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INTRODUCTION We aimed to identify imaging-based findings that can differentiate between spinal subchondral bone metastasis with focal pathologic endplate fracture and oedematous Schmorl's nodes that have been histopathologically confirmed. METHODS Between March 2010 and April 2016, 11 patients who had undergone spinal magnetic resonance (MR) imaging or computed tomography (CT) with final radiologic reports that included 'subchondral bone metastasis with focal pathologic endplate fracture' or 'edematous Schmorl's node' and had also undergone percutaneous imaging-guided spinal biopsies were included. Two radiologists retrospectively evaluated the following imaging features in consensus: size, location, presence of sclerotic margin, presence of intralesional or perilesional enhancement and opposite endplate enhancement of the involved disc, presence of disc height loss and presence of metabolic uptake at a corresponding lesion on nuclear medicine imaging. RESULTS A total of 11 patients, including six patients with spinal subchondral bone metastasis with focal pathologic endplate fracture and five patients with oedematous Schmorl's nodes, were included in this study (median age, 58 years; range, 50-63 years; six men). Sclerotic margin (P = 0.002) and enhancement on the opposite endplate of the involved disc (P = 0.047) were significantly different between oedematous Schmorl's node and subchondral bone metastasis with focal pathologic endplate fracture. CONCLUSION Sclerotic margin and enhancement on the opposite endplate of the involved disc suggest oedematous Schmorl's node rather than subchondral bone metastasis with focal pathologic endplate fracture. Decreased disc height is likely to be an oedematous Schmorl's node rather than subchondral bone metastasis with focal pathologic endplate fracture.

To assess the diagnostic accuracy of conventional MRI for detecting and grading subscapularis (SSC) tears by applying the Yoo and Rhee classification. A total of 179 patients who underwent MRI followed by arthroscopic rotator cuff surgery were enrolled. Two musculoskeletal radiologists evaluated the SSC using axial, oblique sagittal, and oblique coronal MRI according to the Yoo and Rhee classification. Using arthroscopic findings as the reference standard, the sensitivity, specificity, accuracy, and interobserver agreement of SSC tears were analyzed. Arthroscopy confirmed that the numbers of type I, IIA, IIB, III, IV, and V tears were 35, 70, 35, 9, 9, and 0, respectively. The sensitivity, specificity, and accuracy of readers 1 and 2 for the detection of tears (type IIA or higher) were 85%, 75%, and 82%, and 89%, 70%, and 83%, respectively, while those for the detection of surgical candidates (type IIB or higher) were 77%, 75%, and 75%, and 77%, 83%, and 82%, respectively. The interobserver agreement for detecting SSC tear presence was substantial (κ = 0.70) for reader 1 vs. reader 2, and those for detecting the surgical candidate group was substantial (κ = 0.68) for reader 1 vs. reader 2. The interobserver agreement for grading SSC tears was excellent (κ = 0.86) for reader 1 vs. reader 2. Conventional MRI showed 82.5% and 78.5% average accuracy in detecting IIA and IIB or higher tears by applying the Yoo and Rhee classification for the diagnosis of SSC tears with an excellent interobserver agreement in tear grading.

The objectives of this study were to assess changes in apparent diffusion coefficient (ADC) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) parameters after radiation therapy (RT) for bone metastases from hepatocellular carcinoma (HCC) and to evaluate their prognostic value. This prospective study was approved by the Institutional Review Board. Fourteen patients with HCC underwent RT (30 Gy in 10 fractions once daily) for bone metastases. The ADC and DCE-MRI parameters and the volume of the target lesions were measured before (baseline) and one month after RT (post-RT). The Wilcoxon signed-rank test was used to compare the parameters between the baseline and post-RT MRI. The parameters were compared between patients with or without disease progression in RT fields using the Mann–Whitney test. Intraclass correlation coefficients were used to evaluate the interobserver agreement. The medians of the ADC, rate constant [kep], and volume fraction of the extravascular extracellular matrix [ve] in the baseline and post-RT MRI were 0.67 (range 0.61–0.72) and 0.75 (range 0.63–1.43) (× 10–3 mm2/s) (P = 0.027), 836.33 (range 301.41–1082.32) and 335.80 (range 21.86–741.87) (× 10–3/min) (P = 0.002), and 161.54 (range 128.38–410.13) and 273.99 (range 181.39–1216.95) (× 10–3) (P = 0.027), respectively. The medians of the percent change in the ADC of post-RT MRI in patients with progressive disease and patients without progressive disease were − 1.35 (range − 6.16 to 6.79) and + 46.71 (range 7.71–112.81) (%) (P = 0.011), respectively. The interobserver agreements for all MRI parameters were excellent (intraclass correlation coefficients > 0.8). In conclusion, the ADC, kep, and ve of bone metastases changed significantly after RT. The percentage change in the ADC was closely related to local tumor progression.

Olive flounder (Paralichthys olivaceus) is one of the major cultured fish species in Asia including Korea. However, the mass mortality of olive flounder caused by various pathogens leads to huge economic loss. The pathogens that lead to fish mortality include parasites, bacteria, and viruses that can cause various kinds of diseases. The purpose of this study was to investigate the protein expression patterns in the gills and spleens of olive flounder after artificial infection. We hypothesized that proteomics levels in gills and spleen may be differentially expressed depending on infectious agents. To investigate the expression pattern of proteins in gills and spleens, olive flounders were experimentally infected with VHSV (virus), S. parauberis (bacteria), or M. avidus (pathogenic ciliate). Proteins were extracted from the gills and spleens of infected olive flounder. We used 2-DE analysis with LC–MS/MS to investigate proteome changes in infected olive flounders. The results of the LC–MS/MS analyses showed different protein expression profiles depending on pathogenic sources and target organs. Proteins related to cytoskeletal structure like keratin, calmodulin and actin were mostly expressed in the infected gills. Proteins involved in the metabolism pathway like glycolysis were expressed mainly in the spleens. The protein profiles of S. parauberis and VHSV infection groups had many similarities, but the profile of the M. avidus infection group was greatly different in the gill and spleen. Our results indicate that measures according to the characteristics of each pathogen are necessary for disease prevention and treatment of farmed fish.

In this study, we explored whether the use of Streptococcus thermophilus LM1012 (TL-LM1012) as a safe probiotic exerts hepatoprotective effects by suppressing oxidative stress and inflammation in vitro and alleviating aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) production in vivo. In a series of safety tests, TL-LM1012 was found to have a negative response to hemolysis and biogenic amines, as well as susceptibility to antibiotics. TL-LM1012 protected cell viability and suppressed cytotoxicity by inhibiting oxidative stress and induced heme oxygenase-1 and superoxide dismutase activity in a dose-dependent manner in diesel exhaust particulate matter (DEPM)-treated HepG2 cells. Moreover, proinflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-6, and IL-1β, were suppressed in DEPM-treated splenocytes. In DEPM-treated mice, oral administration of TL-LM1012 regulated AST, ALT, and LDH production in the serum after 14 days of treatment. These findings indicate that TL-LM1012, a safe probiotic, provides a potent preventive or therapeutic effect against liver disease caused by air pollution.

Viral hemorrhagic septicemia (VHS) is a serious viral disease that infects the olive flounder in South Korea. The Korean aquaculture industry experienced an economic loss caused by the high infectivity and mortality. This study aimed to evaluate the infection density of VHSV in various organs of the olive flounder including spleen, liver, kidney, stomach, esophagus, intestine, gill, muscle, heart, and brain. Olive flounders were collected from a local fish farm and injected subcutaneously with 106 PFU/fish. Each 15 fish were sampled at 0, 3, and 7 days post challenge (dpc), respectively, to perform quantitative analysis of VHSV using SYBR-green based real-time PCR in various tissues including spleen, liver, head-kidney, body-kidney, muscle, esophagus, stomach, intestine, gill, and brain. Organs infected with VHSV were obtained after 3 and 7 days. Each organs were examined for viral infection using real-time PCR. The data obtained from this experiment revealed copy numbers higher than 10 copies per 100 ng cDNA in the spleen (15.26 ± 3.11 copies/100 ng of cDNA), muscle (11.24 ± 2.25 copies), and gill (14.23 ± 6.26 copies), but lower in liver, head-kidney, body-kidney, esophagus, brain and stomach. The present study, together with previous data, demonstrated that the gill, spleen, and muscle are the major target organs of VHSV in olive flounder. Therefore, central monitoring of spleen, gill and muscle should be considered and might be necessary if anti-VHSV treatment is to be successful in infected olive flounder.

Purpose Spinal muscular atrophy (SMA) is a genetic progressive neuromuscular disorder, and nusinersen has shown to improve its symptoms. Scoliosis is a frequent symptom in patients with SMA and complicates the intrathecal injection of nusinersen. The aim of this study was to investigate the safety and effectiveness of fluoroscopy-guided intrathecal injections in patients with SMA with severe scoliosis. Methods We retrospectively reviewed the medical records of 11 patients with SMA treated with nusinersen intrathecal injections at the Samsung Medical Center from 2018 to 2020. We assessed the type of SMA, genetic results, spine computed tomography or fluoroscopy findings, and adverse effects associated with the injection. Results Of 11 patients with SMA, six were diagnosed with severe scoliosis, four of whom underwent an operation for scoliosis. The six patients with severe scoliosis started receiving the nusinersen injection at a median age of 15.7 years. A total of 25 injections were completely performed with the interlaminar approach (ILA) at the lumbar level under C-arm fluoroscopy guidance. No adverse effects other than mild headache occurred. In one patient who underwent the complete fusion operation for scoliosis, laminectomy was performed for the nusinersen injection, and 3 doses were administered intrathecally via the interlaminar route at the lumbar level. Conclusion Fluoroscopy-guided ILA is a safe method for the intrathecal injection of nusinersen in patients with SMA with severe scoliosis. When defining the route, laminectomy might be necessary to open the window for the ILA route at the lumbar level.

The objectives of this study were to assess the fat fraction (FF) and cross-sectional area (CSA) of the sciatic nerve in Charcot-Marie-Tooth disease type 1A (CMT1A) patients using Dixon-based proton density fat quantification MRI and to elucidate its potential association with clinical parameters. Thigh MRIs of 18 CMT1A patients and 18 age- and sex-matched volunteers enrolled for a previous study were reviewed. Analyses for FF and CSA of the sciatic nerve were performed at three levels (proximal to distal). CSA and FF were compared between the two groups and among the different levels within each group. The relationship between the MRI parameters and clinical data were assessed in the CMT1A patients. The CMT1A patients showed significantly higher FF at level 3 (p = 0.0217) and significantly larger CSA at all three levels compared with the control participants (p < 0.0001). Comparisons among levels showed significantly higher FF for levels 2 and 3 than for level 1 and significantly larger CSA for level 2 compared with level 1 in CMT1A patients. CSA at level 3 correlated positively with the CMT Neuropathy Score version 2 (CMTNSv2). In conclusion, the sciatic nerve FF of CMT1A patients was significantly higher on level 3 compared with both the controls and the measurements taken on more proximal levels, suggesting the possibility of increased intraepineurial fat within the sciatic nerves of CMT1A patients, with a possible distal tendency. Sciatic nerve CSA at level 3 correlated significantly and positively with CMTNSv2, suggesting its potential value as an imaging marker for clinical severity.

Although radiation therapy (RT) plays an important role in the palliation of localized bone metastases, there is no consensus on a reliable method for evaluating treatment response. Therefore, we retrospectively evaluated the potential of magnetic resonance imaging (MRI) using apparent diffusion coefficient (ADC) maps and conventional images in whole-tumor volumetric analysis of texture features for assessing treatment response after RT. For this purpose, 28 patients who received RT for osteolytic bone metastasis and underwent both pre- and post-RT MRI were enrolled. Volumetric ADC histograms and conventional parameters were compared. Cox regression analyses were used to determine whether the change ratio in these parameters was associated with local disease progression-free survival (LDPFS). The ADCmaximum, ADCmean, ADCmedian, ADCSD, maximum diameter, and volume of the target lesions after RT significantly increased. Change ratios of ADCmean < 1.41, tumor diameter ≥ 1.17, and tumor volume ≥ 1.55 were significant predictors of poor LDPFS. Whole-tumor volumetric ADC analysis might be utilized for monitoring patient response to RT and potentially useful in predicting clinical outcomes.

We report a one-pot synthesis method based on two-step sequential thiol–ene reactions for the facile preparation of azobenzene-interconnected photoresponsive polymers (azo-ICPRPs). In the first step, block-length-controlled azobenzene prepolymers (azo-prepolymers) are prepared in situ in a molten reaction mixture by using the nucleophile-catalyzed chemoselective thiol-Michael reaction. In the second step, the formed azo-prepolymers are further crosslinked with ultraviolet (UV)-transparent monomers by a free radical-initiated thiol–ene “click” reaction, yielding a crosslinked polymer system with rubbery storage moduli (Er) ranging from 3.6 to 6.7 MPa and glass transition temperatures (Tg) ranging from 21 to 28 °C. The interconnection of azobenzene moieties in azo-ICPRPs is found to greatly amplify the photo-actuation performance. Compared to single-step polymerized polymers with the same monomer composition, azo-ICPRPs with long-block-length showed up to 7 times higher photostrains, with 50 times faster kinetics. Consequently, the specific actuation work and power output during each stroke were also greatly amplified by the interconnection of azobenzene. The maximum measured specific stroke work and power output under 15 mW cm−2 UV activation were 121.3 kJ m−3 and 34 W kg−1, respectively, which are comparable to those for skeletal muscles.

To examine the correlation of diffusion-weighted and dynamic contrast-enhanced magnetic resonance imaging (MRI) parameters with Ki-67 labeling index (LI) in soft tissue sarcoma (STS). The institutional review board approved this retrospective study, and the requirement for informed consent was waived. Thirty-six patients with STS who underwent 3.0-T MRI, including diffusion-weighted and dynamic contrast-enhanced MRI, between July 2011 and February 2018, were included in this study. The mean and minimum apparent diffusion coefficients (ADCs) (ADCmean and ADCmin, respectively), volume transfer constant, reflux rate, and volume fraction of the extravascular extracellular matrix of each lesion were independently analyzed by two readers. Their relationship with the Ki-67 LI was examined using Spearman’s correlation analyses. Differences between low- and high-proliferation groups based on Ki-67 LI were evaluated statistically. Optimal cut-off points were determined using the area under the curve analysis for significant parameters. Interobserver agreement was assessed with the intraclass correlation coefficient. ADCmean (ρ = − 0.333, p = 0.047) was significantly and inversely correlated with Ki-67 LI. The high-proliferation group showed a significantly lower ADCmean than did the low-proliferation group (median, 1.08 vs. 1.20; p = 0.048). When a cut-off ADCmean value of 1.16 × 10−3 mm2/s was used, the sensitivity, specificity, and area under the curve for differentiating low- and high-proliferation groups were 75.0%, 60.0%, and 0.712, respectively. Interobserver agreements between the two readers were almost perfect for all parameters. ADCmean was correlated with Ki-67 LI and could help differentiate between STS with low and high proliferation potential. • ADC mean was significantly and inversely correlated with Ki-67 labeling index in soft tissue sarcoma. • In the high-proliferation group, ADC mean values were significantly lower than those of the low-proliferation group.

The present study investigated the immunomodulatory activity and associated mechanisms of heat-treated Lactobacillus plantarum LM1004 (HT-LM1004) in a cyclophosphamide (CTX)-induced mouse model of immunosuppression. HT-LM1004 induced phagocytic activity and nitric oxide production in RAW264.7 macrophages and stimulated the release of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-2, and IL-12p70. In mice with CTX-induced immunosuppression, oral HT-LM1004 administration restored thymus and spleen indices, including spleen weight. Consistent with the in vitro results, HT-LM1004 increased TNF-α, IFN-γ, IL-2, and IL-12p70 levels in mice after 14 days of treatment and enhanced the natural killer (NK) cell activity of splenocytes from mice with CTX-induced immunosuppression against YAC-1 lymphoma cells. The method of HT-LM1004 generation influenced this activity: L. plantarum LM1004 grown in a membrane bioreactor, which reduced the size of the cells to

Background This study aimed to evaluate the potential value of 3D multiple gradient echo Dixon‐based magnetic resonance imaging (MRI) sequence as a tool for thigh intramuscular fat quantification in Charcot–Marie–Tooth disease (CMT) patients. Methods A prospective comparison study comprising 18 CMT patients and 18 age/sex‐matched volunteers was performed. MRI including 3D multiple gradient echo Dixon‐based imaging was performed for each subject. Region of interest analyses were performed at the upper and lower third of both thighs. The two‐sample t‐test or Wilcoxon rank sum test was used for intergroup comparison of the mean muscle fat fraction. Intraclass correlation coefficients were used to evaluate the interobserver agreement and test–retest reproducibility. Semiquantitive analysis using the Goutallier classification (Grades 0–4) was performed on T1‐weighted images in upper thigh muscles. For Goutallier Grade 0 muscles, comparison of the mean intramuscular fat fraction between volunteers and CMT patients was performed. Results The interobserver agreements were excellent for all measurements (intraclass correlation coefficients > 0.8). Mean muscle fat fractions were significantly higher in all the measured muscles of CMT patients (P

Miamiensis avidus is the major parasitic pathogen affecting the olive flounder, Paralichthys olivaceus. Recent epidemiological studies have shown that M. avidus infections are becoming increasingly severe and frequent in the olive flounder farming industry. This study aimed to evaluate the infection density of M. avidus in various organs of the olive flounder including spleen, liver, kidney, stomach, esophagus, intestine, gill, muscle, heart, and brain. Olive flounders were collected from a local fish farm. Each fish was injected subcutaneously with 2.75 × 103 CFU M. avidus/ fish. Organs infected with M. avidus were obtained after 7 and 25 days. Each organ was examined for parasitic infection using real-time PCR. The primers were designed according to the sequences of 28 s in M. avidus, which was used as a target gene. Each organ was examined for parasitic infection using real-time PCR. The primers were designed according to the sequences of 28 s in M. avidus, which was used as a target gene. The levels of 28 s rRNA were used to calculate quantitative gene copy number. Real-time PCR of brain (60.58 ± 38.41), heart (64.03 ± 62.40), muscle (6.10 ± 3.12), gill (5.06 ± 4.56), intestine (2.38 ± 1.69), esophagus (4.22 ± 3.72), stomach (3.25 ± 2.68), kidney (0.81 ± 0.15), liver (0.63 ± 0.15), and spleen (11.18 ± 4.08) was performed at 3 days post-infection. At 7 days post-infection, heart (754.15 ± 160.85), brain (247.90 ± 62.91), spleen (38.81 ± 17.52), liver (7.47 ± 4.54), kidney (10.90 ± 3.41), stomach (19.50 ± 8.86), esophagus (39.37 ± 14.10), intestine (17.54 ± 12.63), gill (38.27 ± 20.20), and muscle (33.62 ± 15.07) were measured. The present study, together with previous data, demonstrated that the gill, intestine, and brain are the major target organs of M. avidus in olive flounder. However, this does not mean that tiny amounts of DNA extracted from those tissues of fish during the early stages of infection can guarantee successful detection and/or quantification of M. avidus. Our data suggest that the brain might be the best organ for detection in the early stage.

Long-term evaluation from 2000 to 2020 of a temperate reservoir indicated that water quality and trophic status were not critically controlled by the inter-annual dynamics of monsoon precipitation. The fluctuation of annual concentrations of TP, TSS, and EC did not always correlate with the variation of precipitation. BOD and COD demonstrated monotonically increasing trends with Sen’s slope of 0.02 and 0.01, respectively, while Chl-a manifested a decreasing trend (slope = −0.23). The increases of different magnitudes in the levels of TP, TSS, and Chl-a in the monsoon and the early post-monsoon periods were observed in the drought, flood, and normal years. The drought years showed distinct seasonal variations in many parameters, while those in the flood and the normal years were very similar. Pearson correlation and empirical regression analyses resulted in weaker correlation between water quality and hydrological parameters than other reservoirs, which, along with low impact of precipitation, was attributed to the low drainage ratio (28.8) of the study area. BOD/COD ratios were higher than 0.5 in the reservoir, indicating the presence of a significant fraction of biodegradable organic matter. The ratio increased in the longitudinal flow direction (&gt, 50% in the drought years), implying the possibility of autochthonous sources of organic matter. TSID evaluation resulted in variation of limiting factors not related to the fluctuation of annual precipitation. The loadings of the significant principal components were very similar among the different precipitation groups, supporting the other findings that annual precipitation governed by monsoon intensity would not solely control the water quality dynamics of the study area.

BACKGROUND Rock bream iridovirus (RBIV) is one of the most dangerous pathogens that causes the highest mortality in the aquaculture of rock bream (Oplegnathus fasciatus). Even though RBIV infection leads to huge economic loss, proteome studies on RBIV-infected rock bream have not been conducted to provide information about the differential protein expression pattern by the host protection system. OBJECTIVE The purpose of this study was to investigate the protein expression patterns in spleens of rock bream olive after infection by RBIV or mixed infection by RBIV and bacteria. METHODS Depending on the infection intensity and sampling time point, fish were divided into five groups: uninfected healthy fish at week 0 as the control (0C), heavily infected fish at week 0 (0H), heavily mixed RBIV and bacterial infected fish at week 0 (0MH), uninfected healthy fish at week 3 (3C), and lightly infected fish at week 3 (3L). Proteins were extracted from the spleens of infected rock bream. We used 2-DE analysis with LC-MS/MS to investigate proteome changes in infected rock bream. RESULTS The results of the LC-MS/MS analyses showed different protein expression profiles after infection. Proteins related to oxygen transport and energy generation, such as hemoglobin, beta-globin, and ATP synthase, were mostly expressed in the infected spleen. Whereas proteins involved in structure and cell movement, such as tubulin, myosin, actin binding proteins, and intermediate filament proteins, were down-regulated in the infected spleens. The protein expression profiles between infection by RBIV and mixed infection by RBIV and bacteria showed similar patterns. CONCLUSIONS Our results indicated that infection by RBIV or mixed infection by RBIV and bacteria triggered energy generation and oxygen-transport, but cell migration and constructional changes in the spleen were extremely decreased.

Charcot–Marie–Tooth disease (CMT) is the most common inherited peripheral neuropathy. Mutations in the GNB4 gene cause dominant intermediate CMT type F (CMTDIF). The aim of this study is to investigate phenotypic heterogeneities and characteristics of CMT patients with GNB4 mutations. We enrolled 1143 Korean CMT families and excluded 344 families with a PMP22 duplication. We further analyzed the 799 remaining families to find their GNB4 mutations using whole-exome sequencing (WES). We identified two mutations (p.Gly77Arg and p.Lys89Glu) in three families, among which a heterozygous p.Gly77Arg mutation was novel. In addition, a significant uncertain variant (p.Thr177Asn) was observed in one family. The frequency of the GNB4 mutation in the Korean population is 0.38% in PMP22 duplication-negative families. All three families showed de novo mutation. Electrophysiological findings regarding the p.Lys89Glu mutation showed that the motor nerve conduction velocity (MNCV) of the median nerve was markedly reduced, indicating demyelinating neuropathy, and sural nerve biopsy revealed severe loss of myelinated axons with onion bulb formation. Lower extremity Magnetic Resonance Imaging (MRI) demonstrated relatively more severe intramuscular fat infiltrations in demyelinating type (p.Lys89Glu mutation) patients compared to intermediate type (p.Gly77Arg mutation) patients. The anterolateral and superficial posterior compartment muscles of the distal calf were preferentially affected in demyelinating type patients. Therefore, it seems that the investigated GNB4 mutations do cause not only the known intermediate type but also demyelinating-type neuropathy. We first presented three Korean families with GNB4 mutations and found phenotypic heterogeneities of both intermediate and demyelinating neuropathy. We suggest that those findings are useful for the differential diagnosis of CMT patients with unknown GNB4 variants.

Background Charcot‐Marie‐Tooth disease (CMT) is the most common disorder of inherited peripheral neuropathies characterized by distal muscle weakness and sensory loss. CMT is usually classified into three types, demyelinating, axonal, and intermediate neuropathies. Mutations in myelin protein zero (MPZ) gene which encodes a transmembrane protein of the Schwann cells as a major component of peripheral myelin have been reported to cause various type of CMT. Methods This study screened MPZ mutations in Korean CMT patients (1,121 families) by whole exome sequencing and targeted sequencing. Results We identified 22 pathogenic or likely pathogenic MPZ mutations in 36 families as the underlying cause of the CMT1B, CMTDID, or CMT2I subtypes. Among them, five mutations were novel. The frequency of CMT patients with the MPZ mutations was similar or slightly lower compared to other ethnic groups. Conclusions We showed that the median onset ages and clinical phenotypes varied by subtypes: the most severe in the CMT1B group, and the mildest in the CMT2I group. This study also observed a clear correlation that earlier onsets cause more severe symptoms. We believe that this study will provide useful reference data for genetic and clinical information on CMT patients with MPZ mutations in Korea., Mutations in myelin protein zero (MPZ) gene which encodes a transmembrane protein of the Schwann cells have been reported to cause various type of CMT.We identified 22 pathogenic or likely pathogenic MPZ mutations in 36 families as the underlying cause of the CMT1B, CMTDID, or CMT2I subtypes.The mean onset ages and clinical phenotypes varied by subtypes: the most severe in the CMT1B group, and the mildest in the CMT2I group.

This study aimed to investigate whether in vivo MR-electrical properties tomography (MR-EPT) is feasible in musculoskeletal tissues by evaluating the conductivity of muscle, cartilage, and peripheral nerve around the knee joint, and to explore whether these measurements change after exercise. This prospective study was approved by the institutional review board. On February 2020, ten healthy volunteers provided written informed consent and underwent MRI of the right knee using a three-dimensional balanced steady-state free precession (bSSFP) sequence. To test the effect of loading, the subjects performed 60 squatting exercises after baseline MRI, immediately followed by post-exercise MRI with the same sequences. After reconstruction of conductivity map based on the bSSFP sequence, conductivity of muscles, cartilages, and nerves were measured. Measurements between the baseline and post-exercise MRI were compared using the paired t-test. Test–retest reliability for baseline conductivity was evaluated using the intraclass correlation coefficient. The baseline and post-exercise conductivity values (mean ± standard deviation) [S/m] of muscles, cartilages, and nerves were 1.73 ± 0.40 and 1.82 ± 0.50 (p = 0.048), 2.29 ± 0.47 and 2.51 ± 0.37 (p = 0.006), and 2.35 ± 0.57 and 2.36 ± 0.57 (p = 0.927), respectively. Intraclass correlation coefficient for the baseline conductivity of muscles, cartilages, and nerves were 0.89, 0.67, and 0.89, respectively. In conclusion, in vivo conductivity measurement of musculoskeletal tissues is feasible using MR-EPT. Conductivity of muscles and cartilages significantly changed with an overall increase after exercise.

Recently, non-canonical roles of Lysyl-tRNA Synthetase (KRS), which is associated with cell migration and cancer metastasis, have been reported. Therefore, KRS has emerged as a promising target for the treatment of cell migration-related diseases, especially cancer metastasis, although the satisfying chemical inhibitors targeting KRS have not yet been identified. Here, we report the discovery of novel, mechanistically unique, and potent cell migration inhibitors targeting KRS, including the chemical and biological studies on the most effective N,N-dialkylthiazolo [5,4-b]pyridin-2-amine (SL-1910). SL-1910 exhibited highly potent migration inhibition (EC50 = 81 nM against the mutant KRS-overexpressed MDA-MB-231 cells) and was superior to the previously reported KRS inhibitor (migration inhibitory EC50 = 8.5 μM against H226 cells). The KRS protein binding study via fluorescence-based binding titration and KRS protein 2D-NMR mapping study, in vitro concentration-dependent cell migration inhibition, and in vivo anti-metastatic activity of SL-1910, which consists of a new scaffold, have been reported in this study. In addition, in vitro absorption, distribution, metabolism, and excretion studies and mouse pharmacokinetics experiments for SL-1910 were conducted.

Atlas fracture occurs in 3%-13% of all cervical spinal injuries and is often associated with other injuries. The factors associated with concomitant transverse ligament disruption and vertebral artery injury remain underexamined.We retrospectively reviewed 97 consecutive cases of atlas fractures. We analyzed demographic and clinic characteristics, including mechanism of injury, fracture type, and associated injuries. We identified factors independently associated with vertebral artery injury and/or transverse ligament disruption.On multivariable analysis, vertebral artery injury was independently, positively associated with injury to the transverse ligament (odds ratio [OR], 8.51 [1.17, 61.72], P = 0.034), associated facial injury (OR, 7.78 [1.05, 57.50]; P = 0.045), intoxication at presentation (OR, 51.42 [1.10, 2408.82]; P = 0.045), and negatively associated with type 3 fractures (OR, 0.081 [0.0081, 0.814]; P = 0.033). There was a trend toward a positive association with a violence mechanism of injury (OR, 33.47 [0.75, 1487.89]; P = 0.070). Transverse ligament injury was independently associated with other injuries to the spine (OR, 13.07362 [2.43, 70.28]; P = 0.003), atlantodental interval (OR, 2.63 [1.02, 6.75]; P = 0.045), lateral mass displacement (OR, 1.78 [1.32, 2.39]; P0.001), and male sex (OR, 7.07 [1.47, 34.06]; P = 0.015). There was a trend toward a positive association with injury to the vertebral artery (OR, 5.13 [0.96, 27.35]; P = 0.056).Among patients with atlas fractures, vertebral artery injury and transverse ligament disruption are associated with each other. Mechanism of injury, fracture type, and intoxication at the time of injury were associated with vertebral artery injury, and atlantodental interval and lateral mass displacement are associated with magnetic resonance imaging-confirmed injury to the transverse ligament.

Background Adenoid cystic carcinoma (ACC) is the second most common malignancy of the salivary glands, accounting for ~ 1% of malignant tumors of the head and neck region and 10% of salivary gland neoplasms. Predicting the long-term outcomes of patients with ACC is still challenging, as reliable prognostic biomarkers are not available. Among salivary gland tumors, Myb overexpression is highly specific for ACC. In addition, the MYB-NF1B fusion translocation is a hallmark of ACC, and although the detection of this translocation does not appear to impact prognosis, the MYB-NF1B fusion is also implicated in MYB upregulation. Myb has recently been identified as an activator of the Wnt/β-catenin signaling pathway, and aberrant cytoplasmic expression of β-catenin has been observed in many salivary gland malignancies. In this study, we aim to analyze the impact of Myb and β-catenin expression on prognosis in ACC. Methods A tissue microarray constructed from archival tissue from 64 patients with ACC was stained for Myb and β-catenin; both localization and intensity were evaluated. In parallel, we abstracted demographic data, tumor characteristics, survival data, and outcomes, including local recurrence, regional recurrence, and distant metastasis from the medical record. Statistical analysis was performed. Results Our analysis supports that ACC patients negative for Myb by immunohistochemical methods have a higher risk of developing metastasis than patients with Myb staining (HR: 4.06, 95% CI: 1.02–14.96, p-value: 0.03). Although not statistically significant, cytoplasmic localization of β-catenin is may suggest a diminished rate of relapse-free survival (HR 2.45, 95%CI: 0.9–6.7, p = 0.08). Furthermore, Myb expression correlated with β-catenin expression, increasing 1.69 in staining intensity units with each increase in β-catenin staining intensity (p-value: 0.04). Conclusions Our study suggests that Myb expression is protective; Myb positive patients have diminished risk of distant metastasis. In contrast, there is a trend towards increased hazard of death in ACC patients with cytoplasmic β-catenin expression. Additional analyses will be necessary to establish Myb and β-catenin as independent protective and adverse biomarkers, respectively.

To explore whether texture features using T1-weighted images correlate with fat fraction, and whether they differ between Charcot-Marie-Tooth (CMT) disease patients and volunteers. The institutional review board approved this retrospective study, and the requirement for informed consent was waived; data of eighteen CMT patients and eighteen healthy volunteers from a previous study was used. Texture features of the muscles including mean, standard deviation (SD), skewness, kurtosis, and entropy of the signal intensity were derived from T1-weighted images. Spearman’s correlation analysis was used to assess the relationship between texture features and fat fraction measured by 3D multiple gradient echo Dixon-based sequence. Mann-Whitney U test was used to compare the texture features between CMT patients and volunteers. Intraobserver and interobserver agreements for the texture features were assessed using the intraclass correlation coefficient. The SD (ρ = 0.256, p

Adenoid cystic carcinoma (ACC) is the second most common malignancy of the salivary gland. Although characterized as an indolent tumor, ACC often leads to incurable metastatic disease. Patients with ACC respond poorly to currently available therapeutic drugs and factors contributing to the limited response remain unknown. Determining the role of molecular alterations frequently occurring in ACC may clarify ACC tumorigenesis and advance the development of effective treatment strategies. Applying Splice Expression Variant Analysis and outlier statistics on RNA sequencing of primary ACC tumors and matched normal salivary gland tissues, we identified multiple alternative splicing events (ASE) of genes specific to ACC. In ACC cells and patient-derived xenografts, FGFR1 was a uniquely expressed ASE. Detailed PCR analysis identified three novel, truncated, intracellular domain-lacking FGFR1 variants (FGFR1v). Cloning and expression analysis suggest that the three FGFR1v are cell surface proteins, that expression of FGFR1v augmented pAKT activity, and that cells became more resistant to pharmacologic FGFR1 inhibitor. FGFR1v-induced AKT activation was associated with AXL function, and inhibition of AXL activity in FGFR1v knockdown cells led to enhanced cytotoxicity in ACC. Moreover, cell killing effect was increased by dual inhibition of AXL and FGFR1 in ACC cells. This study demonstrates that these previously undescribed FGFR1v cooperate with AXL and desensitize cells to FGFR1 inhibitor, which supports further investigation into combined FGFR1 and AXL inhibition as an effective ACC therapy. This study identifies several FGFR1 variants that function through the AXL/AKT signaling pathway independent of FGF/FGFR1, desensitizing cells to FGFR1 inhibitor suggestive of a potential resistance mechanism in ACC. Significance: This study identifies several FGFR1 variants that function through the AXL/AKT signaling pathway independent of FGF/FGFR1, desensitizing cells to FGFR1 inhibitor, suggestive of a potential resistance mechanism in ACC.

Despite numerous reports on the beneficial effects of catechin or epicatechin contained in tea and cacao extract on human health, a conclusive and precise molecular mechanism has not been elucidated. Metabolism of chemical compounds in gut microbiota recently gained significant attention, and extensive studies have been devoted in this field. In conjunction with these results, our group focused on the anti-inflammatory effects of both enantiomers of DHPV (5-(3&prime, 4&prime, dihydroxyphenyl)-&gamma, valerolactone), produced in the intestine by microbiota metabolism, on IEC-6 cells. Divergent and efficient enantioselective synthesis of (S)- and (R)-DHPV was efficiently achieved by cross-metathesis and Sharpless asymmetric dihydroxylation as a key reaction for four steps in 16% and 14% overall yields, respectively. The anti-inflammatory effects of two enantiomers were tested on IEC-6 cells, and we found that (S)-DHPV was more active than (R)-DHPV. This result implicates that the metabolite produced in the gut has beneficial effects on IEC-6 cells of rat intestines, and the chirality of the metabolite is important for its anti-inflammatory activity. This also provided information for the future discovery of novel small molecular therapeutics for the treatment of inflammatory bowel disease.

This study aimed to evaluate whether diffusion tensor imaging (DTI) parameters and cross-sectional area (CSA) can differentiate between the sciatic nerve of Charcot–Marie–Tooth (CMT) disease type I (demyelinating form) patients and that of controls. This prospective comparison study included 18 CMT type I patients and 18 age/sex-matched volunteers. Magnetic resonance imaging including DTI and axial T2-weighted Dixon sequence was performed for each subject. Region of interest analysis was independently performed by two radiologists on each side of the sciatic nerve at four levels: hamstring tendon origin (level 1), lesser trochanter of the femur (level 2), gluteus maximus tendon insertion (level 3), and mid-femur (level 4). Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated. The CSA of the sciatic nerve bundle was measured using axial water-only image at each level. Comparisons of DTI parameters between the two groups were performed using the two-sample t test and Mann–Whitney U test. Interobserver agreement analysis was also conducted. Interobserver agreement was excellent for all DTI parameter analyses. FA was significantly lower at all four levels in CMT patients than controls. RD, MD, and CSA were significantly higher at all four levels in CMT patients. AD was significantly higher at level 2 in CMT patients. DTI assessment of the sciatic nerve is reproducible and can discriminate the demyelinating nerve pathology of CMT type I patients from normal nerves. The CSA of the sciatic nerve is also a potential parameter for diagnosing nerve abnormality in CMT type I patients. • Diffusion tensor imaging parameters of the sciatic nerve at proximal to mid-femur level revealed significant differences between the Charcot–Marie–Tooth disease patients and controls. • The cross-sectional area of the sciatic nerve was significantly larger in the Charcot–Marie–Tooth disease patients. • Interobserver agreement was excellent (intraclass coefficient > 0.8) for all diffusion tensor imaging parameter analyses.

Summary Background Linezolid improves the treatment outcomes of multidrug-resistant tuberculosis substantially. We investigated whether use of linezolid instead of ethambutol increases the proportion of sputum culture conversion at 8 weeks of treatment in patients with pulmonary tuberculosis. Methods We did a phase 2, multicentre, randomised, open-label trial for patients with pulmonary tuberculosis at the three affiliated hospitals to Seoul National University and National Medical Center (Seoul–Seongnam, South Korea). Patients, aged 20–80 years, with a positive sputum for pulmonary tuberculosis, but without resistance to rifampicin, and current treatment administered for 7 days or fewer, were randomly assigned at a 1:1:1 ratio into three groups. The control group received ethambutol (2 months) with isoniazid, rifampicin, and pyrazinamide. The second group used linezolid (600 mg/day) for 2 weeks and the third group for 4 weeks instead of ethambutol for 2 months. We used a minimisation method to randomise, and stratified according to institution, cavitation on chest radiographs, and diabetes. The primary endpoint was the proportion of patients with negative culture conversion of sputum in liquid media after 8 weeks of treatment. The results of this trial were analysed primarily in the modified intention-to-treat population. The trial is registered with ClinicalTrials.gov, number NCT01994460. Findings Between Feb 19, 2014, and Jan 13, 2017, a total of 429 patients were enrolled and 428 were randomly assigned into either the control group (142 patients), the linezolid 2 weeks group (143 patients), or the linezolid 4 weeks group (143 patients). Among them, 401 were eligible for primary efficacy analyses. In the modified intention-to-treat analyses, negative cultures in liquid media at 8 weeks of treatment were observed in 103 (76·9%) of 134 control patients, 111 (82·2%) of 135 in the linezolid 2 weeks group, and 100 (75·8%) of 132 in the linezolid 4 weeks groups. The difference from the control group was 5.4% (95% CI −4·3 to 15·0, p=0·28) for the linezolid 2 weeks group and −1·1% (−11·3 to 9·1, p=0·83) for the linezolid 4 weeks group. Numbers of patients who experienced at least one adverse event were similar across the groups (86 [62·8%] of 137 in control, 79 [57·2%] of 138 in the linezolid 2 weeks group, and 75 [62·0%] of 121 in the linezolid 4 weeks group). Resistance to linezolid was not identified in any patient. Interpretation Higher rates of culture conversion at 8 weeks of treatment with short-term use of linezolid were not observed. However, safety analyses and the resistance profile suggested the potential role of linezolid in shortening of treatment for drug-susceptible tuberculosis. Funding Ministry of Health and Welfare, South Korea.

Context:Allium senescens Linn. (Liliaceae) (ASL) has been traditionally used in Korea and other Asian countries for improving digestive and liver functions. Objective: The anti-hepatofibrosis effect of ASL ethanol extract in cellular and experimental fibrosis rat model was investigated. Materials and methods:In vitro cell viability, cell cycle and apoptosis in hepatic stellate cells (HSCs) were studied using MTT assay, flow cytometry and Annexin V-FITC/PI staining. Thioacetamide (TAA; 200 mg/kg, i.p.)-induced liver fibrosis model using Sprague Dawley rats (n = 10) was developed in vivo by injecting TAA twice per week for 13 weeks. ASL (25 and 100 mg/kg) and silymarin (50 mg/kg) were administered through oral gavage 2 times per week from 7th to 13th week. Specific fibrotic-related biomarkers such as aspartate transaminase (AST), alanine transaminase (ALT), glutathione and hydroxyproline levels in serum were analyzed by spectrophotometer using commercial kits. Morphological, histopathological and fibrotic-related gene expression such as TGF-β, Col1α1 and α-SMA in liver tissues was estimated by hematoxylin and eosin staining, Picrosirius red stain and quantitative real-time polymerase chain reaction, respectively. Results: ASL (0.1 mg/mL) and silymarin (0.05 mg/mL) treatment induced apoptosis (4.06% and 8.67%) in activated HSC-T6 cells, compared with control group (3.7%). The altered morphology in activated primary HSCs was also restored by ASL (0.1 mg/mL) treatment. Further, ASL (100 and 25 mg/kg) ameliorated the TAA-induced altered fibrotic-related biomarkers, histopathological changes and fibrotic-related gene expression significantly (p

The objectives of this study were to determine the diagnostic yield of percutaneous biopsy of osseous spinal lesions under CT and fluoroscopy guidance and to analyze lesion-related and technical factors affecting higher diagnostic yield.We retrospectively reviewed 247 consecutive percutaneous spinal biopsies and recorded the following information: size, anatomic location, and bone matrix of lesions; guiding modality; years of attending physicians' experience; number of approaches; pathologic result of initial biopsy; and final diagnosis. The pathologic results of the initial biopsies were classified as diagnostic or nondiagnostic. All variables were compared using Pearson chi-square test or Fisher exact test. Multivariate logistic regression was also conducted.Of the initial 247 biopsies, 197 (80%) biopsies were diagnostic. On multivariate analysis, size, bone matrix, and final diagnosis of lesion were significant factors affecting biopsy yield. Biopsies of large lesions (≥ 20 mm) showed higher diagnostic yield than biopsies of small lesions (p = 0.006). Biopsies of lytic lesions had the highest diagnostic yield (88%), followed by biopsies of mixed (84%), sclerotic (67%), and isodense lesions (61%). Differences were significant for diagnostic yields of biopsies of lytic versus sclerotic lesions (p = 0.004) and lytic versus isodense lesions (p = 0.031). Biopsies of metastases had significantly highest diagnostic yield (97%), followed by biopsies of primary malignancies (84%) and benign lesions (39%) (p0.05).For percutaneous image-guided biopsies of spinal tumorous lesions, diagnostic yield was 80%. Size, bone matrix, and final diagnosis of lesions affected diagnostic yield of percutaneous image-guided biopsies.

Background/Aims In suspected malignant biliary strictures (MBSs), the diagnostic yield of endoscopic retrograde cholangiopancreatography (ERCP)-based tissue sampling is limited. Transpapillary forceps biopsy (TPB) under intraductal ultrasonography (IDUS) guidance is expected to improve the diagnostic accuracy in patients with indeterminate biliary strictures. We evaluated the usefulness of IDUS-guided TPB in patients with suspected MBS. Methods Consecutive patients with suspected MBS were prospectively enrolled in the study. ERCP with IDUS was performed in all patients. Both conventional TPB and IDUS-guided TPB on fluoroscopy were performed in each patient. The primary outcome was the diagnostic accuracy of conventional TPB and IDUS-guided TPB. Results The technical success rate of IDUS-guided TPB was 97.0% (65/67 patients). Of these 65 patients, the final diagnosis was malignancy in 61 patients (93.8%). On IDUS, the most common finding of IDUS was an intraductal infiltrating lesion in 29 patients (47.5%). The overall diagnostic accuracy was significantly higher using IDUS-guided TPB than that using conventional TPB (90.8% vs 76.9%, p=0.027). According to the subgroup analysis based on the tumor morphology, IDUS-guided TPB had a significantly higher cancer detection rate than conventional TPB for intraductal infiltrating lesions (89.6% vs 65.5%, p=0.028). Conclusions IDUS-guided TPB appears to improve the accuracy of histological diagnosis in patients with MBS.

Backgrounds: Identification of precursors of atrial fibrillation (AF) may lead to early detection and prevent associated morbidity and mortality. Atrial premature complexes (APCs) are commonly seen in healthy subjects. However, there was limited data about the clinical and electrocardiographic (ECG) characteristics for prediction of new-onset AF in asymptomatic patients with APCs in the long-term follow up. Methods: The Kosin University (No. 2014-02-04) 24-h holter monitoring, echocardiography, ECG database were reviewed from 2008 to 2016 to identify new- onset AF in patients with APCs. We analyzed demographic and clinical features and the nature of the APCs by ECG according to new-onset AF in those patients. Results: Among 652 patients who underwent 24-h holter monitoring, 226 (34.4%) patients had new-onset AF. There was no difference of the baseline characteristics between new-onset AF group and non-AF group. In univariate analysis, hypertension (HTN), renal failure (CRF), high APC burdens, fastest APC running heart rate (HR), minimal HR, left ventricular ejection fraction (LVEF), left atrial volume index, peak mitral flow velocity of the early rapid filling wave and tricuspid regurgitation grade were significantly associated with new-onset AF. In multivariate analysis, higher APCs burden (P = 0.047), higher fastest APCs running HR (P = 0.034) and lower minimal HR (P = 0.025) were independent risk factors for new-onset AF in asymptomatic patients with APCs. Conclusion: Higher APCs burden, higher fastest APCs running HR and lower minimal HR were associated with new-onset AF in asymptomatic patients with APCs in the long-term follow up. Keywords: Atrial premature complex, New onset atrial fibrillation, Electrocardiographic characteristics, Clinical outcomes

Introduction: Premature ventricular complex (PVCs) detected from long-term ECG recordings have been associated with an increased risk of ischemic stroke. However, there was limited data about the association between high PVCs burdens (>10%) and stroke-like symptoms without a prior diagnosis of stroke or transient ischemic attack in the long-term follow up. Methods: The Kosin University 24-hours holter monitoring, echocardiography, electrocardiogram (ECG) database were reviewed from 2013 to 2015 to identify patients with frequent PVCs (>10%). We compared the long-term clinical outcomes between the patients with frequent PVCs (>10%) and control group without PVC. Results: Among 572 patients who underwent 24-hours holter monitoring, finally, 373 consecutive patients (mean age; 59.5 ± 15.8 years, 45.2% male) were enrolled. Among them, 203(54.4%) patients had high PVCs burdens (>10%). There was no difference of the baseline characteristics. In the long term follow-up, PVCs burden was not associated with PVCs -related symptoms (P = 0.210). In univariate analysis, female, non-sustained ventricular tachycardia (VT), sinus QRS duration, PVC coupling interval (CI), post- PVC CI, and late precordial R-wave transition of PVCs were associated with PVCs-related symptoms. In multivariate analysis, non-sustained VT (P = 0.022) and late precordial R-wave transition of PVCs (P = 0.044) were independent risk factors for PVCs-related stroke-like symptoms with frequent idiopathic PVCs > 10%. Conclusion: High PVCs burdens (>10%) were associated with and stroke-like symptoms without a prior diagnosis of stroke or transient ischemic attack in the long-term follow up, suggesting more intensive medical therapy with close clinical follow-up will be required. Keywords: Premature ventricular complex, Stroke-like symptoms, Transient ischemic attack, Clinical outcomes

An integrated optimal structural design method for a diagrid structure and control device was developed. A multi-objective genetic algorithm was used and a 60-story diagrid building structure was developed as an example structure. Artificial wind and earthquake loads were generated to assess the wind-induced and seismic responses. A smart tuned mass damper (TMD) was used as a structural control system and an MR (magnetorheological) damper was employed to develop a smart TMD (STMD). The multi-objective genetic algorithm used five objectives including a reduction of the dynamic responses, additional stiffness and damping, mass of STMD, capacity of the MR damper for the integrated optimization of a diagrid structure and a STMD. From the proposed method, integrated optimal designs for the diagrid structure and STMD were obtained. The numerical simulation also showed that the STMD provided good control performance for reducing the wind-induced and seismic responses of a tall diagrid building structure.

Background Jefferson fractures, or burst fractures of the C1 vertebra, can be managed surgically or conservatively, depending on their stability. Methods We identified all patients who were treated for a C1 fracture at our institution between 1999 and 2016 for retrospective analysis. Patients with any other concurrent cervical fractures or nontraumatic etiology of fracture were excluded. Stability was defined as either lateral mass displacement ≥7 mm on computed tomography or presence of transverse atlantal ligament disruption on magnetic resonance imaging. We collected data on patients' demographic, clinical, and radiographic presentation and identified variables independently associated with instability at presentation and failure to achieve fusion at follow-up. Results We identified 65 patients. On multivariable regression, instability at presentation was independently associated with atlantodens interval (odds ratio [OR] 2.357, 95% confidence interval [CI] [0.0629–1.271], P = 0.099) and type 3 fracture (OR 6.081, 95% CI [1.068–34.612], P = 0.042). Failure to achieve fusion was independently associated with age (OR 1.226, 95% CI [1.007–1.495], P = 0.043), motor vehicle collision as mechanism of injury (OR 22834.3, 95% CI [3.135–1.66e8], P = 0.027), and type 2 fracture (OR 168.537, 95% CI [1.743–16292.92], P = 0.028). Type 3 fracture was positively associated with halo vest for management (OR 17.171, 95% CI [2.882–102.289], P = 0.002) and negatively associated with a rigid cervical collar for management (OR 0.0616, 95% CI [0.0104–0.3653], P = 0.002). All 4 patients who underwent surgery presented with unstable fracture (P = 0.0187). Conclusions Atlantodens interval, mechanism of injury, and fracture type affect Jefferson fracture management decisions and outcomes, including instability at presentation and fusion at follow-up. Most fractures were managed nonsurgically regardless of stability.

Background Myocardial perfusion reserve index (MPRI) and extracellular volume fraction (ECV) on cardiac magnetic resonance (CMR) are known to quantify coronary microvascular dysfunction and myocardial fibrosis, respectively. Purpose To demonstrate that cardiovascular risk factors such as hypertension, diabetes, hyperlipidemia, and smoking are correlated with MPRI and ECV on CMR in asymptomatic individuals. Material and Methods Between October 2013 and July 2014, 196 individuals underwent CMR. After excluding those with chest pain, arrhythmia, and obstructive coronary artery disease, participants were divided into five groups: those without risk factor (n = 26) and those with one (n = 43), two (n = 35), three (n = 24), or four (n = 6) risk factors. MPRI and ECV were obtained on perfusion CMR and pre- and post-T1 mapping, respectively. Results A total of 134 asymptomatic individuals (109 men, 25 women; mean age = 54.4 ± 7.08 years; body mass index [BMI] = 24.96 ± 2.76 kg/m2; Framingham risk score [FRS] = 7.71 ± 5.21) were included. The Jonckheere-Terpstra test demonstrated trends of increasing BMI, FRS, and left ventricular mass index (all P values Conclusion We demonstrated that an increasing number of cardiovascular risk factors is significantly associated with reduced MPRI, but not with ECV on CMR.

The asymmetric total synthesis of the marine natural product (+)-(3E)-pinnatifidenyne was accomplished. The key features of the synthesis involve the construction of an eight-membered cyclic ether by the abnormally regioselective Pd(0)-catalyzed cyclization, the installation of a double bond in the oxocene skeleton by sequential in situ deconjugative isomerization, and the efficient introduction of the crucial chloride mediated by the substrate-controlled diastereoselective reduction.

Objectives Blood pressure variation (BPV) and metabolic syndrome is an independent risk factor for cardiovascular events. Ambulatory blood Pressure (ABP) has been shown to be more closely related to cardiovascular events in hypertensive patients than conventional office BP (OBP). Using both OBP and ABP, 4 groups of patients were identified: (1) normotensive patients (NT); (2) white coat hypertensives (WCHT); (3) masked hypertensives (MHT); and (4) sustainedhypertensives (SHT). We investigated the significance of BPV and metabolic risks of these 4 groups. Methods This study is a retrospective analysis of patients between January 2008 and May 2013. Echocardiography and 24 hour ABP monitoring were performed. Results BMI was significantly higher in the MHT compared with the NT. There were progressive increases in fasting glucose level from NT to WCHT, MHT, and SHT.MHT and SHT had higher 24h and nighttime BPV than NT.MHT was significantly related with BMI (r = 0.139, P = 0.010), creatinine (r = 0.144, P = 0.018), fasting glucose (r = 0.128, P = 0.046), daytime systolic BPV (r = 0.130, P = 0.017), and daytime diastolic BPV (r = 0.130, P = 0.017). Dyslipidemia (r = 0.110, P = 0.043), nighttime systolic BPV (r = 0.241, P < 0.001) and nighttime diastolic BPV (r = 0.143, P = 0.009) shown correlation with SHT. In multivariate logistic regression, MHT was independently associated with Body mass index (OR 1.086, 95% CI 1.005–1.174, P = 0.038) and creatinine (OR 1.005, 95% CI 1.001–1.010, P = 0.045). Conclusions BPV and metabolic risk factors were found to be greater in MHT and SHT compared with NT and WCHT. This suggests that BPV and metabolic risks may contribute to the elevated cardiovascular risk observed in patients with MHT and SHT.

Although Streptococcus parauberis is the major bacterial pathogen affecting olive flounder, the translocation and dissemination of this pathogen in infected fish are not well understood. Therefore, we conducted real-time PCR and histopathologic examination to monitor the intensity of infection in multiple organs of the olive flounder after challenge with S. parauberis through subcutaneous injection. The bacterial burden in the fish kidney, when sampled at 0, 3, and 7 dpc, was 0, 6.2 ± 4.5 × 105, and 6.7 ± 5.5 × 106 CFU/100 mg of tissue, respectively, indicating that the infection progressed rapidly over time. Of the ten different tissues sampled, the heart and the brain were the major target organs of S. parauberis based on highest copy number as detected by our modified real-time PCR method. Histopathologic examination also showed that S. parauberis caused severe inflammation accompanied by leucocyte infiltration, connective tissue expansion, and a loss of cardiomyocytes in the brain and heart of fish sampled at dpc 7. However, the number of S. parauberis-positive fish at 3 dpc was much higher in the spleen (6/8 fish) than in the remaining organs, suggesting that the spleen is targeted in the early stages of infection relative to the heart (2/8 fish) or brain (3/8 fish). This study provides essential information for studies to find treatments for the effective elimination of S. parauberis in target organs (i.e., the brain and heart) of olive flounder.

Background:N-terminal pro-B-type natriuretic peptide (NT-proBNP), a well-known marker of cardiac disease, may be elevated in acute infections and other non-cardiac diseases. The aim of this study was to evaluate NT-proBNP levels in cardiac and non-cardiac diseases and found out the patient’s clinical status that affects the NT-proBNP levels.Methods:NT-proBNP levels were measured in three groups of children: a cardiac disease group, an infectious disease group, and a non-cardiac, non-infectious disease group.Result:In total, 348 children were enrolled, including 134 patients (38.5%) with cardiac disease, 170 patients (48.9%) with infectious disease, and 44 patients (12.6%) with non-cardiac, non-infectious disease. The NT-proBNP level of the cardiac disease group (median: 548 pg/mL; range: 5–35,000 pg/mL) was significantly higher than that of the infectious disease group (median: 193 pg/mL; range: 10–35,000 pg/mL) and the non-cardiac, non-infectious disease group (median: 280 pg/mL; range: 6–35,000 pg/mL). Regarding clinical status, the NT-proBNP levels were significantly higher in patients who needed mechanical ventilation support, oxygen therapy, or inotropic medication or had a change in mental status than in other patients. However, the systemic inflammatory response syndrome and mortality were not related to the NT-proBNP level.Conclusion:Among heterogeneous group of children, NT-proBNP level can be a useful marker of cardiac disease. Furthermore, the NT-proBNP levels were related to patients’ clinical deteriorations, such as shock rather than the inflammatory status of patients.

BACKGROUND Recent studies have demonstrated that angiotensin receptor neprilysin inhibitors (ARNIs) can reverse the cardiac remodeling effects that occur in heart failure with reduced ejection fraction (HFrEF). These studies have also suggested that ARNIs have favorable effects on ventricular dyssynchrony. We assessed the changes in QRS duration associated with ARNIs in patients with HFrEF. METHODS We retrospectively investigated patients with HFrEF (defined by a left ventricular ejection fraction [LVEF] ≤ 35%) who were treated with ARNIs for at least six months. We divided the patients into QRS shortening and non-QRS shortening groups according to their electrocardiogram (ECG) findings. We also compared changes in echocardiographic parameters between the groups. RESULTS A total of 68 patients with HFrEF were included (mean age: 62.5 years, 74.6% male). Twenty-one patients had significant ischemic heart disease (IHD). Thirty-five patients exhibited QRS-duration shortening on follow-up ECGs (mean change: -7.8 msec), and 33 patients showed no changes or increased QRS duration (mean change: 5.1 msec). The QRS shortening group exhibited significant improvement in LVEF (12.5 ± 15.3% vs. 1.7 ± 9.5%; p < 0.001) when compared with the non-QRS shortening group. The QRS shortening group also had significantly lower LV end-diastolic dimension (LVEDD), LV end-systolic dimension (LVESD) and LV mass index (LVMI) than did the non-QRS shortening group. The change in QRS duration was significantly correlated with the change in LVEF (r = -0.329, p = 0.011) and LVESD (r = 0.298, p = 0.022). CONCLUSIONS Among patients with HFrEF treated with ARNIs, the QRS shortening group showed favorable LV systolic function recovery, and reversal of cardiac remodeling compared to those of the non-QRS shortening group. Change in the QRS duration, which reflects LV synchrony, may be associated with response to ARNIs in patients with HFrEF.

Purpose Excision of metastatic lesions is an important treatment strategy in patients with malignant melanoma, both at the initial diagnosis and upon recurrence. Since nonpalpable lesions cannot be easily visualized in the surgical field, we evaluated the effectiveness of ultrasound (US)-guided tattooing using a charcoal suspension for the localization of nonpalpable metastatic lesions of malignant melanoma. Methods Between November 2009 and June 2019, we retrospectively reviewed 65 nonpalpable lesions in 29 patients with malignant melanoma who underwent preoperative US-guided tattooing using a charcoal suspension for histologically confirmed or suspected metastases. The characteristics of the tattooed lesions were analyzed. The effectiveness of the procedure was evaluated based on the detection rate in the surgical field and the presence or absence of residua on postoperative follow-up US. Procedure-related complications were also analyzed. Results Of 65 lesions, 33 (50.8%) were histologically confirmed as metastases before the tattooing procedure, while the other 32 were suspected of being metastases based on imaging studies. The mean lesion size was 9.8 mm (range, 1.3 to 24.4 mm). The final pathology revealed metastases in 59 lesions (90.8%), including lymph node (n=51), muscle (n=5), and in-transit (n=3) metastases. Sixty-one lesions (93.8%) were successfully detected intraoperatively and removed without residua on follow-up US. Four residual lesions were removed after repeated localization (n=2) or by intraoperative US (n=2). No relevant complications were noted. Conclusion Preoperative US-guided tattooing localization can safely and effectively delineate nonpalpable metastatic melanoma lesions to aid in successful surgical excision.

Objectives To compare magnetic resonance imaging (MRI) parameters of small, deeply located non-malignant and malignant soft-tissue tumors (STTs). Methods Between May 2011 and December 2017, 95 MRIs in 95 patients with pathologically proven STTs of small size (

Objectives To retrospectively determine the diagnostic ability of MRI in differentiating between intradural extramedullary spinal schwannomas and meningiomas. Methods A total of 199 patients with spinal intradural extramedullary tumors who underwent preoperative contrast-enhanced MRI between January 2012 and December 2018 were included in this study. Two radiologists independently analyzed the presence of cystic change, dural tail sign, and neural foraminal extension. Clinical and MRI features between the two groups were compared by univariable and multivariable analyses using logistic regression. Interobserver agreements were calculated using kappa statistics. Results Patients with schwannoma showed significantly higher frequency of cystic change (96% vs 24%, P < 0.001), neural foraminal extension (29% vs 3%, P = 0.001), and lumbar location (41% vs 5%, P = 0.008). Patients with meningioma showed significantly higher frequency of dural tail sign (64% vs 1%, P < 0.001), thoracic location (75% vs 31%, P = 0.007), older age (59.7 years vs 47.6 years, P < 0.001), higher female predominance (83% vs 50%, P < 0.001), and smaller size (19.8 cm vs 28.8 cm, P < 0.001). Multivariable analysis showed that cystic change (P < 0.001; odds ratio [OR], 0.02), dural tail sign (P < 0.001; OR, 36.23), age (P = 0.032; OR, 1.06), and lumbar location (P = 0.006; OR, 0.02) were independent factors. Interobserver agreements were almost perfect for all analyses. Conclusions MRI features were useful in differentiating between intradural extramedullary schwannomas from meningiomas. The presence of cystic change and dural tail sign were independently significant discriminators.

Aims: The purpose of this study was to investigate the health-related quality of life (HRQOL) of patients with cardiovascular disease and its relationship to hospital readmission. Methods: The cross-sectional study used data from 1037 adults aged ⩾19 years diagnosed with myocardial infarction or angina pectoris. Raw data were obtained from the fourth to sixth Korea National Health and Nutrition Examination Survey (2007–2014). Results: Readmission was found to be associated with age, living status, education level, unemployment, individual income level, stroke, osteoarthritis, diabetes, depression, low stress level, walking days per week, and activity limitations due to cardiovascular disease. Conclusion: In summary, readmission was related to HRQOL among patients with myocardial infarction. Interventions that consider efforts to reduce readmission through improved diagnosis and development of systematic management of cardiovascular disease symptoms are required.

An 81-year-old male patient presented with complaint of a pulsating neck mass. The patient had a previous history of cervical lymphadenopathy by non-tuberculous mycobacterium infection. Rapid growth of the mass on admission and contrast enhanced computed tomography of the neck resulted in a diagnosis of non-tuberculous mycobacterium induced pseudoaneurysm. The patient underwent emergency open repair of the pseudoaneurysm. Pseudoaneurysm of the common carotid artery is regularly reported, but here we report a rare case of non-tuberculous mycobacterium induced pseudoaneurysm of the common carotid artery.

BACKGROUND In this study, we aimed to investigate the relationship between echocardiographic epicardial fat thickness (EFT), neutrophil to lymphocyte ratio (NLR; an important inflammatory marker), and diurnal blood pressure (BP) changes in patients with recently diagnosed essential hypertension. METHODS A total of 647 patients underwent echocardiography and 24 hours of ambulatory BP monitoring. EFT was measured by echocardiography, while NLR was measured by dividing the neutrophil count by the lymphocyte count. Patients were categorized into three groups according to BP pattern: the normotensive group, the dipper group, and the non-dipper group. RESULTS The mean EFT was highest in the non-dipper group (non-dipper group, 7.3 ± 3.0 mm; dipper group, 6.1 ± 2.0 mm; control group, 5.6 ± 2.0 mm; p < 0.001). NLR was also highest in the non-dipper group (non-dipper, 2.75 ± 2.81; dipper, 2.01 ± 1.32; control, 1.92 ± 1.11; p < 0.001). EFT was significantly correlated with age (r = 0.160, p < 0.001) and NLR (r = 0.353, p < 0.001). Furthermore, an EFT ≥ 7.0 mm was associated with the non-dipper BP pattern with 51.3% sensitivity and 71.6% specificity [95% confidence interval (CI) = 0.56-0.65, p < 0.001]. In a multivariate analysis, EFT [adjusted odds ratio (OR) = 3.99, 95% CI = 1.22-13.10, p = 0.022] and NLR (OR = 1.34, 95% CI = 1.05-1.71, p = 0.018) were independent parameters that distinguished a non-dipper pattern after adjustment for cardiovascular risk factors. CONCLUSION EFT and NLR are independently associated with impaired diurnal BP profiles in hypertensive individuals. EFT (as measured by echocardiography) and NLR appear to be helpful in stratifying cardiometabolic risk.