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1.  Multi-Surface and Multi-Field Co-Segmentation of 3-D Retinal Optical Coherence Tomography 
IEEE transactions on medical imaging  2014;33(12):2242-2253.
When segmenting intraretinal layers from multiple optical coherence tomography (OCT) images forming a mosaic or a set of repeated scans, it is attractive to exploit the additional information from the overlapping areas rather than discarding it as redundant, especially in low contrast and noisy images. However, it is currently not clear how to effectively combine the multiple information sources available in the areas of overlap. In this paper, we propose a novel graph-theoretic method for multi-surface multi-field co-segmentation of intraretinal layers, assuring consistent segmentation of the fields across the overlapped areas. After 2-D en-face alignment, all the fields are segmented simultaneously, imposing a priori soft interfield-intrasurface constraints for each pair of overlapping fields. The constraints penalize deviations from the expected surface height differences, taken to be the depth-axis shifts that produce the maximum cross-correlation of pairwise-overlapped areas. The method’s accuracy and reproducibility are evaluated qualitatively and quantitatively on 212 OCT images (20 nine-field, 32 single-field acquisitions) from 26 patients with glaucoma. Qualitatively, the obtained thickness maps show no stitching artifacts, compared to pronounced stitches when the fields are segmented independently. Quantitatively, two ophthalmologists manually traced four intraretinal layers on 10 patients, and the average error (4.58±1.46 μm) was comparable to the average difference between the observers (5.86±1.72 μm). Furthermore, we show the benefit of the proposed approach in co-segmenting longitudinal scans. As opposed to segmenting layers in each of the fields independently, the proposed co-segmentation method obtains consistent segmentations across the overlapped areas, producing accurate, reproducible, and artifact-free results.
PMCID: PMC4326334  PMID: 25020067
Graph theory; image co-segmentation; mosaicing; ophthalmology; retinal layer segmentation
2.  Epithelial Adhesion Mediated by Pilin SpaC Is Required for Lactobacillus rhamnosus GG-Induced Cellular Responses 
Applied and Environmental Microbiology  2014;80(16):5068-5077.
Lactobacillus rhamnosus GG is a widely used probiotic, and the strain's salutary effects on the intestine have been extensively documented. We previously reported that strain GG can modulate inflammatory signaling, as well as epithelial migration and proliferation, by activating NADPH oxidase 1-catalyzed generation of reactive oxygen species (ROS). However, how strain GG induces these responses is unknown. Here, we report that strain GG's probiotic benefits are dependent on the bacterial-epithelial interaction mediated by the SpaC pilin subunit. By comparing strain GG to an isogenic mutant that lacks SpaC (strain GGΩspaC), we establish that SpaC is necessary for strain GG to adhere to gut mucosa, that SpaC contributes to strain GG-induced epithelial generation of ROS, and that SpaC plays a role in strain GG's capacity to stimulate extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling in enterocytes. In addition, we show that SpaC is required for strain GG-mediated stimulation of cell proliferation and protection against radiologically inflicted intestinal injury. The identification of a critical surface protein required for strain GG to mediate its probiotic influence advances our understanding of the molecular basis for the symbiotic relationship between some commensal bacteria of the gut lumen and enterocytes. Further insights into this relationship are critical for the development of novel approaches to treat intestinal diseases.
PMCID: PMC4135752  PMID: 24928883
3.  Cetaceans evolution: insights from the genome sequences of common minke whales 
BMC Genomics  2015;16(1):13.
Whales have captivated the human imagination for millennia. These incredible cetaceans are the only mammals that have adapted to life in the open oceans and have been a source of human food, fuel and tools around the globe. The transition from land to water has led to various aquatic specializations related to hairless skin and ability to regulate their body temperature in cold water.
We present four common minke whale (Balaenoptera acutorostrata) genomes with depth of ×13 ~ ×17 coverage and perform resequencing technology without a reference sequence. Our results indicated the time to the most recent common ancestors of common minke whales to be about 2.3574 (95% HPD, 1.1521 – 3.9212) million years ago. Further, we found that genes associated with epilation and tooth-development showed signatures of positive selection, supporting the morphological uniqueness of whales.
This whole-genome sequencing offers a chance to better understand the evolutionary journey of one of the largest mammals on earth.
Electronic supplementary material
The online version of this article (doi:10.1186/s12864-015-1213-1) contains supplementary material, which is available to authorized users.
PMCID: PMC4311506  PMID: 25609461
Cetaceans; Common minke whale; Positive selection; Genome
4.  Roles of Major Histocompatibility Complex Class II in Inducing Protective Immune Responses to Influenza Vaccination 
Journal of Virology  2014;88(14):7764-7775.
Major histocompatibility complex class II-deficient (MHC-II KO; Aβ−/−) mice were used to assess the roles of MHC-II molecules in inducing protective immune responses to vaccination. After vaccination with influenza A/PR8 virus-like particle (VLP) vaccine, in vivo and in vitro vaccine antigen-specific IgG isotype antibodies were not detected in MHC-II KO mice, which is quite different from CD4 T cell-deficient mice that induced vaccine-specific IgG antibodies. The deficiency in MHC-II did not significantly affect the induction of antigen-specific IgM antibody in sera. MHC-II KO mice that were vaccinated with influenza VLP, whole inactivated influenza virus, or live attenuated influenza virus vaccines were not protected against lethal infection with influenza A/PR8 virus. Adoptive transfer of fractionated spleen cells from wild-type mice to MHC-II KO mice indicated that CD43+ cell populations with MHC-II contributed more significantly to producing vaccine-specific IgG antibodies than CD43− B220+ conventional B cell or CD4 T cell populations, as well as conferring protection against lethal infection. Bone marrow-derived dendritic cells from MHC-II KO mice showed a significant defect in producing interleukin-6 and tumor necrosis factor alpha cytokines. Thus, results indicate that MHC-II molecules play multiple roles in inducing protective immunity to influenza vaccination.
IMPORTANCE Major histocompatibility complex class II (MHC-II) has been known to activate CD4 T helper immune cells. A deficiency in MHC-II was considered to be equivalent to the lack of CD4 T cells in developing host immune responses to pathogens. However, the roles of MHC-II in inducing protective immune responses to vaccination have not been well understood. In the present study, we demonstrate that MHC-II-deficient mice showed much more significant defects in inducing protective antibody responses to influenza vaccination than CD4 T cell-deficient mice. Further analysis showed that CD43 marker-positive immune cells with MHC-II, as well as an innate immunity-simulating adjuvant, could rescue some defects in inducing protective immune responses in MHC-II-deficient mice. These results have important implications for our understanding of host immunity-inducing mechanisms to vaccination, as well as in developing effective vaccines and adjuvants.
PMCID: PMC4097762  PMID: 24760891
5.  A Study of Mental Health Literacy Among North Korean Refugees in South Korea 
This study aimed to investigate North Korean refugees’ knowledge of mental illnesses and treatments and analyze the factors affecting this knowledge.
Subjects were selected via a snowball sampling method, and the survey outcomes of 152 North Korean refugee participants were analyzed. The factors affecting knowledge of mental illnesses were analyzed via a regression analysis by constructing a multivariate model with mental illness knowledge score as the dependent variable.
The North Korean refugees’ mental illness scores ranged from 3 to 24 points, with an average score of 13.0. Regarding the factors that influence mental illness knowledge, the subjects with South Korean spouses and those who had spent more time in South Korea had higher knowledge scores. Furthermore, the subjects who considered the mental health of North Korean refugees to be a serious issue revealed lower knowledge scores than those who did not believe it was a serious issue. The subjects who visit psychiatric clinics showed higher knowledge scores than those who do not. The South Korean subjects who had at least a college education exhibited higher scores than did those without advanced education. The subjects who are satisfied with life in South Korea manifested a higher mental illness knowledge score than those who are not.
This study is significant as being the first study to ever measure and evaluate the level of North Korean refugees’ knowledge of mental illnesses. In addition, the evaluations of North Korean refugees’ mental illness knowledge and influencing factors while residing in South Korea created basic data that formed the foundation of an effort to enhance mental health literacy and provide proper mental health services. The results of this study can be utilized to solve mental health problems that might frequently occur during the unification process of North and South Korea in the future.
PMCID: PMC4322519  PMID: 25652712
Democratic People’s Republic of Korea; Refugees; Mental health; Mental illness; Knowledge
6.  Hypoxia-Responsive MicroRNA-101 Promotes Angiogenesis via Heme Oxygenase-1/Vascular Endothelial Growth Factor Axis by Targeting Cullin 3 
Antioxidants & Redox Signaling  2014;21(18):2469-2482.
Aims: Hypoxia induces expression of various genes and microRNAs (miRs) that regulate angiogenesis and vascular function. In this study, we investigated a new functional role of new hypoxia-responsive miR-101 in angiogenesis and its underlying mechanism for regulating heme oxygenase-1 (HO-1) and vascular endothelial growth factor (VEGF) expression. Results: We found that hypoxia induced miR-101, which binds to the 3′untranslated region of cullin 3 (Cul3) and stabilizes nuclear factor erythroid-derived 2-related factor 2 (Nrf2) via inhibition of the proteasomal degradation pathway. miR-101 overexpression promoted Nrf2 nuclear accumulation, which was accompanied with increases in HO-1 induction, VEGF expression, and endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) production. The elevated NO-induced S-nitrosylation of Kelch-like ECH-associated protein 1 and subsequent induction of Nrf2-dependent HO-1 lead to further elevation of VEGF production via a positive feedback loop between the Nrf2/HO-1 and VEGF/eNOS axes. Moreover, miR-101 promoted angiogenic signals and angiogenesis both in vitro and in vivo, and these events were attenuated by inhibiting the biological activity of HO-1, VEGF, or eNOS. Moreover, these effects were also observed in aortic rings from HO-1+/− and eNOS−/− mice. Local overexpression of miR-101 improved therapeutic angiogenesis and perfusion recovery in the ischemic mouse hindlimb, whereas antagomiR-101 diminished regional blood flow. Innovation: Hypoxia-responsive miR-101 stimulates angiogenesis by activating the HO-1/VEGF/eNOS axis via Cul3 targeting. Thus, miR-101 is a novel angiomir. Conclusion: Our results provide new mechanistic insights into a functional role of miR-101 as a potential therapeutic target in angiogenesis and vascular remodeling. Antioxid. Redox Signal. 21, 2469–2482.
PMCID: PMC4245877  PMID: 24844779
7.  Body Mass Index and Depressive Symptoms in Older Adults: A Cross-Lagged Panel Analysis 
PLoS ONE  2014;9(12):e114891.
There are conflicting results about the association between body mass index (BMI) and depressive symptoms in older adults. The present study examined the relationship between weight and depressive symptoms over time in older adults in South Korea.
We used data from three waves of the Korean Longitudinal Study of Aging and ran a series of cross-lagged panel models to test the reciprocal relationship between depressive symptoms and obesity in older Korean adults. We assumed a temporally stable relationship between depressive symptoms and obesity and, thus imposed equality constraints over time.
After controlling for the effect of depressive symptoms two years prior, underweight older adults had a higher depressive symptom score than those of normal weight. When controlling for obesity status from two years prior, older adults with higher levels of depressive symptoms were more likely to be underweight and less likely to be overweight than normal weight. The same patterns were observed in data from 2006 to 2008 and from 2008 to 2010.
These results show that there is a correlation between depressive symptoms and weight status. In middle-aged and elderly Asian populations, depression can lead to weight loss rather than obesity, and underweight may develop depressive symptoms.
PMCID: PMC4263712  PMID: 25501372
8.  Mucosal Adjuvants for Influenza Virus-Like Particle Vaccine 
Viral Immunology  2013;26(6):385-395.
To find an effective mucosal adjuvant for influenza virus-like particles (VLPs), we compared the effects of known adjuvants Alum, CpG DNA, monophosphoryl lipid A (MPL), poly IC, gardiquimod, and cholera toxin (CT). Mice that were intranasally immunized with Alum, CpG, MPL, and CT adjuvanted VLPs showed higher levels of antibodies in both sera and mucosa. Hemagglutination inhibition and virus neutralizing activities were enhanced in groups adjuvanted with Alum, MPL, or CT. Influenza virus specific long-lived cells secreting IgG and IgA antibodies were found at high levels both in bone marrow and spleen in the Alum, CpG and CT adjuvanted groups. A similar level of protection was observed among different adjuvanted groups, except the CT adjuvant that showed a higher efficacy in lowering lung viral loads after challenge. Alum and CT adjuvants differentially increased influenza VLP-mediated activation of dendritic cells and splenocytes in vitro, supporting the in vivo pattern of antibody isotypes and cytokine production. These results suggest that Alum, MPL, or CpG adjuvants, which have been tested clinically, can be developed as an effective mucosal adjuvant for influenza VLP vaccines.
PMCID: PMC3868302  PMID: 24236855
9.  Acid-degradable Core-shell Nanoparticles for Reversed Tamoxifen-resistance in Breast Cancer by Silencing Manganese Superoxide Dismutase (MnSOD) 
Biomaterials  2013;34(38):10228-10237.
Drug resistance acquired by cancer cells is a significant challenge in the clinic and requires impairing the responsible pathological pathway. Administering chemotherapeutics along with silencing resistance-basis activity using RNA interference (RNAi) is expected to restore the activity of the chemotherapeutic. generate synergistic cancer eradication. This study attempted to reverse tamoxifen (TAM)-resistance in breast cancer by silencing a mitochondrial enzyme, manganese superoxide dismutase (MnSOD), which dismutates TAM-induced reactive oxygen species (ROS) (i.e., superoxide) to less harmful hydrogen peroxide and hampers therapeutic effects. Breast cancer cells were co-treated with TAM and MnSOD siRNA-delivering nanoparticles (NPs) made of a siRNA/poly(amidoamine) (PAMAM) dendriplex core and an acid-degradable polyketal (PK) shell. The (siRNA/PAMAM)-PK NPs were designed for the PK shell to shield siRNA from nucleases, minimize detrimental aggregation in serum, and facilitate cytosolic release of siRNA from endosomal compartments. This method of forming the PK shell around the siRNA/PAMAM core via surface-initiated photo-polymerization enables ease of tuning NPs’ size for readily controlled siRNA release kinetics. The resulting NPs were notably homogenous in size, resistant to aggregation in serum, and invulnerable to heparan sulfate-mediated disassembly, compared to siRNA/PAMAM dendriplexes. Gel electrophoresis and confocal microscopy confirmed efficient siRNA release from the (siRNA/PAMAM)-PK NPs upon stimuli-responsive hydrolysis of the PK shell. Sensitization of TAM-resistant MCF7-BK-TR breast cancer cells with (MnSOD siRNA/PAMAM)-PK NPs restored TAM-induced cellular apoptosis in vitro and significantly suppressed tumor growth in vivo, as confirmed by biochemical assays and histological observations. This study implies that combined gene silencing and chemotherapy is a promising strategy to overcoming a significant challenge in cancer therapy.
PMCID: PMC3989112  PMID: 24055523
RNA interference; drug-resistant tumor model; apoptosis; gene therapy; stimuli-responsive nanoparticles
10.  Indoor Gateball’s Influence on Life Satisfaction and the Prevention of Falls by the Elderly 
Journal of Physical Therapy Science  2014;26(12):1885-1886.
[Purpose] The purpose of this study was to investigate the effects of indoor gateball exercise on life satisfaction and the prevention of falls by the elderly. [Subjects] Sixteen elderly subjects aged 65 or more, residents in nursing care facilities, were randomly divided into two groups. [Methods] One group performed indoor gateball exercise for 30 minutes a day, five times per week. The Tetrax fall index and life satisfaction were measured before and after four weeks of gateball exercise. [Results] The indoor gate ball exercise group showed significant improvements in the fall index and life satisfaction. [Conclusion] The indoor gateball exercise used in this study should be considered as a therapeutic method for the elderly, for improving their life satisfaction and because of its effectiveness in preventing falls.
PMCID: PMC4273049  PMID: 25540489
Key wordsElderly; Fall; Life satisfaction
11.  Chemically and Biologically Synthesized CPP-Modified Gelonin for Enhanced Anti-tumor Activity 
The ineffectiveness of small molecule drugs against cancer has generated significant interest in more potent macromolecular agents. Gelonin, a plant-derived toxin that inhibits protein translation, has attracted much attention in this regard. Due to its inability to internalize into cells, however, gelonin exerts only limited tumoricidal effect. To overcome this cell membrane barrier, we modified gelonin, via both chemical conjugation and genetic recombination methods, with low molecular weight protamine (LMWP), a cell-penetrating peptide (CPP) which was shown to efficiently ferry various cargos into cells. Results confirmed that gelonin-LMWP chemical conjugate (cG-L) and recombinant gelonin-LMWP chimera (rG-L) possessed N-glycosidase activity equivalent to that of unmodified recombinant gelonin (rGel); however, unlike rGel, both gelonin-LMWPs were able to internalize into cells. Cytotoxicity studies further demonstrated that cG-L and rG-L exhibited significantly improved tumoricidal effects, with IC50 values being 120-fold lower than that of rGel. Moreover, when tested against a CT26 s.c. xenograft tumor mouse model, significant inhibition of tumor growth was observed with rG-L doses as low as 2 μg/tumor, while no detectable therapeutic effects were seen with rGel at 10-fold higher doses. Overall, this study demonstrated the potential of utilizing CPP-modified gelonin as a highly potent anticancer drug to overcome limitations of current chemotherapeutic agents.
PMCID: PMC3849409  PMID: 23973813
Gelonin; LMWP; Cell penetrating peptide; Cancer; Ribosome-inactivating protein; Toxin
12.  Trends in the Epidemiological Aspects and Mortality of Alcoholic Liver Disease in Korea in the Decade Between 2000 and 2009 
Alcohol consumption and related alcohol liver disease (ALD) have substantially increased in Korea during the last decade. The objective of this study was to evaluate the trends in the epidemiological aspects and mortality rate (MR) of Korea in the decade between 2000 and 2009.
The raw data analyzed in this study were obtained from the website of “the ALD” managed by Korea Center for Disease Control and Prevention (KCDC), Korea Public Health Association (KPHA), and statistics website of Statistics Korea. The data analyses were performed using Excel 2007 statistical software (Microsoft Corp., USA).
The amount of alcohol-consumption-per-capita-per-year (ACCY) in Korea was 8.38 L in 2000 and 8.54 L in 2009. The most taken alcoholic beverage was soju, followed by beer. There were a total of 1,403 case-fatalities (CF) with an MR of 2.98 per 100,000 populations of ALD in 2000, while a total of 3,588 CF with an MR of 7.21 in 2009 (P < 0.01). The CF and MR of ALD in males were significantly higher than those in females (P < 0.01). In over 40-year-old age groups, the CF and MR were significantly increased (P < 0.01). Moreover, occupational classification revealed that the mistress/students/jobless (MSJ) were the most risky group. The comparison of overall CF and MR of ALD by six key classifications (International Classification of Diseases (ICD)) showed that alcoholic cirrhosis (229 CF and 16.3%) in 2000 tended to be increased in 2009 (2,803 CF and 78.1%), while alcoholic fibrosis and sclerosis (607 CF and 43.3%) in 2000 significantly decreased in 2009 (120 CF and 3.3%), respectively.
ALD is one of the most severe diseases in Korea, as indicated by its high CF and MR in this study. As over-consumption of alcoholic beverages is relatively common in Korea, more efforts should be made toward prevention of ALD by raising awareness of the risk factors of ALD by public health education.
PMCID: PMC4245059  PMID: 25436025
Epidemiology; ALD; Case-fatality; Mortality rate; ICD
13.  Global identification of target recognition and cleavage by the Microprocessor in human ES cells 
Nucleic Acids Research  2014;42(20):12806-12821.
The Microprocessor plays an essential role in canonical miRNA biogenesis by facilitating cleavage of stem-loop structures in primary transcripts to yield pre-miRNAs. Although miRNA biogenesis has been extensively studied through biochemical and molecular genetic approaches, it has yet to be addressed to what extent the current miRNA biogenesis models hold true in intact cells. To address the issues of in vivo recognition and cleavage by the Microprocessor, we investigate RNAs that are associated with DGCR8 and Drosha by using immunoprecipitation coupled with next-generation sequencing. Here, we present global protein–RNA interactions with unprecedented sensitivity and specificity. Our data indicate that precursors of canonical miRNAs and miRNA-like hairpins are the major substrates of the Microprocessor. As a result of specific enrichment of nascent cleavage products, we are able to pinpoint the Microprocessor-mediated cleavage sites per se at single-nucleotide resolution. Unexpectedly, a 2-nt 3′ overhang invariably exists at the ends of cleaved bases instead of nascent pre-miRNAs. Besides canonical miRNA precursors, we find that two novel miRNA-like structures embedded in mRNAs are cleaved to yield pre-miRNA-like hairpins, uncoupled from miRNA maturation. Our data provide a framework for in vivo Microprocessor-mediated cleavage and a foundation for experimental and computational studies on miRNA biogenesis in living cells.
PMCID: PMC4227787  PMID: 25326327
14.  The Use of Low Molecular Weight Protamine Chemical Chimera to Enhance Monomeric Insulin Intestinal Absorption 
Biomaterials  2013;34(31):7733-7743.
Although oral delivery of insulin offers a number of unmatched advantages, it nevertheless is beset by the poor permeability of insulin molecules through the epithelial cell membranes of the intestinal mucosal layer. We previously reported the development of low molecular weight protamine (LMWP) as a nontoxic yet potent cell penetrating peptide, of which via covalent linkage was capable of translocating protein cargos through the membranes of almost all cell types. It is therefore hypothesized that LMWP could be practically employed as a safe and effective tool to deliver insulin across the intestinal mucosal membrane, thereby augmenting its absorption through the GI tract. However, formulating 1:1 monomeric insulin/LMWP conjugate presents a tall order of challenge, as the acidic insulin and basic LMWP would automatically form tight aggregates through electrostatic interactions. In this paper, we developed an innovative conjugation strategy to solve this problem, by using succinimidyl-[(N-maleimidopropionamido)-polyethyleneglycol] ester (NHS-PEG-MAL) as an intermediate cross-linker during the coupling process. Both SDS-PAGE and MALDI-TOF mass spectroscopy confirmed the formation of a homogeneous, monomeric (1:1 ratio) insulin/LMWP conjugate without encountering the conventional problem of substrate aggregation. Cell culture studies demonstrated that transport of the Insulin-PEG-LMWP conjugate across the intestinal mucosal monolayer was augmented by almost five folds compared to native insulin. Furthermore, results from the in situ loop absorption tests in rats showed that systemic pharmacological bioavailability of insulin was significantly enhanced after its conjugation with LMWP. Overall, the presented chemical conjugation with LMWP could offer a reliable and safe means to improve the intestinal permeability of therapeutic peptides/proteins, shedding light of the possibility for their effective oral delivery.
PMCID: PMC3766633  PMID: 23863452
Cell-penetrating peptide; intestinal absorption; low molecular weight protamine; insulin; monomeric conjugation; permeation enhancement
15.  Acetabular cup positioning in revision total hip arthroplasty with Paprosky type III acetabular defects: Martell radiographic analysis 
International Orthopaedics  2013;37(10):1905-1910.
This study evaluates acetabular cup position in the setting of revision total hip arthroplasty (THA) with severe acetabular bone defects.
With a definition of safe zone of abduction (30–50°) and anteversion (5–25°), acetabular cup position was measured by a digital image analysis program for 34 patients with Paprosky type III acetabular bone defects.
There were 24 cups (71 %) for abduction and 26 cups (76 %) for anteversion located in the safe zone. Nineteen cups (56 %) were within the safe zone for both abduction and anteversion. There was no dislocation, however one cup out of the safe zone resulted in early cup failure due to aseptic loosening.
The acetabular cup positioning in patients with Paprosky type III defects was 'optimal' in half of the cases. The prevalence of optimal acetabular cup position was similar to those reported in primary THA, suggesting that the presence of a large acetabular bone defect may not be a significant risk factor for suboptimal acetabular cup positioning in the setting of revision THA.
PMCID: PMC3779547  PMID: 23881062
Total hip arthroplasty; Revision; Acetabular bone defect; Paprosky type III; Cup position; Martell technique
16.  Factors associated with self-rated health among North Korean defectors residing in South Korea 
BMC Public Health  2014;14(1):999.
The number of North Korean refugees entering South Korea has increased recently. The health status of refugees is a significant factor in determining their success in resettlement; therefore, this study examined both the self-rated health status of North Korean defectors who have settled in South Korea and the factors associated with their self-rated health status.
This study utilized data gained from face-to-face interviews with 500 North Korean defectors who arrived in South Korea in 2007. The interviews were structured and conducted by ‘Yonsei University Research Team for North Korean defectors’. A stepwise multivariable linear regression was performed to determine the factors associated with their self-rated health status.
North Korean defectors who were female, elderly, or had low annual household income, disability or chronic diseases reported lower health status. However, self-rated health status was higher among those who had settled in South Korea for 18 months or more, who were satisfied with government support or their current life, and who had experienced more traumatic events in North Korea.
Government policies and refugee assistance programs should consider and reflect the factors relevant to the health status of North Korean defectors.
PMCID: PMC4192277  PMID: 25257402
17.  Periodontal Responses to Augmented Corticotomy with Collagen Membrane Application during Orthodontic Buccal Tipping in Dogs 
BioMed Research International  2014;2014:873918.
This prospective randomized split-mouth study was performed to examine the effects of absorbable collagen membrane (ACM) application in augmented corticotomy using deproteinized bovine bone mineral (DBBM), during orthodontic buccal tipping movement in the dog. After buccal circumscribing corticotomy and DBBM grafting into the decorticated area, flaps were repositioned and sutured on control sides. ACM was overlaid and secured with membrane tacks, on test sides only, and the flaps were repositioned and sutured. Closed coil springs were used to apply 200 g orthodontic force in the buccolingual direction on the second and third premolars, immediately after primary flap closure. The buccal tipping angles were 31.19 ± 14.60° and 28.12 ± 11.48° on the control and test sides, respectively. A mean of 79.5 ± 16.0% of the buccal bone wall was replaced by new bone on the control side, and on the test side 78.9 ± 19.5% was replaced. ACM application promoted an even bone surface. In conclusion, ACM application in augmented corticotomy using DBBM might stimulate periodontal tissue reestablishment, which is useful for rapid orthodontic treatment or guided bone regeneration. In particular, ACM could control the formation of mesenchymal matrix, facilitating an even bone surface.
PMCID: PMC4174977  PMID: 25276824
18.  Increased sensitivity of glioma cells to 5-fluorocytosine following photo-chemical internalization enhanced nonviral transfection of the cytosine deaminase suicide gene 
Journal of neuro-oncology  2014;118(1):29-37.
Despite advances in surgery, chemotherapy and radiotherapy, the outcomes of patients with GBM have not significantly improved. Tumor recurrence in the resection margins occurs in more than 80 % of cases indicating aggressive treatment modalities, such as gene therapy are warranted. We have examined photochemical internalization (PCI) as a method for the non-viral transfection of the cytosine deaminase (CD) suicide gene into glioma cells. The CD gene encodes an enzyme that can convert the nontoxic antifungal agent, 5-fluorocytosine, into the chemotherapeutic drug, 5-fluorouracil. Multicell tumor spheroids derived from established rat and human glioma cell lines were used as in vitro tumor models. Plasmids containing either the CD gene alone or together with the uracil phosphoribosyl transferase (UPRT) gene combined with the gene carrier protamine sulfate were employed in all experiments. PCI was performed with the photosensitizer AlPcS2a and 670 nm laser irradiance. Protamine sulfate/CD DNA polyplexes proved nontoxic but inefficient transfection agents due to endosomal entrapment. In contrast, PCI mediated CD gene transfection resulted in a significant inhibition of spheroid growth in the presence of, but not in the absence of, 5-FC. Repetitive PCI induced transfection was more efficient at low CD plasmid concentration than single treatment. The results clearly indicate that AlPcS2a-mediated PCI can be used to enhance transfection of a tumor suicide gene such as CD, in malignant glioma cells and cells transfected with both the CD and UPRT genes had a pronounced bystander effect.
PMCID: PMC4153358  PMID: 24610460
Glioma; Gene Therapy; PDT; PCI; Cytosine deaminase; 5-FC
19.  Circumferential iris trans-illumination defects in exfoliation syndrome 
Journal of glaucoma  2013;22(7):555-558.
We identified a pattern of concentric circular transillumination defects in a few patients with exfoliation syndrome using an infrared detection system. This pattern of iris abnormality has also been observed in a mouse model of exfoliation syndrome. The objective of the current study is to determine if concentric iris transillumination defects are specific to exfoliation syndrome and may have some diagnostic utility for identifying early cases of disease.
Materials and Methods
A total of 68 volunteers from the University of Iowa Glaucoma Clinic with normal eyes (n=21) or diagnoses of either exfoliation syndrome (n=12), pigment dispersion syndrome (n=8), or primary open angle glaucoma (n=27) were enrolled in the study. The irides of these subjects were each examined by four ophthalmologists masked to their diagnosis, using infrared videography. The presence of concentric, circular transillumination defects on the videos was graded as none (grade 0), possible (grade 1), definite (grade 2), or prominent (grade 3) by four examiners. We searched for an association between the presence of concentric bands of trans-illumination and the diagnosis of exfoliation syndrome after removing the effect of different raters was evaluated using the Cochran-Mentel-Haenszel test. We performed the same analysis for pigment dispersion syndrome and for primary open angle glaucoma.
The presence of any concentric, circular iris trans-illumination defects (grades 1–3) was detected in a mean of 38% normal subjects, 35% POAG patients, 53% pigment dispersion syndrome patients, and 77% of exfoliation syndrome patients. When the frequency of concentric, circular iris transillumination (grades 1–3 pooled) was compared between each of the patient groups and normal controls, a significant difference was detected between exfoliation syndrome patients and controls (p-value = 0.000019). No significant difference was detected between POAG and controls (p=0.64) or between pigment dispersion syndrome and controls (p=0.20). Furthermore, prominent concentric, circular iris trans-illumination (grade 3) was only observed in exfoliation syndrome.
Detection of concentric, circular iris transillumination defects with an infrared system is easy, inexpensive, rapid, and relatively specific in exfoliation syndrome. Future larger studies will be needed to confirm the findings of this small pilot study. Furthermore, this examination technique has the potential to help physicians to make earlier diagnoses of exfoliation syndrome and to better plan for future surgeries to minimize risk of complication.
PMCID: PMC3502723  PMID: 22525123
exfoliation syndrome; iris transillumination defects; diagnostic sign
20.  Multiple heterologous M2 extracellular domains presented on virus-like particles confer broader and stronger M2 immunity than live influenza A virus infection 
Antiviral research  2013;99(3):328-335.
The influenza M2 ectodomain (M2e) is poorly immunogenic and has some amino acid changes among isolates from different host species. We expressed a tandem repeat construct of heterologous M2e sequences (M2e5x) derived from human, swine, and avian origin influenza A viruses on virus-like particles (M2e5x VLPs) in a membrane-anchored form. Immunization of mice with M2e5x VLPs induced protective antibodies cross-reactive to antigenically different influenza A viruses and conferred cross protection. Anti-M2e antibodies induced by heterologous M2e5x VLPs showed a wider range of cross reactivity to influenza virus at higher levels than those by live virus infection, homologous M2e VLPs, or M2e monoclonal antibody 14C2. Fc receptors were found to be important for mediating protection by immune sera from M2e5x VLP vaccination. The present study provides evidence that heterologous recombinant M2e5x VLPs can be more effective in inducing protective M2e immunity than natural virus infection and further supports an approach for developing an effective universal influenza vaccine.
PMCID: PMC3788098  PMID: 23811283
M2e VLPs; M2e cross-reactivity; cross protection
21.  Copy Number Deletion Has Little Impact on Gene Expression Levels in Racehorses 
Copy number variations (CNVs), important genetic factors for study of human diseases, may have as large of an effect on phenotype as do single nucleotide polymorphisms. Indeed, it is widely accepted that CNVs are associated with differential disease susceptibility. However, the relationships between CNVs and gene expression have not been characterized in the horse. In this study, we investigated the effects of copy number deletion in the blood and muscle transcriptomes of Thoroughbred racing horses. We identified a total of 1,246 CNVs of deletion polymorphisms using DNA re-sequencing data from 18 Thoroughbred racing horses. To discover the tendencies between CNV status and gene expression levels, we extracted CNVs of four Thoroughbred racing horses of which RNA sequencing was available. We found that 252 pairs of CNVs and genes were associated in the four horse samples. We did not observe a clear and consistent relationship between the deletion status of CNVs and gene expression levels before and after exercise in blood and muscle. However, we found some pairs of CNVs and associated genes that indicated relationships with gene expression levels: a positive relationship with genes responsible for membrane structure or cytoskeleton and a negative relationship with genes involved in disease. This study will lead to conceptual advances in understanding the relationship between CNVs and global gene expression in the horse.
PMCID: PMC4150202  PMID: 25178379
Copy Number Variation; Genome-wide Expression; Horse; Thoroughbred
22.  Neurological Outcome after Surgical Treatment of Intramedullary Spinal Cord Tumors 
Korean Journal of Spine  2014;11(3):121-126.
Recently, surgical outcomes of patients with intramedullary spinal cord tumors (IMSCT) have been improved due to advances of medicine. The purposes of our study were to evaluate the recent neurological outcomes after surgical treatment of IMSCTs.
We retrospectively reviewed 69 patients who underwent surgical treatment for IMSCT in our hospital between 1998 and 2013. Patient's age, sex, histological origin and grade, tumor location, tumor extension, preoperative neurological state, initial presenting symptom, and extend of tumor resection were analyzed to evaluate predictive factors that affect postoperative functional outcome.
The neurological states at last follow-up were improved in 16 patients (23.2%), unchanged in 47 (68.1%), aggravated in 6 (8.7%). In all patients, the functional outcomes were good in 52 patients (75.4%), fair in 10 (14.5%), poor in 7 (10.1%). Preoperative good neurological state was the strongest positive predictor of good functional outcome (p<0.05). In tumor location, functional outcomes of thoracic tumors were poor than those in cervical and conus medullaris region (p=0.011). High-grade tumor shows poor outcome compare to low-grade tumor (p=0.03).
The most reliable predicting factor of surgical outcome was the preoperative neurological state. In addition, IMSCTs in thoracic region and high-grade tumor showed relatively bad outcome and had a risk of postoperative morbidity.
PMCID: PMC4206956  PMID: 25346757
Intramedullary spinal cord tumor; Outcome; Predictors
23.  Central Decompressive Laminoplasty for Treatment of Lumbar Spinal Stenosis : Technique and Early Surgical Results 
Lumbar spinal stenosis is a common degenerative spine disease that requires surgical intervention. Currently, there is interest in minimally invasive surgery and various technical modifications of decompressive lumbar laminectomy without fusion. The purpose of this study was to present the author's surgical technique and results for decompression of spinal stenosis.
The author performed surgery in 57 patients with lumbar spinal stenosis between 2006 and 2010. Data were gathered retrospectively via outpatient interviews and telephone questionnaires. The operation used in this study was named central decompressive laminoplasty (CDL), which allows thorough decompression of the lumbar spinal canal and proximal two foraminal nerve roots by undercutting the lamina and facet joint. Kyphotic prone positioning on elevated curvature of the frame or occasional use of an interlaminar spreader enables sufficient interlaminar working space. Pain was measured with a visual analogue scale (VAS). Surgical outcome was analyzed with the Oswestry Disability Index (ODI). Data were analyzed preoperatively and six months postoperatively.
The interlaminar window provided by this technique allowed for unhindered access to the central canal, lateral recess, and upper/lower foraminal zone, with near-total sparing of the facet joint. The VAS scores and ODI were significantly improved at six-month follow-up compared to preoperative levels (p<0.001, respectively). Excellent pain relief (>75% of initial VAS score) of back/buttock and leg was observed in 75.0% and 76.2% of patients, respectively.
CDL is easily applied, allows good field visualization and decompression, maintains stability by sparing ligament and bony structures, and shows excellent early surgical results.
PMCID: PMC4217056  PMID: 25368762
Spinal stenosis; Decompression; Laminoplasty; Facet joint; Stability
24.  Long-Term Clinical and Radiologic Outcomes of Minimally Invasive Posterior Cervical Foraminotomy 
To report long-term clinical and radiological outcomes of minimally invasive posterior cervical foraminotomy (MI-PCF) performed in patients with unilateral single-level cervical radiculopathy.
Of forty-six patients who underwent MI-PCF for unilateral single-level radiculopathy between 2005 and 2013, 33 patients were included in the study, with a mean follow-up of 32.7 months. Patients were regularly followed for clinical and radiological assessment. Clinical outcome was measured by visual analogue scale (VAS) for the neck/shoulder and arm, and the neck disability index (NDI). Radiological outcome was measured by focal/global angulation and disc height index (DHI). Outcomes after MI-PCF were evaluated as changes of clinical and radiological parameters from the baseline. Mixed effect model with random patients' effect was used to test for differences in the clinical and radiological parameters repeat measures.
There were no complications and all patients had an uneventful recovery during the early postoperative period. VAS scores for neck/shoulder and arm improved significantly in the early postoperative period (3 months) and were maintained with time (p<0.001). NDI improved significantly post-operatively and tended to decrease gradually during the follow-up period (p<0.001). There were no statistically significant changes in focal and global angulation at follow-up. Percent DHIs of the upper adjacent or operated disc were maintained without significant changes with time. During the follow-up, same site recurrence was not noted and adjacent segment disease requiring additional surgery occurred in two patients (6%) on the contra-lateral side.
MI-PCF provides long-term pain relief and functional restoration, accompanied by good long-term radiological outcome.
PMCID: PMC4217059  PMID: 25368765
Cervical spine; Foraminotomy; Surgical procedures; Minimally invasive; Radiculopathy; Patient outcome assessment
25.  Spatial patterns, ecological niches, and interspecific competition of avian brood parasites: inferring from a case study of Korea 
Ecology and Evolution  2014;4(18):3689-3702.
Since obligate avian brood parasites depend completely on the effort of other host species for rearing their progeny, the availability of hosts will be a critical resource for their life history. Circumstantial evidence suggests that intense competition for host species may exist not only within but also between species. So far, however, few studies have demonstrated whether the interspecific competition really occurs in the system of avian brood parasitism and how the nature of brood parasitism is related to their niche evolution. Using the occurrence data of five avian brood parasites from two sources of nationwide bird surveys in South Korea and publically available environmental/climatic data, we identified their distribution patterns and ecological niches, and applied species distribution modeling to infer the effect of interspecific competition on their spatial distribution. We found that the distribution patterns of five avian brood parasites could be characterized by altitude and climatic conditions, but overall their spatial ranges and ecological niches extensively overlapped with each other. We also found that the predicted distribution areas of each species were generally comparable to the realized distribution areas, and the numbers of individuals in areas where multiple species were predicted to coexist showed positive relationships among species. In conclusion, despite following different coevolutionary trajectories to adapt to their respect host species, five species of avian brood parasites breeding in South Korea occupied broadly similar ecological niches, implying that they tend to conserve ancestral preferences for ecological conditions. Furthermore, our results indicated that contrary to expectation interspecific competition for host availability between avian brood parasites seemed to be trivial, and thus, play little role in shaping their spatial distributions and ecological niches. Future studies, including the complete ranges of avian brood parasites and ecological niches of host species, will be worthwhile to further elucidate these issues.
PMCID: PMC4224541  PMID: 25478158
Avian brood parasitism; Cuculus; ecological niche; interspecific competition; spatial distribution; species distribution modeling

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