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1.  The Effect of Exercise on Prevention of the Common Cold: A Meta-Analysis of Randomized Controlled Trial Studies 
Korean Journal of Family Medicine  2014;35(3):119-126.
Because there is no specific treatment for the common cold, many previous studies have focused on prevention of the common cold. There were some studies reporting that regular, moderate-intensity exercise increases immunity and prevents the common cold. We conducted a meta-analysis to determine the effects of exercise on prevention of the common cold.
We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL for studies released through June 2013. We manually searched the references. Two authors independently extracted the data. To assess the risk of bias of included literature, Cochrane Collaboration's tool for assessing risk of bias was used. Review Manager ver. 5.2 (RevMan, Cochrane Collaboration) was used for statistical analysis.
Four randomized controlled trials were identified. A total of 281 participants, 134 in the exercise group and 147 in the control group, were included. The effect of exercise on the prevention of the common cold had a relative risk (RR) of 0.73 (95% confidence interval [CI], 0.56 to 0.95; I2 = 7%). The mean difference of mean illness days between exercise group and control group was -3.50 (95% CI, -6.06 to -0.94; I2 = 93%). In the subgroup analysis, the RR of under 16 weeks exercise was 0.79 (95% CI, 0.58 to 1.08).
In this meta-analysis, regular, moderate-intensity exercise may have an effect on the prevention of the common cold. But numbers of included studies and participants were too small and quality of included studies was relatively poor. Subsequent well-designed studies with larger sample size are needed to clarify the association.
PMCID: PMC4040429  PMID: 24921030
Exercise; Common Cold; Meta-Analysis; Prevention
2.  Contribution of Six Flagellin Genes to the Flagellum Biogenesis of Vibrio vulnificus and In Vivo Invasion 
Infection and Immunity  2014;82(1):29-42.
Vibrio vulnificus is a halophilic pathogenic bacterium that is motile due to the presence of a single polar flagellum. V. vulnificus possesses a total of six flagellin genes organized into two loci (flaFBA and flaCDE). We proved that all six of the flagellin genes were transcribed, whereas only five (FlaA, -B, -C, -D, and -F) of the six flagellin proteins were detected. To understand roles of the six V. vulnificus flagellins in motility and virulence, mutants with single and multiple flagellin deletions were constructed. Mutations in flaB or flaC or the flaCDE locus resulted in a significant decrease in motility, adhesion, and cytotoxicity, whereas single mutations in the other flagellin genes or the flaFBA locus showed little or no effect. The motility was completely abolished only in the mutant lacking all six flagellin genes (flaFBA flaCDE). Surprisingly, a double mutation of flaB and flaD, a gene sharing 99% identity with the flaB at the amino acid level, resulted in the largest decrease in motility, adhesion, and cytotoxicity except for the mutant in which all six genes were deleted (the hexa mutant). Additionally, the 50% lethal doses (LD50s) of the flaB flaD and the flaFBA flaCDE mutants increased 23- and 91-fold in a mouse model, respectively, and the in vitro and in vivo invasiveness of the mutants was significantly decreased compared to that of the wild type. Taken together, the multiple flagellin subunits differentially contribute to the flagellum biogenesis and the pathogenesis of V. vulnificus, and among the six flagellin genes, flaB, flaD, and flaC were the most influential components.
PMCID: PMC3911872  PMID: 24101693
3.  A Comparison of the Efficacy and Safety of Non-Steroidal Anti-Inflammatory Drugs versus Acetaminophen in Symptom Relief for the Common Cold: A Meta-Analysis of Randomized Controlled Trial Studies 
Korean Journal of Family Medicine  2013;34(4):241-249.
Non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen are widely used for common cold symptom relief. The objective of this study was to evaluate and compare the efficacy and safety of acetaminophen and NSAIDs in common cold symptom relief using meta-analysis of randomized controlled trial.
We searched MEDLINE (PubMed), Cochrane, EMBASE, CINAHL, KMbase, KoreaMed, National Assembly Library, and Riss4u for studies released through June 2012. Two authors independently extracted the data. To assess the risk of bias, the Cochrane Collaborations risk of bias tool was used. The Review Manager ver. 5.1 (RevMan) was used for statistics.
We identified 5 studies. The relative benefit for participants with pain relief was 1.00 (95% confidence interval [CI], 0.96 to 1.05) and I2 = 0%. The existence of the heterogeneity between studies was not important in this study, thus subgroup analysis was not implemented. The relative benefit for participants with rhinorrhea was 1.02 (95% CI, 0.77 to 1.35) and I2 = 0%, which also indicates the existence of heterogeneity was not important. The relative risk of adverse events was 1.14 (95% CI, 0.93 to 1.40), I2 = 0%. There was no apparent asymmetry in the funnel plot.
There was no difference between NSAIDs and acetaminophen in common cold symptom relief.
PMCID: PMC3726791  PMID: 23904953
Common Cold; Non-Steroidal Anti-Inflammatory Agents; Acetaminophen; Meta-Analysis
4.  Identification of Dermatophytes by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism Analysis of Metalloproteinase-1 
Annals of Dermatology  2014;26(3):338-342.
Transgenic research on metalloproteinase-1 is an emerging field in the area of plant molecular biology. The new method reported here can similarly be applied in fungal molecular biology to identify different dermatophytes. Our method is more accurate than traditional methods such as molecular analyses.
To identify Trichophyton rubrum, T. mentagrophytes var. mentagrophytes, T. tonsurans, T. mentagrophytes var. interdigitale, Microsporum canis and M. gypseum, by using the restriction fragment length polymorphism (RFLP) analysis and polymerase chain reaction (PCR) to detect polymorphisms in the metalloproteinase-1 gene (MEP1).
From each fungal strain, we isolated genomic DNA and performed PCR to amplify the region coding for metalloproteinase-1. Primers for the metalloproteinase-1 gene were designed based on the sequence in NCBI GenBank. Subsequently, we purified the amplified PCR product and performed RFLP analysis. After restriction enzyme digestion, BsrDI (NEB, England), the samples were subjected to electrophoresis. Four different patterns of DNA fragments were observed among 6 fungal species.
The DNA fragments for T. mentagrophytes var. mentagrophytes, T. mentagrophytes var. interdigitale and T. tonsurans showed similar patterns on electrophoresis and were not distinguishable, whereas T. rubrum, M. canis, and M. gypseum showed different patterns.
To our knowledge, it is the first study to introduce the analysis of the nucleotide sequence of metalloproteinase-1 enzyme to study differentiation in dermatophytes. Based on our results, more accurate differentiation and subtyping of T. rubrum and T. mentagrophytes var. interdigitale might be possible. This might contribute to better understanding of the epidemiology and pathogenesis of dermatophyte.
PMCID: PMC4069644  PMID: 24966633
Metalloproteinases; Microsporum; Polymerase chain reaction; Restriction fragment length polymorphism; Trichophyton
5.  The Effect of Probiotics on Prevention of Common Cold: A Meta-Analysis of Randomized Controlled Trial Studies 
Probiotics are currently under focus for their immune improvement function. Many studies have been performed to assess the potential efficacy of probiotics in allergic disease, viral disease, respiratory disease, as well as gastrointestinal disease. This study performed a systematic review to determine the effects of probiotics on the prevention of the common cold.
We searched MEDLINE (PubMed), EMBASE, CINAHL, and Cochrane CENTRAL for studies released through June 2011. Two authors independently extracted the data. To assess the risk of bias of included literatures, Cochrane Collaboration's risk of bias tool was used.
We identified 10 studies in 7 articles. A total 2,894 participants, 1,588 in the probiotics group and 1,306 in the control group, were included. The effect of probiotics on the prevention of the common cold had a relative risk (RR) of 0.92 (95% CI, 0.85 to 1.00, I2 = 26%). In the subgroup analysis, the RR of administration of probiotics for 3 months or less was 0.82 (95% CI, 0.70 to 0.97). The RR of administration of probiotics over 3 months was 1.00 (95% CI, 0.92 to 1.09). The RR of administration of probiotics without any active intervention (vitamin and mineral) was 0.87 (95% CI, 0.78 to 0.97).
In this meta-analysis, there was marginal effect of probiotics on the prevention of the common cold. The results implied that probiotics had a modest effect in common cold reduction. The balance of benefit and harms needs to be considered when using probiotics for common cold prevention.
PMCID: PMC3560336  PMID: 23372900
Probiotics; Common Cold; Meta-Analysis
6.  Effects of Having Usual Source of Care on Preventive Services and Chronic Disease Control: A Systematic Review 
Korean Journal of Family Medicine  2012;33(6):336-345.
Having usual source of care has been associated with improved receipt of preventive services and control of chronic diseases (such as hypertension, diabetes, and hypercholesterolemia). The objective of this study was to examine whether having usual source of care is associated with improved receipt of preventive services and control of chronic diseases.
We searched MEDLINE, EMBASE, Cochrane, CINAHL, KMbase, KoreaMed, RiSS4U, National Assembly Library, and KISS for studies released through May 31st 2011. Two authors independently extracted the data. We manually searched the references and twenty recent related articles on PubMed. To assess the risk of bias RoBANS tool was used.
We identified 10 studies. Most having usual source of care were associated with improved receipt of preventive services (cervical cancer screening, clinical breast exam, mammogram, prostate cancer screening, and flu shot) compared with no usual source of care. However, gastric cancer and colon cancer screening were difficult to conclude and blood pressure checkup showed mixed results. Overall there was no association between having usual source of care and smoking behaviors and the effect on chronic disease control was difficult to conclude.
Having usual source of care was associated with improved receipt of preventive services and overall the results were consistent. So, the results suggested that having usual source of care may help to receive preventive services. Hereafter, cohort studies are needed to evaluate casual relationships and more studies are needed in various countries and systems.
PMCID: PMC3526716  PMID: 23267419
Usual Source of Care; Preventive Services; Chronic Disease Control; Systematic Review
7.  A Comparison of Efficacy and Safety of Non-steroidal Anti-inflammatory Drugs versus Acetaminophen in the Treatment of Episodic Tension-type Headache: A Meta-analysis of Randomized Placebo-controlled Trial Studies 
Korean Journal of Family Medicine  2012;33(5):262-271.
Non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen are widely used in the treatment of tension headache. The objective of this study was to evaluate and compare the efficacy and safety of single doses of acetaminophen and NSAIDs using meta-analysis of randomized placebo-controlled trial studies.
We searched MEDLINE, EMBASE, CINAHL, Cochrane, KMbase, KoreaMed, RiCH, National Assembly Library, Riss4u, and DBPIA for studies released through 27th July 2010. Two authors independently extracted the data. To assess the risk of bias, the Cochrane Collaborations risk of bias tool was used. Review Manager 5.0 was used for statistics.
We identified 6 studies. The relative benefit of the NSAIDs group compared to the acetaminophen group for participants with at least 50% pain relief was 1.18 (95% confidence interval [CI], 0.99 to 1.39; I2 = 85%). We did subgroup analysis based on allocation concealment versus non-allocation concealment, and low-dose NSAIDs versus high-dose NSAIDs. The relative benefit of the low-dose NSAIDs subgroup to the acetaminophen group was 0.98 (95% CI, 0.91 to 1.06; I2 = 0%). However, the heterogeneity of other subgroup analysis was not settled. The relative risk for using rescue medication of the NSAIDs group compared to the acetaminophen group was 0.84 (95% CI, 0.64 to 1.12; I2 = 47%). The relative risk for adverse events was 1.31(95% CI, 0.96 to 1.80; I2 = 0%).
In this meta-analysis, there was no difference between low-dose NSAIDs and acetaminophen in the efficacy of the treatment for tension type headache. The results suggested that high-dose NSAIDs have more effect but also have more adverse events. The balance of benefit and harm needs to be considered when using high-dose NSAIDs for tension headache.
PMCID: PMC3481025  PMID: 23115700
Tension-type Headache; Non-steroidal Anti-inflammatory Drugs; Acetaminophen; Meta-analysis
8.  ATHB17 Is a Positive Regulator of Abscisic Acid Response during Early Seedling Growth 
Molecules and Cells  2013;35(2):125-133.
We performed activation tagging screen to isolate abscisic acid (ABA) response mutants. One of the mutants, designated ahs10 (ABA-hypersensitive10), exhibited ABA-hypersensitive phenotypes. TAIL-PCR analysis of the mutant revealed that T-DNA was inserted in the promoter region of the Arabidopsis gene, At2g01430, which encodes a homeodomain-leucine zipper protein ATHB17. Subsequent expression analysis indicated that ATHB17 was activated in ahs10. To recapitulate the mutant phenotypes, we prepared ATHB17 OX lines and investigated their phenotypes. The results showed that ATHB17 confers ABA-hypersensitivity and drought tolerance. On the contrary, ATHB17 knockout lines were ABA-insensitive and drought-sensitive, further demonstrating that ATHB17 is involved in ABA and water-stress responses. Interestingly, the ATHB17 effect on seedling growth in the presence of ABA was observed only during the postgermination seedling establishment stage, suggesting that it functions during a narrow developmental window of early seedling growth.
PMCID: PMC3887901  PMID: 23456334
abscisic acid (ABA); activation tagging; drought tolerance; HD-Zip protein
9.  The Quality of Reporting of Cohort, Case-Control Studies in the Korean Journal of Family Medicine 
The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement was developed to improve the reporting of observational studies. We aimed to evaluate the quality of reporting in cohort studies and case-control studies among observational studies published in the Korean Journal of Family Medicine.
We searched for cohort studies and case-control studies published as original articles in the Journal of the Korean Academy of Family Medicine during the period January 1992 through December 2009. The main outcome measures were the number and proportion of cohort studies and case-control studies that reported each of 22 checklist items of STROBE.
We identified a total of 84 articles, of which 46 articles were cohort studies and 38 were case-control studies. Concerning methods, study designs (10%), bias (13%), study size (0%), statistical methods (12-c and 12-e items, 0%; 12-d item, cohort study, 6%) have been poorly reported. Of results, participants (5-6%), descriptive data (14-b item, 5%), and funding (1%) among other information have been poorly reported.
The degree of adherence the STROBE recommendations was relatively low in cohort studies and case-control studies published in the Korean Journal of Family Medicine. An effort to improve the reporting of observational studies by application and recommendation of the STROBE statement is required.
PMCID: PMC3383501  PMID: 22745891
Korean Journal of Family Medicine; Cohort Studies; Case-Control Studies; STROBE; Quality of Reporting
10.  Misinterpreting Odds Ratio in the Articles Published in Korean Journal of Family Medicine 
In reporting results of case-control studies, odds ratios are useful methods of reporting findings. However, odds ratios are often misinterpreted in the literature and by general readers.
We searched all original articles which were published in the Korean Journal of Family Medicine from 1980 to May 2011 and identified those that report "odds ratios." Misinterpretation of odds ratios as relative risks has been identified. Estimated risk ratios were calculated when possible and compared with odds ratios.
One hundred and twenty-eight articles using odds ratios were identified. Among those, 122 articles were analyzed for the frequency of misinterpretation of odds ratios as relative risks. Twenty-two reports out of these 122 articles misinterpreted odds ratios as relative risks. The percentage of misinterpreting reports decreased over years. Seventy-seven reports were analyzed to compare the estimated risk ratios with odds ratios. In most of these articles, odds ratios were greater than estimated risk ratios, 60% of which had larger than 20% standardized differences.
In reports published in the Korean Journal of Family Medicine, odds ratios are frequently used. They were misinterpreted in part of the reports, although decreasing trends over years were observed.
PMCID: PMC3383504  PMID: 22745892
Odds Ratio; Relative Risk; Korean Journal of Family Medicine; Misinterpretation
11.  Duplicate Publication Rate Decline in Korean Medical Journals 
Journal of Korean Medical Science  2014;29(2):172-175.
The purpose of this study was to examine trends in duplicate publication in Korean medical articles indexed in the KoreaMed database from 2004 to 2009, before and after a campaign against scientific misconduct launched by the Korean Association of Medical Journal Editors in 2006. The study covered period from 2007 to 2012; and 5% of the articles indexed in KoreaMed were retrieved by random sampling. Three authors reviewed full texts of the retrieved articles. The pattern of duplicate publication, such as copy, salami slicing (fragmentation), and aggregation (imalas), was also determined. Before the launching ethics campaign, the national duplication rate in medical journals was relatively high: 5.9% in 2004, 6.0% in 2005, and 7.2% in 2006. However, duplication rate steadily declined to 4.5% in 2007, 2.8% in 2008, and 1.2 % in 2009. Of all duplicated articles, 53.4% were classified as copies, 27.8% as salami slicing, and 18.8% as aggregation (imalas). The decline in duplicate publication rate took place as a result of nationwide campaigns and monitoring by KoreaMed and KoreaMed Synapse, starting from 2006.
Graphical Abstract
PMCID: PMC3923993  PMID: 24550641
Publishing Ethics; Duplicate Publication as Topic; Periodicals as Topic; Trends; Korea
12.  Molecular characterization of vulnibactin biosynthesis in Vibrio vulnificus indicates the existence of an alternative siderophore 
Vibrio vulnificus is a halophilic estuarine bacterium that causes fatal septicemia and necrotizing wound infections in humans. Virulent V. vulnificus isolates produce a catechol siderophore called vulnibactin, made up of one residue of 2, 3-dihydroxybenzoic acid (2, 3-DHBA) and two residues of salicylic acid (SA). Vulnibactin biosynthetic genes (VV2_0828 to VV2_0844) are clustered at one locus of chromosome 2, expression of which is significantly up-regulated in vivo. In the present study, we decipher the biosynthetic network of vulnibactin, focusing specifically on genes around SA and 2, 3-DHBA biosynthetic steps. Deletion mutant of isochorismate pyruvate lyase (VV2_0839) or 2, 3-dihydroxybenzoate-2, 3-dehydrogenase (VV2_0834) showed retarded growth under iron-limited conditions though the latter showed more significant growth defect than the former, suggesting a dominant role of 2, 3-DHBA in the vulnibactin biosynthesis. A double deletion mutant of VV2_0839 and VV2_0834 manifested additional growth defect under iron limitation. Though the growth defect of respective single deletion mutants could be restored by exogenous SA or 2, 3-DHBA, only 2, 3-DHBA could rescue the double mutant when supplied alone. However, double mutant could be rescued with SA only when hydrogen peroxide was supplied exogenously, suggesting a chemical conversion of SA to 2, 3-DHBA. Assembly of two SA and one 2, 3-DHBA into vulnibactin was mediated by two AMP ligase genes (VV2_0836 and VV2_0840). VV2_0836 deletion mutant showed more significant growth defect under iron limitation, suggesting its dominant function. In conclusion, using molecular genetic analytical tools, we confirm that vulnibactin is assembled of both 2, 3-DHBA and SA. However, conversion of SA to 2, 3-DHBA in presence of hydrogen peroxide and growth profile of AMP ligase mutants suggest a plausible existence of yet unidentified alternative siderophore that may be composed solely of 2, 3-DHBA.
PMCID: PMC3900857  PMID: 24478763
V. vulnifiucus; siderophore; salicylate; 2; 3-DHBA; hydroxyl radical; AMP ligase
13.  Coffee Consumption and Risk of Osteoporosis 
PMCID: PMC3912260  PMID: 24501663
14.  Use it and/or lose it—experience effects on brain remodeling across time after stroke 
The process of brain remodeling after stroke is time- and neural activity-dependent, and the latter makes it inherently sensitive to behavioral experiences. This generally supports targeting early dynamic periods of post-stroke neural remodeling with rehabilitative training (RT). However, the specific neural events that optimize RT effects are unclear and, as such, cannot be precisely targeted. Here we review evidence for, potential mechanisms of, and ongoing knowledge gaps surrounding time-sensitivities in RT efficacy, with a focus on findings from animal models of upper extremity RT. The reorganization of neural connectivity after stroke is a complex multiphasic process interacting with glial and vascular changes. Behavioral manipulations can impact numerous elements of this process to affect function. RT efficacy varies both with onset time and its timing relative to the development of compensatory strategies with the less-affected (nonparetic) hand. Earlier RT may not only capitalize on a dynamic period of brain remodeling but also counter a tendency for compensatory strategies to stamp-in suboptimal reorganization patterns. However, there is considerable variability across injuries and individuals in brain remodeling responses, and some early behavioral manipulations worsen function. The optimal timing of RT may remain unpredictable without clarification of the cellular events underlying time-sensitivities in its effects.
PMCID: PMC4072969  PMID: 25018715
upper extremity function; restorative plasticity; motor skill learning; learned non-use; motor cortex
15.  Plagiarism Detection 
PMCID: PMC3856277  PMID: 24340157
16.  Duplicate Publications in Korean Medical Journals Indexed in KoreaMed 
Journal of Korean Medical Science  2008;23(1):131-133.
Duplicate publication is considered unethical. It has several negative impacts. To estimate the frequency and characteristics of duplicate publications in Korean medical journals, we reviewed some portion of Korean journal articles. Among 9,030 articles that are original articles indexed in KoreaMed from January to December 2004, 455 articles (5%) were chosen by random sampling. PubMed, Google scholar, KMbase, and KoreaMed were searched by two librarians. Three authors reviewed titles, abstracts, and full text of index articles and suspected articles independently. Point of disagreement were reconciled by discussion. Criteria for a duplicate publication defined by editors of cardiothoracic journals and International Committee of Medical Journal Editors were used. A total of 455 articles were evaluated, of which 27 (5.93%) index articles were identified with 29 duplicate articles. Among 27 index articles, 1 was quadruple publication and 26 were double publications. Of 29 duplicated articles, 19 were classified as copy, 4 as fragmentation, and 6 as disaggregation. The proportion of duplicate publications in Korean medical journals appears to be higher than expected. Education on publication ethics to researchers is needed.
PMCID: PMC2526492  PMID: 18303213
Duplicate Publication as Topics; Korea; Periodicals as Topic; Publishing
17.  Publication Delay in the Korean Journal of Family Medicine 
PMCID: PMC3791336  PMID: 24106581
18.  Blood–brain barrier dysfunction–induced inflammatory signaling in brain pathology and epileptogenesis 
Epilepsia  2012;53(0 6):37-44.
The protection of the brain from blood-borne toxins, proteins, and cells is critical to the brain’s normal function. Accordingly, a compromise in the blood–brain barrier (BBB) function accompanies many neurologic disorders, and is tightly associated with brain inflammatory processes initiated by both infiltrating leukocytes from the blood, and activation of glial cells. Those inflammatory processes contribute to determining the severity and prognosis of numerous neurologic disorders, and can both cause, and result from BBB dysfunction. In this review we examine the role of BBB and inflammatory responses, in particular activation of transforming grown factor β (TGFβ) signaling, in epilepsy, stroke, and Parkinson’s disease.
PMCID: PMC3703535  PMID: 23134494
Blood–brain barrier; Epileptogenesis; Inflammation; TGF-beta; Cholinergic system
19.  An isoform of retinoid-related orphan receptor β directs differentiation of retinal amacrine and horizontal interneurons 
Nature communications  2013;4:1813.
Amacrine and horizontal interneurons integrate visual information as it is relayed through the retina from the photoreceptors to the ganglion cells. The early steps that generate these interneuron networks remain unclear. Here we show that a distinct RORβ1 isoform encoded by the retinoid-related orphan nuclear receptor β gene (Rorb) is critical for both amacrine and horizontal cell differentiation in mice. A fluorescent protein cassette targeted into Rorb revealed RORβ1 as a novel marker of immature amacrine and horizontal cells and of undifferentiated, dividing progenitor cells. RORβ1-deficient mice lose expression of pancreas-specific transcription factor 1a (Ptf1a) but retain forkhead box n4 factor (Foxn4), two early-acting factors necessary for amacrine and horizontal cell generation. RORβ1 and Foxn4 synergistically induce Ptf1a expression, suggesting a central role for RORβ1 in a transcriptional hierarchy that directs this interneuron differentiation pathway. Moreover, ectopic RORβ1 expression in neonatal retina promotes amacrine cell differentiation.
PMCID: PMC3671912  PMID: 23652001
orphan nuclear receptor; forkhead box transcription factor Foxn4; basic helix-loop-helix factor Ptf1a; neurogenesis; inhibitory interneuron
20.  Is Prostate-Specific Antigen Effective for Population Screening of Prostate Cancer? A Systematic Review 
Annals of Laboratory Medicine  2013;33(4):233-241.
The effectiveness of prostate-specific antigen (PSA) for population screening has presented controversial results in large trials and prior reviews. We investigated the effectiveness of PSA population screening in a systematic review.
The study was conducted using existing systematic reviews. We searched Ovid MEDLINE, Embase, Cochrane library, and the major Korean databases. The quality of the systematic reviews was assessed by two reviewers independently using AMSTAR. Randomized controlled trials were assessed using the risk of bias tool in the Cochrane group. Meta-analyses were conducted using Review Manager. The level of evidence of each outcome was assessed using GRADE.
Prostate-cancer-specific mortality was not reduced based on similar prior reviews (relative risk [RR] 0.93; 95% confidence interval [CI], 0.81-1.07, P=0.31). The detection rate of stage 1 prostate cancer was not greater, with a RR of 1.67 (95% CI, 0.95-2.94) and high heterogeneity. The detection rate of all cancer stages in the screening group was high, with a RR of 1.45 (95% CI, 1.13-1.85). No difference in all-cause mortality was observed between the screening and control groups (RR, 0.99; 95% CI, 0.98-1.01, P=0.50). Prostate-cancer-specific mortality, all-cause mortality, and diagnosis of prostate cancer at stages 3-4 showed moderate levels of evidence.
Differently from prior studies, our review included updated Norrköping data and assessed the sole effect of PSA testing for prostate cancer screening. PSA screening alone did not increase early stage prostate cancer detection and did not lower mortality.
PMCID: PMC3698300  PMID: 23826558
Prostatic neoplasm; Mass screening; Mortality; Prostate specific antigen; Review; Meta-analysis
21.  Intranasal immunization with a flagellin-adjuvanted peptide anticancer vaccine prevents tumor development by enhancing specific cytotoxic T lymphocyte response in a mouse model 
Human papillomavirus (HPV) is a significant cause of cervical cancer-related deaths worldwide. Because HPV is a sexually transmitted mucosal pathogen, enhancement of antigen-specific mucosal immune response likely serves good strategy for vaccination. However, mucosal vaccines generally do not induce strong enough immune responses. Previously we proved that a bacterial flagellin, Vibrio vulnificus FlaB, induce strong antigen-specific immune responses by stimulating the Toll-like receptor 5. In this study, we tested whether FlaB could serve as an effective mucosal adjuvant for a peptide-based HPV preventive cancer vaccine.
Materials and Methods
Mice were intranasally administered with a mixture of FlaB and E6/E7 protective peptides in 5-day interval for a total of two times. Five-days after the last vaccination, cellular immune responses of the vaccinated mice were analyzed. Tumor growth was also observed after a subcutaneous implantation of TC-1 cells bearing E6/E7 antigens.
Intranasal administration of the E6/E7 peptide mixture with FlaB elicited a strong antigen-specific cytotoxic T lymphocyte activity and antigen-specific interferon-γ production from splenocytes and cervical lymph node cells. Furthermore, FlaB, as a mucosal adjuvant, conferred an excellent protection against TC-1 tumor challenge with high survival rates in E6/E7 immunized animals.
These results indicate that FlaB can be a promising mucosal adjuvant for nasal HPV vaccine development.
PMCID: PMC3710921  PMID: 23858404
Flagellin; Adjuvant; Neoplasms; Vaccines
22.  Efficacy versus Effectiveness 
PMCID: PMC3726789  PMID: 23904951
23.  Overexpression of Arabidopsis Translationally Controlled Tumor Protein Gene AtTCTP Enhances Drought Tolerance with Rapid ABA-Induced Stomatal Closure 
Molecules and Cells  2012;33(6):617-626.
Translationally controlled tumor protein (TCTP), also termed P23 in human, belongs to a family of calcium- and tubulin-binding proteins, and it is generally regarded as a growth-regulating protein. Recently, Arabidopsis TCTP (AtTCTP) has been reported to function as an important growth regulator in plants. On the other hand, plant TCTP has been suggested to be involved in abiotic stress signaling such as aluminum, salt, and water deficit by a number of microarray or proteomic analyses. In this study, the biological functions of AtTCTP were investigated by using transgenic Arabidopsis plants overexpressing AtTCTP. Interestingly, AtTCTP overexpression enhanced drought tolerance in plants. The expression analysis showed that AtTCTP was expressed in guard cells as well as in actively growing tissues. Physiological studies of the overexpression lines showed increased ABA- and calcium-induced stomatal closure ratios and faster stomatal closing responses to ABA. Furthermore, in vitro protein-protein interaction analysis confirmed the interaction between AtTCTP and microtubules, and microtubule cosedimentation assays revealed that the microtubule binding of AtTCTP increased after calcium treatment. These results demonstrate that the overexpression of AtTCTP confers drought tolerance to plants by rapid ABA-mediated stomatal closure via the interaction with microtubules in which calcium binding enhances the interaction. Collectively, the present results suggest that the plant TCTP has molecular properties similar to animal TCTPs, such as tubulin- and calcium-binding, and that it functions in ABA-mediated stomatal movement, in addition to regulating the growth of plants.
PMCID: PMC3887759  PMID: 22610367
abscisic acid; drought tolerance; microtubule; stomatal closure; translationally controlled tumor protein
24.  Association of the Length of Doctor-Patient Relationship with Primary Care Quality in Seven Family Practices in Korea 
Journal of Korean Medical Science  2013;28(4):508-515.
Countries with historically unlimited patient choice of medical provider, such as Korea, have been promoting rational health care pathways. Factors related to the length of doctor-patient relationship (DPR) for enhancing primary care in those countries should be studied. Participants were patients who had visited their family practices on six or more occasions over a period of more than 6 months. Five domains (21 items) of the Korean Primary Care Assessment Tool (first contact, coordination function, comprehensiveness, family/community orientation, and personalized care) and general questions were administered in the waiting rooms. From seven practices, the response rate was 83.7% (495/591). The older the age, the lower the income, the shorter the duration of education, the more the number of diseases the patients had, and in provincial cities rather than in Seoul, the longer length of DPR ( ≥ 4 yr) was shown. The long-term DPR was associated with total primary care quality score (upper [ ≥ 71.4] vs lower [ < 71.4], OR, 1.74; 95% CI, 1.10-2.76), especially with coordination function (OR, 1.01; 95% CI, 1.00-1.02), being adjusted for confounding variables. Strengthening the coordination function may have to be the first consideration in primary care policy in countries like Korea.
PMCID: PMC3617301  PMID: 23580064
Primary Health Care; Quality Assurance; Health Care Policy; Korea
25.  Assessment of the Quality of Clinical Practice Guidelines in Korea Using the AGREE Instrument 
Journal of Korean Medical Science  2013;28(3):357-365.
The objective of this study was to conduct the systematic evaluation of methodological quality of clinical practice guidelines (CPGs) in Korea. The authors conducted a very comprehensive literature search to identify potential CPGs for evaluation. CPGs were selected which were consistent with a predetermined criteria. Four reviewers evaluated the quality of the CPGs using the Appraisal of Guidelines, Research and Evaluation (AGREE) Instrument. AGREE item scores and standardized domain scores were calculated. The inter-rater reliability of each domain was evaluated using the intra-class correlation coefficient (ICC). Consequently, 66 CPGs were selected and their quality evaluated. ICCs for CPG appraisal using the AGREE Instrument ranged from 0.626 to 0.877. Except for the "Scope and Purpose" and "Clarity and Presentation domains", 80% of CPGs scored less than 40 in all other domains. This review shows that many Korean research groups and academic societies have made considerable efforts to develop CPGs, and the number of CPGs has increased over time. However, the quality of CPGs in Korea were not good according to the AGREE Instrument evaluation. Therefore, we should make more of an effort to ensure the high quality of CPGs.
PMCID: PMC3594597  PMID: 23487579
Clinical Practice Guideline; Quality Improvement

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