Manipulation of mitochondrial genes and mtDNA heteroplasmy.

Most patients with mitochondrial DNA (mtDNA) mutations have a mixture of mutant and wild-type mtDNA in their cells. This phenomenon, known as mtDNA heteroplasmy, provides an opportunity to develop therapies by selectively eliminating the mutant fraction. In the last decade, several enzyme-based gene editing platforms were developed to cleave specific DNA sequences. We have taken advantage of these enzymes to develop reagents to selectively eliminate mutant mtDNA. The replication of intact mitochondrial genomes normalizes mtDNA levels and consequently mitochondrial function. In this chapter, we describe the methodology used to design and express these nucleases in mammalian cells in culture and in vivo.

Adolescent health behaviour and similarity-attraction: friends share smoking habits (really), but much else besides.

Smoking habits and related attitudes were assessed in a sample of 4059 11- to 16-year-olds who also identified their best friends from among their fellow respondents. Subjects' responses were directly collated with those of their friends and indicated a clear covariation of smoking status (controlling for sex and age) as anticipated from previous research in which adolescents have been asked to report on the smoking habits of their friends. Such covariation, however, was not specific to smoking habits, but generalized to related measures of attitude and normative beliefs, alcohol use, health locus of control, school performance, spending habits and socio-economic status. Similarities on these other attributes were much the same, whether or not friends shared each others' smoking habits. It is concluded that these data argue against a simplistic view of unidirectional 'peer group influence' and invite an interpretation of friendship choice based on multiple dimensions of similarity.

Health locus of control and health beliefs in relation to adolescent smoking.

Results from a survey of 10,579 schoolchildren aged 11-16 years indicated various relationships between age, smoking behaviour, health locus of control beliefs, expressed concern with different consequences of illness and beliefs in the efficacy of different strategies for staying healthy. In particular, smokers, compared with non-smokers, showed less belief in the importance of 'powerful others' or 'personal control' but more belief in the importance of 'chance' as an influence on health outcomes. With regard to consequences of illness, smokers cared more than non-smokers about not being allowed to see friends, but less about getting behind in school or being a nuisance to others; they were also less convinced of the benefits of preventive health behaviours such as eating good food and taking exercise. Implications for health education approaches are discussed.

Adolescent smoking: attitudes, norms and parental influence.

The self-reported smoking habits and intentions of over 10,000 adolescents, aged 11 to 16 years, were related to a variety of attitudinal and normative variables. Current or previous smoking experience was a more important predictor of future intention to smoke than attitude or subjective norm (others' perceived tolerance of subjects' smoking). Parental opposition to smoking was a more important direct predictor of subjects' smoking intention than parental smoking behaviour.

Prospective study of factors predicting uptake of smoking in adolescents.

Risk factors for the uptake of cigarette smoking were examined prospectively in 2159 non-smoking secondary schoolchildren aged 11-13 who participated in a survey in 1983 and were followed up 30 months later, by which time 35 per cent had taken up smoking. In a multivariate logistic model, the strongest predictors to emerge were prior experimentation with cigarettes and sex, with more girls (41%) than boys (30%) starting to smoke. Other predictors of taking up smoking were being uncertain about smoking in the future, reporting having been drunk, having a boy or girl friend, believing teachers and friends would not mind if they took up smoking, and giving lower estimates of prevalence of smoking among teachers. Parental smoking behaviour and attitudes, beliefs about the effects of smoking on health, opinions about smoking and perceived strictness of parents did not predict take up of smoking when other variables were controlled for. The odds of taking up smoking varied from 0.24 (risk = 0.19) for a child with the most favourable combination of risk factors to 3.49 (risk = 0.78) for a child with the worst prognosis. These results differ from those of many cross sectional studies and hence indicate the importance of a prospective approach to this type of research.

The personal characteristics and life-style of the young drinker: the results of a survey of British adolescents.

It is argued that studying the drinking patterns of adolescents can add much to our understanding of alcohol use. The present paper hypothesises that heavy drinkers will be experiencing more stress than light, moderate or non-drinkers and that consequently, they will perceive themselves as doing worse in school and will report more conflict with their parents. It is predicted that heavy drinkers will have failed to learn norms controlling alcohol use. It is anticipated that social norms are learnt through controlled drinking in a family setting and thus it is predicted that heavy drinkers will be less likely to drink with their parents and more likely to drink with their peers, than other groups of drinkers. It is argued that heavy drinkers will be more involved in peer group activities and less concerned about their health, than light, moderate or non-drinkers. These hypotheses were tested in a survey of 10 579 British adolescents (5068 boys), and support was found for all but one of these hypothesis (i.e., the hypothesis that heavy drinkers would be less likely to drink with their parents than light or moderate drinkers).

Passive exposure to tobacco smoke: saliva cotinine concentrations in a representative population sample of non-smoking schoolchildren.

Saliva cotinine concentrations in 569 non-smoking schoolchildren were strongly related to the smoking habits of their parents. When neither parent smoked the mean concentration was 0.44 ng/ml, rising to 3.38 ng/ml when both parents were cigarette smokers. Mothers' smoking had a stronger influence than did fathers' (p less than 0.01). In addition, there was a small independent effect of number of siblings who smoked (p less than 0.01). The dose of nicotine received from fathers' smoking was estimated as equivalent to the active smoking of 30 cigarettes a year, that from mothers' smoking as equivalent to smoking 50 cigarettes a year, and that from both parents smoking as equivalent to smoking 80 cigarettes a year. This unsolicited burden may be prolonged throughout childhood and poses a definite risk to health.