Identification of histone deacetylase inhibitors with (arylidene)aminoxy scaffold active in uveal melanoma cell lines

Uveal melanoma (UM) represents an aggressive type of cancer and currently, there is no effective treatment for this metastatic disease. In the last years, histone deacetylase inhibitors (HDACIs) have been studied as a possible therapeutic treatment for UM, alone or in association with other chemotherapeutic agents. Here we synthesised a series of new HDACIs based on the SAHA scaffold bearing an (arylidene)aminoxy moiety. Their HDAC inhibitory activity was evaluated on isolated human HDAC1, 3, 6, and 8 by fluorometric assay and their binding mode in the catalytic site of HDACs was studied by molecular docking. The most promising hit was the quinoline derivative VS13, a nanomolar inhibitor of HDAC6, which exhibited a good antiproliferative effect on UM cell lines at micromolar concentration and a capability to modify the mRNA levels of HDAC target genes similar to that of SAHA

Maternal-foetal attachment independently predicts the quality of maternal-infant bonding and post-partum psychopathology

Purpose: The aim of this study was to evaluate the association of maternal antenatal attachment and post-partum psychopathology, maternal–infant bonding, while checking for antenatal psychopathology, for lifetime psychiatric diagnosis and for the known risk factors for peripartum depression. Methods: One hundred and six women recruited at the first month of pregnancy (T0) were evaluated with the structured interview for DSM-IV TR (SCID-I) to assess the presence of lifetime psychiatric diagnosis and with the Perinatal Depression Predictor Inventory-Revised (PDPI-R), the Edinburgh Postnatal Depression Scale (EPDS), and the State–Trait Anxiety Inventory (STAI). At the sixth month of pregnancy (T1) and at the first month post-partum (T2), all patients were evaluated with the PDPI-R, the EPDS, the STAI, at T1, with the Maternal Antenatal Attachment Scale (MAAS), and at T2 with the Maternal Postnatal Attachment Scale (MPAS). Results: Multivariate regression analyses showed that maternal–foetal attachment was the variable most significantly associated with postnatal symptoms of depression and anxiety and with quality of maternal-infant attachment. The logistic regression analyses showed that antenatal attachment may predict postnatal depressive and anxiety symptoms (respectively, OR: 0.83–IC [0.74 − 0.95], p =.005, OR: 0.88–IC [0.79 − 0.98], p =.02), and the quality of maternal postnatal attachment (OR: 1.17–IC [1.08 − 1.27], p <.001), also after taking into account the known risk factors for perinatal depression, the sociodemographic variables and lifetime psychiatric diagnosis. Conclusion: The quality of maternal–foetal bonding may independently predict the quality of maternal–infant attachment and post-partum depressive and anxiety symptoms. A comprehensive assessment of maternal risk factors for perinatal psychopathology during pregnancy should include the evaluation of antenatal attachment that could be modifiable by specific interventions promoting the quality of maternal bonding

Two-step analytical procedure for the characterization and quantification of metal soaps and resinates in paint samples

Metal soaps and resinates are known to be spontaneously formed in artistic paintings, as a product of the reaction between aliphatic and terpenoid acids released by hydrolysis and oxidation of the organic media and certain cations contained in some inorganic pigments. In this paper we present an optimization and the validation of a GC/MS method for the qualitative and quantitative analysis of mixtures of terpenoid acids and aliphatic mono and dicarboxylic acids and metal carboxylates of terpenoid and aliphatic mono and dicarboxylic acids in the same paint microsample. This is based on a two-step analytical approach entailing the subsequent use of two silylating agents, N,O-bis(trimethylsilyl)trifluoroacetamide for the analysis of free acids and metal carboxylates, and 1,1,1,3,3,3-hexamethyldisilazane for the analysis of free acids. The application of this approach is possible because of the good stability at room temperature of the TMS derivatives of aliphatic and terpenoid species, characterized by high boiling points and relatively low vapour pressures. The method was then applied to the characterization of samples collected from two reference paint layers aged for 20 years, a paint sample taken from a pulpit, and sample of the varnish coating of a wooden writing desk, both from the second half of the seventeenth century

Women's Preferences for Treatment of Perinatal Depression and Anxiety : A Discrete Choice Experiment

Perinatal depression and anxiety (PNDA) are an international healthcare priority, associated with significant short- and long-term problems for women, their children and families. Effective treatment is available but uptake is suboptimal: some women go untreated whilst others choose treatments without strong evidence of efficacy. Better understanding of women's preferences for treatment is needed to facilitate uptake of effective treatment. To address this issue, a discrete choice experiment (DCE) was administered to 217 pregnant or postnatal women in Australia, who were recruited through an online research company and had similar sociodemographic characteristics to Australian data for perinatal women. The DCE investigated preferences regarding cost, treatment type, availability of childcare, modality and efficacy. Data were analysed using logit-based models accounting for preference and scale heterogeneity. Predicted probability analysis was used to explore relative attribute importance and policy change scenarios, including how these differed by women's sociodemographic characteristics. Cost and treatment type had the greatest impact on choice, such that a policy of subsidising effective treatments was predicted to double their uptake compared with the base case. There were differences in predicted uptake associated with certain sociodemographic characteristics: for example, women with higher educational attainment were more likely to choose effective treatment. The findings suggest policy directions for decision makers whose goal is to reduce the burden of PNDA on women, their children and families

Morfologia social e contextualização topográfica: a micro-história de Edoardo Grendi

Il saggio prende in considerazione il ruolo di Edoardo Grendi nella teorizzazione della proposta microstorica italiana, generalmente sconosciuto o sottostimato nel panorama accademico sudamericano

Internally-headed relative clauses in literary Somali?

After an overview of some features of grammatical variation across different Somali authors, the paper discusses several cases where a the head of a relative clause (RC) is preceded by an internal constiutuent of that RC, resulting in what looks like an internally-headed RC. This pattern also occurs when the head of the RC has the function of a complementizer for temporal and other kinds of subordinate clauses. In the corpus of prose texts that has been analysed only one constituent may occur before the head, whereas in poetry also instances of two constituents preceding the head have been observed