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Πέμπτη 16 Φεβρουαρίου 2017

Size-resolved characterization of the polysaccharidic and proteinaceous components of sea spray aerosol

Publication date: April 2017
Source:Atmospheric Environment, Volume 154
Author(s): Josephine Y. Aller, JoAnn C. Radway, Wendy P. Kilthau, Dylan W. Bothe, Theodore W. Wilson, Robert D. Vaillancourt, Patricia K. Quinn, Derek J. Coffman, Benjamin J. Murray, Daniel A. Knopf
Dissolved organic polymers released by phytoplankton and bacteria abiologically self-assemble in surface ocean waters into nano-to micro-sized gels containing polysaccharides, proteins, lipids and other components. These gels concentrate in the sea surface microlayer (SML), where they can potentially contribute to sea spray aerosol (SSA). Sea spray is a major source of atmospheric aerosol mass over much of the earth's surface, and knowledge of its properties (including the amount and nature of the organic content), size distributions and fluxes are fundamental for determining its role in atmospheric chemistry and climate. Using a cascade impactor, we collected size-fractionated aerosol particles from ambient air and from freshly generated Sea Sweep SSA in the western North Atlantic Ocean together with biological and chemical characterization of subsurface and SML waters. Spectrophotometric methods were applied to quantify the polysaccharide-containing transparent exopolymer (TEP) and protein-containing Coomassie stainable material (CSM) in these particles and waters. This study demonstrates that both TEP and CSM in surface ocean waters are aerosolized with sea spray with the greatest total TEP associated with particles <180 nm in diameter and >5 000 nm. The higher concentrations of TEP and CSM in particles >5 000 nm most likely reflects collection of microorganism cells and/or fragments. The greater concentration of CSM in larger size particles may also reflect greater stability of proteinaceous gels compared to polysaccharide-rich gels in surface waters and the SML. Both TEP and CSM were measured in the ambient marine air sample with concentrations of 2.1 ± 0.16 μg xanthan gum equivalents (XG eq.) m−3 and 14 ± 1.0 μg bovine serum albumin equivalents (BSA eq.) m−3. TEP in Sea Sweep SSA averaged 4.7 ± 3.1 μg XG eq. m−3 and CSM 8.6 ± 7.3 μg BSA eq. m−3. This work shows the transport of marine biogenic material across the air-sea interface through primary particle emission and the first demonstration of particle size discriminated TEP and CSM characterization of SSA and ambient aerosol under field conditions.

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Ectopic tissue engineered ligament with silk collagen scaffold for ACL regeneration: A preliminary study

Publication date: Available online 16 February 2017
Source:Acta Biomaterialia
Author(s): Jisheng Ran, Yejun Hu, Huihui Le, Yangwu Chen, Zefeng Zheng, Xiao Chen, Zi Yin, Ruijian Yan, Zhangchu Jin, Chenqi Tang, Jiayun Huang, Yanjia Gu, Langhai Xu, Shengjun Qian, Wei Zhang, Boon Chin Heng, Pioletti Dominique, Weishan Chen, Lidong Wu, Weiliang Shen, Hongwei Ouyang
Anterior cruciate ligament (ACL) reconstruction remains a formidable clinical challenge because of the lack of vascularization and adequate cell numbers in the joint cavity. In this study, we developed a novel strategy to mimic the early stage of repair in vivo, which recapitulated extra-articular inflammatory response to facilitate the early ingrowth of blood vessels and cells. A vascularized ectopic tissue engineered ligament (ETEL) with silk collagen scaffold was developed and then transferred to reconstruct the ACL in rabbits without interruption of perfusion. At 2 weeks after ACL reconstruction, more well-perfused cells and vessels were found in the regenerated ACL with ETEL, which decreased dramatically at the 4 and 12 week time points with collagen deposition and maturation. ACL treated with ETEL exhibited more mature ligament structure and enhanced ligament-bone healing post-reconstructive surgery at 4 and 12 weeks, as compared with the control group. In addition, the ETEL group was demonstrated to have higher modulus and stiffness than the control group significantly at 12 weeks post-reconstructive surgery. In conclusion, our results demonstrated that the ETEL can provide sufficient vascularity and cellularity during the early stages of healing, and subsequently promote ACL regeneration and ligament-bone healing, suggesting its clinic use as a promising therapeutic modality.Statement of SignificanceEarly inflammatory cell infiltration, tissue and vessels ingrowth were significantly higher in the extra-articular implanted scaffolds than theses in the joint cavity. By mimicking the early stages of wound repair, which provided extra-articular inflammatory stimulation to facilitate the early ingrowth of blood vessels and cells, a vascularized ectopic tissue engineered ligament (ETEL) with silk collagen scaffold was constructed by subcutaneous implantation for 2 weeks. The fully vascularized TE ligament was then transferred to rebuild ACL without blood perfusion interruption, and was demonstrated to exhibit improved ACL regeneration, bone tunnel healing and mechanical properties.

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Aspirin-triggered resolvin D1-modified materials promote the accumulation of pro-regenerative immune cell subsets and enhance vascular remodeling

Publication date: Available online 16 February 2017
Source:Acta Biomaterialia
Author(s): Mary Caitlin P. Sok, Maxianne C. Tria, Claire E. Olingy, Cheryl L. San Emeterio, Edward A. Botchwey
Many goals in tissue engineering rely on modulating cellular localization and polarization of cell signaling, including the inhibition of inflammatory infiltrate, facilitation of inflammatory cell egress, and clearance of apoptotic cells. Omega-3 polyunsaturated fatty acid-derived resolvins are gaining increasing recognition for their essential roles in inhibition of neutrophil invasion into inflamed tissue and promotion of macrophage phagocytosis of cellular debris as well as their egress to the lymphatics. Biomaterial-based release of lipid mediators is a largely under-explored approach that provides a method to manipulate local lipid signaling gradients in vivo and direct the recruitment and/or polarization of anti-inflammatory cell subsets to suppress inflammatory signaling and enhance angiogenesis and tissue regeneration. The goal of this study was to encapsulate Aspirin-Triggered Resolvin D1 (AT-RvD1) into a degradable biomaterial in order to elucidate the effects of sustained, localized delivery in a model of sterile inflammation. Flow cytometric and imaging analysis at both 1 and 3 days after injury showed that localized AT-RvD1 delivery was able significantly increase the accumulation of anti-inflammatory monocytes and M2 macrophages while limiting the infiltration of neutrophils. Additionally, cytokine profiling and longitudinal vascular analysis revealed a shift towards a pro-angiogenic profile with increased concentrations of VEGF and SDF-1α, and increased arteriolar diameter and tortuosity. These results demonstrate the ability of locally-delivered AT-RvD1 to increase pro-regenerative immune subpopulations and promote vascular remodeling.Statement of SignificanceThis work is motivated by our efforts to explore the underlying mechanisms of inflammation resolution after injury and to develop biomaterial-based approaches to amplify endogenous mechanisms of resolution and repair. Though specific lipid mediators have been identified that actively promote the resolution of inflammation, biomaterial-based localized delivery of these mediators has been largely unexplored. We loaded Aspirin-Triggered Resolvin D1 into a PLGA scaffold and examined the effects of sustained, localized delivery on the innate immune response. We found that biomaterial delivery of resolvin was able to enhance the accumulation of pro-regenerative populations of immune cells, including anti-inflammatory monocytes, population that has never before been shown to respond to resolvin treatment, and also enhance vascular remodeling in response to tissue injury.

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Gelatin-Based 3D Conduits for Transdifferentiation of Mesenchymal Stem Cells into Schwann Cell-like Phenotypes

Publication date: Available online 16 February 2017
Source:Acta Biomaterialia
Author(s): Metin Uz, Melda Buyukoz, Anup D. Sharma, Donald S. Sakaguchi, Sacide Alsoy Altinkaya, Surya K. Mallapragada
In this study, gelatin-based 3D conduits with three different microstructures (nanofibrous, macroporous and ladder-like) were fabricated for the first time via combined molding and thermally induced phase separation (TIPS) technique for peripheral nerve regeneration. The effects of conduit microstructure and mechanical properties on the transdifferentiation of bone marrow-derived mesenchymal stem cells (MSCs) into Schwann cell (SC) like phenotypes were examined to help facilitate neuroregeneration and understand material-cell interfaces. Results indicated that 3D macroporous and ladder-like structures enhanced MSC attachment, proliferation and spreading, creating interconnected cellular networks with large numbers of viable cells compared to nanofibrous and 2D-tissue culture plate counterparts. 3D-ladder-like conduit structure with complex modulus of ∼0.4x106 Pa and pore size of ∼150 µm provided the most favorable microenvironment for MSC transdifferentiation leading to ∼85% immunolabeling of all SC markers. On the other hand, the macroporous conduits with complex modulus of ∼4x106 Pa and pore size of ∼100 µm showed slightly lower (∼65% for p75, ∼75% for S100 and ∼85% for S100β markers) immunolabeling. Transdifferentiated MSCs within 3D-ladder-like conduits secreted significant amounts (∼2.5 pg/mL NGF and ∼0.7 pg/mL GDNF per cell) of neurotrophic factors, while MSCs in macroporous conduits released slightly lower (∼1.5 pg/mL NGF and 0.7 pg/mL GDNF per cell) levels. PC12 cells displayed enhanced neurite outgrowth in media conditioned by conduits with transdifferentiated MSCs. Overall, conduits with macroporous and ladder-like 3D structures are promising platforms in transdifferentiation of MSCs for neuroregeneration and should be further tested in vivo.Statement of SignificanceThis manuscript focuses on the effect of microstructure and mechanical properties of gelatin-based 3D conduits on the transdifferentiation of mesenchymal stem cells to Schwann cell-like phenotypes. This work builds on our recently accepted manuscript in Acta Biomaterialia focused on multifunctional 2D films, and focuses on 3D microstructured conduits designed to overcome limitations of current strategies to facilitate peripheral nerve regeneration. The comparison between conduits fabricated with nanofibrous, macroporous and ladder-like microstructures showed that the ladder-like conduits showed the most favorable environment for MSC transdifferentiation to Schwann-cell like phenotypes, as seen by both immunolabeling as well as secretion of neurotrophic factors. This work demonstrates the importance of controlling the 3D microstructure to facilitate tissue engineering strategies involving stem cells that can serve as promising approaches for peripheral nerve regeneration.

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Self-assembled tumor-targeting hyaluronic acid nanoparticles for photothermal ablation in orthotopic bladder cancer

Publication date: Available online 15 February 2017
Source:Acta Biomaterialia
Author(s): Tingsheng Lin, Ahu Yuan, Xiaozhi Zhao, Huibo Lian, Junlong Zhuang, Wei Chen, Qing Zhang, Guangxiang Liu, Shiwei Zhang, Wei Chen, Wenmin Cao, Chengwei Zhang, Jinhui Wu, Yiqiao Hu, Hongqian Guo
Bladder cancer is one of the most frequent malignancies in the urinary system. Radical cystectomy is inevitable when bladder cancer progresses to a muscle-invasive disease. However, cystectomy still causes a high risk of death and a low quality of life (such as ureter-abdomen ostomy, uroclepsia for ileal-colon neobladder). Therefore, more effective treatments as well as bladder preservation are needed. We developed self-assembled tumor-targeting hyaluronic acid-IR-780 nanoparticles for photothermal ablation in over-expressing CD44 (the receptor for HA) bladder cancer, which show high tumor selectivity, high treatment efficacy, good bioavailability, and excellent biocompatibility. The nanoparticles demonstrated a stable spherical nanostructure in aqueous conditions with good mono-dispersity, and their average size was 171.3±9.14 nm. The nanoparticles can be degraded by hyaluronidase when it is over-expressed in bladder cells; therefore, they appear to have a hyaluronidase-responsive "OFF/ON" behavior of a fluorescence signal. HA-IR-780 NPs also showed high photothermal efficiency; 2.5, 5, 10 and 20 μg/mL of NPs had a maximum temperature increase of 11.2±0.66°C, 18.6±0.75°C, 26.8±1.11°C and 32.3±1.42°C. The in vitro cell viability showed that MB-49 cells could be efficiently ablated by combining HA-IR-780 NPs with 808 nm laser irradiation. Then, in vivo biodistribution showed the HA-IR-780 NPs are targeted for accumulation in bladder cancer cells but have negligible accumulation in normal bladder wall. The photothermal therapeutic efficacy of HA-IR-780 NPs in the orthotopic bladder cancer model showed tumors treated with NPs had a maximum temperature of 48.1 ± 1.81°C after 6 min of laser irradiation. The tumor volume was approximately 65-75 mm3 prior to treatment. After 12 days, the tumor sizes for the PBS, PBS plus laser irradiation and HA-IR-780 NPs-treated groups were 784.75 mm3, 707.5 mm3, and 711.37 mm3, respectively. None of the tumors in the HA-IR-780 NPs plus laser irradiation-treated group were visible to the naked eye. A toxicity study showed HA-IR-780 NPs (2.5-20 mg/kg, i.v.) were nontoxic and safe for in vivo applications. HA-IR-780 nanoparticles address current clinical challenges, treating locally aggressive lesions and preserving the bladder. They have enormous potential to improve the bladder cancer treatment strategies in clinic.Statement of SignificanceBladder cancer is one of the most frequent malignancies in the urinary system. Radical cystectomy is inevitable while bladder cancer progress to muscle-invasive disease.We developed self-assembled tumor-targeting hyaluronic acid-IR-780 nanoparticles for photothermal ablation in over-expressing CD44 (the receptor for HA) bladder cancerPhotothermal therapeutic efficacy of HA-IR-780 NPs in orthotopic bladder cancer model showed tumors were completely ablated.HA-IR-780 nanoparticles address current clinical challenges, treating locally aggressive lesions as well as for bladder preservation.

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Boronic acid-tethered amphiphilic hyaluronic acid derivative-based nanoassemblies for tumor targeting and penetration

Publication date: Available online 16 February 2017
Source:Acta Biomaterialia
Author(s): Jae Young Jeong, Eun-Hye Hong, Song Yi Lee, Jae-Young Lee, Jae-Hyoung Song, Seung-Hak Ko, Jae-Seong Shim, Sunghwa Choe, Dae-Duk Kim, Hyun-Jeong Ko, Hyun-Jong Cho
(3-Aminomethylphenyl)boronic acid (AMPB)-installed hyaluronic acid–ceramide (HACE)-based nanoparticles (NPs), including manassantin B (MB), were fabricated for tumor-targeted delivery. The amine group of AMPB was conjugated to the carboxylic acid group of hyaluronic acid (HA) via amide bond formation, and synthesis was confirmed by spectroscopic methods. HACE-AMPB/MB NPs with a 239-nm mean diameter, narrow size distribution, negative zeta potential, and > 90% drug encapsulation efficiency were fabricated. Exposed AMPB in the outer surface of HACE-AMPB NPs (in the aqueous environment) may react with sialic acid of cancer cells. The improved cellular accumulation efficiency, in vitro antitumor efficacy, and tumor penetration efficiency of HACE-AMPB/MB NPs, compared with HACE/MB NPs, in MDA-MB-231 cells (CD44 receptor-positive human breast adenocarcinoma cells) may be based on the CD44 receptor-mediated endocytosis and phenylboronic acid-sialic acid interaction. Enhanced in vivo tumor targetability, infiltration efficiency, and anti-tumor efficacies of HACE-AMPB NPs, compared with HACE NPs, were observed in a MDA-MB-231 tumor-xenografted mouse model. In addition to passive tumor targeting (based on an enhanced permeability and retention effect) and active tumor targeting (interaction between HA and CD44 receptor), the phenylboronic acid-sialic acid interaction can play important roles in augmented tumor targeting and penetration of HACE-AMPB NPs.Statement of significance(3-Aminomethylphenyl)boronic acid (AMPB)-tethered hyaluronic acid-ceramide (HACE)-based nanoparticles (NPs), including manassantin B (MB), were fabricated and their tumor targeting and penetration efficiencies were assessed in MDA-MB-231 (CD44 receptor-positive human adenocarcinoma) tumor models. MB, which exhibited antitumor efficacies via the inhibition of angiogenesis and hypoxia inducible factor (HIF)-1, was entrapped in HACE-AMPB NPs in this study. Phenylboronic acid located in the outer surface of HACE-AMPB/MB NPs (in the aqueous milieu) may react with the sialic acid over-expressed in cancer cells and intramolecular B‒O bond can be formed. This phenylboronic acid-sialic acid interaction may provide additional tumor targeting and penetration potentials together with an enhanced permeability and retention (EPR) effect (passive tumor targeting) and HA-CD44 receptor interaction (active tumor targeting). Developed HACE-AMPB NP may be one of promising nanocarriers for the imaging and therapy of CD44 receptor-expressed cancers.

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Effect of processing conditions of dicalcium phosphate cements on graft resorption and bone formation

Publication date: Available online 15 February 2017
Source:Acta Biomaterialia
Author(s): Zeeshan Sheikh, Yu Ling Zhang, Faleh Tamimi, Jake Barralet
Dicalcium phosphate cements (brushite and monetite) are resorbable biomaterials with osteoconductive potential for bone repair and regeneration that have yet to gain widespread commercial use. Brushite can be converted to monetite by heat treatments additionally resulting in various changes in the physico-chemical properties. However, since conversion is most commonly performed using autoclave sterilisation (wet heating), it is uncertain whether the properties observed for monetite as a result of heating brushite under dry conditions affect resorption and bone formation favourably. This study was designed to produce monetite grafts of differing physical form by autoclaving and dry heating (under vacuum) to be compared with brushite biomaterials in an orthotopic pre-clinical implantation model in rabbit for 12 weeks. It was observed that monetite grafts had higher porosity and specific surface area than their brushite precursors. The autoclaved monetite grafts had compressive strength reduced by 50% when compared with their brushite precursors. However, the dry heat converted monetite grafts had compressive strength comparable with brushite. Results from in vivo experiments revealed that both types of monetite graft materials resorbed faster than brushite and more bone formation was achieved. There was no significant difference in the amount of bone formed between the two types of monetite grafts. The implanted brushite grafts underwent phase transformation to form hydroxyapatite, which ultimately limited bioresorption. However, this was not observed in both types of monetite grafts. In summary, both autoclaving and dry heating the preset brushite cement grafts resulted in monetite biomaterials which were more resorbable with potential to be investigated and optimized for orthopaedic and maxillofacial bone repair and regeneration applications.

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T012 Transcranial alternating current stimulation: Models, EEG/MEG, and cognition

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Publication date: March 2017
Source:Clinical Neurophysiology, Volume 128, Issue 3
Author(s): C. Herrmann
It has been repeatedly demonstrated that EEG oscillations reflect cognitive processes. So far, however, EEG oscillations have only been correlated with cognitive functions. A new method now allows to demonstrate their causal role in brain function. During transcranial alternating current stimulation (tACS) an alternating current is applied to the scalp of human subjects and interferes with EEG oscillations. In order to determine the placement of stimulation electrodes, finite element models are used to predict intracranial current flow at the target location. A network of simulated neurons is used to demonstrate that tACS results in an entrainment of ongoing brain oscillations. Multiple experiments will be introduced that all apply tACS at different frequencies in order to modulate both EEG oscillations and cognitive processes. The results demonstrate that tACS can modulate ongoing EEG oscillations. This modulation, in turn, seems to modulate cognitive processes such as detection and perception.



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T029 Where do we stimulate M1? A combined neurophysiological and modelling approach

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Publication date: March 2017
Source:Clinical Neurophysiology, Volume 128, Issue 3
Author(s): A. Thielscher
Much of our knowledge on the physiological mechanisms of transcranial magnetic stimulation (TMS) stems from studies which targeted the human motor cortex. Very surprisingly, however, it is still unclear which part of M1 is stimulated by TMS when a muscle twitch is elicited. Considering that the motor cortex consists of functionally and histologically distinct subareas, this also renders the hypotheses on the physiological TMS effects uncertain.I will report on two recent studies which combined electrophysiological measurements of muscle responses to TMS with realistic estimates of the induced electric field, based on the finite-element method (FEM) and MRI-derived individual head models. In the first study, the orientation of a standard figure 8 coil was systematically varied and the field changes in different subparts of the motor cortex were compared with the electrophysiological threshold changes. In the second study, three figure 8 coils having different field decays were used and the differences in the electrophysiological thresholds were correlated with the differences in the calculated field distributions. Both studies consistently demonstrate that TMS stimulates the region around the gyral crown and that the maximal electric field strength in this region is significantly related to the electrophysiological response.Our studies are one of the most extensive comparisons between FEM-based field calculations and physiological TMS effects so far, being based on data for two hand muscles in 9 subjects. The results help to improve our understanding of the basic mechanisms of TMS. They also pave the way for a systematic exploration of realistic field estimates for dosage control in TMS.



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Contents

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Publication date: March 2017
Source:Clinical Neurophysiology, Volume 128, Issue 3





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T020 Intracranial electric field measurements during TES in human and non-human primates. What can we learn for accurately modelling TES?

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Publication date: March 2017
Source:Clinical Neurophysiology, Volume 128, Issue 3
Author(s): A. Opitz
Transcranial electric stimulation (TES) is an emerging technique to non-invasively modulate brain function. However the spatiotemporal distribution of electric fields during TES remains poorly understood.In this study we perform direct intracranial measurements of the electric field generated by transcranial alternating current (tACS) in epilepsy patients and cebus monkeys and evaluate the capacity of finite element method (FEM) models to predict the spatial distribution of measured electric fields.



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T008 rTMS in depression – Is more always better?

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Publication date: March 2017
Source:Clinical Neurophysiology, Volume 128, Issue 3
Author(s): P. Fitzgerald
QuestionRepetitive transcranial magnetic stimulation (rTMS) is now a well-established new treatment modality for patients with depressive disorders that has been assessed across a large range of controlled studies. However, limited research has explored the basic parameters used in the design of rTMS treatment protocols especially in regards to variables determining the dose of treatment. Over time, dose has generally increased without the impact of this being systematically assessed. Therefore, we have been exploring aspects of treatment dose and how they relate to treatment outcomes.MethodsWe have conducted several studies designed to address rTMS dose related issues. First, we have conducted several studies using TMS-EEG and TMS-NIRS methods to explore the effects of stimulation at increasing intensities on the prefrontal cortex. Second, we have conducted a large multi-site trial investigating the effect of pulse number as a dose variable on clinical response to rTMS in depression.ResultsTMS-NIRS studies have indicated that there is a clearly bimodal response to increasing TMS stimulation intensity which is likely to have implications for the determination of optimal dosing for clinical outcomes. Our randomised controlled data do not suggest that increasing pulse number in an rTMS treatment protocol above standard levels is associated with improved outcomes.ConclusionsImprovements in the application of rTMS treatment are likely to be possible but 'more does not always seem to be better'. Improved outcomes may be achieved but optimising stimulation intensity but not increasing pulse number in individual treatment sessions.



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T016 Repetitive transcranial magnetic stimulation and post-stroke dysphagia

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Publication date: March 2017
Source:Clinical Neurophysiology, Volume 128, Issue 3
Author(s): E. Khedr
Considerable effort in recent years has been devoted to investigating neurophysiological changes in the brain after stroke and in developing novel strategies to enhance recovery particularlyin the limbs and trunk. In contrast, although dysphagia is a severe complication and can be life threatening in a considerable number of stroke patients, it has not yet received the attention devoted to limb control. In this review, we discuss how introduction of (a) transcranial magnetic stimulation (TMS) to test noninvasively the integrity of the cortico-bulbar swallowing system and (b) the plasticity provoking protocols of rTMS and transcranial direct current stimulation have recently stimulated research into dysphagia after stroke and led to new potential avenues for treatment. We discuss the neural control of swallowing and discuss the contributions of TMS to understand how different brain areas are involved in dysphagia. We also consider recent studies using noninvasive brain stimulation to interact with synaptic plasticity in cortex and enhance recovery of dysphagia following stroke. Although further studies are needed, these investigations provide an important starting point to understand the stimulation parameters and patient characteristics that may influence the optimal response to therapeutic noninvasive brain stimulation. These techniques need to be refined further through a multicenter study so that they can become an essential tool that can be used in academic centers of excellence as well as in a general hospital setting.



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T024 Modulation of gamma oscillations dynamics by weak electric fields

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Publication date: March 2017
Source:Clinical Neurophysiology, Volume 128, Issue 3
Author(s): D. Reato, M. Bikson, L. Parra
We are interested in the acute effects of weak electric fields on gamma oscillations, which is a critical neural substrate of information processing in the hippocampus. Stimulation with weak currents is known to have a relatively small effect on the firing of individual neurons. Yet, when applying stimulation during gamma activity in rodent slices, we find that the effects of fields are significantly amplified by the neuronal network. Using a computational model we demonstrate that this amplification is the result of the dynamic push and pull of the excitatory/inhibitory feedback loop, which is the hallmark of gamma oscillations. The recorded effects have a mixed spatial distribution in CA3, which is the hippocampal region with the strongest recursive feedback and the main generator of gamma activity. This recursive structure is sometimes thought to be the core processing unit for associative memories. Interestingly, when applying constant current stimulation, the enhancement of gamma activity and neuronal firing outlast the period of stimulation by several minutes, suggesting plastic effects of DC stimulation on this important associative neuronal network.



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Editorial Board

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Publication date: March 2017
Source:Clinical Neurophysiology, Volume 128, Issue 3





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T010 Generating evidence: On the validity of metaanalyses of transcranial stimulation trials

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Publication date: March 2017
Source:Clinical Neurophysiology, Volume 128, Issue 3
Author(s): R. Hamilton
Recent years have witnessed and explosive expansion in the number of investigations in clinical and translational neuroscience that employ transcranial direct current stimulation (tDCS). In healthy individuals tDCS offers a tool for testing causal relationships between brain regions and their underlying cognitive functions, while in clinical populations tDCS is being investigated for a wide variety of potential indications, ranging from psychiatric conditions to deficits caused by stroke and other neurological disorders. Hundreds of researchers use the technique, and there have been over a thousand publications involving tDCS in the last decade. However, the data currently being gathered across many studies in this field have important limitations, including generally small sample sizes and a high degree of heterogeneity with respect to stimulation parameters (e.g. polarity, intensity, electrode location, etc.). Meta-analysis is an important approach that enables investigators to partially overcome these limitations in order to make broader inferences about the effects of tDCS on cortical physiology and cognition. In this talk, several recent tDCS meta-analyses will be surveyed, in order to highlight the ways in which meta-analysis can contribute novel knowledge to tDCS research. However, research involving meta-analysis is also susceptible to common pitfalls, which will also be discussed. First, concerns related to the selection of studies and to the selection of data from individual studies will be addressed. Subsequently, issues related to the appropriate aggregation of data across studies will be discussed.



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T014 A brain network perspective on tDCS induced neuroplasticity: Single versus dual or multiple sites stimulation

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Publication date: March 2017
Source:Clinical Neurophysiology, Volume 128, Issue 3
Author(s): S. Jaberzadeh, M. Zoghi
It is becoming increasingly recognized that many behavioral indicators of neurological and psychiatric disease are not solely the result of abnormality in one isolated brain region but represent alterations in functionally connected regions of the brain networks. In this context, brain networks become the target of neuromodulatory interventions such as transcranial direct current stimulation (a-tDCS) for induction of neuroplastic changes within the brain.Advances in different neuroimaging techniques are letting us to non-invasively visualize brain networks in humans during different behavioral tasks with high degree of resolution. Furthermore, new technologies have also become available today which support stimulation of more than one regions the brain networks. However, due to non-local effects of tDCS, which are caused by propagation effects of the applied currents and structural and functional connectivities between regions of a network, defining the ideal configuration of a dual or multi-site stimulation is complicated. Full potential of this targeting approach requires the ability to simultaneously excite or inhibit multiple sites across the surface of the cortex.In this presentation we intended to stimulate the continuing efforts in understanding the optimal configuration of dual or multi-site tDCS in induction of the neuroplastic changes in primary motor cortex. It also aims to broaden the attention not only to the researchers who are currently working on these areas but to the general scientific audience who are interested in the brain structures and functions as well.



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T018 Stimulation outside of motor cortex

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Publication date: March 2017
Source:Clinical Neurophysiology, Volume 128, Issue 3
Author(s): C. Miniussi
In recent years, there has been remarkable progress in the understanding and practical use of transcranial direct current stimulation (tDCS) techniques. The main idea that has been driving the use of tDCS is that whereas anodal tDCS increase neuronal excitability and may consequently enhance behavioural performance, cathodal tDCS decreases neuronal excitability and subsequently worsens behavioural performance. Although these effects of tDCS are well documented for the motor cortex, there is evidence that such facilitationinhibition is not always present at behaviour level and may even be reversed depending on when and how stimulation is applied in respect to task execution, and on the type of task. I will underline that applying this simplistic, sliding-scale reasoning (from excitation to inhibition or vice versa) does not always lead to the desired results at behavioural level. I will provide a picture of what we know about the theoretical models of tES that have been proposed in this field to date.



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T022 Shaping the temporal characteristics of transcranial magnetic stimulation

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Publication date: March 2017
Source:Clinical Neurophysiology, Volume 128, Issue 3
Author(s): A. Peterchev
The pulse waveform of transcranial magnetic stimulation (TMS) affects the degree to which various neuronal elements and populations are activated as well as the strength of neuromodulation resulting from repetitive TMS. Conventional TMS devices allow very limited pulse waveform adjustment; therefore we developed TMS devices with controllable pulse parameters (cTMS). So far cTMS has been used, by our and other groups, to study strength-duration curves in motor cortex and the associated neural membrane time constants; pulse-width dependence of motor input–output curves, cortical neuron recruitment, paired-pulse paradigms, and scalp sensation; and pulse-shape dependence of neuromodulatory effects. These studies show that changing the pulse width, shape, and/or direction may alter the neural elements that are preferentially activated in cortex, as evidenced by differences in motor evoked potential latencies and membrane time constants. These parameters also affect the changes of neural excitability resulting from 1Hz and intermittent theta burst stimulation. For the 1Hz protocol, the near rectangular cTMS pulses produced stronger inhibition than conventional sinusoidal pulses, with unidirectional cTMS pulses having the strongest effect. As well, cTMS has been used to optimize new repetitive paired-pulse stimulation protocols. cTMS was also used to show that the slope of motor input–output curves depends on pulse width via the same mechanism driving the strength-duration relationship of motor threshold. Finally, the pulse width affects the perceived scalp sensation of TMS, with briefer pulses feeling sharper and slightly more uncomfortable than longer pulses. In parallel with exploring the capabilities afforded by cTMS, we are developing a next generation ultraflexible TMS device called a modular pulse synthesizer (MPS) that would allow the generation of essentially any pulse shape and pulse sequence/train within the energy levels practical for TMS. The development and adoption of cTMS and MPS could enable expanded utilization of the temporal characteristics of TMS as a means of enhancing functional targeting, noninvasive biomarkers, neuromodulatory potency, and tolerability.



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T027 tACS and tDCS for vision restoration

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Publication date: March 2017
Source:Clinical Neurophysiology, Volume 128, Issue 3
Author(s): B.A. Sabel, R. Alber
Alternating current stimulation (tACS), when applied near the eye, forces retinal ganglion cells to fire at predetermined frequencies. Repeating this for extended time periods might strengthen the synaptic connectivity through mechanisms of neuroplasticity and thus induce long-lasting after-effects of brain synchronization. To check clinical efficacy in the treatment of vision loss, patients suffering from optic nerve damage received tACS for 10days (20–40min daily, AC–current bursts of.



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T031 One solution for variability of the long term effect induced by NIBSs

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Publication date: March 2017
Source:Clinical Neurophysiology, Volume 128, Issue 3
Author(s): Y. Ugawa
The interindividual variability of the synaptic plasticity (SP) in human brain induced by NIBSs is one of topics in this field. In this communication, I will show which factors explain this variability and how to exclude such factors in MEP experiments in humans.How stable QPSThe significant responder rate of QPS5 and QPS50 were 80% and 63%, respectively. Their rate of non-significant responder was 17% and 37%, but the opposite responder rate was 3% and 0%. The comparisons between several parameters QPSs suggested that the monophasic TMS pulse to use and 30 minutes duration of the QPS procedure have critical roles for stable SP induction.Factors for variabilityTwo groups of variability may affect SP. Biological variability: BDNF polymorphism, meta-plasticity, baseline condition and so on. They may play a small role because QPS was not affected by them, and we are not able to control these factors. Methodological variability: Which synapse is the target for SP induction? SP induction of one synapse is better to see a clear effect. The direction of induced current and TMS pulse for the intervention (mono or bi phasic pulses) markedly affect this factor. How stable SP is induced? PSP, STP, early LTP or late LTP? The duration of the intervention may affect this factor. In QPS, monophasic TMS may induce quite pure SP and 30 minutes duration may induce a considerably stable SP. MEP recording after the intervention: MEP size should be affected by the excitability of cortical synapse, axonal excitability of the corticospinal tract, spinal synapse, motoneurons, neuromuscular junction and muscle. We should record MEPs mainly reflecting the excitability of motor cortical synapse on which SP is induced.My proposal (one solution)To use monophasic TMS pulses in the intervention as long as 30 minutes. During monitoring MEPs, we should use small intensity stimulation inducing the currents in the same direction as those used in the plasticity induction procedure, and also MEPs should be recorded in an active target muscle (Nakamura et al., in press).



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T007 Neural predictors of the effect of transcranial electrical stimulation on learning

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Publication date: March 2017
Source:Clinical Neurophysiology, Volume 128, Issue 3
Author(s): R. Cohen Kadosh
QuestionCurrent attempts to improve cognitive skills using brain stimulation have yielded mixed results, leading to the imperative question: can brain stimulation produce genuine cognitive enhancement?MethodsIn the first part of the talk will focus on data coming from three arithmetic training experiments (n=93). We examined how compared to sham stimulation, transcranial random noise stimulation (tRNS) over the dorsolateral prefrontal cortex modulates online and offline learning over the 5days of training. In the second part of the talk will present data from a collaborative project between Oxford, Harvard, Honeywell, and Northeastern University, that focuses on executive functions training (n=412) and its effect on fluid intelligence. We examined the progress on the 11days training as a function of tRNS and transcranial direct current stimulation in comparison to sham stimulation.ResultsA between-groups comparison such as active stimulation versus sham stimulation produced misleading results. Instead, integrating relevant measures at the interindividual-level can substantially increase the precision of conclusions about the efficacy of brain stimulation.ConclusionsThese results lead to the idea that a consideration of the neurocognitive factors characterising the individuals in the experiment can lead to a much clearer understanding of effects than considering only the group they belong to. This approach yields advancement at the basic and translational level. It would enable the improvement and individualisation of interventions, and produce a better understanding of the underlying neurocognitive mechanisms.



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T009 Animal models of brain stimulation – TMS

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Publication date: March 2017
Source:Clinical Neurophysiology, Volume 128, Issue 3
Author(s): K. Funke
Animal TMS models are especially useful for studying the cellular and molecular effects related to the lasting effects achieved with prolonged stimulation of a particular pattern (rTMS). In translational terms, it is exceptionally challenging to realize stimulation conditions resembling those supposed to occur in the human brain. Due to the very different ratio of coil-to-brain sizes, a focal stimulation of small animal brains as can be achieved in humans using figure-of-eight coils is hardly realistic today. Attempts to develop small (e.g. rodent coils) are confronted with reduced field power or limited number of high-frequency train pulses due to heating problems. Nevertheless, animal TMS models will be helpful in terms of studying relationships between stimulation-induced changes in neuronal activity and plasticity and changes in behavioral phenotypes. Differences in rTMS effects found in Parkinson patients compared to healthy controls which appear to be related to disturbed synaptic plasticity could be replicated in a rat Parkinson disease model (Hsieh et al., 2015) and beneficial stimulation effects related to modulation of striatal dopamine content have been reported (Ghiglieri et al., 2012). Principally, global brain stimulation using rTMS appears adequate if studying neuromodulatory effects not confined to a particular system as is found with changes in extracellular levels of dopamine or glutamate, brain-derived neurotrophic factor (BDNF), pro- or anti-inflammatory mediators and changes in the excitatory-inhibitory balance (Suppa et al., 2016). Nonfocal cortical and/or subcortical stimulation should be suitable to also answer the question if distinct types of neurons (including their genesis and developmental state) or their compartments are more sensitive to a particular stimulation protocol than others if analyzing neuronal activity and plasticity markers. Even if those changes have been achieved with limited focal stimulation in vivo, matched in vitro studies on isolated neuronal systems allow estimating the relevance of focal stimulation as recently demonstrated for the entorhino-hippocampal pathway in mice (Lenz et al., 2016).Focal electric stimulation applied in a way to either mimic the timing of spatially distant evoked activity – as in case of interhemispheric stimulation (Barry et al., 2014)-, or to mimic the electric field distribution likely achieved with an imaginary focal coil could further help to evaluate the differences between focal and global stimulation. However, it has to be kept in mind that magnetic fields induced a different electric field distribution within the tissue as can be achieved with contact electrodes, both with regard to spatial current density and also with regard to extra- and intracellular induction of electric field gradients. In this respect, animal studies demonstrating neuronal effects with patterned magnetic stimulation of rather low field strength (10–100mT) are of further interest, indicating modulation of molecular processes like intracellular calcium release and gene expression even in the absence of detectable electric responses (Grehl et al., 2015). Even if animal models cannot imitate TMS of human cortex in a one-to-one fashion, they definitely offer new ways to investigate how magnetically induced electric field can interact with neuronal processes and which factors determine a variable result of stimulation.



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T011 Influence of anti-Parkinson’s disease drugs on the neuro-plasticity induced by quadripulse transcranial magnetic stimulation (QPS)

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Publication date: March 2017
Source:Clinical Neurophysiology, Volume 128, Issue 3
Author(s): R. Hanajima, H. Enomoto, N. Tanaka, R. Tsutsumi, T. Shimizu, Y. Shirota, Y. Terao, M. Abe, Y. Ugawa
The relation between plasticity and dopamine has been recently investigated by several investigators. L-dopa enhanced bidirectional synaptic plasticity in the primary motor cortex (M1) of the human brain. Abnormally reduced plasticity was normalized by L-dopa in Parkinson's disease (PD) patients. Some clinical symptoms significantly correlated with the plasticity abnormalities. Other anti-Parkinson's disease drugs may have some influence on the cortical plasticity.We studied how anti-Parkinson's disease drugs modulate the LTP induced by quadripulse transcranial magnetic stimulation (QPS) in the human brain. L-dopa enhanced both LTP and LTD in normal volunteers. In contrast, pramipexole have no influence on either LTP or Ltd. Zonisamide (ZNS) (25ms) tended to enhance LTP in aged healthy volunteers in total. In the aged group, 10 in 24 volunteers were non-responders, defined as those whose average MEP ratio was equal or less than 1. ZNS significantly enhanced the plasticity in 10 non-responders. A single-dose of caffeine (200mg), which inhibits both adenosine A1 and A2A receptors, significantly reduced LTP in the responders (4 in 12 healthy young volunteers). A new anti-Parkinson's disease drug (Istradefylline), adenosine A2A receptor antagonist also decreased LTP.Based on our results and basic knowledge about the dopamine innervation of the primary motor cortex, we conclude that the motor cortical plasticity studied by QPS over M1 must be influenced by D1 projection from ventral tegmentum area to M1. This plasticity evaluation by QPS may reflect some symptoms in PD patients.



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T013 What do we learn from the interaction between physical activities and effects of transcranial brain stimulation?

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Publication date: March 2017
Source:Clinical Neurophysiology, Volume 128, Issue 3
Author(s): Y.- Z. Huang
Several forms of transcranial brain stimulation have been developed to produce after-effects on the cortical excitability outlasting the stimulation itself for a period of time in the conscious human's brain. Several lines of evidence suggest that transcranial brain stimulation change the excitability of the neuronal circuits through plasticity-like mechanisms.Such plasticity that is induced by transcranial brain stimulation in the motor cortex can be modulated by voluntary contraction that has no plasticity effect on its own. Not only the timing, but also the pattern of contraction is known to be crucial in determining the amount and direction of plasticity happening around the movement. Moreover, brief tonic voluntary contraction could modify plasticity induced in the motor cortex controlling the antagonist muscle, indicating not only the activity in the targeting area, but also that in a remote area connecting to this area, could modulate the effect of transcranial brain stimulation. Similar interactions have been also found in the visual cortex.The interaction between physical activities and the effects of transcranial brain stimulation may be explained by metaplasticity and reversal of plasticity, i.e. depotentiation and de-depression, and suggests that the physiological activity and synapses work synergistically in learning. The physiological activity during practice may fine tune the amount and direction of plasticity to improve learning. However, when a specific kind of plasticity is aimed to induce, the physiological activity should be well controlled to maintain a predictable result.In summary, the modulation effect of physical activities on the after-effect of transcranial brain stimulation has opened a door to further understand physiological mechanism of learning. On the other hand, by learning from such influence on the after-effect, the state of neuronal activity should be carefully controlled for a stable and predictable effect of transcranial brain stimulation.



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T015 Optimizing rTMS protocols by enhancing conductance of neural networks

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Publication date: March 2017
Source:Clinical Neurophysiology, Volume 128, Issue 3
Author(s): A. Goldental, I. Halawa, Y. Shirota, I. Kanter, W. Paulus
The recent emergence of better rTMS stimulators allows the generation of various pulse sequences and patterns and the following question arise - how to optimize the efficiency of rTMS scheduling in clinical trials? While the existing literature reports seemingly contradicting results, the phase-space for such an exhaustive optimization search is large and includes many dimensions such as repetition frequency, pulse intensity, pulse duration, number of pulses, pulse shape and intervals between repeated treatments. We try to identify the relevant guidelines and trends to optimize the efficiency of rTMS scheduling. The underlying physical mechanism is the network conductance which is significantly affected by neuronal plasticity in the form of neuronal response failures (NRFs).



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T017 Hebbian plasticity in the parieto-frontal network

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Publication date: March 2017
Source:Clinical Neurophysiology, Volume 128, Issue 3
Author(s): G. Koch
Transcranial magnetic stimulation (TMS) provides a unique opportunity to test the causal neurophysiological interactions between interconnnected brain areas. This can be done by applying two coils over two different brain areas and deliver subsequent TMS pulses with a certain time interval in the range of few milliseconds (dual-site TMS). In these paradigms, a conditioning stimulus (CS) is first used to activate putative pathways to the motor cortex (M1) from the site of stimulation, while a second, test stimulus (TS), delivered a few ms later probes any changes in excitability that are produced by the input. Dual-site TMS can be used to investigate mechanisms of spike timing dependent plasticity within a certain network. LTP- and LTD-like effects can be induced in M1 following the repeated application of paired pulses over interconnected areas such as contralateral M1, ventral premotor cortex, supplementary motor area or the posterior parietal cortex (PPC). A crucial question is whether dual site TMS effects are limited to M1 or can be used to measure the activity of the other targeted non motor areas. The combination of dual site TMS with electroencephalography (EEG) is a promosing way to overcome these issues (Veniero et al., 2013; Picazio et al., 2014). TMS/EEG allows to measure physiological signals generated at the cortical level by TMS, including those generated in the so-called silent-areas such as PPC and to assess modifications of cortical connectivity.



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DNA-wrapped multi-walled carbon nanotube modified electrochemical biosensor for the detection of Escherichia coli from real samples

Publication date: 1 May 2017
Source:Talanta, Volume 166
Author(s): Dilsat Ozkan-Ariksoysal, Yasin Ugur Kayran, Fethiye Ferda Yilmaz, Anton Alexandru Ciucu, Iulia Gabriela David, Vasile David, Mine Hosgor-Limoncu, Mehmet Ozsoz
This paper introduces DNA-wrapped multi-walled carbon nanotube (MWCNT)-modified genosensor for the detection of Escherichia coli (E. coli) from polymerase chain reaction (PCR)-amplified real samples while Staphylococcus aureus (S. aureus) was used to investigate the selectivity of the biosensor. The capture probe specifically recognizing E. coli DNA and it was firstly interacted with MWCNTs for wrapping of single-stranded DNA (ssDNA) onto the nanomaterial. DNA-wrapped MWCNTs were then immobilised on the surface of disposable pencil graphite electrode (PGE) for the detection of DNA hybridization. Electrochemical behaviors of the modified PGEs were investigated using Raman spectroscopy and differential pulse voltammetry (DPV). The sequence selective DNA hybridization was determined and evaluated by changes in the intrinsic guanine oxidation signal at about 1.0V by DPV. Numerous factors affecting the hybridization were optimized such as target concentration, hybridization time, etc. The designed DNA sensor can well detect E. coli DNA in 20min detection time with 0.5pmole of detection limit in 30µL of sample volume.

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Editorial Board

Publication date: 1 May 2017
Source:Talanta, Volume 166





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Amperometric biosensors based on carboxylated multiwalled carbon nanotubes-metal oxide nanoparticles-7,7,8,8-tetracyanoquinodimethane composite for the determination of xanthine

Publication date: 15 May 2017
Source:Talanta, Volume 167
Author(s): Berna Dalkıran, Pınar Esra Erden, Esma Kılıç
A comparison of the analytical performances of two xanthine biosensors, based on the use of different metal oxide nanoparticles (MONPs: Co3O4 or Fe3O4)-modified carboxylated multiwalled carbon nanotubes (c-MWCNTs)-7,7′,8,8′-tetracyanoquinodimethane (TCNQ)-chitosan (CHIT) composite, is discussed. Xanthine oxidase (XOD) enzyme was covalently attached to c-MWCNTs/MONPs/TCNQ/CHIT/GCE via N-ethyl-N′-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxy succinimide (NHS) chemistry and the electrode surface was further modified with Nafion in order to minimize the effect of possible interfering substances. The results showed that analytical performance of the Fe3O4 based biosensor was better than the Co3O4 based biosensor. The linear working range, limit of detection and sensitivity were found to be 1.9×10−6–2.3×10−4M, 0.20μM (S/N=3), 25.07μAmM−1cm−2 for the Fe3O4 based biosensor and 1.9×10−6–1.2×10−4M, 0.36μM (S/N=3), 13.24μAmM−1cm−2 for the Co3O4 based biosensor, respectively. The purposed biosensors were applied in the determination of xanthine in coffee samples, and satisfactory results were obtained.

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Sensitive determination of Hg together with Mn, Fe, Cu by combined photochemical vapor generation and pneumatic nebulization in the programmable temperature spray chamber and inductively coupled plasma optical emission spectrometry

Publication date: 15 May 2017
Source:Talanta, Volume 167
Author(s): Jacek Giersz, Magdalena Bartosiak, Krzysztof Jankowski
Continuous photo-induced generation of mercury cold vapor has been successfully coupled with conventional pneumatic nebulization in programmable temperature spray chamber (PCVG–PN–PTSC) allowing fast, sensitive and easy multi-element analysis. The applied technique enabled simultaneous determination of non-volatile forming elements (Fe, Cu, Mn) and volatile Hg, while 15%v/v formic acid is present in the sample. PTSC elevated temperature (40°C) causes partial conversion of sample matrix into vapor form, thus improving plasma robustness. The efficiency of Hg vapor generation and its transport to the plasma is close to 100%. Moreover, spray chamber temperature stabilization improved the precision of the measurements (Hg signal RSD below 0.5%). The achieved limit of detection for Hg (90pgmL−1) at 194.23nm with no monochromator purge is better by almost two orders of magnitude than that obtained by conventional PN-ICP-OES. On the other hand, LODs for non-vapor forming elements are comparable to those obtained with pneumatic nebulization. The linear dynamic ranges for all examined elements are at least three orders of magnitude up to 1000ngmL−1. None mutual interference between examined analytes (Hg, Fe, Cu, Mn) has been observed. The method was validated by the analysis of two CRM materials of different matrix composition (waste water ERM CA713 and estuarine sediment ERM CC580) giving satisfactory results. As low as 2 ppb of Hg can he directly determined in waste water. The proposed procedure uses mild reagents and allows for fast multi-element analysis, and matches green chemistry requirements.

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Inside front cover

Publication date: 1 May 2017
Source:Talanta, Volume 166





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Graphene quantum dots decorated with maleimide and zinc tetramaleimido-phthalocyanine: Application in the design of “OFF-ON” fluorescence sensors for biothiols

Publication date: 1 May 2017
Source:Talanta, Volume 166
Author(s): Ojodomo J. Achadu, Tebello Nyokong
The fabrication of maleimide-derivatized graphene quantum dots (M-GQDs) and zinc phthalocyanine (2) as novel sensor probes for the selective detection of biothiols (cysteine, homocysteine or glutathione) through the rapid and specific Michael addition reaction between biothiols and the maleimide-derivatized probes is presented in this study. GQDs directly functionalized with maleimide units (M-GQDs) were synthesized and deployed for biothiols recognition following the principle of Michael addition. M-GQDs probe was found to be highly sensitive and selective towards biothiols detection in the nanomolar range in aqueous solution and at physiological pH (7.0). On the other hand, non-covalent interaction between pristine GQDs and novel zinc tetramaleimido-derivatized phthalocyanine resulted in the quenching of the pristine GQDs fluorescence emission which was switched back to the "ON" mode by Michael addition mechanism in the presence of biothiols. Tested relevant biomolecules did not interfere in the quantitative recognition of the biothiols. The probes showed to be highly sensitive, specific and selective for biothiols sensing in simulated real samples.

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Low-serum culture with novel medium promotes maxillary/mandibular bone marrow stromal cell proliferation and osteogenic differentiation ability

Abstract

Objectives

The purpose of this study was to evaluate the effect of low-serum STK2 medium on the isolation and osteogenic differentiation of human maxillary/mandibular bone marrow stromal cells (MBMSCs).

Materials and methods

Human MBMSCs were obtained from patients undergoing dental implant treatment. These cells were cultured in serum-free medium or STK2 medium containing 1  % fetal bovine serum (low-serum) or α-MEM containing 10  % fetal bovine serum (control). Proliferation on the culture surface, cell surface antigen expression, and mRNA levels of neural crest and osteogenic markers were examined. Alkaline phosphatase assay and Alizarin red staining were used to assess osteogenic differentiation potential. Immunoblotting analysis was performed to detect ERK phosphorylation.

Results

Low-serum and control MBMSCs were positive for CD73, CD90, and CD105 and negative for CD14, CD34, CD45, CD271, and HLA-DR. CD140a was absent in low-serum cells but present in control cells. Low-serum MBMSCs proliferated more than control MBMSCs. After induction of osteogenic differentiation, alkaline phosphatase activity and osteocalcin mRNA levels were higher in low-serum MBMSCs than in control cells, and Alizarin red staining was stronger in low-serum MBMSCs than in control cells. Low-serum culture promoted ERK phosphorylation.

Conclusions

MBMSCs precultured in low-serum medium exhibited a greater cumulative cell number and a higher osteogenic differentiation capacity than those cultured in control medium.

Clinical relevance

These findings indicate that low-serum STK2 culture might be useful to promote MBMSC proliferation and osteogenic differentiation. This method requires less autologous blood collection for cell expansion than conventional methods, thus reducing the burden on patients.



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Archaeometallurgy in the Paraná Delta (Argentina): Composition, manufacture, and indigenous routes

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Publication date: September 2017
Source:Journal of Anthropological Archaeology, Volume 47
Author(s): Mariano Bonomo, Edgardo D. Cabanillas, Ricardo Montero
The results of macroscopic, microscopic, and metallographic studies of archaeological metal objects from the Delta of the Paraná River (Argentina, South America) are presented. The aim of these studies was to determine the chemical composition and the manufacturing techniques of these allochthonous objects frequently placed in human burials. The results were discussed taking into account archaeological and ethnohistorical information in order to understand the significance of metals and the indigenous routes to the Paraná River. We concluded that the metal pendants and beads recovered in the Paraná Delta were manufactured from copper by casting in open moulds and hammering. Finished metal objects reached the Paraná River as a result of exchange circuits involving transport across pre-Hispanic routes from the production centres in the Andes. Metal objects from distant geographical areas were used to mark social ranks within the groups and were symbols of prestige displayed by local leaders.



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Qing-Hua Granule induces GLP-1 secretion via bitter taste receptor in db/db mice

Publication date: May 2017
Source:Biomedicine & Pharmacotherapy, Volume 89
Author(s): Junyan Li, Jie Xu, Ruifang Hou, Xin Jin, Jingyi Wang, Na Yang, Li Yang, Li Liu, Feng Tao, Hao Lu
Qing-Hua Granule (QHG), the modified formulation of a classical Chinese prescription named Gegen Qinlian Decoction, was clinically employed to treat type 2 diabetes mellitus (T2DM) through regulation of glucagon-like peptide-1 (GLP-1). However, the potential mechanism is unknown. We investigate whether QHG induces GLP-1 secretion via activation of bitter taste receptor (TAS2R) pathway in the gastrointestinal tract of db/db mice. The db/db mice were intragastrically (i.g.) administered QHG (low/medium/high dose) once daily for 8 weeks. GLP-1 secretion was evaluated. The bitter receptor signaling pathway, which regulates GLP-1 secretion, including TAS2R5 (a subtype of TAS2R), α-gustducin (Gαgust), 1-phosphatidylinositol-4, 5-bisphosphate phosphodiesterase beta-2 (PLCβ2), transient receptor potential cation channel subfamily M member 5 (TRPM5), was assessed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot and immunohistochemistry (IHC). The biochemical observations of ileum and pancreas tissue were detected histopathologically. Acquity Ultra Performance LCTM − Micromass ZQ 2000 (UPLC–MS) was used for the phytochemical analysis. QHG exhibited significant and dose-dependent effect on GLP-1 secretion in db/db mice, along with significant up-regulation of TAS2R5 mRNA level and activation of TAS2R pathway (p<0.05). In addition, QHG improved the histopathological structure of ileum and pancreatic tissue. Seventeen compounds were identified in QHG. In conclusion, QHG induces GLP-1 secretion in db/db mice, most likely through the bitter taste receptor pathway.



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Child t-shirt size data set from 3D body scanner anthropometric measurements and a questionnaire

Publication date: Available online 16 February 2017
Source:Data in Brief
Author(s): A. Pierola, I. Epifanio, S. Alemany
A dataset of a fit assessment study in children is presented. Anthropometric measurements of 113 children were obtained using a 3D body scanner. Children tested a t-shirt of different sizes and a different model for boys and girls, and their fit was assessed by an expert. This expert labeled the fit as 0 (correct), −1 (if the garment was small for that child), or 1 (if the garment was large for that child) in an ordered factor called Size-fit. Moreover, the fit was numerically assessed from 1 (very poor fit) to 10 (perfect fit) in a variable called Expert evaluation. This data set contains the differences between the reference mannequin of the evaluated size and the child's anthropometric measurements for 27 variables. Besides these variables, in the data set, we can also find the gender, the size evaluated, and the size recommended by the expert, including if an intermediate, but nonexistentsize between two consecutive sizes would have been the right size. In total, there are 232 observations. The analysis of these data can be found in [2].



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Data on the effect of hypomyelinating leukodystrophy 6 (HLD6)-associated mutations on the TUBB4A properties

Publication date: Available online 16 February 2017
Source:Data in Brief
Author(s): Yuki Miyamoto, Tomohiro Torii, Kazuko Kawahara, Nanami Hasegawa, Akito Tanoue, Yoichi Seki, Takako Morimoto, Megumi Funakoshi-Tago, Hiroomi Tamura, Keiichi Homma, Masahiro Yamamoto, Junji Yamauchi
Hypomyelinating leukodystrophy (HLD) is genetic demyelinating or dismyelinating disease and is associated with at least 13 responsible genes. The mutations seem likely cause the functional deficiency of their gene products. HLD4- and HLD5-associated HSPD1 and FAM126A mutations affect biochemical properties of the gene products [1, 2]. Herein we provide the data regarding the effects of HLD6-associated tubulin beta 4A (TUBB4A) mutations on the properties.



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BET, Thermal Degradation, and FTIR Spectras of Triazine Polyamine Polymers

Publication date: Available online 16 February 2017
Source:Data in Brief
Author(s): Mustafa Can
Here we show effect of the polyamine polymer chain length to BET isotherms. According to IUPAC classification [1], all three polymers are fitting type 1 physical adsorption isotherm with H3 hysteresis (except for EDA having H2 hysteresis). Moreover, TG and TGA analysis of polymers triazine-ethylenediamine (EDA) and triazine-triethylenetetramine (TETA) are provided. Due to the similarities of the structure, main decomposition temperatures are close to each other (between 593K and 873K). In order to understand change of FTIR spectra with adsorption and stripping Au(III), fresh, Au(III) adsorbed and recycled spectras of polymers measured. For further discussions about the effect of chain length to adsorption of Au(III) onto triazine polyamine polymer particles "Au (III) Uptake by Triazine Polyamine Polymers: Mechanism, Kinetic and Equilibrium Studies" Can et al. [2] article(in press).



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Nutrient and antinutrient composition of yellow yam (Dioscorea cayenensis) products

Publication date: Available online 16 February 2017
Source:Data in Brief
Author(s): Adepoju, Oladejo Thomas, Boyejo, Oluwatosin, Adeniji, Paulina Olufunke
The data presented in this article are related to research article titled "Effects of processing methods on nutrient and antinutrient composition of yellow yam (Dioscorea cayenensis) products" (O. T. Adepoju, O. Boyejo, P. O. Adeniji 2016) [1]. This article documented information on nutrient and antinutrient composition as well as nutrient retention of Dioscorea cayenensis products. Fresh Dioscorea cayenensis tubers obtained from Bodija market were prepared into raw sample and local delicacies and analysed for proximate, mineral, vitamin and antinutrient composition using AOAC methods [2]. Data obtained were analysed using ANOVA, and level of significance set at p<0.05. Processing significantly improved macronutrients and energy content of yam products, and led to significant reduction in values of all antinutrient content of the products (p<0.05).



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The role of nurse functional types in seedling recruitment dynamics of alternative states in rangelands

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Publication date: February 2017
Source:Acta Oecologica, Volume 79
Author(s): Dardo R. López, Laura Cavallero
In arid ecosystems, recruitment dynamics are limited by harsh environmental conditions and greatly depend on the net outcome of the balance between facilitation and competition. This outcome can change as a consequence of degradation caused by livestock overgrazing. Also, distinct plant species may show a differential response to a common neighbour under the same environmental conditions. Therefore, ecosystem degradation could affect the net balance of plant-plant interactions, which can also depend on the functional traits of potential nurse species. The aim of this study is to assess the influence of alternative degradation states on (i) the density of seedlings of perennial species emerging in four microsite types, and on (ii) the relative interaction intensity (RII) between seedlings and potential nurses belonging to three functional types (deep- and shallow-rooted shrubs, and tussock grasses). During three years, we recorded seedling density of perennial species in four alternative degradation states in grass-shrubby steppes from northwestern Patagonia. The density of emerged seedlings of perennial species decreased sharply as degradation increased, showing non-linear responses in most microsites. Seedling density underneath deep-rooted shrubs was higher than underneath shallow-rooted shrubs and tussock grasses. Also, deep-rooted shrubs were the only functional type that recorded seedling emergence in highly degraded states. Deep-rooted shrubs had facilitative effects on the seedlings emerging and surviving underneath them, independently of ecosystem degradation. In contrast, RII between shallow-rooted shrubs and recently emerged seedlings, switched from positive effects in the less degraded states, to negative effects in the most degraded state. Tussock grasses recorded the weakest intensity of facilitative interactions with recently emerged seedlings, switching to competitive interactions as degradation increased. Our results suggest that species with key functional traits should be considered in management and restoration plans for rangelands with different degradation levels, since they have a strong influence in the net outcome of plant-plant interactions and in the recruitment dynamics of arid ecosystems.



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Scavenging efficiency and red fox abundance in Mediterranean mountains with and without vultures

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Publication date: February 2017
Source:Acta Oecologica, Volume 79
Author(s): Zebensui Morales-Reyes, José A. Sánchez-Zapata, Esther Sebastián-González, Francisco Botella, Martina Carrete, Marcos Moleón
Vertebrate scavenging assemblages include two major functional groups: obligate scavengers (i.e., vultures), which depend totally on carrion and are undergoing severe declines around the globe, and facultative scavengers, which exploit carrion opportunistically and are generally ubiquitous. Our goal was to investigate the hypothesis that vultures can indirectly regulate the abundance of mesopredators (i.e., facultative scavengers) through modulating their access to carrion resources. We studied scavenging efficiency and red fox (Vulpes vulpes) abundance in two neighbouring areas of South-eastern Spain where vultures (mainly griffon vultures Gyps fulvus) are present (Cazorla) and absent (Espuña). To do so, we monitored ungulate carcasses consumption during winter and summer, and counted red fox scats along walking transects as a proxy of fox density. Our results confirmed that scavenging efficiency was higher in Cazorla and in carcasses visited by vultures. This resulted in increasing scavenging opportunities for facultative scavengers where vultures were absent. Accordingly, mean red fox abundance was higher in Espuña. These results suggest the existence of a vulture-mediated mesopredator release (i.e., an increase of mesopredator numbers following vulture loss), which could trigger important indirect ecological effects. Also, our study demonstrates that facultative scavengers are hardly able to functionally replace vultures, mainly because the former exploit carrion on a slower time scale.



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Correlation between facial nerve axonal load and age and its relevance to facial reanimation.

Purpose: Two-stage facial reanimation procedures with a cross-facial nerve graft often have unsatisfactory results in the older patient. Although the cause of result variability is likely multifactorial, some studies suggest that increased donor nerve axonal load improves function of a free muscle transfer after a cross-facial nerve graft. This study attempts to characterize the relationship between age and facial nerve axonal load. Methods: 63 fresh, cadaveric heads were dissected to expose the facial nerve. For each hemi-face, two facial nerve samples were taken: one proximal as the nerve exits the stylomastoid foramen, and one distal at the buccal branch (at a point 1cm proximal to the anterior parotid border). Nerve samples were stained and quantified. Correlation analysis was completed using a Pearson's correlation coefficient. Results: 36 females and 27 males were dissected with an average age of 71 (age range 22-97). At the proximal (r = -.26; p

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Micro Free Orbital Fat Grafts to the Tear Trough Deformity during Lower Blepharoplasty.

Background: The tear trough deformity is challenging in lower eyelid rejuvenation. Surgical treatment has evolved with more modern techniques preserving orbital fat and using autologous fat transposition. The author reviewed his own experience in targeting the tear trough in lower lid blepharoplasty and presented a new technique that incorporates the addition of micro free fat grafts which adds direct volume to the underlying anatomical depression using a transcutaneous skin-muscle approach. Methods: Medical records of lower lid blepharoplasty patients performed from February of 2011 and February of 2016 were reviewed. Patients who had tear trough deformities with the addition of micro free fat grafts were included. Standard patient characteristics were collected, complications identified, and assessment of postoperative results were performed. Results: There were 32 patients included in the study with a median follow-up of 392 days (range 45 to 1709 days). Scleral show requiring operative correction occurred in one patient (3 percent). Additional complications included chemosis in 4 patients (13 percent) which resolved in all patients. No patients had infections, ectropion, lid retraction, palpable or visible grafts. Conclusions: The use of micro free orbital fat grafts is an effective and safe technique to treat the tear trough deformity without increased complication rates and good patient and surgeon satisfaction and should be considered a surgical adjunct during an open blepharoplasty technique. (C)2017American Society of Plastic Surgeons

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Early post-operative results of percutaneous needle fasciotomy in 451 patients with Dupuytren disease.

Background: Percutaneous needle fasciotomy (PNF) is a minimally invasive treatment modality for Dupuytren disease (DD). In this study we analyzed the efficacy and complication-rate of PNF using a statistical method that takes the multi-level structure of data, regarding multiple measurements from the same patients, into account. Methods: The data of 470 treated rays from 451 patients with Dupuytren disease that underwent percutaneous needle fasciotomy (PNF) were analyzed retrospectively. We described the early postoperative results of PNF and we applied linear mixed models to compare mean correction of PED between joints and efficacy of primary versus secondary PNF. Results: Mean preoperative PED's at the metacarpophalangeal (MCP), proximal interphalangeal (PIP) and distal interphalangeal (DIP) joints were 37[spacing ring above], 40[spacing ring above] and 31[spacing ring above] respectively. Mean preoperative TPED was 54[spacing ring above]. Results were excellent, with a mean TPED correction of 85%. PNF was most effective for MCP-joints and less effective for PIP and DIP-joints. Secondary PNF was as effective as primary PNF. Complications were rare and mostly minor. Conclusions: The results of this study confirm that PNF is an effective and safe treatment modality for patients with mild to moderate disease who prefer a minimally invasive procedure. (C)2017American Society of Plastic Surgeons

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A New Classification of Helix Fabrication Methods with Autogenous Costal Cartilage in Microtia Reconstruction.

Background: The complex architecture of the auricle poses one of the most demanding challenges for the plastic surgeon to recreate. The fabrication of the prominent helix is crucial to the final contour of the constructed ear. The success of helix carving depends greatly on the complicated characteristics of the cartilage used, which is commonly the eighth costal cartilage. The authors elaborate on the relevant details for helix sculpting based on different qualities of cartilage. Methods: A series of 415 microtia patients underwent autogenous costal cartilage auricular reconstruction between 2012 and 2015. Because the cartilage used for helix reconstruction is always imperfect or insufficient for the fabrication of anatomical structures, we have devised perfect helix duplication by using individualized eighth rib cartilage with different cartilage lengths, widths and flexibilities. Four possible scenarios in helix fabrication have been elaborated, and the corresponding methods were introduced. Results: Selective methods for different scenarios in helix fabrication have been shown to produce favorable results. The results reveal that a harmonious helix was achieved and provide a cohesive framework for the integrity of a reconstructed ear. Conclusions: A new classification of helix fabrication methods with autogenous costal cartilage is elaborated, and a favorable framework with harmonious proportions is achieved by precise carving using corresponding measures for different cartilage characteristics. This approach enhances helix aesthetics and helps attain a satisfactory contour of the auricle. (C)2017American Society of Plastic Surgeons

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Combining Smoothened Agonist (SAG) and NEL-like protein-1 (NELL-1) Enhances Bone Healing.

Background: Non-healing bone defects represent an immense biomedical burden. Despite recent advances in protein based bone regeneration, safety concerns over bone morphogenetic protein-2 have prompted the search for alternative factors. Previously, we examined the additive / synergistic effects of Hedgehog (Hh) and Nel-like protein-1 (NELL-1) on the osteogenic differentiation of mesenchymal stem cells in vitro. Here, we sought to leverage our previous findings by applying the combination of Smoothened agonist (SAG), Hh signal activator, and NELL-1 to an in vivo critical size bone defect model. Methods: A 4 mm parietal bone defect was created in mixed gender CD-1 mice. Treatment groups included control (n = 6), SAG (n = 7), NELL-1 (n = 7) or SAG + NELL-1 (n = 7). A custom fabricated poly(lactic-co-glycolic acid) disc with hydroxyapatite coating was used as an osteoinductive scaffold. Results: Results at 4 and 8 weeks showed increased bone formation by micro-computed tomography analyses with either stimulus alone (SAG or NELL-1), but significantly greater bone formation with both components combined (SAG + NELL-1). This included greater bone healing scores, increased bone volume and bone thickness. Histologic analyses confirmed a significant increase in new bone formation with the combination therapy SAG + NELL-1, accompanied by increased defect vascularization. Conclusions: In summary, our results suggest that combining the Hh signaling agonist SAG and NELL-1 has potential as a novel therapeutic strategy for the healing of critical-sized bone defects. Future directions will include optimization of dosage and delivery strategy for a SAG + NELL-1 combination product. (C)2017American Society of Plastic Surgeons

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Should Immediate Autologous Breast Reconstruction be considered in Women who require Post-Mastectomy Radiation Therapy? A Prospective Analysis of Outcomes.

Background: In women who require post-mastectomy radiation therapy, immediate autologous breast reconstruction is often discouraged. We aim to prospectively evaluate postoperative morbidity and satisfaction reported by women undergoing delayed or immediate autologous breast reconstruction in the setting of post-mastectomy radiation therapy. Methods: Patients enrolled in the Mastectomy Reconstruction Outcomes Consortium Study, who received post-mastectomy radiotherapy and had immediate or delayed free abdominal-based autologous breast reconstruction were identified. Postoperative complications at one and two years after reconstruction were assessed. Patient reported outcomes were evaluated using the BREAST-Q questionnaire preoperatively, at one and two-years postoperatively. Bivariate analyses and mixed-effects regression models were used to compare outcomes. Results: A total of 175 patients met our inclusion criteria. Immediate reconstructions were performed in 108 patients and delayed reconstructions in 67 patients. 93.5% of the immediate reconstructions were performed at a single center. Overall complication rates were similar based on reconstructive timing (25.9% immediate and 26.9% delayed at one year; p=0.54). Patients with delayed reconstruction reported significantly lower pre-reconstruction scores (p

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Memory and Hashimoto’s thyroiditis under levothyroxine treatment: is there a placebo or nocebo effect?



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A Retrospective Look at Integrating a Novel Regenerative Medicine Approach in Plastic Limb Reconstruction

imageFull-thickness wounds that have rendered patients candidates for amputation may require techniques that may include a combinatorial approach above traditional standard of care. The purpose of this retrospective study was to evaluate the effectiveness of an innovative approach whereby several therapies were combined to avoid amputation. Patients with full-thickness wounds who were previously recommended for amputation and were treated with the combinatorial approach of muscle flap reconstruction and concentrated bone marrow aspirate, platelet-rich plasma, INTEGRA Wound matrix, vacuum-assisted closure, and split-thickness skin grafts were assessed retrospectively. The mean age of the patients identified was 48 years (range, 34–66 years). The average size of the defects was 19.6 cm2. All defects were successfully covered with medial hemisoleus, lateral hemisoleus, or peroneus brevis muscle flaps combined with split-thickness skin grafts, concentrated bone marrow aspirate, and platelet-rich plasma. All flaps healed with an average time to fixator removal of 8.3 weeks; there was 1 above-knee amputation that occurred approximately after successful wound closing and fixator removal. The combinatorial approach described here including several regenerative medicine tools is an effective means of lower limb reconstruction to avoid amputation.

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Stabilized uniform deformation in a high-strength ferrite-cementite steel with multiscale lamellar structure

Publication date: 15 April 2017
Source:Materials & Design, Volume 120
Author(s): Jiang-li Ning, Ya-tong Zhang, Lu Huang, Yun-li Feng
In order to ameliorate the ductility and stabilize the uniform deformation of ultrafine-grained (UFG) ferrite-cementite steel while retaining its high strength, a multiscale lamellar structure was developed and compared with the UFG structure. Microstructures were characterized and tensile behaviors were analyzed in the samples with multiscale lamellar and UFG structures; the mechanisms underlying the different strain-hardening capabilities were studied. Plastic instability dominated during the tensile deformation of spheroidized UFG carbon steel, because of its low strain-hardening owing to the uniform UFG structure with high dislocation density. However, the steel with multiscale lamellar structure exhibited a marked improvement in the balance between strength and uniform deformation, ascribing to the enhanced strain-hardening capability. This result was primarily attributed to the extra strain-hardening generated by the strain gradient and stress state change caused by the multiscale lamellar structure.

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Wafer-scale fabrication of conformal atomic-layered TiO2 by atomic layer deposition using tetrakis (dimethylamino) titanium and H2O precursors

Publication date: 15 April 2017
Source:Materials & Design, Volume 120
Author(s): Serge Zhuiykov, Mohammad Karbalaei Akbari, Zhenyin Hai, Chenyang Xue, Hongyan Xu, Lachlan Hyde
The synthesis of ultra-thin atomic-layered oxides with precise thickness controllability and excellent uniformity remains a significant challenge in the fields of photovoltaics and opto-electronics. The wafer–scale synthesis and conformal growth of atomic-layered TiO2 film on Si/SiO2 substrate achieved by the atomic layer deposition (ALD) using tetrakis (dimethylamino) titanium (TDMAT) precursor and H2O as an oxidation agent. Spectroscopic ellipsometry and atomic force microscopy (AFM) studies confirmed the conformal growth of TiO2 layer with the average thickness of ~0.37±0.04nm over 4-inch Si/SiO2 wafer. Atomic-layered TiO2 films were obtained by the careful selection of the deposition temperature and the number of precursor's cycles, which were summarized into developed recipe. Fourier transform infrared (FTIR) spectroscopy revealed the vibration mode of Ti-O-Ti and Ti-O-Si on the deposited film confirming the development of structural bonding between ALD-developed TiO2 layer and Si/SiO2 substrate. In-situ X-ray diffraction (XRD) measurement showed the crystalline structure of developed film. It was confirmed that postdeposition annealing of TiO2 films improved their electrical conductivity. In particular, the atomic-layered TiO2 films annealed at 150°C demonstrated that their bandgap has been widen to 3.37eV compare to the previously reported values for bulk rutile (3.03eV) and anatase (3.20eV).

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Effect of a hyper deformation drawing process on mechanical behaviour of thin wires of Ti-26Nb (at.%) alloys

Publication date: 15 April 2017
Source:Materials & Design, Volume 120
Author(s): Xavier Gabrion, Sébastien Thibaud, Yudong Zang, Pierre Charbonnier, Pascal Laheurte, Yves Gaillard
This paper investigates the mechanical properties of hyper deformed wires of Ti-26at.%Nb (Ti-26Nb) alloy that can be equally expressed as Ti-40.5wt.%Nb. These wires obtained by hot drawing process have a diameter of 85μm and 285μm, respectively. The effect of a short heat treatment at 748K for 600s was also investigated. The influence of the heat treatment and the diameter of the wires evaluated by mechanical tests, such as nano indentation, quasi-static tensile, and fatigue tests, and microstructure investigations. The quasi-static tensile tests show that the mechanical properties, like elasticity modulus and ultimate tensile strength, are improved with the decrease of the diameter. An increase of 55% and 26% in strength is obtained for the non-treated state and the heat treated state, respectively. The improvements in the mechanical properties for the 285μm diameter wire are due to the refinement of grains to submicron scale between 100 and 200nm. The short heat treatment induces an increase of the Young's modulus and a decrease of the ultimate tensile strength by the emergence of a dual phase (α and β) microstructure. For fatigue tests, the increase of frequency from 4Hz to 30Hz leads to an increase of 45% of the fatigue life time.

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Thin-walled high temperature alloy structures fabricated from additively manufactured polymer templates

Publication date: 15 April 2017
Source:Materials & Design, Volume 120
Author(s): John H. Martin, David S. Ashby, Tobias A. Schaedler
Additive manufacturing is enabling a paradigm shift in design and production, but conventional techniques reach their limits when metallic structures require walls with <0.5mm thickness. Here we introduce an approach for indirect additive manufacturing of thin-walled alloy structures. First a polymer template is additively manufactured, then metal layers are deposited by electroplating, physical or chemical vapor deposition. After removal of the polymer, the metal layers can be interdiffused to form an alloy via homogenization heat treatments. Three different alloys designed for three elevated temperature regimes are demonstrated: Monel alloys based on Ni-Cu-Al-Ti, nickel superalloys based on Ni-Cr-Al and refractory rhenium alloys based on Re-Co. A process was developed to co-deposit rhenium and cobalt via aqueous electroplating, resulting in an alloy with a melting point of 2000°C and a Vickers hardness of 480±50HV0.2 after homogenization. Two applications of interest for the aerospace industry were chosen to demonstrate the technology. High temperature truss core sandwich structures and rocket engine thruster demos where fabricated.

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Deformation and plastic coordination in WC-Co composite — Molecular dynamics simulation of nanoindentation

Publication date: 15 April 2017
Source:Materials & Design, Volume 120
Author(s): Qing Feng, Xiaoyan Song, Hongxian Xie, Haibin Wang, Xuemei Liu, Fuxing Yin
The deformation characteristics and plasticity mechanisms of the WC-Co composite were demonstrated by the molecular dynamics simulations on the atomic scale. It was found that the nucleation, expansion and interaction of dislocations are distinctly dependent on the orientation where the load is applied. At the same indentation depth, the dislocation density in WC is lower by an order of magnitude than in Co. When the indentation is applied on the WC basal plane, the dislocations form firstly on the pyramidal planes and are inclined to slip on the prismatic planes. At the incoherent WC/Co interface in the WC-Co composite, the distortion occurs with loading. In contrast, at the semi-coherent WC/Co interface containing dislocation network, the stress concentration is coordinated, and the nucleation of dislocations in Co is triggered. This is favorable to enhance the resistance against intergranular fracture of the WC-Co composite.

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Micro-patterning by thermoplastic forming of Ni-free Ti-based bulk metallic glasses

Publication date: 15 April 2017
Source:Materials & Design, Volume 120
Author(s): Supriya Bera, Baran Sarac, Sascha Balakin, Parthiban Ramasamy, Mihai Stoica, Mariana Calin, Jürgen Eckert
The development of bulk metallic glasses for biomedical applications has become the focus of intense research interest. In this work, we report on the unique thermoplastic behavior of two Ni-free Ti-based bulk metallic glasses by utilizing the dramatic softening of the amorphous structure in the super cooled liquid region. Ti40Zr10Cu34Pd14Ga2 and Ti40Zr10Cu34Pd14Sn2 bulk glassy alloys were produced by copper mold casting. Ga and Sn micro-alloying (2at%) improve the glass-forming ability and mechanical properties of Ti40Zr10Cu36Pd14 alloy effectively. The cast rods were thermo-mechanically characterized to determine the most suitable processing temperature and time, and the load that has to be applied for thermoplastic net-shaping of the BMGs into anisotropically etched cavities of silicon chips. Periodic features with high surface smoothness and uniform height (24μm high circular bumps with sub-μm roughness) were created on the surface of the BMGs. The surface patterning with controllable roughness of Ti-based BMGs can be useful in biomedical studies by mediating material - cell interactions.

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A new biodegradable composite with open cell by combining modified starch and plant fibers

Publication date: 15 April 2017
Source:Materials & Design, Volume 120
Author(s): Chuan-wei Zhang, Fang-yi Li, Jian-feng Li, Li-ming Wang, Qi Xie, Jie Xu, Shuai Chen
Biodegradable composites with open cell structure were prepared through thermo-cavity foam molding using plant fibers and modified starch as main raw materials, and other additives as active agents. Oxidized starch (OS), thermoplastic starch (TPS), and thermoplastic oxidized starch (TPOS) were utilized to increase compatibility between starch and plant fibers and to improve mechanical properties of composites. Prepared composites were evaluated using tensile, compressive, and static compression tests. Results showed that TPOS improved the tensile strength by 69% in comparison with native starch (NS)-based composites. Considerable improvement was not observed in tensile strengths of OS-based and TPS-based composites. Following crystalline, hydrogen bond, and micro-structure of modified starch were researched to gain comprehensive view on mechanism of mechanical property changes in composites with NS, OS, TPS and TPOS. Fourier transform infrared analysis showed that new hydrogen bonds were formed between the plasticizer, oxidizer, and starch. X-ray diffraction analysis indicated that the crystallization was eliminated in TPOS. Restraining of starch re-crystallization was recognized as cause of changes in mechanical properties of composites. Scanning electron microscopy images showed that TPOS bonded tightly with plant fibers forming uniform open cell structure in the biodegradable composites.

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Nanostructured silicon/silicide/carbon composite anodes with controllable voids for Li-ion batteries

Publication date: 15 April 2017
Source:Materials & Design, Volume 120
Author(s): Inyeong Kang, Juyoung Jang, Moon-Soo Kim, Jin-Woo Park, Jae-Hun Kim, Young Whan Cho
Three-dimensional (3D) carbon-network-supported Si/silicide nanocomposite anodes with controllable voids are prepared using ferrosilicon, NaCl, and polyfurfuryl alcohol (PFA) resin as the starting materials. Analysis of the microstructures and the phase compositions confirms the complete removal of NaCl and the consequent formation of voids supported by a glassy carbon network, residing in between the nanostructured Si/silicide composite particles. Coin-half cell tests demonstrate the significantly improved cycling performance of the Si/silicide/carbon nanocomposites compared with that of the alloy powder without controllable voids. The electrode prepared from the coated alloy with voids maintains approximately 66% of its initial capacity after 100cycles and its Coulombic efficiency rapidly increases to 99% after several cycles.

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The role of strain glass state in the shape memory alloy Ni50+xTi50−x: Insight from an atomistic study

Publication date: 15 April 2017
Source:Materials & Design, Volume 120
Author(s): Sheng-Jian Qin, Jia-Xiang Shang, Fu-He Wang, Yue Chen
Molecular dynamics simulations are performed to study the influence of Ni concentration on the phase transformations in Ni50+xTi50−x(0 ≤ x ≤ 2) alloys during thermal cycling between 100K and 500K. We successfully reproduce the experimental observations that the martensitic transformation temperature and the thermal hysteresis decrease with increasing Ni concentration when x ≤ 1.5, and the thermally induced martensitic transformation is prohibited when x > 1.5. Three types of martensitic twins are observed; increasing disorder from local distortion in martensitic variants is revealed with increasing Ni concentration at 100K. Furthermore, a strain glass state with disordered local lattice distortion exists when x > 1.5. In addition, it is found that the atomic distributions of the Ni-Ni and Ti-Ni pairs in strain glass can be significantly altered by temperature. Shape memory effect and pseudoelasticity in strain glass are also analyzed. It is found that the shape memory effect can be characterized by the transformation from frozen strain glass to the martensitic B191′twin and the following detwinning, while the pseudoelasticity can be characterized by the transformation from unfrozen strain glass to the B191′phase.

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Regulating the chemical foaming reaction to control the porosity of geopolymer foams

Publication date: 15 April 2017
Source:Materials & Design, Volume 120
Author(s): Ailar Hajimohammadi, Tuan Ngo, Priyan Mendis, Jay Sanjayan
In lightweight geopolymers foamed with aluminium powder, it is desirable to increase the porosity without increasing the amount of aluminium usage. In this study, the kinetics of aluminium reaction is manipulated to increase the porosity of geopolymers without adding extra foaming agent, and the impact on porosity development and the characteristics of binding skeleton is investigated. It is shown that adjusting the ratio of alkali activators regulates the oxidation rate of aluminium powder and impacts the extent of foaming. Samples with higher aluminium oxidation rate developed higher porosities and reached lower densities without adding more foaming agent. Size distribution of the voids becomes wider, and their circularity is reduced in higher chemical foaming reaction rates. Also, by increasing the foaming rate, lower silica to alumina ratios contribute in geopolymer gel network, and geopolymer binder loses its compactness.

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Τετάρτη 15 Φεβρουαρίου 2017

Fisetin inhibits IL-1β-induced inflammatory response in human osteoarthritis chondrocytes through activating SIRT1 and attenuates the progression of osteoarthritis in mice

Publication date: April 2017
Source:International Immunopharmacology, Volume 45
Author(s): Wenhao Zheng, Zhenhua Feng, Shengban You, Hui Zhang, Zhenyu Tao, Quan Wang, Hua Chen, Yaosen Wu
Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation and inflammation. Fisetin, a polyphenol extracted from fruits and vegetables, has been reported to have anti-inflammatory effects. Our study aimed to investigate the effect of fisetin on OA both in vitro and in vivo. In vitro, chondrocytes were pretreated with fisetin alone or fisetin combined with sirtinol (an inhibitor of SIRT1) for 2h before IL-1β stimulation. Production of NO, PGE2, TNF-α and IL-6 were evaluated by the Griess reaction and ELISAs. The mRNA (COX-2, iNOS, MMP-3, MMP-13, ADAMTS-5, Sox-9, aggrecan and collagen-II) and protein expression (COX-2, iNOS, MMP-3, MMP-13, ADAMTS-5 and SIRT1) were measured by qRT-PCR and Western blot respectively. Immunofluorescence was used to assess the expression of collagen-II and SIRT1. SIRT1 activity was quantified with SIRT1 fluorometric assay kit. The in vivo effect of fisetin was evaluated by gavage in mice OA models induced by destabilization of the medial meniscus (DMM). We found that fisetin inhibited IL-1β-induced expression of NO, PGE2, TNF-α, IL-6, COX-2, iNOS, MMP-3, MMP-13, ADAMTS-5. Besides, fisetin remarkably decreased IL-1β-induced degradation of Sox-9, aggrecan and collagen-II. Furthermore, fisetin significantly inhibited IL-1β-induced SIRT1 decrease and inactivation. However, the inhibitory effect of fisetin was obvious abolished by sirtinol, suggesting that fisetin exerts anti-inflammatory effects through activating SIRT1. In vivo, fisetin-treated mice exhibited less cartilage destruction and lower OARSI scores. Moreover, fisetin reduced subchondral bone plate thickness and alleviated synovitis. Taken together, these findings indicate that fisetin may be a potential agent in the treatment of OA.

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Role of MRI in differentiating benign from malignant breast lesions using dynamic contrast enhanced MRI and diffusion weighted MRI

Publication date: Available online 15 February 2017
Source:Alexandria Journal of Medicine
Author(s): Mohamed Ahmed Youssef, Hanan Mohamed Saleh Elahwal, Mohamed Morsi Alwageeh, Sally Elbially Attya
ObjectiveTo evaluate the role of MRI in differentiation of benign from malignant breast lesions using dynamic contrast enhanced MRI (DCE-MRI) and diffusion weighted MRI (DW-MRI).Patients and methodsThe study included 33 female patients with clinically suspicious breast lesions detected by mammography and/or breast ultrasound. Cases were referred from general surgery departments in Tanta university hospital. The patients underwent full history taking and clinical examination, full field digital mammography and US, for those patients cases diagnosed on sonomammography as BI-RADS 3 & 4 were selected for MRI examination.ResultsQuantitative analysis of DWI was done for the 33 breast lesions and their ADC values are recorded at 3 different b-values (250, 600, and 1000). Seventeen lesions showed facilitated diffusion, proved to be benign and 10 lesions showed restricted diffusion, 9 lesions of them proved to be malignant and one proved to be benign. There are 6 lesions showed mixed restricted and facilitated diffusion proved to be malignant.ConclusionDWI improves the diagnostic ability of the DCE-MRI of the breast. It is a better method for detecting breast lesions than either T1- or T2-weighted imaging, but it is better to be performed in conjunction with contrast enhanced MRI.



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