Signalling-Dependent Adverse Health Effects of Carbon Nanoparticles Are Prevented by the Compatible Solute Mannosylglycerate (Firoin) In Vitro and In Vivo

The inhalation of combustion-derived nanoparticles leads to adverse health effects in the airways. In this context the induction of membrane-coupled signalling is considered as causative for changes in tissue homeostasis and pro-inflammatory reactions. The identification of these molecular cell reactions allowed to seek for strategies which interfere with these adverse effects. In the current study, we investigated the structurally different compatible solutes mannosylglycerate (firoin) from thermophilic bacteria and ectoine from halophilic bacteria for their capability to reduce signalling pathways triggered by carbon nanoparticles in target cells in the lung. The pre-treatment of lung epithelial cells with both substances decreased the particle-specific activation of mitogen-activated protein kinases and also the endpoints proliferation and apoptosis. Firoin applied into the lungs of animals, like ectoine, led to a significant reduction of the neutrophilic lung inflammation induced by particle exposure. The pro-inflammatory effect of carbon nanoparticles on human neutrophil granulocytes ex vivo was significantly reduced by both substances via the reduction of the anti-apoptotic membrane-dependent signalling. The data of this study together with earlier studies demonstrate that two structurally non-related compatible solutes are able to prevent pathogenic reactions of the airways to carbon nanoparticles by interfering with signalling events. The findings highlight the preventive or therapeutic potential of compatible solutes for adverse health effects caused by particle exposure of the airways.     

On the use of the substitution method in left-censored environmental data

In risk assessment and environmental monitoring studies, concentration measurements frequently fall below detection limits (DL) of measuring instruments, resulting in left-censored data. The principal approaches for handling censored data include the substitution-based method, maximum likelihood estimation, robust regression on order statistics, and Kaplan-Meier. In practice, censored data are substituted with an arbitrary value prior to use of traditional statistical methods. Although some studies have evaluated the substitution performance in estimating population characteristics, they have focused mainly on normally and lognormally distributed data that contain a single DL. We employ Monte Carlo simulations to assess the impact of substitution when estimating population parameters based on censored data containing multiple DLs. We also consider different distributional assumptions including lognormal, Weibull, and gamma. We show that the reliability of the estimates after substitution is highly sensitive to distributional characteristics such as mean, standard deviation, skewness, and also data characteristics such as censoring percentage. The results highlight that although the performance of the substitution-based method improves as the censoring percentage decreases, its performance still depends on the population's distributional characteristics. Practical implications that follow from our findings indicate that caution must be taken in using the substitution method when analyzing censored environmental data.     

Prognostic Significance of Matrix Metalloproteinase-7 in Gastric Cancer Survival: A Meta-Analysis

The prognostic role of matrix metalloproteinase-7 in gastric cancer survival has been widely evaluated. However, the results are controversial. We aimed to set up a meta-analysis to reach a conclusion on the prognostic significance of metalloproteinase-7 in gastric cancer survival as well as its association with clinicopathological parameters. We searched popular databases from 1988 until October 2014 to gather eligible peer-reviewed papers addressing the prognostic effect of matrix metalloproteinase-7 in gastric cancer patients'' survival. The CASP check list was used for quality appraisal. Pooled hazard ratio (HR) for survival and odds ratio (OR) for association with their 95% confidence interval (CI) were considered as summary measurements. Finally, 1208 gastric cancer patients from nine studies were included in the meta-analysis. Pooled HR estimate for survival was 2.01 (95% CI = 1.62 – 2.50, P < 0.001), which indicated a significant poor prognostic effect for matrix metalloproteinase-7. Sensitivity analysis detected no dominancy for any study. No publication bias was detected according to Egger’s and Begg’s tests. Clinicopathological assessment revealed that higher matrix metalloproteinase-7 expression is associated with deeper invasion (pooled OR = 3.20; 95% CI = 1.14 – 8.96; P = 0.026), higher TNM stage (pooled OR = 3.67; 95% CI = 2.281-5.99; P<0.001), lymph node metastasis (pooled OR = 2.84; 95% CI = 1.89 – 4.25; P<0.001), and distant metastasis (pooled OR = 3.68; 95% CI = 1.85 – 7.29; P<0.001), but not with histological grade. This meta-analysis indicated a significant poor prognostic effect of matrix metalloproteinase-7 in gastric cancer survival. Additionally it was associated with aggressive tumor phenotype.     

BMI and Lifetime Changes in BMI and Cancer Mortality Risk

Body Mass Index (BMI) is known to be associated with cancer mortality, but little is known about the link between lifetime changes in BMI and cancer mortality in both males and females. We studied the association of BMI measurements (at baseline, highest and lowest BMI during the study-period) and lifetime changes in BMI (calculated over different time periods (i.e. short time period: annual change in BMI between successive surveys, long time period: annual change in BMI over the entire study period) with mortality from any cancer, and lung, colorectal, prostate and breast cancer in a large cohort study (n=8,645. Vlagtwedde-Vlaardingen, 1965-1990) with a follow-up on mortality status on December 31^st 2008. We used multivariate Cox regression models with adjustments for age, smoking, sex, and place of residence. Being overweight at baseline was associated with a higher risk of prostate cancer mortality (hazard ratio (HR) =2.22; 95% CI 1.19-4.17). Obesity at baseline was associated with a higher risk of any cancer mortality [all subjects (1.23 (1.01-1.50)), and females (1.40 (1.07-1.84))]. Chronically obese females (females who were obese during the entire study-period) had a higher risk of mortality from any cancer (2.16 (1.47-3.18), lung (3.22 (1.06-9.76)), colorectal (4.32 (1.53-12.20)), and breast cancer (2.52 (1.15-5.54)). We found no significant association between long-term annual change in BMI and cancer mortality risk. Both short-term annual increase and decrease in BMI were associated with a lower mortality risk from any cancer [all subjects: (0.67 (0.47-0.94)) and (0.73 (0.55-0.97)), respectively]. In conclusion, a higher BMI is associated with a higher cancer mortality risk. This study is the first to show that short-term annual changes in BMI were associated with lower mortality from any type of cancer.     

Detection of Cobalt Ion Based on Surface Plasmon Resonance of L-Cysteine Functionalized Silver Nanotriangles

Plasmonics - A facile and sensitive spectroscopic detection method for the detection of cobalt ion was introduced by the use of the surface plasmon resonance of silver nanotriangles (AgTrngs)....     

Effects of the Positive Action Program on Indicators of Positive Youth Development Among Urban Youth

This study evaluated effects of Positive Action, a school-based social-emotional and character development intervention, on indicators of positive youth development (PYD) among a sample of low-income, ethnic minority youth attending 14 urban schools. The study used a matched-pair, cluster-randomized controlled design at the school level. A multiple-measure self-report protocol assessed four key strengths and resources for PYD: self-concept, peer affiliations, ethics, and social skills. Students (n = 1170) were assessed from grades 3 to 8; the duration of the intervention, with drop-outs and late entrants was included in analyses. Growth curve analyses revealed evidence of favorable program effects on each of the four types of resources. The study contributes to PYD research by providing evidence for school-based interventions in low-income, urban contexts for ethnic minority youth.