A Case Report of a Woman Affected with Rapid Cycling Bipolar Disorder I and Methabolic Syndrome Improved with Aripiprazole Monotherapy

Introduction We present the case of a 51-years-old Caucasian woman with Bipolar Disorder I (BDI), treated for a long time with typical antipsychotics and mood stabilizers. She referred to our outpatient service because she wished to revise her precriptions, which had caused several side-effects, including metabolic syndrome, gain of body weight, sedation, cognitive impairments, and extrapiramidal symptoms. Moreover, treatment was poorly effective, the patient's compliance was lacking and she experienced frequent relapses. Aims We started treating the patient with aripiprazole at a daily dose of 15 mg. Our aim is to describe the substantial clinical and metabolic improvements of a patient who poorly responded to previous prescriptions. Methods Psychometric measures for the assessment of mood and social functioning were administered at baseline and at the follow-up interviews. Body Mass Index was monitored and blood tests were performed to evaluate the lipid profile (LDL, HDL, total cholesterol, triglycerides), blood glucose, and glycated haemoglobin. Results In the last two years the patient has regularly taken her therapies and attended to follow-up visits. Her social functioning and tolerance to stressful situations have improved, as well as her metabolic profile. Noteworthy, she had not needed further hospitalizations. Conclusions Our clinical observations support the efficacy of aripiprazole in the treatment of BDI. Switching to aripiprazole should be considered in cases similar to the one we have described, characterized by poor compliance, obesity or metabolic syndrome, sensitivity to manifest extrapiramidal syndrome (especially tardive dyskinesia) and other side effects such as sedation and cognitive impairments

The tyrosine-phosphorylated hepatocyte growth factor/scatter factor receptor associates with phosphatidylinositol 3-kinase.

The receptor for hepatocyte growth factor, also known as scatter factor (HGF/SF), has recently been identified as the 190-kDa heterodimeric tyrosine kinase encoded by the MET proto-oncogene (p190MET). The signaling pathway(s) triggered by HGF/SF are unknown. In A549 cells, a lung epithelial cell line, nanomolar concentrations of HGF/SF induced tyrosine phosphorylation of the p190MET receptor. The autophosphorylated receptor coprecipitated with phosphatidylinositol 3-kinase (PI 3-kinase) activity. In GTL16 cells, a cell line derived from a gastric carcinoma, the p190MET receptor, overexpressed and constitutively phosphorylated on tyrosine, coprecipitated with PI 3-kinase activity and with the 85-kDa PI 3-kinase subunit. In these cells activation of protein kinase C or the increase of intracellular [Ca2+] inhibits tyrosine phosphorylation of the p190MET receptor as well as the association with both PI 3-kinase activity and the 85-kDa subunit of the enzyme. In an in vitro assay, tyrosine phosphorylation of the immobilized p190MET receptor was required for binding of PI 3-kinase from cell lysates. These data strongly suggest that the signaling pathway activated by the HGF/SF receptor includes generation of D-3-phosphorylated inositol phospholipids

Hepatocyte growth factor/scatter factor stimulates the Ras-guanine nucleotide exchanger

Hepatocyte growth factor/scatter factor (HGF/SF) induces mitogenesis and cell dissociation upon binding to the protein-tyrosine kinase receptor encoded by the MET proto-oncogene (p190MET). The signal transduction pathways downstream from the receptor activation are largely unknown. We show that HGF/SF activates Ras protein. HGF/SF stimulation of metabolically labeled A549 cells raised the amount of Ras-bound radiolabeled guanine nucleotides by over 5-fold. Furthermore, following HGF/SF stimulation of these cells, 50% of Ras was in the GTP-bound active state. The uptake by Ras of radiolabeled GTP was also increased by 5-fold following HGF/SF stimulation in digitonin-permeabilized A549 cells. Moreover, HGF/SF treatment of A549 cells leads to stimulation of the cytosolic Ras-guanine nucleotide exchange activity, measured as accelerated release of [3H]GDP from purified recombinant Ras protein in vitro, in a dose- and time-dependent manner. Likewise, treatment with the protein-tyrosine kinase inhibitor 3-(1',4'-dihydroxytetralyl)methylene-2-oxindole of GTL-16 cells (featuring a p190MET receptor constitutively active) significantly decreased the cytosolic Ras-guanine nucleotide exchange activity. These data demonstrate that HGF/SF activates Ras protein by shifting the equilibrium toward the GTP-bound state and increases the uptake of guanine nucleotides by Ras, through mechanism(s) including the activation of a Ras-guanine nucleotide exchanger

Surfactants, nanomedicines and nanocarriers: a critical evaluation on clinical trials

Advances, perspectives and innovation in drug delivery have increased in recent years; however, there is limited information available regarding the actual presence of surfactants, nanomed-icines and nanocarriers in investigational medicinal products submitted as part of a request for authorization of clinical trials, particularly for those authorized in the European Economic Area. We retrieve, analyze and report data available at the Clinical Trial Office of the Italian Medicines Agency (AIFA), increasing the transparency and availability of relevant information. An analysis of quality documentation submitted along with clinical trials authorized by the AIFA in 2018 was carried out, focusing on the key terms “surfactant”, “nanomedicine” and “nanocarrier”. Results suggest potential indications and inputs for further reflection and actions for regulators to actively and safely drive innovation from a regulatory perspective and to transpose upcoming evolution of clinical trials within a strong regulatory framework

Automotive Communications in LTE: A Simulation-Based Performance Study

2017 IEEE 86th Vehicular Technology Conference (VTC-Fall)The integration of automotive communications in 5G systems must build on a clear understanding of the performance of services for connected vehicles in today's LTE deployments. In this paper, we carry out a simulation-based performance evaluation of automotive communications in LTE, with particular attention to realism: to that end, we investigate the impact of different road traffic models, employ a state-of-the-art commercial LTE tool, and study a practical service use case. Our results demonstrate that unrealistic road traffic datasets can bias network simulations in urban vehicular environments, and provide insights on the limitations of the current radio access architecture, when confronted to connected vehicles.This research has received funding from the People Pro-gramme (Marie Curie Actions) of the European Unions Sev-enth Framework Programme (FP7/2007- 2013) under REA grant agreement n.630211, ReFleX. Also, this work has been performed in the framework of the H2020-ICT-2014-2 project 5G NORMA

Network-based localized IP mobility management: Proxy Mobile IPv6 and current trends in standardization

IP mobility support has been a hot topic over the last years, recently fostered by the role of IP in the evolution of the 3G mobile communication networks. Standardization bodies, namely IETF, IEEE and 3GPP are working on different aspects of the mobility aiming at improving the mobility experience perceived by users. Traditional IP mobility support mechanisms, Mobile IPv4 or Mobile IPv6, are based on the operation of the terminal to keep ongoing sessions despite the movement. The current trend is towards network-based solutions where mobility support is based on network operation. Proxy Mobile IPv6 is a promising specification that allows network operators to provide localized mobility support without relying on mobility functionality or configuration present in the mobile nodes, which greatly eases the deployment of the solution. This paper presents Proxy Mobile IPv6 and the different extensions that are been considered by the standardization bodies to enhance the basic protocol with interesting features needed to offer a richer mobility experience, namely, flow mobility, multicast and network mobility support.European Community's Seventh Framework ProgramThe research leading to the results presented in this paper has received funding from the Spanish MICINN through the I-MOVING project (TEC2010-18907) and from the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement 258053 (MEDIEVAL project).Publicad

Platelets activate a pathogenic response to blood-stage Plasmodium infection but not a protective immune response

© 2017 by The American Society of Hematology. Clinical studies indicate that thrombocytopenia correlates with the development of severe falciparum malaria, suggesting that platelets either contribute to control of parasite replication, possibly as innate parasite killer cells or function in eliciting pathogenesis. Removal of platelets by anti-CD41 mAb treatment, platelet inhibition by aspirin, and adoptive transfer of wild-type (WT) platelets to CD40-KO mice, which do not control parasite replication, resulted in similar parasitemia compared with control mice. Human platelets at a physiologic ratio of 1 platelet to 9 red blood cells (RBCs) did not inhibit the in vitro development or replication of blood-stage Plasmodium falciparum. The percentage of Plasmodium-infected (iRBCs) with bound platelets during the ascending parasitemia in Plasmodium chabaudi- and Plasmodium berghei-infected mice and the 48-hour in vitro cycle of P falciparum was <10%. P chabaudi and P berghei iRBCs with apoptotic parasites (TdT1) exhibited minimal platelet binding (<5%), which was similar to nonapoptotic iRBCs. These findings collectively indicate platelets do not kill bloodstage Plasmodium at physiologically relevant effector-to-target ratios.Pchabaudi primary andsecondary parasitemiawassimilar in mice depleted of platelets by mAb-injection just before infection, indicating that activation of the protective immune response does not require platelets. In contrast to the lack of an effect on parasite replication, adoptive transfer ofWTplatelets to CD40-KOmice, which are resistant to experimental cerebral malaria, partially restored experimental cerebral malaria mortality and symptoms in CD40-KO recipients, indicating platelets elicit pathogenesis and platelet CD40 is a key molecule

The HIV-1 Nef Protein Interferes with Phosphatidylinositol 3-Kinase Activation 1

nef is a human immunodeficiency virus (HIV) gene encoding a 27-kDa myristoylated protein with structural features of a signal transducing molecule, but whose functions are largely unknown. We studied the interactions of Nef with the signal transduction pathways triggered by the platelet-derived growth factor (PDGF) receptor. The association of phosphatidylinositol (PI) 3-kinase with the activated receptor was severely impaired by nef expression. Conversely, PDGF-induced receptor tyrosine phosphorylation, binding to phospholipase C-gamma and to Ras-GAP were not modified. Microtubule-associated protein kinase activation and intracellular calcium influx in response to PDGF were either unaffected or only slightly enhanced. Nef significantly reduced the proliferative response to the growth factor, while the chemotactic response was unchanged. These data show that Nef affects selectively the PI 3-kinase signaling pathway and suggest that this interference results in some of the HIV adverse effects on host cell functions

5G-MoNArch use case for ETSI ENI: elastic resource management and orchestration

Proceeding of: 2018 IEEE Conference on Standards for Communications and Networking (CSCN)5G networks will grant spectacular improvements of the most relevant Key Performance Indicators (KPIs) while allowing resource multi-tenancy through network slicing. However, the other side of the coin is represented by the huge increase of the management complexity and the need for efficient algorithms for resource orchestration. Therefore, the management and orchestration of the network through Artificial Intelligence (AI) and Machine Learning (ML) algorithms is considered a promising solution, as it allows to reduce the human interaction (usually expensive and error-prone) and scale to large scenario composed by thousands of slices in heterogeneous environments. In this paper, we provide a review of the current standardization efforts in this field, mostly due to the work performed by the Experiential Network Intelligence (ENI) industry specification group (ISG) within the European Telecommunications Standards Institute (ETSI). Then, we thoroughly describe an exemplary use case on elastic network management and orchestration through learning solutions proposed by the 5GPPP project 5G-MoNArch and recently approved at ETSI ENI

On the benefits of bringing cloud-awareness to network virtual functions

Proceeding of: 2018 European Conference on Networks and Communications (EuCNC), June 18-21, Ljubljana, SloveniaWe are currently observing the softwarization of communication networks, where network functions are translated from monolithic pieces of equipment to programs running over a shared pool of computational, storage, and communication resources. As the amount of this resources might vary over time, in this paper we discuss the potential benefits of introducing resource awareness to softwarized network functions. More specifically, we focus on the case of computational elasticity, namely, the ability to endure shortages of computational resources while providing an adequate (although non-ideal) service. We discuss how to enable this ability by re-designing network functions, and illustrate the potential benefits of this approach with a numerical evaluation