Publication date: Available online 5 August 2017
Source:Pathology - Research and Practice
Author(s): T.B. de Lima, A.H.R. Paz, P.V. Rados, R. Leonardi, P. Bufo, M.C. Pedicillo, A. Santoro, S. Cagiano, G. Aquino, G. Botti, G. Pannone, F. Visioli
ObjectiveThe aim of this study was to evaluate the levels of autophagy in oral leukoplakia and squamous cell carcinoma and to correlate with clinical pathological features, as well as, the evolution of these lesions.Methodology7 Normal oral mucosa, 51 oral leukoplakias, and 120 oral squamous cell carcinomas (OSCC) were included in the study. Histological sections of the mucosa and leukoplakias were evaluated throughout their length, while the carcinomas were evaluated using Tissue Microarray. After the immunohistochemical technique, LC3-II positive cells were quantified in the different epithelial layers of the mucosa and leukoplakias and in the microarrays of the squamous cell carcinomas. The correlation between positive cells with the different clinical-pathological variables and with the evolution of the lesions was tested using the t test, ANOVA, and Kaplan-Meier survival analysis.ResultsWe observed increased levels of autophagy in the oral squamous cell carcinomas (p <0.001) in relation to the other groups, but without any association with poorer evolution or survival of these patients. Among the leukoplakias, we observed a higher percentage of positive cells in the intermediate layer of the dysplastic leukoplakias (p=0.0319) and in the basal layer of lesions with poorer evolution (p=0.0133).ConclusionThe levels of autophagy increased during the process of oral carcinogenesis and are correlated with poorer behavior of the leukoplakias.
http://ift.tt/2ud5xXQ
Σάββατο 5 Αυγούστου 2017
Autophagy Analysis in Oral Carcinogenesis
Black hollow silicon oxide nanoparticles as highly efficient photothermal agents in the second near-infrared window for in vivo cancer therapy
Source:Biomaterials, Volume 143
Author(s): Xujiang Yu, Kai Yang, Xiaoyuan Chen, Wanwan Li
Semiconductor nanoparticles with localized surface plasmon resonance (LSPR) have gained increasing interest due to their potential for use in nanomedicine, particularly in the area of cancer photothermal therapy. In this study, we have synthesized non-stoichiometric hollow silicon oxide nanoparticles (H-SiOx NPs) using a magnesiothermic reduction process. The black NPs generated a desired LSPR in the second near-infrared (NIR-II) window, as was demonstrated by a photothermal conversion efficiency of up to 48.6% at 1064 nm. Such an efficiency is the highest reported among the noble metal and semiconductor-based NPs as NIR-II PTT photothermal agents. In addition, H-SiOx NPs exhibited excellent in vivo photoacoustic (PA) imaging properties, and thus can be used for highly efficient in vivo cancer treatment via irradiation with a 1064 nm laser, even at 0.6 W cm−2. The findings described are the first to demonstrate the existence of LSPR in non-stoichiometric silicon-based nanoparticles with a low-toxicity degradation pathway for in vivo application, and provide new insights towards understanding the role of new semiconductor nanoparticles in nanomedicine.
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Activation of brain glucose metabolism ameliorating cognitive impairment in APP/PS1 transgenic mice by electroacupuncture
Publication date: November 2017
Source:Free Radical Biology and Medicine, Volume 112
Author(s): Weilin Liu, Peiyuan Zhuo, Long Li, Hao Jin, Bingbing Lin, Yingzheng Zhang, Shengxiang Liang, Jie Wu, Jia Huang, Zhifu Wang, Ruhui Lin, Lidian Chen, Jing Tao
An essential feature of Alzheimer's disease (AD) is implicated in brain energy metabolic impairment that is considered underlying pathogenesis of cognitive impairment. Therefore, therapeutic interventions to allay cognitive deficits that target energy metabolism may be an efficacy strategy in AD. In this study, we found that electroacupuncture (EA) at the DU20 acupoint obviously increased glucose metabolism in specific brain regions such as cortex, hippocampus, cingulate gyrus, basal forebrain septum, brain stem, and cerebellum in APP/PS1 transgenic mice by animal 18F-Fluoro-2-deoxy-D-Glucose (18F-FDG)/positron emission tomography (PET) imaging, accompanied by cognitive improvements in the spatial reference learning and memory and memory flexibility and novel object recognition performances. Further evidence shown energy metabolism occurred in neurons or non-neuronal cells of the cortex and hippocampus in terms of the co-location of GLUT3/NeuN and GLUT1/GFAP. Simultaneously, metabolic homeostatic factors were critical for glucose metabolism, including phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and AKT serine/threonine kinase. Furthermore, EA-induced phosphorylated AMPK and AKT inhibited the phosphorylation level of the mammalian target of rapamycin (mTOR) to decrease the accumulation of amyloid-beta (Aβ) in the cortex and hippocampus. These findings are concluded that EA is a potential therapeutic target for delaying memory decline and Aβ deposition of AD. The AMPK and AKT are implicated in the EA-induced cortical and hippocampal energy metabolism, which served as a contributor to improving cognitive function and Aβ deposition in a transgenic mouse model of AD.
Graphical abstract
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Euphorbia factor L1 inhibits osteoclastogenesis by regulating cellular redox status and induces Fas-mediated apoptosis in osteoclast
Publication date: November 2017
Source:Free Radical Biology and Medicine, Volume 112
Author(s): Seong-Eun Hong, Jiae Lee, Dong-Hyun Seo, Hye In Lee, Doo Ri Park, Gong-Rak Lee, You-Jin Jo, Narae Kim, Minjung Kwon, Hansem Shon, Eun Kyoung Seo, Han-Sung Kim, Soo Young Lee, Woojin Jeong
Excessive bone resorption caused by increased osteoclast number or activity leads to a variety of bone diseases including osteoporosis, rheumatoid arthritis and periodontitis. Thus, the therapeutic strategy for these diseases has been focused primarily on the inhibition of osteoclast formation and function. This study shows that euphorbia factor L1 (EFL1), a diterpenoid isolated from Euphorbia lathyris, inhibited osteoclastogenesis and induced osteoclast apoptosis. EFL1 suppressed osteoclast formation and bone resorption at both initial and terminal differentiation stages. EFL1 inhibited receptor activator of NF-κB ligand (RANKL)-induced NFATc1 induction with attenuated NF-κB activation and c-Fos expression. EFL1 decreased the level of reactive oxygen species by scavenging them or activating Nrf2, and inhibited PGC-1β that regulates mitochondria biogenesis. In addition, EFL1 induced apoptosis in differentiated osteoclasts by increasing Fas ligand expression followed by caspase activation. Moreover, EFL1 inhibited inflammation-induced bone erosion and ovariectomy-induced bone loss in mice. These findings suggest that EFL1 inhibits osteoclast differentiation by regulating cellular redox status and induces Fas-mediated apoptosis in osteoclast, and may provide therapeutic potential for preventing or treating bone-related diseases caused by excessive osteoclast.
Graphical abstract
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Importance of NADPH oxidase-mediated redox signaling in the detrimental effect of CRP on pancreatic insulin secretion
Publication date: November 2017
Source:Free Radical Biology and Medicine, Volume 112
Author(s): Pei-Chi Chan, Ya-Chin Wang, Yi-Ling Chen, Wan-Ning Hsu, Yu-Feng Tian, Po-Shiuan Hsieh
Elevations in C-reactive protein (CRP) levels are positively correlated with the progress of type 2 diabetes mellitus. However, the effect of CRP on pancreatic insulin secretion is unknown. Here, we showed that purified human CRP impaired insulin secretion in isolated mouse islets and NIT-1 insulin-secreting cells in dose- and time-dependent manners. CRP increased NADPH oxidase-mediated ROS (reactive oxygen species) production, which simultaneously promoted the production of nitrotyrosine (an indicator of RNS, reactive nitrogen species) and TNFα, to diminish cell viability, insulin secretion in islets and insulin-secreting cells. These CRP-mediated detrimental effects on cell viability and insulin secretion were significantly reversed by adding NAC (a potent antioxidant), apocynin (a selective NADPH oxidase inhibitor), L-NAME (a non-selective nitric oxide synthase (NOS) inhibitor), aminoguanidine (a selective iNOS inhibitor), PDTC (a selective NFκB inhibitor) or Enbrel (an anti-TNFα fusion protein). However, CRP-induced ROS production failed to change after adding L-NAME, aminoguanidine or PDTC. In isolated islets and NIT-1 cells, the elevated nitrotyrosine contents by CRP pretreatment were significantly suppressed by adding L-NAME but not PDTC. Conversely, CRP-induced increases in TNF-α production were significantly reversed by administration of PDTC but not L-NAME. In addition, wild-type mice treated with purified human CRP showed significant decreases in the insulin secretion index (HOMA-β cells) and the insulin stimulation index in isolated islets that were reversed by the addition of L-NAME, aminoguanidine or NAC. It is suggested that CRP-activated NADPH-oxidase redox signaling triggers iNOS-mediated RNS and NFκB-mediated proinflammatory cytokine production to cause β cell damage in state of inflammation.
Graphical abstract
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Epigenetic regulation of EC-SOD expression in aging lung fibroblasts: Role of histone acetylation
Publication date: November 2017
Source:Free Radical Biology and Medicine, Volume 112
Author(s): Jesse Roman, Jianxin Zhu, Jeffrey D. Ritzenthaler, Igor N. Zelko
Lung disorders characterized by fibroproliferation and excessive deposition of extracellular matrices occur in late adulthood, and their pathological manifestations become more prominent with aging. The exact mechanisms linking aging and fibroproliferative disorders are unknown, but increased oxidative stress resulting in the accumulation of damaged proteins, DNA, and lipids is considered a major factor. In the lung, and especially in the pulmonary fibroblasts, the extracellular superoxide dismutase (EC-SOD) is a major antioxidant enzyme that has been implicated in pulmonary fibrosing disorders, among others. Here, we investigate the regulation of EC-SOD in pulmonary lung fibroblasts derived from young (up to 3 month) and old (24 month) C57BL6 mice. We found that old fibroblasts have marginally elevated levels of reactive oxidant species (ROS), which coincides with attenuated expression a number of antioxidant enzymes including EC-SOD. Exposure of old fibroblasts to the DNA methyltransferase inhibitor 5-aza-dC did not restore expression of EC-SOD. On the other hand, repression of EC-SOD expression was associated with deacetylation of lysine 9 on histone H3 and lysines 5, 8, 12 and 16 on histone H4 located at the gene promoter. Interestingly, the repressive tri-methylation of lysine 27 on histone H3 was elevated in old compared to young fibroblasts. In addition, exposure of old lung fibroblasts to HDAC class 1 and class 2 inhibitors restored EC-SOD expression to the level observed in young fibroblasts. While the exact mechanism of age-dependent downregulation of EC-SOD is yet to be defined, our studies indicate a potential role of epigenetic mechanisms including histone deacetylation in this process.
Graphical abstract
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Intermittent hypoxia-induced cardiomyopathy and its prevention by Nrf2 and metallothionein
Publication date: November 2017
Source:Free Radical Biology and Medicine, Volume 112
Author(s): Shanshan Zhou, Xia Yin, Jingpeng Jin, Yi Tan, Daniel J. Conklin, Ying Xin, Zhiguo Zhang, Weixia Sun, Taixing Cui, Jun Cai, Yang Zheng, Lu Cai
The mechanism for intermittent hypoxia (IH)-induced cardiomyopathy remains obscure. We reported the prevention of acute and chronic IH-induced cardiac damage by selective cardiac overexpression of metallothionein (MT). Herein we defined that MT-mediated protection from IH-cardiomyopathy is via activation of nuclear factor erythroid 2-related factor 2 (Nrf2), a critical redox-balance controller in the body. For this, mice were exposed to IH for 3 days (acute) or 4 or 8 weeks (chronic). Cardiac Nrf2 and MT expression in response to IH were significantly increased acutely yet decreased chronically. Interestingly, cardiac overexpression (Nrf2-TG) or global deletion of the Nrf2 gene (Nrf2-KO) made mice highly resistant or highly susceptible, respectively, to IH-induced cardiomyopathy and MT expression. Mechanistically, 4-week IH exposure significantly decreased cardiac Nrf2 binding to the MT gene promoter, and thus, depressed both MT transcription and translation in WT mice but not Nrf2-TG mice. Likewise, cardiac MT overexpression prevented chronic IH-induced cardiomyopathy and down-regulation of Nrf2 likely via activation of a PI3K/Akt/GSK-3β/Fyn-dependent signaling pathway. These results reveal an integrated relationship between cardiac Nrf2 and MT expression in response to IH -- acute compensatory up-regulation followed by chronic down-regulation and cardiomyopathy. Cardiac overexpression of either Nrf2 or MT offered cardioprotection from IH via complicated PI3K/Akt/GSK3B/Fyn signaling. Potential therapeutics may target either Nrf2 or MT to prevent chronic IH-induced cardiomyopathy.
Graphical abstract
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Peroxyl radical- and photo-oxidation of glucose 6-phosphate dehydrogenase generates cross-links and functional changes via oxidation of tyrosine and tryptophan residues
Publication date: November 2017
Source:Free Radical Biology and Medicine, Volume 112
Author(s): Fabian Leinisch, Michele Mariotti, Martin Rykaer, Camilo Lopez-Alarcon, Per Hägglund, Michael J. Davies
Protein oxidation is a frequent event as a result of the high abundance of proteins in biological samples and the multiple processes that generate oxidants. The reactions that occur are complex and poorly understood, but can generate major structural and functional changes on proteins. Current data indicate that pathophysiological processes and multiple human diseases are associated with the accumulation of damaged proteins. In this study we investigated the mechanisms and consequences of exposure of the key metabolic enzyme glucose-6-phosphate dehydrogenase (G6PDH) to peroxyl radicals (ROO•) and singlet oxygen (1O2), with particular emphasis on the role of Trp and Tyr residues in protein cross-linking and fragmentation. Cross-links and high molecular mass aggregates were detected by SDS-PAGE and Western blotting using specific antibodies. Amino acid analysis has provided evidence for Trp and Tyr consumption and formation of oxygenated products (diols, peroxides, N-formylkynurenine, kynurenine) from Trp, and di-tyrosine (from Tyr). Mass spectrometric data obtained after trypsin-digestion in the presence of H216O and H218O, has allowed the mapping of specific cross-linked residues and their locations. These data indicate that specific Tyr-Trp and di-Tyr cross-links are formed from residues that are proximal and surface-accessible, and that the extent of Trp oxidation varies markedly between sites. Limited modification at other residues is also detected. These data indicate that Trp and Tyr residues are readily modified by ROO• and 1O2 with this giving products that impact significantly on protein structure and function. The formation of such cross-links may help rationalize the accumulation of damaged proteins in vivo.
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Antioxidant defense in quiescent cells determines selectivity of electron transport chain inhibition-induced cell death
Publication date: November 2017
Source:Free Radical Biology and Medicine, Volume 112
Author(s): Jan Blecha, Silvia Magalhaes Novais, Katerina Rohlenova, Eliska Novotna, Sandra Lettlova, Sabine Schmitt, Hans Zischka, Jiri Neuzil, Jakub Rohlena
Mitochondrial electron transport chain (ETC) targeting shows a great promise in cancer therapy. It is particularly effective in tumors with high ETC activity where ETC-derived reactive oxygen species (ROS) are efficiently induced. Why modern ETC-targeted compounds are tolerated on the organismal level remains unclear. As most somatic cells are in non-proliferative state, the features associated with the ETC in quiescence could account for some of the specificity observed. Here we report that quiescent cells, despite increased utilization of the ETC and enhanced supercomplex assembly, are less susceptible to cell death induced by ETC disruption when glucose is not limiting. Mechanistically, this is mediated by the increased detoxification of ETC-derived ROS by mitochondrial antioxidant defense, principally by the superoxide dismutase 2 – thioredoxin axis. In contrast, under conditions of glucose limitation, cell death is induced preferentially in quiescent cells and is correlated with intracellular ATP depletion but not with ROS. This is related to the inability of quiescent cells to compensate for the lost mitochondrial ATP production by the upregulation of glucose uptake. Hence, elevated ROS, not the loss of mitochondrially-generated ATP, are responsible for cell death induction by ETC disruption in ample nutrients condition, e.g. in well perfused healthy tissues, where antioxidant defense imparts specificity. However, in conditions of limited glucose, e.g. in poorly perfused tumors, ETC disruption causes rapid depletion of cellular ATP, optimizing impact towards tumor-associated dormant cells. In summary, we propose that antioxidant defense in quiescent cells is aided by local glucose limitations to ensure selectivity of ETC inhibition-induced cell death.
Graphical abstract
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Hydrogen peroxide, nitric oxide and ATP are molecules involved in cardiac mitochondrial biogenesis in Diabetes
Publication date: November 2017
Source:Free Radical Biology and Medicine, Volume 112
Author(s): Silvina S. Bombicino, Darío E. Iglesias, Ivana A. Rukavina-Mikusic, Bruno Buchholz, Ricardo J. Gelpi, Alberto Boveris, Laura B. Valdez
This study, in an experimental model of type I Diabetes Mellitus in rats, deals with the mitochondrial production rates and steady-state concentrations of H2O2 and NO, and ATP levels as part of a network of signaling molecules involved in heart mitochondrial biogenesis. Sustained hyperglycemia leads to a cardiac compromise against a work overload, in the absence of changes in resting cardiac performance and of heart hypertrophy. Diabetes was induced in male Wistar rats by a single dose of Streptozotocin (STZ, 60mg × kg-1, ip.). After 28 days of STZ-injection, rats were sacrificed and hearts were isolated. The mitochondrial mass (mg mitochondrial protein × g heart-1), determined through cytochrome oxidase activity ratio, was 47% higher in heart from diabetic than from control animals. Stereological analysis of cardiac tissue microphotographs showed an increase in the cytosolic volume occupied by mitochondria (30%) and in the number of mitochondria per unit area (52%), and a decrease in the mean area of each mitochondrion (23%) in diabetic respect to control rats. Additionally, an enhancement (76%) in PGC-1α expression was observed in cardiac tissue of diabetic animals. Moreover, heart mitochondrial H2O2 (127%) and NO (23%) productions and mtNOS expression (132%) were higher, while mitochondrial ATP production rate was lower (~ 40%), concomitantly with a partial-mitochondrial depolarization, in diabetic than in control rats. Changes in mitochondrial H2O2 and NO steady-state concentrations and an imbalance between cellular energy demand and mitochondrial energy transduction could be involved in the signaling pathways that lead to the novo synthesis of mitochondria. However, this compensatory mechanism triggered to restore the mitochondrial and tissue normal activities, did not lead to competent mitochondria capable of supplying the energetic demands in diabetic pathological conditions.
Graphical abstract
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How Linguistic Metaphor Scaffolds Reasoning
Publication date: Available online 5 August 2017
Source:Trends in Cognitive Sciences
Author(s): Paul H. Thibodeau, Rose K. Hendricks, Lera Boroditsky
Language helps people communicate and think. Precise and accurate language would seem best suited to achieve these goals. But a close look at the way people actually talk reveals an abundance of apparent imprecision in the form of metaphor: ideas are 'light bulbs', crime is a 'virus', and cancer is an 'enemy' in a 'war'. In this article, we review recent evidence that metaphoric language can facilitate communication and shape thinking even though it is literally false. We first discuss recent experiments showing that linguistic metaphor can guide thought and behavior. Then we explore the conditions under which metaphors are most influential. Throughout, we highlight theoretical and practical implications, as well as key challenges and opportunities for future research.
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Foliar application of aspartic acid lowers cadmium uptake and Cd-induced oxidative stress in rice under Cd stress
Abstract
Cadmium (Cd) contamination of farmland soils is a widespread problem around the globe, and rice (Oryza sativa L.) tends to accumulate more Cd and is considered as one of the major sources of Cd intake in humans, especially consuming rice-derived products. The current study investigated the effects of foliar applied aspartic acid (Asp) on growth parameters, biomass, chlorophyll concentration, gas exchange characteristics, Cd uptake, and antioxidative capacity in the shoots and roots of rice seedlings exposed to Cd stress. For this, 30-day-old rice nursery was transferred in the soil with aged Cd contamination (2.86 mg kg−1). After 2 weeks of growth, different concentrations (0, 10, 15, and 20 mg L−1) of Asp were foliar applied four times with a 7-day interval, and the crop was harvested after 10 weeks of transplanting. Foliar applied Asp increased the plant height, shoot and root dry weight, chlorophyll concentration, and gas exchange parameters, while it reduced the Cd concentrations in both shoots and roots as well as shoot to root Cd translocation factor compared to the control. Foliar application of Asp reduced the malondialdehyde content and electrolyte leakage in rice parts compared to the control in a dose-additive manner. The activities of key antioxidant enzymes increased while peroxidase activity decreased by exogenous Asp. The increase in plant weight and photosynthesis might be due to lower Cd concentrations in plants which may reduce the oxidative stress and also help the plants to minimize direct damage caused by Cd to the photosynthetic organs.
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IFC-EDITORIAL BOARD
Source:Research in Developmental Disabilities, Volume 68
http://ift.tt/2wvNNb9
Copyright-Page
Publication date: September 2017
Source:Anesthesiology Clinics, Volume 35, Issue 3
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Contributors
Publication date: September 2017
Source:Anesthesiology Clinics, Volume 35, Issue 3
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Contents
Publication date: September 2017
Source:Anesthesiology Clinics, Volume 35, Issue 3
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Forthcoming Issues
Publication date: September 2017
Source:Anesthesiology Clinics, Volume 35, Issue 3
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Transplantation
Publication date: September 2017
Source:Anesthesiology Clinics, Volume 35, Issue 3
Author(s): Aman Mahajan, Christopher Wray
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Overview of Immunosuppressive Therapy in Solid Organ Transplantation
Publication date: September 2017
Source:Anesthesiology Clinics, Volume 35, Issue 3
Author(s): Curtis D. Holt
Teaser
Mechanisms of rejection, new pharmacologic approaches, and genomic medicine are major foci for current research in transplantation. It is hoped that these new agents and personalized immunosuppression will provide for less toxic regimens that are effective in preventing both acute and chronic allograft rejection. Until new agents are available, practitioners must use various combinations of currently approved agents to find the best regimens for improved long-term outcomes.http://ift.tt/2vB8rcn
4D cardiac imaging at clinical 3.0T provides accurate assessment of murine myocardial function and viability
Source:Magnetic Resonance Imaging
Author(s): Lindsey A. Crowe, Fabrizio Montecucco, Federico Carbone, Iris Friedli, Anne-Lise Hachulla, Vincent Braunersreuther, François Mach, Jean-Paul Vallée
ObjectivesWe validate a 4D strategy tailored for 3T clinical systems to simultaneously quantify function and infarct size in wild type mice after ischemia/reperfusion, with improved spatial and temporal resolution by comparison to previous published protocols using clinical field MRI systems.MethodsC57BL/6J mice underwent 60min ischemia/reperfusion (n=14) or were controls without surgery (n=6). Twenty-four hours after surgery mice were imaged with gadolinium injection and sacrificed for post-mortem MRI and histology with serum also taken for Troponin I levels. The double ECG and respiratory-triggered 3D FLASH (Fast Low Angle Shot) gradient echo (GRE) cine sequence had an acquired isotropic resolution of 344μm, TR/TE of 7.8/2.9ms and acquisition time 25–35min. The conventional 2D FLASH cine sequence had the same in-plane resolution of 344μm, 1mm slice thickness and TR/TE 11/5.4ms for an acquisition time of 20–25min plus 5min for planning. Left ventricle (LV) and right ventricle (RV) volumes were measured and functional parameters compared 2D to 3D, left to right and for inter and intra observer reproducibility. MRI infarct volume was compared to histology.ResultsFor the function evaluation, the 3D cine outperformed 2D cine for spatial and temporal resolution. Protocol time for the two methods was equivalent (25–35min). Flow artifacts were reduced (p=0.008) and epi/endo-cardial delineation showed good intra and interobserver reproducibility. Paired t-test comparing ejection volume left to right showed no significant difference for 3D (p=0.37), nor 2D (p=0.30) and correlation slopes of left to right EV were 1.17 (R2=0.75) for 2D and 1.05 (R2=0.50) for 3D.Quantifiable 'late gadolinium enhancement' infarct volume was seen only with the 3D cine and correlated to histology (R2=0.89). Left ejection fraction and MRI-measured infarct volume correlated (R2>0.3).ConclusionsThe 4D strategy, with contrast injection, was validated in mice for function and infarct quantification from a single scan with minimal slice planning.
http://ift.tt/2vsZYIR
Microstructural evolution of the as-cast and the peak-aged Mg–xYb–0.5Zn–0.4Zr (x = 0.5, 1, 2, and 3 wt.%) alloy
Publication date: 5 December 2017
Source:Journal of Alloys and Compounds, Volume 726
Author(s): Deping Zhang, Qiang Yang, Dongdong Zhang, Qi Sui, Xin Qiu, Hui Li, Kai Guan, Hong Zhou, Jian Meng
Detailed microstructures of the as-cast and the peak-aged metal mould casting Mg–xYb–0.5Zn–0.4Zr (x = 0.5, 1, 2, and 3 wt.%) alloys were thoroughly investigated. The results indicate that Yb has better grain refinement effect on the Mg–Zn–Zr based alloys compared with the conventional rare earth elements such as Nd, Sm, and Gd, and the dominant intermetallic phase in the as-cast samples is Mg2Yb, although with a few Mg41Sm5 particles. In addition, the studied alloys also exhibit good aging hardening response when aged at 200 °C. During aging treatment, obvious precipitation of T phase formed on grain boundaries can be observed in the alloys with Yb is less than 2 wt.%, while Mg2Yb precipitate chains in the grain center and discrete Mg2Yb particles homogeneously distributed near grain boundaries in the samples with Yb addition over 2 wt.%. Finally, ultra-fine needle-like precipitates were detected in all peak-aged samples, although with distinct difference on sizes and distribution densities. Based on energy dispersive spectrometer mappings of Mg, Yb, Zn and Zr and the SAED patterns, the needle-like precipitates were identified as γ′ phase (MgZnRE containing, hexagonal structure, a = 0.55 nm and c = 0.52 nm) and followed an orientation relationship as (11¯.0)γ′||(11.0)Mg and [00.1]γ′||[00.1]Mg.
http://ift.tt/2wvA6ZR
In vivo isotopic fractionation of zinc and biodynamic modeling yield insights into detoxification mechanisms in the mayfly Neocloeon triangulifer
Publication date: 31 December 2017
Source:Science of The Total Environment, Volume 609
Author(s): Richard B. Wanty, Laurie S. Balistrieri, Jeff S. Wesner, David M. Walters, Travis S. Schmidt, Craig A. Stricker, Johanna M. Kraus, Ruth E. Wolf
Diversity and biomass of aquatic insects decline in metal-rich aquatic environments, but the mechanisms by which insects from such environments cope with potentially toxic metal concentrations to survive through adulthood are less well understood. In this study, we measured Zn concentrations and isotopes in laboratory-reared diatoms and mayflies (Neocloeon triangulifer) from larval through adult stages. The larvae were fed Zn-enriched diatoms, and bio-concentrated Zn by a factor of 2.5–5 relative to the diatoms but maintained the same Zn-isotopic ratio. These results reflect the importance of dietary uptake and the greater rate of uptake relative to excretion or growth. Upon metamorphosis to subimago, Zn concentrations declined by >70%, but isotopically heavy Zn remained in the subimago bodies. We surmised that the loss of isotopically light Zn during metamorphosis was due to the loss of detoxified Zn and retention of metabolically useful Zn. Through the transition from subimago to imago, Zn concentrations and isotope ratios were virtually unchanged. Because the decrease in Zn body concentration and increase in heavier Zn are seen in the subimagos relative to the larvae, the compartmentalization of Zn must be occurring within the larvae. A biodynamic model was constructed, allowing for isotopic fractionation and partitioning of Zn between metabolically essential and detoxified Zn reservoirs within larvae. The model provides a consistent set of rate and fractionation constants that successfully describe the experimental observations. Specifically, metabolically essential Zn is isotopically heavier and is tightly held once assimilated, and excess, isotopically light Zn is sequestered, detoxified, and ultimately lost during the metamorphosis of larvae to subimagos. To our knowledge, this is the first documentation of in vivo isotopic fractionation in insects, offering an improved understanding of the mechanisms and rates by which the N. triangulifer larvae regulate excess Zn in their bodies.
Graphical abstract
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A comprehensive analysis of heavy metals in urban road dust of Xi'an, China: Contamination, source apportionment and spatial distribution
Publication date: 31 December 2017
Source:Science of The Total Environment, Volume 609
Author(s): Huiyun Pan, Xinwei Lu, Kai Lei
A detailed investigation was conducted to study heavy metal contamination in road dust from four regions of Xi'an, Northwest China. The concentrations of eight heavy metals Co, Cr, Cu, Mn, Ni, Pb, Zn and V were determined by X-Ray Fluorescence. The mean concentrations of these elements were: 30.9mgkg−1 Co, 145.0mgkg−1 Cr, 54.7mgkg−1 Cu, 510.5mgkg−1 Mn, 30.8mgkg−1 Ni, 124.5mgkg−1 Pb, 69.6mgkg−1 V and 268.6mgkg−1 Zn. There was significant enrichment of Pb, Zn, Co, Cu and Cr based on geo-accumulation index value. Multivariate statistical analysis showed that levels of Cu, Pb, Zn, Co and Cr were controlled by anthropogenic activities, while levels of Mn, Ni and V were associated with natural sources. Principle component analysis and multiple linear regression were applied to determine the source apportionment. The results showed that traffic was the main source with a percent contribution of 53.4%. Natural sources contributed 26.5%, and other anthropogenic pollution sources contributed 20.1%. Clear heavy metal pollution hotspots were identified by GIS mapping. The location of point pollution sources and prevailing wind direction were found to be important factors in the spatial distribution of heavy metals.
Graphical abstract
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Accuracy and reproducibility of a newly developed tool for volume measurements of the arm using 3D stereophotogrammetry
Lymph edema of the arm is a common complication after breast cancer treatment. To evaluate lymph edema volume and treatment outcome, an easy to use, objective quantification method of arm volume is necessary. Most of the times, water displacement is used to measure arm volume, as it is an easy and robust method that can be performed at any place with some simple equipment. However, when using water displacement, no exact localization of volume differences can be seen. To accurately measure hand and forearm volume separately, an in house developed device was made for accurate landmark placement.
http://ift.tt/2ue18rM
Uptake and transformations of engineered nanomaterials: Critical responses observed in terrestrial plants and the model plant Arabidopsis thaliana
Publication date: 31 December 2017
Source:Science of The Total Environment, Volumes 607–608
Author(s): Angelina Montes, Mary A. Bisson, Joseph A. Gardella, Diana S. Aga
With the applications of engineered nanomaterials (ENMs) continually expanding and production quickly growing, residues of ENMs will end up in the environment at levels that may be harmful to non-target organisms. Many of the tunable properties that have made them desirable, such as type, size, charge, or coating, also contribute to the current difficulties in understanding the fate of ENMs in the environment. This review article focuses on studies that investigate plant-ENM interactions, including techniques used to study these interactions and documented plant responses due to the phytotoxic effects of ENMs. The many variables which can be altered for an experiment, such as type, size, and concentration of ENMs, make it difficult to formulate generalizations about the uptake mechanism involved, or to make an inference on the subcellular localization and distribution of the internalized ENMs in plant tissue. In order to avoid these challenges, studies can utilize a model organism such as Arabidopsis thaliana, and a combination of analytical techniques that can reveal complementary information in order to assess how the different experimental conditions influence the uptake and phytotoxicity of ENMs. This review presents recent studies regarding plant-ENM interactions employing Arabidopsis to demonstrate how the use of this model plant can advance our understanding of plant-ENM interactions and guide additional studies using other plant species. Overarching results suggest that more sensitive tests and consistency in experimental designs are needed to fully assess and understand the phytotoxic effects of ENMs in the environment.
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Risk of Major Limb Amputation in diabetic foot ulcer and accompanying disease: A meta-analysis
Limb amputation in diabetic patients raises important issues regarding lower quality of life and survival rates. This meta-analysis is aimed to identify predictive factors accompanying diseases with high major amputation rates in diabetic patients.
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Highly efficient and stable Ru/K-OMS-2 catalyst for NO oxidation
Publication date: 15 December 2017
Source:Applied Catalysis B: Environmental, Volume 219
Author(s): S. Adjimi, J.M. García-Vargas, J.A. Díaz, L. Retailleau, S. Gil, M. Pera-Titus, Y. Guo, A. Giroir-Fendler
The influence of addition of a series of non noble and noble metals to a manganese oxide octahedral molecular sieve (OMS) with a cryptomelane structure (K-OMS-2) has been studied for NO oxidation in view of fast selective catalytic reduction applications. Fe, Cu, Zn, Pt, Pd, Ru and Ag were selected as dopant metals with a metal loading around 2wt.%. The catalysts were characterized in detail by ICP-OES, N2 adsorption/desorption at 77K, XRD, H2-TPR and HR-TEM. The highest NO conversion was obtained for a K-OMS-2 catalyst modified with ruthenium, showing a reaction rate up to 5.3μmolg−1s−1 at 584K. A markedly higher catalyst reducibility upon incorporation of ruthenium can be proposed as an underlying reason for the enhanced catalytic performance.
Graphical abstract
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Assessing the Effort Associated with Teaching Residents
Intraoperative resident education is an integral mission of academic medical centers and serves as the basis for training the next generation of surgeons. The actual effort associated with teaching residents, as it pertains to additional operative time, is unknown. Using a large validated multi-institutional dataset, this study aims to quantify the effect on operative time of having a resident present in common plastic surgery procedures. Future directions for developing standardized methods to record and report teaching time are proposed, which can help inform prospective studies.
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Invited Commentary: Analysis of Risk Factors Associated with Unplanned Re-Operations following Pediatric Plastic Surgery
Jubbal et al. have used data from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) Pediatric database to identify parameters associated with an increased likelihood of unplanned reoperation following plastic surgery in children under 18 years of age.1 To interpret this study, it is important to understand a little of the background to the database from which it was drawn.
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Body size, brain size, and sexual dimorphism in Homo naledi from the Dinaledi Chamber
Source:Journal of Human Evolution, Volume 111
Author(s): Heather M. Garvin, Marina C. Elliott, Lucas K. Delezene, John Hawks, Steven E. Churchill, Lee R. Berger, Trenton W. Holliday
Homo erectus and later humans have enlarged body sizes, reduced sexual dimorphism, elongated lower limbs, and increased encephalization compared to Australopithecus, together suggesting a distinct ecological pattern. The mosaic expression of such features in early Homo, including Homo habilis, Homo rudolfensis, and some early H. erectus, suggests that these traits do not constitute an integrated package. We examined the evidence for body mass, stature, limb proportions, body size and dental size dimorphism, and absolute and relative brain size in Homo naledi as represented in the Dinaledi Chamber sample. H. naledi stature and body mass are low compared to reported values for H. erectus, with the exception of some of the smaller bodied Dmanisi H. erectus specimens, and overlap with larger Australopithecus and early Homo estimates. H. naledi endocranial volumes (465–560 cc) and estimates of encephalization quotient are also similar to Australopithecus and low compared to all Homo specimens, with the exception of Homo floresiensis (LB1) and the smallest Dmanisi H. erectus specimen (D4500). Unlike Australopithecus, but similar to derived members of genus Homo, the Dinaledi assemblage of H. naledi exhibits both low levels of body mass and dental size variation, with an estimated body mass index of sexual dimorphism less than 20%, and appears to have an elongated lower limb. Thus, the H. naledi bauplan combines features not typically seen in Homo species (e.g., small brains and bodies) with those characteristic of H. erectus and more recent Homo species (e.g., reduced mass dimorphism, elongated lower limb).
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Factors influencing adsorption and desorption of trimethoprim on marine sediments: mechanisms and kinetics
Abstract
Adsorption-desorption behavior of ionic antibiotics in natural aquatic environment is complex, especially in coastal or estuary area where influencing factors such as pH and salinity usually varied in a wide range. In this study, batch-type and stirred flow chamber (SFC) experiments were carried out to simulate the sorption-desorption behavior of trimethoprim (TMP) in seawater-sediment system. Equilibrium and kinetic modeling were carried out to determine the rate and extent of TMP sorption on two marine sediments with different properties. Sediment BHB (K d , 6.40 L kg−1) has a greater sorption capacity compared with sediment LZB (K d , 3.40 L kg−1), which is related to the higher content of organic carbon and clay of sediment BHB. Adsorption of TMP varied in the pH range of 6.9 to 8.1 with maximum adsorption at pH 7.4. Increasing salinity and presence of phosphate and nitrate led to decreased TMP sorption. Attenuated total reflection Fourier transform infrared (ATR-FTIR) analysis demonstrated the formation of hydrogen bond between TMP and marine sediments. Adsorption of TMP on marine sediments was a non-equilibrium process that can be described with second-order kinetic model. Our analysis suggested that chemical non-equilibrium was the rate controlling process and intraparticle diffusion was also involved in TMP adsorption. A moderate desorption percentage (16.4–22.8% for LZB and 32.5–42.0%for BHB) was observed. Overall, the results showed that environmental factors and time-dependent processes need to be considered in modeling the fate and transport of TMP in coastal/estuarine waters.
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Quantitative diffusion-weighted magnetic resonance imaging assessment of chemotherapy treatment response of pediatric osteosarcoma and Ewing sarcoma malignant bone tumors
Publication date: Available online 5 August 2017
Source:Clinical Imaging
Author(s): Andrew J. Degnan, Chul Y. Chung, Amisha J. Shah
ObjectiveAssessment of tumor response to chemotherapy is essential in managing malignant pediatric bone tumors prior to resection.Subjects and methodsPre-chemotherapy and post-chemotherapy osteosarcoma and Ewing sarcoma cases (n=18) were analyzed with apparent diffusion coefficient (ADC) values measured by two readers.ResultsTreated tumors demonstrated significantly greater ADC values compared to untreated tumors (p<0.001). Intraclass correlation coefficients ranged between 0.858 and 0.935. No significant tumor volume differences were observed. Regression analysis demonstrated average ADC as the best predictor of treatment.ConclusionsOur study suggests that ADC values may be useful for evaluating chemotherapeutic response of malignant pediatric bone tumors.
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The flavonol-enriched Cistus albidus chloroform extract possesses in vivo anti-inflammatory and anti-nociceptive activity
Publication date: 14 September 2017
Source:Journal of Ethnopharmacology, Volume 209
Author(s): Ouahiba Tahiri, Dina Atmani-Kilani, Susana Sanchez-Fidalgo, Marina Aparicio-Soto, Catalina Alarcón-de-la-Lastra, Enrique Barrajón-Catalán, Vicente Micol, Djebbar Atmani
Ethnopharmacological relevanceCistus albidus L. (Cistaceae) has been traditionally used to treat various inflammatory diseases, but no systematic studies on the anti-inflammatory and anti-nociceptive actions of C. albidus and its putative mechanism have been reported. We aimed to explore the anti-inflammatory and anti-nociceptive effects of this plant and to characterize its polyphenolic composition by liquid chromatography coupled to mass spectrometry (MS).Materials and methodsA chloroform extract derived from C. albidus leaves was obtained by solid-liquid and liquid-liquid extraction. The tail immersion test and acetic-acid-induced writhing test were used to evaluate the anti-nociceptive action, while the experimental λ-carrageenan-induced paw edema model was used to test the anti-inflammatory action. Changes in cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) expression, as well as the role of mitogen-activated protein kinases (MAPKs) and the nuclear transcription factor kappa B (NF-kB) signaling pathways on lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages were analyzed by western blotting. HPLC with diode array detection coupled to tandem mass spectrometry detection with electrospray ionization (HPLC-DAD-ESI-MS/MS) was performed to determine the phytochemical profile of the extract.ResultsSignificant anti-nociceptive activity was observed both in the tail immersion (59.63% reduction at 120min) and in the acetic acid (65.94% inhibition) tests at 100mg/kg. The extract (50mg/kg) exhibited a substantial reduction in paw edema (51.6%) and significantly inhibited nitrite generation (72.62%) without affecting cell viability of LPS-stimulated murine peritoneal macrophages. These results were concomitant with a down-regulation of the pro-inflammatory enzymes COX-2 and iNOS in extract-treated macrophages and a decrease in p38 MAPK phosphorylation. HPLC-DAD-ESI-MS/MS analysis revealed that flavonols such as kaempferol and quercetin derivatives were potentially responsible for such effects.ConclusionThese results support the widespread use of C. albidus in popular medicine and indicate that this plant has therapeutic potential with analgesic and anti-inflammatory properties based on the presence of flavonol derivatives.
Graphical abstract
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Anti-inflammatory properties of an extract of M. ilicifolia in the human intestinal epithelial Caco-2 cell line
Publication date: Available online 5 August 2017
Source:Journal of Ethnopharmacology
Author(s): Ruth Wonfor, Manuela Natoli, Ifat Parveen, Manfred Beckman, Robert Nash, Deborah Nash
Ethnopharmacology relevanceMaytenus ilicifolia is a Celastracea plant used in traditional medicine to alleviate digestive tract inflammatory disorders.Aim of the studyWe investigated anti-inflammatory properties of M. ilicifolia crude extract towards Caco-2 cell line, as a model of Toll-like Receptor 2 (TLR-2) inflammatory pathway.Materials and MethodsToxicity was assessed following culture of Caco-2 with M. ilicifolia, using apparent cell permeability and trans-epithelial electric resistance. Anti-inflammatory properties of M. ilicifolia were assessed through IL-8 secretion and TLR-2 associated gene expression of Caco-2 cells with or without an LTA challenge.ResultsM. ilicifolia was not toxic to Caco-2 cells. M. ilicifolia down-regulated TLR2 expression with and without LTA challenge but had no effect on other genes. Following LTA challenge of Caco-2 cells, 100 and 200µg/mL M. ilicifolia abrogated IL-8 secretion.ConclusionsWe provide preliminary data for some M. ilicifolia anti-inflammatory properties. Further research must establish the full extent and mode of action on particular inflammatory pathways.
Graphical abstract
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Banxia-houpu decoction restores glucose intolerance in CUMS rats through improvement of insulin signaling and suppression of NLRP3 inflammasome activation in liver and brain
Publication date: Available online 4 August 2017
Source:Journal of Ethnopharmacology
Author(s): Ke-Ke Jia, Yan-Jing Zheng, Yan-Xiu Zhang, Jia-Hui Liu, Rui-Qing Jiao, Ying Pan, Ling-Dong Kong
Ethnopharmacological relevanceBanxia-houpu decoction is a famous formula in traditional Chinese medicine (TCM) with the powerful anti-depressant activity.Aim of the studyThis study aimed to investigate the effect of Banxia-houpu decoction on glucose intolerance associated with anhedonia in chronic unpredictable mild stress (CUMS) rats, then to explore its underlying pharmacological mechanisms.Materials and methodsAfter 6-week CUMS procedure, male Wistar rats were given Banxia-houpu decoction (3.29 and 6.58g/kg, intragastrically) for 6 weeks. Sucrose solution consumption test was employed to evaluate the anhedonia behavior. Oral glucose tolerance test (OGTT) was used to determine glucose tolerance. Serum levels of corticosterone, corticotropin-releasing factor (CRF), insulin and interleukin-1 beta (IL-1β) were measured by commercial enzyme-linked immunosorbent assay kits, respectively. Furthermore, the key proteins for insulin signaling, as well as nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, were analyzed by Western blot in periphery liver and brain regions hypothalamus, hippocampus and prefrontal cortex, respectively.ResultsBanxia-houpu decoction significantly increased sucrose solution consumption and decreased serum corticosterone and CRF levels in CUMS rats, further demonstrating its antidepressant activity. More importantly, Banxia-houpu decoction improved glucose tolerance in OGTT in this animal model. Furthermore, it protected against CUMS-induced insulin signaling impairment in the liver, as well as hypothalamus and prefrontal cortex in rats. Although without significant effect on serum IL-1β levels, Banxia-houpu decoction inhibited NLRP3 inflammasome activation in the liver, hypothalamus, hippocampus and prefrontal cortex of CUMS rats, respectively.ConclusionsThe present study demonstrates that Banxia-houpu decoction suppresses NLRP3 inflammasome activation and improves insulin signaling impairment in both periphery liver and brain regions in CUMS rats, possibly contributing to its anti-depressive effect with glucose tolerance improvement. These results may provide the evidence that Banxia-houpu decoction is a potential antidepressant with the advantage to reduce the risk of comorbid depression with type 2 diabetes mellitus.
Graphical abstract
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Frontmatter
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 8
Pages: i-iii
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Endocrine aspects in cystic fibrosis
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 8
Pages: 805-806
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A retrospective analysis of longitudinal changes in bone mineral content in cystic fibrosis
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 8
Pages: 807-814
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Cystic-fibrosis related-diabetes (CFRD) is preceded by and associated with growth failure and deteriorating lung function
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 8
Pages: 815-821
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Partial clinical remission in type 1 diabetes: a comparison of the accuracy of total daily dose of insulin of
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 8
Pages: 823-830
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Concentrations of leptin, adiponectin and other metabolic parameters in non-obese children with Down syndrome
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 8
Pages: 831-837
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Parent reported nutritional risk and laboratory indices of cardiometabolic risk and in preschool-aged children
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 8
Pages: 839-846
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Multinodular goiter in children: treatment controversies
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 8
Pages: 847-850
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Atopy as a risk factor for subclinical hypothyroidism development in children
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 8
Pages: 851-856
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Mutation analysis of the NKX2.5 gene in Iranian pediatric patients with congenital hypothyroidism
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 8
Pages: 857-862
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Health-related quality of life among children with Turner syndrome: controlled cross-sectional study
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 8
Pages: 863-868
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Growth and pubertal patterns in young survivors of childhood acute lymphoblastic leukemia
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 8
Pages: 869-877
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Clinical features and genotyping of patients with primary carnitine deficiency identified by newborn screening
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 8
Pages: 879-883
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Sensitivity and specificity of cystic fibrosis-related diabetes screening methods: which test should be the reference method?
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 8
Pages: 885-887
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Type 1 rhizomelic chondrodysplasia punctata with a homozygous PEX7 mutation
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 8
Pages: 889-892
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Severe hypertriglyceridemia at new onset type 1 diabetes mellitus
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 8
Pages: 893-897
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45,X/46,XY ovotesticular disorder of sex development revisited: undifferentiated gonadal tissue may be mistaken as ovarian tissue
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 8
Pages: 899-904
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MRI in medium-chain acyl-coenzyme a dehydrogenase deficiency: neuroimaging during the first month
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 8
Pages: 905-908
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Growing Cyst-Like White Matter Lesions in Children with Neurofibromatosis Type 1
Source:Pediatric Neurology
Author(s): Ji Eun Kim, Jung-Eun Cheon, In-One Kim, Young-Hun Choi, Woo Sun Kim
BackgroundNeurofibromatosis type 1 (NF1) is an autosomal dominant disease with prominent neurocutaneous manifestations. The most common intracranial imaging finding of NF1 on brain magnetic resonance imaging (MRI) is the high-signal intensity foci without a mass effect or growth in size.Patient DescriptionWe describe two children with NF1 in whom brain MRI showed growing cystic lesions and adjacent white matter signal abnormalities, which were confirmed as non-neoplastic cystic degeneration and reactive gliosis.ConclusionGrowing cyst-like white matter lesions can be seen on serial brain MRI in children with NF1. Reactive gliosis with cystic degeneration could be a pathogenic basis of these cystic lesions.
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Somatostatin Analogs: How we choose, and why
Publication date: Available online 4 August 2017
Source:Seminars in Oncology
Author(s): Diane Reidy-Lagunes, Nitya Raj, Leonard Saltz
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In reply
Publication date: Available online 4 August 2017
Source:Seminars in Oncology
Author(s): Michele Boisdron-Celle, Olivier Capitain, Roger Faroux, Christophe Borg, Jean Philippe Metges, Marie Pierre Galais, Mehdi Kaassis, Jaafar Bennouna, Karine Bouhier-Leporrier, Eric Francois, Isabelle Baumgaertner, Véronique Guerin-Meyer, Oana Cojocarasu, Celia Roemer-Becuwe, Claire Stampfli, Ludovic Rosenfeld, Thierry Lecompte, Virginie Berger, Alain Morel, Erick Gamelin
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Comparison of the RECIST and EORTC PET criteria in the tumor response assessment: a pooled analysis and review
Abstract
Purpose
The EORTC PET criteria (EORTC criteria) are used to assess metabolic tumor response in patients with solid tumors. We conducted this pooled study to compare tumor responses according to the RECIST and EORTC criteria.
Methods
Electronic databases were searched for eligible articles with the terms of "RECIST" or "EORTC criteria". We found seven articles with the data on the comparison of tumor responses by the RECIST and EORTC criteria.
Results
A total of 181 patients were recruited from the seven studies. Ninety-two patients (50.8%) received cytotoxic chemotherapy and 89 were treated with targeted agents. The agreement of tumor responses between the RECIST and EORTC criteria was moderate (k = 0.493). Of 181 patients, 66 (36.5%) showed disagreement in the tumor responses: tumor response was upgraded in 54 patients and downgraded in 12 when adopting the EORTC criteria. The estimated overall response rates were significantly different between the two criteria (52.5% by the EORTC vs. 29.8% by the RECIST, P < 0.0001). When comparing the two criteria according to the anti-cancer treatments (chemotherapy or targeted therapy), the levels of agreement in tumor responses were not excellent (k = 0.461 for chemotherapy and k = 0.524 for targeted therapy, respectively) regardless of therapeutic types.
Conclusion
This pooled study indicates that the concordance of tumor responses between the RECIST and EORTC criteria is not excellent. When adopting the EORTC criteria instead of the RECIST, the overall response rate was significantly increased.
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Mathematical model for the transport of fluoroquinolone and its resistant bacteria in aquatic environment
Abstract
Development of antibiotic resistance in environmental bacteria is a direct threat to public health. Therefore, it becomes necessary to understand the fate and transport of antibiotic and its resistant bacteria. This paper presents a mathematical model for spatial and temporal transport of fluoroquinolone and its resistant bacteria in the aquatic environment of the river. The model includes state variables for organic matter, fluoroquinolone, heavy metals, and susceptible and resistant bacteria in the water column and sediment bed. Resistant gene is the factor which makes bacteria resistant to a particular antibiotic and is majorly carried on plasmids. Plasmid-mediated resistance genes are transferable between different bacterial species through conjugation (horizontal resistance transfer). This model includes plasmid dynamics between susceptible and resistant bacteria by considering the rate of horizontal resistance gene transfer among bacteria and the rate of losing resistance (segregation). The model describes processes which comprise of advection, dispersion, degradation, adsorption, diffusion, settling, resuspension, microbial growth, segregation, and transfer of resistance genes. The mathematical equations were solved by using numerical methods (implicit-explicit scheme) with appropriate boundary conditions. The development of the present model was motivated by the fact that the Musi River is heavily impacted by antibiotic pollution which led to the development of antibiotic resistance in its aquatic environment. The model was simulated for hypothetical pollution scenarios to predict the future conditions under various pollution management alternatives. The simulation results of the model for different cases show that the concentration of antibiotic, the concentration of organic matter, segregation rate, and horizontal transfer rate are the governing factors in the variation of population density of resistant bacteria. The treatment of effluents for antibiotics might be costly for the bulk drug manufacturing industries, but the guidelines can be made to reduce the organic matter which can limit the growth rate of microbes and reduce the total microbial population in the river. The reduction in antibiotic concentration can reduce the selection pressure on bacteria and can limit the population of resistant culture and its influence zone in the river stretch; however, complete removal of antibiotics may not result in complete elimination of antibiotic-resistant bacteria.
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Engineered silica nanoparticles alleviate the detrimental effects of Na + stress on germination and growth of common bean ( Phaseolus vulgaris )
Abstract
During the past 10 years, exploiting engineered nanoparticles in agricultural sector has been rapidly increased. Nanoparticles are used to increase the productivity of different crops particularly under biotic and abiotic stresses. This study aims to test the ability of nanosilica (NS) to ameliorate the detrimental impact of Na+ with different concentrations on the seed germination and the growth of common bean seedlings. Five doses of Na+ have been prepared from NaCl, i.e., 1000, 2000, 3000, 4000, and 5000 mg L−1, and distilled water was applied as a control. Seeds and seedlings were treated with three different NS concentrations (100, 200, and 300 mg L−1). The results proved that Na+ concentrations had detrimental effects on all measured parameters. However, treating seeds and seedlings with NS improved their growth and resulted in higher values for all measurements. For instance, the addition of 300 mg L−1 NS leads to an increase of the final germination percentage, vigor index, and germination speed for seeds irrigated with 5000 mg Na+ L−1 by 19.7, 80.7, and 22.6%, respectively. Although common bean seedlings could not grow at the highest level of Na+, fortification seedlings with NS helped them to grow well under 5000 mg L−1 of Na+. An increase of 11.1 and 23.1% has been measured for shoot and root lengths after treating seedlings with 300 mg L−1 NS under irrigation with 5000 mg Na+ L−1 solutions, and also at the same treatment, shoot and root dry masses are enhanced by 110.9 and 328.0%, respectively. These results proved the importance of using NS to relieve the detrimental effects of Na+-derived salinity. This finding could be reinforced by low Na content which was measured in plant tissues after treating seedlings with 300 mg L−1 of NS.
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Supported Employment for Veterans with Traumatic Brain Injury: Provider Perspectives
Publication date: Available online 5 August 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Terri K. Pogoda, Kathleen F. Carlson, Katelyn E. Gormley, Sandra G. Resnick
ObjectiveIn 2006, 13 sites were provided with one-time pilot funding to provide supported employment (SE) to Veterans with traumatic brain injury (TBI) history. In 2014, we surveyed SE providers at pilot and non-pilot sites that did not receive this funding. Our objectives were to identify any pilot and non-pilot site differences regarding current: (1) provision of SE to Veterans with TBI; (2) staffing and communication between the SE and polytrauma/TBI teams; and (3) provider perceptions on facilitators and barriers to providing, and suggestions for improving, SE.SettingVeterans Health Administration (VHA) SE programs.DesignMixed methods cross-sectional survey study.ParticipantsProviders included a total of 54 SE supervisors and 90 vocational rehabilitation specialists (VRSs).InterventionsNot applicable.Main Outcome MeasuresWeb-based surveys of forced-choice and open-ended items included questions on SE team characteristics, communication with polytrauma/TBI teams, and experiences with providing SE to Veterans with TBI history.ResultsSE was provided to Veterans with TBI at 100% of pilot and 59.2% of non-pilot sites (p = .09). However, VRSs at pilot sites reported that communication with the polytrauma/TBI team about SE referrals was more frequent than at non-pilot sites (p = .003). In open-ended items, suggestions for improving SE were similar across pilot and non-pilot sites, and included increasing staffing for VRSs and case management, enhancing communication and education between SE and polytrauma/TBI teams, and expanding the scope of the SE program so that eligibility is based on employment support need, rather than diagnosis.ConclusionsThese findings may contribute to an evidence base that informs SE research and clinical directions on service provision, resource allocation, team integration efforts, and outreach to Veterans with TBI who have employment support needs.
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Mobility device quality impacts participation outcomes among people with disabilities: A structural equation modeling analysis
Publication date: Available online 5 August 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Susan Magasi, Alex W.K. Wong, Ana Miskovic, David Tulsky, Allen W. Heinemann
ObjectiveTo test the effect that indicators of mobility device quality have on participation outcomes among community dwelling adults with spinal cord injuries (SCI), traumatic brain injuries (TBI) and stroke using structural equation modeling.DesignSurvey, cross-sectional study, and model testing.SettingClinical research space at 2 academic medical centers and one free-standing rehabilitation hospital in the Midwestern United States (St. Louis, Ann Arbor, Chicago).ParticipantsCommunity-dwelling adults (mean age= 48 years(SD 14.3)) with SCI, TBI and Stroke (n=250).InterventionsNot applicableMain Outcomes MeasuresThe Mobility Device Impact Scale, PROMIS Social Health (v2.0) questionnaires, including Ability to Participate in Social Roles and Activities and Satisfaction with Social Roles and Activities questionnaires and the 2 Community Participation Indicators' Enfranchisement Scales. Details about device quality (reparability, reliability, ease of maintenance) and device type were also collected.ResultsRespondents used ambulation aids (30%), manual (34%), and power wheelchairs (30%). Indicators of device quality had a moderating association with participation outcomes, with three device quality variables, ease of repairs and maintenance, and device reliability accounting for 20% of the variance in participation. Wheelchair users reported lower participation enfranchisement than persons using ambulation aids.ConclusionMobility device quality plays an important role in participation outcomes. It is critical that people have access to mobility devices and that these devices be reliable.
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Les traitements biologiques du psoriasis freinent la progression de l’athérosclérose coronaire
Source:Annales de Dermatologie et de Vénéréologie
Author(s): J.-L. Schmutz
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Papules croûteuses du cuir chevelu révélatrices d’une histiocytose de Langerhans
Source:Annales de Dermatologie et de Vénéréologie
Author(s): A. Blind, C. Sachs, G. Blaison, J. Second, H. Herrscher, A. Mahé
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L’acantholyse
Publication date: Available online 5 August 2017
Source:Annales de Dermatologie et de Vénéréologie
Author(s): A. Welfringer-Morin, M. Battistella
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Trisomy 12 assessment by conventional fluorescence in-situ hybridization (FISH), FISH in suspension (FISH-is) and laser scanning cytometry (LSC) in chronic lymphocytic leukemia.
Source:Cancer Genetics
Author(s): Cuc H. Do, Karen M. Lower, Cindy Macardle, Bryone J. Kuss
Chronic lymphocytic leukemia (CLL) has an extremely heterogeneous clinical course, and prognostication is based on common genetic abnormalities which are detected by standard cytogenetic methods. However, current methods are restricted by the low number of cells able to be analyzed, resulting in the potential to miss clinically relevant sub-clonal populations of cells. A novel high throughput methodology called fluorescence in situ hybridization in suspension (FISH-IS) incorporates a flow cytometry-based imaging approach with automated analysis of thousands of cells. Here we have demonstrated that the FISH-IS technique is applicable to aneuploidy detection in CLL samples for a range of chromosomes using appropriate centromere probes. This method is able to accurately differentiate between monosomy, disomy and trisomy with a sensitivity of 1% in CLL. An analysis comparing conventional FISH, FISH-IS and laser scanning cytometry (LSC) is presented.
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An online adaptive screening procedure for selective neuronal responses
Source:Journal of Neuroscience Methods
Author(s): S. Knieling, J. Niediek, E. Kutter, J. Bostroem, C.E. Elger, F. Mormann
BackgroundA common problem in neurophysiology is to identify stimuli that elicit neuronal responses in a given brain region. Particularly in situations where electrode positions are fixed, this can be a time-consuming task that requires presentation of a large number of stimuli. Such a screening for response-eliciting stimuli is employed, e.g., as a standard procedure to identify 'concept cells' in the human medial temporal lobe.New MethodOur new method evaluates neuronal responses to stimuli online during a screening session, which allows us to successively exclude stimuli that do not evoke a response. Using this method, we can screen a larger number of stimuli which in turn increases the chances of finding responsive neurons and renders time-consuming offline analysis unnecessary.ResultsOur method enabled us to present 30% more stimuli in the same period of time with additional presentations of the most promising candidate stimuli. Our online method ran smoothly on a standard computer and network.Comparison with an Existing MethodTo analyze how our online screening procedure performs in comparison to an established offline method, we used the Wave_Clus software package. We did not observe any major drawbacks in our method, but a much higher efficiency and analysis speed.ConclusionsBy transitioning from a traditional offline screening procedure to our new online method, we substantially increased the number of visual stimuli presented in a given time period. This allows to identify more response-eliciting stimuli, which forms the basis to better address a great number of questions in cognitive neuroscience.
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Modelling of the dissolution and reprecipitation of uranium under oxidising conditions in the zone of shallow groundwater circulation
Source:Journal of Environmental Radioactivity, Volumes 178–179
Author(s): Ekaterina M. Dutova, Aleksei N. Nikitenkov, Vitaly D. Pokrovskiy, David Banks, Bjørn S. Frengstad, Valerii P. Parnachev
Generic hydrochemical modelling of a grantoid-groundwater system, using the Russian software "HydroGeo", has been carried out with an emphasis on simulating the accumulation of uranium in the aqueous phase. The baseline model run simulates shallow granitoid aquifers (U content 5 ppm) under conditions broadly representative of southern Norway and southwestern Siberia: i.e. temperature 10 °C, equilibrated with a soil gas partial CO2 pressure (PCO2, open system) of 10−2.5 atm. and a mildly oxidising redox environment (Eh = +50 mV). Modelling indicates that aqueous uranium accumulates in parallel with total dissolved solids (or groundwater mineralisation M – regarded as an indicator of degree of hydrochemical evolution), accumulating most rapidly when M = 550–1000 mg L−1. Accumulation slows at the onset of saturation and precipitation of secondary uranium minerals at M = c. 1000 mg L−1 (which, under baseline modelling conditions, also corresponds approximately to calcite saturation and transition to Na-HCO3 hydrofacies). The secondary minerals are typically "black" uranium oxides of mixed oxidation state (e.g. U3O7 and U4O9). For rock U content of 5–50 ppm, it is possible to generate a wide variety of aqueous uranium concentrations, up to a maximum of just over 1 mg L−1, but with typical concentrations of up to 10 μg L−1 for modest degrees of hydrochemical maturity (as indicated by M). These observations correspond extremely well with real groundwater analyses from the Altai-Sayan region of Russia and Norwegian crystalline bedrock aquifers. The timing (with respect to M) and degree of aqueous uranium accumulation are also sensitive to Eh (greater mobilisation at higher Eh), uranium content of rocks (aqueous concentration increases as rock content increases) and PCO2 (low PCO2 favours higher pH, rapid accumulation of aqueous U and earlier saturation with respect to uranium minerals).
http://ift.tt/2whnWUM
Influence of Northeast Monsoon cold surges on air quality in Southeast Asia
Source:Atmospheric Environment, Volume 166
Author(s): M.J. Ashfold, M.T. Latif, A.A. Samah, M.I. Mead, N.R.P. Harris
Ozone (O3) is an important ground-level pollutant. O3 levels and emissions of O3 precursors have increased significantly over recent decades in East Asia and export of this O3 eastward across the Pacific Ocean is well documented. Here we show that East Asian O3 is also transported southward to tropical Southeast (SE) Asia during the Northeast Monsoon (NEM) season (defined as November to February), and that this transport pathway is especially strong during 'cold surges'. Our analysis employs reanalysis data and measurements from surface sites in Peninsular Malaysia, both covering 2003–2012, along with trajectory calculations. Using a cold surge index (northerly winds at 925 hPa averaged over 105–110°E, 5°N) to define sub-seasonal strengthening of the NEM winds, we find the largest changes in a region covering much of the Indochinese Peninsula and surrounding seas. Here, the levels of O3 and another key pollutant, carbon monoxide, calculated by the Monitoring Atmospheric Composition and Climate (MACC) Reanalysis are on average elevated by, respectively, >40% (∼15 ppb) and >60% (∼80 ppb) during cold surges. Further, in the broader region of SE Asia local afternoon exceedances of the World Health Organization's air quality guideline for O3 (100 μg m−3, or ∼50 ppb, averaged over 8 h) largely occur during these cold surges. Day-to-day variations in available O3 observations at surface sites on the east coast of Peninsular Malaysia and in corresponding parts of the MACC Reanalysis are similar, and are clearly linked to cold surges. However, observed O3 levels are typically ∼10–20 ppb lower than the MACC Reanalysis. We show that these observations are also subject to influence from local urban pollution. In agreement with past work, we find year-to-year variations in cold surge activity related to the El Nino-Southern Oscillation (ENSO), but this does not appear to be the dominant influence of ENSO on atmospheric composition in this region. Overall, our study indicates that the influence of East Asian pollution on air quality in SE Asia during the NEM could be at least as large as the corresponding, well-studied spring-time influence on North America. Both an enhanced regional observational capability and chemical modelling studies will be required to fully untangle the importance of this long-range influence relative to local processes.
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Mechanical and optical properties of monolithic CAD-CAM restorative materials
Source:The Journal of Prosthetic Dentistry
Author(s): Nazmiye Sen, Yesim Olcer Us
Statement of problemAchieving natural tooth appearance with sufficient mechanical strength is one of the most challenging issues of computer-assisted design and computer-assisted manufacturing (CAD-CAM) materials. However, limited evidence is available regarding their optical and mechanical properties for proper and evidence-based material selection in clinical practice.PurposeThe purpose of this in vitro study was to assess and compare the translucency and biaxial flexural strength of 5 monolithic CAD-CAM restorative materials.Material and methodsDisk-shaped specimens (n=30) of each material (Lava Ultimate [LU], Vita Enamic [VE], Vitablocs Mark II [VMII], Vita Suprinity [VS], and IPS e.max CAD [IPS]) with a diameter of 12 mm and a thickness of 1.2 ±0.05 mm were prepared. A spectrophotometer was used to measure the translucency parameter. The specimens were then subjected to a biaxial flexure test using 3 balls and loaded with a piston in a universal testing machine at a cross-head speed of 0.5 mm/min until failure occurred (International Organization for Standardization standard 6872). Weibull statistics were used to evaluate the characteristic strength and reliability of each material. Chemical compositions were analyzed using an energy dispersive spectrometer, and microstructural analysis was conducted using scanning electron microscopy. Data were analyzed using 1-way ANOVA and the Tukey honest significant difference test (α=.05).ResultsSignificant differences were found among the materials concerning translucency and biaxial flexural strength (P<.05). The highest mean transparency value was obtained in the VS group, whereas the lowest mean value was obtained in the VE group. The VS group produced the highest mean biaxial flexural strength, followed by the IPS, LU, VE, and VMII groups.ConclusionsBased on the results of the present study, zirconia-reinforced glass-ceramic revealed higher mean translucency and biaxial flexural strength than resin nanoceramic, feldspathic ceramic, lithium disilicate ceramic, and dual-network ceramic.
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Effect of thixotropic agents as additives on the mechanical properties of maxillofacial silicone elastomers
Source:The Journal of Prosthetic Dentistry
Author(s): Abdel Rahim M. Bibars, Zeid Al-Hourani, Yousef Khader, Mark Waters
Statement of problemThe incorporation of thixotropic agents to prevent slumping during the silicone packing procedure may alter some favorable mechanical properties of the silicone elastomers and could possibly influence the success of the prosthesis.PurposeThe purpose of this in vitro study was to evaluate the effect of adding thixotropic agents on the mechanical properties of 3 commonly used silicone elastomers.Material and methodsSpecimens of 3 maxillofacial silicones (M511, Z004; Technovent Ltd, and A2000; Factor II Inc) were prepared according to the manufacturers' instructions. Tear and tensile strength values and percentages of elongation and hardness were evaluated for each material with and without thixotropic agents. Data were analyzed using 1-way ANOVA and the Bonferroni post hoc test (α=.05).ResultsResults showed that the 3 types of silicone elastomers had significantly different (P<.001) tensile and tear strength and hardness values and percentages of elongation. Z004 silicone showed the highest tensile and tear strength followed by A2000 and M511, regardless of the addition of thixotropic agent. The addition of a thixotropic agent decreased the tear strength (P<.001) but not the tensile strength for all types of silicone. Percentage of elongation was the highest in M511 and the lowest in A2000 and was significantly higher (P<.001) for silicones with no added thixotropic agent. Hardness was highest in A2000 and lowest in M511. Adding a thixotropic agent decreased hardness significantly (P<.001) for Z004 and A2000 only.ConclusionsThe incorporation of thixotropic agents into the 3 maxillofacial silicone elastomers used in this study reduced some favorable mechanical properties, particularly tear strength and percentage of elongation. Z004 showed superior mechanical properties among the 3 tested silicones.
http://ift.tt/2vAfZw6
Immediate implant placement and complete mouth rehabilitation with CAD-CAM titanium frameworks and cemented crowns for a patient with severe periodontal disease: A clinical report
Source:The Journal of Prosthetic Dentistry
Author(s): Pei Wang, Chunbo Tang, Yi Tang, Yunong Wu
The technique of immediate implantation has been widely used to reduce treatment time and bone loss after extraction. However, immediate implant placement in infected extraction sockets is generally contraindicated. This clinical report describes a treatment protocol for immediate implantation after the extraction of teeth with generalized chronic periodontitis. The technique used for the oral rehabilitation used computer-assisted design and computer-assisted manufacturing (CAD-CAM) titanium frameworks and cemented zirconia crowns. The titanium frameworks overcame suboptimal implant position and the cemented crowns provided excellent function and esthetics despite the locations of screw-access openings. No clinical complications occurred during a 13-month follow-up.
http://ift.tt/2ubrZ3y
Accuracy of stereolithography additive casts used in a digital workflow
Source:The Journal of Prosthetic Dentistry
Author(s): Hiba Al-Imam, Mia Gram, Ana R. Benetti, Klaus Gotfredsen
Statement of problemDespite the increasing demand for a digital workflow in the fabrication of indirect restorations, information on the accuracy of the resulting definitive casts is limited.PurposeThe purpose of this in vitro study was to compare the accuracy of definitive casts produced with digital scans and conventional impressions.Material and methodsChamfer preparations were made on the maxillary right canine and second molar of a typodont. Subsequently, 9 conventional impressions were made to produce 9 gypsum casts, and 9 digital impressions were made to produce stereolithography additive (SLA) casts from 2 manufacturers: 9 Dreve SLA casts and 9 Scanbiz SLA casts. All casts were then scanned 9 times with an extraoral scanner to produce the reference data set. Trueness was evaluated by superimposing the data sets obtained by scanning the casts with the reference data set. Precision was evaluated by analyzing the deviations among repeated scans. The root mean square (RMS) and percentage of points aligned within the nominal values (±50 μm) of the 3-dimensional analysis were calculated by the software.ResultsGypsum had the best alignment (within 50 μm) with the reference data set (median 95.3%, IQR 16.7) and the least RMS (median 25.8 μm, IQR 14.6), followed by Dreve and Scanbiz. Differences in RMS were observed between gypsum and the SLA casts (P<.001). Within 50 μm, gypsum was superior to Scanbiz (P<.001). Gypsum casts exhibited the highest precision, showing the best alignment (within 50 μm) and the least RMS, followed by Scanbiz and Dreve.ConclusionsThis study found that gypsum casts had higher accuracy than SLA casts. Within 50 μm, gypsum casts were better than Scanbiz SLA casts, while gypsum casts and Dreve SLA casts had similar trueness. Significant differences were found among the investigated SLA casts used in the digital workflow.
http://ift.tt/2vAg2Ir
Effects of image and education on the precision of the measurement method for evaluating prosthesis misfit
Source:The Journal of Prosthetic Dentistry
Author(s): Hang-Nga Mai, Kyeong Eun Lee, Jung-Hong Ha, Du-Hyeong Lee
Statement of problemVarious methods for measuring prosthesis misfit have been suggested. Although the cross-sectional images between the crown and abutment are used to evaluate the misfit, the effects of the image and the observer's knowledge on the precision of measurement are unknown.PurposeThe purpose of this in vitro study was to investigate the effects of the image and of education on the precision of prosthesis misfit measurement methods using inter- and intraobserver variability analyses.Material and methodsThe cross-sectional images in the margin were obtained using the computer-aided replica technique (CART), silicone replica technique (RT), and sectioning technique (ST). Twenty-five observers measured the absolute marginal discrepancy values in the images obtained from each group 4 times at an interval of 2 weeks; the observers went through different education sessions regarding the selection of the measurement points. The precision of measurement was determined and compared using the likelihood-ratio test statistic (α=.05) and the intraclass correlation coefficient with the linear mixed-effects model.ResultsThe CART group exhibited the smallest deviations in the measurement variations, followed by the ST and RT groups (P<.001). Additional education on misfit measurements generally decreased the deviation values in all the groups, but without any significant differences.ConclusionsThe cross-sectional image obtained from the measurement methods and education on the evaluation method affected the precision of the prosthesis misfit measurement. Digital methods might be a useful tool to significantly enhance the precision of the measurements.
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1-Hz rTMS in the treatment of tinnitus: A sham-controlled, randomized multicenter trial
Source:Brain Stimulation
Author(s): Michael Landgrebe, Göran Hajak, Stefan Wolf, Frank Padberg, Philipp Klupp, Andreas J. Fallgatter, Thomas Polak, Jacqueline Höppner, Rene Haker, Joachim Cordes, Thomas Klenzner, Carlos Schönfeldt-Lecuona, Thomas Kammer, Erika Graf, Michael Koller, Tobias Kleinjung, Astrid Lehner, Martin Schecklmann, Timm B. Pöppl, Peter Kreuzer, Elmar Frank, Berthold Langguth
BackgroundChronic tinnitus is a frequent, difficult to treat disease with high morbidity.ObjectiveThis multicenter randomized, sham-controlled trial investigated the efficacy and safety of 1-Hz repetitive transcranial magnetic stimulation (rTMS) applied to the left temporal cortex in patients with chronic tinnitus.MethodsTinnitus patients were randomized to receive 10 sessions of either real or sham 1-Hz-rTMS (2000 stimuli, 110% motor threshold) to the left temporal cortex. The primary outcome was the change in the sum score of the tinnitus questionnaire (TQ) of Goebel and Hiller from baseline to end of treatment.ResultsA total of 163 patients were enrolled in the study (real rTMS: 75; sham rTMS: 78). At day 12, the baseline mean of 43.1 TQ points in 71 patients assigned to real rTMS changed by −0.5 points; it changed by 0.5 points from a baseline of 42.1 in 75 patients randomized to sham rTMS (adjusted mean difference between groups: −1.0; 95.19% confidence interval: −3.2 to 1.2; p = 0.36). All secondary outcome measures including measures of depression and quality of life showed no significant differences either (p > 0.11). The number of participants with side-effects or adverse events did not differ between groups.ConclusionReal 1-Hz-rTMS over the left temporal cortex was well tolerated but not superior compared with sham rTMS in improving tinnitus severity. These findings are in contrast to results from studies with smaller sample sizes and put the efficacy of this rTMS protocol for treatment of chronic tinnitus into question.Trial RegistrationControlled Trials: http://ift.tt/2vzTtn0.
http://ift.tt/2ubmK46
Stereotactic Radiosurgery with or without Whole Brain Radiotherapy for Limited Brain Metastases: A Secondary Analysis of the NCCTG N0574 (Alliance) Randomized Controlled Trial
Publication date: Available online 5 August 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Thomas M. Churilla, Karla V. Ballman, Paul D. Brown, Erin L. Twohy, Kurt Jaeckle, Elana Farace, Jane H. Cerhan, S. Keith Anderson, Xiomara W. Carrero, Yolanda I. Garces, Fred G. Barker, Richard Deming, Jesse G. Dixon, Stuart H. Burri, Caroline Chung, Cynthia Ménard, Volker W. Stieber, Bruce E. Pollock, Evanthia Galanis, Jan C. Buckner, Anthony L. Asher
BackgroundThere are conflicting data regarding a potential survival benefit to adjuvant whole brain radiotherapy (WBRT) among patients with limited brain metastases treated with stereotactic radiosurgery (SRS). We sought to determine if WBRT is associated with improved overall survival among non-small cell lung cancer (NSCLC) patients with favorable prognoses at diagnosis.MethodsIn the N0574 trial, patients with 1-3 brain metastases were randomized to receive SRS or SRS+WBRT with a primary endpoint of cognitive deterioration. We calculated diagnosis-specific graded prognostic assessment (DS-GPA) scores for NSCLC patients and evaluated overall survival according to receipt of WBRT and DS-GPA score using two separate cut-points (> 2.0 vs. <2.0 and > 2.5 vs. < 2.5).ResultsA total of 126 NSCLC patients were included for analysis with median follow up of 14.2 months. Data for DS-GPA calculation was available for 86.3% of all enrolled NSCLC patients. Overall, 50.0% of patients had DS-GPA score > 2.0 and 23.0% of patients had DS-GPA scores > 2.5. The SRS and SRS+WBRT groups were well balanced with regard to prognostic factors. The median survival according to receipt of WBRT was 11.3 months (+WBRT) and 17.9 months (-WBRT) for patients with DS-GPA > 2.0 (favorable prognoses, p=0.63; HR, 0.86; 95%CI, 0.47-1.59). Median survival was 3.7 months (+WBRT) and 6.6 months (-WBRT) for patients with DS-GPA < 2.0 patients (unfavorable prognoses, p=0.85; HR, 0.95; 95%CI, 0.56-1.62). Outcomes according to the receipt of WBRT and DS-GPA remained similar utilizing DS-GPA > 2.5 as a cutoff for favorable prognoses. There was no interaction between the continuum of the DS-GPA groups and WBRT on overall survival (p=0.53).ConclusionsWe observed no significant differences in survival according to receipt of WBRT in favorable prognosis NSCLC patients. This study further supports the approach of SRS alone in the majority of patients with limited brain metastases.
Teaser
There are conflicting data regarding whether adjuvant whole brain radiotherapy (WBRT) improves survival among patients with 1-3 brain metastases and favorable prognostic factors. Our post-hoc analysis of the N0574 trial demonstrated that overall survival did not differ according to the use of WBRT among non-small cell lung cancer patients with favorable (p=0.63) or unfavorable (p=0.85) diagnosis-specific graded prognostic assessment scores. In patients with limited (1-3) brain metastases, stereotactic radiosurgery alone remains a preferred treatment approach.http://ift.tt/2whe9hJ
The Incidence of Totally Implantable Venous Access Devices Insertion and the Associated Abnormalities in Patients With Cancer Revealed in 18F-FDG PET-CT Imaging
Source:Academic Radiology
Author(s): Pan-Fu Kao, Jui-Hung Weng, Yeu-Sheng Tyan, Shun-Fa Yang, Thomas Chang-Yao Tsao
Rationale and ObjectivesThe purpose of this retrospective study was to evaluate the incidence of totally implantable venous access devices, also called ports, implantation and the associated abnormalities in 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography-computed tomography (PET-CT) images for patients with cancer, and to determine the percentage of abnormalities identified in the original reports.Materials and MethodsThe study aimed to perform a retrospective review of all FDG PET-CT imaging in a 3-year period. Cases of port-associated abnormalities found on the FDG PET-CT images were identified and then correlated with X-ray reports and clinical treatment or follow-up.ResultsIn total, 2442 FDG PET-CT scans were retrospectively reviewed. Among them, 897 (897 of 2442, 36.7%) demonstrated port implantation. Abnormalities, including 22 port fractures (22 of 897, 2.45%), 14 malposition (1.56%), one infection (0.11%), and one embraced by a fibrin sheath or tumor (0.11%) were found. Only the infectious one had clinical symptoms. Among the 22 fractured ports, eight fractured catheters migrated and became dislodged. All of the malpositioned ports, except two in the contralateral subclavian vein, were found in the ipsilateral jugular vein. Both the port infection and the port embraced by a fibrin sheath or tumor occurred at the tips of the devices, which demonstrated FDG uptake in the mediastinal region. Only seven of the 38 (18.42%) images of port abnormalities had been identified in the original reports.ConclusionsBased on this study, we recommend that the interpretation of FDG PET-CT scans should include a checklist to record all metallic device implantations and to interpret the whole-body X-ray topography as a standard part of PET-CT image report.
http://ift.tt/2v8MX4w
Neutrophilic Inflammation in Asthma and Association with Disease Severity
Publication date: Available online 4 August 2017
Source:Trends in Immunology
Author(s): Anuradha Ray, Jay K. Kolls
Asthma is a chronic inflammatory disorder of the airways. While the local infiltration of eosinophils and mast cells, and their role in the disease have long been recognized, neutrophil infiltration has also been assessed in many clinical studies. In these studies, airway neutrophilia was associated with asthma severity. Importantly, neutrophilia also correlates with asthma that is refractory to corticosteroids, the mainstay of asthma treatment. However, it is now increasingly recognized that neutrophils are a heterogeneous population, and a more precise phenotyping of these cells may help delineate different subtypes of asthma. Here, we review current knowledge of the role of neutrophils in asthma and highlight future avenues of research in this field.
http://ift.tt/2vsbVhY
New Developments in the Rapid Actions of Steroids and their Receptors
Publication date: Available online 5 August 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Eric R. Prossnitz
http://ift.tt/2ub6DUb
Radiosensitization by gold nanoparticles: Will they ever make it to the clinic?
Source:Radiotherapy and Oncology
Author(s): Lei Cui, Sohyoung Her, Gerben R. Borst, Robert G. Bristow, David A. Jaffray, Christine Allen
The utilization of gold nanoparticles (AuNPs) as radiosensitizers has shown great promise in pre-clinical research. In the current review, the physical, chemical, and biological pathways via which AuNPs enhance the effects of radiation are presented and discussed. In particular, the impact of AuNPs on the 5 Rs in radiobiology, namely repair, reoxygenation, redistribution, repopulation, and intrinsic radiosensitivity, which determine the extent of radiation enhancement effects are elucidated. Key findings from previous studies are outlined. In addition, crucial parameters including the physicochemical properties of AuNPs, route of administration, dosing schedule of AuNPs and irradiation, as well as type of radiation therapy, are highlighted; the optimal selection and combination of these parameters enable the achievement of a greater therapeutic window for AuNP sensitized radiotherapy. Future directions are put forward as a means to provide guidelines for successful translation of AuNPs to clinical applications as radiosensitizers.
http://ift.tt/2vrHisX
Role of glial-cell-derived neurotrophic factor in salivary gland stem cell response to irradiation
Source:Radiotherapy and Oncology
Author(s): Xiaohong Peng, Kärt Varendi, Martti Maimets, Jaan-Olle Andressoo, Rob P. Coppes
Background and purposeRecently, stem cell therapy has been proposed to allow regeneration of radiation damaged salivary glands. It has been suggested that glial-cell-derived neurotrophic factor (GDNF) promotes survival of mice salivary gland stem cells (mSGSCs). The purpose of this study was to investigate the role of GDNF in the modulation of mSGSC response to irradiation and subsequent salivary gland regeneration.MethodsSalivary gland sphere derived cells of Gdnf hypermorphic (Gdnfwt/hyper) and wild type mice (Gdnfwt/wt) were irradiated (IR) with γ-rays at 0, 1, 2, 4 and 8Gy. mSGSC survival and stemness were assessed by calculating surviving fraction measured as post-IR sphere forming potential and population doublings. Flow cytometry was used to determine the CD24hi/CD29hi stem cell (SC) population. QPCR and immunofluorescence was used to detect GDNF expression.ResultsThe IR survival responses of mSGSCs were similar albeit resulted in larger spheres and an increased cell number in the Gdnfwt/hyper compared to Gdnfwt/wt group. Indeed, mSGSC of Gdnfwt/hyper mice showed high sphere forming efficiency upon replating. Interestingly, GDNF expression co-localized with receptor tyrosine kinase (RET) and was upregulated after IR in vitro and in vivo, but normalized in vivo after mSGSC transplantation.ConclusionGDNF does not protect mSGSCs against irradiation but seems to promote mSGSCs proliferation through the GDNF-RET signaling pathway. Post-transplantation stimulation of GDNF/RET pathway may enhance the regenerative potential of mSGSCs.
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Carbon-ion re-irradiation for recurrences after initial treatment of stage I non-small cell lung cancer with carbon-ion radiotherapy
Source:Radiotherapy and Oncology
Author(s): Masataka Karube, Naoyoshi Yamamoto, Hiroshi Tsuji, Nobuyuki Kanematsu, Mio Nakajima, Hideomi Yamashita, Keiichi Nakagawa, Tadashi Kamada
PurposeTo investigate carbon-ion radiotherapy (CIRT) for in-field recurrence of stage I non-small cell lung cancer (NSCLC) initially treated with CIRT.Materials and methodsFrom January 2007 to March 2014, patients initially treated for stage I NSCLC with CIRT and relapsed in-field were candidates. Overall survival (OS) rate, local control (LC) rate, progressive free survival (PFS) rate, dose to the lungs and skin, and adverse effects were analyzed.ResultsTwenty-nine patients were eligible. Median age at re-irradiation was 74years (range 53–90). Median observation period from the first day of re-irradiation was 29months (4–88months). Median prescribed dose was 46.0Gy (RBE) as initial treatment and 66.0Gy (RBE) in 12 fractions as re-irradiation. Two-year OS, LC, and PFS rates after re-irradiation were 69.0% (95% CI: 50.3–83.0), 66.9% (95% CI: 47.5–81.9), and 51.7% (95% CI: 34.1–68.9). Median skin maximum dose was 53.8Gy (RBE) (range 4.4–103.1) and median of mean lung dose was 7.3Gy (RBE) (range 2.6–14.0). There were no severer than grade 2 adverse effects except one (3.4%) grade 3 bacterial pneumonia, which was not considered radiation-induced.ConclusionCIRT for stage I NSCLC local recurrence is an acceptable definitive re-treatment.
http://ift.tt/2vrH6Kb
Preclinical validation of 111In-girentuximab-F(ab′)2 as a tracer to image hypoxia related marker CAIX expression in head and neck cancer xenografts
Source:Radiotherapy and Oncology
Author(s): Fokko J. Huizing, Bianca A.W. Hoeben, Gerben Franssen, Jasper Lok, Sandra Heskamp, Egbert Oosterwijk, Otto C. Boerman, Johan Bussink
Background and purposeHypoxia is a major cause of radio- and chemoresistance. Carbonic anhydrase IX (CAIX) is an endogenous hypoxia-related marker and an important prognostic marker. Assessment of CAIX expression may allow patient selection for hypoxia or CAIX-targeted treatment. The radioactive tracer 111In-girentuximab-F(ab′)2 targets CAIX and can be used for SPECT imaging. Aim of this study was to validate and optimize 111In-girentuximab-F(ab′)2 for imaging of CAIX expression in head and neck tumor xenografts.Material and methodsAffinity and internalization kinetics of 111In-girentuximab-F(ab′)2 were determined in vitro using CAIX-expressing SK-RC-52 cells. Tumor targeting characteristics were determined in athymic mice with six different head and neck squamous cell carcinoma (SCCNij) xenografts. Tracer uptake was measured by ex vivo radioactivity counting. Intratumoral distribution of tracer uptake was measured using autoradiography and CAIX expression was determined immunohistochemically.Results26% of the tracer was internalized into the SK-RC-52 cells within 24h. The half maximal inhibitory concentration (IC50) was 0.69±0.08nM. In biodistribution studies SCCNij153 tumors showed the highest tracer uptake: 4.1±0.8ID/g at 24h p.i. Immunohistochemical and autoradiographic analyses of the xenografts showed a distinct spatial correlation between localization of the tracer and CAIX expression.Conclusion111In-girentuximab-F(ab′)2 has a high affinity for CAIX. In vivo tumor uptake correlated strongly with CAIX expression in different head and neck xenografts. These results suggest that 111In-girentuximab-F(ab′)2 is a promising tracer for imaging of hypoxia-related CAIX expression.
http://ift.tt/2v8MqQ8
Protective effects of high-potency FMDV O1 Manisa monovalent vaccine in cattle challenged with FMDV O/SKR/2010 at 7 or 4 days post vaccination
Source:Vaccine
Author(s): Jacquelyn Horsington, Claudia Beascoechea Perez, Eduardo Maradei, Sabrina Galdo Novo, Jose L. Gonzales, Nagendrakumar B. Singanallur, Paula Bonastre, Wilna Vosloo
Serotype O foot-and-mouth disease (FMD) virus belonging to the SEA topotype continues to be a significant problem in the Eastern Asia region, with outbreaks in Japan and South Korea resulting in the culling of over 3.5 million cattle and pigs in recent years. High-potency O1 Manisa vaccine was previously shown to provide protection in cattle 21days post vaccination (dpv) following challenge with a representative virus, O/SKR/2010. This study tested the ability of the O1 Manisa vaccine to protect cattle from infection and disease with the O/SKR/2010 virus within just 4 or 7days post vaccination. The vaccine protected 50% of cattle from clinical disease when administered 7days prior to challenge, but was not protective with just 4days between vaccination and challenge. Viraemia was significantly reduced in animals challenged 7 dpv but not 4 dpv, compared to unvaccinated controls, however, there were no effects on the level of virus detected in nasal and oral secretions regardless of vaccination time. The level of neutralising antibodies detected in cattle challenged 7 dpv correlated with protection from clinical disease. All animals seroconverted to FMDV non-structural proteins, suggesting no sterile protection. An equal number of animals became persistently infected in both vaccine groups. The results indicated that high-potency O1 Manisa vaccine administered just 7days prior to challenge should provide partial protection of cattle if an outbreak of O/SKR/2010, or related viruses, occurs, and would be useful to limit spread of FMDV when used in conjunction with other control measures.
http://ift.tt/2vAbKk2
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Summary Insulinomas are rare neuroendocrine tumours that classically present with fasting hypoglycaemia. This case report discusses an un...
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