Using Surface Composition and Energy to Control the Formation of Either Tetrahexahedral or Hexoctahedral High-Index Facet Nanostructures.

High-index facet nanoparticles with structurally complex shapes, such as tetrahexahedron (THH) and hexoctahedron (HOH), represent a class of materials that are important for catalysis, and the study of them provides a fundamental understanding of the relationship between surface structures and catalytic properties. However, the high surface energies render them thermodynamically unfavorable compared to low-index facets, thereby making their syntheses challenging. Herein, we report a method to control the shape of high-index facet Cu nanoparticles (either THH with {210} facets or HOH with {421} facets) by tuning the facet surface energy with trace amounts of Te atoms. Density functional theory (DFT) calculations reveal that the density of Te atoms on Cu nanoparticles can change the relative stability of the high-index facets associated with either the THH or HOH structures. By controlling the annealing conditions and the rate of Te dealloying from CuTe nanoparticles, the surface density of Te atoms can be deliberately adjusted, which can be used to force the formation of either THH (higher surface Te density) or HOH (lower surface Te density) nanoparticles.

Massilia litorea sp. nov., Marinobacter salinisoli sp. nov. and Rhodobacter xanthinilyticus sp. nov., isolated from coastal environments.

Three bacterial strains, namely LPB0304T, LPB0319T and LPB0142T, were isolated from coastal environments. The 16S rRNA gene sequences of the three isolates were found to show the highest sequence similarities to Massilia litorea (98.44 %), Marinobacter salinisoli (97.55 %) and Rhodobacter lacus (97.60 %), respectively. The low (<98.7 %) sequence similarities and tree topologies implied the novelty of the three isolates, representing novel genomic species of the genus Massilia, Marinobacter and Rhodobacter. Numerous biochemical and physiological features also supported the distinctiveness of the isolates from previously known species. Based on the phenotypic and phylogenetic data presented in this study, three novel species are suggested with the following names: Massilia litorea sp. nov. (LPB0304T=KACC 21523T=ATCC TSD-216T), Marinobacter salinisoli sp. nov. (LPB0319T=KACC 21522T=ATCC TSD-218T) and Rhodobacter xanthinilyticus sp. nov. (LPB0142T=KACC 18892T=JCM 31567T).

Coronal Diffusion-Weighted Imaging Does Not Improve Detection of Posterior Fossa Infarcts Compared With Conventional Axial Diffusion-Weighted Imaging.

PURPOSE: Recent publications have suggested incorporating coronal diffusion-weighted imaging (DWI) sequences and axial DWI sequences to enhance the detection of posterior fossa infarcts (PFIs). This study evaluated the utility of coronal DWIs compared with axial DWIs for assessing PFIs in the emergency department (ED). METHODS: A retrospective, institutional review board-approved study was conducted at a level I stroke center, including 118 patients who presented to the ED between 2016 and 2023 with suspected PFI. Inclusion criteria involved patients who underwent emergent 1.5 T magnetic resonance imaging (MRI) and had axial and coronal DWI sequences. Two neuroradiologists independently evaluated the DWI sequences for PFI detection in 2 rounds, with a 4-week interval between rounds. The neuroradiologists assessed the quality of axial and coronal DWIs using a 5-point Likert scale. Descriptive statistics, interrater reliability, and marginal homogeneity tests were performed. RESULTS: Among the 118 MRI scans, 23 (19%) showed PFI on axial and coronal DWI sequences. All 23 cases were identified on axial DWI, whereas 8 cases of PFI (35%) were not detected on coronal DWI (P value = 0.013). No PFIs were observed on coronal DWI that was not identified on axial DWI. The quality scores for both raters were significantly higher for axial DWIs than coronal DWIs (P value <0.00001). CONCLUSION: Despite recent recommendations advocating for the inclusion of coronal DWI in PFI detection, this study's findings indicate no improvement in PFI detection or image quality using coronal DWI. Further research is necessary to validate these results and explore the potential benefits of incorporating coronal DWI in assessing posterior fossa strokes.

Multisystem factors contributing to redundant intracranial vascular imaging in the ED.

PURPOSE: To evaluate the multisystem factors contributing to redundant neurovascular orders in the ED. METHODS: This was an IRB-approved, retrospective study, performed at a single institution examining a 5-year history of redundant CTA/MRA head and neck (HN) exams performed in the ED for patients with no documented clinical change in mental status/neurological exam necessitating additional imaging. Factors contributing to redundant ordering including provider experience, synchronous order placement, and radiologist recommendations were examined. Additionally, the impact of duplicative imaging in terms of medical cost and ED length of stay was evaluated. RESULTS: 250 patients met inclusion criteria with both CTA/MRA of the HN performed during a single ED encounter (total 500 exams). 190 (76%) redundant exams were not recommended by a radiologist and contributed to an added ED length of stay of 3.6 h on average. Provider experience was not a significant contributing factor. 60 (24%) of redundant exams were recommended by a radiologist and were most frequently CTAs needed to clarify an area of artifact/high-grade stenosis/occlusion on a primary MRA exam. CONCLUSION: Evaluation of contributing factors to redundant CTA/MRA HN exams ordering has highlighted multiple associated factors including provider experience, recommendations by radiologists for clarification of MRA findings, as well as systems processes related to synchronous CTA/MRA order placement.

Combinatorial Synthesis and Screening of Mixed Halide Perovskite Megalibraries.

A significant bottleneck in the discovery of new mixed halide perovskite (MHP) compositions and structures is the time-consuming and low-throughput nature of current synthesis and screening methods. Here, a high-throughput strategy is presented that can be used to synthesize combinatorial libraries of MHPs with deliberate control over the halide mixing ratio and particle size (for example, CsPb(Br1-xClx)3 (0 < x < 1) with sizes between ∼100 and 400 nm). This strategy combines evaporation-crystallization polymer pen lithography (EC-PPL) and defect-engineered anion exchange to spatially encode particle size and composition, respectively. Laser exposure is used to selectively modify the defect concentration of individual particles, and thus the degree of subsequent anion exchange, allowing the preparation for ultra-high-density arrays of distinct compositions (>1 unique particle/µm2). This method was utilized to rapidly generate a library of ∼4000 CsPb(Br1-xClx)3 particles that was then screened for high-efficiency blue photoemission, which yielded CsPb(Br0.6Cl0.4)3 as the composition with the highest photoluminescence intensity. The combinatorial synthesis and screening strategy provided here, and the mechanistic understanding of the defect-engineering process gleaned from it, will enable the rapid discovery of exceptional MHP optoelectronic materials.

The Cobra Catheter: A Novel Concept and Device for the Thru-Septal Myocardium Approach.

Objectives: In our previous study, we suggested the novel septal traversing technique as effective and safe in catheter-based approach for septal myocardium. However, it is limited by its dependence on the septal perforator vein. This study aimed to evaluate the Cobra catheter as a backup catheter to overcome this limitation in swine. Methods: We designed the guiding Cobra catheter. It consisted of three major parts (the external pull-wire steerable distal tip, the C-shaped shaft, and the steering adjustment handle). We tested the difference in force between the guidewire passing through the muscle and the vessel wall using a push-pull gauge. We performed a septal wire engage procedure in swine using the Cobra catheter. The guidewire engagement of the septal vein and Cobra catheter were compared visually and histopathologically. Results: A total of ten swine were enrolled in this study. The success rate was 100% under fluoroscopy. The experiments confirmed the medical potential of the septal approach even in a location irrelevant to the septal perforator vein anatomy and confirmed that the wire passed well in the target direction in the harvested heart. There was no serious physical damage or pathological abnormalities in the vessel wall and myocardium. Conclusion: These results showed that the novel Cobra catheter with a septal vein-independent trans-septal approach may be a safe and effective alternative for the treatment of structural heart diseases.

Optimal ICG dosage of preoperative colonoscopic tattooing for fluorescence-guided laparoscopic colorectal surgery.

BACKGROUND: Indocyanine green (ICG) is a multifunctional dye used in tumor localization, tissue perfusion, and lymph node (LN) mapping during fluorescence-guided laparoscopic colorectal surgery. PURPOSE: This study aimed to establish the optimal protocol for preoperative endoscopic submucosal ICG injection to perform fluorescence lymph node mapping (FLNM), along with undisturbed fluorescent tumor localization and ICG angiography during a single surgery. METHODS: Colorectal cancer patients (n = 192) were enrolled from May 2017 to December 2019. Colonoscopic submucosal ICG injection was performed 12 to 18 h before surgery. ICG injection protocols were modified based on the total injected ICG (mg) and tattooing site number. The concentrations of ICG were gradually decreased from the standard dose (2.5 mg/ml) to the minimum dose (0.2 mg/ml). Successful FLNM (FLNM-s) was defined as distinct fluorescent LNs observed under NIR camera. The patient's age, sex, body mass index (BMI), stage, cancer location, obstruction, and laboratory findings were compared between the FLNM-s and failed FLNM (FLNM-f) groups to identify clinical and pathological factors that affect FLNM. RESULTS: In the ICG dose section of 0.5 to 1 mg, the success rate was highest within all functions including FLNM, fluorescent tumor localization, and ICG angiography. FLNM-s was related to ICG dose (0.5-1 mg), multiple submucosal injections, location of cancer, camera light source, and lower BMI. In the multivariate analysis, camera light source, non-obesity, and multiple injections were independent factors for FLNM-s). The mean total number of harvested LNs was significantly higher in the FLNM-s group than that in the FLNM-f group (p < 0.001). The number of metastatic lymph nodes was comparable between the two groups (p = 0.859). CONCLUSIONS: Preoperative, endoscopic submucosal ICG injection with dose range 0.5 to 1 mg would be optimal protocol for multifunctional ICG applications during fluorescence-guided laparoscopic colorectal surgery.

Quantification of bone marrow edema using dual-energy CT at fracture sites in trauma.

PURPOSE: The purpose of our study was to analyze the change in water and fat density within the bone marrow using the GE Revolution dual-energy computed tomography (DECT) platform using two-material decomposition analyses at extremity, spine, and pelvic fracture sites compared to normal bone marrow at equivalent anatomic sites in adult patients who sustained blunt trauma. METHODS: This retrospective study included 26 consecutive adults who sustained blunt torso trauma and an acute fracture of the thoracolumbar vertebral body, pelvis, or upper and lower extremities with a total of 32 fractures evaluated. Two-material decomposition images were analyzed for quantitative analysis. Statistical analysis was performed using the paired t-test and Shapiro-Wilk test for normality. RESULTS: There were statistically significant differences in the water and fat densities in the bone marrow at the site of an extremity, vertebral body, or pelvic fracture when compared to the normal anatomic equivalent (p < 0.01). CONCLUSION: In this preliminary study, DECT basis material images, using water (calcium) and fat (calcium) decomposition illustrated significant differences in water and fat content between fracture sites and normal bone in a variety of anatomical sites.

Design Guidelines of a Computer-Based Intervention for Computer Vision Syndrome: Focus Group Study and Real-World Deployment.

BACKGROUND: Prolonged time of computer use increases the prevalence of ocular problems, including eye strain, tired eyes, irritation, redness, blurred vision, and double vision, which are collectively referred to as computer vision syndrome (CVS). Approximately 70% of computer users have vision-related problems. For these reasons, properly designed interventions for users with CVS are required. To design an effective screen intervention for preventing or improving CVS, we must understand the effective interfaces of computer-based interventions. OBJECTIVE: In this study, we aimed to explore the interface elements of computer-based interventions for CVS to set design guidelines based on the pros and cons of each interface element. METHODS: We conducted an iterative user study to achieve our research objective. First, we conducted a workshop to evaluate the overall interface elements that were included in previous systems for CVS (n=7). Through the workshop, participants evaluated existing interface elements. Based on the evaluation results, we eliminated the elements that negatively affect intervention outcomes. Second, we designed our prototype system LiquidEye that includes multiple interface options (n=11). Interface options included interface elements that were positively evaluated in the workshop study. Lastly, we deployed LiquidEye in the real world to see how the included elements affected the intervention outcomes. Participants used LiquidEye for 14 days, and during this period, we collected participants' daily logs (n=680). Additionally, we conducted prestudy and poststudy surveys, and poststudy interviews to explore how each interface element affects participation in the system. RESULTS: User data logs collected from the 14 days of deployment were analyzed with multiple regression analysis to explore the interface elements affecting user participation in the intervention (LiquidEye). Statistically significant elements were the instruction page of the eye resting strategy (P=.01), goal setting of the resting period (P=.009), compliment feedback after completing resting (P<.001), a mid-size popup window (P=.02), and CVS symptom-like effects (P=.004). CONCLUSIONS: Based on the study results, we suggested design implications to consider when designing computer-based interventions for CVS. The sophisticated design of the customization interface can make it possible for users to use the system more interactively, which can result in higher engagement in managing eye conditions. There are important technical challenges that still need to be addressed, but given the fact that this study was able to clarify the various factors related to computer-based interventions, the findings are expected to contribute greatly to the research of various computer-based intervention designs in the future.

Clinical and laboratory parameters in blunt pelvic trauma not associated with subsequent positive conventional angiography in patients with positive CTA.

PURPOSE: This study evaluates clinical and laboratory parameters, as well as extravasation and hematoma size on CTA as potential predictors of conventional angiogram (CA) results. METHODS: This is a retrospective study of 380 adult patients presenting with pelvic trauma over a 9-year period. Of these patients, 91 were found to have active arterial extravasation on initial CTA. Statistical analysis between the two groups +CA versus -CA was performed to determine whether clinical and laboratory parameters, as well as extravasation size and hematoma size could predict CA results. RESULTS: There were no significant differences in all clinical and laboratory data, including hemodynamic instability (defined as systolic blood pressure < 90 mmHg) on presentation (22.2% vs. 21.4%), except for Glasgow Coma Scale (p = 0.015) when comparing the two groups. Extravasation size and hematoma size as continuous or categorical variables were not predictive of subsequent positive CA. Secondary analysis demonstrated no association between select parameters (i.e., hematocrit, systolic blood pressure, and lactate) and subsequent positive CA while controlling for extravasation size or hematoma size. CONCLUSION: Clinical and laboratory parameters in blunt pelvic trauma with arterial hemorrhage were not significantly associated with subsequent conventional angiography results, once accounting for degree of hemorrhage. The area of the foci of active extravasation and hematoma size in the axial plane were not significantly associated with the need for embolization. We conclude from these findings that catheter angiography should be considered in patients with blunt pelvic trauma found to have active arterial extravasation, regardless of size of bleed or the patient's clinical or laboratory values.

Vasodilatory Effect of Phellinus linteus Extract in Rat Mesenteric Arteries.

Phellinus linteus is a well-known medicinal mushroom that is widely used in Asian countries. In several experimental models, Phellinus linteus extracts were reported to have various biological effects, including anti-inflammatory, anti-cancer, hepatoprotective, anti-diabetic, neuroprotective, and anti-angiogenic activity. In the present study, several bioactive compounds, including palmitic acid ethyl ester and linoleic acid, were identified in Phellinus linteus. The intermediate-conductance calcium-activated potassium channel (IKCa) plays an important role in the regulation of the vascular smooth muscle cells' (VSMCs) contraction and relaxation. The activation of the IKCa channel causes the hyperpolarization and relaxation of VSMCs. To examine whether Phellinus linteus extract causes vasodilation in the mesenteric arteries of rats, we measured the isometric tension using a wire myograph. After the arteries were pre-contracted with U46619 (a thromboxane analogue, 1 µM), Phellinus linteus extract was administered. The Phellinus linteus extract induced vasodilation in a dose-dependent manner, which was independent of the endothelium. To further investigate the mechanism, we used the non-selective K+ channel blocker tetraethylammonium (TEA). TEA significantly abolished Phellinus linteus extract-induced vasodilation. Thus, we tested three different types of K+ channel blockers: iberiotoxin (BKca channel blocker), apamin (SKca channel blocker), and charybdotoxin (IKca channel blocker). Charybdotoxin significantly inhibited Phellinus linteus extract-induced relaxation, while there was no effect from apamin and iberiotoxin. Membrane potential was measured using the voltage-sensitive dye bis-(1,3-dibutylbarbituric acid)-trimethine oxonol (DiBAC4(3)) in the primary isolated vascular smooth muscle cells (VSMCs). We found that the Phellinus linteus extract induced hyperpolarization of VSMCs, which is associated with a reduced phosphorylation level of 20 KDa myosin light chain (MLC20).

Upregulation of P21-Activated Kinase 1 (PAK1)/CREB Axis in Squamous Non-Small Cell Lung Carcinoma.

BACKGROUND/AIMS: p21-activated Ser/Thr kinase 1 (PAK1) is essential for the genesis and development of many cancers. The purpose of this study was to investigate the role of the PAK1-cyclic AMP response element-binding (CREB) axis in non-small cell lung cancer (NSCLC) tumorigenesis and its related mechanisms. METHODS: Western blot assay and immunohistochemical staining were employed to investigate the PAK1 and CREB expression in the tissue microarray of human squamous NSCLC. Co-immunoprecipitation and immunofluorescence confocal assays were performed to determine the link between PAK1 and CREB. NSCLC xenograft models were used to study oncogenic function of PAK1 in vivo. RESULTS: We observed that PAK1 and CREB expression levels were significantly elevated in human squamous NSCLC-tissue specimens, compared with those in adjacent normal bronchial or bronchiolar epithelial-tissue specimens, as well as their phosphorylated forms, based on western blotting. We showed in vitro that PAK1 knockdown by small-interfering RNA (siRNA) blocked CREB phosphorylation, whereas plasmid-based PAK1 overexpression resulted in CREB phosphorylation at Ser133, based on western blotting. In addition, PAK1 interacted with CREB in co-immunoprecipitation assays. Additionally, our in vitro findings detected by flow cytometry revealed that PAK1 silencing attenuated cell cycle progression, inducing apoptosis. Inhibition of PAK1 expression reduced tumor sizes and masses by modulating CREB expression and activation in xenograft models. CONCLUSION: These results suggest a novel mechanism whereby the PAK1-CREB axis drives carcinogenesis of squamous-cell carcinomas, and have important implications in the development of targeted therapeutics for squamous-cell lung cancer.

A cancer/testis antigen, NY-SAR-35, induces EpCAM, CD44, and CD133, and activates ERK in HEK293 cells.

The cancer/testis (CT) antigen NY-SAR-35 gene is located on the X chromosome and is aberrantly expressed in various cancers but not in normal tissues, other than testes. Previously, we reported the expression of NY-SAR-35 enhanced cell growth, proliferation, and invasion in HEK293 and cancer cells. To extend understanding of the NY-SAR-35 gene, we used a next generation sequencing (NGS) approach. NY-SAR-35 expression induced growth, proliferation, metastasis, and stemness genes, as indicated by the up-regulations of CXCR4, EpCAM, CD133, and CD44, at the mRNA and protein levels. The expression of NY-SAR-35 in HEK293 cells significantly increased ERK phosphorylation, but not the phosphorylation of AKT. In HEK293/NY-SAR-35 cells, the expressions of pro-apoptotic proteins, including p53, Bax, and p21, were reduced and that of cyclin E was increased. Also, NY-SAR-35 increased the expressions of pluripotency genes (Nanog, Oct-4, and Sox2) and the ability of HEK293 cells to form colonies. Taken together, the present study indicates NY-SAR-35 functions as a CT antigen that triggers oncogenesis and self-renewal.

Comparative Analysis of Intranodal Lymphangiography with Percutaneous Intervention for Postsurgical Chylous Effusions.

PURPOSE: To evaluate clinical success and time to resolution of intranodal lymphangiography (INL) alone or with thoracic duct embolization (TDE) or thoracic duct disruption (TDD) based on initial effusion volume for postsurgical chylothorax. MATERIALS AND METHODS: Retrospective review was performed of 57 patients (mean age 63 y; 65% male) undergoing INL alone or in conjunction with other percutaneous techniques for postsurgical chylous effusions. INL alone was performed when chylothorax output was ≤ 500 mL/d and no leak was identified during fluoroscopy. RESULTS: INL was technically successful in all patients. There was 1 major and 2 minor complications. Clinical success rate was 71% (40/56). Clinical success rate meeting algorithmic inclusion criteria was 71.4% (5/7) for INL only, 41.7% (5/12) in INL with TDD, and 90.5% (19/21) in INL with TDE. Hazard ratio (HR) of clinical success of INL with TDE versus INL only was not statistically significant (HR 2.3, 95% confidence interval [CI], 0.70-5.87, P = .19). Median time to resolution was 14 days for INL only (95% CI, 0 days to not reached), 7 days for INL with TDD (95% CI, 4 days to not reached), and 3 days for INL with TDE (95% CI, 2 to 5 days) (P = .007). No statistically significant difference in median time to resolution existed between INL with TDE and INL only (P = .04). CONCLUSION: In patients with postsurgical chylothorax, INL alone had similar rates of clinical success and time to resolution compared with INL with TDE when initial effusion volume was ≤ 500 mL/d and no leak was visualized during fluoroscopy.

Selective Encaging of N2O in N2O-N2 Binary Gas Hydrates via Hydrate-Based Gas Separation.

The crystal structure and guest inclusion behaviors of nitrous oxide-nitrogen (N2O-N2) binary gas hydrates formed from N2O/N2 gas mixtures are determined through spectroscopic analysis. Powder X-ray diffraction results indicate that the crystal structure of all the N2O-N2 binary gas hydrates is identified as the structure I (sI) hydrate. Raman spectra for the N2O-N2 binary gas hydrate formed from N2O/N2 (80/20, 60/40, 40/60 mol %) gas mixtures reveal that N2O molecules occupy both large and small cages of the sI hydrate. In contrast, there is a single Raman band of N2O molecules for the N2O-N2 binary gas hydrate formed from the N2O/N2 (20/80 mol %) gas mixture, indicating that N2O molecules are trapped in only large cages of the sI hydrate. From temperature-dependent Raman spectra and the Predictive Soave-Redlich-Kwong (PSRK) model calculation, we confirm the self-preservation of N2O-N2 binary gas hydrates in the temperature range of 210-270 K. Both the experimental measurements and the PSRK model calculations demonstrate the preferential occupation of N2O molecules rather than N2 molecules in the hydrate cages, leading to a possible process for separating N2O from gas mixtures via hydrate formation. The phase equilibrium conditions, pseudo-pressure-composition (P-x) diagram, and gas storage capacity of N2O-N2 binary gas hydrates are discussed in detail.

Oxygen thermomigration in acceptor-doped perovskite.

The recent proposal of possible oxygen-thermomigration as a plausible mechanism for unipolar resistive switching of oxide memristors is now widely employed in modelling or simulating their memristive function on the grounds of the conventional picture that the mobile component O is always thermophobic, with its reduced heat-of-transport being equal to its migrational enthalpy (qO* = ΔHm > 0). At 1000 °C, we measured the thermomigration of mobile-component O in a prototype memristive perovskite, CaTi0.90Sc0.10O2.95+δ, across its near-stoichiometric regime (δ ≈ 0), where oxygen vacancy concentration is essentially fixed by doping acceptor impurities (i.e., ). It has been found that the reduced heat-of-transport of mobile O (qO*) varies systematically in the range of -2 < qO*/eV ≤ +2, as the composition varies from hypo-(δ < 0) to hyper-stoichiometry (δ > 0), exhibiting a sign reversal or thermomigration direction change from thermophilic (qO* < 0) to thermophobic (qO* > 0). This sign-reversal is attributed to the change in the electronic ambipolar company of from electrons to holes crossing the stoichiometric composition δ = 0. The numerical data for qO* together with the measurement details are reported.

2,4-Bis(1,1-dimethylethyl)phenol from Cinnamomum loureirii Improves Cognitive Deficit, Cholinergic Dysfunction, and Oxidative Damage in TMT-Treated Mice.

We previously reported that the extract of Cinnamomum loureirii (C. loureirii) significantly inhibited acetylcholinesterase (AChE), and identified 2,4-bis(1,1-dimethylethyl)phenol (BP) from C. loureirii as a potential AChE inhibitor. The present study, therefore was undertaken to demonstrate the effects of BP from C. loureirii on learning and memory impairment in trimethyltin (TMT)-treated ICR mice. Y-maze and passive avoidance tests were used to test cognitive ability. Further, changes in biochemical parameters in the brain tissue were also assessed in response to TMT injection and BP intervention. BP pre-administration (20, 40 mg/kg/d) in mice significantly protected cognitive dysfunction induced by TMT (p<0.05). Moreover, BP reduced AChE activity and lipid peroxidation but increased acetylcholine levels in the brain. In conclusion, we suggested that BP protected against TMT-induced cognitive dysfunction, and might be a potential agent for alleviating symptoms of neurodegenerative disorders, such as Alzheimer's disease, via modulating cholinergic functions.

Agarivorans aestuarii sp. nov., an agar-degrading bacterium isolated from a tidal flat.

A Gram-reaction-negative, aerobic, non-spore forming, rod-shaped bacterium motile with a single polar flagellum, designated strain hydD622T, was isolated from the sediment of a tidal flat at Asan Bay, Korea. Strain hydD622T exhibited an agarolytic activity. Comparison of 16S rRNA gene sequences revealed that strain hydD622T was closely related to Agarivorans litoreus KCTC 42116T, Agarivorans albus KCTC 22256T and Agarivorans gilvus KCTC 32555T with similarities of 98.4, 98.0 and 96.5 %, respectively. Strain hydD622T was clustered distantly from the other genera in the family Alteromonadaceae but formed a unique clade within the genus Agarivorans based on the 16S rRNA gene sequence. The DNA-DNA relatedness with Agarivorans litoreus KCTC 42116T and Agarivorans. albus KCTC 22256T was 39.0 and 37.8 %, respectively. The major fatty acids (>10 %) were C16 : 0,C16 : 1ω6c/C16 : 1ω7c and C18 : 1ω6c/C18 : 1ω7c. The respiratory quinone was ubiquinone-8, and the polar lipid profile consisted of phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol and an unidentified lipid. The DNA G+C content was 44 mol%. On the basis of physiological, chemotaxonomic and phylogenetic analyses, strain hydD622T represents a novel species within the genus Agarivorans, for which the name Agarivorans aestuarii sp. nov. is proposed. The type strain of Agarivorans aestuarii sp. nov. is hydD622T (=KCTC 32543T=CGMCC 1.12692T).

A randomized phase l pharmacokinetic study comparing SB4 and etanercept reference product (Enbrel®) in healthy subjects.

AIMS: SB4 has been developed as a biosimilar of etanercept. The primary objective of the present study was to demonstrate the pharmacokinetic (PK) equivalence between SB4 and European Union -sourced etanercept (EU-ETN), SB4 and United States-sourced etanercept (US-ETN), and EU-ETN and US-ETN. The safety and immunogenicity were also compared between the treatments. METHODS: This was a single-blind, three-part, crossover study in 138 healthy male subjects. In each part, 46 subjects were randomized at a 1:1 ratio to receive a single 50 mg subcutaneous dose of the treatments (part A: SB4 or EU-ETN; part B: SB4 or US-ETN; and part C: EU-ETN or US-ETN) in period 1, followed by the crossover treatment in period 2 according to their assigned sequences. PK equivalence between the treatments was determined using the standard equivalence margin of 80-125%. RESULTS: The geometric least squares means ratios of AUCinf , AUClast and Cmax were 99.04%, 98.62% and 103.71% (part A: SB4 vs. EU-ETN); 101.09%, 100.96% and 104.36% (part B: SB4 vs. US-ETN); and 100.51%, 101.27% and 103.29% (part C: EU-ETN vs. US-ETN), respectively, and the corresponding 90% confidence intervals were completely contained within the limits of 80-125 %. The incidence of treatment-emergent adverse events was comparable, and the incidence of the antidrug antibodies was lower in SB4 compared with the reference products. CONCLUSIONS: The present study demonstrated PK equivalence between SB4 and EU-ETN, SB4 and US-ETN, and EU-ETN and US-ETN in healthy male subjects. SB4 was well tolerated, with a lower immunogenicity profile and similar safety profile compared with those of the reference products.

Population pharmacokinetic analysis to recommend the optimal dose of udenafil in patients with mild and moderate hepatic impairment.

AIMS: The aim of this study was to develop a population pharmacokinetic (PK) model of udenafil and its active metabolite, DA-8164, in healthy subjects and patients with hepatic impairment (HI) and to estimate the optimal dosing recommendations for patients with HI. METHODS: An open label, three parallel group, age and weight matched control study was conducted in 18 volunteers, six healthy subjects (n = 6) and patients with mild (Child-Pugh class A, n = 6) and moderate HI (Child-Pugh class B, n = 6). Serial blood samples were collected for up to 72 h after a single administration of udenafil 100 mg. A population PK model was developed using non-linear mixed effects modelling (nonmem, ver. 7.2). The simulated data from the final PK model and original data of healthy subjects were compared to identify the optimal dose for patients with HI. RESULTS: A two compartment model for both udenafil and DA-8164 best described the data. Prothrombin time on metabolic clearance of udenafil to DA-8164 was included in the final model as a covariate. Compared with the AUC(0,tlast ) value after administration of udenafil 100 mg to healthy subjects, the geometric mean ratios (95% confidence interval) after 100 mg and 75 mg udenafil administration were 1.21 (1.10, 1.32) and 0.74 (0.67, 0.81) in patients with mild HI, respectively. Meanwhile, those were 1.55 (1.43, 1.67) and 1.02 (0.92, 1.12) in patients with moderate HI, respectively. CONCLUSIONS: This study suggests that the recommended doses of udenafil are 100 mg and 75 mg in patients with mild and moderate HI, respectively.