Psychological processes mediating the association between developmental trauma and specific psychotic symptoms in adults: a systematic review and meta‐analysis

Experiencing psychological trauma during childhood and/or adolescence is associated with an increased risk of psychosis in adulthood. However, we lack a clear knowledge of how developmental trauma induces vulnerability to psychotic symptoms. Understanding the psychological processes involved in this association is crucial to the development of preventive interventions and improved treatments. We sought to systematically review the literature and combine findings using meta‐analytic techniques to establish the potential roles of psychological processes in the associations between developmental trauma and specific psychotic experiences (i.e., hallucinations, delusions and paranoia). Twenty‐two studies met our inclusion criteria. We found mediating roles of dissociation, emotional dysregulation and post‐traumatic stress disorder (PTSD) symptoms (avoidance, numbing and hyperarousal) between developmental trauma and hallucinations. There was also evidence of a mediating role of negative schemata, i.e. mental constructs of meanings, between developmental trauma and delusions as well as paranoia. Many studies to date have been of poor quality, and the field is limited by mostly cross‐sectional research. Our findings suggest that there may be distinct psy­chological pathways from developmental trauma to psychotic phenomena in adulthood. Clinicians should carefully ask people with psychosis about their history of developmental trauma, and screen patients with such a history for dissociation, emotional dysregulation and PTSD symptoms. Well conducted research with prospective designs, including neurocognitive assessment, is required in order to fully understand the biopsychosocial mechanisms underlying the association between developmental trauma and psychosis.     

Frondoside A Suppressive Effects on Lung Cancer Survival,Tumor Growth,Angiogenesis, Invasion,and Metastasis

A major challenge for oncologists and pharmacologists is to develop less toxic drugs that will improve the survival of lung cancer patients. Frondoside A is a triterpenoid glycoside isolated from the sea cucumber, Cucumaria frondosa and was shown to be a highly safe compound. We investigated the impact of Frondoside A on survival, migration and invasion in vitro, and on tumor growth, metastasis and angiogenesis in vivo alone and in combination with cisplatin. Frondoside A caused concentration-dependent reduction in viability of LNM35, A549, NCI-H460-Luc2, MDA-MB-435, MCF-7, and HepG2 over 24 hours through a caspase 3/7-dependent cell death pathway. The IC50 concentrations (producing half-maximal inhibition) at 24 h were between 1.7 and 2.5 µM of Frondoside A. In addition, Frondoside A induced a time- and concentration-dependent inhibition of cell migration, invasion and angiogenesis in vitro. Frondoside A (0.01 and 1 mg/kg/day i.p. for 25 days) significantly decreased the growth, the angiogenesis and lymph node metastasis of LNM35 tumor xenografts in athymic mice, without obvious toxic side-effects. Frondoside A (0.1–0.5 µM) also significantly prevented basal and bFGF induced angiogenesis in the CAM angiogenesis assay. Moreover, Frondoside A enhanced the inhibition of lung tumor growth induced by the chemotherapeutic agent cisplatin. These findings identify Frondoside A as a promising novel therapeutic agent for lung cancer.     

The tandem PDZ domains of syntenin promote cell invasion

Syntenin is a tandem PDZ protein that has recently been shown to be overexpressed in several cancer cells and tissues, and that might play an active role in tumor cell invasion and metastasis. Here we show that overexpression of the tandem PDZ domains of syntenin in non-invasive cells is necessary and sufficient to stimulate these cells to invade a collagen I matrix, and this effect can be regulated by ligand binding to the PDZ domains. Furthermore, we show that syntenin-induced invasion requires signaling through ras, rho and PI3K/MAPK signaling pathways and involves changes in cell-cell adhesion. Inversely, when we used RNA interference to inhibit syntenin expression in different invasive cancer cell lines, we observed a drastically decreased ability of these cells to migrate and invade into collagen type I or Matrigel. RNAi-treated cells also show increased cell aggregation, indicating that syntenin is important for cell-cell adhesion in epithelial cells. Together, these results suggest that downregulation of syntenin by RNA interference could provide a means of inhibiting tumor invasion and possibly metastasis in different cancers, and point to syntenin as a potential cancer biomarker and drug target.     

Aggregation of measures to produce an overall assessment of animal welfare. Part 1: a review of existing methods

Several systems have been proposed for the overall assessment of animal welfare at the farm level for the purpose of advising farmers or assisting public decision-making. They are generally based on several measures compounded into a single evaluation, using different rules to assemble the information. Here we discuss the different methods used to aggregate welfare measures and their applicability to certification schemes involving welfare. Data obtained on a farm can be (i) analysed by an expert who draws an overall conclusion; (ii) compared with minimal requirements set for each measure; (iii) converted into ranks, which are then summed; or (iv) converted into values or scores compounded in a weighted sum (e.g. TGI35L) or using ad hoc rules. Existing methods used at present (at least when used exclusively) may be insufficiently sensitive or not routinely applicable, or may not reflect the multidimensional nature of welfare and the relative importance of various welfare measures. It is concluded that different methods may be used at different stages of the construction of an overall assessment of animal welfare, depending on the constraints imposed on the aggregation process.     

Signaling through integrin LFA-1 leads to filamentous actin polymerization and remodeling,resulting in enhanced T cell adhesion

The integrins can activate signaling pathways, but the final downstream outcome of these pathways is often unclear. This study analyzes the consequences of signaling events initiated by the interaction of the leukocyte integrin LFA-1 with its ligand, dimeric ICAM-1. We show that the active form of LFA-1 regulates its own function on primary human T cells by directing the remodeling of the F-actin cytoskeleton to strengthen T cell adhesion to ICAM-1. Confocal microscopy revealed that both F-actin bundling and overall levels of F-actin are increased in the ICAM-1-adhering T cells. This increase in F-actin levels and change in F-actin distribution was quantitated for large numbers of T cells using the technique of laser scanning cytometry and was found to be significant. The study went on to show that clustering of conformationally altered LFA-1 is essential for the changes in F-actin, and a model is proposed in which clustered, high-avidity T cell LFA-1, interacting with multivalent ICAM-1, causes LFA-1 signaling, which results in F-actin polymerization and higher-order F-actin bundling. The findings demonstrate that LFA-1 acts not only as an adhesion receptor but also as a signaling receptor by actively initiating the F-actin reorganization that is essential for many T cell-dependent processes.     

Chronic rejection pathology after orthotopic lung transplantation in mice: the development of a murine BOS model and its drawbacks

Almost all animal models for chronic rejection (CR) after lung transplantation (LTx) fail to resemble the human situation. It was our attempt to develop a representative model of CR in mice. Orthotopic LTx was performed in allografts receiving daily immunosuppression with steroids and cyclosporine. Controls included isografts and mice only undergoing thoracotomy (SHAM). Allografts were sacrificed 2, 4, 6, 8, 10 or 12 weeks after LTx. Pulmonary function was measured repeatedly in the 12w allografts, isografts and SHAM mice. Histologically, all allografts demonstrated acute rejection (AR) around the blood vessels and airways two weeks after LTx. This decreased to 50-75% up to 10 weeks and was absent after 12 weeks. Obliterative bronchiolitis (OB) lesions were observed in 25-50% of the mice from 4-12 weeks. Isografts and lungs of SHAM mice were normal after 12 weeks. Pulmonary function measurements showed a decline in FEV(0.1), TLC and compliance in the allografts postoperatively (2 weeks) with a slow recovery over time. After this initial decline, lung function of allografts increased more than in isografts and SHAM mice indicating that pulmonary function measurement is not a good tool to diagnose CR in a mouse. We conclude that a true model for CR, with clear OB lesions in about one third of the animals, but without a decline in lung function, is possible. This model is an important step forward in the development of an ideal model for CR which will open new perspectives in unraveling CR pathogenesis and exploring new treatment options.     

Prevention and treatment of tail biting in weaned piglets

The aims of this study were to evaluate four preventive measures and two curative treatments of tail biting. The preventive measures were: chain, rubber hose, straw rack (5 g/pig/day) and the provision of straw on the floor twice daily by hand (2 × 10 g/pig/day). The two curative treatments, which were applied following the onset of tail biting in a pen were: straw twice daily (as in the fourth preventive measure) and the removal of the biter. In total, 960 undocked weaned piglets (10 piglets per pen) were observed during 5 weeks. Tail lesions (none, bite marks and wounds) were recorded daily. The incidence of pens with wounded pig tails was significantly lower when straw was provided twice daily (8% of pens) compared to the chain (58% of pens) and rubber hose (54% of pens) treatment, but did not differ significantly from the straw rack treatment (29% of pens). Tails with bite marks were significantly less common in pens with twice daily straw (16% of pens) compared to chain (88% of pens), rubber hose (79% of pens) and straw rack (75% of pens). No significant difference was found between the curative treatments. Both treatments showed a reduced incidence of red fresh blood on the tails at days 1–9 following curative treatment, compared to day 0. However, neither curative treatment eliminated tail biting entirely. In conclusion, this study indicates that tail biting is best prevented with a small amount of straw, provided twice daily, and to a lesser extent with a straw rack, compared to providing a chain or a rubber hose. Once tail biting has occurred, providing a small amount of straw twice daily and removing the biter appears to be equally effective.