Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,
Ετικέτες
Κυριακή 22 Απριλίου 2018
The Cost of Contralateral Prophylactic Mastectomy in Women with Unilateral Breast Cancer
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Evolution in Monitoring of Free Flap Autologous Breast Reconstruction After Nipple-Sparing Mastectomy: Is There a Best Way?
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Aseptic Freeze Dried vs. Sterile Wet-Packaged Human Cadaveric Acellular Dermal Matrix (ADM) in Immediate Tissue Expander Breast Reconstruction: A Propensity Score Analysis Study
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Modeling white matter microstructure with fiber ball imaging

Source:NeuroImage, Volume 176
Author(s): Emilie T. McKinnon, Joseph A. Helpern, Jens H. Jensen
Fiber ball imaging (FBI) provides a means of calculating the fiber orientation density function (fODF) in white matter from diffusion MRI (dMRI) data obtained over a spherical shell with a b-value of about 4000 s/mm2 or higher. By supplementing this FBI-derived fODF with dMRI data acquired for two lower b-value shells, it is shown that several microstructural parameters may be estimated, including the axonal water fraction (AWF) and the intrinsic intra-axonal diffusivity. This fiber ball white matter (FBWM) modeling method is demonstrated for dMRI data acquired from healthy volunteers, and the results are compared with those of the white matter tract integrity (WMTI) method. Both the AWF and the intra-axonal diffusivity obtained with FBWM are found to be significantly larger than for WMTI, with the FBWM values for the intra-axonal diffusivity being more consistent with recent results obtained using isotropic diffusion weighting. An important practical advantage of FBWM is that the only nonlinear fitting required is the minimization of a cost function with just a single free parameter, which facilitates the implementation of efficient and robust numerical routines.
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Carrying the past to the future: Distinct brain networks underlie individual differences in human spatial working memory capacity

Source:NeuroImage, Volume 176
Author(s): Siwei Liu, Jia-Hou Poh, Hui Li Koh, Kwun Kei Ng, Yng Miin Loke, Joseph Kai Wei Lim, Joanna Su Xian Chong, Juan Zhou
Spatial working memory (SWM) relies on the interplay of anatomically separated and interconnected large-scale brain networks. EEG studies often observe load-associated sustained negative activity during SWM retention. Yet, whether and how such sustained negative activity in retention relates to network-specific functional activation/deactivation and relates to individual differences in SWM capacity remain to be elucidated. To cover these gaps, we recorded concurrent EEG-fMRI data in 70 healthy young adults during the Sternberg delayed-match-to-sample SWM task with three memory load levels. To a subset of participants (N = 28) that performed the task properly and had artefact-free fMRI and EEG data, we employed a novel temporo-spatial principal component analysis to derive load-dependent negative slow wave (NSW) from retention-related event-related potentials. The associations between NSW responses with SWM capacity were divergent in the higher (N = 14) and lower (N = 14) SWM capacity groups. Specifically, larger load-related increase in NSW amplitude was associated with greater SWM capacity for the higher capacity group but lower SWM capacity for the lower capacity group. Furthermore, for the higher capacity group, larger NSW amplitude was related to greater activation in bilateral parietal areas of the fronto-parietal network (FPN) and greater deactivation in medial frontal gyrus and posterior mid-cingulate cortex of the default mode network (DMN) during retention. In contrast, the lower capacity group did not show similar pattern. Instead, greater NSW was linked to higher deactivation in right posterior middle temporal gyrus. Our findings shed light on the possible differential EEG-informed neural network mechanism during memory maintenance underlying individual differences in SWM capacity.
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Polymorphic structures phase diagram of shear-induced isotactic polypropylene/carbon fiber cylindrites
Publication date: 15 July 2018
Source:Materials & Design, Volume 150
Author(s): Jing Zhao, Chen Lu, Shuo Guo, Ke Wang, Qiang Fu
Depending on the thermal and mechanical conditions of pulling fiber in the supercooled melts of isotactic polypropylene (iPP), three kinds of cylindrite with variable polymorphic structure could be achieved, i.e., pure α-cylindrite, mixed α/β cylindrite, and β-rich cylindrite. However, precisely assessing the synergic action of thermal and mechanical factors on polymorphic structure of cylindrite is still challenging. Thanks to the great convenience of temperature gradient (T-g) technique in surveying structural transitions arisen from temperature variation, a crystallization temperature (Tc)-pulling rate (Rpull) dependent phase diagram of polymorphs in iPP/carbon fiber (CF) cylindrite was achieved readily through adopting different Rpulls. It was intriguing to suggest that (1) the temperature regime of mixed α/β cylindrite became narrower and narrower as increasing Rpull, implying a sudden transition from β-polymorph to α-polymorph upon intensive shearing; and (2) the upper threshold temperature that allowing generation of β fan-shaped domain was independent on Rpull, around 145 °C. Moreover, the structural difference between mixed α/β cylindrite and β-rich cylindrite was revealed in detail by scanning electron microscopy. An approximately regular nucleation line of β-form appeared in β-rich cylindrite, due to prevailing α-to-β bifurcation arisen from the edge-on α-lamellae. Whereas, occasional α/β bifurcation was found among a tremendous number of α-lamellae within the mixed α/β regime. Constructing the polymorphs phase diagram is of significance in manipulation of interfacial crystallization entities and fabrication of fiber-reinforced semi-crystalline polymers with high performances.Brief abstractIn this study, the combined effect of crystallization temperature (Tc) and pulling rate (Rpull) on the polymorphic structure of shear-induced cylindrite in isotactic polypropylene (iPP)/carbon fiber (CF) composite was well ascertained by using the T-g field technique. It was found that reducing Tc or improving Rpull might induce the transformations of polymorphism from pure α-cylindrite to mixed α/β cylindrite up to β-rich cylindrite. A crystallization temperature (Tc)-pulling rate (Rpull) dependent phase diagram of polymorphs in iPP/CF cylindrite was achieved readily. It was intriguing to suggest that (1) the temperature regime of mixed α/β cylindrite became narrower and narrower as increasing Rpull, implying a sudden transition from β-polymorph to α-polymorph upon intensive shearing; and (2) the upper threshold temperature that allowing generation of β fan-shaped domain was independent on Rpull, around 145 °C. The findings of this study are meaningful for construction of appropriate interfacially-crystallized structure, which could efficiently induce interfacial enhancement in polymer/fiber composites.
Graphical abstract
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Surface plasmon resonance aided analysis of quantum wells for photonic device applications
Publication date: 15 July 2018
Source:Materials & Design, Volume 150
Author(s): Sheetal Dewan, Ayushi Paliwal, Monika Tomar, Ashok K. Kapoor, R.P. Tandon, Vinay Gupta
The present report aims at analyzing the quantum well (QW) structures using the highly sensitive surface plasmon resonance (SPR) technique in Otto configuration. The optical properties of ZnO and Ni doped ZnO (NiZnO) based QW structures grown using Pulsed laser deposition technique are investigated. An optimal value of QW width (8nm) is deduced from the SPR study for maximum charge carrier confinement which is in coherence with the photoluminescence (PL) studies conducted on the same QW structures. The metal-dielectric interfaces were modelled primarily for the design of QW structures to be analysed experimentally. The mechanism behind the coupling of QWs with SP excitation has been proposed theoretically and experimentally to substantiate the results of PL and SPR studies. The variation in the SPR curves observed as a function of the QW width can be attributed to the interaction of evanescent SP field originating at the Au/QW interface and electroabsorptive behaviour of QWs towards the SP field.
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Interfacial bonding during multi-material fused deposition modeling (FDM) process due to inter-molecular diffusion
Publication date: 15 July 2018
Source:Materials & Design, Volume 150
Author(s): Jun Yin, Chaohua Lu, Jianzhong Fu, Yong Huang, Yixiong Zheng
Multi-material fused deposition modeling (FDM) is an effective tool to realize the optimal design and manufacturing with various materials, but how to achieve an adequate level of interfacial bonding strength between dissimilar materials is still a critical problem. Herein, the influence of three multi-material FDM processing parameters, i.e. nozzle temperature, building stage temperature and printing speed, on the interfacial bonding strength of thermoplastic polyurethane (TPU)/acrylonitrile butadiene styrene (ABS) bi-material structures was experimentally investigated. It was found that the interfacial bonding strength was significantly improved from 0.86 to 1.66 MPa (increased by 93%) when the building stage temperature increased from 30 to 68 °C, which was the most effective processing parameter. Then, a heat transfer-based polymer inter-molecular diffusion theory was developed to understand the interfacial bonding mechanism. The interfacial temperature profiles during multi-material FDM process were experimentally measured by inserting thermocouples into printing specimens, and the theoretical model was well validated due to the good agreement between experimental and numerical data of interfacial temperature and bonding strength. The model provided an accurate prediction of interfacial bonding strength based on the understanding of thermally-driven diffusion of multi-material filaments; which would help improving the mechanical properties of products fabricated by multi-material FDM.
Graphical abstract
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Optimising in-situ nitridation in piled aluminium flakes for novel closed cell composites with high fracture stress and toughness
Publication date: 15 July 2018
Source:Materials & Design, Volume 150
Author(s): Andrey A. Chernousov, Ben Y.B. Chan
Modified aluminium foams, such as syntactic aluminium foams (SAFs) that contain tiny ceramic hollow spheres, are widely used for the protection of modern lightweight vehicles in mechanical impacts. Due to the typical compromises between strength and toughness, conventional SAFs absorb <5 J g−1 of mechanical energy before fracture.In this study, we demonstrate that a nacre-like structure of piled aluminium flakes with in-situ grown AlN layers can provide a specific toughness of up to ~50 J g−1. At the optimum toughness, the compressive yield strength σ0.2%, fracture strength σT and strain εT reach ≈110 MPa, 481 MPa and 0.35, respectively. The improved properties originate from the efficient nitridation-driven spreading of the partially melted Al of the flakes through the permeable nitride layers. In an N2 atmosphere at about 833 K, an optimal composite structure is formed with a porosity ϕE and AlN volume fraction vAlN of 0.26 and 0.12, respectively. The pre- and post-optimal annealing temperatures lead to a relatively small area of Al-AlN bonding, as a result of overgrowth and undergrowth of the AlN surfaces, respectively.This straightforward technology offers an affordable way to produce novel lightweight composites for state-of-the-art protection of vehicles and dynamic machinery in many industrial areas.
Graphical abstract
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A new approach to rapidly generate random periodic representative volume elements for microstructural assessment of high volume fraction composites
Publication date: 15 July 2018
Source:Materials & Design, Volume 150
Author(s): Geng Li, Farzad Sharifpour, Aram Bahmani, John Montesano
An algorithm based on event-driven molecular dynamics theory was developed to rapidly generate periodic representative volume elements (RVEs) with nonuniform distributions for both unidirectional fibre-reinforced and spherical particle-reinforced composites. Detailed statistical analyses were conducted for assessing the ability to generate RVEs with nonuniformly dispersed microstructures and either constant or random inclusion sizes for a wide range of volume fractions. The generated microstructures were directly compared with available microstructural optical images of a composite material, showing excellent statistical correlation and providing validation for the developed RVE generation approach. For further validation, finite element analysis was conducted using the generated RVEs in order to evaluate volume averaged elastic constants. The expected isotropic characteristics of the RVEs were correctly calculated, and excellent correlations with experimental data from the literature provided additional support for the algorithm accuracy. The versatile algorithm can rapidly generate RVEs with realistic reinforcement dispersions and high volume fractions up to 80%, which is advantageous compared to other algorithms. The proposed algorithm can be used as a design tool to accurately evaluate and tailor the mechanical properties of distinct composite material systems, and for their microstructural assessment including local damage predictions.
Graphical abstract
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The role of defects and critical pore size analysis in the fatigue response of additively manufactured IN718 via crystal plasticity
Publication date: 15 July 2018
Source:Materials & Design, Volume 150
Author(s): Veerappan Prithivirajan, Michael D. Sangid
The inherent defects associated with materials produced by selective laser melting (SLM) limits their usage in safety-critical applications. In our work, a crystal plasticity (CP) based framework is developed to identify the critical porosity characteristics, which quantifies the limiting scenarios of fatigue crack initiation at a pore rather than the crystallographic features. 3D virtual microstructures are developed based on the characterization of SLM IN718 for use in the CP simulations. Damage indicator parameters, such as the plastic strain accumulation, elastic stress anisotropy, resolved shear stress and triaxiality, obtained from the CP simulations are used to identify the most probable locations of crack initiation. Pores are explicitly added to the microstructure instantiations in a systematic manner by varying the size, location, and proximity between pores. The critical pore size is defined as the size beyond which the location of crack nucleation transitions from crystallographic features to the pore vicinity, which is determined to be 20 μm in the material of interest with an average grain size of 48 μm. This work is beneficial in qualifying SLM materials given the natural porosity inherent to the manufacturing process, by reducing the number of fatigue experiments.
Graphical abstract
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Mechanisms of WC plastic deformation in cemented carbide
Publication date: 15 July 2018
Source:Materials & Design, Volume 150
Author(s): Xuemei Liu, Jianlong Zhang, Chao Hou, Haibin Wang, Xiaoyan Song, Zuoren Nie
The WC-Co cemented carbides with ultracoarse and ultrafine grain structures were tested by the bonded interface technique to investigate the deformation behaviour of WC. The electron backscattering diffraction assisted trace analysis and transmission electron microscopy were combined to examine the microstructural details in the deformation region. It was found that the plastic characteristics of the ultracoarse WC originate from both the prismatic (e.g. {101¯0} ⟨1¯21¯3⟩) and pyramidal (e.g. {01¯11} ⟨01¯10⟩) slip systems. The deformation mechanisms of the ultracoarse and ultrafine cemented carbides were compared. It was proposed that different from the ultrafine cemented carbides in which the plastic deformation is mainly attributed to the metal binder, the dislocations and stacking faults in WC make significant contributions to the plastic deformation hence the fracture toughness of the ultracoarse cemented carbide.
Graphical abstract
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High temperature thermodynamics of spinodal decomposition in arc deposited TixNbyAlzN coatings
Publication date: 15 July 2018
Source:Materials & Design, Volume 150
Author(s): F. Tasnádi, L. Rogström, J. Zhu, F. Wang, T.-W. Hsu, H. Lind, I.A. Abrikosov, M.P. Johansson-Jõesaar, M. Odén
Using first principles calculations and experimental methods we show that B1 structured solid solution TixNbyAlzN can be grown. The mixing free energy surface indicates that the alloys should decompose. Theoretical analysis of the thermodynamic driving force towards the spinodal decomposition shows that the force can be different in alloys with equally low thermodynamic stability but different Nb content, indicating that the detailed picture of the decomposition should also be different. Electron microscopy and nanoindentation underlines different age hardening of the samples. We demonstrate that an alloy with the optimized composition, Ti0.42Nb0.17Al0.41N combines high thermal stability and age hardening behavior.
Graphical abstract
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Mechanism of heat affected zone cracking in Ni-based superalloy DZ125L fabricated by laser 3D printing technique
Publication date: 15 July 2018
Source:Materials & Design, Volume 150
Author(s): Yao Li, Kai Chen, Nobumichi Tamura
Laser 3D printing is a promising technique to repair damaged Ni-based superalloy components. However, the occurrence of heat affected zone (HAZ) cracking severely limits its applicability. Here we unravel the cracking mechanism by studying the element, phase, defect, and strain distribution around an intergranular crack that initiated from the primary HAZ. Using synchrotron X-ray Laue microdiffraction, we measured high tensile strain/stress transverse to the building direction in both the primary HAZ and the cladding layers, as well as high-density dislocations, which resulted from the thermal contraction and rapid precipitation of γ′ phase. The crack initiated because the transverse tensile strain/stress tore up the liquid film formed by the low-melting point preexisting phases in the primary HAZ, such as γ/γ′ eutectics and coarse γ′ precipitates. The incoherent carbide particles were frequently observed near the crack root as local strain concentrators. In the cladding layers, micro-segregation could not be completely avoided, thus the hot crack continued to propagate over several layers with the assistance of the transverse tensile stress. Our investigations provide a useful guideline for the optimization of the 3D printing process to repair Ni-based superalloys with high susceptibility to hot cracking.
Graphical abstract
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Inkjet printed polyethylene glycol as a fugitive ink for the fabrication of flexible microfluidic systems
Publication date: 15 July 2018
Source:Materials & Design, Volume 150
Author(s): Ahmed Alfadhel, Jing Ouyang, Chaitanya G. Mahajan, Farzad Forouzandeh, Denis Cormier, David A. Borkholder
This paper demonstrates a novel and simple processing technique for the realization of scalable and flexible microfluidic microsystems by inkjet-printing polyethylene-glycol (PEG) as a sacrificial template, followed by embedding in a structural layer (e.g. soft elastomers). The printing technology allows production of an array of PEG droplets simultaneously, reducing cost and manufacturing time. The PEG can be removed through heating above its phase-change temperature after the formation of the structural layer, with hydraulic flow removing the material. The developed technique allows easy modulation of the shape and dimensions of the pattern with the ability to generate complex architectures without using lithography. The method produces robust planar and multilayer microfluidic structures that can be realized on wide range of substrates. Moreover, microfluidics can be realized on other systems (e.g. electrodes and transducers) directly without requiring any bonding or assembling steps, which often limit the materials selection in conventional microfluidic fabrication. Multilayer Polydimethylsiloxane (PDMS) microfluidic channels were created using this technique to demonstrate the capability of the concept to realize flexible microfluidic electronics, drug delivery systems, and lab-on-a-chip devices. By utilizing conductive liquid metals (i.e. EGaIn) as the filling material of the channels, flexible passive resistive components and sensors have been realized.
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Editorial Board
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Source:Medical Hypotheses, Volume 115
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Tracking single membrane targets of human autoantibodies using single nanoparticle imaging

Source:Journal of Neuroscience Methods
Author(s): Julie Jézéquel, Julien P. Dupuis, François Maingret, Laurent Groc
BackgroundOver the past decade, an increasing number of neurological and neuropsychiatric diseases have been associated with the expression of autoantibodies directed against neuronal targets, including neurotransmitter receptors. Although cell-based assays are routinely used in clinics to detect the presence of immunoglobulins, such tests often provide heterogeneous outcomes due to their limited sensitivity, especially at low titers. Thus, there is an urging need for new methods allowing the detection of autoantibodies in seropositive patients that cannot always be clinically distinguished from seronegative ones.New MethodHere we make a case for single nanoparticle imaging approaches as a highly sensitive antibody detection assay. Through high-affinity interactions between functionalized nanoparticles and autoantibodies that recognize extracellular domains of membrane neuronal targets, single nanoparticle imaging allows a live surface staining of transmembrane proteins and gives access to their surface dynamics.Results and Comparison with Existing Method(s)We show here that this method is well-suited to detect low titers of purified immunoglobulin G (IgG) from first-episode psychotic patients and demonstrate that these IgG target glutamatergic N-Methyl-D-Aspartate receptors (NMDAR) in live hippocampal neurons. The molecular behaviors of targeted membrane receptors were indistinguishable from those of endogenous GluN1 NMDAR subunit and were virtually independent of the IgG concentration present in the sample contrary to classical cell-based assays.ConclusionsSingle nanoparticle imaging emerges as a real-time sensitive method to detect IgG directed against neuronal surface proteins, which could be used as an additional step to rule out ambiguous seropositivity diagnoses.
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A comparison of seven different dti-derived estimates of corticospinal tract structural characteristics in chronic stroke survivors

Source:Journal of Neuroscience Methods
Author(s): Bokkyu Kim, Beth E. Fisher, Nicolas Schweighofer, Richard M. Leahy, Justin P. Haldar, Soyoung Choi, Dorsa B. Kay, James Gordon, Carolee J. Winstein
BackgroundDifferent diffusion tensor imaging (DTI) has been used to estimate corticospinal tract (CST) structure in the context of stroke rehabilitation research. However, there is no gold standard for the estimate of CST structure in chronic stroke survivors. This study aims to determine the most accurate DTI-derived CST estimate that is associated with a clinical motor outcome measure.MethodsWe obtained imaging and behavioral data from a phase-I stroke rehabilitation clinical trial. We included thirty seven chronic stroke survivors with mildtomoderate motor impairment. Imaging data were processed using BrainSuite16a software. We calculated mean FA for each of 7 different ROIs/VOIs that include manually drawn 2-D ROIs and 3-D VOIs of CST from individual tractography or standard atlas. We compared ipsi- and contralesional CST FA for each method. Partial correlation was conducted between each CST FA asymmetry index and a time-based motor outcome measure, controlling for age and chronicity.ResultsIpsilesional CST FA was significantly lower than contralesional CST FA for each of the 7 methods Only CST FA asymmetry from the 3-D individual CST tractography showed a significant correlation with the primary motor outcome (r = 0.46, p = .005), while CST FA from the other six methods did not.Comparison with existing methodsCompared to the six other methods, CST FA asymmetry from 3-D individual tractography is the most accurate estimate of CST structure in this cohort of stroke survivors.ConclusionWe recommend this method for future research seeking to understand brain-behavior mechanisms of motor recovery in chronic stroke survivors.
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Tumor necrosis factor α‐308 G/A and interleukin 1 β‐511 C/T gene polymorphisms in patients with scarring acne
Journal of Cosmetic Dermatology, EarlyView.
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Nerve entrapment syndromes in dermatology: Review and practical approach to treatment
Australasian Journal of Dermatology, EarlyView.
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Oral lichenoid drug eruption in association with drinking tonic water
Australasian Journal of Dermatology, EarlyView.
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Dermoscopic features in two cases of acroangiodermatitis
Australasian Journal of Dermatology, EarlyView.
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Acute‐onset, painful acral granuloma annulare with unusual microcalcification
Australasian Journal of Dermatology, EarlyView.
https://ift.tt/2K4wci4
Report from the fifth international consensus meeting to harmonize core outcome measures for atopic eczema/dermatitis clinical trials (HOME initiative)
British Journal of Dermatology, EarlyView.
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Issue Information
British Journal of Dermatology, Volume 178, Issue 4, Page i-v, April 2018.
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Stress and more stress: the importance in skin disease of worrying about what others think
British Journal of Dermatology, Volume 178, Issue 4, Page 821-822, April 2018.
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A comprehensive approach to evaluating and classifying sun‐protective clothing
British Journal of Dermatology, Volume 178, Issue 4, Page e299-e299, April 2018.
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A pleiotropic effect of the APOE gene: association of APOE polymorphisms with multibacillary leprosy in Han Chinese from Southwest China
British Journal of Dermatology, Volume 178, Issue 4, Page e300-e300, April 2018.
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Core outcome sets in dermatology: report from the second meeting of the International Cochrane Skin Group Core Outcome Set Initiative
British Journal of Dermatology, Volume 178, Issue 4, Page e297-e297, April 2018.
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HLA‐Cw6和银屑病
British Journal of Dermatology, Volume 178, Issue 4, Page e320-e320, April 2018.
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Herbal interventions: make the grass greener!
British Journal of Dermatology, Volume 178, Issue 4, Page 827-829, April 2018.
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Long‐term management of moderate‐to‐severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a critical appraisal
British Journal of Dermatology, Volume 178, Issue 4, Page e311-e311, April 2018.
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Association of APOE polymorphisms with multibacillary leprosy
British Journal of Dermatology, Volume 178, Issue 4, Page 833-834, April 2018.
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Photodynamic therapy is more effective than imiquimod for actinic keratosis in organ transplant recipients: a randomized intraindividual controlled trial
British Journal of Dermatology, Volume 178, Issue 4, Page e298-e298, April 2018.
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A platinum era for dermatology therapeutics?
British Journal of Dermatology, Volume 178, Issue 4, Page 836-837, April 2018.
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Image Gallery: Brimonidine gel for facial erythema in Netherton syndrome
British Journal of Dermatology, Volume 178, Issue 4, Page e277-e277, April 2018.
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Atopic dermatitis: risk estimates for hand eczema
British Journal of Dermatology, Volume 178, Issue 4, Page 827-827, April 2018.
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Use of the hCONSORT criteria as a reporting standard for herbal interventions for common dermatoses: a systematic review
British Journal of Dermatology, Volume 178, Issue 4, Page e310-e310, April 2018.
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The Garment Protection Factor: further advances in labelling sun‐protective clothing
British Journal of Dermatology, Volume 178, Issue 4, Page 835-836, April 2018.
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对于患有光化性角化病的器官移植受者来说,光动力疗法比咪喹莫特更加有效:一项随机个体对照试验
British Journal of Dermatology, Volume 178, Issue 4, Page e313-e313, April 2018.
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Defining the psychological comorbidity in vitiligo: systematically casting the net wide
British Journal of Dermatology, Volume 178, Issue 4, Page 826-826, April 2018.
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Stress and skin disease quality of life: the moderating role of anxiety sensitivity social concerns
British Journal of Dermatology, Volume 178, Issue 4, Page e304-e304, April 2018.
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HLA‐C*06 and psoriasis: susceptibility, phenotype, course and response to treatment
British Journal of Dermatology, Volume 178, Issue 4, Page 825-825, April 2018.
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Differences in fundamental and functional properties of HPMC co-processed fillers prepared by fluid-bed coating and spray drying
Publication date: 1 July 2018
Source:European Journal of Pharmaceutical Sciences, Volume 119
Author(s): QianQian Dong, MiaoMiao Zhou, Xiao Lin, Lan Shen, Yi Feng
This study aimed to develop novel co-processed tablet fillers based on the principle of particle engineering for direct compaction and to compare the characteristics of co-processed products obtained by fluid-bed coating and co-spray drying, respectively. Water-soluble mannitol and water-insoluble calcium carbonate were selected as representative fillers for this study. Hydroxypropyl methylcellulose (HPMC), serving as a surface property modifier, was distributed on the surface of primary filler particles via the two co-processing methods. Both fundamental and functional properties of the products were comparatively investigated. The results showed that functional properties of the fillers, like flowability, compactibility, and drug-loading capacity, were effectively improved by both co-processing methods. However, fluid-bed coating showed greater advantages over co-spray drying in some aspects, which was mainly attributed to the remarkable differences in some fundamental properties of co-processed powders, like particle size, surface topology, and particle structure. For example, the more irregular surface and porous structure induced by fluid-bed coating could contribute to better compaction properties and lower lubricant sensitivity due to the increasing contact area and mechanical interlocking between particles under pressure. More effective surface distribution of HPMC during fluid-bed coating was also a contributor. In addition, such a porous agglomerate structure could also reduce the separation of drug and excipients after mixing, resulting in the improvement in drug loading capacity and tablet uniformity. In summary, fluid-bed coating appears to be more promising for co-processing than spray drying in some aspects, and co-processed excipients produced by it have a great prospect for further investigations and development.
Graphical abstract
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Liposomal CpG-ODN: An in vitro and in vivo study on macrophage subtypes responses, biodistribution and subsequent therapeutic efficacy in mice models of cancers
Publication date: 1 July 2018
Source:European Journal of Pharmaceutical Sciences, Volume 119
Author(s): Sara Nikoofal-Sahlabadi, Maryam Matbou Riahi, Kayvan Sadri, Ali Badiee, Amin Reza Nikpoor, Mahmoud Reza Jaafari
CpG oligodeoxynucleotides (CpG-ODN), a common immune stimulator and vaccine adjuvant, was reported to switch Tumor Associated Macrophages (TAMs) from M2 to M1 phenotype inducing anti-tumor responses. Liposomes are of the successfully applied carriers for CpG-ODN. The aim of present study was design and preparation of a liposomal formulation containing phosphodiester CpG-ODN, evaluation of its effect on macrophages responses, and subsequent antitumor responses in mice. Liposomal formulations containing phosphodiester CpG-ODN or non-CpG-ODN were prepared and characterized. MTT reduction assay in four different cell lines, uptake, arginase and iNOS activity evaluation in macrophage cell lines, biodistribution study and therapeutic anti-tumor effects of formulations in mice bearing C26 colon carcinoma or B16F0 melanoma were carried out. The size of liposomes containing CpG-ODN was ~200 nm with the encapsulation efficiency of 33%. The iNOS activity assay showed high nitric oxide (NO) level in M2 phenotype of macrophage cell lines treated by liposomes containing CpG-ODN. In mice which received liposomes containing CpG-ODN as a monotherapy, maximum tumor growth delay with remarkable survival improvement was observed compared to control groups. Biodistribution study showed the accumulation of liposomal formulation in tumor micro-environment. In conclusion, considerable anti-tumor responses observed by liposomes containing CpG-ODN was due to enhanced delivery of CpG-ODN to immune cells and subsequent initiation of anti-tumoral immune responses.
Graphical abstract
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Additive potential of combination therapy against cryptococcosis employing a novel amphotericin B and fluconazole loaded dual delivery system
Publication date: 1 July 2018
Source:European Journal of Pharmaceutical Sciences, Volume 119
Author(s): Azmat Ali Khan, Amer M. Alanazi, Mumtaz Jabeen, Shahanavaj Khan, Abdul Malik
Cryptococcus neoformans is one of the most lethal fungi causing mortality across the globe. Immuno-competent patients and patients taking immuno-suppressive medications are extremely susceptible to its infection. For effective removal of cryptococcal burden, there is an urgent need for new forms of therapy. In the present study, we have explored the potential effects of amphotericin B (AMB) and fluconazole (FLC) in combination, against cryptococcosis in Swiss albino mice. To enhance the therapeutic potential of the tested drugs, they were entrapped into fibrin microspheres; a dual delivery vehicle comprising of poly-lactide co-glycolide (PLGA) microsphere that was additionally encapsulated into the fibrin cross-linked plasma bead. Dynamics of fibrin microspheres included survival and fungal burden in lung, liver and spleen of treated mice. While each drug was effective in combination or alone, prominent additive potential of AMB and FLC were clearly observed when used in fibrin microsphere. Significant reduction in fungal burden and increase in survival rate of AMB + FLC-fibrin microspheres treated mice shows an extensive accessibility of both tested drugs without any side-effects. A full potential of two-drug combination encapsulated in fibrin microspheres proposes an effective approach of safe delivery to the target site in their intact form and decrease the drug associated toxicities.
Graphical abstract
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Coumestrol/hydroxypropyl-β-cyclodextrin association incorporated in hydroxypropyl methylcellulose hydrogel exhibits wound healing effect: in vitro and in vivo study
Publication date: 1 July 2018
Source:European Journal of Pharmaceutical Sciences, Volume 119
Author(s): Sara E. Bianchi, Barbara E.K. Machado, Marília G.C. da Silva, Michelle M.A. da Silva, Lidiane Dal Bosco, Magno S. Marques, Ana P. Horn, Lara Persich, Fabiana C. Geller, Débora Argenta, Helder F. Teixeira, Cláudia M.O. Simões, Cristiana L. Dora, Valquíria L. Bassani
Several beneficial effects on the skin have been reported for coumestrol (COU), such as protection against photoaging and improvement of skin elasticity and thickness in postmenopausal women. However no reports on the effect of COU on wound healing were found. Nevertheless, COU has low aqueous solubility, which is a crucial limitation for biological tests. The present study was designed as a two-step experiment to evaluate the wound healing effect of COU. First, we used fibroblasts and the experimental in vitro artificial wound model, scratch assay, to compare the effects of COU free, dissolved in dimethyl sulfoxide (DMSO) or Dulbecco's modified Eagle's medium (DMEM), or associated with hydroxypropyl-β-cyclodextrin (HPβCD). The 50 μM (66.1%) and 10 μM (56.3%) COU/HPβCD association induced cell proliferation and migration in inflicted wounds. Subsequently, the in vivo wound healing experimental model (Wistar rats) revealed that COU/HPβCD incorporated into hypromellose (HPMC) hydrogel had similar efficacy in wound healing in comparison to the positive control (Dersani®), with the advantage that 50% wound healing was achieved within a shorter period. In summary, the results successfully demonstrated, for the first time, the wound healing effect of COU/HPβCD incorporated into HPMC hydrogel and describe the feasibility of the biological tests with the use of HPβCD instead DMSO.
Graphical abstract
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FAK- and YAP/TAZ dependent mechanotransduction pathways are required for enhanced immunomodulatory properties of adipose-derived mesenchymal stem cells induced by aligned fibrous scaffolds

Source:Biomaterials, Volume 171
Author(s): S. Wan, X. Fu, Y. Ji, M. Li, X. Shi, Y. Wang
Adipose-derived mesenchymal stem cells (ASCs) represent an excellent candidate for tissue engineering due to their multipotency and paracrine functions. Physical cues provided by the scaffolds have been shown to direct a variety of cellular behaviors of ASCs; however, their effects on the paracrine functions of ASCs, especially immunomodulatory functions, remain largely unexplored. Thus, PLLA electrospun fibrous scaffolds, with fibers oriented either randomly or aligned, were used as a model to investigate the effects of fiber orientation on the immunomodulatory paracrine secretion of ASCs. ASCs cultured on aligned fibers produced significantly higher levels of immunomodulatory factors than those cultured on random fibers. By using the conditioned media from ASCs cultured on aligned fibers, the enhanced immunomodulatory functions of ASCs were confirmed by the M2 phenotypic change seen in macrophages. The enhanced immunomodulation of ASCs correlated with the activation of FAK signaling, as evidenced by a decreased production of immunomodulatory factors in ASCs after treatment with inhibitors of the FAK pathway. In addition, aligned fibers promoted the activation of YAP signaling in ASCs. The inhibited immunomodulatory properties of ASCs by a YAP inhibitor indicated that YAP signaling was also involved in mediating the increased immunomodulatory functions of ASCs on aligned fibers. Our findings identify both FAK and YAP/TAZ signaling as required mechanotransduction pathways through which aligned fibers stimulate the immunomodulatory function of ASCs and highlight fiber orientation as a key design parameter for immunomodulatory fibrous engineered scaffolds.
https://ift.tt/2K3z9zv
Fabrication of nanofibrous microcarriers mimicking extracellular matrix for functional microtissue formation and cartilage regeneration
Publication date: July 2018
Source:Biomaterials, Volume 171
Author(s): Yansen Wang, Xueling Yuan, Kun Yu, Haoye Meng, Yudong Zheng, Jiang Peng, Shibi Lu, Xiaotong Liu, Yajie Xie, Kun Qiao
Cartilage has rather limited capacities for self-repair and regeneration. To repair complexly shaped cartilage tissue defects, we propose the application of microtissues fabricated from bone marrow-derived mesenchymal stem cells (BMSCs) cultured in natural bionic nanofibrous microcarriers (NF-MCs). The NF-MCs were structurally and functionally designed to mimic natural extracellular matrix (ECM) by crosslinking dialdehyde bacterial cellulose (DBC) with DL-allo-hydroxylysine (DHYL) and complexing chitosan (CS) with DHYL through electrostatic interactions. The orthogonal design allows for fine tuning of fiber diameter, pore size, porosity, mechanical properties, and biodegradation rate of the NF-MC. BMSCs cultured in NF-MCs showed improved proliferation compared with those cultured in chitosan microcarriers (CS-MCs). After three-week culture under microgravity conditions, functional cartilage microtissues were generated. When implanted into a knee articular cartilage defect in mice, the microtissue showed superior in vivo cartilage repair as characterized by cell tracking, histology, micro CT image, and gait analysis. Versatile in natural biopolymer design and biomimetic in nanofibrous component embedded in macroporous microcarriers, these injectable NC-MCs demonstrate to be effective carriers for cell proliferation and differentiation. Furthermore, the functional microtissues also show their prospect in repair of cartilage tissue, and suggest their potential for other tissues in general.
Graphical abstract
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Comparing ex vivo and in vitro translocation of silver nanoparticles and ions through human nasal epithelium

Source:Biomaterials, Volume 171
Author(s): Jonathan L. Falconer, Jeremiah A. Alt, David W. Grainger
Silver nanomaterials are widely used in clinically approved devices, consumer goods, and over-the-counter nutraceutical products. Despite the increase in silver nanomaterial research, few investigations have specifically distinguished the biological effects resulting from silver nanoparticles (AgNPs) versus silver ions released from AgNPs. This is in part, due to the complex analytical methods required to characterize silver ion release from AgNPs in biological media. This study sought to analyze silver ion release from AgNPs in biological media, compare silver transport from soluble AgNO3 and AgNPs through ex vivo full thickness sinus human tissue explants and human nasal epithelium and determine fractional AgNP internalization by human nasal epithelial cells. Rapid silver ion release is observed from AgNPs in human nasal epithelial cell medium over 3 h (9.6% of total silver mass). Significantly lower translocation of AgNPs is observed through human nasal epithelial cell monolayers and ex vivo human sinus tissue explants compared to silver ion (AgNO3). AgNP internalization is directly observed in AgNP-exposed human nasal epithelial cell monolayers by live cell scanning transmission electron microscopy (STEM), providing one potential mechanism for AgNP transcytosis. However, in vitro AgNP dissolution experiments suggest that silver in human nasal epithelium is primarily silver ion. Ionic AgNO3 produces significantly higher silver translocation, supporting previous results claiming silver ion as primarily responsible for biological effects of AgNPs.
https://ift.tt/2K3yYnP
Porcine epidemic diarrhea vaccine efficacy evaluation by vaccination timing and frequencies

Source:Vaccine, Volume 36, Issue 20
Author(s): Jung-Eun Park, Hyun-Jin Shin
Porcine epidemic diarrhea (PED) virus is a causative agent of enteric disease characterized by watery diarrhea and dehydration. Because PED has high morbidity and mortality, especially in suckling piglets, it causes a great economic loss to swine farms worldwide. Although various PED vaccines have been developed and commercialized, their efficacies are still controversial. In particular, current PED vaccination protocol (vaccination at 2 and 4 weeks before farrowing) may cause stress in pregnant sows. In this study, we compared the effects of PED vaccination timing and frequency for its efficacy by measuring the PED virus-specific antibodies. We found that vaccination at early stages of pregnancy induces similar levels of serum and colostrum antibodies with those at late stages of pregnancy. As the number of vaccinations increased, the amounts of antibody in serum and colostrum, and neutralizing activities increased. Our results provide important information for establishing a more efficient PED vaccination protocol.
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Is varicella vaccination associated with pediatric arterial ischemic stroke? A population-based cohort study

Source:Vaccine, Volume 36, Issue 20
Author(s): Shannon E. MacDonald, Douglas C. Dover, Michael D. Hill, Adam Kirton, Kimberley A. Simmonds, Lawrence W. Svenson
Background and purpose: Varicella disease is a risk factor for pediatric Arterial Ischemic Stroke (AIS). Isolated case reports have emerged suggesting that varicella vaccination may also pose a risk for AIS. Methods: This retrospective population-based cohort study assessed the risk of AIS in children who received a varicella-containing vaccine, as compared to those who did not. The study cohort consisted of children born between January 1, 2006 and December 31, 2013, in the Canadian province of Alberta, where all routine childhood vaccinations are publicly-funded, and recorded in a central immunization repository. These data were linked with hospital discharge abstract data to identify children diagnosed with AIS. A Cox proportional hazard model assessed the risk of AIS in the 12 months following vaccination for children receiving a varicella vaccine between 11 and 23 months of age, as compared to non-vaccinated children. Results: Of the 368,992 children in the cohort, 325,729 were vaccinated with a varicella-containing vaccine between 11 and 23 months of age. The rate of AIS was 7.8 (95% CI 4.8–10.9) per 100,000 person years at risk in the 12 months following varicella vaccination, as compared to 6.8 (95% CI 1.3–12.2) for children who did not receive a varicella vaccine. The adjusted Hazard Ratio for the risk of AIS, controlling for other AIS risk factors, in vaccinated children as compared to non-vaccinated children was 1.6 (95% CI 0.7–3.7) in the 12 months following vaccination and 1.7 (95% CI 0.5–4.9) in the 30 days following vaccination. Conclusions: Our study found no evidence of an increased risk of AIS following varicella vaccination. This population-based cohort study provides reassurance to parents and clinicians regarding the safety of varicella vaccination.
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Editorial Board/Aims and Scope
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Source:Vaccine, Volume 36, Issue 20
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Lipopolysaccharide-specific memory B cell responses to an attenuated live cholera vaccine are associated with protection against Vibrio cholerae infection

Source:Vaccine, Volume 36, Issue 20
Author(s): Douglas J. Haney, Michael D. Lock, Marc Gurwith, Jakub K. Simon, Glenn Ishioka, Mitchell B. Cohen, Beth D. Kirkpatrick, Caroline E. Lyon, Wilbur H. Chen, Marcelo B. Sztein, Myron M. Levine, Jason B. Harris
BackgroundThe single-dose live attenuated vaccine CVD 103-HgR protects against experimental Vibrio cholerae infection in cholera-naïve adults for at least 6 months after vaccination. While vaccine-induced vibriocidal seroconversion is associated with protection, vibriocidal titers decline rapidly from their peak 1–2 weeks after vaccination. Although vaccine-induced memory B cells (MBCs) might mediate sustained protection in individuals without detectable circulating antibodies, it is unknown whether oral cholera vaccination induces a MBC response.MethodsIn a study that enrolled North American adults, we measured lipopolysaccharide (LPS)- and cholera toxin (CtxB)-specific MBC responses to PXVX0200 (derived from the CVD 103-HgR strain) and assessed stool volumes following experimental Vibrio cholerae infection. We then evaluated the association between vaccine-induced MBC responses and protection against cholera.ResultsThere was a significant increase in % CT-specific IgG, % LPS-specific IgG, and % LPS-specific IgA MBCs which persisted 180 days after vaccination as well as a significant association between vaccine-induced increase in % LPS-specific IgA MBCs and lower post-challenge stool volume (r = −0.56, p < 0.001).DiscussionOral cholera vaccination induces antigen-specific MBC responses, and the anamnestic LPS-specific responses may contribute to long-term protection and provide correlates of the duration of vaccine-induced protection.Clinical trials registration: NCT01895855.
https://ift.tt/2K3yJJr
A toddler PCV booster dose following 3 infancy priming doses increases circulating serotype-specific IGG levels but does not increase protection against carriage

Source:Vaccine, Volume 36, Issue 20
Author(s): Ron Dagan, Shalom Ben-Shimol, Birgit Simell, David Greenberg, Nurith Porat, Helena Käyhty, Noga Givon-Lavi
BackgroundWe compared PCV7 serological response and protection against carriage in infants receiving 3 doses (2, 4, 6 months; 3+0 schedule) to those receiving a booster (12 months; 3+1).MethodsA prospective, randomized controlled study, conducted between 2005 and 2008, before PCVs were implemented in Israel. Healthy infants were randomized 1:1:1 to receive 3+1, 3+0 and 0+2 (control group; 12, 18 months doses). Nasopharyngeal/oropharyngeal swabs were obtained at all visits. Serum serotype-specific IgG concentrations and opsonic activities (OPA) were measured at 2, 7, 13 and 19 months. This study was registered with Current Controlled Trials, Ltd. ISRCTN28445844.ResultsOverall, 544 infants were enrolled: 3+1 (n = 178), 3+0 (n = 178) and 0+2 (n = 188).Post-priming (7 months), antibody concentrations were similar in both groups, except for serotype 18C (higher in 3+0). Post-booster (13, 19 months), ELISA and OPA levels were significantly higher in 3+1 than in 3+0 group.Nasopharyngeal/oropharyngeal cultures were positive for Streptococcus pneumoniae in 2673 (54.3%) visits. Acquisition rates (vaccine and non-vaccine serotypes) were similar for 3+1 and 3+0 groups at 7–30 months and for 0+2 group at 19–30 months.ConclusionsPCV7 booster after 3 priming doses increased substantially IgG concentrations but did not further reduced vaccine-serotype nasopharyngeal acquisition, suggesting that protection from pneumococcal carriage does not depend primarily on serum IgG.
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Local thermal reaction after influenza vaccination: Quantification by infrared imaging and biometric considerations

Source:Vaccine, Volume 36, Issue 20
Author(s): Andreas Hoffmann, Claudia Dumke, Kay-Martin Ove Hanschmann, Sabine Wicker
BackgroundExtensive clinical investigations are mandatory to evaluate the safety and reactogenicity of vaccines. The recording of common adverse events like injection site soreness or general discomfort derives from individual subjective perceptions. Thermal imaging at the injection site possibly provides a non-subjective and a non-invasive approach to supplement this evaluation.ResultsA protocol for quantified injection-site infrared imaging included 86 participants during a flu vaccine campaign, 40% of whom had a thermal reaction of 1 °C; 25–30% had no thermal response. There was little subjective pain reporting and no clinical correlations were observed except with post-vaccination erythema.Higher responses were linked with advanced age and multiple previous vaccinations.ConclusionEvan if influenza vaccine was only moderately reactogenic, a thermal response was detectable in about 70% of vaccinees, though no relationship to reactogenicity was seen.Infrared imaging might however be a prospective tool for individual studies of vaccine-induced vascular responses.
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Direct-to-adolescent text messaging for vaccine reminders: What will parents permit?

Source:Vaccine, Volume 36, Issue 20
Author(s): James R. Roberts, Kristen Morella, Erin H. Dawley, Christi A. Madden, Robert M. Jacobson, Charlene Pope, Boyd Davis, David Thompson, Elizabeth S. O'Brien, Paul M. Darden
BackgroundDirect-to-adolescent text messaging may be a consideration for vaccine reminders, including human papilloma virus (HPV), but no studies have explored the minimum age at which parents would allow adolescents to receive a text message.MethodsWe distributed a survey to parents of 10–17 year olds during any office visit in two practice based research networks in South Carolina and Oklahoma. We asked about parental preference for receiving vaccine reminders for their adolescent, whether they would allow the healthcare provider to directly message their adolescent, and if so, what would be the acceptable minimum age.ResultsIn 546 surveys from 11 practices, parents of females were more supportive of direct-to-teen text message reminders than were parents of males, (75% v. 60%, p < .001). The median age at which parents would allow direct text messages from physicians' offices was 14 in females compared to 15 in males, p = .049. We found a correlation between the child's age and the youngest age at which parents would allow a direct text message. Of the parents who permitted a text message directly to their adolescent, most reported an allowable age higher than their adolescent's current age until the age of 15.ConclusionOur study suggests that direct-to-adolescent text messaging would be allowed by parents for older adolescents. This supports an intervention aimed at older adolescents, such as for receipt of MCV4 dose #2, delayed HPV vaccine series completion and annual influenza vaccination.
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Inclusion of the murine IgGκ signal peptide increases the cellular immunogenicity of a simian adenoviral vectored Plasmodium vivax multistage vaccine

Source:Vaccine, Volume 36, Issue 20
Author(s): Jairo A. Fonseca, Jessica N. McCaffery, Juan Caceres, Elena Kashentseva, Balwan Singh, Igor P. Dmitriev, David T. Curiel, Alberto Moreno
IntroductionCellular and humoral immune responses are both involved in protection against Plasmodium infections. The only malaria vaccine available, RTS,S, primarily induces short-lived antibodies and targets only a pre-erythrocytic stage antigen. Inclusion of erythrocytic stage targets and enhancing cellular immunogenicity are likely necessary for developing an effective second-generation malaria vaccine. Adenovirus vectors have been used to improve the immunogenicity of protein-based vaccines. However, the clinical assessment of adenoviral-vectored malaria vaccines candidates has shown the induction of robust Plasmodium-specific CD8+ but not CD4+ T cells. Signal peptides (SP) have been used to enhance the immunogenicity of DNA vaccines, but have not been tested in viral vector vaccine platforms.ObjectivesThe objective of this study was to determine if the addition of the SP derived from the murine IgGκ light chain within a recombinant adenovirus vector encoding a multistage P. vivax vaccine candidate could improve the CD4+ T cell response.MethodsIn this proof-of-concept study, we immunized CB6F1/J mice with either the recombinant simian adenovirus 36 vector containing the SP (SP-SAd36) upstream from a transgene encoding a chimeric P. vivax multistage protein or the same SAd36 vector without the SP. Mice were subsequently boosted twice with the corresponding recombinant proteins emulsified in Montanide ISA 51 VG. Immunogenicity was assessed by measurement of antibody quantity and quality, and cytokine production by T cells after the final immunization.ResultsThe SP-SAd36 immunization regimen induced significantly higher antibody avidity against the chimeric P. vivax proteins tested and higher frequencies of IFN-γ and IL-2 CD4+ and CD8+ secreting T cells, when compared to the unmodified SAd36 vector.ConclusionsThe addition of the murine IgGκ signal peptide significantly enhances the immunogenicity of a SAd36 vectored P. vivax multi-stage vaccine candidate in mice. The potential of this approach to improve upon existing viral vector vaccine platforms warrants further investigation.
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School-age children and adolescents suspected of having been to be infected with pertussis in Japan

Source:Vaccine, Volume 36, Issue 20
Author(s): Yosuke Yasui, Toshikatsu Mitsui, Tomoyasu Nishimura, Keiko Uchida, Mikako Inokuchi, Masaaki Mori, Mitsuaki Tokumura, Tetsuo Nakayama
Many countries including Japan have adapted acellular pertussis vaccines combined with diphtheria and tetanus toxoids (DTaP). DTaP vaccine coverage is approximately >90%, but pertussis re-emergence has been observed since 2000 in Japan. In the present study, anti-pertussis antibodies were investigated among school-age children and adolescents from 2013 to 2015. The positive rate of anti-pertussis toxin (PT) antibodies was higher among children aged 12–13 years (60.0%. 95%CI; 56.0–63.9%) in 2014 and 18–19 years (73.0%. 95%CI; 61.4–82.6%) in 2013, compared with 6–7 years (47.1%. 95%CI; 40.7–53.6%). The mean PT antibody titer was higher among children aged 12–13 years (23.8 EU/ml. 95%CI; 21.9–25.8) in 2014 and 18–19 years (29.3 EU/ml. 95%CI; 23.0–35.6) in 2013, compared with 6–7 years (18.3 EU/ml. 95%CI; 15.5–21.2). Distributions of pertussis antibodies and mean titers at their same grade of school-age were similar from 2013 to 2015. Although school-age children were immunized with 4 doses of DTaP, the data suggested the decay of vaccine-acquired immunity and possibility of asymptomatic infection in school age, indicating the additional DTaP vaccination before the entry of elementary school, preventing household contact.
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Analysis of adenovirus-induced immunity to infection with Listeria monocytogenes: Fading protection coincides with declining CD8 T cell numbers and phenotypic changes

Source:Vaccine, Volume 36, Issue 20
Author(s): Marie Louise Jahn, Maria Abildgaard Steffensen, Jan Pravsgaard Christensen, Allan Randrup Thomsen
Defining correlates of T cell mediated protection is important in order to accelerate the development of efficient T cell based vaccines conferring long-term immunity.Extensive studies have provided important insight regarding the characteristics and functional properties of the effector and memory CD8 T cells induced by viral vector based vaccines. However, long-term protection has been difficult to achieve with T cell inducing vaccines, and the determinants underlying this loss in protection over time are still not fully defined.In this study we analyzed different parameters of the CD8 T cell response as a function of time after vaccination with a human serotype 5 adenovector expressing the glycoprotein (GP) of LCMV tethered to the MHC class II-associated invariant chain. Using this vector we have previously found that CD8 T cells mediate protection from challenge with GP-expressing Listeria monocytogenes at 60 days post vaccination, but only little protection after further 60 days, and we now confirm this observation. A comparison of vaccine-primed CD8 T cells early and late after vaccination revealed a minor decline in the overall numbers of antigen specific memory CD8 T cells during this interval. More importantly, we also observed phenotypic changes over time with a distinct decline in the frequency and number of KLRG1+ CD8 T cells, and, notably, adoptive transfer studies confirmed that memory CD8 T cells expressing KLRG1 are central to protection from systemic L. monocytogenes infection. Together these findings imply that multiple factors including changes in memory T cell numbers and phenotypic composition over time influence the longevity of CD8 T-cell mediated protection.
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Intramuscular vaccination of guinea pigs with the live-attenuated human herpes simplex vaccine VC2 stimulates a transcriptional profile of vaginal Th17 and regulatory Tr1 responses

Source:Vaccine, Volume 36, Issue 20
Author(s): Brent A. Stanfield, Paul J.F. Rider, John Caskey, Fabio Del Piero, Konstantin G. Kousoulas
Herpes simplex virus is a common causative agent of oral and genital diseases. Novel vaccines and therapeutics are needed to combat herpes infections especially after the failure of subunit vaccines in human clinical trials. We have shown that the live-attenuated HSV-1 VC2 vaccine strain is unable to establish latency in vaccinated animals and produces a robust immune response capable of completely protecting mice against lethal vaginal HSV-1 or HSV-2 infections. The guinea pig represents the best small animal model of genital HSV-2 disease. Reported here, twenty-one female Hartley guinea pigs received intramuscular injection with either the VC2 vaccine, or equal volume of conditioned tissue culture media. Animals received 2 booster vaccinations at 21 day intervals following the initial vaccination. After vaccination, animals were challenged with the highly virulent HSV-2 (G) strain. Histologically, VC2 vaccinated animals had little to no apparent inflammation/disease following challenge. Unvaccinated animals developed moderate to severe erosive and ulcerative vaginitis. Quantitative reverse-transcriptase PCR analysis in VC2 vaccinated and challenged animals identified transcriptional signatures of Th17 and regulatory Tr1 cells associated with the inflammatory response primed by VC2 vaccination. Treatment of cultured human vaginal epithelial cells (VK2 cells) with a combination of IL-17A and IL-22 resulted in the significant induction of beta-defensin 3 expression. Further, treatment of VK2 cells with IL-17A, IL-22, IL-36 or beta-defensin 3 resulted in diminished HSV-2 replication. Overall, these results suggest that intramuscular vaccination with the live-attenuated vaccine VC2 primes a mucosal immune response predisposing the adaptive expression of transcripts associated with a Th17 response to challenge and these responses contribute to antiviral immunity.
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Ag85A-specific CD4+ T cell lines derived after boosting BCG-vaccinated cattle with Ad5-85A possess both mycobacterial growth inhibition and anti-inflammatory properties

Source:Vaccine, Volume 36, Issue 20
Author(s): Hannah J. Metcalfe, Lucia Biffar, Sabine Steinbach, Efrain Guzman, Tim Connelley, Ivan Morrison, H. Martin Vordermeier, Bernardo Villarreal-Ramos
There is a need to improve the efficacy of the BCG vaccine against human and bovine tuberculosis. Previous data showed that boosting bacilli Calmette-Guerin (BCG)-vaccinated cattle with a recombinant attenuated human type 5 adenovirally vectored subunit vaccine (Ad5-85A) increased BCG protection and was associated with increased frequency of Ag85A-specific CD4+ T cells post-boosting. Here, the capacity of Ag85A-specific CD4+ T cell lines – derived before and after viral boosting – to interact with BCG-infected macrophages was evaluated. No difference before and after boosting was found in the capacity of these Ag85A-specific CD4+ T cell lines to restrict mycobacterial growth, but the secretion of IL-10 in vitro post-boost increased significantly. Furthermore, cell lines derived post-boost had no statistically significant difference in the secretion of pro-inflammatory cytokines (IL-1β, IL-12, IFNγ or TNFα) compared to pre-boost lines. In conclusion, the protection associated with the increased number of Ag85A-specific CD4+ T cells restricting mycobacterial growth may be associated with anti-inflammatory properties to limit immune-pathology.
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A follow-up comparative safety analysis of pandemic H1N1 vaccination during pregnancy and risk of infant birth defects among U.S. military mothers

Source:Vaccine, Volume 36, Issue 20
Author(s): Ava Marie S. Conlin, Anna T. Bukowinski, Jordan A. Levine, Zeina G. Khodr, Navjot Kaur, Susan C. Farrish, Carter J. Sevick
ObjectiveTo update a previous assessment of birth defects among infants born to active duty U.S. military mothers who received the 2009–2010 pandemic H1N1 vaccine, in comparison to the 2008–2009 seasonal influenza vaccine, during pregnancy. Here, we updated the previous comparative analyses with a more refined definition for birth defects using an additional year of follow-up data from both inpatient and outpatient medical encounters.MethodsThe study population included 15,510 live born infants born to active duty mothers vaccinated during pregnancy with either the 2009–2010 pandemic H1N1 vaccine (n = 9033) or the 2008–2009 seasonal influenza vaccine (n = 6477). Birth defect cases were defined as those infants who received a birth defect diagnosis on one inpatient record or two outpatient records on different days within the first year of life. Multivariable logistic regression models were conducted to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for the association between birth defects and maternal vaccination during pregnancy with pandemic H1N1 vaccine versus seasonal influenza vaccine.ResultsInfants born to mothers vaccinated during pregnancy with the pandemic H1N1 vaccine, versus the seasonal influenza vaccine, were not at increased odds of birth defects in univariable (OR: 1.13, 95% CI: 0.95–1.34) or multivariable (OR: 1.14, 95% CI: 0.96–1.35) models. Findings were not significant when further limited to first trimester exposure. Multivariable models were adjusted for infant sex and plurality; maternal age, race/ethnicity, marital status, service branch, military rank, and occupation; timing of vaccination; and receipt of vaccination(s) not routinely recommended during pregnancy.ConclusionComparable to our previous analyses assessing birth defects diagnosed at birth, no significant association was found between the pandemic H1N1 vaccination during pregnancy and birth defects, versus the seasonal influenza vaccine. These findings are reassuring and provide additional support for H1N1-containing seasonal influenza vaccination during pregnancy.
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Post-immunization leucocytosis and its implications for the management of febrile infants

Source:Vaccine, Volume 36, Issue 20
Author(s): Sarah Prentice, Zephyrian Kamushaaga, Stephen B. Nash, Alison M. Elliott, Hazel M. Dockrell, Stephen Cose
AimsClinical guidelines for management of infants with fever but no evident focus of infection recommend that those aged 1–3 months with a white cell count >15 × 109/l have a full septic screen and be admitted for parenteral antibiotics. However, there is limited information about leucocyte changes following routine immunization, a common cause of fever. We investigated white cell counts shortly after routine immunization in Ugandan infants under 3 months of age.MethodsWhite cell counts were measured in 212 healthy infants following routine immunizations (DTwP-HepB-Hib, oral polio and pneumococcal conjugate 7 vaccines) received prior to 3 months of age.ResultsMean leucocyte counts increased from 9.03 × 109/l (95% confidence interval 8.59–9.47 × 109/l) pre-immunizations to 16.46 × 109/l (15.4–17.52 × 109/l) at one-day post-immunizations at 6 weeks of age, and 15.21 × 109/l (14.07–16.36 × 109/l) at one-day post-immunizations at 10 weeks of age. The leucocytosis was primarily a neutrophilia, with neutrophil percentages one-day post-immunization of 49% at 6 weeks of age and 46% at 10 weeks of age. White cell parameters returned to baseline by two-days post-immunization. No participant received antibiotics when presenting with isolated fever post-immunization and all remained well at follow-up.ConclusionsIn our study almost half the children <3 months old presenting with fever but no evident focus of infection at one-day post-immunization met commonly used criteria for full septic screen and admission for parenteral antibiotics, despite having no serious bacterial infection. These findings add to the growing body of literature that questions the utility of white blood cell measurement in identification of young infants at risk of serious bacterial infections, particularly in the context of recent immunizations, and suggest that further exploration of the effect of different immunization regimes on white cell counts is needed.This observational work was nested within a clinical trial, registration number ISRCTN59683017.
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A novel method for strict intranasal delivery of non-replicating RSV vaccines in cotton rats and non-human primates

Source:Vaccine, Volume 36, Issue 20
Author(s): Michael P. Citron, Manishkumar Patel, Mona Purcell, Shu-An Lin, Daniel J. Rubins, Paul McQuade, Cheryl Callahan, Alexa Gleason, Ioan Petrescu, Walter Knapp, Chinedu Orekie, Sai Chamarthy, Zhiyun Wen, Sinoeun Touch, Matthew Pine, Jane Fontenot, Cameron Douglas, Xiaoping Liang, Amy S. Espeseth
Respiratory syncytial virus (RSV) is the most common viral cause of bronchiolitis and pneumonia in children twelve months of age or younger and a significant cause of lower respiratory disease in older adults. As various clinical and preclinical candidates advance, cotton rats (Sigmodon hispidus) and non-human primates (NHP) continue to play a valuable role in RSV vaccine development, since both animals are semi-permissive to human RSV (HRSV). However, appropriate utilization of the models is critical to avoid mis-interpretation of the preclinical findings. Using a multimodality imaging approach; a fluorescence based optical imaging technique for the cotton rat and a nuclear medicine based positron emission tomography (PET) imaging technique for monkeys, we demonstrate that many common practices for intranasal immunization in both species result in inoculum delivery to the lower respiratory tract, which can result in poor translation of outcomes from the preclinical to the clinical setting. Using these technologies we define a method to limit the distribution of intranasally administered vaccines solely to the upper airway of each species, which includes volume restrictions in combination with injectable anesthesia. We show using our newly defined methods for strict intranasal immunization that these methods impact the immune responses and efficacy observed when compared to vaccination methods resulting in distribution to both the upper and lower respiratory tracts. These data emphasize the importance of well-characterized immunization methods in the preclinical assessment of intranasally delivered vaccine candidates.
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Nasal vaccination with r4M2e.HSP70c antigen encapsulated into N-trimethyl chitosan (TMC) nanoparticulate systems: Preparation and immunogenicity in a mouse model
Publication date: 11 May 2018
Source:Vaccine, Volume 36, Issue 20
Author(s): Mehran Dabaghian, Ali Mohammad Latifi, Majid Tebianian, Hamid NajmiNejad, Seyyed Mahmoud Ebrahimi
In this study, the potential of N-trimethyl chitosan (TMC) nanoparticles as a carrier system for the nasal delivery of the r4M2e.HSP70c, as an M2e-based universal recombinant influenza virus vaccine candidate, was investigated in mice. The anti-M2e specific cellular and humoral immune responses were assessed and the protective efficacy against a 90% lethal dose (LD90) of influenza A/PR/8/34 (H1N1) in a mice model was evaluated.Our results showed that the intranasal immunization of mice with r4M2e.HSP70c+TMC rather than the control groups, r4M2e+TMC, r4M2e and PBS (Phosphate buffer saline), significantly elevated both longevity and serum level of the total M2e-specific IgG antibody with a significant shift in the IgG2a/IgG1 ratio toward IgG2a, induced a Th1 skewed humoral and cellular immune responses, increased IFN-γ, IgG, and IgA in the bronchoalveolar lavage fluid (BALF), and promoted the proliferation of peripheral blood lymphocytes with lower morbidity and mortality rate against viral challenge.In conclusion, based on evidence to our finding, nasal vaccination with r4M2e.HSP70c antigen encapsulated into N-Trimethyl Chitosan (TMC) nanoparticulate system showed to induce a long lasting M2e-specific humoral and cellular immune responses and also provided full protection against a 90% lethal dose (LD90) of the influenza virus A/PR/8/34 (H1N1). It seems, protective immunity following intranasal administration of r4M2e could be resulted by the cooperation of both adjuvants, TMC and HSP70c.
https://ift.tt/2K1GFdX
Vaccine delivery to newly arrived refugees and estimated costs in selected U.S. clinics, 2015

Source:Vaccine, Volume 36, Issue 20
Author(s): Clelia Pezzi, Audrey McCulloch, Heesoo Joo, Jennifer Cochran, Laura Smock, Ellen Frerich, Blain Mamo, Kailey Urban, Stephen Hughes, Colleen Payton, Kevin Scott, Brian Maskery, Deborah Lee
BackgroundNewly arrived refugees are offered vaccinations during domestic medical examinations. Vaccination practices and costs for refugees have not been described with recent implementation of the overseas Vaccination Program for U.S.-bound Refugees (VPR). We describe refugee vaccination during the domestic medical examination and the estimated vaccination costs from the US government perspective in selected U.S. clinics.MethodsSite-specific vaccination processes and costs were collected from 16 clinics by refugee health partners in three states and one private academic institution. Vaccination costs were estimated from the U.S. Vaccines for Children Program and Medicaid reimbursement rates during fiscal year 2015.ResultsAll clinics reviewed overseas vaccination records before vaccinating, but all records were not transferred into state immunization systems. Average vaccination costs per refugee varied from $120 to $211 by site. The total average cost of domestic vaccination was 15% less among refugees arriving from VPR- vs. nonVPR-participating countries during a single domestic visit.ConclusionOur findings indicate that immunization practices and costs vary between clinics, and that clinics adapted their vaccination practices to accommodate VPR doses, yielding potential cost savings.
https://ift.tt/2JihrXL
Mayor campo de actuación de la cardiología nuclear
Publication date: May–June 2018
Source:Revista Española de Medicina Nuclear e Imagen Molecular, Volume 37, Issue 3
Author(s): I. Casáns Tormo
https://ift.tt/2Jg0Cwm
The mixed potential type gas sensor based on stabilized zirconia and molybdate MMoO4 (M: Ni, Co and Zn) sensing electrode aiming at detecting triethylamine
Publication date: 15 August 2018
Source:Sensors and Actuators B: Chemical, Volume 267
Author(s): Fangmeng Liu, Junming He, Zijie Yang, Rui You, Jing Wang, Lianjing Zhao, Qingji Wang, Xishuang Liang, Peng Sun, Xu Yan, Geyu Lu
The mixed potential type gas sensors utilizing yttria stabilized zirconia (YSZ) solid electrolyte and molybdates MMoO4 (M: Ni, Co and Zn) sensing electrodes (SEs) were fabricated aiming at detecting triethylamine (TEA) at 600 °C. Results indicated that the device attached with NiMoO4-SE exhibited the highest response value of −71 mV to 50 ppm TEA and low detection limit of 100 ppb at 600 °C. Moreover, the response time of the developed sensor to 50 ppm TEA was 3 s, which signified the fast response rate. The response value of fabricated sensor displayed the piecewise linear relationship to logarithm of TEA concentrations and the sensitivities were −4 mV/decade (0.1–1 ppm) and −37 mV/decade (1–100 ppm), respectively. More importantly, the present sensor also exhibited good repeatability, selectivity, slight effect of humidity and stability of 10 days, indicating a great candidate for use in detection of TEA. Furthermore, the device based on mixed potential mechanism was proposed and further verified using polarization curve.
https://ift.tt/2Haiicm
Zinc fertilizers influence greenhouse gas emissions and nitrifying and denitrifying communities in a non-irrigated arable cropland
Publication date: 1 September 2018
Source:Geoderma, Volume 325
Author(s): Mónica Montoya, Antonio Castellano-Hinojosa, Antonio Vallejo, José Manuel Álvarez, Eulogio J. Bedmar, Jaime Recio, Guillermo Guardia
Fertilization with micronutrients (e.g., zinc, Zn) is essential in order to overcome the global nutritional problems associated with human micronutrient deficiencies. However, little is known about the effect of micronutrient fertilizers and their interaction with nitrogen (N) on greenhouse gas (GHG) emissions and soil microbial processes involved in nitrous oxide (N2O) fluxes. In this context, a one-year field experiment was carried out using a winter wheat (Triticum aestivum L.) crop in Central Spain. Winter wheat was treated with different Zn sources (Zn-sulphate, Zn-lignosulphonate, Zn with a mixture of synthetic chelating compounds DTPA-HEDTA-EDTA and Zn-humic/fulvic acids) and N rates (0, 120 and 180 kg N ha−1). Zn sources were applied at 10 kg Zn ha−1 for Zn-sulphate and 0.36 kg Zn ha−1 for the rest of treatments. Nitrous oxide, methane (CH4) and respiration fluxes were measured (two-three times per week during the first month after each fertilization and thereafter with decreasing frequency), as were the total abundances of soil Bacteria and Archaea, ammonia-oxidizing Bacteria and Archaea, and denitrifying bacteria. The DTPA-HEDTA-EDTA reduced cumulative N2O losses by 21.4% and respiration fluxes by 24.4% from those of the no Zn application. The chelating of metal co-factors (mainly copper, Cu) of the enzymes involved in the nitrification and denitrification steps was the probable mechanism for the reduction of N2O emissions as bacterial amoA, nirK, nirS and norB gene abundances, as well as the extractable Cu content, decreased in this treatment. Unexpectedly, the DTPA-HEDTA-EDTA increased the copy number of nosZ by 31.2% over that of the no Zn application. The Zn applied together with the humic/fulvic acids mixture caused significant increases of total bacterial abundance and nitrifier and denitrifier communities, particularly the norB gene, thereby leading to the highest N2O emissions. The optimum N rate was 120 kg N ha−1 since it resulted in the lowest yield-scaled N2O losses and N surplus. The application of synthetic Zn chelates can be recommended as a win-win mitigation and adaptation strategy aimed at reducing yield-scaled GHG emissions and at the enhancement of Zn biofortification.
https://ift.tt/2JbBZ43
Anodic stripping voltammetric determination of zinc at a 3-D printed carbon nanofiber–graphite–polystyrene electrode using a carbon pseudo-reference electrode
Publication date: 15 August 2018
Source:Sensors and Actuators B: Chemical, Volume 267
Author(s): Kevin C. Honeychurch, Zuhayr Rymansaib, Pejman Iravani
The application of a novel fully 3-D printed carbon nanofiber–graphite–polystyrene electrode has been investigated for the trace determination of Zn2+ by differential pulse anodic stripping voltammetry. The possibility of utilising a carbon pseudo-reference electrode was found to be successful. The effect of accumulation potential and time were investigated and optimised. Using an accumulation potential of −2.9 V (vs. C) and an accumulation time of 75 s a single sharp anodic stripping peak was recorded exhibiting a linear response from 12.7 μg/L to 450 μg/L. The theoretical detection limit (3σ) was calculated as 8.6 μg/L. Using the optimised conditions a mean recovery of 97.8%, (%CV = 2.0%, n = 5) for a tap water sample fortified at 0.990 μg/mL was obtained indicating the method holds promise for the determination of Zn2+ in such samples.
https://ift.tt/2qPMh3a
Cross-regulation between Notch signaling pathway and miRNA machinery in cancer

Source:DNA Repair
Author(s): Maryam Majidinia, Saber Ghazizadeh Darband, Mojtaba Kaviani, Seyed Mohammad Nabavi, Rana Jahanban-Esfahlan, Bahman Yousefi
Despite their simple structure, the Notch family of receptors regulates a wide-spectrum of key cellular processes including development, tissue patterning, cell-fate determination, proliferation, differentiation and, cell death. On the other hand, accumulating date pinpointed the role of non-coding microRNAs, namely miRNAs in cancer initiation/progression via regulating the expression of multiple oncogenes and tumor suppressor genes, as such the Notch signaling. It is now documented that these two partners are in one or in the opposite directions and rule together the cancer fate. Here, we review the current knowledge relevant to this tricky interplay between different miRNAs and components of Notch signaling pathway. Further, we discuss the implication of this crosstalk in cancer progression/regression in the context of cancer stem cells, tumor angiogenesis, metastasis and emergence of multi-drug resistance. Understanding the molecular cues and mechanisms that occur at the interface of miRNA and Notch signaling would open new avenues for development of novel and effective strategies for cancer therapy.
https://ift.tt/2qQCnNM
International Organization of Psychophysiology
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Source:International Journal of Psychophysiology, Volume 127
https://ift.tt/2JfdGlS
Editorial Board
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Source:International Journal of Psychophysiology, Volume 127
https://ift.tt/2qORzM3
No effect of prenatal vitamin D deficiency on autism-relevant behaviours in multiple inbred strains of mice

Source:Behavioural Brain Research, Volume 348
Author(s): M. Langguth, M. Fassin, S. Alexander, K.M. Turner, T.H.J. Burne
Autism Spectrum Disorders (ASD) is a group of neurodevelopmental disorders commonly characterised by verbal and non-verbal communication deficits, impaired social interaction and repetitive, stereotypic behaviours. The aetiology of ASD is most likely a combination of genetic and environmental factors. Epidemiological evidence suggests that prenatal vitamin D deficiency is associated with an increased incidence of ASD. The overall aim of this study was to investigate prenatal vitamin D deficiency on ASD-related behavioural phenotypes in multiple inbred strains of mice. We included two commonly used inbred mouse strains (C57BL/6J and BALB/c) as well as inbred BTBR mice, which show ASD-related behaviours, such as excessive self-grooming, hyperlocomotion, social interaction deficits and altered communication. We also studied the effect of prenatal vitamin D deficiency in a fourth strain; an F1 cross of C57BL/6J x BTBR mice, which have a partial BTBR phenotype. To implement prenatal vitamin D deficiency, female mice were placed on vitamin D deplete diets for ten weeks, including mating and gestation, until littering, when all dams were switched to the control diet. Behavioural symptoms related to ASD were measured, including isolation-induced ultrasonic vocalisations to measure communication, the three-chambered social interaction task to observe social interaction, the open field test to examine hyperlocomotion, assessment of grooming and rearing behaviour and finally the active place avoidance task to observe spatial learning and memory in response to a mild foot shock. Prenatal vitamin D deficiency had a negative impact on preference for social novelty in C57BL/6J mice, despite similar vocalisation phenotypes, and prenatal vitamin D-deficient F1 mice were found to be hypolocomotive in the open field test yet performed better on the active place avoidance task. Despite clear differences between strains, there were no other consistent significant main effects of maternal diet on the behaviour of the offspring. Vitamin D deficiency has been implicated as a risk factor for ASD and these data show that there is greater variation between different inbred strains in ASD-related behaviour, suggesting that prenatal vitamin D deficiency is not sufficient to recapitulate an ASD phenotype in multiple inbred strains of mice.
https://ift.tt/2qPU6oL
Serotonin-specific lesions of the dorsal raphe disrupt maternal aggression and caregiving in postpartum rats

Source:Behavioural Brain Research, Volume 348
Author(s): M. Allie Holschbach, Erika M. Vitale, Joseph S. Lonstein
The behavioral modifications associated with early motherhood, which include high aggression, caring for the young, and low anxiety, are all affected by acute pharmacological manipulation of serotonin signaling. However, the effects on all these behaviors of permanently disrupting serotonin signaling from one of its primary sources, the dorsal raphe nucleus (DR), have not been examined in detail. To address this, serotonin-specific lesions centered on the dorsomedial DR (DRdm; DR subregion strongly implicated in emotional behaviors) were induced at mid-pregnancy (day 15) or early postpartum (day 2) in rats using a saporin-conjugated neurotoxin targeting the serotonin transporter (Anti-SERT-SAP). Prepartum or postpartum Anti-SERT-SAP reduced DRdm serotonin immunoreactivity by ∼40–65%, and postpartum Anti-SERT-SAP also reduced it in the ventromedial and lateral wings of the DR, as well as in the median raphe. Serotonin-immunoreactive fibers were significantly reduced in the anterior hypothalamus, but not medial preoptic area, of lesioned dams. Pre- or postpartum lesions both greatly reduced maternal aggression, but while prepartum lesions did not affect later undisturbed maternal caregiving, the larger postpartum lesions prevented the postpartum decline in kyphotic nursing and reduced pup licking. Serotonin lesions did not affect pup retrieval, but the prepartum lesions temporarily increased maternal hovering over and licking the pups observed immediately after the disruptive retrieval tests. Dams' anxiety-like behaviors and litter weight gains were unaffected by the lesions. These findings suggest that DRdm serotonin projecting to the AH is particularly critical for maternal aggression, but that more widespread disruption of midbrain raphe serotonin is necessary to greatly impair maternal caregiving. Postpartum anxiety may rely more on other neurochemical systems or different midbrain serotonergic cell populations.
https://ift.tt/2Hi4BvS
The strength of reward-related learning depends on the degree of activation of ventral tegmental area dopamine neurons

Source:Behavioural Brain Research, Volume 348
Author(s): E. Galaj, R. Ranaldi
We tested whether (1) the capacity of a reward-associated conditioned stimulus (CS) to cause conditioned activation of ventral tegmental area (VTA) dopamine (DA) neurons is associated with its capacity to elicit conditioned approach responses and (2) whether the acquisition of these capacities by a CS requires N-methyl-D-aspartate (NMDA) and muscarinic acetylcholine (mACh) receptor stimulation. Rats were trained to emit a conditioned approach response to a light CS that was previously paired with food and were treated systemically with scopolamine (a mACh receptor antagonist) or MK-801 (an NMDA receptor antagonist) either prior to each conditioning session (during which animals experienced paired CS and food presentations) or prior to the conditioned approach (CS-only) test. Brains were harvested after the CS-only test and processed for tyrosine hydroxylase (TH) (DA cells) and c-fos in the VTA. When animals received scopolamine or MK-801 treatment prior to conditioning sessions we observed significantly fewer TH-labeled (i.e., DA) cells in the VTA that expressed c-fos and significantly less conditioned approach responding during the CS-only test. Further analysis showed a correlation between the number of VTA DA cells activated and the number of conditioned approach responses. Treatments made prior to the CS-only test did not affect responding. Altogether these results suggest that the degree to which a CS elicits conditioned approach depends partially on the degree to which the CS activates VTA DA cells and that the acquisition of both of these capacities by a CS requires mACh and NMDA receptor stimulation.
https://ift.tt/2qSoDC7
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Publication date: September 2017 Source: Free Radical Biology and Medicine, Volume 110 Author(s): Lucía Fernández-del-Río, Anish Nag, Elen...
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Abstract Noise pollution is a major factor of environmental complaints in many cities, which has significant impacts on human health. As a...