Exploring the association between school-based peer networks and smoking according to socioeconomic status and tobacco control context: a systematic review.

BACKGROUND: Whilst prevalence of youth smoking in middle and high income countries has decreased, inequality has prevailed. The introduction of legislation regulating tobacco use in public spaces varies across countries, impacting the tobacco control context. Thus reviewing our knowledge of how social networks may influence smoking differently within different contexts is required to facilitate the development of context-specific interventions. METHODS: The search, conducted on 31st May 2019, included the following smoking-related terms; schools, adolescents, peers and social networks. Inclusion and exclusion criteria were applied throughout the title and abstract screening and full text screening. Quality assessment and synthesis followed. Studies were narratively synthesised to identify changes according to legislative context. This synthesis was conducted separately for findings relating to three categories: socioeconomic status; social selection and influence; and network position. RESULTS: Thirty studies were included. Differences in the relationship between network characteristics and smoking according to socioeconomic status were measured in five out of fifteen studies in Europe. Results varied across studies, with differences in network characteristics and their association with smoking varying both between schools of a differing and those of a similar socioeconomic composition. For studies conducted both before and after the introduction of comprehensive smoking legislation, the evidence for selection processes was more consistent than influence, which varied according to reciprocity. Findings showed that isolates were more likely to smoke and in-degree and out-degree centrality were related to smoking both before and after the introduction of legislation. The relationship between popularity and smoking was contingent on school level smoking prevalence in studies conducted before the introduction of legislation, but not after. CONCLUSIONS: Overall, effects according to socioeconomic status were underreported in the included studies and no consistent evidence of change after the introduction of a comprehensive smoking ban was observed. Further network analyses are required using more recent data to obtain a comprehensive understanding of how network processes may influence smoking differently according to socioeconomic status, and how adaptation could be used to enhance intervention effectiveness. SYSTEMATIC REVIEW REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42019137358 .

Choosing adolescent smokers as friends: the role of parenting and parental smoking.

The present study examined whether parenting and parental smoking can prevent children from selecting smoking friends during adolescence. 254 Adolescents of one Belgian secondary school participated. Self-administered questionnaires were distributed among 2nd-4th graders (mean ages = 14.2-16.2 years) during spring 2006. Follow-up was conducted 12 months later. Data was analyzed conducting longitudinal social network analyses. Results showed adolescents perceiving high parental psychological control had a significant higher tendency to select smoking friends. Perceived behavioral control and perceived parental support did not affect the selection of smoking friends. Furthermore, maternal smoking behavior affected the selection of smoking friends, although no effect of paternal smoking behavior on the selection of smoking friends was found. Adolescent smoking prevention efforts should focus on the influence of parents through their smoking behavior and their psychological control to decrease adolescents' tendency to select smoking friends resulting in fewer opportunities for negative peer influences to occur.

The effectiveness of school-based smoking prevention interventions among low- and high-SES European teenagers.

Preventing smoking initiation among adolescents of lower socio-economic groups is crucial for the reduction of socio-economic inequalities in health. The aim of the present study was to examine whether effective smoking prevention interventions in Europe are equally effective among adolescents of low- and high-socio-economic status (SES). As part of the European Union-funded TEENAGE project, three school-based smoking prevention intervention studies in Europe were selected for secondary analyses: (i) a Dutch class competition intervention, (ii) the European Smoking Prevention Framework (ESFA) study and (iii) the A Stop Smoking in Schools Trial (ASSIST) intervention. All three studies differed in effectiveness by SES. The Dutch class competition study only had a significant effect among higher SES adolescents. The results for the ESFA study and ASSIST study were mixed and depended on which SES indicator was used. The conclusion of the study is that stratified analyses provide important insights in differential intervention effects for higher and lower socio-economic groups. Although findings from the different studies were mixed, interventions that use a social network approach in which youngsters are allowed to deliver the intervention themselves may be a successful strategy in targeting adolescents from lower socio-economic groups.

Are physical activity interventions equally effective in adolescents of low and high socio-economic status (SES): results from the European Teenage project.

The aim was to study whether physical activity (PA) interventions in European teenagers are equally effective in adolescents of low versus high socio-economic status (SES). Based on a systematic review (Project TEENAGE), three school-based studies for secondary analyses were selected. SES stratified analyses were run in: (i) a Belgian multi-component intervention, (ii) a French multi-component intervention and (iii) a Belgian computer-tailored education trial. Results of the secondary analyses showed that no overall significant differences between low and high SES groups were found, but some interesting specific effects were revealed. Results from the first study showed an increase in objective PA in the low SES group (P = 0.015) compared with no significant effects in the high SES group. In the second study, larger effects were found in adolescents of high SES (increase of 11 min day(-1) P < 0.001), compared with adolescents of lower SES (increase of 7 min day(-1), P = 0.02) at the longer term. The third study showed a positive effect on school-related PA in adolescents of high SES (P < 0.05) and on leisure time transportation in adolescents of low SES (P < 0.05). To conclude, we were not able to show a significant widening or narrowing of inequalities in European adolescents.

No smoke without fire: The impact of future friends on adolescent smoking behaviour.

OBJECTIVE: This study examined the impact of future friends and the contribution of different social influence and selection processes in predicting adolescents' smoking behaviour by extending the theory of planned behaviour (TPB). We investigated the impact of previous smoking, direct pressure from friends, descriptive norms of present and future friends, smoking-based selection of future friends, and distinguished between reciprocal and desired friends. DESIGN: A longitudinal design with three measurements was used. METHODSL: The sample consisted of 1,475 Dutch high school students (mean age = 12.7 years) that participated as a control group in the European Smoking prevention Framework Approach study at three measurements. RESULTS: Structural equation modelling revealed that adolescent smoking was influenced by intention, previous smoking, descriptive norms of parents and siblings, and that desired as well as reciprocal friends were selected based on similar smoking behaviour. Future friends indirectly influenced adolescent smoking through intention, as did attitude, subjective norms of parents and siblings, previous smoking, and descriptive norms of reciprocal friends and siblings. CONCLUSIONS: The present results suggest that descriptive norms and selection of friends need to be considered as major factors explaining smoking behaviour among adolescents besides the TPB components. These insights contribute to the further refinement of smoking prevention strategies.

Tackling smoking among out of school youth in South Africa: An analysis of friendship ties.

BACKGROUND: Friendships during adolescence play a significant role in the initiation and maintenance of tobacco use. Smoking behaviour among adolescent friends has not been explored among out of school youth (OSY) in South Africa. Out of school youth (OSY), described as those between 13 and 20 years old, have not completed their schooling and are not currently enrolled in school, are at greater risk for tobacco use. AIM: The main aim of this study is to examine whether the smoking behaviour of OSY is associated with that of their OSY friends. METHODS: Respondent driven sampling was used to recruit OSY and their OSY friends. A mixed effects logistic regression with a random intercept across school-province combinations was used to analyse survey data. Race and gender were also incorporated into the analyses as effect moderators (n = 391). RESULTS: Results of this study confirm that cigarette smoking was common among OSY and their OSY friends, with 53.5% of the respondents smoking in the past month (SD = 0.44). When OSY friends were either all non-smokers or half their friends were non-smokers, Coloured (mixed race) OSY were less likely to smoke compared to Black African and Other (mostly Asian descent) OSY. CONCLUSION: Cultural norms and values associated with the different race groups may play a role in the smoking behaviour of out of school youth friends. Understanding this relationship is useful for identifying those OSY that are vulnerable to the behaviours that place them at risk of tobacco related morbidity and mortality.

Challenges to the peer influence paradigm: results for 12-13 year olds from six European countries from the European Smoking Prevention Framework Approach study.

OBJECTIVE: To examine whether smoking onset in young adolescents is predicted by peer or parental smoking. DESIGN: Longitudinal design with one pretest and one follow-up at 12 months. SETTING: Schools in Finland, Denmark, the Netherlands, the United Kingdom, Spain and Portugal. PARTICIPANTS: 7102 randomly selected adolescents from six countries. Mean age was 12.78 years. MAIN OUTCOME MEASURES: Smoking behaviour of adolescents, peers and parents. RESULTS: No support was found for peer smoking as an important predictor of smoking onset in most countries. Support was found for the selection paradigm, implying that adolescents choose friends with similar smoking behaviour. Support for the impact of parents on adolescent behaviour and the choice of friends was also found. CONCLUSIONS: Smoking uptake in this age cohort may be more strongly influenced by personal and parental influences than initially believed. Hence, social inoculation programmes teaching youngsters to resist the pressures to smoke may be less appropriate if youngsters have a positive attitude towards smoking, associate smoking with various advantages and look for peers with similar values. For this group attitudes towards smoking may thus guide future friend selection.

Transcriptional effects in GH3 cells of Gs alpha mutants associated with human pituitary tumors: stimulation of adenosine 3',5'-monophosphate response element-binding protein-mediated transcription and of prolactin and growth hormone promoter activity via protein kinase A.

Somatic mutations of the alpha-subunit of Gs (Gs alpha) have been detected previously at high frequency in human PRL- and/or GH-producing pituitary tumors. To test whether these mutants are responsible for the increased production of these hormones, we used transient cotransfection assays to analyze their genomic effects in GH3 rat pituitary cells. We first show that guanosine triphosphatase (GTPase)-deficient Gs alpha subunits (mutated at amino acid 201 or 227) stimulate transcription from a reporter construct bearing the consensus cAMP response element (CRE; TGACGTCA). Using GAL4-CRE-binding protein fusion constructs, we further show that this stimulatory effects of Gs alpha on the CRE is probably mediated by the transacting factor CRE-binding protein. Then, in experiments using a reporter gene driven by the human promoters for either the PRL (position -250 to 18) or GH (position -500 to 13) genes, we show that these mutant Gs alpha subunits stimulate expression driven by either the PRL or GH promoter. Finally, we show that a dominant inhibitory mutant of cAMP-dependent kinase (protein kinase A) completely blocks the ability of these Gs alpha mutants to stimulate the activity of either the PRL or GH promoter, implying that GTPase-deficient Gs alpha subunits stimulation of the activities of these promoters is mediated entirely via the cAMP/protein kinase A pathway. Taken together, these results imply that activation of this pathway by the GTPase-deficient mutants found in human pituitary tumors stimulates the expression of PRL and GH genes. The transcriptional effects exerted via this pathway may thus provide a basis for the secretory phenotype and endocrine disorders associated with these tumors.

The 5'-end of bovine thyroglobulin mRNA encodes a hormonogenic peptide.

The sequence of 370 bases at the 5'-end of bovine thyroglobulin mRNA has been determined. A 41 base untranslated segment was found preceeding the ATG initiator codon. It is followed by an open reading frame providing the first data on thyroglobulin primary structure. Analysis of the amino acid sequence demonstrated the presence of an 18 residue hydrophobic segment representing a putative signal peptide. Comparison of the amino terminal sequence of thyroglobulin with that of peptides known to contain thyroid hormones [7,8] demonstrated that the first tyrosine in native thyroglobulin is mainly found as thyroxine in the mature iodinated protein [8]. Our results clearly identify the amino-terminal region of thyroglobulin as an important hormonogenic domain of the protein.

Baculovirus-infected cells do not produce the amyloid peptide of Alzheimer's disease from its precursor.

The amyloid peptide (Abeta) of Alzheimer's disease (AD) is produced by proteolytic cleavage of a larger precursor, the amyloid peptide precursor or APP. The discovery of pathogenic mutations in the APP gene provides strong evidence for the hypothesis that APP metabolism is involved in the etiology of AD. To study the metabolism of the protein, human APP has been expressed in several mammalian cell types. Insect cells, infected by a recombinant baculovirus carrying the human APP sequence, also provide an interesting expression system because these cells do not produce endogenous APP. Baculovirus-infected cells synthesize very high amounts of extracellular soluble APP, after cleavage of the transmembrane protein, as described for mammalian cells. However, we demonstrate here that insect cells do not produce Abeta from APP. These results suggest that while the enzymatic activity needed for the production of soluble APP is conserved between insect and mammalian cells, the enzymes required for the production of Abeta from APP are only expressed in mammalian cells.

Alternative splicing may be responsible for heterogeneity of thyroglobulin structure.

During the cloning of the bovine thyroglobulin cDNA, the restriction map of one of the recombinant plasmids was in disagreement with that of the full-length double-stranded thyroglobulin cDNA. When compared to the bovine Tg mRNA sequence, this cDNA clone exhibits a 333-nucleotide deletion which corresponds precisely to 2 exons of the Tg gene. It is thus likely that alternative processing of the premessenger RNA is at the origin of the deletion. The presence of giant introns in the vicinity of the dispensable exons may also reflect some error level in the splicing mechanism. Together with previous results the alternative splicing described in this study indicates that alternative processing of the Tg transcripts may be at the origin of thyroglobulin isoforms.

Studies on the structures of the normal and abnormal goat thyroglobulin genes.

We have cloned the thyroglobulin (Tg) gene of normal goats and goitrous goats which have a Tg synthesis defect. At the 5'-end of the gene, we studied cosmid clones covering a region from 20 kilobases (kb) upstream from the Tg gene to 42 kb into it. Electron microscopy and restriction mapping show that this part of the gene contains 20 exons of 90-1190 bp, in total 4.9 kb of exonic information (56% of the mRNA) split by 19 introns of 150-9100 bp. The exons comprise 12% of the 5' sequences cloned. At the 3'-end, 55 kb were cloned, containing 10 kb of the gene which comprises only 3 exons of 550 bp in total. Sequence analysis of the 3'-end of the normal and abnormal Tg genes has revealed one transition mutation 3' to the reading frame in a stem-loop structure region of the last exon near the poly(A) addition site. Analysis of the promoter site and the first 5 exons has revealed only one difference between the normal and goitrous Tg genes: a Ser----Leu transition in exon 5. We also found an insertion in the fifth intron of the abnormal gene.

Molecular cloning, functional expression, pharmacological characterization and chromosomal localization of the human metabotropic glutamate receptor type 3.

Glutamic acid is the major excitatory amino acid of the central nervous system which interacts with two receptor families, the ionotropic and metabotropic glutamate receptors. The metabotropic glutamate receptors (mGluRs) are coupled to G proteins and can be divided into three subgroups based on their sequence homology, signal transduction pathway and pharmacology. In this study, we describe the cloning of the cDNA encoding the human metabotropic glutamate receptor type 3 (HmGluR3). It was obtained by reverse transcription-polymerase chain reaction (RT-PCR) with degenerate oligonucleotides corresponding to highly conserved sequences between rat mGluRs. The receptor shows 879 amino acids with 96% amino acid sequence identity with rat mGluR3. It is strongly expressed in fetal and adult whole brain, especially in caudate nucleus and corpus callosum. The gene was identified by fluorescence in situ hybridization on chromosome 7 band q22. Activation of the human mGluR3, permanently expressed in Baby Hamster Kidney (BHK) cells, by excitatory amino acid inhibits the forskolin-stimulated accumulation of intracellular cAMP. The rank order of potency is L-glutamic acid > or = (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R)-ACPD) >> ibotenic acid > quisqualic acid. (RS)-alpha-methyl-4-carboxyphenylglycine [(RS)-MCPG, 1 mM] is without effect on inhibition of forskolin-induced cAMP accumulation by L-glutamic acid.

Gs alpha availability to cholera toxin-catalysed ADP-ribosylation is decreased in membranes of retinoic acid-treated leukemic cell lines HL-60 and THP-1. A posttranslational effect.

Retinoic acid (RA) induces HL-60 and THP-1 leukemic cell lines to differentiate into granulocyte-like and monocyte-like cells. Limited data are available concerning the effects of RA on components of the cyclic AMP pathway in human myeloid leukemic cells. We showed previously a decrease in adenylate cyclase activity in the presence of histamine, prostaglandin E1 and forskolin in RA-treated HL-60 cells as compared to untreated cells. We examined the elements of the signal transduction pathway utilized by RA in the human myeloid cell line HL-60 and the human monocytic cell line THP-1. We therefore studied the effect of RA on the activity of the stimulatory G-protein (Gs). We demonstrate that addition of RA to two human myeloid leukemia cell lines, HL-60 and THP-1, does not induce a reduction of the 2 subunit of Gs (Gs alpha) RNA or Gs alpha protein in the plasma membrane but leads to a rapid decrease in the cholera toxin (CTX)-catalysed ADP-ribosylation of Gs alpha. In addition, this effect seems to be specific to RA, since there was no modification in Gs alpha ADP-ribosylation in the membranes of cells treated with dimethyl sulfoxide (DMSO), another inducer of differentiation in HL-60 cells.

Proteolytical processing of mutated human amyloid precursor protein in transgenic mice.

The evidence that betaA4 is central to the pathology of Alzheimer's disease (AD) came from the identification of several missense mutations in the amyloid precursor protein (APP) gene co-segregating with familial AD (FAD). In an attempt to study the proteolytical processing of mutated human APP in vivo, we have created transgenic mice expressing the human APP695 isoform with four FAD-linked mutations. Expression of the transgene was controlled by the promoter of the HMG-CR gene. Human APP is expressed in the brain of transgenic mice as shown by Western blot and immunohistology. The proteolytic processing of human APP in the transgenic mice leads to the generation of C-terminal APP fragments as well as to the release of betaA4. Despite substantial amounts of betaA4 detected in the brain of the transgenic mice, neither signs of Alzheimer's disease-related pathology nor related behavioural deficits could be demonstrated.

Phosphorylation of tau protein is not affected in mice lacking apolipoprotein E.

An interaction between the apolipoprotein E (apoE) type 3 and the microtubule-associated protein tau has been demonstrated in vitro and suggested to modulate tau phosphorylation and/or formation of paired helical filaments. To evaluate in vivo the potential interaction between tau and apoE, we have investigated the expression and phosphorylation status of tau in the brain of apoE-deficient mice, using a panel of antibodies reacting with tau in a phosphorylation-dependent manner. The pattern and intensity of immunohistochemical labelling and the pattern of tau immunoreactivity on Western blots were similar in control and apoE-deficient mice. These results suggest that a lack of expression of apoE does not interfere with the expression, distribution and phosphorylation status of tau proteins.

[Structure and expression of thyroglobulin gene]. / Structure et expression du gène de la thyroglobuline.

Thyroglobulin is composed of two 300000 dalton polypeptide chains, translated from an 8000 base mRNA. Preparation of a full length cDNA and its cloning in E. coli have lead to the demonstration that the polypeptides of thyroglobulin protomers were identical. Used as molecular probes, the cloned cDNA allowed the isolation of a fragment of thyroglobulin gene. Electron microscopic studies have demonstrated that this gene contains more than 90% intronic material separating small size exons (less than 200 bp). Sequencing of bovine thyroglobulin structural gene is in progress. Preliminary results show evidence for the existence of repetitive segments. Availability of cloned DNA complementary to bovine and human thyroglobulin mRNA allows the study of genetic defects of thyroglobulin gene expression in the human and in various animal models.

A nonsense mutation causes hereditary goitre in the Afrikander cattle and unmasks alternative splicing of thyroglobulin transcripts.

The hereditary goitre of Afrikander cattle is an autosomal recessive disease characterized in homozygotes by the production of abnormal thyroglobulin (Tg) and the coexistence in the thyroid of normal-sized 8.4-kilobase (kb) Tg mRNA with a misspliced 7.3-kb message having lost exon 9. We have cloned and sequenced the cDNA segment corresponding to the abnormal exon 8-exon 10 junction and the relevant genomic DNA region. The mutation responsible for the disease is a cytosine to thymine transition creating a stop codon at position 697 in exon 9. The original reading frame is maintained in the 7.3-kb mRNA, which, as it lacks the mutated exon, is translatable into a potentially functional protein. This puzzling phenotype in which a mutated exon is apparently removed selectively from transcripts by alternative splicing leads us to suggest that the 7.3-kb transcript could be present in normal animals. Using a sensitive oligonucleotide hybridization assay, we have demonstrated that a 7.3-kb mRNA lacking exon 9 does exist in normal thyroids as a minor mRNA species. As it is fully translatable, the 7.3-kb mRNA is expected to be more stable than the normal-sized 8.4-kb message. This probably accounts for the higher proportion of 7.3-kb transcript found in the goitre.

Identification of hormonogenic domains in the carboxyl terminal region of bovine thyroglobulin.

A segment of 986 nucleotides corresponding to the 3' end of the 8.5 kb bovine thyroglobulin (Tg) mRNA has been sequenced. An open reading frame of 302 codons was found, ending with TGA and preceding an 80 nucleotide long 3' untranslated sequence. The encoded protein sequence provided the first data on the carboxyl terminal portion of Tg. Lysine was identified as the last residue. Comparison of the amino acid sequence with that of peptides known to contain thyroid hormones in the mature protein, lead to the identification of three regions involved in thyroid hormone formation. Two closely linked thyroxine- forming sites were found 182 and 196 amino acids from the carboxyl terminus respectively. The antepenultimate amino acid of the protein corresponded to the recently described triiodothyronine-forming site. Together with the previous localization of the main thyroxine-containing peptide at the amino terminus, the present results provide a map of all hormonogenic sites identified to date in Tg.