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Recent studies have suggested that statins, an established drug group in the prevention of cardiovascular mortality, could delay or prevent breast cancer recurrence but the effect on disease-specific mortality remains unclear. We evaluated risk of breast cancer death among statin users in a population-based cohort of breast cancer patients. The study cohort included all newly diagnosed breast cancer patients in Finland during 1995–2003 (31,236 cases), identified from the Finnish Cancer Registry. Information on statin use before and after the diagnosis was obtained from a national prescription database. We used the Cox proportional hazards regression method to estimate mortality among statin users with statin use as time-dependent variable. A total of 4,151 participants had used statins. During the median follow-up of 3.25 years after the diagnosis (range 0.08–9.0 years) 6,011 participants died, of which 3,619 (60.2%) was due to breast cancer. After adjustment for age, tumor characteristics, and treatment selection, both post-diagnostic and pre-diagnostic statin use were associated with lowered risk of breast cancer death (HR 0.46, 95% CI 0.38–0.55 and HR 0.54, 95% CI 0.44–0.67, respectively). The risk decrease by post-diagnostic statin use was likely affected by healthy adherer bias; that is, the greater likelihood of dying cancer patients to discontinue statin use as the association was not clearly dose-dependent and observed already at low-dose/short-term use. The dose- and time-dependence of the survival benefit among pre-diagnostic statin users suggests a possible causal effect that should be evaluated further in a clinical trial testing statins’ effect on survival in breast cancer patients. | [
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] |
BACKGROUND: Preclinical studies have shown that statins, particularly simvastatin, can prevent growth in breast cancer cell lines and animal models. We investigated whether statins used after breast cancer diagnosis reduced the risk of breast cancer-specific, or all-cause, mortality in a large cohort of breast cancer patients. METHODS: A cohort of 17,880 breast cancer patients, newly diagnosed between 1998 and 2009, was identified from English cancer registries (from the National Cancer Data Repository). This cohort was linked to the UK Clinical Practice Research Datalink, providing prescription records, and to the Office of National Statistics mortality data (up to 2013), identifying 3694 deaths, including 1469 deaths attributable to breast cancer. Unadjusted and adjusted hazard ratios (HRs) for breast cancer-specific, and all-cause, mortality in statin users after breast cancer diagnosis were calculated using time-dependent Cox regression models. Sensitivity analyses were conducted using multiple imputation methods, propensity score methods and a case-control approach. RESULTS: There was some evidence that statin use after a diagnosis of breast cancer had reduced mortality due to breast cancer and all causes (fully adjusted HR = 0.84 [95% confidence interval = 0.68-1.04] and 0.84 [0.72-0.97], respectively). These associations were more marked for simvastatin 0.79 (0.63-1.00) and 0.81 (0.70-0.95), respectively. CONCLUSIONS: In this large population-based breast cancer cohort, there was some evidence of reduced mortality in statin users after breast cancer diagnosis. However, these associations were weak in magnitude and were attenuated in some sensitivity analyses. | [
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] |
The aims of this study were to determine the concentrations of 4-nonylphenol (NP) and 4-octylphenol (OP) in 59 human milk samples and to examine related factors including mothers' demographics and dietary habits. Women who consumed over the median amount of cooking oil had significantly higher OP concentrations (0.98 ng/g) than those who consumed less (0.39 ng/g) (P < 0.05). OP concentration was significantly associated with the consumption of cooking oil (beta = 0.62, P < 0.01) and fish oil capsules (beta = 0.39, P < 0.01) after adjustment for age and body mass index (BMI). NP concentration was also significantly associated with the consumption of fish oil capsules (beta = 0.38, P < 0.01) and processed fish products (beta = 0.59, P < 0.01). The food pattern of cooking oil and processed meat products from factor analysis was strongly associated with OP concentration in human milk (P < 0.05). These determinations should aid in suggesting foods for consumption by nursing mothers in order to protect their infants from NP/OP exposure. 2010 Elsevier Ltd. All rights reserved. | [
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Epilepsy or seizure disorder is one of the most common neurological diseases in humans. Although genetic mutations in ion channels and receptors and some other risk factors such as brain injury are linked to epileptogenesis, the underlying cause for the majority of epilepsy cases remains unknown. Gene-environment interactions are thought to play a critical role in the etiology of epilepsy. Exposure to environmental chemicals is an important risk factor. Methylmercury (MeHg) is a prominent environmental neurotoxicant, which targets primarily the central nervous system (CNS). Patients or animals with acute or chronic MeHg poisoning often display epileptic seizures or show increased susceptibility to seizures, suggesting that MeHg exposure may be associated with epileptogenesis. This mini-review highlights the effects of MeHg exposure, especially developmental exposure, on the susceptibility of humans and animals to seizures, and discusses the potential role of low level MeHg exposure in epileptogenesis. This review also proposes that a preferential effect of MeHg on the inhibitory GABAergic system, leading to disinhibition of excitatory glutamatergic function, may be one of the potential mechanisms underlying MeHg-induced changes in seizure susceptibility. | [
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Hit Reaction Time latencies (HRT) in the Continuous Performance Test (CPT) measure the speed of visual information processing. The latencies may involve different neuropsychological functions depending on the time from test initiation, i.e., first orientation, learning and habituation, then cognitive processing and focused attention, and finally sustained attention as the dominant demand. Prenatal methylmercury exposure is associated with increased reaction time (RT) latencies. We therefore examined the association of methylmercury exposure with the average HRT at age 14 years at three different time intervals after test initiation. A total of 878 adolescents (87% of birth cohort members) completed the CPT. The RT latencies were recorded for 10 minutes, with visual targets presented at 1000 ms intervals. After confounder adjustment, regression coefficients showed that CPT-RT outcomes differed in their associations with exposure biomarkers of prenatal methylmercury exposure: During the first two minutes, the average HRT was weakly associated with methylmercury (beta (SE) for a ten-fold increase in exposure, (3.41 (2.06)), was strongly for the 3-to-6 minute interval (6.10 (2.18)), and the strongest during 7–10 minutes after test initiation (7.64 (2.39)). This pattern was unchanged when simple reaction time and finger tapping speed were included in the models as covariates. Postnatal methylmercury exposures did not affect the outcomes. Thus, these findings suggest that sustained attention as a neuropsychological domain is particularly vulnerable to developmental methylmercury exposure, indicating probable underlying dysfunction of the frontal lobes. When using CPT data as a possible measure of neurotoxicity, test results should therefore be analyzed in regard to time from test initiation and not as overall average reaction times. | [
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"Elevated phosphate (P) levels are seen in advanced renal failure and, together with dysregulated ca(...TRUNCATED) | [-0.042440928518772125,0.012168212793767452,-0.0162751954048872,0.027087651193141937,0.0274464711546(...TRUNCATED) | [0.10268155485391617,0.5126685500144958,0.28089338541030884,0.2650844156742096,0.051504943519830704,(...TRUNCATED) |
"Excessive dietary phosphorus may increase cardiovascular risk in healthy individuals as well as in (...TRUNCATED) | [0.0016089619603008032,0.015552339144051075,-0.010663608089089394,0.033104535192251205,-0.0041484874(...TRUNCATED) | [0.37867632508277893,0.36764195561408997,-0.1912037432193756,-0.01661459542810917,-0.047209661453962(...TRUNCATED) |
"This review explores the potential adverse impact of the increasing phosphorus content in the Ameri(...TRUNCATED) | [-0.006503799930214882,0.018954318016767502,-0.013480369001626968,0.03771843761205673,0.029499366879(...TRUNCATED) | [0.2288038730621338,0.4387767016887665,-0.4980906546115875,-0.029263874515891075,0.5350295305252075,(...TRUNCATED) |
"OBJECTIVE: Among plant foods, grain products, legumes, and seeds are important sources of phosphoru(...TRUNCATED) | [-0.0014228648506104946,-0.0033392622135579586,-0.014978200197219849,0.02616908587515354,-0.00488585(...TRUNCATED) | [0.3195676803588867,-0.028411123901605606,-0.4474698305130005,0.014483434148132801,-0.14164353907108(...TRUNCATED) |
"OBJECTIVE: Meat and milk products are important sources of dietary phosphorus (P) and protein. The (...TRUNCATED) | [-0.008382679894566536,-0.0038657360710203648,-0.006725442595779896,0.026242248713970184,0.020549753(...TRUNCATED) | [0.5159772038459778,-0.04613855481147766,-0.34890636801719666,0.008197071962058544,-0.19551353156566(...TRUNCATED) |
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