Cumulative Lead Exposure and Age at Menopause in the Nurses’ Health Study Cohort

Background: Early menopause has been associated with many adverse health outcomes, including increased risk of cardiovascular disease morbidity and mortality. Lead has been found to be adversely associated with female reproductive function, but whether exposures experienced by the general population are associated with altered age at menopause has not been explored. Objective: Our goal was to assess the association between cumulative lead exposure and age at natural menopause. Methods: Self-reported menopausal status and bone lead concentration measured with K-shell X-ray fluorescence—a biomarker of cumulative lead exposure—were obtained from 434 women participants in the Nurses’ Health Study. Results: The mean (± SD) age at natural menopause was 50.8 ± 3.6 years. Higher tibia lead level was associated with younger age at menopause. In adjusted analyses, the average age of menopause for women in the highest tertile of tibia lead was 1.21 years younger (95% CI: –2.08, –0.35) than for women in the lowest tertile (p-trend = 0.006). Although the number of cases was small (n = 23), the odds ratio for early menopause (< 45 years of age) was 5.30 (95% CI: 1.42, 19.78) for women in the highest tertile of tibia lead compared with those in the lowest tertile (p-trend = 0.006). There was no association between patella or blood lead and age at menopause. Conclusions: Our results support an association between low-level cumulative lead exposure and an earlier age at menopause. These data suggest that low-level lead exposure may contribute to menopause-related health outcomes in older women through effects on age at menopause. Citation: Eum KD, Weisskopf MG, Nie LH, Hu H, Korrick SA. 2014. Cumulative lead exposure and age at menopause in the Nurses’ Health Study Cohort. Environ Health Perspect 122:229–234; http://dx.doi.org/10.1289/ehp.120639

Interaction and engagement with an anxiety management app: Analysis using large-Scale behavioral data

© Paul Matthews, Phil Topham, Praminda Caleb-Solly. Background: SAM (Self-help for Anxiety Management) is a mobile phone app that provides self-help for anxiety management. Launched in 2013, the app has achieved over one million downloads on the iOS and Android platform app stores. Key features of the app are anxiety monitoring, self-help techniques, and social support via a mobile forum (“the Social Cloud”). This paper presents unique insights into eMental health app usage patterns and explores user behaviors and usage of self-help techniques. Objective: The objective of our study was to investigate behavioral engagement and to establish discernible usage patterns of the app linked to the features of anxiety monitoring, ratings of self-help techniques, and social participation. Methods: We use data mining techniques on aggregate data obtained from 105,380 registered users of the app’s cloud services. Results: Engagement generally conformed to common mobile participation patterns with an inverted pyramid or “funnel” of engagement of increasing intensity. We further identified 4 distinct groups of behavioral engagement differentiated by levels of activity in anxiety monitoring and social feature usage. Anxiety levels among all monitoring users were markedly reduced in the first few days of usage with some bounce back effect thereafter. A small group of users demonstrated long-term anxiety reduction (using a robust measure), typically monitored for 12-110 days, with 10-30 discrete updates and showed low levels of social participation. Conclusions: The data supported our expectation of different usage patterns, given flexible user journeys, and varying commitment in an unstructured mobile phone usage setting. We nevertheless show an aggregate trend of reduction in self-reported anxiety across all minimally-engaged users, while noting that due to the anonymized dataset, we did not have information on users also enrolled in therapy or other intervention while using the app. We find several commonalities between these app-based behavioral patterns and traditional therapy engagement

Versatile RNA Interference Nanoplatform for Systemic Delivery of RNAs

Development of nontoxic, tumor-targetable, and potent in vivo RNA delivery systems remains an arduous challenge for clinical application of RNAi therapeutics. Herein, we report a versatile RNAi nanoplatform based on tumor-targeted and pH-responsive nanoformulas (NFs). The NF was engineered by combination of an artificial RNA receptor, Zn(II)-DPA, with a tumor-targetable and drug-loadable hyaluronic acid nanoparticle, which was further modified with a calcium phosphate (CaP) coating by in situ mineralization. The NF can encapsulate small-molecule drugs within its hydrophobic inner core and strongly secure various RNA molecules (siRNAs, miRNAs, and oligonucleotides) by utilizing Zn(II)-DPA and a robust CaP coating. We substantiated the versatility of the RNAi nanoplatform by demonstrating effective delivery of siRNA and miRNA for gene silencing or miRNA replacement into different human types of cancer cells in vitro and into tumor-bearing mice in vivo by intravenous administration. The therapeutic potential of NFs coloaded with an anticancer drug doxorubicin (Dox) and multidrug resistance 1 gene target siRNA (siMDR) was also demonstrated in this study. NFs loaded with Dox and siMDR could successfully sensitize drug-resistant OVCAR8/ADR cells to Dox and suppress OVCAR8/ADR tumor cell proliferation in vitro and tumor growth in vivo. This gene/drug delivery system appears to be a highly effective nonviral method to deliver chemo- and RNAi therapeutics into host cells.National Institute for Biomedical Imaging and Bioengineering (U.S.)National Institutes of Health (U.S.)AXA Research Fund (Postdoctoral Fellowship)National Research Foundation of Korea (Postdoctoral Fellowship 2013R1A6A3A03)National Research Foundation of Korea (Grant 2009-0080734

Relation of Cumulative Low-Level Lead Exposure to Depressive and Phobic Anxiety Symptom Scores in Middle-Age and Elderly Women

Background: Different lines of evidence suggest that low-level lead exposure could be a modifiable risk factor for adverse psychological symptoms, but little work has explored this relation

The factor structure and psychometric properties of the Clinical Outcomes in Routine Evaluation - Outcome Measure (CORE-OM) in Norwegian clinical and non-clinical samples

Background The Clinical Outcomes in Routine Evaluation - Outcome Measure (CORE-OM) is a 34-item instrument developed to monitor clinically significant change in out-patients. The CORE-OM covers four domains: well-being, problems/symptoms, functioning and risk, and sums up in two total scores: the mean of All items, and the mean of All non-risk items. The aim of this study was to examine the psychometric properties of the Norwegian translation of the CORE-OM. Methods A clinical sample of 527 out-patients from North Norwegian specialist psychiatric services, and a non-clinical sample of 464 persons were obtained. The non-clinical sample was a convenience sample consisting of friends and family of health personnel, and of students of medicine and clinical psychology. Students also reported psychological stress. Exploratory factor analysis (EFA) was employed in half the clinical sample. Confirmatory (CFA) factor analyses modelling the theoretical sub-domains were performed in the remaining half of the clinical sample. Internal consistency, means, and gender and age differences were studied by comparing the clinical and non-clinical samples. Stability, effect of language (Norwegian versus English), and of psychological stress was studied in the sub-sample of students. Finally, cut-off scores were calculated, and distributions of scores were compared between clinical and non-clinical samples, and between students reporting stress or no stress. Results The results indicate that the CORE-OM both measures general (g) psychological distress and sub-domains, of which risk of harm separates most clearly from the g factor. Internal consistency, stability and cut-off scores compared well with the original English version. No, or only negligible, language effects were found. Gender differences were only found for the well-being domain in the non-clinical sample and for the risk domain in the clinical sample. Current patient status explained differences between clinical and non-clinical samples, also when gender and age were controlled for. Students reporting psychological distress during last week scored significantly higher than students reporting no stress. These results further validate the recommended cut-off point of 1 between clinical and non-clinical populations. Conclusions The CORE-OM in Norwegian has psychometric properties at the same level as the English original, and could be recommended for general clinical use. A cut-off point of 1 is recommended for both genders

A computational approach to chemical etiologies of diabetes.

Computational meta-analysis can link environmental chemicals to genes and proteins involved in human diseases, thereby elucidating possible etiologies and pathogeneses of non-communicable diseases. We used an integrated computational systems biology approach to examine possible pathogenetic linkages in type 2 diabetes (T2D) through genome-wide associations, disease similarities, and published empirical evidence. Ten environmental chemicals were found to be potentially linked to T2D, the highest scores were observed for arsenic, 2,3,7,8-tetrachlorodibenzo-p-dioxin, hexachlorobenzene, and perfluorooctanoic acid. For these substances we integrated disease and pathway annotations on top of protein interactions to reveal possible pathogenetic pathways that deserve empirical testing. The approach is general and can address other public health concerns in addition to identifying diabetogenic chemicals, and offers thus promising guidance for future research in regard to the etiology and pathogenesis of complex diseases