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1.  mAChRs activation induces epithelial-mesenchymal transition on lung epithelial cells 
Background
Epithelial-mesenchymal transition (EMT) has been proposed as a mechanism in the progression of airway diseases and cancer. Here, we explored the role of acetylcholine (ACh) and the pathway involved in the process of EMT, as well as the effects of mAChRs antagonist.
Methods
Human lung epithelial cells were stimulated with carbachol, an analogue of ACh, and epithelial and mesenchymal marker proteins were evaluated using western blot and immunofluorescence analyses.
Results
Decreased E-cadherin expression and increased vimentin and α-SMA expression induced by TGF-β1 in alveolar epithelial cell (A549) were significantly abrogated by the non-selective mAChR antagonist atropine and enhanced by the acetylcholinesterase inhibitor physostigmine. An EMT event also occurred in response to physostigmine alone. Furthermore, ChAT express and ACh release by A549 cells were enhanced by TGF-β1. Interestingly, ACh analogue carbachol also induced EMT in A549 cells as well as in bronchial epithelial cells (16HBE) in a time- and concentration-dependent manner, the induction of carbachol was abrogated by selective antagonist of M1 (pirenzepine) and M3 (4-DAMP) mAChRs, but not by M2 (methoctramine) antagonist. Moreover, carbachol induced TGF-β1 production from A549 cells concomitantly with the EMT process. Carbachol-induced EMT occurred through phosphorylation of Smad2/3 and ERK, which was inhibited by pirenzepine and 4-DAMP.
Conclusions
Our findings for the first time indicated that mAChR activation, perhaps via M1 and M3 mAChR, induced lung epithelial cells to undergo EMT and provided insights into novel therapeutic strategies for airway diseases in which lung remodeling occurs.
doi:10.1186/1471-2466-14-53
PMCID: PMC3975135  PMID: 24678619
Epithelial-mesenchymal transition (EMT); Lung epithelial cells; Non-neuronal cholinergic system; Signaling pathway
2.  APPROXIMATE SAMPLING FORMULAS FOR GENERAL FINITE-ALLELES MODELS OF MUTATION 
Advances in applied probability  2012;44(2):408-428.
Many applications in genetic analyses utilize sampling distributions, which describe the probability of observing a sample of DNA sequences randomly drawn from a population. In the one-locus case with special models of mutation such as the infinite-alleles model or the finite-alleles parent-independent mutation model, closed-form sampling distributions under the coalescent have been known for many decades. However, no exact formula is currently known for more general models of mutation that are of biological interest. In this paper, models with finitely-many alleles are considered, and an urn construction related to the coalescent is used to derive approximate closed-form sampling formulas for an arbitrary irreducible recurrent mutation model or for a reversible recurrent mutation model, depending on whether the number of distinct observed allele types is at most three or four, respectively. It is demonstrated empirically that the formulas derived here are highly accurate when the per-base mutation rate is low, which holds for many biological organisms.
doi:10.1239/aap/1339878718
PMCID: PMC3953561  PMID: 24634516
Sampling probability; coalescent theory; urn models; martingale
3.  Impact of Clinical Performance Examination on Incoming Interns' Clinical Competency in Differential Diagnosis of Headache 
Background
In Korea, clinical performance examination (CPX) has been included in license examination for medical doctors since 2009 in order to improve clinical performance of medical students. This study aimed to evaluate the contribution of CPX to medical education.
Methods
Clinical competency in the differential diagnosis of secondary headache was compared between the incoming interns in 2009 unexposed to CPX and the incoming interns in 2010 exposed to CPX, using the data of patients who visited the emergency department due to headache (181 patients seen by 60 CPX non-exposed interns and 150 patients seen by 50 CPX-exposed interns). We obtained the data by reviewing electronic medical records and nominal lists of doctors. Clinical competency was assessed by sensitivity and specificity between the diagnostic impression by interns and the final diagnosis. The association between CPX exposure and clinical competency in secondary headache diagnosis was evaluated using multiple logistic regression analysis.
Results
When we assessed clinical competency on the basis of all listed diagnostic impressions, sensitivity and specificity were 67.9% and 80.0%, respectively, for headaches seen by CPX-exposed interns, and 51.7%, and 71.7%, respectively, for headaches seen by CPX non-exposed interns. Multivariable adjusted logistic regression analysis showed exposure to CPX was not associated with increased competency for identifying secondary headache.
Conclusion
Exposure to CPX as a part of the medical license examination was not effective for the improvement of clinical competency of interns in identifying secondary headache.
doi:10.4082/kjfm.2014.35.2.56
PMCID: PMC3978186  PMID: 24724000
Competency-Based Education; Clinical Performance Examination; Headache; Internship and Residency; Medical Student
4.  Validation and Reliability of a Smartphone Application for the International Prostate Symptom Score Questionnaire: A Randomized Repeated Measures Crossover Study 
Background
Smartphone-based assessment may be a useful diagnostic and monitoring tool for patients. There have been many attempts to create a smartphone diagnostic tool for clinical use in various medical fields but few have demonstrated scientific validity.
Objective
The purpose of this study was to develop a smartphone application of the International Prostate Symptom Score (IPSS) and to demonstrate its validity and reliability.
Methods
From June 2012 to May 2013, a total of 1581 male participants (≥40 years old), with or without lower urinary tract symptoms (LUTS), visited our urology clinic via the health improvement center at Soonchunhyang University Hospital (Republic of Korea) and were enrolled in this study. A randomized repeated measures crossover design was employed using a smartphone application of the IPSS and the conventional paper form of the IPSS. Paired t test under a hypothesis of non-inferior trial was conducted. For the reliability test, the intraclass correlation coefficient (ICC) was measured.
Results
The total score of the IPSS (P=.289) and each item of the IPSS (P=.157-1.000) showed no differences between the paper version and the smartphone version of the IPSS. The mild, moderate, and severe LUTS groups showed no differences between the two versions of the IPSS. A significant correlation was noted in the total group (ICC=.935, P<.001). The mild, moderate, and severe LUTS groups also showed significant correlations (ICC=.616, .549, and .548 respectively, all P<.001).There was selection bias in this study, as only participants who had smartphones could participate.
Conclusions
The validity and reliability of the smartphone application version were comparable to the conventional paper version of the IPSS. The smartphone application of the IPSS could be an effective method for measuring lower urinary tract symptoms.
doi:10.2196/jmir.3042
PMCID: PMC3936272  PMID: 24513507
smartphone; International Prostate Symptom Score; lower urinary tract symptoms; health survey; questionnaires
5.  Complement component 3 inhibition by an antioxidant is neuroprotective after cerebral ischemia and reperfusion in mice 
Journal of neurochemistry  2012;124(4):523-535.
Oxidative stress after stroke is associated with the inflammatory system activation in the brain. The complement cascade, especially the degradation products of complement component 3, is a key inflammatory mediator of cerebral ischemia. We have shown that proinflammatory complement component 3 is increased by oxidative stress after ischemic stroke in mice using DNA array. In this study, we investigated whether up-regulation of complement component 3 is directly related to oxidative stress after transient focal cerebral ischemia in mice and oxygen-glucose deprivation in brain cells. Persistent up-regulation of complement component 3 expression was reduced in copper/zinc-superoxide dismutase transgenic mice, and manganese-superoxide dismutase knockout mice showed highly increased complement component 3 levels after transient focal cerebral ischemia. Antioxidant N-tert-butyl-α-phenylnitrone treatment suppressed complement component 3 expression after transient focal cerebral ischemia. Accumulation of complement component 3 in neurons and microglia was decreased by N-tert-butyl-α-phenylnitrone, which reduced infarct volume and impaired neurological deficiency after cerebral ischemia and reperfusion in mice. Small interfering RNA specific for complement component 3 transfection showed a significant increase in brain cells viability after oxygen-glucose deprivation. Our study suggests that the neuroprotective effect of antioxidants through complement component 3 suppression is a new strategy for potential therapeutic approaches in stroke.
doi:10.1111/jnc.12111
PMCID: PMC3557607  PMID: 23199288
antioxidant; complement component 3; focal cerebral ischemia; oxidative stress
6.  An explicit transition density expansion for a multi-allelic Wright-Fisher diffusion with general diploid selection 
Characterizing time-evolution of allele frequencies in a population is a fundamental problem in population genetics. In the Wright-Fisher diffusion, such dynamics is captured by the transition density function, which satisfies well-known partial differential equations. For a multi-allelic model with general diploid selection, various theoretical results exist on representations of the transition density, but finding an explicit formula has remained a difficult problem. In this paper, a technique recently developed for a diallelic model is extended to find an explicit transition density for an arbitrary number of alleles, under a general diploid selection model with recurrent parent-independent mutation. Specifically, the method finds the eigenvalues and eigenfunctions of the generator associated with the multi-allelic diffusion, thus yielding an accurate spectral representation of the transition density. Furthermore, this approach allows for efficient, accurate computation of various other quantities of interest, including the normalizing constant of the stationary distribution and the rate of convergence to this distribution.
doi:10.1016/j.tpb.2012.10.006
PMCID: PMC3568258  PMID: 23127866
7.  Tractography of the Brainstem in Major Depressive Disorder Using Diffusion Tensor Imaging 
PLoS ONE  2014;9(1):e84825.
Background
The brainstem is the main region that innervates neurotransmitter release to the Hypothalamic-Pituitary Adrenal (HPA) axis and fronto-limbic circuits, two key brain circuits found to be dysfunctional in Major Depressive Disorder (MDD). However, the brainstem’s role in MDD has only been evaluated in limited reports. Using Diffusion Tensor Imaging (DTI), we investigated whether major brainstem white matter tracts that relate to these two circuits differ in MDD patients compared to healthy controls.
Methods
MDD patients (n = 95) and age- and gender-matched controls (n = 34) were assessed using probabilistic tractography of DTI to delineate three distinct brainstem tracts: the nigrostriatal tract (connecting brainstem to striatum), solitary tract (connecting brainstem to amygdala) and corticospinal tract (connecting brainstem to precentral cortex). Fractional anisotropy (FA) was used to measure the white matter integrity of these tracts, and measures were compared between MDD and control participants.
Results
MDD participants were characterized by a significant and specific decrease in white matter integrity of the right solitary tract (p<0.009 using independent t-test), which is a “bottom up” afferent pathway that connects the brainstem to the amygdala. This decrease was not related to symptom severity.
Conclusions
The results provide new evidence to suggest that structural connectivity between the brainstem and the amygdala is altered in MDD. These results are interesting in light of predominant theories regarding amygdala-mediated emotional reactivity observed in functional imaging studies of MDD. The characterization of altered white matter integrity in the solitary tract in MDD supports the possibility of dysfunctional brainstem-amygdala connectivity impacting vulnerable circuits in MDD.
doi:10.1371/journal.pone.0084825
PMCID: PMC3897382  PMID: 24465436
8.  Association between the hemodialysis adequacy and sexual dysfunction in chronic renal failure: a preliminary study 
BMC Urology  2014;14:4.
Background
The core question of the study was whether adequately achieved HD affected the sexual dysfunction in women on hemodialysis (HD) with chronic renal failure (CRF).
Methods
Thirty-seven female patients on HD, including 18 women with adequate HD and 19 women with non-adequate HD, and 36 healthy controls were included in this study. Demographic and clinical variables, including the sexual hormones estradiol and testosterone, were recorded. Sexual function was assessed according to the Female Sexual Function Index (FSFI) and results were compared between groups. Adequate HD was defined as an average urea clearance of over 1.3 (Kt/V) over three consecutive months.
Results
All domains of the FSFI questionnaire, with the exception of satisfaction, were higher in the control group than in the HD group. In comparing the adequate and non-adequate HD groups, there was no difference in any of the six domains of the FSDI questionnaire. Among the clinical variables, the number of menopausal women was higher in the HD group than in the control group (P = 0.023). Estradiol and testosterone levels were higher in the control group than in the HD group (P = 0.003, 0.027, respectively). The number of menopausal women and estradiol and testosterone levels showed no differences between the adequate and non-adequate HD groups. Correlation analysis between Kt/V and FSFI showed no significant relationship, but estrogen did show a significant relationship with FSFI (correlation coefficient = 0.399, P = 0.001).
Conclusions
HD adequacy alone does not have a significant impact on sexual dysfunction. Other treatments options should be considered to treat sexual dysfunction in women with CRF.
doi:10.1186/1471-2490-14-4
PMCID: PMC3925321  PMID: 24401120
Hemodialysis; Hemodialysis adequacy; Urea clearance; Female; Sexual dysfunction
9.  Correction: The Influence of Relatives on the Efficiency and Error Rate of Familial Searching 
PLoS ONE  2014;9(1):10.1371/annotation/2544c2e3-0065-4d14-ab1c-3d3fcb0fee84.
doi:10.1371/annotation/2544c2e3-0065-4d14-ab1c-3d3fcb0fee84
PMCID: PMC3883487
10.  A New Anti-c-Met Antibody Selected by a Mechanism-Based Dual-Screening Method: Therapeutic Potential in Cancer 
Molecules and Cells  2012;34(6):523-529.
c-Met, the high affinity receptor for hepatocyte growth factor (HGF), is one of the most frequently activated tyrosine kinases in many human cancers and a target for cancer therapy. However, inhibitory targeting of c-Met with antibodies has proven difficult, because most antibodies have intrinsic agonist activity. Therefore, the strategy for reducing the agonism is critical for successful development of cancer therapies based on anti-c-Met antibodies. Here we developed a mechanism-based assay method for rapid screening of anti-c-Met antibodies, involving the determination of Akt phosphorylation and c-Met degradation for agonism and efficacy, respectively. Using the method, we identified an antibody, F46, that binds to human c-Met with high affinity (Kd = 2.56 nM) and specificity, and induces the degradation of c-Met in multiple cancer cells (including MKN45, a gastric cancer cell line) with minimal activation of c-Met signaling. F46 induced c-Met internalization in both HGF-dependent and HGF-independent cells, suggesting that the degradation of c-Met results from antibody-mediated receptor internalization. Further-more, F46 competed with HGF for binding to c-Met, resulting in the inhibition of both HGF-mediated invasion and angiogenesis. Consistently, F46 inhibited the proliferation of MKN45 cells, in which c-Met is constitutively activated in an HGF-independent manner. Xenograft analysis revealed that F46 markedly inhibits the growth of subcutaneously implanted gastric and lung tumors. These results indicate that F46, identified by a novel mechanism-based assay, induces c-Met degradation with minimal agonism, implicating a potential role of F46 in therapy of human cancers.
doi:10.1007/s10059-012-0194-z
PMCID: PMC3887825  PMID: 23180291
Akt; anti-c-Met antibody; cancer therapy; c-Met; HGF
11.  Excess Winter Mortality and Cold Temperatures in a Subtropical City, Guangzhou, China 
PLoS ONE  2013;8(10):e77150.
Background
A significant increase in mortality was observed during cold winters in many temperate regions. However, there is a lack of evidence from tropical and subtropical regions, and the influence of ambient temperatures on seasonal variation of mortality was not well documented.
Methods
This study included 213,737 registered deaths from January 2003 to December 2011 in Guangzhou, a subtropical city in Southern China. Excess winter mortality was calculated by the excess percentage of monthly mortality in winters over that of non-winter months. A generalized linear model with a quasi-Poisson distribution was applied to analyze the association between monthly mean temperature and mortality, after controlling for other meteorological measures and air pollution.
Results
The mortality rate in the winter was 26% higher than the average rate in other seasons. On average, there were 1,848 excess winter deaths annually, with around half (52%) from cardiovascular diseases and a quarter (24%) from respiratory diseases. Excess winter mortality was higher in the elderly, females and those with low education level than the young, males and those with high education level, respectively. A much larger winter increase was observed in out-of-hospital mortality compared to in-hospital mortality (45% vs. 17%). We found a significant negative correlation of annual excess winter mortality with average winter temperature (rs=-0.738, P=0.037), but not with air pollution levels. A 1 °C decrease in monthly mean temperature was associated with an increase of 1.38% (95%CI:0.34%-2.40%) and 0.88% (95%CI:0.11%-1.64%) in monthly mortality at lags of 0-1 month, respectively.
Conclusion
Similar to temperate regions, a subtropical city Guangzhou showed a clear seasonal pattern in mortality, with a sharper spike in winter. Our results highlight the role of cold temperature on the winter mortality even in warm climate. Precautionary measures should be strengthened to mitigate cold-related mortality for people living in warm climate.
doi:10.1371/journal.pone.0077150
PMCID: PMC3792910  PMID: 24116214
12.  Stem Cell Therapy in Bladder Dysfunction: Where Are We? And Where Do We Have to Go? 
BioMed Research International  2013;2013:930713.
To date, stem cell therapy for the bladder has been conducted mainly on an experimental basis in the areas of bladder dysfunction. The therapeutic efficacy of stem cells was originally thought to be derived from their ability to differentiate into various cell types. Studies about stem cell therapy for bladder dysfunction have been limited to an experimental basis and have been less focused than bladder regeneration. Bladder dysfunction was listed in MESH as “urinary bladder neck obstruction”, “urinary bladder, overactive”, and “urinary bladder, neurogenic”. Using those keywords, several articles were searched and studied. The bladder dysfunction model includes bladder outlet obstruction, cryoinjured, diabetes, ischemia, and spinal cord injury. Adipose derived stem cells (ADSCs), bone marrow stem cells (BMSCs), and skeletal muscle derived stem cells (SkMSCs) are used for transplantation to treat bladder dysfunction. The main mechanisms of stem cells to reconstitute or restore bladder dysfunction are migration, differentiation, and paracrine effects. The aim of this study is to review the stem cell therapy for bladder dysfunction and to provide the status of stem cell therapy for bladder dysfunction.
doi:10.1155/2013/930713
PMCID: PMC3787556  PMID: 24151627
13.  Efficacy and Safety of Taeeumjowi-tang in Obese Korean Adults: A Double-Blind, Randomized, and Placebo-Controlled Pilot Trial 
Objective. The purpose of this study was to assess the efficacy and safety of Taeeumjowi-tang (TJ001) as well as to estimate obesity-related factors. Methods. This was a 12-week trial with 5 visits. A total of 102 participants of both genders were randomized to either TJ001 (n = 57) group or the placebo group (n = 55). Subjects were administered 7 g of either TJ001 or placebo 3 times a day. The primary outcome was a rate of subjects who lost 5% or more of initial weight. Secondary outcomes included anthropometric parameters, lipid profiles, and body fat composition. Results. The subject response rate of ≥5% weight loss compared to baseline was similar in both groups, and no statistically significant difference was observed (P = 0.87). Changes in anthropometric parameters were greater during the first 4 weeks in the treatment group (P < 0.0001). There were no significant changes in both within groups and between groups for lipid profile and body fat composition. No adverse event was reported in either group. Conclusion. Although the difference between the groups regarding a rate of subjects who lost 5% or more of initial weight did not show statistical significance, TJ001 appears to be beneficial in safely controlling weight.
doi:10.1155/2013/498935
PMCID: PMC3770019  PMID: 24062784
14.  The Influence of Relatives on the Efficiency and Error Rate of Familial Searching 
PLoS ONE  2013;8(8):e70495.
We investigate the consequences of adopting the criteria used by the state of California, as described by Myers et al. (2011), for conducting familial searches. We carried out a simulation study of randomly generated profiles of related and unrelated individuals with 13-locus CODIS genotypes and YFiler® Y-chromosome haplotypes, on which the Myers protocol for relative identification was carried out. For Y-chromosome sharing first degree relatives, the Myers protocol has a high probability () of identifying their relationship. For unrelated individuals, there is a low probability that an unrelated person in the database will be identified as a first-degree relative. For more distant Y-haplotype sharing relatives (half-siblings, first cousins, half-first cousins or second cousins) there is a substantial probability that the more distant relative will be incorrectly identified as a first-degree relative. For example, there is a probability that a first cousin will be identified as a full sibling, with the probability depending on the population background. Although the California familial search policy is likely to identify a first degree relative if his profile is in the database, and it poses little risk of falsely identifying an unrelated individual in a database as a first-degree relative, there is a substantial risk of falsely identifying a more distant Y-haplotype sharing relative in the database as a first-degree relative, with the consequence that their immediate family may become the target for further investigation. This risk falls disproportionately on those ethnic groups that are currently overrepresented in state and federal databases.
doi:10.1371/journal.pone.0070495
PMCID: PMC3743829  PMID: 23967076
15.  Inhibition of tumor growth and histopathological changes following treatment with a chemokine receptor CXCR4 antagonist in a prostate cancer xenograft model 
Oncology Letters  2013;6(4):933-938.
The stromal derived factor-1 (SDF-1)/CXCR4 axis is associated with tumor aggressiveness and metastasis in prostate cancer. The present study aimed to explore the potential therapeutic effects of a CXCR4 antagonist in prostate cancer. The effect of SDF-1 and a CXCR4-specific antagonist, AMD3100, on human prostate cancer PC-3 cell proliferation and protein kinase B (Akt) signaling was assessed. Moreover, a PC-3 tumor xenograft model was used to evaluate the effect of AMD3100 on tumor growth and to identify the histopathological changes and immunohistochemical differences between AMD3100-treated and untreated groups. Cell proliferation was not significantly affected by SDF-1 or AMD3100 treatment in vitro. Western blot analysis revealed that SDF-1 stimulation enhanced the expression of phosphorylated Akt in the PC-3 cells, but that the SDF-1-induced expression of phosphorylated Akt was abrogated in the AMD3100-treated PC-3 cells. In the PC-3 tumor xenograft model, AMD3100 significantly inhibited tumor growth, while AMD3100-treated PC-3 tumors had lower levels of microvessel formation and a lower immunoreactivity for the proliferation marker Ki-67 and the anti-apoptotic marker Bcl-2 compared to control tumors in vivo. The CXCR4-specific antagonist inhibits SDF-1-induced CXCR4/Akt signal transduction, and effectively suppresses tumor growth in the PC-3 xenograft model. The present study indicates that CXCR4 targeting may represent a novel strategy for the treatment of castration-resistant prostate cancer (CRPC).
doi:10.3892/ol.2013.1515
PMCID: PMC3796427  PMID: 24137439
prostatic neoplasms; receptors; CXCR4; chemokine; CXCL12
16.  Blockwise HMM computation for large-scale population genomic inference 
Bioinformatics  2012;28(15):2008-2015.
Motivation: A promising class of methods for large-scale population genomic inference use the conditional sampling distribution (CSD), which approximates the probability of sampling an individual with a particular DNA sequence, given that a collection of sequences from the population has already been observed. The CSD has a wide range of applications, including imputing missing sequence data, estimating recombination rates, inferring human colonization history and identifying tracts of distinct ancestry in admixed populations. Most well-used CSDs are based on hidden Markov models (HMMs). Although computationally efficient in principle, methods resulting from the common implementation of the relevant HMM techniques remain intractable for large genomic datasets.
Results: To address this issue, a set of algorithmic improvements for performing the exact HMM computation is introduced here, by exploiting the particular structure of the CSD and typical characteristics of genomic data. It is empirically demonstrated that these improvements result in a speedup of several orders of magnitude for large datasets and that the speedup continues to increase with the number of sequences. The optimized algorithms can be adopted in methods for various applications, including the ones mentioned above and make previously impracticable analyses possible.
Availability: Software available upon request.
Supplementary Information: Supplementary data are available at Bioinformatics online.
Contact: yss@eecs.berkeley.edu
doi:10.1093/bioinformatics/bts314
PMCID: PMC3400961  PMID: 22641715
17.  Ectopic Prostate Tissue at the Bladder Dome Presenting as a Bladder Tumor 
The World Journal of Men's Health  2013;31(2):176-178.
The presence of ectopic prostate tissue in the bladder is common, but the involvement of the bladder dome has rarely been reported. This case report describes a 72-year-old man who presented with gross painless hematuria. Cystoscopy revealed a smooth sessile mass at the dome region of the bladder. A complete transurethral resection of the mass was performed. Histopathological examination of the mass revealed the presence of benign ectopic prostatic tissue.
doi:10.5534/wjmh.2013.31.2.176
PMCID: PMC3770854  PMID: 24044114
Urinary bladder; Choristoma; Prostate
18.  Trends in Cervical Cancer Mortality by Socioeconomic Status in Korean Women between 1998 and 2009 
Korean Journal of Family Medicine  2013;34(4):258-264.
Background
Death from uterine cervical cancer could be preventable by an active participation of women at risk in a screening program such as the Papanicolaou test. In order to examine the presence of socioeconomic disparity in preventable deaths, we evaluated the time trends of cervical cancer mortality by socioeconomic status in Korean women.
Methods
We selected level of educational attainment and marital status as surrogate indices of socioeconomic status. Using death certificate data and Korean Population and Housing Census data from Korea National Statistical office, we calculated age-standardized yearly mortality rates from cervical cancer between 1998 and 2009 according to the level of education as well as marital status.
Results
Cervical cancer mortality peaked in 2003 and then decreased gradually over time. Cervical cancer mortality was the highest in the group with the lowest level of educational attainment in all age groups and the gap between the lowest and the highest educational level has increased over time. Cervical cancer mortality was lower in married women than unmarried women in all age groups, and the degree of difference did not change over time.
Conclusion
In the Korean population, socioeconomic differential in cervical cancer mortality has persisted over time.
doi:10.4082/kjfm.2013.34.4.258
PMCID: PMC3726793  PMID: 23904955
Uterine Cervical Neoplasms; Mortality; Social Class; Educational Status; Marital Status
19.  PADÉ APPROXIMANTS AND EXACT TWO-LOCUS SAMPLING DISTRIBUTIONS 
For population genetics models with recombination, obtaining an exact, analytic sampling distribution has remained a challenging open problem for several decades. Recently, a new perspective based on asymptotic series has been introduced to make progress on this problem. Specifically, closed-form expressions have been derived for the first few terms in an asymptotic expansion of the two-locus sampling distribution when the recombination rate ρ is moderate to large. In this paper, a new computational technique is developed for finding the asymptotic expansion to an arbitrary order. Computation in this new approach can be automated easily. Furthermore, it is proved here that only a finite number of terms in the asymptotic expansion is needed to recover (via the method of Padé approximants) the exact two-locus sampling distribution as an analytic function of ρ; this function is exact for all values of ρ ∈ [0, ∞). It is also shown that the new computational framework presented here is flexible enough to incorporate natural selection.
doi:10.1214/11-AAP780
PMCID: PMC3685441  PMID: 23788830
population genetics; recombination; sampling distribution; asymptotic expansion; Padé approximants
20.  Aortic Valve Replacement Using Balloon Catheter for Thoracic Endovascular Aortic Repair to Patient with Calcified Aorta 
A 79-year-old man was admitted to Samsung Changwon Hospital due to chest pain and dyspnea. The ejection fraction was 31% and mean pressure gradient between the left ventricle and aorta was 69.4 mmHg on echocardiography. Chest computed tomography showed severe calcification of the ascending aorta. Aortic valve replacement was successfully performed using a thoracic endovascular aortic repair balloon catheter without classic aortic cross clamping. The patient was discharged on the eleventh postoperative day.
doi:10.5090/kjtcs.2013.46.3.212
PMCID: PMC3680608  PMID: 23772410
Aortic valve; Aorta; Calcification
21.  Anomalous Separate Origin of Left Anterior Descending Coronary Artery: Presented as Acute Anterior Myocardial Infarction 
Korean Circulation Journal  2013;43(6):408-410.
Coronary artery anomalies are rare presentations in primary percutaneous coronary interventions of acute myocardial infarction. Herein, we report the case of a 59-year-old man with acute anterior myocardial infarction who had anomalous separate origin of left anterior descending artery (LAD) and left circumflex artery (LCX) from the left coronary aortic sinus. Coronary angiography showed a normal right coronary artery and LCX, but no visualization of the LAD. After several unsuccessful attempts to cannulate the LAD, we found the LAD ostium located by the side of the LCX ostium. There was total occlusion at proxymal LAD. Coronary computed tomography angiography demonstrated the precise, separate origin of LAD and LCX from the left coronary aortic sinus.
doi:10.4070/kcj.2013.43.6.408
PMCID: PMC3717424  PMID: 23882290
Coronary vessel anomalies; Acute anterior wall myocardial infarction
22.  Association of the Vaginal Microbiota with Human Papillomavirus Infection in a Korean Twin Cohort 
PLoS ONE  2013;8(5):e63514.
Human papillomavirus (HPV) is the most important causative agent of cervical cancers worldwide. However, our understanding of how the vaginal microbiota might be associated with HPV infection is limited. In addition, the influence of human genetic and physiological factors on the vaginal microbiota is unclear. Studies on twins and their families provide the ideal settings to investigate the complicated nature of human microbiota. This study investigated the vaginal microbiota of 68 HPV-infected or uninfected female twins and their families using 454-pyrosequencing analysis targeting the variable region (V2–V3) of the bacterial 16S rRNA gene. Analysis of the vaginal microbiota from both premenopausal women and HPV-discordant twins indicated that HPV-positive women had significantly higher microbial diversity with a lower proportion of Lactobacillus spp. than HPV-negative women. Fusobacteria, including Sneathia spp., were identified as a possible microbiological marker associated with HPV infection. The vaginal microbiotas of twin pairs were significantly more similar to each other than to those from unrelated individuals. In addition, there were marked significant differences from those of their mother, possibly due to differences in menopausal status. Postmenopausal women had a lower proportion of Lactobacillus spp. and a significantly higher microbiota diversity. This study indicated that HPV infection was associated with the composition of the vaginal microbiota, which is influenced by multiple host factors such as genetics and menopause. The potential biological markers identified in this study could provide insight into HPV pathogenesis and may represent biological targets for diagnostics.
doi:10.1371/journal.pone.0063514
PMCID: PMC3661536  PMID: 23717441
23.  Factors Associated with Persistent Smoking after the Diagnosis of Cardiovascular Disease 
Korean Journal of Family Medicine  2013;34(3):160-168.
Background
Although cigarette smoking is a major modifiable risk factor for the occurrence of primary and secondary cardiovascular disease (CVD), not all survivors from CVD attacks can successfully stop smoking. However, little is known about the factors associated with the change in smoking behavior after CVD attack.
Methods
Study subjects included 16,807 participants (≥19 years) in the fourth Korean National Health and Nutrition Examination Surveys. From them, we selected 180 persons who had previous CVD diagnosis (angina pectoris, myocardial infarction, or stroke) and were smoking at the time of CVD diagnosis. Then, we categorized the 180 persons into two groups according to change in smoking status after the CVD: quitter and non-quitter. Logistic regression analysis was done to evaluate multivariable-adjusted association.
Results
Even after CVD diagnosis, 63.60% continued to smoke. Fully-adjusted analysis revealed that regular drinking (odds ratio [OR], 4.44) and presence of smokers among family members (OR, 5.86) were significantly (P < 0.05) associated with greater risk of persistent smoking, whereas lower education level (OR, 0.20), larger amount of smoking (OR, 0.95), longer time since diagnosis (OR, 0.88), and diabetes (OR, 0.36) were significantly (P < 0.05) associated with decreased risk of persistent smoking after CVD.
Conclusion
A great proportion of CVD patients tended to continue smoking in the Korean population. In order to reduce smoking rates among CVD patients further, more aggressive efforts towards smoking cessation should be continuously made with consideration of individual socioeconomic, behavioral, and clinical characteristics of CVD patients.
doi:10.4082/kjfm.2013.34.3.160
PMCID: PMC3667223  PMID: 23730483
Cardiovascular Diseases; Health Surveys; Korean; Risk Factors; Smoking Cessation
24.  Release of mitochondrial apoptogenic factors and cell death are mediated by CK2 and NADPH oxidase 
Activation of the NADPH oxidase subunit, NOX2, and increased oxidative stress are associated with neuronal death after cerebral ischemia and reperfusion. Inhibition of NOX2 by casein kinase 2 (CK2) leads to neuronal survival, but the mechanism is unknown. In this study, we show that in copper/zinc-superoxide dismutase transgenic (SOD1 Tg) mice, degradation of CK2α and CK2α′ and dephosphorylation of CK2β against oxidative stress were markedly reduced compared with wild-type (WT) mice that underwent middle cerebral artery occlusion. Inhibition of CK2 pharmacologically or by ischemic reperfusion facilitated accumulation of poly(ADP-ribose) polymers, the translocation of apoptosis-inducing factor (AIF), and cytochrome c release from mitochondria after ischemic injury. The eventual enhancement of CK2 inhibition under ischemic injury strongly increased 8-hydroxy-2′-deoxyguanosine and phosphorylation of H2A.X. Furthermore, CK2 inhibition by tetrabromocinnamic acid (TBCA) in SOD1 Tg and gp91 knockout (KO) mice after ischemia reperfusion induced less release of AIF and cytochrome c than in TBCA-treated WT mice. Inhibition of CK2 in gp91 KO mice subjected to ischemia reperfusion did not increase brain infarction compared with TBCA-treated WT mice. These results strongly suggest that NOX2 activation releases reactive oxygen species after CK2 inhibition, triggering release of apoptogenic factors from mitochondria and inducing DNA damage after ischemic brain injury.
doi:10.1038/jcbfm.2011.176
PMCID: PMC3318149  PMID: 22146192
casein kinase 2; middle cerebral artery occlusion; NADPH oxidase; NOX2; reactive oxygen species
25.  Homogeneity Among the Korean International Prostate Symptom Score Questionnaires Used in Real Practice 
Korean Journal of Urology  2013;54(4):249-251.
Purpose
We analyzed whether any problems existed in terms of the homogeneity of the Korean International Prostate Symptom Score (IPSS) questionnaire used in real practice.
Materials and Methods
Between July 2012 and August 2012, 48 Korean IPSS questionnaires used in real practice were collected. All the items on the questionnaire, including the quality of life (QoL) questions, were compared and we then determined the homogeneity of each question in comparison with the originally validated Korean version of the IPSS from 1996.
Results
Only 5 of 48 sources (10.4%) of the Korean IPSS totally corresponded with the original Korean version of the IPSS questionnaire. The consistency rate with the originally validated version was generally low for the answer choice items for each question, ranging from 16.6% for "less than half the time" to 35.4% for "almost always," with the exception of the item "not at all" (100.0%). The consistency rate was 60.4% for question 3 (intermittency) and 18.8% for question 6 (straining). No homogeneity was found in any of the QoL-related questions. The average consistency rate with the originally validated version was 42.2% and ranged from 22.9% for "unhappy" to the highest rate of 95.8% for "mostly satisfied."
Conclusions
Compared with the originally validated Korean version of the IPSS, various Korean IPSS questionnaires used in real practice had significant problems in terms of homogeneity for both the questions and the answer choice items. Efforts are needed to ensure the uniform use of the validated Korean version of the IPSS questionnaire.
doi:10.4111/kju.2013.54.4.249
PMCID: PMC3630344  PMID: 23614062
Questionnaires; Reproducibility of results

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