Association Signals Unveiled by a Comprehensive Gene Set Enrichment Analysis of Dental Caries Genome-Wide Association Studies

Gene set-based analysis of genome-wide association study (GWAS) data has recently emerged as a useful approach to examine the joint effects of multiple risk loci in complex human diseases or phenotypes. Dental caries is a common, chronic, and complex disease leading to a decrease in quality of life worldwide. In this study, we applied the approaches of gene set enrichment analysis to a major dental caries GWAS dataset, which consists of 537 cases and 605 controls. Using four complementary gene set analysis methods, we analyzed 1331 Gene Ontology (GO) terms collected from the Molecular Signatures Database (MSigDB). Setting false discovery rate (FDR) threshold as 0.05, we identified 13 significantly associated GO terms. Additionally, 17 terms were further included as marginally associated because they were top ranked by each method, although their FDR is higher than 0.05. In total, we identified 30 promising GO terms, including 'Sphingoid metabolic process,' 'Ubiquitin protein ligase activity,' 'Regulation of cytokine secretion,' and 'Ceramide metabolic process.' These GO terms encompass broad functions that potentially interact and contribute to the oral immune response related to caries development, which have not been reported in the standard single marker based analysis. Collectively, our gene set enrichment analysis provided complementary insights into the molecular mechanisms and polygenic interactions in dental caries, revealing promising association signals that could not be detected through single marker analysis of GWAS data. © 2013 Wang et al

Comparison of the Adherence to the American Diabetes Association Guidelines of Diabetes Care in Primary Care and Subspecialty Clinics

Abstract Background Diabetes mellitus is a major public health problem with significant morbidity and mortality. Evidence based guidelines have been proposed to reduce the micro and macrovascular complications, but studies have shown that these goals are not being met. We sought to compare the adherence to the American Diabetes Association guidelines for measurement and control of glycohemoglobin (A1c), blood pressure (BP), lipids (LDL) and microalbuminuria (MA) by subspecialty and primary care clinics in an academic medical center. Methods 390 random charts of patients with diabetes from Family Practice (FP), Internal Medicine (IM) and Diabetes (DM) clinics at Michigan State University were reviewed. Results We reviewed 131, 134 and 125 charts from the FP, IM and DM clinics, respectively. DM clinic had a higher percentage of patients with type 1 diabetes 43/125 (34.4%) compared with 7/131 (5.3%) in FP and 7/134 (5.2%) in IM clinics. A1c was measured in 99%, 97.8% and 100% subjects in FP, IM and DM clinics respectively. B.P. was measured in all subjects in all three clinics. Lipids were checked in 97.7%, 95.5% and 92% patients in FP, IM and DM clinics respectively. MA was measured at least once during the year preceding the office visit in 85.5%, 82.8% and 76.8% patients in FP, IM and DM clinics respectively. A1C was controlled (<7%) in 38.9, 43.3, 28.8% of patients in the FP, IM and DM clinics, respectively (p = 0.034). LDL was controlled (<100 mg/dl or 2.586 mmol/l) in 71.8, 64.9, 64% of patients in the FP, IM and DM clinics, respectively. MA was controlled (<30 mg/gm creatinine) in 60.3%, 51.5% and 60% patients in FP, IM and DM clinics respectively (P = 0.032). BP was controlled (<130/80) in 59.5, 67.2 and 52.8% patients in the FP, IM and DM clinics, respectively. Conclusion Testing rates for A1C, LDL, and MA were high, in both subspecialty and primary care clinics. However, the degree of control was not optimal. Significantly fewer patients in the DM clinic had A1c <7%, the cause of which may be multifactorial.http://deepblue.lib.umich.edu/bitstream/2027.42/111055/1/40200_2015_Article_158.pd

Exposure to Bisphenol A and Other Phenols in Neonatal Intensive Care Unit Premature Infants

Objective: We previously demonstrated that exposure to polyvinyl chloride plastic medical devices containing di(2-ethylhexyl) phthalate (DEHP) was associated with higher urinary concentrations of several DEHP metabolites in 54 premature infants in two neonatal intensive care units than in the general population. For 42 of these infants, we evaluated urinary concentrations of several phenols, including bisphenol A (BPA), in association with the use of the same medical devices. Measurements: We measured the urinary concentrations of free and total (free plus conjugated) species of BPA, triclosan, benzophenone-3, methyl paraben, and propyl paraben. Results: The percentage of BPA present as its conjugated species was > 90% in more than three-quarters of the premature infants. Intensity of use of products containing DEHP was strongly associated with BPA total concentrations but not with any other phenol. Adjusting for institution and sex, BPA total concentrations among infants in the group of high use of DEHP-containing products were 8.75 times as high as among infants in the low use group (p < 0.0001). Similarly, after adjusting for sex and DEHP-containing product use category, BPA total concentrations among infants in Institution A were 16.6 times as high as those among infants in Institution B (p < 0.0001). Conclusion: BPA geometric mean urinary concentration (30.3 μg/L) among premature infants undergoing intensive therapeutic medical interventions was one order of magnitude higher than that among the general population. Conjugated species were the primary urinary metabolites of BPA, suggesting that premature infants have some capacity to metabolize BPA. The differences in exposure to BPA by intensity of use of DEHP-containing medical products highlight the need for further studies to determine the specific source(s) of exposure to BPA

Global surveillance of oral tobacco products : total nicotine, unionised nicotine and tobacco-specific N-nitrosamines

OBJECTIVE: Oral tobacco products contain nicotine and carcinogenic tobacco-specific N-nitrosamines (TSNAs) that can be absorbed through the oral mucosa. The aim of this study was to determine typical pH ranges and concentrations of total nicotine, unionised nicotine (the most readily absorbed form) and five TSNAs in selected oral tobacco products distributed globally. METHODS: A total of 53 oral tobacco products from 5 World Health Organisation (WHO) regions were analysed for total nicotine and TSNAs, including 4-(methylnitrosamino)- 1-(3-pyridyl)-1-butanol (NNAL), using gas chromatography or liquid chromatography with mass spectrometric detection. Unionised nicotine concentrations were calculated using product pH and total nicotine concentrations. Fourier transform infrared spectroscopy was used to help categorise or characterise some products. RESULTS: Total nicotine content varied from 0.16 to 34.1 mg/g product, whereas, the calculated unionised nicotine ranged from 0.05 to 31.0 mg/g product; a 620-fold range of variation. Products ranged from pH 5.2 to 10.1, which translates to 0.2% to 99.1% of nicotine being in the unionised form. Some products have very high pH and correspondingly high unionised nicotine (eg, gul powder, chimo´, toombak) and/or high TSNA (eg, toombak, zarda, khaini) concentrations. The concentrations of TSNAs spanned five orders of magnitude with concentrations of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) ranging from 4.5 to 516 000 ng/g product. CONCLUSIONS: These data have important implications for risk assessment because they show that very different exposure risks may be posed through the use of these chemically diverse oral tobacco products. Because of the wide chemical variation, oral tobacco products should not be categorised together when considering the public health implications of their use.This work was funded by the U.S. Government, Department of Health and Human Services. This study was also funded internally at the Centers for Disease Control and Prevention, with funds directly provided by the U.S. federal government.http://tobaccocontrol.bmj.com

Effects of perfluorooctanoic acid on mouse mammary gland development and differentiation resulting from cross-foster and restricted gestational exposures

The adverse consequences of developmental exposures to perfluorooctanoic acid (PFOA) are established in mice, and include impaired development of the mammary gland (MG). However, the relationships between timing or route of exposure, and consequences in the MG have not been characterized. To address the effects of these variables on the onset and persistence of MG effects in female offspring, timed pregnant CD-1 dams received PFOA by oral gavage over various gestational durations. Cross-fostering studies identified the 5 mg/kg dose, under either lactational- or intrauterine-only exposures, to delay MG development as early as postnatal day (PND) 1, persisting beyond PND 63. Intrauterine exposure during the final days of pregnancy caused adverse MG developmental effects similar to that of extended gestational exposures. These studies confirm a window of MG sensitivity in late fetal and early neonatal life, and demonstrate developmental PFOA exposure results in early and persistent MG effects, suggesting permanent consequences