The cell cycle inhibitor, p16INK4a may be a useful surrogate biomarker of cervical intraepithelial neoplasia (CIN); however, there is currently no consensus of p16INK4a genetic alterations throughout the multiple step process of CIN. Our goal was to identify the methylation frequency of p16INK4a in each step of CIN that is associated with human papillomavirus (HPV) infection, using several different detection methods of p16INK4a methylation to correlate the data. The present study included a total of 43 patients, including 38 with CIN, and 5 normal patients. Three different methods were used to detect hypermethylation of CpG islands, methylation-specific PCR (MSP) amplification of different primer sets of M1, M2, and M3, pyrosequencing of each forward primer region, and immunohistochemistry of p16INK4a. Analysis of MSP showed that 20 of the 38 CIN patients (52.6%) revealed hypermethylation in at least 1 primer set of the p16INK4a promoter. A complete loss of p16INK4a protein expression was observed in 11 cases (28.9%). There was no observed association of methylation of the p16INK4a gene with either CIN grading (P=0.0698) or HPV status (P=0.2811): specifically 42.9% (3/7) was found in CIN 1, 57.1% (8/14) in CIN 2, and 52.9% (9/17) in CIN 3. In concordance with immunohistochemistry results, hypermethylation of the p16INK4a promoter was significantly correlated with a lack of p16 protein expression (P=0.0145). All positive peaks from pyrosequencing matched the MSP results, which ranged from 6.3% to 24.5%. In conclusion, p16INK4a gene silencing during CIN was not determined to be a particularly rare event; however, it does not correlate with either HPV status or CIN grading.

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This study examined whether the well-established racial/ethnic differences in mental health service utilization among individuals with mental illness are reflected in the treatment utilization patterns of individuals experiencing both mental illness and substance use disorders, particularly in regards to the use of contemporaneous mental health and substance abuse treatment. Using pooled data from the National Survey on Drug Use and Health (2009-2013), the patterns of mental health and substance use treatment utilization of 8748 White, Black, or Latino individuals experiencing both mental illness and substance use disorders were analyzed. Multinomial logistic regression was conducted to test the relationships among racial/ethnic groups and the receipt of contemporaneous treatment, mental health treatment alone, and substance use treatment alone as compared with no treatment utilization. Results indicated that Black and Latino respondents were less likely to receive contemporaneous treatment than Whites respondents. Also, significantly associated with outcomes were several interactions between race/ethnicity and predisposing, need and enabling factors known to be associated with service utilization. The findings suggest that an underlying mechanism of racial/ethnic differences among individuals with co-occurring mental illness and substance use disorders in the treatment utilization may differ by the specific types of treatment and between Blacks and Latinos. Therefore, efforts to reduce these disparities should consider specialty in each treatment settings and heterogeneity within diverse racial/ethnic groups.

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