The effect of transmucosal 0.2mg/kg Midazolam premedication on dental anxiety, anaesthetic induction and psychological morbidity in children undergoing general anaesthesia for tooth extraction

<b>Background:</b> The project aims were to evaluate the benefit of transmucosal Midazolam 0.2mg/kg pre-medication on anxiety, induction behaviour and psychological morbidity in children undergoing general anaesthesia (GA) extractions. <b>Method:</b> 179 children aged 5-10 years (mean 6.53 years) participated in this randomised, double blind, placebo controlled trial. Ninety children had Midazolam placed in the buccal pouch. Dental anxiety was recorded pre operatively and 48 hours later using a child reported MCDAS-FIS scale. Behaviour at anaesthetic induction was recorded and psychological morbidity was scored by the parent using the Rutter Scale pre-operatively and again one-week later. Subsequent dental attendance was recorded at one, three and six months after GA. <b>Results:</b> Whilst levels of mental anxiety did not reduce overall, the most anxious patients demonstrated a reduction in anxiety after receiving midazolam premedicationmay (p=0.01). Neither induction behaviour nor psychological morbidity improved. Irrespective of group, parents reported less hyperactive (p= 0.002) and more prosocial behaviour (p=0.002) after the procedure:;, older children improved most (p=0.048), Post GA Dental attendance was poor and unrelated to after the procedure and unaffected by premedication. <b>Conclusion:</b> 0.2mg/kg buccal Midazolam provided some evidence for reducing anxiety in the most dentally anxious patients. However, induction behaviour, psychological morbidity and subsequent dental attendance were not found to alter between the premedication groups

FOXA1 repression is associated with loss of BRCA1 and increased promoter methylation and chromatin silencing in breast cancer

FOXA1 expression correlates with the breast cancer luminal subtype and patient survival. RNA and protein analysis of a panel of breast cancer cell lines revealed that BRCA1 deficiency is associated with the downregulation of FOXA1 expression. Knockdown of BRCA1 resulted in the downregulation of FOXA1 expression and enhancement of FOXA1 promoter methylation in MCF-7 breast cancer cells, whereas the reconstitution of BRCA1 in Brca1-deficent mouse mammary epithelial cells (MMECs) promoted Foxa1 expression and methylation. These data suggest that BRCA1 suppresses FOXA1 hypermethylation and silencing. Consistently, the treatment of MMECs with the DNA methylation inhibitor 5-aza-2'-deoxycitydine induced Foxa1 mRNA expression. Furthermore, treatment with GSK126, an inhibitor of EZH2 methyltransferase activity, induced FOXA1 expression in BRCA1-deficient but not in BRCA1-reconstituted MMECs. Likewise, the depletion of EZH2 by small interfering RNA enhanced FOXA1 mRNA expression. Chromatin immunoprecipitation (ChIP) analysis demonstrated that BRCA1, EZH2, DNA methyltransferases (DNMT)1/3a/3b and H3K27me3 are recruited to the endogenous FOXA1 promoter, further supporting the hypothesis that these proteins interact to modulate FOXA1 methylation and repression. Further co-immunoprecipitation and ChIP analysis showed that both BRCA1 and DNMT3b form complexes with EZH2 but not with each other, consistent with the notion that BRCA1 binds to EZH2 and negatively regulates its methyltransferase activity. We also found that EZH2 promotes and BRCA1 impairs the deposit of the gene silencing histone mark H3K27me3 on the FOXA1 promoter. These associations were validated in a familial breast cancer patient cohort. Integrated analysis of the global gene methylation and expression profiles of a set of 33 familial breast tumours revealed that FOXA1 promoter methylation is inversely correlated with the transcriptional expression of FOXA1 and that BRCA1 mutation breast cancer is significantly associated with FOXA1 methylation and downregulation of FOXA1 expression, providing physiological evidence to our findings that FOXA1 expression is regulated by methylation and chromatin silencing and that BRCA1 maintains FOXA1 expression through suppressing FOXA1 gene methylation in breast cancer.Oncogene advance online publication, 22 December 2014; doi:10.1038/onc.2014.421.published_or_final_versio

Socioeconomic and demographic predictors of selected cardiovascular risk factors among adults living in Pohnpei, Federated States of Micronesia

Background The burden of cardiovascular disease (CVD) is increasing in low-to-middle income countries (LMIC). Although strong evidence for inverse associations between socioeconomic position and health outcomes in high-income countries exists, less is known about LMIC. Understanding country-level differences is critical to tailoring effective population health policy and interventions. We examined the association of socioeconomic position and demographic characteristics in determining CVD risk factors among adults living in Pohnpei, Federated States of Micronesia. Methods We used data from the cross-sectional World Health Organization’s STEPwise approach to surveillance 2002 Pohnpei dataset and logistic regression analyses to examine the association of socioeconomic position (education, income, employment) and demographics (age, sex) with selected behavioral and anthropometric CVD risk factors. The study sample consisted of 1638 adults (642 men, 996 women; 25–64 years). Results In general, we found that higher education (≥13 years) was associated with lower odds for daily tobacco use (odds ratio [OR]: 0.46, confidence interval [CI]: 0.29–0.75, p = 0.004) and low physical activity (OR: 0.55, CI: 0.34–0.87, p = 0.027). Men had over three times the odds of daily tobacco use than women (OR: 3.18, CI: 2.29–4.43, p  $10,000 was associated with over twice the odds of high blood pressure (BP) (OR: 2.24, CI: 1.43–3.51, p = 0.003), versus lower-income (<$5,000). Men had over twice the odds of high BP (OR: 2.01, CI: 1.43–2.83, p < 0.001) than women. Paid employment nearly doubled the odds of central obesity with the magnitude of association increasing by more than 20% adjusted for sex and age. Men reporting paid employment had three times the odds of central obesity (OR: 3.00, CI: 1.56–5.78, p < 0.001) than those unemployed. Conclusion Our analysis revealed associations between socioeconomic position and selected CVD risk factors, which varied by risk-factor, sex and age characteristics, and direction of association. The 2002 Pohnpei dataset provides country-level baseline information; further population health surveillance might define trends. Stronger country-level data might help decision-makers tailor population-based prevention strategies