InternationaL cross-sectIonAl and longItudinal assessment on aSthma cONtrol in European adult patients : the LIAISON study protocol

The study is funded by Chiesi Farmaceutici S.p.A., Parma, ItalyPeer reviewedPublisher PD

Acid epimerization of 20-keto pregnane glycosides is determined by 2D-NMR spectroscopy

Carbohydrates influence many essential biological events such as apoptosis, differentiation, tumor metastasis, cancer, neurobiology, immunology, development, host-pathogen interactions, diabetes, signal transduction, protein folding, and many other contexts. We now report on the structure determination of pregnane glycosides isolated from the aerial parts of Ceropegia fusca Bolle (Asclepiadaceae). The observation of cicatrizant, vulnerary and cytostatic activities in some humans and animals of Ceropegia fusca Bolle, a species endemic to the Canary Islands, encouraged us to begin a pharmacological study to determine their exact therapeutic properties. High resolution 1H-NMR spectra of pregnane glycosides very often display well-resolved signals that can be used as starting points in several selective NMR experiments to study scalar (J coupling), and dipolar (NOE) interactions. ROESY is especially suited for molecules such that ωτc ~ 1, where τc are the motional correlation times and ω is the angular frequency. In these cases the NOE is nearly zero, while the rotating-frame Overhauser effect spectroscopy (ROESY) is always positive and increases monotonically for increasing values of τc. The ROESY shows dipolar interactions cross peaks even in medium-sized molecules which are helpful in unambiguous assignment of all the interglycosidic linkages. Selective excitation was carried out using a double pulsed-field gradient spin-echo sequence (DPFGSE) in which 180° Gaussian pulses are sandwiched between sine shaped z-gradients. Scalar interactions were studied by homonuclear DPFGSE-COSY and DPFGSE-TOCSY experiments, while DPFGSE-ROESY was used to monitor the spatial environment of the selectively excited proton. Dipolar interactions between nuclei close in space can be detected by the 1D GROESY experiment, which is a one-dimensional counterpart of the 2D ROESY method. The C-12 and C-17 configurations were determined by ROESY experiments

3D APPLICATIONS IN DISASTER MITIGATION AND MANAGEMENT: CORE RESULTS OF DITAC PROJECT

According to statistical data, natural disasters as well as the number of people affected by them are occurring with increasing frequency compared to the past. This situation is also seen in Europe Union; So, Strengthening the EU capacity to respond to Disasters is very important. This paper represents the baseline results of the FP-7 founded DITAC project, which aims to develop a holistic and highly structured curriculum for responders and strategic crisis managers. Up-to-date geospatial information is required in order to create an effective disaster response plan. Common sources for geospatial information such as Google Earth, GIS databases, and aerial surveys are frequently outdated, or insufficient. This limits the effectiveness of disaster planning. Disaster Management has become an issue of growing importance. Planning for and managing large scale emergencies is complex. The number of both victims and relief workers is large and the time pressure is extreme. Emergency response and triage systems with 2D user interfaces are currently under development and evaluation. Disasters present a number of spatially related problems and an overwhelming quantity of information. 3D user interfaces are well suited for intuitively solving basic emergency response tasks. Such tasks include commanding rescue agents and prioritizing the disaster victims according to the severity of their medical condition. Further, 3D UIs hold significant potential for improving the coordination of rescuers as well as their awareness of relief workers from other organizations. This paper describes the outline of a module in a Disaster Management Course related to 3D Applications in Disaster Mitigation and Management. By doing this, the paper describes the gaps in existing systems and solutions. Satellite imageries and digital elevation data of Turkey are investigated for detecting sites prone to natural hazards. Digital image processing methods used to enhance satellite data and to produce morphometric maps in order to contribute to the detection of causal factors related to landslides, local site conditions influencing and/or experiencing earthquake damage intensity or those of tsunami and storm surge hazard sites at the coasts

Test for CCR5 tropism and treatment with maraviroc in Sicily: an observational retrospective multicentre study

Purpose of the study: Maraviroc (MVC) is the first CCR5 inhibitor licensed for clinical use. A pre-treatment test is mandatory to identify R5 tropic patients. Aim of this study is to detect indications and results of tropism test and to evaluate efficacy and tolerability of MVC-based regimen. Methods: An observational retrospective multicentre study was performed in Sicily in 15 Infectious Diseases Units. Clinical records of 213 screened for tropism HIV+ subjects were reviewed for age, sex, risk, clinical stage (CDC, CD4 cell count, HIV RNA viral load), therapeutic line, indication and result of test for tropism; within subjects treated with MVC, HIV RNA, CD4 cell count and metabolic parameters trend and adverse events were analysed. Summary of results: Median age 44 (IQR 30–50) years, 67.1% males; 46.3% heterosexuals, 28.6% MSMs, 21.4% IVDUs; 23.7% CDC A, 32.1% CDC B, 44.2% CDC C; median CD4 was 217 (IQR 121–374) cells/µl and mean of HIV RNA was 4.72 (Cl 95% 4.07–4.67) log10 copies/ml; median therapeutic line was 4 (IQR 2–7). 80.8% were submitted to Trofile™ test, 19.2% to genotypic test, 75.5% after a therapeutic failure. 56.8% of subjects screened were R5, 7.5% X4, 21.6% DM, 14% undefined. All X4 patients were tested after a therapeutic failure; patients screened for toxicity were more frequently R5 (75%) (p<0.01). 76 (35.7%) multi-experienced (at baseline 8% HIV RNA<50 copies/ml, median CD4 cell count 219 (IQR 124–345) cells/µl) subjects were treated with MVC plus an optimized background treatment: MVC was associated in 74% of cases with a protease inhibitors (56% darunavir/ritonavir), in 42% with raltegravir, in 56% with a NUC-sparing regimen. After 12 months of treatment 56.8% (ITT analysis) and 61.7% (AT) of patients had HIV RNA<50 copies/ml; median CD4 cell count was 387 (IQR 222–455) cells/µl. After 24 months 64.8% (ITT) 80% (AT) had HIV-RNA<50 copies/ml. Median CD4 cell count was 381 (IQR 218.515) cells/µl with a median increase of 168 (IQR 54–274) cells/µl. At 24 months median value of total and HDL cholesterol and triglycerides were within the normal range. 7 patients stopped the treatment: 2 died, 1 adverse event, 4 virological failure. Conclusions: Although the test has been proposed to patients with long treatment history and failure, only 3/5 of R5 tropic patients were treated with MVC. An high number of multi-experienced subjects treated with a MVC-based regimen obtained HIV RNA<50 copies/ml and a satisfactory increase of CD4 cell count

RHIC Performance for FY2011 Au+Au Heavy Ion Run

Following the Fiscal Year (FY) 2010 (Run-10) Relativistic Heavy Ion Collider (RHIC) Au+Au run, RHIC experiment upgrades sought to improve detector capabilities. In turn, accelerator improvements were made to improve the luminosity available to the experiments for this run (Run-11). These improvements included: a redesign of the stochastic cooling systems for improved reliability; a relocation of 'common' RF cavities to alleviate intensity limits due to beam loading; and an improved usage of feedback systems to control orbit, tune and coupling during energy ramps as well as while colliding at top energy. We present an overview of changes to the Collider and review the performance of the collider with respect to instantaneous and integrated luminosity goals. At the conclusion of the FY 2011 polarized proton run, preparations for heavy ion run proceeded on April 18, with Au+Au collisions continuing through June 28. Our standard operations at 100 GeV/nucleon beam energy was bracketed by two shorter periods of collisions at lower energies (9.8 and 13.5 GeV/nucleon), continuing a previously established program of low and medium energy runs. Table 1 summarizes our history of heavy ion operations at RHIC

RHIC Polarized proton performance in run-8

During Run-8, the Relativistic Heavy Ion Collider (RHIC) provided collisions of spin-polarized proton beams at two interaction regions. Physics data were taken with vertical orientation of the beam polarization, which in the 'Yellow' RHIC ring was significantly lower than in previous years. We present recent developments and improvements as well as the luminosity and polarization performance achieved during Run-8, and we discuss possible causes of the not as high as previously achieved polarization performance of the 'Yellow' ring

DMT1 Expression and Iron Levels at the Crossroads Between Aging and Neurodegeneration

Iron homeostasis is an essential prerequisite for metabolic and neurological functions throughout the healthy human life, with a dynamic interplay between intracellular and systemic iron metabolism. The development of different neurodegenerative diseases is associated with alterations of the intracellular transport of iron and heavy metals, principally mediated by Divalent Metal Transporter 1 (DMT1), responsible for Non-Transferrin Bound Iron transport (NTBI). In addition, DMT1 regulation and its compartmentalization in specific brain regions play important roles during aging. This review highlights the contribution of DMT1 to the physiological exchange and distribution of body iron and heavy metals during aging and neurodegenerative diseases. DMT1 also mediates the crosstalk between central nervous system and peripheral tissues, by systemic diffusion through the Blood Brain Barrier (BBB), with the involvement of peripheral iron homeostasis in association with inflammation. In conclusion, a survey about the role of DMT1 and iron will illustrate the complex panel of interrelationship with aging, neurodegeneration and neuroinflammation

Analysis of different geometrical features to achieve close-to-bone stiffness material properties in medical device: A feasibility numerical study

Background and objective: In orthopedic medical devices, elasto-plastic behavior differences between bone and metallic materials could lead to mechanical issues at the bone-implant interface, as stress shielding. Those issue are mainly related to knee and hip arthroplasty, and they could be responsible for implant failure. To reduce mismatching-related adverse events between bone and prosthesis mechanical properties, modifying the implant's internal geometry varying the bulk stiffness and density could be the right approach. Therefore, this feasibility study aims to assess which in-body gap geometry improves, by reducing, the bulk stiffness. Methods: Using five finite element models, a uniaxial compression test in five cubes with a 20 mm thickness was simulated and analyzed. The displacements, strain and Young Modulus were calculated in four cubes, each containing internal prismatic gaps with different transversal sections (squared, hexagonal, octagonal, and circular). Those were compared with a fifth full-volume cube used as control. Results: The most significant difference have been achieved in displacement values, in cubes containing internal gaps with hexagonal and circular transversal sections (82 µm and 82.5 µm, respectively), when compared to the full-volume cube (69.3 µm). Conclusions: This study suggests that hexagonal and circular shape of the gaps allows obtaining the lower rigidity in a size range of 4 mm, offering a starting approach to achieve a “close-to-bone” material, with a potential use in prosthetic devices with limited thickness