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Uterine leiomyoma is a benign tumor that grows within the muscle tissue of the uterus. Ulipristal acetate (UPA) is a pre‑operative drug used to reduce the size of leiomyoma. The aim of the present study was to examine the in vitro mechanistic details of action of UPA on uterine leiomyomas. Primary cultures of leiomyoma cells were isolated from patient myomectomy specimens and incubated in the presence or absence of UPA at various concentrations. The proliferation, cell viability and doubling time properties of the treated cells were analyzed. In addition, the mRNA and protein expression levels of p21, p27, cyclin E, cyclin‑dependent kinase 2 (CDK2), matrix metalloproteinase (MMP)‑2 and MMP‑9 were examined, as well as the structure of F‑actin in the primary‑cultured leiomyoma cells. The results demonstrated that UPA exerted inhibitory effects on proliferation of primary‑cultured leiomyoma cells. Expression of p21 and p27 was upregulated, while cyclin E and CDK2 were downregulated in UPA‑treated primary‑cultured leiomyoma cells. An increased expression of MMP‑2 was observed in primary‑cultured leiomyoma cells and a leiomyoma tissue sample of a patient with previous history of UPA treatment. Furthermore, a pronounced formation of F‑actin stress fibers was observed in leiomyoma cells of the UPA‑treated patient. These data suggest that UPA treatment attenuated the proliferation of uterine fibroid cells via upregulation of p21 and p27, resulting in cell cycle delay. The findings in the current study also suggest that UPA may cause extracellular matrix constriction, leading to the shrinkage in size of the leiomyoma possibly via stimulation of MMP‑2 expression and induction of actin stress fibers.

This article was migrated. The article was marked as recommended. Introduction Medical educators need to demonstrate that their trainees meet expected competency levels when progressing through medical education. This study aimed to develop competency-based pass/fail cut-scores for a graduation required Objective Structured Clinical Examination (OSCE), and examine validity evidence for new standards. Methods Six clinicians used the modified Angoff method to determine the cut-scores for an 8-station OSCE. The clinicians estimated the percentage of minimally competent students who would answer each checklist item correctly. Inter-rater reliability, differences in other academic achievements between pass/fail groups, educational impact, and response process were examined. Results One hundred seventy-four rising 4th-year medical students participated in the OSCE. The cut-scores determined for the OSCE resulted in a substantially lower failure rate (5% vs. 29% of the previous year). The inter-rater reliability across domains and cases was .98 (95% CI = .97 - .99). The pass/fail groups significantly differed in six of the eight measures of academic achievements included in the study. Discussion The impact of the standards setting was substantial as it significantly reduced the failure rate and burdens of remediation for both students and faculty. The very high inter-rater reliability indicates that the modified Angoff method produced reliable cut-scores. The significant differences between the pass/fail groups in other measures support external validity of the standards and ensure no false passes. The study also supports response process validity by including discussion among judges and check of previous student performances, as well as recruiting and training multiple clinician educators experienced in medical student teaching. Conclusion Findings of the study provide strong evidence supporting validity of the new cut-scores from a wide spectrum of validity metrics, including response process, internal structure, relations to other variables, and consequences. The study also added to the literature the value of the modified Angoff method in determining competency-based standards for OSCEs., (Copyright: © 2018 Lee M et al.)

Herein, we hypothesized that ZIP11 variants would be important risk factors for chronic gastritis and that there would be an interaction effect of the relationship between their variants and spicy food intake on the development of chronic gastritis. Participants in this cross-sectional study (n = 3882 + 252) were recruited from a cohort of the Korean Genome and Epidemiology Study in 2001. Age, sex, education, smoking and drinking status, exercise, stress, and income level of all participants were determined by a questionnaire. Demographic and anthropometric data were collected. Fasting blood samples were collected to determine the serum levels of glucose, insulin, total bilirubin, total cholesterol, high-density lipoprotein cholesterol, and triglycerides. The presence of chronic gastritis was defined as a confirmed diagnosis by a physician. Food consumption was determined using a semiquantitative food frequency questionnaire. We found 8 different single nucleotide polymorphisms (SNPs) that are significantly different between subjects without gastritis and those with gastritis. Of these 8 SNPs, 3 SNP (rs17183225 [C/T], rs17780814 [A/C], and rs17780820 [A/G]) are closely located in the intronic region of zinc transporter SLC39A11, commonly known as ZIP11, and show linkage disequilibrium (D' = 1.0). We also found that participants with (TCA + TCG) haplotype of ZIP11 at high levels of dietary intake of spicy foods show a significantly increasing tendency in the odds of having chronic gastritis when compared with those with CAA haplotype (odds ratio, 2.620; 95% confidence interval, 1.207-5.689). The data indicate positive associations between higher meal frequency and lower spicy food preference and gastritis. In conclusion, we found that zinc transporter gene ZIP11 is associated with chronic gastritis in the Korean population and it may interact with spicy food, which suggests ZIP11 as a therapeutic target for precision nutrition., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The effects of each blood pressure index [systolic and diastolic blood pressure (SBP, DBP), pulse pressure (PP), mean arterial pressure (MAP)] on the occurrence of mortality and cardiovascular (CV) events have not yet been investigated in prehypertensive populations., Methods: A total of 30,258 prehypertensive Korean participants underwent periodic health examination between 2003 and 2004 were enrolled, and the associations of BP components with mortality and CV events were investigated. Moreover, based on the DBP [80 ≤ DBP <90 mmHg (N = 21,323) and DBP <80 mmHg (N = 8,935)], the effects of BP components were also evaluated., Results: Multivariate Cox analyses in prehypertensive group revealed that the hazard ratios (HRs) were 1.121 and 1.130 per 10 mmHg increase in SBP and PP for mortality, respectively. Additionally, 10 mmHg increase of SBP (HR:1.090) was still significantly, but increase of PP (HR:1.060) was marginally associated with higher incidence of CV events. However, there were no significant associations with increase in DBP or MAP on adverse clinical outcomes in prehypertensive group. In the prehypertensive subjects with DBP <80 mmHg, CV events more frequently occurred by 38.8% and 28.5% per 10 mmHg increase in SBP and PP, respectively., Conclusions: Prehypertensive subjects might need to be cautioned when they have high SBP or PP with low DBP even in healthy populations. Key message Prehypertensive subjects should be cautioned when they have high-systolic blood pressure or pulse pressure with low-diastolic blood pressure, even without previous hypertension, diabetes mellitus or chronic kidney disease.

Post-translational modifications (PTMs) are chemical alterations that occur in proteins that play critical roles in various cellular functions. Lysine acetylation is an important PTM in eukaryotes, and it is catalyzed by lysine acetyltransferases (KATs). KATs transfer acetyl-coenzyme A to the internal lysine residue of substrate proteins. Arrest defective 1 (ARD1) is a member of the KAT family. Since the identification of its KAT activity 15 years ago, many studies have revealed that diverse cellular proteins are acetylated by ARD1. ARD1-mediated lysine acetylation is a key switch that regulates the enzymatic activities and biological functions of proteins and influences cell biology from development to pathology. In this review, we summarize protein lysine acetylation mediated by ARD1 and describe the biological meanings of this modification.

Clostridium perfringens is one of the most common causes of food-borne illness. The increasing prevalence of multidrug-resistant bacteria requires the development of alternatives to typical antimicrobial treatments. Here, we isolated and characterized a C. perfringens -specific virulent bacteriophage CPS2 from chicken feces. The CPS2 phage contains a 17,961 bp double-stranded DNA genome with 25 putative ORFs, and belongs to the Picovirinae , subfamily of Podoviridae . Bioinformatic analysis of the CPS2 genome revealed a putative endolysin, LysCPS2, which is homologous to the endolysin of Clostridium phage phiZP2 and phiCP7R. The enzyme showed strong lytic activity against C. perfringens with optimum conditions at pH 7.5⁻10, 25⁻65 °C, and over a broad range of NaCl concentrations. Interestingly, LysCPS2 was found to be highly thermostable, with up to 30% of its lytic activity remaining after 10 min of incubation at 95 °C. The cell wall binding domain in the C-terminal region of LysCPS2 showed a binding spectrum specific to C. perfringens strains. This is the first report to characterize highly thermostable endolysin isolated from virulent C. perfringens bacteriophage. The enzyme can be used as an alternative biocontrol and detection agent against C. perfringens ., Competing Interests: The authors declare no conflict of interest.

Introduction: Overweight or obesity might be protective factors of tuberculosis (TB), but the evidence is inconclusive. The objective of study was to evaluate association between BMI and incident TB., Methods: The National Health Insurance database was used. Eligible participants were individuals aged 20-89 years without history of TB before 2007, and who underwent national health examinations between January 2002 and December 2006. The latest record of BMI was used as the exposure and categorized as follows: <18.5, 18.5-23, 23-25, 25-30, and ≥30 kg/m2. TB was defined as the first recorded diagnosis of TB, using ICD-10 between January 2007 and December 2013., Results: Among 301,081 individuals, 3,772 (1.26%) incident TB cases were detected. The incidence rate of the event was 19.65 per 10,000 person-years. After adjusting age, sex, household income, smoking status, alcohol use, and diabetes, incident TB was decreased as BMI was increased in an inverse dose-response relationship. However, when stratified by age and sex, BMI >30 kg/m2 did not show protective effect of TB in female under 50 years. Additionally, BMI >30 kg/m2 did not decrease incident TB in diabetics., Conclusion: Our study suggests that high BMI might be associated with decreased risk of TB. However, very high BMI did not reduce the risk of TB in young females or diabetics participants with in Korean population.

Few birth cohort studies have examined the role of traffic-related air pollution (TRAP) in the development of infantile atopic dermatitis (AD), but none have investigated the role of preventive factors such as green spaces. The aim of this study was to investigate whether exposure to nitrogen dioxide (NO₂) and particulate matter with an aerodynamic diameter of <10 μm (PM 10 ) during pregnancy is associated with increased risk of development of AD in 6-month-old children and also to examine how this association changes with residential green space. This study used prospective data from 659 participants of the Mothers and Children's Environmental Health study. Subjects were geocoded to their residential addresses and matched with air pollution data modeled using land-use regression. Information on infantile AD was obtained by using a questionnaire administered to the parents or guardians of the children. The association between infantile AD and exposure to NO₂ and PM 10 was determined using logistic regression models. We assessed the effects of residential green spaces using stratified analyses and by entering product terms into the logistic regression models. The risk of infantile AD significantly increased with an increase in air pollution exposure during the first trimester of pregnancy. The adjusted odds ratio (OR) and 95% confidence interval (CI) were 1.219 (1.023-1.452) per 10 μg/m³ increase in PM 10 and 1.353 (1.027-1.782) per 10 ppb increase in NO₂. An increase in the green space within 200 m of residence was associated with a decreased risk of AD (OR = 0.996, 95% CI: 0.993-0.999). The stratified analysis of residential green space revealed stronger associations between infantile AD and PM 10 and NO₂ exposure during the first trimester in the areas in the lower tertiles of green space. This study indicated that exposure to TRAP during the first trimester of pregnancy is associated with infantile AD. Less residential green space may intensify the association between TRAP exposure and infantile AD., Competing Interests: The authors declare no conflict of interest.

Repeated exposure to traumatic experiences may put professional firefighters at increased risk of developing posttraumatic stress disorder (PTSD). To date, however, the rate of PTSD symptoms, unmet need for mental health treatment, and barriers to treatment have only been investigated in subsamples rather than the total population of firefighters. We conducted a nationwide, total population-based survey of all currently employed South Korean firefighters (n = 39,562). The overall response rate was 93.8% (n = 37,093), with 68.0% (n = 26,887) complete responses for all variables. The rate of current probable PTSD was estimated as 5.4%. Among those with current probable PTSD (n = 1,995), only a small proportion (9.7%) had received mental health treatment during the past month. For those who had not received treatment, perceived barriers of accessibility to treatment (29.3%) and concerns about potential stigma (33.8%) were reasons for not receiving treatment. Although those with higher PTSD symptom severity and functional impairment were more likely to seek treatment, greater symptom severity and functional impairment were most strongly associated with increased concerns about potential stigma. This nationwide study points to the need for new approaches to promote access to mental health treatment in professional firefighters.

Obesity is an important contributing factor to progression of chronic kidney disease. Cyanate, known as uremic toxin, is an electrophile produced spontaneously from urea or by myeloperoxidase-catalyzed oxidation of thiocyanate. Herein, we explored metabolic effects of cyanate in normal chow diet (NCD)- and high fat diet (HFD)-fed mice. Mice were treated with cyanate (1 mg/mL in drinking water) and fed NCD or HFD. Peritoneal glucose tolerance test (PGTT) and insulin tolerance test (ITT) were performed. Blood urea nitrogen (BUN) and creatinine concentrations were determined. Kidney and liver tissues were analyzed for reactive oxygen species (ROS) and lipid accumulations. Human albumin was carbamylated and evaluated for ROS scavenging activities. Contrary to our expectations, we found that cyanate treatment improved increased insulin sensitivity and alleviated hepatic steatosis in NCD- and HFD-fed mice. PGTT and ITT revealed faster and immediate glucose clearance in cyanate-treated NCD- and HFD-fed mice. Histological analysis of kidney and serum levels of BUN and creatinine showed no significant differences between cyanate-treated and control mice groups. Cyanate treatment reduced appetite and body weight in both NCD- and HFD-fed mice groups. Cyanate also decreased lipid peroxidation levels in the sera and the kidney, attenuated ROS levels in the kidney, which lead us to the findings that cAlb significantly reduced ROS levels compared to Alb in Caki-1 kidney and human umbilical vein endothelial cells. The results in this study may indicate that cyanate improves insulin sensitivity and hepatic steatosis possibly via exerting anorexic and antioxidative effects., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Heat shock protein 90 (Hsp90) is a ubiquitous molecular chaperone that is responsible for the stabilization and maturation of many oncogenic proteins. Therefore, Hsp90 has emerged as an attractive target in the field of cancer chemotherapy. In this study, we report the design, synthesis, and biological evaluation of a series of Hsp90 inhibitors. In particular, compound 30f shows a significant Hsp90α inhibitory activity with IC 50 value of 5.3 nM and an excellent growth inhibition with GI 50 value of 0.42 μM against non-small cell lung cancer cells, H1975. Compound 30f effectively reduces the expression levels of Hsp90 client proteins including Her2, EGFR, Met, Akt, and c-Raf. Consequently, compound 30f promotes substantial cleavages of PARP, Caspase 3, and Caspase 8, indicating that 30f induces cancer cell death via apoptotic pathway. Moreover, cytochrome P450 assay indicates that compound 30f has weak inhibitory effect on the activities of five major P450 isoforms (IC 50  > 5 μM for 1A2, 2C9, 2C19, 2D6, and 3A), suggesting that clinical interactions between 30f and the substrate drugs of the five major P450 isoforms are not expected. Compound 30f also inhibits the tumor growth in a mouse xenograft model bearing subcutaneous H1975 without noticeable abnormal behavior and body weight changes. The immunostaining and western immunoblot analysis of EGFR, Met, Akt in xenograft tissue sections of tumor further demonstrate a good agreement with the in vitro results., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

The objective of this study was to investigate stability of cognitive development during the first five years of life in relation to heavy metal concentrations in umbilical cord blood in Korean children. This research is part of the Mothers' and Children's Environmental Health (MOCEH) study, a multi-center prospective birth cohort study of pregnant women in Korea who were recruited from 2006 to 2010. We analyzed the complete follow-up data of children who were 5years-old in 2016. We measured lead, mercury, and cadmium levels in the umbilical cord blood of 251 children, and analyzed them, for whom neurodevelopmental data were available. We determined stability of cognitive development scores using three methods. First, we used partial correlation analyses to examine the stability of cognitive development at each measurement time. Second, we used Cramer's V to investigate the magnitude and direction of changes in cognitive development scores at each follow-up period among three groups (high, medium, and low scores). The results showed that cognitive development scores measured at the closest times had the strongest correlations, and the stability of cognitive development scores increased with age, from 6 to 60months. Groups at the extreme ends of cognitive development (high or low scores) had more stable scores, and this tendency was also stronger in infants >24months-old. The stability of cognitive development was unrelated to the umbilical cord level of heavy metals, based on analysis with Fisher's transformation. In conclusion, the present study showed that the cognitive development scores in a cohort of infants (6 to 60months-old) were stable., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The present study assessed the associations of heavy metal concentrations in pregnant women with the concentrations in their children during early childhood. This study is a part of the Mothers' and Children's Environmental Health (MOCEH) study, a Korean multi-center prospective birth cohort study of 1751 pregnant women who were recruited from 2006 to 2010. We completed the follow-up of children who were 5years-old in 2016. Lead, total mercury, and cadmium were measured in women during early and late pregnancy, in cord blood, and in children who were 2, 3, and 5years-old. Lead concentration was lowest in cord blood, highest in 24month-old children, and then decreased with child age. Total mercury concentration was highest in cord blood, and gradually decreased with child age. Cadmium concentration was lowest in cord blood, and increased with child age. After adjusting for child sex, maternal age, and maternal education level, we found strong correlations between the levels of lead and total mercury in women during late pregnancy with the levels in cord blood; however, there were weak correlations between the levels of these metals in women during late pregnancy and cord blood with the levels in their children. In conclusion, maternal lead and mercury concentrations correlated with the levels in cord blood and in children up to age 60months. This correlation may be due to high trans-placental transmission of these metals and shared living environment such as environmental exposure, food consumption, and lifestyle., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background and Purpose: Branchial cleft cyst is a common congenital lesion of the neck. This study evaluated the efficacy and safety of ethanol ablation as an alternative treatment to surgery for branchial cleft cyst., Materials and Methods: Between September 2006 and October 2016, ethanol ablation was performed in 22 patients who refused an operation for a second branchial cleft cyst. After the exclusion of 2 patients who were lost to follow-up, the data of 20 patients were retrospectively evaluated. All index masses were confirmed as benign before treatment. Sonography-guided aspiration of the cystic fluid was followed by injection of absolute ethanol (99%) into the lesion. The injected volume of ethanol was 50%-80% of the volume of fluid aspirated. Therapeutic outcome, including the volume reduction ratio, therapeutic success rate (volume reduction ratio of >50% and/or no palpable mass), and complications, was evaluated., Results: The mean index volume of the cysts was 26.4 ± 15.7 mL (range, 3.8-49.9 mL). After ablation, the mean volume of the cysts decreased to 1.2 ± 1.1 mL (range, 0.0-3.5 mL). The mean volume reduction ratio at last follow-up was 93.9% ± 7.9% (range, 75.5%-100.0%; P < .001). Therapeutic success was achieved in all nodules (20/20, 100%), and the symptomatic ( P < .001) and cosmetic ( P < .001) scores had improved significantly by the last follow-up. In 1 patient, intracystic hemorrhage developed during the aspiration; however, no major complications occurred in any patient., Conclusions: Ethanol ablation is an effective and safe treatment for patients with branchial cleft cysts who refuse, or are ineligible for, an operation., (© 2017 by American Journal of Neuroradiology.)

Thyroid hormones (THs) as a therapeutic intervention to treat obesity has been tried but the effect of THs on body weight and the mechanistic details of which are far from clear. This study was designed to determine and elucidate the mechanistic details of metabolic action of THs in high-fat diet (HFD) fed Sprague Dawley (SD) rats. Rats were made surgically hypothyroid (thyroidectomy, Thx). Body weights and food and water intake profoundly decreased in HFD fed thyroidectomized group (HN Thx). Results showed that delayed insulin response, increased total cholesterol, high-density lipoprotein, and low-density lipoprotein in HN Thx. Unexpectedly, however, Thx reduced serum and hepatic triglyceride concentrations. Further studies revealed that Thx dramatically increased circulating GLP-1 as well as increased expressions of GLP-1 in small intestine. Diminished hepatic expressions of lipogenic genes, were observed in HN Thx group. Beta-catenin and glutamine synthetase, a known target of β-catenin, were up-regulated in the liver of HN Thx group. The expressions of gluconeogenic genes G6P and PCK were reduced in the liver of HN Thx group. The results may suggest that surgery-induced hypothyroidism increases GLP-1, the actions of which may in part be responsible for the reduction in water intake, appetite and hepatic steatosis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background and Purpose: Procedural rupture of an intracranial aneurysm is a devastating complication in endovascular treatment. The purpose of this study was to evaluate the clinical outcomes of patients with procedural rupture of unruptured saccular intracranial aneurysms compared with those with spontaneously ruptured aneurysms., Materials and Methods: A retrospective review was performed for 1340 patients with 1595 unruptured saccular intracranial aneurysms that underwent endovascular coil embolization between February 2010 and December 2014. The clinical outcomes of patients with procedural rupture of unruptured saccular intracranial aneurysms were compared with those of 198 patients presenting with spontaneously ruptured aneurysms., Results: In this series, procedural rupture developed in 19 patients (1.4% per patient and 1.2% per aneurysm), and the morbidity related to procedural rupture was 26.3% (95% confidence interval, 8.5%-61.4%) with no mortality. Hunt and Hess scale grades and hospitalization days of patients with procedural rupture were equivalent to those of patients presenting with spontaneous aneurysm rupture. Subsequent treatment procedures after hemorrhage (including lumbar drainage, extraventricular drainage, decompressive craniectomy, and permanent shunt) showed no difference between the 2 groups. The hemorrhage volumes were smaller in the procedural-rupture group ( P = .03), and the endovascular vasospasm therapies tended to be more frequently required in the spontaneous aneurysm-rupture group ( P = .08). At postictus 6 months, the proportion of modified Rankin Scale scores of ≥2 were lower in the procedural-rupture group (5.3% versus 26.8%, P = .049). In multivariate analysis, spontaneous aneurysm rupture was a significant risk factor for worse clinical outcome (OR = 14.9; 95% CI, 1.2-193.1; P = .039)., Conclusions: This study showed better clinical outcomes in the procedural-rupture group. Even though there is a potential chance of aneurysm rupture during treatment, the clinical outcomes after procedural bleeds seem to be more favorable than those of spontaneous rupture., (© 2017 by American Journal of Neuroradiology.)

Background/aims: Cancer-induced bone pain (CIBP) is one of the most common pains in patients with advanced neoplasms. Because of treatment-associated side effects, more than half of cancer patients are reported to have inadequate and undermanaged pain control. New mechanism-based therapies must be developed to reduce cancer pain. Quetiapine is a commonly used atypical antipsychotic drug. We report a study of the potential analgesic effects of quetiapine in a mouse model of CIBP and examine the mechanism of bone pain by analyzing the expression of various nociceptors., Methods: Fifteen male C3H/HeN mice were arbitrarily divided into five groups: control and, CIBP with no treatment, quetiapine treatment, opioid treatment, and melatonin treatment. The mice were tested for mechanical hyperalgesia by determining the nociceptive hind paw withdrawal pressure threshold. Tissues from tibia were removed and subjected to quantitative and qualitative evaluations of transient receptor potential vanilloid 1 (TRPV1), TRPV4, acid-sensing ion channel 1 (ASIC1), ASIC2, and ASIC3 expression., Results: Paw withdrawal pressure threshold was improved in the quetiapine treatment group compared with the CIBP group. Expression of TRPV1, TRPV4, ASIC1, ASIC2, and ASIC3 in the CIBP with quetiapine treatment group was significantly lower than that in the CIBP group., Conclusions: Our results suggest an analgesic effect of quetiapine in the CIBP animal model and implicate TRPV and ASICs as potential targets for cancer pain management.

The objective of the present study was to investigate the relationship of IQ in children with maternal blood mercury concentration during late pregnancy. The present study is a component of the Mothers and Children's Environmental Health (MOCEH) study, a multi-center birth cohort project in Korea that began in 2006. The study cohort consisted of 553 children whose mothers underwent testing for blood mercury during late pregnancy. The children were given the Korean language version of the Wechsler Preschool and Primary Scale of Intelligence, revised edition (WPPSI-R) at 60 months of age. Multivariate linear regression analysis, with adjustment for covariates, was used to assess the relationship between verbal, performance, and total IQ in children and blood mercury concentration of mothers during late pregnancy. The results of multivariate linear regression analysis indicated that a doubling of blood mercury was associated with the decrease in verbal and total IQ by 2.482 (95% confidence interval [CI], 0.749-4.214) and 2.402 (95% CI, 0.526-4.279), respectively, after adjustment. This inverse association remained after further adjustment for blood lead concentration. Fish intake is an effect modifier of child IQ. In conclusion, high maternal blood mercury level is associated with low verbal IQ in children., Competing Interests: The authors have no potential conflicts of interest to disclosure., (© 2017 The Korean Academy of Medical Sciences.)

Background: Hypertension is a major cause of end-stage renal disease, and blood pressure (BP) control is crucial in patients with chronic kidney disease (CKD). However, it is generally inadequately controlled in CKD patients. We investigated the prevalence of CKD patients with inadequate BP control and its related factors, based on the CKD stage., Methods: We analyzed the health examination sample cohort database, which consisted of the randomly selected participants among all the citizens who received the health examination provided by National Health Insurance Service of Korea in 2012 and 2013., Results: There were 27,350 CKD patients (7.9%) out of a total of 345,044 participants. As CKD stage progressed, there were more patients with poorly controlled hypertension compared to those with well-controlled hypertension. In addition, systolic BP increased with CKD stage progression, while diastolic BP was not significantly different. Age, female, body mass index, increased pulse pressure, CKD stage, and levels of fasting glucose, total cholesterol, hemoglobin, and proteinuria were significant factors associated with poor control of BP in hypertensive CKD patients., Conclusion: The proportion of CKD patients with poorly controlled hypertension significantly increased as CKD progressed, mainly associated with the increase in pulse pressure. However, future investigation for causal relationship between poorly controlled hypertension and its related factors is needed., (© American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Bone age (BA) advancement in prepubertal children may be associated with earlier onset of puberty and obesity. This study aimed to define the effects of adrenal androgen levels on the advancement of BA in prepubertal children, independent of obesity. During July and August 2011, we examined BA in 200 prepubertal children aged 7-9 years who were part of the Ewha Birth & Growth Cohort Study. BA was assessed by the Greulich-Pyle method. An index of BA advancement was calculated as the ratio of BA to chronological age (CA) (BA/CA), and this ratio was classified into 3 tertiles. We analyzed the relationship between BA advancement and anthropometric characteristics and adrenal hormone levels. The number of overweight children increased from the first group to the third group (P(Trend) = 0.03). The levels of adrenal androgens showed a significant positive correlation with the tertile groups after adjusting for age and sex (testosterone: r = 0.26, P < 0.001; dehydroepiandrosterone: r = 0.21, P < 0.001; androstenedione: r = 0.20, P < 0.001). Further, after controlling for body mass index (BMI), sex, and age, the BA/CA was found to be positively correlated with androstenedione (β = 0.04, R² = 3.7%) and testosterone levels (β = 0.05, R² = 4.7%). Based on our results, it is suggested that adrenal androgen levels are associated with BA advancement independent of BMI., Competing Interests: We have no potential conflicts of interest to disclose., (© 2017 The Korean Academy of Medical Sciences.)

Herein we demonstrate a systematic investigation of chemically functionalizable, non-biofouling agarose films over large-area glass surfaces. Agarose films, prepared with various concentrations of aqueous agarose, were activated by using periodate oxidation to generate aldehyde groups at the termini of the agarose chains. The non-biofouling efficacy and binding capabilities of the activated films were evaluated by using protein and cellular patterning, performed by using a microarrayer, microcontact printing, and micromolding in capillaries. Characterization by using a fluorescence slide scanner and a scanning-probe microscope revealed that the pore sizes of the agarose films played an important role in achieving desirable film performance; the 0.2 wt % agarose film exhibited the optimum efficacy in this work., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background Although there are many well-known prognostic predictors of medullary thyroid carcinoma (MTC), the ultrasonography (US) findings of MTC have not been sufficiently validated in this regard. Purpose To investigate the US findings of MTC and their relationship with the biological behavior of MTC. Material and Methods The US findings and clinical and pathology records of 123 MTC nodules from 108 patients were retrospectively analyzed at two tertiary referral hospitals. MTCs were classified according to US findings, i.e. MTC with benign (B-MTC) and malignant US findings (M-MTC). We then compared the clinical and pathology findings between the two groups. Results Eighty-two M-MTCs (66.7%) and 41 B-MTCs (33.3%) were identified. M-MTCs showed a significantly higher prevalence of lateral lymph node metastases as well as extrathyroidal and extranodal extension (all P < 0.05). M-MTCs larger than 1 cm showed a significantly higher prevalence of multifocality, recurrence, extrathyroidal and extranodal extension than B-MTCs larger than 1 cm in the largest dimension (all P < 0.05). Tumors > 1 cm were more likely to be B-MTC and one-third of all MTCs had benign US features. The common findings of B-MTC included a solid, ovoid to round shape, with a smooth margin, hypoechogenicity, and without calcification. Conclusion The biological behavior of M-MTCs results in poorer outcomes than that of B-MTCs.

Background/objectives: The prevalence of obesity has markedly increased and is closely related to insulin resistance. Although lifestyle and genetic predisposition are significant factors influencing the pathophysiology within the body, endocrine-disrupting chemicals (EDCs) are also important triggers of metabolic disturbance. We investigated the relationship between exposure to EDCs and insulin resistance and obesity in healthy, reproductive-aged women., Subjects/methods: This cross-sectional analysis included 296 healthy, reproductive-aged women between 30 and 49 years. Metabolically healthy was defined as an absence of the components of metabolic syndrome. Urinary levels of bisphenol A (BPA), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono-n-butyl phthalate (MnBP) were measured by high-performance liquid chromatography and tandem mass spectroscopy (LC-MS). Homoeostatic model analysis of insulin resistance (HOMA-IR) was utilized as an index of insulin resistance., Results: Urinary BPA levels were positively correlated with BMI, waist circumference, fasting serum insulin and HOMA-IR. MEHHP, MEOHP and MnBP were not associated with any of the above parameters. In the multiple regression analysis, the BPA levels were significantly associated with BMI and waist circumference after adjusting for age, smoking and alcohol consumption status, triglycerides (TG), total cholesterol (TC) and high-density lipoprotein (HDL). Fasting insulin and HOMA-IR values were also significantly related to urinary BPA concentration after adjusting for confounding variables. Metabolically unhealthy women exhibited significantly higher levels of urinary BPA (P = 0·01) compared to metabolically healthy women., Conclusions: Higher urinary BPA levels are associated with obesity, insulin resistance and metabolic disruption in Korean reproductive-aged women. BPA could play an important role in the pathogenesis of metabolic abnormalities. Further studies are required to elucidate the relationship between EDCs and metabolic disturbances in various age and sex groups., (© 2016 John Wiley & Sons Ltd.)

Hydrogen generation from water using noble metal-free photocatalysts presents a promising platform for renewable and sustainable energy. Copper-based chalcogenides of earth-abundant elements, especially Cu 2 ZnSnS 4 (CZTS), have recently arisen as a low-cost and environment-friendly material for photovoltaics and photocatalysis. Herein, we report a new heterostructure consisting of CZTS nanoparticles anchored onto a MoS 2 -reduced graphene oxide (rGO) hybrid. Using a facile two-step method, CZTS nanoparticles were in situ grown on the surface of MoS 2 -rGO hybrid, which generated high density of nanoscale interfacial contact between CZTS and MoS 2 -rGO hybrid. The photoexcited electrons of CZTS can be readily transported to MoS 2 through rGO backbone, reducing the electron-hole pair recombination. In photocatalytic hydrogen generation under visible light irradiation, the presence of MoS 2 -rGO hybrids enhanced the hydrogen production rate of CZTS by 320%, which can be attributed to the synergetic effect of increased charge separation by rGO and more catalytically active sites from MoS 2 . Furthermore, this CZTS/MoS 2 -rGO heterostructure showed much higher photocatalytic activity than both Au and Pt nanoparticle-decorated CZTS (Au/CZTS and Pt/CZTS) photocatalysts, indicating the MoS 2 -rGO hybrid is a better co-catalyst for photocatalytic hydrogen generation than the precious metal. The CZTS/MoS 2 -rGO system also demonstrated stable photocatalytic activity for a continuous 20 h reaction.

Mercury pollution and its impacts on human health is of global concern. The authors of this paper were members of the Plenary Panel on Human Health in the 12th International Conference on Mercury as a Global Pollutant held in Korea in June 2015. The Panel was asked by the conference organizers to address two questions: what is the current understanding of the impacts of mercury exposure on human health and what information is needed to evaluate the effectiveness of the Minamata Convention in lowering exposure and preventing adverse effects. The authors conducted a critical review of the literature published since January 2012 and discussed the current state-of-knowledge in the following areas: environmental exposure and/or risk assessment; kinetics and biomonitoring; effects on children development; effects on adult general populations; effects on artisanal and small-scale gold miners (ASGM); effects on dental workers; risk of ethylmercury in thimerosal-containing vaccines; interactions with nutrients; genetic determinants and; risk communication and management. Knowledge gaps in each area were identified and recommendations for future research were made. The Panel concluded that more knowledge synthesis efforts are needed to translate the research results into management tools for health professionals and policy makers., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Disulfide bonds provide a bioactivatable connection with applications in imaging and therapy. The circulation stability and intracellular release of disulfides are problematically coupled in that increasing stability causes a corresponding decrease in cleavage and payload release. However, an antibody offers the potential for a reversible stabilization. We examined this by attaching a small molecule directly to engineered cysteines in an antibody. At certain sites this unhindered disulfide was stable in circulation yet cellular internalization and antibody catabolism generated a disulfide catabolite that was rapidly reduced. We demonstrated that this stable connection and facile release is applicable to a variety of payloads. The ability to reversibly stabilize a labile functional group with an antibody may offer a way to improve targeted probes and therapeutics.

The phospholipase D (PLD) enzymatic superfamily regulates a wide range of cell biological and physiological pathways, including platelet activation, immune responses, cancer, and spermatogenesis. The three main enzymatic actions of the superfamily entail (i) hydrolyzing membrane phospholipids (phosphatidylcholine (PC) and cardiolipin) to generate choline and the second messenger signaling lipid phosphatidic acid (PA), (ii) using ethanol to transphosphatidylate PC to generate the long-lived metabolite phosphatidylethanol, and (iii) hydrolyzing RNA transcripts to generate piRNAs, the third form of endogenous RNAi. We discuss briefly previously published methods for in vitro and in vivo detection and imaging of PA, and focus on production, purification, and in vitro endonuclease activity analysis for human PLD6, a mitochondrial-tethered isoform with roles in fertility, cancer, and neuronal homeostasis., (© 2017 Elsevier Inc. All rights reserved.)

Background: The objective of this study was to investigate serial changes for histology of joint capsule and range of motion of the glenohumeral joint after immobilization in rats. We hypothesized that a rat shoulder contracture model using immobilization would be capable of producing effects on the glenohumeral joint similar to those seen in patients with frozen shoulder., Methods: Sixty-four Sprague-Dawley rats were randomly divided into one control group (n = 8) and seven immobilization groups (n = 8 per group) that were immobilized with molding plaster for 3 days, or for 1, 2, 3, 4, 5, or 6 weeks. At each time point, eight rats were euthanized for histologic evaluation of the axillary recess and for measurement of the abduction angle., Results: Infiltration of inflammatory cells was found in the synovial tissue until 2 weeks after immobilization. However, inflammatory cells were diminished and fibrosis was dominantly observed in the synovium and subsynovial tissue 3 weeks after immobilization. From 1 week after immobilization, the abduction angle of all immobilization groups at each time point was significantly lower than that of the control group., Conclusions: Our study demonstrated that a rat frozen shoulder model using immobilization generates the pathophysiologic process of inflammation leading to fibrosis on the glenohumeral joint similar to that seen in patients with frozen shoulder. This model was attained within 3 weeks after immobilization. It may serve as a useful tool to investigate pathogenesis at the molecular level and identify potential target genes that are involved in the development of frozen shoulder.

Background: Persistent organic pollutants (POPs) are endocrine disruptors and have been suggested as possible risk factors for diabetes. Few studies have been performed to investigate this association among children., Objectives: In this study, we prospectively examined the relationship between the serum concentration of POPs and glucose metabolism in children., Methods: Data were collected from the Ewha Birth & Growth Cohort Study, an ongoing birth cohort study initially constructed between 2001 and 2006. In 2010-2012, the POP concentration was measured in serum from a total of 214 children, 7-9 years of age. Using fasting glucose and insulin measurements at both baseline and the second year of follow-up, the homeostatic model assessment of beta-cell function (HOMA-β) and homeostatic model assessment of insulin resistance (HOMA-IR) were calculated. Multiple linear regression analysis and a linear mixed-effects model were used to determine the relationship between POP tertiles and metabolic biomarkers., Results: Compared with the lowest tertile of total marker PCBs, participants in the third tertile had decreased HOMA-β values, after adjustment for age, sex, body mass index z-score, mother's education, ponderal index, and history of breastfeeding (-18.94%; 95% CI: -32.97%, -1.98%). In a linear mixed model, the HOMA-β values were still lower in subjects in the highest compared with the lowest tertile of total PCBs at the 2-year follow-up period (108.3 vs. 135.0, respectively)., Conclusion: The results of the study suggested that exposure to POPs among children might affect insulin secretory function, which could lead to an increased risk of developing diabetes. Citation: Park SH, Ha EH, Hong YS, Park H. 2016. Serum levels of persistent organic pollutants and insulin secretion among children age 7-9 years: a prospective cohort study. Environ Health Perspect 124:1924-1930; http://dx.doi.org/10.1289/EHP147., Competing Interests: The authors declare they have no actual or potential competing financial interests.

The molecular chaperone Hsp90 plays an important role in cancer cell survival and proliferation by regulating the maturation and stabilization of numerous oncogenic proteins. Due to its potential to simultaneously disable multiple signaling pathways, Hsp90 has emerged as an attractive therapeutic target for cancer treatment. In this study, the design, synthesis, and biological evaluation of a series of Hsp90 inhibitors are described. Among the synthetic compounds, 6,7-dihydrothieno [3,2-c]pyridin-5(4H)-yl amide 19 exhibits a remarkable binding affinity to the N-terminus of Hsp90 in a fluorescence polarization (FP) binding assay (IC 50  = 50.3 nM). Furthermore, it effectively inhibits the proliferation of H1975 non-small cell lung cancer (NSCLC) and Skbr3 breast cancer cell lines with GI 50 values of 0.31 μM and 0.11 μM, respectively. Compound 19 induces the degradation of the Hsp90 client proteins including EGFR, Her2, Met, c-Raf, and Akt, and consequently promotes apoptotic cancer cell death. Compound 19 also inhibits the growth of H1975 xenografts in NOD-scid IL2R gamma null mice without any apparent body-weight loss. The immunohistologic evaluation indicates that compound 19 decreases the expression of Akt in xenograft tumor tissue via an inhibition of the Hsp90 chaperon function. Additionally, the cytochrome P450 assay indicates that compound 19 has no effect on the activities of five major P450 isoforms (IC 50  > 50 μM for 1A2, 2C9, 2C19, 2D6, and 3A), suggesting that clinical interactions between compound 19 and the substrate drugs of the five major P450 isoforms are not expected. Overall, compound 19 represents a new class of Hsp90 inhibitor with its 6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl-amide structure, and it has the therapeutic potential to overcome drug resistance in cancer chemotherapy., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Objectives: A stable follow-up participation rate is a very important factor for validity in a cohort study. This study analyzed the factors that affect the participation rate at one hospital-based birth cohort in South Korean., Methods: The participants were recruited from the Mothers' and Children's Environmental Health study between 2006 and 2010. The analysis targeted 1751 mothers who participated in a birth cohort. We conducted analyses of general characteristics during pregnancy and those of infants at birth that affect the participation rate of the 6-month follow-up survey., Results: The participation rate for the 6-month follow-up survey was 60.4%. The participation rate in the follow-up of the subsequent period decreased within a 5% to 10% range compared to the number of subjects. The participation rate of premature infants was 16.9% lower than that of a full-term infant (52.6% vs. 69.5%). Analysis showed a 16.7% difference between the participation rate of low-birthweight infants in follow-ups (53.7%) and the participation rate of infants with normal weight (70.4%). The participation rate of mothers who were employed during pregnancy was significantly lower for the 6-month follow-up compared to the participation rate of mothers who were unemployed during pregnancy., Conclusions: In this study, factors such as premature birth, low-birthweight, and the employment status of the mother during pregnancy affected the participation rate of the follow-up survey for the birth cohort at six months. A specific strategy is needed to encourage survey participation for the high risk groups in the follow-ups., Competing Interests: The authors have no conflicts of interest associated with the material presented in this paper.

Background and Purpose: Prophylactic antiplatelet medication is beneficial in decreasing thromboembolic complications during endovascular treatment of unruptured intracranial aneurysms. The efficacy may be limited by variability of individual response to antiplatelet medication, especially clopidogrel. We compared the efficacy of 2 antiplatelet medications, low-dose prasugrel and clopidogrel, in patients undergoing endovascular treatment of unruptured aneurysms., Materials and Methods: From November 2014 to July 2015, 194 patients with a total of 222 unruptured aneurysms underwent endovascular treatment at a single institution. Laboratory and clinical data from the prospectively maintained registry were used in this study. Antiplatelet medication was given the day before endovascular treatment (prasugrel 20 mg or 30 mg or clopidogrel 300 mg). Response to the antiplatelet medication was measured by the VerifyNow system. Periprocedural adverse event rates between the 2 groups were compared., Results: There were no significant differences in the baseline characteristics of patients and aneurysms between the 2 groups. The P2Y12 reaction unit values were lower (clopidogrel group versus prasugrel group, 242.7 ± 69.8 vs 125.7 ± 79.4; P < .0001) and percentage inhibition values were higher (22.1% ± 19.7% vs 60.2 ± 24.7%; P < .0001) in the prasugrel group. There were no thromboembolic events, but there was 1 procedural bleed in each group, without any clinical consequences., Conclusions: The prasugrel group showed more effective and consistent platelet inhibition. We may omit the antiplatelet response assay with the low-dose prasugrel premedication before the endovascular treatment of patients with unruptured aneurysms. Further study is required to determine whether there is benefit of this strategy regarding clinical outcome., (© 2016 by American Journal of Neuroradiology.)

Purpose: To evaluate the ultrasound characteristics of the spinal accessory nerve (SAN) and correlate nerve location with neck lymph node level. Materials and Methods: 50 participants with 100 SANs were enrolled in this study. The SAN was traced from the trapezius muscle to the upper neck and was identified by a hypoechoic linear structure without color Doppler flow. The ultrasound characteristics of the SAN, such as visibility, diameter, relationship with adjacent structures, and its correlation with lymph node levels, were evaluated. Results: The SAN was identified in 96 %-100 % of segments. The mean diameter of the SAN was 0.54 ± 0.09 mm. The SANs was located between the trapezius and levator scapulae muscles and 90.8 % were traced into the trapezius muscle. In the upper neck, the SAN passed deep into the sternocleidomastoid (SCM) muscle in 38 % of cases and between the two heads of the SCM muscle in 62 % of cases. The SAN was found at neck lymph node levels II, III, IV, and V, but not I or VI. Conclusion: Continuous ultrasound monitoring of the SAN and its correlation with lymph node levels is possible in most patients. Our current findings may assist in the future prevention of SAN injury during ultrasound-guided procedures., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Due to the high 5-year overall survival rate (>95 %) for early gastric cancer (EGC), patients now face risks of developing comorbidities. Cardiovascular disease (CVD) is one of the most common causes of death not only in the general population and but also in cancer patients. Thus, we determined the effect of gastrectomy on cardiovascular risk factors by analyzing changes in lipid profiles of patients who underwent curative gastrectomy for EGC., Methods: Seventy-three patients who received curative gastrectomy for EGC were included and divided into gastroduodenostomy (GD) and duodenal bypass (DB) groups according to the anastomosis. Changes in visceral fat area (VFA), subcutaneous fat area (SFA), and lipid profiles [total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)] were evaluated in both groups 1 year after gastrectomy., Results: Body weight, VFA, SFA, TG, LDL-C, and TC decreased significantly while HDL-C increased (p < 0.001) after the surgery. We observed a weak negative correlation between percent change of VFA and HDL-C (r = -0.245, p = 0.036). When compared with the GD group, the DB group lost more SFA (p < 0.001), body weight (p = 0.008), and TC (p = 0.031). We also found that the degree of BMI change (∆BMI) was greater in the obese patients than in the non-obese patients (p < 0.001)., Conclusions: Curative gastrectomy reduces VFA, SFA, and body weight and improves lipid profiles in patients with EGC, all of which indicates reduced cardiovascular risk. Therefore, prospective studies are required to verify whether gastrectomy in EGC patients has favorable effects on future CVD mortality.

We demonstrated protein and cellular patterning with a soft lithography technique using poly[2-aminoethyl methacrylate-co-oligo(ethylene glycol) methacrylate] films on gold surfaces without employing a backfilling process. The backfilling process plays an important role in successfully generating biopatterns; however, it has potential disadvantages in several interesting research and technical applications. To overcome the issue, a copolymer system having highly reactive functional groups and bioinert properties was introduced through a surface-initiated controlled radical polymerization with 2-aminoethyl methacrylate hydrochloride (AMA) and oligo(ethylene glycol) methacrylate (OEGMA). The prepared poly(AMA-co-OEGMA) film was fully characterized, and among the films having different thicknesses, the 35 nm-thick biotinylated, poly(AMA-co-OEGMA) film exhibited an optimum performance, such as the lowest nonspecific adsorption and the highest specific binding capability toward proteins., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

RNA interference (RNAi) gene silencing technologies have shown significant potential for treating various diseases, including cancer. However, clinical success in cancer therapy remains elusive, mainly owing to suboptimal in vivo delivery of RNAi therapeutics such as small interference RNA (siRNA) to tumors. Herein, we developed a library of polymers that respond to a narrow pH change (ultra-pH-responsive), and demonstrated the utility of these materials in targeted and deep tumor-penetrating nanoparticle (NP) for in vivo RNAi. The new NP platform is mainly composed of the following key components: i) internalizing RGD (iRGD) to enhance tumor targeting and tissue penetration; ii) polyethylene glycol (PEG) chains to prolong blood circulation; and iii) sharp pH-responsive hydrophobic polymer to improve endosome escape. Through systematic studies of structure-function relationship, the optimized RNAi NPs (<70 nm) showed efficient gene silencing and significant inhibition of tumor growth with negligible toxicities in vivo., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Our objective is to evaluate the relationships between prenatal maternal stress and depressive symptoms, respectively, and infant neurodevelopment at 6 months, adjusted for heavy metals and oxidative stress. This research is a part of a multi-center birth cohort study in South Korea. Information on stress and depressive symptoms was collected during the first trimester using Psychosocial Well-Being Index Short Form (PWI-SF) and Center for Epidemiological Studies Depression Scale (CES-D). The Korean Bayley Scales of Infant Development-II assessment (BSID-II), which includes the standardized mental development index (MDI) and psychomotor developmental index (PDI), and Korean Ages & Stages Questionnaires (K-ASQ) were applied to infants at six months of age. A higher index score indicates better development. Among 641 babies, 320 were female (50%). Maternal PWI ≥ 29 (vs. PWI ≤ 18) during early pregnancy was associated with a decrease in MDI scores of 5.37 points (P = 0.02) after adjusting for socioeconomic factors. Maternal CES-D ≥ 26 (vs. CES-D ≤ 10) during early pregnancy was associated with a decrease in MDI scores of 8.18 points (P = 0.01). The associations remained significant even after adjustment for lead, cadmium, and MDA levels (P < 0.05). However, no association was found between maternal PWI/CES-D and PDI score. No interaction was observed between stress and lead exposure. We found an inverse association between prenatal maternal stress and depressive symptoms, and MDI scores in 6-month-old infants after adjustment for prenatal lead exposure, which is known to affect cognitive function negatively.

Bariatric surgery alleviates obesity and ameliorates glucose tolerance. Using metabolomic and proteomic profiles, we evaluated metabolic changes in serum and liver tissue after duodenal-jejunal bypass (DJB) surgery in rats fed a normal chow diet. We found that the levels of vitamin B 12 in the sera of DJB rates were decreased. In the liver of DJB rats, betaine-homocysteine S-methyltransferase levels were decreased, whereas serine, cystathionine, cysteine, glutathione, cystathionine β-synthase, glutathione S-transferase, and aldehyde dehydrogenase levels were increased. These results suggested that DJB surgery enhanced trans-sulfuration and its consecutive reactions such as detoxification and the scavenging activities of reactive oxygen species. In addition, DJB rats showed higher levels of purine metabolites such as ATP, ADP, AMP, and inosine monophosphate. Decreased guanine deaminase, as well as lower levels of hypoxanthine, indicated that DJB surgery limited the purine degradation process. In particular, the AMP/ATP ratio and phosphorylation of AMP-activated protein kinase increased after DJB surgery, which led to enhanced energy production and increased catabolic pathway activity, such as fatty acid oxidation and glucose transport. This study shows that bariatric surgery altered trans-sulfuration and purine metabolism in the liver. Characterization of these mechanisms increases our understanding of the benefits of bariatric surgery., (Copyright © 2016 the American Physiological Society.)

We investigated the association between breastfeeding and cognitive development in infants during their first 3 years. The present study was a part of the Mothers' and Children's Environmental Health (MOCEH) study, which was a multi-center birth cohort project in Korea that began in 2006. A total of 697 infants were tested at age 12, 24, and 36 months using the Korean version of the Bayley Scales of Infant Development II (K-BSID-II). The use and duration of breastfeeding and formula feeding were measured. The relationship between breastfeeding and the mental development index (MDI) score was analyzed by multiple linear regression analysis. The results indicated a positive correlation between breastfeeding duration and MDI score. After adjusting for covariates, infants who were breastfed for ≥ 9 months had significantly better cognitive development than those who had not been breastfed. These results suggest that the longer duration of breastfeeding improves cognitive development in infants.

Background: Smoking is a well-known risk factor of cancer, chronic disease, and cerebrovascular disease. Hospital admission is a good time to quit smoking but patients have little opportunity to take part in an intensive smoking cessation intervention. The purpose of this study was to identify the factors of successful smoking cessation among stroke patients who undergo an intensive cessation intervention during the hospitalization period., Methods: Thirty-nine male smokers who were admitted with stroke were enrolled in the study. They participated in a smoking cessation intervention during hospitalization. Smoking status was followed up by telephone 3 months later. Nicotine dependence, sociodemographic factors, and other clinical characteristics were assessed., Results: After 3 months post-intervention, the number of patients who stopped smoking was 27 (69.2%). In addition, there was no significant difference in nicotine dependence, sociodemographic factors, and clinical characteristics. Only the stages of readiness for smoking cessation were a significant predictor (odds ratio, 18.86; 95% confidence interval, 1.59-223.22)., Conclusion: This study shows that a patient's willingness to quit is the most significant predictor of stopping smoking after Inpatient cessation Intervention for stroke Patients.

Background: MicroRNAs (miRNAs) are endogenous noncoding small ribonucleic acids that have emerged as one of the central players of gene expression regulation. This study was designed to determine and identify miRNAs that are associated with Roux-en-Y gastric bypass (RYGB)., Methods: Male Sprague-Dawley rats were divided into two groups: sham and RYGB. Changes in food intake and body weight were measured. miRNA microarray analyses on the brain hypothalamus and heart were performed. The expressions of miR-122 were analyzed, and the activities of adenosine monophosphate-activated protein kinase (AMPK) were determined in the hypothalamus, heart, and liver. Antisense oligonucleotide miR-122 was transfected into hepatocellular carcinoma cells to validate in vivo results., Results: Body weights decreased in the RYGB group compared with those in sham group. Food intake was different between sham and RYGB groups. Of 350 miRNAs that were investigated, we observed that miR-122, being predominantly found in the liver, markedly increased (>35-fold) in the hypothalamus and decreased (>4-fold) in the heart. Quantitative polymerase chain reaction analysis revealed that expression of miR-122 was induced in hypothalamus but attenuated in the heart and liver of the RYGB group. Activities of AMPK were decreased in the hypothalamus but increased in the heart and liver. Knockdown of miR-122 in hepatocellular carcinoma cells stimulated phosphorylation levels AMPK., Conclusions: The results in this study suggest that RYGB regulates the expressions of miR-122 in the hypothalamus, heart, and liver, which in turn may modulate the activities of AMPK, the master regulator of metabolism., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: We evaluated metabolic changes after vertical sleeve gastrectomy (VSG) surgery in a rat model using proteomics and metabolomic profiling in liver and serum., Methods: Rats were randomly divided into two groups: sham (n = 10) and VSG (n = 12). Food intake, body weight, blood glucose, insulin, and thyroid hormone levels were measured. Two-dimensional electrophoresis, nuclear resonance spectroscopy, mass spectroscopy, immunofluorescence, and immunoblot analyses were used to determine and validate changes in metabolites and proteins in liver tissue and serum samples., Results: Food intake and body weight decreased after VSG group (p < 0.05 and p < 0.05, respectively). Random blood glucose (sham, 183.3 ± 5.6 mg/dL; VSG, 138.5 ± 3.7 mg/dL) decreased while random insulin (sham, 0.45 ± 0.16 μg/L; VSG, 1.05 ± 0.18 μg/L) increased after VSG (p < 0.05 and p < 0.01, respectively). We found that expressions of gluconeogenic enzymes (phosphoenolpyruvate carboxykinase-1 and glucose-6-phosphatase) and concentrations of pyruvate and malate decreased while lactate, NADH, NADPH, glucose, and AMP/ATP ratio increased after VSG. Thyroid hormones, triiodothyronine (T3) and free thyroxine (fT4), decreased after VSG., Conclusion: This study proves that VSG suppresses hepatic glucose production.

Native electrospray ionization (ESI) mass spectrometry (MS) is often used to monitor noncovalent complex formation between peptides and ligands. The relatively low throughput of this technique, however, is not compatible with extensive screening. Laser ablation electrospray ionization (LAESI) MS combined with ion mobility separation (IMS) can analyze complex formation and provide conformation information within a matter of seconds. Islet amyloid polypeptide (IAPP) or amylin, a 37-amino acid residue peptide, is produced in pancreatic beta-cells through proteolytic cleavage of its prohormone. Both amylin and its precursor can aggregate and produce toxic oligomers and fibrils leading to cell death in the pancreas that can eventually contribute to the development of type 2 diabetes mellitus. The inhibitory effect of the copper(II) ion on amylin aggregation has been recently discovered, but details of the interaction remain unknown. Finding other more physiologically tolerated approaches requires large scale screening of potential inhibitors. Here, we demonstrate that LAESI-IMS-MS can reveal the binding stoichiometry, copper oxidation state, and the dissociation constant of human amylin-copper(II) complex. The conformations of hIAPP in the presence of copper(II) ions were also analyzed by IMS, and preferential association between the β-hairpin amylin monomer and the metal ion was found. The copper(II) ion exhibited strong association with the -HSSNN- residues of the amylin. In the absence of copper(II), amylin dimers were detected with collision cross sections consistent with monomers of β-hairpin conformation. When copper(II) was present in the solution, no dimers were detected. Thus, the copper(II) ions disrupt the association pathway to the formation of β-sheet rich amylin fibrils. Using LAESI-IMS-MS for the assessment of amylin-copper(II) interactions demonstrates the utility of this technique for the high-throughput screening of potential inhibitors of amylin oligomerization and fibril formation. More generally, this rapid technique opens the door for high-throughput screening of potential inhibitors of amyloid protein aggregation.

Background and Purpose: Medullary thyroid carcinoma is an uncommon malignancy that is challenging to diagnose. Our aim was to present our experience using core needle biopsy for the diagnosis of medullary thyroid carcinoma compared with fine-needle aspiration., Materials and Methods: Between January 2000 and March 2012, 202 thyroid nodules in 191 patients were diagnosed as medullary thyroid cancer by using sonography-guided fine-needle aspiration, core needle biopsy, or surgery. One hundred eighty-three thyroid nodules in 172 patients were included on the basis of the final diagnosis. We evaluated the sensitivity and positive predictive value of fine-needle aspiration and core needle biopsy for the diagnosis of medullary thyroid cancer. We compared the rate of a delayed diagnosis, a diagnostic surgery, and surgery with an incorrect diagnosis for fine-needle aspiration and core needle biopsy and investigated the factors related to the fine-needle aspiration misdiagnosis of medullary thyroid cancer., Results: Fine-needle aspiration showed 43.8% sensitivity and 85.1% positive predictive value for the diagnosis of medullary thyroid cancer; 25.7% (44/171) of patients had a delayed diagnosis, while 18.7% (32/171) underwent an operation for accurate diagnosis, and 20.5% (35/171) underwent an operation with an incorrect diagnosis. Core needle biopsy achieved 100% sensitivity and positive predictive value without a delay in diagnosis (0/22), the need for a diagnostic operation (0/22), or an operation for an incorrect diagnosis (0/22). A calcitonin level of <100 pg/mL was the only significant factor for predicting the fine-needle aspiration misdiagnosis of medullary thyroid cancer (P = .034)., Conclusions: Core needle biopsy showed a superior sensitivity and positive predictive value to fine-needle aspiration and could optimize the surgical management in patients with medullary thyroid cancer. Because the ability of fine-needle aspiration to diagnose medullary thyroid cancer significantly decreases in patients with serum calcitonin levels of <100 pg/mL, core needle biopsy could be indicated for these patients to optimize their surgical management., (© 2015 by American Journal of Neuroradiology.)

Carbamylation is a cyanate-mediated posttranslational modification. We previously reported that carbamylated low-density lipoprotein (cLDL) increases reactive oxygen species and apoptosis via a lectin-like oxidized LDL receptor mediated pathway in human umbilical vein endothelial cells. A recent study reported an association between cLDL and type 2 diabetes mellitus (T2DM). In the current study, the effects of cLDL on glucose transport were explored in skeletal muscle cells. The effect of cLDL on glucose uptake, glucose transporter 4 (GLUT4) translocation, and signaling pathway were examined in cultured rat L6 muscle cells using 2-deoxyglucose uptake, immunofluorescence staining and western blot analysis. The quantity of nitric oxide (NO) was evaluated by the Griess reaction. The effect of native LDL (nLDL) from patients with chronic renal failure (CRF-nLDL) on glucose uptake was also determined. It was observed that cLDL significantly attenuated glucose uptake and GLUT4 translocation to the membrane, which was mediated via the increase in inducible nitric oxide synthase (iNOS)-induced NO production. Tyrosine nitration of the insulin receptor substrate-1 (IRS‑1) was increased. It was demonstrated that CRF-nLDL markedly reduced glucose uptake compared with nLDL from healthy subjects. Collectively, these findings indicate that cLDL, alone, attenuates glucose uptake via NO-mediated tyrosine nitration of IRS‑1 in L6 rat muscle cells and suggests the possibility that cLDL is involved in the pathogenesis of T2DM.

Background: Evidence relating childhood cancer to high birthweight is derived primarily from registry and case-control studies. We aimed to investigate this association, exploring the potential modifying roles of age at diagnosis and maternal anthropometrics, using prospectively collected data from the International Childhood Cancer Cohort Consortium., Methods: We pooled data on infant and parental characteristics and cancer incidence from six geographically and temporally diverse member cohorts [the Avon Longitudinal Study of Parents and Children (UK), the Collaborative Perinatal Project (USA), the Danish National Birth Cohort (Denmark), the Jerusalem Perinatal Study (Israel), the Norwegian Mother and Child Cohort Study (Norway), and the Tasmanian Infant Health Survey (Australia)]. Birthweight metrics included a continuous measure, deciles, and categories (≥ 4.0 vs. < 4.0 kilogram). Childhood cancer (377 cases diagnosed prior to age 15 years) risk was analysed by type (all sites, leukaemia, acute lymphoblastic leukaemia, and non-leukaemia) and age at diagnosis. We estimated hazard ratios (HR) and 95% confidence intervals (CI) from Cox proportional hazards models stratified by cohort., Results: A linear relationship was noted for each kilogram increment in birthweight adjusted for gender and gestational age for all cancers [HR = 1.26; 95% CI 1.02, 1.54]. Similar trends were observed for leukaemia. There were no significant interactions with maternal pre-pregnancy overweight or pregnancy weight gain. Birthweight ≥ 4.0 kg was associated with non-leukaemia cancer among children diagnosed at age ≥ 3 years [HR = 1.62; 95% CI 1.06, 2.46], but not at younger ages [HR = 0.7; 95% CI 0.45, 1.24, P for difference = 0.02]., Conclusion: Childhood cancer incidence rises with increasing birthweight. In older children, cancers other than leukaemia are particularly related to high birthweight. Maternal adiposity, currently widespread, was not demonstrated to substantially modify these associations. Common factors underlying foetal growth and carcinogenesis need to be further explored., (© 2015 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.)

The purpose of this study was to evaluate the expression of acid-sensing ion channels (ASICs) in the capsule and synovial fluid of patients with frozen shoulder. Capsular tissue and synovial fluid were obtained from 18 patients with idiopathic frozen shoulder (FS group) and 18 patients with instability of the shoulder (control group). The expressions of ASIC1, ASIC2, and ASIC3 in the capsule were determined using the reverse transcriptase-polymerase chain reaction, immunoblot analysis, and immunohistochemistry (IHC). The concentrations in synovial fluid were evaluated using an enzyme-linked immunosorbent assay. The mRNA expression of ASIC1, ASIC2 and ASIC3 in the capsule were significantly increased in the FS group compared with the control group. The protein levels of these three ASICs were also increased. The increased expressions were confirmed by IHC. Of the ASICs, ASIC3 showed the greatest increase in both mRNA and levels of expression compared with the control group. The levels of ASIC1 and ASIC3 in synovial fluid were significantly increased in the FS group. This study suggests that ASICs may play a role as mediators of inflammatory pain and be involved in the pathogenesis of frozen shoulder., (©2015 The British Editorial Society of Bone & Joint Surgery.)

Although several new therapeutic approaches have improved outcomes in the treatment of hematologic malignancies, unmet need persists in acute myeloid leukemia (AML), multiple myeloma (MM) and non-Hodgkin's lymphoma. Here we describe the proteomic identification of a novel cancer target, SAIL (Surface Antigen In Leukemia), whose expression is observed in AML, MM, chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). While SAIL is widely expressed in CLL, AML, MM, DLBCL and FL patient samples, expression in cancer cell lines is mostly limited to cells of AML origin. We evaluated the antitumor activity of anti-SAIL monoclonal antibodies, 7-1C and 67-7A, conjugated to monomethyl auristatin F. Following internalization, anti-SAIL antibody-drug conjugates (ADCs) exhibited subnanomolar IC50 values against AML cell lines in vitro. In pharmacology studies employing AML cell line xenografts, anti-SAIL ADCs resulted in significant tumor growth inhibition. The restricted expression profile of this target in normal tissues, the high prevalence in different types of hematologic cancers and the observed preclinical activity support the clinical development of SAIL-targeted ADCs.

Introduction: The objective of this review is to systematically evaluate the effectiveness of moxibustion for treating allergic rhinitis (AR)., Methods and Analysis: The following databases will be searched from their inception to January 2015: MEDLINE, EMBASE, CINAHL, AMED, Web of Science, Ovid Healthstar, PubMed, SciELO, the China National Knowledge Infrastructure Database, the Chongqing VIP Chinese Science and Technology Periodical Database, the Chinese Biomedical Database, the Wanfang Database, the Japanese Medical Research Database, and Korean Medical Databases. The methodological quality will be assessed using the Cochrane risk of bias tool. The primary outcome is total nasal symptoms, which may be evaluated by any appropriate scores or other forms of measurement. Secondary outcome measures will include quality of life, total non-nasal symptoms, use of daily medication and laboratory indicators., Ethics and Dissemination: Because this study will not involve patients, institutional review body permission is not required. The systematic review will be published in a peer-reviewed journal. The review will also be disseminated electronically and in print to help guide healthcare practice and policy., Trial Registration Number: PROSPERO CRD42014013275., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)