Atomoxetine Enhances Connectivity of Prefrontal Networks in Parkinson's Disease.

Cognitive impairment is common in Parkinson's disease (PD), but often not improved by dopaminergic treatment. New treatment strategies targeting other neurotransmitter deficits are therefore of growing interest. Imaging the brain at rest ('task-free') provides the opportunity to examine the impact of a candidate drug on many of the brain networks that underpin cognition, while minimizing task-related performance confounds. We test this approach using atomoxetine, a selective noradrenaline reuptake inhibitor that modulates the prefrontal cortical activity and can facilitate some executive functions and response inhibition. Thirty-three patients with idiopathic PD underwent task-free fMRI. Patients were scanned twice in a double-blind, placebo-controlled crossover design, following either placebo or 40-mg oral atomoxetine. Seventy-six controls were scanned once without medication to provide normative data. Seed-based correlation analyses were used to measure changes in functional connectivity, with the right inferior frontal gyrus (IFG) a critical region for executive function. Patients on placebo had reduced connectivity relative to controls from right IFG to dorsal anterior cingulate cortex and to left IFG and dorsolateral prefrontal cortex. Atomoxetine increased connectivity from the right IFG to the dorsal anterior cingulate. In addition, the atomoxetine-induced change in connectivity from right IFG to dorsolateral prefrontal cortex was proportional to the change in verbal fluency, a simple index of executive function. The results support the hypothesis that atomoxetine may restore prefrontal networks related to executive functions. We suggest that task-free imaging can support translational pharmacological studies of new drug therapies and provide evidence for engagement of the relevant neurocognitive systems.This work was funded by the Wellcome trust (103838), Parkinson’s UK, National Institute for Health Research’s Cambridge Biomedical Research Centre and the Medical Research Council (MC_US_A060_0016 and RG62761) and the James F McDonnell Foundation (21st century science initiative on Understanding Human Cognition). The BCNI is supported by a joint award from the Wellcome Trust and Medical Research Council.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/npp.2016.1

How sulphate-reducing microorganisms cope with stress: lessons from systems biology

Sulphate-reducing microorganisms (SRMs) are a phylogenetically diverse group of anaerobes encompassing distinct physiologies with a broad ecological distribution. As SRMs have important roles in the biogeochemical cycling of carbon, nitrogen, sulphur and various metals, an understanding of how these organisms respond to environmental stresses is of fundamental and practical importance. In this Review, we highlight recent applications of systems biology tools in studying the stress responses of SRMs, particularly Desulfovibrio spp., at the cell, population, community and ecosystem levels. The syntrophic lifestyle of SRMs is also discussed, with a focus on system-level analyses of adaptive mechanisms. Such information is important for understanding the microbiology of the global sulphur cycle and for developing biotechnological applications of SRMs for environmental remediation, energy production, biocorrosion control, wastewater treatment and mineral recovery

Metallurgical analysis and fatigue resistance of WaveOne and ProTaper Nickel–Titanium instruments

The aim of the study was to evaluate cyclic fatigue resistance of two NiTi instruments and to analyse their surface, fractographic and matrix morphology under ESEM/EDS and optical microscopy. WaveOne Primary and ProTaper Universal F2 brand new instruments were subjected to fatigue testing in an artificial canal with 5.0 mm radius and 60 angle of curvature. Seventy-two instruments were divided into three groups (n = 24), according to the selected kinematics: WaveOne using reciprocation (A); ProTaper using reciprocation (B) or rotation (C). Time to fracture was recorded. Data were analysed with ANOVA and Tukey test. ESEM/EDS analysis was conducted on new files to examine surface characteristics and on fractured fragments to identify the fractographic features. Metallographic analysis was performed with optical microscope on new instruments to evaluate alloy properties. Significant differences were found with Group A, which was statistically more resistant to cyclic fatigue (P\0.05) than the other groups. Surface analysis of new instruments showed both in WaveOne and ProTaper files the presence of deep milling marks. ESEM fractographic analysis of WaveOne showed multiple crack origins with an area of fatigue propagation wider than ProTaper instruments, in which a single crack origin could be detected. EDS analysis confirmed the equiatomic NiTi composition. Metallographic analysis under optical microscope revealed in WaveOne instruments the presence of nano-crystalline martensitic grains embedded in austenite matrix, presence which could not be found in ProTaper files. WaveOne NiTi files revealed higher resistance to fatigue stress, suggesting extended working time in clinical applications