A Protocol of a Pilot Experimental Study Using Social Network Interventions to Examine the Social Contagion of Attitudes Towards Childhood Vaccination in Parental Social Networks

Increasing vaccination hesitancy that burdens global health and safety can be attributed to multiple reasons. Individuals’ social environment seems to be the catalyst for vaccination hesitancy perpetuation, thus it is important to examine the influence of different social network mechanisms in vaccination attitudes’ contagion. The proposed pilot experiment will examine the social contagion of childhood vaccination attitudes within a parental community using social network interventions. By identifying centrally-located people or groups of like-minded individuals from a parents’ community, we will examine whether the position of a person within a social group can have a greater impact in spreading positive vaccination messages to other community members. Parents will be recruited from social media and will be randomly assigned into three groups. Firstly, each group will participate in an online game to map their social networks and identify members with certain network position, who will then receive a short training about valid vaccination information provisions. All groups’ members will participate in daily vaccination discussion groups for one week, where the selected members will spread positive vaccination attitudes to others. We hypothesize that centrally located individuals and like-minded group of people will more likely cause a change on the childhood-vaccination attitudes and will sustain a long-term change at 3 months follow-up, compared to randomly located people

Pathogenic and low-frequency variants in children with central precocious puberty

Background: Central precocious puberty (CPP) due to premature activation of GnRH secretion results in early epiphyseal fusion and to a significant compromise in the achieved final adult height. Currently, few genetic determinants of children with CPP have been described. In this translational study, rare sequence variants in MKRN3, DLK1, KISS1, and KISS1R genes were investigated in patients with CPP. Methods: Fifty-four index girls and two index boys with CPP were first tested by Sanger sequencing for the MKRN3 gene. All children found negative (n = 44) for the MKRN3 gene were further investigated by whole exome sequencing (WES). In the latter analysis, the status of variants in genes known to be related with pubertal timing was compared with an in-house Cypriot control cohort (n = 43). The identified rare variants were initially examined by in silico computational algorithms and confirmed by Sanger sequencing. Additionally, a genetic network for the MKRN3 gene, mimicking a holistic regulatory depiction of the crosstalk between MKRN3 and other genes was designed. Results: Three previously described pathogenic MKRN3 variants located in the coding region of the gene were identified in 12 index girls with CPP. The most prevalent pathogenic MKRN3 variant p.Gly312Asp was exclusively found among the Cypriot CPP cohort, indicating a founder effect phenomenon. Seven other CPP girls harbored rare likely pathogenic upstream variants in the MKRN3. Among the 44 CPP patients submitted to WES, nine rare DLK1 variants were identified in 11 girls, two rare KISS1 variants in six girls, and two rare MAGEL2 variants in five girls. Interestingly, the frequent variant rs10407968 (p.Gly8Ter) of the KISS1R gene appeared to be less frequent in the cohort of patients with CPP. Conclusion: The results of the present study confirm the importance of the MKRN3-imprinted gene in genetics of CPP and its key role in pubertal timing. Overall, the results of the present study have emphasized the importance of an approach that aligns genetics and clinical aspects, which is necessary for the management and treatment of CPP

Weight gain in early infancy impacts appetite regulation in the first year of life. A prospective study of infants living in Cyprus

BACKGROUND: Eating behaviour is associated with weight gain in infancy and childhood. Few studies found a bi-directional association between weight gain and eating behaviour development in childhood but there is little data on the association in early infancy, a period critical for the programming of obesity risk. OBJECTIVE: We investigated the bi-directional association between appetite traits and weight gain during the first year of life. METHODS: Participants were part of a cohort of 432 infants born in Cyprus. Appetite traits were measured using the BEBQ or the CEBQ at age 2-4 weeks, 6 and 12 months. Weight and length were collected at birth, 4 weeks, 6 and 12 months. Multivariable linear regression was used to analyse associations between appetite traits at 2-4 weeks and 6 months and weight for age Z-score change (WFAZC) between 4 weeks-6 months and 6-12 months. Associations were also analysed in the opposite direction, between WFAZC from birth to 4 weeks, 4 weeks to 6 months, 6-12 months and appetite traits at 4 weeks, 6 months and 12 months. RESULTS: Satiety responsive (SR) at 2-4 weeks was associated with lower WFAZC from 4 weeks to 6 months (β=-0.17; 95%CI: -0.30, -0.04) and SR at age 6 months was associated with lower WFAZC from 6 to 12 months (β=-0.09; 95%CI: -0.17, -0.02). WFAZC from 4 weeks to 6 months was associated with higher EF at 12 months (β=0.11; 95%CI: 0.01, 0.20), higher FR at 12 months (β=0.17; 95%CI: 0.04, 0.30) and lower SR at both 6 (β=-0.11; 95%CI: -0.21, -0.01) and 12 months (β=-0.14; 95%CI: -0.24, -0.03) CONCLUSIONS: We found a bi-directional association between weight gain and appetite traits in infancy, suggesting that the effect of postnatal weight gain on obesity development is partly mediated by programming of appetite traits

Pathogenic and Low-Frequency Variants in Children With Central Precocious Puberty

Background Central precocious puberty (CPP) due to premature activation of GnRH secretion results in early epiphyseal fusion and to a significant compromise in the achieved final adult height. Currently, few genetic determinants of children with CPP have been described. In this translational study, rare sequence variants in MKRN3, DLK1, KISS1, and KISS1R genes were investigated in patients with CPP Methods Fifty-four index girls and two index boys with CPP were first tested by Sanger sequencing for the MKRN3 gene. All children found negative (n = 44) for the MKRN3 gene were further investigated by whole exome sequencing (WES). In the latter analysis, the status of variants in genes known to be related with pubertal timing was compared with an in-house Cypriot control cohort (n = 43). The identified rare variants were initially examined by in silico computational algorithms and confirmed by Sanger sequencing. Additionally, a genetic network for the MKRN3 gene, mimicking a holistic regulatory depiction of the crosstalk between MKRN3 and other genes was designed. Results Three previously described pathogenic MKRN3 variants located in the coding region of the gene were identified in 12 index girls with CPP. The most prevalent pathogenic MKRN3 variant p.Gly312Asp was exclusively found among the Cypriot CPP cohort, indicating a founder effect phenomenon. Seven other CPP girls harbored rare likely pathogenic upstream variants in the MKRN3. Among the 44 CPP patients submitted to WES, nine rare DLK1 variants were identified in 11 girls, two rare KISS1 variants in six girls, and two rare MAGEL2 variants in five girls. Interestingly, the frequent variant rs10407968 (p.Gly8Ter) of the KISS1R gene appeared to be less frequent in the cohort of patients with CPP. Conclusion The results of the present study confirm the importance of the MKRN3-imprinted gene in genetics of CPP and its key role in pubertal timing. Overall, the results of the present study have emphasized the importance of an approach that aligns genetics and clinical aspects, which is necessary for the management and treatment of CPP