Piccolipiù, a multicenter birth cohort in Italy: protocol of the study.

BACKGROUND: The fetal and infant life are periods of rapid development, characterized by high susceptibility to exposures. Birth cohorts provide unique opportunities to study early-life exposures in association with child development and health, as well as, with longer follow-up, the early life origin of adult diseases. Piccolipiù is an Italian birth cohort recently set up to investigate the effects of environmental exposures, parental conditions and social factors acting during pre-natal and early post-natal life on infant and child health and development. We describe here its main characteristics. METHODS/DESIGN: Piccolipiù is a prospective cohort of expected 3000 newborns, who will be recruiting in six maternity units of five Italian cities (Florence, Rome, Trieste, Turin and Viareggio) since October 2011. Mothers are contacted during pregnancy or at delivery and are offered to participate in the study. Upon acceptance, their newborns are recruited at birth and followed up until at least 18 years of age. At recruitment, the mothers donate a blood sample and complete a baseline questionnaire. Umbilical cord blood, pieces of umbilical cord and heel blood spots are also collected. Postnatal follow-up currently occurs at 6, 12, and 24 months of age using on-line or postal self administered questionnaire; further questionnaires and medical examinations are envisaged. Questionnaires collect information on several factors, including mother's and/or child's environmental exposures, anthropometric measures, reproductive factors, diet, supplements, medical history, cognitive development, mental health and socioeconomic factors. Health promotion materials are also offered to parents. DISCUSSION: Piccolipiù will broaden our understanding of the contribution of early-life factors to infant and child health and development. Several hypotheses on the developmental origins of health can be tested or piloted using the data collected from the Piccolipiù cohort. By pooling these data with those collected by other existing birth cohorts it will be possible to validate previous findings and to study rare exposures and outcomes.

Depressive symptoms in patients admitted to a semi-intensive stroke unit.

Aim of this study was to evaluate depressive symptoms in a semi-intensive Stroke Unit (SI-SU) by a scale specifically devised to assess depression in patients with stroke and to identify the symptoms better contributing to the early detection of post stroke depression (PSD). Fifty-four patients admitted to a SI-SU because of suffering from single, first-ever hemispheric stroke were enrolled. Depressive symptoms were assessed by the Post Stroke Depression Rating Scale (PSDRS). All patients were also evaluated by the National Institute of Health Stroke Scale (NIHSS), the modified Rankin scale, the Mini-Mental State Examination (MMSE) and the Frontal Assessment Battery (FAB). The PSDRS detected depressive symptoms in twenty-two patients (40%). The PSDRS scores were not influenced by severity of stroke, functional outcome, site of lesion and type of stroke. Three psychopathological factors were identified inside the PSDRS: "reactivity", "melancholic" and "apathetic", with significant inverse correlations with cognitive measures found only with the "apathetic" factor Less than one-half items of the PSDRS were able to identify overt depressive symptoms. Depressive symptoms are a frequent and early complication in patients referred to a SI-SU with the PSDRS being a suitable tool to detect depressive symptoms in acute phases of stroke.

Systemic effects of Heterobasidion annosum s.s. infection on severity of Diplodia pinea tip blight and terpenoid metabolism in Italian stone pine (Pinus pinea).

Three-year-old seedlings of Pinus pinea L. were inoculated near the stem base with one of two Heterobasidion annosum (Fr.) Bref. sensu stricto (s.s.) strains belonging to two populations: the North American P-group (NAm-P) and the European P-group (Eur-P). The NAm-P strain caused smaller H. annosum stem lesions than the Eur-P strain. Three weeks after the stem inoculations with H. annosum, apical shoots were inoculated with Diplodia pinea (Desmaz.) J. Kick. Basal stem infection with H. annosum resulted in D. pinea causing longer necrotic lesions in the shoots, indicating systemic induced susceptibility (SIS) to this shoot blight pathogen. Furthermore, stem induction with the NAm-P strain resulted in higher susceptibility to D. pinea than stem induction with the Eur-P strain. Total terpene accumulation was suppressed by about 50% in the shoots under attack by D. pinea when seedlings were induced with H. annosum. Total terpene concentration in shoots inoculated with D. pinea was negatively correlated with lesion size, both overall and by stem treatment. Stem base inoculation with H. annosum induced whole-plant changes in terpenoid profiles, but these were not associated with the SIS phenotype. We discuss our findings on modulation of systemic response of P. pinea to fungal attack in the context of tripartite ecological interactions.

Sphingosine kinase 1 overexpression is regulated by signaling through PI3K, AKT2, and mTOR in imatinib-resistant chronic myeloid leukemia cells.

OBJECTIVE: As a better understanding of the molecular basis of carcinogenesis has emerged, oncogene-specific cell-signaling pathways have been successfully targeted to treat human malignances. Despite impressive advances in oncogene-directed therapeutics, genetic instability in cancer cells often manifest acquired resistance. This is particularly noted in the use of tyrosine kinase inhibitors therapies and not more evident than for chronic myeloid leukemia. Therefore, it is of great importance to understand the molecular mechanisms affecting cancer cell sensitivity and resistance to tyrosine kinase inhibitors. MATERIALS AND METHODS: In this study, we used continuous exposure to stepwise increasing concentrations of imatinib (0.6-1 µM) to select imatinib-resistant K562 cells. RESULTS: Expression of BCR-ABL increased both at RNA and protein levels in imatinib-resistant cell lines. Furthermore, expression levels of sphingosine kinase 1 (SphK1) were increased significantly in resistant cells, channeling sphingoid bases to the SphK1 pathway and activating sphingosine-1-phosphate-dependent tyrosine phosphorylation pathways that include the adaptor protein Crk. The partial inhibition of SphK1 activity by N,N-dimethylsphingosine or expression by small interfering RNA increased sensitivity to imatinib-induced apoptosis in resistant cells and returned BCR-ABL to baseline levels. To determine the resistance mechanism-induced SphK1 upregulation, we used pharmacological inhibitors of the phosphoinositide 3-kinase/AKT/mammalian target of rapamycin signaling pathway and observed robust downmodulation of SphK1 expression and activity when AKT2, but not AKT1 or AKT3, was suppressed. CONCLUSIONS: These results demonstrate that SphK1 is upregulated in imatinib-resistant K562 cells by a pathway contingent on a phosphoinositide 3-kinase/AKT2/mammalian target of rapamycin signaling pathway. We propose that SphK1 plays an important role in development of acquired resistance to imatinib in chronic myeloid leukemia cell lines.