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EPO analogues are representative glycoprotein drugs composed of heterogeneous, multiple antennary N‐glycans. NESP® and Aranesp® are hyperglycosylated EPO, marketed under the same international nonproprietary name as darbepoetin alfa. The multiple antennary N‐glycans are a key factor that increases the half‐life of the drug in the body, which is closely related to efficacy. Thus, control of N‐glycosylation is important in providing patients with consistent efficacy. This paper reports on the comprehensive characterization of N‐glycosylation of darbepoetin alfa products. The results of N‐glycan analysis of NESP® and Aranesp® showed difference in the ratio of N‐glycans containing N‐acetyllactosamine and O‐acetylated sialic acid. Although there were some differences, the overall N‐glycan structures and profiles were comparable. In particular, darbepoetin alfa products accounted for the largest proportion of tetra‐sialo N‐glycans, greater than 75%. This study increases understanding of N‐glycan profiles and structural information of darbepoetin alfa. [ABSTRACT FROM AUTHOR]

Abstract We investigated strontium oxide (SrO) as an interlayer material to enhance the UV stability of a CH 3 NH 3 PbI 3 perovskite solar cell. Moisture and over 400 nm wavelength of light were excluded to investigate the effect of UV light only. Two different interlayer fabrication processes were examined to optimize the performance of this solar cell. Devices fabricated by dipping for 30 min in SrO solution exhibited photoconversion efficiencies of 15.5%, whereas those fabricated with 60-min dipping showed photoconversion efficiencies of 15% and exhibited local Sr agglomeration. Devices with SrO displayed lower initial efficiencies than those without any SrO layer (17.6%), However, a device without SrO retained only 34.4% of its initial efficiency after 100 h of UV exposure. In contrast, SrO-incorporated devices retained almost 60.0% of their initial efficiency. Severe μ-PL mapping intensity degradation was observed in devices that did not include the interlayer, but no degradation was observed in those with the SrO interlayer. This can be attributed to the passivation of the degradation sites by SrO. Graphical abstract Image 1 Highlights • Perovskite UV stability was tested under conditions except moisture, oxygen and wavelengths exceeding 400 nm. • With high resolution μ-PL mapping technique, direct evidence is provided about the area perovskite UV degradation begins. • UV degradation is initiated at the ETL/perovskite interface. • Effect of the SrO interlayer on UV stability was examined in an inert atmosphere. • UV stability is enhanced by SrO interface passivation. [ABSTRACT FROM AUTHOR]

Purpose This first-in-human study with SB3 was designed to evaluate the pharmacokinetic (PK) equivalence between SB3 and trastuzumab sourced in the European Union (EU trastuzumab), between SB3 and trastuzumab sourced in the United States (US trastuzumab), and between EU and US trastuzumab (NCT02075073). Methods In this randomized, double-blind, parallel group, single-dose comparative PK study, 109 healthy male subjects were randomized to receive a single 6-mg/kg IV dose of SB3, EU -trastuzumab, or US trastuzumab. The PK parameters were calculated using noncompartmental methods. The PK equivalence in terms of AUC 0-–∞) , AUC 0–last , and C max for the pairwise comparisons (SB3 vs EU trastuzumab, SB3 vs US trastuzumab, and EU trastuzumab vs US trastuzumab) were determined using the predefined equivalence margin of 0.8 to 1.25. Findings Baseline demographic characteristics for the randomized subjects were similar across the 3 groups. The 90% CIs for the geometric least square means of the AUC 0–∞ , AUC 0–last , and C max were completely contained within the margin of 0.8 to 1.25. The proportions of subjects who experienced adverse events related to the study drug were 36.1%, 44.4%, and 61.1% in the SB3, EU trastuzumab, and US trastuzumab groups, respectively. The most frequently reported adverse events related to the study drug was infusion-related reactions. No subjects had positive results for antidrug antibodies after a single dose of SB3, EU trastuzumab, or US trastuzumab. Implications This study revealed PK equivalence between SB3 and EU trastuzumab, between SB3 and US trastuzumab, and between EU trastuzumab and US trastuzumab. SB3 is well tolerated without tolerability concerns after single-dose administration in healthy male subjects. [ABSTRACT FROM AUTHOR]

Abstract: Background: A sustained-release (SR) formulation of cilostazol was recently developed in Korea and was expected to yield a lower Cmax and a similar AUC to the immediate-release (IR) formulation. Objective: The goal of the present study was to compare the pharmacokinetic profiles of a newly developed SR formulation and an IR formulation of cilostazol after single- and multiple-dose administration and to evaluate the influence of food in healthy Korean subjects. This study was developed as part of a product development project at the request of the Korean regulatory agency. Methods: This was a randomized, 3-part, sequential, open-label, 2-period crossover study. Each part consisted of different subjects between the ages of 19 and 55 years. In part 1, each subject received a single dose of SR (200 mg × 1 tablet, once daily) and IR (100 mg × 2 tablets, BID) formulations of cilostazol orally 7 days apart in a fasted state. In part 2, each subject received a single dose of the SR (200 mg × 1 tablet, once daily) formulation of cilostazol 7 days apart in a fasted and a fed state. In part 3, each subject received multiple doses of the 2 formulations for 8 consecutive days 21 days apart. Blood samples were taken for 72 hours after the dose. Cilostazol pharmacokinetics were determined for both the parent drug and its metabolites (OPC-13015 and OPC-13213). Adverse events were evaluated through interviews and physical examinations. Results: Among the 92 enrolled subjects (66 men, 26 women; part 1, n = 26; part 2, n = 26; part 3, n = 40), 87 completed the study. In part 1, all the primary pharmacokinetic parameters satisfied the criterion for assumed bioequivalence both in cilostazol and its metabolites, yielding 90% CI ratios of 0.9624 to 1.2323, 0.8873 to 1.1208, and 0.8919 to 1.1283 for Cmax and 0.8370 to 1.0134, 0.8204 to 0.9807, and 0.8134 to 0.9699 for AUC0–last of cilostazol, OPC-13015, and OPC-13213, respectively. In part 2, food intake increased Cmax and AUC significantly (P < 0.0001), yielding geometric mean ratios of 3.2879, 2.9894, and 3.0592 for Cmax and 1.7001, 1.7689, and 1.6976 for AUC0–last of cilostazol, OPC-13015, and OPC-13213. In part 3, only the Cssmax of clilostazol in the reference formulation did not satisfy the criterion for assumed bioequivalence, yielding 90% CI ratios of 1.2693 to 1.4238 and 1.2038 to 1.3441, respectively. When each dose was normalized, the Cmax for the SR formulation was significantly lower (P < 0.005 for cilostazol). Headache was the most frequently noted adverse effect (part 1, a total of 14 subjects with the IR formulation and 14 with the SR formulation; part 2, a total of 10 without food and 23 with a high-fat meal; part 3, a total of 10 with the IR formulation and 24 with the SR formulation), followed by nausea (part 1, none; part 2, only 1 without food and 3 with a high-fat meal; part 3, a total of 3 with the IR formulation and 3 with the SR formulation), and then dizziness (parts 1 and 2, none; part 3, a total of 4 with the IR formulation and 5 with the SR formulation). All other AEs, including fever, cough, vomiting, palpitation, diarrhea, and epigastric pain, occurred in <3 subjects. Conclusions: These findings suggest that in this select group of healthy Korean volunteers, the SR formulation of cilostazol was not significantly different in AUC compared with that of the IR formulation, although it did display a significantly lower Cmax per dose in both the single- and multiple-dose groups. Food significantly increased the bioavailability of the SR formulation. The cilostazol SR and IR formulations were well tolerated in all parts of the study, with no serious adverse events reported. ClinicalTrials.gov identifier: NCT01455558. [Copyright &y& Elsevier]

Abstract: Background:: Tacrolimus is a macrolide immunosuppressant used in transplantation. It has been shown to have a comparable therapeutic effect and a low adverse drug reaction profile relative to cyclosporme. Objective:: The present study compared the pharmacokinetics of twice-daily doses of 2 tacrolimus formulations used in clinical practice in Korea: a conventional (reference) formulation and a more recently developed (test) formulation. The bioavailability of the 2 formulations was evaluated based on the requirement of 20% deviation at a power of 80%. Methods:: This study had a randomized, open-label, 2-period, crossover, noninferiority design. There was a 96-hour treatment period for each formulation, with a 3-week washout period between formulations. Each healthy adult subject received two 1-mg capsules of the reference or test formulation of tacrolimus twice daily (morning and evening), for a total daily dose of 4 mg. Blood samples were obtained during the 96-hour period after the first dose in each treatment period, with tolerability assessments performed up to 2 weeks after the first dose in each period. The primary pharmacokinetic parameters were Cmax and AUC from time 0 to the last measured concentration and extrapolated to infinity. Secondary pharmacokinetic parameters were Tmax, t1/2, Cmin0–24, AUC0-24, and C96. Results:: The study enrolled 29 healthy Korean volunteers (22 men, 7 women; mean [SD] age, 29 [7] years; age range, 20-51 years; mean weight, 66 [10] kg; mean height, [171 17] cm). All volunteers completed both treatment periods. The 90% Cls for the ratios of the pharmacokinetic parameters (test:reference drug) were 119.25–161.29 for Cmax, 95.29-129.04 for AUC0-t, and 95.63–131.42 for AUC0–∞. Based on the 80% to 125% bioequivalence criterion, these results indicated that pharmacokinetic exposure to the test drug was not inferior to that of the reference drug. Both formulations were well tolerated, with no serious adverse events reported. Conclusion:: In these healthy Korean adults, there were no statistically significant differences between the pharmacokinetic parameters of the more recently developed oral formulation of tacrolimus and the conventional formulation. [Copyright &y& Elsevier]

Atherosclerosis is a prominent vascular lesion, and potentially causing ischemic alterations in the brain and heart. Recent studies have reported that physiological and pathological alterations in atherosclerosis and extracellular vesicles (EV) are related. This study aimed to investigate the association between the extent of atherosclerotic lesions and the number of serum EVs in a mouse model of atherosclerosis (wild-type). Eighteen 3-week-old C57BL/6 N male mice(wild-type) were purchased. Twelve mice were fed a 45% high-fat diet (HFD) for six months. Six mice were provided standard laboratory chow for six months. The entire aorta, from the aortic sinus to the division of the iliac artery, was dissected out from each mouse. Furthermore, the degree of atherosclerosis was microscopically determined. Serum EVs were quantified by size via nanoparticle tracking analysis. The number of EVs in the high-atherosclerotic score group (1.43 × 109) was higher than that in the low- atherosclerotic score group (0.7 × 109) in the range of 211.5–222.5 nm (p = 0.033). Enumeration of EVs is a potential method of detecting atherosclerosis. [ABSTRACT FROM AUTHOR]

Mesenchymal tumors of the breast, which originate from the mammary stroma, are rare accounting for only approximately 0.5%-1% of all breast tumors. Pathologically, they can exist on a spectrum, ranging from benign to malignant. Such tumors may present with nonspecific findings on breast imaging, including mammography, ultrasound, and MRI, which can lead to diagnostic challenges. In the 2019 revised 5th edition of the World Health Organization classification, breast mesenchymal tumors are categorized into six groups. The current pictorial essay aimed to explore the clinical, pathological, and imaging characteristics of representative lesions in each category according to this six-group classification, with the ultimate goal of enhancing awareness for early diagnosis., Competing Interests: Conflicts of Interest: The authors have no potential conflicts of interest to disclose., (Copyrights © 2025 The Korean Society of Radiology.)

Exploring a computing paradigm that blends memory and computation functions is essential for artificial synapses. While memristors for artificial synapses are widely studied due to their energy-efficient structures, random filament conduction in general memristors makes them less preferred for endurability in long-term synaptic modulation. Herein, the topotactic phase transition (TPT) in brownmillerite-phased (110)-SrCoO 2.5 (SCO 2.5 ) is harnessed to enhance the reversibility of oxygen ion migration through 1-D oxygen vacancy channels. By employing a heteroepitaxial structured 2-terminal configuration of Au/SCO 2.5 /SrRuO 3 /SrTiO 3 , the brownmillerite SCO 2.5 -based synapse artificial synapses are exploited. Demonstration of the TPT behavior is corroborated by comparing oxygen migration energy by density-functional theory calculations and experimental results, and by monitoring the voltage pulse-induced peak shift in the Raman spectra of SCO 2.5 . With the voltage pulse-driven TPT behaviors, it is reliably characterized by linear, symmetric, and endurable long-term potentiation and depression performances. Notably, the durability of the TPT-based weight control mechanism is demonstrated by achieving consistent and noise-free weight updates over 32 000 iterations across 640 cycles. Furthermore, learning performances based on deep neural networks and convolutional neural networks on various image datasets yielded very high recognition accuracy. The work offers valuable insights into designing memristive synapses that enable reliable weight updates in neural networks., (© 2024 Wiley‐VCH GmbH.)

As electronic circuit integration intensifies, there is a rising demand for dielectric insulators that provide both superior insulation and high dielectric constants. This study focuses on developing high-k dielectric insulators by controlling the phase of the Hf 0.5 Zr 0.5 O 2 (HZO) film with additional doping, utilizing yttrium (Y), tantalum (Ta), gallium (Ga), silicon (Si), and aluminum (Al) as dopants. Doping changes the ratio of tetragonal to monoclinic phases in doped HZO films, and Y-doped HZO (Y:HZO) films specifically exhibit a high tetragonal phase ratio and a dielectric constant of 40.9, indicating superior insulating properties compared to undoped HZO films. To clarify the fundamental mechanism driving the enhancement in dielectric properties, we have carried out various analyses combined with density functional theory (DFT) calculations. Through the optimization of the post-deposition annealing (PDA) process and the heterojunction structure with Al 2 O 3 , an Al 2 O 3 /Y:HZO heterojunction with a high dielectric constant and even lower leakage current compared to a single layer was developed. The thin-film transistor (TFT) with the Au/Ti/amorphous InGaZnO 4 (a-IGZO)/Al 2 O 3 /YHZO/TiN heterojunction structure exhibits low subthreshold swing (SS) values within a narrow gate-source voltage ( V sg ) range. This study advances knowledge on how the controlled-phase doped HZO films affect the dielectric constant and leakage current and will contribute to semiconductor technology advancements by overcoming the limitations of conventional high-k dielectric insulators.

Primary malignant fibrous histiocytoma (MFH) is a malignant tumor of mesenchymal origin that rarely occurs in the urinary tract, particularly in the urinary bladder. Unlike urothelial carcinoma, which accounts for most bladder cancers, it occurs in the submucosal portion of the bladder wall and consists of the lamina propria, muscularis propria, and adventitia. It is presumed to originate from poorly differentiated pluripotent mesenchymal cells in which fibroblasts and histiocytes are partially differentiated. Radiologically, it is known as the "non-papillary tumor" and is commonly diagnosed as a large mass without necrosis, which shows invasion beyond the muscularis propia. Although the prognosis of this rare malignancy depends on pathological parameters, it generally has a poor prognosis with high local tumor recurrence. Here, we present a case of primary MFH in the urinary bladder with clinical symptoms of lower abdominal pain without gross hematuria that recurred rapidly and showed an aggressive disease course., Competing Interests: Conflicts of Interest: The authors have no potential conflicts of interest to disclose., (Copyrights © 2024 The Korean Society of Radiology.)

Preventing ferroelectric materials from losing their ferroelectricity over a low thickness of several nanometers is crucial in developing multifunctional nanoelectronics. Epitaxially grown 5 at. % yttrium-doped Hf 0.5 Zr 0.5 O 2 (YHZO) thin films exhibit an atomically smooth surface, an ability to maintain ferroelectricity even at a thickness of 10 nm, and excellent insulating properties, making them suitable for use as gate oxides in ferroelectric thin film transistors (FeTFTs). Through the epitaxial growth of a YHZO/La 0.67 Sr 0.33 MnO 3 (LSMO)/SrTiO 3 (STO) heterostructure, YHZO effectively retains its ferroelectricity and orthorhombic single phase, leading to enhancing electron mobility (∼19.74 cm 2 V -1 s -1 ) and memory window (3.7 V) in the amorphous InGaZnO 4 (a-IGZO)/YHZO/LSMO/STO FeTFTs. These FeTFTs demonstrate a consistent memory function with remarkable endurance (∼10 6 cycles) and retention (∼10 4 s). Furthermore, they sustain a constant memory window even under ±6 V bias stress for 10 4 s and exhibit excellent stability even under ±6 V/1 ms pulse cycling for 10 7 cycles. For comparison, a transistor with the same structure was fabricated using epitaxial nonferroelectric LaAlO 3 (LAO) and epitaxial undoped Hf 0.5 Zr 0.5 O 2 (HZO) as alternatives to YHZO. This study presents a novel approach to exploit the potential of YHZO in FeTFTs, contributing to the development of next-generation logic-in-memory.

Metal-insulator transition (MIT) coupled with an ultrafast, significant, and reversible resistive change in Mott insulators has attracted tremendous interest for investigation into next-generation electronic and optoelectronic devices, as well as a fundamental understanding of condensed matter systems. Although the mechanism of MIT in Mott insulators is still controversial, great efforts have been made to understand and modulate MIT behavior for various electronic and optoelectronic applications. In this review, recent progress in the field of nanoelectronics utilizing MIT is highlighted. A brief introduction to the physics of MIT and its underlying mechanisms is begun. After discussing the MIT behaviors of various Mott insulators, recent advances in the design and fabrication of nanoelectronics devices based on MIT, including memories, gas sensors, photodetectors, logic circuits, and artificial neural networks are described. Finally, an outlook on the development and future applications of nanoelectronics utilizing MIT is provided. This review can serve as an overview and a comprehensive understanding of the design of MIT-based nanoelectronics for future electronic and optoelectronic devices., (© 2023 Wiley-VCH GmbH.)

Glucosinolates are sulfur-containing phytochemicals generally abundant in cruciferous vegetables such as pak choy. Glucosinolates participate in a range of biological activities essential for promoting a healthy human body. In this study, we aimed to elucidate glucosinolate variability present in pak choy germplasm that are under conservation at the Rural Development Administration Genebank, Jeonju, Republic of Korea. The Acquity Ultra-Performance Liquid Chromatography (UHPLC) analytical system was used in profiling the glucosinolate content in leaf samples of various accessions. We identified a total of 17 glucosinolates in the germplasm. Based on principal compoment analysis performed, three separate groups of the accessions were obtained. Group 1 contained the cultivar cheongsacholong which recorded high content of glucobrassicin (an indole), glucoerucin (aliphatic), gluconasturtiin (aromatic) and glucoberteroin (aliphatic). Group 2 consisted of six accessions, BRA77/72, Lu ling gaogengbai, 9041, Wuyueman, RP-75 and DH-10, predominatly high in aliphatic compounds including glucoiberin, glucocheirolin, and sinigrin. Group 3 comprised the majority of the accessions which were characterized by high content of glucoraphanin, epiprogoitrin, progoitrin, and glucotropaeolin. These results revealed the presence of variability among the pak choy germplasm based on their glucosinolate content, providing an excellent opprtunity for future breeding for improved glucosinolate content in the crop.

Hand-foot-and-mouth disease (HFMD) is a viral infectious disease that occurs in children under 5 years of age. Its main causes are coxsackievirus (CV) and enterovirus (EV). Since there are no efficient therapeutics for HFMD, vaccines are effective in preventing the disease. To develop broad coverage against CV and EV, the development of a bivalent vaccine form is needed. The Mongolian gerbil is an efficient and suitable animal model of EV71 C4a and CVA16 infection used to investigate vaccine efficacy following direct immunization. In this study, Mongolian gerbils were immunized with a bivalent inactivated EV71 C4a and inactivated CVA16 vaccine to test their effectiveness against viral infection. Bivalent vaccine immunization resulted in increased Ag-specific IgG antibody production; specifically, EV71 C4a-specific IgG was increased with medium and high doses and CVA16-specific IgG was increased with all doses of immunization. When gene expression of T cell-biased cytokines was analysed, Th1, Th2, and Th17 responses were found to be highly activated in the high-dose immunization group. Moreover, bivalent vaccine immunization mitigated paralytic signs and increased the survival rate following lethal viral challenges. When the viral RNA content was determined from various organs, all three doses of bivalent vaccine immunization were found to significantly decrease viral amplification. Upon histologic examination, EV71 C4a and CVA16 induced tissue damage to the heart and muscle. However, bivalent vaccine immunization alleviated this in a dose-dependent manner. These results suggest that the bivalent inactivated EV71 C4a/CVA16 vaccine could be a safe and effective candidate HFMD vaccine.

Background: Diffuse large B-cell lymphomas are the most common type of non-Hodgkin lymphoma. Because cutaneous lymphomas predominantly originate from the T cells, primary cutaneous diffuse large B-cell lymphomas are considered a rare subtype of extranodal diffuse large B-cell lymphomas that commonly involve the subcutaneous tissues of the trunk and extremities. To date, only a single case of facial primary cutaneous diffuse large B-cell lymphoma has been reported in the literature., Case Report: We present a case of primary cutaneous diffuse large B-cell lymphoma presented with a small painless nodule in the right nasolabial fold that had persisted for 10 days in a 67-year-old man. Ultrasonographic findings of this lesion mimicked the features of a complicated epidermal inclusion cyst. Primary cutaneous diffuse large B-cell lymphoma was confirmed by an excisional biopsy of the mass., Conclusion: The diagnosis of primary cutaneous diffuse large B-cell lymphomas presenting as "oops lesions" in daily clinical practice can be challenging due to their rarity and nonspecific clinical and radiological findings. Therefore, clinical suspicion and awareness are critical for the accurate diagnosis and management of patients with palpable soft tissue masses in the head and neck region., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Eggplant is one of the most economically and nutritionally important vegetables worldwide. The study of the association of phenotypic traits with genetic factors is vital for the rapid and efficient identification and selection of eggplant genetic resources for breeding purposes with desired traits. The eggplant resources (587) collected from different countries, including Korea, were used for establishing the core collection. A total of 288 accessions were selected from 587 Solanum accessions based on 52 single nucleotide polymorphisms (SNPs) markers together with 17 morphological traits. This core collection was further used to analyze the genetic associations of eggplant morphological variations. A large variation was found among the evaluated eggplant accessions for some agro-morphological traits. Stem prickles and leaf prickles showed a significant positive correlation (r = 0.83***), followed by days to flowering and days to maturity (r = 0.64***). A total of 114,981 SNPs were filtered and used for phylogenetic tree analysis, population structure analysis, and genome-wide association study (GWAS). Among the agro-morphological traits, significantly associated SNPs were found for six traits. A total of 377 significantly associated SNPs with six agro-morphological traits were identified. These six traits and the number of SNPs were: days to maturity (51), flower size (121), fruit width (20), harvest fruit color (42), leaf prickles (38), and stem prickles (105). The largest fraction of significant SNPs (11.94%) was obtained on chromosome Ch01, followed by Ch07 and Ch06 with 11.67% and 10.08%, respectively. This study will help to develop markers linked to the most important agro-morphological traits of eggplant genetic resources and support the selection of desirable traits for eggplant breeding programs.

Purpose: The aim of the study was to evaluate the clinical implication of multigene panel testing of beyond BRCA genes in Korean patients with BRCA1/2 mutation-negative breast cancer., Materials and Methods: Between 2016 and 2019, a total of 700 BRCA1/2 mutation-negative breast cancer patients received comprehensive multigene panel testing and genetic counseling. Among them, 347 patients completed a questionnaire about cancer worry, genetic knowledge, and preference for the method of genetic tests during pre- and post-genetic test counseling. The frequency of pathogenic and likely pathogenic variants (PV/LPV) were analyzed., Results: At least one PV/LPV of 26 genes was found in 76 out of 700 patients (10.9 %). The rate for PV/LPV was 3.4% for high-risk genes (17 PALB2, 6 TP53, and 1 PTEN). PV/LPVs of clinical actionable genes for breast cancer management, high-risk genes and other moderate-risk genes such as ATM, BARD1, BRIP, CHEK2, NF1, and RAD51D, were observed in 7.4%. Patients who completed the questionnaire showed decreased concerns about the risk of additional cancer development (average score, 4.21 to 3.94; p < 0.001), influence on mood (3.27 to 3.13; p < 0.001), influence on daily functioning (3.03 to 2.94; p=0.006); and increased knowledge about hereditary cancer syndrome (66.9 to 68.8; p=0.025) in post-test genetic counseling. High cancer worry scales (CWSs) were associated with age ≤ 40 years and the identification of PV/LPV. Low CWSs were related to the satisfaction of the counselee., Conclusion: Comprehensive multigene panel test with genetic counseling is clinically applicable. It should be based on interpretable genetic information, consideration of potential psychological consequences, and proper preventive strategies.

Controlling phase transitions in correlated materials yields emergent functional properties, providing new aspects to future electronics and a fundamental understanding of condensed matter systems. With vanadium dioxide (VO 2 ), a representative correlated material, an approach to control a metal-insulator transition (MIT) behavior is developed by employing a heteroepitaxial structure with a ferroelectric BiFeO 3 (BFO) layer to modulate the interaction of correlated electrons. Owing to the defect-alleviated interfaces, the enhanced coupling between the correlated electrons and ferroelectric polarization is successfully demonstrated by showing a nonvolatile control of MIT of VO 2 at room temperature. The ferroelectrically-tunable MIT can be realized through the Mott transistor (VO 2 /BFO/SrRuO 3 ) with a remanent polarization of 80 µC cm -2 , leading to a nonvolatile MIT behavior through the reversible electrical conductance with a large on/off ratio (≈10 2 ), long retention time (≈10 4 s), and high endurance (≈10 3 cycles). Furthermore, the structural phase transition of VO 2 is corroborated by ferroelectric polarization through in situ Raman mapping analysis. This study provides novel design principles for heteroepitaxial correlated materials and innovative insight to modulate multifunctional properties., (© 2022 Wiley-VCH GmbH.)

In resistive switching memories or artificial synaptic devices, halide perovskites have attracted attention for their unusual features such as rapid ion migration, adjustable composition, and facile synthesis. Herein, the environmentally friendly and highly air stable CsCu 2 I 3 perovskite films are used as the active layer in the Au/CsCu 2 I 3 /ITO/glass artificial synapses. The device shows variable synaptic plasticities such as long-term and short-term synaptic plasticity, paired-pulse facilitation, and spike-timing-dependent plasticity by combining potentiation and depression along the formation of conductive filaments. The performances of the devices are maintained for 160 days under ambient conditions. Additionally, the accuracy evaluation of the CsCu 2 I 3 -based artificial synapses performs exceptionally well with the MNIST and Fashion MNIST data sets, demonstrating high learning accuracy in deep neural networks. Using the novel B-site engineered halide perovskite material with extreme air stability, this study paves the way for artificial synaptic devices for next-generation in-memory hardware.

Acid spills cause large-scale environmental damage and casualties. To respond to such incidents, a sensor capable of detecting acid leaks is required. Cellulose is a useful substrate material for the fast detection of acid leaks because it has high hydrophilicity and porosity. On the other hand, methods of manufacturing cellulose-based sensors are still complicated or time-consuming. Thus, in this study, a simple and rapid synthesis method for a cellulose-based pH sensor was proposed. The functionalization of α-cellulose was achieved via chloroacetyl chloride, and Congo red was covalently immobilized to the functionalized cellulose for detecting strong acids. The manufacturing process was composed of two steps as above and finished within 8 h. The developed sensor exhibited absorbance changes in the pH range of 0.2 to 3.0, and response time was shorter than 1 s. A prototype system using this sensor was manufactured and tested, and it detected acid leaks easily and quickly., Competing Interests: No other competing interests., (© 2022 The Authors.)

The mechanism of nonalcoholic fatty liver disease (NAFLD) has not been completely revealed. In this study, we investigated the association of liver histological changes and long noncoding RNAs (lncRNAs) in the NAFLD zebrafish model. Forty zebrafish were fed a high-cholesterol diet (1.5 g per day) for 8 weeks. We measured fatty liver changes in the zebrafish liver using oil red O staining and divided them into two groups based on high and low scores. We pooled each group of zebrafish livers and identified lncRNAs, miRNAs, and mRNAs using Next-generation sequencing. Human homologs of lncRNAs were identified using ZFLNC, Ensembl, and NONCODE. We found several significant genes, including 32 lncRNAs, 5 miRNA genes, and 8 protein-coding genes, that were associated with liver metabolism and NAFLD-related functions in zebrafish. In particular, eight conserved human homologs of lncRNAs were found. We discovered the human homologs of eight lncRNA candidates from fatty liver zebrafish for the first time. The spectrum of biological mechanisms by which lncRNAs mediate their functional roles in NAFLD in a high cholesterol diet adult zebrafish model remains to be uncovered., (© 2021. The Author(s).)

Purpose: The aim of this study was to evaluate the feasibility and satisfaction of an online global health education course for medical students in comparison with an in-person of the course and to assess students' preferences regarding online methods of delivery., Methods: Second-year medical students enrolled in this course in 2019 (in-person) and 2020 (online). The attendance rate, satisfaction in the course evaluation survey, and academic achievement on the written final examination were utilized to compare the two different methods of course delivery. The medical students who took the online course were also asked about their preferences regarding the method of course delivery and the advantages and drawbacks of each method of online lectures., Results: There was no significant difference in the attendance rate and overall satisfaction between the two groups. The mean score on the written examination of the online course (84.1±19.6) showed comparable effects to the in-person course (78.0±18.3). The percentages of students who achieved high performance (55.5%) and the achieved minimum requirement (95.9%) were also maintained compared to the in-person course (14.6% and 93.6%, respectively). Medical students preferred the online course to the in-person course; in particular, they preferred prerecorded videos over live streaming online lectures., Conclusion: The participation, satisfaction, and the academic achievement of the online course were comparable to those of the in-person course. However, the greatest drawback of the online course was the lack of interaction between peer learners. Therefore, diverse methods for online education should be considered to increase students' sense of belonging to a learning community.

Purpose: To compare pharmacokinetics, safety, tolerability, and immunogenicity between SB8, a bevacizumab biosimilar, and the European Union (EU) and United States (US) reference products (bevacizumab-EU, bevacizumab-US)., Methods: In this randomized, double-blind, parallel-group, and single-dose study, healthy volunteers were randomized to receive a 3 mg/kg dose of SB8, bevacizumab-EU, or bevacizumab-US via intravenous infusion. Primary endpoints were area under the concentration-time curve from time zero to infinity (AUC inf ) and to the last quantifiable concentration (AUC last ), and maximum observed serum concentration (C max ). Bioequivalence was achieved if 90% confidence intervals (CIs) for the ratios of the geometric least squares means (LSMeans) of primary endpoints were within the predefined bioequivalence margins of 80.00-125.00%. Safety and immunogenicity were also investigated., Results: The 90% CIs for the geometric LSMean ratios of AUC inf , AUC last and C max were all within the prespecified bioequivalence margins. Geometric LSMean ratios for SB8/bevacizumab-EU, SB8/bevacizumab-US and bevacizumab-EU/bevacizumab-US were 88.01%, 88.48% and 100.54% for AUC inf , 88.65%, 89.08% and 100.49% for AUC last and 99.59%, 101.15% and 101.56% for C max , respectively. Incidence of treatment-emergent adverse events (TEAEs) across treatment groups was comparable (SB8: 50.0%, bevacizumab-EU: 37.5%, bevacizumab-US: 53.8%). Most TEAEs were mild and considered as not related to the study drug. No deaths or treatment discontinuations due to adverse events occurred. Incidence of anti-drug antibodies was also comparable between all groups and no neutralizing antibodies were detected., Conclusion: This study demonstrated pharmacokinetic bioequivalence and similar safety and immunogenicity profiles of SB8 to both reference products, bevacizumab-EU and bevacizumab-US, and of bevacizumab-EU to bevacizumab-US. CLINICALTRIALS., Gov Identifier: NCT02453672 (submitted date); EudraCT number: 2015-001,026-41.

Organometallic and all-inorganic halide perovskites (HPs) have recently emerged as promising candidate materials for resistive switching (RS) nonvolatile memory due to their current-voltage hysteresis caused by fast ion migration. Lead-free and all-inorganic HPs have been researched for non-toxic and environmentally friendly RS memory devices. However, only HP-based devices with electrochemically active top electrode (TE) exhibit ultra-low operating voltages and high on/off ratio RS properties. The active TE easily reacts to halide ions in HP films, and the devices have a low device durability. Herein, RS memory devices based on an air-stable lead-free all-inorganic dual-phase HP (AgBi 2 I 7 -Cs 3 Bi 2 I 9 ) are successfully fabricated with inert metal electrodes. The devices with Au TE show filamentary RS behavior by conducting-bridge involving Ag cations in HPs with ultra-low operating voltages (<0.15 V), high on/off ratio (>10 7 ), multilevel data storage, and long retention times (>5 × 10 4 s). The use of a closed-loop pulse switching method improves reversible RS properties up to 10 3 cycles with high on/off ratio above 10 6 . With an extremely small bending radius of 1 mm, the devices are operable with reasonable RS characteristics. This work provides a promising material strategy for lead-free all-inorganic HP-based nonvolatile memory devices for practical applications., (© 2020 Wiley-VCH GmbH.)

Mitophagy has been implicated in mitochondrial quality control and in various human diseases. However, the study of in vivo mitophagy remains limited. We previously explored in vivo mitophagy using a transgenic mouse expressing the mitochondria-targeted fluorescent protein Keima (mt-Keima). Here, we generated mt-Keima Drosophila to extend our efforts to study mitophagy in vivo . A series of experiments confirmed that mitophagy can be faithfully and quantitatively measured in mt-Keima Drosophila . We also showed that alterations in mitophagy upon environmental and genetic perturbation can be measured in mt-Keima Drosophila . Analysis of different tissues revealed a variation in basal mitophagy levels in Drosophila tissues. In addition, we found a significant increase in mitophagy levels during Drosophila embryogenesis. Importantly, loss-of-function genetic analysis demonstrated that the phosphatase and tensin homolog-induced putative kinase 1 (PINK1)-Parkin pathway is essential for the induction of mitophagy in vivo in response to hypoxic exposure and rotenone treatment. These studies showed that the mt-Keima Drosophila system is a useful tool for understanding the role and molecular mechanism of mitophagy in vivo . In addition, we demonstrated the essential role of the PINK1-Parkin pathway in mitophagy induction in response to mitochondrial dysfunction.-Kim, Y. Y., Um, J.-H., Yoon, J.-H., Kim, H., Lee, D.-Y., Lee, Y. J., Jee, H. J., Kim, Y. M., Jang, J. S., Jang, Y.-G., Chung, J., Park, H. T., Finkel, T., Koh, H., Yun, J. Assessment of mitophagy in mt-Keima Drosophila revealed an essential role of the PINK1-Parkin pathway in mitophagy induction in vivo .

Studies have previously shown sugammadex works faster and more effectively than neostigmine/glycopyrrolate at reversal of neuromuscular blockade by rocuronium and vecuronium. The purpose of this quality improvement study was to evaluate for differences in patient time spent in the operating room (OR), post-anesthesia care unit (PACU), and patient responsiveness between the sugammadex and neostigmine/glycopyrrolate groups at a small surgical center. Additionally, a cost analysis was conducted to assess potential savings associated with sugammadex use, taking into account the differences in OR time, PACU time, and medication acquisition cost. We conducted a prospective analysis of OR time, PACU time, and responsiveness for a total of 152 patients, 76 patients receiving neostigmine/glycopyrrolate and 76 patients receiving sugammadex, undergoing planned surgery over an 8-week period. We identified an average decrease in total OR time of 6 minutes in the sugammadex group (neostigmine/glycopyrrolate [Mean: 86 min, Median: 77 min, Range 32-211 min] vs sugammadex [Mean: 80 min, Median: 77 min, Range 40-150 min]). Furthermore, there was an average decrease in total PACU time of 6 minutes in the sugammadex group (neostigmine/glycopyrrolate [Mean: 60 min, Median: 56 min, Range 32-154 min] vs sugammadex [Mean: 54 min, Median: 51 min, Range: 28-94 min]). Additionally, the percent of patients fully awake at the end of PACU stay was higher in the sugammadex group than the neostigmine/glycopyrrolate group (86% vs 79% respectively). Cost was evaluated for generating hypotheses. The additional cost of using sugammadex was estimated at $77 per person when compared to neostigmine/glycopyrrolate. However, if the use of sugammadex decreased the time in OR and PACU by an average of 12 minutes per patient, it is possible that it could provide a potential savings of $579 per patient after estimating a soft savings of reduced OR, PACU, and staff time. Overall cost saving per patient with sugammadex, which was calculated after subtracting additional medication acquisition cost, is $502. It is possible that if this value is extrapolated to 988 patients, this might suggest a potential cost savings of $495,976 per year. We hope this study provokes future research to determine if Sugammadex is a potentially viable economical option for the routine reversal of neuromuscular blockade., (© Individual authors.)

The familial Creutzfeldt-Jakob disease (fCJD) usually has similar clinical and neuroimaging features as sporadic CJD (sCJD). A 57-year-old man presented with a four-month history of rapidly progressive dementia (RPD). Laboratory tests for RPD were all normal. Brain MRI demonstrated diffuse cortical atrophy and no abnormal cortical or striatal hyperintensities on fluid-attenuated inversion recovery (FLAIR)/diffusion weighted imaging (DWI). Electroencephalography revealed intermittent slow waves in the bilateral hemispheres. Cerebrospinal fluid (CSF) examination showed elevated cell counts and protein concentrations. After 10 days of empirical treatment with antiviral agents, the patient was eventually diagnosed with fCJD with M232R mutation based on the results of positivity for 14-3-3 protein, CSF PrP sc in real-time quaking-induced conversion assay and genetic test for PRNP gene. The striatal or cortical FLAIR/DWI hyperintensities are reliable radiographic markers in the diagnosis of both sCJD and fCJD. However, this case suggests that clinical work-up for CJD including genetic test is essential to do a differential diagnosis of RPD, regardless of FLAIR/DWI findings., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Surgery for reconstruction of defects after surgery should be performed selectively and the many points must be considered. The authors conducted this study to compare the local flap and skin graft by facial location in the reconstruction after resection of facial skin cancer., Methods: The authors performed the study in patients that had received treatment in Department of Plastic Surgery, Gyeongsang National University. The cases were analyzed according to the reconstruction methods for the defects after surgery, sex, age, tumor site, and tumor size. Additionally, the authors compared differences of aesthetic satisfaction (out of 5 points) of patients in the local flap and skin graft by facial location after resection of facial skin cancer by dividing the face into eight areas., Results: A total of 153 cases were confirmed. The most common facial skin cancer was basal cell carcinoma (56.8%, 87 cases), followed by squamous cell carcinoma (37.2%, 57 cases) and bowen's disease (5.8%, 9 cases). The most common reconstruction method was local flap 119 cases (77.7%), followed by skin graft 34 cases (22.3%). 86 patients answered the questionnaire and mean satisfaction of the local flap and skin graft were 4.3 and 3.5 ( p =0.04), respectively, indicating that satisfaction of local flap was significantly high., Conclusion: When comparing satisfaction of patients according to results, local flap shows excellent effects in functional and cosmetic aspects would be able to provide excellent results rather than using a skin graft with poor touch and tone compared to the surrounding normal skin., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported.

Background/aims: Serrated polyposis syndrome (SPS) has been shown to increase the risk of colorectal cancer (CRC). However, little is known about the characteristics of Asian patients with SPS. This study aimed to identify the clinicopathological features and risk of CRC in Korean patients with SPS as well as the differences between Korean and Western patients based on a literature review., Methods: This retrospective study included 30 patients with SPS as defined by World Health Organization classification treated at Samsung Medical Center, Korea, between March 1999 and May 2011., Results: Twenty patients (67%) were male. The median patient age at diagnosis was 56 years (range, 39-76 years). A total of 702 polyps were identified during a median follow-up of 43 months (range, 0-149 months). Serrated polyps were noted more frequently in the distal colon (298/702, 55%). However, large serrated polyps and serrated adenomas were mainly distributed throughout the proximal colon (75% vs. 25% and 81% vs. 19%, respectively); 73.3% had synchronous adenomatous polyps. The incidence of CRC was 10% (3/30 patients), but no interval CRC was detected. A total of 87% of the patients underwent esophagogastroduodenoscopy and 19.2% had significant lesions., Conclusions: The phenotype of SPS in Korean patients is different from that of Western patients. In Korean patients, SPS is more common in men, there were fewer total numbers of serrated adenoma/polyps, and the incidence of CRC was lower than that in Western patients. Korean patients tend to more frequently have abnormal gastric lesions. However, the prevalence of synchronous adenomatous polyps is high in both Western and Korean patients., Competing Interests: Conflict of interest: None.

Cutaneous leiomyosarcoma is an uncommon superficial soft tissue sarcoma and mainly found in the middle aged to elderly males. It can occur in any part of the body, mostly affecting the extremities and rarely affecting the face. It grows relatively slowly, can be diagnosed by biopsy and is treated by surgical excision. It needs to be distinguished from other spindle cell neoplasms, and immunohistochemical markers are usually required to attain an accurate diagnosis. We report a case of cutaneous leiomyosarcoma appeared on the left cheek within 6 month of a 73-year-old female patient suspected with malignant melanoma before surgery., Competing Interests: No potential conflict of interest relevant to this article was reported.

An odontogenic cutaneous fistula is a pathological communication between the outer skin surface of the face and the oral cavity. Facial cutaneous fistula is a complication of odontogenic infection that is often misdiagnosed with skin infection. We report a rare case, which was diagnosed as basal cell carcinoma based on the biopsy of skin lesions in the patient who had been diagnosed with odontogenic cutaneous fistula. A 64-year-old male patient presented with a cutaneous odontogenic fistula. The patient had undergone surgical extraction of fistula tract and loose tooth before dermatology or plastic surgery consultation. With the biopsy and computed tomography, it was confirmed that fistula and basal cell carcinoma. However, the connection between the fistula and skin cancer was not clear. Positron emission tomography-computed tomography scan was performed and was not detected as other local or distant metastasis. After that, wide excision of the skin lesion was performed. Although skin cancer is not commonly observed, it is necessary to rule out this disease entity by performing biopsy of skin lesions., Competing Interests: No potential conflict of interest relevant to this article was reported.

EUS-FNA becomes one of the most important diagnostic modalities for PDACs. However, acquired tissue specimens were sometimes insufficient to make a definite cytological diagnosis. On the other hand, KRAS mutation is the most frequently acquired genetic alteration found more than 90% of PDACs. To investigate the way to improve diagnostic accuracy for PDACs using both cytological examination and KRAS mutation analysis would be a great help. Therefore, the aims of this study were to evaluate usefulness of conventional cytological examination combined with KRAS mutation analysis with modified PCR technology to improve the sensitivity and the accuracy. We enrolled 43 patients with solid pancreatic masses and 86 EUS-FNA specimens were obtained. During the EUS-FNA, the needle catheter was flushed with 2 cc of saline and the washed fluid was collected for KRAS mutation analysis for the first 2 passes; PNAClamp™ KRAS Mutation Detection Kit. There were 46 specimens from the 23 PDACs and 40 specimens from the 20 other pancreatic diseases. The sensitivity, specificity and accuracy were as follows; conventional cytopathologic examination: 63%, 100% and 80%; combination of cytopathologic examination and K-ras mutation analysis: 87%, 100% and 93%. Furthermore, KRAS mutation was detected 11 out of 17 PDAC samples whose cytopathology results were inconclusive. KRAS mutation analysis with PNAClamp™ technique using washing fluid from EUS-FNA along with cytological examination may not only improve the diagnostic accuracy of PDACs, but also establish the platform using genetic analysis which would be helpful as diagnostic modality for PDACs.

Background: Zygomatic arch is a bony arch constituting the lateral midface, which consists of 25% of all midface fractures. There are a number of ways to evaluate the extent of zygomatic arch fracture. Some authors have reported successful treatment outcomes using ultrasound (U/S). To add to the previous methods, we have considered ways to accurately display the location of the fracture line while using U/S with 23 gauge needle marking. We introduce our method, which provided satisfactory results for reduction using a portable U/S, and it can evaluate the fracture line simultaneously when reduction of an isolated zygomatic arch fracture is necessary, and needle marking, which can easily point out the fracture line on U/S., Methods: We studied 21 patients with an isolated zygomatic arch fracture who underwent closed reduction using U/S and needle marking between 2013 and 2015., Results: We achieved satisfactory results in all our cases with respect to reduction by using the Dingman elevator after performing a temporal approach incision, while confirming relative positioning between needle marking and zygomatic fracture at the same time, after insertion of a 23 gauge needle in the skin above the zygomatic arch fracture line parallel to it., Conclusion: We treated 21 patients with an isolated zygomatic arch fracture using U/S and the needle marking method, which provided satisfactory results because the extent of reduction of the fracture could be evaluated in real-time during the operation and exposure to radiation was reduced., Competing Interests: No potential conflict of interest relevant to this article was reported.

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., (© 2016 Samsung Bioepis Co., Ltd. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background/aims: Several precut techniques have been used to gain biliary access for difficult cases. The aim of this study was to evaluate the success and complication rates of two precut techniques, transpancreatic septotomy (TPS) and needle knife infundibulotomy (NKI), in difficult biliary cannulation due to the presence of unintended pancreatic cannulation., Methods: Eighty-six patients who failed standard biliary cannulation were included. TPS was performed when we failed to achieve biliary access despite 5 minutes of attempted cannulation or when more than three attempted unintended pancreatic cannulations occurred. If deep cannulation was not achieved within 5 minutes for any duct, NKI was performed. If this failed, we crossed over to the other technique in the second attempt., Results: The initial total success rate of biliary cannulation was 88.4% (86.6% for the TPS group and 94.7% for the NKI group, p=0.447). After crossover of the techniques, the final success rate was 95.3%. The complication rate was 20.9% in patients with TPS and 15.8% in patients with NKI (p=0.753)., Conclusions: The use of different strategies based on the presence of unintended pancreatic cannulation may help increase the success rate for difficult biliary cannulation without increasing complication rates.

Symptoms of a peritoneal progression from ovarian cancer are nonspecific such as abdominal pain, abdominal distention and more. Many imaging studies and serum CA-125 help diagnosis. However, it is difficult to exclude the instances of the diffuse peritoneal diseases that mimic carcinomatosis. The elevated CA-125 level usually correlates with the peritoneal carcimatosis, but it is often found in other peritoneal diseases. Therefore, the pathologic confirmation is necessary because of other mimicking diseases. In our case, CA-125 levels were elevated. Abdominal computed tomography finding was suspected a peritoneal tuberculosis but the pathologic result was the peritoneal carcimatosis, eventually.

Background: The sequential organ failure assessment (SOFA) score is easy to calculate and has been well validated as an outcome predictor in critically ill adult patients. However, its use in children has been limited, mainly because of differences in basal reference levels of serum creatinine., Methods: Data include 87 patients requiring continuous renal replacement therapy (CRRT) between January 2005 and July 2011. We modified the SOFA score by excluding the renal component to an extrarenal SOFA score, based on the assumption that CRRT may mitigate the renal effect on outcome and investigated the utility in predicting outcome with comparison with pediatric risk of mortality (PRISM) III, pediatric logistic organ dysfunction (PELOD), and SOFA scores., Results: Results showed that 95.4 % (n = 83) had multiple organ dysfunction syndrome with an overall mortality of 50.6 %. The extrarenal SOFA score at CRRT initiation and ≥20 % fluid overload were significantly associated with mortality. In comparison with the predictive power of various scoring systems, the extrarenal SOFA score showed the largest area under the receiver operating characteristic curve (extrarenal SOFA 0.774, SOFA 0.770, PRISM III 0.660, and PELOD 0.650)., Conclusions: The extrarenal SOFA score may be a useful prognostic marker in critically ill children treated with CRRT.

Severe vaso-occlusive retinopathy is a relatively rare form of retinopathy in systemic lupus erythematosus (SLE). We report two patients with severe vaso-occlusive retinopathy in SLE who were treated with intravitreal bevacizumab (IVB). (Patient 1) A 35-year-old woman presented with left visual loss and was diagnosed with SLE after systemic evaluation. Despite systemic immunosuppressive therapy, retinal vascular obstruction progressed and neovascularization of the disk (NVD) developed. The patient was treated with IVB and pan retinal photocoagulation. The progression of vascular obstruction ceased and regressed. (Patient 2) A 24-year-old man with SLE presented with left visual loss. There was retinal vascular obstruction with macular edema in both eyes, and then the patient was treated with IVB. One month after injection, minimal capillary nonperfusion increased to 10 disk area, and 5 months later, neovascularization elsewhere (NVE) developed in the right eye. Six months after injection, vitreous hemorrhage with florid NVE and NVD developed in the left eye. In selected severe vaso-occlusive retinopathy in SLE patients, IVB may be an adjuvant option for treatment.

Background: Health-related quality of life (HRQOL) is an essential subject for children with end-stage renal disease (ESRD) and their families., Methods: We performed a cross-sectional investigation of HRQOL in children undergoing renal replacement therapies, such as dialysis and renal transplantation, using the 34-item Pediatric Quality of Life Inventory 3.0 End-Stage Renal Disease (PedsQL 3.0 ESRD) module. We assessed 92 ESRD patients aged 2-18 from four Korean university hospitals., Results: The male:female ratio was 44:48, and the most common cause of ESRD was chronic glomerulonephritis. Fifty-five children were treated by dialysis, and 37 received renal transplantation. Transplant patients had better HRQOL than dialysis patients in two domains in parent proxy reports: "About my kidney disease" and "Worry." In child self-reports, transplant patients had better HRQOL than dialysis patients in one domain: Treatment problems. However, there were no significant differences in total QOL scores between peritoneal dialysis (PD) and transplant patients in child self-reports. In addition, there were differences in the ESRD module scores between child self- and parent proxy reports. Children usually reported better QOL than their parents. Child self-reports showed significantly higher QOL scores than parent proxy reports in the domains of General fatigue, Family & peer interaction, and Worry. Children on PD self-reported a significantly higher QOL than children on hemodialysis (HD)., Conclusions: The PedsQL 3.0 ESRD module may be useful as an ESRD-specific instrument to evaluate HRQOL in children; however, a larger, longitudinal prospective study is warranted.

Background: Fusobacterium species are uncommon causes of osteomyelitis. These organisms are normal flora of the oral cavity. Therefore, they mostly cause osteomyelitis of the head and neck. Hematogenous osteomyelitis at distant sites other than the head and neck has rarely been reported in pediatric or immunocompromised patients. Here, we report the first case of osteomyelitis of a long bone combined with a muscle abscess due to Fusobacterium nucleatum in an otherwise healthy adult., Case Presentation: A 59-year-old Korean man was admitted for pain and swelling of the right lower leg, which had been persistent for two weeks. Magnetic resonance imaging showed osteomyelitis of the right fibula with a surrounding muscle abscess of the right lower leg. Incision and drainage was performed, and repetitive tissue cultures grew F. nucleatum. In this patient, it was presumed that recurrent periodontitis caused hematogenous seeding of F. nucleatum to a distant site leading to osteomyelitis with a muscle abscess. The patient was successfully treated with intravenous ampicillin-sulbactam for three weeks and oral amoxicillin-clavulanate for eight weeks. He also underwent repeated surgical drainage. He has no evidence of recurrence after seven months of follow-up., Conclusions: Clinicians should be aware that F. nucleatum could be the etiologic agent of hematogenous osteomyelitis of a long bone in an immunocompetent patient.

Sibutramine is a pharmacologic intervention for the treatment of obesity. The effect of CYP2B6 genotypes on the pharmacokinetics of sibutramine and its active metabolites (desmethylsibutramine [M1] and didesmethylsibutramine [M2]) was evaluated in 57 healthy subjects. Each subject received a single oral dose of 10 or 15 mg sibutramine, and blood samples were collected up to 72 hours after dosing. The relationship between the genotypes and the pharmacokinetics of sibutramine, M1, and M2 was examined. A statistically significant difference in the elimination half-life (t(1/2)) of sibutramine M1 was found among the 3 genotype groups (P = .0006), between the *1/*1 and *1/*6 groups (P = .0001), and between the *1/*4 and *1/*6 groups (P = .012). The mean value of M1 t(1/2) in *1/*6 (33.3 ± 10.5 hours) was about 58% and 61% greater than that of the *1/*1 group (21.0 ± 7.4 hours) and the *1/*4 group (20.7 ± 9.8 hours), respectively. No significant differences in area under the concentration-time curve or maximum plasma drug concentration were observed between the groups. The CYP2B6*6 allele may be associated with a lower metabolic clearance of the M1 metabolite of sibutramine in human subjects.

Two lower molecular mass OMT genes (ROMT-15 and -17) were cloned from rice and expressed in Escherichia coli as glutathione S-transferase fusion proteins. ROMT-15 and -17 metabolized caffeoyl-CoA, flavones and flavonols containing two vicinal hydroxyl groups, although they exhibited different substrate specificities. The position of methylation in both luteolin and quercetin was determined to be the 3' hydroxyl group and myricetin and tricetin were methylated not only at 3' but also at 5' hydroxyl groups. ROMT-15 and -17 are cation-dependent and mutation of the predicted metal binding sites resulted in the loss of the enzyme activity, indicating that the metal ion has a critical role in the enzymatic methylation.

We investigated the reconstruction of feet in older diabetic patients, assessing the factors that affect the survival of transplantation tissue and successful transplantation with a prospective survey. From October 2004 to December 2005, the patients, who underwent reconstruction of diabetic feet with an anterolateral thigh perforator free flap, were all over 55 years old at the time of operation. We performed hematologic, hemodynamic, diabetic, bacteriologic, and radiological tests prior to the surgery, evaluating the condition of blood vessels at the donor site and the recipient site and the condition of transplantation tissues. After the surgery, we determined the survival or death of transplantation tissue. Fifteen of 16 patients were evaluated. In one case, transplantation failed, and in four cases, partial graft tissue-necrosis occurred. All assayed terms of the patients and the chart were similar except for peak blood flow velocity (PBFV), which was measured by Doppler ultrasonography at the artery recipient site. The PBFV in failed patients was 20 cm/s. In cases of delayed wound-healing, the PBFV was 30 cm/s. All patients with PBFVs over 40 cm/s had successful results. So using free flap transplantation to remedy diabetic foot ulcers can produce excellent or good results, especially in patients with PBFVs over 40 cm/s at the recipient artery.

Glycosyltransferase family 1 (UGT) uses small chemicals including phenolics, antibiotics, and alkaloids as substrates to have an influence in biological activities. A glycosyltransferase (XcGT-2) from Xanthomonas campestris was cloned and consisted of a 1,257 bp open reading frame encoding a 45.5 kDa protein. In order to use this for the modification of phenolic compounds, XcGT-2 was expressed in Escherichia coli as a glutathione S-transferase fusion protein. With the E. coli transformant expressing XcGT-2, biotransformation of flavonoids was carried out. Flavonoids having a double bond between carbons 2 and 3, and hydroxyl groups at both C-3' and C-4', were glycosylated and the glycosylation position was determined to be at the hydroxyl group of C-3', using nuclear magnetic resonance spectroscopy. These results showed that XcGT-2 regiospecifically transferred a glucose molecule to the 3'-hydroxyl group of flavonoids containing both 3' and 4'-hydroxyl groups.

Purpose: This study was to describe nurses' research activities, perceptions and performances of evidence-based practice and barriers to the use of research evidence in nursing practice in Korea., Method: A cross-sectional survey design was used. A questionnaire, except for Barriers Scale, was developed for the study. Data was collected from a convenient sample of 437 registered nurses working at research and education oriented university hospitals., Result: Nurses' research-related activities were relatively low compared to previous studies. Also perceptions and performances of evidence based nursing practice were low. Preferred informational resources for clinical decision making were identified as ward manuals/clinical guidelines, manager/senior nurses, and literature/research. The major barriers to research utilization were a lack of implication for practice along with inadequate facilitation to implement research evidence and difficulty understanding research written in English. Priorities of barriers factor were Administrator, Communication, Adopter, and Research., Conclusion: The findings provide directions for future training, education, and managerial policy to achieve successful evidence based nursing practice.

Background/aims: Tamoxifen has been tried in patients with hepatocellular carcinoma (HCC), however, its inhibitory mechanism remains unknown. In this study, we evaluated the effects of tamoxifen on HCC cell growth and the expression of transforming growth factor-beta1 (TGF-beta1) which had been known as an important cytokine in growth of HCC., Methods: Hep 3B cells were cultivated in estrogen free media with 0.1 micro M, 0.5 micro M, 1 micro M, 5 micro M, and 10 micro M of tamoxifen for 6 days. Viable cells were counted daily and the TGF-beta1 concentrations in supernatant were measured by ELISA method., Results: The number of viable HCC cells increased rather significantly after the treatment of tamoxifen of lower concentration (0.1micro M) compared with that of the control (2.59x10(7) vs. 1.97x107; p<0.05). As the concentration of treated tamoxifen was higher, the number of viable HCC cells became gradually less, resulting in the significant decrease of it at the highest concentration (10micro M) compared with that of the control (1.40x10(7) vs. 1.97x10(7); p<0.05). TGF-beta1 concentration in supernatant of tamoxifen-treated samples was significantly decreased compared with those of controls, regardless of the amount of treated tamoxifen., Conclusions: These results suggest that tamoxifen may suppress TGF-beta1 expression to an extent, although it has different effects on the proliferation of HCC cells, at the various concentrations of this agent in vitro. Such effects of tamoxifen on TGF-beta1 expression may inhibit the growth and progression of HCCs over-expressing TGF-beta1 in vivo.