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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.

Aims: The study aims to examine how therapists trained in motivational interviewing (MI) respond to resistance and whether this has an impact on subsequent client speech., Methods: Fifty recorded Motivational Enhancement Therapy sessions were examined using a sequential behavioural coding method for speech. Client counter-change talk formed the baseline for coding and categorizing subsequent therapist speech and the following client speech. Transitional analysis identified the probable occurrence of specific therapist and client utterances at each stage., Results: Following client expressed resistance or counter-change talk, MI consistent therapist utterances were most commonly observed. A moderate to strong predictive relationship was found between MI-consistent therapist speech and subsequent client change talk. A moderate predictive relationship was found between therapist MI-consistent behaviours and client ambivalence. A moderate to strong predictive relationship was found between MI-inconsistent therapist speech and subsequent client counter-change talk and a weak negative predictive relationship was found between MI-inconsistent therapist speech and client expressed ambivalence., Conclusions: In the face of initial expressed resistance to change, MI-consistent therapist speech appears to increase subsequent client utterances regarding intentions to change drinking behaviour., (© The Author(s) 2019. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

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.

Background: Depression and binge drinking behaviours are common clinical problems, which cause substantial functional, economic and health impacts. These conditions peak in young adulthood, and commonly co-occur. Comorbid depression and binge drinking are undertreated in young people, who are reluctant to seek help via traditional pathways to care. The iTreAD project (internet Treatment for Alcohol and Depression) aims to provide and evaluate internet-delivered monitoring and treatment programs for young people with depression and binge drinking concerns., Methods: Three hundred sixty nine participants will be recruited to the trial, and will be aged 18-30 years will be eligible for the study if they report current symptoms of depression (score 5 or more on the depression subscale of the Depression Anxiety Stress Scale) and concurrent binge drinking practices (5 or more standard drinks at least twice in the prior month). Following screening and online baseline assessment, participants are randomised to: (a) online monthly self-assessments, (b) online monthly self-assessments + 12-months of access to a 4 week online automated cognitive behaviour therapy program for binge drinking and depression (DEAL); or (c) online monthly assessment + DEAL + 12-months of access to a social networking site (Breathing Space). Independent, blind follow-up assessments occur at 26, 39, 52 and 64-weeks post-baseline., Discussion: The iTreAD project is the first randomised controlled trial combining online cognitive behaviour therapy, social networking and online monitoring for young people reporting concerns with depression and binge drinking. These treatments represent low-cost, wide-reach youth-appropriate treatment, which will have significantly public health implications for service design, delivery and health policy for this important age group., Trial Registration: Australian and New Zealand Clinical Trials Registry ACTRN12614000310662. Date registered 24 March 2014.

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.)

Background and Aim: Residential camps have been used to deliver weight-loss interventions to paediatric populations, but very little is known about how children perceive and evaluate attending such camps. Therefore, this study examined children's perceptions of attending a residential paediatric weight-loss camp., Methods: Fifteen attendees (mean age = 13.56) of the 2002 Carnegie International Camp-UK (CIC-UK) were engaged in semi-structured interviews, which were transcribed verbatim and subjected to an inductive analysis procedure., Results: Results reflected pre-camp issues including worries (boot camp fears, being bullied) and goals and aspirations (weight loss goals, reducing bullying, increasing self-esteem and making friends). Negative elements pertaining to the camp experience were homesickness and dietary concerns. Positive elements of the camp experience were enjoyment, peer support, staff support and choice of activities., Conclusion: Enjoyment, support from peers and staff and choice over activities appear to be important aspects in the delivery of residential obesity treatments for children.

Objectives: To investigate the change in body image, self-esteem, and worries in obese adolescents attending a residential, weight-loss camp., Design: A longitudinal intervention study, with a nonintervention comparison group of lean adolescents., Participants: A total of 57 obese adolescents (age: 13,11; BMI: 32.6 kg/m(2)) and 38 normal weight comparison adolescents., Measures: Self-esteem, salience of weight-related issues, body shape preference, weight and height at the start, and end of the weight-loss camp (mean stay: 4 weeks)., Results: The obese adolescents lost 5.6 kg, reduced their BMI by 2.1 kg/m(2), and BMI s.d. score by 0.28 while comparison children gained weight. Body shape dissatisfaction significantly decreased and self-esteem increased on measures of global self-worth, athletic competence, and physical appearance, in the camp attendees. This improvement took place without any exacerbation of existing worries about appearance or weight., Conclusions: While obese adolescents had lower self-worth and greater body dissatisfaction relative to the comparison children at the start of the camp, the intervention improved their psychological state. Greater weight loss was associated with greater psychological improvement, indicating the value of the intervention and the relevance of psychological change in effective treatment.