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Michael Crone,1,2 Kelly Hallman,1,2 Victoria Lloyd,1,2 Monica Szmyd,1,2 Briana Badamo,1,2 Mia Morse,1,2 Sumi Dinda1,2 1Department of Biomedical Diagnostic and Therapeutic Sciences, School of Health Sciences, Oakland University, Rochester, MI 48309-4476, USA; 2Institute for Stem Cell and Regenerative Medicine and Center of Biomedical Sciences, Oakland University, Rochester, MI 48309-4476, USA Background: Black cohosh (BC) is an herbal remedy often used by women to treat symptoms associated with menopause. Research has shown that the molecular activity of BC is associated with estrogen receptor alpha (ER-α) regulation. Progesterone receptor (PR) expression is found to be consistent with ER expression and mutations in the BRCA1 gene, a tumor-suppressor gene, are known to be responsible for about 40%–45% of hereditary breast cancers. Purpose: The objective of this study was to determine the effects of BC alone, as well as in combination with hormones and antihormones, on cell viability and expression of ER-α, PR, and BRCA1 in both T-47D and MCF-7 cell lines. Methods: Cells were cultured in charcoal-stripped serum prior to their treatment and subsequent protein extraction. Western blot analyses were performed following a Bio-Rad Bradford protein assay and SDS-PAGE gel electrophoresis, with ECL luminescence and Image Studio Lite software. Cellular viability assays were performed using propidium iodine (PI) staining, and the distribution of fluorescent structures was evaluated through confocal microscopy. RT-qPCR analysis was performed on extracted cellular RNA. All statistical analyses were performed using SPSS software, and data was subjected to Kruskal-Wallis testing, followed by post-hoc analysis using the Mann-Whitney U-test to determine the statistical significance of all findings. Results: Western blot analysis displayed significant alterations of ER-α, PR, and BRCA1 protein levels after 24-hour treatment with 80–500 μM BC. BC displayed a concentration-dependent decrease on ER-α and BRCA1 expression, with an 87% reduction of ER-α expression and a 43% of BRCA1 expression in T-47D cells compared to control. After six days of treatment with 400 μM BC, a 50% decrease in cell proliferation was observed. Following 24 hours of co-treatment with 400 μM BC and 10 nM E2, ER-α was downregulated by 90% and BRCA1 expression was reduced by 70% compared to control. The expression of PR, following the same treatment, exhibited similar effects. The proliferative effect of E2 was reduced in the presence of BC. Conclusion: Black Cohosh demonstrates substantial anti-cancer properties, and this study may significantly aid in the understanding of the molecular effects of BC on ER-α, PR, and BRCA1 in breast cancer cells. Keywords: tumor suppressor, MCF-7, T-47D, antitumor agent, natural anticancer, cancer treatment

Several intersectoral community approaches targeting childhood obesity (IACOs) have been launched in the Netherlands. Translation of these approaches into practice is however arduous and implementation. We therefore studied the implementation of five IACOs in the Netherlands for one-and-a-half years. IACO implementation was evaluated via an adapted version of the MIDI questionnaire, consisting of 18 theory-based constructs. A response rate of 62% was obtained. A hierarchical multivariate linear regression model was used to analyse our data; the final regression model predicted 65% of the variance in adherence. Higher levels of self-efficacy, being an implementer embedded in community B, and having more than 1 year of experience with IACO implementation were associated with higher degrees of adherence. Formal ratification of implementation by management and being prescribed a higher number of activities were related to lower degrees of adherence. We advise that, when designing implementation strategies, emphasis should be placed on the enhancement of professionals' self-efficacy, limitation of the number of activities prescribed and allocation of sufficient time to get acquainted and experienced with IACO implementation. Longitudinal studies are needed to further evaluate interaction between and change within critical determinants while progressing through the innovation process.

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.

The Canadian Neuromuscular Disease Registry (CNDR) is a pan-neuromuscular disease registry that prospectively collects spinal muscular atrophy (SMA)-specific data in 32 clinics across Canada. The CNDR captures a comprehensive SMA dataset to evaluate long-term real-world experience with available and emerging therapies. The objective of this study is to describe real-world data from the CNDR-SMA patient population. The CNDR has 417 SMA patients registered, 207 adult patients (170 with clinical data) and 198 pediatric patients (181 with clinical data). This represents a large percentage of expected Canadians with SMA. Of those with complete data, Median age is 37 (18-80) for adults, and 9 (1-17) for pediatric patients. 243 (66%) patients have SNM2 copy number reported, 69 (28%) have 2 copies, 134 (55%) have 3 copies, 38 (16%) have 4 copies, and 119 are unknown/not reported. 93 (26%) patients are ambulatory. There are three disease modifying therapies (DMTs) approved for the treatment of SMA: risdiplam, nusinersen, and onasemnogene abeparvovec that all showed efficacy in clinical trials. Real-world effectiveness must be assessed across a broader range of patients presenting with variable comorbidities and disease severity. The CNDR collects DMT-specific real-world data to contextualize the effects of DMTs and to further access to treatment options in Canada. DMT's are differentially accessible across Canada, based on reimbursement recommendations of provincial payers. DMT use has been reported in 222 CNDR SMA patients: 184 on nusinersen, 41 on risdiplam, 36 on zolgensma (152 pediatric, and 71 adult), and 75 with no DMT use. In conclusion, the CNDR captures a comprehensive SMA dataset that prospectively evaluates real-world data, supporting post-marketing surveillance of novel therapies in Canada. Analysis is ongoing and available longitudinal follow-up data will be presented with descriptive statistics for both naive and DMT patients. [ABSTRACT FROM AUTHOR]

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This meta-analysis focuses on parent training programs for ethnic minority families and reports on (i) the adaptation of program content and (ii) the process that informs these adaptations. Relevant studies are reviewed to determine the adaptations made and the impact of the adaptations on parenting and child outcomes. Studies were eligible for inclusion if they enrolled predominantly ethnic minority parents with children aged 0-12 years, used a randomized controlled trial design with post-intervention assessments, focused on group-based parent training programs and on prevention of parenting problems, and reported parenting behavior outcomes. A total of 18 studies were included in the analysis. The results show that parent training programs targeting ethnic minority parents have a small but significant effect on improving parenting behavior (k = 18, Cohen's d = 0.30), child outcomes (k = 16, Cohen's d = 0.13), and parental perspectives (k = 8, Cohen's d = 0.19). Most of the programs made adaptations related to surface and deep structure sensitivity. Programs with cultural adaptations, especially deep structure sensitivity (k = 7, Cohen's d = 0.54), are more effective in improving parenting behavior. Because only a third of the included studies provided details on the processes that guided the adaptations made, additional studies are needed to provide information on the process of adaptation; this will enable others to learn from the procedures that can be undertaken to culturally adapt interventions. [ABSTRACT FROM AUTHOR]

We have previously shown that bone density (BD) is significantly reduced (with a T score Forty one typical CD patients (31 females, mean age 48) and 18 screened CD patients [...]