methods: Forty‐one female Sprague‐Dawley rats were used. The rats were divided into normal female rats and rats with vaginal distension (VD), which mimics stress urinary incontinence (SUI) in humans. Under urethane anesthesia, the sneeze‐induced amplitude of urethral responses (AUR) and baseline pressure (BP) were examined after intravenous injection of tramadol using a microtransducer‐tipped catheter in both rat groups. The effect of intrathecal cyprodime, a selective µ‐opioid receptor antagonist, following intravenous tramadol injection was examined in normal rats. The tilt leak point pressure (tilt LPP) after intravenous tramadol injection was also evaluated in both groups. Results: In normal rats, tramadol enhanced the AUR and BP by 33.2% and 19.5%, respectively. Tramadol also increased BP by 13.9% in rats with VD, but it did not change AUR. Intrathecal cyprodime alone did not change AUR, but it decreased BP. However, tramadol‐provoked increments in AUR were blocked by intrathecal cyprodime, while BP was recovered to the level that it was before administration of cyprodime. Tramadol was associated with a significant elevation in tilt LPP: 24.8% and 19.5% in normal and VD rats, respectively. Conclusions: These findings suggest that tramadol effectively enhances the AUR at the spinal level and BP peripherally. Therefore, stimulation of the spinal µ‐opioid receptors may be useful for the treatment of SUI. [ABSTRACT FROM AUTHOR]

Aims: We aimed to investigate the age‐associated changes in movement coordination between the urinary bladder and the urethra in rats. Methods: A total of 17 female Sprague‐Dawley rats were used. The rats were divided into young (3 months old) and middle‐aged (12‐15 months old) groups. In both groups, isovolumetric cystometry and urethral perfusion pressure (UPP) measurements were performed under urethane anesthesia. After the rhythmic bladder contractions stabilized, L‐arginine, a nitric oxide (NO) substrate (100 mg/kg), was administered intravenously in both groups. Subsequently, N‐nitro‐L‐arginine methyl ester hydrochloride (L‐NAME) (50 mg/kg) was injected intravenously to inhibit NO synthase activity in both groups. Results: UPP change, defined as UPP nadir minus baseline UPP, was significantly smaller in middle‐aged rats (64%) than in young rats (P < 0.05). The mean amplitude of high‐frequency oscillations (HFOs) of the external urethral sphincter was also significantly lower (62%) in middle‐aged rats than that in young rats (P < 0.05). Urethral contraction during UPP change was also noted in middle‐aged rats. This urethral contraction disappeared after L‐arginine administration. UPP nadir during bladder contraction was inhibited by L‐NAME in both groups. UPP change was greater in middle‐aged rats than in young rats, and 3 out of 9 middle‐aged rats showed a detrusor‐sphincter dyssynergia pattern after L‐NAME. Conclusions: The results indicated that aging induces dysfunction in movement coordination between the urinary bladder and the urethra. Thus, age‐associated urethral dysfunctions may lead to inefficient voiding with increased post‐void residual urine volume, which is often observed in elderly populations. [ABSTRACT FROM AUTHOR]

Direct depolymerization of crystalline cellulose into water-soluble sugars by solvent-free ball milling was examined in the presence of a strongly acidic layered metal oxide, HNbMoO6, resulting in full conversion with 72% yield of water-soluble sugars. Measurements by 13C cross-polarization magic angle spinning NMR spectroscopy and X-ray diffraction revealed that amorphization of cellulose occurred rapidly within 10 min. Scanning electron microscopy equipped with an energy dispersive X-ray indicated that the substrate and the catalyst were well mixed during milling. The time course of the product distribution showed that most of the resultant water-soluble sugars were produced not by successive degradation of oligosaccharides but by direct depolymerization of cellulose chains. The products included glucose, mannose, and cellooligomers, as well as anhydrosugars. Addition of small amounts of polar solvents increased the sugar yield, whereas further addition of water decreased the selectivity to anhydrosugars. Calculations of the mechanical energy required for the ball-milling process showed that 0.02% was utilized for the chemical transformation under the conditions examined in this study. [ABSTRACT FROM AUTHOR]

Objectives: Effect of tadalafil on lower urinary tract symptoms (LUTS), erectile function and quality of life (QoL) were prospectively evaluated in patients with benign prostatic hyperplasia (BPH) at multicenter. Methods: Eligible men were ≥40 years who had no treatment with alpha‐blocker for BPH, with total International Prostate Symptom Score (IPSS) ≥8, IPSS‐QOL ≥2 and prostate volume ≥20 mL. Data were collected on age, body mass index (BMI), and prostate specific antigen (PSA). Patients were asked to complete a self‐reported questionnaire regarding the IPSS, Overactive Bladder Symptom Score (OABSS), International Index of Erectile Function 5 (IIEF5), and Medical Outcome Study 8‐Item Short‐Form Health Survey (SF‐8). These measures were assessed at baseline, 4‐, 8‐, 12‐week of tadalafil treatment. In addition, uroflowmetry was also performed at baseline, and 12‐week end point visit. Results: Thirty five patients with mean age 67.3 years, mean BMI 23.6 kg/m2, mean prostate volume 36 mL, and mean PSA 3.4 ng/mL were enrolled. Treatment with tadalafil significantly improved IPSS total score, IPSS voiding subscore, IPSS storage subscore, OABSS and IPSS‐QoL score after 4 weeks and these improvements were maintained for 12‐week treatment period. IIEF5 score and general health in SF‐8 are significantly improved with the treatment of tadalafil. However, maximum flow rate and postvoiding residual volume were not significantly changed. There were not any serious adverse events. Conclusions: These results indicate that tadalafil 5 mg once daily would be effective and well tolerated treatment in Japanese men with BPH‐LUTS. [ABSTRACT FROM AUTHOR]

Objectives In this study, we evaluated the prevalence of lower urinary tract symptoms and the associated clinical features in patients with chronic stroke. Methods Patients with stroke who had been regularly followed up at general medical hospitals in Okinawa, Japan were enrolled in the study. The patients were asked to complete a self-reported questionnaire regarding their physical activity, medical history, and the core lower urinary tract symptom score (CLSS) questionnaire, with anonymity. The association between each urinary disturbance category and the clinical characteristics of the patients such as age, gender, physical activity, and underlying disease was evaluated. Results In total, 51 patients (33 men and 18 women; mean age, 71.7 years) were eligible for analysis. The average time after the first stroke onset was 8.5 years. Nocturia and urgency incontinence had the greatest impact on the quality of life. Overactive bladder symptoms such as nocturia, urgency, urgency incontinence, and stress urinary incontinence were associated with age, female sex, and having a co-existing medical condition (such as ischemic heart disease, hypertension, and depression). Voiding symptoms such as slow stream and straining were associated with age and physical activity after stroke. Conclusions Storage symptom is associated with not only neurological deficits but also sex and the presence of general diseases, whereas voiding symptom is influenced by physical activity in patients with chronic stroke. Therefore, lower urinary tract symptoms should be carefully monitored and physical rehabilitation should also be considered in patients with stroke. [ABSTRACT FROM AUTHOR]

Aim The aim of this study was to identify the clinical features of patients with obstructive sleep apnea syndrome (OSAS) and investigate the impact of continuous positive airway pressure (CPAP) treatment on nocturnal urine volume. Materials and Methods This study enrolled 53 patients with moderate-to-severe OSAS and an apnea-hypoxia index of >20/hr. Data were collected on serum brain natriuretic peptide (BNP) level, International Prostate Symptom Score-Quality of Life (IPSS-QOL) score, Overactive Bladder Symptom Score (OABSS), International Consultation on Incontinence Modular Questionnaire-Nocturia QOL (ICIQ-NQOL) score, Epworth Sleepiness Scale (ESS) score, and the frequency volume chart. Only patients who continued CPAP treatment for 3 months were included in the analysis. Results In total, 40 patients (33 men and 7 women) completed the study (75.5%). The mean age was 56.9 years. The night-time frequency to void was significantly decreased from 2.1 to 1.2 after CPAP treatment ( P < 0.01). The mean scores as assessed by ESS, IPSS-QOL, OABSS, and ICIQ-NQOL significantly improved after CPAP ( P < 0.01). The mean diastolic blood pressure significantly decreased after CPAP treatment. However, there was no significant change in the BNP level before and after CPAP treatment. In the frequency volume chart, hours of undisturbed sleep, total nocturnal voided volume, and nocturnal polyuria index significantly improved after CPAP treatment ( P < 0.05). However, 24-hr voided volume and mean voided volume during night-time did not change after CPAP treatment. Conclusion CPAP treatment decreases night-time urinary frequency by reducing nocturnal urine production and improves QOL in patients with OSAS. Neurourol. Urodynam. 36:376-379, 2017. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Rhabdomyosarcoma ( RMS) is a malignant mesenchymal tumor and the most common soft tissue sarcoma in children. Because of several complications associated with intensive multimodal therapies, including growth disturbance and secondary cancer, novel therapies with less toxicity are urgently needed. C-type natriuretic peptide ( CNP), an endogenous peptide secreted by endothelial cells, exerts antiproliferative effects in multiple types of mesenchymal cells. Therefore, we investigated whether CNP attenuates proliferation of RMS cells. We examined RMS patient samples and RMS cell lines. All RMS clinical samples expressed higher levels of guanylyl cyclase B ( GC-B), the specific receptor for CNP, than RMS cell lines. GC-B expression in RMS cells decreased with the number of passages in vitro. Therefore, GC-B stable expression lines were established to mimic clinical samples. CNP increased cyclic guanosine monophosphate ( cGMP) levels in RMS cells in a dose-dependent manner, demonstrating the biological activity of CNP. However, because cGMP is quickly degraded by phosphodiesterases ( PDEs), the selective PDE5 inhibitor sildenafil was added to inhibit its degradation. In vitro, CNP, and sildenafil synergistically inhibited proliferation of RMS cells stably expressing GC-B and decreased Raf-1, Mitogen-activated protein kinase kinase ( MEK), and extracellular signal-regulated kinase ( ERK) phosphorylation. These results suggested that CNP in combination with sildenafil exerts antiproliferative effects on RMS cells by inhibiting the Raf/ MEK/ ERK pathway. This regimen exerted synergistic effects on tumor growth inhibition without severe adverse effects in vivo such as body weight loss. Thus, CNP in combination with sildenafil represents a promising new therapeutic approach against RMS. [ABSTRACT FROM AUTHOR]

Matrix-assisted laser desorption/ionisation (MALDI) imaging mass spectrometry (IMS) allows for the simultaneous detection and imaging of several molecules in brain tissue. However, the detection of glycerolipids such as diacylglycerol (DAG) and triacylglycerol (TAG) in brain tissues is hindered inMALDI-IMS because of the ion suppression effect from excessive ion yields of phosphatidylcholine (PC). In this study, we describe an approach that employs a homogeneously deposited metal nanoparticle layer (or film) for the detection of glycerolipids in rat brain tissue sections using IMS. Surface-assisted laser desorption/ionisation IMS with sputter-deposited Pt film (Pt-SALDI-IMS) for lipid analysis was performed as a solvent-free and organic matrix-free method. Pt-SALDI produced a homogenous layer of nanoparticles over the surface of the rat brain tissue section. Highly selective detection of lipids was possible by MALDI-IMS and Pt-SALDI-IMS; MALDI-IMS detected the dominant ion peak of PC in the tissue section, and there were no ion peaks representing glycerolipids such as DAG and TAG. In contrast, Pt-SALDI-IMS allowed the detection of these glycerolipids, but not PC. Therefore, using a hybrid method combining MALDI and Pt-SALDI (i.e., matrix-enhanced [ME]-Pt-SALDI-IMS), we achieved the simultaneous detection of PC, PE and DAG in rat brain tissue sections, and the sensitivity for the detection of these molecules was better than that of MALDI-IMS or Pt-SALDI alone. The present simple ME-Pt-SALDI approach for the simultaneous detection of PC and DAG using two matrices (sputter-deposited Pt film and DHB matrix) would be useful in imaging analyses of biological tissue sections. [ABSTRACT FROM AUTHOR]

Aims To investigate the role of the glutamatergic pathway and its relationship to noradrenergic and serotonergic pathways in modulation of the urethral continence reflex during sneezing in rats. Methods In female Sprague-Dawley rats under urethane anesthesia, the effects of an α-amino-3-hydroxy-5-meth-ylisoxazole-4-propionic acid (AMPA) glutamate receptor antagonist, a norepinephrine reuptake inhibitor and a serotonin [5-hydeoxytripitamine (5-HT)]2B/2C agonist on the amplitude of urethral responses during sneezing (AURS), urethral baseline pressure (UBP), and sneeze-induced leak point pressure (S-LPP) were investigated. Results Intrathecal application (i.t.) of NBQX disodium salt (an AMPA receptor antagonist) decreased AURS dose-dependently by approximately 60% without affecting UBP and caused stress urinary incontinence (SUI) during sneezing in 60% of normal rats. Nisoxetine (i.t.), a norepinephrine reuptake inhibitor, and mCPP (i.t.), a 5-HT2B/2C, agonist increased AURS, and NBQX (i.t.) abolished these excitatory effects of nisoxetine (i.t.) and mCPP (i.t.), whereas nisoxetine (i.t.) and mCPP (i.t.) did not enhance AURS in the presence of NBQX (i.t.). Conclusion These results indicate that the glutamatergic pathway acting through AMPA receptors plays a crucial role on the active urethral closure reflex during sneezing at the spinal level, and noradrenergic and serotonergic pathways modulate the reflex via the spinal glutamatergic system in rats. Neurourol. Urodynam. 34:475-481, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Objectives We evaluated the prevalence of and risk factors in patients with nocturia at a general medical clinic in Naha, Japan. Methods We enrolled patients who had been regularly followed-up at a general medical clinic in Naha. Patients were asked to complete a self-reported questionnaire regarding medical history and the frequency of nocturnal voids in the last month with anonymity. Univariate and multivariate logistic regression tests were used to evaluate the risk factors for clinically significant nocturia. Results In total, 357 patients (men, 192; women, 165; mean age, 60 years) were eligible for analysis. The prevalence rate of clinically significant nocturia in patients was 33.8%. Univariate, as well as multivariate, analysis revealed that age, gender, and hypertension were significant risk factors for nocturia. Conclusion Clinically significant nocturia is common among patients seen at a general medical clinic. Age and gender are the most definitive risk factors for nocturia. Hypertension may also be related to nocturia. Thus, it is important to evaluate not only urological problems but other medical problems in patients with nocturia. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives Differences in facial height and breadth between Okinawa Islanders and mainland Japanese have been reported in previous craniometric and somatometric studies. This study using three-dimensional (3D) images aimed to identify more detailed characteristics of facial morphology in each population. Methods Using a hand-held 3D scanner, we obtained 60 facial surface images each from Okinawa Islanders and mainland Japanese. Twenty-one landmarks were plotted on a computer and 27 measurements of distances and angles between the landmarks were taken. Statistical analyses such as t test, principal component analysis (PCA), regression analysis, and discriminant analysis were performed to identify sex and regional differences, the patterns of facial features, factors explaining the facial patterns, and other features. Results Okinawa Islanders showed lower facial and nasal heights than mainland Japanese. Furthermore, we identified larger protrusions of the glabella and nasal root in Okinawa Islanders than in mainland Japanese. In the PCA, we observed components of facial shape patterns. These components mainly represented facial size (PC1), facial depth (PC2), the prominence of the glabella and nasal root (PC3), and facial breadth (PC4). We identified that the population difference is strongly associated with PC3. Conclusions This study quantitatively identified differences in the facial morphology between Okinawa Islanders and mainland Japanese using 3D digital images, with special emphases on the differences in the nasal height and the prominence of the glabella and nasal root. Am. J. Hum. Biol. 26:538-548, 2014. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Aims The urethral continence reflex during stress conditions such as sneezing or coughing is an important mechanism preventing stress urinary incontinence (SUI). Although the spinal noradrenergic and serotonergic pathways are known to modulate this reflex activity, the role of spinal cholinergic pathways in the control of urethral continence reflex has not been elucidated. We therefore investigated the effect of intrathecal administration of an acetylcholine esterase (AChE) inhibitor, which increases ACh in synaptic terminals, and anti-cholinergic agents on the sneeze-induced urethral reflex in rats. Methods Female SD rats were anesthetized with urethane. Urethral function was evaluated during sneezing induced by insertion of the rat whisker into the nostril. Effects of an AChE inhibitor, neostigmine, and muscarinic or nicotinic receptor antagonists administered at the level of L6-S1 spinal cord were examined. Results Neostigmine dose-dependently and significantly decreased the amplitude of urethral responses during sneezing (A-URS) with an approximately 70% reduction at 3 nmol, without changing urethral baseline pressure. The neostigmine-induced decrease in A-URS was significantly reversed by pretreatment with atropine (nonselective muscarinic receptor antagonist), methoctramine (M2 receptor antagonist) or 4-DAMP (M3 receptor antagonist), but not with pirenzepine (M1 receptor antagonist), tropicamide (M4 receptor antagonist), or mecamylamine (nicotinic receptor antagonist). Conclusions These results indicate that an increase in endogenous ACh in the lumbosacral spinal cord inhibits the sneeze-induced urethral continence reflex via activation of M2 and/or M3-muscarinic receptors, implying the inhibitory role of spinal cholinergic pathways in the control of urethral continence reflex under stress conditions such as sneezing. Neurourol. Urodynam. 33:443-448, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background The functions of the lower urinary tract, to store and periodically release urine, are dependent on the activity of smooth and striated muscles in the urinary bladder, urethra, and external urethral sphincter. This activity is in turn controlled by neural circuits in the brain, spinal cord, and peripheral ganglia. Aims This paper will review recent advances in our understanding of the pathophysiology of voiding disorders, especially focusing on the central nervous system. Methods Various neurotransmitters, including acetylcholine, norepinephrine, dopamine, serotonin, excitatory and inhibitory amino acids, adenosine triphosphate, nitric oxide, and neuropeptides, have been implicated in the neural regulation of the lower urinary tract. Results Injuries or diseases of the nervous system, as well as drugs and disorders of the peripheral organs, can produce voiding dysfunctions such as urinary frequency, urgency, or incontinence. Conclusion We discuss the potential targets in the central nervous system and new modalities for the treatment of voiding dysfunction. Neurourol. Urodynam. 33:59-66, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Chloride induced-corrosion of steel bars in concrete can make cracks and exfoliation in near-surface regions in reinforced concrete structures. In this paper, we described the basic concept and practice of steel bars corrosion protection method by the combination of galvanic anode (zinc wire) and the penetration of nitrite ions from mortar layers containing a large amount of lithium nitrite. [ABSTRACT FROM AUTHOR]

ABSTRACT We have investigated the aroma of yuzu ( Citrus junos Sieb. ex Tanaka). Application of the aroma extract dilution analysis technique allowed us to determine a sequence of the odour-active compounds in yuzu volatile oil. In this study, we confirmed the presence of an unknown odorant that possesses a sweaty odour and a relatively high flavour dilution factor. In order to identify the unknown compound, the concentrated volatile acid fraction of yuzu volatile oil was obtained, using an enrichment procedure consisting of the combination of the sub-extraction of an acidic component with a basic aqueous solution and subsequent affinity chromatography with an Oasis MAX cartridge. Gas chromatography-olfactometry and multi-dimensional gas chromatography-mass spectrometry analyses revealed that the unknown compound was ( E)-4-methyl-3-hexenoic acid [( E)-4M3H]. ( E)-4M3H was identified for the first time as an odour-active unsaturated aliphatic acid in yuzu. Additionally, both ( Z)- and ( E)-4M3H were stereoselectively synthesised over two steps comprised of the iron-catalysed carbometalations of homopropargylic alcohols with Grignard reagents, followed by oxidation. On the basis of sensory evaluation, the orthonasal odour detection threshold of the ( E)-isomer was 10-fold to 100-fold lower than that of the ( Z)-isomer. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Lower urinary tract dysfunction is caused by functional and pathophysiological alterations of the peripheral organs, including the urothelium and detrusor smooth muscle, as well as peripheral and central nervous systems. Recent research in this field has increased our understanding of the mechanisms of lower urinary tract dysfunction, and new drugs have been developed, leading to increased treatment options and changing medical care for lower urinary tract symptoms. Nevertheless, clinicians still often experience refractory and treatment-resistant cases against conventional therapeutic modalities. For such cases, gene therapy targeting for the lower urinary tract and its afferent pathway is anticipated to offer a new therapeutic approach. Therefore, in this article, we review the possibility and current status of gene therapy for lower urinary tract dysfunction. [ABSTRACT FROM AUTHOR]

Stress urinary incontinence is the most common type of urinary incontinence in women. Stress urinary incontinence involves involuntary leakage of urine in response to abdominal pressure caused by activities, such as sneezing and coughing. The condition affects millions of women worldwide, causing physical discomfort as well as social distress and even social isolation. This type of incontinence is often seen in women after middle age and it can be caused by impaired closure mechanisms of the urethra as a result of a weak pelvic floor or poorly supported urethral sphincter (urethral hypermobility) and/or a damaged urethral sphincter system (intrinsic sphincter deficiency). Until recently, stress urinary incontinence has been approached by clinicians as a purely anatomic problem as a result of urethral hypermobility requiring behavioral or surgical therapy. However, intrinsic sphincter deficiency has been reported to be more significantly associated with stress urinary incontinence than urethral hypermobility. Extensive basic and clinical research has enhanced our understanding of the complex neural circuitry regulating normal function of the lower urinary tract, as well as the pathophysiological mechanisms that might underlie the development of stress urinary incontinence and lead to the development of potential novel strategies for pharmacotherapy of stress urinary incontinence. Therapeutic targets include adrenergic and serotonergic receptors in the spinal cord, and adrenergic receptors at the urethral sphincter, which can enhance urethral reflex activity during stress conditions and increase baseline urethral pressure, respectively. This article therefore reviews the recent advances in stress urinary incontinence research and discusses the neurophysiology of urethral continence reflexes, the etiology of stress urinary incontinence and potential targets for pharmacotherapy of stress urinary incontinence. [ABSTRACT FROM AUTHOR]

Intracerebroventricular administration of neuromedin U (NMU) exerts an anorexigenic effect in a goldfish model. However, little is known about the NMU receptor and its signalling system in fish. In the present study, we isolated and cloned two cDNAs encoding different proteins comprising 429 and 388 amino acid residues from the goldfish brain based on the nucleotide sequences of human NMU receptor 1 (NMU-R1) and receptor 2 (NMU-R2). Hydropathy and phylogenetic analyses suggested that these two proteins were orthologues of NMU-R1 and -R2 of goldfish. We established two human embryonic kidney 293 cell lines stably expressing putative NMU-R1 and -R2, respectively, and showed that NMU induced an increase in intracellular calcium concentration ([Ca]) in these cells. We examined the presence of NMU-R1 and -R2 in the goldfish brain by western blotting analysis using affinity-purified antisera raised against peptide fragments derived from these receptors. NMU-R1-specific and NMU-R2-specific antisera detected a 49-kDa and 45-kDa immunopositive bands, respectively, in the brain extract. The mass of each band corresponded to that of the deduced respective primary structures. Reverse transcriptase-polymerase chain reaction analysis showed that NMU-R1 and -R2 transcripts were detected in several tissues. In particular, both mRNAs were strongly expressed in the goldfish brain. By contrast, NMU-R2 mRNA was also expressed in the gut. These results indicate for the first time that NMU-R orthologues exist in goldfish, and suggest physiological roles of NMU and its receptor system in fish. [ABSTRACT FROM AUTHOR]

Eyelid dermatitis and/or periocular dermatitis (ED/PD) is commonly seen in a variety of skin diseases such as seborrheic dermatitis, atopic dermatitis and psoriasis, but is most often associated with allergic contact dermatitis (ACD). Here, a case of ACD in an 82-year-old man is described; he used 0.1% diclofenac sodium eye drops and exhibited pruritic erythema on the eyelids. Patch test for diclofenac sodium eye drops was positive. Further patch tests revealed a positive reaction to diclofenac sodium (monosodium 2-[2, 6-dichlorophenylamino] phenylacetate), which was the main component in the eye drop medicine. Diclofenac sodium is a non-steroidal anti-inflammatory drug (NSAID), and is frequently used in everyday oral medications, topical ointments, gel agents and eye drops. Case reports on ACD caused by diclofenac sodium eye drops are extremely rare. Nevertheless, it is necessary to consider ACD due to diclofenac sodium when a patient with ED/PD has a history of use of diclofenac sodium eye drops. [ABSTRACT FROM AUTHOR]

Neuromedin U (NMU) was originally isolated from porcine spinal cord and shown to be distributed in numerous tissues, including the gastrointestinal tract. However, little is known about the role of NMU in the regulation of gastrointestinal functions. We established a radioimmunoassay system that is exceptionally specific for mouse NMU and found high NMU content in the gastrointestinal tract, particularly in the Auerbach's and Meissner's plexi, suggesting a possible role of NMU in gastrointestinal motility. NMU promoted small intestinal transit, and NMU deficiency resulted in lowered intestinal motility rate and diminished the effect of serotonin-induced defecation and diarrhea. These results indicate that NMU promotes intestinal transit and maintains intestinal homeostasis. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to examine the effect of foot baths on the cardiac parasympathetic outflow of five pregnant (31-32 weeks; mid-pregnancy) women and 16 non-pregnant women. Methods: The cardiac parasympathetic outflow was assessed by using the respiratory variability of the R-R interval under controlled breathing according to three different methods: (i) respiratory sinus arrhythmia; (ii) a respiratory-synchronized component of the power spectrum of R-R interval variability with a fast Fourier transform; and (iii) a high-frequency component (HF at 0.15-0.40 Hz) of the power spectrum of R-R interval variability with a maximum entropy method. Results: The rate and amplitude of spontaneous respiration and arterial blood pressure at rest were the same between the non-pregnant and pregnant women. However, the baseline R-R interval was shorter and the respiratory-synchronized and HF components of the power spectrum of R-R interval variability were smaller in the pregnant women, indicating a decreased baseline cardiac parasympathetic outflow with mid-pregnancy. Although a foot bath for 15 min did not significantly affect the systemic hemodynamics and body temperature of both groups, the foot bath reduced the respiratory arrhythmia and the respiratory-synchronized and HF components of the power spectrum of R-R interval variability in both groups. The reduction in the respiratory R-R interval became more prominent in the pregnant group. Conclusion: A foot bath, used as part of midwives' daily nursing care, is able to decrease the cardiac parasympathetic outflow of pregnant women. [ABSTRACT FROM AUTHOR]

Objectives: We investigated the time course of changes in bladder activity as well as in spinal and serum levels of glutamate and glycine after partial bladder outlet obstruction (BOO) in rats. Methods: A total of 36 female rats were divided into six groups: sham operation (control); 3 days, 14 days, and 28 days after BOO; 3 days and 28 days after relief of BOO. Under urethane anesthesia, isovolumetric cystometry was carried out in each group. Then, spinal and serum levels of glutamate and glycine were measured. Results: The interval between bladder contractions was shorter in all of the groups compared with the control group. The amplitude and duration of bladder contractions was decreased at 3 days, 14 days, and 28 days after BOO, and at 3 days after relief of BOO. Spinal and serum glutamate levels showed no changes. However, the spinal glycine level was decreased at 14 days and 28 days after BOO, and at 28 days after relief of BOO. Serum glycine level was also decreased at 28 days after BOO and 28 days after relief of BOO. Conclusions: Detrusor overactivity during the chronic phase of partial BOO is partly caused by a decrease of glycinergic neuronal activity in the lumbosacral cord. A 3-day period of BOO produces detrusor overactivity, which might be due to an irreversible decrease of spinal glycinergic neuronal activity. [ABSTRACT FROM AUTHOR]

Aims Nocturia is a common symptom in the elderly, and various contributing factors have been suggested. Therefore, in order to investigate which factors are strongly related to occurrence of nocturia, we performed a suite of examinations. Methods One hundred eighty volunteers were divided into three groups: a young adult control group (60 healthy persons without nocturia), an elderly control group (60 healthy persons with a low mean frequency of nocturnal urination, i.e., twice per night) in the elderly. Neurourol. Urodynam. 27:205-211, 2008. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Cryptococcus neoformans is eradicated by macrophages via production of NO. Unmethylated CpG-ODN protect mice from infection with this fungal pathogen by inducing IFN-γ. The present study was designed to elucidate the effect of C. neoformans on the synthesis of NO by alveolar macrophages. For this purpose, MH-S, an alveolar macrophage cell line, was stimulated with CpG-ODN in the presence of IFN-γ. A highly virulent strain of C. neoformans with thick capsule suppressed the production of NO. Capsular polysaccharides were not essential for this suppression, because there was no difference between acapsular mutant (Cap67) and its parent strain. Physical or close interaction of Cap67 with MH-S was necessary, as shown by the loss of such effect when direct contact was interfered by nitrocellulose membrane. Similar effects were observed by disrupted as well as intact Cap67. Whereas the inhibitory effect of intact Cap67 was completely abrogated by heat treatment, disrupted Cap67 did not receive such influence. Finally, disrupted Cap67 did not show any inhibitory effect on the TLR9-mediated activation of NF-κB in a luciferase reporter assay with HEK293T cells, although the TLR4-mediated activation was suppressed. These results revealed that C. neoformans suppressed the synthesis of NO by CpG-ODN and IFN-γ-stimulated macrophages in a fashion independent of capsular polysaccharides, although the precise mechanism remains to be elucidated. [ABSTRACT FROM AUTHOR]