Crystalline silica has been classified as a human carcinogen by the International Agency for Research on Cancer (Lyon, France); however, few previous studies have provided quantitative data on silica exposure, silicosis, and/or smoking. We investigated a cohort in China (in 1960–2003) of 34,018 workers without exposure to carcinogenic confounders. Cumulative silica exposure was estimated by linking a job-exposure matrix to work history. Cox proportional hazards model was used to conduct exposure-response analysis and risk assessment. During a mean 34.5-year follow-up, 546 lung cancer deaths were identified. Categorical analyses by quartiles of cumulative silica exposure (using a 25-year lag) yielded hazard ratios of 1.26, 1.54, 1.68, and 1.70, respectively, compared with the unexposed group. Monotonic exposure-response trends were observed among nonsilicotics (P for trend < 0.001). Analyses using splines showed similar trends. The joint effect of silica and smoking was more than additive and close to multiplicative. For workers exposed from ages 20 to 65 years at 0.1 mg/m3 of silica exposure, the estimated excess lifetime risk (through age 75 years) was 0.51%. These findings confirm silica as a human carcinogen and suggest that current exposure limits in many countries might be insufficient to protect workers from lung cancer. They also indicate that smoking cessation could help reduce lung cancer risk for silica-exposed individuals.

BackgroundShift work has been associated with adverse health effects by disturbing circadian rhythms. However,its potential long-term health effects and the persistent effects after leaving shifts have not been well established.Methods and ResultsWe studied 26,463 workers from Tongji-Dongfeng Cohort in China. All the participants are retired employees of Dongfeng Motor Company. Information on demographics, occupational history and medical history were gathered through questionnaires. After adjusting potential confounders in the logistic regression models, shift work was associated with poor sleeping quality, diabetes and hypertension independently. We observed significant effects of shift work on poor sleeping quality, diabetes and hypertension; the ORs (95%CI) are 1.18 (1.09–1.27), 1.10 (1.03–1.17) and 1.05 (1.01–1.09) respectively. In the further analysis, we found elevated ORs (95%CI) for participants with poor sleeping quality, the ORs (95%CI) are 1.34 (1.08–1.60), 1.13 (1.05–1.21), 1.05 (1.03–1.07) and 1.05 (1.01–1.09) for 1–4, 5–9, 10–19, ≥20 years of shift work respectively. However, with the extension of leaving shift work duration, the effects of shift work on sleep quality gradually reduced.ConclusionsShift work may be an independent risk factor for sleeping quality, diabetes and hypertension even in retired workers. Applicable intervention strategies are needed for prevention of sleep loss, diabetes, and hypertension for shift workers.

Highlights d Kibra WW tandem domains bind to Dendrin with lownanomolar affinity d Structure of Kibra WW domains bound to Dendrin PY motifs reveals the binding mechanism d Disruption of the Kibra/Dendrin interaction impairs learning and memory in mice d A Kibra mutation associated with Tourette syndrome causes defects in Dendrin binding

BackgroundProfound synapse loss is one of the major pathological hallmarks associated with Alzheimer’s disease, which might underlie memory impairment. Our previous work demonstrates that magnesium ion is a critical factor in controlling synapse density/plasticity. Here, we tested whether elevation of brain magnesium, using a recently developed compound (magnesium-L-threonate, MgT), can ameliorate the AD-like pathologies and cognitive deficits in the APPswe/PS1dE9 mice, a transgenic mouse model of Alzheimer’s disease.ResultsMgT treatment reduced Aβ-plaque, prevented synapse loss and memory decline in the transgenic mice. Strikingly, MgT treatment was effective even when the treatment was given to the mice at the end-stage of their Alzheimer’s disease-like pathological progression. To explore how elevation of brain magnesium ameliorates the AD-like pathologies in the brain of transgenic mice, we studied molecules critical for APP metabolism and signaling pathways implicated in synaptic plasticity/density. In the transgenic mice, the NMDAR signaling pathway was downregulated, while the BACE1 expression were upregulated. MgT treatment prevented the impairment of these signaling pathways, stabilized BACE1 expression and reduced sAPPβ and β-CTF in the transgenic mice. At the molecular level, elevation of extracellular magnesium prevented the high Aβ-induced reductions in synaptic NMDARs by preventing calcineurin overactivation in hippocampal slices.ConclusionsOur results suggest that elevation of brain magnesium exerts substantial synaptoprotective effects in a mouse model of Alzheimer’s disease, and hence it might have therapeutic potential for treating Alzheimer’s disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s13041-014-0065-y) contains supplementary material, which is available to authorized users.