Search

Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) are a class of targeted anticancer agents that include pazopanib, sunitinib, axitinib, and others. Currently, VEGFR-TKIs are widely used in the clinical treatment of various tumors, which can prolong patients' survival and even cure tumors. However, the use of VEGFR-TKIs is frequently associated with the occurrence of cardiovascular adverse events, with hypertension being the most prevalent. Hypertension and its complications can significantly impact the prognosis of patients, potentially jeopardizing their lives and resulting in the reduction or even cessation of treatment in severe cases. This review addresses the incidence of hypertension due to VEGFR-TKIs, mechanisms of toxicity, management strategies, and future research directions. In addition, hypertension due to VEGFR-TKIs may be associated with salt sensitivity, and possible mechanisms of hypertensive side effects are vasodilator imbalance, decreased capillary density, renal injury, impaired endothelial function due to oxidative stress, decreased lymphatic vascular density, and "off-target effect". A comprehensive understanding of hypertension toxicity due to cancer treatment with VEGFR-TKIs, can enhance clinical practice, thereby improving the prognostic outcomes of VEGFR-TKIs in oncology patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The study proposes a way to measure the relatedness between countries and movies (movie-country relatedness density) and to test whether this relatedness is an important factor in predicting the popularity of a movie in a certain country. The results show that both movie-country relatedness density and movie ubiquity (i.e., popularity across many countries) are positively associated with a movie appearing in a country's top 20 list even after considering other covariates. Based on these findings, we suggest an OTT (Over-the-tops) movie launching strategy with regard to movie-country relatedness density for both global and local OTT companies. Our study contributes to a growing body of research on movie consumption patterns and provides insights into the factors that determine a movie's success on a global scale. The importance of cultural similarity in adopting films and television shows is widely recognized, but the concept of movie-country compatibility is introduced to take into account the content attributes that cannot be explained by cultural differences. The results suggest that movies that are related to other popular movies in a given country and movies that are popular across many countries are more likely to appear in a country's top 20 list., Competing Interests: The authors declare that they have no conflict of interest., (Copyright: © 2024 Lee, Ji. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Beta toxin (CPB) is a lethal toxin and plays a key role in enterotoxemia of ruminants caused by Clostridium perfringens type C strain. The existing vaccines based on crude CPB need time-consuming detoxification and difficult quality control steps. In this study, we synthesized the rCPB m4 of C. perfringens type C strain and small ubiquitin-like modifier (SUMO)-tag CPB m4 (rSUMO-CPB m4 ) by introducing four amino acid substitutions: R212E, Y266A, L268G, and W275A. Compared with rCPB m4 , rSUMO-CPB m4 was expressed with higher solubility in Escherichia coli BL21 (DE3). Neither rCPB m4 nor rSUMO-CPB m4 was lethal to mice. Although rCPB m4 and rSUMO-CPB m4 were reactogenic with polyclonal antibodies against crude CPB, rabbits vaccinated with rSUMO-CPB m4 developed significant levels of toxin-neutralizing antibody (TNA) titers that conferred protection against crude toxin challenge. These data suggest that genetically detoxified rSUMO-CPB m4 is a promising subunit vaccine candidate for C. perfringens type C beta enterotoxemia.

Objective: To investigate the safety and efficacy of novel CD19-KIRS2/Dap12-BB chimeric antigen receptor T cells (CAR-T cells) in the treatment of relapsed/refractory B-cell malignancy (R/R BCM)., Methods: Three patients with R/R BCM treated with novel CD19-KIRS2/Dap12-BB CAR-T cells from June 2020 to November 2020 were enrolled, including 1 case of B-cell acute lymphoblastic leukaemia (B-ALL) and 2 cases of non-Hodgkin's lymphoma (NHL), and the efficacy and adverse reactions were observed., Results: After CAR-T cells infusion, patient with B-ALL achieved complete remission (CR) and minimal residual disease (MRD) turned negative, and 2 patients with NHL achieved partial remission (PR). Grade 2 cytokine release syndrome (CRS) occurred in B-ALL patient, grade 1 CRS occurred in 2 NHL patients, and grade II to IV hematologic adverse reactions occurred in 3 patients, all of which were controllable and reversible. The progression-free survival (PFS) of the 3 patients was 143, 199, and 91 days, and overall survival (OS) was 282, 430, and 338 days, respectively., Conclusion: The novel CD19-KIRS2/Dap12-BB CAR-T cells in treatment of 3 patients with R/R BCM have significant short-term efficacy and controllable adverse reactions, but the long-term efficacy needs to be further improved.

Geochemical maps can be used for a variety of purposes, one of which is to establish regional or local geochemical thresholds for the analyzed elements. In the case of vanadium, as industrial demand and use increase, it is necessary to expand the development of vanadium in Korea. However, the environmental management standards are insufficient. Therefore, in this study, using geochemical data, we derived geochemical threshold values for the entire country and areas with potential for the development of vanadium deposits. The regional (country-wide) threshold value was derived using logarithmic transformation of raw data (N = 23,548) of the first- and second-order stream sediments collected across the country in the late 1990s and the early 2000s. The median + 2 median absolute deviation (MAD) and Tukey inner fence (TIF) values were 116 mg/kg and 200 mg/kg, respectively. Of these, the TIF standard, which showed 0.6% of data exceeding the threshold, was judged to be appropriate for distinguishing clear enrichment or contamination of vanadium. In the case of the Geumsan and Pocheon, areas with potential for vanadium development, the TIF and median + 2 MAD values of 259 mg/kg and 218 mg/kg, respectively, can be used as the criteria for evaluating the impact of environmental pollution before and after deposit development. Likewise, by deriving threshold values of the target elements using geochemical map data, it is possible to provide basic environmental information for geochemical evaluation and follow-up management in advance during large-scale site development., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

In this study, the shear performance of a reinforced concrete (RC) beam with Fe-based shape memory alloy (Fe-SMA) stirrups was evaluated experimentally and analytically. Five specimens that had a possibility of shear failure under four-point loading were prepared. The major experimental variables were the spacings (300 and 200 mm) between the Fe-SMA stirrups and whether the stirrups were activated or non-activated. The shear strength of the specimen reinforced with the Fe-SMA stirrups at a spacing of 200 mm was 27.1% higher than that of the specimen reinforced at a spacing of 300 mm. The activation of the Fe-SMA stirrups, which produced active confining pressure, increased the shear strength by up to 7.6% and decreased the number of shear cracks compared to the case of the non-activated specimen. Therefore, the use of Fe-SMA stirrups could significantly improve the usability of concrete members by increasing their shear strength and initial stiffness and by controlling crack formation. Furthermore, finite element method (FEM) analysis was conducted using LS-DYNA, a commercial software program, to predict the shear performance of the RC beam reinforced with the Fe-SMA stirrups. The ultimate load and displacement of each specimen were predicted with errors less than 1.4 and 9.4%, respectively. Furthermore, the FEM predicted the change in failure mode and the stiffness improvement due to the activation of the Fe-SMA stirrups. Therefore, the proposed finite element analysis model can effectively predict the behavior of an RC beam reinforced with Fe-SMA stirrups.

In this paper, we propose a deterministic secure quantum communication (DSQC) protocol based on the BB84 system. We developed this protocol to include quantum entity authentication in the DSQC procedure. By first performing quantum entity authentication, it was possible to prevent third-party intervention. We demonstrate the security of the proposed protocol against the intercept-and-re-send attack and the entanglement-and-measure attack. Implementation of this protocol was demonstrated for quantum channels of various lengths. Especially, we propose the use of the multiple generation and shuffling method to prevent a loss of message in the experiment.

Purpose: This study aimed to compare the image quality and adverse events between Iopamidol 250 and Ioversol 320 usage during transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC)., Materials and Methods: Medical records and hepatic angiography from 113 patients who underwent TACE with Iopamidol 250 (44 patients) and Ioversol 320 (69 patients) were retrospectively reviewed. Vessel perception on hepatic angiography was graded into three categories by two radiologists for hepatic subsegmental arteries, the right gastroepiploic artery, right gastric artery, and pancreaticoduodenal artery. Imaging concordance was assessed by comparing the number of detected HCCs on hepatic angiography and CT. The adverse events before and after hepatic angiography were evaluated., Results: The mean vessel perception scores were 2.92 and 2.94 for Iopamidol 250 and Ioversol 320, respectively. The imaging concordance was 31 (70.5%) and 46 (66.7%) patients for Iopamidol 250 and Ioversol 320, respectively. There were no statistical differences in vessel perception or imaging concordance ( p > 0.05). One and six patients experienced nausea for Iopamidol 250 and Ioversol 320, respectively. There was no statistical difference in adverse events ( p = 0.24)., Conclusion: Iopamidol 250 can be used in hepatic angiography for TACE without significant difference in image quality or occurrence of adverse events from Ioversol 320., Competing Interests: Conflicts of Interest: The authors have no potential conflicts of interest to disclose., (Copyrights © 2020 The Korean Society of Radiology.)

Malaria remains one of the world's most significant human infectious diseases and cerebral malaria (CM) is its most deadly complication. CM pathogenesis remains incompletely understood, hindering the development of therapeutics to prevent this lethal complication. Elevated levels of the chemokine CXCL10 are a biomarker for CM, and CXCL10 and its receptor CXCR3 are required for experimental CM (ECM) in mice, but their role has remained unclear. Using multiphoton intravital microscopy, CXCR3 receptor- and ligand-deficient mice and bone marrow chimeric mice, we demonstrate a key role for endothelial cell-produced CXCL10 in inducing the firm adhesion of T cells and preventing their cell detachment from the brain vasculature. Using a CXCL9 and CXCL10 dual-CXCR3-ligand reporter mouse, we found that CXCL10 was strongly induced in the brain endothelium as early as 4 days after infection, while CXCL9 and CXCL10 expression was found in inflammatory monocytes and monocyte-derived DCs within the blood vasculature on day 8. The induction of both CXCL9 and CXCL10 was completely dependent on IFN-γ receptor signaling. These data demonstrate that IFN-γ-induced, endothelium-derived CXCL10 plays a critical role in mediating the T cell-endothelial cell adhesive events that initiate the inflammatory cascade that injures the endothelium and induces the development of ECM.

In this paper, a high dynamic range (HDR) imaging method based on the stereo vision system is presented. The proposed method uses differently exposed low dynamic range (LDR) images captured from a stereo camera. The stereo LDR images are first converted to initial stereo HDR images using the inverse camera response function estimated from the LDR images. However, due to the limited dynamic range of the stereo LDR camera, the radiance values in under/over-exposed regions of the initial main-view (MV) HDR image can be lost. To restore these radiance values, the proposed stereo matching and hole-filling algorithms are applied to the stereo HDR images. Specifically, the auxiliary-view (AV) HDR image is warped by using the estimated disparity between initial the stereo HDR images and then effective hole-filling is applied to the warped AV HDR image. To reconstruct the final MV HDR, the warped and hole-filled AV HDR image is fused with the initial MV HDR image using the weight map. The experimental results demonstrate objectively and subjectively that the proposed stereo HDR imaging method provides better performance compared to the conventional method., Competing Interests: The authors declare no conflict of interest.

Objective: To investigate the incidence and pathogen distribution of ventilator-associated pneumonia (VAP) among preterm infants admitted to level Ⅲ neonatal intensive care units (NICU) in China. Method: A prospective study was conducted in 25 level Ⅲ NICU, enrolling all preterm infants <34 weeks gestational age admitted to the participating NICU within the first 7 days of life from May 2015 to April 2016. Chi-square test, t test and Mann-Whitney U test were used for statistical analysis. Result: A total of 7 918 patients were enrolled, within whom 4 623(58.4%) were males. The birth weight was (1 639±415) g and the gestational age was (31.4±2.0) weeks; 4 654(58.8%) infants required non-invasive mechanical ventilation and 2 154(27.2%) required intubation. Of all the mechanically ventilated patients, VAP occurred in 95 patients. The overall VAP rate was 7.0 episodes per 1 000 ventilator days, varying from 0 to 34.4 episodes per 1 000 ventilator days in different centers. The incidence of VAP was 9.6 and 6.0 per 1 000 ventilator days in children's hospitals and maternity-infant hospitals respectively, without significant differences ( t =1.002, P =0.327). Gram - negative bacilli (76 strains, 91.6%) were the primary VAP microorganisms, mainly Acinetobacter baumannii (24 strains, 28.9%), Klebsiella pneumonia (23 strains, 27.7%), and Pseudomonas aeruginosa (10 strains, 12.0%). Conclusion: The incidence of VAP in China is similar to that in developed counties, with substantial variability in different NICU settings. More efforts are needed to monitor and evaluate the preventable factors associated with VAP and conduct interventions that could effectively reduce the occurrence of VAP.

Quantum steering-a strong correlation to be verified even when one party or its measuring device is fully untrusted-not only provides a profound insight into quantum physics but also offers a crucial basis for practical applications. For continuous-variable (CV) systems, Gaussian states among others have been extensively studied, however, mostly confined to Gaussian measurements. While the fulfilment of Gaussian criterion is sufficient to detect CV steering, whether it is also necessary for Gaussian states is a question of fundamental importance in many contexts. This critically questions the validity of characterizations established only under Gaussian measurements like the quantification of steering and the monogamy relations. Here, we introduce a formalism based on local uncertainty relations of non-Gaussian measurements, which is shown to manifest quantum steering of some Gaussian states that Gaussian criterion fails to detect. To this aim, we look into Gaussian states of practical relevance, i.e. two-mode squeezed states under a lossy and an amplifying Gaussian channel. Our finding significantly modifies the characteristics of Gaussian-state steering so far established such as monogamy relations and one-way steering under Gaussian measurements, thus opening a new direction for critical studies beyond Gaussian regime.

We theoretically propose and experimentally demonstrate a nonclassicality test of a single-mode field in phase space, which has an analogy with the nonlocality test proposed by Banaszek and Wódkiewicz [Phys. Rev. Lett. 82, 2009 (1999)]. Our approach to deriving the classical bound draws on the fact that the Wigner function of a coherent state is a product of two independent distributions as if the orthogonal quadratures (position and momentum) in phase space behave as local realistic variables. Our method detects every pure nonclassical Gaussian state, which can also be extended to mixed states. Furthermore, it sets a bound for all Gaussian states and their mixtures, thereby providing a criterion to detect a genuine quantum non-Gaussian state. Remarkably, our phase-space approach with invariance under Gaussian unitary operations leads to an optimized test for a given non-Gaussian state. We experimentally show how this enhanced method can manifest quantum non-Gaussianity of a state by simply choosing phase-space points appropriately, which is essentially equivalent to implementing a squeezing operation on a given state.

Mining activities have caused serious environmental problems including acid mine drainage (AMD), the dispersion of mine tailings and dust, and extensive mine waste. In particular, AMD contaminates soil and water downstream of mines and generally contains mainly valuable metals such as Cu, Zn, and Ni as well as Fe and Al. In this study, we investigated the selective recovery of Fe, Al, Cu, Zn, and Ni from AMD. First, the speciation of Fe, Al, Cu, Zn, and Ni as a function of the equilibrium solution pH was simulated by Visual MINTEQ. Based on the simulation results, the predicted pHs for the selective precipitation of Fe, Al, Cu, and Zn/Ni were determined. And recovery yield of metals using simulation is over 99 %. Experiments using artificial AMD based on the simulation results confirmed the selective recovery of Fe, Al, Cu, and Zn/Ni, and the recovery yields of Fe/Al/Cu/Zn and Fe/Al/Cu/Ni mixtures using Na2CO3 were 99.6/86.8/71.9/77.0 % and 99.2/85.7/73.3/86.1 %, respectively. After then, the simulation results were applied to an actual AMD for the selective recovery of metals, and the recovery yields of Fe, Al, Cu, and Zn using NaOH were 97.2, 74.9, 66.9, and 89.7 %, respectively. Based on the results, it was concluded that selective recovery of dissolved metals from AMD is possible by adjusting the solution pH using NaOH or Na2CO3 as neutralizing agents.

In Korea, the heavy metal pollution from about 1,000 abandoned mines has been a serious environmental issue. Especially, the surface waters, groundwaters, and soils around mines have been contaminated by heavy metals originating from acid mine drainage (AMD) and mine tailings. So far, AMD was considered as a waste stream to be treated to prevent environmental pollutions; however, the stream contains mainly Fe and Al and valuable metals such as Ni, Zn, and Cu. In this study, Visual MINTEQ simulation was carried out to investigate the speciation of heavy metals as functions of pH and neutralizing agents. Based on the simulation, selective pH values were determined to form hydroxide or carbonate precipitates of Cu, Zn, and Ni. Experiments based on the simulation results show that the recovery yield of Zn and Cu were 91 and 94 %, respectively, in a binary mixture of Cu and Zn, while 95 % of Cu and 94 % of Ni were recovered in a binary mixture of Cu and Ni. However, the recovery yield and purity of Zn and Ni were very low because of similar characteristics of Zn and Ni. Therefore, the mixture of Cu and Zn or Cu and Ni could be recovered by selective precipitation via pH adjustment; however, it is impossible to recover selectively Zn and Ni in the mixture of them.

This experiment was conducted to establish a system for detecting trace cobalt ions in water and plant tissues using a voltammetric in vivo sensor. Cyclic and stripping voltammetry was devised from hand-made, macro-type implantable three-electrode systems. The results reached micro and nano working ranges at 100 sec accumulation time. The statistical detection limit (S/N) was attained at 6.0 ng L(-1). For the in vivo application, direct assay of cobalt ions was carried out in Eichhornia crassipes (EC) deep tissue in real time with a preconcentration time of 100 s. Interfaced techniques can be interlocked with other control systems.

Pilot-scale field-testing of passive bioreactors was performed to evaluate the efficiency of a mixture of four substrates (cow manure compost, mushroom compost, sawdust, and rice straw) relative to mushroom compost alone, and of the effect of the Fe/Mn ratio, during the treatment of acid mine drainage (AMD) over a 174-day period. Three 141 L columns, filled with either mushroom compost or the four substrate mixture (in duplicate), were set-up and fed with AMD from a closed mine site, in South Korea, using a 4-day hydraulic retention time. In the former bioreactor, effluent deterioration was observed over 1-2 months, despite the good efficiency predicted by the physicochemical characterization of mushroom compost. Steady state effluent quality was then noted for around 100 days before worsening in AMD source water occurred in response to seasonal variations in precipitation. Such changes in AMD quality resulted in performance deterioration in all reactors followed by a slow recovery toward the end of testing. Both substrates (mushroom compost and mixtures) gave satisfactory performance in neutralizing pH (6.1-7.8). Moreover, the system was able to consistently reduce sulfate from day 49, after the initial leaching out from organic substrates. Metal removal efficiencies were on the order of Al (∼100%) > Fe (68-92%) > Mn (49-61%). Overall, the mixed substrates showed comparable performance to mushroom compost, while yielding better effluent quality upon start-up. The results also indicated mushroom compost could release significant amounts of Mn and sulfate during bioreactor operation., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

We present a formalism to derive entanglement criteria beyond the Gaussian regime that can be readily tested by only homodyne detection. The measured observable is the Einstein-Podolsky-Rosen (EPR) correlation. Its arbitrary functional form enables us to detect non-Gaussian entanglement even when an entanglement test based on second-order moments fails. We illustrate the power of our experimentally friendly criteria for a broad class of non-Gaussian states under realistic conditions. We also show rigorously that quantum teleportation for continuous variables employs a specific functional form of EPR correlation., (© 2012 American Physical Society)

This study was carried out to evaluate longevity of available organic materials used for sulfate-reducing bacteria (SRB) activity in vertical flow ponds (VFPs) to treat mine drainage in South Korea. Spent mushroom compost samples (SMC) were tested as substrates in VFPs and analyzed for total organic carbon in VFPs, and were collected to analyze total organic carbon (TOC), T-N, T-P, K, metals and residual cellulose to check the longevity assessment. Chemical analysis revealed that the average contents of Fe, Al and Mn in SMC of VFPs were 19,907, 32,137 and 434 mg/kg, respectively. The contents of Fe and Al in SMC of VFPs were much higher than those of the unused SMC (control), but to the contrary, those of Mn showed a reversed tendency. Average TOC content of the controls was 64.19% but in one of the VFP substrates was as low as 15.92%. This might be resulted from SRB consumed the available organic carbon in SMC as VFPs system aged. Contents of T-N in VFPs tended to decrease as VFPs aged. The residual cellulose ranged from 3.88 to 6.72% (g/g). There existed a negative relationship between residual cellulose contents and ages of VFPs. Assuming that SMC in all VFPs had similar compositions when the VFPs were initially established, trend analysis predicted that the amount of carbon source for SRB might be available for 12-15 years further, depending on VFPs.

The objective of this study was to assess the changes in mine water quality as an underground mine flooded from July 2005 to October 2008. The effect of air injection with a blower into the water was used to evaluate the potential to convert ferrous to ferric iron and to provide in situ treatment and precipitation. Mine flooding averaged 31 cm/day with a linear shape until November 2007, when it flattened out due to outflow. During flooding, mine water pH remained around 6, but Eh shifted from 200 to -150 mV. After the mine water level stabilized, contents of elements such as Fe and SO(4) tended to decrease as time passed. Air was injected by diffusers (150 L/min/each) at three different depths of 2, 3, and 5 m below the water level in the shaft. Dissolved oxygen eventually increased to 4 or 5 mg/L depending on the depth of the diffusers. Aeration caused conversion of ferrous iron to ferric iron and about 30 mg/l of iron was removed from the mine water. Therefore, air injection shows potential as a semi-active treatment or part of conventional treatment to precipitate iron in the mine pool.

A cover system for mine tailings with a solidified layer (called an engineered hardpan) was developed in this study to reduce water infiltration, acid generation and sulfide oxidation. Hydrated lime and waterglass were used to produce calcium silicate, which can serve as a binder when constructing a hardpan layer. The compressive strength of each solidified/stabilized material was found to be sufficient in the lab, and the amounts of heavy metals were significantly reduced in chemical leaching tests. Various characteristics of tailings may affect the layer's mechanical strength early on, but a long curing period is capable of compensating for these effects. Heavy metals were stabilized as carbonate-bound phases and sulfide minerals were surrounded by calcium silicate matrix, thereby preventing further reaction. To evaluate the field performance of the system, a hardpan layer was installed on top of tailings on a pilot scale. Leachate with high salt content was generated in the tailings layer in the early stages of monitoring, but after approximately 6 months, the objective was achieved as the hardpan layer gradually stabilized. Notably, during the heavy rainfall season of the later monitoring stage, water infiltration was continuously prevented by the system., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Objective: To evaluate antiviral effects of Peg-IFNa-2a in patients with chronic hepatitis B., Methods: 92 chronic hepatitis B patients were enrolled to receive the treatment with Peg-IFNa-2a 180 μg subcutaneous injection once weekly. The patients who did not get early response were divided into 3 groups: group 1, extend the treatment to 72 weeks; group 2, combined with nucleus(s)ide analogue (entecavir or adefovir) treatment; group 3, continue the treatment until 48 weeks. HBV DNA and quantitative HBsAg were assessed at baseline, week 12, 24, 36 and after 24 weeks follow-up., Results: Patients in group 1 had significantly higher SVR rate (78.3%) than patients in group 3 (38.1%, X2=7.33, P<0.05). The mean reduction of HBsAg in group 1 at 24 weeks of post-treatment follow up was higher than that in group 3 (t=2.11, P<0.05). In group 2 the mean reductions of HBV DNA at 24 weeks of post-treatment follow up were (3.9+/-1.1) log10 copy/ml and (3.7+/-1.3) log10 copy/ml respectively with combination of entecavir or adefovir, both of which were significantly higher than that in group 3(t=8.45 and 6.31, P<0.05); the SVR rates in the entecavir group and the adefovir group (83.3% and 85.7%, respectively) were significantly higher than that in group 3 (X2=8.20 and 7.78, P<0.05); the mean reductions of HBsAg in the entecavir group and the adefovir group [(0.8+/-0.5) log10 IU/ml and (0.9+/-0.3) log10 IU/ml, respectively ] were significantly greater than group 3[(0.4+/-0.3) log10 IU/ml, t=3.05 and 4.58, P<0.05]. The level of HBV DNA and C genotype were the main predictors of response., Conclusion: Individualizing therapy by prolonging the duration of Peg-IFNa-2a treatment to 72 weeks or adding nucleoside analogues such as entecavir and adefovir in patients without early response may substantially increase the SVR rate and lead to the decrease of HBsAg.

Bioreactors are one possible best sustainable technology to address the mine-impacted water problems. Several prospective substrates (mushroom compost, cow manure, sawdust, wood chips, and cut rice straw) were characterized for their ability to serve as a source of food and energy for sulfate-reducing bacteria. Twenty bench-scale batch bioreactors were then designed and set up to investigate relative effectiveness of various mixtures of substrates to that of mushroom compost, the most commonly used substrate in field bioreactors, for treating mine drainage with acidic (pH 3) and moderate pH (pH 6). Overall, reactive mixtures showed satisfactory performances in generating alkalinity, reducing sulfate and removing metals (Al>Fe>Mn) (up to 100%) at both pH conditions, for all substrates. The mixture of sawdust and cow manure was found as the most effective whereas the mixture containing 40% cut rice straw gave limited efficiency, suggesting organic carbon released from this substrate is not readily available for biodegradation under anaerobic conditions. The mushroom compost-based bioreactors released significant amount of sulfate, which may raise a more concern upon the start-up of field-scale bioreactors. The correlation between the extent of sulfate reduction and dissolved organic carbon/SO(4)(2-) ratio was weak and this indicates that the type of dissolved organic carbon plays a more important role in sulfate reduction than the absolute concentration and that the ratio is not sensitive enough to properly describe the relative effectiveness of substrate mixtures., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

We derive two classes of multimode Bell inequalities under local realistic assumptions, which are violated only by the entangled states negative under partial transposition in accordance with the Peres conjecture. Remarkably, the failure of local realism can be manifested by exploiting wave and particle correlations of readily accessible continuous-variable states, with very large violation of inequalities insensitive to detector efficiency, which makes a strong case for a loophole-free test.

Objective: To analyze antiviral effects of telbivudine in patients with chronic hepatitis B., Method: 72 chronic hepatitis B patients without prior history of antiviral therapy were treated with telbivudine 600mg once daily., Results: At week 4, 37.5% of the patients achieved undetectable HBV DNA, and 33.3% achieved ALT normalization. At week 108, 87.5% of the patients achieved undetectable HBV DNA, and 91.7% achieved ALT normalization. HBeAg seroconversion occurred in 23.9% of the 46 HBeAg positive patients. The rates of undetectable HBV DNA and HBeAg seroconversion at week 108 in the patients with HBV DNA < 3 log(10) copies/ml at week 12 were significant higher than those in patients with HBV DNA >or= 3 log(10) copies/ml. The rate of undetectable HBV DNA at week 108 in the patients with HBV DNA < 3 log(10) copies/ml at week 24 was significantly higher than that in patients with HBV DNA >or= 3 log(10) copies/ml, and the rate of antiviral resistance rate at week 108 in the patients with HBV DNA < 3 log(10) copies/ml at week 24 was significantly lower than that in patients with HBV DNA >or= 3 log(10) copies/ml. Antiviral therapy could significantly improve Child-Pugh score in patients with liver cirrhosis., Conclusion: Telbivudine treatment results in suppression of HBV and high HBeAg seroconversion, and improvement of Child-Pugh score in the patients with liver cirrhosis.

Objective: To analyze antiviral effects of entecavir in patients with hepatitis B virus-related cirrhosis., Methods: 104 patients of hepatitis B virus-related cirrhosis with no previous history of antiviral therapy were treated with entecavir 0.5 mg once daily. 37 patients were taken hepatic histologic examination before and after the treatment., Results: Mean reductions of serum HBV DNA was 5.1 log10 96 weeks after the treatment, HBV DNA became undetectable in 98.1% patients, and ALT became normal in 80.7% patients; HBeAg seroconversion occurred in 13.9% of the 72 HBeAg positive patients; 61.5% of these patients were infected with genotype C HBV, and 26.9% were infected with genotype B HBV. The genotype of HBV was not associated with the therapeutical effect. Child-pugh score was associated with the progression of the disease: the proportion of patients with disease progression was highest in Child-Pugh C grade patients and lowest in Child-Pugh A grade patients. The level of the HBV DNA load was positively correlated with Knodell HAI score at the baseline and 96 weeks after the treatment., Conclusion: Entecavir treatment results in suppression of HBV replication and delayed progression of fibrosis in patients with hepatitis B virus-related cirrhosis.

In a study of the 29 operating passive systems for acid mine drainage (AMD) treatment, 19 systems showed various performance problems. Some systems showed very low efficiency even without visible leakage or overflow. Though systems show fairly good efficiency in metal removal (mainly iron) and pH control, sulfate removal rates were very low which indicates the possibility of very poor sulfate reductions by Sulfate Reducing Bacteria (SRB). As an alternative method, In-Adit-Sulfate-Reducing System (IASRS), the method of placing the SAPS inside the adit, to have temperature constant at about 15 degrees C, was suggested. Lab-scale model experiments of IASRS were carried out. The models 1 and 2 were run at 15 degrees C and 25 degrees C, respectively. The model 1 contained about a half of COD in the beginning of the operation than that of model 2. Metal removal ratios were higher than 90% in both systems. Both systems showed the sulfate removal ratios of 23% and 27%, respectively, which were still considerably low, even though higher than those of presently operating systems. However, since the synthetic AMD used was very low in pH (2.8) and very high in sulfate concentration, if some suggested modifications were applied to the standard design, it is presumed that the sulfate removal ratio would have increased.

Background/aims: Bacterial gastroenteritis seems to be a risk factor of irritable bowel syndrome (IBS). The incidence of post-infectious IBS (PI-IBS) was reported to be in the range of 7-31%, but few studies have reported long term follow-up results. So, we investigated the clinical course and prognosis of PI-IBS three years after shigella infection., Methods: The subjects were recruited from our previous study, in which we investigated the incidence and risk factors of PI-IBS. We had a questionnaire based on interview with 120 controls and 124 patients who had shigella infection three years ago. Both groups were evaluated for the presence of IBS, functional bowel disorders (FBD) except IBS before, one and three years after the infection, respectively., Results: Ninety-five patients (76.6%) and 105 controls (87.5%) completed the questionnaire. In patients group, 7 cases had IBS prior to infection (previous IBS), 12 cases (13.8%) had IBS after 1 year (PI-IBS). Four cases developed IBS newly after 3 years (new IBS). Thirteen cases (14.9%) in patients and 4 cases (4.5%) in controls had IBS over 3 years (OR 3.93: 1.20-12.86). The recovery rate over 3 years were 50.0% (2/4) in previous IBS and 25% (3/12) in PI-IBS. The incidence of PI-IBS after 3 years in previous FBD subjects was 28.6% and was 10.6% in normals (p<0.05). The female gender was a risk factor for FBD., Conclusions: Bacterial gastroenteritis is a trigger factor of IBS. About a quarter of PI-IBS patients are recovered over 3 years. Previous FBD except IBS is a risk factor after 3 years.

Background: Octreotide and terlipressin are widely used in acute variceal hemorrhage to reduce the bleeding rate. They purportedly act by mesenteric arterial vasoconstriction, thus reducing portal venous flow (PVF) and portal pressure. Little is known about the immediate-early hemodynamic effects of these drugs., Aim: To compare the acute hemodynamic effects of octreotide and terlipressin in patients with cirrhosis., Patients: Forty-two cirrhotic patients with a history of variceal bleeding were randomized to receive either octreotide 100 microg intravenous bolus followed by a continuous infusion at 250 microg/h (n = 21), or terlipressin 2 mg intravenous bolus (n = 21)., Methods: Mean arterial pressure (MAP), heart rate (HR), hepatic venous pressure gradient (HVPG), and PVF, assessed by duplex Doppler ultrasonography, were measured before and at 1, 5, 10, 15, 20, and 25 min after the start of drug administration., Results: Octreotide markedly decreased HVPG (-44.5 +/- 17.8%) and PVF (-30.6 +/- 13.6%) compared to the baseline at 1 min (p < 0.05). Thereafter, both variables rapidly returned toward the baseline, and by 5 min, no significant differences in HVPG (-7.1 +/- 28.9%) and PVF (10.2 +/- 26.2%) were noted. A similar transient effect on MAP and HR was observed. Terlipressin significantly decreased HVPG (-18.3 +/- 11.9%) and PVF (-32.6 +/- 10.5%) at 1 min (p < 0.05) and sustained these effects at all time points. The effects on arterial pressure and HR were also sustained., Conclusions: Octreotide only transiently reduced portal pressure and flow, whereas the effects of terlipressin were sustained. These results suggest that terlipressin may have more sustained hemodynamic effects in patients with bleeding varices.

Background/aims: Inflammation-induced alterations in smooth muscle contractility may be due to the effects on smooth muscle itself, neurotransmitters or enteric nerves. In dextran sulfate sodium-induced colitic rat, the delay in colonic transit was caused by decreased activity and production of neuronal nitric oxide synthase (nNOS) in the myenteric plexus of the distal colon. The aim of this study was to investigate the relationship between the delay in colonic transit and the distribution of inducible NOS (iNOS) and nNOS immunoreactive cells in the myenteric plexus of trinitrobenzene sulfonic acid (TNBS)-induced colitic guinea pig., Methods: Sacrificed and their colonic tissues of forty-five TNBS-induced colitic guinea pigs were used to measure the colonic transit, and analyzed by immunohistochemistry., Results: Colonic transit was delayed significantly at 3, 7 and 14 days after administration of TNBS. In control, nNOS immunoreactivity was present in the mucosa, submucosa, lamina propria, and ganglion cells of the myenteric plexus, while after TNBS treatment, reduced nNOS cells were found. However, the number of nNOS ganglion cells in the myenteric plexus was similar to those seen in controls. After administration of TNBS, iNOS immunoreactivity was increased in the mucosa and submucosa, but the number of iNOS positive ganglion cells in the myenteric plexus was not changed compared to control., Conclusions: It is suggested that in TNBS-induced guinea pig colitis, delayed colonic transit is not associated with the expression of nNOS nor iNOS in the myenteric plexus.

Background: Hyperdynamic circulation due to reduced peripheral vascular resistance and increased cardiac output, and the development of portal hypertension are the hemodynamic changes observed in patients with liver cirrhosis. Such hemodynamic abnormalities appear in patients with late stage liver cirrhosis. Therefore, hemodynamic indices, which represent hyperdynamic circulation and portal hypertension, are significant for the prognosis of patients with liver cirrhosis. The aim of this study was to determine the hemodynamic indices associated with the prognosis of patients with liver cirrhosis., Methods: A total of 103 patients diagnosed with liver cirrhosis between December 1999 and June 2003, with a mean follow-up period of 73 weeks, ranging from 7 to 168 weeks, were recruited. Using Child-Pugh classification, the mean arterial pressure, heart rate and hepatic venous pressure gradient (HVPG) were measured. The indices of Doppler ultrasonography, including the portal and splenic venous flows, and the resistance of the hepatic, splenic, and renal arteries were also measured using the arterial pulsatility index (PI). The prognostic values of these indices were determined by their comparison with the patient survivals., Results: Significant hemodynamic indices for a bad prognosis were high HVPG (> or = 15 mmHg) and renal arterial PI (> or = 1.14)(p<0.05). A Child-Pugh score > or = 10 was important for a poor prognosis (p<0.05)., Conclusion: Severe portal hypertension (HVPG > or = 15 mmHg) and high renal arterial resistance (PI +/- 1.14) were valuable hemodynamic indices for the prognosis of patients with liver cirrhosis. Therefore, it was concluded that the measurement of these hemodynamic indices, in addition to the Child-Pugh classification, is helpful in the prognosis of patients with liver cirrhosis.

Background/aims: The clinical usefulness of urinary trypsinogen-2 dipstick test is still in controversy. We evaluated the usefulness of urinary trypsinogen-2 dipstick test in patients with acute pancreatitis., Methods: Urinary trypsinogen-2 dipstick test was prospectively performed in 50 patients with acute pancreatitis, 50 patients with non-pancreatic abdominal pain, and 50 healthy controls., Results: On admission, urinary trypsinogen-2 dipstick test was positive in 36 of 50 patients with acute pancreatitis (sensitivity, 72%) and in 4 of 50 patients with non-pancreatic abdominal pain (specificity, 92%). On the other hand, it was all negative in controls. The sensitivity and specificity of serum lipase were 78% and 94%, respectively. At 24 hours after admission, the positive rate of urinary trypsinogen-2 dipstick test rose from 72% to 94% (p=0.02). The results of urinary trypsinogen-2 dipstick test was positive in 14 of 15 patients with severe pancreatitis and 22 of 35 patients with mild pancreatitis according to the criteria by Atlanta International Symposium, 1992., Conclusions: Urinary trypsinogen-2 dipstick test is comparable to serum lipase in diagnosing acute pancreatitis. Delayed measurement and severe pancreatitis are more likely to yield positive results with urinary trypsinogen-2 dipstick test. Thus, we suggest that the cut-off value of urinary trypsinogen-2 dipstick test should be lowered to increase its sensitivity.

Background/aims: The blended current is usually used for endoscopic sphincterotomy (EST) to minimize bleeding. The pure cutting current may induce less edema of the ampulla and therefore result in less injury to the pancreas theoretically. The aim of this study was to evaluate effects of electric currents used on the development of serum pancreatic enzyme evaluation, clinical pancreatitis or bleeding after EST., Methods: One hundred and eighteen consecutive patients who underwent EST with standard papillotome alone for the treatment of choledocholithiasis were reviewed. All EST had been performed by two endoscopists whose experience on EST was similar: one uses 'blended current' (BC group, n=74), while the other uses 'pure cutting current' (PC group, n=44)., Results: Baseline clinical, laboratory, and procedural parameters were similar in both groups. The incidences of hyperamylasemia and hyperlipasemia were similar between two groups. There was no significant difference in the incidence of clinical pancreatitis between two groups (BC 6.8% vs PC 0.0%, p=0.1557). All episodes of pancreatitis were mild. No episodes of significant bleeding occurred after EST. The incidences of sepsis, cholangitis and perforation were also not different between two groups., Conclusions: Development of complications after standard EST such as hyperamylasemia, clinical pancreatitis, and bleeding may not depend on the electric current used.

The mechanisms of prokinetic action of tegaserod in the gastrointestinal tract has not been studied in detail. The aim of this study was to investigate the effect of tegaserod on peristaltic reflexes and propagating peristaltic waves in guinea pig ileum. A partitioned organ bath divided into three chambers was used to investigate the effect of tegaserod on peristaltic reflexes. A sensory stimulus was applied to the intermediate chamber, and changes in the circular muscle tension were monitored in a peripheral chamber. Another peristaltic bath was used to investigate the effect of tegaserod on peristaltic waves induced by intraluminal perfusion. Guinea pig ileum exhibited contractions in the circular muscle both orally and anally in response to mucosal stroking. Tegaserod (10(-8) - 10(-6) M) did not influence the maximal amplitude and the area under the curve of contraction both orally and anally to a mucosal stimulus. Intraluminal perfusion of fluid containing tegaserod (10(-8) - 10(-6) M) significantly increased the number of peristaltic waves in a concentration-dependent manner (P<0.05). Also, tegaserod (10(-8) - 10(-6) M) significantly increased the area under the curve of peristaltic waves (P<0.05). It is concluded that tegaserod has prokinetic action on guinea pig ileum by increasing the number of the circular muscle contractions during peristalsis.

Mosapride citrate (Mosapride) is a new prokinetic agent that enhances the gastrointestinal (GI) motility by stimulation of 5-HT4 receptors. This agent stimulates acetylcholine release from enteric cholinergic neurons in the GI wall. It was reported in several studies that mosapride selectively enhanced the upper, but not lower, GI motor activity. However, in these studies other 5-HT4 receptor agonists exerted stimulating effects on the motility of the colon. Moreover, it is well known that the receptors of 5-HT4 are also located in the colon. The purpose of this study was to estimate the effect of mosapride on the motility of the stomach, ileum and colon in the guinea pig and to investigate whether or not mosapride influenced the colonic motility. Mosapride significantly increased the amplitude of the contraction waves in the guinea pig stomach by electrical stimulation. In addition, it significantly increased the number of peaks, the area under the curve and the propagation velocity of the peristaltic contraction of the guinea pig ileum in a concentration dependent fashion. Mosapride also significantly shortened the transit time of the guinea pig colon. Accordingly, we concluded that mosapride exerted prokinetic effect on the entire GI tract of the guinea pig. Based on the possibility of similar results in humans, we suggest the potential use of mosapride for lower GI motor disorders such as constipation and upper GI motor disorders such as gastroesophageal reflex disease or gastroparesis.