Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com

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! # Ola via Alexandros G.Sfakianakis on Inoreader

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Σάββατο 12 Αυγούστου 2017

Acid activation of upper Eocene Ca-bentonite for soybean oil clarification

Abstract

In central Tunisia, many upper Eocene outcrops supply smectitic claystone which are characterized by several analytical techniques (calcimetry, XRD, SediGraph, chemical analysis, surface area, etc.). Beidellite is the main mineral detected by the XRD method. Representative raw samples M1, taken from Henchir Souar (Zaghouan, Tunisia), were acid activated in order to improve their physicochemical properties. This study consists in optimizing the activation conditions with HCl 3 N by varying the following parameters: time (2, 4, and 6 h) and temperature (25, 50, 75, and 90 °C). The characterization by XRD and chemical analysis was carried out on the samples (M1, activated for 2 and 6 h at 75 °C), showing a structural modification of the clay by reduction of intensity reflection 001 order of smectite and dissolution of metal ions (Al3+, Fe3+, and Mg2+) from clay structure. Optimum condition for soybean oil clarification is obtained using a variety of amount raw clays (0.5, 0.75, and 1%). Thus, the best clarification yield is given at 0.75% of clay, showing a capacity of about 55%. Various forms of activated materials were used with a 75% proportion to leach soybean oil. Results were compared with commercial bentonite (Tonsil) having surface area (378 m2/g). The activated sample M1 during 4 h at 75 °C possesses a decolorizing capacity of about 85% greater than the oil treated by Tonsil in laboratory (58%).



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Temperature drop and the risk of asthma: a systematic review and meta-analysis

Abstract

The relationship between asthma and temperature changes remains controversial. The aim of this study was to investigate the association between temperature changes and the risk of asthma. A total of 26 studies (combined total number of subjects N > 26 million), covering 13 countries and Costa Rica, were identified by using a series of keywords in different combinations and searching the papers in PubMed, EMBSEA, Web of Science, MEDLINE, AIM, LILACS, and WPRIM before February 2016. Most of the papers were published in English. Random-effects meta-analyses were performed to evaluate the effect of temperature drop on risk of asthma. Several secondary analyses were also calculated based on stratification for different age, season, latitude, and region on risk of asthma. The odds ratio (OR) estimate between temperature drop and asthma was 1.05 (95% CI 1.02, 1.08) in the meta-analysis. For children, the overall OR was 1.09 (95% CI 1.03, 1.15). Dose-effect analyses showed stronger associations in asthma risk for each 1°1 °C decrement in short-term temperature (OR 1.055, 95% CI 1.00, 1.11). Further stratifications showed that winter (OR 1.03, 95% CI 1.01, 105) and low latitude (OR 1.72, 95% CI 1.23, 2.41) have a statistically significant association with the increased risk of asthma. Exposure of people to short-term temperature drop (per 1 °C decrement) was significantly associated with the risk of lower respiratory tract infections (LRTI) with asthma (OR 1.02, 95% CI 1.00, 1.04). Results suggest an adverse effect of temperature drop on asthma risk, especially in children and low-latitude areas. It may be opportune to consider the preventive actions against temperature drop, including simple face masks, to decrease the risk of asthma.



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Life cycle environmental impacts of bioethanol production from sugarcane molasses in Iran

Abstract

In recent years, bioethanol from sugarcane molasses has been produced on an industrial scale in Iran. The aim of this study was to evaluate molasses-based bioethanol production from an environmental point of view. Data were collected from Debel Khazai agro-industry situated in southern region of Iran by using face-to-face interviews and annual statistics of 2010 to 2016 (6-year life cycle of sugarcane cultivation). Ten impact categories including abiotic depletion (AD), acidification (AC), eutrophication (EP), global warming potential (GWP), ozone layer depletion (OLD), human toxicity (HT), freshwater aquatic ecotoxicity (FE), marine aquatic ecotoxicity (ME), terrestrial ecotoxicity (TE), and photochemical oxidation (PO) were selected based on CML methodology. Inventory data for production of the inputs were taken from Ecoinvent, BUWAL 250, and IDMAT 2001 databases. The results revealed that in sugarcane cultivation process, electricity and trash burning were the most important contributors to all impact categories except OLD and TE. In industrial phase, natural gas had the highest contribution to the most impact categories. Greenhouse gas (GHG) emission for production of 1000 L molasses-based bioethanol was 1322.78 kg CO2 eq. By comparing total GHG emissions from 1000 L bioethanol to gasoline, the net avoided GHG emissions came out at 503.17 kg CO2 eq. According to results, it is clear that with increasing irrigation efficiency and improving performance of heating systems in industrial phase, environmental burdens would be significantly reduced.



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Repeated Exposure to Two Stressors in Sequence Demonstrates that Corticosterone and PVN Interleukin-1β Responses Habituate Independently

Abstract

A wide range of stress-related pathologies such as post-traumatic stress disorder are thought to arise from aberrant or maladaptive forms of stress adaptation. The hypothalamic-pituitary-adrenal (HPA) axis readily adapts to repeated stressor exposure, yet little is known about adaptation in neuroimmune responses to repeated or sequential stress challenges. In Experiment 1, rats were exposed to ten days of restraint alone (60 min daily), forced swim alone (30 min daily), or daily sequential exposure to restraint (60 min) followed immediately by forced swim (30 minutes), termed sequential stress exposure. Habituation of the corticosterone (CORT) response occurred to restraint by 5 days and swim at 10 days, whereas rats exposed to sequential stress exposure failed to display habituation to the combined challenge. Experiment 2 compared 1 or 5 days of forced swim to sequential stress exposure and examined how each affected expression of several neuroimmune and cellular activation genes in the paraventricular nucleus of the hypothalamus (PVN), prefrontal cortex (PFC), and hippocampus (HPC). Sequential exposure to restraint and swim increased IL-1β in the PVN, an effect that was attenuated after 5 days. Sequential stress exposure also elicited IL-6 and TNF-α responses in the HPC and PFC, respectively, that did not habituate after 5 days. Experiment 3 tested whether prior habituation to restraint (5 days) would alter the IL-1β response evoked by swim exposure imposed immediately after the 6th day of restraint. Surprisingly, a history of repeated exposure to restraint attenuated the PVN IL-1β response after swim in comparison to acutely-exposed subjects despite an equivalent CORT response. Overall, these findings suggest that habituation of neuroimmune responses to stress proceeds (a) independent of HPA axis habituation; (b) likely requires more daily sessions of stress to develop; and that (c) IL-1β displays a greater tendency to habituate after repeated stress challenges than other stress-reactive cytokines.

This article is protected by copyright. All rights reserved.



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Hidden Markov Modeling of Frequency-Following Responses to Mandarin Lexical Tones

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Publication date: Available online 12 August 2017
Source:Journal of Neuroscience Methods
Author(s): Fernando Llanos, Zilong Xie, Bharath Chandrasekaran
BackgroundThe frequency-following response (FFR) is a scalp-recorded electrophysiological potential reflecting phase-locked activity from neural ensembles in the auditory system. The FFR is often used to assess the robustness of subcortical pitch processing. Due to low signal-to-noise ratio at the single-trial level, FFRs are typically averaged across thousands of stimulus repetitions. Prior work using this approach has shown that subcortical encoding of linguistically-relevant pitch patterns is modulated by long-term language experience.New methodWe examine the extent to which a machine learning approach using hidden Markov modeling (HMM) can be utilized to decode Mandarin tone-categories from scalp-record electrophysiolgical activity. We then assess the extent to which the HMM can capture biologically-relevant effects (language experience-driven plasticity). To this end, we recorded FFRs to four Mandarin tones from 14 adult native speakers of Chinese and 14 of native English. We trained a HMM to decode tone categories from the FFRs with varying size of averages.Results and comparisons with existingmethods Tone categories were decoded with above-chance accuracies using HMM. The HMM derived metric (decoding accuracy) revealed a robust effect of language experience, such that FFRs from native Chinese speakers yielded greater accuracies than native English speakers. Critically, the language experience-driven plasticity was captured with average sizes significantly smaller than those used in the extant literature.ConclusionsOur results demonstrate the feasibility of HMM in assessing the robustness of neural pitch. Machine-learning approaches can complement extant analytical methods that capture auditory function and could reduce the number of trials needed to capture biological phenomena.



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Widespread functional opsin transduction in the rat cortex via convection-enhanced delivery optimized for horizontal spread

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Publication date: Available online 12 August 2017
Source:Journal of Neuroscience Methods
Author(s): Zeyang Yu, Arto Nurmikko, Ilker Ozden
BackgroundWidespread opsin expression in the cortex of rats, where transgenic models have not been established, is not practical to achieve with the traditional diffusion-based virus transduction methods (DBD).New MethodWe developed protocols for convection-enhanced delivery (CED) of virus for optogenetic transduction of the rat cortex. Targeting the motor forelimb area as an example, we performed dual-site CED (6 μL of virus per site, 3 mm pitch between sites) in the rat motor cortex.ResultsWe identified injection parameters optimized for horizontal spread of infusate in the agarose gel model and then demonstrated in vivo widespread opsin expression over the cortical area (7.4±1.0mm in the AP direction, 4.4±1.1mm in the ML direction, N=13 rats) using CED. The optogenetic transduction was also functionally robust, in which both optical modulation of neuronal activity and elicitation of overt motor responses was reliably observed.Comparison with Existing Method(s)CED led to about 24-fold increase in the volume of opsin expression, compared with the conventional DBD method. The total injection time was also reduced by at least 10 times, if similar extent of expression were to be achieved with the conventional DBD method.ConclusionsCED is a reliable and effective method of virus delivery for optogenetic transduction of planar superficial structures, such as the cortex in rats.



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Comparing brain graphs in which nodes are regions of interest or independent components: a simulation study

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Publication date: Available online 12 August 2017
Source:Journal of Neuroscience Methods
Author(s): Qingbao Yu, Yuhui Du, Jiayu Chen, Hao He, Jing Sui, Godfrey Pearlson, Vince D. Calhoun
BACKGROUNDA key challenge in building a brain graph using fMRI data is how to define the nodes. Spatial brain components estimated by independent components analysis (ICA) and regions of interest (ROIs) determined by brain atlas are two popular methods to define nodes in brain graphs. It is difficult to evaluate which method is better in real fMRI data.NEW METHODHere we perform a simulation study and evaluate the accuracies of a few graph metrics in graphs with nodes of ICA components, ROIs, or modified ROIs in four simulation scenarios.RESULTSGraph measures with ICA nodes are more accurate than graphs with ROI nodes in all cases. Graph measures with modified ROI nodes are modulated by artifacts. The correlations of graph metrics across subjects between graphs with ICA nodes and ground truth are higher than the correlations between graphs with ROI nodes and ground truth in scenarios with large overlapped spatial sources. Moreover, moving the location of ROIs would largely decrease the correlations in all scenarios.COMPARISON WITH EXISTING METHOD (S)Evaluating graphs with different nodes is promising in simulated data rather than real data because different scenarios can be simulated and measures of different graphs can be compared with a known ground truth.CONCLUSIONSince ROIs defined using brain atlas may not correspond well to real functional boundaries, overall findings of this work suggest that it is more appropriate to define nodes using data-driven ICA methods: than ROI approaches in real fMRI data.



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High resolution simultaneous imaging of intracranial and extracranial arterial wall with improved cerebrospinal fluid suppression

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Publication date: Available online 12 August 2017
Source:Magnetic Resonance Imaging
Author(s): Lei Zhang, Na Zhang, Jun Wu, Xin Liu, Yiu-Cho Chung
PurposeTo develop a technique for three dimensional (3D) high resolution joint imaging of intracranial and extracranial arterial walls with improved cerebrospinal fluid (CSF) suppression and good blood suppression based on T1 weighted sampling perfection with application optimized contrast using different angle evolutions (T1w-SPACE) and to compare this technique (hereafter, iSPACE) with alternating with nutation for tailored excitation (DANTE) prepared SPACE sequence (DANTE-SPACE) for their CSF suppression performance around the mid cerebral arteries (MCA) and blood suppression at carotid arteries.Materials and methodsEight volunteers and twelve patients were prospectively recruited in this institutional review board approved study. A custom designed 32-channel coil set covering the intracranial and extracranial arteries was used for signal reception. Imaging was performed in each subject using DANTE-SPACE and iSPACE. Signal-to-noise ratios (SNR) of the vessel walls at the MCA and carotid arteries, and contrast-to-noise ratios (CNR) between vessel wall and CSF at the MCA and between vessel wall and lumen at carotid arteries from the two sequences were compared.ResultsIn volunteers, contrast between CSF and white matter (surrogate for vessel wall signal) at the M2 segments in iSPACE was 67.9% higher than in DANTE-SPACE. At the carotid region, the SNR of vessel wall in iSPACE was 11.6% higher than DANTE-SPACE while the CNR in iSPACE was 13% higher than DANTE-SPACE. In patients, images with 0.6mm isotropic resolution were obtained in 7.5min. iSPACE showed 70.9% improvement in CNR between plaque and CSF at the M2 segments compared to DANTE-SPACE.ConclusionSimultaneous extracranial and intracranial arterial wall imaging using iSPACE improved CSF suppression significantly at the M2 segment of MCA while blood suppression was comparable to DANTE-SPACE. The technique achieved 3D images with 0.6mm isotropic spatial resolution and took 7.5min using a custom made coil set. Using this technique, intracranial plaque visualization was improved with no observable image SNR degradation.



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Editorial Board/Reviewing Committee



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Toxic effects of copper on liver and cholinesterase of Clarias gariepinus

Abstract

The release of pollutants, especially heavy metals, into the aquatic environment is known to have detrimental effects on such an environment and on living organisms including humans when those pollutants are allowed to enter the food chain. The aim of this study is to analyse the damage to Clarias gariepinus' liver caused by exposure to different concentrations of copper. In the present study, samples of C. gariepinus were exposed to sub-lethal copper sulphate (CuSO4) concentrations (from 0.2 to 20.0 mg/L) for 96 h. Physiological and behavioural alterations were observed with respect to their swimming pattern, mucus secretion and skin colour. Mortality was also observed at high concentrations of copper. Histopathological alterations of the liver were analysed under light, transmission and scanning electron microscopies. The liver of the untreated group showed normal tissue structures, while histopathological abnormalities were observed in the treated fish under light and electron microscopes with increased copper concentrations. Histopathological abnormalities include necrosis, melanomacrophage, hepatic fibrosis and congested blood vessels. In addition, the enzyme activity of liver cholinesterase (ChE) was also found to be affected by copper sulphate, as 100% of cholinesterase activity was inhibited at 20.0 mg/L. Thus, liver enzyme activity and histopathological changes are proven to be alternative sources for biomarkers of metal toxicity.



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Enhanced phosphorus removal in intermittently aerated constructed wetlands filled with various construction wastes

Abstract

Phosphorus (P) loss by various pathways in constructed wetlands (CWs) is often variable. The effects of intermittent aeration and different construction waste substrates (gravel, red brick, fly-ash brick) on P processing using six batch-operated vertical flow constructed wetlands (VFCWs) were studied for decentralized domestic wastewater treatment. Average removal of total phosphorus (TP) in three aerated CWs was markedly higher (21.06, 24.83, and 27.02 mg m−2 day−1, respectively) than non-aerated CWs (10.64, 18.16, and 25.09 mg m−2 day−1, respectively). Fly-ash brick offered superior TP removal efficiency in both aerated and non-aerated batch-operated VFCWs, suggesting its promising application for P removal in CWs. Aeration greatly promoted plant growth and thusly increased plant uptake of P by 0.57–1.45 times. Substance storage was still the main P sink accounting for 23.92–59.47% of TP removal. Other process including microbial uptake was revealed to be a very important P removal pathway (accounting for 14.86–34.84%). The contribution of microbial uptake was also indicated by microbial analysis. Long-term results suggested that the contribution of microbial P uptake could be always ignored and underestimated in most CWs. A combination of intermittent aeration and suitable substrates is effective to intensify P transformation in CWs.



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Transmission surface plasmon resonance techniques and their potential biosensor applications

Publication date: 15 January 2018
Source:Biosensors and Bioelectronics, Volume 99
Author(s): Chutiparn Lertvachirapaiboon, Akira Baba, Sanong Ekgasit, Kazunari Shinbo, Keizo Kato, Futao Kaneko
Transmission surface plasmon resonance (TSPR) is an unusual extraordinary optical transmission that is more transparent at certain wavelengths than expected by classical theory. The three main plasmonic structures that providing this phenomenon are nanohole arrays, diffraction gratings, and nanoslit arrays. This extraordinary optical transmission phenomenon is produced as a result of surface plasmon excitations. The shifting in TSPR responses upon changing of dielectric environment at the surface of a metallic film was observed. After TSPR was discovered from metallic nanohole arrays in 1998, the number of papers about this topic rapidly increased. In the 20 years since, TSPR has been utilized to improve the detection limits, sensitivity, selectivity, and dynamic range of biosensing devices, resulting in them having greater potential for commercialization. This review gives a broad overview of the TSPR phenomenon, the development of this technique, and the typical experimental setups used to acquire TSPR signals; it also describes how they are applied in the field of research into biosensors.



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Sleep Location and Parent-Perceived Sleep Outcomes in Older Infants

Initial studies indicate more independent and consolidated sleep in infants in the first few months who sleep separately. Little is known, however, about the relationship of sleep location (separate room, room-sharing, bed-sharing) with sleep outcomes in older infants (ages 6 to 12 months). It was expected that those who sleep in a separate room would have better parent-perceived sleep outcomes and more positive sleep health behaviors.

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Preoperative Signs and Symptoms as Prognostic Markers in Nasal Septoplasty

Identification of preoperative signs and symptoms that may predict the outcome of surgery is important, for both patient selection and the development of interventions for improving outcomes. The purpose of this study was to assess the value of some selected preoperative signs and symptoms for predicting outcomes of nasal septoplasty. Patients undergoing septoplasty with or without turbinoplasty responded to the Nasal Surgical Questionnaire (NSQ) preoperatively and six months postoperatively. The questionnaire contains visual analogue scales (VAS) for nasal obstruction during the day and at night. We compared preoperative and postoperative VAS scores in patients with unilateral versus bilateral septal deviation and patients with low versus high preoperative scores. Of 446 patients undergoing septoplasty from September 2014 to December 2015 who had responded to the preoperative NSQ, 286 (64.1%) also returned the postoperative version. There was greater improvement in obstruction in patients with preoperative unilateral compared to bilateral septal deviation (day scores, ). The grade of deviation and the presence of concomitant bony conchal hypertrophy did not influence results. Patients with lower preoperative VAS scores obtained better end results than those with higher scores (). Type of septal deviation and preoperative VAS scores may aid in predicting outcome of nasal surgery.

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Preoperative Signs and Symptoms as Prognostic Markers in Nasal Septoplasty

Identification of preoperative signs and symptoms that may predict the outcome of surgery is important, for both patient selection and the development of interventions for improving outcomes. The purpose of this study was to assess the value of some selected preoperative signs and symptoms for predicting outcomes of nasal septoplasty. Patients undergoing septoplasty with or without turbinoplasty responded to the Nasal Surgical Questionnaire (NSQ) preoperatively and six months postoperatively. The questionnaire contains visual analogue scales (VAS) for nasal obstruction during the day and at night. We compared preoperative and postoperative VAS scores in patients with unilateral versus bilateral septal deviation and patients with low versus high preoperative scores. Of 446 patients undergoing septoplasty from September 2014 to December 2015 who had responded to the preoperative NSQ, 286 (64.1%) also returned the postoperative version. There was greater improvement in obstruction in patients with preoperative unilateral compared to bilateral septal deviation (day scores, ). The grade of deviation and the presence of concomitant bony conchal hypertrophy did not influence results. Patients with lower preoperative VAS scores obtained better end results than those with higher scores (). Type of septal deviation and preoperative VAS scores may aid in predicting outcome of nasal surgery.

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Selective and sensitive detection of Zn(II) ion using a simple peptide-based sensor

Publication date: February 2018
Source:Sensors and Actuators B: Chemical, Volume 255, Part 1
Author(s): Jiajia Wan, Wenxiu Duan, Kai Chen, Yanduo Tao, Jun Dang, Kehao Zeng, Yushu Ge, Jiang Wu, Dan Liu
The development of biocompatible chemosensors is becoming increasingly important for chemical analyses in environmental sampling, the food industry, and clinical medicine. Many current chemosensors have limited utility as they represent potential secondary pollutants. To circumvent this problem, researchers are evaluating peptide-based fluorescent chemosensors because of their well-established synthesis protocols, good biological compatibility, and generally low cytotoxicity, which makes them suitable for bioimaging. In this study, we report the development of a peptide-based fluorescent chemosensor HL (fluorophore-Cys-Pro-Gly-His) for divalent zinc ions (Zn2+). The objective of this study was to select a suitable peptide sequence and associated fluorophore exhibiting high selectivity and sensitivity to Zn2+-binding, and enhanced fluorescent response. Results of this study, both in vitro and in living cells, indicated that HL exhibited high selectivity and sensitivity for Zn2+, with a limit of detection (LOD) of about 82nM. The sensor also exhibited very low cell cytotoxicity and strong fluorescence emission in living cells, which indicates that it may find application as a novel chemosensor for selective Zn2+ detection in biological environments.



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The potential benefits of glucagon-like peptide-1 receptor agonists for diabetic retinopathy

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Publication date: Available online 12 August 2017
Source:Peptides
Author(s): Baoying Pang, Huanran Zhou, Hongyu Kuang
For a long time, diabetic retinopathy (DR) has been one of the most severe complications of diabetes. The early treatment of DR is not clearly recognized. The additional benefit of hypoglycemic agents for DR has become a new research field. Glucagon-like peptide-1 receptor (GLP-1R) has been shown to be widely expressed in tissues including retina. Glucagon-like peptide-1 receptor agonists (GLP-1RA) have been generally used in the treatment of diabetic patients. Studies shows that GLP-1RA could inhibit nerve damage by decrease apoptosis of nerve cells and activation of glial cells. In addition, GLP-1RA plays a protective role for tight junction (TJ) and cells of blood retinal barrier (BRB). It also protects retina from BRB damage. In this review, we discuss the potential protective mechanisms of GLP-1RA for DR beyond the hypoglycemic effects.



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Comparaison des effets des corticostéroïdes par voie nasale et du montélukast sur les fonctions olfactives chez les patients atteints de rhinite allergique

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Publication date: September 2017
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 134, Issue 4
Author(s): A. Dalgic, M.E. Dinc, S. Ulusoy, D. Dizdar, A. Is, M. Topak
ObjectifLe dysfonctionnement olfactif est l'une des comorbidités associées à la rhinite allergique (RA) et celle-ci est l'une des causes les plus fréquentes de troubles olfactifs. Notre objectif était d'évaluer les effets des corticostéroïdes par voie nasale et des antagonistes des leucotriènes utilisés dans la rhinite allergique, sur les fonctions olfactives à l'aide du test Sniffin' Sticks.MéthodesTrente patients atteints de rhinite saisonnière ont été inclus dans cette étude. Les patients ont été randomisés en trois groupes de 10 patients ; le groupe 1 a été traité par montélukast sodique et furoate de mométasone, le groupe 2 a été traité uniquement par montélukast, et le groupe 3 uniquement par furoate de mométasone. Les fonctions olfactives des patients ont été déterminées à l'aide du test olfactif Sniffin' Sticks avant et après un mois de traitement.RésultatsLes valeurs de seuil, de discrimination, d'identification et de TDI (somme du seuil, de la discrimination et de l'identification) n'étaient pas significativement différentes entre les groupes avant le traitement. Pour les patients du groupe 1 et du groupe 3, des différences statistiquement significatives ont été observées en termes de valeurs de seuil, de discrimination, d'identification et de TDI avant et après le traitement (p<0,05) (test des rangs signés de Wilcoxon). Pour les patients du groupe 2, aucune différence significative n'a été observée concernant les valeurs de seuil, de discrimination, d'identification et de TDI avant et après le traitement (p>0,05).ConclusionLes résultats de notre étude montrent que le furoate de mométasone (FM) est plus efficace que le montélukast en terme d'amélioration de la fonction olfactive. Bien que le montélukast se soit avéré efficace pour traiter les symptômes de RA, son effet sur la fonction olfactive n'a pas été démontré dans cette étude.



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La chondroplastie par injection : remodelage enzymatique des greffes de cartilage

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Publication date: September 2017
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 134, Issue 4
Author(s): J.R. Gandy, A. Foulad, K.K. Chao, B.J.F. Wong
ObjectifDévelopper une technique d'injection d'enzymes assouplissant sélectivement le tissu cartilagineux pour le remodelage des structures cartilagineuses de la tête et du cou.Matériel et méthodesÀ partir d'oreilles de lapin, deux groupes ont été formés : (1) le groupe « oreille de lapin entière » et (2) le groupe « greffon composite » (échantillons de 2,5mm×3,0cm prélevés dans la région centrale du pavillon). Des injections séquentielles sous-périchondrales utilisant trois enzymes (hyaluronidase, pronase et collagénase de type II) ont été réalisées sur les échantillons de chaque groupe. Dans les échantillons témoins, une solution saline tamponnée au phosphate a été injectée de la même façon. Les oreilles entières ont ensuite été photographiées, maintenues en position anatomique verticale, pour évaluer leur déformation lors d'une compression afin de juger de l'intégrité du cartilage. De plus, une photographie à contre-jour a été réalisée pour tous les échantillons afin d'évaluer davantage les effets des enzymes, de manière à ce qu'une zone d'intensité lumineuse plus forte représente une augmentation du remodelage cartilagineux.RésultatsL'application des enzymes digestives a entraîné une réduction marquée de la résistance de la matrice des tissus cartilagineux, tout en préservant les couches superficielles sus-jacentes. Les pavillons entiers traités par les enzymes ont été remodelés au niveau du site d'injection des enzymes. Les images à contre-jour ont révélé une augmentation de l'intensité lumineuse locale dans les zones de digestion enzymatique. Il n'y a pas eu de destruction évidente de la peau sus-jacente lors de l'inspection visuelle.ConclusionCette étude démontre la faisabilité de la chondroplastie par injection comme une potentielle méthode alternative à la chirurgie conventionnelle pour le remodelage du cartilage auriculaire. Les injections séquentielles de hyaluronidase, de pronase et de collagénase de type II dans l'espace sous-périchondral peuvent être réalisées pour remodeler et assouplir les structures cartilagineuses avec une atteinte minimale des tissus environnants. Les études futures devront inclure des tests de viabilité des chondrocytes et l'optimisation des techniques d'injection.



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Images et comptes cellulaires de cochlées intactes et transparentes de gerbille de Mongolie par microscopie confocale à balayage laser

Publication date: September 2017
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 134, Issue 4
Author(s): M. Risoud, J. Sircoglou, G. Dedieu, M. Tardivel, C. Vincent, N.-X. Bonne
ObjectifsRéaliser le protocole de clarification sur des cochlées de gerbilles de Mongolie et évaluer la possibilité de quantifier et d'analyser la cytoarchitecture tri-dimensionelle (3D) de ces cochlées transparisées.Matériels et méthodesLes oreilles internes fraîchement disséquées étaient préparées suivant un protocole de 13jours : fixation, microdissection, post-fixation, décalcification, pré-traitement (amplification du signal, perméabilisation et blocage), marquage fluorescent (immunomarquage indirect et marquage direct), déshydratation, transparisation en solution de Spalteholz (méthyl salicylate et benzoate de benzyl [MSBB]) et montage. L'acquisition des images était réalisée par microscopie confocale à balayage laser. Le logiciel ImageJ était utilisé pour mesurer la longueur analysée de l'organe de Corti analysée et compter les cellules ciliées internes et externes.RésultatsQuatre cochlées ont été imagées. Les reconstructions 3D permettaient l'analyse de grandes longueurs d'organes de Corti. La longueur moyenne d'organe de Corti analysée était de 1269 (±346) μm. Le nombre moyen de cellules ciliées par longueur d'organe de Corti était : 142 (±44) cellules ciliées internes et 400 (±122) cellules ciliées externes.ConclusionLa transparisation cochléaire par le MSBB peut être réalisée chez la gerbille de Mongolie, permettant d'obtenir des images en haute résolution d'oreilles internes marquées en immunofluorescence. Ceci constitue, à notre connaissance, la première application de cette technique dans cette espèce. Elle permet ainsi des comptes cellulaires, sans dissection traumatique, sur de grandes longueurs d'organe de Corti.



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Dysplasie fibreuse osseuse cranio-faciale : à propos de 10 cas

Publication date: September 2017
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 134, Issue 4
Author(s): A. Couturier, O. Aumaître, L. Gilain, B. Jean, T. Mom, M. André
ObjectifsLa dysplasie fibreuse osseuse (DFO) est une maladie osseuse bénigne, congénitale, sporadique et rare dans laquelle l'os est remplacé par du tissu fibro-osseux renfermant une ostéogenèse immature. Une évolution sarcomateuse est exceptionnelle. Les lésions sont soit uniques (forme monostotique), soit multiples (forme polyostotique). La DFO peut être associée à une hyperpigmentation maculaire cutanée et à une endocrinopathie dans le cadre du syndrome de McCune-Albright ou à des myxomes dans le syndrome de Mazabraud.MéthodesNous rapportons dix observations de patients suivis pour une DFO cranio-faciale dans notre centre entre 2010 et 2015.RésultatsL'âge moyen était de 43 ans (10–72 ans). Les symptômes cliniques étaient des céphalées (n=3), et des troubles neurosensoriels (uvéite antérieure à répétition [n=1], une baisse progressive de l'acuité visuelle épiphora et syndrome vestibulaire [n=1] et hypoacousie [n=1]). Tous présentaient une forme monostotique. La lésion de DFO était frontale (n=1), fronto-ethmoïdale (n=1), ethmoïdale (n=1), sphénoïdale (n=5), temporale (n=1) et étendue (fronto-ethmoïdo-sphénoïdale ; n=1). Cinq patients ont été traités par pamidronate, un bisphosphonate injectable : trois ont évolué favorablement entre 1 et 6 mois après le début du traitement (disparition des céphalées ou du syndrome vestibulaire), les 2 autres étaient cliniquement stables. Deux patients ont été opérés.ConclusionLe diagnostic de DFO cranio-faciale doit être évoqué devant des céphalées, des névralgies faciales, des atteintes sensorielles, des troubles fonctionnels ou des complications infectieuses de la sphère ORL. Une approche médico-chirurgicale est utile à la prise en charge de ces patients.



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Editorial Board

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Publication date: September 2017
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 134, Issue 4





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Mélanomes muqueux des cavités nasosinusiennes : revue de la littérature à propos d’une série de 44 cas

Publication date: September 2017
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 134, Issue 4
Author(s): M. Dréno, M. Georges, F. Espitalier, C. Ferron, A. Charnolé, B. Dréno, O. Malard
ObjectifsLes mélanomes muqueux des fosses nasales et des sinus sont des tumeurs rares : ils représentent 4 % des tumeurs des cavités nasosinusiennes. L'objectif de cette étude est d'évaluer les caractéristiques cliniques de cette pathologie, ses modalités d'évolution, sa prise en charge thérapeutique et d'identifier des facteurs pronostiques.Matériel et méthodesÉtude rétrospective à partir d'une série de 44 patients traités pour un mélanome muqueux des cavités nasosinusiennes, dans le service d'ORL et de chirurgie cervicofaciale du CHU de Nantes entre 1988 et 2015.RésultatsL'âge moyen des patients était de 71,2 ans. Les 2 principaux signes rhinologiques lors du diagnostic étaient l'épistaxis et l'obstruction nasale unilatérale. Au moment de la prise en charge, 25 % des patients étaient classés T4. Un traitement chirurgical a été effectué chez 42 patients. Une radiothérapie postopératoire a été délivrée dans 19 cas et une immunothérapie adjuvante dans 14 cas. La durée moyenne de suivi était de 50 mois. Le taux de survie globale cumulée était de 71,5 % à 1 an, 33 % à 5 ans. Cliniquement, la présence de céphalées, d'algies faciales ou d'anesthésie du V2 étaient des facteurs significatifs de mauvais pronostic. L'atteinte exclusive des fosses nasales était également de meilleur pronostic sur la survie globale que l'atteinte sinusienne. La réalisation d'une radiothérapie adjuvante augmentait de façon non significative le contrôle local.ConclusionsLes mélanomes muqueux des cavités nasosinusiennes sont des tumeurs de mauvais pronostic en raison de leur potentiel métastatique élevé. L'exérèse chirurgicale suivie d'une radiothérapie est le traitement principal. Il n'existe pas actuellement de consensus concernant l'intérêt des nouveaux traitements adjuvants médicamenteux dans cette indication contrairement au traitement du mélanome cutané primitif.



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L’immunotherapie antiallergenique dans la rhinite allergique

Publication date: September 2017
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 134, Issue 4
Author(s): G. Mortuaire, J. Michel, J.-F. Papon, O. Malard, D. Ebbo, L. Crampette, R. Jankowski, A. Coste, E. Serrano
La rhinite allergique (RA) est une pathologie fréquente dont la sévérité ou le mauvais contrôle peut aboutir à une altération significative de la qualité de vie des patients. L'immunothérapie antiallergénique (ITA) constitue à l'heure actuelle le seul traitement étiologique susceptible de modifier l'histoire naturelle de la maladie allergique. Bien connue des allergologues, cette option thérapeutique est encore insuffisamment maîtrisée par les ORL. Cette mise au point basée sur les méta-analyses et les essais les plus récents souligne l'efficacité de l'ITA sur l'amélioration des symptômes de la RA et sur la réduction de la consommation des traitements médicaux (corticoïdes, antihistaminiques). L'ITA serait aussi susceptible de réduire le risque d'apparition d'un asthme et de nouvelles sensibilisations lorsqu'elle est introduite suffisamment précocement. Les analyses immunobiologiques montrent bien une modification du profil inflammatoire après ITA en faveur d'une immunotolérance impliquant les lymphocytes T régulateurs et la production d'IgG. La voie sublinguale en gouttes apporte des résultats comparables à ceux de la voie sous-cutanée tout en proposant une utilisation plus simple réduisant le risque anaphylactique. Une standardisation des protocoles d'étude en termes de mesure de l'effet thérapeutique et de gradation des effets indésirables est néanmoins nécessaire pour améliorer les études comparatives. Les formes sublinguales en comprimés plus récemment introduites constituent une réelle opportunité pour ouvrir le champ de l'ITA aux ORL dans la RA pollinique et prochainement la RA aux acariens.



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Les clés du traitement « conservateur » des carcinomes épidermoïdes de stade « précoce » de la région amygdalienne

Publication date: September 2017
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 134, Issue 4
Author(s): O. Laccourreye, P. Castelnau-Marchand, F. Rubin, C. Badoual, P. Halimi, P. Giraud
Analyse de la littérature médicale scientifique consacrée au bilan, à l'épidémiologie, au contrôle local, à la survie ainsi qu'aux complications et séquelles après traitement conservateur des carcinomes épidermoïdes de stade « précoce » de la région amygdalienne. Analyse de la base de données PubMed (1975–2016) avec les mots clés et les associations qui suivent : « amygdale/loge amygdalienne/oropharynx » et « cancer épidermoïde » et « stade précoce (I–II ; T1-T2N0M0) » et « radiothérapie » ou « chirurgie conservatrice/oropharyngectomie/chirurgie transorale/amygdalectomie radicale ». Cette recherche électronique trouvait dix articles rétrospectifs qui analysaient spécifiquement survie et contrôle local au sein de séries de plus de 50 patients avec un recul minimum de 2 ans après traitement conservateur et aucun article prospectif, méta-analyse et/ou étude Cochrane. L'imagerie par résonance magnétique nucléaire est l'examen radiologique clef du bilan d'extension locale. L'infestation par l'human papilloma virus est un facteur de risque à rechercher systématiquement, car il favorise la radiosensibilité tumorale et expose à des secondes localisations synchrones et métachrones spécifiques. Quel que soit le traitement conservateur réalisé, des taux de contrôle local et de survie supérieure à 85 % étaient notés. La modulation d'intensité réduisait la morbidité de la radiothérapie. La chirurgie transorale avait une faible morbidité/mortalité tout en permettant la réalisation d'un évidement ganglionnaire ipsilatéral et en préservant la radiothérapie pour le traitement des secondes localisations métachrones. La chirurgie transorale semble l'option thérapeutique à privilégier dans la majorité des cas. Un suivi à vie adapté au statut HPV doit être réalisé. La mise en place de vaccination anti-HPV ne doit pas faire perdre de vue l'importance de la lutte contre le tabagisme et l'énolisme.



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Sténose bilatérale des artères linguales – une complication rare et tardive de la chimio-radiothérapie

Publication date: September 2017
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 134, Issue 4
Author(s): F. Holtz, Y. Monnier, U. Borner, L. Nisa
IntroductionL'atteinte des artères carotides suite à la radiothérapie (RT) est un facteur de risque établi pour le développement d'atteintes cérébro-vasculaires avec risque ultérieur d'accident vasculaire cérébral ou accident vasculaire cérébral transitoire. En comparaison, l'atteinte de petits vaisseaux cervicaux suite à la RT est une complication plus rarement décrite.Présentation de casNous rapportons le cas d'un patient de 61 ans qui a développé une nécrose linguale partielle 4 ans après chirurgie et radio-chimiothérapie postopératoire pour un carcinome épidermoïde du plancher buccal. Un CT-scan avec injection de contraste a confirmé l'occlusion totale à subtotale des deux artères linguales. Le débridage chirurgical de la nécrose a permis une guérison complète des lésions.DiscussionL'atteinte des petits vaisseaux est une complication possible chez les patients irradiés pour des carcinomes de la région cervico-faciale. Bien que le risque de développement de telles complications n'ait pas de rapport direct avec la dose totale de RT, de plus hautes doses semblent accélérer le développement de lésions vasculaires. Les praticiens devraient garder en tête la possibilité de telles complications, surtout auprès des survivants au-delà de 5 ans.



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Exérèse par voie endonasale d’un neurofibrome solitaire de la portion externe du nez

Publication date: September 2017
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 134, Issue 4
Author(s): H.J. Min, K.S. Kim
IntroductionLe neurofibrome solitaire développé dans la portion externe du nez est extrêmement rare et, à notre connaissance, seuls 3 cas ont été rapportés dans la littérature anglophone. Il peut se développer à partir des branches ophtalmique (V1) et maxillaire (V2) du nerf trijumeau.Cas cliniqueNous présentons un cas rare de neurofibrome solitaire développé à partir de la portion externe du nez dont l'exérèse complète a été réalisée par voie endonasale après incision cartilagineuse.ConclusionCe cas met en lumière deux points importants. Tout d'abord, nous devons garder à l'esprit que cette entité clinique est incluse dans le diagnostic différentiel des masses tissulaires développées à partir de la portion externe du nez. Ensuite, nous devons choisir la meilleure approche chirurgicale pour l'exérèse complète avec préservation de l'aspect cosmétique.



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Fracture du stapes évoquée devant une tympanométrie anormale

Publication date: September 2017
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 134, Issue 4
Author(s): C. Aussedat, C. Bobiller, K. Gaillot, E. Lescanne, D. Bakhos
IntroductionLes fractures de l'os temporal sont fréquemment associées à des disjonctions ou des fractures ossiculaires. L'osselet le plus fréquemment impliqué est l'incus. À notre connaissance, le cas d'une fracture isolée de la branche postérieure du stapes n'a pas été rapporté.Résumé du cas cliniqueUn patient de 20 ans a consulté pour une hypoacousie gauche persistante plusieurs mois après un traumatisme crânien. Une tomodensitométrie initiale de l'os temporal montrait une fracture de l'os temporal simple, sans autre anomalie détectée. Le diagnostic a été évoqué sur les résultats de l'impédancemétrie. L'aspect de compliance augmentée a conduit à réaliser une nouvelle tomodensitométrie temporale en coupes fines, évoquant une fracture de la branche postérieure du stapes. Une exploration chirurgicale par voie endaurale a permis de confirmer le diagnostic et a permis la mise en place de ciment ionomère au niveau de la branche postérieure.DiscussionUne fracture ou une disjonction ossiculaire doit être évoquées s'il persiste une surdité de transmission associée à un aspect de compliance augmentée sur la tympanométrie, même si la tomodensitométrie de l'os temporal ne montre pas de rupture de chaîne ou une fracture ossiculaire. La réhabilitation de l'audition peut être réalisée par la mise en place d'audioprothèse ou par reconstruction ossiculaire chirurgicale.



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Une tuméfaction parotidienne

Publication date: September 2017
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 134, Issue 4
Author(s): C.A. Righini, A. Baguant, I. Atallah




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Une tumeur rare du pavillon de l’oreille

Publication date: September 2017
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 134, Issue 4
Author(s): M. Volkan Akdoğan, O. Topal, H. Erinanç




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État de mal convulsif révélant une tumeur naso-sinusienne chez l’enfant

Publication date: September 2017
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 134, Issue 4
Author(s): H. Dimassi, S. Kedous, I. Ben Said




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Maladie de Kimura orbitaire : un défi diagnostique moderne

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Publication date: September 2017
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 134, Issue 4
Author(s): P. Clarós, J.V. Fokouo, F. Nyada, A. Clarós




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Hidradénocarcinome du cuir chevelu d’évolution fatale : une nouvelle observation

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Publication date: September 2017
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 134, Issue 4
Author(s): J. Elbenaye, M. Moumine, M. Sinaa, M. Elhaouri




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The influence of yttrium-segregation-dependent phase partitioning and residual stresses on the aging and fracture behaviour of 3Y-TZP ceramics

Publication date: Available online 12 August 2017
Source:Acta Biomaterialia
Author(s): Dušan Bučevac, Tomaž Kosmač, Andraž Kocjan
The yttrium-segregation-dependent phase partitioning and residual stress development that influence both the aging and the fracture behaviour in 3Y-TZP bioceramics were studied by sintering alumina-free 3Y-TZP, varying the sintering temperature and the time, to yield ceramics with identical grain size distributions, but with different phase compositions. The structure and stability of the resulting tetragonal phases, in the form of transformable, yttria-lean t-ZrO2 (YLZ) and non-transformable, yttria-rich t"-ZrO2 and/or t'-ZrO2 (YRZ), were studied by X-ray diffraction (XRD) and focused ion beam scanning electron microscopy (FIB-SEM). The accelerated aging kinetics was fitted to the Mehl-Avrami-Johnson equation. The specimen sintered at the lowest sintering temperature but with the longest dwell time contained the smallest and the largest concentrations of yttria in the YLZ and YRZ phases, respectively, as well as the largest amount of YRZ. As a consequence, it exhibited the fastest linear aging kinetics accompanied by more extensive micro-cracking of the transformed layer, as well as largest amount of intergranular fracture and the greatest resistance to fracture. These properties were ascribed to the increased transformability of the YLZ phase and the greatest propensity of the YRZ phase to relax the accumulated residual stresses during transformation (tetragonal to monoclinic, t-m) manifested as a ∼2.4% unit-cell volume increase. The observed relaxation provides additional understanding of the t–m transformation mechanism, which governs both the aging and fracture behaviour in 3Y-TZP.Statement of significanceA novel approach to understanding the effect of yttrium segregation on t–m transformation of 3Y-TZP zirconia bioceramics is presented. Carefully designed sintering strategy facilitated fabrication of ceramics with identical grain size distributions but with different yttrium concentrations. The influence of phase partitioning on stability and structure of transformable yttria-lean tetragonal phase (YLZ) and non-transformable yttria-rich phases (YRZ; t"– and t'–prime) and on the formation of residual stresses in YRZ were investigated. It is shown that YRZ phases are under compressive stresses in YLZ matrix, since a systematic relaxation after ageing was observed and explained for the first time. It puts additional perspective on the understanding of the t–m transformation mechanism ultimately governing both the ageing and fracture behaviour in 3Y-TZP.

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The synergistic effects of Sr and Si bioactive ions on osteogenesis, osteoclastogenesis and angiogenesis for osteoporotic bone regeneration

Publication date: Available online 12 August 2017
Source:Acta Biomaterialia
Author(s): Lixia Mao, Lunguo Xia, Jiang Chang, Jiaqiang Liu, Lingyong Jiang, Chengtie Wu, Bing Fang
AbstractsBioactive ions released from bioceramics play important roles in bone regeneration; however, it is unclear how each ionic composition in complex bioceramics exerts its specific effect on bone regeneration. The aim of this study is to elucidate the functional effects of Sr and Si ions in bioceramics on the regeneration of osteoporotic bone. A model bioceramic with Sr- and Si-containing components (SMS) was successfully fabricated and the effects of ionic products from SMS bioceramics on the osteogenic, osteoclastic and angiogenic differentiation of rBMSCs-OVX and RANKL-induced osteoclasts were investigated. The results showed that SMS bioceramics could enhance ALP activity and expression of Col 1, OCN, Runx2, and angiogenic factors including VEGF and Ang-1. SMS bioceramics not only rebalanced the OPG/RANKL ratio of rBMSCs-OVX at early stage, but also repressed RANKL-induced osteoclast formation and expression of TRAP, DC-STAMP, V-ATPase a3, and NFATc1. The synergistic effects of Sr and Si ions were further investigated as compared with those of similar concentrations of Sr and Si ions alone. Sr and Si ions possessed synergistic effects on osteogenesis, osteoclastogenesis, and angiogenesis, attributed to the dominant effects of Sr ions on enhancing angiogenesis and repressing osteoclastogenesis, and the dominant effects of Si ions on stimulating osteogenesis. The in vivo study using critical-size mandibular defects of OVX rat models showed that SMS bioceramics could significantly enhance bone formation and mineralization compared with β-TCP bioceramics. Our results are the first to elucidate the specific effect of each ion from bioceramics on osteogenesis, osteoclastogenesis and angiogenesis for osteoporotic bone regeneration, paving the way for the design of functional biomaterials with complex compositions for tissue engineering and regenerative medicine.Statement of significanceBioactive ions released from bioceramics play important roles for bone regeneration; however, it is unclear how each of ionic compositions in complex bioceramics exerts its specific effect on bone regeneration. The aim of present study is to elucidate the functional effects of Sr and Si ions in complex bioceramics on the regeneration of osteoporotic bone. A model bioceramic with Sr and Si-containing components (SMS) was successfully fabricated and the effects of ionic products from SMS bioceramics on the osteogenic, osteoclastic and angiogenic differentiation of rBMSCs-OVX and RANKL-induced osteoclasts were investigated. The results showed that SMS bioceramics could enhance ALP activity and expression of Col 1, OCN, Runx2 and angiogenic factors including VEGF and Ang-1. SMS bioceramics not only rebalanced the ratio of OPG/RANKL of OVX-BMSCs at early stage, but also repressed RANKL-induced osteoclast formation and expression of TRAP, DC-STAMP, V-ATPase a3, and NFATc1. The synergistic effects of Sr and Si ions were further investigated as compared with the similar concentration of Sr and Si ions alone. It was found that Sr and Si ions possessed synergistic effects on osteogenesis, osteoclastogenesis and angiogenesis, attributed to the dominant effects of Sr ions on enhancing angiogenesis and repressing osteoclastogenesis, and the dominant effects of Si ions on stimulating osteogenesis. The in vivo study using critical-size mandibular defects of OVX rat models showed that SMS bioceramics could significantly enhance bone formation and mineralization as compared with β-TCP bioceramics. It is suggested that SMS bioceramics may be a promising biomaterial for osteoporotic bone regeneration.To our knowledge, this is the first time to elucidate the specific effect of each ion from bioceramics on osteogenesis, osteoclastogenesis and angiogenesis for osteoporotic bone regeneration, paving the way to design functional biomaterials with complex compositions for tissue engineering and regenerative medicine.

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Acute ethanol administration results in a protective cytokine and neuroinflammatory profile in traumatic brain injury

Publication date: October 2017
Source:International Immunopharmacology, Volume 51
Author(s): Akila Chandrasekar, Florian olde Heuvel, Annette Palmer, Birgit Linkus, Albert C. Ludolph, Tobias M. Boeckers, Borna Relja, Markus Huber-Lang, Francesco Roselli
Ethanol intoxication is a common comorbidity in traumatic brain injury. To date, the effect of ethanol on TBI pathogenic cascades and resulting outcomes remains debated. A closed blunt weight-drop murine TBI model has been implemented to investigate behavioral (by sensorimotor and neurological tests), and neuro-immunological (by tissue cytokine arrays and immuno-histology) effects of ethanol intoxication on TBI. The effect of the occurrence of traumatic intracerebral hemorrhage was also studied. The results indicate that ethanol pretreatment results in a faster and better recovery after TBI with reduced infiltration of leukocytes and reduced microglia activation. These outcomes correspond to reduced parenchymal levels of GM-CSF, IL-6 and IL-3 and to the transient upregulation of IL-13 and VEGF, indicating an early shift in the cytokine profile towards reduced inflammation. A significant difference in the cytokine profile was still observed 24h post injury in the ethanol pretreated mice, as shown by the delayed peak in IL-6 and by the suppression of GM-CSF, IFN-γ, and IL-3. Seven days post-injury, ethanol-pretreated mice displayed a significant decrease both in CD45+ cells infiltration and in microglial activation. On the other hand, in the case of traumatic intracerebral hemorrhage, the cytokine profile was dominated by KC, CCL5, M-CSF and several interleukins and ethanol pretreatment did not produce any modification. We can thus conclude that ethanol intoxication suppresses the acute neuro-inflammatory response to TBI, an effect which is correlated with a faster and complete neurological recovery, whereas, the presence of traumatic intracerebral hemorrhage overrides the effects of ethanol.



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Circulating follicular helper T cells presented distinctively different responses toward bacterial antigens in primary biliary cholangitis

Publication date: October 2017
Source:International Immunopharmacology, Volume 51
Author(s): Zun-Qiang Zhou, Da-Nian Tong, Jiao Guan, Mei-Fang Li, Qi-Ming Feng, Min-Jie Zhou, Zheng-Yun Zhang
Primary biliary cholangitis (PBC) is a chronic and progressive cholestatic liver disease with unknown causes. The initiation of PBC is associated with bacterial infections and abnormal immune correlates, such as the presence of self-reactive anti-mitochondrial antibodies and shifted balance of T cell subsets. In particular, the CD4+CXCR5+ follicular helper T (Tfh) cells are highly activated in PBC patients and are significantly associated with PBC severity, but the underlying reasons are unknown. In this study, we found that the circulating CD4+CXCR5+ T cells were enriched with the interferon (IFN)-γ-secreting Th1-subtype and the interleukin (IL)-17-secreting Th17-subtype, but not the IL-4-secreting Th2 subtype. We further demonstrated that a host of microbial motifs, including Pam3CSK4, poly(I:C), LPS, imiquimod, and CpG, could significantly stimulate IFN-γ, IL-17, and/or IL-21 from circulating CD4+CXCR5+ T cells in PBC patients, especially in the presence of monocytes and B cells. Whole bacterial cells of Escherichia coli, Novosphingobium aromaticivorans, and Mycobacterium gordonae, could also potently stimulate IFN-γ, IL-17, and/or IL-21 production from circulating CD4+CXCR5+ T cells. But interestingly, while the whole cell could potently stimulate circulating CD4+CXCR5+ T cells from both healthy controls and PBC patients, the cell protein lysate could only potently stimulate circulating CD4+CXCR5+ T cells from PBC patients, but not those from healthy controls, suggesting that circulating CD4+CXCR5+ T cells in PBC patients had distinctive antigen-specificity from those in healthy individuals. Together, these data demonstrated that bacterial antigen stimulation is a potential source of aberrant Tfh cell activation in PBC patients.



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Submucosal injection of dexamethasone and methylprednisolone for the control of postoperative sequelae after third molar surgery: randomized controlled trial

Pain, swelling, and trismus are known sequelae of third molar surgery that can significantly affect the individual's quality of life (QOL). These should be minimized to improve QOL. The purpose of this study was to compare the effects of the preoperative submucosal administration of equivalent doses of two commonly used steroids on these postoperative sequelae. A randomized controlled clinical trial was conducted involving 60 subjects requiring the removal of impacted mandibular third molars. Extraction cases with a similar difficulty index were included.

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Intelligibility of degraded speech and the relationship between symptoms of inattention, hyperactivity/impulsivity and language impairment in children with suspected auditory processing disorder

To compare the sensitivity and specificity of Auditory Figure Ground subtests of the SCAN-3 battery, using signal to noise ratio (SNR) of +8 dB (AFG+8) and 0dB (AFG0), in identifying auditory processing disorder (APD). A secondary objective was to evaluate any difference in auditory processing (AP) between children with symptoms of inattention versus combined sub-types of Attention Deficit Hyperactivity Disorder (ADHD).

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Significance of Frequencies, Compositions, and/or Antileukemic Activity of (DC-stimulated) Invariant NKT, NK and CIK Cells on the Outcome of Patients With AML, ALL and CLL

imageInvariant natural killer T (iNKT)/natural killer (NK)/cytokine-induced killer (CIK) cells are important for immune surveillance. (I) Novel combinations of antibody 6B11 (targeting the Vα24-Jα18-invariant T-cell receptor) with CD4/CD8/CD1d/Vα24 for iNKT subset detection and "T/NK cell-like"-iNKT subsets were defined. Compared with healthy peripheral blood mononuclear cells (MNC) (significantly) lower proportions of iNKT cells (6B11+/6B11+CD3+/6B11+CD161+), NK cells (CD3−CD56+/CD3−CD161+), and CIK cells (CD3+CD56+/CD3+CD161+) were found in peripheral blood MNC from acute myeloid (AML)/acute myeloid, lymphoid (ALL)/chronic lymphoid leukemia (CLL) patients in acute disease stages. Subtyping of iNKT cells revealed (significantly) higher proportions of CD3+ T cells and CD161+ NK cells in AML/ALL/CLL expressing 6B11 compared with healthy MNC. Prognostic evaluations showed higher proportions of iNKT/NK/CIK cells in favorable AML subgroups (younger age, primary, no extramedullary disease, achievement/maintenance of complete remission) or adult ALL and CLL patients. (II) iNKT/NK/CIK cell frequencies increased after (vs. before) mixed lymphocyte cultures of T-cell–enriched immune reactive cells stimulated with MNC/whole blood with or without pretreatment with "cocktails" (dendritic cells generating methods/kits inducing blasts' conversion to leukemia-derived dendritic cells from AML patients). Individual "cocktails" leading to "highest" iNKT cell frequencies could be defined. Antileukemic blast lytic activity correlated significantly with frequencies of iNKT/NK/CIK cells. In summary healthy MNC show significantly more iNKT/NK/CIK cells compared with AML/ALL/CLL MNC, a shift in the iNKT cell composition is seen in healthy versus leukemic samples and iNKT/NK/CIK cell-proportions in AML/ALL/CLL MNC samples correlate with prognosis. "Cocktail"-treated AML blasts lead to higher iNKT/NK/CIK cell frequencies and samples with antileukemic activity show significantly higher frequencies of iNKT/NK/CIK cells. Proportions of iNKT/NK/CIK cells should regularly be evaluated in AML/ALL/CLL diagnosis panels for quantitative/prognostic estimation of individual patients' antileukemic potential and their role in dendritic cells/leukemia-derived dendritic cells triggered immune surveillance.

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Zebularine Treatment Induces MAGE-A11 Expression and Improves CTL Cytotoxicity Using a Novel Identified HLA-A2-restricted MAGE-A11 Peptide

imageMelanoma-associated antigen-A11 (MAGE-A11) is frequently expressed in breast cancer and is associated with poor prognosis. Therefore, MAGE-A11 is a potential immunotherapy target in breast cancer. MAGE-A11 expression, however, is downregulated in many patients, thus constraining the application of immunotherapy. The induction of MAGE-A11 expression is crucial for the recognition and killing of breast cancer cells by cytotoxic T lymphocytes (CTL). In this study, a series of HLA-A2-restricted candidate MAGE-A11 peptides were predicted, synthesized, and tested. Of the selected peptides, p350 (FLFGEPKRL) elicited peptide-specific CTLs from healthy HLA-A*0201-positive donors. The induced CTLs can lyse MAGE-A11-expressing breast cancer cells but not MAGE-A11-negative tumor cells. To improve antitumor immune response, zebularine, a DNA methyltransferase inhibitor, was used to induce MAGE-A11 expression and upregulate the cytotoxicity of antigen-specific T cells in breast cancer cell lines and primary breast cancer cells. The present findings suggested that peptide p350 induces peptide-specific cytolytic activity and is thus a potential candidate for tumor vaccination or T-cell therapy. Epigenetic modulation by zebularine can induce MAGE-A11 expression in breast cancer cells and facilitate cytotoxicity via MAGE-A11-specific CTL.

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Antigen Presentation by Individually Transferred HLA Class I Genes in HLA-A, HLA-B, HLA-C Null Human Cell Line Generated Using the Multiplex CRISPR-Cas9 System

imageHuman leukocyte antigens (HLAs) are essential immune molecules that affect transplantation and adoptive immunotherapy. When hematopoietic stem cells or organs are transplanted with HLA-mismatched recipients, graft-versus-host disease or graft rejection can be induced by allogeneic immune responses. The function of each HLA allele has been studied using HLA-deficient cells generated from mutant cell lines or by RNA interference, zinc finger nuclease, and the CRISPR/Cas9 system. To improve HLA gene editing, we attempted to generate an HLA class I null cell line using the multiplex CRISPR/Cas9 system by targeting exons 2 and 3 of HLA-A, HLA-B, and HLA-C genes simultaneously. Multiplex HLA editing could induce the complete elimination of HLA class I genes by bi-allelic gene disruption on target sites which was defined by flow cytometry and target-specific polymerase chain reaction. Furthermore, artificial antigen-presenting cells were generated by transfer of a single HLA class I allele and co-stimulatory molecules into this novel HLA class I null cell line. Artificial antigen-presenting cells showed HLA-restricted antigen presentation following antigen processing and were successfully used for the efficient generation of tumor antigen-specific cytotoxic T cells in vitro. The efficient editing of HLA genes may provide a basis for universal cellular therapies and transplantation.

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Inflammatory Myopathy and Axonal Neuropathy in a Patient With Melanoma Following Pembrolizumab Treatment

Immune-mediated adverse effects of immune checkpoint inhibitors are rather common, but neuromyopathic immune-related adverse events are very rare. In this report, we present a unique case of a patient with a complex neuromyopathic syndrome with axonal neuropathy and inflammatory myopathy after a single dose of pembrolizumab. An 82-year-old patient with a previously untreated stage IIIc melanoma developed ptosis in the left eye, generalized weakness, and neck and shoulder pain 15 days after pembrolizumab administration. He had left-sided ptosis and miosis, with a normal pupillary light reflex, horizontal diplopia, and voice hoarseness, along with weakness of the neck muscles and a hypokinetic right vocal cord at laryngoscopy. The laboratory evaluation was remarkable for the marked increase in the serum lactate dehydrogenase and creatine phosphokinase levels. Further evaluation revealed findings compatible with axonal neuropathy and inflammatory myopathy. The patient was treated with corticosteroids, immunoglobulin, and plasmapheresis, with a minor response; the patient eventually died. This case represents a newly described syndrome probably associated with pembrolizumab administration.

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Diabetic Ketoacidosis as an Immune-related Adverse Event from Pembrolizumab in Non–Small Cell Lung Cancer

imageProgrammed cell death protein 1 pathway inhibitors are now routinely administered to patients with non–small cell lung cancer, and prompt recognition of immune-related adverse events is critical to managing serious drug toxicities. Here, we describe a 66-year-old man with no known history of diabetes who presented with diabetic ketoacidosis after receiving 3 doses of pembrolizumab for lung adenocarcinoma. Autoimmune diabetes is a rare but potentially life-threatening complication of programmed cell death protein 1 inhibitors

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How similar are the treatment responses to biosimilars in patients with psoriasis? A systematic review of statistical margins in comparative clinical trials

Publication date: September 2017
Source:Journal of the American Academy of Dermatology, Volume 77, Issue 3
Author(s): Marilyn T. Wan, Bruce E. Strober, Jashin J. Wu, Daniel B. Shin, Joel M. Gelfand




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Radiation therapy for nonmelanoma skin cancer, a cost comparison: 2016 coding changes to radiation therapy

Publication date: September 2017
Source:Journal of the American Academy of Dermatology, Volume 77, Issue 3
Author(s): Christopher M. Wolfe, Armand B. Cognetta




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PDL1 expression in desmoplastic melanoma is associated with tumor aggressiveness and progression

Publication date: September 2017
Source:Journal of the American Academy of Dermatology, Volume 77, Issue 3
Author(s): Stefan Kraft, Maria-Teresa Fernandez-Figueras, Nina A. Richarz, Keith T. Flaherty, Mai P. Hoang
BackgroundThe prognostic role of programmed death ligand 1 (PDL1), CD8, and forkhead box p3 (FoxP3) expression in desmoplastic melanomas is unclear.MethodsWe correlated PDL1, p53, and Ki-67 expression with CD8+ and FoxP3+ immune infiltrates with clinicopathologic variables and patient outcomes in a series of 66 desmoplastic melanomas.ResultsTumoral PDL1 expression (≥25%), which was seen in 21% of patients (14 of 66), significantly correlated with mixed histology, tumor thickness, mitoses, recurrence, and metastasis. According to linear regression analysis, tumoral PDL1 expression correlated with thickness (P = .0041); p53 expression (P = .019); Ki-67 proliferation index (P = .0018); and tumoral CD8 (P = .0084), stromal CD8 (P < .0001), and FoxP3 (P < .0001) T-cell counts. According to univariate analyses, PDL1 expression of 25% or higher correlated with shorter progression-free survival (P < .0001) and melanoma-specific survival (P = .034). According to multivariate analyses, PDL1 expression of 25% or more (P = .026) and mixed histology (P = .039) independently predicted shorter progression-free survival, and presence of lymphovascular invasion predicted shorter overall survival (P = .018).LimitationsSmall study size.ConclusionTumoral and stromal CD8+ and FoxP3+ lymphocyte counts correlated with tumoral PDL1 expression, which is supportive of an adaptive immune response. PDL1 expression in desmoplastic melanoma was associated with tumor aggressiveness and progression. Although PDL1 expression is typically low in melanoma, its frequency and level of expression in desmoplastic melanoma may identify a subset of melanomas that are likely to respond to immunotherapy.



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JAAD Case Reports Article List

Publication date: September 2017
Source:Journal of the American Academy of Dermatology, Volume 77, Issue 3





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A prospective, randomized, double-blinded, split-face/chest study of prophylactic topical dapsone 5% gel versus moisturizer for the prevention of cetuximab-induced acneiform rash

Publication date: September 2017
Source:Journal of the American Academy of Dermatology, Volume 77, Issue 3
Author(s): Viswanath R. Belum, Michael A. Marchetti, Stephen W. Dusza, Andrea Cercek, Nancy E. Kemeny, Mario E. Lacouture




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Journal Based CME Instructions and Information

Publication date: September 2017
Source:Journal of the American Academy of Dermatology, Volume 77, Issue 3





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Fractionated cryotherapy

Publication date: September 2017
Source:Journal of the American Academy of Dermatology, Volume 77, Issue 3
Author(s): Somesh Gupta, Savita Yadav, Suman Patra, Sanjeev Gupta




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Etiologies and management of cutaneous flushing

Publication date: September 2017
Source:Journal of the American Academy of Dermatology, Volume 77, Issue 3
Author(s): Azeen Sadeghian, Hailey Rouhana, Brittany Oswald-Stumpf, Erin Boh
The flushing phenomenon may represent a physiologic or a pathologic reaction. Although flushing is usually benign, it is prudent that the physician remains aware of potentially life-threatening conditions associated with cutaneous flushing. A thorough investigation should be performed if the flushing is atypical or not clearly associated with a benign underlying process. The diagnosis often relies on a pertinent history, review of systems, physical examination, and various laboratory and imaging modalities, all of which are discussed in the 2 articles in this continuing medical education series. This article reviews flushing associated with fever, hyperthermia, emotions, menopause, medications, alcohol, food, hypersensitivity reactions, rosacea, hyperthyroidism, dumping syndrome, superior vena cava syndrome, and neurologic etiologies.



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CME examination

Publication date: September 2017
Source:Journal of the American Academy of Dermatology, Volume 77, Issue 3





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Answers to CME examination

Publication date: September 2017
Source:Journal of the American Academy of Dermatology, Volume 77, Issue 3





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Smoking and risk of psoriasis: A nationwide cohort study

Publication date: September 2017
Source:Journal of the American Academy of Dermatology, Volume 77, Issue 3
Author(s): Eun Joo Lee, Kyung Do Han, Ju Hee Han, Ji Hyun Lee




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Etiologies and management of cutaneous flushing

Publication date: September 2017
Source:Journal of the American Academy of Dermatology, Volume 77, Issue 3
Author(s): Azeen Sadeghian, Hailey Rouhana, Brittany Oswald-Stumpf, Erin Boh
The second article in this 2-part continuing medical education series reviews the following malignant causes of flushing: mastocytosis, medullary thyroid carcinoma, pheochromocytoma, carcinoid tumors, gastroenteropancreatic neuroendocrine tumors, bronchogenic carcinoma, vasointestinal polypeptide secreting tumors, and renal cell carcinoma. The information provided will allow physicians to better distinguish patients who have worrisome presentations that require a more thorough investigation. Appropriate diagnostic workup and treatment options for these malignancies are reviewed.



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Keratinocyte carcinoma data for Hispanic patients undergoing Mohs micrographic surgery in Miami, Florida from 2011 to 2014

Publication date: September 2017
Source:Journal of the American Academy of Dermatology, Volume 77, Issue 3
Author(s): Marina Perper, Vidhi Shah, John Tsatalis, Ariel Eva Eber, Chengcheng Zheng, Keyvan Nouri




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CME examination

Publication date: September 2017
Source:Journal of the American Academy of Dermatology, Volume 77, Issue 3





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Spontaneous upper eyelid ecchymosis: A cutaneous clue to increased intracranial pressure

Publication date: September 2017
Source:Journal of the American Academy of Dermatology, Volume 77, Issue 3
Author(s): Muhammed Razmi T, Deeksha Katoch, Sunil Dogra




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Answers to CME examination

Publication date: September 2017
Source:Journal of the American Academy of Dermatology, Volume 77, Issue 3





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Mortality and Prehospital Blood Pressure in Patients with Major Traumatic Brain Injury

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Publication date: August 2017
Source:The Journal of Emergency Medicine, Volume 53, Issue 2
Author(s): John Michael Rague




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Issue Highlights

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Publication date: August 2017
Source:The Journal of Emergency Medicine, Volume 53, Issue 2





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Contents

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Publication date: August 2017
Source:The Journal of Emergency Medicine, Volume 53, Issue 2





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Relation of Prolonged P-Wave Duration to Risk of Sudden Cardiac Death in the General Population (from the Atherosclerosis Risk in Communities Study)

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Publication date: August 2017
Source:The Journal of Emergency Medicine, Volume 53, Issue 2
Author(s): Mario Andres Camacho




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Modeling Contagion Through Social Networks to Explain and Predict Gunshot Violence in Chicago, 2006 to 2014

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Publication date: August 2017
Source:The Journal of Emergency Medicine, Volume 53, Issue 2
Author(s): Stephanie Diebold




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Instructions for Authors

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Publication date: August 2017
Source:The Journal of Emergency Medicine, Volume 53, Issue 2





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Editorial Board

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Publication date: August 2017
Source:The Journal of Emergency Medicine, Volume 53, Issue 2





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Changes in US Lifetime Heroin Use and Heroin Use Disorder Prevalence From the 2001-2002 to 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions

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Publication date: August 2017
Source:The Journal of Emergency Medicine, Volume 53, Issue 2
Author(s): Mario Andres Camacho




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Imaging gently? Higher rates of computed tomography imaging for pediatric appendicitis in non-children's hospitals

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Publication date: August 2017
Source:The Journal of Emergency Medicine, Volume 53, Issue 2
Author(s): Stephanie Diebold




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Clinical Mimics: An Emergency Medicine–Focused Review of Asthma Mimics

Publication date: August 2017
Source:The Journal of Emergency Medicine, Volume 53, Issue 2
Author(s): Kristen Kann, Brit Long, Alex Koyfman
BackgroundAsthma is a common diagnosis or preexisting condition, and many patients with acute asthma exacerbation may present to the emergency department with wheezing and respiratory distress. However, many conditions may mimic this presentation.ObjectivesThis review provides an overview of common asthma mimics and an approach to evaluation and management.DiscussionAsthma is characterized by an obstructive pulmonary disease with recurrent exacerbations. The disease may present with a variety of symptoms, including wheezing, chest tightness, shortness of breath, and even respiratory failure. Mimics include anaphylaxis, angioedema, central airway obstruction, heart failure, allergic reaction, foreign body aspiration, pulmonary embolism, and vocal cord dysfunction. The approach to evaluation and management of these patients includes assessment for life-threatening conditions while treatment and resuscitation is underway. Providers should assess for red flags, including no history of asthma, lack of severe asthma, and no improvement with standard treatments. Focused assessment with history, physical examination, chest imaging, electrocardiogram, and laboratory studies may provide benefit. Through consideration of these mimics and treatment, providers can provide rapid management.ConclusionsWhile asthma is a common disease, many asthma mimics exist. Through consideration of other diseases with wheezing and assessing for red flags, such as patients presenting without a history of asthma or patients with a history of only mild asthma presenting with severe symptoms, emergency providers may decrease the chance of early diagnostic closure and anchoring while improving the care of these patients.



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Factors Associated with Nontransfer in Trauma Patients Meeting American College of Surgeons' Criteria for Transfer at Nontertiary Centers

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Publication date: August 2017
Source:The Journal of Emergency Medicine, Volume 53, Issue 2
Author(s): Ryan Murphy




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All-Terrain Vehicle Injury in Children and Youth: Examining Current Knowledge and Future Needs

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Publication date: August 2017
Source:The Journal of Emergency Medicine, Volume 53, Issue 2
Author(s): Andrea N. Doud, Regina Moro, Stephen Gray Wallace, Michael D. Smith, Marcia McCall, Laura J. Veach, Thomas Pranikoff
BackgroundAll-terrain vehicle (ATV)-related injuries remain a large public health problem in the United States and disproportionately affect American youth. Although children account for only 14–18% of ATV riders, they comprise 37–57% of those injured in ATV-related accidents. Since the U.S. Consumer Product Safety Commission began collecting data in 1982, 23% of ATV-related deaths have occurred in children.ObjectiveWith this review, we outline the major risk factors for injuries among young ATV riders in the United States and suggest research-based interventions to successfully modify such risk factors.DiscussionWe reviewed data from 16 published reviews regarding epidemiology and risk factors among ATV-related injuries in American children. All data pointed to young driver age and lack of appropriate safety equipment as major risk factors for such injuries. Although these risk factors are modifiable, legislation and programs designed to mitigate such risks have been unsuccessful. Among adults, the brief intervention model has become widely used among trauma patients exhibiting risky behaviors. Additionally, peer-to-peer interventions have demonstrated success with respect to drug and alcohol use in school-aged children. Both the brief and peer-to-peer interventions are promising avenues for decreasing risky ATV-related behavior in youths but have not been studied in this field.ConclusionsATV-related injuries disproportionately affect American youths. Although risk factors for such injuries are modifiable, current methods for intervention (mainly legislation) have not been successfully implemented. The brief intervention and peer-to-peer interventions have shown promise in other fields and should be studied with respect to pediatric ATV use.



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Novel oral anticoagulants and trauma: The results of a prospective American Association for the Surgery of Trauma Multi-Institutional Trial

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Publication date: August 2017
Source:The Journal of Emergency Medicine, Volume 53, Issue 2
Author(s): Mario Andres Camacho




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Air and its Sonographic Appearance: Understanding the Artifacts

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Publication date: August 2017
Source:The Journal of Emergency Medicine, Volume 53, Issue 2
Author(s): Simran Buttar, Denrick Cooper, Patrick Olivieri, Michael Barca, Aaran B. Drake, Melvin Ku, Gabriel Rose, Sebastian D. Siadecki, Turandot Saul
BackgroundAlthough air has traditionally been considered a barrier to sonographic imaging, when encountered in unusual settings it can serve as an important indicator of various pathologic states as well. Clinician recognition and thorough understanding of the characteristic pattern of artifacts generated by air are critical for making a number of important diagnoses.Case SeriesWe present five emergency department cases in which air was visualized in a pathologic location. Pneumothorax, pneumoperitoneum, necrotizing fasciitis, or Fournier's gangrene, and subcutaneous emphysema and pneumomediastinum, can be rapidly and easily identified on ultrasound by the presence of air artifacts. The relevant sonographic findings are described and discussed in this article.Why Should an Emergency Physician Be Aware of This?Due to its inherent impedance mismatch with other human tissues, air has a characteristic appearance on ultrasound that includes irregular hyperechoic structures, "dirty shadowing," A-lines, and decreased visualization of deeper structures. Knowledge of the sonographic appearance of air artifacts can assist the physician in making a diagnosis, selecting appropriate additional imaging, and enlisting specialist consultation.



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Association Between Concurrent Use of Prescription Opioids and Benzodiazepines and Overdose: Retrospective Analysis

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Publication date: August 2017
Source:The Journal of Emergency Medicine, Volume 53, Issue 2
Author(s): John Michael Rague




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Short Term Use of Oral Corticosteroids and Related Harms Among Adults in the United States: Population Based Cohort Study

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Publication date: August 2017
Source:The Journal of Emergency Medicine, Volume 53, Issue 2
Author(s): John Michael Rague




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Pelvic fracture pattern predicts the need for hemorrhage control intervention—Results of an AAST multi-institutional study

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Publication date: August 2017
Source:The Journal of Emergency Medicine, Volume 53, Issue 2
Author(s): Stephanie Diebold




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Faster Clean Catch Urine Collection (Quick-Wee method) from Infants: Randomised Controlled Trial

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Publication date: August 2017
Source:The Journal of Emergency Medicine, Volume 53, Issue 2
Author(s): Ryan Murphy




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Value of MDCT and Clinical and Laboratory Data for Predicting the Need for Surgical Intervention in Suspected Small-Bowel Obstruction

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Publication date: August 2017
Source:The Journal of Emergency Medicine, Volume 53, Issue 2
Author(s): Ryan Murphy




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Duration of tracheostomy dependence and development of tracheocutaneous fistula in children

Objective

To determine whether the risk of developing a tracheocutaneous fistula (TCF) increases with longer tracheostomy dependence times in children.

Study Design

Retrospective review of medical records.

Method

A retrospective chart review was conducted for all children who both underwent tracheotomy and were decannulated between 2002 and 2011 at a tertiary children's hospital. Charts were analyzed for duration of tracheostomy and evidence of TCF up to 12 months. Data for these criteria was available on 164 out of 182 patients.

Results

A significant difference in the duration of tracheostomy dependence between children with and without resultant TCF was determined by the Wilcoxon signed rank test (P = 0.0003). The relative risk (RR) of a persistent TCF was significantly increased when the duration of tracheostomy dependence was greater than 24 months (RR = 2.5217, P < 0.005) when compared to those decannulated before 12 months. The mean tracheostomy dependence times for children with and without TCF were 33.1 and 23.4 months, respectively. Overall, 94 children (57.3%) developed a TCF.

Conclusion

To our knowledge, this study represents the largest collection of data for children who have been decannulated following tracheostomy placement. These data demonstrate that the risk of developing a TCF increases with longer tracheostomy dependence times in children.

Level of Evidence

4. Laryngoscope, 2017



http://ift.tt/2vPOUph

Duration of tracheostomy dependence and development of tracheocutaneous fistula in children

Objective

To determine whether the risk of developing a tracheocutaneous fistula (TCF) increases with longer tracheostomy dependence times in children.

Study Design

Retrospective review of medical records.

Method

A retrospective chart review was conducted for all children who both underwent tracheotomy and were decannulated between 2002 and 2011 at a tertiary children's hospital. Charts were analyzed for duration of tracheostomy and evidence of TCF up to 12 months. Data for these criteria was available on 164 out of 182 patients.

Results

A significant difference in the duration of tracheostomy dependence between children with and without resultant TCF was determined by the Wilcoxon signed rank test (P = 0.0003). The relative risk (RR) of a persistent TCF was significantly increased when the duration of tracheostomy dependence was greater than 24 months (RR = 2.5217, P < 0.005) when compared to those decannulated before 12 months. The mean tracheostomy dependence times for children with and without TCF were 33.1 and 23.4 months, respectively. Overall, 94 children (57.3%) developed a TCF.

Conclusion

To our knowledge, this study represents the largest collection of data for children who have been decannulated following tracheostomy placement. These data demonstrate that the risk of developing a TCF increases with longer tracheostomy dependence times in children.

Level of Evidence

4. Laryngoscope, 2017



http://ift.tt/2vPOUph

Transport and transformation of mercury during wet flue gas cleaning process of nonferrous metal smelting

Abstract

Reducing mercury emission is hot topic for international society. The first step for controlling mercury in fuel gas is to investigate mercury distribution and during the flue gas treatment process. The mercury transport and transformation in wet flue gas cleaning process of nonferrous smelting industry was studied in the paper with critical important parameters, such as the solution temperature, Hg0 concentration, SO2 concentration, and Hg2+ concentration at the laboratory scale. The mass ratio of the mercury distribution in the solution, flue gas, sludge, and acid fog from the simulated flue gas containing Hg2+ and Hg0 was 49.12~65.54, 18.34~35.42, 11.89~14.47, and 1.74~3.54%, respectively. The primary mercury species in the flue gas and acid fog were gaseous Hg0 and dissolved Hg2+. The mercury species in the cleaning solution were dissolved Hg2+ and colloidal mercury, which accounted for 56.56 and 7.34% of the total mercury, respectively. Various mercury compounds, including Hg2Cl2, HgS, HgCl2, HgSO4, and HgO, existed in the sludge. These results for mercury distribution and speciation are highly useful in understanding mercury transport and transformation during the wet flue gas cleaning process. This research is conducive for controlling mercury emissions from nonferrous smelting flue gas and by-products.



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Nitrate pollution in the Warta River (Poland) between 1958 and 2016: trends and causes

Abstract

The article presents analyses of long-term water quality data from the Warta River between 1958 and 2016. A clear increasing trend in nitrate concentrations was observed from 1958 to the early 1990s. This trend was mainly related to the increasing use of fertilizers in Poland in this period. Then, after the early 1990s, a slow decreasing trend related to improvements in water and sewage management and more rational fertilizer use was observed after political and economic changes in Poland. The influence of long-term hydrological droughts on nitrate concentrations was also investigated. Sharp increases in the nitrate concentration in surface water were related to the accumulation of contaminants in the soil and aeration zone during drought periods and the subsequent transport of these contaminants to groundwater and surface water via recharge infiltration after each drought period. The presented results highlight the importance of surface water–groundwater interactions and suggest that groundwater protection in an entire catchment area is essential for surface water quality protection.



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Polymorphisms in XRCC1, ERCC2, and ERCC3 DNA repair genes, CYP1A1 xenobiotic metabolism gene, and tobacco are associated with bladder cancer susceptibility in Tunisian population

Abstract

Other than the established environmental risk factors associated with bladder cancer (BC), little is known about the genetic variations determining the individual susceptibility of this complex disease. This study aimed to investigate the relationship of BC with environmental agents and polymorphisms in XRCC1, ERCC2, and ERCC3 DNA repair genes and CYP1A1, CYP2D6, NAT1, and NAT2 xenobiotic metabolism genes through a hospital-based case-control study in Tunisia. The selection of the single nucleotide polymorphisms (SNPs) (rs25487, rs 13181, rs415407, rs446421, rs1058172, rs4921880, and rs1208) was performed using the dbSNP database. DNA genotyping was determined by PCR-RFLP after DNA extraction from whole blood. The risks of BC associated with every polymorphism as well as the studied environmental factors were estimated by multivariate-adjusted logistic regression using R software. In addition, gene–gene interactions were analyzed using generalized multifactor dimensionality reduction (GMDR) methods. Results showed that tobacco smoking and chewing parameters were significantly associated with BC risk. Single-gene variant analysis showed significant associations of the TT genotype of CYP1A1 and the rare GG genotype of ERCC2 with bladder cancer susceptibility (OR = 1.34, 95% CI 1.22–1.40, P < 0.0001). According to GMDR analysis, our findings indicated a significant association between BC and gene–gene interaction among the CYP1A1, ERCC3, and XRCC1. The present results suggest a potential role of XRCC1, ERCC2, ERCC3, and CYP1A1 besides tobacco intake in susceptibility to BC.



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Microbial volatile compounds alter the soil microbial community

Abstract

Volatile organic compounds (VOCs) from soil bacteria are likely to have an important role in the interactions among soil microorganisms. However, their effects on the soil microbial community have not been extensively studied. In this study, the effect of bacterial VOCs generated by growing Bacillus amyloliquefaciens NJN-6 on modified MS medium on soil microbial community was evaluated. B. amyloliquefaciens NJN-6 was able to produce 48 volatile compounds as determined by solid-phase microextraction-GC/MS. MiSeq sequencing data showed that bacterial VOCs could alter the composition of both soil bacterial and soil fungal communities and could decrease the alpha-diversity of the soil microbial community. Taxonomic analysis revealed that bacterial VOCs significantly increased the relative abundance of Proteobacteria, Bacteroidetes, and Firmicutes. Moreover, bacterial VOCs significantly increased the relative abundance of Ascomycota. The qPCR data showed that bacterial VOCs of strain NJN-6 decreased the soil fungal biomass and increased the soil bacterial biomass. Further evaluation of the effect of bacterial VOCs on functional genes revealed that VOCs could reduce the copies of nifH, nirS, and a gene encoding nonribosomal peptide synthase, while increasing the copy number of the ammonium-oxidizing bacteria gene. The effect on gene encoding polyketide synthase was insignificant. Results from this study indicated that bacterial VOCs could influence the soil microbial community as well as functional gene abundance.



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Measurements of ionic concentrations along with endocochlear potential in wild-type and claudin 14 knockout mice

To examine whether the changes in endolymphatic ion concentrations were involved in hair cells degeneration in claudin-14 knockout (KO) mice (Cldn14−/−), we measured the endocochlear potential (EP) along with concentrations of K+, Na+, H+, or Ca2+ ([K]e, [Na]e, pHe, [Ca]e) in Cldn14−/−, in which hair cells were selectively damaged, and compared with measurements in wild type mice (Wt).

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Measurements of ionic concentrations along with endocochlear potential in wild-type and claudin 14 knockout mice

To examine whether the changes in endolymphatic ion concentrations were involved in hair cells degeneration in claudin-14 knockout (KO) mice (Cldn14−/−), we measured the endocochlear potential (EP) along with concentrations of K+, Na+, H+, or Ca2+ ([K]e, [Na]e, pHe, [Ca]e) in Cldn14−/−, in which hair cells were selectively damaged, and compared with measurements in wild type mice (Wt).

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Neutralization of interferon-γ reverts clinical and laboratory features in a mouse model of macrophage activation syndrome

In a murine model of MAS, the IFNγ pathway is activated and has a pathogenic role, as neutralization of IFNγ reverts the disease. These results provide the rationale for the therapeutic targeting of IFNγ in MAS.

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Discovery of a novel B-cell lymphoma 6 (BCL6)–corepressor interaction inhibitor by utilizing structure-based drug design

Publication date: 1 September 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 17
Author(s): Takeshi Yasui, Takeshi Yamamoto, Nozomu Sakai, Kouhei Asano, Takafumi Takai, Yayoi Yoshitomi, Melinda Davis, Terufumi Takagi, Kotaro Sakamoto, Satoshi Sogabe, Yusuke Kamada, Weston Lane, Gyorgy Snell, Masashi Iwata, Masayuki Goto, Hiroshi Inooka, Jun-ichi Sakamoto, Yoshihisa Nakada, Yasuhiro Imaeda
B-cell lymphoma 6 (BCL6) is a transcriptional repressor that can form complexes with corepressors via protein–protein interactions (PPIs). The complexes of BCL6 and corepressors play an important role in the formation of germinal centers (GCs), and differentiation and proliferation of lymphocytes. Therefore, BCL6–corepressor interaction inhibitors would be drug candidates for managing autoimmune diseases and cancer. Starting from high-throughput screening hits 1a and 2a, we identified a novel BCL6–corepressor interaction inhibitor 8c (cell-free enzyme-linked immunosorbent assay [ELISA] IC50=0.10µM, cell-based mammalian two-hybrid [M2H] assay IC50=0.72µM) by utilizing structure-based drug design (SBDD) based on an X-ray crystal structure of 1a bound to BCL6. Compound 8c also showed a good pharmacokinetic profile, which was acceptable for both in vitro and in vivo studies.

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Recent synthetic and medicinal perspectives of tryptanthrin

Publication date: 1 September 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 17
Author(s): Ramandeep Kaur, Sundeep Kaur Manjal, Ravindra K. Rawal, Kapil Kumar
Tryptanthrin is a natural alkaloidal compound having basic indoloquinazoline moiety. It is obtained from various natural plant sources as well as different cell cultures including yeast etc. Trptanthrin is considered as biogenetic precursor for phaitanthrin A–C, pyrroloindoloquinazoline, (±)-cruciferane. Different synthetic approaches for the synthesis of tryptanthrin have been very well reported. It has broad spectrum of biological activities including anticancer activity, anti-inflammatory, antiprotozoal, antiallergic, antioxidant, and antimicrobial. In this review, our focus will be, on the various approaches for the synthesis of tryptanthrins and its derivatives along with the biological activities.

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Synthesis and evaluation of osimertinib derivatives as potent EGFR inhibitors

Publication date: 1 September 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 17
Author(s): Hongying Gao, Zimo Yang, Xinglin Yang, Yu Rao
Osimertinib has been identified as a promising therapeutic drug targeting for EGFR T790M mutant non-small cell lung cancer (NSCLC). A new series of N-oxidized and fluorinated osimertinib derivatives were designed and synthesized. The cellular anti-proliferative activity, kinase inhibitory activity and the activation of EGFR signaling pathways of 1–6 in vitro were determined against L858R/T790M and wild-type EGFR, the antitumor efficacy in NCI-H1975 xenografts in vivo were further studied. Compound 2, the newly synthesized N-oxide metabolite in N,N,N′-trimethylethylenediamine side chain of osimertinib, showed a comparable kinase selectivity in vitro and a slightly better antitumor efficacy in vivo to osimertinib, making it valuable and suitable for the potential lung cancer therapy.

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Isolation and lipolytic activity of eurycomanone and its epoxy derivative from Eurycoma longifolia

Publication date: 1 September 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 17
Author(s): Lucy Lahrita, Ryota Hirosawa, Eisuke Kato, Jun Kawabata
Eurycomanone (1) and 13β,21-epoxyeurycomanone (2) were isolated from Eurycoma longifolia for studies of lipolytic activity. Compound 1 enhanced lipolysis in adipocytes with an EC50 of 14.6μM, while its epoxy derivate, compound 2, had a stronger activity with an EC50 of 8.6μM. Based on molecular mechanistic study using several specific inhibitors to lipolytic signaling pathways, it was found that PKA inhibitor totally diminished the lipolytic activity of 1 and 2. Further immunoblotting analysis confirmed the activation of phosphorylated PKA by both 1 and 2. With the growing need to develop new anti-obesity agents, eurycomanone and its epoxy derivate can be used as promising lead compounds to target lipid catabolism.

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1,3-Oxazole-based selective picomolar inhibitors of cytosolic human carbonic anhydrase II alleviate ocular hypertension in rabbits: Potency is supported by X-ray crystallography of two leads

Publication date: 1 September 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 17
Author(s): Marta Ferraroni, Laura Lucarini, Emanuela Masini, Mikhail Korsakov, Andrea Scozzafava, Claudiu T. Supuran, Mikhail Krasavin
Two lead 1,3-oxazole-based carbonic anhydrase inhibitors (CAIs) earlier identified as selective, picomolar inhibitors of hCA II (a cytosolic target for treatment of glaucoma) have been investigated further. Firstly, they were found to be conveniently synthesized on multigram scale, which enables further development. These compounds were found to be comparable in efficacy to dorzolamide eye drops when applied in the eye drop form as well. Finally, the reasons for unusually high potency of these compounds became understood from their high-resolution X-ray crystallography structures. These data significantly expand our understanding of heterocycle-based primary sulfonamides, many of which have recently emerged from our labs - particularly, from the corneal permeability standpoint.

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9,19-Cycloartenol glycoside G3 from Cimicifuga simplex regulates immune responses by modulating Th17/Treg ratio

Publication date: 1 September 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 17
Author(s): Yang Su, Lun Wu, Guangrui Mu, Qiuhong Wang, Bingyou Yang, Genhong Cheng, Haixue Kuang
Cimicifuga simplex is a medicinal herb which has a wide range of biological activities. We isolated seven 9,19-cycloartenol glycosides from the roots of C. simplex, and among the glycosides, G3 exhibited the strongest inhibitory effect on immune responses, including suppressing the differentiation of CD4+ T cells and directly suppressing the cytokine-induced JAK/STAT signaling pathways. In the IL-23-induced mouse ear model of skin disease, G3 repressed disease development by inhibiting the expression of pro-inflammatory mediators in murine ear skin. Moreover, G3 affected the maturation of DCs in vitro, thereby inducing T cell differentiation, resulting in an increased Treg phenotype and decreased Th17 phenotype. This study provides new evidence that G3 might ameliorate chronic inflammatory skin diseases by suppressing pathogenic CD4+ T cell differentiation and the IL-17+RORγt+/IL-10+FoxP3+ ratio. These findings suggest that G3 might mediate the therapeutic effects observed in psoriasis patients following treatment with C. simplex.

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