MED1 is a base excision repair enzyme that interacts with the mismatch repair protein MLH1 and maintains genomic integrity by binding methylated DNA and repairing spontaneous deamination events. MED1 mutations have been associated with microsatellite instability and accelerated colorectal cancer (CRC) tumorigenesis. We propose that promoter methylation may serve as an alternative epigenetic mechanism for MED1 gene suppression during sporadic CRC tumorigenesis. Methylation status of the MED1 promoter was investigated in a panel of ovarian and colorectal cancer cell lines. The MED1 promoter region was sequenced following bisulfite treatment and sequence analysis identified a CpG island within the MED1 promoter which is frequently and preferentially methylated (≥ 50%) in ovarian and colorectal cancer cell lines with low/reduced MED1 expression. In vitro reversal of methylation restored MED1 expression. In colorectal cancer patients, when MED1 methylation was present, both tumor and matched mucosa were affected equally (mean frequency of methylation 24%) and there was no correlation between methylation and tumor stage. Patients without history of CRC showed significantly lower frequency of methylation (mean 14%, p<0.05). Decreased MED1 transcript levels were observed in matched normal mucosa when compared to controls (median fold difference 8.0). Additional decreased expression was seen between mucosa and matched tumor (median fold decrease 4.4). Thus, MED1 promoter methylation and gene silencing occur in sporadic CRC patients and represent an early event in CRC tumorigenesis. Detection of MED1 methylation and gene suppression in normal colon mucosa may contribute to identifying patients at higher risk of developing CRC during screening procedures.

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The main findings of the project indicate that using a process that encourages staff involvement in identification of issues and actions can facilitate change in the practice of resident care. The action research groups identified specific gaps in knowledge and skill leading to targeted education that addressed areas of need. The importance of presenting information and learning opportunities for staff in a variety of formats was also recognized, as was the importance of organizational context, management support and empowerment of staff to make change.

School mental health practitioners, including social workers, are mandated through federal, state, and professional entities to provide evidence-based practices to students. Nevertheless, rates of use of evidence-based practices among mental health professionals in schools remain low, even as knowledge about effective practices increases. This study aimed to further knowledge about how to promote and support the use of evidence-based practices among school practitioners using online technology. School social workers attending a summer professional development event took part in focus groups exploring (a) their current perceptions of evidence-based practices, (b) their experiences finding evidence-based practice information online, and (c) their preferences for the formatting and content of online resources. Participants described a willingness to use evidence-based practice, efforts to find information, and difficulties encountered with online sources. Preferences for readily available, searchable, brief, and understandable online information were expressed. Implications for meeting the needs of school social workers with online resources are discussed.