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1.  Helicobacter pylori Infection with Atrophic Gastritis Is an Independent Risk Factor for Advanced Colonic Neoplasm 
Gut and Liver  2016;10(6):902-909.
Helicobacter pylori is a major risk factor for atrophic gastritis (AG) and gastric cancer. The correlation between H. pylori, AG and colorectal neoplasm (CRN) has only been examined in a limited number of studies, and findings have been inconclusive. We aimed to investigate the association between H. pylori infection status, AG and advanced CRN.
This cross-sectional study investigated the relationship between the presence of serum anti-H. pylori IgG antibodies, AG, and advanced CRN in 6,351 consecutive asymptomatic subjects who underwent a screening colonoscopy.
A total of 316 participants (5.0%) had advanced CRN. H. pylori seropositivity was 61.3%. In a univariate analysis, the presence of H. pylori infection was associated with advanced CRN (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.17 to 1.91; p=0.001). H. pylori infection was associated with an increased risk of advanced CRN after adjusting for clinically relevant confounders (OR, 1.34; 95% CI, 1.04 to 1.72; p=0.023). H. pylori-related AG was significantly associated with the risk of advanced CRN (OR, 1.40; 95% CI, 1.03 to 1.91; p=0.030), whereas H. pylori infection without AG was not.
H. pylori infection increased the risk of advanced CRN, especially when it was combined with AG. Strict colonoscopy screening and surveillance may be warranted in those with H. pylori-positive AG.
PMCID: PMC5087929  PMID: 27458180
Helicobacter pylori; Gastritis; Atrophy; Neoplasms
2.  Abdominal Wall Hematoma as a Rare Complication following Percutaneous Coronary Intervention 
Korean Circulation Journal  2016;46(3):408-411.
Abdominal wall hematoma is a rare but potentially serious vascular complication that may develop after coronary angiographic procedures. In particular, an oblique muscle hematoma caused by an injury of the circumflex iliac artery is very rare, yet can be managed by conservative treatment including hydration and transfusion. However, when active bleeding continues, angiographic embolization or surgery might be needed. In this study, we report an uncommon case of injury to the circumflex iliac artery by an inappropriate introduction of the hydrophilic guidewire during the performance of a percutaneous coronary intervention.
PMCID: PMC4891606  PMID: 27275178
Percutaneous coronary intervention; Hematoma; Femoral artery
3.  Laparoscopic repair of indirect inguinal hernia containing endometriosis, ovary, and fallopian tube in adult woman without genital anomalies 
Obstetrics & Gynecology Science  2014;57(6):557-559.
Indirect inguinal hernia containing an ovary is a rare condition, especially in adult women who do not have any other genital tract anomalies. In addition, inguinal hernia containing an ovary and endometriosis is exceedingly rare. In the present report, we describe a case of indirect inguinal hernia containing an ovary, fallopian tube, and endometriosis. Laparoscopic repair was performed successfully using polypropylene mesh for the treatment of the inguinal hernia.
PMCID: PMC4245355  PMID: 25469350
Endometriosis; Hernia, inguinal; Laparoscopic repair; Ovary
4.  Hypomania Induced by Subthalamic Nucleus Stimulation in a Parkinson’s Disease Patient: Does It Suggest a Dysfunction of the Limbic Circuit? 
Journal of Movement Disorders  2012;5(1):14-17.
The aim of this report was to describe a case of hypomania after deep brain stimulation of the subthalamic nucleus (STN DBS) in a Parkinson’s disease (PD) patient. 59-year-old man with a 15-year history of PD underwent bilateral implantation of electrodes to the STN. Immediately after surgery, his motor function was markedly improved and his mood was elevated to hypomania. Fusion images of the preoperative MRI and postoperative CT scan showed that the electrodes were located in the medial portion of the STN. In this case, behavioral mood change was related to the deep brain stimulation. Moreover, the anatomical location and the functional alteration of the STN after the DBS surgery might be related to the regulatory system of the associative and limbic cortico-subcortical circuits.
PMCID: PMC4027680  PMID: 24868407
Deep brain stimulation; Subthalamic stimulation; Non motor symptom; Hypomania; Mood
5.  Blue-Green Algae Inhibit the Development of Atherosclerotic Lesions in Apolipoprotein E Knockout Mice 
Journal of Medicinal Food  2015;18(12):1299-1306.
Hyperlipidemia and inflammation contribute to the development of atherosclerotic lesions. Our objective was to determine antiatherogenic effect of edible blue-green algae (BGA) species, that is, Nostoc commune var. sphaeroides Kützing (NO) and Spirulina platensis (SP), in apolipoprotein E knockout (ApoE−/−) mice, a well-established mouse model of atherosclerosis. Male ApoE−/− mice were fed a high-fat/high-cholesterol (HF/HC, 15% fat and 0.2% cholesterol by wt) control diet or a HF/HC diet supplemented with 5% (w/w) of NO or SP powder for 12 weeks. Plasma total cholesterol (TC) and triglycerides (TG) were measured, and livers were analyzed for histology and gene expression. Morphometric analysis for lesions and immunohistochemical analysis for CD68 were conducted in the aorta and the aortic root. NO supplementation significantly decreased plasma TC and TG, and liver TC, compared to control and SP groups. In the livers of NO-fed mice, less lipid droplets were present with a concomitant decrease in fatty acid synthase protein levels than the other groups. There was a significant increase in hepatic low-density lipoprotein receptor protein levels in SP-supplemented mice than in control and NO groups. Quantification of aortic lesions by en face analysis demonstrated that both NO and SP decreased aortic lesion development to a similar degree compared with control. While lesions in the aortic root were not significantly different between groups, the CD68-stained area in the aortic root was significantly lowered in BGA-fed mice than controls. In conclusion, both NO and SP supplementation decreased the development of atherosclerotic lesions, suggesting that they may be used as a natural product for atheroprotection.
PMCID: PMC4685491  PMID: 26566121
atherosclerosis; blue-green algae; Nostoc commune var. sphaeroids kutzing
6.  Hypolipidemic Effect of a Blue-Green Alga (Nostoc commune) Is Attributed to Its Nonlipid Fraction by Decreasing Intestinal Cholesterol Absorption in C57BL/6J Mice 
Journal of Medicinal Food  2015;18(11):1214-1222.
We previously demonstrated that Nostoc commune var. sphaeroids Kützing (NO), a blue-green alga (BGA), exerts a hypolipidemic effect in vivo and its lipid extract regulates the expression of genes involved in cholesterol and lipid metabolism in vitro. The objective of this study was to investigate whether the hypolipidemic effect of NO is attributed to an algal lipid or a delipidated fraction in vivo compared with Spirulina platensis (SP). Male C57BL/6J mice were fed an AIN-93M diet containing 2.5% or 5% of BGA (w/w) or a lipid extract equivalent to 5% of BGA for 4 weeks to measure plasma and liver lipids, hepatic gene expression, intestinal cholesterol absorption, and fecal sterol excretion. Plasma total cholesterol (TC) was significantly lower in 2.5% and 5% NO-fed groups, while plasma triglyceride (TG) levels were decreased in the 5% NO group compared with controls. However, neither NO organic extract (NOE) nor SP-fed groups altered plasma lipids. Hepatic mRNA levels of sterol regulatory element-binding protein 2, 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR), carnitine palmitoyltransferase-1α, and acyl-CoA oxidase 1 were induced in 5% NO-fed mice, while there were no significant changes in hepatic lipogenic gene expression between groups. NO, but not NOE and SP groups, significantly decreased intestinal cholesterol absorption. When HepG2 cells and primary mouse hepatocytes were incubated with NOE and SP organic extract (SPE), there were marked decreases in protein levels of HMGR, low-density lipoprotein receptor, and fatty acid synthase. In conclusion, the nonlipid fraction of NO exerts TC and TG-lowering effects primarily by inhibiting intestinal cholesterol absorption and by increasing hepatic fatty acid oxidation, respectively.
PMCID: PMC4638206  PMID: 26161942
blue-green algae; hypolipidemia; Nostoc commune var; sphaeroids Kützing; Spirulina platensis
7.  Blueberry, blackberry, and blackcurrant differentially affect plasma lipids and pro-inflammatory markers in diet-induced obesity mice 
Nutrition Research and Practice  2016;10(5):494-500.
Evidence indicates that berry anthocyanins are anti-atherogenic, antioxidant, and anti-inflammatory. However, berries differ vastly in their anthocyanin composition and thus potentially in their biological and metabolic effects. The present study compared hypolipidemic, antioxidant, and anti-inflammatory properties of blueberry (BB), blackberry (BK), and blackcurrant (BC) in a diet-induced obesity (DIO) mouse model.
Male C57BL/6J mice were fed a high fat (HF; 35% fat, w/w) control diet or a HF diet supplemented with freeze-dried 5% BB, 6.3% BK or 5.7% BC for 12 weeks (10 mice/group) to achieve the same total anthocyanin content in each diet. Plasma lipids, antioxidant status and pro-inflammatory cytokines were measured. The expression of genes involved in antioxidant defense, inflammation, and lipid metabolism was determined in the liver, epididymal adipose tissue, proximal intestine, and skeletal muscle. Histological analysis was performed to identify crown-like structure (CLS) in epididymal fat pads to determine macrophage infiltration.
No differences were noted between the control and any berry-fed groups in plasma levels of liver enzymes, insulin, glucose, ferric reducing antioxidant power, superoxide dismutase, and tumor necrosis factor α. However, BK significantly lowered plasma triglyceride compared with the HF control and other berries, whereas BC significantly reduced F4/80 mRNA and the number of CLS in the epididymal fat pad, indicative of less macrophage infiltration.
The present study provides evidence that BB, BK and BC with varying anthocyanin composition differentially affect plasma lipids and adipose macrophage infiltration in DIO mice, but with no differences in their antioxidant capacity and anti-inflammatory potential.
PMCID: PMC5037066  PMID: 27698956
Berry anthocyanins; antioxidant capacity; hypolipidemic effects; inflammation; macrophage
8.  Eliciting the mitochondrial unfolded protein response by nicotinamide adenine dinucleotide repletion reverses fatty liver disease in mice 
Hepatology (Baltimore, Md.)  2015;63(4):1190-1204.
With no approved pharmacological treatment, nonalcoholic fatty liver disease (NAFLD) is now the most common cause of chronic liver disease in Western countries and its worldwide prevalence continues to increase along with the growing obesity epidemic. Here, we show that a high‐fat high‐sucrose (HFHS) diet, eliciting chronic hepatosteatosis resembling human fatty liver, lowers hepatic nicotinamide adenine dinucleotide (NAD+) levels driving reductions in hepatic mitochondrial content, function, and adenosine triphosphate (ATP) levels, in conjunction with robust increases in hepatic weight, lipid content, and peroxidation in C57BL/6J mice. To assess the effect of NAD+ repletion on the development of steatosis in mice, nicotinamide riboside, a precursor of NAD+ biosynthesis, was added to the HFHS diet, either as a preventive strategy or as a therapeutic intervention. We demonstrate that NR prevents and reverts NAFLD by inducing a sirtuin (SIRT)1‐ and SIRT3‐dependent mitochondrial unfolded protein response, triggering an adaptive mitohormetic pathway to increase hepatic β‐oxidation and mitochondrial complex content and activity. The cell‐autonomous beneficial component of NR treatment was revealed in liver‐specific Sirt1 knockout mice (Sirt1hep−/−), whereas apolipoprotein E‐deficient mice (Apoe −/−) challenged with a high‐fat high‐cholesterol diet affirmed the use of NR in other independent models of NAFLD. Conclusion: Our data warrant the future evaluation of NAD+ boosting strategies to manage the development or progression of NAFLD. (Hepatology 2016;63:1190–1204)
PMCID: PMC4805450  PMID: 26404765
9.  How Best to Obtain Valid, Verifiable Data Online From Male Couples? Lessons Learned From an eHealth HIV Prevention Intervention for HIV-Negative Male Couples 
As interest increases in the development of eHealth human immunodeficiency virus (HIV)-preventive interventions for gay male couples, Web-based methods must also be developed to help increase the likelihood that couples enrolled and data collected from them represent true unique dyads. Methods to recruit and collect reliable and valid data from both members of a couple are lacking, yet are crucial for uptake of novel sexual health and HIV-prevention eHealth interventions. Methods to describe best practices to recruit male couples using targeted advertisements on Facebook are also lacking in the literature, yet could also help in this uptake.
The objective of our study was to describe challenges and lessons learned from experiences from two phases (developmental phase and online randomized controlled trial [RCT]) of an eHealth HIV-prevention intervention for concordant HIV-negative male couples in terms of (1) recruiting male couples using targeted advertisements on Facebook, (2) validating that data came from two partners of the couple, and (3) verifying that the two partners of the couple are in a relationship with each other.
The developmental phase refined the intervention via in-person focus groups, whereas the pilot-testing phase included an online RCT. For both phases, couples were recruited via targeted Facebook advertisements. Advertisements directed men to a study webpage and screener; once eligible, participants provided consent electronically. A partner referral system was embedded in the consenting process to recruit the relationship partner of the participant. Both men of the couple had to meet all eligibility criteria—individually and as a couple—before they could enroll in the study. Verification of couples’ relationships was assessed via the concurrence of predetermined screener items from both partners, done manually in the developmental phase and electronically in the pilot-testing phase. A system of decision rules was developed to assess the validity that data came from two unique partners of a couple.
Several important lessons were learned from these experiences, resulting in recommendations for future eHealth studies involving male couples. Use of certain “interests” and types of images (eg, shirtless) in targeted Facebook advertisements should be avoided or used sparingly because these interests and types of images may generate adverse reactions from a broader audience. Development of a systematic approach with predetermined criteria and parameters to verify male couples’ relationships is strongly recommended. Further, researchers are encouraged to develop a system of decision rules to detect and handle suspicious data (eg, suspicious email addresses/names, multiple entries, same IP address used in multiple entries) to help validate the legitimacy of male couples’ relationships online.
These lessons learned combined with recommendations for future studies aim to help enhance recruitment efforts and the validity and reliability of collecting dyadic data from male couples for novel eHealth HIV-preventive interventions.
PMCID: PMC5050384  PMID: 27649587
eHealth, male couples; dyadic data; recruitment; validation; verification
10.  Effects of Poor Maternal Nutrition during Gestation on Bone Development and Mesenchymal Stem Cell Activity in Offspring 
PLoS ONE  2016;11(12):e0168382.
Poor maternal nutrition impairs overall growth and development of offspring. These changes can significantly impact the general health and production efficiency of offspring. Specifically, poor maternal nutrition is known to reduce growth of bone and muscle, and increase adipose tissue. Mesenchymal stem cells (MSC) are multipotent stem cells which contribute to development of these tissues and are responsive to changes in the maternal environment. The main objective was to evaluate the effects of poor maternal nutirtion during gestation on bone and MSC function in offspring. Thirty-six ewes were fed 100%, 60%, or 140% of energy requirements [NRC, 1985] beginning at day 31 ± 1.3 of gestation. Lambs from ewes fed 100% (CON), 60% (RES) and 140% (OVER) were euthanized within 24 hours of birth (1 day; n = 18) or at 3 months of age (n = 15) and bone and MSC samples were collected. Dual X-ray absorptiometry was performed on bones obtained from day 1 and 3 months. Proliferation, differentiation, and metabolic activity were determined in the MSC isolated from lambs at day 1. Data were analyzed using mixed procedure in SAS. Maternal diet negatively affected offspring MSC by reducing proliferation 50% and reducing mitochondrial metabolic activity. Maternal diet did not alter MSC glycolytic activity or differentiation in culture. Maternal diet tended to decrease expression of P2Y purinoreceptor 1, but did not alter expression of other genes involved in MSC proliferation and differentiation. Maternal diet did not alter bone parameters in offspring. In conclusion, poor maternal diet may alter offspring growth through reduced MSC proliferation and metabolism. Further studies evaluating the potential molecular changes associated with altered proliferation and metabolism in MSC due to poor maternal nutrition are warranted.
PMCID: PMC5152907  PMID: 27942040
11.  Self-Deprecating Humor Versus Other-Deprecating Humor in Health Messages 
Journal of health communication  2015;20(10):1185-1195.
Humor is sometimes employed in health messages. However, little is known about contingencies under which different types of humor may or may not be effective. This experiment crossed humorous vs. non-humorous and self- vs. other-deprecating messages about binge drinking, and tested how differences in personal investment in alcohol use moderates the effects of such messages on college binge drinkers. Results showed significant three-way interaction effects on subjective norms and behavioral intentions largely consistent with hypotheses. Assessment of significant differences in the interactions indicated that for binge drinkers who weren’t high in personal investment in alcohol use, other-deprecating humor tended to reduce their perceived subjective norms about the acceptability of binge drinking behavior and their behavioral intentions. The effect of the experimental manipulation on subjective norms among these binge drinkers was shown to mediate the effect on intentions to binge drink in the future. Theoretical and practical implications are discussed.
PMCID: PMC4958488  PMID: 26020507
12.  Retrospective growth kinetics and radiosensitivity analysis of various human xenograft models 
Laboratory Animal Research  2016;32(4):187-193.
The purpose of this study was to delineate the various factors that affect the growth characteristics of human cancer xenografts in nude mice and to reveal the relationship between the growth characteristics and radiosensitivity. We retrospectively analyzed 390 xenografts comprising nine different human cancer lines grown in nude mice used in our institute between 2009 and 2015. Tumor growth rate (TGR) was calculated using exponential growth equations. The relationship between the TGR of xenografts and the proliferation of the cells in vitro was examined. Additionally, we examined the correlations between the surviving fractions of cells after 2 Gy irradiation in vitro and the response of the xenograft to radiation. The TGR of xenografts was positively related to the proliferation of the cells in vitro (rP=0.9714, p<0.0001), whereas it was independent of the histological type of the xenografts. Radiation-induced suppression of the growth rate (T/C%) of xenografts was positively related to the radiosensitivity of the cells in vitro (SF2; rP=0.8684, p=0.0284) and TGR (rP=0.7623, p=0.0780). The proliferation of human cancer cells in vitro and the growth rate of xenografts were positively related. The radiosensitivity of cancer cells, as judged from the SF2 values in vitro, and the radiation-induced suppression of xenograft growth were positively related. In conclusion, the growth rate of human xenografts was independent of histological type and origin of the cancer cells, and was positively related to the proliferation of the cancer cells in vitro.
PMCID: PMC5206224  PMID: 28053611
Human xenograft model; retrospective analysis; radiation; cell line characteristics; in vitro-in vivo correlation
13.  Community health center patients' response to and beliefs about outreach promoting clinical preventive services 
We sought community health center (CHC) patients' feedback regarding an outreach intervention promoting primary prevention of cardiovascular disease to patients at increased risk. We performed a telephone survey that assessed whether patients recalled receiving the intervention, what actions occurred in response to the intervention, and patient attitudes regarding receipt of preventive service messages from their CHC. Participants (n = 80) were 89% male, and 59% were black. Among the 88% of respondents who reported a healthcare visit, 84% reported a discussion about cholesterol or heart disease risk with their provider, of these 44% reported a statin was recommended and 89% reported currently taking it. Participants reported high acceptability of receiving preventive service messages, but were less likely to agree that they wanted to receive preventive service messages via text or email compared to other modes of contact. Our results show that outreach programs to promote indicated preventive services were viewed positively by this patient group. We also identified areas where the CVD prevention program may have lost effectiveness.
•Health center patients usually had clinic visits following preventive CVD outreach.•Patient-identified barriers to making a visit or taking medication were infrequent.•Cholesterol-lowering medication was recommended less than half of the time.•Health center outreach promoting preventive care services was viewed favorably.•Text or email messages were less preferred than phone, mail or in-person outreach.
PMCID: PMC5148778  PMID: 27957409
Cardiovascular disease; Primary prevention; Patient outreach
14.  Anti-Inflammatory Effects of Spirulina platensis Extract via the Modulation of Histone Deacetylases 
Nutrients  2016;8(6):381.
We previously demonstrated that the organic extract of Spirulina platensis (SPE), an edible blue-green alga, possesses potent anti-inflammatory effects. In this study, we investigated if the regulation of histone deacetylases (HDACs) play a role in the anti-inflammatory effect of SPE in macrophages. Treatment of macrophages with SPE rapidly and dose-dependently reduced HDAC2, 3, and 4 proteins which preceded decreases in their mRNA levels. Degradation of HDAC4 protein was attenuated in the presence of inhibitors of calpain proteases, lysosomal acidification, and Ca2+/calmodulin-dependent protein kinase II, respectively, but not a proteasome inhibitor. Acetylated histone H3 was increased in SPE-treated macrophages to a similar level as macrophages treated with a pan-HDAC inhibitor, with concomitant inhibition of inflammatory gene expression upon LPS stimulation. Knockdown of HDAC3 increased basal and LPS-induced pro-inflammatory gene expression, while HDAC4 knockdown increased basal expression of interleukin-1β (IL-1β), but attenuated LPS-induced inflammatory gene expression. Chromatin immunoprecipitation showed that SPE decreased p65 binding and H3K9/K14 acetylation at the Il-1β and tumor necrosis factor α (Tnfα) promoters. Our results suggest that SPE increased global histone H3 acetylation by facilitating HDAC protein degradation, but decreases histone H3K9/K14 acetylation and p65 binding at the promoters of Il-1β and Tnfα to exert its anti-inflammatory effect.
PMCID: PMC4924221  PMID: 27338466
Spirulina platensis; histone deacetylases; anti-inflammatory; inflammation; epigenetics
15.  The Role of Genetic Risk Score in Predicting the Risk of Hypertension in the Korean population: Korean Genome and Epidemiology Study 
PLoS ONE  2015;10(6):e0131603.
Hypertension is regarded as a multifactorial disease with a modest contribution of genetic factors and strongly affected by environmental factors. Recent genome-wide association studies have identified specific loci associated with high blood pressure (BP) and hypertension. This study aimed to examine the association between the genetic risk score (GRS), a linear function of multiple single nucleotide polymorphisms (SNPs) associated with hypertension, and high BP and prevalent hypertension at baseline examination and to evaluate the efficacy of the GRS for predicting incident hypertension with longitudinal data in Korean subjects. Data for 8,556 participants, aged 40 to 69, in a community-based cohort study were analyzed. Unweighted GRS (cGRS) and weighted GRS (wGRS) were constructed from 4 SNPs related to high BP or hypertension in previous genome-wide association and its replication studies for the Korean middle-aged population. Cross-sectional analysis (n=8,556) revealed that cGRS was significantly associated with prevalent hypertension (odds ratio=1.15 per risk allele; 95%CI, 1.09-1.20). Additionally, the odds ratios (ORs) of prevalent hypertension for those who in medium and the highest tertile compared with those who in the lowest tertile of wGRS were 1.31 (95% CI, 1.15-1.50) and 1.59 (95%CI, 1.38-1.82), respectively. In a longitudinal analysis (n=5,632), participants in the highest tertile of wGRS had a 1.22-fold (OR=1.22, 95%CI, 1.02‒1.46) greater risk of incident hypertension relative to those in the lowest tertile, after adjusting for a number of confounding factors. However, wGRS topped with traditional risk factors had no significant effect on discrimination ability (c-statistics with and without wGRS were 0.811 and 0.810, P=0.1057). But, reclassification analysis showed that the addition of GRS to the model with conventional risk factors led to about 9% significant increment in category-free net reclassification improvement. GRSs based on 4 SNPs were independently associated with hypertension and may provide a statistically significant improvement over the existing model for prediction of incident hypertension.
PMCID: PMC4482533  PMID: 26110887
16.  The Effect of FLT1 Variant on Long-Term Cardiovascular Outcomes: Validation of a Locus Identified in a Previous Genome-Wide Association Study 
PLoS ONE  2016;11(10):e0164705.
Data on genetic variants that can predict follow-up cardiovascular events are highly limited, particularly for Asians. The aim of this study was to validate the effects of two variants in FLT1 and 9p21 on long-term cardiovascular outcomes in high-risk Korean patients.
We examined the prognostic values of the rs9508025 and rs1333049 variants that were found to be associated with coronary artery disease (CAD) risk in a previous Korean genome-wide association study. A total of 2693 patients (mean age: 55.2 years; male: 55.2%) with CAD or its risk factors at baseline were enrolled and followed for major adverse cardiac events (MACE).
During the mean follow-up of 8.8 years, 15.4% of the patients experienced MACE. Kaplan-Meier curves showed that MACE-free survival was different according to the genotype of rs9508025 (log rank p = 0.02), whereas rs1333049 genotype did not correlate with the prognosis. Multivariate Cox proportional hazard analysis showed that C-allele of rs9508025 was significantly associated with a high rate of MACE, while rs1333049 was not. Further analyses demonstrated that the association of the rs9508025 variant with MACE was mainly due to its relation to coronary revascularization, which was also associated with the rs1333049 variant. In an additional analysis, rs9508025 was found to be an independent determinant of the outcome only in the subgroup with history of CAD.
rs9508025 in FLT1 was significantly associated with long-term cardiovascular events, particularly in patients with prior CAD. The association of rs1333049 in 9p21 was not significant.
PMCID: PMC5063388  PMID: 27736948
17.  Efficacy and Toxicity of Mammalian Target Rapamycin Inhibitors in Patients with Metastatic Renal Cell Carcinoma with Renal Insufficiency: The Korean Cancer Study Group GU 14-08 
We evaluated the efficacy and toxicity of mammalian target rapamycin inhibitors in Korean patients with metastatic renal cell carcinoma (mRCC) with chronic renal insufficiency not requiring dialysis.
Materials and Methods
Korean patients with mRCC and chronic renal insufficiency not requiring dialysis treated with everolimus or temsirolimus between January 2008 and December 2014 were included. Patient characteristics, clinical outcomes, and toxicities were evaluated. Overall survival (OS) and progression-free survival (PFS) durations were evaluated according to the degree of renal impairment.
Eighteen patients were considered eligible for the study (median age, 59 years). The median glomerular filtration rate was 51.5 mL/min/1.73 m2. The best response was partial response in six patients and stable disease in 11 patients. The median PFS and OS durations were 8 months (95% confidence interval [CI], 0 to 20.4) and 32 months (95% CI, 27.5 to 36.5), respectively. The most common non-hematologic and grade 3/4 adverse events included stomatitis, fatigue, flu-like symptoms, and anorexia as well as elevated creatinine level.
Mammalian target rapamycin inhibitors were efficacious and did not increase toxicity in Korean patients with mRCC and chronic renal insufficiency not requiring dialysis.
PMCID: PMC5080820  PMID: 26875195
TOR serine-threonine kinases; Renal cell carcinoma; Renal insufficiency
18.  Predictors of Cholesterol Treatment Discussions and Statin Prescribing for Primary Cardiovascular Disease Prevention in Community Health Centers 
Preventive medicine  2016;88:176-181.
Although cholesterol guidelines emphasize cardiovascular disease (CVD) risk to guide primary prevention, predictors of statin use in practice are unknown. We aimed to identify factors associated with a cholesterol treatment discussion and statin prescribing in a high-risk population.
We used data from a trial conducted among participants in community health centers without CVD or diabetes and a 10-year coronary heart disease (CHD) risk ≥10%. Cholesterol treatment discussion was assessed at 6 months and statin prescription at 1 year. We used logistic regressions to identify factors associated with each outcome.
We analyzed 646 participants (89% male, mean age 60 ± 9.5 years). Cholesterol treatment discussion occurred in 19% and statin prescription in 12% of participants. Ten-year CHD risk was not associated with treatment discussion (OR 1.11 per 1 SD increase, 95% CI 0.91-1.33) but was associated with statin prescription (OR 1.41 per 1 SD increase, 95% CI 1.13-1.75) in unadjusted models. After adjusting for traditional CVD risk factors that contribute to CHD risk, low-density lipoprotein cholesterol (LDL-C) was independently associated with statin prescription (OR 1.82 per 1 SD increase, 95% CI 1.66-1.99). Antihypertensive medication use was independently associated with both cholesterol treatment discussion (OR 3.68, 95% CI 2.35-5.75) and statin prescription (OR 3.98, 95% CI 3.30-4.81). Other drivers of CVD risk (age, smoking, and systolic blood pressure) were not associated with statin use.
Single risk factor management strongly influences cholesterol treatment discussions and statin prescribing patterns. Interventions that promote risk-based statin utilization are needed.
PMCID: PMC5040465  PMID: 27090436
cardiovascular disease prevention; cholesterol; risk assessment
19.  Imaging Features of Breast Dermatofibrosarcoma Protuberans in Various Modalities Including FDG-PET CT 
Iranian Journal of Radiology  2016;13(2):e33916.
Dermatofibrosarcoma protuberans is an uncommon malignant mesenchymal tumor of the dermis, which most commonly appears on the body and extremities. A preoperative diagnosis of dermatofibrosarcoma protuberans is extremely difficult, because it is a very rare entity and its appearance is often similar to that of benign breast lesion. Here, we presented a case of breast dermatofibrosarcoma protuberans with associated radiological mammography, ultrasound, magnetic resonance imaging and fludeoxyglucose-positron emission tomography computerized tomography (FDG-PET CT) features. To our knowledge, our case is the first report of PET-CT findings of breast dermatofibrosarcoma protuberans. Furthermore, we reviewed characteristic radiologic features of this rare entity, which are helpful for differentiating it from other primary benign breast lesions.
PMCID: PMC5037929  PMID: 27703659
Dermatofibrosarcoma Protuberans; Breast; Ultrasound; MRI; PET
20.  Effects of Long-Term Supplementation of Blue-Green Algae on Lipid Metabolism in C57BL/6J mice 
Dyslipidemia is a primary risk factor for cardiovascular disease. In this study, we investigated the effect of long-term supplementation of two blue-green algae (BGA) species, i.e., Nostoc commune var. sphaeroides Kützing (NO) and Spirulina platensis (SP), on lipid metabolism in vivo. Male C57BL/6J mice were fed an AIN-93G/M diet supplemented with 2.5 or 5% (wt/wt) NO or SP for 6 months. Mice fed NO and SP showed lower plasma total cholesterol (TC) and triglyceride (TG) concentrations than control at certain months during 6 month experimental period. Both BGA supplementation for 6 months significantly increased hepatic TC contents whereas SP-fed groups had significantly less TG levels in the liver compared with control and NO groups. None of BGA-fed animals showed significantly different mRNA levels of sterol regulatory element binding protein 2, while 3-hydroxy-3-methylglutaryl coenzyme A reductase and low-density lipoprotein receptor (LDLR) expression was higher in NO groups than the other groups in the liver. Furthermore, NO supplementation increased the hepatic expression of acetyl-CoA carboxylase 1, stearoyl CoA desaturase 1, carnitine palmitoyltransferase 1α, and acyl-CoA oxidase 1 but SP did not elicit any significant changes in mRNA levels of the genes compared with control. LDLR protein level was significantly higher in NO 2.5% and SP 5%, as compared to the control and NO 5% groups; while the level of fatty acid synthase protein in the liver was significantly higher in NO 5% and SP 5%, than that in the control group. In conclusion, our results suggest that long-term supplementation of NO and SP decreased plasma TC and TG concentrations. Therefore, supplementation of NO and SP may be potentially beneficial for preventing dyslipidemia-associated chronic diseases.
PMCID: PMC4299668  PMID: 25614902
Blue-green algae; Cholesterol; Nostoc commune var. sphaeroides Kützing; Spirulina platensis; Triglyceride
21.  Crystallization and preliminary X-ray analysis of the C-terminal fragment of Ski7 from Saccharomyces cerevisiae  
C-terminal domains 2 and 3 of Ski7 from S. cerevisiae were purified and crystallized. The crystals diffracted to 2.0 Å resolution.
Ski7 (superkiller protein 7) plays a critical role in the mRNA surveillance pathway. The C-terminal fragment of Ski7 (residues 520–747) from Saccharo­myces cerevisiae was heterologously expressed in Escherichia coli and purified to homogeneity. It was successfully crystallized and preliminary X-ray data were collected to 2.0 Å resolution using synchrotron radiation. The crystal belonged to a trigonal space group, either P3121 or P3221, with unit-cell parameters a = b = 73.5, c = 83.6 Å. The asymmetric unit contains one molecule of the C-terminal fragment of Ski7 with a corresponding crystal volume per protein mass (V M) of 2.61 Å3 Da−1 and a solvent content of 52.8% by volume. The merging R factor is 6.6%. Structure determination by MAD phasing is under way.
PMCID: PMC4157430  PMID: 25195903
mRNA surveillance; nonstop decay; RNA degradation; Saccharomyces cerevisiae; Ski7
22.  Cooperative dynamics of intact AMPA and NMDA glutamate receptors – similarities and subfamily-specific differences 
Structure (London, England : 1993)  2015;23(9):1692-1704.
Ionotropic glutamate receptors (iGluRs) are tetrameric ion channels that mediate excitatory neurotransmission. Recent structures of AMPA and NMDA receptors permit a comparative analysis of whole-receptor dynamics for the first time. Despite substantial differences in the packing of their two-domain extracellular region, the two iGluRs share similar dynamics, elucidated by elastic network models. Motions accessible to either structure enable conformational interconversion, such as compression of the AMPAR towards the more tightly packed NMDAR conformation, which has been linked to allosteric regulation. Pivoting motions coupled to concerted rotations of the transmembrane ion channel are prominent between dimers of distal N-terminal domains in the loosely-packed AMPAR. The occurrence and functional relevance of these motions is verified by cross-linking experiments designed to probe the computationally predicted distance changes. Together with the identification of hot-spot residues acting as mediators of allosteric communication, our data provide a glimpse into the dynamic spectrum of iGluRs.
PMCID: PMC4558295  PMID: 26256538
ionotropic glutamate receptors; AMPA and NMDA receptors; NTD-LBD coupling; conformational dynamics; allosteric events; signal transduction; effector residues; elastic network models; crosslinking; mutagenesis
23.  Treatment outcomes of IMEP as a front-line chemotherapy for patients with peripheral T-cell lymphomas 
Blood research  2016;51(3):187-192.
This study aimed to assess the treatment outcomes of ifosphamide, mesna, etoposide, and prednisolone (IMEP) combination regimen as a front-line chemotherapy in patients with peripheral T-cell lymphomas (PTCLs).
Clinical data of 38 newly diagnosed PTCLs patients who underwent IMEP at Busan Paik Hospital from January 2002 to December 2013 were retrospectively analyzed.
The overall response rate was 68.5%, with 21 (55.3%) complete response/complete response unconfirmed and 6 (15.8%) partial response (PR). The median follow-up duration was 25.5 months (range, 0.2-87.3). The median overall survival was not reached and 2-year survival rate was 67%. The median progression free survival was 23 months. The most frequently reported adverse effects higher than grade 3 were hematologic toxicities including neutropenia (68.4%), thrombocytopenia (42.1%). There was no treatment-related mortality.
IMEP regimen is effective and safe as a front-line chemotherapy in patients with PTCLs.
PMCID: PMC5054251  PMID: 27722130
Peripheral T-cell lymphomas; IMEP; Ifosphamide; Etoposide; Prednisolone
24.  Modulatory Effect of Eui-E-In-Tang on Serum Leptin Concentration in Obese Korean Female Adults: A Randomized Controlled Trial 
Background. Obesity is associated with chronic inflammation and cytokines. However, to date, the relationship between the serum levels of cytokines in obese individuals and taking herbal drugs remains largely unexplored. Methods. Serum cytokines were assessed by multiplex cytokine profiling assay. Serum samples of obese female Korean adults (obese group; n = 20) as well as normal female Korean adults (normal group; n = 21) were collected at the start and end of study period. Twenty obese female Korean adults were randomized to receive Eui-E-In-Tang (Eui-E-In-Tang group; n = 9) at a daily dose of 9 g or a matched placebo (placebo group; n = 11) for 12 weeks. Results. According to investigating serum cytokine levels at the start point of this study, the serum C-peptide, insulin, leptin, lipocalin-2, and adipsin levels in the obese group were found to be significantly higher than in the normal group. And the investigation of serum cytokine levels at the end point of this study demonstrated that mean serum leptin of Eui-E-In-Tang group was found to be significantly reduced (P = 0.037). Conclusions. This study provides preliminary evidence that Eui-E-In-Tang may exert immunomodulatory effect via altering the circulating concentration of leptin in Korean female adults.
PMCID: PMC5007306  PMID: 27630731
25.  The impact of positive peritoneal cytology on prognosis in patients with cervical cancer: a meta-analysis 
British Journal of Cancer  2015;113(4):595-602.
The impact of positive peritoneal cytology on the prognosis of cervical cancer is controversial. Thus, we performed a meta-analysis to determine its impact on recurrence, and to investigate correlations between abnormal cytology and/or lymph node metastasis in cervical cancer.
A systematic literature review was conducted through July 2014. Odds ratios (ORs) and their 95% confidence intervals (95% CIs) were calculated by standard meta-analysis techniques with the fixed-effects models, if there was no significant statistical heterogeneity across studies by using I2.
Of 303 studies retrieved, 6 were included in the meta-analysis. These six case–control observational studies included 1360 cervical cancer patients who showed negative peritoneal cytology and 64 who showed positive peritoneal cytology. Over the combined study period, 20 of 45 in the positive peritoneal cytology group experienced recurrence, whereas 88 of 539 controls did. The meta-analysis based on the fixed-effects model indicated a significant increase in the risk of recurrence in the positive peritoneal cytology group relative to the control group (OR: 4.47; 95% CI: 2.33–8.58, P<0.001, I2=0.0%). Moreover, the results of our meta-analysis suggested that the positive peritoneal cytology group displayed more lymph node metastasis than the negative peritoneal cytology group (OR: 3.73; 95% CI: 2.13–6.53, P<0.001, I2=0.0%).
Although based mainly on retrospective observational studies, our meta-analysis indicates that abnormal peritoneal cytology may be strongly associated with poor prognosis in patients with cervical cancer. Future research should verify this relationship through prospective observational studies over a longer term.
PMCID: PMC4647682  PMID: 26225551
cervical cancer; peritoneal cytology; prognosis; meta-analysis

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