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1.  Test-retest reliability of the safe driving behavior measure for community-dwelling elderly drivers 
Journal of Physical Therapy Science  2016;28(6):1716-1719.
[Purpose] The Safe Driving Behavior Measure (SDBM) is a self-report measurement tools that assesses the safe-driving behaviors of the elderly. The purpose of this study was to evaluate the test-retest reliability of the SDBM among community-dwelling elderly drivers. [Subjects and Methods] A total of sixty-one community-dwelling elderly were enrolled to investigate the reliability of the SDBM. The SDBM was assessed in two sessions that were conducted three days apart in a quiet and well-organized assessment room. That test-retest reliability of overall scores and three domain scores of the SDBM were statistically evaluated using intraclass correlation coefficients [ICC (2.1)]. Pearson correlation coefficients were used to quantify bivariate associations among the three domains of the SDBM. [Results] The SDBM demonstrated excellent rest-retest reliability for community-dwelling elderly drivers. The Cronbach alpha coefficients of the three domains of person-vehicle (0.979), person-environment (0.944), and person-vehicle-environment (0.971) of the SDBM indicate high internal consistency. [Conclusion] The results of this study suggest that the SDBM is a reliable measure for evaluating the safe- driving of automobiles by community-dwelling elderly, and is adequate for detecting changes in scores in clinical settings.
PMCID: PMC4932042  PMID: 27390401
Automobile driving; Community-dwelling; Elderly
2.  The effects of mental practice on unilateral neglect in patients with chronic stroke: a randomized controlled trial 
Journal of Physical Therapy Science  2015;27(12):3803-3805.
[Purpose] This study aims to investigate the effects of mental practice on unilateral neglect in patients with chronic stroke. [Subjects] The subjects of this study included 30 patients with chronic unilateral neglect. [Methods] The subjects were randomly divided into either the experimental group (EG) or control group (CG). All subjects received a standard rehabilitation program. In addition to the standard rehabilitation, the EG subjects received mental practice (5 days a week for 4 weeks) for 10 minutes. To compare two groups, line bisection test (LBT) and star cancellation test (SCT) were conducted. [Results] Both groups showed significant improvement in the LBT and SCT. There were statistically significant differences in the changes in LBT, but there were no significant differences in the changes in the SCT between both groups. [Conclusion] This study demonstrated that mental practice may be a valuable additional rehabilitation method in the chronic stage of neglect.
PMCID: PMC4713795  PMID: 26834356
Mental practice; Stroke; Unilateral neglect
3.  Ovarian Clear Cell Carcinoma Sub-Typing by ARID1A Expression 
Yonsei Medical Journal  2016;58(1):59-66.
Loss of AT-rich DNA-interacting domain 1A (ARID1A) has been identified as a driving mutation of ovarian clear cell carcinoma (O-CCC), a triple-negative ovarian cancer that is intermediary between serous and endometrioid subtypes, in regards to molecular and clinical behaviors. However, about half of O-CCCs still express BAF250a, the protein encoded by ARID1A. Herein, we aimed to identify signatures of ARID1A-positive O-CCC in comparison with its ARID1A-negative counterpart.
Materials and Methods
Seventy cases of O-CCC were included in this study. Histologic grades and patterns of primary tumor, molecular marker immunohistochemistry profiles, and clinical outcomes were analyzed.
Forty-eight (69%) O-CCCs did not express BAF250a, which were designated as "ARID1A-negative." The other 22 (31%) O-CCCs were designated as "ARID1A-positive." ARID1A-positive tumors were more likely to be histologically of high grades (41% vs. 10%, p=0.003), ERβ-positive (45% vs. 17%, p=0.011), and less likely to be HNF1β-positive (77% vs. 96%, p=0.016) and E-cadherin-positive (59% vs. 83%, p=0.028) than ARID1A-negative tumors. Patient age, parity, tumor stage were not significantly different in between the two groups. Cancer-specific survival was not significantly different either.
We classified O-CCCs according to ARID1A expression status. ARID1A-positive O-CCCs exhibited distinct immunohistochemical features from ARID1A-negative tumors, suggesting a different underlying molecular event during carcinogenesis.
PMCID: PMC5122653  PMID: 27873496
Adenocarcinoma, clear cell; ovarian neoplasms; AT rich interactive domain 1A (SWI- like), human; estrogen receptor 2 (ER beta), human; endometriosis; prognosis
4.  Transcriptome Analysis of the Small Brown Planthopper, Laodelphax striatellus Carrying Rice stripe virus 
The Plant Pathology Journal  2013;29(3):330-337.
Rice stripe virus (RSV), the type member of the genus Tenuivirus, transmits by the feeding behavior of small brown planthopper (SBPH), Laodelphax striatellus. To investigate the interactions between the virus and vector insect, total RNA was extracted from RSV-viruliferous SBPH (RVLS) and non-viruliferous SBPH (NVLS) adults to construct expressed sequence tag databases for comparative transcriptome analysis. Over 30 million bases were sequenced by 454 pyrosequencing to construct 1,538 and 953 of isotigs from the mRNA of RVLS and NVLS, respectively. The gene ontology (GO) analysis demonstrated that both libraries have similar GO structures, however, the gene expression pattern analysis revealed that 17.8% and 16.8% of isotigs were up- and down-regulated significantly in the RVLS, respectively. These RSV-dependently regulated genes possibly have important roles in the physiology of SBPH, transmission of RSV, and RSV and SBPH interaction.
PMCID: PMC4174806  PMID: 25288960
Laodelphax striatellus; Rice stripe virus; small brown planthopper; tenuivirus; transcriptome
5.  Bumblebee Venom Serine Protease Increases Fungal Insecticidal Virulence by Inducing Insect Melanization 
PLoS ONE  2013;8(4):e62555.
Insect-killing (entomopathogenic) fungi have high potential for controlling agriculturally harmful pests. However, their pathogenicity is slow, and this is one reason for their poor acceptance as a fungal insecticide. The expression of bumblebee, Bombus ignitus, venom serine protease (VSP) by Beauveria bassiana (ERL1170) induced melanization of yellow spotted longicorn beetles (Psacothea hilaris) as an over-reactive immune response, and caused substantially earlier mortality in beet armyworm (Spodopetra exigua) larvae when compared to the wild type. No fungal outgrowth or sporulation was observed on the melanized insects, thus suggesting a self-restriction of the dispersal of the genetically modified fungus in the environment. The research is the first use of a multi-functional bumblebee VSP to significantly increase the speed of fungal pathogenicity, while minimizing the dispersal of the fungal transformant in the environment.
PMCID: PMC3633896  PMID: 23626832
6.  Pulmonary Leukocytoclastic Vasculitis as an Initial Presentation of Myelodysplastic Syndrome 
Systemic vasculitis involving the lung is a rare manifestation of myelodysplastic syndrome (MDS), and secondary vasculitis is considered to have poor prognosis. A 44-year-old man presented with fever and dyspnea of 1 month duration. A chest radiograph revealed bilateral multiple wedge shaped consolidations. In addition, the results of a percutaneous needle biopsy for non-resolving pneumonia were compatible with pulmonary vasculitis. Bone marrow biopsy was performed due to the persistence of unexplained anemia and the patient was diagnosed with MDS. We reported a case of secondary vasculitis presenting as non-resolving pneumonia, later diagnosed as paraneoplastic syndrome of undiagnosed MDS. The cytopenia and vasculitis improved after a short course of glucocorticoid treatment, and there was no recurrence despite the progression of underlying MDS.
PMCID: PMC5077735  PMID: 27790283
Myelodysplastic Syndromes; Vasculitis, Leukocytoclastic, Cutaneous; Paraneoplastic Syndromes; Pneumonia
7.  Comparison of a Hemorrhoidectomy With Ultrasonic Scalpel Versus a Conventional Hemorrhoidectomy 
Annals of Coloproctology  2016;32(3):111-116.
A variety of instruments, including circular staplers, ultrasonic scalpels, lasers, and bipolar electrothermal devices, are currently used when performing a hemorrhoidectomy. This study compared outcomes between hemorrhoidectomies performed with an ultrasonic scalpel and conventional methods.
The study was a randomized prospective review of data available between May 2013 and December 2013, involving 50 patients who had undergone a hemorrhoidectomy for grade III or IV internal hemorrhoids. The hemorrhoidal pedicle was coagulated with an ultrasonic device in the ultrasonic scalpel group (n = 25) and sutured with 3-0 vicryl material after excision in the conventional method group (n = 25).
The patients' demographics, clinical characteristics, and lengths of hospital stay were similar in both groups. The mean ages of the conventional and the ultrasonic scalpel groups were, respectively, 20.8 ± 1.6 and 22.4 ± 5.0 years (P = 0.240). In comparison with the conventional method group, the ultrasonic scalpel group had a shorter operation time (P < 0.005), less postoperative pain on the visual analogue scale score (for example, P = 0.211 on postoperative day 1), and less postoperative bleeding (P = 0.034). No significant differences in postoperative complications were observed between the 2 groups.
A hemorrhoidectomy using an ultrasonic scalpel is an effective and safe procedure. The ultrasonic scalpel reduces the operation time, the postoperative blood loss, and the postoperative pain. Long-term follow-up with larger-scale studies is required to evaluate normal activity after a hemorrhoidectomy performed with an ultrasonic scalpel.
PMCID: PMC4942526  PMID: 27437393
Hemorrhoidectomy; Ultrasonic scalpel; Conventional method
8.  Transcriptome-wide analysis of compression-induced microRNA expression alteration in breast cancer for mining therapeutic targets 
Oncotarget  2016;7(19):27468-27478.
Tumor growth–generated mechanical compression may increase or decrease expression of microRNAs, leading to tumor progression. However, little is known about whether mechanical compression induces aberrant expression of microRNAs in cancer and stromal cells. To investigate the relationship between compression and microRNA expression, microRNA array analysis was performed with breast cancer cell lines and cancer-associated fibroblasts (CAFs) exposed to different compressive conditions. In our study, mechanical compression induced alteration of microRNA expression level in breast cancer cells and CAFs. The alteration was greater in the breast cancer cells than CAFs. Mechanical compression mainly induced upregulation of microRNAs rather than downregulation. In a parallel mRNA array analysis, more than 25% of downregulated target genes were functionally involved in tumor suppression (apoptosis, cell adhesion, and cell cycle arrest), whereas generally less than 15% were associated with tumor progression (epithelial-mesenchymal transition, migration, invasion, and angiogenesis). Of all cells examined, MDA-MB-231 cells showed the largest number of compression-upregulated microRNAs. miR-4769-5p and miR-4446-3p were upregulated by compression in both MDA-MB-231 cells and CAFs. Our results suggest that mechanical compression induces changes in microRNA expression level, which contribute to tumor progression. In addition, miR-4769-5p and miR-4446-3p may be potential therapeutic targets for incurable cancers, such as triple negative breast cancer, in that this would reduce or prevent downregulation of tumor-suppressing genes in both the tumor and its microenvironment simultaneously.
PMCID: PMC5053664  PMID: 27027350
compression; microRNA; transcriptome; breast cancer; incurable cancer therapy
9.  A study on effects of backrest thickness on the upper arm and trunk muscle load during wheelchair propulsion 
Journal of Physical Therapy Science  2016;28(5):1493-1495.
[Purpose] The purpose of this study was to investigate the effects of the thickness of a wheelchair backrest provided for support and comfort on upper arm and trunk muscle load during wheelchair propulsion by using accelerometers. [Subjects and Methods] The Fourteen healthy participants were enrolled in this study. The study compared effects of three backrest conditions including no pad, a 3-cm-thick lumbar pad, and a 6-cm-thick lumbar pad. The instruments used for measurement were used two accelerometers. The participants were asked to propel their wheelchairs, which had been equipped with two accelerometers, 30 times. [Results] The intensity of muscle movement with the 3-cm-thick lumbar pad was significantly lower than the intensities with no lumbar pad and the 6-cm-thick lumbar pad. The muscle intensity did not differ significantly between the no pad and 6-cm-thick lumbar pad conditions. [Conclusion] An appropriately thick backrest has good effects on upper arm and trunk muscles during wheelchair propulsion. In the future, we must consider the appropriate backrest thickness for providing wheelchair users with a comfortable wheelchair.
PMCID: PMC4905896  PMID: 27313357
Accelerometer; Backrest; Wheelchair
10.  Estrogen Receptor Status Predicts Late-Onset Skeletal Recurrence in Breast Cancer Patients 
Medicine  2016;95(8):e2909.
Estrogen receptor-positive (ER+) breast cancer (BCa) often recurs after long latency, and is known to favor bone as a metastatic site. We hypothesized that skeletal recurrence of ER+ BCa follows a different chronological pattern from that of nonskeletal recurrence.
We retrospectively evaluated 434 matched pairs of ER+ and ER− female patients who underwent surgery for clinically localized BCa between 2005 and 2009. Patient age, tumor size, lymph node involvement, and adjuvant treatment biases were adjusted by the propensity score method. We conducted competing risk analysis to determine the prognostic significance of ER expression status on the risk of overall recurrence and late recurrence (after 3 years). We also compared chronological patterns of ER+ and ER− tumor recurrence, stratified by the first metastatic site (skeletal vs nonskeletal).
After 3 postoperative years, ER+ tumor had a significantly higher risk of overall distant recurrence than ER− tumor (P = 0.02). When further stratified by first site of metastasis, only late skeletal recurrence was significantly associated with ER status (P = 0.029). In multivariate analysis, ER and lymph node involvement status were significant prognostic factors for late skeletal recurrence, with adjusted hazard ratios of 5.2 (95% CI = 1.2–22.4, P = 0.025) and 5.2 (1.7–16.3, P = 0.005), respectively. For nonskeletal distant recurrence, tumor size (>2 cm) was the only significant risk factor with adjusted hazard ratio of 2.8 (1.4–5.7, P = 0.005). Annual hazard of skeletal recurrence events of ER+ tumors continued to exist up to 10 years, while annual hazard of nonskeletal recurrences decreased after peaking at 5 years. ER− tumor recurrences exhibited similar annual hazard patterns across skeletal and nonskeletal sites.
ER expression and lymph node involvement status were strong predictors of BCa late-onset (>3 years) recurrences, especially in skeletal sites. Therefore, skeletal system surveillance is mandatory for long-term follow-up of this subpopulation.
PMCID: PMC4779030  PMID: 26937933
11.  The frequency of and risk factors for osteoporosis in Korean patients with rheumatoid arthritis 
The aim of this study was to investigate the prevalence of osteoporosis in rheumatoid arthritis (RA) patients and to analyze the risk factors in these patients using the KORean Observational study Network for Arthritis (KORONA) database.
Among the RA patients in the KORONA who were recruited between July 2009 and December 2011, postmenopausal women with bone mineral density (BMD) results within one year from the time of KORONA enrollment were included in this study. The baseline characteristics of patients in three groups, defined by BMD results, were compared. The BMD measurement rates and prevalence of osteoporosis in the study patients were calculated in accordance with age and gender subgroups. Multivariable logistic regression analysis was used to explore the association between osteoporosis and demographics and disease-related risk factors.
Of 1322 postmenopausal woman patients with RA in whom BMD was measured within one year of study enrollment, 619 patients (46.8 %) were in the osteoporosis group (T-score ≤ −2.5 SD). RA patients with osteoporosis had a higher frequency of previous fractures than those in other groups, especially fractures of the femur (p = 0.004) and wrist (p = 0.042). Advanced age (≥70 years; OR = 2.28, 95 % CI: 1.40–3.58), lower body mass index (<25; OR = 2.14, 95 % CI:1.52–3.02), longer disease duration (≥10 years; OR = 1.46, 95 % CI: 1.07–2.00), higher cumulative glucocorticoid dose (OR = 1.03, 95 % CI: 1.01–1.05), and higher Health Assessment Questionnaire score (OR = 1.37, 95 % CI:1.11–1.69) were independent risk factors for osteoporosis.
A large percentage (90.8 %) of RA patients enrolled in the KORONA cohort had osteoporosis and osteopenia. Nevertheless, BMD measurement rates in this population remained low, despite high risk groups of fractures.
PMCID: PMC4765070  PMID: 26912147
Osteoporosis; Rheumatoid arthritis; Frequency; Risk factors
13.  Association between genetic polymorphisms in cortactin and susceptibility to gastric cancer 
Overexpression of cortactin (CTTN) in human tumors has been proposed to result in increased cell migration and metastatic potential. Here, we determined the frequencies of CTTN g.-9101C>T, g.-8748C>T, and g.72C>T polymorphisms in apparently healthy subjects and gastric cancer patients, respectively, and the influence of the CTTN polymorphisms on gastric cancer susceptibility.
Blood samples were collected from 267 patients and 533 controls. CTTN g.-8748C>T and g.-9101C>T polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism; the g.72C>T polymorphism was determined using the TaqMan method.
Genotype frequencies of the CTTN g.-9101C>T polymorphism were 97.5% (TT), 2.5% (TC), and 0% (CC) in the patient group, and 98.6% (TT), 1.4% (TC), and 0% (CC) in the control group. Genotype frequencies of the CTTN g.-8748C>T polymorphism were 93.3% (TT), 6.8% (TC), and 0% (CC) in the patient group, and 94.2% (TT), 5.8% (TC), and 0% (CC) in the control group. Genotype frequencies of the CTTN g.72C>T polymorphism were 82.4% (CC), 17.2% (CT), and 0.4% (TT) in the patient group, and 78.0% (CC), 20.1% (CT), and 1.9% (TT) in the control group. Genotype and allele frequencies of the CTTN g.-9101C>T polymorphism differed significantly between the advanced gastric cancer and control groups. Patients with advanced gastric cancer, possessing the TC genotype, had a significantly poorer prognosis than the group with the TT genotype.
The CTTN g.-9101C>T polymorphism might influence advanced gastric cancer susceptibility. However, the role of the CTTN g.-9101C>T, g.-8748C>T, and g.72C>T polymorphisms requires careful interpretation and confirmation through larger studies.
PMCID: PMC4518033  PMID: 26236696
Human CTTN protein; Genetic polymorphism; Stomach neoplasms
15.  Application of a Novel Diagnostic Rule in the Differential Diagnosis between Acute Gouty Arthritis and Septic Arthritis 
Journal of Korean Medical Science  2015;30(6):700-704.
Septic arthritis and gout are major diseases that should be suspected in patients with acute monoarthritis. These two diseases are clinically similar and often indistinguishable without the help of synovial fluid analysis. Recently, a novel diagnostic rule for gout without synovial fluid analysis was developed and showed relevant performances. This study aimed to determine whether this diagnostic rule could perform well in distinguishing gout from septic arthritis. The diagnostic rule comprises 7 clinical and laboratory variables, each of which is given a specified score. The probability of gout is classified into 3 groups according to the sum of the scores: high (≥ 8), intermediate (> 4 to < 8) and low probability (≤ 4). In this retrospective study, we applied this diagnostic rule to 136 patients who presented as acute monoarthritis and were subsequently diagnosed as acute gout (n = 82) and septic arthritis (n = 54) based on synovial fluid analysis. The mean sum of scores of acute gout patients was significantly higher than that of those with septic arthritis (8.6 ± 0.2 vs. 3.6 ± 0.32, P < 0.001). Patients with acute gout had significantly more 'high', and less 'low' probabilities compared to those with septic arthritis (Eta[η]: 0.776). The prevalence of acute gouty arthritis, as confirmed by the presence of monosodium crystal, was 95.5% (61/64), 57.5% (19/33), and 5.1% (2/39) in high, intermediate and low probability group, respectively. The recently introduced diagnostic rule properly discriminates acute gout from septic arthritis. It may help physicians diagnose gout in cases difficult to be differentiated from septic arthritis.
Graphical Abstract
PMCID: PMC4444468  PMID: 26028920
Gout; Arthritis, Infectious; Diagnosis, Differential; Diagnostic Test
16.  Effects of chewing gum on driving performance as evaluated by the STISIM driving simulator 
Journal of Physical Therapy Science  2015;27(6):1823-1825.
[Purpose] The purpose of this study was to determine the effects of chewing gum on driving performance in a driving simulator. [Subjects] In total, 26 young licensed drivers participated. [Methods] The driving scenario was typical of an urban environment: a single-carriageway, two-way road consisting of a mix of curved and straight sections, with considerable levels of traffic, pedestrians, and parked cars. Mean distance driven above the speed limit, lane position, mean distance driven across the center line, and mean distance driven off the road were used as estimates of brake, accelerator, and steering control. The results were compared with those of a non-chewing gum control condition. [Results] The driving performance while chewing gum was significantly better: the mean distance driven above the speed limit was 26.61% shorter, and the mean distance driven off the road was 31.99% shorter. Lane position and mean distance driven across the center line did not differ significantly between the two conditions. [Conclusion] Chewing gum appears to enhance driving performance during a sustained attention driving task.
PMCID: PMC4499992  PMID: 26180329
Attention; Driver; Performance
17.  Targeted sequencing with enrichment PCR: a novel diagnostic method for the detection of EGFR mutations 
Oncotarget  2015;6(15):13742-13749.
Epidermal growth factor receptor (EGFR) is an important mediator of tumor cell survival and proliferation. The detection of EGFR mutations can predict prognoses and indicate when treatment with EGFR tyrosine kinase inhibitors should be used. As such, the development of highly sensitive methods for detecting EGFR mutations is important. Targeted next-generation sequencing is an effective method for diagnosing mutations. We compared the abilities of enrichment PCR followed by ultra-deep pyrosequencing (UDP), UDP alone, and PNA-mediated RT-PCR clamping to detect low-frequency EGFR mutations in tumor cell lines and tissue samples. Using enrichment PCR-UDP, we were able to detect the E19del and L858R mutations at minimum frequencies of 0.01% and 0.05%, respectively, in the PC-9 and H197 tumor cell lines. We also confirmed the sensitivity of detecting the E19del mutation by performing a titration analysis in FFPE tumor samples. The lowest mutation frequency detected was 0.0692% in tissue samples. EGFR mutations with frequencies as low as 0.01% were detected using enrichment PCR-UDP, suggesting that this method is a valuable tool for detecting rare mutations, especially in scarce tissue samples or those with small quantities of DNA.
PMCID: PMC4537046  PMID: 25915533
Enrichment ultra-deep pyrosequencing; EGFR mutation; lung cancer; diagnostic technique
18.  Sensitivity of the accelerometer as a measurement tool for upper extremity movement by stroke patients: a comparison with the action research arm test 
Journal of Physical Therapy Science  2015;27(4):1053-1054.
[Purpose] This study investigated the sensitivity of an accelerometer in a comparison with the Action Research Arm Test (ARAT). [Subjects] Fifteen stroke patients participated in this study. [Methods] Subjects wore accelerometers on both wrists and performed the ARAT items. We then compared the data measured by the accelerometer with that of the ARAT. [Results] ARAT scores were higher on the non-affected side than the affected side, while the amount of upper extremity movement was higher on the affected side. The correlation coefficients for the two tools were not significantly different. [Conclusion] Our findings indicate that an accelerometer is a useful and sensitive instrument for clinically measuring the upper extremity activity of patients with stroke.
PMCID: PMC4433975  PMID: 25995554
Accelerometer; Action Research Arm Test; Stroke
19.  RNA-Dependent RNA Polymerase (NIb) of the Potyviruses Is an Avirulence Factor for the Broad-Spectrum Resistance Gene Pvr4 in Capsicum annuum cv. CM334 
PLoS ONE  2015;10(3):e0119639.
Potyviruses are one of the most destructive viral pathogens of Solanaceae plants. In Capsicum annuum landrace CM334, a broad-spectrum gene, Pvr4 is known to be involved in resistance against multiple potyviruses, including Pepper mottle virus (PepMoV), Pepper severe mosaic virus (PepSMV), and Potato virus Y (PVY). However, a potyvirus avirulence factor against Pvr4 has not been identified. To identify the avirulence factor corresponding to Pvr4 in potyviruses, we performed Agrobacterium-mediated transient expressions of potyvirus protein coding regions in potyvirus-resistant (Pvr4) and -susceptible (pvr4) pepper plants. Hypersensitive response (HR) was observed only when a RNA-dependent RNA polymerase (NIb) of PepMoV, PepSMV, or PVY was expressed in Pvr4-bearing pepper leaves in a genotype-specific manner. In contrast, HR was not observed when the NIb of Tobacco etch virus (TEV), a virulent potyvirus, was expressed in Pvr4-bearing pepper leaves. Our results clearly demonstrate that NIbs of PepMoV, PepSMV, and PVY serve as avirulence factors for Pvr4 in pepper plants.
PMCID: PMC4356556  PMID: 25760376
20.  Seasonality of Gout in Korea: A Multicenter Study 
Journal of Korean Medical Science  2015;30(3):240-244.
The object of this study was to evaluate the seasonality of gout in Korea. We retrospectively examined data from 330 patients seen at nine rheumatology clinics, treated with urate lowering therapy (ULT) more than one year after stopping prophylactic medication. Demographic data, clinical and laboratory features, and seasonality of gout onset and flares were collected. Season was classified in three-month intervals. The mean age was 52.2 yr and mean disease duration was 26.8 months. The male to female count was 318:12. The onset of acute gouty attacks was obtained in 256 patients. Gout developed most commonly in summer season (36.7%) (P<0.001) and in June (15.6%, P=0.002). During ULT, there were 147 (male 97.3%) gout flares. Although there was no statistically significant difference, gout flares were more common in summer (30.6%). Aggravating factors were identified in 57 flares: alcohol (72.0%) was most common. In the patients who attained target serum uric acid (<6 mg/dL) at the end of prophylaxis, gout flares were high in fall (35.8%) and September (17.0%). In Korea, the summer is most common season of gout onset and there is a tendency for gout flares to increase during ULT in summer/fall season.
Graphical Abstract
PMCID: PMC4330476  PMID: 25729244
Gout Onset; Flares; Seasonality; Summer; Korea
21.  Genetic and Epigenetic Regulation in Age-related Macular Degeneration 
Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the older population worldwide. While strong genetic risk factors have been associated with AMD etiology, environmental influences through epigenetic regulation are also likely to play a role. Recent advances in epigenetic studies have resulted in the development of numerous epigenetic drugs for the treatment of cancer and inflammation. Here, we review the current literature on the genetic and epigenetic mechanisms of AMD and suggest that understanding the cooperation of epigenetic and genetic mechanisms will greatly advance the clinical management of AMD.
PMCID: PMC3755470  PMID: 23997991
22.  Are glucocorticoid-induced osteoporosis recommendations sufficient to determine antiosteoporotic treatment for patients with rheumatoid arthritis? 
We investigated differences in identifying candidates for antiosteoporotic treatment in rheumatoid arthritis (RA) patients according to two available clinical guidelines.
We prospectively enrolled 100 female patients aged 50 years or older with RA who visited Hanyang University Hospital for periodic examinations between April 2011 and August 2011. We applied the glucocorticoid-induced osteoporosis (GIOP) recommendations and the National Osteoporosis Foundation (NOF) guidelines to RA patients and examined agreement between the guidelines for identifying candidates for antiosteoporotic treatment. We also analyzed the impact of screening vertebral fractures (VFs) in determining the treatment of osteoporosis in RA patients.
The 57 patients taking glucocorticoids were classified into high-risk (n = 23), medium-risk (n = 16), and low-risk (n = 18) groups according to the GIOP recommendations. Based on the NOF guidelines, 36 of 57 patients were candidates for antiosteoporotic treatment and the agreement between two guidelines was high (κ = 0.76). Two of the 18 patients in the low-risk group and 19 of 43 patients not eligible per the GIOP recommendations were classified as candidates for antiosteoporotic treatment by the NOF guidelines.
In determining antiosteoporotic treatment for RA patients, using only the GIOP recommendations is insufficient. Application of the NOF guidelines in patients not eligible for or classified into the low-risk group per the GIOP recommendations and screening for VFs may be helpful in deciding on antiosteoporotic treatment in RA patients.
PMCID: PMC4101598  PMID: 25045299
Glucocorticoids; Osteoporosis; Arthritis, rheumatoid; Guideline
23.  The Influence of Vertebral Fracture on the Functional Disability of Patients with Rheumatoid Arthritis 
Journal of Korean Medical Science  2014;29(6):859-863.
The aim of the present study was to identify the influence of vertebral fracture (VF) on the functional disability in patients with rheumatoid arthritis (RA). This study consecutively enrolled 100 female patients aged 50 yr or older with RA. All participants underwent lateral imaging of the thoracolumbar spine by simple radiography to identify any VFs. They also completed questionnaires via interview regarding demographics, medical history, and disease outcomes including functional disability. We used univariate analysis to evaluate associations between functional disability and VF, and made multivariate logistic regression models to test independent effect of the presence of VF, the number of VFs, and the severity of VF on functional disability. Among the 100 RA patients, 47 had at least one VF, but 34 of them were asymptomatic that they had experienced a fracture. The multiple VFs ≥ 3 (OR, 8.95; 95% CI, 1.77-44.15, P = 0.01) and moderate or severe VF (OR, 3.38; 95% CI, 1.26-9.04, P = 0.02) were related to disability in univariate analysis. The multiple VFs ≥ 3 (OR, 6.13; 95% CI, 1.02-36.94, P = 0.048) was associated with functional disability of RA patients after adjusting various confounders and it was mainly in walking and arising. The VF might be an important factor which affects functional disability in RA patients.
Graphical Abstract
PMCID: PMC4055822  PMID: 24932090
Arthritis, Rheumatoid; Spinal Fractures; Health Assessment Questionaire
24.  Notch Intracellular Domain Expression in Various Skin Fibroproliferative Diseases 
Annals of Dermatology  2014;26(3):332-337.
The effects of the Notch signaling pathway in fibroproliferative skin diseases have not been fully elucidated.
The aim of this study was to investigate the expression of activated Notch signaling molecules in various skin fibroproliferative diseases.
Immunohistochemical analysis of Notch intracellular domain (NICD) expression in keloid, hypertrophic scar, morphea, dermatofibroma, and normal control skin specimens was performed, and the clinical characteristics of patients with various skin fibroproliferative diseases were analyzed.
NICD was highly expressed in fibroblasts of keloids and moderately to highly expressed in hypertrophic scars and dermatofibromas, whereas low or no expression was detected in the fibroblasts of normal skin specimens and morpheas. NICD was constitutively expressed in keratinocytes, endothelial cells, and immune cells in normal skin specimens.
NICD was significantly expressed in human fibroproliferative skin disorders, especially keloids, suggesting that an activated Notch signaling pathway is involved in the pathogenesis of skin fibrosis.
PMCID: PMC4069643  PMID: 24966632
Benign fibrous histiocytoma; Hypertrophic cicatrix; Keloid; Localized scleroderma; Notch receptors
25.  The Autographa californica Multiple Nucleopolyhedrovirus ORF78 Is Essential for Budded Virus Production and General Occlusion Body Formation 
Journal of Virology  2013;87(15):8441-8450.
ORF78 (ac78) of Autographa californica multiple nucleopolyhedrovirus (AcMNPV) is a baculovirus core gene of unknown function. To determine the role of ac78 in the baculovirus life cycle, an AcMNPV mutant with ac78 deleted, Ac78KO, was constructed. Quantitative PCR analysis revealed that ac78 is a late gene in the viral life cycle. After transfection into Spodoptera frugiperda cells, Ac78KO produced a single-cell infection phenotype, indicating that no infectious budded viruses (BVs) were produced. The defect in BV production was also confirmed by both viral titration and Western blotting. However, viral DNA replication was unaffected, and occlusion bodies were formed. An analysis of BVs and occlusion-derived viruses (ODVs) revealed that AC78 is associated with both forms of the virions and is an envelope structural protein. Electron microscopy revealed that AC78 also plays an important role in the embedding of ODV into the occlusion body. The results of this study demonstrate that AC78 is a late virion-associated protein and is essential for the viral life cycle.
PMCID: PMC3719795  PMID: 23698311

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