Trichothecenes NIV and DON modulate the maturation of murinedendritic cells

Nivalenol (NIV) and Deoxynivalenol (DON), mycotoxins of the trichothecene family are considered very common food contaminants. In this work, we investigated whether the immunotoxic effects ascribed to these trichothecenes may be mediated by perturbations in the activity of dendritic cells (DCs). Murine bone marrow-derived DCs were used to evaluate the effects of NIV and DON on the LPS-induced maturation process.We found that the expression of the class II MHC and of the accessory CD11c molecules, but not of the costimulatory CD86 marker, was down-regulated by NIV and DON exposure in LPS-treated DCs, as well as nitric oxide (NO) production. Interestingly, NIV, but not DON, induced DC necrosis. Moreover, the analysis of the cytokine pattern showed that IL-12 and IL-10 expressions induced by LPS exposure were suppressed by both trichothecenes in a dose-dependent fashion. On the other hand, the secretion of the proinflammatory cytokine TNFa was increased as a direct consequence of DON and NIV exposure. Taken together, our data indicated that the immunotoxicity of NIV and DON was related to the capacity of both trichothecenes to interfere with phenotypic and functional features of maturing DCs

CAM04-1: Admission control in self aware networks

The worldwide growth in broadband access and multimedia traffic has led to an increasing need for Quality- of-Service (QoS) in networks. Real time network applications require a stable, reliable, and predictable network that will guarantee packet delivery under QoS constraints. Network self- awareness through on-line measurement and adaptivity in response to user needs is one way to advance user QoS when overall network conditions can change, while admission control (AC) is an approach that has been commonly used to reduce traffic congestion and to satisfy users' QoS requests. The purpose of this paper is to describe a novel measurement-based admission control algorithm which bases its decision on different QoS metrics that users can specify. The self-observation and self- awareness capabilities of the network are exploited to collect data that allows an AC algorithm to decide whether to admit users based on their QoS needs, and the QoS impact they will have on other users. The approach we propose finds whether feasible paths exist for the projected incoming traffic, and estimates the impact that the newly accepted traffic will have on the QoS of pre-existing connections. The AC decision is then taken based on the outcome of this analysis

Dosimetry by 90Y internal pair production PET imaging after liver radioembolization: How well can we quantify the absorbed dose to lesions?

Radioembolization is a catheter-based liver-directed therapy indicated mainly in a palliative setting for primary and secondary hepatic malignancies. It involves the administration of 90Y-loaded microspheres in the arterial vasculature of the liver by use of percutaneous transarterial techniques. Previous studies showed that the decay of 90Y has a minor branch to the 0+ first excited state of 90Zr at 1.76MeV, that is followed by a β+/β− emission. In recent years, a number of authors have used the small positronic emission of 90Y, (3.186±0.047)·10−5, to obtain highresolution positron emission tomography (PET) images of 90Y biodistribution after liver radioembolization. At present, it is generally accepted that the possibility of detecting β+ emissions from 90Y by PET scanners may pave the way for an accurate patient-specific dosimetry. The present paper has a twofold purpose. Firstly, a brief overview of imaging modalities currently used to assess microsphere biodistribution after liver radioembolization is presented. Secondly, the paper focuses on 90Y-PET dosimetry. A benchmark between a number of dosimetric approaches for accurate dosimetry after liver radioembolization with 90Y-PET dosimetry is presented

Triggering the catalytic activity of SrTiO3-based ceramics by flash sintering

Confinement of charge carriers in nanoscopic systems has revealed to be an effective strategy to confer ceramic materials unconventional conductive properties by exploiting particle size effects and interfaces characteristics[1]. Strontium titanate (SrTiO3) is a piezoelectric oxide that requires to be doped by acceptor species (e.g. Fe substitution of Ti centers) in order to acquire fair chemical reactivity[2]. Please click Additional Files below to see the full abstract

Preliminary report in treatment of proximal humeral fracture with closed reduction and DOS external fixation System: a multicentric study

Introduction: Proximal humerus fractures are the seventh most frequent fracture in adults, and the third in patients over 65 years old, 5.7% of whole diagnosed fractures. Most of these fractures can be treated conservatively and achieve good results. However, more and more frequently we are confronted with dislo-cated and multifragmentary fractures, and with elderly and high functional demanding patients. In patients with osteoporosis and poor general conditions external fixation can be performed as rapid and mininvasive procedure with good outcome and low complication rates. The authors investigated the use of external fixa-tion in the treatment of proximal humerus fractures. The objective is to demonstrate the effectiveness of this method as a valid alternative to other surgical techniques. Materials and Methods: A multicentre study was conducted at 7 hospitals in Italy from 2014 through 2018. We recruited all proximal humeral fractures (as classified with the Neer system) that are surgically treated with the same external fixator DOS, for a total of 110 patients, evaluated later with Oxford Shoulder Scale (OSS) and disability of the arm, shoulder and hand score (DASH) at 1, 2 and 6 months. Results:The patients have passed from a score of 75,37 in the first month to a score of 29,47in the sixth month at the DASH and from 47,02 to 27,71 at the OSS. The data further confirm the increased incidence of these fractures in women and in a mean age of about 65. Conclusions:Al-though it does not represent the golden standard in the treatment of fractures of the proximal humerus, in our experience the minimal osteosynthesis with external fixator turned out to be a very valid help especially for the simplicity and speed of the method, as well as for the exciting functional results. sometimes superior to other methods. The preliminary results from the different centers have confirmed this hypothesis. We hope this will be a good starting point for further in-depth studies

Dried blood spot UHPLC-MS/MS analysis of oseltamivir and oseltamivircarboxylate—a validated assay for the clinic

The neuraminidase inhibitor oseltamivir (Tamiflu®) is currently the first-line therapy for patients with influenza virus infection. Common analysis of the prodrug and its active metabolite oseltamivircarboxylate is determined via extraction from plasma. Compared with these assays, dried blood spot (DBS) analysis provides several advantages, including a minimum sample volume required for the measurement of drugs in whole blood. Samples can easily be obtained via a simple, non-invasive finger or heel prick. Mainly, these characteristics make DBS an ideal tool for pediatrics and to measure multiple time points such as those needed in therapeutic drug monitoring or pharmacokinetic studies. Additionally, DBS sample preparation, stability, and storage are usually most convenient. In the present work, we developed and fully validated a DBS assay for the simultaneous determination of oseltamivir and oseltamivircarboxylate concentrations in human whole blood. We demonstrate the simplicity of DBS sample preparation, and a fast, accurate and reproducible analysis using ultra high-performance liquid chromatography coupled to a triple quadrupole mass spectrometer. A thorough validation on the basis of the most recent FDA guidelines for bioanalytical method validation showed that the method is selective, precise, and accurate (≤15% RSD), and sensitive over the relevant clinical range of 5–1,500 ng/mL for oseltamivir and 20–1,500 ng/mL for the oseltamivircarboxylate metabolite. As a proof of concept, oseltamivir and oseltamivircarboxylate levels were determined in DBS obtained from healthy volunteers who received a single oral dose of Tamiflu®

Sol-gel derived mesoporous Pt and Cr-doped WO(3) thin films: the role played by mesoporosity and metal doping in enhancing the gas sensing properties

Mesoporous Cr or Pt-doped WO(3) thin films to be employed as ammonia gas sensors were prepared by a fast one-step sol-gel procedure, based on the use of triblock copolymer as templating agent. The obtained films were constituted by aggregates of interconnected WO(3) nanocrystals (20-50 nm) separated by mesopores with dimensions ranging between 2 and 15 nm. The doping metals, Pt and Cr, resulted differently hosted in the WO(3) mesoporous matrix. Chromium is homogeneously dispersed in the oxide matrix, mainly as Cr(III) and Cr(V) centers, as revealed by EPR spectroscopy; instead platinum segregated as Pt (0) nanoparticles (4 nm) mainly included inside the WO(3) nanocrystals. The semiconductor layers containing Pt nanoclusters revealed, upon exposure to NH(3), remarkable electrical responses, much higher than Cr-doped and undoped layers, particularly at low ammonia concentration (6.2 ppm). This behavior was attributed to the presence of Pt nanoparticles segregated inside the semiconductor matrix, which act as catalysts of the N-H bond cleavage, decreasing the activation barrier in the ammonia dissociation. The role of the mesoporous structure in influencing the chemisorption and the gas diffusion in the WO(3) matrix appeared less decisive than the electronic differences between the two examined doping metals. The overall results suggest that a careful combination between mesoporous architecture and metal doping can really promote the electrical response of WO(3) toward ammonia

Combinations of QT-prolonging drugs: towards disentangling pharmacokinetic and pharmaco-dynamic effects in their potentially additive nature.

Background: Whether arrhythmia risks will increase if drugs with electrocardiographic (ECG) QT-prolonging properties are combined is generally supposed but not well studied. Based on available evidence, the Arizona Center for Education and Research on Therapeutics (AZCERT) classification defines the risk of QT prolongation for exposure to single drugs. We aimed to investigate how combining AZCERT drug categories impacts QT duration and how relative drug exposure affects the extent of pharmacodynamic drug–drug interactions. Methods: In a cohort of 2558 psychiatric inpatients and outpatients, we modeled whether AZCERT class and number of coprescribed QT-prolonging drugs correlates with observed rate-corrected QT duration (QTc) while also considering age, sex, inpatient status, and other QTc-prolonging risk factors. We concurrently considered administered drug doses and pharmacokinetic interactions modulating drug clearance to calculate individual weights of relative exposure with AZCERT drugs. Because QTc duration is concentration-dependent, we estimated individual drug exposure with these drugs and included this information as weights in weighted regression analyses. Results: Drugs attributing a ‘known’ risk for clinical consequences were associated with the largest QTc prolongations. However, the presence of at least two versus one QTc-prolonging drug yielded nonsignificant prolongations [exposure-weighted parameter estimates with 95% confidence intervals for ‘known’ risk drugs + 0.93 ms (–8.88;10.75)]. Estimates for the ‘conditional’ risk class increased upon refinement with relative drug exposure and coadministration of a ‘known’ risk drug as a further risk factor. Conclusions: These observations indicate that indiscriminate combinations of QTc-prolonging drugs do not necessarily result in additive QTc prolongation and suggest that QT prolongation caused by drug combinations strongly depends on the nature of the combination partners and individual drug exposure. Concurrently, it stresses the value of the AZCERT classification also for the risk prediction of combination therapies with QT-prolonging drugs