Vegetative growth after flowering through gibberellin biosynthesis regulates pod setting rate in soybean (Glycine max (L.) Merr.).

Pod setting rate in soybean is an important trait that determines pod number, which is highly correlated with seed yield. Using two soybean cultivars with different pod setting rates, we examined the relationship between plant growth regulation by gibberellin (GA) and pod setting rate. Plant growth rate (PGR) after flowering was significantly higher in 'Fukuyutaka' (low pod setting rate) than in 'Kariyutaka' (high pod setting rate); this difference was caused by increasing of GA biosynthesis-related genes expression. Additionally, pod setting rate in 'Fukuyutaka' was lower than that in 'Kariyutaka'. Furthermore, when 'Kariyutaka' was treated with GA after flowering, the PGR increased and pod setting rate decreased. These results suggest that pod setting rate in soybean is regulated by vegetative growth after flowering through GA biosynthesis.

Determining an optimal dose of linaclotide for use in Japanese patients with irritable bowel syndrome with constipation: A phase II randomized, double-blind, placebo-controlled study.

BACKGROUND: Clinical testing to determine a suitable dose of linaclotide for Japanese patients with irritable bowel syndrome with constipation (IBS-C) was needed. METHODS: This was a randomized, double-blind, placebo-controlled, dose-finding trial. Japanese patients with IBS-C diagnosed using Rome III criteria (n = 559, men/women: 49/510) were randomly assigned to 1 of 4 linaclotide doses (0.0625, 0.125, 0.25, or 0.5 mg) or placebo for the 12-week treatment period. The primary endpoint was responder rate of global assessment of relief of IBS symptoms during 12 weeks. The secondary endpoints included responder rates of complete spontaneous bowel movement (CSBM), SBM and abdominal pain/discomfort relief and others. KEY RESULTS: The primary endpoint was 23.2%, 36.2%, 38.7%, 34.8%, and 38.3% in placebo (n = 112), 0.0625 (n = 116), 0.125 (n = 111), 0.25 (n = 112), and 0.5 (n = 107) mg of linaclotide groups with the difference from the placebo group in each linaclotide group (13.0%, 15.5%, 11.6%, 15.1%, P > .05). Monthly responder rate of global assessment of relief of IBS symptoms at month 3 (48.6%), responder rate of CSBM during 12 weeks (45.8%), and responder rate of abdominal pain/discomfort relief during 12 weeks (32.7%) in the 0.5 mg were significantly higher than those in placebo group (29.5%, P < .01; 25.9%, P < .01; and 18.8%, P < .05 respectively). The most frequent adverse event in the linaclotide groups was diarrhea. CONCLUSIONS & INFERENCES: This study suggests that a linaclotide dose of 0.5 mg may be appropriate in Japanese patients with IBS-C.

A laser-induced pulsed water jet for layer-selective submucosal dissection of the esophagus.

Background and aims: Conventional water jet devices have been used for injecting fluid to lift up lesions during endoscopic submucosal dissection or endoscopic mucosal resection procedures. However, these devices cannot dissect the submucosal layer effectively. Here we aim to elucidate the dissection capability of a laser-induced pulsed water jet and to clarify the mechanism of dissection with layer selectivity. Materials (Subjects) and methods: Pulsed water jets were ejected from a stainless nozzle by accelerating saline using the energy of a pulsed holmium: yttrium-aluminum-garnet laser. The impact force (strength) of the jet was evaluated using a force meter. Injection of the pulsed jet into the submucosal layer was documented by high-speed imaging. The physical properties of the swine esophagus were evaluated by measuring the breaking strength. Submucosal dissection of the swine esophagus was performed and the resection bed was evaluated histologically. Results: Submucosal dissection of the esophagus was accomplished at an impact force of 1.11-1.47 N/pulse (laser energy: 1.1-1.5 J/pulse; standoff distance: 60 mm). Histological specimens showed clear dissection at the submucosal layer without thermal injury. The mean static breaking strength of the submucosa (0.11 ± 0.04 MPa) was significantly lower than that of the mucosa (1.32 ± 0.18 MPa), and propria muscle (1.45 ± 0.16 MPa). Conclusions: The pulsed water jet device showed potential for achieving selective submucosal dissection. It could achieve mucosal, submucosal, and muscle layer selectivity owing to the varied breaking strengths.

Clinical Features and Outcomes of Diffuse Alveolar Hemorrhage During Antithrombotic Therapy: A Retrospective Cohort Study.

PURPOSE: Antithrombotic therapy could trigger diffuse alveolar hemorrhage (DAH), and there are several case reports of DAH that occurred during antithrombotic therapy (DAH-AT). However, little is known about the clinical features and outcomes of DAH-AT. The purpose of this study was to clarify the features and mortality of DAH-AT. METHODS: 76 consecutive patients with DAH who were admitted to our hospital between January 2003 and April 2014 were retrospectively reviewed to identify the clinical features and outcomes of DAH-AT. The primary outcome was 90-day mortality. RESULTS: Of the 76 patients with DAH, 39 patients (51 %) had DAH-AT, and 37 patients (49 %) had DAH that occurred with no antithrombotic therapy (DAH-NAT). Of the patients with DAH-AT, 25 (64 %) were taking aspirin, 14 (36 %) were taking warfarin, 5 (13 %) were taking clopidogrel sulfate, and 4 (10 %) were taking cilostazol. Pre-existing cardiac disease was present in 23 (59 %) DAH-AT cases and 5 (14 %) DAH-NAT cases. Logistic regression analysis was used to assess the effect of antithrombotic therapy on the mortality of DAH patients, and no significant difference in survival was seen with antithrombotic therapy (OR 1.18, 95 % CI 0.38-3.78). CONCLUSIONS: Antithrombotic therapies had no effect on the 90-day mortality of DAH patients.

All-atom molecular dynamics calculation study of entire poliovirus empty capsids in solution.

Small viruses that belong, for example, to the Picornaviridae, such as poliovirus and foot-and-mouth disease virus, consist simply of capsid proteins and a single-stranded RNA (ssRNA) genome. The capsids are quite stable in solution to protect the genome from the environment. Here, based on long-time and large-scale 6.5 × 10(6) all-atom molecular dynamics calculations for the Mahoney strain of poliovirus, we show microscopic properties of the viral capsids at a molecular level. First, we found equilibrium rapid exchange of water molecules across the capsid. The exchange rate is so high that all water molecules inside the capsid (about 200,000) can leave the capsid and be replaced by water molecules from the outside in about 25 µs. This explains the capsid's tolerance to high pressures and deactivation by exsiccation. In contrast, the capsid did not exchange ions, at least within the present simulation time of 200 ns. This implies that the capsid can function, in principle, as a semipermeable membrane. We also found that, similar to the xylem of trees, the pressure of the solution inside the capsid without the genome was negative. This is caused by coulombic interaction of the solution inside the capsid with the capsid excess charges. The negative pressure may be compensated by positive osmotic pressure by the solution-soluble ssRNA and the counter ions introduced into it.

Measurement and analysis of internal stress distributions created in gelatin simulated-brain tissue by a pulsed laser-induced liquid jet.

Transsphenoidal surgery is currently employed to treat complex lesions beyond the sella turcica; however, the procedure can be limited by difficulties encountered in dealing with small blood vessels, deep and narrow working spaces, and awkward working angles. To overcome these problems, we have developed a pulsed laser-induced liquid jet system that can dissect tumor tissue while preserving fine blood vessels within deep and narrow working spaces. We have previously evaluated the utility and safety of this procedure. However, the effects of the pulsejet after being injected into the brain are not yet well understood. Especially, the behavior of the stress distribution created by the jet is important because it has recently been reported that high acoustic pressures can affect the brain. In this study, we measured internal stress distributions in a gelatin simulated-brain using photoelasticity experiments. We used a high-speed camera with an image sensor on which an array of micropolarizers was attached to measure the stresses and the shear wave created when the pulsejet enters the simulated brain.

Analysis of liquid reservoir effect induced by pulsed laser liquid jet.

A pulsed-laser-induced liquid jet (LILJ) is a new device used in neurosurgery to simultaneously crush, incise, and aspirate tissues and tumors, preserving blood vessels and nerves. In addition, a feature of a pulsed LILJ is its ability to excavate tissue at constant depth while a liquid jet is being repeatedly focused at the same point. To clarify the mechanisms of constant depth of excavation, we employed a gelatin phantom and extracted brain tissue using a high-speed camera, and we then confirmed that the liquid-reservoir-induced LILJ played an important role in enabling the safe usage of an LILJ.

Removal of high concentration ammonia from wastewater by a combination of partial nitrification and anammox treatment.

Attached growth reactors were developed separately for solids retention time (SRT)-controlled partial nitrification and for anaerobic ammonia oxidation (Anammox) treatment, and a new nitrogen removal process is proposed for wastewater containing highly concentrated ammonia. For partial nitrification, an attached growth medium of polyurethane foam was used. Partial nitrification was achieved stably under a SRT of 4 days, and the abundance ratio of NO2(-)-N to the sum of NH4(+)-N, NO2(-)-N and NO3(-)-N was approximately 0.8 after 10 days. Under a SRT of4 days, the amoA gene concentrations of ammonia-oxidizing bacteria increased from 1 x 10(8) to 7 x 10(8) copies/l, whereas the 16S ribosomal RNA (16S rRNA) gene concentrations of nitrite-oxidizing bacteria did not increase. These results indicate that SRT-controlled operation is a promising technology for achieving partial nitrification. For the Anammox treatment, an attached growth medium of non-woven fabric was used. Inorganic nitrogen removal of approximately 80-90% was observed at an inorganic nitrogen loading rate of over 10 kgN/(m3-medium.d) and an influent nitrogen concentration of 400 mgN/l. Our non-woven fabric reactor showed similar or superior Anammox performance to that reported previously. By using a combination of these two rectors, we can develop a method that combines partial nitrification and Anammox treatment for effective and stable nitrogen removal.

Real-time monitoring of liver damage during experimental ischaemia-reperfusion using a nitric oxide sensor.

BACKGROUND: Hepatic ischaemia-reperfusion (IR) injury may lead to liver damage during liver surgery, and intrahepatic nitric oxide (NO) levels may play a role in this context. The aim of this study was to demonstrate real-time changes in intrahepatic NO concentration during IR and to correlate potential hepatic NO production with liver damage using a selective NO sensor. METHODS: Wistar rats were exposed to 15 min of hepatic ischaemia followed by reperfusion, after which changes in intrahepatic NO levels were measured using an NO sensor. Additionally, rats were exposed to five successive periods of IR, each consisting of 15 min ischaemia followed by 5 or 15 min reperfusion, and hepatic damage was evaluated by blood tests and histological examination. Hepatic expression of Akt, phosphorylated Akt, endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS was examined at different time points during and after IR by western blot and immunohistochemical analysis. RESULTS: During ischaemia, intrahepatic NO levels increased and reached a plateau at approximately 10 min. Repeated 15 min ischaemia-5 min reperfusion cycles reduced the maximum amount of NO produced during ischaemia gradually, and almost no NO production was observed during the fifth period of ischaemia. NO production following repeated ischaemia was proportional to the degree of hepatic viability. Phosphorylated eNOS was upregulated and correlated with the level of NO production during hepatic ischaemia. CONCLUSION: Intrahepatic NO levels decrease during repeated IR in rats. Real-time monitoring of intrahepatic NO levels is useful for the prediction of IR-related liver injury during experimental liver surgery.

Bmi1 is a MYCN target gene that regulates tumorigenesis through repression of KIF1Bbeta and TSLC1 in neuroblastoma.

Recent advances in neuroblastoma (NB) research addressed that epigenetic alterations such as hypermethylation of promoter sequences, with consequent silencing of tumor-suppressor genes, can have significant roles in the tumorigenesis of NB. However, the exact role of epigenetic alterations, except for DNA hypermethylation, remains to be elucidated in NB research. In this paper, we clarified the direct binding of MYCN to Bmi1 promoter and upregulation of Bmi1 transcription by MYCN. Mutation introduction into an MYCN binding site in the Bmi1 promoter suggests that MYCN has more important roles in the transcription of Bmi1 than E2F-related Bmi1 regulation. A correlation between MYCN and polycomb protein Bmi1 expression was observed in primary NB tumors. Expression of Bmi1 resulted in the acceleration of proliferation and colony formation in NB cells. Bmi1-related inhibition of NB cell differentiation was confirmed by neurite extension assay and analysis of differentiation marker molecules. Intriguingly, the above-mentioned Bmi1-related regulation of the NB cell phenotype seems not to be mediated only by p14ARF/p16INK4a in NB cells. Expression profiling analysis using a tumor-specific cDNA microarray addressed the Bmi1-dependent repression of KIF1Bbeta and TSLC1, which have important roles in predicting the prognosis of NB. Chromatin immunoprecipitation assay showed that KIF1Bbeta and TSLC1 are direct targets of Bmi1 in NB cells. These findings suggest that MYCN induces Bmi1 expression, resulting in the repression of tumor suppressors through Polycomb group gene-mediated epigenetic chromosome modification. NB cell proliferation and differentiation seem to be partially dependent on the MYCN/Bmi1/tumor-suppressor pathways.

Plasma atrial natriuretic peptide in healthy calves and calves with congenital heart disease.

BACKGROUND: The basic and clinical implications of evaluating plasma atrial natriuretic peptide (ANP) concentration in calves are unknown. OBJECTIVE: To investigate the relationship between the plasma ANP concentration and left ventricular end-diastolic pressure (LVEDP) in healthy calves subjected to volume overload (Study 1), and to compare the plasma ANP concentration in calves with or without heart disease (Study 2). ANIMALS: Six healthy calves were used in Study 1; disease calves and sick calves with (n = 9) and without congenital heart disease (CHD) (n = 9) were used in Study 2. METHODS: In Study 1, LVEDP in anesthetized calves was manipulated by IV administration of acetated Ringer's solution (rate of 100 mL/kg/h for 20 minutes) and furosemide. In Study 2, disease calves were identified by blood examination and echocardiography or pathological examination. The plasma ANP concentration was determined by a chemiluminescence enzyme immunoassay for human alpha-ANP. RESULTS: In Study 1, preloading significantly increased the plasma ANP concentration (36 +/- 20-185 +/- 156, P < .01) and LVEDP (-11 +/- 7-2 +/- 12, P < .01) from the baseline. Furthermore, plasma ANP concentrations were strongly correlated with LVEDP (r= 0.61). In Study 2, the plasma ANP concentration was significantly higher in the calves with CHD than in the calves without heart disease (220 [67-970] versus 31 [10-86]; mean [range], P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Measurement of plasma ANP concentrations in calves can provide additional information useful for predicting hemodynamic abnormalities.

Efficacy, tolerability and side-effect profile of fluvoxamine for major depression: meta-analysis.

Fluvoxamine, one of the oldest selective serotonin reuptaking inhibitors, is commonly prescribed to patients with major depression. Several studies have reviewed the efficacy and tolerability of fluvoxamine for the treatment of major depression. However, these reviews are outdated, have not been systematic and/or suffered from several methodological weaknesses. We conducted a systematic review to synthesize the best available evidence on the efficacy of fluvoxamine for adult patients suffering from major depression in comparison with other active antidepressive agents. Relevant randomized controlled trials were identified through a comprehensive search. The primary outcome was a relative risk of response, and the secondary outcome was a relative risk of remission. Tolerability and side-effect profile were also examined. Fifty-three trials were included. There were no large differences between fluvoxamine and any other antidepressants in terms of efficacy and tolerability. There is evidence of differing side effect profiles, especially when comparing gastrointestinal side effects between fluvoxamine and tricyclics. Clinicians should focus on practically or clinically relevant differences including those in side-effect profiles.

[Experience of chest wall reconstruction with newly developed material].

After the chest wall resection, its reconstruction is often needed. A 45-year-old male lung adenocarcinoma patient with chest wall invasion underwent upper lobectomy of the right lung with partial resection of 4-6th ribs. The size of the removed chest wall was 11 x 6.5 cm. We reconstructed the chest wall with Bard Composix E/X Mesh. This prosthesis is consisted of a polypropylene mesh and an expanded polytetrafluoroethylene sheet This material is seems to be useful in the reconstruction of chest wall in both preventing pulmonary adhesion and enabling good wound healing.

A laser-induced liquid jet catheter system: a novel endovascular device for rapid and reliable fibrinolysis in acute cerebral embolism.

OBJECTIVE: Mechanical removal of intravascular clots in addition to administration of tissue plasminogen activator are both desirable for improved outcome in acute embolic stroke. We have developed a novel endovascular catheter system for rapid and reliable mechanical recanalization of cerebral embolisms with little or no requirement for fibrinolytic agents. Here, we describe the evaluation of this device in vitro. MATERIALS: Pulsed liquid jets were generated and ejected from the catheter exit by accelerating cold physiological saline (4 degrees C, 40 mL/h) using the energy of a pulsed holmium:yttrium-aluminum-garnet (YAG) laser (3 Hz, 1.2 W). Accessibility beyond the tortuous cavernous portion of the internal carotid artery to the M1 and A1 regions was confirmed using a transparent model of the human cerebral artery. Mechanical characteristics of the liquid jets were evaluated with a high-speed camera. Liquid jets of physiological saline or urokinase solution (1,200 IU/mL) were exposed to artificial thrombi made of human blood under temperature monitoring. Remnants of thrombi were collected and incubated at 37 degrees C for 10 min for estimation of fibrinolysis rates. RESULTS: The jet velocity (maximum: 5 m/s) was controlled by changing the laser energy. The fibrinolysis rates (mean+/-SD) after exposure to jets of saline or urokinase solution for 45 s were 62.2+/-16.4 and 94.0+/-3.4%, respectively, and were significantly better than the rate of 8.1+/-2.0% with administration of urokinase alone. The local temperature rise was less than 8 degrees C. CONCLUSIONS: The results show that the laser-induced liquid jet catheter system may be a powerful tool for mechanical destruction of emboli and augmentation of the effect of fibrinolytic agents beyond the tortuous part of the internal carotid artery.

N-MYC promotes cell proliferation through a direct transactivation of neuronal leucine-rich repeat protein-1 (NLRR1) gene in neuroblastoma.

Neuronal leucine-rich repeat protein-1 (NLRR1) gene encodes a type I transmembrane protein with unknown function. We have previously described that NLRR1 gene is highly expressed in unfavorable neuroblastomas as compared with favorable tumors and its higher expression levels correlate significantly with poor clinical outcome. In this study, we have found that NLRR1 gene is one of direct target genes for N-MYC and its gene product contributes to N-MYC-dependent growth promotion in neuroblastoma. Expression levels of NLRR1 were significantly associated with those of N-MYC in various neuroblastoma cell lines as well as primary neuroblastoma tissues. Indeed, enforced expression of N-MYC resulted in a remarkable induction of the endogenous NLRR1. Consistent with these results, we have identified two functional E-boxes within the promoter region and intron 1 of NLRR1 gene. Intriguingly, c-myc also transactivated NLRR1 gene. Enforced expression of NLRR1 promoted cell proliferation and rendered cells resistant to serum deprivation. In support with these observations, small-interfering RNA-mediated knockdown of the endogenous NLRR1-reduced growth rate and sensitized cells to serum starvation. Collectively, our present findings provide a novel insight into understanding molecular mechanisms behind aggressive neuroblastoma with N-MYC amplification.

Neonatal hepatitis with hepatofugal portal flow and collateral veins: report of three cases.

Neonatal hepatitis, a syndrome occurring in children, has various etiologies, such as viral infection, unidentified disorders of bile salt synthesis, and other poorly understood metabolic diseases. It is characterized by jaundice, giant cell hepatitis, and, rarely, liver failure necessitating liver transplantation. We experienced 3 cases of idiopathic neonatal hepatitis with unusual progressive fibrosis presenting with retrograde portal flow and portal-systemic shunt. Clinical manifestations were hyperammonemia, hyperbilirubinemia, and coagulopathy. Characteristic histological findings were giant cell transformation of hepatocytes and progressive severe fibrosis. Two patients underwent living donor liver transplantation. We consider that liver transplantation is indicated in cases of neonatal hepatitis with hepatofugal portal flow and collateral vein formation.

Pseudo-subarachnoid hemorrhage found in patients with postresuscitation encephalopathy: characteristics of CT findings and clinical importance.

BACKGROUND AND PURPOSE: High-attenuation areas (HDAs) called pseudo-subarachnoid hemorrhages (SAHs) may develop in some patients resuscitated from cardiopulmonary arrest (CPA), though no hemorrhage has occurred. We investigated the imaging characteristics and clinical significance of this phenomenon. MATERIALS AND METHODS: CT images of consecutive patients resuscitated from nontraumatic CPA were reviewed and classified into cases with pseudo-SAH (pseudo-SAH[+] group, n = 9), those without pseudo-SAH (pseudo-SAH[-] group, n = 28), and those with true SAH (SAH-CPA group, n = 8). Typical patients with SAH (SAH group, n = 13) and 20 healthy individuals were also extracted as control groups. The degree of brain edema was scored visually as none, mild, or severe, and the CT values of the HDAs and brain parenchyma were measured. These parameters were compared among the groups. We also compared the prognosis between the pseudo-SAH(+) and pseudo-SAH(-) groups. RESULTS: On CT, pseudo-SAH was associated with severe brain edema, whereas there was mild or no edema without pseudo-SAH. The CT values of the HDAs in the pseudo-SAH(+) group were significantly lower than those of the CPA-SAH and SAH groups (P < .0001). The brain parenchyma of the pseudo-SAH(+) group had the lowest CT values among all of the groups (P < .0001). The prognosis of the pseudo-SAH(+) group was significantly poorer than that of the pseudo-SAH(-) group in terms of both clinical outcome (P = .02) and survival (P = .046). CONCLUSION: The findings of pseudo-SAH have several imaging characteristics differing from SAH and predict a poor prognosis. This provides important information that can be used for deciding treatment strategies.

Experience with ultrasonographically guided vacuum-assisted resection of benign breast tumors.

AIM: To evaluate the feasibility and safety of vacuum-assisted resection of benign breast tumours using an 8 G handheld device. MATERIALS AND METHODS: Over a 2-year period, 22 patients with 26 breast tumours diagnosed as benign using aspiration biopsy cytology were enrolled. The mean patient age was 38 years, and the mean maximal diameter of the tumour was 13 mm. A handheld Aloka SSD 6500 ultrasonography device with a linear-type 7.5 MHz transducer was inserted into the posterior aspect of the tumour with the patient under local anaesthesia, and the tumour was resected under ultrasonographic guidance. RESULTS: This method was employed successfully in all patients, and the mean operation time was 33 min. Post-procedure complications included subcutaneous bleeding in 12 cases and haematoma in one. The pathological diagnoses were fibroadenoma in 16 cases, mastopathy in six, and tubular adenoma and pseudoangiomatous stromal hyperplasia in two cases each, respectively. Follow-up ultrasonography revealed residual tumours in four cases (15.4%). CONCLUSIONS: Although this method is feasible and safe without severe complications, it is necessary to select appropriate patients, and to obtain informed consent regarding the possibility of recurrence or residual tumour.