Sensitivity and specificity of classification systems for fatness in adolescents

BACKGROUND: Various body mass index (BMI) standards have been proposed for defining overweight in adolescence, but few studies have evaluated their diagnostic accuracy. OBJECTIVE: We compared the sensitivity and specificity of BMI-based classification systems for detecting excess fatness in adolescents. DESIGN: A cross-sectional analysis of 474 adolescents aged 17 y was used. Body composition was measured by using densitometry. The international BMI-based systems recommended by the International Obesity Task Force and the World Health Organization were evaluated on the basis of their sensitivity and specificity for detecting excess body fat. Receiver operating characteristic analysis was performed to derive cutoffs to maximize the sum of sensitivity and specificity. True positives were defined by using the percentage body fat cutoffs proposed by Williams et al (Am J Public Health 1992;82:358-63). RESULTS: For both classification systems, the specificity for overweight was high for both sexes (0.95-1.00). The sensitivity was fairly high for the males (0.72-0.84) but was very low for the females (0.22-0.25). For the males, a BMI cutoff equal to the 85th percentile on a Swedish BMI reference chart maximized the sum of sensitivity and specificity while having both high sensitivity (0.92) and high specificity (0.92). For the females, larger tradeoffs in specificity were needed to improve sensitivity. The mean (+/-SE) areas under the receiver operating characteristic curves for the males and the females were 0.97 +/- 0.02 and 0.85 +/- 0.02, respectively. CONCLUSIONS: Recommended international classification systems have very high specificity, which results in few cases of non-overweight adolescents being mislabeled as overweight. However, the sensitivity is very low in female adolescents. Thus, many overweight female adolescents could be missed in intervention programs that use the proposed international BMI cutoffs as selection criteria.     

Genetically modified tumour vaccines

Two genes, the gene coding for IL-2 and the gene encoding the CD80 molecule, were inserted into murine sarcoma MC12 cells. Tumorigenicity of a variety of cell clones with different expression of the inserted genes was assessed. Most of the genetically manipulated MC12 cell clones were less tumorigenic than the parental MC12 cell population. Tumorigenicity of the clones declined with increasing production of IL-2 as well as with the increasing expression of the CD80 molecule. When the tumorigenicity of the clones carrying an inserted IL-2 gene was compared with that of the clones carrying an inserted CD80 gene, it was found that the insertion of the IL-2 gene suppresses tumorigenicity more efficiently than insertion of the CD80 gene. Admixture of the IL-2-producing MC12 clones to the tumorigenic CD80(+) MC12 cell doses could completely inhibit the tumorigenicity of the CD80(+) cells. Insertion of the CD80 gene into sarcoma cells substantially enhanced the adhesive interaction between the MC12 sarcoma and syngeneic T lymphocytes.     

Vehicular Traffic–Related Polycyclic Aromatic Hydrocarbon Exposure and Breast Cancer Incidence: The Long Island Breast Cancer Study Project (LIBCSP)

Background

Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental pollutants, known human lung carcinogens, and potent mammary carcinogens in laboratory animals. However, the association between PAHs and breast cancer in women is unclear. Vehicular traffic is a major ambient source of PAH exposure.

Objectives

Our study aim was to evaluate the association between residential exposure to vehicular traffic and breast cancer incidence.

Methods

Residential histories of 1,508 participants with breast cancer (case participants) and 1,556 particpants with no breast cancer (control participants) were assessed in a population-based investigation conducted in 1996–1997. Traffic exposure estimates of benzo[a]pyrene (B[a]P), as a proxy for traffic-related PAHs, for the years 1960–1995 were reconstructed using a model previously shown to generate estimates consistent with measured soil PAHs, PAH–DNA adducts, and CO readings. Associations between vehicular traffic exposure estimates and breast cancer incidence were evaluated using unconditional logistic regression.

Results

The odds ratio (95% CI) was modestly elevated by 1.44 (0.78, 2.68) for the association between breast cancer and long-term 1960–1990 vehicular traffic estimates in the top 5%, compared with below the median. The association with recent 1995 traffic exposure was elevated by 1.14 (0.80, 1.64) for the top 5%, compared with below the median, which was stronger among women with low fruit/vegetable intake [1.46 (0.89, 2.40)], but not among those with high fruit/vegetable intake [0.92 (0.53, 1.60)]. Among the subset of women with information regarding traffic exposure and tumor hormone receptor subtype, the traffic–breast cancer association was higher for those with estrogen/progesterone-negative tumors [1.67 (0.91, 3.05) relative to control participants], but lower among all other tumor subtypes [0.80 (0.50, 1.27) compared with control participants].

Conclusions

In our population-based study, we observed positive associations between vehicular traffic-related B[a]P exposure and breast cancer incidence among women with comparatively high long-term traffic B[a]P exposures, although effect estimates were imprecise.

Citation

Mordukhovich I, Beyea J, Herring AH, Hatch M, Stellman SD, Teitelbaum SL, Richardson DB, Millikan RC, Engel LS, Shantakumar S, Steck SE, Neugut AI, Rossner P Jr., Santella RM, Gammon MD. 2016. Vehicular traffic–related polycyclic aromatic hydrocarbon exposure and breast cancer incidence: the Long Island Breast Cancer Study Project (LIBCSP). Environ Health Perspect 124:30–38; http://dx.doi.org/10.1289/ehp.1307736     

Polymorphisms in DNA repair genes,traffic‐related polycyclic aromatic hydrocarbon exposure and breast cancer incidence

Vehicular traffic polycyclic aromatic hydrocarbons (PAHs) have been associated with breast cancer incidence in epidemiologic studies, including our own. Because PAHs damage DNA by forming adducts and oxidative lesions, genetic polymorphisms that alter DNA repair capacity may modify associations between PAH‐related exposures and breast cancer risk. Our goal was to examine the association between vehicular traffic exposure and breast cancer incidence within strata of a panel of nine biologically plausible nucleotide excision repair (NER) and base excision repair (BER) genotypes. Residential histories of 1,508 cases and 1,556 controls were assessed in the Long Island Breast Cancer Study Project between 1996 and 1997 and used to reconstruct residential traffic exposures to benzo[a]pyrene, as a proxy for traffic‐related PAHs. Likelihood ratio tests from adjusted unconditional logistic regression models were used to assess multiplicative interactions. A gene‐traffic interaction was evident (p = 0.04) for ERCC2 (Lys751); when comparing the upper and lower tertiles of 1995 traffic exposure estimates, the odds ratio (95% confidence interval) was 2.09 (1.13, 3.90) among women with homozygous variant alleles. Corresponding odds ratios for 1960–1990 traffic were also elevated nearly 2–3‐fold for XRCC1(Arg194Trp), XRCC1(Arg399Gln) and OGG1(Ser326Cys), but formal multiplicative interaction was not evident. When DNA repair variants for ERCC2, XRCC1 and OGG1 were combined, among women with 4–6 variants, the odds ratios were 2.32 (1.22, 4.49) for 1995 traffic and 2.96 (1.06, 8.21) for 1960–1990 traffic. Our study is first to report positive associations between traffic‐related PAH exposure and breast cancer incidence among women with select biologically plausible DNA repair genotypes.     

Expression of beta-Secretase mRNA in the brain of rats with immunohistochemical destruction of basal forebrain cholinergic system

We studied properties of cloned BACE mRNA (beta-site of the enzyme cleaving amyloid precursor protein) and evaluated the possibility of using this clone for identification and/or prediction of neurodegenerative disorders associated with cholinergic deficiency. Wistar rats subjected to immunohistochemical destruction of the basal forebrain cholinergic system were used as the experimental model. Nonradioactive in situ hybridization and immunohistochemical visualization of the astroglia revealed strong hybridization signal of BACE mRNA in neurons of the cortex, hippocampus, and thalamus. Astrocytes remained unstained. Immunohistochemical destruction of the basal forebrain produced no significant changes in the distribution of BACE mRNA.     

Split-Cre Complementation Indicates Coincident Activity of Different Genes In Vivo

Cre/LoxP recombination is the gold standard for conditional gene regulation in mice in vivo. However, promoters driving the expression of Cre recombinase are often active in a wide range of cell types and therefore unsuited to target more specific subsets of cells. To overcome this limitation, we designed inactive “split-Cre” fragments that regain Cre activity when overlapping co-expression is controlled by two different promoters. Using transgenic mice and virus-mediated expression of split-Cre, we show that efficient reporter gene activation is achieved in vivo. In the brain of transgenic mice, we genetically defined a subgroup of glial progenitor cells in which the Plp1- and the Gfap-promoter are simultaneously active, giving rise to both astrocytes and NG2-positive glia. Similarly, a subset of interneurons was labelled after viral transfection using Gad67- and Cck1 promoters to express split-Cre. Thus, split-Cre mediated genomic recombination constitutes a powerful spatial and temporal coincidence detector for in vivo targeting.     

Health impact of air pollution to children

Health impact of air pollution to children was studied over the last twenty years in heavily polluted parts of the Czech Republic during. The research program (Teplice Program) analyzed these effects in the polluted district Teplice (North Bohemia) and control district Prachatice (Southern Bohemia).     

Biomarkers of exposure and effect��interpretation in human risk assessment

The effect of exposure to carcinogenic polycyclic aromatic hydrocarbons adsorbed onto respirable air particles (PM2.5, diameter 相似文献   

Formation of perineuronal nets in organotypic mouse brain slice cultures is independent of neuronal glutamatergic activity

Perineuronal nets (PNs) are a specialized form of the extracellular matrix and cover specific sets of neurons in distinct brain areas. Animal experiments on sensory visual deprivation have demonstrated that the generation of PNs around neurons of the visual cortex is dependent on neuronal activity during the critical period of visual experience. The importance of the activity of specific neurotransmitter systems for PN formation has, however, not yet been demonstrated. Based on the predominantly glutamatergic innervation of the visual cortex we hypothesized that reduced glutamatergic activity impairs the development of PNs. To address this question, genetic mouse models with compromised glutamate release [Munc13-1-knockout (KO) and Munc13-1/2 double-KO (DKO)] and chronic pharmacological treatments interfering with specific steps of glutamatergic transmission were used. Under experimental conditions of glutamatergic hypofunction PN formation was studied in organotypic brain slice cultures with Wisteria floribunda lectin binding and with aggrecan immunohistochemistry. After cultivation for 21 days a regular PN formation was observed in brain slices (i) derived from Munc13-1-KO and Munc13-1/2-DKO mice, (ii) after blockade of metabotropic and ionotropic glutamate receptors with MCPG and kynurenate, and (iii) after suppression of glutamate release by blockade of presynaptic Ca++ channels with riluzole. Nonselective suppression of neuronal activity by blockade of voltage-gated sodium channels with tetrodotoxin clearly inhibited PN formation. These results indicate that neuronal activity is required but that the glutamatergic system is not essential for PN development.