In vivo "real-time" monitoring of glucose in the brain with an amperometric enzyme-based biosensor based on gold coated tungsten (W-Au) microelectrodes

Biosensors based on Pt or Pt/Ir based needle-type microelectrodes have been successfully employed for continuous in vivo real-time brain biomonitoring of biomarkers such as glutamate and glucose. However, when implanted, these biosensors often bend, thereby damaging its surface and degrading its bioanalytical properties. In addition, downscaling of Pt and Pt/Ir needle-type biosensors, to improve the spatial resolution and decrease tissue damage, is technically challenging. In that sense, we investigated whether the use of a material with low malleability, tungsten (W), coated with a highly conductive material, gold (Au) could be as an alternative for conventional needle-type based biosensors. Therefore, we developed implantable needle-type (50 tim 0) gold coated tungsten (W-Au) amperometric microbiosensors. First, we evaluated electrochemically, the ability of W-Au microelectrodes (50 tim 0) to continuously monitor changes in H2O2. After, we functionalized, using a layer-by-layer assembly, the surface of W-Au microelectrodes. First with permselective membrane(s) (Nafion and Nafion-PPD) and after with an enzymatic hydrogel, containing an enzyme selective for glucose (glucose oxidase). Both the enzyme loading and the applied potential were optimized and the performance of functionalized W-Au microelectrodes and fully assembled biosensors was evaluated electrochemically. Additionally, the surface of bare and functionalized microelectrodes was also characterized by imaging techniques (scanning electron microscopy). In vivo experiments revealed that, W-Au based glucose biosensors, were able to accurately monitor, in real-time, changes in brain glucose in response to relevant pharmacological challenges. (C) 2018 Elsevier B.V. All rights reserved

Enzalutamide Reduces Oxycodone Exposure in Men with Prostate Cancer

BACKGROUND AND OBJECTIVE: Up to 90% of patients with castration-resistant prostate cancer (CRPC) will develop symptomatic bone metastases requiring pain medication, with opioids being the mainstay of therapy in treating moderate and severe pain. Enzalutamide is an androgen receptor antagonist for the treatment of CRPC and a strong inducer of cytochrome P450 (CYP)3A4. Hereby, enzalutamide potentially reduces the exposure of oxycodone, an opioid metabolized by CYP3A4 and CYP2D6. Our objective was to evaluate the potential drug-drug interaction of enzalutamide and oxycodone.METHODS: A prospective, nonrandomized, open-label, two-arm parallel study was performed. All patients received a single dose of 15 mg normal-release oxycodone. Patients in the enzalutamide arm (ENZ-arm) received enzalutamide 160 mg once daily. Plasma concentrations of oxycodone and its metabolites were quantified using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method.RESULTS: Twenty-six patients (13 ENZ-arm; 13 control arm) were enrolled in the study. Enzalutamide decreased the mean AUC 0-8 h and C max of oxycodone with, respectively, 44.7% (p &lt; 0.001) and 35.5% (p = 0.004) compared with the control arm. The AUC 0-8 h and C max of the active metabolite oxymorphone were 74.2% (p &lt; 0.001) and 56.0% (p = 0.001) lower in the ENZ-arm compared with the control arm. In contrast, AUC 0-8 h and C max of the inactive metabolites noroxycodone and noroxymorphone were significantly increased by enzalutamide. CONCLUSION: Co-administration of enzalutamide significantly reduced exposure to oxycodone and its active metabolite oxymorphone in men with prostate cancer. This should be taken into account when prescribing enzalutamide combined with oxycodone.</p

Floquet scattering theory of quantum pumps

We develop the Floquet scattering theory for quantum mechanical pumping in mesoscopic conductors. The nonequilibrium distribution function, the dc charge and heat currents are investigated at arbitrary pumping amplitude and frequency. For mesoscopic samples with discrete spectrum we predict a sign reversal of the pumped current when the pump frequency is equal to the level spacing in the sample. This effect allows to measure the phase of the transmission coefficient through the mesoscopic sample. We discuss the necessary symmetry conditions (both spatial and temporal) for pumping.Comment: 11 pages, 5 figure

Charge Pumping in Mesoscopic Systems coupled to a Superconducting Lead

We derive a general scattering-matrix formula for the pumped current through a mesoscopic region attached to a normal and a superconducting lead. As applications of this result we calculate the current pumped through (i) a pump in a wire, (ii) a quantum dot in the Coulomb blockade regime, and (iii) a ballistic double-barrier junction, all coupled to a superconducting lead. Andreev reflection is shown to enhance the pumped current by up to a factor of 4 in case of equal coupling to the leads. We find that this enhancement can still be further increased for slightly asymmetric coupling.Comment: 5 pages, 2 figure

Ultrashort filaments of light in weakly-ionized, optically-transparent media

Modern laser sources nowadays deliver ultrashort light pulses reaching few cycles in duration, high energies beyond the Joule level and peak powers exceeding several terawatt (TW). When such pulses propagate through optically-transparent media, they first self-focus in space and grow in intensity, until they generate a tenuous plasma by photo-ionization. For free electron densities and beam intensities below their breakdown limits, these pulses evolve as self-guided objects, resulting from successive equilibria between the Kerr focusing process, the chromatic dispersion of the medium, and the defocusing action of the electron plasma. Discovered one decade ago, this self-channeling mechanism reveals a new physics, widely extending the frontiers of nonlinear optics. Implications include long-distance propagation of TW beams in the atmosphere, supercontinuum emission, pulse shortening as well as high-order harmonic generation. This review presents the landmarks of the 10-odd-year progress in this field. Particular emphasis is laid to the theoretical modeling of the propagation equations, whose physical ingredients are discussed from numerical simulations. Differences between femtosecond pulses propagating in gaseous or condensed materials are underlined. Attention is also paid to the multifilamentation instability of broad, powerful beams, breaking up the energy distribution into small-scale cells along the optical path. The robustness of the resulting filaments in adverse weathers, their large conical emission exploited for multipollutant remote sensing, nonlinear spectroscopy, and the possibility to guide electric discharges in air are finally addressed on the basis of experimental results.Comment: 50 pages, 38 figure

Large-scale associations between the leukocyte transcriptome and BOLD responses to speech differ in autism early language outcome subtypes.

Heterogeneity in early language development in autism spectrum disorder (ASD) is clinically important and may reflect neurobiologically distinct subtypes. Here, we identified a large-scale association between multiple coordinated blood leukocyte gene coexpression modules and the multivariate functional neuroimaging (fMRI) response to speech. Gene coexpression modules associated with the multivariate fMRI response to speech were different for all pairwise comparisons between typically developing toddlers and toddlers with ASD and poor versus good early language outcome. Associated coexpression modules were enriched in genes that are broadly expressed in the brain and many other tissues. These coexpression modules were also enriched in ASD-associated, prenatal, human-specific, and language-relevant genes. This work highlights distinctive neurobiology in ASD subtypes with different early language outcomes that is present well before such outcomes are known. Associations between neuroimaging measures and gene expression levels in blood leukocytes may offer a unique in vivo window into identifying brain-relevant molecular mechanisms in ASD

Influence of family and friend smoking on intentions to smoke and smoking-related attitudes and refusal self-efficacy among 9-10 year old children from deprived neighbourhoods: a cross-sectional study.

BACKGROUND: Smoking often starts in early adolescence and addiction can occur rapidly. For effective smoking prevention there is a need to identify at risk groups of preadolescent children and whether gender-specific intervention components are necessary. This study aimed to examine associations between mother, father, sibling and friend smoking and cognitive vulnerability to smoking among preadolescent children living in deprived neighbourhoods. METHODS: Cross-sectional data was collected from 9-10 year old children (n =1143; 50.7% girls; 85.6% White British) from 43 primary schools in Merseyside, England. Children completed a questionnaire that assessed their smoking-related behaviour, intentions, attitudes, and refusal self-efficacy, as well as parent, sibling and friend smoking. Data for boys and girls were analysed separately using multilevel linear and logistic regression models, adjusting for individual cognitions and school and deprivation level. RESULTS: Compared to girls, boys had lower non-smoking intentions (P = 0.02), refusal self-efficacy (P = 0.04) and were less likely to agree that smoking is 'definitely' bad for health (P < 0.01). Friend smoking was negatively associated with non-smoking intentions in girls (P < 0.01) and boys (P < 0.01), and with refusal self-efficacy in girls (P < 0.01). Sibling smoking was negatively associated with non-smoking intentions in girls (P < 0.01) but a positive association was found in boys (P = 0.02). Boys who had a smoking friend were less likely to 'definitely' believe that the smoke from other people's cigarettes is harmful (OR 0.57, 95% CI: 0.35 to 0.91, P = 0.02). Further, boys with a smoking friend (OR 0.38, 95% CI: 0.21 to 0.69, P < 0.01) or a smoking sibling (OR 0.45, 95% CI: 0.21 to 0.98) were less likely to 'definitely' believe that smoking is bad for health. CONCLUSION: This study indicates that sibling and friend smoking may represent important influences on 9-10 year old children's cognitive vulnerability toward smoking. Whilst some differential findings by gender were observed, these may not be sufficient to warrant separate prevention interventions. However, further research is needed