A multivariable analysis of patient dental satisfaction and oral health-related quality-of-life. A cross-sectional study based on DVSS and OHIP-14

Objective. The aim of this paper was to study the association between dental satisfaction and oral health-related quality-of-life (OHRQoL) when controlling for individual, clinical and psychological factors. Materials. Secondary analysis was conducted using data from a large study carried out in the Swedish region of Värmland in 2004. The questionnaire included demographic variables, clinical assessment and the following instruments: the Dental Visit Satisfaction Scale (DVSS), the short version of Oral Health Impact Profile (OHIP-14) and a modified version of the revised helping alliance questionnaire. Internal consistency analysis was undertaken on the instruments to assess reliability; bivariate comparisons were assessed to compare DVSS scores with individual factors (age, gender and education). In addition, a three step hierarchical multiple regression analysis was performed with DVSS as a dependent variable. Results. Data were completed for 485 randomly selected patients. The mean age of participants was 43.5 years, 54.6% were women,and 41.2% had high education. The median DVSS score was 48 (range 10–50) and the median OHIP was 3.0 (range 0–56). All the instruments showed good reliability. Bivariate analysis showed that females were more satisfied than males (p ≤ 0.01) and patients of 50 years or older were more satisfied than the younger ones (p ≤ 0.05). Finally, the following variables explained 31% of the variance of being very satisfied with dental visit: a good OHRQoL and patients' positive perceptions of the relationship with their care provider. Conclusion. This study showed positive associations between dental satisfaction and OHRQoL when controlling for related factors. The result suggests that care providers should take into account the various dimensions of OHRQoL rather than use only clinical measurements when they evaluate patient satisfaction.     

Perinatal Exposure to Bisphenol A or Diethylstilbestrol Increases the Susceptibility to Develop Mammary Gland Lesions After Estrogen Replacement Therapy in Middle-Aged Rats

The development of the mammary gland is a hormone-regulated event. Several factors can dysregulate its growth and make the gland more susceptible to cellular transformation. Among these factors, perinatal exposure to xenoestrogens and hormone replacement therapy has been associated with increased risk of developing breast cancer. Here, we assessed the effects induced by estrogen replacement therapy (ERT) in ovariectomized (OVX) middle-aged rats and whether perinatal exposure to diethylstilbestrol (DES) or bisphenol A (BPA) modified these effects in the mammary gland. Pregnant rats were orally exposed to vehicle, 5 μg DES/kg/day, or 0.5 or 50 μg BPA/kg/day from gestational day 9 until weaning. Then, 12-month-old offspring were OVX and treated with 17β-estradiol for 3 months. Morphological changes and the percentage of epithelial cells that proliferated or expressed estrogen receptor alpha (ESR1) and progesterone receptor (PR) were analyzed in mammary gland samples of 15-month-old animals. ERT induced lobuloalveolar hyperplasia and ductal cysts in the mammary gland of middle-aged rats, associated with a higher proliferation index of epithelial cells. Perinatal exposure to DES followed by ERT increased the number of cysts and induced the formation of fibroadenoma and ductal carcinoma in situ, without modifying the expression of ESR1 or PR. Also, after 3 months of ERT, BPA-exposed rats had a higher incidence of ductal hyperplasia and atypical lobular hyperplasia than animals under ERT alone. In conclusion, perinatal exposure to xenoestrogens increases the susceptibility of the mammary gland to develop cysts and hyperplastic lesions when confronted with ERT later in life.     

Melatonin down‐regulates MDM2 gene expression and enhances p53 acetylation in MCF‐7 cells

Compelling evidence demonstrated that melatonin increases p53 activity in cancer cells. p53 undergoes acetylation to be stabilized and activated for driving cells destined for apoptosis/growth inhibition. Over‐expression of p300 induces p53 acetylation, leading to cell growth arrest by increasing p21 expression. In turn, p53 activation is mainly regulated in the nucleus by MDM2. MDM2 also acts as E3 ubiquitin ligase, promoting the proteasome‐dependent p53 degradation. MDM2 entry into the nucleus is finely tuned by two different modulations: the ribosomal protein L11, acts by sequestering MDM2 in the cytosol, whereas the PI3K‐AkT‐dependent MDM2 phosphorylation is mandatory for MDM2 translocation across the nuclear membrane. In addition, MDM2‐dependent targeting of p53 is regulated in a nonlinear fashion by MDM2/MDMX interplay. Melatonin induces both cell growth inhibition and apoptosis in MCF7 breast cancer cells. We previously reported that this effect is associated with reduced MDM2 levels and increased p53 activity. Herein, we demonstrated that melatonin drastically down‐regulates MDM2 gene expression and inhibits MDM2 shuttling into the nucleus, given that melatonin increases L11 and inhibits Akt‐PI3K‐dependent MDM2 phosphorylation. Melatonin induces a 3‐fold increase in both MDMX and p300 levels, decreasing simultaneously Sirt1, a specific inhibitor of p300 activity. Consequently, melatonin‐treated cells display significantly higher values of both p53 and acetylated p53. Thus, a 15‐fold increase in p21 levels was observed in melatonin‐treated cancer cells. Our results provide evidence that melatonin enhances p53 acetylation by modulating the MDM2/MDMX/p300 pathway, disclosing new insights for understanding its anticancer effect.