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Objectives: To characterize the perioperative morbidity of transurethral resection of bladder tumor (TURBT) in order to identify important determinants of both quality and cost in the delivery bladder cancer care., Methods: We identified 24,100 patients aged 18-89 years who underwent TURBT from 2010 to 2015 in the National Surgical Quality Improvement Program database. Multivariable logistic regression was performed to evaluate the associations of patient features and tumor size (<2 cm, 2-5 cm, or >5 cm) with 30-day perioperative outcomes., Results: Thirty-day postoperative complications occurred in 5.1% of patients, perioperative blood transfusion in 1.5% of patients, hospital readmission in 3.7% of patients, reoperation in 1.5% of patients, and mortality in 0.8% of patients. The most common reasons for readmission were bleeding (29%) and infectious (21%) complications. Although several patient features were associated with increased perioperative morbidity on multivariable analysis, including congestive heart failure, renal failure, higher American Society of Anesthesiology class, and dependent functional status, only larger tumor size was independently associated with increased risks of all perioperative endpoints., Conclusion: Perioperative morbidity following TURBT is substantial and represents an important target for quality improvement. Extent of resection, patient functional status, and specific comorbidities are independently associated with increased risks of perioperative morbidity and mortality. These results have implications for patient counseling, perioperative management, and quality improvement programs., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Soy foods are the richest sources of isoflavones, mainly daidzein and genistein. Soy isoflavones are structurally similar to the steroid hormone 17β-estradiol and may protect against breast cancer. S-(-)equol, a metabolite of the soy isoflavone daidzein, has a higher bioavailability and greater affinity for estrogen receptor β than daidzein. Approximately one-third of the Western population is able to produce S-(-)equol, and the ability is linked to certain gut microbes. We hypothesized that the prevalence of breast cancer, ductal hyperplasia, and overall breast pathology will be lower among S-(-)equol producing, as compared with nonproducing, postmenopausal women undergoing a breast biopsy. We tested our hypothesis using a cross-sectional study design. Usual diets of the participants were supplemented with 1 soy bar per day for 3 consecutive days. Liquid chromatography-multiple reaction ion monitoring mass spectrometry analysis of urine from 143 subjects revealed 25 (17.5%) as S-(-)equol producers. We found no statistically significant associations between S-(-)equol producing status and overall breast pathology (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.23-1.89), ductal hyperplasia (OR, 0.84; 95% CI, 0.20-3.41), or breast cancer (OR, 0.56; 95% CI, 0.16-1.87). However, the mean dietary isoflavone intake was much lower (0.3 mg/d) than in previous reports. Given that the amount of S-(-)equol produced in the gut depends on the amount of daidzein exposure, the low soy intake coupled with lower prevalence of S-(-)equol producing status in the study population favors toward null associations. Findings from our study could be used for further investigations on S-(-)equol producing status and disease risk., (Published by Elsevier Inc.)

It has been hypothesized that micronutrient levels play a role in the immune response to vaccination; however, population-level research on the association between micronutrient levels and immune response to influenza vaccination is needed. In this study, we hypothesized that decreasing levels of nutrients would be associated with decreased hemagglutination inhibition (HAI) responses to influenza vaccination. Therefore, the purpose of this study was to determine whether serum vitamin A, vitamin E, or zinc levels are associated with influenza vaccine response determined by HAI titer in adults 65 years or older. Participants in this study included 205 community-dwelling adults 65 years or older who resided in Marshfield, WI, USA, from fall 2008 through spring 2009. Participants received trivalent influenza vaccine and donated blood samples before and 21 to 28 days after vaccination. Prevaccination levels of serum retinol, α-tocopherol, and zinc as well as prevaccination and postvaccination HAI titer levels were measured. No participants were vitamin A or vitamin E deficient; 20% had low serum zinc levels (<70 μg/dL). Continuous variables and categorical quartiles coding for vitamin A, vitamin E, and zinc levels were not related to prevaccination or postvaccination seroprotection or seroconversion for any of the vaccine components (influenza A [H1N1], A [H3N2], or B), after adjusting for age, sex, body mass index, and prevaccination HAI geometric mean titer. In conclusion, our study population showed no association between variations in levels of serum vitamin A, vitamin E, or zinc and influenza vaccine response as measured by HAI in adults older than 65 years. Thus, associations between micronutrients and other measures of vaccine response, such as cell-mediated immune parameters, should also be explored., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Organophosphate flame retardants (OPFRs) are commonly added to consumer products to reduce their flammability. Based on levels of OPFRs in indoor environments, human exposure is likely chronic and ubiquitous. Animal studies suggest that exposure to some OPFRs may result in adverse health impacts, particularly for Tris (1,3-dichloropropyl) phosphate (TDCPP); however, human data on the impacts of exposure to OPFRs are lacking. To design human studies, more information is needed on the stability of measured OPFRs in human samples over time. In this study, we sought to assess the degree of temporal variability of urinary TDCPP and triphenyl phosphate (TPP) metabolites throughout pregnancy in a cohort of women from central North Carolina. Eight pregnant women provided multiple urine samples: 3 during the 18th week of pregnancy, 1 during the 28th week, and 1 shortly after the child's birth. Bis (1,3-dichloropropyl) phosphate (BDCPP) and diphenyl phosphate (DPP), the respective metabolites of TDCPP and TPP, were measured in urine samples using liquid chromatography-tandem mass spectrometry. BDCPP and DPP were each detected in 38 of 39 urine samples and were not normally distributed. Geometric mean BDCPP and DPP concentrations were 1.3ng/mL (interquartile range (IQR): 0.8, 2.7ng/mL) and 1.9ng/mL (IQR: 0.9, 3.5ng/mL), respectively. BDCPP and DPP were moderately to strongly reliable over one week (intraclass correlation coefficient (ICC)=0.5; 95% confidence interval (CI): 0.4, 0.7 and ICC=0.7; 95% CI: 0.5, 0.8, respectively), and over the entire pregnancy (ICC=0.5 95% CI: 0.3, 0.7 and ICC=0.6; 95% CI: 0.4, 0.7, respectively). These data suggest that exposures to TDCPP and TPP are widespread and variable for pregnant women, and that a single measure of BDCPP or DPP, taken in the second trimester, likely captures information on the rank order of exposure throughout pregnancy., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Few epidemiological data are available since the introduction of 13-valent pneumococcal vaccine (PCV13) in 2010. We conducted a cross-sectional study to estimate the prevalence of Streptococcus pneumoniae (SP) nasopharyngeal carriage in healthy Italian infants and young children and to evaluate the impact of PCV13 on pneumococcal colonization. In the trimester September-December 2011 nasopharyngeal swabs were collected from healthy children aged 3-59 months presenting for routine well careat 16 primary care pediatricians in Milan. SP carriage isolates were serotyped and tested for antimicrobial resistance using EUCAST breakpoints. Among 1250 enrolled children, 618 had received at least 1 dose of PCV13, 292 at least 1 dose of PCV7, 94 a combination of the two vaccines and 246 were not vaccinated. The prevalence of SP carriage was 27% (95% confidence interval [CI] 25-30). At multivariable analysis, age≥25 months (prevalence ratio [PR]=0.74) and use of antibiotics in the previous 3 months (PR=0.67) were associated with lower SP carriage prevalence. Having siblings (PR=1.79 for 1 sibling and PR=2.23 for ≥2 siblings), day-care attendance (PR=2.27) and respiratory tract infections in the previous 3 months (PR=1.39) were associated with higher SP carriage prevalence. The immunization status for SP was not associated with SP carriage at univariable or at multivariable analysis. The most common carriage isolates were 6C, 19A and 23A. The prevalence of the six additional PCV13 serotypes carriage in children appropriately vaccinated with PCV13 was lower than in children appropriately vaccinated with PCV7 (0 vs. 0.060); the greater reduction in prevalence of carriage was observed for serotype 19A (0 vs. 0.041). Serotype 6C was the most common drug-resistant serotype (17.2%). Further epidemiological studies are needed to assess changes in circulating SP serotypes following the large-scale introduction of PCV13., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: A new meningococcal serogroup B (Men B) vaccine has been licensed in the European Union (EU) and Australia. This study aimed to assess community and parental attitudes to introduction of new Men B vaccines and identify facilitators and barriers to vaccine implementation., Methods: Cross-sectional survey including face-to-face interviews with adolescents, parents and adults from randomly selected households in South Australia in 2012. Survey data were weighted to the age, gender and geographical area profile of the population., Results: 3055 interviews were conducted with individuals aged 15-97 years, including 966 parents. Participation rate was 66.4%. 82.5% (95% CI 79.7-85.4) of parents (797/966) wanted their child to receive the Men B vaccine, with 12.2% (9.7-14.7) (118/966) unsure. Main parental concerns included potential side effects (41.3% (26.7-46.0)) and adequate vaccine testing (11.7% (9.4-14.1)). Potential for an extra injection at an immunisation visit resulted in 15.7% (12.8-18.5) of parents (n=152/966) less likely to have their child immunised. Potential redness/swelling at the injection site or mild/moderate fever resulted in only 8.5% (6.3-10.7) and 10.8% (8.5-13.2) of parents, respectively, less likely to have their child immunised. Children being up to date with vaccinations and recommendation from family physician were the strongest independent predictors of parents agreeing their children should be immunised with Men B vaccine (OR=6.58; p=0.006 and OR=4.15; p<0.001, respectively). Only 16.4% (14.9-17.9) of adults (501/3055) stated that they would not want to receive a Men B vaccine, with family physician recommendation the strongest independent predictor of acceptance (OR=3.81; p<0.001)., Conclusions: There is strong community support for introduction of Men B vaccines, with parental willingness to have children immunised, impacted more by number of injections than potential for adverse events such as local reactions or fever., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Protection of motoneurons is an important goal in the treatment of spinal cord injury (SCI). We tested whether neuroprotective microRNAs (miRs) like miR-206, miR-17, miR-21, miR-7-1, and miR-106a could enhance efficacy of estrogen receptor (ER) agonists such as 1,3,5-tris (4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT, ERα agonist), Way200070 (WAY, ERβ agonist), and estrogen (EST, ERα and ERβ agonist) in preventing apoptosis in the calcium ionophore (CI)-insulted ventral spinal cord 4.1 (VSC4.1) motoneurons. We determined that 200 nM CI induced 70% cell death. Treatment with 50 nM PPT, 100 nM WAY, and 150 nM EST induced overexpression of ERα, ERβ, and both receptors, respectively, at mRNA and protein levels. Treatment with ER agonists significantly upregulated miR-206, miR-17, and miR-7-1 in the CI-insulted VSC4.1 motoneurons. Transfection with miR-206, miR-17, or miR-7-1 mimic potentiated WAY or EST to inhibit apoptosis in the CI-insulted VSC4.1 motoneurons. Overexpression of miR-7-1 maximally increased efficacy of WAY and EST for down regulation of pro-apoptotic Bax and upregulation of anti-apoptotic Bcl-2. A search using microRNA database (miRDB) indicated that miR-7-1 could inhibit the expression of L-type Ca(2+) channel protein alpha 1C (CPα1C). miR-7-1 overexpression and WAY or EST treatment down regulated CPα1C but upregulated p-Akt to trigger cell survival signaling. The same therapeutic strategy increased expression of the Ca(2+)/calmodulin-dependent protein kinase II beta (CaMKIIβ) and the phosphorylated cAMP response element binding protein (p-CREB) so as to promote Bcl-2 transcription. Whole cell membrane potential and mitochondrial membrane potential studies indicated that miR-7-1 highly potentiated EST to preserve functionality in the CI-insulted VSC4.1 motoneurons. In conclusion, our data indicated that miR-7-1 most significantly potentiated efficacy of EST for functional neuroprotection and this therapeutic strategy could be used in the future to attenuate apoptosis of motoneurons in SCI., (Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.)

Under normal conditions, the acoustic pitch percept of a pure tone is determined mainly by the tonotopic place of the stimulation along the cochlea. Unlike acoustic stimulation, electric stimulation of a cochlear implant (CI) allows for the direct manipulation of the place of stimulation in human subjects. CI sound processors analyze the range of frequencies needed for speech perception and allocate portions of this range to the small number of electrodes distributed in the cochlea. Because the allocation is assigned independently of the original resonant frequency of the basilar membrane associated with the location of each electrode, CI users who have access to residual hearing in either or both ears often have tonotopic mismatches between the acoustic and electric stimulation. Here we demonstrate plasticity of place pitch representations of up to three octaves in Hybrid CI users after experience with combined electro-acoustic stimulation. The pitch percept evoked by single CI electrodes, measured relative to acoustic tones presented to the non-implanted ear, changed over time in directions that reduced the electro-acoustic pitch mismatch introduced by the CI programming. This trend was particularly apparent when the allocations of stimulus frequencies to electrodes were changed over time, with pitch changes even reversing direction in some subjects. These findings show that pitch plasticity can occur more rapidly and on a greater scale in the mature auditory system than previously thought possible. Overall, the results suggest that the adult auditory system can impose perceptual order on disordered arrays of inputs., (Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.)

Purpose: Endothelin 1 (EDN1) is a strong angiogenic and mitogenic factor, playing a key role in hypervascularization, thyroid follicle cell hyperplasia, and lymphocyte infiltration in the thyroid gland of patients with Graves' disease (GD). EDN1 induces angiogenesis and mitogenesis via endothelin receptor type A (EDNRA). This study examined the possible association of EDN1 (G5665T and T-1370G) and EDNRA (C+70G and G-231A) single nucleotide polymorphisms (SNPs) with the occurrence of GD, and evaluates the relationship between genotypes and clinical/laboratory manifestations of GD., Materials and Methods: We analyzed genotype and allele distributions of EDN1 and EDNRA polymorphisms in 165 patients with GD and 181 healthy controls by real-time PCR combined with melting curve analysis., Results: No significant associations between GD and variant alleles of the studied polymorphisms were observed. However, the anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-TG) levels in EDN1 G5665T GG genotype were higher than those in T allele carriers (GT+TT) (p=0.001 and p=0.026, respectively). In addition, anti-TPO levels in EDN1 T-1370G wild-type homozygous patients were found to be higher than in mutant gene carrying patients (GT+GG) (p=0.006). The presence of EDNRA+70G allele was associated with 3.37-fold increased risk for development of ophthalmopathy in GD patients (p=0.009)., Conclusion: Although there were no associations between EDN1 (G5665T and T-1370G) and EDNRA (C+70G and G-231A) SNPs and susceptibility to GD, EDN1 G5665T and T-1370G polymorphisms were related to alterations of autoantibody production and EDNRA C+70G polymorphism is related with increased risk for ophthalmopathy in GD patients., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Epidemiologic studies have reported an inverse association between dairy product consumption and cardiometabolic risk factors in adults, but this relation is relatively unexplored in adolescents. We hypothesized that a higher dairy product intake is associated with lower cardiometabolic risk factor clustering in adolescents. To test this hypothesis, a cross-sectional study was conducted with 494 adolescents aged 15 to 18 years from the Azorean Archipelago, Portugal. We measured fasting glucose, insulin, total cholesterol, high-density lipoprotein cholesterol, triglycerides, systolic blood pressure, body fat, and cardiorespiratory fitness. We also calculated homeostatic model assessment and total cholesterol/high-density lipoprotein cholesterol ratio. For each one of these variables, a z score was computed using age and sex. A cardiometabolic risk score (CMRS) was constructed by summing up the z scores of all individual risk factors. High risk was considered to exist when an individual had at least 1 SD from this score. Diet was evaluated using a food frequency questionnaire, and the intake of total dairy (included milk, yogurt, and cheese), milk, yogurt, and cheese was categorized as low (equal to or below the median of the total sample) or "appropriate" (above the median of the total sample).The association between dairy product intake and CMRS was evaluated using separate logistic regression, and the results were adjusted for confounders. Adolescents with high milk intake had lower CMRS, compared with those with low intake (10.6% vs 18.1%, P = .018). Adolescents with appropriate milk intake were less likely to have high CMRS than those with low milk intake (odds ratio, 0.531; 95% confidence interval, 0.302-0.931). No association was found between CMRS and total dairy, yogurt, and cheese intake. Only milk intake seems to be inversely related to CMRS in adolescents., (© 2013.)

Background: Perfluoroalkyl substances (PFASs) are widespread and persistent environmental pollutants. Previous studies, primarily among non-pregnant individuals, suggest positive associations between PFAS levels and certain blood lipids. If there is a causal link between PFAS concentrations and elevated lipids during pregnancy, this may suggest a mechanism by which PFAS exposure leads to certain adverse pregnancy outcomes, including preeclampsia., Methods: This cross-sectional analysis included 891 pregnant women enrolled in the Norwegian Mother and Child (MoBa) Cohort Study in 2003-2004. Non-fasting plasma samples were obtained at mid-pregnancy and analyzed for nineteen PFASs. Total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, and triglycerides were measured in plasma. Linear regression was used to quantify associations between each PFAS exposure and each lipid outcome. A multiple PFAS model was also fitted., Results: Seven PFASs were quantifiable in >50% of samples. Perfluorooctane sulfonate (PFOS) concentration was associated with total cholesterol, which increased 4.2mg/dL per inter-quartile shift (95% CI=0.8, 7.7) in adjusted models. Five of the seven PFASs studied were positively associated with HDL cholesterol, and all seven had elevated HDL associated with the highest quartile of exposure. Perfluoroundecanoic acid showed the strongest association with HDL: HDL increased 3.7 mg/dL per inter-quartile shift (95% CI=2.5, 4.9)., Conclusion: Plasma concentrations of PFASs were positively associated with HDL cholesterol, and PFOS was positively associated with total cholesterol in this sample of pregnant Norwegian women. While elevated HDL is not an adverse outcome per se, elevated total cholesterol associated with PFASs during pregnancy could be of concern if causal., (© 2013.)

Consumption of sugar-sweetened beverages (SSBs) increased greatly from the late 1970s to the early part of this decade. Although recent data show that consumption of SSB may now be declining, consumption levels still remain much higher than recommended. Using data from the National Health and Nutrition Examination Survey, we assessed trends in intakes of SSB and levels of chronic disease biomarkers from 1999 to 2010 and examined the associations of SSB intake and biomarkers of chronic disease risk. We hypothesized that SSB intake will decrease and biomarkers of chronic disease risk will improve, therefore indicating that high intake of SSB is associated with greater chronic disease risk. Univariate analysis showed that from 1999 to 2010, SSB consumption decreased (P for trend = .0026), high-density lipoprotein increased (P for trend < .0001), low-density lipoprotein decreased (P for trend = .0007), and C-reactive protein decreased (P for trend = .0096). Using multivariate analysis, we showed that higher intakes of SSB were associated with lower high-density lipoprotein (P for trend < .0001), in an unadjusted model and all models with increasing numbers of covariates, and higher C-reactive protein (P for trend < .05), in an unadjusted model and in models with age, race/ethnicity, sex, education level, and poverty income ratio adjustments. We conclude that SSB consumption is associated with biomarkers of chronic disease risk, independent of demographic and lifestyle factors., (© 2014.)

Purpose: To examine the validity of billing, procedural, or diagnosis code, or pharmacy claim-based algorithms used to identify patients with systemic lupus erythematosus (SLE) in administrative and claims databases., Methods: We searched the MEDLINE database from 1991 to September 2012 using controlled vocabulary and key terms related to SLE. We also searched the reference lists of included studies. Two investigators independently assessed the full text of studies against pre-determined inclusion criteria. The two reviewers independently extracted data regarding participant and algorithm characteristics and assessed a study's methodologic rigor using a pre-defined approach., Results: Twelve studies included validation statistics for the identification of SLE in administrative and claims databases. Seven of these studies used the ICD-9 code of 710.0 in selected populations of patients seen by a rheumatologist or patients who had experienced the complication of SLE-associated nephritis, other kidney disease, or pregnancy. The other studies looked at limited data in general populations. The algorithm in the selected populations had a positive predictive value (PPV) in the range of 70-90% and of the limited data in general populations it was in the range of 50-60%., Conclusions: Few studies use rigorous methods to validate an algorithm for the identification of SLE in general populations. Algorithms including ICD-9 code of 710.0 in physician billing and hospitalization records have a PPV of approximately 60%. A requirement that the code is obtained from a record based on treatment by a rheumatologist increases the PPV of the algorithm but limits the generalizability in the general population., (Copyright © 2013. Published by Elsevier Ltd.)

Purpose: To review the evidence supporting the validity of billing, procedural, or diagnosis code, or pharmacy claim-based algorithms used to identify patients with rheumatoid arthritis (RA) in administrative and claim databases., Methods: We searched the MEDLINE database from 1991 to September 2012 using controlled vocabulary and key terms related to RA and reference lists of included studies were searched. Two investigators independently assessed the full text of studies against pre-determined inclusion criteria and extracted the data. Data collected included participant and algorithm characteristics., Results: Nine studies reported validation of computer algorithms based on International Classification of Diseases (ICD) codes with or without free-text, medication use, laboratory data and the need for a diagnosis by a rheumatologist. These studies yielded positive predictive values (PPV) ranging from 34 to 97% to identify patients with RA. Higher PPVs were obtained with the use of at least two ICD and/or procedure codes (ICD-9 code 714 and others), the requirement of a prescription of a medication used to treat RA, or requirement of participation of a rheumatologist in patient care. For example, the PPV increased from 66 to 97% when the use of disease-modifying antirheumatic drugs and the presence of a positive rheumatoid factor were required., Conclusions: There have been substantial efforts to propose and validate algorithms to identify patients with RA in automated databases. Algorithms that include more than one code and incorporate medications or laboratory data and/or required a diagnosis by a rheumatologist may increase the PPV., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Reduction in the prevalence of vaccine type HPV infection in young women is an early indication of the impact of the HPV immunisation programme and a necessary outcome if the subsequent impact on cervical cancer is to be realised., Methods: Residual vulva-vaginal swab (VVS) specimens from young women aged 16-24 years undergoing chlamydia screening in community sexual health services (formerly known as family planning clinics), general practice (GP), and youth clinics in 2010-2012 were submitted from 10 laboratories in seven regions around England. These specimens were linked to demographic and sexual behaviour data reported with the chlamydia test, anonymised, and tested for type-specific HPV DNA using a multiplex PCR and Luminex-based genotyping test. Estimated immunisation coverage was calculated and findings were compared to a baseline survey conducted prior to the introduction of HPV immunisation in 2008., Results: A total of 4664 eligible specimens were collected and 4178 had a valid test result. The post-immunisation prevalence of HPV 16/18 infection was lowest in this youngest age group (16-18 years) and increased with age. This increase with age was a reversal of the pattern seen prior to immunisation and was inversely associated with estimates of age-specific immunisation coverage (65% for 16-18 year olds). The prevalence of HPV 16/18 infection in the post-immunisation survey was 6.5% amongst 16-18 year olds, compared to 19.1% in the similar survey conducted prior to the introduction of HPV immunisation., Conclusions: These findings are the first indication that the national HPV immunisation programme is successfully preventing HPV 16/18 infection in sexually active young women in England. The reductions seen suggest, for the estimated coverage, high vaccine effectiveness and some herd-protection benefits. Continued surveillance is needed to determine the effects of immunisation on non-vaccine HPV types., (Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.)

Background: This clinical trial examined the safety and immunogenicity of annual revaccination with Fluzone(®) Intradermal (Sanofi Pasteur, Swiftwater, PA) vaccine compared to a standard intramuscular (IM) split-virion trivalent influenza vaccine (Fluzone(®), Sanofi Pasteur)., Methods: This phase II, active-controlled, multi-centre, open-label trial was conducted in 2009 and 2010, and enrolled 1250 adults 18-64 years of age who were randomly selected from participants in a phase III influenza vaccine trial the previous year (NCT00772109). Subjects who had previously received the ID vaccine were randomized 2:1 to be revaccinated with the ID or IM vaccine and those who previously received the IM vaccine were randomized 1:1. Solicited reactions were recorded on the day of vaccination and continuing for the next 7 days, non-serious adverse events for 28 days, and serious adverse events for 6 months after vaccination. Hemagglutination inhibition antibody titres were assessed pre-vaccination and at day 28., Results: Reactions were well-tolerated and resolved in the first 7 days, but erythema, induration, swelling, pruritus and ecchymosis were reported by more subjects receiving the ID vaccine than the IM vaccine. Compared to receipt of IM vaccine in the previous year, ID vaccine in the previous year led to statistically higher rates of erythema, swelling and induration after IM vaccine in the second year. Injection-site pain and systemic reactions did not differ between ID and IM vaccines. No treatment-related serious adverse events were reported. Geometric mean antibody titres, seroprotection rates, and seroconversion rates were non-inferior for the ID and IM vaccines for all three viral strains., Conclusions: The ID vaccine was as immunogenic as the IM vaccine, and raised no safety concerns. It can be used interchangeably with the IM vaccine for annual revaccination in adults 18-64 years of age in consecutive years without safety concerns., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: The genomic diversity of high-risk human papillomaviruses (HPV) has been associated with viral persistence and HPV-induced lesions. Studies on HPV56 persistence are still pending., Objective: To assess the association between HPV56 polymorphism and HPV56 persistence and presence of high-grade cervical intraepithelial neoplasia (CIN2,3) or cancer., Study Design: HPV56-positive cervical specimens from 204 women selected from a total of 4669 participants recruited in 5 epidemiological studies (parent studies) were further analyzed by PCR-sequencing of the long control region (LCR)., Results: Of the 81 women followed prospectively in cohort studies who could be classified, 34 had persistent and 47 had transient HPV56 infections. Variant HPV56-LCR-MTL-21 was detected more frequently in persistent infections (52.9%, 95% CI: 36.7-68.6%) than in transient infections (25.5%, 95% CI: 15.1-39.4). Considering only women recruited in a cohort of women infected or at high risk for HIV infection, infection with variant HPV56-LCR-MTL-21 (OR=4.4, 95% CI: 1.3-14.5) was significantly associated with HPV56 persistence controlling in multivariate analysis for high risk HPV detection and HIV infection. A variation at nucleotide 7800 in HPV56-LCR-MTL-21 resulted in the loss of a binding site for Elf-1 embedded in one of the E2 binding sites, a potential activator or repressor of expression of the HPV genome. HPV56 polymorphism was not associated with CIN2,3 or cancer in women enrolled in cross-sectional and case-control studies., Conclusion: Polymorphism in HPV56 may influence the risk that infections with this type will persist., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Introduction: The CLSI-M53-A, Criteria for Laboratory Testing and Diagnosis of Human Immunodeficiency Virus (HIV) Infection; Approved Guideline includes an algorithm in which samples that are reactive on a 4th generation EIA screen proceed to a supplemental assay that is able to confirm and differentiate between antibodies to HIV-1 and HIV-2. The recently CE-marked Bio-Rad Geenius HIV-1/2 Confirmatory Assay was evaluated as an alternative to the FDA-approved Bio-Rad Multispot HIV-1/HIV-2 Rapid Test which has been previously validated for use in this new algorithm., Methods: This study used reference samples submitted to the Canadian - NLHRS and samples from commercial sources. Data was tabulated in 2×2 tables for statistical analysis; sensitivity, specificity, predictive values, kappa and likelihood ratios., Results: The overall performance of the Geenius and Multispot was very high; sensitivity (100%, 100%), specificity (96.3%, 99.1%), positive (45.3, 181) and negative (0, 0) likelihood ratios respectively, high kappa (0.96) and low bias index (0.0068). The ability to differentiate HIV-1 (99.2%, 100%) and HIV-2 (98.1%, 98.1%) Ab was also very high., Conclusion: The Bio-Rad Geenius HIV-1/2 Confirmatory Assay is a suitable alternative to the validated Multispot for use in the second stage of CLSI M53 algorithm-I. The Geenius has additional features including traceability and sample and cassette barcoding that improve the quality management/assurance of HIV testing. It is anticipated that the CLSI M53 guideline and assays such as the Geenius will reduce the number of indeterminate test results previously associated with the HIV-1 WB and improve the ability to differentiate HIV-2 infections., (Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.)

The intervention program for autism known as Treatment and Education of Autistic and Related Communication Handicapped Children (TEACCH) is considered an emerging practice for autism. In the present study we used state-of-the-art meta-analytical procedures to examine the pooled clinical effects of TEACCH in a variety of outcomes. A total of 13 studies were selected for meta-analysis totaling 172 individuals with autism exposed to TEACCH. Standardized measures of perceptual, motor, adaptive, verbal and cognitive skills were identified as treatment outcomes. We used inverse-variance weighted random effects meta-analysis supplemented with quality assessment, sensitivity analysis, meta-regression, and heterogeneity and publication bias tests. The results suggested that TEACCH effects on perceptual, motor, verbal and cognitive skills were of small magnitude in the meta-analyzed studies. Effects over adaptive behavioral repertoires including communication, activities of daily living, and motor functioning were within the negligible to small range. There were moderate to large gains in social behavior and maladaptive behavior. The effects of the TEACCH program were not moderated by aspects of the intervention such as duration (total weeks), intensity (hours per week), and setting (home-based vs. center-based). While the present meta-analysis provided limited support for the TEACCH program as a comprehensive intervention, our results should be considered exploratory owing to the limited pool of studies available., (© 2013.)

Background: Vitamin E includes eight natural antioxidant compounds (four tocopherols and four tocotrienols), but α-tocopherol has been the main focus of investigation in studies of cognitive impairment and Alzheimer's disease., Objective: To investigate the association between serum levels of tocopherols and tocotrienols, markers of vitamin E oxidative/nitrosative damage (α-tocopherylquinone, 5-nitro-γ-tocopherol) and incidence of cognitive impairment in a population-based study., Design: A sample of 140 non-cognitively impaired elderly subjects derived from the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study was followed-up for 8years to detect cognitive impairment, defined as development of mild cognitive impairment (MCI) or Alzheimer's dementia. The association between baseline serum vitamin E and cognitive impairment was analyzed with multiple logistic regression after adjusting for several confounders., Results: The risk of cognitive impairment was lower in subjects in the middle tertile of the γ-tocopherol/cholesterol ratio than in those in the lowest tertile: the multiadjusted odds ratio (OR) with 95% confidence interval (CI) was 0.27 (0.10-0.78). Higher incidence of cognitive impairment was found in the middle [OR (95% CI): 3.41 (1.29-9.06)] and highest [OR (95% CI): 2.89 (1.05-7.97)] tertiles of the 5-NO2-γ-tocopherol/γ-tocopherol ratio. Analyses of absolute serum levels of vitamin E showed lower risk of cognitive impairment in subjects with higher levels of γ-tocopherol, β-tocotrienol, and total tocotrienols., Conclusions: Elevated levels of tocopherol and tocotrienol forms are associated with reduced risk of cognitive impairment in older adults. The association is modulated by concurrent cholesterol concentration. Various vitamin E forms might play a role in cognitive impairment, and their evaluation can provide a more accurate measure of vitamin E status in humans., (© 2013.)

Background: In 2002, the sero-prevalence of human immunodeficiency virus-1 (HIV) in the Emergency Department (ED), University Hospital, Newark, New Jersey was 10.4%. Both HIV and hepatitis C virus (HCV) are transmitted by injection drug use (IDU) or sexual contact. However, the degree of concurrent positive HCV antibody status in HIV-infected ED patients is unknown., Objectives: In this study we determined the sero-prevalence of HIV and HIVHCV in HIV-positive patients in the ED., Study Design: A cross-sectional study using an anonymous sero-prevalence survey was conducted from 7/1/2008 to 8/23/2008. Medical records were reviewed and de-identified; remnant blood specimens were also de-identified and tested for HIV antibody, and if positive, HCV antibody., Results: Of 3488 specimens, 225 (6.5%, 95% CI: 5.7-7.3%) were positive for HIV antibody. Seventy-four patients 74/225 (32.9%, 95% CI: 33.8-46.5%) were unaware of their sero-positivity. Forty percent of HIV positive patients (90/225, 95% CI: 33.8-46.5%) were HCV antibody positive. The highest seroprevalence of HIVHCV antibody was among older patients (≥ 45 years), and patients with positive urine toxicology and elevated liver function tests., Discussion: Given the high prevalence of HIV and HIVHCV antibody in the ED, routine testing is important for patients ≥ 45 years with positive urine toxicology and elevated liver function tests., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: A multisite study was conducted to evaluate the performance of the Bio-Rad 4th generation GS HIV Combo Ag/Ab EIA versus Abbott 4th generation ARCHITECT HIV Ag/Ab Combo. The performance of two 3rd generation EIAs, Ortho Diagnostics Anti-HIV 1+2 EIA and Siemens HIV 1/O/2 was also evaluated., Objective: Study objective was comparison of analytical HIV-1 p24 antigen detection, sensitivity in HIV-1 seroconversion panels, specificity in blood donors and two HIV false reactive panels., Study Design: Analytical sensitivity was evaluated with International HIV-1 p24 antigen standards, the AFFSAPS (pg/mL) and WHO 90/636 (IU/mL) standards; sensitivity in acute infection was compared on 55 seroconversion samples, and specificity was evaluated on 1000 negative blood donors and two false reactive panels., Results: GS HIV Combo Ag/Ab demonstrated better analytical HIV antigen sensitivity compared to ARCHITECT HIV Ag/Ab Combo: 0.41 IU/mL versus 1.2 IU/mL (WHO) and 12.7 pg/mL versus 20.1 pg/mL (AFSSAPS); GS HIV Combo Ag/Ab EIA also demonstrated slightly better specificity compared to ARCHITECT HIV Ag/Ab Combo (100% versus 99.7%). The 4th generation HIV Combo tests detected seroconversion 7-11 days earlier than the 3rd generation HIV antibody only EIAs., Conclusion: Both 4th generation immunoassays demonstrated excellent performance in sensitivity, with the reduction of the serological window period (7-11 days earlier detection than the 3rd generation HIV tests). However, GS HIV Combo Ag/Ab demonstrated improved HIV antigen analytical sensitivity and slightly better specificity when compared to ARCHITECT HIV Ag/Ab Combo assay, with higher positive predictive values (PPV) for low prevalence populations., (Copyright © 2013 Elsevier B.V. All rights reserved.)

To examine the association between dietary habits, cognitive functioning and brain volumes in older individuals, data from 194 cognitively healthy individuals who participated in the Prospective Investigation of the Vasculature in Uppsala Seniors cohort were used. At age 70, participants kept diaries of their food intake for 1week. These records were used to calculate a Mediterranean diet (MeDi) score (comprising dietary habits traditionally found in Mediterranean countries, e.g. high intake of fruits and low intake of meat), with higher scores indicating more pronounced MeDi-like dietary habits. Five years later, participants' cognitive capabilities were examined by the seven minute screening (7MS) (a cognitive test battery used by clinicians to screen for dementia), and their brain volumes were measured by volumetric magnetic resonance imaging. Multivariate linear regression analyses were constructed to examine the association between the total MeDi score and cognitive functioning and brain volumes. In addition, possible associations between MeDi's eight dietary features and cognitive functioning and brain volumes were investigated. From the eight dietary features included in the MeDi score, pertaining to a low consumption of meat and meat products was linked to a better performance on the 7MS test (P=0.001) and greater total brain volume (i.e. the sum of white and gray matter, P=0.03) when controlling for potential confounders (e.g. BMI) in the analysis. Integrating all dietary features into the total MeDi score explained less variance in cognitive functioning and brain volumes than its single dietary component meat intake. These observational findings suggest that keeping to a low meat intake could prove to be an impact-driven public health policy to support healthy cognitive aging, when confirmed by longitudinal studies. Further, they suggest that the MeDi score is a construct that may mask possible associations of single MeDi features with brain health domains in elderly populations., (© 2013. Published by Elsevier Inc. All rights reserved.)

Manganese (Mn) can interact with cadmium (Cd) in environments and influence the toxic effect of Cd on plants. However, few studies have investigated the relationship between the Mn/Cd ratio and plant Cd-toxicity along Cd concentrations. In this paper, we studied the effects of external Mn/Cd molar ratios (0, 10, 30, 50 and 60) on Cd toxicity in the Mn hyperaccumulator and Cd tolerant plant, Phytolacca acinosa Roxb., at three Cd levels (50, 100 and 200 μM) under hydroponic conditions. Our result showed that seedling growth (y) under Cd stress was strongly positively related to the solution Mn/Cd molar ratio (SMCR). The relationship between the two variables under solution Cd concentrations was well explained by the linear regression model y=a+b1 (SMCR)+b2 (Solution-Cd). Increasing SMCR significantly reduced the Cd concentration and increased the Mn concentration in plant tissues. However, seedling growth was consistent with the shoot Mn/Cd molar ratio rather than with the Mn or Cd concentrations in plant tissues. At low levels of SMCR (e.g. 0 and 10), elevation of Mn distribution in shoot tissues might be a mechanism in P. acinosa seedlings to defend against Cd-toxicity. In comparison with low levels of SMCR, high levels of SMCR (e.g. 50 and 60) greatly alleviated lipid peroxidation and plant water-loss, and enhanced photosynthesis. However, the alleviated lipid peroxidation in the Mn-mitigation of Cd toxicity was likely to be the secondary effect resulting from the antagonism between Mn and Cd in the plant., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

In developing countries, risk of human papillomavirus (HPV) infection may be increased by the high prevalence of human immunodeficiency virus (HIV) infection. We evaluated the safety and immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine in HIV-infected women in South Africa. Asymptomatic HIV-positive women aged 18-25 years (N=120) were stratified by CD4⁺ T-cell count and randomised (1:1) to receive HPV-16/18 vaccine (Cervarix®; GlaxoSmithKline Vaccines) or placebo (Al[OH]3) at 0, 1 and 6 months (double-blind). HIV-negative women (N=30) received HPV-16/18 vaccine (open label). Anti-HPV-16/18 antibody and CD4⁺ T-cell responses, CD4⁺ T-cell count, HIV viral load, HIV clinical stage and safety were evaluated for 12 months. The safety and reactogenicity profile of the HPV-16/18 vaccine was comparable in HIV-positive and HIV-negative women. Irrespective of baseline HPV status, all HIV-positive and HIV-negative women who received the HPV-16/18 vaccine were seropositive for both HPV-16 and HPV-18 after the second vaccine dose (month 2) and remained seropositive for both antigens at month 12. Anti-HPV-16/18 antibody titres at month 12 remained substantially above levels associated with natural infection. The HPV-16/18 vaccine induced sustained anti-HPV-16/18 CD4⁺ T-cell responses in both HIV-positive and HIV-negative women. No impact of baseline CD4⁺ T-cell count or HIV viral load was observed on the magnitude of the immune response in HIV-positive women. In HIV-positive women, CD4⁺ T-cell count, HIV viral load and HIV clinical stage were unaffected by HPV-16/18 vaccine administration. In conclusion, the HPV-16/18 AS04-adjuvanted vaccine appears immunogenic and well-tolerated in women with HIV infection. Study ID: 107863/NCT00586339., (Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Given the concurrent administration of multiple vaccines during routine pediatric immunizations, efforts to elucidate the potential interference of any vaccine on the immune response to the concomitantly administered antigens are fundamental to prelicensure clinical research., Methods: This phase 3 randomized controlled trial of 13-valent pneumococcal conjugate vaccine (PCV13) versus 7-valent PCV (PCV7) assessed immune responses of concomitantly administered meningococcal group C conjugated to diphtheria toxin cross-reactive material 197 (MnCCV-CRM197) in a 2-dose infant series and 15-month toddler dose., Results: 619 subjects were randomized, 315 to PCV13 and 304 to PCV7. MnCCV-CRM197-induced immune responses were similar between the PCV13 and PCV7 groups, with >97% of the subjects achieving a ≥1:8 meningococcal serum bactericidal assay (SBA) titer after both dose 2 and the toddler dose. Geometric mean titers were lower in the PCV13 group 191.22 (167.72, 218.02) versus 266.19 (234.86, 301.71) following dose 2 and 432.28 (361.22, 517.31) versus 730.84 (642.05, 831.91) following the toddler dose. The geometric mean (GM) meningococcal SBA titer ratios (PCV13/PCV7) were 0.72 after dose 2 and 0.59 after the toddler dose. The criteria for MnCCV-CRM197 non-inferiority for GM titers were satisfied after dose 2. Percent responders was similar up to titers of 1:128. PCV13 elicited substantial antipneumococcal responses against all 13 serotypes, with ≥90% of the subjects achieving an antibody concentration ≥0.35μg/mL after dose 3 in the infant series. Safety and tolerability were similar between the vaccine groups., Conclusions: Immunogenicity results of MnCCV-CRM197 for PCV13 compared with PCV7 included lower GMTs, but the clinical significance of this is unknown as the proportion of infants achieving protective MenC antibody titers was comparable in the two groups. Percent responders were similar up to titers of 1:128. PCV13 has an acceptable safety profile in infants and toddlers, while providing expanded coverage against pneumococcal disease., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

NDUFV1 mutations have been related to encephalopathic phenotypes due to mitochondrial energy metabolism disturbances. In this study, we report two siblings affected by a diffuse leukodystrophy, who carry the NDUFV1 c.1156C>T (p.Arg386Cys) missense mutation and a novel 42-bp deletion. Bioinformatic and molecular analysis indicated that this deletion lead to the synthesis of mRNA molecules carrying a premature stop codon, which might be degraded by the nonsense-mediated decay system. Our results add information on the molecular basis and the phenotypic features of mitochondrial disease caused by NDUFV1 mutations., (Copyright © 2013 Elsevier B.V. and Mitochondria Research Society. All rights reserved. All rights reserved.)

Objective: Coronary artery disease (CAD) is a complex disease resulting from a combination of environmental and genetic factors. We hypothesized that polymorphisms in methionine sulfoxide reductase A (MSRA: rs10903323 G/A) and vascular endothelial growth factor A (VEGFA: rs699947 C/A, rs2010963 G/C, and rs3025039 C/T) contribute to CAD susceptibility., Designs and Methods: We examined the association between the four polymorphisms and the risk of CAD in a Chinese population of 435 CAD patients and 480 controls. Genotyping was performed using matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI/TOF-MS)., Results: When the MSRA rs10903323 GG homozygous genotype was used as the reference group, the GA and GA/AA genotypes were associated with a significantly increased risk of CAD (GA vs GG: adjusted OR=1.36, 95% CI=1.02-1.82, p=0.038; GA/AA vs GG: adjusted OR=1.33, 95% CI=1.01-1.76, p=0.042). The AA homozygous genotype was not associated with a risk of CAD. In the recessive model, when the MSRA rs10903323 GG/GA genotypes were used as the reference group, the AA homozygous genotype was not associated with a risk of CAD. Logistic regression analyses revealed that the VEGFA rs699947 C/A, VEGFA rs2010963 G/C, and VEGFA rs3025039 C/T polymorphisms were not associated with a risk of CAD., Conclusions: These findings suggest that the functional MSRA rs10903323 G/A polymorphism is associated with CAD development. However, our results allow only a preliminary conclusion, which must be validated with a larger study of a more diverse ethnic population., (© 2013.)

Indoor pesticide exposure is a growing concern, particularly for pyrethroids, a commonly used class of pesticides. Pyrethroid concentrations may be especially high in homes of immigrant farm worker families, who often live in close proximity to agricultural fields and are faced with poor housing conditions, potentially causing high pest infestation and pesticide use. We investigate levels of pyrethroids in the house dust of farm worker family homes in a study of mothers and children living in Mendota, CA, within the population-based Mexican Immigration to California: Agricultural Safety and Acculturation (MICASA) Study. We present pesticide use data and levels of pyrethroid pesticides in indoor dust collected in 2009 as measured by questionnaires and a GC/MS analysis of the pyrethroids cis- and trans-permethrin, cypermethrin, deltamethrin, esfenvalerate and resmethrin in single dust samples collected from 55 households. Cis- and trans-permethrin had the highest detection frequencies at 67%, with median concentrations of 244 and 172ng/g dust, respectively. Cypermethrin was detected in 52% of the homes and had a median concentration of 186ng/g dust. Esfenvalerate, resmethrin and deltamethrin were detected in less than half the samples. We compared the pyrethroid concentrations found in our study to other studies looking at both rural and urban homes and daycares. Lower detection frequencies and/or lower median concentrations of cis- and trans-permethrin and cypermethrin were observed in our study as compared to those studies. However, deltamethrin, esfenvalerate and resmethrin were detected more frequently in the house dust from our study than in the other studies. Because households whose children had higher urinary pyrethroid metabolite levels were more likely to be analyzed in this study, a positive bias in our estimates of household pyrethroid levels may be expected. A positive association was observed with reported outdoor pesticide use and cypermethrin levels found in the indoor dust samples (rs=0.28, p=0.0450). There was also a positive association seen with summed pyrethroid levels in house dust and the results of a pesticide inventory conducted by field staff (rs=0.32, p=0.018), a potentially useful predictor of pesticide exposure in farm worker family homes. Further research is warranted to fully investigate the utility of such a measure., (© 2013.)

Introduction: Although the prevalence of preterm births ranges from 5 to 13% and represents the leading cause of perinatal mortality and morbidity in developed countries, the etiology of preterm birth remains uncertain. We aimed to evaluate the effect of short-term exposure to high and low temperatures and air pollution on preterm delivery and to identify socio-demographic and clinical maternal risk factors enhancing individual susceptibility., Methods: We analyzed all singleton live births by natural delivery that occurred in Rome in 2001-2010. A time-series approach was used to estimate the effect of exposure to minimum temperature, maximum apparent temperature, heat waves, particulate matter with an aerodynamic diameter of 10μm or less (PM10), ozone, and nitrogen dioxide in the month preceding delivery; the analysis was conducted separately for cold and warm seasons. Socio-demographic and clinical risk factors were included as interaction terms., Results: Preterm births comprised nearly 6% of our cohort. An increase of 1.9% (95% confidence interval (CI) 0.86-2.87) in daily preterm births per 1°C increase in maximum apparent temperature in the 2days preceding delivery was estimated for the warm season. Older women, women with higher education levels, and women with obstetric or chronic pathologies reported during delivery had a lower effect of temperature on the risk of preterm birth, while women with a chronic disease in the two years before delivery and mothers<20years showed a higher effect. A +19% (95% CI 7.91-31.69) increase in preterm births was observed during heat waves. Temperature had no effect during the cold season. We detected a significant effect of PM10 on preterm-birth risk at a lag period of 12-22days during the warm season (+0.69%; 95% CI 0.23-1.15, for 1μg/m(3) increase of pollutant); women with obstetric pathologies and with a higher education level showed a higher risk., Conclusions: Our results suggest a possible short-term effect of heat and a more delayed and prolonged effect of PM10 exposure on preterm-birth risk, as well as the existence of more susceptible subgroups of women. Our observations support the few reported investigations, and may help to increase awareness among public-health stakeholders and clinicians regarding the role of these environmental exposures as risk factors for premature birth and health consequences for children later in life., (© 2013.)

We estimated the seroprevalences of varicella-zoster virus (VZV), herpes simplex virus (HSV) and cytomegalovirus (CMV) in this cross-sectional database study. Serum samples collected during the National Health and Nutrition survey (ENSANUT 2006) were obtained from subjects aged 1-70 years between January and October 2010. Serological assays for the determination of antibodies against VZV, HSV and CMV were performed. The overall seroprevalences of VZV, HSV-1, HSV-2 and CMV were 85.8%, 80.9%, 9.9% and 89.2%, respectively. Seroprevalences of VZV, HSV-1 and CMV were comparable between males and females. For HSV-2, although the seroprevalence rate was higher in females when compared to males, this difference in seroprevalence was not statistically significant. Seroprevalence rates for VZV, HSV-1, HSV-2 and CMV increased with age (p-value<.0001). Differences in seroprevalence rate for VZV by socioeconomic status (SES) were significant (p-value<0001). Results of the serological analyses reported high VZV seroprevalence, indicating high transmission in the Mexican population with children and adolescents at risk of acquiring VZV. Global HSV-1 seroprevalence was high, especially in adults. HSV-1 and HSV-2 seroprevalences were consistently higher in women than men, particularly for HSV-2. CMV seroprevalence was higher in Mexico when compared to developed countries. Seroepidemiological data on VZV supports the fact that varicella vaccination may serve as an alternative effective solution to reduce transmission in the Mexican population. For CMV and HSV, since no vaccines are available, activities to reduce transmission are important to reduce the risk of complications and therefore need to be considered., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Preeclampsia is the major cause of maternofetal and neonatal morbi-mortality including intrauterine growth retardation, miscarriages and stillbirths. Inadequate vascular dilation and angiogenesis represent the crucial underlying defect of gravidic hypertension, denoting a failed response to the vasodilatory and pro-angiogenic challenge imposed by pregnancy, especially if multifetal. A similar pathogenesis appears involved in gestational diabetes. In this review we aimed to provide a hint on understanding the deeply involved angiogenic disorders which eventually culminate in utero-placental failure. The key players in these complex processes may be found in an intricate network of growth factors (GFs) and GF inhibitors, controlled by several vascular risk factors modulated by environment and genes, which eventually impact on early and late cardiovascular outcomes of mother and fetus., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: Esophageal cancer is the sixth leading cause of cancer-associated deaths worldwide and represents a particularly aggressive type of cancer. Genetic polymorphisms may partly explain individual differences in esophageal cancer susceptibility., Designs and Methods: We conducted a hospital-based case-control study to evaluate the genetic effects of functional single nucleotide polymorphisms (SNPs) in the interleukin 1 (IL1A and IL1B), IL1f7, IL3 and IL7Ra genes on the development of esophageal cancer. A total of 380 esophageal squamous cell carcinoma (ESCC) cases and 380 controls were recruited for this study. The genotypes were determined using a custom-by-design 48-Plex SNPscan™ Kit., Results: When the IL1B rs16944 GG homozygote genotype was used as the reference group, the GA genotype was associated with a significantly decreased risk of ESCC (GA vs. GG: adjusted OR=0.69, 95% CI=0.49-0.99, p=0.041). However, there were no significant associations between the other five SNPs and ESCC risk. Stratified analyses indicated no significantly different risks of ESCC associated with the IL1B rs16944 G>A polymorphism according to sex, age, smoking status or alcohol consumption. IL3 rs2073506 G>A polymorphism was associated with an increased risk for ESCC higher tumor, nodal, and metastatic (TNM) stages., Conclusions: These findings indicated that the functional IL1B rs16944 G>A polymorphism might contribute to ESCC susceptibility. IL3 rs2073506 G>A polymorphism was associated with an increased risk for ESCC higher TNM stages. However, the results were based on a limited sample size and larger well-designed studies are warranted to confirm these initial findings., (Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Perfluoroalkyl acids (PFAAs) are persistent organic pollutants that are used in a wide range of consumer products. Recent epidemiological studies have shown that prenatal exposure to toxic levels of PFAAs in the environment may adversely affect fetal growth and humoral immune response in infants and children. Here we have characterized levels of prenatal exposure to PFAA between 2003 and 2011 in Hokkaido, Japan, by measuring PFAA concentrations in plasma samples from pregnant women. The study population comprised 150 women who enrolled in a prospective birth cohort study conducted in Hokkaido. Eleven PFAAs were measured in maternal plasma samples using simultaneous analysis by ultra-performance liquid chromatography coupled to triple quadrupole tandem mass spectrometry. At the end of the study, in 2011, age- and parity-adjusted mean concentrations of perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorododecanoic acid (PFDoDA), perfluorotridecanoic acid (PFTrDA), perfluorohexane sulfonate (PFHxS), and perfluorooctane sulfonate (PFOS) were 1.35ng/mL, 1.26ng/mL, 0.66ng/mL, 1.29ng/mL, 0.25ng/mL, 0.33ng/mL, 0.28ng/mL, and 3.86ng/mL, respectively. Whereas PFOS and PFOA concentrations declined 8.4%/y and 3.1%/y, respectively, PFNA and PFDA levels increased 4.7%/y and 2.4%/y, respectively, between 2003 and 2011. PFUnDA, PFDoDA, and PFTrDA were detected in the vast majority of maternal samples, but no significant temporal trend was apparent. Future studies must involve a larger population of pregnant women and their children to determine the effects of prenatal exposure to PFAA on health outcomes in infants and children., (© 2013.)

Valproic acid is a widely-used first-generation antiepileptic drug, prescribed predominantly in epilepsy and psychiatric disorders. VPA has good efficacy and pharmacoeconomic profiles, as well as a relatively favorable safety profile. However, adverse drug reactions have been reported in relation with valproic acid use, either as monotherapy or polytherapy with other antiepileptic drugs or antipsychotic drugs. This systematic review discusses valproic acid adverse drug reactions, in terms of hepatotoxicity, mitochondrial toxicity, hyperammonemic encephalopathy, hypersensitivity syndrome reactions, neurological toxicity, metabolic and endocrine adverse events, and teratogenicity., (Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Objectives: Ovarian cancer is the most lethal gynecological malignancy in North America. Although survival rates are high when the disease is diagnosed at an early stage, this decreases exponentially in late-stage diagnoses. As such, there is a need for novel early detection biomarkers. Through an integrated approach to ovarian cancer biomarker discovery that combines proteomics with transcriptomics and bioinformatics, our laboratory has identified folate-receptor 1 (FOLR1) and Dickkopf-related protein 3 (Dkk-3) as putative biomarkers. The objective of this study was to measure the levels of FOLR1 and Dkk-3 in the serum of patients with ovarian cancer, benign gynecological conditions and healthy women., Design and Methods: FOLR1 and Dkk-3 were analyzed in serum of 100 ovarian cancer patients, 100 patients with benign gynecological conditions, and 100 healthy women using enzyme-linked immunosorbent assays (ELISAs). All specimens were analyzed in triplicate., Results: FOLR1 was significantly elevated in the serum of ovarian cancer patients compared to serum of both healthy controls (P<0.0001) and patients with benign gynecological conditions (P<0.0001). Furthermore, FOLR1 was strongly correlated with CA125 as both were elevated in the serous histotype and in late-stage disease. FOLR1 did not outperform CA125 in receiver operating characteristic curve analysis and there was no significant complementarity between the two markers. Dkk-3 was not significantly different between the three serum cohorts and was not correlated with CA125., Conclusions: FOLR1 is a new biomarker for ovarian cancer which correlates closely with CA125. The role of FOLR1 in the pathogenesis of ovarian cancer warrants further investigation., (Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: A high prevalence of reactivation of hepatitis B has been documented among immunosuppressed individuals in the inactive phase of chronic hepatitis B; However, the proportion of and the risk factors for reactivation are largely unknown among non-immunosuppressed persons., Objectives: Estimate the incidence rate of and risk factors for hepatitis B reactivation in a population-based cohort of persons in the inactive phase of chronic hepatitis B in Alaska., Study Design: A cohort of 414 Alaska Native Persons in the inactive phase of hepatitis B (HBV DNA<2000 IU/mL and normal alanine aminotransferase (ALT) for 12 months) was followed-up for 10 years. Reactivation of hepatitis B was defined as HBV DNA≥2000 IU/mL and ALT≥40 IU/L. Cox-proportional hazards regression models were used to identify factors associated with reactivation., Results: A total of 36 (9%) persons had reactivation during 2984 person-years of follow-up, with an annual incidence of 1.2%. Persons aged ≥50 years (1.8%) at study entry had the highest incidence rates of reactivation although incidence rates were not significantly different by age group. Risk factors for hepatitis B reactivation were male sex (Hazard Ratio (HR)=2.41; 95% Confidence Interval (CI): 1.17-4.96), HBV DNA≥1000 IU/mL at study entry (HR=7.61; 95% CI: 2.81-20.6), and HBV genotype B (HR=6.08; 95% CI: 1.32-28.0)., Conclusions: The incidence of hepatitis B reactivation was low during the 10 years of follow-up. However, given the higher risk of reactivation than their counterparts, males, and those with HBV DNA≥1000 IU/mL need to be followed-up more frequently., (Published by Elsevier B.V.)

Scant evidence is available worldwide on the relative influence of occupational social class and educational level on body concentrations of persistent organic pollutants (POPs) in the general population. The objective was to analyse such influence in a representative sample of the general population of Catalonia, Spain. Participants in the Catalan Health Interview Survey aged 18-74 were interviewed face-to-face, gave blood, and underwent a physical exam. The role of age, body mass index (BMI), and parity was analysed with General Linear Models, and adjusted geometric means (GMs) were obtained. Crude (unadjusted) concentrations were higher in women and men with lower education, and in women, but not men, in the less affluent social class. After adjusting for age, in women there were no associations between POP levels and social class or education. After adjusting for age and BMI, men in the less affluent class had higher p,p'-DDE concentrations than men in class I (p-value=0.016), while men in class IV had lower HCB than men in the upper class (p-value<0.03). Also in contrast with some expectations, positive associations between education and POP levels were observed after adjusting for age and BMI in men; e.g., men with university studies had higher HCB concentrations than men with first stage of primary schooling (adjusted GM 153.9 and 80.5ng/g, respectively) (p-value<0.001). When education and social class were co-adjusted for, some positive associations with education in men remained statistically significant, whereas class remained associated only with p,p'-DDE. Educational level influenced blood concentrations of POPs more than occupational social class, especially in men. In women, POP concentrations were mainly explained by age/birth cohort, parity and BMI. In men, while concentrations were also mainly explained by age/birth cohort and BMI, both social class and education showed positive associations. Important characteristics of socioeconomic groups as age and BMI may largely explain crude differences among such groups in internal contamination by POPs. The absence of clear patterns of relationships between blood concentrations of POPs and indicators of socioeconomic position may fundamentally be due to the widespread, lifelong, and generally invisible contamination of human food webs. Decreasing historical trends would also partly explain crude socioeconomic differences apparently due to birth cohort effects., (© 2013 Elsevier Ltd. All rights reserved.)

Background: Spatially-resolved air pollution models can be developed in large areas. The resulting increased exposure contrasts and population size offer opportunities to better characterize the effect of atmospheric pollutants on respiratory health. However the heterogeneity of these areas may also enhance the potential for confounding. We aimed to discuss some analytical approaches to handle this trade-off., Methods: We modeled NO2 and PM10 concentrations at the home addresses of 1082 pregnant mothers from EDEN cohort living in and around urban areas, using ADMS dispersion model. Simulations were performed to identify the best strategy to limit confounding by unmeasured factors varying with area type. We examined the relation between modeled concentrations and respiratory health in infants using regression models with and without adjustment or interaction terms with area type., Results: Simulations indicated that adjustment for area limited the bias due to unmeasured confounders varying with area at the costs of a slight decrease in statistical power. In our cohort, rural and urban areas differed for air pollution levels and for many factors associated with respiratory health and exposure. Area tended to modify effect measures of air pollution on respiratory health., Conclusions: Increasing the size of the study area also increases the potential for residual confounding. Our simulations suggest that adjusting for type of area is a good option to limit residual confounding due to area-associated factors without restricting the area size. Other statistical approaches developed in the field of spatial epidemiology are an alternative to control for poorly-measured spatially-varying confounders., (© 2013 Elsevier Ltd. All rights reserved.)

Whether the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7) guidelines can be applied to the Asian population remains unclear. We aim to test the hypothesis that adherence to the JNC-7 guidelines is associated with hypertension in a representative sample of the Korean population in the fourth Korea National Health and Nutrition Examination Survey. Participants completed a non-quantitative food frequency questionnaire and 24-hour diet recall through interviews. Blood pressure, height, and weight were directly measured, and questions about physical activity and other lifestyle factors were administered. A total of 500 hypertensive and 4567 normotensive participants were identified. We estimated the odds ratio and 95% confidence intervals using a multivariate logistic regression. The following components of the JNC-7 guidelines were considered: dietary approaches to stop a hypertension style diet, moderate consumption of alcohol, adequate physical activity, and a normal body mass index. Those individuals who fell in the low-risk category for all 4 lifestyle components had an odds ratio of 0.48 (95% confidence interval, 0.30-0.78) compared with the remainder of the participants. In conclusion, we found an inverse association between adherence to the JNC-7 guidelines and hypertension prevalence among Korean adults, suggesting the importance of lifestyle modification for the prevention and management of hypertension., (© 2013 Elsevier Inc. All rights reserved.)

Objectives: Bladder tumor fibronectin (BTF) has been related as a promising biomarker for the early diagnosis of bladder tumor. The meta-analysis was used to establish the diagnostic value of bladder tumor fibronectin in diagnosing bladder tumor., Methods: Relevant literatures evaluating the value of BTF in the diagnosis of bladder tumor were searched in PubMed, Embase, China National Knowledge Infrastructure (CNKI), Technology of Chongqing (VIP), and Wan Fang Data. Summary estimates were used to evaluate the value of BTF in the diagnosis of bladder tumor by using the Meta-DiSc and STATA 11.0 statistical software., Results: The meta-analysis included 5 studies (649 patients, 291 controls). The summary estimates revealed that the pooled sensitivity was 81% (95% confidence interval [CI]: 74%-85.1%) and specificity was 80% (95%CI 74%-84%). In addition, the area under the summary ROC curve (AUC) was 0.86 (95%CI 0.82-0.89)., Conclusion: BTF is a potential marker for the diagnosis of bladder tumor, and more prospective studies are needed in the future., (Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Hydrogen peroxide (H2O2) and glutathione (GSH) are involved in the stress response in plants. To elucidate the role of H2O2 in the acclimation of CO2 assimilation under sub- or supra-optimal growth temperatures, we examined the effect and interaction of H2O2 manipulation on the photosynthetic metabolism of cucumber plants (Cucumis sativus L.) grown under five temperature regimes spanning above and below the optimal growth temperature; 11/9, 18/15, 25/20, 32/27, and 39/33 °C (day/night), with or without dimethylthiourea (DMTU) or H2O2 treatment. As expected, exposure to sub- or supra-optimal growth temperatures resulted in decreased plant growth, associated with a decline in CO2 assimilation (Asat), Rubisco content, and activities of enzymes involved in the CO2 assimilation, as well as a decrease in the ratio of reduced (GSH) to oxidized (GSSG) glutathione (GSH/GSSG). Foliar application of H2O2 promoted, whilst DMTU retarded the capacity of plants to acclimate to non-optimal growth temperatures; this was consistently shown in altered activity of redox-sensitive enzymes involved in CO2 assimilation. These results strongly suggest that the influence of growth temperature on CO2 assimilation was primarily targeted at the activities of the redox-sensitive enzymes of CO2 assimilation. Meanwhile, the data suggest that the cellular H2O2 level is an important signal for the glutathione-dependent regulation of redox-sensitive enzymes of CO2 assimilation in cucumber plants., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Background: This study (NCT00979602) evaluated the immunogenicity and relative protective efficacy of one dose of influenza A(H1N1)pdm09 vaccine with or without AS03 (an α-tocopherol oil-in-water emulsion based Adjuvant System)., Methods: Four thousands and forty-eight healthy adults aged ≥ 18 years were randomized (1:1) to receive one dose of either the adjuvanted split virion (3.75 μg hemagglutinin antigen [HA]/AS03) or non-adjuvanted (15 μg HA) vaccine. Hemagglutination inhibition [HI] antibody response was evaluated before vaccination and at Days 21, 42 and 182 (Month 6). Safety of the study vaccines was evaluated during the entire study duration., Results: At Day 21, both study vaccines induced HI immune responses meeting the US regulatory criteria in subjects 18-64 years (seroprotection rate [SPR]: 98.0% [97.1-98.6]; seroconversion rate [SCR]: 89.7% [88.0-91.2] in the AS03-adjuvanted group; SPR: 91.4% [89.9-92.8]; SCR: 74.6% [72.3-76.9] in the non-adjuvanted group) and >64 years of age (SPR: 86.0% [82.5-89.0]; SCR: 75.3% [71.1-79.2] in the AS03-adjuvanted group; SPR: 69.1% [64.6-73.3]; SCR: 56.7% [52.0-61.3] in the non-adjuvanted group). The AS03-adjuvanted vaccine induced higher HI geometric mean titers than the non-adjuvanted vaccine at all time points. At Month 6, only subjects 18-64 years of age from both vaccine groups still met the US regulatory criteria (SPR: 82.1% [80.0-84.1]; SCR: 62.3% [59.6-64.8] in the AS03-adjuvanted group; SPR: 75.3% [72.9-77.5]; SCR: 53.7% [51.0-56.4] in the non-adjuvanted group). Protective efficacy was not evaluated due to low number of RT-qPCR-confirmed A(H1N1)pdm09 influenza cases. Through Month 12, 216 serious adverse events (in 157 subjects: 84 in the AS03-adjuvanted and 73 in the non-adjuvanted group) and 12 potentially immune mediated diseases (5 in the AS03-adjuvanted and 7 in the non-adjuvanted group) were reported., Conclusion: A single dose of either adjuvanted or non-adjuvanted influenza A(H1N1)pdm09 vaccine induced protective HI antibody levels against the A/California/7/2009 strain that persisted through Month 6 in the 18-64 years population., (Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Hepatitis B virus (HBV) is highly endemic in Cambodia with an estimated pre-vaccine hepatitis B surface antigen (HBsAg) prevalence of 9%. By 2005, a hepatitis B vaccination program was implemented to decrease infection rates in children. We conducted a serosurvey to evaluate the impact of the vaccination program in 2011., Methods: A cross-sectional two-stage cluster survey was conducted to estimate HBsAg prevalence among children born from 2006 to 2007 in three provinces: Phnom Penh (urban), Kratie (rural), and Ratanakiri (remote). Demographic data, as well as written or oral vaccination history were collected. Children were tested for HBsAg. Factors associated with undervaccination and HBsAg positivity were modeled., Results: Coverage of timely hepatitis B vaccine birth dose (administered at ≤ 24 h) was 55% in Phnom Penh, 36% in Kratie, and 22% in Ratanakiri. Coverage with ≥ 3 hepatitis B vaccine doses (HepB3) was 91% in Phnom Penh, 82% in Kratie, and 64% in Ratanakiri. When compared with children who were born in health facilities with a skilled birth attendant (SBA), children born at home without a SBA were more likely not to have received a timely BD (adjusted relative risk [aRR]=1.94; 95% CI=1.75-2.15) as were children born at home with an SBA (aRR=1.54; 95% CI=1.32-1.80). The proportion of children who tested positive for HBsAg was 0.33% in Phnom Penh, 1.41% in Kratie, and 3.45% in Ratanakiri. In all three provinces, children who received their first dose after 7 days of life and children who never received hepatitis B vaccine had the highest HBsAg prevalence., Conclusions: Progress has been made in Cambodia in decreasing the burden of chronic HBV infection among children. Improvements in vaccination coverage will further decrease the burden of disease., (Copyright © 2013 World Health Organization. Published by Elsevier Ltd.. All rights reserved.)

Cortical spontaneous activity reflects an animal's behavioral state and affects neural responses to sensory stimuli. The correlation between excitatory and inhibitory synaptic input to single neurons is a key parameter in models of cortical circuitry. Recent measurements demonstrated highly correlated synaptic excitation and inhibition during spontaneous "up-and-down" states, during which excitation accounted for approximately 80% of inhibitory variance (Shu et al., 2003; Haider et al., 2006). Here we report in vivo whole-cell estimates of the correlation between excitation and inhibition in the rat visual cortex under pentobarbital anesthesia, during which up-and-down states are absent. Excitation and inhibition are weakly correlated, relative to the up-and-down state: excitation accounts for less than 40% of inhibitory variance. Although these correlations are lower than when the circuit cycles between up-and-down states, both behaviors may arise from the same circuitry. Our observations provide evidence that different correlational patterns of excitation and inhibition underlie different cortical states., (Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.)

Prenatal exposure to bisphenol A (BPA) may be associated with adverse health effects in the developing fetus; however, little is known about predictors of BPA exposure during pregnancy. We examined BPA exposure in 491 pregnant women from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) cohort and explored the role of living in the United States on significant dietary predictors of BPA exposure. Women provided urine samples up to two times during pregnancy (n=866 total samples). We computed the intraclass correlation coefficient (ICC) to evaluate variability in concentrations between collections and used generalized estimating equation (GEE) models to assess predictors of exposure. Geometric mean (GSD) BPA concentrations were 0.9 (2.8)μg/L and 1.0 (2.6)μg/L at the first and second prenatal visits, respectively. We observed greater within- than between-woman variability in urinary BPA concentrations (ICC=0.22). GEE models suggest that women who lived in the United States their entire life had 38% (CI: -0.1, 89.3) higher urinary BPA concentrations compared with other immigrant women. Additionally, women who consumed ≥3 sodas per day or hamburgers three times a week or more had 58% (CI: 18.0, 112.1) and 20% (CI: -0.2, 45.2) higher urinary BPA concentrations, respectively, compared with women who consumed no sodas or hamburgers. A higher percentage of women who lived their entire life in the United States reported increased consumption of sodas and hamburgers compared with other immigrant women. Independent of other factors, BPA urinary concentrations were slightly higher when the sample was collected later in the day. As in previous studies, high within-woman variability in urinary BPA concentrations confirms that several samples are needed to properly characterize exposure during pregnancy. Results also suggest that some factors could be modified to minimize exposures during pregnancy in our study participants (e.g., reducing soda and hamburger intake) and that factors associated with acculturation might increase BPA concentrations., (Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Urinary sugars excretion has been proposed as a potential biomarker for intake of sugars. In this study, we compared 2 analytical methods (gas chromatography [GC] and enzymatic reactions-UV absorption) for quantifying urinary fructose and sucrose using 24-hour urine samples from a randomized crossover controlled feeding study. All samples were successfully quantified by the GC method; however, 21% and 1.9% of samples were below the detection limit of the enzymatic method for sucrose and fructose, respectively. Although the correlation between the 2 methods was good for fructose (Pearson correlation, 0.71), the correlation was weak for sucrose (Pearson correlation, 0.27). We favor the GC method because of its better sensitivity, simplicity, and the ability to quantify fructose and sucrose directly in the same run. Of the 106 samples from 53 participants with complete urine collection after 2 study diets, 24-hour urinary fructose excretion was significantly associated with fructose intake. The sum of 24-hour urinary fructose and sucrose was significantly associated with total sugars consumption. However, variation in intakes of sugars explained only a modest amount of variation in urinary sugars excretion. In the unadjusted models, fructose intake explained 24.3% of urinary fructose excretion, and intake of total sugars explained 16.3% of the sum of urinary fructose and sucrose. The adjusted models explained 44.3% of urinary fructose excretion and 41.7% of the sum of urinary fructose and sucrose. Therefore, we caution using these biomarkers to predict sugars consumption before other factors that determine urinary sugars excretion are understood., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: DNA methylation changes are potential pathways of environmentally induced health effects. We investigated whether exposure to ambient concentrations of NO2, PM10, PM2.5 and O3 and traffic parameters were associated with global DNA methylation in blood of healthy adults., Methods: 48 non-smoking adults (25 males) with a median age of 39years were sampled in winter and summer. Global DNA methylation in whole blood (% 5-methyl-2'-deoxycytidine, %5mdC) was analyzed with HPLC. Exposure to air pollutants at the home address was assessed using interpolated NO2, PM10, PM2.5 and O3 concentrations for various exposure windows (60- to 1-day moving average exposures and yearly averages) and GIS-based traffic parameters. Associations between pollutants and %5mdC were tested with multiple mixed effects regression models., Results: Average %5mdC (SD) was 4.30 (0.08) in winter and 4.29 (0.08) in summer. Men had higher %5mdC compared to women both in winter (4.32 vs. 4.26) and summer (4.31 vs. 4.27). When winter and summer data were analyzed together, various NO2, PM10 and PM2.5 moving average exposures were associated with changes in %5mdC (95% CI) ranging from -0.04 (-0.09 to 0.00) to -0.14 (-0.28 to 0.00) per IQR increase in pollutant. NO2, PM10, PM2.5 and O3 moving average exposures were associated with decreased %5mdC (95% CI) varying between -0.01 (-0.03 to 0.00) and -0.17 (-0.27 to -0.06) per IQR increase in pollutant in summer but not in winter., Conclusion: Decreased global DNA methylation in whole blood was associated with exposure to NO2, PM10, PM2.5 and O3 at the home addresses of non- adults. Most effects were observed for the 5- to 30-day moving average exposures., (© 2013.)

Phytoestrogens (PEs) are naturally occurring chemical constituents of certain plants. The internal PE exposures, mainly from diet, vary among different populations and in different regions due to various eating habits. To investigate the potential relationship between urinary PE levels and idiopathic male infertility and semen quality in Chinese adult males, 608 idiopathic infertile men and 469 fertile controls were recruited by eligibility screening procedures. Individual exposure to PEs was measured using UPLC-MS/MS as spot urinary concentrations of 6 PEs (daidzein, DAI; equol, EQU; genistein, GEN; naringenin, NAR; coumestrol, COU; and secoisolariciresinol, SEC), which were adjusted with urinary creatinine (CR). Semen quality was assessed by sperm concentration, number per ejaculum and motility. We found that exposures to DAI, GEN and SEC were significantly associated with idiopathic male infertility (P-value for trend=0.036; 0.002; and 0.0001, respectively), while these exposures had stronger association with infertile subjects with at least one abnormal semen parameter than those with all normal semen parameters. Exposures to DAI, GEN and SEC were also related to idiopathic male infertility with abnormal sperm concentration, number per ejaculum and motility (P-value for trend<0.05), while these exposures had stronger association with the infertile men with abnormal sperm number per ejaculum. These findings provide the evidence that PE exposures are related to male reproductive function and raise a public health concern because that exposure to PEs is ubiquitous in China., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Cadmium exposure is associated with increased urinary calcium excretion. Hypercalciuria is recognised as a major risk factor for kidney stone formation. Increased prevalence of kidney stones among those occupationally exposed to cadmium has previously been suggested. Food is the main source of cadmium exposure in the general population with tobacco representing an important additional source among smokers. We aimed to assess the association between dietary cadmium exposure and kidney stone incidence in two large population-based, prospective cohorts of men (Cohort of Swedish Men; COSM) and women (The Swedish Mammography Cohort; SMC). Those with a history of kidney stones were excluded. At baseline 1997, men (45-79yrs) and women (48 to 83yrs), completed a self-administered questionnaire on diet and lifestyle. During 12years of follow-up, we ascertained 707 cases of kidney stones in men and 290 in women through linkage of the cohorts to the national inpatient and outpatient registers. Individual dietary cadmium exposure was estimated using dietary data and concentrations of cadmium in food. Hazard ratios (HR) were calculated using the Cox proportional hazards regression models with adjustment for other risk factors. Estimated dietary cadmium exposure was not associated with increased kidney stone incidence among men HR 0.97 (95% confidence interval (CI): 0.77-1.23) or women HR 0.99 (95% CI: 0.89-1.43), comparing the highest tertile with the lowest. In conclusion, our results do not support a strong association between dietary cadmium and kidney stone risk at the exposure levels seen in the general population., (Copyright © 2013 Elsevier Ltd. All rights reserved.)