Subgroup analysis of Asian patients in the INPULSIS® trials of nintedanib in idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVE: In the two-replicate randomized Phase III INPULSIS® trials in patients with idiopathic pulmonary fibrosis (IPF), nintedanib 150 mg bd significantly reduced the annual rate of decline in forced vital capacity (FVC) compared with placebo. The key secondary endpoints were time to first investigator-reported acute exacerbation and change from baseline in St George's Respiratory Questionnaire total score, both over 52 weeks. Here, we assessed the effect of nintedanib in Asian patients. METHODS: Pre-specified subgroup analyses of the effect of nintedanib on the primary and key secondary endpoints in Asian versus White patients were undertaken based on pooled data from the two INPULSIS® trials. Safety data were analyzed descriptively. RESULTS: Of the treated patients, 322 were Asian (nintedanib n = 194; placebo n = 128) and 608 were White (nintedanib n = 360; placebo n = 248). In Asian patients, the nintedanib versus placebo difference in the adjusted annual rate of decline in FVC was 94.1 mL/year (95% CI: 33.7, 154.6). The treatment effect of nintedanib on the annual rate of decline in FVC in Asian and White patients was similar (treatment-by-subgroup interaction P = 0.72) and consistent with the overall population. No significant treatment-by-subgroup interaction was observed for the key secondary endpoints between Asian and White patients. In Asian patients, the most common adverse event in the nintedanib group was diarrhoea (56.2% of patients vs 15.6% for placebo). CONCLUSION: In pre-specified subgroup analyses of Asian versus White patients with IPF in the INPULSIS® trials, race did not influence the effect of nintedanib on disease progression.

Preparation of activated carbons from peach stone by H4P2O7 activation and its application for the removal of Acid Red 18 and dye containing wastewater.

The present study consists of the preparation of activated carbon from peach stone (PSAC) by H4P2O7 activation and its detailed characterization. The influence of different activants and various operational conditions including; soaking time, activation time, and activation temperature during PSAC preparation were systematically investigated. The chemical properties and morphology of prepared activated carbon was characterized by various analytical techniques (FTIR, SEM and EDX). TG-DTA analysis showed that the pore development of PSAC was significant at temperatures > 450°C. The prepared PSAC were utilized for the rapid removal and adsorption of Acid Red 18 (AR18) from aqueous solution that follows pseudo-second-order kinetics. The Langmuir isotherm model corresponded well with equilibrium data than the others, implying that the adsorption of AR18 onto prepared PSAC from the aqueous solutions proceeds by a monolayer formation. Thermodynamic investigations showed that the adsorption process is an exothermic and spontaneous process. During reusability studies, PSAC showed complete removal of AR18 upto seventh cycle increasing its practical applicability. Finally the prepared PSAC showed the best adsorptive capacity as compared to commercial AC for dye removal from actual industrial wastewater. This confers the possibility of applying PSAC economically viable option for the treatment of industrial wastewaters containing dye pollutants using suitable reactor.

Exploiting the efficacy of Lysinibacillus sp. RGS for decolorization and detoxification of industrial dyes, textile effluent and bioreactor studies.

Complete decolorization and detoxification of Reactive Orange 4 within 5 h (pH 6.6, at 30°C) by isolated Lysinibacillus sp. RGS was observed. Significant reduction in TOC (93%) and COD (90%) was indicative of conversion of complex dye into simple products, which were identified as naphthalene moieties by various analytical techniques (HPLC, FTIR, and GC-MS). Supplementation of agricultural waste extract considered as better option to make the process cost effective. Oxido-reductive enzymes were found to be involved in the degradation mechanism. Finally Loofa immobilized Lysinibacillus sp. cells in a fixed-bed bioreactor showed significant decolorization with reduction in TOC (51 and 64%) and COD (54 and 66%) for synthetic and textile effluent at 30 and 35 mL h(-1) feeding rate, respectively. The degraded metabolites showed non-toxic nature revealed by phytotoxicity and photosynthetic pigments content study for Sorghum vulgare and Phaseolus mungo. In addition nitrogen fixing and phosphate solubilizing microbes were less affected in treated wastewater and thus the treated effluent can be used for the irrigation purpose. This work could be useful for the development of efficient and ecofriendly technologies to reduce dye content in the wastewater to permissible levels at affordable cost.

Adsorption features of heavy metal ions on activated carbon in single and multisolute systems.

The main purpose of this study was to investigate the adsorption characteristics of cobalt, nickel and copper ions, which are harmful heavy metals released from various industries, in single, binary and ternary systems. The results showed that the adsorption extent decreased as the system changed from a single to a ternary system but adsorption percentages were not below 79%. The adsorption percentage of cobalt ion was superior to that of the other ions regardless of the type of system. In this study, the Langmuir isotherm was adapted for every adsorption result, and an extended version of the Langmuir isotherm was employed for the binary and ternary systems. The qmax value became smaller and KL value increased in the binary and ternary systems compared with that of the single system. The equilibrium parameter (RL) was between 0 and 1 under every condition, which indicated that adsorption was favorable. Finally, an adsorption experiment for real wastewater was performed, and the results were compared with those obtained for artificial wastewater.

Influence of parameters on the photocatalytic degradation of phenolic contaminants in wastewater using TiO2/UV system.

The photocatalytic degradation of phenol in aqueous suspension using commercial TiO2 powder (Degussa P-25) irradiated with UV light was investigated. Photodegradation was compared using a photocatalyst (TiO2 alone), direct photolysis (UV alone) and TiO2/UV in a single batch reactor with mercury lamp irradiation. The study focused on the influence of various operating parameters on phenol treatment efficiency, including catalyst dosage, initial concentration of phenol, temperature, pH and change in pH were systematically investigated. The highest phenol degradation rate was obtained at pH 9.0, temperature 60°C and catalyst dose of 2 g L(-1) with higher mineralization efficiency (in terms of TOC reduction). Experimental results showed that under optimized conditions the phenol removal efficiency was 98% and 100% for the TiO2/UV and TiO2/UV/H2O2 system, respectively. No significant effect on addition of chloride and metal ions was observed. Photodegradation of phenol followed first-order kinetics. To test whether the phenol removal was possible for wastewater using a TiO2/UV system, the degradation study was conducted with the real obtained wastewater. The removal of phenol from obtained wastewater and the synthetic wastewater containing phenol was comparable. The TiO2/UV system developed here is expected to be useful for the treatment of wastewater containing phenol.

Influence of molybdenum layer on the laser plasma generated from interfacing copper layer.

The results for laser-induced breakdown spectroscopy (LIBS) measurement of thin Cu films (1 µm) on soda-lime glass (SLG) substrates with and without a supporting thin Mo layer (1 µm) are reported. The ablation was carried out using a nanosecond Q-switched Nd:YAG laser (λ=1064 nm, τ=4 ns, spot diameter=50 µm, top-hat profile) in the laser fluence range of 19.16-65.97 J/cm(2). It was found that, under the same laser irradiance conditions, the depth and morphology of ablation craters produced with and without the Mo layer were completely different. The electron number densities of the plasma from the two samples calculated from the measured LIBS spectra differed by a factor of 4 as 4.1×10(17) cm(-3) (Cu/Mo/SLG) and 17.7×10(17) cm(-3) (Cu/SLG), which was attributed to the matrix effects resulting from ionization of Na atoms diffused into the Mo layer. It is demonstrated that a nanosecond-laser-based LIBS is applicable for the characterization and composition analysis of thin film layers of a few micrometer thickness on glass substrates, especially for the measurement of Na contents of each layer.

Methylene blue adsorption from aqueous solution by activated carbon: effect of acidic and alkaline solution treatments.

The removal of Methylene Blue (MB) from aqueous solution using activated carbon (AC) has been investigated. Adsorption experiments were conducted and the maximum adsorption capacity was determined. The effect of experimental parameters such as pH, dye concentration and temperature were studied on the adsorption process. Equilibrium data were mathematically modeled using the Langmuir and Freundlich adsorption models to describe the equilibrium isotherms at different dye concentrations and temperature. Parameters of best-fit model were calculated and discussed. To understand the mechanism of adsorption, kinetic models were employed to follow the adsorption processes; the pseudo-first-order best described the adsorption of MB onto AC. It was found that pH plays a major role in the adsorption process; adsorption capacity was influenced by the physical and surface chemical properties of carbon and the pH of the solution. 99.0% MB removal was achieved at equilibrium.

Gene structure and differential modulation of multiple rockbream (Oplegnathus fasciatus) hepcidin isoforms resulting from different biological stimulations.

Hepcidin, an antimicrobial and iron-regulating peptide, is a key molecule of the innate immune system of bony fish. In this study, four isoforms of hepcidin genes were characterized from a marine Perciform fish, rockbream (Oplegnathus fasciatus), and the transcriptional modulations of these isoforms in response to different biological stimulations were also examined. All rockbream hepcidin isoform genes exhibited a tripartite structure and their promoter regions displayed typical binding motifs for the transcription factors including C/EBP, HNF, AP, NF-kbeta, GATA, USF and/or STAT. Hepcidin transcripts in juvenile or fingerling tissues were dramatically induced during experimental challenges with various bacterial species, iron overload and rockbream iridovirus infection. The transcription ofhepcidins was regulated in an isoform- and tissue-specific fashion. In addition, we identified for the first time that partially processed hepcidin transcripts were significantly elevated during bacterial infection and iron overload. Results from this study provide a good basis to better understand the isoform-specific role of hepcidin in the fish innate immune system.

Comparison of postoperative voice outcomes after postauricular facelift robotic hemithyroidectomy and conventional transcervical hemithyroidectomy.

BACKGROUND: The purpose of this study was to determine whether postauricular robotic and conventional hemithyroidectomy result in significantly different voice outcomes. METHODS: We prospectively compared the voice handicap index (VHI)-10 and acoustic parameters of a postauricular facelift robotic group and a conventional group preoperatively, 1 week, 1 month, and 6 months after surgery. RESULTS: Forty-two patients in the postauricular group and 68 patients in the conventional group completed the VHI-10 questionnaire and acoustic analysis. The postoperative VHI-10 scores were not significantly different between the two groups. In female patients, the highest frequency was higher and the frequency range was wider in the postauricular group compared to the conventional group postoperatively until 1 month after surgery. CONCLUSION: Postauricular facelift robotic thyroidectomy has advantages over conventional thyroidectomy in terms of postoperative voice pitch.

Time course of the changes in right and left ventricle function and associated factors after transcatheter closure of atrial septal defects.

OBJECTIVE: The purpose of this study was to evaluate the changes in right ventricle (RV) and left ventricle (LV) function after transcatheter atrial septal defect (ASD) closure and to assess the influence of the age and the amount of shunt. DESIGN: Retrospective study PATIENTS: Fifty-three adult patients who underwent transcatheter closure were enrolled, then divided into subgroups according to the age (< 40 years vs ≥ 40 years), and the amount of shunt flow (QpQs < 2.5 vs QpQs ≥ 2.5). OUTCOME MEASURES: Two-dimensional tissue Doppler imaging was performed in a four-chamber view at the basal ventricular septum (VS) and tricuspid valve annulus (TVA) before and at 1 month and 6 months after closure. Myocardial velocities, the myocardial performance index (MPI), and isovolumic acceleration (IVA) were assessed. RESULTS: At the TVA, the MPI decreased slightly and then greatly increased at 6 months after closure (P = .002). The IVA improved in all patients (P < .001), and the E'/A' ratio decreased, especially in the old age group (P = .031) and larger shunt group (P = .035). At the VS, S' and the IVA decreased and had not recovered until 6 months in the old age (P = .02) and larger shunt (P = .02). The Qp/Qs showed a significant reverse correlation with a decrease in the E'/A' at the TVA (r = -0.37, P = .008), and age of patient was correlated with a decrease in the IVA at the VS (r = -0.32, P = .019). The age at closure (ß = -0.36, P = .002), the Qp/Qs ratio (ß = -0.45, P = .01), and RV MPI changes (ß = -7.64, P < .001) were found to be associated factors with IVA decrease at the VS. CONCLUSIONS: After ASD closure, RV global function might be impaired. In elderly patients and patients with a large shunt, impairment of LV contractility developed until 6 months after closure. Close long-term observation is required after closure, especially in old-age patients with a large shunt.

Pharmacokinetics of DA-8159, a new erectogenic, after intravenous and oral administration to rats: hepatic and intestinal first-pass effects.

The purposes of this study were to report dose-independent (after intravenous administration) and dose-dependent (after oral administration) area under the curve of plasma concentration versus time from time zero to time infinity (AUC), and gastric, intestinal, and/or hepatic first-pass effects (after intravenous, intraportal, intragastric, and intraduodenal administration) of DA-8159 [5-[2-propyloxy-5-(1-methyl-2-pyrollidinylethylamidosulfonyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-one], a new erectogenic, in rats. After intravenous administration at doses of 5, 10, and 30 mg/kg, the AUCs and time-averaged total body clearances (CLs) were dose-independent. However, the AUCs were dose-dependent after oral administration at doses of 20, 30, 50, and 100 mg/kg. This result could be due to saturation of first-pass effects at high doses. The extent of absolute oral bioavailability (F) of DA-8159 was 38.0% at a dose of 30 mg/kg. Considering almost complete absorption of DA-8159 from rat gastrointestinal tract ( approximately 99% of oral dose of 30 mg/kg), the low F could be due to considerable hepatic, gastric, and/or intestinal first-pass effects. After intravenous administration at three doses, the CLs were considerably slower than the reported cardiac output in rats, suggesting almost negligible first-pass effect of DA-8159 in the heart and lung. The AUCs were not significantly different between intragastric and intraduodenal administration of DA-8159 at a dose of 30 mg/kg (131 and 127 microg x min/mL), suggesting that gastric first-pass effect of DA-8159 was almost negligible in rats. However, the values were significantly smaller than that after intraportal administration (311 microg x min/mL), indicating considerable intestinal first-pass effect of DA-8159 in rats of approximately 58% of the oral dose. Approximately 23% of DA-8159 at a dose of 30 mg/kg absorbed into the portal vein was eliminated by the liver (hepatic first-pass effect) based on AUC difference between intravenous and intraportal administration (the value, 23%, was equivalent to approximately 9.6% of oral dose). The low F of DA-8159 after oral administration at a dose of 30 mg/kg to rats was mainly due to considerable intestinal ( approximately 58%) first-pass effects.

Treatment of malachite green-containing wastewater using poultry feathers as adsorbent.

The feasibility of using feathers, a waste from poultry as an absorbent for malachite green in dye wastewater was studied. The batch adsorption tests were shown to be influenced by the concentration of the dye, reaction temperature, solution pH, and pre-treatment with ethanol. In order to establish the equilibrium state of the process, a kinetic study was conducted for an optimal practice of adsorption treatment process. The adsorption reached equilibrium within 120 min in the range of dye concentration studied. It was found that the adsorption rate increases especially at low concentrations of dye and the adsorption data fitted well to the first-order reaction kinetics over all dye concentration range. Absolute amount of adsorbed malachite green at equilibrium condition decreased as concentration decreases. Adsorption of malachite green on poultry feathers fitted well to the Langmuir isotherm model. As temperature increases, the adsorbed amount of malachite green at equilibrium also increased, indicating an endothermic adsorption reaction. In addition, the color removal of malachite green rapidly increased with increase in dye's water pH. The pre-treatment of adsorbent with ethanol produced initial slow rate of malachite green removal but after about 100 min of reaction time, same removal rate was observed compare with the untreated feathers.

Azo dye Acid Red 27 decomposition kinetics during ozone oxidation and adsorption processes.

To elucidate the effects of ozone dosage, catalysts, and temperature on azo dye decomposition rate in treatment processes, the decomposition kinetics of Acid Red 27 by ozone was investigated. Acid Red 27 decomposition rate followed the first-order reaction with complete dye discoloration in 20 min of ozone reaction. The dye decay rate increases as ozone dosage increases. Using Mn, Zn and Ni as transition metal catalysts during the ozone oxidation process, Mn displayed the greatest catalytic effect with significant increase in the rate of decomposition. The rate of decomposition decreases with increase in temperature and beyond 40 degrees C, increase in decomposition rate was followed by a corresponding increase in temperature. The FT-IR spectra in the range of 1,000-1,800 cm(-1) revealed specific band variations after the ozone oxidation process, portraying structural changes traceable to cleavage of bonds in the benzene ring, the sulphite salt group, and the C-N located beside the -N = N- bond. From the (1)H-NMR spectra, the breaking down of the benzene ring showed the disappearance of the 10 H peaks at 7-8 ppm, which later emerged with a new peak at 6.16 ppm. In a parallel batch test of azo dye Acid Red 27 adsorption onto activated carbon, a low adsorption capacity was observed in the adsorption test carried out after three minutes of ozone injection while the adsorption process without ozone injection yielded a high adsorption capacity.

Pharmacokinetic changes of DA-8159, a new erectogenic, and one of its metabolites, DA-8164 after intravenous and oral administration of DA-8159 to spontaneously hypertensive rats and DOCA-salt-induced hypertensive rats.

The pharmacokinetics of DA-8159 and one of its metabolites, DA-8164, were compared after intravenous and oral administration of DA-8159 at a dose of 30 mg/kg to spontaneously hypertensive rats (SHRs) at 16 and 6 weeks old and their respective age-matched control normotensive Kyoto-Wistar rats (KW rats), and deoxycorticosterone acetate-salt-induced hypertensive rats (DOCA-salt rats) at 16 weeks old and their age-matched control Sprague-Dawley rats. After oral administration of DA-8159 to 16-week-old SHRs, the AUC values of both DA-8159 (157 versus 103 microg min/ml) and DA-8164 (215 versus 141 microg min/ml) were significantly greater, but the values of DA-8159 were reversed in 16-week-old DOCA-salt rats (125 versus 200 microg min/ml). However, the AUC values of both DA-8159 and DA-8164 were not significantly different between the 6-week-old SHRs and their control rats. The above AUC differences in 16-week-old SHRs may be due to neither hereditary characteristics of SHRs nor the hypertensive state itself.

Physiologic characteristics of cold perfluorocarbon-induced hypothermia during partial liquid ventilation in normal rabbits.

UNLABELLED: Because perfluorocarbon (PFC) liquid contacts closely with the alveolar capillaries during partial liquid ventilation (PLV), PLV with cold PFC may be used for the induction of hypothermia. Twenty rabbits were randomized to PFC-induced hypothermia (PH) (n = 7; core temperature 35 degrees +/- 1 degrees C), surface hypothermia (SH) (n = 7; 35 degrees +/- 1 degrees C), or normothermia (n = 6; 39 degrees +/- 1 degrees C). We induced PH by repeated in situ exchanges of 0 degrees C perfluorodecalin during PLV. At the establishment (0 min) of hypothermia in the PH group, oxygen consumption (P = 0.04) and oxygen extraction ratio (P = 0.01) decreased from normothermic condition. Metabolic (oxygen consumption, oxygen extraction ratio, serum lactate level) and hemodynamic variables (heart rate, blood pressure, cardiac output, pulmonary artery pressure) of the PH group were not different from those of the SH group at 0, 30, 60, 90, and 120 min of hypothermia. The difference in temperature between the pulmonary artery and rectum during the hypothermic period was smaller in the PH group compared with the SH group (P = 0.033). In conclusion, hypothermia may be induced during PLV by using cold PFC. This "pulmonary method" of cooling was comparable to a systemic method of cooling with regard to a few important physiologic variables, while maintaining a narrower interorgan temperature difference. IMPLICATIONS: The induction of moderate hypothermia was feasible in rabbits by administrating cold perfluorocarbon liquid into the lung. Physiologic changes induced by this pulmonary cooling were comparable to those induced by systemic cooling. Our method may be regarded as a methodological advance in the field of therapeutic hypothermia.