Isocyanide terpene metabolites of Phyllidiella pustulosa, a nudibranch from the South China Sea

A series of isocyanides, compounds 4-11, including diterpenes never before found in Phyllidiid nudibranchs, have been isolated from a Chinese population of the nudibranch Phyllidiella pustulosa. Three new sesquiterpenes (8, 10, and 11), with eudesmane, guaiane, and bisabolane skeletons, respectively, have been characterized by spectral methods and chemical comparison with known related molecules. The absolute stereochemistry of the major metabolite, the isocyanide 8, an enantiomer of the known sponge metabolite stylotelline (12), has also been determined.     

Anxiety-related behaviour in C57BL/6 <--> BALB/c chimeric mice

In a previous study on anxiety-related behaviours of the genetically and behaviourally distant inbred mouse strains C57BL/6 and BALB/c using the Elevated plus-maze (EPM) and Open-field (OF) apparatuses, we identified a number of variables, the factorial scores of which were grouped by principal component analysis (PCA) into factors specifically describing each inbred strain [4]. We have now studied the effect of C57BL/6 and BALB/c haploid sets of genes on this behaviour by comparing EPM and OF variables of C57BL/6 and BALB/c versus C57BL/6×BALB/c F1 hybrids (B6CBF1) and chimeric C57BL/6×BALB/c (CHIM) mice. CHIM mice were made by embryo aggregation and the chimerism degree of their brain was inferred from coat black/white distribution. Discriminant analysis of EPM and OF factorial scores of C57BL/6, BALB/c and CHIM mice showed that CHIM mice with an exceeding (≥80%) C57BL/6 or BALB/c coat component had behaviours similar to those of the predominant strain, whereas CHIM mice with intermediate chimerism differed from both inbred strains. Additional MANOVA analysis showed that the anxiety behaviour of CHIM mice with intermediate chimerism was similar to that of B6CBF1 mice as for factors not describing the inbred strains, including a motor activity mostly limited to protected areas, with attempts to approach the anxiogenic areas while processing/storing the external information. We conclude that the balanced presence of both C57BL/6 and BALB/c genetic backgrounds, either when carried by the same cell or by different cells, gives rise to a novel stress coping strategy described by factors different from those of the inbred strains.     

Nerve growth factor (NGF) and lenses: effects of NGF in an in vitro rat model of cataract

Background The aims of this study are to investigate the presence and production of nerve growth factor (NGF) in the rat lens in basal conditions and to evaluate, in vitro, the role of NGF in a model of xylose-induced cataract.Methods Rat lenses were dissected and the expression of NGF, NGF mRNA and high-affinity NGF-receptor (TrkA) was evaluated by immunohistochemistry, immunoenzymatic assay (ELISA) and in-situ hybridization (ISH) techniques. To investigate the role of NGF in cataract formation we used an in vitro model of sugar-induced cataract by culturing rat lenses for 48 h in Eagle's minimum essential medium (MEM) supplemented with xylose. To evaluate the potential protective effect of NGF on xylose-induced cataract formation, exogenous NGF at different concentrations or antibodies neutralizing endogenous NGF (NGF-Ab) or aspecific antibodies were added to xylose-cultured lenses, and the following cataract-related parameters were evaluated and compared to xylose-treated lenses. Cataract formation was evaluated using three different parameters: staging of the cataract by lens photography, quantification of lens transparency in terms of gray level medium (GLM) and evaluation of the hydration percentage (H%) of the lens. To investigate the role of endogenous NGF in cataract onset, NGF levels were evaluated and compared in lenses cultured in xylose supplemented medium versus lenses cultured in control culture medium.Results The epithelium from fresh rat lenses expresses NGF-receptor, NGF protein and NGF-mRNA. NGF levels in fresh lens were 54.0±24.5 pg/g as quantified by ELISA. Xylose-cultured lenses develop cataract changes, including a decrease of GLM and an increase in hydration percentage, associated with a decrease in NGF levels when compared to lenses cultured in the control culture medium. The addition of NGF to xylose-cultured lenses reduces cataract formation, increasing GLM and decreasing the hydration percentage as compared to xylose-treated lenses. On the other hand, the addition of NGF-Ab induces an increase in cataract formation and lens hydration.Conclusions This study demonstrates that rat lens epithelium expresses and synthesizes NGF. Moreover, immunohistochemistry shows that lens epithelial cells also express the NGF receptor. Although the functional significance of TrkA on lens epithelium is at present not clear, the expression of NGF and its high-affinity receptor on the same cells together with our experimental results suggest that NGF is involved in supporting trophism and/or the function of the lens epithelium.     

Front-line paclitaxel/cisplatin-based chemotherapy in brain metastases from non-small-cell lung cancer

OBJECTIVE: Paclitaxel-cisplatin is considered to be a standard therapy for metastatic non-small-cell lung cancer (NSCLC). The aim of this study was to evaluate the activity and toxicity of this combination with vinorelbine or gemcitabine as front-line therapy in brain metastases from NSCLC. METHODS: Twenty-six chemotherapy-naive patients with an ECOG performance status of 0-2 were treated with paclitaxel (135 mg/m(2)) on day 1, cisplatin (120 mg/m(2)) on day 1, and either vinorelbine (30 mg/m(2)) on days 1 and 15 or gemcitabine (800 mg/m(2)) on days 1 and 8. Whole-brain irradiation was offered early in case of progression and later as consolidation treatment. RESULTS: All patients were evaluated for toxicity and 25 for response. An intracranial response rate was observed in 38% of the patients (95% CI: 22-59%). WHO grade 3-4 neutropenia and thrombocytopenia occurred in 31 and 4% of the patients, respectively. There was one treatment-related death. Non-hematological toxicities were mild. After a median follow-up of 46 months, the median overall survival for all patients was 21.4 weeks and the median time to progression was 12.8 weeks. CONCLUSIONS: Paclitaxel and cisplatin combined with vinorelbine or gemcitabine as front-line therapy in brain metastases seem to achieve responses similar to those for extracranial disease, suggesting a meaningful role in this setting.     

Influence of disturbances on the control of PC-mouse,goal-directed arm movements

This study concerns the influence of visuomotor rotating disturbance on motion dynamics and brain activity. It involves using a PC-mouse and introducing a predefined bias angle between the direction of motion of the mouse pointer and that of the screen cursor. Subjects were asked to execute three different tasks, designed to study the effect of visuomotor rotation on direction control, extent control or the two together. During each task, mouse movement, screen cursor movement and electroencephalograph (EEG) signals were recorded. An algorithm was used to detect and discard EEG signals contaminated by artifacts. Movement performance indexes and brain activity are used to evaluate motion control, tracking ability, learning and control. The results suggest the direction control is planned before the movement and controlled by an adaptive control while extent control is controlled by a real-time feedback. The measurements also confirm that increased motion and/or brain activity occur for bias angles in the ranges ±(90–120°) for both direction and extension controls. After-effects when changing the angle of visual rotation have been seen to be proportional to the variation in the adaptation angle.     

Are Patients With Twin‐Twin Transfusion Syndrome and a Very Short Cervix Candidates for Laser Surgery?

Objectives. The purpose of this study was to determine the relationship between cervical length (CL) and perinatal outcomes in cases of twin‐twin transfusion syndrome (TTTS) treated with laser surgery and to assess whether patients with a very short cervix (0.5–1.9 cm) are appropriate candidates for laser surgery. Methods. All women who underwent laser surgery for TTTS from March 2006 to April 2008 at the study institution were evaluated consecutively. Patients were grouped according to pre‐operative CL: greater than 2.5, 2 to 2.5, and 0.5 to 1.9 cm. The gestational age at delivery, latency from laser surgery to delivery, and 30‐day neonatal survival were documented prospectively and compared among these groups. Results. The 99 women in the study population were grouped by CL: greater than 2.5 cm (n = 76), 2 to 2.5 cm (n = 13), and 0.5 to 1.9 cm (n = 10). For these groups, the median gestational ages at delivery were 34, 32.29, and 31.86 weeks, respectively (P = .411). The median latencies from laser surgery to delivery were 12.79, 11, and 11.07 weeks (P = .424). The frequency rates of at least 1 surviving twin were 69 of 76 (91%), 13 of 13 (100%), and 8 of 10 (80%) (P = .254). Finally, dual survivors were observed in 54 of 76 (71%), 12 of 13 (92%), and 5 of 10 (50%) (P = .08). Conclusions. In cases of TTTS complicated by a very short cervix (0.5–1.9 cm), treatment with laser surgery resulted in perinatal outcomes that were sufficiently favorable to justify the surgery, suggesting that these patients should not be excluded from undergoing laser surgery for TTTS.     

One-year experience of a regional service model of teleconsultation for planning and treatment of complex thoracoabdominal aortic disease

Objective

The objective of this study was to report the methodology and 1-year experience of a regional service model of teleconsultation for planning and treatment of complex thoracoabdominal aortic disease (TAAD).

Neural basis of generation of conclusions in elementary deduction

In everyday life, people untrained in formal logic draw simple deductive inferences from linguistic material (i.e., elementary propositional deductions). Presently, we have limited information on the brain areas implicated when such conclusions are drawn. We used event-related fMRI to identify these brain areas. A set of multiple and independent criteria was derived from the two main theories in the field of reasoning to maximize the reliability of detection of areas in which activity is specifically associated with deductive inferences. Two left lateralized clusters of areas, one in frontal cortex (Brodmann Area 44 and 6) and one in parietal lobe (BA 40), satisfied all criteria; activation was present at the moment of inference, it was shared by both conditional ("if-based") and disjunctive ("or-based") inferences but was greater for disjunctive clauses. Identification of the reasoning network was corroborated by the observation that activity in these areas was greater the longer the reasoning time. Taken together with results from preceding studies, our findings suggest possible theoretically relevant dissociations between elementary propositional deductions and other types of deductive reasoning.