Stable nebulization and muco-trapping properties of regdanvimab/IN-006 support its development as a potent, dose-saving inhaled therapy for COVID-19.

The respiratory tract represents the key target for antiviral delivery in early interventions to prevent severe COVID-19. While neutralizing monoclonal antibodies (mAb) possess considerable efficacy, their current reliance on parenteral dosing necessitates very large doses and places a substantial burden on the healthcare system. In contrast, direct inhaled delivery of mAb therapeutics offers the convenience of self-dosing at home, as well as much more efficient mAb delivery to the respiratory tract. Here, building on our previous discovery of Fc-mucin interactions crosslinking viruses to mucins, we showed that regdanvimab, a potent neutralizing mAb already approved for COVID-19 in several countries, can effectively trap SARS-CoV-2 virus-like particles in fresh human airway mucus. IN-006, a reformulation of regdanvimab, was stably nebulized across a wide range of concentrations, with no loss of activity and no formation of aggregates. Finally, nebulized delivery of IN-006 resulted in 100-fold greater mAb levels in the lungs of rats compared to serum, in marked contrast to intravenously dosed mAbs. These results not only support our current efforts to evaluate the safety and efficacy of IN-006 in clinical trials, but more broadly substantiate nebulized delivery of human antiviral mAbs as a new paradigm in treating SARS-CoV-2 and other respiratory pathologies.

Preclinical assessment and randomized Phase I study of CT-P63, a broadly neutralizing antibody targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in significant morbidity and mortality worldwide. Despite a successful vaccination programme, the emergence of mutated variants that can escape current levels of immunity mean infections continue. Herein, we report the development of CT-P63, a broad-spectrum neutralizing monoclonal antibody. In vitro studies demonstrated potent neutralizing activity against the most prevalent variants, including Delta and the BA.1 and BA.2 sub-lineages of Omicron. In a transgenic mouse model, prophylactic CT-P63 significantly reduced wild-type viral titres in the respiratory tract and CT-P63 treatment proved efficacious against infection with Beta, Delta, and Omicron variants of SARS-CoV-2 with no detectable infectious virus in the lungs of treated animals. A randomized, double-blind, parallel-group, placebo-controlled, Phase I, single ascending dose study in healthy volunteers (NCT05017168) confirmed the safety, tolerability, and pharmacokinetics of CT-P63. Twenty-four participants were randomized and received the planned dose of CT-P63 or placebo. The safety and tolerability of CT-P63 were evaluated as primary objectives. Eight participants (33.3%) experienced a treatment-emergent adverse event (TEAE), including one grade ≥3 (blood creatine phosphokinase increased). There were no deaths, treatment-emergent serious adverse events, TEAEs of special interest, or TEAEs leading to study drug discontinuation in the CT-P63 groups. Serum CT-P63 concentrations rapidly peaked before declining in a biphasic manner and systemic exposure was dose proportional. Overall, CT-P63 was clinically safe and showed broad-spectrum neutralizing activity against SARS-CoV-2 variants in vitro and in vivo.

Ulmus macrocarpa Hance extract modulates intestinal microbiota in healthy adults: a randomized, placebo-controlled clinical trial.

The stem and root bark of Ulmus macrocarpa Hance has been used as traditional pharmacological agent against inflammation related disorders. The objective of this study was to explore the impact of Ulmus macrocarpa Hance extract (UME) on human gut microbiota. A randomized placebo-controlled clinical study was conducted in healthy adults. The study subjects were given 500 mg/day of UME or placebo orally for 4 weeks. Eighty fecal samples were collected at baseline and 4 weeks of UME or placebo intervention. The gut microbiota variation was evaluated by 16S rRNA profiling. The microbial response was highly personalized, and no statistically significant differences was observed in both species richness and abundance. The number of bacterial species identified in study subjects ranged from 86 to 182 species. The analysis for taxonomical changes revealed an increase in Eubacterium ventriosum, Blautia faecis, Ruminococcus gnavus in the UME group. Functional enrichment of bacterial genes showed an increase in primary and secondary bile acid biosynthesis in UME group. Having known from previous studies Eubacterium regulated bile acid homeostasis in protecting gut microbial architecture and immunity, we suggest that UME supplementation might enhance host immunity by modulating gut microbiota. This is the first stage study and forthcoming clinical studies with larger participants are needed to confirm these findings.

Defining variant-resistant epitopes targeted by SARS-CoV-2 antibodies: A global consortium study.

Antibody-based therapeutics and vaccines are essential to combat COVID-19 morbidity and mortality after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Multiple mutations in SARS-CoV-2 that could impair antibody defenses propagated in human-to-human transmission and spillover or spillback events between humans and animals. To develop prevention and therapeutic strategies, we formed an international consortium to map the epitope landscape on the SARS-CoV-2 spike protein, defining and structurally illustrating seven receptor binding domain (RBD)­directed antibody communities with distinct footprints and competition profiles. Pseudovirion-based neutralization assays reveal spike mutations, individually and clustered together in variants, that affect antibody function among the communities. Key classes of RBD-targeted antibodies maintain neutralization activity against these emerging SARS-CoV-2 variants. These results provide a framework for selecting antibody treatment cocktails and understanding how viral variants might affect antibody therapeutic efficacy.

The in vitro and in vivo efficacy of CT-P59 against Gamma, Delta and its associated variants of SARS-CoV-2.

The SARS-CoV-2 variant is rapidly spreading across the world and causes to resurge infections. We previously reported that CT-P59 presented its in vivo potency against Beta variants, despite its reduced activity in cell experiments. Yet, it remains uncertain to exert the antiviral effect of CT-P59 on Gamma, Delta and its associated variants (L452R). To tackle this question, we carried out cell tests and animal studies. CT-P59 showed neutralization against Gamma, Delta, Epsilon, and Kappa variants in cells, with reduced susceptibility. The mouse challenge experiments with Gamma and Delta variants substantiated in vivo potency of CT-P59 showing symptom remission and virus abrogation in the respiratory tract. Collectively, cell and animal studies showed that CT-P59 is effective against Gamma and Delta variants infection, hinting that CT-P59 has therapeutic potential for patients infected with Gamma, Delta and its associated variants.

Ecological Risk Assessment of Amoxicillin, Enrofloxacin, and Neomycin: Are Their Current Levels in the Freshwater Environment Safe?

Veterinary pharmaceuticals may cause unexpected adverse effects on non-target aquatic species. While these pharmaceuticals were previously identified as priority compounds in ambient water, their ecological risks are relatively unknown. In this study, a series of chronic toxicity tests were conducted for these pharmaceuticals using algae, two cladocerans, and a fish. After a 21-d exposure to amoxicillin, enrofloxacin, and neomycin, no observed effect concentration (NOEC) for the reproduction of Daphnia magna was detected at 27.2, 3.3, and 0.15 mg/L, respectively. For the survival of juvenile Oryzias latipes following the 40-d exposure, NOEC was found at 21.8, 3.2, and 0.87 mg/L, respectively. Based on the results of the chronic toxicity tests and those reported in the literature, predicted no-effect concentrations (PNECs) were determined at 0.078, 4.9, and 3.0 µg/L for amoxicillin, enrofloxacin, and neomycin, respectively. Their hazard quotients (HQs) were less than 1 at their average levels of occurrence in ambient freshwater. However, HQs based on the maximum detected levels of amoxicillin and enrofloxacin were determined at 21.2 and 6.1, respectively, suggesting potential ecological risks. As the potential ecological risks of these veterinary pharmaceuticals at heavily contaminated sites cannot be ignored, hotspot delineation and its management are required.

Therapeutic effect of CT-P59 against SARS-CoV-2 South African variant.

The global circulation of newly emerging variants of SARS-CoV-2 is a new threat to public health due to their increased transmissibility and immune evasion. Moreover, currently available vaccines and therapeutic antibodies were shown to be less effective against new variants, in particular, the South African (SA) variant, termed 501Y.V2 or B.1.351. To assess the efficacy of the CT-P59 monoclonal antibody against the SA variant, we sought to perform as in vitro binding and neutralization assays, and in vivo animal studies. CT-P59 neutralized B.1.1.7 variant to a similar extent as to wild type virus. CT-P59 showed reduced binding affinity against a RBD (receptor binding domain) triple mutant containing mutations defining B.1.351 (K417N/E484K/N501Y) also showed reduced potency against the SA variant in live virus and pseudovirus neutralization assay systems. However, in vivo ferret challenge studies demonstrated that a therapeutic dosage of CT-P59 was able to decrease B.1.351 viral load in the upper and lower respiratory tracts, comparable to that observed for the wild type virus. Overall, although CT-P59 showed reduced in vitro neutralizing activity against the SA variant, sufficient antiviral effect in B.1.351-infected animals was confirmed with a clinical dosage of CT-P59, suggesting that CT-P59 has therapeutic potential for COVID-19 patients infected with SA variant.

A therapeutic neutralizing antibody targeting receptor binding domain of SARS-CoV-2 spike protein.

Vaccines and therapeutics are urgently needed for the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we screen human monoclonal antibodies (mAb) targeting the receptor binding domain (RBD) of the viral spike protein via antibody library constructed from peripheral blood mononuclear cells of a convalescent patient. The CT-P59 mAb potently neutralizes SARS-CoV-2 isolates including the D614G variant without antibody-dependent enhancement effect. Complex crystal structure of CT-P59 Fab/RBD shows that CT-P59 blocks interaction regions of RBD for angiotensin converting enzyme 2 (ACE2) receptor with an orientation that is notably different from previously reported RBD-targeting mAbs. Furthermore, therapeutic effects of CT-P59 are evaluated in three animal models (ferret, hamster, and rhesus monkey), demonstrating a substantial reduction in viral titer along with alleviation of clinical symptoms. Therefore, CT-P59 may be a promising therapeutic candidate for COVID-19.

A Simple and Fast Algorithm for L1-Norm Kernel PCA.

We present an algorithm for L1-norm kernel PCA and provide a convergence analysis for it. While an optimal solution of L2-norm kernel PCA can be obtained through matrix decomposition, finding that of L1-norm kernel PCA is not trivial due to its non-convexity and non-smoothness. We provide a novel reformulation through which an equivalent, geometrically interpretable problem is obtained. Based on the geometric interpretation of the reformulated problem, we present a "fixed-point" type algorithm that iteratively computes a binary weight for each observation. As the algorithm requires only inner products of data vectors, it is computationally efficient and the kernel trick is applicable. In the convergence analysis, we show that the algorithm converges to a local optimal solution in a finite number of steps. Moreover, we provide a rate of convergence analysis, which has been never done for any L1-norm PCA algorithm, proving that the sequence of objective values converges at a linear rate. In numerical experiments, we show that the algorithm is robust in the presence of entry-wise perturbations and computationally scalable, especially in a large-scale setting. Lastly, we introduce an application to outlier detection where the model based on the proposed algorithm outperforms the benchmark algorithms.

Comparison of thyroid hormone disruption potentials by bisphenols A, S, F, and Z in embryo-larval zebrafish.

Several structural analogues of bisphenol A (BPA), e.g., bisphenol F (BPF), bisphenol S (BPS), and bisphenol Z (BPZ), have been used as its substitutes in many applications and consequently detected in the environment, and human specimen such as urine and serum. While BPA has been frequently reported for thyroid hormone disruption in both experimental and epidemiological studies, less is known for the BPA analogues. In the present study, thyroid hormone disrupting effects of BPF, BPS and BPZ, were investigated, and compared with those of BPA, using embryo-larval zebrafish (Danio rerio). At 120 hpf, significant increases in T3 and/or T4 were observed in the larval fish following exposure to BPA, BPF, or BPS. Moreover, transcriptional changes of the genes related to thyroid development (hhex and tg), thyroid hormone transport (ttr) and metabolism (ugt1ab) were observed as well. Thyroid hormone (T4) disruption by BPF was observed even at the concentration (2.0 mg/L) lower than the effective concentration determined for BPA (>2.0 mg/L). Delayed hatching was observed by all tested bisphenols. Our results clearly show that these BPA analogues can disrupt thyroid function of the larval fish, and their thyroid hormone disruption potencies could be even greater than that of BPA. The concentrations which disrupt thyroid function of the larval fish were orders of magnitude higher than those occurring in the ambient environment. However, thyroid hormone disruption by longer term exposure and its consequences in the fish population, deserve further investigation.

Landscape of Actionable Genetic Alterations Profiled from 1,071 Tumor Samples in Korean Cancer Patients.

PURPOSE: With the emergence of next-generation sequencing (NGS) technology, profiling a wide range of genomic alterations has become a possibility resulting in improved implementation of targeted cancer therapy. In Asian populations, the prevalence and spectrum of clinically actionable genetic alterations has not yet been determined because of a lack of studies examining high-throughput cancer genomic data. MATERIALS AND METHODS: To address this issue, 1,071 tumor samples were collected from five major cancer institutes in Korea and analyzed using targeted NGS at a centralized laboratory. Samples were either fresh frozen or formalin-fixed, paraffin embedded (FFPE) and the quality and yield of extracted genomic DNA was assessed. In order to estimate the effect of sample condition on the quality of sequencing results, tissue preparation method, specimen type (resected or biopsied) and tissue storage time were compared. RESULTS: We detected 7,360 non-synonymous point mutations, 1,164 small insertions and deletions, 3,173 copy number alterations, and 462 structural variants. Fifty-four percent of tumors had one or more clinically relevant genetic mutation. The distribution of actionable variants was variable among different genes. Fresh frozen tissues, surgically resected specimens, and recently obtained specimens generated superior sequencing results over FFPE tissues, biopsied specimens, and tissues with long storage duration. CONCLUSION: In order to overcome, challenges involved in bringing NGS testing into routine clinical use, a centralized laboratory model was designed that could improve the NGS workflows, provide appropriate turnaround times and control costs with goal of enabling precision medicine.

Pharmaceutical residues in streams near concentrated animal feeding operations of Korea - Occurrences and associated ecological risks.

Concentrated animal feeding operations (CAFOs) have been suggested to be the most significant source of pharmaceutical release into the environment. However, limited information is available on the occurrence of veterinary pharmaceutical residues and the associated ecological risks to the aquatic environment near CAFO areas. In this study, ten commonly used veterinary antibiotics, including sulfonamides, tetracyclines, and cephalosporins, along with three analgesics, were measured in water samples collected from the streams that run near two CAFOs in Korea in 2013 (n = 16) and 2014 (n = 10). In addition, the associated ecological risks were estimated by calculating risk quotient. The pharmaceuticals were detected in a higher amount in the samples collected downstream from the CAFO than in those collected upstream. Acetaminophen, sulfamethazine, sulfathiazole, and oxytetracycline were detected at maximum concentrations of 38.8 µg/L, 21.3 µg/L, 17.4 µg/L, and 16.9 µg/L, respectively. Relatively higher concentrations of pharmaceuticals were observed in locations adjacent to the CAFO and the downstream area, suggesting the influence of the CAFO. Except for acetaminophen, lower concentrations of the target pharmaceuticals were detected in the samples collected during the high-flow season. The concentrations of most of the target pharmaceuticals exceeded the risk quotient of one, suggesting potential ecological effects in the areas affected by CAFOs. Our observations show that the water environment near a CAFO could be heavily affected by veterinary pharmaceuticals and analgesic drugs that are also frequently used among humans. Hence, the ecological consequences of pharmaceutical residues in the water bodies near CAFOs warrant further investigation.

Device Management and Data Transport in IoT Networks Based on Visible Light Communication.

LED-based Visible Light Communication (VLC) has been proposed as the IEEE 802.15.7 standard and is regarded as a new wireless access medium in the Internet-of-Things (IoT) environment. With this trend, many works have already been made to improve the performance of VLC. However, the effectively integration of VLC services into IoT networks has not yet been sufficiently studied. In this paper, we propose a scheme for device management and data transport in IoT networks using VLC. Specifically, we discuss how to manage VLC transmitters and receivers, and to support VLC data transmission in IoT networks. The proposed scheme considers uni-directional VLC transmissions from transmitter to receivers for delivery of location-based VLC data. The backward transmission from VLC receivers will be made by using platform server and aggregation agents in the network. For validation and performance analysis, we implemented the proposed scheme with VLC-capable LED lights and open sources of oneM2M. From the experimental results for virtual museum services, we see that the VLC data packets can be exchanged within 590 ms, and the handover between VLC transmitters can be completed within 210 ms in the testbed network.

Endocrine disrupting potential of PAHs and their alkylated analogues associated with oil spills.

Polycyclic aromatic hydrocarbons (PAHs) and alkylated PAHs are known to be major toxic contaminants in spills of petroleum hydrocarbons (oil). Spilled oil undergoes weathering and over time, PAHs go through a series of compositional changes. PAHs can disrupt endocrine functions, and the type of functions affected and associated potencies vary with the type and alkylation status of PAH. In this study, the potential of five major PAHs of crude oil, i.e., naphthalene, fluorene, dibenzothiophene, phenanthrene, and chrysene, and their alkylated analogues (n = 25), to disrupt endocrine functions was evaluated by use of MVLN-luc and H295R cell lines. In the MVLN-luc bioassay, seven estrogen receptor (ER) agonists were detected among 30 tested PAHs. The greatest ER-mediated potency was observed for 1-methylchrysene (101.4%), followed by phenanthrene and its alkylated analogues (range of %-E2max from 1.6% to 47.3%). In the H295R bioassay, significantly greater syntheses of steroid hormones were observed for 20 PAHs. For major PAHs and their alkylated analogues, disruption of steroidogenesis appeared to be more significant than ER-mediated effects. The number and locations of alkyl-moieties alone could not explain differences in the types or the potencies of toxicities. This observation shows that disruption of endocrine functions by some constituents of oil spills could be underestimated if only parent compounds are considered in assessments of hazard and risk.

Mitral Loop Cerclage Annuloplasty for Secondary Mitral Regurgitation: First Human Results.

OBJECTIVES: This is an early feasibility clinical test of mitral loop cerclage annuloplasty to treat secondary mitral valve regurgitation. BACKGROUND: Secondary mitral regurgitation is characterized by cardiomyopathy, mitral annular enlargement, and leaflet traction contributing to malcoaptation. Transcatheter mitral loop cerclage applies circumferential compression to the mitral annulus by creating a loop through the coronary sinus across the interventricular septum, protecting entrapped coronary arteries from compression, and interactive annular reduction under echocardiographic guidance. This is the first human test of mitral loop annuloplasty. METHODS: Five subjects with severe symptomatic secondary mitral regurgitation underwent mitral loop cerclage, with echocardiographic and computed tomography follow-up over 6 months. RESULTS: Mitral loop cerclage was successful in 4 of 5 subjects and aborted in 1 of the 5 because of unsuitable septal coronary vein anatomy. Immediately and over 6 months, measures of both mitral valve regurgitation (effective orifice area and regurgitation fraction) and chamber dimensions (left atrial and left ventricular volumes) were reduced progressively and ejection fractions increased. Two with persistent and permanent atrial fibrillation spontaneously reverted to sinus rhythm during follow-up. One subject experienced a small myocardial infarction from an unrecognized small branch coronary occlusion. Another, experiencing cardiogenic shock at baseline, died of intractable heart failure after 6 weeks. CONCLUSIONS: In this first human test, mitral loop cerclage annuloplasty was successful in 4 of 5 attempts, caused reverse remodeling (reduction in secondary mitral regurgitation and heart chamber volumes), and suggested electrical remodeling (reversion of atrial fibrillation). Further evaluation is warranted.

Thyroid hormone disrupting potentials of bisphenol A and its analogues - in vitro comparison study employing rat pituitary (GH3) and thyroid follicular (FRTL-5) cells.

As adverse health effects of bisphenol A (BPA) become a growing public health concern, the chemicals substituting BPA have been increasingly used in everyday lives. BPA substitutes have been frequently detected in both environment and biota in increasing levels. However, very limited toxicological information is available for these chemicals. In the present study, thyroid disrupting effects of nine structural analogues of BPA were evaluated along with BPA, using rat pituitary (GH3) and thyroid follicular (FRTL-5) cells. Similar to BPA, its analogues caused significant down-regulation of tshß, trα, trß, dio1 or dio2 genes in GH3 cells, and some analogues, such as BPF, BPM or BPZ, showed even greater potency compared to BPA. In FRTL-5 cells, the genes responsible for hormone synthesis, e.g., pax8, nis, tg or tpo genes, exhibited over 1.5-fold up-regulation following exposure to BPA analogues, such as BPS. The effects on gene regulation was different by the cell line. Our results clearly show that the BPA substituting chemicals may influence thyroid hormone homeostasis by affecting thyroid regulation and hormone synthesis, often at lower doses compared to BPA. Thyroid effects of the BPA analogues deserve further investigations in experimental organisms and in human populations.

Protective effects of Fructus sophorae extract on collagen-induced arthritis in BALB/c mice.

Styphnolobium japonicum (L.) is utilized in Korean medicine for the treatment of various inflammatory diseases. The aim of the present study was to explore the effects of Fructus sophorae extract (FSE) isolated from the dried ripe fruit of S. japonicum (L.) on the development of type II collagen-induced arthritis (CIA) in BALB/c mice. The CIA mice were orally administered FSE or saline daily for 2 weeks. The incidence and severity of disease and the inflammatory response in the serum and the joint tissues were assessed. Macroscopic and histological investigation indicated that FSE protected against CIA development. FSE was associated with a significant reduction in the levels of total immunoglobulin G2a and proinflammatory cytokines and mediators in the serum. In addition, FSE suppressed the gene expression levels of proinflammatory cytokines and mediators, the mediator of osteoclastic bone remodeling, the receptor activator of nuclear factor κ-B ligand and matrix metalloproteinases in the joint tissues. The present results suggest that FSE may protect against inflammation and bone damage, and would be a valuable candidate for further investigation as a novel anti-arthritic agent.

Searching for novel modes of toxic actions of oil spill using E. coli live cell array reporter system - A Hebei Spirit oil spill study.

Oil is a complex mixture of numerous compounds. Therefore, oil spills near shore can cause various adverse effects on coastal ecosystems. However, most toxicological assessments conducted on oil spill sites have focused on limited modes of toxic actions. In the present study, we utilized the Escherichia coli (E. coli) live cell array system (LCA) to identify novel modes of toxicities of the oil spill-affected sediments. For this purpose, sediment samples were collected from an area heavily polluted by Hebei Spirit oil spill (HSOS) incident of 2007. A total of 93 E. coli reporter genes were used to study responses to the chemicals in the mixture. E. coli K12 strains were exposed to extracts of oil or the sediment, and changes in gene expression were measured. Exposure to extracts of crude and weathered oil resulted in decreased expression in ∼30% of tested genes. However, changes in expression observed after exposure to sediment extracts varied. Sediment extracts containing large concentrations of polycyclic aromatic hydrocarbons (PAH) caused down-regulation of >70% of the genes, while extracts containing lesser total concentrations of PAHs exhibited different trends: genes involved in drug resistance were generally up-regulated, while genes responsive to DNA damage were up-regulated in only two extracts. Results suggest that oil pollution can modulate several toxic response pathways related to DNA repair and antibiotic responses. Results from LCA obtained from the sediment and oil samples were different from those observed in the H4IIE-luc assay. Toxicological implications of such observations deserve further examination. Overall, LCA is a promising tool for screening samples and identifying potential modes of toxicities of environmental samples associated with oil spills.

A predictive model for estimating regional skeletal muscle size by two-point dixon magnetic resonance imaging in healthy Koreans.

This study was undertaken to develop and cross-validate reference and individual predictive models for estimating functional thigh muscle cross-sectional area (TCSA) by 2-point Dixon magnetic resonance imaging (MRI). TCSAs of dominant sides at the mid-thigh level were measured by 2-point Dixon MRI (MRITCSA). Functional MRITCSA were compared with the predictive models in a sample of 92 younger (20-40 years; 28.55±4.87; n=50) and older (>65years; 71.22±4.82; n=42) Koreans. Lean body masses were measured by dual energy X-ray absorptiometry (DXALBM), and thigh isokinetic muscle strengths, extension peak torque at 60°/sec, were measured using a Biodex® dynamometer (BiodexEPT). Multiple regression analysis generated the reference model (R2=0.75 and SEE=1472.63mm2 (8%)) as follows: The reference model: functional TCSA(mm2)=-1230.49+62.81*height+3061.78*gender -2692.57*age+58.91*weight. The individual model (R2=0.80, SEE=1158.34mm2 (7%)) was as follows: The individual model: functional TCSA(mm2)=1631.62+1.76* DXALBM+9.51*BiodexEPT where height is in centimeters; weight is in kilograms; for gender, female=0 and male=1; and for age, age under 40=1 and age over 65=2. PRESS statistics of R2 and SEE were 0.78 and 1382.98mm2 for the reference model, and 0.88 and 979.02mm2 for the individual model. The 2-point Dixon MRI appears to be valid for measuring functional muscle size. Our results suggest that the reference and individual models provide acceptable estimates of functional thigh muscle CSA in healthy Korean adults. Therefore, the models developed in the study could be useful as a research tool to establish indexes for functional muscle composition in healthy Koreans.

Reconnaissance of dioxin-like and estrogen-like toxicities in sediments of Taean, Korea-seven years after the Hebei Spirit oil spill.

Oil spills near the coastlines may damage marine and intertidal ecosystem. Constituents of the oil have been reported to cause toxic consequences mediated by aryl hydrocarbon receptor (AhR), and estrogen receptor (ER). In the present study, AhR- and ER-mediated toxicities of coastal sediments of Taean were investigated seven years after Hebei Spirit oil spill (HSOS). Sediment samples were collected on June and October 2014 from seven locations along the Taean coastline, where signs of oil spill were detected. Sediment samples were extracted in Soxhlet extractors and further processed through activated silica gels to separate into four fractions; F1 (saturate hydrocarbons), F2 (aromatic hydrocarbons), F3 (resins and polar compounds), and F4 (residues). ER-mediated and AhR-mediated potencies (% E2max and % TCDDmax) of each fraction were determined using MVLN cells and H4IIE-luc cells, respectively. F2 and F3 fractions of Sinduri 1, Sinduri 2, and Sogeunri 1 samples showed greater AhR-mediated potencies (up to 107% TCDDmax). Chemical analysis revealed that PAH components are correlated with AhR-binding activities. The % E2max results varied by sample: While there was no noticeable induction of ER-dependent responses (<45%), some aromatics fractions (F2) exhibited the highest ER-mediated responses. Compared with previous reports from the same sites, both AhR-mediated and ER-mediated potencies have decreased over time. Nevertheless, AhR-mediated potencies could be identified in the environmental samples even after 7 years of the incident. Therefore, possible ecosystem implications of these findings should be further investigated.