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Πέμπτη 23 Μαρτίου 2017

Improved thermal shock resistance of magnesia-graphite refractories by the addition of MgO-C pellets

Publication date: 15 June 2017
Source:Materials & Design, Volume 124
Author(s): Tianbin Zhu, Yawei Li, Shaobai Sang, Zhipeng Xie
Magnesia-graphite (MgO-C) refractories with 12–20wt% carbon contents are extensively used for the taphole sleeve bricks, bottom blowing elements, slag line bricks, etc. in steelmaking operations. To reduce the carbon content but to have the same or even superior thermal shock resistance with commercial available material compositions (14wt% flaky graphite), we report here a new approach based on the granulating treatment of flaky graphite to improve the thermal shock resistance of MgO-C refractories (10wt% flaky graphite). MgO-C pellets are firstly prepared by the crushing granulation method, and then introduced into such refractories. Addition of MgO-C pellets has no apparent influence on their flexural strength, but enhances their flexural strength after thermal shocks and residual strength ratio. Particularly, when 10wt% flaky graphite of the specimens is replaced totally by MgO-C pellets, their thermal shock resistance is superior to that of the specimens containing 14wt% flaky graphite. This new method opens up possibilities to obtain MgO-C refractories with improved thermal shock resistance.

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Construction of polycationic film coated cotton and new inductive effect to remove water-soluble dyes in water

Publication date: 15 June 2017
Source:Materials & Design, Volume 124
Author(s): Qian Jia, Chunli Song, Hongyan Li, Yuanyuan Huang, Lina Liu, Yikai Yu
In order to realize the high efficient purification of dyeing waste-water, we designed the construction of the polycationic film coated on cotton. We firstly detected that the crystallization spaces of natural cotton could be decreased by triethanolamine pretreatment, so that the cationic reagent:3-chloro-2-hydroxypropylmethyldiallylammonium chloride (CMDA) could be grafted more efficiently, in turn forming the higher cationic degrees of grafting cotton (G-cotton). Subsequently, a copolymerization of another cationic monomer: dimethyldiallylammonium chloride (DMAC) with the cationic CMDA units in G-cotton was carried out, to obtain the polycationic film coated cotton (PF-cotton). Under equal conditions, the G-cotton adsorption capacity of anionic dyes was 15.70 times of that of activated carbon, while the PF-cotton adsorption capacity was near to that of G-cotton, but the average adsorption rate of PF-cotton was 2.8 times of that of G-cotton, indicating that the obtained PF-cotton was very suitable to purify the dyeing waste-water. Moreover, the PF-cotton had a wide range of application universal, e.g., enlarged use, adsorbing different dye solutions and simulated dyeing waste-water, being a filtering filler, and recycling utilization. In addition, we also detected that a new inductive effect occurred in the process of PF-cotton adsorption, playing an important role in speeding up the adsorption.

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Tuning the coercivity of Cu/Ni multilayer nanowire arrays by tailoring multiple parameters

Publication date: 5 June 2017
Source:Materials & Design, Volume 123
Author(s): Huijun Yao, Lu Xie, Yaxiong Cheng, Jinglai Duan, Yonghui Chen, Shuangbao Lyu, Youmei Sun, Jie Liu
Cu/Ni multilayer nanowire arrays with well controlled diameters, Cu and Ni layer thickness and varying periodicity were fabricated by multi potential deposition technique in etched ion-track template at room temperature. A facile method was adopted to confirm the different layer thickness and corresponding component by only removing the Cu layer. The pure Ni and Cu layer were confirmed in the Cu/Ni multilayer nanowires by using the new method and XRD analysis. The relationships between the coercivity and nanowire diameter, layer thickness and periodicity were obtained by carrying out vibrating sample magnetometry (VSM) measurement. The results indicated that the coercivity of multilayer nanowire arrays can be tuned significantly by nanowire diameter, periodicity, Cu and Ni layer thickness. In order to explain the experimental phenomena, Pant's model was modified and adopted to successfully explain the variation of demagnetizing field in Cu/Ni multilayer nanowire arrays after tailoring multiple parameters.

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Review on magnetic nanoparticles for magnetic nanofluid hyperthermia application

Publication date: 5 June 2017
Source:Materials & Design, Volume 123
Author(s): Ziba Hedayatnasab, Faisal Abnisa, Wan Mohd Ashri Wan Daud
Hyperthermia cancer atherapy designed by magnetic particles as heating nano-mediators has been greatly applied for in vitro purposes to make reliable and certain conditions for in vivo trials. This intracellular treatment has found higher efficiency as compared to conventional ones due to generating heat locally through superparamagnetic nanoparticles for inaccessible tumors with minimal damage to the healthy cells nearby. The main challenges of this novel cancer therapy are the enhancement of heating power of such nanoparticles and the control of the local tumoral temperature. Those hyperthermia factors basically derived from magnetic nanoparticles as well as magnetic field. Thereby, the efficiency of magnetic hyperthermia is principally dependent on the proper determination of their features. This study tried to provide a comprehensive evaluation on the magnetic hyperthermia therapy through the determination of magnetic nanoparticles such as surface chemistry, intrinsic and extrinsic magnetic properties. In addition, the features of the magnetic field that substantially play on induction heating power and hyperthermia temperature are reviewed.

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Effect of laser beam configuration on microstructure evolution and joint performance in laser joining AA 6111 panels

Publication date: 5 June 2017
Source:Materials & Design, Volume 123
Author(s): Guang Yang, Junjie Ma, Blair Carlson, Hui-Ping Wang, Radovan Kovacevic
Control of solidification through the selection of laser beams is an approach to improve the quality of visible coach-peel joints in automotive bodies. Laser joining of aluminum alloy 6111 panels with the addition of AA 4047 filler wire was investigated in this study using three types of laser beam, single-beam, in-line beam, and cross-beam. To compare the effect of laser beam arrangement on the weld qualities, the transient heat flow, cooling rate, and solidification rate were analyzed by three-dimensional finite element thermal models using ANSYS software. Microstructure evolution, surface roughness, and fracture mechanism of joints were investigated accordingly. Using the same processing parameters for the three joining processes, cross-beam laser generated the highest peak temperature and solidification rate, as well as the smallest molten pool size. Fusion-brazing joining achieved by the cross-beam laser resulted in the best weld surface quality with acceptable mechanical properties for application as non-load-bearing components. Therefore, cross-beam laser is recommended to join aluminum closure panels in the automotive body-in-white fabrication.

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End-organ radiographic manifestations of cranial neuropathies: A concise review

Publication date: Available online 23 March 2017
Source:Clinical Imaging
Author(s): Vijay A. Patel, Thomas T. Zacharia, David Goldenberg, Johnathan D. McGinn
BackgroundCranial neuropathies are a spectrum of disorders associated with dysfunction of one or more of the twelve cranial nerves and the subsequent anatomic structures they innervate.ObjectiveThe purpose of this article is to review radiographic imaging findings of end-organ aberrations secondary to cranial neuropathies.MethodAll articles related to cranial neuropathies were retrieved through the PubMed MEDLINE NCBI database from January 1, 1991 to August 31, 2014. These manuscripts were analyzed for their relation to cranial nerve end-organ disease pathogenesis and radiographic imaging.ResultsThe present review reveals detectable end-organ changes on CT and/or MRI for the following cranial nerves: olfactory nerve, optic nerve, oculomotor nerve, trochlear nerve, trigeminal nerve, abducens nerve, facial nerve, vestibulocochlear nerve, glossopharyngeal nerve, vagus nerve, accessory nerve, and hypoglossal nerve.ConclusionRadiographic imaging can assist in the detailed evaluation of end-organ involvement, often revealing a corresponding cranial nerve injury with high sensitivity and diagnostic accuracy. A thorough understanding of the distal manifestations of cranial nerve disease can optimize early pathologic detection as well as dictate further clinical management.



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Diagnosis of Grave's disease with pulmonary hypertension on chest CT

Publication date: Available online 23 March 2017
Source:Clinical Imaging
Author(s): Hwa Yeon Lee, Seung Min Yoo, Hye Rin Kim, Eun Ju Chun, Charles S. White
ObjectiveTo evaluate the diagnostic accuracy of chest CT findings to diagnose Grave's disease in pulmonary hypertension.MethodsWe retrospectively evaluated chest CT and the medical records of 13 patients with Grave's disease with (n=6) or without pulmonary hypertension (n=7) and in 17 control patients.ResultsPresence of iso-attenuation of diffusely enlarged thyroid glands compared with adjacent neck muscle on non-enhanced CT as a diagnostic clue of Grave's disease, and assessment of pulmonary hypertension on CT has high diagnostic accuracy.ConclusionChest CT has the potential to diagnose Grave's disease with pulmonary hypertension in the absence of other information.



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Nanodiamond/MoS2 nanorod composite as a novel sorbent for fast and effective vortex-assisted micro solid phase extraction of lead(II) and copper(II) for their flame atomic absorption spectrometric detection

Publication date: Available online 23 March 2017
Source:Journal of Molecular Liquids
Author(s): Neda Baghban, Erkan Yilmaz, Mustafa Soylak
This study is a report on the synthesizing nanodiamond/MoS2 nanorod composite using the hydrothermal method and its application as adsorbent in micro solid phase extraction of lead(II) and copper(II) prior their determination through flame atomic absorption spectroscopy. The nanodiamond/MoS2 nanorod composite was characterized using Raman spectroscopy, BET surface analysis and scanning electronic microscopy (SEM). The optimal conditions including amount of used adsorbent, pH, vortex time, elution condition and volume investigated. Quantitative recoveries for both analytes were obtained at pH3.0. The preconcentration factor is 35, and the sorption capacity of synthesized adsorbent for lead(II) and copper(II) is 19.87 and 49.33mgg−1. The relative standard deviation is 0.9 and 1.5% for lead(II) and copper(II) at a level of 200μgL−1 (n=6), and the detection limit is 42 and 22μgL−1 for lead(II) and copper(II), respectively. The procedure accuracy was proved via analyzing the standard reference materials (SPS-WW2 Waste water Level 2 and TMDA-53.35). The presented procedure was applied for the determination of copper and lead contents of the water samples from Turkey.



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An update on application of nanotechnology and stem cells in spinal cord injury regeneration

Publication date: June 2017
Source:Biomedicine & Pharmacotherapy, Volume 90
Author(s): Kazem Nejati-Koshki, Yousef Mortazavi, Younes Pilehvar-Soltanahmadi, Sumit Sheoran, Nosratollah Zarghami
Spinal cord injury (SCI) is damage to the spinal cord that leads to sudden loss of motor and autonomic function and sensory under the level of the injury. The pathophysiological advancement of SCI is divided into two categories: primary injury and secondary injury. Due to the loss of motor, sensory, or cognitive function, a patient's quality of life is likely reduced and places a great burden on society in order to supply health care costs. Therefore, it is important to develop suitable therapeutic strategies for SCI therapy. Nano biomedical systems and stem cell based therapy have the potential to provide new therapeutic availability and efficacy over conventional medicine. Due to their unique properties, nanomaterials and mesenchymal stem cells can be used to offer efficient treatments. Nanoparticles have a potential to deliver therapeutic molecules to the target tissue of interest, reducing side effects of untargeted therapies in unwanted areas. Mesenchymal stem cells (MSCs) can reduce activating inflammation responses that lead to cell death and promote functional recovery and cell growth. We review recent uses of nanomaterials and stem cells in regeneration of SCI.



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Ribonuclease attenuates hepatic ischemia reperfusion induced cognitive impairment through the inhibition of inflammatory cytokines in aged mice

Publication date: June 2017
Source:Biomedicine & Pharmacotherapy, Volume 90
Author(s): Gang Ma, Chan Chen, Haixia Jiang, Yanhua Qiu, Yansong Li, Xiaoqiang Li, Xiyang Zhang, Jin Liu, Tao Zhu
BackgroundElderly patients undergoing major surgery often develop cognitive dysfunction, and no optimum treatment exists for this postoperative complication. Ribonuclease, the counterpart of ribonucleic acid, has mostly been reported in terms of its use as a potential modality in anticancer therapy, and recent studies have demonstrated that ribonuclease can exert organ-protective effects in several pathological conditions. Our study also demonstrated that ribonuclease protects the liver against ischemia reperfusion injury. Nevertheless, it is unknown whether ribonuclease can attenuate the cognitive dysfunction that is induced by liver ischemia reperfusion. In this study, we aimed to evaluate the effect of ribonuclease on cognitive function after liver ischemia reperfusion.MethodsAged mice underwent sham surgery or 60min of hepatic ischemia reperfusion, vehicle or ribonuclease, which were administered subcutaneously. The primary observation endpoint was the Morris water maze; following 24h, 3days, and 7days of reperfusion, the levels of serum and hippocampus proinflammatory cytokines were measured to reveal the underlying mechanism.ResultsA probe test was conducted on day 3 and a reversal probe test was conducted on day 7 after surgery; the results demonstrated a reduction in cognitive function after liver ischemia reperfusion and that ribonuclease treatment attenuated cognitive impairment. The levels of serum and hippocampus proinflammatory cytokines (interleukin-6 and interleukin-1β) and extracellular ribonucleic acid were significantly increased at 24h after reperfusion, but ribonuclease treatment markedly reduced the proinflammatory cytokine increase.ConclusionThe results of the study suggested that hepatic ischemia reperfusion leads to cognitive impairment in aged mice and an increase in inflammatory cytokine expression in both serum and the hippocampus; more importantly, ribonuclease showed protective effects against cognitive impairment through inhibiting the release of inflammatory cytokines.



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Breviscapine confers a neuroprotective efficacy against transient focal cerebral ischemia by attenuating neuronal and astrocytic autophagy in the penumbra

Publication date: June 2017
Source:Biomedicine & Pharmacotherapy, Volume 90
Author(s): Zhang Pengyue, Guo Tao, He Hongyun, Yang Liqiang, Deng Yihao
Breviscapine is a flavonoid derived from a traditional Chinese herb Erigerin breviscapus (Vant.) Hand-Mazz, and has been extensively used in clinical treatment for cerebral stroke in China, but the underlying pharmacological mechanisms are still unclear. In present study, we investigated whether breviscapine could confer a neuroprotection against cerebral ischemia injury by targeting autophagy mechanisms. A cerebral stroke model in Sprague-Dawley rats was prepared by middle cerebral artery occlusion (MCAO), rats were then randomly divided into 5 groups: MCAO+Bre group, rats were treated with breviscapine; MCAO+Tat-Beclin-1 group, animals were administrated with specific autophagy inducer Tat-Beclin-1; MCAO+Bre+Tat-Beclin-1 group, rats were treated with both breviscapine and Tat-Beclin-1, MCAO+saline group, rats received the same volume of physiological saline, and Sham surgery group. The autophagy levels in infarct penumbra were evaluated by western blotting, real-time PCR and immunofluorescence 7days after the insult. Meanwhile, infarct volume, brain water content and neurological deficit score were assessed. The results illustrated that the infarct volume, brain water content and neurofunctional deficiency were significantly reduced by 7days of breviscapine treatment in MCAO+Bre group, compared with those in MCAO+saline group. Meanwhile, the western blotting, quantitative PCR and immunofluorescence showed that the autophagy in both neurons and astrocytes at the penumbra were markedly attenuated by breviscapine admininstration. Moreover, these pharmacological effects of breviscapine could be counteracted by autophagy inducer Tat-Beclin-1. Our study suggests that breviscapine can provide a neuroprotection against transient focal cerebral ischemia, and this biological function is associated with attenuating autophagy in both neurons and astrocytes.



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Cratoxy formosum leaf extract inhibits proliferation and migration of human breast cancer MCF-7 cells

Publication date: June 2017
Source:Biomedicine & Pharmacotherapy, Volume 90
Author(s): Benjaporn Buranrat, Nootchanat Mairuae, Ampa Konsue
In this study we investigated how Cratoxy formosum (CF) leaf extract affects the viability and migration of human breast cancer cells including the mechanism(s) responsible. Our results showed that CF leaf extract strongly induced MCF-7 cell death in a concentration- and time-dependent manner, with IC50 values of 85.70±4.52μg/mL and 53.74±3.02μg/mL at 24h and 48h, respectively. Additionally, CF leaf extract potentiated the activity of 4 anticancer drugs with the greatest synergy occurring between CF and 5-FU. CF leaf extract also caused a dose-dependent decrease in colony forming ability with IC50 values of 36.37+1.80 μg/mL and cell migration, with IC50 values of 43.68±0.86μg/mL. Moreover, CF significantly induced ROS formation, increased caspase 3 activities, and reduced the mitochondrial membrane potential, leading to cancer cell apoptosis and cell death. In addition, the extract inhibited cancer cell migration at 25μg/mL by reducing MMP 2 and MMP 9 protein expression. Moreover, CF leaf extracts strongly decreased expression of the cell cycle regulatory protein Rac1 and downstream protein, cdk6. CF leaf extract significantly stimulated p21 and this correlated with a reduction in cyclin D1 protein levels. In summary, CF leaf extract can inhibit cell proliferation, induce cell apoptosis, and reduce cell migration in the MCF-7 cell line. It could also be beneficial for enhancing the activity of anticancer drugs used to treat breast cancer.

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Repression of DOK7 mediated by DNMT3A promotes the proliferation and invasion of KYSE410 and TE-12 ESCC cells

Publication date: June 2017
Source:Biomedicine & Pharmacotherapy, Volume 90
Author(s): Shou-mei Yang, Su-yi Li, Hao-bin Yu, Jie-ru Li, Lei-lei Sun
Increasing evidence shows that aberrant epigenetic regulation of tumor suppressor genes is a contributing factor to their altered expression in esophageal squamous cell carcinoma (ESCC). In the current study, we investigate the role of DOK7 in ESCC cells. We found that enforced expression of DOK7 inhibited the proliferation and invasion of ESCC cells. We also found that treatment of ESCC cells with the DNA methylation inhibitor, 5-aza-2-deoxycytidine (5-azadC), induced the demethylation of DOK7 in promoter and DOK7 expression. Moreover, silencing DNMT3A decreased methylation of DOK7 and increased DOK7 expression, followed by repressing the proliferation and invasion of ESCC cells. Collectively, our data indicated that silencing DNMT3A inhibits proliferation and invasion in ESCC cells by inducing demethylation of DOK7.



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Linc00152 promotes cancer progression in hepatitis B virus-associated hepatocellular carcinoma

Publication date: June 2017
Source:Biomedicine & Pharmacotherapy, Volume 90
Author(s): Xin Deng, Xiao fang Zhao, Xing qiu Liang, Ran Chen, Yi feng Pan, Jian Liang
BackgroundThe X protein (HBx) plays as a key role in hepatocarcinogenesis associated with hepatitis B virus (HBV) infections. The study aimed to figure out the role of Linc00152 in hepatocellular carcinoma (HCC) and the association between the expression levels of Linc00152 and HBx.MethodsQRT-PCR assays were applied to analyzed the expression levels of Linc00152 and HBx. Kaplan-Meier survival curve was performed to identify the association between LINC00152 and the over survival time (OS) in HCC patients. Cell growth and invasion ability was evaluated by CCK8 cell proliferation and transwell invasion assays. Western-blot analysis was detected the protein expression. RNA immunoprecipitation (RIP), RNA-pull down and chromatin Immunoprecipitation (ChIP) assays was also been carried out.ResultsWe demonstrated that LINC00152 expression in hepatocellular carcinoma (HCC) patients was significantly higher compared with adjacent non-tumour tissues and positively correlated with tumor size, HBV infection (HBsAg) and tumor number. Patient with hepatitis B virus (HBV) infection HCC was higher expression than that without HBV. Furthermore, the expression levels of Linc00152 were positively correlated with HBx expression in HCC tissues and higher Linc00152 expression levels were correlated with poor prognosis of HCC patients. In vitro, Linc00152 was up-regulated in Huh-7 and SM7721 cells after overexpression of HBx and down-regulated after silencing HBx. Furthermore, silencing Linc00152 suppressed the cell proliferation and invasion. Moreover, we found that Linc00152 inhibited the E-cadherin expression via interacting with EZH2 and promoted the Epithelial-mesenchymal transition (EMT) phenomenon in HCC cells.ConclusionsThese results suggested that HBx enhanced LINC00152 expression and inhibition of LINC00152 could provide a therapeutic target for HCC.



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The activation of Akt/mTOR pathway by bleomycin in Epithelial-to-mesenchymal transition of human submandibular gland cells: A treatment mechanism of bleomycin for mucoceles of the salivary glands

Publication date: June 2017
Source:Biomedicine & Pharmacotherapy, Volume 90
Author(s): Yu Cai, Rui Sun, Rong Wang, Jian-Gang Ren, Wei Zhang, Yi-Fang Zhao, Ji-Hong Zhao
ObjectiveBleomycin (BLM) has been found safe and highly effective in the treatment of the mucoceles by intralesional injection in our previous study. The present research was designed to investigate whether epithelial-to-mesenchymal transition (EMT) contributes to the therapeutic effects of BLM for mucoceles of the salivary glands.Material and methodsThe cell proliferation and apoptosis of human submandibular gland cells (HSG cells) were examined by Cell Counting Kit-8 assay and Annexin V binding assay respectively. Epithelial and mesenchymal markers of HSG cells were measured by real-time quantitative PCR and Western blot analysis. Acinar differentiation and cell migration assays were performed to evaluate HSG cells function.ResultsHigh-dose BLM (≥0.5μg/mL) significantly inhibited the cell proliferation and induced the cell apoptosis, while the treatment with low-dose BLM (0.05 and 0.1μg/mL) for 48h induced EMT in HSG cells. Furthermore, Akt/mTOR pathway, rather than MAPK pathway, was activated through treated with 0.05 and 0.1μg/mL BLM, as well as activation of the transcription factor Slug and Zeb 1. The migration of HSG cells was also enhanced through 0.05 and 0.1μg/mL BLM, but the ability of acinar differentiation was diminished.ConclusionOur results indicated that an EMT process was involved in the BLM-induced therapeutic effects on the HSG cells through the Akt/mTOR pathway. Importantly, the results indicated the potential role of this process in the BLM sclerotherapy of mucoceles of the salivary glands.



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Analgesia effect of baicalein against NTG-induced migraine in rats

Publication date: June 2017
Source:Biomedicine & Pharmacotherapy, Volume 90
Author(s): Xiao-Fan Zhang, Wen-Jun Zhang, Cui-lan Dong, Wan-Li Hu, Yu-Yao Sun, Yarigui Bao, Chun-Feng Zhang, Chang-Run Guo, Chong-Zhi Wang, Chun-Su Yuan
BackgroundMigraine is a complex nervous system disease characterized by typical throbbing and unilateral headache, which causes severe healthy and social issues worldwide. The purpose of this study was to investigate the effect of baicalein (BAI) on the treatment of migraine.Material and methodsTwenty-four rats were randomly divided equally into four groups, including a blank group, model group, positive group (ibuprofen tablets 82mg/kg), and BAI group (60mg/kg). All rats were intragastrically treated with the corresponding treatment for 10 consecutive days, and they were subcutaneously injected with NTG (10mg/kg) 1h after the last treatment, except in the blank group. After model establishment, the behaviors of all rats, including scratching head and shaking body were observed continuously for 100min. Four hours after NTG treatment, all rats were anaesthetized and the blood was collected. Thereafter, nitric oxide (NO) in plasma was determined by colorimetric method, the level of calcitonin gene-related peptide (CGRP) and endothelin (ET) were detected by radioimmunoassay method. In addition, immunohistochemistry was applied to detect c-Fos neuronal activity in trigeminal nucleus caudalis (TNC).ResultsBehavioral research showed that BAI administration alleviated the hyperalgesia in migraine rats. Compared with the model group, the levels of NO and CGRP in BAI administration groups were markedly decreased (p<0.01), and the levels of ET was significantly increased (p<0.01). Meanwhile, immunohistochemistry results showed that NTG treatment significantly activated c-Fos neurons while BAI treatment inhibited the expression of c-Fos.ConclusionsBAI could alleviate the migraine-like headache induced by NTG, which is related to the regulation of vasoactive substances. These findings may contribute to the further study of BAI as a potential drug for migraine pharmacotherapy.

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Syringocystadenocarcinoma Papilliferum: Clinicopathologic Analysis of Ten Cases

Abstract

Background

Syringocystadenocarcinoma papilliferum (SCACP) is an exceedingly rare cutaneous adnexal neoplasm. We aimed to investigate the clinicopathologic and immunophenotypic features of SCACP, and to discuss the prognosis of this rare entity.

Method

We retrospectively collected clinical, pathological and follow-up data of 10 cases with SCACP.

Results

There were 8 males and 2 females, with ages ranging from 26 to 74 years. The chest was most frequently involved. Histologically, one case only demonstrated SCACP in situ, nine cases presented with variable invasive components of adenocarcinoma and/or squamous cell carcinoma in addition to areas of in situ. Apocrine differentiation with decapitation was evident in 4 cases and mucinous metaplasia was noted in 1 cases. P63 was positive in invasive squamous cell carcinoma, while CK7 was variably positive in invasive adenocarcinoma. Regional lymph node metastasis was confirmed by pathological examination in four patients. Follow-up was available for 9 patients, ranging from 3 months to 112 months. Three patients died of the disease within 1 year after recurrences.

Conclusions

Due to high rates of regional lymph node metastasis and mortality in our patients, clinical behaviour of SCACP seems to be more aggressive than that previously reported.



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Tanshinone IIA Elicits Neuroprotective Effect Through Activating the Nuclear Factor Erythroid 2-Related Factor-Dependent Antioxidant Response

Rejuvenation Research , Vol. 0, No. 0.


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Multidisciplinary teamwork: Collaborating on diabetes



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Taxes on sugar-sweetened beverages (Editorial)Effects of taxing sugar-sweetened beverages on caries and treatment costs



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Oral health: Welcome progress



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Are you seeking high performing but affordable dental implants?



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Child dental health: Forty year overview



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Natural tooth preservation versus extraction and implant placement: patient preferences and analysis of the willingness to pay



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Dental radiography: Vanishing implant



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The latest goodwill results



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Dental education: Oral biology teaching



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NiHiliStic Dentistry



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Outreach teachers essential



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Meeting and greeting in the clinical setting – are we doing what patients want?



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Dental research: Trainee collaborations



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The Hall Technique 10 years on: Questions and answers



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Restorative dentistry: Occlusal hypervigilance



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The safer solution for babies



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PTFE tape inspiration



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It's back and bigger than ever!



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Honours, awards, appointments



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Statistical analyses on Si microwire solar cells

Publication date: June 2017
Source:Data in Brief, Volume 12
Author(s): Hong-Sik Kim, Joondong Kim
In this data, the statistical analyses of silicon microwire (SiMW) solar cells are presented for the research article entitled "Electrical and optical properties of Si microwire solar cells" (H.-S. Kim, D. B. Patel, H. Kim, M. Patel, K. R. Chauhan, W. Park, and J. Kim) [1]. This article shows the statistical analyses on performances of the various SiMW solar cells. The accuracy of solar cell parameters is discussed on the basis of data sets.



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Description of long-term climate data in Eastern and Southeastern Ethiopia

Publication date: June 2017
Source:Data in Brief, Volume 12
Author(s): Messay Mulugeta, Degefa Tolossa, Gezahegn Abebe
This article presents long-term analyzed climate data from nine weather stations in eastern and southeastern parts of Ethiopia. At the outset of this data process, unrefined meteorological data was obtained from National Meteorological Agency (NMA) of Ethiopia for the analysis. The analyzed data in this article shows patterns of rainfall variability, frequency of drought years, seasonal concentration of precipitation and temperature conditions. As issues related to climate conditions are very intricate, different techniques and indices were applied to analyze and refine the data. The analysis reveals that eastern and southeastern parts Ethiopia are severely affected by recurrent droughts, erratic rainfall, and high and increasing temperature conditions. The long-term (1981–2009) mean annual total rainfall had been fluctuating between about 850mm and 1350mm. Most stations receive maximum rainfall in summer (June, July and August) except Gode which gets over 50% of its rainfall in spring season (March, April and May). The inter-annual rainfall difference was found to be very high. The Precipitation Concentration Index (PCI) is greater than 11 for all the stations showing that rainfall is concentrated in a few months. PCI is extremely high (greater than 20) for very dry stations such as Gode. Food production and consumer price index were found to be fluctuating with rainfall patters.



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Electrocoagulation process to Chemical and Biological Oxygen Demand treatment from carwash grey water in Ahvaz megacity, Iran

Publication date: April 2017
Source:Data in Brief, Volume 11
Author(s): Mohammad Javad Mohammadi, Afshin Takdastan, Sahand Jorfi, Abdolkazem Neisi, Majid Farhadi, Ahmad Reza Yari, Sina Dobaradaran, Yusef Omidi Khaniabadi
In this work, we present the result of an electric coagulation process with iron and aluminum electrodes for removal of chemical and biological oxygen demand (COD and BOD) from grey water in different car washes of Ahvaz, Iran. Nowadays, one of the important dangerous that can contaminate water resources for drinking, agriculture and industrial is Car wash effluent [1,2]. In this study, initial COD and BOD concentration, pH of the solution, voltage power and reaction time was investigated. The concentration level of remaining COD and BOD in samples was measured, using DR/5000 UV–vis HACH spectrophotometer [3,4]. The effects of contact time, initial pH, electrical potential and voltage data on removal of COD and BOD were presented. Statistical analysis of the data was carried out using Special Package for Social Sciences (SPSS 16).



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Platelet-Derived NO in Subjects Affected by Type 2 Diabetes with and without Complications: Is there any Relationship with their Offspring?

09-2016-0353-dia_10-1055-s-0043-102578-1

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0043-102578

Macro- and microvascular complications are currently the principal causes of morbidity and mortality in patients with diabetes mellitus. Aim of this study was to determine if type 2 diabetic patients with nephropathy and coronary artery disease showed altered platelet-derived nitric oxide (NO) production, compared with diabetic subjects without complications, and if this alteration is also present in their diabetic offspring. In this case-control observational study, platelet NO and peroxynitrite content was determined on plasma from 60 male adult type 2 diabetic patients and 60 male offspring type 2 diabetic patients. Plasmatic levels of homocysteine were also determined in the same individuals. Moreover, Western blot analysis of platelet lysates was performed with specific monoclonal antibody for endothelial (eNOS) and inducible (iNOS) nitric oxide synthase. Our study showed a lower piastrinic production of NO in the group of parents without complications (ADH), compared with the group of offspring without complications (YDH) and with the groups of parents with complications. Furthermore, we observed a lower synthesis of peroxynitrite in platelets from the ADH group than in the groups of patients with complications, and in the YDH group compared with all other groups. Subjects from YDH group also showed lower iNOS expression, compared with all other groups. Our data suggest that alterations in nitric oxide metabolism may represent potential risk factors in type 2 diabetes complications, such as nephropathy and cardiovascular diseases, leading to development of new therapeutic strategies in order to delay and prevent the onset of such complications.
[...]

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Radiobiology of stereotactic body radiation therapy (SBRT)

Publication date: Available online 23 March 2017
Source:Reports of Practical Oncology & Radiotherapy
Author(s): Miquel Macià i Garau
Recent advances in the technology of radiotherapy have enabled the development of new therapeutic modalities that deliver radiation with very high accuracy, reduced margins and high dose conformation, allowing the reduction of healthy tissue irradiated and therefore minimizing the risk of toxicity. The next step was to increase the total tumor dose using conventional fractionation (which remains the best way to relatively radioprotect healthy tissues when large volumes are treated) or to use new fractionation schemes with greater biological effectiveness. Based on the experience gained in radiosurgery, the latter way was chosen for small and well-defined tumors in the body. Stereotactic body radiotherapy delivers high doses of radiation to small and well-defined targets in an extreme hypofractionated (and accelerated) scheme with a very high biological effectiveness obtaining very good initial clinical results in terms of local tumor control and acceptable rate of late complications. In fact, we realize a posteriori that it was not feasible to administer such biologically equivalent dose in a conventional fractionation because the treatment could last several months. So far, these new therapeutic modalities have been developed due to technologic advances in image guidance and treatment delivery but without a solid biological basis. It is the role of traditional radiobiology (and molecular radiobiology) to explain the effects of high doses of ionizing radiation on tumor and normal tissues. Only through a better understanding of how high doses of ionizing radiation act, clinicians will know exactly what we do, allowing us in the future to refine our treatments. This article attempts to describe through simple and understandable concepts the known aspects of the biological action of high doses of radiation on tumor and normal tissues, but it is clear that we need much more basic research to better understand the biology of high doses of radiation.



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Management of liver cancer. The Surgeon's point of view

Publication date: Available online 23 March 2017
Source:Reports of Practical Oncology & Radiotherapy
Author(s): Pierre Rabinel, Damien Dousse, Fabrice Muscari, Bertrand Suc
During the last twenty years, a huge progress has been achieved in the treatment of liver cancer and recent strategies include interventional radiology, chemotherapy regimens and surgery. Meanwhile, Stereotactic Body Radiation Therapy (SRBT) has developed in the treatment of all organs with millimetre accuracy, very few side effects and a high control rate. So, SRBT has become a therapeutic weapon in his own right in liver tumour treatment. Many publications have reported encouraging results in colorectal liver metastasis, hepatocellular carcinoma on cirrhosis and peripheric cholangiocarcinoma. It is important that radiation therapists involve systematic multidisciplinary "liver tumour" meetings to discuss therapeutic indications and initiate treatments quickly.



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Esophageal Cancer Genome

Point of Pride

ECAN is incredibly happy and proud to share news of the recent publication of research from The Cancer Genome Atlas (TCGA) study of Esophageal Cancer in the journal Nature. This project is very important to ECAN. It was the first advocacy project that ECAN took on.  ECAN made it a priority because we worried that Esophageal Cancer would once again be left behind as scientific advances were made available in so many other diseases.  The National Cancer Institute (NCI) was expanding its TCGA pilot project just as ECAN was launched in 2009.  When we discovered that NCI had not included Esophageal Cancer on the list of 20 cancer genomes it would map, we began a campaign to get EC on the list.  We believed genomic research was critical to advances in treatment and prevention of our so-often-overlooked and underfunded cancer.

Campaign to Make an Important Difference

When we inquired about why EC was not included, we were told that if we could provide the tissue samples needed to conduct the research, Esophageal Cancer could be on the list. The doctors on ECAN's Board of Directors met to consider whether our organization was up to the challenge of finding the necessary tissue samples.  Though they understood it was a large undertaking, the medical professionals advised their colleagues on the Board that we could do it, though it would not be easy.  When ECAN indicated to the NCI that we would take on that task of collecting the tissue samples, we were informed that NCI no longer had the budget available to start the project.

The Little Advocacy Engine that Could

At the time, ECAN was a fledgling organization, barely a year old with less than $40,000 in the bank and staff comprised of one full-time volunteer.  Despite these hurdles, in the spring of 2011, the ECAN Board of Directors bravely and forcefully pledged to not only find the tissue samples necessary to complete the research but to also raise the $500,000 needed to begin the work.

By the summer of 2011, NCI found the resources to launch the project within its own budget.  But, according to the lead researcher for the Esophageal Cancer project, Dr. Adam Bass, ECAN played a key role in bringing the Esophageal Cancer mapping project to fruition. "I commend ECAN for their tireless advocacy that helped make this project a reality," he said.

Progress Worth the Wait

ECAN's Founder, President and CEO Mindy Mintz Mordecai was asked to serve on the Disease Working Group overseeing the project.   She was honored to join the nation's top Esophageal Cancer researchers who dedicated substantial time and energy toward making this a successful and significant study.  Getting sufficient numbers of the properly stored tissue samples proved to be a daunting and lengthy task.  But the research was completed, submitted for publication, peer reviewed, edited and published on January 4, 2017.

The findings are incredibly important on many levels and will lead to better, more exact treatment for patients in the future.   We hope all ECAN supporters will feel a sense of pride about your work with us and the role you played in making this important research possible.    For those who wish to read a summary of the research findings, click here.  The full study can be found at this link.

The post Esophageal Cancer Genome appeared first on Esophageal Cancer Action Network.



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Primary cutaneous anaplastic large cell lymphoma with intralymphatic involvement associated with chronic lymphedema

Abstract

Chronic lymphedema predisposes to develop malignant cutaneous tumors, including angiosarcoma, Kaposi's sarcoma and B cell lymphoma. T cell malignancy has rarely been associated with chronic lymph stasis. Here we report a case of primary cutaneous anaplastic large cell lymphoma (pcALCL) with lymphatic spread associated with chronic lymphedema. The patient is a 56-year-old man who received orchiectomy and right inguinal lymphadenectomy for malignant seminoma 10 years ago, which led to prominent lymphedema of the right leg. He developed extensive skin nodules on the lymphedematous area for 3 months. Histopathology findings confirmed a diagnosis of pcALCL, which is a subtype of cutaneous T cell lymphoma characterized by the presence of CD30+ T cells. Intralymphatic infiltration of malignant cells is prominent. The pathogenesis of intralymphatic cutaneous anaplastic large cell lymphoma is largely unknown. Our case suggests that chronic lymphedema resulted in persistent CD4+ T cell inflammation, which then may contribute to the development of pcALCL.



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Focusing on People at Risk.

Author: Kennedy, Maureen Shawn MA, RN, FAAN
Page: 7


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Making Patients Partners in Real-Time Electronic Charting.

Author: Drobny, Stephanie D. MS-HSL, RN, CPHQ
Page: 11


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Treating Obesity Starts at Home.

Author: Bice, April A. PhD, RN, CPNP
Page: 13


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Eliminating Intimidating and Disruptive Behavior.

Author: Monteau, Manouchka RN
Page: 13


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Eliminating Intimidating and Disruptive Behavior.

Author: Ashcraft, Jenny MBA, RN
Page: 13


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Managing Medication Errors.

Author: Satorre, Joy RN
Page: 13


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A Beacon in the Labyrinth of the Indian Health Service.

Author: Sofer, Dalia
Page: 14


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OSHA Considers National Standard to Prevent Health Care Workplace Violence.

Author: Halpern, Lucy Wang
Page: 15


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NewsCAP: RNs and community health workers (CHWs) are key players in community team-based care, says the Tri-Council for Nursing.

Author:
Page: 15


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Long-Term NSAIDs and Acetaminophen Linked to Hearing Loss in Women.

Author: Zolot, Joan PA
Page: 16


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NewsCAP: Guidelines updated for thyroid disease in pregnancy and postpartum.

Author:
Page: 16


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NewsCAP: Michigan law grants prescribing privileges to advanced practice registered nurses (APRNs).

Author:
Page: 16


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Peanut Allergy Prevention Starts in Infancy.

Author: Potera, Carol
Page: 17


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NewsCAP: The ADA issues new position statement on the prevention of diabetic neuropathy.

Author:
Page: 17


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FDA Anesthesia Warning for Pregnant Women, Children.

Author: Stockwell, Serena
Page: 18


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Updated Advice About Eating Fish: What Pregnant Women and Parents Should Know.

Author:
Page: 18


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Changing Health Care Delivery, One Company at a Time.

Author: Nelson, Roxanne
Page: 19-20


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Surgical vs. Conservative Interventions for Treating ACL Injuries.

Author: Newsom, Cresilda T. DNP, MSN, RN, CPAN
Page: 21


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AJN On the Cover.

Author: Szulecki, Diane Associate Editor
Page: 23


http://ift.tt/2nOg6RP

AJN On the Web.

Author:
Page: 23


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Drug resistance in pancreatic cancer: Impact of altered energy metabolism

Publication date: Available online 23 March 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Cristoforo Grasso, Gerrit Jansen, Elisa Giovannetti
Pancreatic cancer is a highly deadly disease: almost all patients develop metastases and conventional treatments have little impact on survival. Therapeutically, this tumor is poorly responsive, largely due to drug resistance. Accumulating evidence suggest that this chemoresistance is intimately linked to specific metabolic aberrations of pancreatic cancer cells, notably an increased use of glucose and the amino acid glutamine fueling anabolic processes. Altered metabolism contributes also to modulation of apoptosis, angiogenesis and drug targets, conferring a resistant phenotype. As a modality to overcome chemoresistance, a variety of experimental compounds inhibiting key metabolic pathways emerged as a promising approach to potentiate the standard treatments for pancreatic cancer in preclinical studies. These results warrant confirmation in clinical trials. Thus, this review summarizes the impact of metabolic aberrations from the perspective of drug resistance and discusses possible novel applications of metabolic inhibition for the development of more effective drugs against pancreatic cancer.



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Cutting Edge in IFN Regulation: Inflammatory Caspases Cleave cGAS

Publication date: 21 March 2017
Source:Immunity, Volume 46, Issue 3
Author(s): Simon Heidegger, Tobias Haas, Hendrik Poeck
Caspases have important functions beyond their established role in driving inflammation and apoptosis. In this issue of Immunity, Wang et al. (2017) demonstrate that inflammasome-triggered caspases cleave and inactivate the DNA sensor cGAS, thus restricting the type I interferon response to cytosolic DNA.

Teaser

Caspases have important functions beyond their established role in driving inflammation and apoptosis. Wang et al. (2017) demonstrate that inflammasome-triggered caspases cleave and inactivate the DNA sensor cGAS, thus restricting the type I interferon response to cytosolic DNA.


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Neutrophils acROSs the Enemy Lines

Publication date: 21 March 2017
Source:Immunity, Volume 46, Issue 3
Author(s): Carlos del Fresno, Andrés Hidalgo
In this issue of Immunity, Warnatsch et al. (2017) describe how neutrophils measure their microbial opponents by differential shuttling of reactive oxygen species (ROS), a process that determines their recruitment and distribution and ultimately the strength of anti-microbial responses.

Teaser

In this issue of Immunity, Warnatsch et al. (2017) describe how neutrophils measure their microbial opponents by differential shuttling of reactive oxygen species (ROS), a process that determines their recruitment and distribution and ultimately the strength of anti-microbial responses.


http://ift.tt/2nJiY1U

RECONsidering Sensing of Cyclic Dinucleotides

Publication date: 21 March 2017
Source:Immunity, Volume 46, Issue 3
Author(s): Jonathan Maelfait, Jan Rehwinkel
Detection of cyclic dinucleotides (cdNs) by the STING pathway potently triggers the antiviral response. McFarland et al. now show that the mouse oxidoreductase RECON acts as a sensor for some bacterial cdNs, modulating innate signaling in a manner independent of STING to promote an antibacterial state.

Teaser

Detection of cyclic dinucleotides (cdNs) by the STING pathway potently triggers the antiviral response. McFarland et al. now show that the mouse oxidoreductase RECON acts as a sensor for some bacterial cdNs, modulating innate signaling in a manner independent of STING to promote an antibacterial state.


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Disarming the Killers: Brain Strikes on NK Cells

Publication date: 21 March 2017
Source:Immunity, Volume 46, Issue 3
Author(s): Linda Quatrini, Sophie Ugolini
Brain ischemia induces profound systemic immunosuppression, leading to infectious complications. In this issue of Immunity, Liu et al. (2017) demonstrate that distinct neuroendocrine pathways differentially inhibit natural killer (NK) cell responses in the central nervous system and the periphery after cerebral infarction.

Teaser

Brain ischemia induces profound systemic immunosuppression, leading to infectious complications. In this issue of Immunity, Liu et al. (2017) demonstrate that distinct neuroendocrine pathways differentially inhibit natural killer (NK) cell responses in the central nervous system and the periphery after cerebral infarction.


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Of Human DC Migrants and Residents

Publication date: 21 March 2017
Source:Immunity, Volume 46, Issue 3
Author(s): Elodie Segura, Vassili Soumelis
Migration from peripheral tissues to lymph nodes is a key feature of dendritic cells (DCs), but little is known about the migration patterns of human DCs. By analyzing multiple lymphoid organs and tissues from the same donors, Granot et al. propose that the two main subsets of human DCs display different migratory capacity.

Teaser

Migration from peripheral tissues to lymph nodes is a key feature of dendritic cells (DCs), but little is known about the migration patterns of human DCs. By analyzing multiple lymphoid organs and tissues from the same donors, Granot et al. propose that the two main subsets of human DCs display different migratory capacity.


http://ift.tt/2mWkgC0

The ILC World Revisited

Publication date: 21 March 2017
Source:Immunity, Volume 46, Issue 3
Author(s): Andreas Diefenbach, Marco Colonna, Chiara Romagnani
Immunology has recently witnessed several new developments in understanding the biology of innate lymphocytes. In particular, the discovery of innate lymphoid cells (ILCs) has opened entirely new avenues for research. The exciting new developments in this rapidly expanding field were the focus of the 2ndEMBO Conference on Innate Lymphoid Cells, which took place from November 30 to December 2, 2016 in Berlin, Germany. Here, we summarize the key new developments reported at the conference.

Teaser

Immunology has recently witnessed several new developments in understanding the biology of innate lymphocytes. In particular, the discovery of innate lymphoid cells (ILCs) has opened entirely new avenues for research. The exciting new developments in this rapidly expanding field were the focus of the 2ndEMBO Conference on Innate Lymphoid Cells, which took place from November 30 to December 2, 2016 in Berlin, Germany. Here, we summarize the key new developments reported at the conference.


http://ift.tt/2nJmPMf

ILC-poiesis: Making Tissue ILCs from Blood

Publication date: 21 March 2017
Source:Immunity, Volume 46, Issue 3
Author(s): Jenny Mjösberg, Luca Mazzurana
The development of human innate lymphoid cells (ILCs) remains poorly characterized. In a recent issue of Cell, Lim et al. show that human peripheral-blood CD117+ ILCs harbor ILC precursors (ILCPs) derived from hematopoietic stem cells. Peripheral-blood ILCPs can generate all ILC subsets in vivo and in vitro.

Teaser

The development of human innate lymphoid cells (ILCs) remains poorly characterized. In a recent issue of Cell, Lim et al. show that human peripheral-blood CD117+ ILCs harbor ILC precursors (ILCPs) derived from hematopoietic stem cells. Peripheral-blood ILCPs can generate all ILC subsets in vivo and in vitro.


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Interleukin-17: Why the Worms Squirm

Publication date: 21 March 2017
Source:Immunity, Volume 46, Issue 3
Author(s): Noah J. Silverstein, Jun R. Huh
IL-17 is a cytokine known primarily for its role in inflammation. In a recent issue of Nature, Chen et al. (2017) demonstrate that IL-17 plays a neuromodulatory role in Caenorhabditis elegans by acting directly on neurons to amplify neuronal responses to stimuli and produce changes in animal behavior.

Teaser

IL-17 is a cytokine known primarily for its role in inflammation. In a recent issue of Nature, Chen et al. (2017) demonstrate that IL-17 plays a neuromodulatory role in Caenorhabditis elegans by acting directly on neurons to amplify neuronal responses to stimuli and produce changes in animal behavior.


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Protecting the Newborn and Young Infant from Infectious Diseases: Lessons from Immune Ontogeny

Publication date: 21 March 2017
Source:Immunity, Volume 46, Issue 3
Author(s): Tobias R. Kollmann, Beate Kampmann, Sarkis K. Mazmanian, Arnaud Marchant, Ofer Levy
Infections in the first year of life are common and often severe. The newborn host demonstrates both quantitative and qualitative differences to the adult in nearly all aspects of immunity, which at least partially explain the increased susceptibility to infection. Here we discuss how differences in susceptibility to infection result not out of a state of immaturity, but rather reflect adaptation to the particular demands placed on the immune system in early life. We review the mechanisms underlying host defense in the very young, and discuss how specific developmental demands increase the risk of particular infectious diseases. In this context, we discuss how this plasticity, i.e. the capacity to adapt to demands encountered in early life, also provides the potential to leverage protection of the young against infection and disease through a number of interventions.

Teaser

Infections in the first year of life are common and often severe. The newborn host demonstrates both quantitative and qualitative differences to the adult in nearly all aspects of immunity, which at least partially explain the increased susceptibility to infection. Here we discuss how differences in susceptibility to infection result not out of a state of immaturity, but rather reflect adaptation to the particular demands placed on the immune system in early life. We review the mechanisms underlying host defense in the very young, and discuss how specific developmental demands increase the risk of particular infectious diseases. In this context, we discuss how this plasticity, i.e. the capacity to adapt to demands observed in early life, also provides the potential to leverage protection of the young against infection and disease through a number of interventions.


http://ift.tt/2mWiXmP

Successful and Maladaptive T Cell Aging

Publication date: 21 March 2017
Source:Immunity, Volume 46, Issue 3
Author(s): Jörg J. Goronzy, Cornelia M. Weyand
Throughout life, the T cell system adapts to shifting resources and demands, resulting in a fundamentally restructured immune system in older individuals. Here we review the cellular and molecular features of an aged immune system and discuss the trade-offs inherent to these adaptive mechanisms. Processes include homeostatic proliferation that maintains compartment size at the expense of partial loss in stemness and incomplete differentiation and the activation of negative regulatory programs, which constrain effector T cell expansion and prevent increasing oligoclonality but also interfere with memory cell generation. We propose that immune failure occurs when adaptive strategies developed by the aging T cell system fail and also discuss how, in some settings, the programs associated with T cell aging culminates in a maladaptive response that directly contributes to chronic inflammatory disease.

Teaser

Throughout life, the T cell system adapts to shifting resources and demands, resulting in a fundamentally restructured immune system in older individuals. Goronzy and Weyand review the cellular and molecular features of an aged immune system and discuss the trade-offs inherent to these adaptive mechanisms and their impact in health and disease.


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The IFN-λ-IFN-λR1-IL-10Rβ Complex Reveals Structural Features Underlying Type III IFN Functional Plasticity

Publication date: 21 March 2017
Source:Immunity, Volume 46, Issue 3
Author(s): Juan L. Mendoza, William M. Schneider, Hans-Heinrich Hoffmann, Koen Vercauteren, Kevin M. Jude, Anming Xiong, Ignacio Moraga, Tim M. Horton, Jeffrey S. Glenn, Ype P. de Jong, Charles M. Rice, K. Christopher Garcia
Type III interferons (IFN-λs) signal through a heterodimeric receptor complex composed of the IFN-λR1 subunit, specific for IFN-λs, and interleukin-10Rβ (IL-10Rβ), which is shared by multiple cytokines in the IL-10 superfamily. Low affinity of IL-10Rβ for cytokines has impeded efforts aimed at crystallizing cytokine-receptor complexes. We used yeast surface display to engineer a higher-affinity IFN-λ variant, H11, which enabled crystallization of the ternary complex. The structure revealed that IL-10Rβ uses a network of tyrosine residues as hydrophobic anchor points to engage IL-10 family cytokines that present complementary hydrophobic binding patches, explaining its role as both a cross-reactive but cytokine-specific receptor. H11 elicited increased anti-proliferative and antiviral activities in vitro and in vivo. In contrast, engineered higher-affinity type I IFNs did not increase antiviral potency over wild-type type I IFNs. Our findings provide insight into cytokine recognition by the IL-10R family and highlight the plasticity of type III interferon signaling and its therapeutic potential.

Graphical abstract

image

Teaser

Using an engineered high-affinity IFN-λ, Mendoza et al. solve the structure of the IFN-λ/IFN-λR1/IL-10Rβ ternary signaling complex. The structure reveals how IL-10Rβ can act as both a cross-reactive but cytokine-specific receptor. Structure-activity relationships of engineered type I and III IFNs provide insights into enhancing interferon functional potency.


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Inflammasome Activation Triggers Caspase-1-Mediated Cleavage of cGAS to Regulate Responses to DNA Virus Infection

Publication date: 21 March 2017
Source:Immunity, Volume 46, Issue 3
Author(s): Yutao Wang, Xiaohan Ning, Pengfei Gao, Shuxian Wu, Mengyin Sha, Mengze Lv, Xiang Zhou, Juyi Gao, Run Fang, Guangxun Meng, Xiaodong Su, Zhengfan Jiang
Viral infection triggers host innate immune responses that result in the production of various cytokines including type I interferons (IFN), activation of inflammasomes, and programmed cell death of the infected cells. Tight control of inflammatory cytokine production is crucial for the triggering of an effective immune response that can resolve the infection without causing host pathology. In examining the inflammatory response of Asc−/− and Casp1−/− macrophages, we found that deficiency in these molecules resulted in increased IFN production upon DNA virus infection, but not RNA virus challenge. Investigation of the underlying mechanism revealed that upon canonical and non-canonical inflammasome activation, caspase-1 interacted with cyclic GMP-AMP (cGAMP) synthase (cGAS), cleaving it and dampening cGAS-STING-mediated IFN production. Deficiency in inflammasome signaling enhanced host resistance to DNA virus in vitro and in vivo, and this regulatory role extended to other inflammatory caspases. Thus, inflammasome activation dampens cGAS-dependent signaling, suggesting cross-regulation between intracellular DNA-sensing pathways.

Graphical abstract

image

Teaser

Type I interferons (IFN) can inhibit inflammasome activation. Wang et al. find that upon inflammasome activation, inflammatory caspases cleave cGAS and render it inactive. Their findings reveal a role for inflammasomes in the dampening of IFN activating pathways and suggest a double-negative feedback loop that regulates the output of DNA-sensing pathways.


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The Ubiquitin Binding Protein TAX1BP1 Mediates Autophagasome Induction and the Metabolic Transition of Activated T Cells

Publication date: 21 March 2017
Source:Immunity, Volume 46, Issue 3
Author(s): Michael I. Whang, Rita M. Tavares, Daniel I. Benjamin, Michael G. Kattah, Rommel Advincula, Daniel K. Nomura, Jayanta Debnath, Barbara A. Malynn, Averil Ma
During immune responses, naive T cells transition from small quiescent cells to rapidly cycling cells. We have found that T cells lacking TAX1BP1 exhibit delays in growth of cell size and cell cycling. TAX1BP1-deficient T cells exited G0 but stalled in S phase, due to both bioenergetic and biosynthetic defects. These defects were due to deficiencies in mTOR complex formation and activation. These mTOR defects in turn resulted from defective autophagy induction. TAX1BP1 binding of LC3 and GABARAP via its LC3-interacting region (LIR), but not its ubiquitin-binding domain, supported T cell proliferation. Supplementation of TAX1BP1-deficient T cells with metabolically active L-cysteine rescued mTOR activation and proliferation but not autophagy. These studies reveal that TAX1BP1 drives a specialized form of autophagy, providing critical amino acids that activate mTOR and enable the metabolic transition of activated T cells.

Graphical abstract

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Teaser

Naive T cells undergo major bioenergetic and biosynthetic metabolic transitions as they initiate proliferation in response to T cell activation. Whang et al. now show that the ubiqutin binding protein TAX1BP1 is critical for autophagic flux and L-cysteine-dependent activation of mTORC in newly activated T cells.


http://ift.tt/2mW3EdQ

Reactive Oxygen Species Localization Programs Inflammation to Clear Microbes of Different Size

Publication date: 21 March 2017
Source:Immunity, Volume 46, Issue 3
Author(s): Annika Warnatsch, Theodora-Dorita Tsourouktsoglou, Nora Branzk, Qian Wang, Susanna Reincke, Susanne Herbst, Maximiliano Gutierrez, Venizelos Papayannopoulos
How the number of immune cells recruited to sites of infection is determined and adjusted to differences in the cellular stoichiometry between host and pathogen is unknown. Here, we have uncovered a role for reactive oxygen species (ROS) as sensors of microbe size. By sensing the differential localization of ROS generated in response to microbes of different size, neutrophils tuned their interleukin (IL)-1β expression via the selective oxidation of NF-κB, in order to implement distinct inflammatory programs. Small microbes triggered ROS intracellularly, suppressing IL-1β expression to limit neutrophil recruitment as each phagocyte eliminated numerous pathogens. In contrast, large microbes triggered ROS extracellularly, amplifying IL-1β expression to recruit numerous neutrophils forming cooperative clusters. Defects in ROS-mediated microbe size sensing resulted in large neutrophil infiltrates and clusters in response to small microbes that contribute to inflammatory disease. These findings highlight the impact of ROS localization on signal transduction.

Graphical abstract

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Teaser

Inflammation recruits neutrophils to fight invading pathogens of different size. Warnatsch et al. show that reactive oxygen species localization tunes inflammation to compensate for differences in the number of neutrophils required to clear microbes of different size.


http://ift.tt/2mWbbsZ

Sensing of Bacterial Cyclic Dinucleotides by the Oxidoreductase RECON Promotes NF-κB Activation and Shapes a Proinflammatory Antibacterial State

Publication date: 21 March 2017
Source:Immunity, Volume 46, Issue 3
Author(s): Adelle P. McFarland, Shukun Luo, Fariha Ahmed-Qadri, Meghan Zuck, Elizabeth F. Thayer, Young Ah Goo, Kevin Hybiske, Liang Tong, Joshua J. Woodward
Bacterial and host cyclic dinucleotides (cdNs) mediate cytosolic immune responses through the STING signaling pathway, although evidence suggests that alternative pathways exist. We used cdN-conjugated beads to biochemically isolate host receptors for bacterial cdNs, and we identified the oxidoreductase RECON. High-affinity cdN binding inhibited RECON enzyme activity by simultaneously blocking the substrate and cosubstrate sites, as revealed by structural analyses. During bacterial infection of macrophages, RECON antagonized STING activation by acting as a molecular sink for cdNs. Bacterial infection of hepatocytes, which do not express STING, revealed that RECON negatively regulates NF-κB activation. Loss of RECON activity, via genetic ablation or inhibition by cdNs, increased NF-κB activation and reduced bacterial survival, suggesting that cdN inhibition of RECON promotes a proinflammatory, antibacterial state that is distinct from the antiviral state associated with STING activation. Thus, RECON functions as a cytosolic sensor for bacterial cdNs, shaping inflammatory gene activation via its effects on STING and NF-κB.

Graphical abstract

image

Teaser

Bacterial and host cyclic dinucleotides (cdNs) mediate cytosolic immune responses through the STING pathway. McFarland et al. find that the oxidoreductase RECON acts as a sensor for bacterial cdNs. cdN binding to RECON inhibits its enzymatic activity and promotes a proinflammatory, antibacterial state that is distinct from the antiviral state associated with STING activation.


http://ift.tt/2mWugv3

25-Hydroxycholesterol Protects Host against Zika Virus Infection and Its Associated Microcephaly in a Mouse Model

Publication date: 21 March 2017
Source:Immunity, Volume 46, Issue 3
Author(s): Chunfeng Li, Yong-Qiang Deng, Shuo Wang, Feng Ma, Roghiyh Aliyari, Xing-Yao Huang, Na-Na Zhang, Momoko Watanabe, Hao-Long Dong, Ping Liu, Xiao-Feng Li, Qing Ye, Min Tian, Shuai Hong, Junwan Fan, Hui Zhao, Lili Li, Neda Vishlaghi, Jessie E. Buth, Connie Au, Ying Liu, Ning Lu, Peishuang Du, F. Xiao-Feng Qin, Bo Zhang, Danyang Gong, Xinghong Dai, Ren Sun, Bennett G. Novitch, Zhiheng Xu, Cheng-Feng Qin, Genhong Cheng
Zika virus (ZIKV) has become a public health threat due to its global transmission and link to severe congenital disorders. The host immune responses to ZIKV infection have not been fully elucidated, and effective therapeutics are not currently available. Herein, we demonstrated that cholesterol-25-hydroxylase (CH25H) was induced in response to ZIKV infection and that its enzymatic product, 25-hydroxycholesterol (25HC), was a critical mediator of host protection against ZIKV. Synthetic 25HC addition inhibited ZIKV infection in vitro by blocking viral entry, and treatment with 25HC reduced viremia and conferred protection against ZIKV in mice and rhesus macaques. 25HC suppressed ZIKV infection and reduced tissue damage in human cortical organoids and the embryonic brain of the ZIKV-induced mouse microcephaly model. Our findings highlight the protective role of CH25H during ZIKV infection and the potential use of 25HC as a natural antiviral agent to combat ZIKV infection and prevent ZIKV-associated outcomes, such as microcephaly.

Graphical abstract

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Teaser

Zika virus (ZIKV) presents a major challenge to the global health system. Li et al. find that 25-hydroxycholesterol (25HC) inhibits ZIKV infection in monkeys and human cortical organoids and protects mice from microcephaly. 25HC has potential as a first-line antiviral agent to combat a broad array of pathogenic species, including ZIKV.


http://ift.tt/2mWivoA

Exposure to Bacterial CpG DNA Protects from Airway Allergic Inflammation by Expanding Regulatory Lung Interstitial Macrophages

Publication date: 21 March 2017
Source:Immunity, Volume 46, Issue 3
Author(s): Catherine Sabatel, Coraline Radermecker, Laurence Fievez, Genevieve Paulissen, Svetoslav Chakarov, Claudia Fernandes, Sabine Olivier, Marie Toussaint, Dimitri Pirottin, Xue Xiao, Pascale Quatresooz, Jean-Claude Sirard, Didier Cataldo, Laurent Gillet, Hicham Bouabe, Christophe J. Desmet, Florent Ginhoux, Thomas Marichal, Fabrice Bureau
Living in a microbe-rich environment reduces the risk of developing asthma. Exposure of humans or mice to unmethylated CpG DNA (CpG) from bacteria reproduces these protective effects, suggesting a major contribution of CpG to microbe-induced asthma resistance. However, how CpG confers protection remains elusive. We found that exposure to CpG expanded regulatory lung interstitial macrophages (IMs) from monocytes infiltrating the lung or mobilized from the spleen. Trafficking of IM precursors to the lung was independent of CCR2, a chemokine receptor required for monocyte mobilization from the bone marrow. Using a mouse model of allergic airway inflammation, we found that adoptive transfer of IMs isolated from CpG-treated mice recapitulated the protective effects of CpG when administered before allergen sensitization or challenge. IM-mediated protection was dependent on IL-10, given that Il10−/− CpG-induced IMs lacked regulatory effects. Thus, the expansion of regulatory lung IMs upon exposure to CpG might underlie the reduced risk of asthma development associated with a microbe-rich environment.

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Exposure to unmethylated CpG DNA (CpG) from bacteria is associated with a reduced risk of developing asthma. Sabatel et al. find that CpG exposure leads to higher numbers of lung interstitial macrophages that prevent allergic inflammation through the production of the regulatory cytokine interleukin-10.


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Brain Ischemia Suppresses Immunity in the Periphery and Brain via Different Neurogenic Innervations

Publication date: 21 March 2017
Source:Immunity, Volume 46, Issue 3
Author(s): Qiang Liu, Wei-Na Jin, Yaou Liu, Kaibin Shi, Haoran Sun, Fang Zhang, Chao Zhang, Rayna J. Gonzales, Kevin N. Sheth, Antonio La Cava, Fu-Dong Shi
Brain ischemia inhibits immune function systemically, with resulting infectious complications. Whether in stroke different immune alterations occur in brain and periphery and whether analogous mechanisms operate in these compartments remains unclear. Here we show that in patients with ischemic stroke and in mice subjected to middle cerebral artery occlusion, natural killer (NK) cells display remarkably distinct temporal and transcriptome profiles in the brain as compared to the periphery. The activation of catecholaminergic and hypothalamic-pituitary-adrenal axis leads to splenic atrophy and contraction of NK cell numbers in the periphery through a modulated expression of SOCS3, whereas cholinergic innervation-mediated suppression of NK cell responses in the brain involves RUNX3. Importantly, pharmacological or genetic ablation of innervation preserved NK cell function and restrained post-stroke infection. Thus, brain ischemia compromises NK cell-mediated immune defenses through mechanisms that differ in the brain versus the periphery, and targeted inhibition of neurogenic innervation limits post-stroke infection.

Teaser

Liu and colleagues demonstrate that brain ischemia shapes innate cellular immune responses in the periphery and the brain through different neurogenic and intracellular pathways. Targeted modulation of neurogenic innervation is capable of inhibiting post-stroke infection.


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Dendritic Cells Display Subset and Tissue-Specific Maturation Dynamics over Human Life

Publication date: 21 March 2017
Source:Immunity, Volume 46, Issue 3
Author(s): Tomer Granot, Takashi Senda, Dustin J. Carpenter, Nobuhide Matsuoka, Joshua Weiner, Claire L. Gordon, Michelle Miron, Brahma V. Kumar, Adam Griesemer, Siu-Hong Ho, Harvey Lerner, Joseph J.C. Thome, Thomas Connors, Boris Reizis, Donna L. Farber
Maturation and migration to lymph nodes (LNs) constitutes a central paradigm in conventional dendritic cell (cDC) biology but remains poorly defined in humans. Using our organ donor tissue resource, we analyzed cDC subset distribution, maturation, and migration in mucosal tissues (lungs, intestines), associated lymph nodes (LNs), and other lymphoid sites from 78 individuals ranging from less than 1 year to 93 years of age. The distribution of cDC1 (CD141hiCD13hi) and cDC2 (Sirp-α+CD1c+) subsets was a function of tissue site and was conserved between donors. We identified cDC2 as the major mature (HLA-DRhi) subset in LNs with the highest frequency in lung-draining LNs. Mature cDC2 in mucosal-draining LNs expressed tissue-specific markers derived from the paired mucosal site, reflecting their tissue-migratory origin. These distribution and maturation patterns were largely maintained throughout life, with site-specific variations. Our findings provide evidence for localized DC tissue surveillance and reveal a lifelong division of labor between DC subsets, with cDC2 functioning as guardians of the mucosa.

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Dendritic cells (DCs) function as tissue sentinels, but this role is difficult to study in humans. In this issue of Immunity, Granot et al. show through analysis of lymphoid and mucosal tissues that human DC maturation is tissue specific, associated with migration phenotypes, and predominantly observed among the cDC2 subset.


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Stable subcutaneous cartilage regeneration of bone marrow stromal cells directed by chondrocyte sheet

Publication date: Available online 22 March 2017
Source:Acta Biomaterialia
Author(s): Dan Li, Lian Zhu, Yu Liu, Zongqi Yin, Yi Liu, Fangjun Liu, Aijuan He, Shaoqing Feng, Yixin Zhang, Zhiyong Zhang, Wenjie Zhang, Wei Liu, Yilin Cao, Guangdong Zhou
In vivo niche plays an important role in regulating differentiation fate of stem cells. Due to lack of proper chondrogenic niche, stable cartilage regeneration of bone marrow stromal cells (BMSCs) in subcutaneous environments is always a great challenge. This study explored the feasibility that chondrocyte sheet created chondrogenic niche retained chondrogenic phenotype of BMSC engineered cartilage (BEC) in subcutaneous environments. Porcine BMSCs were seeded into biodegradable scaffolds followed by 4 weeks of chondrogenic induction in vitro to form BEC, which were wrapped with chondrocyte sheets (Sheet group), acellular small intestinal submucosa (SIS, SIS group), or nothing (Blank group) respectively and then implanted subcutaneously into nude mice to trace the maintenance of chondrogenic phenotype. The results showed that all the constructs in Sheet group displayed typical cartilaginous features with abundant lacunae and cartilage specific matrices deposition. These samples became more mature with prolonged in vivo implantation, and few signs of ossification were observed at all time points except for one sample that had not been wrapped completely. Cell labeling results in Sheet group further revealed that the implanted BEC directly participated in cartilage formation. Samples in both SIS and Blank groups mainly showed ossified tissue at all time points with partial fibrogenesis in a few samples. These results suggested that chondrocyte sheet could create a chondrogenic niche for retaining chondrogenic phenotype of BEC in subcutaneous environment and thus provide a novel research model for stable ectopic cartilage regeneration based on stem cells.Statement of significanceIn vivo niche plays an important role in directing differentiation fate of stem cells. Due to lack of proper chondrogenic niche, stable cartilage regeneration of bone marrow stromal cells (BMSCs) in subcutaneous environments is always a great challenge. The current study demonstrated that chondrocyte sheet generated by high-density culture of chondrocytes in vitro could cearte a chondrogenic niche in subcutaneous environment and efficiently retain the chondrogenic phenotype of in vitro BMSC engineered cartilage (vitro-BEC). Furthermore, cell tracing results revealed that the regenerated cartilage mainly derived from the implanted vitro-BEC. The current study not only proposes a novel research model for microenvironment simulation but also provides a useful strategy for stable ectopic cartilage regeneration of stem cells.

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3D Printing for the design and fabrication of polymer-based gradient scaffolds

Publication date: Available online 22 March 2017
Source:Acta Biomaterialia
Author(s): Laura G. Bracaglia, Brandon T. Smith, Emma Watson, Navein Arumugasaamy, Antonios G. Mikos, John P. Fisher
To accurately mimic the native tissue environment, tissue engineered scaffolds often need to have a highly controlled and varied display of three-dimensional (3D) architecture and geometrical cues. Additive manufacturing in tissue engineering has made possible the development of complex scaffolds that mimic the native tissue architectures. As such, architectural details that were previously unattainable or irreproducible can now be incorporated in an ordered and organized approach, further advancing the structural and chemical cues delivered to cells interacting with the scaffold. This control over the environment has given engineers the ability to unlock cellular machinery that is highly dependent upon the intricate heterogeneous environment of native tissue. Recent research into the incorporation of physical and chemical gradients within scaffolds indicates that integrating these features improves the function of a tissue engineered construct. This review covers recent advances on techniques to incorporate gradients into polymer scaffolds through additive manufacturing and evaluate the success of these techniques. As covered here, to best replicate different tissue types, one must be cognizant of the vastly different types of manufacturing techniques available to create these gradient scaffolds. We review the various types of additive manufacturing techniques that can be leveraged to fabricate scaffolds with heterogeneous properties and discuss methods to successfully characterize them.Statement of significanceAdditive manufacturing techniques have given tissue engineers the ability to precisely recapitulate the native architecture present within tissue. In addition, these techniques can be leveraged to create scaffolds with both physical and chemical gradients. This work offers insight into several techniques that can be used to generate graded scaffolds, depending on the desired gradient. Furthermore, it outlines methods to determine if the designed gradient was achieved. This review will help to condense the abundance of information that has been published on the creation and characterization of gradient scaffolds and to provide a single review discussing both methods for manufacturing gradient scaffolds and evaluating the establishment of a gradient.

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Enhancing Oligodendrocyte Differentiation by Transient Transcription Activation via DNA Nanoparticle-Mediated Transfection

Publication date: Available online 23 March 2017
Source:Acta Biomaterialia
Author(s): Xiaowei Li, Stephany Y. Tzeng, Camila Gadens Zamboni, Vassilis E. Koliatsos, Guo-li Ming, Jordan J. Green, Hai-Quan Mao
Current approaches to derive oligodendrocytes from human pluripotent stem cells (hPSCs) need extended exposure of hPSCs to growth factors and small molecules, which limits their clinical application because of the lengthy culture time required and low generation efficiency of myelinating oligodendrocytes. Compared to extrinsic growth factors and molecules, oligodendrocyte differentiation and maturation can be more effectively modulated by regulation of the cell transcription network. In the developing central nervous system (CNS), two basic helix-loop-helix transcription factors, Olig1 and Olig2, are decisive in oligodendrocyte differentiation and maturation. Olig2 plays a critical role in the specification of oligodendrocytes and Olig1 is crucial in promoting oligodendrocyte maturation. Recently viral vectors have been used to overexpress Olig2 and Olig1 in neural stem/progenitor cells (NSCs) to induce the maturation of oligodendrocytes and enhance the remyelination activity in vivo. Because of the safety issues with viral vectors, including the insertional mutagenesis and potential tumor formation, non-viral transfection methods are preferred for clinical translation. Here we report a poly(β-amino ester) (PBAE)-based nanoparticle transfection method to deliver Olig1 and Olig2 into human fetal tissue-derived NSCs and demonstrate efficient oligodendrocyte differentiation following transgene expression of Olig1 and Olig2. This approach is potentially translatable for engineering stem cells to treat injured or diseased CNS tissues.Statement of SignificanceCurrent approaches to derive oligodendrocytes from human pluripotent stem cells (hPSCs) need extended exposure of hPSCs to growth factors and small molecules, which limits their clinical application because of the lengthy culture time required and low generation efficiency of myelinating oligodendrocytes. We described a new approach to enhance oligodendrocyte differentiation through nanoparticle-mediated transcription modulation. We tested an effective transfection method using cell-compatible poly (β-amino ester) (PBAE)/DNA nanoparticles as gene carrier to deliver transcription factor Olig1 and Olig2 into human fetal tissue-derived neural stem/progenitor cells, and showed efficient oligodendrocyte differentiation following transgene expression of Olig1 and Olig2. We believe that this translatable approach can be applied to many other cell-based regenerative therapies as well.

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What is a nutritious snack? Level of processing and macronutrient content influences young adults' perceptions

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Publication date: 1 July 2017
Source:Appetite, Volume 114
Author(s): Nienke M De Vlieger, Clare Collins, Tamara Bucher
Snacking has become more prevalent in developed countries. While poor food choices pose health risks, nutritious choices contribute important nutrients to overall dietary intakes. Young adults consumer snacks frequently and nutritious choices should be promoted among this group.However, how young adults define the term 'nutritious' currently and how they evaluate the nutritiousness of various snack foods required further investigation. The current study used a mixed methods design with 115 young adults invited to sort 32 commonly available snack foods into a line ranging from 'not nutritious' to 'very nutritious'. The sorting data was analysed by hierarchical cluster analysis and multi-dimensional scaling (MDS) analysis. Participants were also asked to define the word 'nutritious', with definitions then categorized and number of counts per category analysed. Predictors of perceived snack nutritiousness were sugar (β = −0.45, P < 0.005), fat (β = −0.43, P < 0.05), nut (β = 0.45, P < 0.05) and fruit/vegetable (β = 0.33, P < 0.05) content. Level of food processing was significantly related to perceived nutritiousness (β = 0.79, P=<0.05). The terms given within the definitions most frequently were: 'vitamins' (40%), 'good for body/body needs' (40%), 'minerals' (39%), 'low in sugars' (36%), 'protein' (32%), 'healthy' (28%) and 'long lasting source of energy' (27%). Results of the current study provide first insight into how young adults interpret the term 'nutritious'. This could help in the design of more effective nutrition education materials and food product labels to guide healthy choices in this age group.



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Eating dependence and weight gain; no human evidence for a ‘sugar-addiction’ model of overweight

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Publication date: 1 July 2017
Source:Appetite, Volume 114
Author(s): C. Rob Markus, Peter J. Rogers, Fred Brouns, Robbie Schepers
Background and aimsThere is an increasing societal concern that consumption of specific foods such as sugar might become 'addictive' and, hence, promote weight gain. Claims about the addictiveness of sugar however are based largely on findings from few animal studies, whereas there is a lack of direct human evidence for symptoms of sugar-related substance dependence. The current study examined in a large sample of human participants whether foods mainly containing sugar in particular might cause 'addiction-like' problems that meet clinical DSM criteria for substance dependence, and, also whether in turn this relates to body weight and negative affectivity (depressed mood).MethodsIn a cross-sectional study, n = 1495 university students from a variety of faculties were assessed for DSM-related signs of food addiction for particular food categories (YFAS), and, also BMI and negative affectivity.ResultsResults revealed that from the total sample, 95% experienced at least one symptom of food dependence and 12.6% met the YFAS classification for 'food addiction' as related to DSM-IV criteria. The majority of respondents experienced these problems for combined high-fat savoury (30%) and high-fat sweet (25%) foods, whereas only a minority experienced such problems for low-fat/savoury (2%) and mainly sugar-containing foods (5%). Overweight correlated only with addictive-like problems for high-fat savoury and high-fat sweet foods (P < 0.0001), while this was not found for foods mainly containing sugar.ConclusionThe current findings indicate that sugary foods contribute minimally to 'food dependence' and increased risk of weight gain. Instead, they are consistent with the current scientific notion that food energy density, and the unique individual experience of eating, plays an important role in determining the reward value of food and promoting excessive energy intake.



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Transformation Diffusion Reconstruction of Three-Dimensional Histology Volumes from Two-Dimensional Image Stacks

Publication date: Available online 23 March 2017
Source:Medical Image Analysis
Author(s): Ramón Casero, Urszula Siedlecka, Matthew Gibb, Jürgen E. Schneider, Peter Kohl, Vicente Grau
Traditional histology is the gold standard for tissue studies, but it is intrinsically reliant on two-dimensional (2D) images. Study of volumetric tissue samples such as whole hearts produces a stack of misaligned and distorted 2D images that need to be reconstructed to recover a congruent volume with the original sample's shape. In this paper, we develop a mathematical framework called Transformation Diffusion (TD) for stack alignment refinement as a solution to the heat diffusion equation. This general framework does not require contour segmentation, is independent of the registration method used, and is trivially parallelizable. After the first stack sweep, we also replace registration operations by operations in the space of transformations, several orders of magnitude faster and less memory-consuming. Implementing TD with operations in the space of transformations produces our Transformation Diffusion Reconstruction (TDR) algorithm, applicable to general transformations that are closed under inversion and composition. In particular, we provide formulas for translation and affine transformations. We also propose an Approximated TDR (ATDR) algorithm that extends the same principles to tensor-product B-spline transformations. Using TDR and ATDR, we reconstruct a full mouse heart at pixel size 0.92 µm x 0.92 µm, cut 10 µm thick, spaced 20 µm (84G). Our algorithms employ only local information from transformations between neighboring slices, but the TD framework allows theoretical analysis of the refinement as applying a global Gaussian low-pass filter to the unknown stack misalignments. We also show that reconstruction without an external reference produces large shape artifacts in a cardiac specimen while still optimizing slice-to-slice alignment. To overcome this problem, we use a pre-cutting blockface imaging process previously developed by our group that takes advantage of Brewster's angle and a polarizer to capture the outline of only the topmost layer of wax in the block containing embedded tissue for histological sectioning.

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Effects of peer mentoring on self-efficacy and hospital readmission following inpatient rehabilitation of individuals with spinal cord injury: a randomized controlled trial

Publication date: Available online 23 March 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Julie Gassaway, Michael L. Jones, W. Mark Sweatman, Minna Hong, Peter Anziano, Karen DeVault
ObjectiveInvestigate the effect of intensive peer mentoring on patient reported outcomes of self-efficacy and unplanned hospital readmissions for persons with spinal cord injury/disease (SCI/D) within the first 6 months after discharge from inpatient rehabilitationDesignRandomized controlled trial;SettingNon-profit inpatient rehabilitation hospital specializing in care of persons with SCI/D and brain injuryParticipants158 patients admitted to the SCI rehabilitation program whose discharge location was a community setting. Participants (51% paraplegia and 49% tetraplegia) were 73% Caucasian and 77% male with a mean age of 38.InterventionsParticipants in the experimental group received initial consult/introduction with a peer support program liaison and were assigned a peer mentor, who met with the participant weekly throughout the inpatient stay and made weekly contact by phone, email or in person for 90 days post-discharge. Participants also were encouraged to participate in regularly scheduled peer support activities. Control group participants were introduced to peer support and provided services only upon request.Main Outcome Measure(s)General Self-efficacy Scale (adapted to SCI/D), project-developed community integration self-efficacy scale, and patient-reported unplanned rehospitalizations.ResultsGrowth rate for self-efficacy in the first 6 months post-discharge was significantly higher for experimental group participants compared to control group participants. Experimental group participants also had significantly fewer unplanned hospital days.ConclusionThis study provides evidence that individuals receiving intensive peer mentoring during and following rehabilitation for SCI/D demonstrate greater gains in self-efficacy over time and have fewer days of unplanned rehospitalization in the first 180 days post-discharge. More research is needed to examine the long-term effects of this intervention on healthcare utilization and the relationship between improved health and patient-reported quality of life outcomes.



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“Resistance training for muscle weakness in multiple sclerosis: direct versus contralateral approach in individuals with ankle dorsiflexors’ disparity in strength.”

Publication date: Available online 23 March 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Andrea Manca, Maria Paola Cabboi, Daniele Dragone, Francesca Ginatempo, Enzo Ortu, Edoardo Rosario De Natale, Beniamina Mercante, Giovanni Mureddu, Guido Bua, Franca Deriu
ObjectiveTo compare effects of contralateral strength training (CST) versus direct strength training (DST) of the more-affected ankle dorsiflexors on muscle performance and clinical-functional outcomes in people with multiple sclerosis (MS) exhibiting inter-limb strength asymmetry.DesignRandomized controlled trialParticipantsIndividuals with relapsing-remitting MS and mild-to-moderate disability (EDSS≤6) presenting with ankle dorsiflexors' strength disparity.InterventionParticipants were randomly assigned to a CST (n=15) or DST (n=15) group performing a 6-week maximal-intensity strength training of the less- or more-affected dorsiflexors, respectively.Main Outcome MeasuresMaximal strength, endurance to fatigue and mobility outcomes were assessed before (PRE), at the intervention end (POST) and at 12-week follow-up. Strength and fatigue parameters were measured after 3 weeks of training (mid-intervention).ResultsIn the more-affected limb of both groups, PRE-to-POST significant increases in maximal strength (p≤0.006) and fatigue endurance (p≤0.04) were detected along with consistent retention of these improvements at follow-up (p≤0.04). At mid-intervention the DST group showed significant improvements (p≤0.002), with no further increase at the POST, despite training continuation. Conversely, the CST group showed non-significant strength gains, increasing to significance at the POST (p≤0.003). In both groups, significant PRE-to-POST improvements in mobility outcomes (p≤0.03), not retained at follow-up, were observed.ConclusionsAfter 6 weeks of training, CST proved as effective as DST in enhancing performance of the more-affected limb with a different time-course, which may have practical implications in management of severely weakened limbs where DST is not initially possible.



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Hippocampal BDNF overexpression or microR124a silencing reduces anxiety- and autism-like behaviors in rats

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Publication date: 30 May 2017
Source:Behavioural Brain Research, Volume 326
Author(s): Amine Bahi
MicroRNA124a (miR124a) has emerged recently as a key player for multiple neuropsychiatric disorders including depression, anxiety, alcoholism, and cocaine addiction. Although we have previously reported that miR124a and its target the brain-derived neutrophic factor (BDNF) play an important role in autism-like behaviors, the molecular and behavioral dysfunctions remain unknown. The aim of this study was to understand the effects of sustained decreases in miR124a and increases of BDNF in the dentate gyrus (DG) on neonatal isolation-induced anxiety-and autism like behaviors in rats. Here we report that lentiviral-mediated silencing of miR124a in the adult DG attenuated neonatal isolation-induced anxiety-like behavior in the elevated plus maze (EPM) and open-field (OF) tests. Also, miR124a silencing decreased autism-like phenotype in the marble burying test (MBT), self-grooming (SG), and social interaction tests. Pearson's correlations demonstrated that high levels of BDNF, a direct target of miR124a, were negatively correlated with miR124a expression. Interestingly, viral-mediated BDNF overexpression in the DG also reversed the neonatal isolation-induced anxiety-and autism like phenotypes. Collectively, these findings suggest that miR124a, through its target BDNF, may influence neonatal isolation-induced anxiety-and autism like behaviors. In conclusion, these results do support the hypothesis that miR124a in discrete hippocampal areas contributes to anxiety- and autism-like behaviors and may be involved in the neuroadaptations underlying the development of autism spectrum disorders as a persistent and lasting condition, and therefore provide a clearer mechanistic framework for understanding the physiopathology of such psychiatric illnesses.



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FGFR a promising druggable target in cancer: molecular biology and new drugs

Publication date: Available online 23 March 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Rut Porta, Roberto Borea, Andreia Coelho, Shahnavaj Khan, Antonio Araujo, Pablo Reclusa, Tindara Franchina, Nele Van Der Steen, Peter Van Dam, Jose Ferri, Rafael Sirera, Aung Naing, David Hong, Christian Rolfo
IntroductionThe Fibroblast Growth Factor Receptor (FGFR) family consists of Tyrosine Kinase Receptors (TKR) involved in several biological functions. Recently, alterations of FGFR have been reported to be important for progression and development of several cancers. In this setting, different studies are trying to evaluate the efficacy of different therapies targeting FGFR.Areas CoveredThis review summarizes the current status of treatments targeting FGFR, focusing on the trials that are evaluating the FGFR profile as inclusion criteria: Multi-Target, Pan-FGFR Inhibitors and anti-FGF (Fibroblast Growth Factor)/FGFR Monoclonal Antibodies.Expert opinionMost of the TKR share intracellular signaling pathways; therefore, cancer cells tend to overcome the inhibition of one tyrosine kinase receptor by activating another. The future of TKI (Tyrosine Kinase Inhibitor) therapy will potentially come from multi-targeted TKIs that target different TKR simultaneously.It is crucial to understand the interaction of the FGF-FGFR axis with other known driver TKRs. Based on this,it is possible to develop therapeutic strategies targeting multiple connected TKRs at once. One correct step in this direction is the reassessment of multi target inhibitors considering the FGFR status of the tumor. Another opportunity arises from assessing the use of FGFR TKI on patients harboring FGFR alterations.



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Academic Remediation

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Publication date: Available online 23 March 2017
Source:Academic Radiology
Author(s): Carol M. Rumack, Jeannette Guerrasio, Alicia Christensen, Eva M. Aagaard
At our institution, we have developed a remediation team of strong, focused experts who help us with struggling learners in making the diagnosis and then coaching on their milestone deficits. It is key for all program directors to recognize struggling residents because early recognition and intervention gives the resident the best chance of success.



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A Tribute to Mark Richard Robbin, MD

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Publication date: Available online 23 March 2017
Source:Academic Radiology
Author(s): Mark E. Mullins, Pablo R. Ros




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Study of trace metal imbalances in the blood, scalp hair and nails of oral cancer patients from Pakistan

Publication date: 1 September 2017
Source:Science of The Total Environment, Volumes 593–594
Author(s): Muhammad Abdul Qayyum, Munir H. Shah
Oral cancer is an important cause of cancer morbidity and mortality globally and exposure to trace metals alongside tobacco, alcohol and HPV are the important etiological factors in its development. Selected essential and toxic trace metals (Cd, Cr, Cu, Fe, Mn, Ni, Pb and Zn) were measured in the blood, scalp hair and nails of oral cancer patients and counterpart controls by atomic absorption spectrometry. Mean concentrations of Cd, Ni and Pb were found to be significantly higher (p<0.05) and those of Cu, Fe and Zn were considerably lower in the blood, scalp hair and nails of the patients than the controls. Most of the metal concentrations exhibited higher dispersion and asymmetry in the blood, scalp hair and nails of the patients compared with the controls. The correlation study revealed significantly diverse relationships among the metals in blood, scalp hair and nails of both donor groups. Variations in the metal levels were also noted for various stages (I, II, III & IV) as well as the types (adenocarcinoma and squamous cell carcinoma) of oral cancer. Multivariate cluster analysis of the metal levels in the patients were also significantly dissimilar than the controls. The study evidenced considerably divergent variations in the metal levels in oral cancer patients in comparison with the controls.

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