Αρχειοθήκη ιστολογίου

Σάββατο 23 Σεπτεμβρίου 2017

Removal of Copper, Lead, Methylene Green 5, and Acid Red 1 by Saccharide-Derived Spherical Biochar Prepared at Low Calcination Temperatures: Adsorption Kinetics, Isotherms, and Thermodynamics

Abstract

Spherical biochar derived from saccharides (glucose, sucrose, and xylose) was prepared through two steps: pre-hydrothermal carbonization at 190 °C and calcination at low temperatures (200–325 °C). The spherical biochar was characterized by Brunauer–Emmett–Teller (BET) surface area analysis, Fourier transform infrared spectroscopy, zeta potential, scanning and transmission electron microscopies, and X-ray diffraction. The result indicated that the spherical biochar exhibited low S BET (15–22 m2/g), but abundant superficial active oxygen-containing functional groups. The spherical biochar possessed a negatively charged surface within solution pH 2.0–11. The adsorption process of Pb2+, Cu2+, and methylene green 5 (MG5) was strongly dependent on the solution pH and reached fast equilibrium at approximately 60 min. The maximum Langmuir adsorption capacity (Q°max) exhibited the following order: glucose-biochar > sucrose-biochar > xylose-biochar prepared at 300 °C. The selective adsorption order of glucose-biochar was Cu2+ (0.894 mmol/g) > Pb2+ (0.848 mmol/g) > MG5 (0.334 mmol/g). The electrostatic attraction played a determining role in the adsorption mechanism of pollutant cations. The adsorption of anionic dye (acid red 1) on the spherical biochar was negligible because of electrostatic repulsion. The spherical biochar can serve as a newer and promising adsorbent to remove toxic pollutant cations from water media.



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Genetic Diversity Loss in Chironomus sancticaroli (Diptera: Chironomidae) Exposed to Pyrimethanil Fungicide: an Analysis Using RAPD Technique

Abstract

In the agricultural cultivation, the Pyrimethanil (4,6-dimethyl-N-phenyl-2-pyrimidinamine) fungicide is one of the most widely used compound in monocultures and has been detected in aquatic ecosystems. These genotoxic products increase the frequency of lesions in the DNA molecule, thereby increasing the risk of replication and transcription of altered DNA sequences. This study aimed to assess the loss of genetic diversity of Chironomus sancticaroli, a Brazilian native insect species, exposed to Pyrimethanil fungicide, using RAPD-PCR (random amplified polymorphic DNA) technique. The results showed that there was significant loss in the genetic diversity in the organisms exposed to high Pyrimethanil concentrations when compared with control site. Our findings reveal that RAPD-PCR is an effective method to access genetic loss derived to fungicide use and that the agriculture application may lead to a decrease in aquatic biota genetic diversity. This finding has important implications for conservation strategies and ecological management environments.



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Comparison of Several Amendments for In-Site Remediating Chromium-Contaminated Farmland Soil

Abstract

Hexavalent chromium (Cr(VI)), which has been classified as a Group A human carcinogens list by the United States Environmental Protection Agency, possesses stronger biological toxicity, and its discharge into farmland has become a pressing environmental problems. To screen the cost-efficient Cr(VI)-contaminated soil in situ amended materials, the effects of ordinary zero-valent iron (ZVI), nanoscale zero-valent iron (nZVI), biochar (B), biochar/zero-valent iron (BZVI), and biochar/nanoscale zero-valent iron (BnZVI) on the immobilization of Cr(VI) in spiked soil (Cr(VI) = 325 mg kg−1, Crtotal = 640 mg kg−1) were compared in this paper. After 15 days remediation by those materials, toxicity characteristic leaching procedure and physiological-based extraction test showed that the Cr(VI) leachability and bioaccessibility were reduced by 14–92% and 4.3–92% respectively, and the order of immobilization was found to be nZVI > BnZVI > BZVI > ZVI > B. Moreover, sequential extraction procedure indicated that all materials can increase the proportion of the residual Cr, and nZVI had the most significant effect. Plant seedling growth test proved that the nanoscale zero-valent iron was able to reduce the toxicity of chromium in plants greatly in a short time, while BnZVI treatment is more favorable to the growth of plants. To sum up, the nano zero-valent iron and biochar combined treatment not only removed Cr(VI) and immobilized total chromium efficiently but also enabled plant growth in relative high chromium-containing soil.



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Double-blind, proof-of-concept (POC) trial of Low-Field Magnetic Stimulation (LFMS) augmentation of antidepressant therapy in treatment-resistant depression (TRD)

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Publication date: Available online 23 September 2017
Source:Brain Stimulation
Author(s): Maurizio Fava, Marlene P. Freeman, Martina Flynn, Bettina B. Hoeppner, Richard Shelton, Dan V. Iosifescu, James W. Murrough, David Mischoulon, Cristina Cusin, Mark Rapaport, Boadie W. Dunlop, Madhukar H. Trivedi, Manish Jha, Gerard Sanacora, Gretchen Hermes, George I. Papakostas
BackgroundLow-Field Magnetic Stimulation (LFMS) is a novel, non-invasive, sub-threshold neuromodulation technique, shown in preliminary studies to have immediate mood elevating effects in both unipolar and bipolar depressed patients.ObjectiveWe aimed to assess the antidepressant augmentation effects at 48 h of LFMS administered on two consecutive days compared to sham treatment in treatment resistant depression (TRD) subjects, using the Sequential Parallel Comparison Design (SPCD).MethodsEighty-four eligible subjects with TRD were randomly assigned to double-blind treatment with LFMS 20 min/day for four days, sham treatment 20 min/day for four days, or sham treatment 20 min/day for 2 days followed by LFMS treatment 20 min/day for two days, using the pre-randomization version of the SPCD (randomization 1:1:1). The SPCD analyses used a repeated measures linear modeling approach with maximum likelihood estimation to use all available data, and using a 60–40 weighting of Stage 1 vs. 2 responses, with the primary outcome being measured after 2 and 4 days.ResultsBoth primary and secondary outcome measures consistently showed no differences between LFMS-treated patients and those treated with sham, with the exception of a slight, non-significantly greater improvement than sham in the visual analogue scale (VAS) sad mood on LFMS-treated patients. LFMS treatment was relatively well tolerated.ConclusionsWe did not observe a significantly greater, rapid efficacy of LFMS compared to sham therapy. Future studies need to examine the possible therapeutic effects of more intensive forms of LFMS, as other forms of neurostimulation typically require longer duration of exposure.



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A Modeling System for Monitoring Water Quality in Lagoons

Abstract

Regular monitoring of key water quality parameters is important for assessing the hydrological status of a lagoon and its management activities. In this study, a new cost-effective technique based on the geo-ecological information-modeling system (GIMS) is implemented employing the combined use of simulation experiments and in-field observations to investigate the problem of optimizing water quality monitoring of a lagoon. The GIMS is accompanied by 39 elements selected in 8 management systems and 31 functional elements, which are described in detail. It is shown that the combined use of model and field observations allows reliable recording of lagoon water quality and optimization of the monitoring regime. Finally, simulation experiments are presented, demonstrating the fidelity of the proposed modeling system to optimize water quality control through regular in-field measurements and simulations.



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Phenol Biodegradation by Pseudomonas putida in an Airlift Reactor: Assessment of Kinetic, Hydrodynamic, and Mass Transfer Parameters

Abstract

An airlift biofilm reactor was employed to study phenol biodegradation by Pseudomonas putida. Hydrodynamic tests were also conducted in a conventional column to facilitate the comparison of the dynamic behavior in different types of columns. The three-phase airlift column offered better aeration than the conventional column as liquid and solid circulation in the downcomer favored bubble breakup, increasing oxygen dissolved in the liquid phase and favoring the phenol biodegradation process. Kinetic parameters of phenol biodegradation by P. putida were obtained in an agitated batch reactor, with the initial phenol concentration varying from 10 to 750 mg/L. Experimental data were fitted using different microbial growth models found in literature. The Yano and Koga model, which considers the formation of multiple inactive enzyme–substrate complexes, fitted well with our experimental data, with a correlation coefficient, R 2 = 0.952. An internal loop airlift bioreactor was used for aerobic phenol biodegradation in which polystyrene particles were utilized to support biomass immobilization. Several tests were performed by varying the influent phenol concentration, hydraulic retention time, upstream flow, and superficial air velocity. It was concluded that until an influent phenol concentration of approximately 300 mg/L, phenol acted as the limiting substrate. For higher phenol concentrations, oxygen became the limiting substrate. An increase in the oxygen concentration resulted in the complete consumption of phenol under high phenol concentration of 500 mg/L.



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Patterns and the Occurrence of KRAS Mutations in Metastatic Colorectal Cancers—a Study from Indian Regional Cancer Centre

Abstract

Mutation analysis of the KRAS oncogene is established as a predictive biomarker in Colorectal cancer (CRC). Many prospective clinical trials have shown that only CRCs with wild-type KRAS respond to anti-epidermal growth factor receptor (EGFR) treatment. Hence, mutation analysis is mandatory before treatment of metastatic CRCs. There are very few studies on the KRAS mutation status in the Indian setting. Hence, this study was done to document the patterns of KRAS mutations in CRCs reporting to a regional cancer centre in South India. Among 150 cases of metastatic colorectal cancer reporting over a period of 20 months, 48 random cases were analyzed for the KRAS mutational status of codons 12 and 13 of the KRAS gene by genomic sequencing. KRAS mutations in codons 12 and 13 were present in 9/48 (18.75%) of all analyzed CRCs. The common types of mutations were glycine to aspartate on codon 12 (p.G12D), glycine to valine on codon 12 (p.G12 V), and glycine to aspartate on codon 13 (p.G13D).



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Genomic signatures as predictive biomarkers of homologous recombination deficiency in ovarian cancer

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Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): Adriaan Vanderstichele, Pieter Busschaert, Siel Olbrecht, Diether Lambrechts, Ignace Vergote
DNA repair deficiency is a common hallmark of many cancers and is increasingly recognised as a target for cancer therapeutics. Selecting patients for these treatments requires a functional assessment of multiple redundant DNA repair pathways. With the advent of whole-genome sequencing of cancer genomes, it is increasingly recognised that multiple signatures of mutational and chromosomal alterations can be correlated with specific DNA repair defects. The clinical relevance of this approach is underlined by the use of poly-(ADP-ribose) polymerase inhibitors (PARPi) in homologous recombination (HR) deficient high-grade serous ovarian cancers. Beyond deleterious mutations in HR-related genes such as BRCA1/2, it is recognised that HR deficiency endows ovarian cancers with specific signatures of base substitutions and structural chromosomal variation. Multiple metrics quantifying loss-of-heterozygosity (LOH) events were proposed and implemented in trials with PARPi. However, it was shown that some of the HR-deficient cases, i.e. CDK12–mutated tumours, were not associated with high LOH-based scores, but with distinct patterns of genomic alterations such as tandem duplication. Therefore, more complex signatures of structural genomic variation were identified and quantified. Ultimately, optimal prediction models for treatments targeting DNA repair will need to integrate multiples of these genomic signatures and will also need to assess multiple resistance mechanisms such as genomic reversion events that partially or fully re-activate DNA repair.



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PIKHER2: A phase IB study evaluating buparlisib in combination with lapatinib in trastuzumab-resistant HER2-positive advanced breast cancer

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Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): Mathilde Guerin, Keyvan Rezai, Nicolas Isambert, Mario Campone, Aurélie Autret, Jihane Pakradouni, Magali Provansal, Jacques Camerlo, Renaud Sabatier, François Bertucci, Emmanuelle Charafe-Jauffret, Alice Hervieu, Jean-Marc Extra, Patrice Viens, François Lokiec, Jean-Marie Boher, Anthony Gonçalves
BackgroundPhosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin pathway is frequently activated in HER2-positive breast cancer and may play a major role in resistance to trastuzumab. Buparlisib is a pan-class-I PI3K inhibitor with potent and selective activity against wild-type and mutant PI3K p110 isoforms.Patients and methodsPIKHER2 phase IB study aimed primarily to determine a maximum tolerated dose (MTD) and propose a recommended phase II dose (RP2D) for buparlisib in combination with lapatinib in HER2-positive, trastuzumab-resistant, advanced breast cancer. Oral buparlisib (40, 60 or 80 mg) and lapatinib (750, 1000 or 1250 mg) were administered daily. A modified continuous reassessment method using an adaptive Bayesian model guided the dose escalation of both agents. Secondary end-points included antitumour activity and pharmacokinetic (PK) assessments.ResultsA total of 24 patients were treated across five dose levels. Dose-limiting toxicities included transaminases elevation, vomiting, stomatitis, hyperglycemia and diarrhoea. MTD was declared at buparlisib 80 mg/d + lapatinib 1250 mg/d, but toxicities and early treatment discontinuation rate beyond cycle 1 led to select buparlisib 80 mg + lapatinib 1000 mg/d as the RP2D. Main drug-related adverse events included diarrhoea, nausea, skin rash, asthenia, depression, anxiety and transaminases increase. There was no significant evidence for drug–drug PK interaction. Disease control rate was 79% [95% confidence interval [CI] 57–92%], one patient obtained a complete remission, and six additional patients experienced stable disease for ≥ 24 weeks (clinical benefit rate of 29% [95% CI 12–51%]).ConclusionCombining buparlisib and lapatinib in HER2-positive trastuzumab-resistant advanced breast cancer was feasible. Preliminary evidence of antitumour activity was observed in this heavily pre-treated population.Trial registration IDNCT01589861.



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Determination of poor prognostic immune features of tumour microenvironment in non-smoking patients with lung adenocarcinoma

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Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): Tomonari Kinoshita, Chie Kudo-Saito, Reiko Muramatsu, Tomonobu Fujita, Miyuki Saito, Haruna Nagumo, Toshiharu Sakurai, Shinobu Noji, Emi Takahata, Tomonori Yaguchi, Nobuo Tsukamoto, Yuichiro Hayashi, Kaoru Kaseda, Ikuo Kamiyama, Takashi Ohtsuka, Kenji Tomizawa, Masaki Shimoji, Tetsuya Mitsudomi, Hisao Asamura, Yutaka Kawakami
We have previously demonstrated that the prognostic significance of tumour-infiltrating CD8+ T cells significantly differs according to histological type and patient smoking habits in non-small cell lung cancer (NSCLC). This work suggested that infiltrating CD8+ T cells may not be activated sufficiently in the immunosuppressive microenvironment in non-smokers with adenocarcinoma. To understand the immunogenic microenvironment in NSCLC, we characterised immune cells comprehensively by performing an immunohistochemical evaluation using an alternative counting method and multicolour staining method (n = 234), and assessed immune-related gene expression by using genetic analytical approaches (n = 58). We found that high infiltration of activated CD8+ T cells expressing interferon gamma (IFN-γ) and granzyme was correlated with postoperative survival in patients with non-adenocarcinoma. On the contrary, CD8+ T-cell accumulation was identified as a worse prognostic factor in patients with adenocarcinoma, particularly in non-smokers. Infiltrating CD8+ T cells were significantly less activated in this microenvironment with high expression of various immunoregulation genes. Potentially immunoregulatory CD8+ FOXP3+ T cells and immunodysfunctional CD8+ GATA3+ T cells were increased in adenocarcinoma of non-smokers. CD4+ FOXP3+ regulatory T cells expressing chemokine receptor-4 (CCR4)- and chemokine ligand (CCL17)-expressing CD163+ M2-like macrophages also accumulated correlatively and significantly in adenocarcinoma of non-smokers. These characteristic immune cells may promote tumour progression possibly by creating an immunosuppressive microenvironment in non-smoking patients with lung adenocarcinoma. Our findings may be helpful for refining the current strategy of personalised immunotherapy including immune-checkpoint blockade therapy for NSCLC.



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Pre-operative Duplex Ultrasonography in Arteriovenous Fistula Creation: Intra- and Inter-observer Agreement

Publication date: Available online 22 September 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Niek Zonnebeld, Tommy M.G. Maas, Wouter Huberts, Magda M. van Loon, Tammo Delhaas, Jan H.M. Tordoir
ObjectiveAlthough clinical guidelines on arteriovenous fistula (AVF) creation advocate minimum luminal arterial and venous diameters, assessed by duplex ultrasonography (DUS), the clinical value of routine DUS examination is under debate. DUS might be an insufficiently repeatable and/or reproducible imaging modality because of its operator dependency. The present study aimed to assess intra- and inter-observer agreement of DUS examination in support of AVF surgery planning.MethodsTen end stage renal disease patients were included, to assess intra- and inter-observer agreement of pre-operative DUS measurements. All measurements were performed by two trained and experienced vascular technicians, blinded to measurement readings. From the routine DUS protocol, representative measurements (venous diameters, and arterial diameters and volume flow in the upper arm and forearm) were selected. For intra-observer agreement the measurements were performed in triplicate, with the probe released from the skin between each. Intraclass correlation coefficients were calculated for intra- and inter-observer agreement, and Bland-Altman plots used to graphically display mean measurement differences and limits of agreement.ResultsTen patients (6 male, 59.4±19.7 years) consented to participate, and all predefined measurements were obtained. Intraclass correlation coefficients for intra-observer agreement of diameter measurements were at least 0.90 (95% CI 0.74–0.97; radial artery). Inter-observer agreement was at least 0.83 (0.46–0.96; lateral diameter upper arm cephalic vein). The Bland-Altman plots showed acceptable mean measurement differences and limits of agreement.ConclusionIn experienced hands, excellent intra- and inter-observer agreement can be reached for the discrete pre-operative DUS measurements advocated in clinical guidelines. DUS is therefore a reliable imaging modality to support AVF surgery planning. The content of DUS protocols, however, needs further standardisation.



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Intra-osseous Hemangioma of the Frontal Bone. Report of a Case and review of the literature

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Publication date: Available online 23 September 2017
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Joshua S. Brandner, Yeshwant B. Rawal, Louis J. Kim, Jasjit K. Dillon
Intra-osseous hemangiomas of the maxillofacial region are rare lesions that comprise less than 1% of all osseous tumors1. A review of the literature on intra-osseous hemangiomas of the skull and facial bones revealed a limited number of publications, much of which was largely limited to case reports. This case report summarizes the workup and surgical treatment of a 39-year-old female with an intra-osseous hemangioma of the left frontal bone. The histology, treatment, and literature are reviewed.



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Bilateral Breast and Axillary Lymph Nodes Metastases of an Ovarian Serous Cystadenocarcinoma



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Dry deposition of NO2 over China inferred from OMI columnar NO2 and atmospheric chemistry transport model

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Publication date: November 2017
Source:Atmospheric Environment, Volume 169
Author(s): X.Y. Zhang, X.H. Lu, L. Liu, D.M. Chen, X.M. Zhang, X.J. Liu, Y. Zhang
The NO2 dry deposition over China was estimated based on an inferential model, in which the surface NO2 concentrations and deposition velocities were derived from OMI columnar NO2 and the simulation results from atmospheric chemistry transport models. Nationally, the annual NO2 dry deposition fluxes ranged from 0.0005 to 8.54 kg N ha−1, with an average of 0.48 kg N ha−1. The total NO2 dry deposition over China was 0.46 Tg N yr−1, mainly contributed by northern and southeast China. Due to contrary seasonal trends of the NO2 concentrations (high in cold months) and deposition velocities (high in warm months), the estimated NO2 dry depositions did not show strong seasonal pattern, instead showing relatively high values from August to October and low ones in February. The annual NO2 dry deposition has an increasing trend from 2007 to 2014, with the highest deposition level achieved in 2011. This research conducts a thorough validation between estimated NO2 dry depositions with ground measurements of NO2 concentrations and provides an objective spatial perspective and insight on the existing NO2 dry deposition maps in China.



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Impact of aromatics and monoterpenes on simulated tropospheric ozone and total OH reactivity

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Publication date: November 2017
Source:Atmospheric Environment, Volume 169
Author(s): William C. Porter, Sarah A. Safieddine, Colette L. Heald
The accurate representation of volatile organic compounds (VOCs) in models is an important step towards the goal of understanding and predicting many changes in atmospheric constituents relevant to climate change and human health. While isoprene is the most abundant non-methane VOC, many other compounds play a large role in governing pollutant formation and the overall oxidative capacity of the atmosphere. We quantify the impacts of aromatics and monoterpenes, two classes of VOC not included in the standard gas-phase chemistry of the chemical transport model GEOS-Chem, on atmospheric composition. We find that including these compounds increases mean total summer OH reactivity by an average of 11% over the United States, Europe, and Asia. This increased reactivity results in higher simulated levels of O3, raising maximum daily 8-h average O3 in the summer by up to 14 ppb at some NOx-saturated locations.



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Minimization of model representativity errors in identification of point source emission from atmospheric concentration measurements

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Publication date: November 2017
Source:Atmospheric Environment, Volume 169
Author(s): Maithili Sharan, Amit Kumar Singh, Sarvesh Kumar Singh
Estimation of an unknown atmospheric release from a finite set of concentration measurements is considered an ill-posed inverse problem. Besides ill-posedness, the estimation process is influenced by the instrumental errors in the measured concentrations and model representativity errors. The study highlights the effect of minimizing model representativity errors on the source estimation. This is described in an adjoint modelling framework and followed in three steps. First, an estimation of point source parameters (location and intensity) is carried out using an inversion technique. Second, a linear regression relationship is established between the measured concentrations and corresponding predicted using the retrieved source parameters. Third, this relationship is utilized to modify the adjoint functions. Further, source estimation is carried out using these modified adjoint functions to analyse the effect of such modifications. The process is tested for two well known inversion techniques, called renormalization and least-square. The proposed methodology and inversion techniques are evaluated for a real scenario by using concentrations measurements from the Idaho diffusion experiment in low wind stable conditions. With both the inversion techniques, a significant improvement is observed in the retrieval of source estimation after minimizing the representativity errors.



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Whole exome sequencing in inborn errors of immunity: use the power but mind the limits.

Purpose of review: Next-generation sequencing, especially whole exome sequencing (WES), has revolutionized the molecular diagnosis of inborn errors of immunity. This review summarizes the generation and analysis of next-generation sequencing data. Recent findings: The focus is on prioritizing strategies for unveiling the potential disease-causing variant. We also highlighted oversights and imperfections of WES and targeted panel sequencing, as well as the need for functional validation. Summary: The information is crucial for a judicious use of WES by researchers, but even more so by the clinical immunologist. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Comparison of the accuracy of maxillary position between conventional model surgery and virtual surgical planning

The aim of this study was to determine whether virtual surgical planning (VSP) is an accurate method for positioning the maxilla when compared to conventional articulator model surgery (CMS), through the superimposition of computed tomography (CT) images. This retrospective study included the records of 30 adult patients submitted to bimaxillary orthognathic surgery. Two groups were created according to the treatment planning performed: CMS and VSP. The treatment planning protocol was the same for all patients.

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Natural variation of the zygomaticomaxillary complex symmetry in normal individuals

The most frequently encountered midfacial fractures are zygomaticomaxillary complex (ZMC) fractures (Gupta et al., 2009; van Hout et al., 2013; Arangio et al., 2014). In ZMC fracture cases, the restoration of facial symmetry is the main treatment goal after functional recovery (Ellis, 2013; Ellis and Perez, 2014) because symmetry plays an important role in the visual perception of faces (Grammer and Thornhill, 1994; Perrett et al., 1998; Rhodes, 2006). Furthermore, a symmetrical face is correlated with perceived healthiness and attractiveness (Rhodes et al., 1998; Jones et al., 2001; Fink et al., 2006).

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Mechanisms of motor learning mediated by synaptic plasticity in rat primary motor cortex

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Publication date: Available online 23 September 2017
Source:Neuroscience Research
Author(s): Hiroyuki Kida, Dai Mitsushima
Motor skill training induces long-term potentiation (LTP) and structural plasticity at dendritic spines in the primary motor cortex (M1). However, little is known about the plasticity of individual M1 neurons. Skilled motor coordination in rodents was recently assessed in studies using an accelerated rotor rod task with 1–2days of training. Using this model, we investigated the effects of motor training on both AMPA receptor-mediated excitatory synapses and GABAA receptor-mediated inhibitory synapses in layer II/III neurons in the M1. One day of the motor training strengthened AMPA receptor-mediated excitatory synapses and drastically reduced presynaptic GABA release probability. Two days of the training further strengthened AMPA receptor-mediated excitatory synapses as well as NMDA receptors, and increased presynaptic glutamate release while also restoring presynaptic GABA release probability. In this review, we discuss the dynamic changes observed in both glutamatergic and GABAergic plasticity as well as intrinsic plasticity after the training.



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Two cases of benign fibrous histiocytomas (dermatofibromas) associated with Langerhans cell histiocytosis

Abstract

We report two cases of fibrous histiocytoma (FH) associated with discrete nodular aggregates of Langerhans cells (LCs) resembling Langerhans cell histiocytosis (LCH). In addition, the LCs showed positivity for BRAF V600E immunohistochemistry, a finding reported in neoplastic but not reactive LCs 1. To our knowledge, these cases represent the first published association of FH and LCH.

This article is protected by copyright. All rights reserved.



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Occipital Artery to Middle Cerebral Artery Bypass: Operative Nuances

Publication date: December 2017
Source:World Neurosurgery, Volume 108
Author(s): Toshikazu Kimura, Akio Morita
BackgroundSuperficial temporal artery (STA)–middle cerebral artery (MCA) anastomosis is a common procedure for vascular neurosurgeons, and it is used in a variety of diseases. However, there are cases in which the STA is absent or is too hypoplastic to be used as a donor for revascularization. Occipital artery (OA)–MCA bypass may be a treatment option in these cases.MethodsWe encountered 4 cases of symptomatic cerebral ischemia in which the STA was absent or unavailable. These cases were treated by revascularization from the OA to the periphery of the MCA.ResultsBy meticulous dissection of the OA to the level of the superior temporal line, the OA could reach the periphery of the angular artery and be anastomosed to it in the usual fashion. The patency of the donor artery was confirmed by magnetic resonance angiography soon after the operation and 3 years later.ConclusionsOA-MCA bypass may be a surgical option for cerebral revascularization when the STA is not available.



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Sound wave propagation on the human skull surface with bone conduction stimulation

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Publication date: Available online 23 September 2017
Source:Hearing Research
Author(s): Ivo Dobrev, Jae Hoon Sim, Stefan Stenfelt, Sebastian Ihrle, Rahel Gerig, Flurin Pfiffner, Albrecht Eiber, Alexander M. Huber, Christof Röösli
BackgroundBone conduction (BC) is an alternative to air conduction to stimulate the inner ear. In general, the stimulation for BC occurs on a specific location directly on the skull bone or through the skin covering the skull bone. The stimulation propagates to the ipsilateral and contralateral cochlea, mainly via the skull bone and possibly via other skull contents. This study aims to investigate the wave propagation on the surface of the skull bone during BC stimulation at the forehead and at ipsilateral mastoid.MethodsMeasurements were performed in five human cadaveric whole heads. The electro-magnetic transducer from a BCHA (bone conducting hearing aid), a Baha® Cordelle II transducer in particular, was attached to a percutaneously implanted screw or positioned with a 5-Newton steel headband at the mastoid and forehead. The Baha transducer was driven directly with single tone signals in the frequency range of 0.25–8 kHz, while skull bone vibrations were measured at multiple points on the skull using a scanning laser Doppler vibrometer (SLDV) system and a 3D LDV system. The 3D velocity components, defined by the 3D LDV measurement coordinate system, have been transformed into tangent (in-plane) and normal (out-of-plane) components in a local intrinsic coordinate system at each measurement point, which is based on the cadaver head's shape, estimated by the spatial locations of all measurement points.ResultsRigid-body-like motion was dominant at low frequencies below 1 kHz, and clear transverse traveling waves were observed at high frequencies above 2 kHz for both measurement systems. The surface waves propagation speeds were approximately 450 m/s at 8 kHz, corresponding trans-cranial time interval of 0.4 ms. The 3D velocity measurements confirmed the complex space and frequency dependent response of the cadaver heads indicated by the 1D data from the SLDV system. Comparison between the tangent and normal motion components, extracted by transforming the 3D velocity components into a local coordinate system, indicates that the normal component, with spatially varying phase, is dominant above 2 kHz, consistent with local bending vibration modes and traveling surface waves.ConclusionBoth SLDV and 3D LDV data indicate that sound transmission in the skull bone causes rigid-body-like motion at low frequencies whereas transverse deformations and travelling waves were observed above 2 kHz, with propagation speeds of approximately of 450 m/s at 8 kHz.



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Can CAD/CAM resin blocks be considered as substitute for conventional resins?

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Publication date: Available online 23 September 2017
Source:Dental Materials
Author(s): Badra Hussain, Minh Khai Le Thieu, Gaute Floer Johnsen, Janne Elin Reseland, Håvard J. Haugen
ObjectiveDentists are facing a myriad of new CAD/CAM product for dental filling therapies. Are the new materials any worthwhile using? Are they succeeding the standard filling materials? Here we compare for the first time the new resin-composite blocks (RCBs) with conventional materials (Filtek Z250 and Tetric EvoCeram).MethodsThe material were tested for residual monomer elution by HPLC, thermogravimetric analysis (TG) was used to determine the percentage of fillers by weight, hardness was evaluated by Vickers method, morphology of fillers and distribution in the matrix were examined by scanning electron microscopy (SEM), elemental analysis for elemental determination of the filler particles was performed by energy-dispersive X-ray spectroscopy (EDX) cytotoxicity using human gingival fibroblasts and an epithelial cell line.ResultsThe RBC outperformed conventional composite regarding mechanical characteristics (hardness) and monomer eluation, but showed some worrisome results regarding cytotoxicity.SignificanceThe cost benefit is not in favour of RBCs in comparison to conventional composites, as the cytotoxicity was found higher for RBCs.



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Pelvic Girdle Pain a Typical Female Condition? What About Men?

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Publication date: October 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 10
Author(s): Jan-Paul van Wingerden




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Cancer Survivors Awaiting Rehabilitation Rarely Achieve Recommended Physical Activity Guidelines

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Publication date: October 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 10
Author(s): Amy Dennett, Casey Peiris, Nora Shields, Nicholas Taylor




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Editorial Board

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Publication date: October 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 10





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TheraBracelet Sensory Stimulation To Enhance Hand Functional Recovery Post Stroke

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Publication date: October 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 10
Author(s): Na Jin Seo, Ryan Downey, Blair Dellenbach, Rosemarie Imburgia, Abigail Lauer, V. Ramakrishnan, Leonardo Bonilha, Michelle Woodbury




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Table of Contents

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Publication date: October 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 10





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Editors' Selections From This Issue: Volume 98 / Number 10 / October 2017

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Publication date: October 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 10





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Manual Therapy: Integration into a Speech and Swallowing Rehabilitation Program for Head and Neck Cancer

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Publication date: October 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 10
Author(s): Jan Lewin, Holly Woodall, Christine Porsche, Martha Barrow, Katherine Hutcheson




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Withdrawn

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Publication date: October 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 10





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Masthead

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Publication date: October 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 10





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Information/Education Pages (I/EPs)

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Publication date: October 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 10





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Study of Therapy and Assessment on Acupuncture Habilitation for Children with Cerebral Palsy

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Publication date: October 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 10
Author(s): Huan Liu




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Long-Term Functional Outcomes Among Childhood Cancer Survivors with Osteonecrosis

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Publication date: October 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 10
Author(s): Brian DeFeo, Mary Relling, Kirsten Ness, Tara Brinkman, Israel Fernandez-Pineda, Michael Neel, Deo Kumar Srivastava, Zhenghong Li, Melissa Hudson, Leslie Robison, Seth Karol, Sue Kaste




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A Medical Home for Individuals with Physical Disabilities: Addressing the Social Determinants of Health

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Publication date: October 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 10
Author(s): Nancy Flinn, Thomas Kelley




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Fatigue and Functional Outcomes in Cancer Rehabilitation

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Publication date: October 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 10
Author(s): Monica Arrigo, Lisa Wood, Lynne Brady-Wagner, Twyla Fink, Karla Garrity, Amanda Mack




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Effects of Real-time Gait Biofeedback on Paretic Propulsion and Gait Biomechanics in Individuals Post-Stroke

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Publication date: October 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 10
Author(s): Katlin Genthe, Christopher Schenck, Steven Eicholtz, Steven Wolf, Trisha Kesar




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Importance of the Correct Use of Extracorporeal Shockwave Therapy

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Publication date: October 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 10
Author(s): Hannes Müller-Ehrenberg, Silvia Ramón, Wolfgang Schaden, Daniel Moya, María Cristina d'Agostino, Carlos Leal, José Ramón Aranzabal, José Eid




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2017 ACRM Annual Conference Abstracts

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Publication date: October 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 10





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Relationship Between Pain, Social Support and Socio-Economic Indicators in Individuals with Spinal Cord Injury

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Publication date: October 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 10
Author(s): Zahra Khazaeipour, Ehsan Ahmadipour, Vafa Rahimi-Movaghar, Fereshteh Ahmadipour, Alexander R. Vaccaro, Babak Babakhani




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Development and Implementation of a Theory-Based Sedentary Behavior Change Intervention for People with Stroke

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Publication date: October 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 10
Author(s): Victor Ezeugwu, Patricia Manns




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Ankle Control Differentiation as a Mechanism for Mobility Limitations

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Publication date: October 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 10
Author(s): Eric James, Jeffrey Hausdorff, Suzanne Leveille, Thomas Travison, Jonathan Bean




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The absence of an association between Interleukin 1β gene polymorphisms and recurrent aphthous stomatitis (RAS)

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Publication date: December 2017
Source:Archives of Oral Biology, Volume 84
Author(s): Zuzanna Ślebioda, Anna Kowalska, Marta Rozmiarek, Ewa Krawiecka, Elżbieta Szponar, Barbara Dorocka-Bobkowska
ObjectivesRecurrent aphthous stomatitis (RAS) is a chronic, ulcerative disease with a probable polygenic mode of inheritance and complex etiology with a strong immunological background. The aim of the present study was to determine the possible association between two single nucleotide polymorphisms (SNPs) of the IL-1β gene: IL-1β−511 T>C (rs16944) and IL-1β+3954C>T (rs1143634) and RAS susceptibility in a moderately large group of patients.DesignOne hundred and four patients with minor, major and herpetiform RAS and 75 healthy volunteers were genotyped at IL-1β−511 T>C (rs16944) and IL-1β+3954C>T (rs1143634) using the PCR-RFLP approach. The results were statistically analysed with chi-square test and test of difference between two rates of structure, with p<0.05 assumed to be a statistically significance level (Statistica 10, StatSoft®, Kraków, Poland).ResultsThere were no statistically significant differences in the genotype distribution for the IL-1β C[+3954]T polymorphism between the RAS and control groups. The frequency of IL-1β*T[-511]/*T[–511] homozygotes among the patients was significantly higher when compared to our study control (p<0.0347). The results after stratification into carriers and non-carriers of C and T alleles did not clearly indicate which SNP may be considered a risk factor for RAS.ConclusionsThe genetic association between the studied SNPs of the IL-1β gene and RAS remains controversial and requires further investigation.



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Dental erosion in archaeological human remains: A critical review of literature and proposal of a differential diagnosis protocol

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Publication date: December 2017
Source:Archives of Oral Biology, Volume 84
Author(s): Isabelle Coupal, Arkadiusz Sołtysiak
ObjectiveAlthough studies of dental wear on archaeological human remains have largely focused on mechanical wear (attrition and abrasion) in the past, chemical wear (erosion) is being increasingly identified as a separate form of wear. This paper aims to review the current state of research and to develop a protocol that may be universally used by biorchaeologists to specifically identify dental erosion.Design and resultsA critical review of literature has been done in order to highlight the issues related to diagnosis of dental erosion in archaeological human remains. The bodies of work based on the analysis of both modern and archaeological dentitions raise their separate problems. In addition to a need to re-evaluate symptoms of dental erosion, notably dentin 'cupping', it is apparent that no specific protocol is adapted from medical to archaeological sciences. Authors rather rely on tooth wear indices and photographs of modern clinical cases for diagnosis. Furthermore, the diagenetic chemical alternation has rarely been considered as a bias.ConclusionsHere we suggest a three-step protocol: the primary method is the microscopic identification of dental erosion by SEM, followed by the exclusion of taphonomic aetiology on surrounding bone and soil pH analysis. Archaeologists should also explore possible causative agents of wear using archaeological and historic knowledge about the population being analyzed.



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In vitro and in vivo anti-microbial activity evaluation of inactivated cells of Lactobacillus salivarius CECT 5713 against Streptococcus mutans

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Publication date: December 2017
Source:Archives of Oral Biology, Volume 84
Author(s): Ana I. Sañudo, Roberto Luque, Mª Paz Díaz-Ropero, Juristo Fonollá, Óscar Bañuelos
ObjectiveDefining the etiology of dental caries is a complex problem. The microbiological approach has included Streptococcus mutans as one of the bacterial species involved in this disease. This research investigates the inhibitory effects of heat-inactivated Lactobacillus salivarius CECT 5713 against S. mutans using in vitro and in vivo assays.DesignOn the one hand, the effect of non-viable L. salivarius CECT 5713 on the in vitro adhesion of S. mutans to hydroxyapatite discs was evaluated. On the other hand, levels of Streptococcus mutans, amount of salivary flow and salivary pH before and after taking the rinse with the non-viable L. salivarius CECT 5713 in healthy volunteers were assessed (self-controlled open-label pilot study).ResultsThe levels of S. mutans seemed to decrease in the in vitro and in vivo assays (p<0.05). The in vitro effect of non-viable L. salivarius was maintained until 36 months of storage. In addition, the reduction of S. mutans salivary concentration in the volunteers was statistically significant from the third day until two weeks of treatment.ConclusionsHeat-inactivated L. salivarius CECT 5713 prevents S. mutans adhesion to hydroxyapatite and could be used as a strategy to reduce the salivary concentration of this oral pathogen.



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Facial skeleton asymmetry and its relationship to mastication in the Early Medieval period (Great Moravian Empire, Mikulčice, 9th–10th century)

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Publication date: December 2017
Source:Archives of Oral Biology, Volume 84
Author(s): Alexandra Ibrová, Ján Dupej, Petra Stránská, Petr Velemínský, Lumír Poláček, Jana Velemínská
ObjectivesThe aim of this study was to analyse the relationship of mastication and directional asymmetry (DA) of upper facial skeleton in Early Medieval sample from the Mikulčice settlement (Czech Republic).DesignThe settlement is divided into two burial areas of presumably different socioeconomic status: the castle and the sub-castle. The material consisted of 193 individuals (125 castle, 68 sub-castle). The relationship of facial skeleton DA and mastication was analysed by examining tooth wear and mandibular shape by means of 3D geometric morphometrics. Tooth wear of premolars and molars was evaluated using appropriate scoring systems. 3D coordinates of 35 mandibular landmarks were scanned using MicroScribe G2X digitizing system.ResultsThe results did not reveal any significant differences in tooth wear DA or mandible DA values between burial areas or sexes. Mandibular shape, however, differed significantly between burial areas and sexes. Directional changes of mandibular landmarks supported a right chewing side preference in the sample. Significant relationship between upper facial skeleton DA and mandible DA was recorded.ConclusionsDifferences in subsistence between burial areas and sexes did not translate into differences in mandible DA and dental wear. However, mandibular shape analysis revealed prominence of areas affected by masticatory muscles in individuals from the castle. Higher consumption of tough material, such as meat, has been proposed as possible explanation. The right side was found to be preferential for chewing. The relationship between upper facial skeleton DA and mandible DA was concluded to be the result of the compensatory and adaptive function of mandible.



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Aims & Scope/Editorial board

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Publication date: November 2017
Source:Archives of Oral Biology, Volume 83





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Optimizing concentration of titanium tetrafluoride solution for human dentine remineralization

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Publication date: November 2017
Source:Archives of Oral Biology, Volume 83
Author(s): Peng Wang, Jianghong Gao, Danyang Wang, Malcolm L. Snead, Juedan Li, Jianping Ruan
ObjectiveThe aim of the present study was to select the optimal concentration of TiF4 solution to facilitate the remineralization of early dentine caries lesions.DesignSixty human dentine specimens were cut and randomly divided into 6 groups (1%, 2%, 3%, 4% TiF4 groups, 2.712% NaF group and distilled deionized water (DDW) control group). Artificial dentine caries-like lesions were created. After being subjected to fluoride treatment and immersed in remineralizing solution for 2weeks, the specimens were observed by microCT, scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). Data were analysed using linear regression analysis (P<0.05).ResultsThe lesion depths of the specimens treated by 2% TiF4 solution were statistically less than those of the other groups. Further, the greyscale values of these lesion areas were greater. The 3% and 4% TiF4 solutions caused further lesion demineralization. The 2.712% NaF solution seemed to be detrimental to remineralization during the experimental time, as the subsurface area remained hypomineralized with a thick precipitation layer on the surface.ConclusionsThe 2% TiF4 solution demonstrated better remineralizing potency than did the other treatments.



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Structural, mechanical and chemical evaluation of molar-incisor hypomineralization-affected enamel: A systematic review

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Publication date: November 2017
Source:Archives of Oral Biology, Volume 83
Author(s): Karim Elhennawy, David John Manton, Felicity Crombie, Paul Zaslansky, Ralf J. Radlanski, Paul-Georg Jost-Brinkmann, Falk Schwendicke
ObjectivesTo systematically assess and contrast reported differences in microstructure, mineral density, mechanical and chemical properties between molar-incisor-hypomineralization-affected (MIH) enamel and unaffected enamel.MethodsStudies on extracted human teeth, clinically diagnosed with MIH, reporting on the microstructure, mechanical properties or the chemical composition and comparing them to unaffected enamel were reviewed. Electronic databases (PubMed, Embase and Google Scholar) were screened; hand searches and cross-referencing were also performed.ResultsTwenty-two studies were included. Fifteen studies on a total of 201 teeth investigated the structural properties, including ten (141 teeth) on microstructure and seven (60 teeth) on mineral density; six (29 teeth) investigated the mechanical properties and eleven (87 teeth) investigated the chemical properties of MIH-affected enamel and compared them to unaffected enamel. Studies unambiguously found a reduction in mineral quantity and quality (reduced Ca and P content), reduction of hardness and modulus of elasticity (also in the clinically sound-appearing enamel bordering the MIH-lesion), an increase in porosity, carbon/carbonate concentrations and protein content compared to unaffected enamel.Findingswere ambiguous with regard to the extent of the lesion through the enamel to the enamel-dentin junction, the Ca/P ratio and the association between clinical appearance and defect severity.ConclusionsThere is an understanding of the changes related to MIH-affected enamel. The association of these changes with the clinical appearance and resulting implications for clinical management are unclear.Clinical significanceMIH-affected enamel is greatly different from unaffected enamel. This has implications for management strategies. The possibility of correlating the clinical appearance of MIH-affected enamel with the severity of enamel changes and deducing clinical concepts (risk stratification etc.) is limited.



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Parathyroid hormone-related peptide (1–34) reduces alveolar bone loss in type 1 diabetic rats

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Publication date: November 2017
Source:Archives of Oral Biology, Volume 83
Author(s): Wen Zhang, Su-Zhen Wu, Jian Zhou, Hong-Min Chen, Ye-Li Gong, Fang-Fang Peng, Bai-Fang Zhang
ObjectiveTo investigate the role of parathyroid hormone related protein (PTHrP) in diabetic periodontitis.MethodsAfter injected with 55mg/kg streptozotocin, diabetic rats were treated subcutaneously with low-dose (40μg/kg, once daily for 5days per week), middle-dose (80μg/kg) or high-dose (160μg/kg) PTHrP(1–34) peptide. Treatment continued for 12 weeks. Changes in periodontal tissues were confirmed by micro-computerized tomography assay and H&E analysis. We used tartrate resistant acid phosphatase (TRAP) staining to identify osteoclast cells. The expression of TNF-α, IL-1β and IL-6 was assessed by immunohistochemistry and Western blot.ResultsTooth-supporting structure loss was observed in periodontal tissues of diabetic rats. PTHrP (1–34) attenuated alveolar bone loss, especially in the middle-dose and high-dose group. Whereas TNF-α, IL-1β and IL-6 protein levels were increased in the diabetic gingival tissues, PTHrP (1–34) treatment inhibited the increase of IL-1β and IL-6, but had no effect on TNF-α.ConclusionType 1 diabetes increased the susceptibility to periodontal disease. Intermittent administration of PTHrP (1–34) exhibited an inhibitory effect on alveolar bone resorption and the gingival inflammation in periodontal tissues of diabetic rats.



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Mechanisms involved in facial heat hyperalgesia induced by endothelin-1 in female rats

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Publication date: November 2017
Source:Archives of Oral Biology, Volume 83
Author(s): Rafael Fernandes de Souza, Luana Lechenakoski de Oliveira, Carina Fernanda Mattedi Nones, Renata Cristiane dos Reis, Erika Ivanna Araya, Caroline Machado Kopruszinski, Giles Alexander Rae, Juliana Geremias Chichorro
ObjectivePronociceptive responses to endothelins in the trigeminal system seem to be mediated by ETA and ETB receptors, which have been shown to be expressed in neurons of the trigeminal ganglion of humans and rats. The present study aimed to evaluate the ability of endothelin-1 (ET-1) to induce facial heat hyperalgesia in female rats, the contribution of ETA and ETB receptors to this response, as well as the mechanisms underlying heat hyperalgesia induced by ET-1.DesignET-1 (100pmol/50μL) was injected into the upper lip and heat hyperalgesia was evaluated for up to 6h. Facial heat hyperalgesia induced by ET-1 was assessed in rats pre-treated locally with BQ-123 or BQ-788 (selective ETA and ETB receptor antagonists, respectively, 30nmol/50μL); BCTC (TRPV1 receptor antagonist; 300μg/50μL); anti-NGF (3μg/50μL); K252a (TrkA inhibitor, 1μg/50μL); or in rats that received intraganglionar resiniferatoxin injection (RTX, 200ng/10μL) to promote C-fibers ablation.ResultsET-1 induced facial heat hyperalgesia that persisted up to 6h and was prevented by BQ-123, BQ-788 or by intraganglionar RTX injection. Likewise, local pre-treatment with BCTC abolished ET-1 induced facial heat hyperalgesia up to 3h. Local pre-treatment with anti-NGF or K252a was effective to prevent ET-1 induced heat hyperalgesia.ConclusionsIn conclusion, ET-1 is able to induce heat hyperagelsia in trigeminal primary afferents of female rats, which is mediated by ETA and ETB receptors. Activation of TRPV1 receptors and NGF-signaling pathways may contribute to heat hyperalgesia induced by ET-1.



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The Significance of L1CAM Expression in Clear Cell Carcinoma of the Endometrium

Abstract

Clear cell carcinoma is an uncommon histotype of endometrial carcinoma, representing less than 1% of cases (1). Although clear cell carcinoma is generally considered to be a clinically aggressive, "high risk" cancer (2), reported patient outcomes have been markedly variable at every stage of disease (3-8), possibly reflecting an underlying biologic heterogeneity that is inherent to the histotype (9). Indeed, somatic mutation profiling of cases classified as clear cell carcinoma have shown them to be markedly heterogeneous at the molecular level, with subsets resembling serous carcinomas, endometrioid carcinoma, neither, or both (10-12).

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Cost-effectiveness of nivolumab for recurrent or metastatic head and neck cancer☆

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Publication date: November 2017
Source:Oral Oncology, Volume 74
Author(s): Matthew C. Ward, Chirag Shah, David J. Adelstein, Jessica L. Geiger, Jacob A. Miller, Shlomo A. Koyfman, Mendel E. Singer
ObjectiveNivolumab is the first drug to demonstrate a survival benefit for platinum-refractory recurrent or metastatic head and neck cancer. We performed a cost-utility analysis to assess the economic value of nivolumab as compared to alternative standard agents in this context.Materials and methodsUsing data from the CheckMate 141 trial, we constructed a Markov simulation model from the US payer's perspective to evaluate the cost-effectiveness of nivolumab compared to physician choice of either cetuximab, methotrexate or docetaxel. Alternative strategies considered included: single-agent cetuximab, methotrexate or docetaxel, or first testing for PD-L1 to select for nivolumab. Costs were extracted from Medicare and utilities from the literature and CheckMate. Probabilistic sensitivity analysis (PSA) was used to evaluate parameter uncertainty. $100,000/QALY was the primary threshold for cost-effectiveness.ResultsWhen comparing nivolumab to the standard arm of CheckMate, nivolumab demonstrated an incremental cost-effectiveness ratio (ICER) of $140,672/QALY. When comparing standard therapies, methotrexate was the most cost-effective with similar results for docetaxel. Nivolumab was cost-effective compared to single-agent cetuximab (ICER $89,786/QALY). Treatment selection by PD-L1 immunohistochemistry did not markedly improve the cost-effectiveness of nivolumab. Factors likely to positively impact the cost-effectiveness of nivolumab include better baseline quality-of-life, poor tolerability of standard treatments and/or a lower cost of nivolumab.ConclusionsNivolumab is preferred to single-agent cetuximab but requires a willingness-to-pay of at least $150,000/QALY to be considered cost-effective when compared to docetaxel or methotrexate. Selection by PD-L1 does not markedly improve the cost-effectiveness of nivolumab. This informs patient selection and clinical care-path development.



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Extracapsular extension is associated with worse distant control and progression-free survival in patients with lymph node-positive human papillomavirus-related oropharyngeal carcinoma

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Publication date: November 2017
Source:Oral Oncology, Volume 74
Author(s): Jeffrey Shevach, Adam Bossert, Richard L. Bakst, Jerry Liu, Krzysztof Misiukiewicz, Jessica Beyda, Brett A. Miles, Eric Genden, Marshall R. Posner, Vishal Gupta
ObjectivesTo determine the prognostic utility of pathologic extracapsular extension (ECE) in human papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma (OPSCC).Materials and MethodsRetrospective analysis was performed on patients who underwent surgery for primary HPV-related OPSCC and received adjuvant radiotherapy (RT) between 2006 and 2015. Locoregional control (LRC), distant control (DC), progression-free survival (PFS) and overall survival (OS) were compared between the groups with and without ECE using univariate Kaplan-Meier and multivariate Cox regression survival analyses.Results75 patients were identified and ECE was demonstrated on the surgical pathology of 26 patients. ECE(+) patients more frequently received chemotherapy (76.9% vs. 32.7%; p<0.0001) and RT doses>66Gy (76.9% vs. 16.3%; p<0.001). With a median follow-up of 29months, patients with ECE had a significantly worse 5-year DC rate than those without ECE (76.7% vs. 97.9%; p=0.046), and patients with ECE had a significantly worse 5-year PFS (54.5% vs. 93.6%; p=0.021) than those without ECE. On multivariate Cox regression analysis, ECE was independently prognostic of worse DC (hazard ratio: 8.26; 95% confidence interval: 1.24–55.21; p=0.029) and worse PFS(HR: 4.64; 95% CI: 1.18–18.29; p=0.028). There was no statistically significant difference in 5-year LRC (93.3% vs. 95.7%) or OS (66.9% vs. 97.0%) between ECE(+) and ECE(−) patients, respectively.ConclusionThis study suggests that ECE is independently prognostic of worse DC and PFS in patients who undergo surgery prior to adjuvant RT for primary HPV-related OPSCC.



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An applied anatomical study of bronchial artery

Abstract

The aim of this study was to reveal the external features of the bronchial artery (BA) system, so as to provide morphological basis for clinic. The BAs in 48 adult cadavers were dissected and analyzed. The number of BAs in 48 cases was 118. The incidence of BA arising from thoracic aorta, right posterior intercostal artery, and right subclavian artery was 69.49, 27.12, and 3.39%, respectively. The origin of BAs in individual specimen might be single, two, or all of them, respectively. According to the different origin and/or origins of BAs, it could be divided into five categories. As for the course of BAs, in this study, all the left BAs arising from thoracic aorta passed forward around the left side of esophagus and then entered left pulmonary hilum; most (n = 15) of the right BAs arising from thoracic aorta passed forward around the left side of esophagus and then entered right pulmonary hilum; a few (n = 8) of the right BAs arising from thoracic passed forward the right side of esophagus and bronchus and then entered right pulmonary hilum. Besides, in our group, the special courses were that right intercostal-bronchial trunk (RICBT) arising from thoracic aorta passed between vertebra and esophagus and gave off BA which curved forward around the right side of esophagus and then entered right pulmonary hilum, common bronchial trunk (CBT) arising from thoracic aorta passed forward around the left side of esophagus laying anterior to bronchus or posterior to bronchus, then dividing into a left and a right BAs entering right and left pulmonary hilum, respectively. In 4 cadavers, the RICBT gave off the radiculomedullary artery and BA in turn, so radiculomedullary artery has the same origin with BA. Of all BAs, the mean diameter of right posterior intercostal artery, CBT, left BA, and right BA was 2.17 ± 0.84, 1.79 ± 0.57, 1.44 ± 0.50, and 1.39 ± 0.38 mm, respectively. The information gained from this study will be of value in clinic application.



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Recovery of Ammonium by Powder Synthetic Zeolites from Wastewater Effluents: Optimization of the Regeneration Step

Abstract

Nitrogen recovery and valorization is gaining interest due to the current need for nitrogen removal, so it is of great interest that ammonium-selective sorbents be evaluated. In this study, a zeolitic material synthesized from coal fly ash (Ze–Na) in sodium form as well as its modification to potassium form (Ze–K) were evaluated as sorbent materials for the recovery of ammonium from wastewater effluents. The sorption performance was assessed through three consecutive sorption-desorption cycles reporting opposite behavior in terms of ammonium sorption capacity. Decreasing in the case of Ze–Na and to slightly increase for Ze–K due to alkaline activation of zeolite surface. The maximum sorption capacities obtained were 109 ± 4 mg NH4/g and 33 ± 1 mg NH4/g for Ze–Na and Ze–K, respectively. It is important to point out that in the case of Ze–Na, the maximum sorbent capacity was obtained during the first sorption cycle whereas in the case of Ze–K, it was obtained during the last working cycle due to the alkaline regeneration. Kinetic studies showed that after every regeneration step, the sorption kinetics turn faster as alkaline desorption increased the zeolite-specific surface, thus increasing the size of porous and enhancing the diffusion through the particle. Results obtained indicate that sorption capacity decreased significantly after every working cycle using Ze–Na whereas Ze–K followed the opposite behavior despite its initial lower sorption capacity.



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Extraskeletal osteosarcoma in the parotid gland: A case report

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Publication date: Available online 22 September 2017
Source:Auris Nasus Larynx
Author(s): Takao Hamamoto, Takashi Kono, Hiromi Furuie, Tsutomu Ueda, Sachio Takeno, Katsuhiro Hirakawa, Koji Arihiro
Extraskeletal osteosarcoma is a very rare tumor and accounts for 4–5% of all osteosarcomas. We describe a 47-year-old Japanese man who presented with a right parotid tumor. The patient underwent total resection with postoperative radiotherapy; however, the tumor recurred in the lung, whereupon he underwent chemotherapy and partial lung resection. After surgery, a hemorrhagic brain metastasis appeared; this tumor was extirpated to prevent bleeding into the brain, after which additional chemotherapy was administered. Nevertheless, the patient developed additional metastases and died 17 months after the total parotidectomy. This tumor was unique in that it arose in the parotid gland; this case provides an instructional example of an extremely rare manifestation of this type of tumor.



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Cochlear Implantation in Children with Anomalous Cochleovestibular Anatomy: Our Experience

Abstract

To report operative findings, postoperative course, and postimplantation performance in patients with cochlear malformations who underwent cochlear implantation. Seventeen patients with malformations which included enlarged vestibular aqueduct (n = 6), Mondini's dysplasia (n = 5) common cavity deformity (n = 3) and incomplete partition type 2 (n = 3) underwent cochlear implantation with Nucleus 22 straight array device at our center. Operative findings described facial nerve anatomy and cerebrospinal fluid leak. Standard tests of speech perception were used to evaluate the postoperative performance for each subject. Operative findings included cerebrospinal fluid leak (thirteen patients) all of which were repaired successfully with graft. None had abnormal facial nerve anatomy. No surgical complications occurred. All the patients except two with common cavity had complete insertion. Electrode thresholds and discomfort levels were variable for several months after implantation. All patients demonstrated improved performance after implantation. Patients with enlarged vestibular aqueduct fared better than patients with other inner ear malformations. Cochlear implantation can be a successful method of rehabilitation in patients with congenital deafness who have cochlear malformations.



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ID(H)entifying checkpoint inhibitor candidates among diffuse glioma

See the article by Berghoff et al on pages XX–YY.

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All the Right Noises: Background Variability Helps Early Word Learning

Abstract

Variability is prevalent in early language acquisition, but, whether it supports or hinders learning is unclear; while target variability has been shown to facilitate word learning, variability in competitor items has been shown to make the task harder. Here, we tested whether background variability could boost learning in a referent selection task. Two groups of 2-year-old children saw arrays of one novel and two known objects on a screen, and they heard a novel or known label. Stimuli were identical across conditions, with the exception that in the constant color condition objects appeared on a uniform white background, and in the variable color condition backgrounds were different, uniform colors. At test, only children in the variable condition showed evidence of retaining label-object associations. These data support findings from the adult memory literature, which suggest that variability supports learning by decontextualizing representations. We argue that these data are consistent with dynamic systems accounts of learning in which low-level entropy adds sufficient noise to the developmental system to precipitate a change in behavior.



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Cancers, Vol. 9, Pages 129: Alcohol Misuse Link to POEMS Syndrome in a Patient

Cancers, Vol. 9, Pages 129: Alcohol Misuse Link to POEMS Syndrome in a Patient

Cancers doi: 10.3390/cancers9100129

Authors: John Neary Susan Goodwin Lawrence Cohen Manuela Neuman

Previously called Crow–Fukase syndrome, POEMS syndrome is characterized by poly-neuropathy, osteo-sclerotic myeloma, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes. Extremely elevated levels of serum vascular endothelial growth factor (VEGF) are characteristic of the syndrome. Chronic hepatitis B (HBV) and C (HCV) infections can also be present in POEMS. The pathogenesis of the syndrome is not well understood. The link between chronic alcohol consumption and this malignant condition has not been reported until now. In addition, no previous study has evaluated the influence of cytokine and chemokines or viruses in the severity and evolution of POEMS. Objectives: (1) to describe a heavy-alcohol user, who was diagnosed with POEMS; (2) to demonstrate the utility of quantitative measurement of serum levels of VEGF in the diagnosis of POEMS and the monitoring of therapeutic interventions; (3) to demonstrate that overproduction of pro-inflammatory cytokines is a characteristic of POEMS. Methods: We describe a case of a POEMS patient presenting HCV and who is a heavy drinker; we compare the serum levels of cytokines and chemokines between the POEMS patient with 80 patients with HCV, 12 healthy controls, and 80 individuals with alcoholic liver disease (ALD). We quantified (ELISA pg/mL) the levels of VEGF, Interferon gamma (IFN-γ), Tumor Necrosis Factor alpha (TNF-α), Regulated-upon-Activation Normal-T-cell-Expressed and presumably-Secreted (RANTES), and Nuclear Factor kappa-B (NFκB). Results: In POEMS patients, VEGF levels were elevated versus control or other diseases, TNFα levels were higher versus control, but lower when compared with HCV or ALD patients. VEGF levels in POEMS patients decreased with therapeutic intervention. Conclusions: Chronic alcohol misuse can be a strong risk factor to rare malignancies such as POEMS syndrome. Extreme elevation of VEGF levels is diagnostic for POEMS syndrome, and should be followed to assess response to therapy. In addition, other comorbidities should be considered individually to ensure personalized therapeutic intervention.



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Chronic IL-33 expression predisposes to viral-induced exacerbations of asthma by increasing type-2 inflammation and dampening antiviral immunity

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Publication date: Available online 22 September 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Rhiannon B. Werder, B Biomed Sci, Vivian Zhang, Jason P. Lynch, Natale Snape, John W. Upham, Kirsten Spann, Simon Phipps
BackgroundRhinovirus infection triggers acute exacerbations of asthma. IL-33 is an instructive cytokine of type-2 inflammation whose expression is associated with viral load during experimental rhinovirus infection of asthmatic subjects.ObjectiveTo determine whether anti-IL-33 therapy is effective during disease progression, established disease, or viral exacerbation using a preclinical model of chronic asthma and in vivo human primary airway epithelial cells (AECs).MethodsTo model disease onset, progression, and chronicity, mice were exposed to pneumonia virus of mouse and cockroach extract in early-life and later-life, then challenged with rhinovirus. Interventions included anti-IL-33 or dexamethasone at various stages of disease. AECs were obtained from asthmatic and healthy patients, and treated with anti-IL-33 following RV infection.ResultsAnti-IL-33 decreased type-2 inflammation in all phases of disease; however, the ability to prevent airway smooth muscle growth was lost after the progression phase. After the chronic phase, IL-33 levels were persistently high and rhinovirus challenge exacerbated the type-2 inflammatory response. Treatment with anti-IL-33 or dexamethasone diminished exacerbation severity and anti-IL-33, but not dexamethasone, promoted antiviral IFN expression and decreased viral load. RV replication was higher and IFN-lambda lower in asthmatic compared to healthy AECs. Anti-IL-33 lowered RV replication and increased IFN-λ at the gene and protein level.ConclusionAnti-IL-33 or dexamethasone suppressed the magnitude of type-2 inflammation during a rhinovirus-induced acute exacerbation, however only anti-IL-33 boosted antiviral immunity and lowered viral replication. The latter phenotype was replicated in RV infected human AECs, suggesting that anti-IL-33 therapy has the additional benefit of enhancing host defence.

Teaser

Using a preclinical model of chronic asthma and primary human AECs we show that anti-IL-33 boosted IFNs and lowered RV replication, suggesting that in addition to attenuating type-2 inflammation, anti-IL-33 therapy may enhance host defence.


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Trichostatin A preferentially reverses the upregulation of gene expression levels induced by gain of chromosome 7 in colorectal cancer cell lines

Abstract

Epithelial cancers are defined by a tumor-specific distribution of chromosomal aneuploidies that are maintained when cells metastasize and are conserved in cell lines derived from primary tumors. Correlations between genomic copy number and gene expression have been observed for different tumors including, colorectal (CRC), breast and pancreatic cancer. These ploidy-driven transcriptional deregulations are characterized by low-level expression changes of most genes on the affected chromosomes. The emergence of these aberrations at an early stage of tumorigenesis and the strong selection for the maintenance of these aneuploidies suggests that aneuploidy-dependent transcriptional deregulations might contribute to cellular transformation and maintenance of the malignant phenotype. The histone deacetylase inhibitor (HDACi) Trichostatin A (TSA) has anticancer effects and is well known to lead to large scale gene expression changes. Here we assessed if TSA could disrupt the aneuploidy-driven gene expression in the aneuploid colon cancer cell line SW480 and the artificially generated aneuploid cell line DLD-1 + 7. We found that TSA increases transcriptional activity throughout the genome, yet inhibits aneuploidy-induced gene expression changes on chromosome 7. Among the TSA affected genes on chromosome 7 we identified potential CRC oncogenes. These experiments represent the first attempt to explain how histone acetylation affects aneuploidy-driven gene expression changes. This article is protected by copyright. All rights reserved.



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Surgical treatment of a lumbar aneurysmal bone cyst using percutaneous endoscopic lumbar discectomy

Abstract

Purpose

Aneurysmal bone cysts of the lumbar spine are usually treated by curettage followed by bone or bioactive ceramics grafting. Here, we present the first case of an aneurysmal bone cyst of the lumbar spine treated by percutaneous endoscopic lumbar discectomy (PELD).

Methods

We describe the clinical characteristics of the patient including the radiological and pathological findings of the tumor and the surgical technique used.

Results

A 15-year-old boy presented with low back pain, and he was diagnosed with an aneurysmal bone cyst of the L3 vertebra based on radiological findings, including plain radiograph, computed tomography, and magnetic resonance imaging. The technique and equipment of PELD were used to perform curettage of the tumor cavity and fill it with hydroxyapatite granules. The skin incision was only 8 mm. The patient was discharged 1 day postoperatively and could walk without assistance. The postoperative course was uneventful and the symptoms improved following surgery.

Conclusion

Endoscopic surgery via PELD can be a treatment option for ABCs of the lumbar spine.



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Sleep disordered breathing in Bardet-Biedl Syndrome

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Publication date: November 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 102
Author(s): Jeffrey C. Yeung, Umakanth A. Katwa, Gi Soo Lee
IntroductionBardet-Biedl Syndrome (BBS) is an autosomal recessive ciliopathy, and obesity is among its defining characteristics. Consequently, the incidence of sleep disordered breathing (SDB) in this population is expected to be high. Due to its relative rarity, the nature of SDB in this population is poorly described. The objective of this study was to review a single institutional experience in the assessment and management of SDB in patients with BBS.MethodsRetrospective chart review of tertiary care, academic pediatric hospital.Results20 patients with BBS were evaluated over a 25-year period. Median age at initial consultation was 69 months; half of these patients were referred before the diagnosis of BBS was made. Eighteen of twenty patients had symptoms of sleep-disordered breathing. Median follow-up duration was 17.5 months. A wide range of polysomnographic outcomes was observed, including obstructive apnea-hypopnea indexes of 0–195 events/hour. Patients were managed with adenotonsillectomy and/or non-invasive positive pressure ventilation.ConclusionsSDB is commonly seen in BBS. These patients should be routinely screened for OSA and if present, a polysomnogram should be obtained. Based on patient characteristics, the failure rate of primary surgical intervention, namely adenotonsillectomy, is expected to be high. Further investigation into the role of ancillary diagnostic testing is still needed.



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Congenital pharyngeal webs: Treatment of a rare clinical entity by endoscopic CO2 laser approach

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Publication date: November 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 102
Author(s): Grégoire B. Morand, Karma Lambercy, Pierre Guilcher, Kishore B. Sandu
ImportanceOesophageal inlet stenosis can promote dysphagia and aspiration. We report the cases of syndromic children with congenital pharyngeal webs successfully treated with endoscopic CO2 laser.ObservationsPharyngeal webs were excised with CO2 laser (Ultrapulse mode) and resurfaced using mucosal advancement flaps to avoid restenosis and/or formation of secondary synechia. This led to a significant enlargement of the oesophageal inlet, which was documented immediately postoperatively and the clinical improvement of dysphagia and decreased aspiration persisted at distant follow-up.Conclusion and relevancePharyngeal webs are congenital anomalies that can be safely and effectively corrected with endoscopic treatment.



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Approach to MPN Symptom Assessment

Abstract

Purpose of Review

Myeloproliferative neoplasms (MPNs) are recognized for their debilitating symptom burdens. The purpose of this review is to understand the complexity of the MPN symptom burden and identify how validated MPN Patient Reported Outcome (PRO) tools may be integrated into clinical practice to assess the MPN symptom burden.

Recent Findings

Significant heterogeneity exists both within and between MPN subtypes. Surrogates of disease burden such as risk scores and MPN chronicity often fail to correlate with symptomatic burden. Validated MPN PROs allow for precise and rapid assessment of the MPN symptom burden in clinical and trial settings. Their growing use among investigators has resulted in improved understanding of how the MPN disease burden and overall patient experience is impacted by novel and traditional therapies.

Summary

PRO tools are an integral part of National Comprehensive Cancer Center (NCCN) guidelines for MPN treatment and should be regularly employed in disease burden assessment.



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Status of implementation and organization of cancer screening in the European Union Member States - summary results from the second European screening report

Abstract

The second report on the implementation status of cancer screening in European Union (EU) was published in 2017. The report described the implementation status, protocols and organization (updated till 2016) and invitation coverage (for index year 2013) of breast, cervical and colorectal cancer screening in the EU. Experts in screening programme monitoring (N=80) from the EU Member States having access to requisite information in their respective countries provided data on breast, cervical and colorectal cancer screening through online questionnaires. Data was collected for screening performed in the framework of publicly mandated programmes only. Filled in questionnaires were received from 26 Member States for all three sites and from one Member State for breast cancer only.

Substantial improvement in screening implementation using population-based approach was documented. Among the age-eligible women, 94.7% were residents of Member States implementing or planning population-based breast cancer screening in 2016, compared to 91.6% in 2007. The corresponding figures for cervical cancer screening were 72.3% and 51.3% in 2016 and 2007 respectively. Most significant improvement was documented for colorectal cancer screening with roll-out ongoing or completed in 17 Member States in 2016, compared to only five in 2007. So the access to population-based screening increased to 72.4% of the age-eligible populations in 2016 as opposed to only 42.6% in 2007. The invitation coverage was highly variable, ranging from 0.2%-111% for breast cancer, 7.6%-105% for cervical cancer and 1.8%-127% for colorectal cancer in the target populations.

In spite of the considerable progress, much work remains to be done to achieve optimal effectiveness. Continued monitoring, regular feedbacks and periodic reporting are needed to ensure the desired impacts of the programmes. This article is protected by copyright. All rights reserved.



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Application of endoscopy in otology: Changes over the last 8years in Korean Otological Society

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Publication date: Available online 22 September 2017
Source:American Journal of Otolaryngology
Author(s): Se-Joon Oh, Eui-Kyung Goh, Hyun-Min Lee, Jae-Hoon Jung, Il Joon Moon, Jong-Woo Chung, Il-Woo Lee
ObjectivesDespite the worldwide availability of endoscope in otology, it still has not replaced the microscopic surgery as it has for nose surgery. In 2008, we administered a questionnaire on the preference of using otoscopes in Korea. In light of the worldwide availability of endoscopic ear surgery, we have now conducted a more detailed survey to determine if this preference has changed over 8years.Subjects and methodsA questionnaire consisting of 10 questions was used to survey members of the Korean Otological Society who were actively performing middle ear surgery. The responses to this questionnaire were compared to those from 2008. The study also determined the preference for endoscope use based on the surgeon's experience.ResultsThe mean surgical experience of the otologists was 12.7years. Endoscopy for tympanoplasty and tympanomastoidectomy increased over a period of 8years. In the outpatient clinic, the use of endoscopy also increased; over 8-year period, it surpassed the microscope as the most preferred diagnostic tool in the outpatient clinic. Greater than half of the operating rooms were equipped with endoscopic sets; however, only 4.5% of otologists acknowledged having endoscopic instruments.ConclusionEndoscopy for surgery and in outpatient clinic assessment increased in otology in Korea; however, endoscopes have consistently been used as an adjuvant to the microscope to improve visualization of the tympanic cavity rather than as a tool for totally endoscopic ear surgery.



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Invariant NKT cells promote skin wound healing by preventing a prolonged neutrophilic inflammatory response

Abstract

The wound-healing process consists of the inflammation, proliferation, and remodeling phases. In chronic wounds, the inflammation phase is prolonged with persistent neutrophil infiltration. The inflammatory response is critically regulated by cytokines and chemokines that are secreted from various immune cells. Recently, we showed that skin wound healing was delayed and the healing process was impaired under conditions lacking invariant natural killer T (iNKT) cells, an innate immune lymphocyte with potent immuno-regulatory activity. In the present study, we investigated the effect of iNKT cell deficiency on the neutrophilic inflammatory response during the wound healing process. Neutrophil infiltration was prolonged in wound tissue in mice genetically lacking iNKT cells (Jα18KO mice) compared with wild-type (WT) control mice on days 1 and 3 after wounding. MIP-2, KC, and IL-17A were produced at a significantly higher level in Jα18KO mice than in WT mice. In addition, neutrophil apoptosis was significantly reduced in the wound tissue in Jα18KO mice compared with WT mice. Treatment with either anti-IL-17A mAb, anti-Gr-1 mAb, or neutrophil elastase inhibitor reversed the impaired wound healing in Jα18KO mice. These results suggest that iNKT cells may promote the wound healing process through preventing the prolonged inflammatory response mediated by neutrophils. This article is protected by copyright. All rights reserved.



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Best practice guidelines for the measurement of physical activity levels in stroke survivors: a secondary analysis of an observational study.

The aim of this study was to investigate the phenomenon of activity (increased activity in response to monitor wear) and determine the minimum wear time of accelerometers when objectively measuring habitual physical activity levels of community dwelling stroke survivors. Exploratory, secondary analyses of cross-sectional data were carried out. Physical activity variables [sitting, standing and stepping time, step count, light physical activity and moderate-to-vigorous physical activity (MVPA)] were measured with two activity monitors for 7 days. Repeated-measures analysis of variance was used to assess reactivity. Minimum wear time was assessed using regression analyses and median absolute differences. Paired t-tests were used to assess differences between weekend and weekday activity levels. There was no evidence of reactivity. Minimum wear time was 3 days for all activity variables, with the exception of MVPA, for which 7 days of monitoring was required. There were no significant differences in weekend and weekday activity levels. To accurately measure activity levels of individuals with stroke, we recommend 3 days of monitoring for all activity variables, with the exception of MVPA, which requires 7 days. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Genomic Rearrangement Signatures and Clinical Outcomes in High-Grade Serous Ovarian Cancer

Abstract
Background
To identify clinically relevant genomic rearrangement signatures in high-grade serous ovarian cancer (HGSOC), we conducted a retrospective analysis of sequenced HGSOC whole-tumor genomes.
Methods
Clinical data and whole-genome sequencing (WGS) reads were obtained for primary HGSOC tumors sequenced by the Australian Ovarian Cancer Study (AOCS; n = 80). Genomic rearrangements were identified, and non-negative matrix factorization (NMF) was used to extract rearrangement signatures. The cohort was then dichotomized around the median signature contribution, and overall survival (OS) was analyzed. An independent cohort from The Cancer Genome Atlas (TCGA) ovarian cancer study (n = 490) was also examined. The TCGA cohort was dichotomized around the median similarity between tumor copy number profile and a prognostic rearrangement signature, and OS was analyzed. Outcomes were assessed using Kaplan-Meier and multivariable Cox regression methods. All statistical tests were two-sided.
Results
We identified five genomic rearrangement signatures (Ov.RS1-5) in HGSOC. Ov.RS3 exhibited 10 kilobase to 10 megabase deletions and tandem duplications, and patients whose tumors exhibited a high contribution from Ov.RS3 had poor OS. The median OS was 22.7 months (95% confidence interval [CI] = 20.2 to 39.0 months) in the Ov.RS3-high group vs 38.2 months (95% CI = 22.7 to 69.1 months) in the Ov.RS3-low group (hazard ratio [HR] = 1.86, 95% CI = 1.12 to 3.09, P = .02). For the independent TCGA cohort, median OS rates were 38.0 months (95% CI = 35.3 to 41.4 months) in the Ov.RS3 high-similarity group vs 48.9 months (95% CI = 44.1 to 57.1 months) in the Ov.RS3 low-similarity group (HR = 1.54, 95% CI = 1.21 to 1.97, P < .001).
Conclusion
A novel genomic rearrangement signature is associated with poor prognosis in HGSOC.

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Table of Contents

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Publication date: 1 October 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 99, Issue 2, Supplement





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ASTRO – Program Description/Statement of Need

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Publication date: 1 October 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 99, Issue 2, Supplement





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Continuing Medical Education

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Publication date: 1 October 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 99, Issue 2, Supplement





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