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To study the role of sclerostin in periodontal ligament (PDL) as a homeostatic regulator in biophysical-force-induced tooth movement (BFTM).BFTM was performed in rats, followed by microarray, immunofluorescence, in situ hybridization, and real-time polymerase chain reaction for the detection and identification of the molecules. The periodontal space was analysed via micro-computed tomography. Effects on osteoclastogenesis and bone resorption were evaluated in the bone-marrow-derived cells in mice. In vitro human PDL cells were subjected to biophysical forces.In the absence of BFTM, sclerostin was hardly detected in the periodontium except in the PDL and alveolar bone in the furcation region and apex of the molar roots. However, sclerostin was up-regulated in the PDL in vivo by adaptable force, which induced typical transfiguration without changes in periodontal space as well as in vitro PDL cells under compression and tension. In contrast, the sclerostin level was unaffected by heavy force, which caused severe degeneration of the PDL and narrowed periodontal space. Sclerostin inhibited osteoclastogenesis and bone resorption, which corroborates the accelerated tooth movement by the heavy force.Sclerostin in PDL may be a key homeostatic molecule in the periodontium and a biological target for the therapeutic modulation of BFTM.

Objectives The patent linkage system upgraded patent challenges to an important factor in granting timely market approval for generic drugs. We aim to understand patent challenges and identify the factors that are associated with successful patent challengers under the patent linkage system in South Korea. Methods We constructed a novel dataset that combined information on manufacturers with detailed data about their patent challenges after introduction of the patent linkage system. Based on the number of successful patent challenges, manufacturers were categorized into non-challengers, passive challengers, and aggressive challengers. Then, two types of logistic models were applied to identify the factors associated with successful and aggressive challengers. Findings Only 39 active ingredients were challenged by 77 manufacturers from March 2015 to December 2019. Of 171 manufacturers, 94 (55 %) were non-challengers, 58 (34 %) were passive challengers who had succeeded in fewer than 4 patent challenges, and 19 (11 %) were aggressive challengers who had succeeded in 4 or more patent challenges. Higher sales, more employees, and a greater number of reimbursed drugs were associated with being a patent challenger, while a greater number of reimbursed drugs was associated with being an aggressive challenger. Conclusion Some manufacturers utilize patent challenges to strengthen their product portfolios in the market. However, under the patent linkage system, the frequency of patent challenges is limited in South Korea compared to the United States. In particular, patent challenges against drugs in injection form and biologics are very rare.

Aim We aimed to identify a key molecule that maintains periodontal tissue homeostasis during biophysical force-induced tooth movement (BTM) by orchestrating alveolar bone (AB) remodelling. Materials and methods Differential display-PCR was performed to identify key molecules for BTM in rats. To investigate the localization and expression of the identified molecules, immunofluorescence, real-time RT-PCR and Western blotting were performed in rats and human periodontal ligament (PDL) cells. Functional test and micro-CT analysis were performed to examine the in vivo effects of the identified molecules on BTM. Results Secretory leucocyte peptidase inhibitor (SLPI) in the PDL was revealed as a key molecule for BTM-induced AB remodelling. SLPI was enhanced in the PDL under both compression and tension, and downregulated by an adenyl cyclases inhibitor. SLPI induced osteoblastogenic genes including runt-related transcription factor 2 (Runx2) and synergistically augmented tension-induced Runx2 expression. SLPI augmented mineralization in PDL cells. SLPI induced osteoclastogenic genes including receptor activator of nuclear factor kappa-Β ligand (RANKL) and synergistically augmented the compression-induced RANKL and macrophage colony-stimulating factor (MCSF) expression. Finally, the in vivo SLPI application into the AB significantly augmented BTM. Conclusions SLPI or its inhibitors might serve as a biological target molecule for therapeutic interventions to modulate BTM.

Much information is currently available for molecules in early odontogenesis, but there is limited knowledge regarding terminal cytodifferentiation of ameloblasts and odontoblasts for the determination of normal crown morphology. The present differential display PCR (DD-PCR) revealed that insulin-like growth factor-binding protein 5 (IGFBP5) was differentially expressed in molar tooth germs between the cap (before crown mineralization) and root formation (after crown mineralization) stages. Real-time PCR confirmed that the expression levels of IGFBP1-4 were not significantly changed but those of IGFBP5-7 were upregulated in a time-dependent manner. Immunoreactivities for IGFBP5-7 were hardly seen in molar germs at the cap/early bell stage and protective-stage ameloblasts at the root formation stage. However, the reactivity was strong in odontoblasts and maturation-stage ameloblasts, which are morphologically and functionally characterized by wide intercellular space and active enamel matrix mineralization. The localization of each IGFBP was temporospatial. IGFBP5 was localized in the nuclei of fully differentiated odontoblasts and ameloblasts, while IGFBP6 was localized in the apical cytoplasm of ameloblasts and odontoblasts with dentinal tubules, and IGFBP7 was mainly found in the whole cytoplasm of odontoblasts and the intercellular space of ameloblasts. IGFBP silencing using specific siRNAs upregulated representative genes for dentinogenesis and amelogenesis, such as DMP1 and amelogenin, respectively, and augmented the differentiation media-induced mineralization, which was confirmed by alizarin red s and alkaline phosphatase staining. These results suggest that IGFBP5-7 may play independent and redundant regulatory roles in late-stage odontogenesis by modulating the functional differentiation of ameloblasts and odontoblasts.

Direct reprogramming, also known as a trans-differentiation, is a technique to allow mature cells to be converted into other types of cells without inducing a pluripotent stage. It has been suggested as a major strategy to acquire the desired type of cells in cell-based therapies to repair damaged tissues. Studies related to switching the fate of cells through epigenetic modification have been progressing and they can bypass safety issues raised by the virus-based transfection methods. In this study, a protocol was established to directly convert fully differentiated fibroblasts into diverse mesenchymal-lineage cells, such as osteoblasts, adipocytes, chondrocytes, and ectodermal cells, including neurons, by means of DNA demethylation, immediately followed by culturing in various differentiating media. First, 24 h exposure of 5-azacytidine (5-aza-CN), a well-characterized DNA methyl transferase inhibitor, to NIH-3T3 murine fibroblast cells induced the expression of stem-cell markers, that is, increasing cell plasticity. Next, 5-aza-CN treated fibroblasts were cultured in osteogenic, adipogenic, chondrogenic, and neurogenic media with or without bone morphogenetic protein 2 for a designated period. Differentiation of each desired type of cell was verified by quantitative reverse transcriptase-polymerase chain reaction/ western blot assays for appropriate marker expression and by various staining methods, such as alkaline phosphatase/alizarin red S/oil red O/alcian blue. These proposed procedures allowed easier acquisition of the desired cells without any transgenic modification, using direct reprogramming technology, and thus may help make it more available in the clinical fields of regenerative medicine.

Two rigid spiro-type TADF emitters (CBZANQ, PXZANQ) were designed and synthesized via a two-step route. CBZANQ and PXZANQ both contain an anthracenone acceptor along with a carbazole‒acridine-fused donor and a phenoxazine‒acridine-fused donor, respectively, where each donor and acceptor are linked by a spiro bridge to form D-σ-A structures with an orthogonal arrangement. Both CBZANQ and PXZANQ have the difference between the singlet and triplet energy values (ΔEST) of 0.05 eV and 0.03 eV, respectively, which are sufficiently small for efficient triplet harvesting. CBZANQ with a weak electron donor (carbazole) exhibited a weak intramolecular charge transfer (ICT) character, resulting in a low photoluminescence quantum yield (PLQY) of 18%. On the other hand, when combined with a strong electron donor (phenoxazine), PXZANQ exhibited a strong ICT character, resulting in a high PLQY of 71%. Organic light-emitting diode (OLED) devices based on CBZANQ emitter and bis[2-(diphenylphosphino)phenyl] ether oxide (DPEPO) host exhibited sky-blue electroluminescence (EL) at 492 nm with a low external quantum efficiency (EQE) of 6.7%. Conversely, the OLED devices fabricated using PXZANQ emitter and DPEPO host exhibited green emission at 528 nm, along with a high EQE of 22.1%. Additionally, the efficiency of PXZANQ-based devices remained high at high luminance, indicating relatively small efficiency roll-off (13.9% EQE under 500 cd/m2).

Two twisted donor-acceptor (D-A) chemical structures, CCDMB and PCDMB, were developed as a new class of thermally activated delayed fluorescence (TADF) emitters for organic light-emitting diodes (OLEDs). Two emitters consist of 3-substituted carbazole as a first donor and trivalent boron as an electron acceptor in common, and carbazole and phenoxazine as second donors with different electron donor ability. While PCDMB with a strong phenoxazine donor decreased the lowest singlet excited state (S1) level and thus showed a small singlet-triplet energy difference (ΔEST) value of 0.13 eV, resulting in effective reverse intersystem crossing (RISC), however, CCDMB with a weak donor showed a large ΔEST value of 0.21 eV. Efficient triplet harvesting of PCDMB was confirmed by a delayed component in transient PL decay curves of 25 wt% PCDMB-doped bis[2-(diphenylphosphino)phenyl] ether oxide (DPEPO) films. OLED devices with a CCDMB emitter showed deep-blue emission with Commission Internationale de l’Eclairage (CIE) of (0.16, 0.12) but a low maximum EQE of 5.5%, indicative of insufficient triplet harvesting. PCDMB-based devices showed green emission with CIE of (0.21, 0.45) and a high maximum EQE of 22.3%. Our study revealed the effect of the electron donor ability of structurally similar emitters on ΔEST values, triplet harvesting, and device efficiency.

Background/Aims: Many chronic obstructive pulmonary disease (COPD) patients have physical limitations. We investigated EuroQol five-dimensions five-level (EQ-5D-5L) of COPD patients to assess quality of life, and assessed indirect bur den including time expenditure to visit doctor, home care rate, and caregiver re lated burden. Methods: We recruited 355 COPD patients according to severity of airflow limita tion that severity was set at 10% mild, 40% moderate, 30% severe, and 20% very severe in two primary and 11 secondary/tertiary hospitals. Eligible patients were aged ≥ 40 years, who have been diagnosed with COPD for more than 1 year. Pa tients were recruited between June 2015 and October 2016. Results: The quality of life tended to decline with age, from mild to very severe impairment, as revealed by the EQ-5D-5L scores and the EQ visual analog scale. Family caregivers accompanied 22.6% of patients who visited outpatient clinics, and 25% of stage IV COPD patients. During emergency visits and hospitalization, this figure increased to > 60%. The home care rates were 28.5% for stage I pa tients, and 34.4, 31.8, and 52% for stage II to IV patients, respectively. The percent age of caregivers who stopped working was 13.6%. The EQ-5D index was strongly associated with the dyspnea scale (r = -0.64, p < 0.001). The average required time to see a doctor and visit the pharmacy was 154 minutes. Conclusions: In patients with COPD, the EQ-5D index decreased and disease-re lated home caregiving increased with airflow limitation. We considered the care giver-related burden when making a strategy for COPD management.

Background The association between diabetes mellitus (DM) and bone diseases is acknowledged. However, the mechanistic pathways leading to the alveolar bone (AB) destruction remain unclear. This study aims to elucidate the mechanical forces (MF)-induced AB destruction in DM and its underlying mechanism. Methods In vivo periodontal tissue responses to MF were evaluated in rats with diabetes. In vitro human periodontal ligament (PDL) cells were either treated with advanced glycation end products (AGEs) alone or with AGEs and MF. Results In vivo, the transcription of VEGF-A, colony stimulating factor-1 (CSF-1), and Ager was upregulated in diabetes, whereas changes in DDOST and Glo1 mRNAs were negligible. DM induced VEGF-A protein in the vascular cells of the PDL and subsequent angiogenesis, but DM itself did not induce osteoclastogenesis. MF-induced AB resorption was augmented in DM, and such augmentation was morphologically substantiated by the occasional undermining resorption as well as the frontal resorption of the AB by osteoclasts. The mRNA levels of CSF-1 and vascular endothelial growth factor (VEGF) during MF application were highly elevated in diabetes, compared with those of the normal counterparts. In vitro, AGEs treatment elevated Glut-1 and CSF-1 mRNA levels via the p38 and JNK pathways, whereas OGT and VEGF levels remained unchanged. Compressive MF especially caused upregulation of VEGF, CSF-1, and Glut-1 levels, and such upregulation was further enhanced by AGEs treatment. Conclusions Overloaded MF and AGEs metabolites may synergistically aggravate AB destruction by upregulating CSF-1 and VEGF. Therefore, regulating the compressive overloading of teeth, as well as the levels of diabetic AGEs, may prove to be an effective therapeutic modality for managing DM-induced AB destruction.

Background: Understanding the burden of disease is important to establish cost-effective treatment strategies and to allocate healthcare resources appropriately. However, little reliable information is available regarding the overall economic burden imposed by chronic obstructive pulmonary disease (COPD) in Korea. Methods: This study is a multicenter observational research on the COPD burden in Korea. Total COPD costs were comprised of three categories: direct medical, direct non-medical, and indirect costs. For direct medical costs, institutional investigation was performed at 13 medical facilities mainly based on the claims data. For direct non-medical and indirect costs, site-based surveys were administered to the COPD patients during routine visits. Total costs were estimated using the COPD population defined in the recent report. Results: The estimated total costs were approximately 1,245 million US dollar (1,408 billion Korean won). Direct medical costs comprised approximately 20% of the total estimated costs. Of these, formal medical costs held more than 80%. As direct non-medical costs, nursing costs made up the largest percentage (39%) of the total estimated costs. Costs for COPD-related loss of productivity formed four fifths of indirect costs, and accounted for up to 33% of the total costs. Conclusion: This study shows for the first time the direct and indirect costs of COPD in Korea. The total costs were enormous, and the costs of nursing and lost productivity comprised approximately 70% of total costs. The results provide insight for an effective allocation of healthcare resources and to inform establishment of strategies to reduce national burden of COPD.

Dept. of Civil Engineering, ChungAng University, Ansung 456-756, KoreaABSTRACT This paper presents a systematic approach for estimating fragility curves and damage probability matrices for dif-ferent frequencies. Fragility curves and damage probability indicate the probabilities that a structure will sustain different degreesof damage at different ground motion levels. The seismic damages are to achieved by probabilistic evaluation because of uncer-tainty of earthquakes. In contrast to previous approaches, this paper presents a method that is based on nonlinear dynamic analysisof the structure using empirical data. This paper presents the probability of damage as a function of peak ground acceleration andestimates the probability of five damage levels for prestressed concrete (PSC) bridge pier subjected to given ground acceleration.At each level, 100 artificial earthquake motions were generated in terms of soil conditions, and nonlinear time domain analyseswas performed for the damage states of PSC bridge pier structures. These damage states are described by displacement ductilityresulting from seismic performance based on existing research results. Using the damage states and ground motion parameters, fivefragility curves for PSC bridge pier with five types of dominant frequencies were constructed assuming a log-normal distribution.The effect of dominant frequences was found to be significant on fragility curves.Keywords : fragility curve, displacement ductility, curvature ductility, frequency

Objective To determine the diameter of the crown, total crown area, individual cusp area, and occlusal table area in Korean maxillary permanent molars, as well as dental characteristics relevant to the hypocone reduction trait. Materials and methods Subjects included 121 dental school students in Korea (81 men and 40 women). A digital image analysis system was used for measurements and we relied on visual scoring to assign categories of hypocone expression. Results The mean crown dimension was larger in the first molar (M1) than in the second molar (M2). Regarding differences according to gender, the crown diameter, total crown area, and individual cusp area were significantly larger in the men than in the women. The mean occlusal table area ratios were 61% for M1 and 57% for M2, and these ratios increased in proportion to the total crown area. With respect to the hypocone and other features of the maxillary molars, differences between the men and women were more prominent for M1 than for M2. The M2 hypocone tended to be smaller than the M1 hypocone, and hypocone reduction was inversely related to the cusp area of the protocone. The protocone area may be considered a reliable parameter for comparing race and/or gender differences in maxillary molars. Conclusion This study concerning characteristics of the maxillary molar occlusal surface in Koreans provides useful information for comparative studies among human races.

The recent developments in performance-based guidelines were triggered by the necessity to develop assessment criteria for existing structures. Thus, safety assessment of such structures necessitated the commitment to various hazards level and performance objectives. Near fault ground motion (NFGM) is a single long period velocity pulse of large magnitude. These earthquakes have caused severe and impulsive damage on various infrastructures when the epicenter is close to the urban area. These characteristics are unique compared to the far-fault ground motion (FFGM), upon which nearly seismic design criteria are based. The objective of this study is to explore the shaking responses of reinforced concrete bridge piers and to assess their seismic safety using the capacity spectrum analysis. The seismic performance of two RC bridge piers under NFGM’s and FFGM’s was investigated on the shake table. In addition, comparative tests were made for RC bridge piers subjected to Pseudo-dynamic loadings and Quasi-Static loadings. Test results showed that NFGM generally induced worse seismic performance than FFGM.

Near fault ground motion (NFGM) is a single long period velocity pulse of large magnitude. These earthquakes have caused severe and impulsive damage on various infrastructures because the epicentre is close to the urban area. These characteristics are unique compared to the far-fault ground motion (FFGM), upon which nearly all seismic design criteria are based. The objective of this study is to explore the shake table response of reinforced concrete bridge piers and to investigate near-fault ground motion effects on reinforced concrete bridge piers compared to those by the far fault ground motion. The seismic performance of two RC bridge piers under near-fault and far fault ground motions was investigated on the shake table. In addition, comparative tests were made for RC bridge piers subjected to Pseudo-dynamic loadings and Quasi-Static loadings. Test results showed that NFGM generally induced worse seismic performance than FFGM.

A rare case of spinal epidural granulocytic sarcoma (GS) preceding acute myelogenous leukemia is described. A 10-year-old boy presented with lower leg weakness. The initial diagnosis was a histiocytic lymphoma, and he was treated accordingly. No evidence of bone marrow involvement was found at that time. The correct diagnosis of epidural GS was made possible in retrospect by using immunoperoxidase staining for lysozyme fourteen months later when the patient showed the full-blown features of leukemia. This rare tumor should be considered in the differential diagnosis of an epidural mass with cord compression in patients with or even without acute leukemia, because early diagnosis followed by appropriate combined chemotherapy and radiation may obviate surgical intervention and eventually prevent leukemic transformation.

Determining the current status of therapeutic results of acute lymphoblastic leukemia (ALL), and identifying the important clinical predictors of survival and relapse are essential for establishing therapeutic strategies. Sixty-two children with ALL who were admitted to Chonnam University Hospital from January 1983 to June 1991 were studied. With a mean follow-up period of 53.7 months, the overall 5-year survival rate (5YSR) was 46.1%. The overall rate of 5-year event-free survival (EFS) was 25.4% and significantly differed between risk groups: 48.7% for standard, 16.3% for high, and 12.5% for very high (p < .05). Overall 4-year survival after initial relapse was 34.2% and there was no significant difference in survival between those who relapsed during maintenance therapy and those who relapsed after completing maintenance. The Cox proportional hazards model identified central nervous system (CNS) irradiation (P < 0.001) as having the most important influence upon EFS, followed by serum alanine aminotransferase level, platelet level, and age. On the other hand, CNS leukemia at diagnosis, followed by mediastinal mass, and hemoglobin level were found to be the most important prognostic predictors for relapse. On the basis that present results differ from those of developed countries, we suggest the necessity of a nation-wide cohort study to delineate the characteristics of Korean ALL in children, to make our own protocols, and ultimately to improve the therapeutic outcome.