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Background: Knee osteoarthritis (OA) causes functional limitation and disability in the elderly. Vitamin D has biological functions on multiple knee joint structures and can play important roles in the progression of knee OA. The metabolism of vitamin D is regulated by PTH. Objective: The objective is to investigate whether serum concentrations of 25(OH)D and PTH, individually and jointly, predict the progression of knee OA. Methods: Serum 25(OH)D and PTH were measured at the 30- or 36-mo visit in 418 participants enrolled in the Osteoarthritis Initiative (OAI) who had ≥1 knee with symptomatic and radiographic knee OA. Progression of knee OA was defined as any increase in the radiographic joint space narrowing (JSN) score between the 24- and 48-mo OAI visits. Results: The mean concentrations of serum 25(OH)D and PTH were 26.2 µg/L and 54.5 pg/mL, respectively. Approximately 16% of the population had serum 25(OH)D < 15 µg/L. Between the baseline and follow-up visits, 14% progressed in JSN score. Participants with low vitamin D [25(OH)D < 15 µg/L] had >2-fold elevated risk of knee OA progression compared with those with greater vitamin D concentrations (≥15 µg/L; OR: 2.3; 95% CI: 1.1, 4.5). High serum PTH (≥73 pg/mL) was not associated with a significant increase in JSN score. However, participants with both low vitamin D and high PTH had >3-fold increased risk of progression (OR: 3.2; 95%CI: 1.2, 8.4). Conclusion: Our results suggest that individuals deficient in vitamin D have an increased risk of knee OA progression. [ABSTRACT FROM AUTHOR]

The overexpression of P-glycoprotein (P-gp) causes resistance to chemotherapy in human ovarian cancer. However, the underlying mechanism remains unclear. In the present study, we showed that, at membrane-bound protein level, P-gp was 'shared' between human ovarian cancer cells by the intercellular transfer of microvesicles (MVs). Paclitaxel-resistant human ovarian cancer cells (A2780/PTX) readily formed and released P-gp-containing MVs into the extracellular space compared with the wild-type parental line (A2780/WT). Shedding MVs bound to the chemosensitive A2780/WT cells in a time- and dose-dependent manner, transferring P-gp via the microenvironment. MV-mediated transfer of P-gp led to redistribution of the chemotherapeutic drug adriamycin in recipient cells (A2780/WT), which displayed 5- and 5-fold higher resistance to adriamycin and paclitaxel, respectively. Thus, these findings demonstrate a new mechanism of drug-resistance acquisition via MVs. [ABSTRACT FROM AUTHOR]

Animal studies have provided direct evidence that dietary factors induce changes in DNA methylation patterns. In humans, studies on diet and DNA methylation have yielded inconsistent findings. Because humans tend to consume foods and nutrients that are highly interrelated, study of dietary patterns may have improved the power of detecting the effect of diet on DNA methylation. Using data collected from 149 participants aged 45-75 yin the North Texas Healthy Heart Study, we examined the relationship between dietary patterns and levels of genomic DNA methylation in peripheral blood leukocytes. Dietary data were collected from study participants using the Block FFQ. Genomic DNA methylation was measured using bisulfite conversion of DNA and real-time PCR (MethyLight) for LINE'l. Two dietary patterns were identified using factor analysis: a "prudent" dietary pattern characterized by a high intake of vegetables and fruits, and a "Western" dietary pattern characterized by a high intake of meats, grains, dairy, oils, and potatoes. The prudent dietary pattern was associated with a lower prevalence of DNA hypomethylation (Q4 vs. Q1 OR = 0.33, 95% Cl: 0.12-0.92) and the association was dose dependent (P-trend = 0.041. There was no apparent association between the Western dietary pattern and global leukocyte DNA methylation (Q4 vs. Q1 OR = 1.28, 95% Cl: 0.47-3.47; P-trend = 0.55). Thus, a dietary pattern characterized by a high intake of vegetables and fruits may protect against global DNA hypomethylation. Future studies with a larger sample size need to confirm that this association holds longitudinally. [ABSTRACT FROM AUTHOR]

PURPOSE: We hypothesized that major American dietary patterns are associated with risk for age-related macular degeneration (AMD). DESIGN: Cross-sectional study. METHODS: We classified 8103 eyes in 4088 eligible participants in the baseline Age-Related Eye Disease Study (AREDS). They were classified into control (n = 2739), early AMD (n = 4599), and advanced AMD (n = 765) by the AREDS AMD Classification System. Food consumption data were collected by using a 90-item food frequency questionnaire. RESULTS: Two major dietary patterns were identified by factor (principal component) analysis based on 37 food groups and named Oriental and Western patterns. The Oriental pattern was characterized by higher intake of vegetables, legumes, fruit, whole grains, tomatoes, and seafood. The Western pattern was characterized by higher intake of red meat, processed meat, high-fat dairy products, French fries, refined grains, and eggs. We ranked our participants according to how closely their diets line up with the 2 patterns by calculating the 2 factor scores for each participant. For early AMD, multivariate-adjusted odds ratio (OR) from generalized estimating equation logistic analysis comparing the highest to lowest quintile of the Oriental pattern score was ORE5O = 0.74 (95% confidence interval (CI): 0.59-0.91; Ptrend = 0.01), and the OR comparing the highest to lowest quintile of the Western pattern score was ORE5W = 1.56 (1.18-2.06; Ptrend = 0.01). For advanced AMD, the ORA5O was 0.38 (0.27- 0.54; Ptrend < 0.0001), and the ORA5W was 3.70 (2.31-5.92; Ptrend < 0.0001). CONCLUSIONS: Our data indicate that overall diet is significantly associated with the odds of AMD and that dietary management as an AMD prevention strategy warrants further study. [ABSTRACT FROM AUTHOR]