From eye rolls to punches: experiences of harm from others' drinking among risky-drinking adolescents across Australia.

OBJECTIVES: Exploration of experience of harms due to another person's drinking within a demographic particularly vulnerable to these consequences. Importance of study: Largest sampling of young Australian risky drinkers, who are underrepresented in general population surveys. The range of harms due to others' drinking reported here is more comprehensive than documented elsewhere. STUDY TYPE: Cross-sectional self-report survey. METHODS: Participants were 14-19 years old and screened as being within the riskiest-drinking 25% for their age cohort. The convenience sample of 3465 was recruited primarily by social media advertising. Face-to-face interviews were conducted in all eight Australian capital cities (n = 596), supplemented by online surveys (n = 2869). Past 12-month experience of 13 harms due to others' drinking was assessed by age, gender and perpetrator. RESULTS: Females were more likely to experience seven harms, mainly characterised by fear and harassment, including being harassed or bothered at a party or some other private setting (41% vs 34% of males, p < 0.001), being given unwanted sexual attention (71% vs 47%, p < 0.001) and being put in fear (33% vs 20%, p < 0.001). Males were more likely to experience three harms, characterised by aggression: being yelled at, criticised or verbally abused (38% vs 33% of females, p = 0.002), being pushed or shoved (42% vs 28%, p < 0.001) and being physically hurt (17% vs 11%, p < 0.001). Teenagers of a legal alcohol-purchase age were more likely to experience harassment in public settings (49% vs 32-34%, p < 0.001) and unwanted sexual attention (66% vs 51-59%, p < 0.001) compared with younger teenagers. Seven of the harms studied were more likely (p < 0.01) to be perpetrated by people the respondents knew, and five (those associated with fear and aggression) were more likely to be perpetrated by strangers. CONCLUSION: Young people who are risky drinkers commonly experience multiple harms from others' drinking. Many of these alcohol harms to others are reported here for the first time, as previous studies of adolescent drinking have focused almost exclusively on the harms young people have experienced from their own drinking. This refocusing on the harms caused by the drinking of others may prompt greater community concern and concomitant calls for better alcohol regulation.

Dual-color encoded DNAzyme nanostructures for multiplexed detection of intracellular metal ions in living cells.

The detection of intracellular metal ions is of great importance in understanding metal homeostasis in cells and related diseases, and yet it remains a significant challenge to achieve this goal. Based on a new self-assembled and dual-color encoded DNAzyme nanostructure, we describe here an approach for multiplexed sensing of UO2(2+) and Pb(2+) in living cells. The fluorescently quenched nanoprobes can be prepared by simple thermal annealing of four ssDNAs containing the metal ion-dependent enzymatic and substrate sequences. The self-assembly formation of the nanostructures are verified by native polyacrylamide gel electrophoresis. The target metal ions can cleave the substrate sequences in the DNAzyme nanostructures to recover fluorescent emissions at different wavelengths for sensitive and selective in vitro multiplexed detection of UO2(2+) and Pb(2+) with the detection limits of 0.6nM and 3.9nM, respectively. Importantly, we demonstrate that these nanoprobes are stable in cell lysates and can enter cells without the aid of any transfection agents for simultaneous imaging intracellular UO2(2+) and Pb(2+). Moreover, the nanoprobes offer excellent biocompatibility and non-cytotoxicity. With these unique features, the dual-color encoded nanostructures presented here can thus offer new opportunities for multiplexed detection of specific intracellular species.

Simvastatin inhibits lipopolysaccharide-induced tumor necrosis factor-alpha expression in neonatal rat cardiomyocytes: The role of reactive oxygen species.

Tumor necrosis factor-alpha (TNF-alpha) is implicated in heart failure and cardiomyocytes themselves can express TNF-alpha. Nevertheless, the mechanisms and regulations of TNF-alpha expression in cardiomyocytes remain poorly understood. The present study was to investigate the effects of simvastatin on TNF-alpha expression in cardiomyocytes and the underlying molecular mechanisms. In neonatal rat cardiomyocytes, RT-PCR and ELISA showed lipopolysaccharide (LPS)-induced TNF-alpha expression was attenuated by simvastatin pretreatment in a dose-dependent manner. The reactive oxygen species (ROS) scavenger N-acetylcysteine and the NADPH oxidase inhibitor diphenyleneiodonium also inhibited the LPS-induced expression of TNF-alpha. Dichlorofluorescein-fluorescence and cytochrome c reduction assay indicated LPS increased ROS generation and NADPH oxidase activity in cardiomyocytes, which were abrogated by simvastatin. Furthermore, similar to LPS, exogenous hydrogen peroxide also increased TNF-alpha secretion, but simvastatin did not significantly affect the hydrogen peroxide-induced TNF-alpha secretion. All the effects of simvastatin as mentioned above were completely reversed by concomitant pretreatment with mevalonate, a key intermediate during cholesterol synthesis. These results suggest that simvastatin attenuates LPS-induced TNF-alpha expression in cardiomyocytes via inhibition of activation of NADPH oxidase and subsequent ROS generation.