BackgroundMammary microcalcifications have a crucial role in breast cancer detection, but the processes that induce their formation are unknown. Moreover, recent studies have described the occurrence of the epithelial–mesenchymal transition (EMT) in breast cancer, but its role is not defined. In this study, we hypothesized that epithelial cells acquire mesenchymal characteristics and become capable of producing breast microcalcifications.MethodsBreast sample biopsies with microcalcifications underwent energy dispersive X-ray microanalysis to better define the elemental composition of the microcalcifications. Breast sample biopsies without microcalcifications were used as controls. The ultrastructural phenotype of breast cells near to calcium deposits was also investigated to verify EMT in relation to breast microcalcifications. The mesenchymal phenotype and tissue mineralization were studied by immunostaining for vimentin, BMP-2, β2-microglobulin, β-catenin and osteopontin (OPN).ResultsThe complex formation of calcium hydroxyapatite was strictly associated with malignant lesions whereas calcium-oxalate is mainly reported in benign lesions. Notably, for the first time, we observed the presence of magnesium-substituted hydroxyapatite, which was frequently noted in breast cancer but never found in benign lesions. Morphological studies demonstrated that epithelial cells with mesenchymal characteristics were significantly increased in infiltrating carcinomas with microcalcifications and in cells with ultrastructural features typical of osteoblasts close to microcalcifications. These data were strengthened by the rate of cells expressing molecules typically involved during physiological mineralization (i.e. BMP-2, OPN) that discriminated infiltrating carcinomas with microcalcifications from those without microcalcifications.ConclusionsWe found significant differences in the elemental composition of calcifications between benign and malignant lesions. Observations of cell phenotype led us to hypothesize that under specific stimuli, mammary cells, which despite retaining a minimal epithelial phenotype (confirmed by cytokeratin expression), may acquire some mesenchymal characteristics transforming themselves into cells with an osteoblast-like phenotype, and are able to contribute to the production of breast microcalcifications.

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Classification of mammary microcalcifications is based on radiological and histological characteristics that are routinely evaluated during the diagnostic path for the identification of breast cancer, or in patients at risk of developing breast cancer. The main aim of this study was to explore the relationship between the imaging parameters most commonly used for the study of mammary microcalcifications and the corresponding histological and chemical properties. To this end, we matched the radiographic characteristics of microcalcifications to breast lesion type, histology of microcalcifications and elemental composition of microcalcifications as obtained by energy dispersive x ray (EDX)-microanalysis. In addition, we investigated the properties of breast cancer microenvironment, under the hypothesis that microcalcification formation could result from a mineralization process similar to that occurring during bone osteogenesis. In this context, breast lesions with and without microcalcifications were compared in terms of the expression of the main molecules detected during bone mineralization (BMP-2, BMP-4, PTX3, RANKL OPN and RUNX2). Our data indicate that microcalcifications classified by mammography as "casting type" are prevalently made of hydroxyapatite magnesium substituted and are associated with breast cancer types with the poorest prognosis. Moreover, breast cancer cells close to microcalcifications expressed higher levels of bone mineralization markers as compared to cells found in breast lesions without microcalcifications. Notably, breast lesions with microcalcifications were characterized by the presence of breast-osteoblast-like cells. In depth studies of microcalcifications characteristics could support a new interpretation about the genesis of ectopic calcification in mammary tissue. Candidating this phenomenon as an integral part of the tumorigenic process therefore has the potential to improve the clinical management of patients early during their diagnostic path.

Evaluation of seasonal influences on ambulatory blood pressure monitoring (ABPM) values in a very large population living in a mild-climate geographic area.Methods: Among patients referred to our Hypertension Center between September 2002 and January 2011 with a reliable ABPM, we considered those in the two hottest (July and August) vs. those in the two coldest (January and February) months.Results: Seven hundred and forty-two men (53.2%) and 653 women (46.8%) were studied; 1245 (89.3%) were hypertensive patients of which 795 (63.9%) were drugtreated. In winter, mean daytime SBP and DBP were higher (P ¼ 0.001 and P < 0.001, respectively), but only 24-h DBP was significantly higher (P ¼ 0.012). On the contrary, higher night-time SBP and pulse pressure were recorded in summer (P ¼ 0.005 and P ¼ 0.023, respectively). Uncontrolled hypertensive patients had the highest mean difference between winter and summer night-time SBP (127.1 AE 13.4 vs. 131.0 AE 12.6 mmHg; P ¼ 0.001). In winter a dipping pattern was prevalent (58.2%), whereas in summer a nondipping pattern prevailed (61.9%; P < 0.001). Isolated nocturnal hypertension (INH) was present in 9.8% in winter vs. 15.2% in summer (P ¼ 0.003). Conclusion:Our data on a very large ABPM sample confirmed that hottest summer months are associated with lower daytime BP and also lower 24-h DBP. However, we found an inverse relationship regarding night-time BP, dipping pattern, and INH that were higher or more common in summer. These findings were even more evident in treated patients, especially when not at target. Different sleeping behaviors or improper dose reduction of drug therapy in summer may explain the findings.

Older adults use the ED appropriately also in Italy. Trauma with complications (fracture) and various presenting complaints underlying medical problems accounted for more than 50 % of ED visits and hospital admissions.