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Objective. High disease activity of ankylosing spondylitis (AS) is associated with poor sleep quality. The purpose of this study was to identify which of the representative tools for evaluating the disease activity of AS best reflect the quality of sleep. Methods. A total of 107 AS patients were enrolled in the study and the sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Age, sex, concomitant medication, erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP) level, Beck Depression Inventory second edition (BDI-II), Bath ankylosing spondylitis disease activity index (BASDAI), ankylosing spondylitis disease activity score (ASDAS)-ESR, ASDAS-CRP, pain visual analog scale, Insomnia Severity Index (ISI), and Epworth Sleepiness Scale (ESS) were analyzed as covariates. Results. Overall, 65% (70/107) of subjects reported poor sleep quality (PSQI＞5). There was a positive correlation between the sleep quality and disease activity as measured by the BASDAI, ASDAS-ESR, and ASDAS-CRP. In addition, the BASDAI demonstrated good correlations with ISI, ESS, and BDI-II, respectively. However, only BASDAI showed reliable correlation with PSQI among the disease activity parameters of AS (adjusted odd ratio 5.36, p=0.023). Conclusion. BASDAI is the most reliable parameter of disease activity associated with the sleep quality in patients with AS. (J Rheum Dis 2021;28:143-149)

Background/Aims: We investigated the distribution of serum uric acid (SUA) lev els and estimated the prevalence of hyperuricemia and hypouricemia in the Kore an population. Methods: This cross-sectional study used data from the Korean Genome and Epi demiology Study and included 172,970 participants (58,981 men and 113,989 wom en) aged 40 to 79 years. Hypouricemia and hyperuricemia were defined as SUA level ≤ 2.0 mg/dL and > 7 mg/dL, respectively. The prevalence of hyperuricemia and hypouricemia was evaluated by age and sex. Results: The mean SUA levels were significantly higher in men than in women (5.71 ± 1.27 mg/dL vs. 4.21 ± 0.96 mg/dL, p < 0.001). The mean SUA levels and prevalence of hyperuricemia increased with age in women but not in men. The overall preva lence of hyperuricemia and that in men and women was 50.82, 133.25, and 8.17 per 1,000 persons, respectively; the overall prevalence of hypouricemia and that in men and women was 4.16, 1.10, and 5.75 per 1,000 persons, respectively. The prev alence of hypouricemia in men was similar across all age groups; however, that in women was the highest in the age group of 40 to 49 years and the lowest in the age group of 50 to 59 years. Conclusions: The distribution of SUA levels and prevalence of hyperuricemia and hypouricemia differed according to age and sex. Age and sex should be considered in studies on uric acid-related diseases.

In this prospective study, we aimed to determine the impact of maternal parenting and attachment on brain development in early childhood. This study...

Background and purpose Behavioral variant frontotemporal dementia (bvFTD) is a subtype of frontotemporal dementia, which has clinical symptoms of progressive personality and behavioral changes with deterioration of social cognition and executive functions. The pathology of bvFTD is known to be tauopathy or TDP-43 equally. We analyzed the 18F-THK5351 positron emission tomography (PET) scans, which were recently developed tau PET, in patients with clinically-diagnosed bvFTD. Methods Forty-eight participants, including participants with behavioral variant frontotemporal dementia (bvFTD, n=3), Alzheimer's disease (AD, n=21) and normal cognition (NC, n=24) who completed 3T magnetic resonance images, 18F-THK5351 PET scans, and detailed neuropsychological tests were included in the study. Voxel-wise statistical analysis and region of interest (ROI)-based analyses were performed to evaluate the retention of THK in bvFTD patients. Results In the voxel-based and ROI-based analyses, patients with bvFTD showed greater THK retention in the prefrontal, medial frontal, orbitofrontal, anterior cingulate, insula, anterior inferior temporal and striatum regions compared to NC participants. Left-right asymmetry was noted in the bvFTD patients. A patient with extrapyramidal symptoms showed much greater THK retention in the brainstem. Conclusions The distribution of THK retention in the bvFTD patients was mainly in the frontal, insula, anterior temporal, and striatum regions which are known to be the brain regions corresponding to the clinical symptoms of bvFTD. Our study suggests that 18F-THK5351 PET imaging could be a supportive tool for diagnosis of bvFTD.

Simple Summary Interleukin (IL) 15 is a proinflammatory cytokine and is well-known as an efficacious cytokine for cancer immunotherapy. Interestingly, the IL-15:IL-15Rα complex, a self-assembling form of IL-15 and its soluble receptor α (IL-15Rα), has shown greater antitumor activity than IL-15 itself. However, the development of a suitable multigene delivery system is needed for further applications of IL-15:IL-15Rα. Baculovirus, an arthropod-specific virus, is known for its adjuvant effect in cancer therapy. Here, we investigated the potential of the BacMam virus, a modified baculovirus for gene delivery into mammalian cells, as a novel multigene delivery system to generate a cell-based cancer vaccine secreting the self-assembling IL-15:IL-15Rα complex. Vaccination with a BacMam-based IL-15:IL-15Rα cancer vaccine triggered antitumor immune responses in a tumor antigen-specific manner. Our findings indicate that the BacMam system is a safe and effective method to produce protective and therapeutic cancer vaccines. Abstract This study reports the use of the BacMam system to deliver and express self-assembling IL-15 and IL-15Rα genes to murine B16F10 melanoma and CT26 colon cancer cells. BacMam-based IL-15 and IL-15Rα were well-expressed and assembled to form the biologically functional IL-15:IL-15Rα complex. Immunization with this IL-15:IL-15Rα cancer vaccine delayed tumor growth in mice by inducing effector memory CD4+ and CD8+ cells and effector NK cells which are tumor-infiltrating. It caused strong antitumor immune responses of CD8+ effector cells in a tumor-antigen specific manner both in vitro and in vivo and significantly attenuated Treg cells which a control virus-infected cancer vaccine could induce. Post-treatment with this cancer vaccine after a live cancer cell injection also prominently delayed the growth of the tumor. Collectively, we demonstrate a vaccine platform consisting of BacMam virus-infected B16F10 or CT26 cancer cells that secrete IL-15:IL-15Rα. This study is the first demonstration of a functionally competent soluble IL-15:IL-15Rα complex-related cancer vaccine using a baculovirus system and advocates that the BacMam system can be used as a secure and rapid method of producing a protective and therapeutic cancer vaccine.

Early- and late-onset Alzheimer’s disease (AD) patients often exhibit distinct features. We sought to compare overall white matter connectivity and evaluate the pathological factors (amyloid, tau, and vascular pathologies) that affect the disruption of connectivity in these two groups. A total of 50 early- and 38 late-onset AD patients, as well as age-matched cognitively normal participants, were enrolled and underwent diffusion-weighted magnetic resonance imaging to construct fractional anisotropy-weighted white matter connectivity maps. [18F]-THK5351 PET, [18F]-Flutemetamol PET, and magnetic resonance imaging were used for the evaluation of tau and related astrogliosis, amyloid, and small vessel disease markers (lacunes and white matter hyperintensities). Cluster-based statistics was performed for connectivity comparisons and correlation analysis between connectivity disruption and the pathological markers. Both patient groups exhibited significantly disrupted connectivity compared to their control counterparts with distinct patterns. Only THK retention was related to connectivity disruption in early-onset AD patients, and this disruption showed correlations with most cognitive scores, while late-onset AD patients had disrupted connectivity correlated with amyloid deposition, white matter hyperintensities, and lacunes in which only a few cognitive scores showed associations. These findings suggest that the pathogenesis of connectivity disruption and its effects on cognition are distinct between EOAD and LOAD.

Background and purpose To analyze 18F-THK5351 positron emission tomography (PET) scans of patients with clinically diagnosed nonfluent/agrammatic variant primary progressive aphasia (navPPA). Methods Thirty-one participants, including those with Alzheimer's disease (AD, n=13), navPPA (n=3), and those with normal control (NC, n=15) who completed 3 Tesla magnetic resonance imaging, 18F-THK5351 PET scans, and detailed neuropsychological tests, were included. Voxel-based and region of interest (ROI)-based analyses were performed to evaluate retention of 18F-THK5351 in navPPA patients. Results In ROI-based analysis, patients with navPPA had higher levels of THK retention in the Broca's area, bilateral inferior frontal lobes, bilateral precentral gyri, and bilateral basal ganglia. Patients with navPPA showed higher levels of THK retention in bilateral frontal lobes (mainly left side) compared than NC in voxel-wise analysis. Conclusions In our study, THK retention in navPPA patients was mainly distributed at the frontal region which was well correlated with functional-radiological distribution of navPPA. Our results suggest that tau PET imaging could be a supportive tool for diagnosis of navPPA in combination with a clinical history.

BACKGROUND Semantic variant primary progressive aphasia (svPPA) has been associated with a variety of proteinopathies, mainly transactive response DNA-binding protein, but also with tau and β-amyloid. Recently selective tau tracers for positron emission tomography (PET) have been developed to determine the presence of cerebral tau deposits in vivo. Here, we investigated the topographical distribution of THK5351 in svPPA patients. MATERIALS AND METHODS Five svPPA patients, 14 Alzheimer's disease patients, and 15 age-matched normal controls underwent [F]-THK5351 PET scans, magnetic resonance imaging, and detailed neuropsychological tests. [F]-fluorodeoxyglucose PET was obtained in 3 svPPA patients, whereas the remaining 2 underwent amyloid PET using [F]-flutemetamol. Tau distribution among the 3 groups was compared using regions of interest-based and voxel-based statistical analyses. RESULTS In svPPA patients, [F]-THK5351 retention was elevated in the anteroinferior and lateral temporal cortices compared with the normal controls group (left>right), and in the left inferior and temporal polar region compared with Alzheimer's disease patients. [F]-THK5351 retention inversely correlated with glucose metabolism, whereas regional THK retention correlated with clinical severity. [F]-flutemetamol scans were negative for β-amyloid. CONCLUSIONS These findings show that [F]-THK5351 retention may be detected in cortical regions correlating with svPPA pathology.

This study aims to evaluate the clinical validity of [18F]THK5351 positron emission tomography (PET) for the assessment of disease progression and symptoms in Alzheimer's disease (AD). Fifty-one patients with AD dementia, 30 patients with amnestic mild cognitive impairment (aMCI), and 43 controls with normal cognition (NC) were included. All subjects underwent [18F]THK5351 PET, 3.0-T magnetic resonance imaging, and detailed neuropsychological tests. Regions of interest and voxel-based statistical analyses were performed. In patients with AD dementia, [18F]THK5351 retention was greater in most association cortices as well as the limbic area compared to NC or aMCI participants. Patients with aMCI also showed higher THK5351 retention in those areas compared to NC. [18F]THK5351 retention significantly correlated with neuropsychological test results. Negative correlations between [18F]THK5351 and [18F] fluorodeoxyglucose were observed in AD dementia and aMCI groups. Mirror images of [18F]THK5351 retention and glucose hypometabolism in [18F] fluorodeoxyglucose were noticeable in the focal variants of AD. [18F]THK5351 PET reflects disease severity and symptoms in AD. Our results suggest [18F]THK5351 is reflective of tau-related AD pathology.

Aim Osteonecrosis (ON), also known as avascular necrosis, is an important cause of physical disability in rheumatic disease. When this condition affects multiple structures, disability is increased. The purpose of this study was to describe the clinical characteristics of Korean patients with multifocal ON associated with rheumatic disease and to compare them with those of previously reported cases. Methods We reviewed the clinical characteristics of eight Korean patients with multifocal ON, defined by the involvement of three or more anatomic sites, associated with rheumatic disease in a single referral academic hospital, and compared them with those of 19 similar cases previously reported in the literature. Results All eight patients were female, with median age of 26 years. All had underlying systemic lupus erythematosus (SLE) and had been using corticosteroids. The most common site affected by ON was the knee joint. However, in contrast to our patients, the previous reported cases had other rheumatic diseases such as myositis, scleroderma and antiphospholipid syndrome. In comparison between Korean multifocal ON patients with SLE and those of previous reports, shoulder joint involvement was higher in previous reports. Common features in patients from both groups were knee joint involvement and prevalent use of corticosteroids. Conclusion Our findings indicate that multifocal ON is common in young SLE patients who have been using corticosteroids and the most commonly involved site is the knee.

Background/Aims: Sleep disturbance is prime concern in patients with Behcet disease. The purpose of this study was to find out the effects of sleep quality, in Korean patients suffering from Behcet disease. We further investigated the relationship between depression, quality of life and the clinical findings of Behcet disease. Methods: The study was performed by the cross-sectional design. Sleep quality was assessed by the Korean version of Pittsburgh sleep quality index (PSQI). Disease activity of Behcet disease was evaluated by Behcet disease current activity form (BDCAF). Depression was assessed by the Korean version of Beck depression inventory second edition (BDI-2). Quality of life was assessed by the Korean version of the Leeds Behcet disease quality of life measure (BDQoL). Results: Among the 100 patients studied, 42% reported poor sleep quality (PSQI ≥ 9). These patients have a higher BDI-2, total BDCAF and pain visual analogue scale (VAS) score (p < 0.001, p = 0.022, and p = 0.005). Considering BDCAF, the frequency of genital ulcer was significantly higher (p = 0.01). Behcet was higher in females. The BDQoL was lower in poor sleeper group (p = 0.004 and p < 0.001). Among 7 PSQI components, daytime dysfunction was higher in patients with high disease activity (p = 0.03). Total PSQI score were strongly correlated with BDCAF, BDI-2, BDQoL, and pain VAS score (p = 0.02, p < 0.001, p < 0.001, and p < 0.001, respectively). Conclusions: Low sleep quality is directly associated with disease activity, depression, and quality of life in Korean patients with Behcet disease.

Alzheimer’s disease (AD) patients are known to have heterogeneous clinical presentation and pathologic patterns. We hypothesize that AD dementia can be categorized into subtypes based on multimodal imaging biomarkers such as magnetic resonance imaging (MRI), tau positron emission tomography (PET), and amyloid PET. We collected 3T MRI, 18F-THK5351 PET, and 18F-flutemetamol (FLUTE) PET data from 83 patients with AD dementia [Clinical Dementia Rating (CDR) ≤1] and 60 normal controls (NC), and applied surface-based analyses to measure cortical thickness, THK5351 standardized uptake value ratio (SUVR) and FLUTE SUVR for each participant. For the patient group, we performed an agglomerative hierarchical clustering analysis using the three multimodal imaging features on the vertices (n = 3 × 79,950). The identified AD subtypes were compared to NC using general linear models adjusting for age, sex, and years of education. We mapped the effect size within significant cortical regions reaching a corrected p-vertex

Background Ankylosing Spondylitis (AS), affecting 0.5% of the population, is a chronic inflammatory rheumatic disease affecting the axial skeleton and peripheral joints. When peripheral arthritis in ankylosing spondylitis (AS) develops early in the disease course it is a predictor of more aggressive disease. SF is in contact with the primary tissues affected by arthritic diseases and has been implicated in disease pathophysiology. Therefore it is an excellent source for discovery of biomarkers. Objectives We used proteomic analysis using SFs from AS patients and other arthritis patients in order to discover novel diagnostic markers for AS. Our aim was to identify differentially expressed protein mediators in synovial fluid of ankylosing spondylitis. Methods A Total of 40 SF samples from 10 AS and each 10 controls [Osteoarthritis (OA), Rheumatoid Arthritis (RA), gouty arthritis (Gout)] were collected. Liquid chromatography and tandem mass spectrometry (LC-MS/MS), to identify differentially expressed proteins based on the ratios of the extracted ion current of each protein between the four groups. Among the 9 proteins showing 1.5 fold change, 8 were verified with the exception of the abundant protein Haptoglobin (HP). Matrix metalloproteinase-1(MMP1) and Matrix metalloproteinase-3(MMP3) were used as a positive control, and the remaining 6 proteins were subjected to western blot analysis. Results We identified 9 proteins that were found to be more than 1.5-fold differentially expressed in SF of AS patients compared to control groups. Proteins such as HP, MMP1, MMP3, Serum amyloid P-component(APCS), Complement factor H-related protein 5(CFHR5), Fumarylacetoacetase(FAH), Mannose-binding lectin2(MBL2), Complement component C9(C9) and Complement C4-A(C4A) were found to be upregulated in the SF of AS patients. CFHR5 and C9 were reported in previous studies with AS serum. APCS was reported in SF as well as serum. However, FAH, C4A and MBL2 were newly discovered through this analysis. We were able to verify the unique expression level of C9 and CFHR5 in AS sample using western blot analysis compared to the other three diseases. Conclusion We performed quantitatively proteomic profiling of the respective SF sample from 4 diseases, i.e., AS, OA, RA, and GOUT, by LC-MS/MS. The systematic comparative proteomic analysis of the four groups together was carried out for the first time, leading to several differentially expressed proteins in AS. Among them, we expect C9 and CFHR5, which expression levels were confirmed by western blot analysis, can be a potential biomarker for AS. References [1] Fischer R, et al. Mol Cell Proteomics2012;11:M111.013904. [2] Bhattacharjee M, et al. Clinical Proteomics2013;10:11 Acknowledgement This research was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2017R1C1B5017278) Disclosure of Interests None declared

Lignin is regarded as a potential source of various aromatic compounds and chemicals, replacing petrochemicals. Catechol and its derivatives are important platform chemicals in many industrial sectors, including agrochemicals and pharmaceuticals. The global market of catechols is expected to increase with emerging demand in end-use industries. Considering that the current production of catechols relies on fossil fuels, it is critical to seek alternative renewable sources to respond to sustainability challenges. In this respect, lignin is viewed as a promising material due to its abundance and renewable character. Also, the structural similarity to catechols has made lignin a potential feedstock for the production of bio-catechols. However, the lignin-to-catechols conversion approach is still in an early stage because the intractable nature of lignin and the complex mixture of the depolymerized products make its valorization less feasible. Herein, we report a selective production of catechols via tandem conversion of lignin, namely, demethylation followed by catalytic hydrogenolysis (DFCH). The DFCH of lignin resulted in catechol- and catechol derivatives-rich liquid, accounting for 80 % in the identified products. The reaction mechanisms were also studied by quantum calculations to provide a fundamental understanding of the conversion. The result proves that selective modification of lignin structure is a promising approach to produce specific platform chemicals, providing insights toward an efficient strategy for lignin valorization.

Background: The stem cell-derived secretome has received considerable attention as an alternative to stem cells for therapeutic applications. However, establishing optimal culture conditions is key to obtaining appropriate secretome contents. Here, the optimal culturing environment for achieving a high-efficiency secretome was determined via hypoxic preconditioning of human adipose-derived stem cells (ASC). Methods: Normoxic conditioned media (NCM) and hypoxic conditioned media (HCM) were obtained after culturing human ASCs under normoxia (20% O2) or hypoxia (1% O2), respectively. Subsequently, both normal and thioacetamide-induced hepatotoxic hepatocytes were treated with NCM or HCM. In addition, partially hepatectomized mice were infused with control saline, NCM, and HCM. The effects on liver regeneration and serum transaminases levels were then compared. Results: Hypoxic preconditioning significantly increased mRNA expression of proinflammatory cytokines (interleukin-6 and tumor necrosis factor-) and growth factors (hepatocyte growth factor and vascular endothelial growth factor). In both normal and thioacetamide-induced hepatotoxic hepatocyte (alpha mouse liver 12 [AML12]) cell lines, HCM treatment resulted in the highest cell viability (122% and 95%, respectively), followed by NCM (111% and 78%, respectively). In addition, intravenous administration of HCM to partially hepatectomized mice resulted in substantially enhanced liver regeneration compared with the NCM group (P

Background The aim of this study was to investigate whether 3 Tesla susceptibility-weighted imaging can detect the alteration of substantia nigra hyperintensity in Parkinson's disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP) and to assess the concordance between the loss of nigral hyperintensity on 3 Tesla susceptibility-weighted imaging and the nigrostriatal dopaminergic degeneration indicated by 123I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane single photon emission computerized tomography. Methods Consecutive subjects with suspected parkinsonism were included, and clinical diagnosis was solidified during clinical follow-up. Two blinded neuroradiologists interpreted the nigral hyperintensity on susceptibility-weighted imaging. The performance of susceptibility-weighted imaging for detection of nigral hyperintensity loss was estimated on the basis of the clinical diagnosis and compared with single photon emission computerized tomography results. Results The study included 210 subjects (126 PD, 11 MSA, 11 PSP patients, 26 healthy controls, 36 disease controls). The presence or absence of nigral hyperintensity was accurately visualized in 112 PD, 7 MSA, and 11 PSP patients and 53 controls. We identified 16 false-negative cases and 11 false-positive cases. The sensitivity and specificity of susceptibility-weighted imaging were 88.8% and 83.6%, respectively. The concordance rate between susceptibility-weighted imaging and single photon emission computerized tomography was 86.2%. Conclusions The loss of nigral hyperintensity on susceptibility-weighted imaging suggested nigrostriatal dopaminergic degeneration in a large portion of patients with parkinsonism, which was indicated by 123I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane single photon emission computerized tomography. In consideration of false-negative and -positive cases, well-designed imaging protocols should be introduced to improve the performance of nigral hyperintensity imaging. © 2016 International Parkinson and Movement Disorder Society

Background:Long noncoding RNAs (lncRNAs) have recently emerged as important biological regulators and the aberrant expression of lncRNAs has been reported in various diseases including cancer, cardiovascular disease, and diabetes mellitus. However, the role of lncRNAs in the pathogenesis of rheumatoid arthritis (RA) remains unknown.Objectives:Thus, we studied lncRNAs influenced by IL-1, which is one of the key mediators in the pathogenesis of RA, and also investigated whether regulation of NF-κB activation, which is known to be induced by IL-1, could lead to the changes of expression of those lncRNAs.Methods:Fibroblast-like synoviocytes (FLS) were obtained from the knee joints of the patients with RA. The next-generation sequencing (NGS) data were analyzed to identify differentially expressed lncRNAs between unstimulated RA FLS and IL-1-stimulated RA FLS. The expression levels of the top 5 candidates in NGS data were validated by RT-qPCR using extended number of unstimulated RA FLS and IL-1-stimulated RA FLS. IMD-0560, an inhibitor of IκB kinase (IKK) was used for the regulation of NF-κB activation. Activation and inhibition of NF-κB were confirmed by Western blotting. Changed expressions of the lncRNAs were identified by RT-qPCR.Results:NGS analysis revealed up-regulated 30 lncRNAs and down-regulated 15 lncRNAs in IL-1-treated RA FLS compared with unstimulated RA FLS. Top 5 lncRNAs were selected among 30 lncRNAs up-regulated by IL-1 in RA FLS based on fold-change with P-value cutoff. The up-regulated lncRNAs including NR_046035, NR_027783, NR_033422, NR_003133, and NR_049759 were validated by RT-qPCR. IMD-0560 inhibited phosphorylation of IκBα induced by IL-1 in RA FLS. Overexpression of lncRNAs induced by IL-1 was also inhibited by IMD-0560 in RA FLS.Conclusion:Our study revealed that IL-1 increased the expression of NR_046035, NR_027783, NR_033422, NR_003133, and NR_049759 in RA FLS. In addition, the expression of these lncRNAs was regulated by inhibition of NF-κB activation. Thus, our data suggest that the lncRNAs might be involved in the pathogenesis of RA through NF-κB signaling pathway.References:[1]Long noncoding RNAs and human disease. Trends Cell Biol. 2011 Jun;21(6):354-61.[2]A long noncoding RNA mediates both activation and repression of immune response genes. Science. 2013 Aug 16;341(6147):789-92.[3]Long noncoding RNA expression profile in fibroblast-like synoviocytes from patients with rheumatoid arthritis. Arthritis Res Ther. 2016 Oct 6;18(1):227.Disclosure of Interests:None declared

Background and purpose Mild cognitive impairment (MCI) is a condition with diverse clinical outcomes and subgroups. Here we investigated the topographic distribution of tau in vivo using the positron emission tomography (PET) tracer [¹⁸F]THK5351 in MCI subgroups. Methods This study included 96 participants comprising 38 with amnestic MCI (aMCI), 21 with nonamnestic MCI (naMCI), and 37 with normal cognition (NC) who underwent 3.0-T MRI, [¹⁸F]THK5351 PET, and detailed neuropsychological tests. [¹⁸F]flutemetamol PET was also performed in 62 participants. The aMCI patients were further divided into three groups: 1) verbal-aMCI, only verbal memory impairment; 2) visual-aMCI, only visual memory impairment; and 3) both-aMCI, both visual and verbal memory impairment. Voxel-wise statistical analysis and region-of-interest -based analyses were performed to evaluate the retention of [¹⁸F]THK5351 in the MCI subgroups. Subgroup analysis of amyloid-positive and -negative MCI patients was also performed. Correlations between [¹⁸F]THK5351 retention and different neuropsychological tests were evaluated using statistical parametric mapping analyses. Results [¹⁸F]THK5351 retention in the lateral temporal, mesial temporal, parietal, frontal, posterior cingulate cortices and precuneus was significantly greater in aMCI patients than in NC subjects, whereas it did not differ significantly between naMCI and NC participants. [¹⁸F] THK5351 retention was greater in the both-aMCI group than in the verbal-aMCI and visualaMCI groups, and greater in amyloid-positive than amyloid-negative MCI patients. The cognitive function scores were significantly correlated with cortical [¹⁸F]THK5351 retention. Conclusions [¹⁸F]THK5351 PET might be useful for identifying distinct topographic patterns of [¹⁸F]THK5351 retention in subgroups of MCI patients who are at greater risk of the progression to Alzheimer's dementia.

Background High levels of serum immunoglobulin G4 (IgG4) would comprise a useful diagnostic tool in IgG4-related disease, but little information is available about IgG4 in conditions other than IgG4-related disease, including rheumatic diseases. Previous studies indicate that the elevated serum IgG4 in rheumatoid arthritis (RA) is common and disproportional to total IgG. Objectives The aim of study is to evaluate the level of serum IgG4 and IgG4/total IgG ratio in patients with RA. Methods Ninety-six patients with RA and one hundred and thirty-five non-RA controls were enrolled between March 2014 and July 2017. All samples were collected before the treatments. The levels of Serum total IgG and IgG4 were determined by nephelometric assay. The cut-off value of serum IgG4 was 135 mg/dL. Data on clinical variables and disease activity markers, such as numbers of tender and swollen joints, levels of acute phase reactants and disease activity score 28 (DAS28) were recorded in RA patients. We compared the levels of serum IgG4 and the ratio of IgG4/total IgG in rheumatoid arthritis with healthy controls and other rheumatic diseases. This study also investigated the difference the relationship between levels of serum IgG4 and disease activity in RA. Results Among 96 RA patients, the mean of serum IgG4 was 48.0±45.4 mg/dL and 6.3% had elevated serum IgG4. The mean serum IgG4/IgG ratio of RA patients was 3.5%±2.8% (range 0.2%∼16.9%). There was no patient with elevated serum IgG4 in ankylosing spondylitis, systemic lupus erythematosus, Sjogren’s syndrome, and inflammatory myositis. When the patients were divided according to clinical activity, the percentages of the positive serum IgG4 were 25% in active disease group and 4% in low activity group. However, the serum IgG4 levels of the RA patients with active disease activity were not significantly higher than those of the RA patients with low disease activity (58.3±44.3 mg/dL vs. 39.9±30.1 mg/dL). No significant relationship was observed between the ratio of IgG4/total IgG and disease activity. The IgG4 concentrations and total IgG/IgG4 ratios were similar between RA and the other autoimmune diseases (p>0.05). Conclusions Our results showed that elevated serum IgG4 in RA is relatively common. However the presence of the elevated serum IgG4 was not associated with disease activity of RA. Further investigations are needed to explore the clinical significance in a larger study population. References [1] Lin G, et al. Elevation of serum IgG subclass concentration in patients with rheumatoid arthritis. Rheumatol Int2010;30:837–40. [2] Yamamoto M, et al. Value of serum IgG4 in the diagnosis of IgG4-related disease and in differentiation from rheumatic diseases and other diseases. Mod Rheumatol2012;22:419–25. [3] Chen LF, et al. Elevated Serum IgG4 Defines Specific Clinical Phenotype of Rheumatoid Arthritis. Mediators Inflamm2014;2014:635293. Disclosure of Interest None declared

Leptin is abnormally elevated in the plasma of patients with systemic lupus erythematosus (SLE), where it is thought to promote and/or sustain pro-inflammatory responses. Whether this association could reflect an increased genetic susceptibility to develop SLE is not known, and studies of genetic associations with leptin-related polymorphisms in SLE patients have been so far inconclusive. Here we genotyped DNA samples from 15,706 SLE patients and healthy matched controls from four different ancestral groups, to correlate polymorphisms of genes of the leptin pathway to risk for SLE. It was found that although several SNPs showed weak associations, those associations did not remain significant after correction for multiple testing. These data do not support associations between defined leptin-related polymorphisms and increased susceptibility to develop SLE. © 2015 Elsevier Inc.

Purpose The purpose of this study was to evaluate serial changes in quadriceps and hamstring muscle strength over the first postoperative year in patients who underwent anterior cruciate ligament (ACL) reconstruction with an autologous hamstring tendon graft and to reveal which of these 2 muscles lost more strength and recovered more slowly after autologous hamstring ACL reconstruction. Methods Isokinetic muscle strength was measured preoperatively and at 6 months and 1 year postoperatively in 20 patients who underwent ACL reconstruction. The maximal torque (60°/s) and total work (180°/s) of the quadriceps and hamstring were evaluated using an isokinetic testing device. The isokinetic muscle strength and endurance of the injured legs were expressed as percentages of those of the uninjured legs at the same time point. Results Both quadriceps and hamstring muscle strength at 60°/s and endurance at 180°/s of the injured relative to the uninjured leg was 50% preoperatively. Quadriceps muscle strength and endurance of the injured leg increased to 70% at 6 months and 80% at 1 year postoperatively, whereas hamstring muscle strength and endurance increased to 80% at 6 months and 80% at 1 year. Conclusions Knee muscle strength recovered progressively after ACL reconstruction using autologous hamstring tendons but did not fully recover, being about 80% that of the uninjured leg even 1 year after surgery. Level of Evidence Level IV, therapeutic case series.

Background Foot involvement in rheumatoid arthritis (RA) patients has been reported to severely affect functional capacity and quality of life. We aimed to determine the impact of midfoot and hindfoot involvement on functional disability in Korean patients with RA. Methods We evaluated the RA involvement and deformity of three regions of the foot (forefoot, midfoot and hindfoot) and ankle using conventional radiography in Korean patients with RA. We compared the clinical features between RA patients with and without foot or ankle involvement. Using multivariable logistic regression analyses, the impact of midfoot or hindfoot involvement on functional disability in RA patients was evaluated. Results Overall, 120 patients with a median age of 48.0 [interquartile range (IQR), 37–56] years and median disease duration of 58.0 (IQR, 10–89) months were included. The prevalence of foot or ankle RA involvement was 74 (61.7%). The number of patients with forefoot, midfoot, hindfoot and ankle involvement was 32 (43.2%), 24 (32.4%), 46 (62.2%) and 4 (5.4%), respectively. Compared to patients without foot or ankle involvement those with such involvement had greater disease activity and functional disability, more of them were treated with biologic agents, and they had a lower health-related quality of life. After adjusting for potential confounders, hindfoot involvement was associated with a higher degree of functional disability. However, walking difficulty was more associated with midfoot involvement rather than with involvement in other regions. Conclusions In Korean patients with RA, hindfoot involvement is associated with functional disability and midfoot involvement affects walking. Electronic supplementary material The online version of this article (doi:10.1186/s12891-017-1726-7) contains supplementary material, which is available to authorized users.

Background and purpose There are three distinct subtypes of primary progressive aphasia (PPA): the nonfluent/agrammatic variant (nfvPPA), the semantic variant (svPPA), and the logopenic variant (lvPPA). We sought to characterize the pattern of [¹⁸F]-THK5351 retention across all three subtypes and determine the topography of [¹⁸F]-THK5351 retention correlated with each neurolinguistic score. Methods We enrolled 50 participants, comprising 13 PPA patients (3 nfvPPA, 5 svPPA, and 5 lvPPA) and 37 subjects with normal cognition (NC) who underwent 3.0-tesla magnetic resonance imaging, [¹⁸F]-THK5351 positron-emission tomography scans, and detailed neuropsychological tests. The PPA patients additionally participated in extensive neurolinguistic tests. Voxel-wise and region-of-interest-based analyses were performed to analyze [¹⁸F]-THK5351 retention. Results The nfvPPA patients exhibited higher [¹⁸F]-THK5351 retention in the the left inferior frontal and precentral gyri. In svPPA patients, [¹⁸F]-THK5351 retention was elevated in the anteroinferior and lateral temporal cortices compared to the NC group (left>right). The lvPPA patients exhibited predominant [¹⁸F]-THK5351 retention in the inferior parietal, lateral temporal, and dorsolateral prefrontal cortices, and the precuneus (left>right). [¹⁸F]-THK5351 retention in the left inferior frontal area was associated with lower fluency scores. Comprehension was correlated with [¹⁸F]-THK5351 retention in the left temporal cortices. Repetition was associated with [¹⁸F]-THK5351 retention in the left inferior parietal and posterior temporal areas, while naming difficulty was correlated with retention in the left fusiform and temporal cortices. Conclusions The pattern of [¹⁸F]-THK5351 retention was well matched with clinical and radiological findings for each PPA subtype, in agreement with the anatomical and functional location of each language domain.

Background/Aims Anti-C-reactive protein (CRP) antibody has been introduced as a potential biologic marker in Systemic lupus erythematosus (SLE). The aim of study is to evaluate the level of anti-CRP antibody in patients with SLE. METHODS This study investigated the relationship between levels of anti-CRP antibodies and disease activity markers, such as complement, anti-double-stranded DNA antibody, and SLE disease activity index in 34 patients with SLE. RESULTS The serum anti-CRP antibody levels of the patients with SLE were significantly higher than those of the healthy controls (11.3 ± 5.6 µg/mL vs. 9.1 ± 2.8 µg/mL). The percentages of the positive anti-CRP antibody were 52.9% in SLE and 27.8% in controls. Disease duration of SLE showed significant correlation with the anti-CRP antibody (r = 0.234, p = 0.026). However no significant relationship was observed between the levels of anti-CRP antibodies and disease activity markers. Conclusions These data show that the anti-CRP antibody levels of the patients with SLE were significantly higher than those of healthy controls. We observed that the presence of the anti-CRP anti-CRP antibody was not associated with disease activity of SLE.

The purpose of this study was the improvement and modification of the HACCP verification checklist in school foodservices. For this, the HACCP verification checklist was modified on the basis of an existing school foodservice format. The modified checklist was composed of 28 items, including CCPs (critical control points), microbial test, and other components of the HACCP system than CCPs. To confirm the suitability of the modified checklist, comparisons were made based on the microbiological quality of cooked foods, utensils, and number of aerial microbes in the working area. In this study, the applicability of the modified checklist was determined by focusing on cooked squid with seasoned fresh vegetables (Ojingeochaesomoochim). The following results were obtained from 14 schools in Changwon. The checklist scores for maintaining hot foods over or serving within 2 hours, microbial tests of drinking water, food contact surfaces and cooking utensils, monitoring tools, and usage of suitable sanitizers were 2 points each (The possible highest score is 2 points). On the contrary, the checklist score for microbial test of cooked foods was the lowest of all the items. The correlation coefficient (r) between the improved checklist and microbiological quality of cooked foods was 0.699 (P

Refractory angina pectoris is defined as angina refractory to optimal medical treatment and standard coronary revascularization procedures. Despite recent therapeutic advances, patients with refractory angina pectoris are not adequately treated. Spinal cord stimulation is a minimally invasive and reversible technique which utilizes electrical neuromodulation by means of an electrode implanted in the epidural space. It has been reported to be an effective and safe treatment for refractory angina pectoris. We report a case of spinal cord stimulation which has effectively relieved chest pain due to coronary artery disease in a 40-year-old man. This is the first report of spinal cord stimulation for treatment of refractory angina pectoris in South Korea.

BACKGROUND Curcumin has been reported to have anti-inflammatory, antioxidant, antiviral, antifungal, antitumor, and antinociceptive activity when administered systemically. We investigated the analgesic efficacy of intrathecal curcumin in a rat model of inflammatory pain. METHODS Male Sprague Dawley rats were prepared for intrathecal catheterization. Pain was evoked by injection of formalin solution (5%, 50 µl) into the hind paw. Curcumin doses of 62.5, 125, 250, and 500 µg were delivered through an intrathecal catheter to examine the flinching responses. The ED(50) values (half-maximal effective dose) with 95% confidence intervals of curcumin for both phases of the formalin test were calculated from the dose-response lines fitted by least-squares linear regression on a log scale. RESULTS In rats with intrathecal administration of curcumin, the flinching responses were significantly decreased in both phases. The slope of the regression line was significantly different from zero only in phase 2, and the ED(50) value (95% confidence interval) of curcumin was 511.4 µg (23.5-1126.5). There was no apparent abnormal behavior following the administration of curcumin. CONCLUSIONS Intrathecal administration of curcumin decreased inflammatory pain in rats, and further investigation to elucidate the precise mechanism of spinal action of curcumin is warranted.

Background: The analgesic mechanisms of cyclooxygenase (COX)-2 inhibitors have been explained mainly on the basis of the inhibition of prostaglandin biosynthesis. However, several lines of evidence suggest that their analgesic effects are mediated through serotonergic or adrenergic transmissions. We investigated the roles of these neurotransmitters in the antinociception of a selective COX-2 inhibitor at the spinal level.Methods: DUP-697, a selective COX-2 inhibitor, was delivered through an intrathecal catheter to male Sprague-Dawley rats to examine its effect on the flinching responses evoked by formalin injection into the hindpaw. Subsequently, the effects of intrathecal pretreatment with dihydroergocristine, prazosin, and yohimbine, which are serotonergic, α1 adrenergic and α2 adrenergic receptor antagonists, respectively, on the analgesia induced by DUP-697 were assessed.Results: Intrathecal DUP-697 reduced the flinching response evoked by formalin injection during phase 1 and 2. But, intrathecal dihydroergocristine, prazosin, and yohimbine had little effect on the antinociception of intrathecal DUP-697 during both phases of the formalin test. Conclusions: Intrathecal DUP-697, a selective COX-2 inhibitor, effectively relieved inflammatory pain in rats. Either the serotonergic or adrenergic transmissions might not be involved in the analgesic activity of COX-2 inhibitors at the spinal level. (Korean J Pain 2011; 24: 179-184)Key Words:analgesia, COX-2 inhibitor, inflammatory pain, mechanism, spinal cord.

Parkinson's disease (PD) is a neurodegenerative disorder resulting from the progressive loss of dopaminergic (DA) neurons in the substantia nigra (SN). In our previous study, attempts were made to directly visualize the SN and quantify the differences in shapes and boundaries of the SN between PD subjects and comparison to the normal control subjects using two-dimensional T2*-weighted 7.0-T MRI images (Cho et al., Mov Disord, accepted for publication). However, a two-dimensional analysis does not represent the entire SN. Therefore, to overcome the limitation of 2D analysis, we acquire 3D image of the SN. For this study, we scanned nine PD patients, along with nine age-matched control subjects, using a research prototype 7.0-T MRI scanner in an attempt to visualize the 3D shape of the SN and quantify differences in the volume of the SN between PD subjects and normal control subjects. The shape change of the ventrolateral boundaries of the SN in PD cases was reconfirmed in this 3D study as well as in our previous 2D study (Cho et al., Mov Disord, accepted for publication). Another interesting finding of this study was that 3D MR imaging study demonstrated the potential of the 7.0-T MRI in the quantification of volume changes in the SN. The measured correlation analyses showed that there is age-dependent correlation and substantially stronger unified Parkinson's disease rating scale motor score-dependent correlation in PD patients. These results suggest that 7.0-T 3D T2*-weighted MR imaging could provide the quantitative estimation of volume changes in the SN in PD patients in vivo for comparison with normal controls in vivo. © 2011 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 21, 253–259, 2011; (Se-Hong Oh and Hye-Jin Jeong contributed equally to this work.)

Parkinson's disease (PD) is a neurodegenerative disorder resulting from progressive loss of dopaminergic neurons in the substantia nigra (SN) pars compacta. Therefore, imaging of the SN has been regarded to hold greatest potential for use in the diagnosis of PD. At the 7.0T magnetic resonance imaging (MRI), it is now possible to delineate clearly the shapes and boundaries of the SN. We scanned eight early and two advanced PD patients, along with nine age-matched control subjects, using a 7.0T MRI in an attempt to directly visualize the SN and quantify the differences in shape and boundaries of SN between PD subjects in comparison with the normal control subjects. In the normal controls, the boundaries between the SN and crus cerebri appear smooth, and clean "arch" shapes that stretch ventrally from posterior to anterior. In contrast, these smooth and clean arch-like boundaries were lost in PD subjects. The measured correlation analyses show that, in PD patients, there is age-dependent correlation and substantially stronger UPDRS motor score-dependent correlation. These results suggest that, by using 7.0T MRI, it appears possible to use these visible and distinctive changes in morphology as a diagnostic marker of PD.

This paper proposes a novel security model for secure query processing in semantic sensor networks. A semantic sensor network (SSN) is a sensor network including semantics of sensory data and context information, and relationships between the semantics by using Semantic Web technologies. Even though much research has been activated on SSN, there is little activity on how to securely access data in semantic sensor networks. Most of storages have been developed based on relational database model and the relational database model provides a secure and robust security support. Therefore, we need to devise a security model considering such a real environment. This paper proposes a new access control model for secure query processing in semantic sensor networks. The proposed security model is based on relational database security model. This paper shows the overall framework and definitions of the proposal, and the experiment and evaluation is described to show validity of our proposal. With the experiment and evaluation, it is clear that the proposed model provides a secure access control support for SSNs.

The purpose of this research is to understand the physiological characteristics of muscular men between the ages of 20 and 34 years who are distinct from the general population due to their muscular development, and to categorize them according to upper body somatotypes. This research was conducted in order to provide basic data necessary for developing clothing products for muscular men. The research method and results were as follows: the "Sheldon`s" and "Heath-Carter" somatotype classification methods were carried out at sports centers, the Athletic College, and military bases in Seoul and Gyeonggi province. Excluding the 32 subjects that did not have a balanced mesomorph, ectomorphic mesomorph or mesomorph-ectomorph, research on the remaining 168 subjects was used in the data analysis. 2. We used the following factor analysis: factor 1 for torso size; factor 2 for upper-arm, armpit, and chest breath size; and 3. The upper body was categorized into four (4) types, and their individual characteristics were as follows: Type 1 had the most developed arms, shoulders, chest muscles, and the shortest height. These subjects had an average of 191 somatotype points and could be classified as a balanced mesomorph. The heights and the lengths of Type 2 were short. They had slim physical structures, averaged 182 somatype points, and could be classified as an ectomorphic mesomorph. somatotype points and were classified as a balanced mesomorph. The heights and the lengths of Type 4 were long. They had slim physical structures, averaged 164 somatotype points, and were classified as a balanced mesomorph-ectomorph. 4. After carrying out a discriminant analysis to validate the categories of muscular men`s upper bodies, we concluded that our model had an accuracy rating of 98.1%.

This study aims at analyzing the characteristics of muscular men's somatotype to develop their clothing pattern. The body sizes of 168 men categorized as the muscular type according to the Somatotype Classification by Sheldon and Heath-Carter, were compared with the 5th Korean body size measurement (KBSM) conducted by SizeKorea in 2003, to analyze the characteristics of muscular men's somatotype. The results are as follows: 1. Compared to the 5th KBSM, the subject's body size is higher in the Chest, Upper Arm, Calf, Hip, and Thigh Circumference, and Thigh Thickness, and Waist Back and Biacromion Length, but lower in the Waist Circumference. 2. The subject group shows the characteristics of a wedge-shaped somatotype which has a broad chest and a slim waist, and of having a back more developed, longer and more curved, compared to the non-muscular men. 3. The study shows the subject group has the characteristics of both the wedged somatotype with wide chest and slim waist, and the X somatotype with projected hips and thighs.

This paper deals with the fuzzy modeling for the complex and uncertain nonlinear systems, in which conventional and mathematical models may fail to give satisfactory results. Finally, we provide numerical examples to evaluate the feasibility and generality of the proposed method in this paper. The expert system which introduces fuzzy logic in order to process uncertainties is called fuzzy expert system. The fuzzy expert system, however, has a potential problem which may lead to inappropriate results due to the ignorance of some information by applying fuzzy logic in reasoning process in addition to the knowledge acquisition problem. In order to overcome these problems, We construct fuzzy inference network by extending the concept of reasoning network in this paper. In the fuzzy inference network, the propositions which form fuzzy rules are represented by nodes. And these nodes have the truth values representing the belief values of each proposition. The logical operators between propositions of rules are represented by links. And the traditional propagation rule is modified.

PURPOSE The purpose of this study was to evaluate the quadriceps and hamstring muscle strength and hamstring-to-quadriceps (HQ) ratio, as well as the relationships of these parameters with dynamic balance, in patients with anterior cruciate ligament (ACL) rupture. MATERIALS AND METHODS We compared 25 patients diagnosed with chronic unilateral ACL tears and 25 age-matched healthy volunteers. The maximal torque of the quadriceps and hamstring and dynamic balance were measured. RESULTS Although the isokinetic maximal peak torques were about 50% lower in the quadriceps (57%, p

Purpose This study was designed to compare the preoperative strengths and endurances of the quadriceps and hamstring muscles in patients with anterior cruciate ligament (ACL) versus posterior cruciate ligament (PCL) tears. Methods Quadriceps and hamstring muscle strength and endurance were compared between 20 prospectively enrolled patients with isolated PCL tears and a retrospective, matched control group of 20 patients with isolated ACL tears. The maximal torque (60°/s) and total work (180°/s) of the quadriceps and hamstring were evaluated with an isokinetic testing device. Results Total work (1,094.4 ± 505.8 J v 797.5 ± 332.7 J, P = .035) and peak torque (129.9 ± 56.2 N ∙ m v 98.2 ± 37.4 N ∙ m, P = .046) of the quadriceps muscle on the involved side were higher in the PCL tear group than in the ACL tear group. However, there were no significant differences between the PCL tear group and ACL tear group in hamstring muscle strength (45.8 ± 42.3 N ∙ m and 46.0 ± 24.4 N ∙ m, respectively; P = .940) and endurance (429.3 ± 238.9 J and 382.4 ± 256.1 J, respectively; P = .574) on the involved side. Conclusions The strength and endurance of the quadriceps muscle of the injured limb were greater after PCL tears than after ACL tears. However, there were no significant between-group differences in hamstring muscle strength and endurance on the involved side. Level of Evidence Level III, retrospective comparative study.

Background/Aims The aim of this study was to compare the sleep quality between rheumatoid arthritis (RA) patients and healthy controls; and to evaluate the relationship between RA disease activity and sleep quality in Korea. Methods A total of 130 RA patients and 67 age- and sex-matched healthy controls were enrolled in a comparative study of sleep quality using the Pittsburgh Sleep Quality Index (PSQI). Age, gender, concomitant medication, erythrocyte sedimentation rate, serum C-reactive protein, Beck Depression Inventory second edition (BDI-II), 28 joints disease activity score (DAS28), pain visual analog scale (VAS), and PSQI were analyzed as covariates. We also analyzed the sleep quality of RA patients according to the disease activity (DAS28 ≤ 3.2, 3.2 < DAS28 < 5.1, and DAS28 ≥ 5.1, respectively). Results The total PSQI score and the frequency of poor sleep quality, were higher in the RA patients (5.62 ± 4.19, 38.5%) than in the control subjects (3.57 ± 2.17, 13.4%). The patients with poor sleep quality (PSQI > 5) were older and had a higher BDI-II and VAS score than the patients without sleep disturbance (PSQI ≤ 5). The score in subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, daytime dysfunction, total PSQI, and frequency of poor sleep quality were increased when RA activity was high. Conclusions Sleep disturbance was observed in RA patients (38.5%), and high RA disease activity was associated with poor sleep quality in Korea.