Ordered mesoporous silica functionalized with beta-cyclodextrin derivative for stereoisomer separation of flavanones and flavanone glycosides by nano-liquid chromatography and capillary electrochromatography

In this paper a chiral stationary phase (CSP) was prepared by the immobilization of a beta-CD derivative (3,5-dimethylphenylcarbamoylated beta-CD) onto the surface of amino-functionalized spherical ordered mesoporous silica (denoted as SM) via a urea linkage using the Staudinger reaction. The CSP was packed into fused silica capillaries 100 mu m I.D. and evaluated by means of nano-liquid chromatography (nano-LC) and capillary electrochromatography (CEC) using model compounds for the enantio- and the diastereomeric separation. The compounds flavanone, 2'-hydroxyflavanone, 4'-hydroxyflavanone, 6hydroxyflavanone, 4'-methoxyflavanone, 7-methoxyfiavanone, hesperetin, hesperidin, naringenin, and naringin were studied using reversed and polar organic elution modes. Baseline stereoisomer resolution and good results in terms of peak efficiency and short analysis time of all studied flavonoids and flavanones glycosides were achieved in reversed phase mode, using as mobile phase a mixture of MeOH/H2O, 10 mM ammonium acetate pH 4.5 at different ratios. For the polar organic mode using 100% of MeOH as mobile phase, the CSP showed better performances and the baseline chiral separation of several studied compounds occurred in an analysis time of less than 10 min. Good results were also achieved by CEC employing two different mobile phases. The use of MeOH/H2O, 5 mM ammonium acetate buffer pH 6.0 (90/10, v/v) was very effective for the chiral resolution of flavanone and its methoxy and hydroxy derivatives. (C) 2017 Elsevier B.V. All rights reserved

Monitoring Risk Factors and Improving Adherence to Therapy in Patients With Chronic Kidney Disease (Smit-CKD Project): Pilot Observational Study

Background: Chronic kidney disease is a major public health issue, with about 13% of the general adult population and 30% of the elderly affected. Patients in the last stage of this disease have an almost uniquely high risk of death and cardiovascular events, with reduced adherence to therapy representing an additional risk factor for cardiovascular morbidity and mortality. Considering the increased penetration of mobile phones, a mobile app could educate patients to autonomously monitor cardiorenal risk factors. Objective: With this background in mind, we developed an integrated system of a server and app with the aim of improving self-monitoring of cardiovascular and renal risk factors and adherence to therapy. Methods: The software infrastructure for both the Smit-CKD server and Smit-CKD app was developed using standard web-oriented development methodologies preferring open source tools when available. To make the Smit-CKD app suitable for Android and iOS, platforms that allow the development of a multiplatform app starting from a single source code were used. The integrated system was field tested with the help of 22 participants. User satisfaction and adherence to therapy were measured by questionnaires specifically designed for this study; regular use of the app was measured using the daily reports available on the platform. Results: The Smit-CKD app allows the monitoring of cardiorenal risk factors, such as blood pressure, weight, and blood glucose. Collected data are transmitted in real time to the referring general practitioner. In addition, special reminders improve adherence to the medication regimen. Via the Smit-CKD server, general practitioners can monitor the clinical status of their patients and their adherence to therapy. During the test phase, 73% (16/22) of subjects entered all the required data regularly and sent feedback on drug intake. After 6 months of use, the percentage of regular intake of medications rose from 64% (14/22) to 82% (18/22). Analysis of the evaluation questionnaires showed that both the app and server components were well accepted by the users. Conclusions: Our study demonstrated that a simple mobile app, created to self-monitor modifiable cardiorenal risk factors and adherence to therapy, is well tolerated by patients affected by chronic kidney disease. Further studies are required to clarify if the use of this integrated system will have long-term effects on therapy adherence and if self-monitoring of risk factors will improve clinical outcomes in this population

The potential of eupraxia@sparc_lab for radiation based techniques

A proposal for building a Free Electron Laser, EuPRAXIA@SPARC_LAB, at the Laboratori Nazionali di Frascati, is at present under consideration. This FEL facility will provide a unique combination of a high brightness GeV-range electron beam generated in a X-band RF linac, a 0.5 PW-class laser system and the first FEL source driven by a plasma accelerator. The FEL will produce ultra-bright pulses, with up to 1012 photons/pulse, femtosecond timescale and wavelength down to 3 nm, which lies in the so called “water window”. The experimental activity will be focused on the realization of a plasma driven short wavelength FEL able to provide high-quality photons for a user beamline. In this paper, we describe the main classes of experiments that will be performed at the facility, including coherent diffraction imaging, soft X-ray absorption spectroscopy, Raman spectroscopy, Resonant Inelastic X-ray Scattering and photofragmentation measurements. These techniques will allow studying a variety of samples, both biological and inorganic, providing information about their structure and dynamical behavior. In this context, the possibility of inducing changes in samples via pump pulses leading to the stimulation of chemical reactions or the generation of coherent excitations would tremendously benefit from pulses in the soft X-ray region. High power synchronized optical lasers and a TeraHertz radiation source will indeed be made available for THz and pump–probe experiments and a split-and-delay station will allow performing XUV-XUV pump–probe experiments.Fil: Balerna, Antonella. Istituto Nazionale Di Fisica Nucleare.; ItaliaFil: Bartocci, Samanta. Università degli studi di Sassari; ItaliaFil: Batignani, Giovanni. Università degli studi di Roma "La Sapienza"; ItaliaFil: Cianchi, Alessandro. Universita Tor Vergata; Italia. Istituto Nazionale Di Fisica Nucleare.; ItaliaFil: Chiadroni, Enrica. Istituto Nazionale Di Fisica Nucleare.; ItaliaFil: Coreno, Marcello. Istituto Nazionale Di Fisica Nucleare.; Italia. Istituto di Struttura della Materia; ItaliaFil: Cricenti, Antonio. Istituto di Struttura della Materia; ItaliaFil: Dabagov, Sultan. Istituto Nazionale Di Fisica Nucleare.; Italia. National Research Nuclear University; Rusia. Lebedev Physical Institute; RusiaFil: Di Cicco, Andrea. Universita Degli Di Camerino; ItaliaFil: Faiferri, Massimo. Università degli studi di Sassari; ItaliaFil: Ferrante, Carino. Università degli studi di Roma “La Sapienza”; Italia. Center for Life Nano Science @Sapienza; ItaliaFil: Ferrario, Massimo. Istituto Nazionale Di Fisica Nucleare.; ItaliaFil: Fumero, Giuseppe. Università degli studi di Roma “La Sapienza”; ItaliaFil: Giannessi, Luca. Elettra-Sincrotrone Trieste; Italia. ENEA C.R. Frascati; ItaliaFil: Gunnella, Roberto. Universita Degli Di Camerino; ItaliaFil: Leani, Juan Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; ArgentinaFil: Lupi, Stefano. Università degli studi di Roma “La Sapienza”; Italia. Istituto Nazionale di Fisica Nucleare (INFN) Sezione di Roma La Sapienza; ItaliaFil: Macis, Salvatore. Università degli Studi di Roma Tor Vergata; Italia. Istituto Nazionale di Fisica Nucleare (INFN) Sezione di Roma Tor Vergata; ItaliaFil: Manca, Rosa. Università degli studi di Sassari; ItaliaFil: Marcelli, Augusto. Istituto Nazionale Di Fisica Nucleare.; Italia. Consiglio Nazionale delle Ricerche; ItaliaFil: Masciovecchio, Claudio. Elettra-Sincrotrone Trieste; ItaliaFil: Minicucci, Marco. Universita Degli Di Camerino; ItaliaFil: Morante, Silvia. Universita Tor Vergata; Italia. Istituto Nazionale Di Fisica Nucleare.; ItaliaFil: Perfetto, Enrico. Universita Tor Vergata; Italia. Consiglio Nazionale delle Ricerche; ItaliaFil: Petrarca, Massimo. Università degli studi di Roma "La Sapienza"; Italia. Istituto Nazionale Di Fisica Nucleare.; ItaliaFil: Pusceddu, Fabrizio. Università degli studi di Sassari; ItaliaFil: Rezvani, Javad. Istituto Nazionale Di Fisica Nucleare.; ItaliaFil: Robledo, José Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; ArgentinaFil: Rossi, Giancarlo. Centro Fermi—Museo Storico della Fisica e Centro Studi e Ricerche “Enrico Fermi”; Italia. Istituto Nazionale Di Fisica Nucleare.; Italia. Universita Tor Vergata; ItaliaFil: Sanchez, Hector Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; ArgentinaFil: Scopigno, Tullio. Center for Life Nano Science @Sapienza; Italia. Università degli studi di Roma "La Sapienza"; ItaliaFil: Stefanucci, Gianluca. Universita Tor Vergata; Italia. Istituto Nazionale Di Fisica Nucleare.; ItaliaFil: Stellato, Francesco. Universita Tor Vergata; Italia. Istituto Nazionale Di Fisica Nucleare.; ItaliaFil: Trapananti, Angela. Universita Degli Di Camerino; ItaliaFil: Villa, Fabio. Istituto Nazionale Di Fisica Nucleare.; Itali

Integrase defective lentiviral vector as a vaccine platform for delivering Influenza antigens

Viral vectors represent an attractive technology for vaccine delivery. We exploited the integrase defective lentiviral vector (IDLV) as a platform for delivering relevant antigens within the context of the ADITEC collaborative research program. In particular, Influenza virus hemagglutinin (HA) and nucleoprotein (NP) were delivered by IDLVs while H1N1 A/California/7/2009 subunit vaccine (HAp) with or without adjuvant was used to compare the immune response in a murine model of immunization. In order to maximize the antibody response against HA, both IDLVs were also pseudotyped with HA (IDLV-HA/HA and IDLV-NP/HA, respectively). Groups of CB6F1 mice were immunized intramuscularly with a single dose of IDLV-NP/HA, IDLV-HA/HA, HAp alone or with HAp together with the systemic adjuvant MF59. Six months after the vaccine prime all groups were boosted with HAp alone. Cellular and antibody responses to influenza antigens were measured at different time points after the immunizations. Mice immunized with HA-pseudotyped IDLVs showed similar levels of anti-H1N1 IgG over time, evaluated by ELISA, which were comparable to those induced by HAp+MF59 vaccination, but significantly higher than those induced by HAp alone. The boost with HAp alone induced an increase of antibodies in all groups, and the responses were maintained at higher levels up to 18 weeks post-boost. The antibody response was functional and persistent overtime, capable of neutralizing virus infectivity, as evaluated by hemagglutination inhibition and microneutralization assays. Moreover, since neuraminidase (NA)-expressing plasmid was included during IDLV preparation, immunization with IDLV-NP/HA and IDLV-HA/HA also induced functional anti-NA antibodies, evaluated by Enzyme-Linked Lectine Assay (ELLA). IFN?-ELISPOT showed evidence of HA-specific response in IDLV-HA/HA immunized animals and persistent NP-specific CD8+ T cell response in IDLV-NP/HA immunized mice. Taken together our results indicate that IDLV can be harnessed for producing a vaccine able to induce a comprehensive immune response, including functional antibodies directed towards HA and NA proteins present on the vector particles in addition to a functional T cell response directed to the protein transcribed from the vector

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Microinductive signal conditioning with resonant differential filters: high-sensitivity biodetection applications

Inductive-based devices integrated with Si technology for biodetection applications are characterized, using simple resonant differential filter configurations. This has allowed the corroboration of the viability of the proposed circuits, which are characterized by their very high simplicity, for microinductive signal conditioning in high-sensitivity sensor devices. The simulation of these simple circuits predicts sensitivities of the differential output voltage which can achieve values in the range of 0.1-1 V/nH, depending on the coil parameters. These very high-sensitivity values open the possibility for the experimental detection of extremely small inductance changes in the devices. For real microinductive devices, both series resistance and parasitic capacitive components contribute to the decrease of the differential circuit sensitivity. Nevertheless, measurements performed using micro-coils fabricated with relatively high series resistance and coupling parasitic effects have allowed detection of changes in the range of 2 nH. which are compatible with biodetection applications with estimated detection limits below the picomolarity range

Sleep and human cerebellar pathology

The organization and the quantitative evaluation of sleep stages were studied in patients with cerebellar syndrome. 25 polygraphic night recordings were scored according to the criteria suggested by Rechtschaffen & Kales (1968) and the sleep parameters investigated were referred to those indicated by Williams et al. (1974). The results matched with a homogeneous sample of normal subjects. Significant alterations were observed for several parameters of sleep, and the possible causes discussed

[Myasthenia and sleep]

A Central Nervous System (CNS) acetylcholine receptors involvement in Myasthenia Gravis (MG) has been suggested but never fully demonstrated. On the other hand, although the question concerning the neurotransmitters connected to REM sleep is still unsettled, the importance of acetylcholine as a neurotransmitter involved in the maintenance of this sleep stage has been outlined. The spontaneous night sleep organization has been studied in 9 male subjects with MG and results are compared with those obtained in normal subjects matched for age and sex. Statistically significant differences have been found: 1) slow-waves sleep better represented in MG patients; 2) average REM period length shorter in MG patients; 3) instability of the EEG consisting in a tendency toward lightening of sleep. These findings may confirm the presence of a disturbance in the CNS cholinergic activity of MG patients

Febbre di origine sconosciuta (FUO): nostra casistica

Viene presentata una casistica di 66 pazienti con FUO e vengono descritti: le cause più frequenti, gli esami diagnostici maggiormente contributivi alla diagnosi ed i fattori associati al fatto di giungere ad una diagnosi conclusiva ed alla etiologia (infettiva o non infettiva)