SIRT1 is involved in oncogenic signaling mediated by GPER in breast cancer.

A number of tumors exhibit an altered expression of sirtuins, including NAD+-dependent histone deacetylase silent information regulator 1 (SIRT1) that may act as a tumor suppressor or tumor promoter mainly depending on the tumor types. For instance, in breast cancer cells SIRT1 was shown to exert an essential role toward the oncogenic signaling mediated by the estrogen receptor-α (ERα). In accordance with these findings, the suppression of SIRT1 led to the inhibition of the transduction pathway triggered by ERα. As the regulation of SIRT1 has not been investigated in cancer cells lacking ER, in the present study we ascertained the expression and function of SIRT1 by estrogens in ER-negative breast cancer cells and cancer-associated fibroblasts obtained from breast cancer patients. Our results show that 17ß-estradiol (E2) and the selective ligand of GPER, namely G-1, induce the expression of SIRT1 through GPER and the subsequent activation of the EGFR/ERK/c-fos/AP-1 transduction pathway. Moreover, we demonstrate that SIRT1 is involved in the pro-survival effects elicited by E2 through GPER, like the prevention of cell cycle arrest and cell death induced by the DNA damaging agent etoposide. Interestingly, the aforementioned actions of estrogens were abolished silencing GPER or SIRT1, as well as using the SIRT1 inhibitor Sirtinol. In addition, we provide evidence regarding the involvement of SIRT1 in tumor growth stimulated by GPER ligands in breast cancer cells and xenograft models. Altogether, our data suggest that SIRT1 may be included in the transduction network activated by estrogens through GPER toward the breast cancer progression.

Prevalence of malocclusion in primary dentition in a population-based sample of Brazilian preschool children.

AIM: The purpose of the present study was to assess the prevalence of malocclusion in the primary dentition in a randomised representative sample of Brazilian preschool children. MATERIALS AND METHODS: A cross-sectional survey was carried out in Belo Horizonte, Brazil, involving 1069 male and female preschool children from 60 to 71 months of age, randomly selected from public and private preschools and daycare centers. A questionnaire addressing demographic data was sent to parents/guardians in order to characterise the sample. The oral examination of the children was performed by a single, previously calibrated dentist (kappa inter-examiner agreement value = 0.82). The criterion for the categorisation of malocclusion was at least one of the following conditions: posterior crossbite, overjet (> 2 mm), anterior crossbite, anterior open bite and deep overbite. Univariate analysis was performed using the SPSS software RESULTS: The prevalence of malocclusion was 46.2%. Deep overbite was the most prevalent alteration (19.7% of the sample). Posterior crossbite was diagnosed in 13.1% of the children; 10.5% had accentuated overjet; 7.9% had anterior open bite; and 6.7% had anterior crossbite. CONCLUSION: Malocclusion in primary dentition is becoming a significant problem. The prevalence in the present study was high, especially vertical and transversal malocclusions.

Predisposing factors for traumatic dental injuries in Brazilian preschool children.

AIM: The aim of the present study was to assess the prevalence of traumatic dental injury (TDI) in primary teeth and determine predisposing factors. MATERIALS AND METHODS: A cross-sectional study was carried out on 388 male and female Brazilian preschool children between 60 and 71 months of age. A questionnaire addressing demographic data and history of TDI was sent to parents/caregivers. Socioeconomic status was determined using the Social Vulnerability Index (SVI), family income, number of people in the household and parents/caregivers' schooling. The chi-square test was used for the statistical analysis. RESULTS: The prevalence of TDI was 62.1%; 61.7% of the teeth were affected by enamel fracture. Statistically significant associations were found between TDI and increased overjet [OR = 2.24, 95% CI = 1.11- 4.55] and anterior crossbite [OR = 0.38, 95% CI=0.17-0.87]. No statistically significant associations were found between TDI and number of people in the household, family income, social vulnerability, parents/caregivers' schooling, lip competence, overbite, anterior open bite and dental caries (p>0.05). CONCLUSION: The prevalence of TDI was high and enamel fracture was the most common sign of TDI. Children with an increased overjet suffer more TDIs. Socioeconomic factors had no influence over the prevalence of TDI.

Exposure to solvents in the shoe and leather goods industries.

The shoe and leather goods industries are two of the main economic sectors in Tuscany. Organic solvents are the most important risk factors responsible for leukaemias and polyneuropathies. Job exposure matrices for solvents have been developed with two different aims: to contribute to the general matrix in different industries involving exposure to solvents and to provide a data source for use by health professionals. The matrices have been constructed on the basis of: scientific literature, notices of chemical compositions of trade products, technical reports collected by local services, the survey of a sample of industries in the province of Florence.

Aplastic anemia, leukemia and other cancer mortality in a cohort of shoe workers exposed to benzene.

Benzene is a well documented carcinogen for the hematic and lymphopoietic system, and experimental research confirms its carcinogenicity for tumors of other sites. This report presents the results of a historical cohort study in a shoe manufacturing plant in Florence where cases of aplastic anemia and leukemia were reported in the 1960s. A total of 1008 men and 1005 women were considered eligible members of the cohort. For total mortality, comparing the rates of the cohort with the national rates, the standardized mortality ratio (SMR) was 79 for the women and 95 for the men. For the men excesses of risk for aplastic anemia [SMR 1566; 95% confidence interval (95% CI) 547-3264] and leukemia (SMR 400, 95% CI 146-870) were observed. The increased risk occurred among workers first employed during the period in which benzene was used, but the expected number of cases in the subsequent period was too small to evaluate whether any reduction in risk had occurred. No increasing pattern with duration of employment was discernible.

Making cooperative living work for psychiatric outpatients.

In the wake of deinstitutionalization, the exploration of alternative placements and living arrangements in the community has come to the fore. After describing a program for cooperative apartment living for female psychiatric outpatients, this article assesses the program's economic cost and its benefits to clients and outlines the authors' recommendations concerning future efforts to develop cooperative living programs.