Engagement of BDCA-2 blocks TRAIL-mediated cytotoxic activity of plasmacytoid dendritic cells

Plasmacytoid dendritic cells (PDC) are a functionally distinct lineage of dendritic cells characterized by the release of large amounts of type I interferon (IFN I). IFN I release is efficiently triggered by viral infection and modulates several aspects of immune reactions including the activation of cytotoxic mechanisms finalized to the elimination of infected cells. In this study, we report that TLR7 and TLR9 ligands can induce the secretion of biologically active TNF-related apoptosis-inducing ligand (TRAIL) by PDC. Accordingly, PDC supernatant is endowed with TRAIL-mediated cytotoxic activity when tested on a TRAIL-sensitive Jurkat cell line. TRAIL production is only partially dependent on the autocrine production of IFN I as documented by the use of a blocking anti-IFNRA antibody and the stimulation with exogenous IFN I. Importantly, both TRAIL secretion and cytotoxic activity of PDC supernatants are completely abolished by BDCA2 ligation. These results provide further insights into the biological role of BDCA-2 and document a negative regulatory pathway of PDC cytotoxic activity that may be relevant in pathological situations such as tumors and autoimmune diseases.     

Cholinesterases in the Antarctic scallop Adamussium colbecki: Characterization and sensitivity to pollutants

Antarctica is affected by man-made contamination and development of sensitive ecotoxicological tools for impact assessment is a priority task. The aims of the present study were to characterize cholinesterase (ChE) activities in an Antarctic key species, the scallop Adamussium colbecki, and to investigate their sensitivity as biological markers (biomarkers) of exposure to pollutants and of their effects. Our results show that ChEs in gills share most characteristics with true acetylcholinesterase. The present results show that ChE activities in A. colbecki are significantly inhibited by organophosphates (OPs) and somehow affected by in vitro exposure to mixtures of marine contaminants such as polycyclic aromatic hydrocarbons (PAHs), even if no concentration-dependent pattern of response was observed and no effect was elicited by polychlorinated biphenyls (PCBs). The present results do not demonstrate ChEs in A. colbecki as sensitive tools to measure exposure to the above chemicals, but they may be worthy of further study considering the importance of the scallop in Antarctic marine ecosystems and its suitability as a sentinel species.     

The relationship between malignant mesothelioma and an asbestos cement plant environmental risk: a spatial case–control study in the city of Bari (Italy)

Objectives  To estimate the mesothelioma risk and environmental asbestos exposure (EAE) due to an asbestos-cement plant. Methods  A spatial case–control study including 48 malignant mesothelioma (MM) cases occurred in the period 1993–2003 selected from the regional mesothelioma register (RMR) and 273 controls. The disease risk was estimated by means of a logistic-regression model, in which the probability of disease-occurrence is expressed as a function of the classes of distances. A non-parametric method was applied to estimate the full relative risk surface. Results  Significant MM odds ratio of 5.29 (95 CI: 1.18–23.74) was found for people living within a range up to 500 m centered on the plant. The non-parametric estimation of relative risk surface unveiled a marked peak near the plant not paralleled by the spatial distribution of controls. Conclusion  Evidence of an association between mesothelioma risk and EAE is highlighted. The role played by the RMR in increasing the public health local authorities awareness is stressed.     

Intramuscular Neridronate in Postmenopausal Women with Low Bone Mineral Density

Compliance to osteoporosis treatment with oral bisphosphonates is very poor. Intermittent intravenous bisphosphonate is a useful alternative, but this route is not readily available. Neridronate, a nitrogen-containing bisphosphonate that can be given intramuscularly (IM), was tested in a phase 2 clinical trial in 188 postmenopausal osteoporotic women randomized to IM treatment with 25 mg neridronate every 2 weeks, neridronate 12.5 or 25 mg every 4 weeks, or placebo. All patients received calcium and vitamin D supplements. The patients were treated over 12 months with 2-year posttreatment follow-up. After 12-month treatment, all three doses were associated with significant bone mineral density (BMD) increases at both the total hip and spine. A significant dose–response relationship over the three doses was observed for the BMD changes at the total hip but not at the spine. Bone alkaline phosphatase decreased significantly by 40–55% in neridronate-treated patients, with an insignificant dose–response relationship. Serum type I collagen C-telopeptide decreased by 58–79%, with a significant dose–response relationship (P < 0.05). Two years after treatment discontinuation, BMD declined by 1–2% in each dose group, with values still significantly higher than baseline at both the spine and the total hip. Bone turnover markers progressively increased after treatment discontinuation, and on the second year of follow-up the values were significantly higher than pretreatment baseline. The results of this study indicate that IM neridronate might be of value for patients intolerant to oral bisphosphonates and unwilling or unable to undergo intravenous infusion of bisphosphonates.     

A feature extraction unsupervised neural network for an environmental data set.

Environmental data sets are characterized by a huge amount of heterogeneous data from external fields. As the number of measured points grows, a strategy is needed to select and efficiently analyze the useful information from the whole data set. One efficient way of obtaining the validation-compression of data sets is the adoption of a restricted set of features that describe, with an assigned accuracy a subset of the whole data set. One characteristic feature of the environmental data is time dependency: in the medium and long term they are not stationary data sets. The aim of this work is to propose a feature extraction technique based on a new model of an unsupervised neural network suitable to analyze this kind of data. The paper reports the results obtained utilizing the above extraction and analysis procedure on a real data set on chemical pollutants. It is shown that the proposed neural network is able to identify correctly human and/or meteorological effects in the environmental data set.     

The Rise of Creativity: From Primary to Tertiary Process*

This discussion praises Object Relations in Psychoanalytic Theory by Jay Greenberg and Stephen Mitchell for the clarity with which it compares various psychoanalytic theories and their pedagogical usefulness. However, it emphasizes that the book views comparative psychoanalysis based on choices and assumptions with which many might differ. “Object relations” is only one of several possible lenses through which psychoanalytic theories might have been compared. By selecting object relations as the organizing perspective the authors ignore some important theorists such as Arlow and Brenner or Erik Erikson. It also notes that Greenberg and Mitchell view the choice of theoretical position as simply a matter of personal preference. This ignores the possibility of scientifically evaluating which psychoanalytic approach is most likely to achieve the best results.     

New Views on the Psychology and Psychopathology of Wit and of the Comic

The article reviews the current state and future of psychodynamic psychotherapies. In the past few decades psychodynamic psychotherapies have fallen into disrepute due to the fractious and dogmatic nature of different psychodynamic schools of thought and the lack of interest in validating some of its major premises or its effectiveness in comparison with other psychotherapy modalities. Despite these self-inflicted wounds, psychodynamic theory and treatment is staging a comeback. Many of the major premises that comprise the complex, layered model of the mind that are the basis of psychodynamic treatments have again begun to be validated. A list of basic psychodynamic concepts is described. The evidence for each of these concepts varies, but as a whole the evidence is broad and deep for the model of the mind posited by psychoanalysis. This evidence is coming from many fields of knowledge that are not necessarily influenced by psychoanalysis. There have also been significant advances in developing methods and tools that can probe systematically into the complex nature of psychodynamic treatment processes. Finally, statistical tools–such as meta-analytic studies–that can aggregate and compare many different studies at once are beginning to show the effectiveness of dynamic psychotherapies in comparison with other modalities of treatment.