Role of Mutagenicity in Asbestos Fiber-Induced Carcinogenicity and Other Diseases

The cellular and molecular mechanisms of how asbestos fibers induce cancers and other diseases are not well understood. Both serpentine and amphibole asbestos fibers have been shown to induce oxidative stress, inflammatory responses, cellular toxicity and tissue injuries, genetic changes, and epigenetic alterations in target cells in vitro and tissues in vivo. Most of these mechanisms are believe to be shared by both fiber-induced cancers and noncancerous diseases. This article summarizes the findings from existing literature with a focus on genetic changes, specifically, mutagenicity of asbestos fibers. Thus far, experimental evidence suggesting the involvement of mutagenesis in asbestos carcinogenicity is more convincing than asbestos-induced fibrotic diseases. The potential contributions of mutagenicity to asbestos-induced diseases, with an emphasis on carcinogenicity, are reviewed from five aspects: (1) whether there is a mutagenic mode of action (MOA) in fiber-induced carcinogenesis; (2) mutagenicity/carcinogenicity at low dose; (3) biological activities that contribute to mutagenicity and impact of target tissue/cell type; (4) health endpoints with or without mutagenicity as a key event; and finally, (5) determinant factors of toxicity in mutagenicity. At the end of this review, a consensus statement of what is known, what is believed to be factual but requires confirmation, and existing data gaps, as well as future research needs and directions, is provided

Circadian rhythms govern cardiac repolarization and arrhythmogenesis

Sudden cardiac death exhibits diurnal variation in both acquired and hereditary forms of heart disease, but the molecular basis of this variation is unknown. A common mechanism that underlies susceptibility to ventricular arrhythmias is abnormalities in the duration (for example, short or long QT syndromes and heart failure) or pattern (for example, Brugada’s syndrome)6 of myocardial repolarization. Here we provide molecular evidence that links circadian rhythms to vulnerability in ventricular arrhythmias in mice. Specifically, we show that cardiac ion-channel expression and QT-interval duration (an index of myocardial repolarization) exhibit endogenous circadian rhythmicity under the control of a clock-dependent oscillator, krüppel-like factor 15 (Klf15). Klf15 transcriptionally controls rhythmic expression of Kv channel- interacting protein 2 (KChIP2), a critical subunit required for generating the transient outward potassium current. Deficiency or excess of Klf15 causes loss of rhythmic QT variation, abnormal repolarization and enhanced susceptibility to ventricular arrhythmias. These findings identify circadian transcription of ion channels as a mechanism for cardiac arrhythmogenesis

Infant Feeding Attitudes and Knowledge among Socioeconomically Disadvantaged Women in Glasgow

Objectives This study: (1) investigated infant feeding attitudes and knowledge among socioeconomically disadvantaged mothers in an urban community with historically low breastfeeding rates, (2) examined the influence of women’s social networks on infant feeding attitudes and decisions, and (3) validated a measure of infant feeding attitudes and knowledge in this population (Iowa Infant Feeding Attitude Scale, IIFAS). Methods Women attending a prenatal clinic (n = 49) reported on: (1) demographics, (2) infant feeding attitudes and knowledge (IIFAS), (3) feeding intent, (4) opinions about breastfeeding in public, and (5) social networks. Feeding method at discharge was abstracted from hospital charts. Social network members (n = 47) identified by the prenatal sample completed interviews covering: (1) demographics, (2) infant feeding attitudes and knowledge (IIFAS), (3) prior infant feeding methods and recommendations, and (4) opinions about breastfeeding in public. Results Mean IIFAS scores were low in both groups, indicating neutral to negative breastfeeding attitudes; mothers’ scores were lower than social network members. Higher maternal IIFAS score was significantly associated with intended and actual breastfeeding. A social network positive towards breastfeeding was significantly associated with mothers’ positive attitude towards breastfeeding. Both mothers and social network members support breastfeeding in public. IIFAS internal consistency was robust for both mothers and social network members. Predictive validity was demonstrated by significant positive association between score and intended and actual feeding methods. Conclusions Knowledge and attitude predict breastfeeding initiation in this population. Social network members may influence mothers’ feeding choices. This research is important because attitudes and knowledge derived from the IIFAS can be used to develop and evaluate breastfeeding promotion programs