Promoting Tropoelastin Expression in Arterial and Venous Vascular Smooth Muscle Cells and Fibroblasts for Vascular Tissue Engineering.

Elastin, critical for its structural and regulatory functions, is a missing link in vascular tissue engineering. Several elastin-inducting compounds have previously been reported, but their relative efficiency in promoting elastogenesis by adult arterial and venous vascular smooth muscle cells (VSMCs) and fibroblasts, four main vascular and elastogenic cells, has not been described. In addition to elasto-inductive substances, microRNA-29a was recently established as a potent post-transcriptional inhibitor of elastogenesis. Here, we explored if stimulating positive regulators or blocking inhibitors of elastogenesis could maximize elastin production. We tested whether the elasto-inducing compounds IGF-1, TGF-ß1, and minoxidil could indeed augment elastin production, and whether microRNA-29a antagonism could block elastin production in adult arterial and venous fibroblasts and VSMCs. The effects on elastin, lysyl oxidase, and fibrillin-1 mRNA expression levels and tropoelastin protein were determined. IGF-1 and minoxidil exerted little effect on tropoelastin mRNA expression levels in all cell types, while TGF-ß1 predominantly enhanced mRNA tropoelastin levels, but this mRNA increase did not impact tropoelastin protein abundance. In contrast, microRNA29a inhibition resulted in the upregulation of tropoelastin mRNA in all cell types, but most pronounced in venous VSMCs. Importantly, microRNA-29a-antagonism also enhanced lysyl oxidase and fibrillin-1 mRNA expression, and revealed a dose-dependent increase in tropoelastin protein expression in venous VSMCs. Our studies suggest that the elastogenic potential of microRNA-29a inhibition in vascular cells is superior to that of established elastin-stimulating compounds IGF-1, TGF-ß1, and minoxidil. Thus, microRNA-29a antagonism could serve as an attractive means of enhancing elastin synthesis in tissue-engineered blood vessels.

Fabrication of multi-well chips for spheroid cultures and implantable constructs through rapid prototyping techniques.

Three-dimensional (3D) culture models are widely used in basic and translational research. In this study, to generate and culture multiple 3D cell spheroids, we exploited laser ablation and replica molding for the fabrication of polydimethylsiloxane (PDMS) multi-well chips, which were validated using articular chondrocytes (ACs). Multi-well ACs spheroids were comparable or superior to standard spheroids, as revealed by glycosaminoglycan and type-II collagen deposition. Moreover, the use of our multi-well chips significantly reduced the operation time for cell seeding and medium refresh. Exploiting a similar approach, we used clinical-grade fibrin to generate implantable multi-well constructs allowing for the precise distribution of multiple cell types. Multi-well fibrin constructs were seeded with ACs generating high cell density regions, as shown by histology and cell fluorescent staining. Multi-well constructs were compared to standard constructs with homogeneously distributed ACs. After 7 days in vitro, expression of SOX9, ACAN, COL2A1, and COMP was increased in both constructs, with multi-well constructs expressing significantly higher levels of chondrogenic genes than standard constructs. After 5 weeks in vivo, we found that despite a dramatic size reduction, the cell distribution pattern was maintained and glycosaminoglycan content per wet weight was significantly increased respect to pre-implantation samples. In conclusion, multi-well chips for the generation and culture of multiple cell spheroids can be fabricated by low-cost rapid prototyping techniques. Furthermore, these techniques can be used to generate implantable constructs with defined architecture and controlled cell distribution, allowing for in vitro and in vivo investigation of cell interactions in a 3D environment.

The significance of reciprocal and unilateral friendships for peer victimization in adolescence.

The present study examined to what extent the number of friends and their social and personal characteristics were related to peer victimization in adolescence. Participants were 2,180 adolescents (1,143 girls), aged 11-18 (M = 14.2), who were classified as victims, bully-victims, or non-involved (i.e., adolescents who neither bullied others nor were victimized by others). Three types of friends were distinguished: reciprocal friends, desired friends (who were unilaterally nominated by a target adolescent) and choosing friends (who unilaterally nominated a target adolescent). Between-group comparisons of the three types of friends showed that victims had fewer reciprocal and choosing friends than non-involved adolescents. Compared to bully-victims and non-involved adolescents, victims had reciprocal friends who were socially less well adjusted. No differences existed with respect to the characteristics of the desired friends. In general, victims' choosing friends scored less positive on the personal characteristics than bully-victims' and non-involved adolescents' choosing friends. Within-group comparisons revealed that victims' reciprocal friends showed lower adjustment than victims' desired friends, but higher adjustment than their choosing friends. For bully-victims and non-involved adolescents, such differences between their three types of friends were largely absent. Our findings seem to suggest that victims' reciprocal friendships may not be totally default associations and that out of all possible friends, victims might tend to select those who score most positive on personal or social factors.

Frequency and seriousness of parental offending and their impact on juvenile offending.

The present study investigated to what extent the frequency and seriousness of parental offending were related to their offspring offending. Police officers in one Dutch province completed a form to register risk factors and the actions undertaken when they came into contact with offenders aged 8-14 years. These juveniles were followed for 18 months to establish whether or not they committed more crimes. In addition, the parents of these children were traced in the police criminal record systems. Data were gathered from 577 children and their parents. Of these children, 34% were exposed to parental criminality, of which 33 delinquents had two criminal parents and 163 had one criminal parent. If both parents were criminal, the child had the highest frequency of offending. Further, the frequency of parental offending was positively related to the frequency of the child's offending. Concerning the seriousness of juvenile crimes, the seriousness of the committed offences of the father showed a positive relation with the seriousness of his child's offending. Unexpectedly, a negative association was found between the seriousness of maternal offending and the seriousness of her child offending. These results offered a better understanding of the influence that parents with a criminal history have on their children. Further research is needed to identify mechanisms underlying this relationship in order to provide appropriate prevention and intervention strategies.

Short-term criminal pathways: type and seriousness of offense and recidivism.

In this longitudinal study, the authors investigated short-term criminal pathways of children and early adolescents starting under the age of 14 years and the extent to which characteristics of the 1st crime influenced criminal pathways. Participants were 387 juvenile offenders with a mean age of 12.1 years (SD = 2.05 years). The authors followed all participants in the police systems for 2 years to get insight into the crimes that they committed. Then, 2 years after the 1st police contact, 46.5% of these offenders were still considered 1st offenders, and 53.5% had become recidivists. Most of the children began their criminal pathway with less serious covert crimes. Further analyses showed that when the 1st crime was a serious overt crime, the risk of recidivism within 1 year increased. The likelihood of committing a serious overt crime increased with age. The results supported the authors' hypotheses in that juvenile offenders who committed both overt and covert delinquent acts had the highest rates of offense, were more aggressive, and committed more serious offenses. Furthermore, children who committed only overt crimes developed even more serious criminal pathways.

Early adolescent empathy, parental support, and antisocial behavior.

In this two-wave prospective study, the authors investigated whether level of dispositional affective empathy moderated the association between parental support and antisocial behavior in early adolescents. The sample consisted of 823 Dutch boys and girls (mean age = 12.8 years) enrolled in the first year of secondary education. Higher levels of affective empathy were associated with less delinquent and aggressive behavior. Contrary to expectations, structural equation modeling did not indicate that youth with higher levels of affective empathy were susceptible to parental support. Further analyses showed that gender moderated the association between parental support and future delinquent and aggressive behavior. Only for girls, were high levels of parental support associated with lower levels of antisocial behavior.

Brief report: Intimacy, passion, and commitment in romantic relationships--validation of a 'triangular love scale' for adolescents.

This study examined the psychometric properties of an adolescent version of the 'triangular love scale' (TLS), which assesses three components of romantic relationships: intimacy, passion, and commitment. Using data from 435 Dutch adolescents aged 12-18 years, we found evidence for convergent validity, showing that dimensions of intimacy, passion, and commitment were all positively correlated with relationship satisfaction and duration. Evidence was also found for divergent validity, as adolescents' perceptions of the main (dis)advantages of being involved in romantic relationships showed a specific pattern of associations with intimacy, passion, and commitment. Finally, CFA analyses in LISREL showed that a model in which all separate questionnaire items were specified to load on three underlying, correlated factors (intimacy, passion, commitment) fit the data adequately. Overall, this measure seems appropriate for use with adolescents.

Stability in bullying and victimization and its association with social adjustment in childhood and adolescence.

This study examined the concurrent and longitudinal associations between stability in bullying and victimization, and social adjustment in childhood and adolescence. Participants were 189 girls and 328 boys who were studied in primary school and in secondary school. The mean age of the participants was 11.1 years in primary school and 14.1 years in secondary school. The measures consisted of peer reported social and personal characteristics. Children who bullied in childhood and adolescence were less liked and more disliked in childhood, and more aggressive and disruptive both in childhood and adolescence, than children who bullied only in childhood or adolescence. Children who bullied or who were victimized only in childhood did not differ largely in adolescence from the children that were never bullies or victims. Children who were victimized in adolescence closely resembled those who were victimized in childhood and adolescence in terms of being liked or disliked, being nominated as a friend, and shyness. The study stresses the need to distinguish between stable and transient bullies and victims.

Longitudinal associations of marital quality and marital dissolution with the incidence of DSM-III-R disorders.

This study examined whether getting divorced was related to the subsequent incidence of DSM-III-R disorders across a 2-year period, controlling for the perceived quality of the marriage prior to the divorce. Data were used from 4,796 adults aged 18 to 64, who had participated in 3 waves (i.e., 1996, 1997, and 1999) of a large-scale epidemiological study conducted in The Netherlands. Results showed that getting divorced was prospectively linked to both the total and new case incidence of alcohol abuse and dysthymia, as well as to the new case incidence of social phobia. Adults who had divorced, however, were not more likely to develop a mental disorder if they had reported low levels of marital quality prior to the divorce. Thus, the marital discord underlying a divorce rather than divorce itself appeared to determine the onset of clinically relevant mental health problems.

Peer group reputation and smoking and alcohol consumption in early adolescence.

Research has shown that substance use might serve beneficial, developmental functions for adolescents, in particular concerning young people's functioning in friendships and intimate relationships. Nonetheless, a major problem in these studies is that information on social functioning is based on adolescent's self-reports, which undoubtedly might lead to an overestimation of the social functions of substance use. In the present study, we collected data of 3361 early and mid-adolescents at secondary schools in the Netherlands. Information on individual student's social behavior and psychological traits were gathered by using sociometric measures. All respondents were asked to evaluate all classmates on measures, such as sociability, self-confidence, achievement, withdrawal, and aggression. Person- and variable-centered analyses clearly showed that highest levels of smoking and drinking were found in adolescents who score high on sociability and self-confidence, and relatively low on aggression-inattentiveness, achievement-withdrawal, and emotionality-nervousness. This suggests that beneficial functions of substance use are not only in the eyes of the beholder, at least not in that of the individual drinker or smoker.

Influence and selection processes in friendships and adolescent smoking behaviour: the role of parental smoking.

Concerning the role of parental smoking on development of adolescent smoking, most studies have exclusively focused on the direct effects of parents' smoking on youths' smoking. However, parental smoking may also play an indirect role by affecting youths' susceptibility to peer influences and by affecting friendship selection. Data were from a three-wave short-term longitudinal study of 1595 adolescents. Findings showed high similarities in smoking between reciprocal friends. Additionally, friend's smoking and parents' smoking were moderately related to adolescent smoking onset, but parents' smoking did not moderate the prospective association between best friend's smoking and adolescent smoking. Finally, parental smoking seemed to affect the selection of new friends: In particular, adolescents with smoking parents were most likely to become affiliated with smoking friends. There was no evidence that parental smoking affected termination of friendships.

Implemented as intended? Recording family worker activities in a Families First program.

In evaluating family preservation services, it is important not only to study the service outcomes and the family characteristics, but also what actually happens during the treatment. This requires a program model. This article describes how a program model works, prescribes how workers should carry it out, and describes how researchers should measure the program's characteristics. The authors use data from Families First in The Netherlands to test the model. Results show that the method of the program meets the specified characteristics. The results are important for treatment, policy, education, and evaluation research.

The implementation of families first in The Netherlands: a one year follow-up.

This study examined whether the American family preservation program Families First was successfully implemented in The Netherlands. Data were collected on 250 children of 177 families who received Families First. At the start of treatment 78% of the children appeared to have serious behavioral problems, 67% of the parents experienced a high level of parental stress, and 63% of the children went through a substantial number of life events during the year preceding the treatment. On average the treatments had the intended duration (about 4 weeks), intensity (about 10 hours a week) and availability (during working hours as well as in evenings and in weekends), and family workers did adhere to important guidelines of treatment delivery. One year after treatment 76% of the children were still living at home. Moreover, children's behavioral problems, parental stress and the number of life events turned out to be significantly decreased. It was concluded that Families First had reached its intended target group, delivered the treatment as intended, and achieved its intended outcomes, suggesting a successful implementation in The Netherlands.