Trends in the total numbers of HBV and HCV carriers in Japan from 2000 to 2011.

We estimated the total number of undiagnosed HBV and HCV carriers and patients with hepatitis virus-related disease in Japan according to 6 different groups classified by their natural histories during 2011. In 2011, the total number of carriers and patients infected with HBV or HCV was estimated according to 6 groups using government reports and reports from the hepatitis epidemiology research group of The Ministry of Health, Labor and Welfare in Japan. In 2011, the total number of hepatitis virus carriers was estimated to be 2 090 128-2 840 128 in which the estimated number of undiagnosed HCV and HBV carriers was 776 826 (HBV: 481 470; HCV: 295 356). The total number of treated patients, as either inpatients or outpatients, was estimated to be 811588 (HBV: 303 366; HCV: 520 600) in 2011. It is presumed that many carriers shirk consultation for many reasons, such as patients' misunderstanding, lack of awareness and forgetfulness of their positive status. The numbers of infected patients who did not seek treatment increased gradually to 501 714-1 251 714 (HBV: 333 791-483 791; HCV: 167 923-767 923) in 2011. Compared to 2000, the number of undiagnosed carriers was significantly reduced in 2011 probably because of the well-organized, effective national hepatitis virus screening system that has been launched by the Japanese government since 2002. Moreover, the increase in the number of untreated persons who are aware of their positive status shows that more effort should be invested in improving the referral system from screening centres to core hospitals.

A clustering approach to identify and characterize the asthma and chronic obstructive pulmonary disease overlap phenotype.

BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous diseases. The phenotypes that have clinical features of both asthma and COPD are still incompletely understood. OBJECTIVE: To clarify the best discriminators of the asthma-COPD overlap phenotype from asthma and COPD subgroups using a clustering approach. METHODS: This study assessed pathophysiological parameters, including mRNA expression levels of T helper cell-related transcription factors, namely TBX21 (Th1), GATA3 (Th2), RORC (Th17) and FOXP3 (Treg), in peripheral blood mononuclear cells in asthma patients (n=152) and in COPD patients (n=50). Clusters were determined using k-means clustering. Exacerbations of asthma and COPD were recorded during the 1-year follow-up period. RESULTS: The cluster analysis revealed four biological clusters: cluster 1, predominantly patients with COPD; cluster 2, patients with an asthma-COPD overlap phenotype; cluster 3, patients with non-atopic and late-onset asthma; and cluster 4, patients with early-onset atopic asthma. Hazard ratios for exacerbation were 2.5 (95% confidence interval [CI], 1.1-5.6) in cluster 1 and 2.3 (95% CI, 1.0-5.0) in cluster 2 compared with patients in other clusters. Cluster 2 was discriminated from other clusters by total serum IgE level ≥310 IU/mL, blood eosinophil counts ≥280 cells/µL, a higher ratio of TBX21/GATA3, FEV1 /FVC ratio <0.67 and smoking ≥10 pack-years with an area under the curve of 0.94 (95% CI, 0.90-0.98) in the receiver operating characteristic analysis. CONCLUSIONS AND CLINICAL RELEVANCE: The asthma-COPD overlap phenotype was characterized by peripheral blood eosinophilia and higher levels of IgE despite the Th2-low endotype.

Systematic review and meta-analysis of hepatitis C virus infection in the Democratic Republic of Congo.

OBJECTIVES: Hepatitis C virus (HCV) infection is endemic in the Democratic Republic of the Congo (DRC), where the prevalence of HCV antibodies (anti-HCV) is reported to range from 0.2% to 13.7%. However, the reported prevalence rates have been inconsistent. Therefore, a meta-analysis of observational studies was conducted to provide updates on the prevalence of HCV infection in the DRC. STUDY DESIGN: Systematic review and meta-analysis. METHODS: Medline, EMBASE and Google Scholar were searched for publications reporting on HCV infection in the DRC up to autumn 2015. In addition, a manual search was undertaken to detect relevant papers. Studies performed in groups at low risk of HCV (blood donors and pregnant women) were used for the meta-analysis. The random effects model was used to estimate the pooled prevalence of anti-HCV. RESULTS: Sixteen studies with 13,799 participants (aged 6 months-71 years) met the inclusion criteria. The studies were performed in blood donors, pregnant women, military personnel, individuals with human immunodeficiency virus, children, commercial sex workers, Congolese patients living in Canada, patients with sickle cell disease and hospitalized patients. The reviewed studies revealed the presence of anti-HCV in almost all studied age groups and did not differ between sexes. The pooled prevalence of anti-HCV was 2.9% [95% confidence interval 1.5-4.3%]. Subgroup analyses revealed that the prevalence rates of anti-HCV in blood donors and pregnant women were 2.7% (95% confidence interval: 1.1-4.4%) and 3.3% (1.4-5.1%), respectively. CONCLUSIONS: HCV infection remains an issue of public concern in the DRC, demonstrating a need for adequate hepatitis control programmes. Efforts must be made to virtually eliminate transfusion-transmitted HCV throughout the country.

Characteristics and roles of the volume-sensitive outwardly rectifying (VSOR) anion channel in the central nervous system.

Cell volume regulation (CVR) is essential for all types of cells in the central nervous system (CNS) to counteract cell volume changes that may be associated with neuronal activities or diseases and with osmosensing in the hypothalamus, to facilitate morphological changes during cell proliferation, differentiation and migration, and to execute apoptosis of cells. The regulation is attained by regulating the net influx or efflux of solutes and water across the plasma membrane. The volume-sensitive outwardly rectifying (VSOR) anion channel plays a major role in providing a pathway for anion flux during the regulation. The VSOR anion channel is permeable not only to Cl(-) ions but also to amino acids like glutamate and taurine. This property confers a means of intercellular communications through the opening of the channel in the CNS. Thus exploring the roles of VSOR anion channels is crucial to understand the basic principles of cellular functions in the CNS. Here we review biophysical and pharmacological characteristics of the VSOR anion channel in the CNS, discuss its activation mechanisms and roles in the CNS reported so far, and give some perspectives on the next issues to be examined in the near future.

Magnetically transportable core-shell emulsion droplets with an antioxidative all-organic paramagnetic liquid shell.

Magnetically-transportable core-shell emulsion droplets with an antioxidative all-organic paramagnetic liquid shell [Nitroxide Radical Liquid (NRL) microcapsules] were demonstrated. We successfully fabricated stable NRL microcapsules with microfluidic devices. The NRL microcapsules are magnetically transportable and are likely to protect the inner phase from oxidants. Consequently, the NRL microcapsules can serve as a flexible antioxidative magnetic carrier for nanoliter cargoes.

Respiratory mechanics and peripheral airway inflammation and dysfunction in asthma.

BACKGROUND: Clinical application of the forced oscillation technique (FOT) has progressed with the spread of commercially available FOT devices. The correlation between respiratory impedance and spirometry has been reported; however, the association with airway inflammation and pulmonary function, in the lung periphery in particular, is unclear. OBJECTIVE: To assess whether respiratory impedance is associated with peripheral airway inflammation and dysfunction in asthma. METHODS: Subjects included 78 patients with overall controlled asthma. We measured whole-breath or within-breath respiratory system resistance (Rrs) and reactance (Xrs) using a commercially available multi-frequency FOT device (MostGraph-01), and assessed the correlation with the fraction of exhaled nitric oxide (FeNO), alveolar nitric oxide concentration (CANO), maximal NO flux in the conductive airways (J'awNO), and the N2 phase III slope of single breath N2 washout (delta N2 ). RESULTS: The differences between inspiratory and expiratory phases of Xrs at 5 Hz (X5), resonant frequency (Fres), and a low-frequency reactance area (ALX) were significantly correlated with CANO; however, there was no correlation between respiratory impedance and FeNO or J'awNO. The delta N2 values were significantly correlated with whole-breath, inspiratory, and expiratory Rrs and Xrs, except for R20. CONCLUSIONS AND CLINICAL RELEVANCE: We conclude that respiratory impedance reflects peripheral airway inflammation and ventilation inhomogeneity.

Prognosis of chronic spontaneous urticaria in 117 patients not controlled by a standard dose of antihistamine.

BACKGROUND: Chronic spontaneous urticaria (CSU) is a common skin disorder, but its clinical course reported so far is largely variable, probably due to the heterogeneity of the clinical background of patients and pathogenesis of this disease. METHODS: To reveal the prognosis of refractory CSU, we retrospectively studied the patients who suffered from spontaneous urticaria for six weeks or longer at their first visit to our outpatient clinic, who were insufficiently controlled by a standard dose of antihistamine, and revisited from 2003 to 2009. RESULTS: Among 223 patients with CSU, 117 patients fulfilled the criteria mentioned above. Mean disease duration at first visit and mean duration of follow-up at our hospital were 27.4 ± 4.2 months and 18.7 ± 1.9 months, respectively. By using Kaplan-Meier methods, the estimated improved rates at 12 months, 24 months, and 60 months were 36.6%, 51.2%, and 66.1%, respectively. The overall improvement rate of childhood cases (<19 years) was significantly higher than that of adult cases (P = 0.007, log-rank test). Moreover, the improvement rate of patients with short disease durations (<1 year at the first visit) was significantly (P = 0.003, log-rank test) higher than that of patients with long disease durations (one year or more). CONCLUSION: Our data indicate that the condition of patients with CSU can be gradually improved even in intractable cases. Information about the clinical course and prognostic factors of CSU in this study could help physicians predict the prognosis of patients and ensure medication adherence of patients with CSU.

Propane reacts with O2 and H2 on gold supported TS-1 to form oxygenates with high selectivity.

Gold nanoparticles supported on a microporous titanosilicate (TS-1) were found to be highly selective (95%) towards the formation of acetone and isopropanol from propane, O(2), and H(2) at moderate temperatures (443 K).

[Aortic valve replacement for the small aortic annulus].

Aortic valve surgery for the small aortic annulus is still challenging for surgeons. Recently, the new types of high performance prosthesis have been developed and the chance of an aortic root enlargement (ARE) is decreasing. In this study, we propose the ideal strategy of the aortic surgery for the small aortic annulus. We analyzed the clinical records of 158 patients who underwent aortic valve replacement from August 1999 to October 2005 in our institution. The small aortic annulus was observed in 38 patients (24%). Fourteen patients of this group underwent ARE. Patient-prosthesis mismatch (PPM) was less frequently observed in patients with ARE compared to those without ARE. The additional time required for ARE was not considerable, and neither ischemic time nor cardiopulmonary bypass time was significantly prolonged by ARE. In conclusion, we have to select a prosthesis with sufficient orifice area to avoid PPM, otherwise we should choose an option of ARE. For this consideration, we definitely need the chart that demonstrates the relationship between the nominal size of various types of prostheses and the size of a patient's annulus that those prostheses actually fit.

[Repair of tetralogy of Fallot with obstruction of right pulmonary artery; report of a case].

Patients with tetralogy of Fallot showing unilateral obstruction of a pulmonary artery, especially the right pulmonary artery, are a high-risk group for pulmonary hypertension after repair. This case of tetralogy of Fallot with the obstruction of the right pulmonary artery received a Blalock-Taussig shunt at 7 months old, and the occluded right pulmonary artery caused empyema after surgery. At 2 years old, a cardiac catheter study showed a pulmonary artery index of 193.6 mm2/m2, so we undertook intracardiac repair. After the repair, she showed a relativery favorable clinical course. Systolic pulmonary artery pressure and right ventricular pressure were about 30 and 50 mmHg, respectively. We considered that tetralogy of Fallot with obstruction of right pulmonary artery could be repaired, as long as the pulmonary artery index was within the limits of indication and the left ventricle was well-developed.

[Short-term results of the Fontan operation in patients with Down syndrome].

Despite an extensive experience with Fontan operation, there is a paucity of information to guide the indication of the procedure in patients with Down syndrome. Of 79 patients who had undergone a Fontan operation in our hospital between 1995 and 2003, 3 had Down syndrome. All 3 patients had complete atrioventricular septal defect with single ventricular physiology. Two patients survived, and 1 died of chylothorax and respiratory infection. The 2 survivors have done well in the short-term without complications. We consider that in appropriately selected patients with Down syndrome in whom biventricular repair is precluded, the Fontan operation is the choice of the procedures.

Three-dimensional mesoporous titanosilicates prepared by modified sol-gel method: Ideal gold catalyst supports for enhanced propene epoxidation.

Mesoporous titanosilicates with 1-12 mol % Ti content and with three-dimensional wormhole-like mesoporosity are prepared by a modified sol-gel technique. Sorption analysis shows that there is little change in the surface properties with increasing Ti concentration in the samples, implying that Ti atoms either are well-dispersed on the walls of the silica matrix or are present inside the framework with no pore blocking effect. Spectroscopic analysis shows that the Ti atoms are atomically dispersed in the silica matrix even at very high Ti concentration and there is no observable Ti aggregate (anatase) present in the samples. These titanosilicate samples after Au deposition followed by trimethylsilylation (for enhanced hydrophobicity) are highly efficient catalysts for vapor-phase propene epoxidation using O2 and H2. It was possible to achieve commercially desirable performance with about 7% propene conversion, >90% propene oxide selectivity, and about 40% hydrogen efficiency.

Central and peripheral concentrations of tumor necrosis factor-alpha in Chinese Meishan pigs stimulated with lipopolysaccharide.

The objective of this study was to investigate the presence of tumor necrosis factor-alpha (TNF-alpha) in the central nervous system and the effects of lipopolysaccharide on central and peripheral concentrations of TNF-alpha, behavioral conditions (standing or lying), elimination scores (defecation or urination), rectal temperature, and food intake (as-fed basis) in Chinese Meishan pigs. Intravenous injections of lipopolysaccharide resulted in increased (P < 0.05) plasma concentrations of TNF-alpha and cortisol. Although urination was not affected by the administration of lipopolysaccharide, defecation was stimulated (P < 0.05). Lipopolysaccharide increased (P < 0.05) rectal temperature and standing rate, and inhibited (P < 0.05) food intake in pigs. To determine whether TNF-alpha is present in the porcine central nervous system as well as in peripheral blood, TNF-alpha and its specific transcripts in brain tissues (hypothalamus, amygdala, or hippocampus) and the pituitary were determined. The abundance of TNF-alpha messenger RNA and immunoreactive TNF-alpha were observed in all tissues, and the concentrations of TNF-alpha were increased (P < 0.05) by the intramuscular injection of lipopolysaccharide. These results suggest that TNF-alpha is present in the central nervous system, and plays some roles in its biological regulation in Chinese Meishan pigs.

[Long-term results of Fontan type operation].

We had experienced 41 Fontan type operations between 1977 and 2002. Twelve patients had an atriopulmonary connection (APC), 3 patients had a lateral tunnel connection, and 2 had internal conduit repair and 24 patients received an external conduit repair. There were 3 operative deaths and 5 late deaths (5 months to 24 years). Kaplan-Meier analysis shows good 5-years survival in both group of atriopulmonary connection and that of total cavoplumonary connection (TCPC). However, survival and clinical status of APC patients deteriorated after 7 years. Atrial fibrillation and right pulmonary vein stenosis by giant right atrium become common in these patients. We recommend that patients with single ventricle have the TCPC type operation and patients with giant right atrium and poor clinical status after APC have the TCPC conversion.

[Experience of coronary artery bypass grafting on the beating heart with right heart bypass; 3 cases of octogenarian].

Right heart bypass (RHB) yields more stable hemodynamics by increasing left ventricular preload and collapse right ventricular chamber during the displacement of the heart on beating heart coronary artery bypass grafting (CABG). Recently beating heart CABG gaining popularity, and the indications for CABG have increasingly expanded to elderly person. Using RHB while exposing posterior branches by displacing the beating heart, we have attempted to make total revascularization in beating heart CABG. We performed beating heart CABG with RHB in 3 cases of octogenarian. All patients had left main trunk lesion and needed revascularization of posterior vessels. Introduction of RHB enabled us to approach to posterior target vessels in better exposure and under greater hemodynamic stability. All three patients had no complications postoperatively. Strictly speaking CABG with RHB is not off-pump CABG, but RHB system does not include either artificial lung or manipulation of the aorta. Therefore we think it is very effective support system which enables multiple coronary revascularization for elderly person.

Ca(2+)-dependent Ca(2+) clearance via mitochondrial uptake and plasmalemmal extrusion in frog motor nerve terminals.

Ca(2+) clearance in frog motor nerve terminals was studied by fluorometry of Ca(2+) indicators. Rises in intracellular Ca(2+) ([Ca(2+)](i)) in nerve terminals induced by tetanic nerve stimulation (100 Hz, 100 or 200 stimuli: Ca(2+) transient) reached a peak or plateau within 6-20 stimuli and decayed at least in three phases with the time constants of 82-87 ms (81-85%), a few seconds (11-12%), and several tens of seconds (less than a few percentage). Blocking both Na/Ca exchangers and Ca(2+) pumps at the cell membrane by external Li(+) and high external pH (9.0), respectively, increased the time constants of the initial and second decay components with no change in their magnitudes. By contrast, similar effects by Li(+) alone, but not by high alkaline alone, were seen only on 200 stimuli-induced Ca(2+) transients. Blocking Ca(2+) pumps at Ca(2+) stores by thapsigargin did not affect 100 stimuli-induced Ca(2+) transients but increased the initial decay time constant of 200 stimuli-induced Ca(2+) transients with no change in other parameters. Inhibiting mitochondrial Ca(2+) uptake by carbonyl cyanide m-chlorophenylhydrazone markedly increased the initial and second decay time constants of 100 stimuli-induced Ca(2+) transients and the amplitudes of the second and the slowest components. Plotting the slopes of the decay of 100 stimuli-induced Ca(2+) transients against [Ca(2+)](i) yielded the supralinear [Ca(2+)](i) dependence of Ca(2+) efflux out of the cytosol. Blocking Ca(2+) extrusion or mitochondrial Ca(2+) uptake significantly reduced this [Ca(2+)](i)-dependent Ca(2+) efflux. Thus Ca(2+)-dependent mitochondrial Ca(2+) uptake and plasmalemmal Ca(2+) extrusion clear out a small Ca(2+) load in frog motor nerve terminals, while thapsigargin-sensitive Ca(2+) pump boosts the clearance of a heavy Ca(2+) load. Furthermore, the activity of plasmalemmal Ca(2+) pump and Na/Ca exchanger is complementary to each other with the slight predominance of the latter.

Effect of zinc deficiency on betacyanin production in a cell suspension culture of table beet (Beta vulgaris L.).

The effect of microelements in the Linsmaier-Skoog (LS) medium on betacyanin production was investigated in suspension cultures of table beet (Beta vulgaris L.). Removing zinc from the medium resulted in a high betacyanin content of the cells, the betacyanin content of the cells decreasing with increasing zinc concentration in the medium. The betacyanin content of cells cultured in the medium without zinc was twice as high as that in the medium containing 0.03 mM of zinc. In the revised LS medium without zinc, the maximum betacyanin yield was obtained of 590 mg/l from a 21-day culture.

TEM and HAADF-STEM study of a Au catalyst supported on a TiO2 nano-rod.

Gold nanoparticles were deposited on TiO2 nano-rods by a deposition precipitation method. This Au/TiO2 nano-rods catalyst is active for CO oxidation even at temperatures less than 273K and is as active as the catalyst of Au supported on conventional TiO2 particles. Transmission electron microscopy (TEM) showed that the TiO2 nano-rods were composed of a single anatase crystal and had a pillar shape with an axis along the <111> direction surrounded by flat four [101] planes. High angle annular dark field scanning TEM (HAADF-STEM) also revealed that a Au platelet with a thickness of 0.5-1 nm was formed at the interface between TiO2 nano-rods. The Au platelet was not observed when conventional round particles of TiO2 were used as a support.

Congestive heart failure caused by aortocaval fistula after nephrectomy.

We treated a 66-year-old man and a 69-year-old woman with high output cardiac failure due to aortocaval fistula. They underwent nephrectomy 40 and 36 years ago, respectively. They suffered from heart failure for a very long time. However, the etiology was not elucidated until recently. The aortogram revealed massive shunt from the aorta to the inferior vena cava via the right renal artery. Three-dimensional computerized tomography clearly delineated the aortocaval fistula. Surgical closure of the fistula promptly improved heart failure. We stress the importance of history taking concerning nephrectomy and the importance of abdominal auscultation in high output cardiac failure.

Hyperhomocysteinemia impairs angiogenesis in response to hindlimb ischemia.

Hyperhomocysteinemia (HH) is an independent risk factor for atherosclerosis, including peripheral arterial occlusive disease (PAOD). Because angiogenesis and collateral vessel formation are important self-salvage mechanisms for ischemic PAOD, we examined whether HH modulates angiogenesis in vivo in a rat model of hindlimb ischemia. Rats were divided into 3 groups: the control group was given tap water, the HH group was given water containing L-methionine (1 g x kg(-1) x d(-1)), and the HH+L-arg group was given water containing methionine (1 g x kg(-1) x d(-1)) and l-arginine (2.25 vol%). At day 14 of the dietary modifications, the left femoral artery and vein were excised, and the extent of angiogenesis and collateral vessels in the ischemic limb were examined for 4 weeks. Plasma homocysteine levels significantly increased (P:<0.001), and plasma and tissue contents of nitrite+nitrate as well as tissue cGMP levels significantly decreased in the HH group compared with the control group (P:<0.01). Laser Doppler blood flowmetry (LDBF) revealed a significant decrease in the ischemic/normal limb LDBF ratio in the HH group at days 7, 14, 21, and 28 (P:<0.01 versus control). Angiography revealed a significant decrease in the angiographic score in the HH group at day 14 (P:<0.001 versus control). Immunohistochemistry of ischemic tissue sections showed a significant reduction in the capillary density in the HH group (P:<0. 001 versus control). Oral l-arginine supplementation in rats with HH (HH+L-arg) restored the decreased plasma and tissue nitrite+nitrate and cGMP contents (P:<0.05) as well as angiogenesis, as assessed by LDBF (P:<0.05 versus HH), angiographic score (P:<0.01 versus HH), and capillary density (P:<0.001 versus HH). In summary, HH impaired ischemia-induced angiogenesis and collateral vessel formation in a rat model of hindlimb ischemia in vivo. The mechanism of the HH-induced impairment of angiogenesis might be mediated in part by a reduced bioactivity of endogenous NO in the HH state.