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Abstract Background Incorrect perceptions of high rates of peer alcohol and tobacco use are predictive of increased personal use in student populations. Correcting misperceptions by providing feedback has been shown to be an effective intervention for reducing licit drug use. It is currently unknown if social norms interventions are effective in preventing and reducing illicit drug use in European students. The purpose of this paper is to describe the design of a multi-site cluster controlled trial of a web-based social norms intervention aimed at reducing licit and preventing illicit drug use in European university students. Methods/Design An online questionnaire to assess rates of drug use will be developed and translated based on existing social norms surveys. Students from sixteen universities in seven participating European countries will be invited to complete the questionnaire. Both intervention and control sites will be chosen by convenience. In each country, the intervention site will be the university that the local principal investigator is affiliated with. We aim to recruit 1000 students per site (baseline assessment). All participants will complete the online questionnaire at baseline. Baseline data will be used to develop social norms messages that will be included in a web-based intervention. The intervention group will receive individualized social norms feedback. The website will remain online during the following 5 months. After five months, a second survey will be conducted and effects of the intervention on social norms and drug use will be measured in comparison to the control site. Discussion This project is the first cross-national European collaboration to investigate the feasibility of a social norms intervention to reduce licit and prevent illicit drug use among European university students. Final trial registration number DRKS00004375 on the ‘German Clinical Trials Register’.

Abstract Background Unhealthy alcohol use amongst university students is a major public health concern. Although previous studies suggest a raised level of consumption amongst the UK student population there is little consistent information available about the pattern of alcohol consumption as they progress through university. The aim of the current research was to describe drinking patterns of UK full-time undergraduate students as they progress through their degree course. Method Data were collected over three years from 5895 undergraduate students who began their studies in either 2000 or 2001. Longitudinal data (i.e. Years 1–3) were available from 225 students. The remaining 5670 students all responded to at least one of the three surveys (Year 1 n = 2843; Year 2 n = 2219; Year 3 n = 1805). Results Students reported consuming significantly more units of alcohol per week at Year 1 than at Years 2 or 3 of their degree. Male students reported a higher consumption of units of alcohol than their female peers. When alcohol intake was classified using the Royal College of Physicians guidelines 1 there was no difference between male and females students in terms of the percentage exceeding recommended limits. Compared to those who were low level consumers students who reported drinking above low levels at Year 1 had at least 10 times the odds of continuing to consume above low levels at year 3. Students who reported higher levels of drinking were more likely to report that alcohol had a negative impact on their studies, finances and physical health. Consistent with the reduction in units over time students reported lower levels of negative impact during Year 3 when compared to Year 1. Conclusion The current findings suggest that student alcohol consumption declines over their undergraduate studies; however weekly levels of consumption at Year 3 remain high for a substantial number of students. The persistence of high levels of consumption in a large population of students suggests the need for effective preventative and treatment interventions for all year groups.

Objective: To identify the approaches and strategies used for ensuring cultural appropriateness, intervention functions and theoretical constructs of the effective and ineffective school-based smoking prevention interventions that were implemented in low-income and middle-income countries (LMICs)., Data Sources: Included MEDLINE, EMBASE, Global Health, PsycINFO, Web of Science and grey literature which were searched through August 2022 with no date limitations., Eligibility Criteria: We included randomised controlled trials (RCTs) with ≥6 months follow-up assessing the effect of school-based interventions on keeping pupils never-smokers in LMICs; published in English or Arabic., Data Extraction and Synthesis: Intervention data were coded according to the Theoretical Domains Framework, intervention functions of Behaviour Change Wheel and cultural appropriateness features. Using narrative synthesis we identified which cultural-adaptation features, theoretical constructs and intervention functions were associated with effectiveness. Findings were mapped against the capability-motivation and opportunity model to formulate the conclusion. Risk of bias was assessed using the Cochrane risk of bias tool., Results: We identified 11 RCTs (n=7712 never-smokers aged 11-15); of which five arms were effective and eight (four of the effective) arms had a low risk of bias in all criteria. Methodological heterogeneity in defining, measuring, assessing and presenting outcomes prohibited quantitative data synthesis. We identified nine components that characterised interventions that were effective in preventing pupils from smoking uptake. These include deep cultural adaptation; raising awareness of various smoking consequences; improving refusal skills of smoking offers and using never-smokers as role models and peer educators., Conclusion: Interventions that had used deep cultural adaptation which incorporated cultural, environmental, psychological and social factors, were more likely to be effective. Effective interventions considered improving pupils' psychological capability to remain never-smokers and reducing their social and physical opportunities and reflective and automatic motivations to smoke. Future trials should use standardised measurements of smoking to allow meta-analysis in future reviews., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

CAG repeat expansion is the genetic cause of nine incurable polyglutamine (polyQ) diseases with neurodegenerative features. Silencing repeat RNA holds great therapeutic value. Here, we developed a repeat-based RNA-cleaving DNAzyme that catalyzes the destruction of expanded CAG repeat RNA of six polyQ diseases with high potency. DNAzyme preferentially cleaved the expanded allele in spinocerebellar ataxia type 1 (SCA1) cells. While cleavage was non-allele-specific for spinocerebellar ataxia type 3 (SCA3) cells, treatment of DNAzyme leads to improved cell viability without affecting mitochondrial metabolism or p62-dependent aggresome formation. DNAzyme appears to be stable in mouse brain for at least 1 month, and an intermediate dosage of DNAzyme in a SCA3 mouse model leads to a significant reduction of high molecular weight ATXN3 proteins. Our data suggest that DNAzyme is an effective RNA silencing molecule for potential treatment of multiple polyQ diseases., (© 2021. The Author(s).)

Cas13a, an effector of type VI CRISPR-Cas systems, is an RNA guided RNase with multiplexing and therapeutic potential. This study employs the Leptotrichia shahii ( Lsh ) Cas13a and a repeat-based CRISPR RNA (crRNA) to track and eliminate toxic RNA aggregates in myotonic dystrophy type 1 (DM1) - a neuromuscular disease caused by CTG expansion in the DMPK gene. We demonstrate that Lsh Cas13a cleaves CUG repeat RNA in biochemical assays and reduces toxic RNA load in patient-derived myoblasts. As a result, Lsh Cas13a reverses the characteristic adult-to-embryonic missplicing events in several key genes that contribute to DM1 phenotype. The deactivated Lsh Cas13a can further be repurposed to track RNA-rich organelles within cells. Our data highlights the reprogrammability of Lsh Cas13a and the possible use of Cas13a to target expanded repeat sequences in microsatellite expansion diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Zhang, Bewick, Xia, Furling and Ashizawa.)

Large expansions of microsatellite DNA cause several neurological diseases. In Spinocerebellar ataxia type 10 (SCA10), the repeat interruptions change disease phenotype; an (ATTCC)n or a (ATCCT)n/(ATCCC)n interruption within the (ATTCT)n repeat is associated with the robust phenotype of ataxia and epilepsy while mostly pure (ATTCT)n may have reduced penetrance. Large repeat expansions of SCA10, and many other microsatellite expansions, can exceed 10,000 base pairs (bp) in size. Conventional next generation sequencing (NGS) technologies are ineffective in determining internal sequence contents or size of these expanded repeats. Using repeat primed PCR (RP-PCR) in conjunction with a high-sensitivity pulsed-field capillary electrophoresis fragment analyzer (FEMTO-Pulse, Agilent, Santa Clara, CA) (RP-FEMTO hereafter), we successfully determined sequence content of large expansion repeats in genomic DNA of SCA10 patients and transformed yeast artificial chromosomes containing SCA10 repeats. This RP-FEMTO is a simple and economical methodology which could complement emerging NGS for very long sequence reads such as Single Molecule, Real-Time (SMRT) and nanopore sequencing technologies., Competing Interests: PacBio provided support in the form of salaries for authors [TC and YCT], but did not have any additional role in the study design, decision to publish, or preparation of the manuscript. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Objectives: Web-based interventions enable organisations to deliver personalised individually tailored brief feedback to individuals without the need of a third party. Web-based interventions are effective in reducing alcohol consumption among university students. There is a paucity of evidence to indicate those who access web-based personalised feedback interventions respond in a way consistent with hypothesised active ingredients. This research uses the think-aloud technique to explore how students respond to instant web-based personalised normative feedback., Methods: Between-subjects experimental design employing qualitative methods. Twenty-one UK university students generated think-aloud transcripts while completing a web-based intervention (Unitcheck). This was followed by a semi-structured interview. One coding frame was developed to classify all utterances., Results: Narrative synthesis revealed five meta-themes: active thinking about alcohol use; comparisons with others; beliefs and knowledge about alcohol consumption; inter-relationship between personal codes and context; and engagement with Unitcheck., Conclusions: Students willingly engaged with the online assessment and personalised feedback. Students consciously engaged with the intervention and this engagement prompted students to actively consider their own behaviour, knowledge, perceptions, and to reflect on future behaviour. The ability of web-based personalised feedback interventions to effect change in individual's behaviours is likely related to their ability to encourage cognitive engagement and active processing of the information provided.

Objective: To compare European students' personal use and approval of illicit substance use with their perceptions of peer behaviours and attitudes, and investigate whether perceptions of peer norms are associated with personal use of illicit substances and attitudes., Method: This study used baseline data from the Social Norms Intervention for the prevention of Polydrug usE (SNIPE) project involving 4482 students from seven European countries in 2012. Students completed an online survey which included questions on personal and perceived peer illicit substance use and personal and perceived peer attitude towards illicit substances., Results: 8.3% of students reported having used illicit substances at least once in their life. 49.7% of students perceived that the majority of their peers have used illicit substances more frequently than themselves. The perception was significantly associated with higher odds for personal illicit substance use (OR: 1.97, 95% CI: 1.53-2.54). The perception that the majority of peers approve illicit substance use was significantly associated with higher odds for personal approval of illicit substance use (OR: 3.47, 95% CI: 2.73-4.41)., Conclusion: Students commonly perceived that their peers used illicit subtances more often than themselves. We found an association between the perceived peer norms/attitudes and reported individual behaviour/attitudes., (Copyright © 2014 Elsevier Inc. All rights reserved.)