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Objective To date motor subtypes of delirium have been evaluated in single-center studies with a limited examination of the relationship between predisposing factors and motor profile of delirium. We sought to report the prevalence and clinical profile of subtypes of delirium in a multicenter study. Methods This is a point prevalence study nested in the “Delirium Day 2015”, which included 108 acute and 12 rehabilitation wards in Italy. Delirium was detected using the 4-AT and motor subtypes were measured with the Delirium Motor Subtype Scale (DMSS). A multinomial logistic regression was used to determine the factors associated with delirium subtypes. Results Of 429 patients with delirium, the DMSS was completed in 275 (64%), classifying 21.5% of the patients with hyperactive delirium, 38.5% with hypoactive, 27.3% with mixed and 12.7% with the non-motor subtype. The 4-AT score was higher in the hyperactive subtype, similar in the hypoactive, mixed subtypes, while it was lowest in the non-motor subtype. Dementia was associated with all three delirium motor subtypes (hyperactive, OR 3.3, 95% CI: 1.2-8.7; hypoactive, OR 2.8, 95% CI: 1.2-6.5; mixed OR 2.6, 95% CI: 1.1-6.2). Atypical antipsychotics were associated with hypoactive delirium (OR 0.23, 95% CI: 0.1-0.7), while intravenous lines were associated with mixed delirium (OR 2.9, 95% CI: 1.2-6.9). Conclusions The study shows that hypoactive delirium is the most common subtype among hospitalized older patients. Specific clinical features were associated with different delirium subtypes. The use of standardized instruments can help to characterize the phenomenology of different motor subtypes of delirium.

Strong evidence suggests that phospholipase Cγ1 (PLCγ1) is a suitable target to counteract tumourigenesis and metastasis dissemination. We recently identified a novel signalling pathway required for PLCγ1 activation which involves formation of a protein complex with 3-phosphoinositidedependent protein kinase 1 (PDK1). In an effort to define novel strategies to inhibit PLCγ1-dependent signals we tested here whether a newly identified and highly specific PDK1 inhibitor, 2-O-benzyl-myoinositol 1,3,4,5,6-pentakisphosphate (2-O-Bn-InsP5), could affect PDK1/PLCγ1 interaction and impair PLCγ1-dependent cellular functions in cancer cells. Here, we demonstrate that 2-O-Bn-InsP5 interacts specifically with the pleckstrin homology domain of PDK1 and impairs formation of a PDK1/PLCγ1 complex. 2-O-Bn-InsP5 is able to inhibit the epidermal growth factor-induced PLCγ1 phosphorylation and activity, ultimately resulting in impaired cancer cell migration and invasion. Importantly, we report that 2-O-Bn-InsP5 inhibits cancer cell dissemination in zebrafish xenotransplants. This work demonstrates that the PDK1/PLCγ1 complex is a potential therapeutic target to prevent metastasis and it identifies 2-O-Bn-InsP5 as a leading compound for development of anti-metastatic drugs.

The aims of this work were the characterisation and the evaluation of potential environmental applications of the bioemulsifiers produced by Variovorax paradoxus 7bCT5. V. paradoxus 7bCT5 produces a mixture of high molecular weight polysaccharides. The extracellular bioemulsifiers were able to produce a thick stable oil/water emulsion and maintained the emulsification activity after boiling and at low temperatures. Environmental behavior and impact of bioemulsifiers release were assessed by evaluating biodegradability, toxicity and soil sorption. Respirometric tests showed that moderate biodegradability occurred by soil bacterial inoculum. Furthermore, the produced compounds did not show any toxic properties through different ecotoxicological tests. The K d values ranged from 1.3 to 7.3L/kg indicating a high sorption affinity of the bioemulsifier molecules to soil particles. The soil sorption affinity likely affected the bioemulsifier ability to remove hydrocarbons from contaminated soils. In fact, V. paradoxus 7bCT5 bioemulsifiers significantly increased the removal of crude-oil from sandy soil compared to water. © 2012 Elsevier Ltd.

Bacteria able to produce biological emulsifiers were isolated from different environments using different isolation media with the aim of discovering the widest diversity. The phylogenetic diversity of the isolates was evaluated by 16S rRNA gene analysis. Among 190 isolated strains, 127 released extracellular emulsifiers able to stabilize oil-water emulsions when grown on low-cost substrates. Among these, the 35 isolates that showed the highest emulsifier production on different substrates were found to belong to 16 different bacterial genera. Overall, this is the first systematic study of the diversity of bioemulsifier-producing bacteria and of their ability to produce bioemulsifiers on low-cost substrates. © 2011 Elsevier Ltd.

Phosphoinositide 3-kinases (PI3Ks) are critical regulators of pancreatic ß cell mass and survival, whereas their involvement in insulin secretion is more controversial. Furthermore, of the different PI3Ks, the class II isoforms were detected in ß cells, although their role is still not well understood. Here we show that down-regulation of the class II PI3K isoform PI3K-C2a specifically impairs insulin granule exocytosis in rat insulinoma cells without affecting insulin content, the number of insulin granules at the plasma membrane, or the expression levels of key proteins involved in insulin secretion. Proteolysis of synaptosomal-associated protein of 25 kDa, a process involved in insulin granule exocytosis, is impaired in cells lacking PI3K-C2a. Finally, our data suggest that the mRNA for PI3K-C2a may be down-regulated in islets of Langerhans from type 2 diabetic compared with non-diabetic individuals. Our results reveal a critical role for PI3K-C2a in ß cells and suggest that down-regulation of PI3K-C2a may be a feature of type 2 diabetes.

The Boyden chamber, initially designed to study leukocyte chemotaxis, has become one of the most used tools to assess cell motility and invasion. The classical Boyden chamber consists of two compartments separated by a membrane representing a physical barrier that cells can overcome only by active migration. Since its initial introduction, a number of different Boyden chamber devices have been developed. The Boyden chamber can be adapted to study tumour cells' invasive properties by coating the membrane with different extracellular matrix proteins. The method described in this chapter is intended specifically for measuring the migration or invasion of human endothelial and cancer cells.

Abnormal activation of phosphoinositide 3-kinase (PI3K) signalling is very common in cancer, leading to deregulation of several intracellular processes normally controlled by this enzyme, including cell survival, growth, proliferation and migration. Mutations in the gene encoding the tumour suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN), which leads to uncontrolled activation of the PI3K pathway, are reported in different cancers. Among the downstream effectors of PI3Ks, 3-phosphoinositide- dependent protein kinase 1 (PDK1) and protein kinase B (PKB)/Akt have a key role in several cancer types. More recent data indicate that alteration of PDK1 is a critical component of oncogenic PI3K signalling in breast cancer, suggesting that inhibition of PDK1 can inhibit breast cancer progression. PDK1 has an essential role in regulating cell migration especially in the context of PTEN deficiency. Downregulation of PDK1 levels inhibits migration and experimental metastasis of human breast cancer cells. PDK1 activates a large number of proteins, including Akt, some PKC isoforms, S6K and SGK. Data also reveal that PDK1 is oncogenic and this is dependent on PI3K pathway. Therefore, accumulating evidence demonstrates that PDK1 is a valid therapeutic target and suggests that PDK1 inhibitors may be useful to prevent cancer progression and abnormal tissue dissemination. This review will focus on published data on the role of PDK1 in cancer and approaches used to inhibit PDK1. © 2011 Bentham Science Publishers Ltd.

Background: The fibroblast growth factors (FGFs) are key regulators of embryonic development, tissue homeostasis and tumour angiogenesis. Binding of FGFs to their receptor(s) results in activation of several intracellular signalling cascades including phosphoinositide 3-kinase (PI3K) and phospholipase C (PLC)?1. Here we investigated the basic FGF (FGF-2)-mediated activation of these enzymes in human umbilical vein endothelial cells (HUVECs) and defined their role in FGF-2-dependent cellular functions. Methodology/Principal Findings: We show that FGF-2 activates PLC?1 in HUVECs measured by analysis of total inositol phosphates production upon metabolic labelling of cells and intracellular calcium increase. We further demonstrate that FGF-2 activates PI3K, assessed by analysing accumulation of its lipid product phosphatidylinositol-3,4,5-P3 using TLC and confocal microscopy analysis. PI3K activity is required for FGF-2-induced PLCc1 activation and the PI3K/PLCc1 pathway is involved in FGF-2-dependent cell migration, determined using Transwell assay, and in FGF-2-induced capillary tube formation (tubulogenesis assays in vitro). Finally we show that PI3K-dependent PLC?1 activation regulates FGF-2-mediated phosphorylation of Akt at its residue Ser473, determined by Western blotting analysis. This occurs through protein kinase C (PKC)a activation since dowregulation of PKCa expression using specific siRNA or blockade of its activity using chemical inhibition affects the FGF-2-dependent Ser473 Akt phosphorylation. Furthermore inhibition of PKCa blocks FGF-2-dependent cell migration. Conclusion/Significance: These data elucidate the role of PLC?1 in FGF-2 signalling in HUVECs demonstrating its key role in FGF-2-dependent tubulogenesis. Furthermore these data unveil a novel role for PLC?1 as a mediator of PI3K-dependent Akt activation and as a novel key regulator of different Akt-dependent processes. a 2009 Maffucci et al.