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Πέμπτη 29 Μαρτίου 2018

Editorial Board



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Point of Care Ultrasound in Trauma

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Publication date: Available online 29 March 2018
Source:Seminars in Ultrasound, CT and MRI
Author(s): Timothy Gleeson, David Blehar
The use of point of care ultrasound (POCUS) in trauma is widespread. Focused Assessment with Sonography for Trauma (FAST) exam is a prototypical bedside exam used by the treating provider to quickly determine need for intervention and appropriate patient disposition. The role of bedside ultrasound in trauma, however, has expanded beyond the FAST exam. Advancements in diagnostics include contrast enhanced ultrasound (CEUS), thoracic, and musculoskeletal applications. Ultrasound is also an important tool for trauma providers for procedural guidance including vascular access and regional anesthesia. Its portability, affordability, and versatility have made ultrasound an invaluable tool in trauma management in resource-limited settings. In this review, we discuss these applications and the supporting evidence for POCUS in trauma.



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Impairment of learning and memory performances induced by BPA: Evidences from the literature of a MoA mediated through an ED

Publication date: Available online 29 March 2018
Source:Molecular and Cellular Endocrinology
Author(s): Sakina Mhaouty-Kodja, Luc P. Belzunces, Marie-Chantal Canivenc, Henri Schroeder, Cécile Chevrier, Elodie Pasquier
Many rodent studies and a few non-human primate data report impairments of spatial and non-spatial memory induced by exposure to bisphenol A (BPA), which are associated with neural modifications, particularly in processes involved in synaptic plasticity. BPA-induced alterations involve disruption of the estrogenic pathway as established by reversal of BPA-induced effects with estrogenic receptor antagonist or by interference of BPA with administered estradiol in ovariectomised animals. Sex differences in hormonal impregnation during critical periods of development and their influence on maturation of learning and memory processes may explain the sexual dimorphism observed in BPA-induced effects in some studies. Altogether, these data highly support the plausibility that alteration of learning and memory and synaptic plasticity by BPA is essentially mediated by disturbance of the estrogenic pathways. As memory function in humans involves similar signaling pathways, this mode of action of BPA has the potential to alter human cognitive abilities.



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A short synthesis of Dronedarone

Publication date: Available online 28 March 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Barbara Piotrkowska, Sven Nerdinger, Erwin Schreiner, Lovro Selič, Piotr P. Graczyk
A modification of the Nenitzescu reaction was used to obtain Dronedarone from quinonimine 15 and 1,3-diketone 18 (R=CH2CH2CH2NBu2) in a two-stage process in almost 55% overall yield. Our results represent significant improvement over other state-of-the-art methods as no extra steps for the decoration of the benzofuran core are required.

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BRADYKININ-POTENTIATING PEPTIDE-10C, AN ARGININOSUCCINATE SYNTHETASE ACTIVATOR, PROTECTS AGAINST H2O2-INDUCED OXIDATIVE STRESS IN SH-SY5Y NEUROBLASTOMA CELLS

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Publication date: Available online 29 March 2018
Source:Peptides
Author(s): Samyr Machado Querobino, César Augusto João Ribeiro, Carlos Alberto-Silva
Bradykinin-potentiating peptides (BPPs – 5a, 7a, 9a, 10c, 11e, and 12b) of Bothrops jararaca (Bj) were described as argininosuccinate synthase (AsS) activators, improving L-arginine availability. Agmatine and polyamines, which are L-arginine metabolism products, have neuroprotective properties. Here, we investigated the neuroprotective effects of low molecular mass fraction from Bj venom (LMMF) and two synthetic BPPs (BPP-10c, <ENWPHPQIPP; BPP-12b, <EWGRPPGPPIPP) in the SH-SY5Y cell line against H2O2-induced oxidative stress. The neuroprotective effects against H2O2-induced were analyzed by reactive oxygen species (ROS – DCFH) production; lipid peroxidation (TBARS); intracellular GSH; AsS, iNOS, and NF-kB expressions; nitrite levels (Griess); mitochondrial membrane potential (TMRM); and antioxidant activity (DPPH). Analysis of variance followed by Tukey's post hoc test were calculated for statistical comparisons. Pre-treatment with both BPPs significantly reduced cell death induced by H2O2, but BPP-10c showed higher protective capacity than BPP-12b. LMMF pretreatment was unable to prevent the reduction of cell viability caused by H2O2. The neuroprotective mechanism of BPP-10c against oxidative stress was investigated. BPP-10c reduced ROS generation and lipid peroxidation in relation to cells treated only with H2O2. BBP-10c increased AsS expression and was not neuroprotective in the presence of MDLA, a specific inhibitor of AsS. BPP-10c reduced iNOS expression and nitrate levels but decreased NF-kB expression. Furthermore, BPP-10c protected the mitochondrial membrane against oxidation. Overall, we demonstrated for the first time neuroprotective mechanisms of BPPs against oxidative stress, opening new perspectives to the study and application of these peptides for the treatment of neurodegenerative diseases.



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Treatment of Radiation and Cisplatin Induced Toxicities With Tempol

Conditions:   Mucositis;   Nephrotoxicity;   Ototoxicity
Interventions:   Drug: Tempol;   Drug: Placebo Solution
Sponsors:   Matrix Biomed, Inc.;   University of Maryland
Not yet recruiting

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Postoperative aRCH With Cisplatin Versus aRCH With Cisplatin and Pembrolizumab in Locally Advanced Head and Neck Squamous Cell Carcinoma

Condition:   HNSCC
Interventions:   Drug: Pembrolizumab 25 MG/1 ML Intravenous Solution [KEYTRUDA];   Other: adjuvant radiochemotherapy
Sponsor:   University of Leipzig
Not yet recruiting

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Proton Beam Therapy in the Treatment of Esophageal Cancer

Conditions:   Esophagus Cancer;   Esophageal Cancer;   Cancer of the Esophagus
Interventions:   Radiation: Proton beam therapy;   Other: Patient-Reported Outcome Measures
Sponsor:   Washington University School of Medicine
Not yet recruiting

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Evaluation of an Oral Care Programme for Head and Neck Cancer Patients

Condition:   Head and Neck Cancer
Intervention:   Procedure: Oral care programme
Sponsors:   Göteborg University;   Ryhov County Hospital;   FUTURUM, Academy of Health and Science;   Swedish Cancer Foundation
Recruiting

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The Inclined Position in Case of Respiratory Discomfort in the One Year Less Infant : Study on the Profits and the Risks in the Home

Conditions:   Obstruction, Airway;   Sudden; Death, Infant
Intervention:   Other: Questionnaires
Sponsor:   Hospices Civils de Lyon
Not yet recruiting

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External beam radiation therapy to hepatocellular carcinoma involving inferior vena cava and/or right atrium: A meta-analysis and systemic review

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Publication date: Available online 29 March 2018
Source:Radiotherapy and Oncology
Author(s): Chai Hong Rim, Chul Yong Kim, Dae Sik Yang, Won Sup Yoon
PurposeHepatocellular carcinoma (HCC) involving inferior vena cava (IVC) and/or right atrium (RA) is a very rare but serious disease. The objective of this meta-analysis was to assess efficacy and safety of external beam radiotherapy (EBRT) for HCC involving IVC and/or RA.Materials and methodsSystematic search of Pubmed, MEDLINE, EMBASE, and Cochrane library published was performed. Primary endpoints were 1-year overall survival (OS) rate and 2-year OS rates. Secondary endpoints were response rate, local control (LC) rate, and grade ≥3 toxicities. According to heterogeneity evaluated with Cochran Q test and I2 statistics, meta-analysis was performed using either random or fixed model.ResultsA total of 8 studies and 9 cohorts were included, encompassing 164 patients. Pooled 1- and 2-year OS rates were 53.6% (95% CI: 45.7–61.3%) and 36.9% (95% CI: 27.2–42.4%), respectively. Pooled response rate and LC rate were 59.2% (95% CI: 39.0–76.7%) and 83.8% (95% CI: 78.8–97.1%), respectively. Only one study reported 2 grade ≥3 toxicities, an esophageal rupture and a pulmonary embolism cases. The overall rate of possible grade ≥3 complications was 1.2% (2 of 164).ConclusionsEBRT is a feasible and safe option to palliate HCC with IVC and/or RA invasion.



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Influence of deformable image registration on 4D dose simulation for extracranial SBRT: A multi-registration framework study

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Publication date: Available online 29 March 2018
Source:Radiotherapy and Oncology
Author(s): Nik Mogadas, Thilo Sothmann, Tobias Knopp, Tobias Gauer, Cordula Petersen, René Werner
Background and purposeTo evaluate the influence of deformable image registration approaches on correspondence model-based 4D dose simulation in extracranial SBRT by means of open source deformable image registration (DIR) frameworks.Material and methodsEstablished DIR algorithms of six different open source DIR frameworks were considered and registration accuracy evaluated using freely available 4D image data. Furthermore, correspondence models (regression-based correlation of external breathing signal measurements and internal structure motion field) were built and model accuracy evaluated. Finally, the DIR algorithms were applied for motion field estimation in radiotherapy planning 4D CT data of five lung and five liver lesion patients, correspondence model formation, and model-based 4D dose simulation. Deviations between the original, statically planned and the 4D-simulated VMAT dose distributions were analyzed and correlated to DIR accuracy differences.ResultsRegistration errors varied among the DIR approaches, with lower DIR accuracy translating into lower correspondence modeling accuracy. Yet, for lung metastases, indices of 4D-simulated dose distributions widely agreed, irrespective of DIR accuracy differences. In contrast, liver metastases 4D dose simulation results strongly vary for the different DIR approaches.ConclusionsEspecially in treatment areas with low image contrast (e.g. the liver), DIR-based 4D dose simulation results strongly depend on the applied DIR algorithm, drawing resulting dose simulations and indices questionable.



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Radiotherapy quality assurance for the RTOG 0834/EORTC 26053-22054/NCIC CTG CEC.1/CATNON intergroup trial “concurrent and adjuvant temozolomide chemotherapy in newly diagnosed non-1p/19q deleted anaplastic glioma”: Individual case review analysis

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Publication date: Available online 29 March 2018
Source:Radiotherapy and Oncology
Author(s): André N. Abrunhosa-Branquinho, Raquel Bar-Deroma, Sandra Collette, Enrico Clementel, Yan Liu, Coen W. Hurkmans, Loïc Feuvret, Karen Van Beek, Martin van den Bent, Brigitta G. Baumert, Damien C. Weber
BackgroundThe EORTC phase III 26053-22054/ RTOG 0834/NCIC CTG CEC.1/CATNON intergroup trial was designed to evaluate the impact on concurrent and adjuvant temozolomide chemotherapy in newly diagnosed non-1p/19q deleted anaplastic gliomas. The primary endpoint was overall survival.We report the results of retrospective individual case reviews (ICRs) for the first patient randomized per institution to detect the compliance with the study protocol.Material and methodsSixty-nine institutions were required to submit the radiotherapy plan of their first randomized patient. Full digital datasets uploaded to the EORTC server were assessed by three independent and blinded reviewers through the EORTC radiotherapy quality assurance platform.ResultsSixty-two (90%) of sixty-nine ICRs were received and assessable. Of the 62 cases, 22 were evaluated as per protocol (35.5%), 11 as acceptable variation (17.7%) and 29 were classified as unacceptable variations (46.8%). Most common unacceptable variations were related to the PTV dose (n = 19, 31%) and delineation (n = 17, 27%) processes.ConclusionsThe ICR analysis showed a significant number of unacceptable variations with potential impact on tumor control and/or toxicity profile. Prospective ICRs are encouraged for future studies to prevent and correct protocol violations before start of treatment.



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Economic data for particle therapy: Dealing with different needs in a heterogeneous landscape

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Publication date: Available online 29 March 2018
Source:Radiotherapy and Oncology
Author(s): Yolande Lievens, Klaus Nagels
BackgroundIn the light of scarce resources to be allocated for cancer care and a steady stream of costly innovations in all modalities applied to treat cancer, particle therapy needs to demonstrate its cost-utility balance to allow its positioning in the context of competing modalities. In the continuous evolving particle therapy landscape, the timely availability of appropriate economic data is crucial.MethodsEconomic data collection and compilation for particle therapy needs to follow health economic standards. Costing related analyses particularly need attention as clinical outcome data follow international standards to provide comparability. Among others, perspective, time horizons and cost categories are critical.ResultsIn this report from the "Health Economics Work Package" of the European Particle Therapy Network, the approaches commonly applied in health economic assessments are described and tailored to the specific needs of particle therapy. Data collection for cost calculation, economic evaluation and budget impact analysis are discussed.ConclusionThe presented data are intended to serve as a guidance for economic data collection, bearing in mind that in each specific case, the heterogeneous requirements of national health systems will need to be considered and assessments adapted accordingly.



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Use of the Ion AmpliSeq Cancer Hotspot Panel in clinical molecular pathology laboratories for analysis of solid tumours: with emphasis on validation with relevant single molecular pathology tests and the Oncomine Focus Assay

Publication date: Available online 29 March 2018
Source:Pathology - Research and Practice
Author(s): Ahwon Lee, Sung-Hak Lee, Chan Kwon Jung, Gyungsin Park, Kyo Young Lee, Hyun Joo Choi, Ki Ouk Min, Tae Jung Kim, Eun Jung Lee, Youn Soo Lee
Targeted application of next-generation sequencing (NGS) technology allows detection of specific mutations that can provide treatment opportunities for cancer patients. We evaluated the applicability of the Ion AmpliSeq Cancer Hotspot Panel V2 (CHV2) using formalin-fixed, paraffin-embedded (FFPE) tissue of clinical specimens.Thirty-five FFPE tumour samples with known mutational status were collected from four different hospitals and sequenced with CHV2 using an Ion Chef System and Ion S5 XL system. Out of 35 cases, seven were sequenced with Oncomine focus Assay Panel for comparison. For the limit of detection test, we used an FFPE reference standard, a cell line that included an engineered 50% EGFR T790 M in an RKO cell line background. Coverage analysis results including number of mapped reads, on target percent, mean depth, and uniformity were not different according to hospitals. Sensitivity for mutation detection down to 3% was demonstrated. NGS results showed 100% concordance with the results from single molecular pathology tests Assay in 30 cases with 24 known positive mutations and 14 known negative mutations, and another NGS panel of the Oncomine focus in seven cases.The CHV2 NGS test for solid tumours using Ion chef system and S5 XL system in clinical molecular pathology laboratories for analysis of solid tumours could be routinely used and could replace some single molecular pathology tests after a stringent and thorough validation process.



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Development of a plug-type IMS-MS instrument and its applications in resolving problems existing in in-situ detection of illicit drugs and explosives by IMS

Publication date: 1 July 2018
Source:Talanta, Volume 184
Author(s): Zhenxia Du, Tangqiang Sun, Jianan Zhao, Di Wang, Zhongxia Zhang, Wenlian Yu
Ion mobility spectrometry (IMS) which acts as a rapid analysis technique is widely used in the field detection of illicit drugs and explosives. Due to limited separation abilities of the pint-sized IMS challenges and problems still exist regarding high false positive and false negative responses due to the interference of the matrix. In addition, the gas-phase ion chemistry and special phenomena in the IMS spectra, such one substance showing two peaks, were not identified unambiguously. In order to explain or resolve these questions, in this paper, an ion mobility spectrometry was coupled to a mass spectrometry (IMS-MS). A commercial IMS is embedded in a custom-built ion chamber shell was attached to the mass spectrometer. The faraday plate of IMS was fabricated with a hole for the ions to passing through to the mass spectrometer. The ion transmission efficiency of IMS-MS was optimized by optimizing the various parameters, especially the distance between the faraday plate and the cone of mass spectrum. This design keeps the integrity of the two original instruments and the mass spectrometry still works with multimode ionization source (i.e., IMS-MS, ESI-MS, APCI-MS modes). The illicit drugs and explosive samples were analyzed by the IMS-MS with 63Ni source. The results showed that the IMS-MS is of high sensitivity. The ionization mechanism of the illicit drug and explosive samples with 63Ni source were systematically studied. In addition, the interferent which interfered the detection of cocaine was identified as dibutyl phthalate (DBP) by this platform. The reason why the acetone solution of amphetamine showed two peaks was explained.

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Reliable determination of new lipid peroxidation compounds as potential early Alzheimer Disease biomarkers

Publication date: 1 July 2018
Source:Talanta, Volume 184
Author(s): Ana García-Blanco, Carmen Peña-Bautista, Camille Oger, Claire Vigor, Jean-Marie Galano, Thierry Durand, Nuria Martín-Ibáñez, Miguel Baquero, Máximo Vento, Consuelo Cháfer-Pericás
Lipid peroxidation plays an important role in Alzheimer Disease, so corresponding metabolites found in urine samples could be potential biomarkers. The aim of this work is to develop a reliable ultra-performance liquid chromatography-tandem mass spectrometry analytical method to determine a new set of lipid peroxidation compounds in urine samples.Excellent sensitivity was achieved with limits of detection between 0.08 and 17 nmol L−1, which renders this method suitable to monitor analytes concentrations in real samples. The method's precision was satisfactory with coefficients of variation around 5–17% (intra-day) and 8–19% (inter-day). The accuracy of the method was assessed by analysis of spiked urine samples obtaining recoveries between 70% and 120% for most of the analytes. The utility of the described method was tested by analyzing urine samples from patients early diagnosed with mild cognitive impairment or mild dementia Alzheimer Disease following the clinical standard criteria. As preliminary results, some analytes (17(RS)−10-epi-SC-Δ15−11-dihomo-IsoF, PGE2) and total parameters (Neuroprostanes, Isoprostanes, Isofurans) show differences between the control and the clinical groups. So, these analytes could be potential early Alzheimer Disease biomarkers assessing the patients' pro-oxidant condition.

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Evaluation of portable near-infrared spectroscopy for organic milk authentication

Publication date: 1 July 2018
Source:Talanta, Volume 184
Author(s): Ningjing Liu, Hector Aya Parra, Annemieke Pustjens, Kasper Hettinga, Philippe Mongondry, Saskia M. van Ruth
Organic products are vulnerable to fraud due to their premium price. Analytical methodology helps to manage the risk of fraud and due to the miniaturization of equipment, tests may nowadays even be rapidly applied on-site. The current study aimed to evaluate portable near infrared spectroscopy (NIRS) in combination with chemometrics to distinguish organic milk from other types of milk, and compare its performance with benchtop NIRS and fatty acid profiling by gas chromatography. The sample set included 37 organic retail milks and 50 non-organic retail milks (of which 36 conventional and 14 green 'pasture' milks). Partial least squares discriminant analysis was performed to build classification models and kernel density estimation (KDE) functions were calculated to generate non-parametric distributions for samples' class probabilities. These distributions showed that portable NIRS was successful to distinguish organic milks from conventional milks, and so were benchtop NIRS and fatty acid profiling procedures. However, it was less successful when 'pasture' milks were considered too, since their patterns occasionally resembled those of the organic milk group. Fatty acid profiling was capable of distinguishing organic milks from both non-organic milks though, including the 'pasture' milks. This comparative study revealed that the classification performance of the portable NIRS for this application was similar to that of the benchtop NIRS.

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A novel surface-enhanced Raman scattering (SERS) detection for natural gas exploration using methane-oxidizing bacteria

Publication date: 1 July 2018
Source:Talanta, Volume 184
Author(s): Weiwei Liang, Qiao Chen, Fang Peng, Aiguo Shen, Jiming Hu
Methane-oxidizing bacteria (MOB), a unique group of Gram-negative bacteria utilizing methane as a sole source of carbon and energy, have been proved to be a biological indicator for gas prospecting. Field and cultivation-free detection of MOB is important but still challenging in current microbial prospecting of oil and gas (MPOG) system. Herein, SERS was used for the first time to our knowledge to investigate two species of methanotrophs and four closely relevant bacteria that universally coexisted in the upper soil of natural gas. A special but very simple approach was utilized to make silver nanoparticles (Ag NPs) sufficiently contact with every single bacterial cell, and highly strong and distinct Raman signals free from any native fluorescence have been obtained, and successfully utilized for distinguishing MOB from other species. A more convincing multi-Raman criterion based on single Raman bands, and further the entire Raman spectrum in combination with statistical analysis (e.g., principal component analysis (PCA)), which were found capable of classifying MOB related bacterial cells in soil with an accuracy of 100%. This study therefore demonstrated sensitive and rapid SERS measurement technique accompanied by complete Raman database of various gas reservoirs related bacteria could aid field exploration of natural gas reservoir.

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Solid phase microextraction method using a novel polystyrene oleic acid imidazole polymer in micropipette tip of syringe system for speciation and determination of antimony in environmental and food samples

Publication date: 1 July 2018
Source:Talanta, Volume 184
Author(s): Abdul Haleem Panhwar, Mustafa Tuzen, Baki Hazer, Tasneem Gul Kazi
A simple, rapid and sensitive solid phase microextraction method was used for the speciation of inorganic antimony (Sb) by using a novel synthesized polymeric material in micropipette tip of syringe system. In present methodology, the specie of Sb (III) made hydrophobic complex with diethyl dithiocarbamate (DDTC) at pH 5.5 and subsequently adsorbed on polystyrene oleic acid imidazole polymer (POIP), whereas Sb(V) did not made complex and adsorbed on the polymer, remained in aqueous solutions. The strategy of multivariate was carried out to screen out the different variables and assessed the optimum values of their experimental values for the extraction efficiency of analyte. Then the analyte was sorbed on the polymer in micropipette tip of syringe system was quantitatively eluted by different types of acids at different levels for 2–6 aspirating/dispensing cycles. The extracted Sb(III) ions with modifiers were directed into the graphite furnace atomic absorption spectrometry for analysis. The limit of detection (LOD), limit of quantification (LOQ) and preconcentration factor (PF) for Sb(III) was found to be 6 ng L−1, 20 ng L−1 and 100. The RSD value was found to be 4.2%. The standard addition method and certified reference materials were checked for accuracy and validity of method. The developed method was effectively applied for the determination of total and inorganic species of Sb(III) and Sb(V) in different types of water samples, whereas only total Sb was determined in acid digested soil, Tuna fish, rice, spinach, black tea, mixed fruit juice and ice tea samples.

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A voltammetric test for the rapid discrimination of β-lactamase-producing Enterobacteriaceae in blood cultures

Publication date: 1 July 2018
Source:Talanta, Volume 184
Author(s): Laetitia Betelli, Catherine Neuwirth, Sébastien Solanas, Benoît Chantemesse, Fabienne Vienney, Alain Hartmann, Murielle Rochelet
The accurate identification of β-lactamases produced by Enterobacteriaceae is a major challenge in clinical laboratories in order to optimize antimicrobial treatment and patient care. We describe here a rapid voltammetric-based method to detect and to discriminate β-lactamase activity in Enterobacteriaceae i.e., penicillinase, cephalosporinase (inducible or overproduced), extended-spectrum beta-lactamase and carbapenemase producers. After a 2-h growth step of the sample under three separate conditions: 1) LB (Luria-Bertani) medium, 2) LB supplemented with 4 μg/mL cefotaxime and 3) LB supplemented with 4 μg/mL cefotaxime and 100 μg/mL potassium clavulanate, the β-lactamase activity was measured by incubating a 0.5 mM nitrocefin solution for 15 min followed by the voltammetric detection of the hydrolyzed nitrocefin with disposable carbon screen-printed sensors. The development and the calibration of the method were carried out by analyzing pure cultures of fifty-seven strains with well characterized β-lactam-resistance phenotypes. Thanks to the combination of the three currents (i1, i2, i3) recorded for each tested bacteria, the proposed procedure allowed to distinguish the different classes of β-lactamase producers. In the second part of the study, the method was applied to the analysis of one hundred and fifteen samples Enterobacteriaceae-positive blood culture samples of bacteraemic patients. Overall data showed that the voltammetric method offered a sensitivity of 100% and a specificity of 80%. Interestingly, all of sixteen samples infected by a third-generation cephalosporins-resistant bacteria (i.e. ESBL and overproduced cephalosporinase producers) were detected. This study clearly demonstrated that the voltammetric assay is an efficient alternative technique for the rapid discrimination of β-lactamases-producing Enterobacteriaceae in blood culture. In contrast to the approved routine assays, the electrochemical test did not require isolated colonies to be performed and was thus carried out in less than 3 h which could allow early administration of an appropriate antibiotic therapy.

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Potential improvements aimed at high precision δ13C isotopic ratio determinations in CO2 mixtures using optical absorption spectrometry

Publication date: 1 July 2018
Source:Talanta, Volume 184
Author(s): Serguei Koulikov, Sergey Assonov, Ales Fajgelj, Pieter Tans
The manuscript explores some advantages and limitations of laser based optical spectroscopy, aimed at achieving robust, high-reproducibility 13C16O2 and 12C16O2 ratio determinations on the VPDB-CO2 δ13C scale by measuring the absorbance of line pairs of 13C16O2 and 12C16O2. In particular, the sensitivities of spectroscopic lines to both pressure (P) and temperature (T) are discussed. Based on the considerations and estimations presented, a level of reproducibility of the 13C16O2/12C16O2 ratio determinations may be achieved of about 10−6. Thus one may establish an optical spectroscopic measurement technique for robust, high-precision 13C16O2 and 12C16O2 ratio measurements aimed at very low uncertainty. (Notably, creating such an optical instrument and developing technical solutions is beyond the scope of this paper.) The total combined uncertainty will also include the uncertainty component(s) related to the accuracy of calibration on the VPDB-CO2 δ13C scale. Addressing high-accuracy calibrations is presently not straightforward - absolute numerical values of 13C/12C for the VPDB-CO2 scale are not well known. Traditional stable isotope mass-spectrometry uses calibrations vs CO2 evolved from the primary carbonate reference materials; which can hardly be used for calibrating commercial optical stable isotope analysers. In contrast to mass-spectrometry, the major advantage of the laser-based spectrometric technique detailed in this paper is its high robustness. Therefore one can introduce a new spectrometric δ13C characterisation method which, being once well-calibrated on the VPDB-CO2 scale, may not require any further (re-)calibrations. This can be used for characterisation of δ13C in CO2–in-air mixtures with high precision and also with high accuracy. If this technique can be realised with the estimated long-term reproducibility (order of 10−6), it could potentially serve as a more convenient Optical Transfer Standard (OTS), characterising large amounts of CO2 gas mixtures on the VPDB-CO2 δ13C scale without having to compare to carbonate-evolved CO2. Furthermore, if the OTS method proves to be successful, it might be considered for re-defining the VPDB-CO2 δ13C-scale as the ratio of selected CO2 spectroscopic absorbance lines measured at pre-defined T & P conditions.The approach can also be expanded to δ18O characterisation (using 16O12C18O and 16O12C16O absorbance lines) of CO2 gas mixtures and potentially to other isotope ratios of other gases.

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Cyanine-based NIR fluorescent probe for monitoring H2S and imaging in living cells and in vivo

Publication date: 1 July 2018
Source:Talanta, Volume 184
Author(s): Jiacheng Xiong, Lili Xia, Qili Huang, Jinxin Huang, Yueqing Gu, Peng Wang
As a critical gaseous signaling molecule, H2S is involved in various biological processes. To deeper study the physiological and pathological roles of H2S, convenient and efficient detection techniques for endogenous H2S in vivo are still in urgent demand. Herein, we reported a new turn-on Near-infrared (NIR) fluorescence probe NIR-H2S based on thiolysis reactions for detection of H2S. The probe possessed many excellent properties including high sensitivity and selectivity, good cell-membrane permeability, and low cytotoxicity. In vitro, NIR-H2S showed a 58-fold fluorescence enhancement when reacted with H2S in a buffer and displayed a good linear relationship (r = 0.9925) in a rather wide concentration range of H2S (0–500 μM). Furthermore, NIR-H2S was successfully employed in monitoring endogenous H2S induced by D-Cys in living cancer cells and mice. These results indicated that NIR-H2S had great potentiality in detecting cellular H2S in living animals and being applied to cancer diagnosis.

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Silver nanoparticles-embedded nanopaper as a colorimetric chiral sensing platform

Publication date: 1 July 2018
Source:Talanta, Volume 184
Author(s): Erhan Zor
Paper-based sensors open new avenue to produce simple, rapid, inexpensive and single-use analytical devices for a wide application fields involving medical diagnosis, food analysis and environmental monitoring. In this study, a new optical sensing platform for enantioselective recognition of chiral analytes was introduced by using in-situ synthesized silver nanoparticles-embedded transparent nanopaper. To this aim, nanopaper was obtained by environment-friendly approach using bacterial cellulose made of nanofibers and silver nanoparticles were embedded within nanopaper by an in-situ generation method. The chiral recognition capability of AgNPs was operated in both solution phase and nanopaper for the tested enantiomers. AgNPs showed a discriminative sensing response toward D-cysteine with a LOD value of 4.88 µM. The principle of optical sensing is the selective interaction of the inherently chiral AgNPs with enantiomers causing to aggregation of AgNPs to display a significant colour change from yellow to purple-brown in both aqueous phase and nanopaper. As for practical use, the obtained plasmonic nanopaper was punched into circular pieces and put on wax-printed PET film to produce disposable two-dimensional cuvette which could be inserted in an ordinary spectrophotometer. The enantiomeric percentage of D-cysteine was successfully determined by the fabricated nanopaper-based cuvettes.

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Cervical myelopathy after high-voltage electrical burn of the head: Report of an unusual case

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Shri Ram Sharma, Masaraf Hussain, Hibo Hibong

Annals of Indian Academy of Neurology 2018 21(1):76-79

High-voltage electrical injuries are uncommonly reported and may predispose to both immediate and delayed neurologic complications. We present a case of 27-year-old male who experienced a high-voltage electrical burn of the head resulting in quadriparesis. High-voltage electrocution injuries are a serious problem with potential for immediate, delayed, and long-term neurologic sequelae. The existing literature regarding effective treatment of neurologic complications is limited. Multidisciplinary management and long-term follow up are required.

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Recent advances in antisense oligonucleotide therapy in genetic neuromuscular diseases

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Ashok Verma

Annals of Indian Academy of Neurology 2018 21(1):3-8

Genetic neuromuscular diseases are caused by defective expression of nuclear or mitochondrial genes. Mutant genes may reduce expression of wild-type proteins, and strategies to activate expression of the wild-type proteins might provide therapeutic benefits. Also, a toxic mutant protein may cause cell death, and strategies that reduce mutant gene expression may provide therapeutic benefit. Synthetic antisense oligonucleotide (ASO) can recognize cellular RNA and control gene expression. In recent years, advances in ASO chemistry, creation of designer ASO molecules to enhance their safety and target delivery, and scientific controlled clinical trials to ascertain their therapeutic safety and efficacy have led to an era of plausible application of ASO technology to treat currently incurable neuromuscular diseases. Over the past 1 year, for the first time, the United States Food and Drug Administration has approved two ASO therapies in genetic neuromuscular diseases. This overview summarizes the recent advances in ASO technology, evolution and use of synthetic ASOs as a therapeutic platform, and the mechanism of ASO action by exon-skipping in Duchenne muscular dystrophy and exon-inclusion in spinal muscular atrophy, with comments on their advantages and limitations.

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Chronic lymphocytic leukemia involvement of central nervous system: Clinical diversity, diagnostic algorithm and therapeutic challenges

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Biljana Mihaljevic, Mihailo Smiljanic, Darko Antic, Nada Kraguljac Kurtovic, Milena Todorovic Balint

Annals of Indian Academy of Neurology 2018 21(1):85-87



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Preventing “neurophobia”: Remodeling neurology education for 21st-century medical students through effective pedagogical strategies for “neurophilia”

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Bhaskara P Shelley, Thomas V Chacko, Balakrishnan R Nair

Annals of Indian Academy of Neurology 2018 21(1):9-18

Neurology has a reputation, particularly as a complex "head-to-toe" discipline for undergraduate medical students. Neurophobia syndrome, a global phenomenon, fundamentally stems from pedagogical deficiencies during the undergraduate curriculum, the lack of vertical integration between basic neurosciences and clinical bedside neurology, the lack of clinical reasoning exercises, cognitive heuristics, and clinical problem-solving, errors in diagnostic competence, and hyposkilia. This ultimately results in poor clinical competence and proficiency in clinical neurology and causes attrition in nurturing a passion for learning the neurology discipline. This article explores plausible factors that contribute to the genesis of neurophobia and multifaceted strategies to nurture interest in neurosciences and provide possible solutions to demystify neurology education, especially the need for evidence-based educational interventions. Remodeling neurology education through effective pedagogical strategies and remedial measures, and using the Miller's pyramid, would provide a framework for assessing clinical competence in clinical bedside neurology. Technology-enhanced education and digital classrooms would undoubtedly stamp out neurophobia in medical students of the 21st century. It will not frighten off another generation of nonneurologist physicians to empower them to hone expertise in order to tackle the increasing burden of neurological disorders in India. Furthermore, promoting neurophilia would facilitate the next generation of medical students in pursuing career options in neurology which would be quintessential not only in closing India's looming neurologist workforce gap but also in fostering interest in research imperatives in the next generation of medical students.

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A viral polymyositis masquerade: Life-threatening case of juvenile dermatomyositis complicated by systemic capillary leak syndrome

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Bhaskara P Shelley, Shrijeet Chakraborti

Annals of Indian Academy of Neurology 2018 21(1):70-74

This is a case report of an 8-year-old boy who developed an atypical, rare subphenotype of autoimmune inflammatory acute juvenile dermatomyositis (JDM), initially masquerading as viral polymyositis (PM)-like presentation, that was complicated by a hitherto unreported fulminant, life-threatening pediatric systemic capillary leak syndrome (SCLS). We highlight the close differential between viral PM and JDM, the baffling clinical syndromic constellation of hypotension with hemoconcentration – a "shock"-like syndrome, hypoalbuminemia without albuminuria, and generalized edema with the atypical JDM presentation, and stress crucial need to implement early aggressive, multipronged immunomodulatory treatment along with intensive fluid resuscitation which saved the life, this patient from a stormy, and turbulent 4-week clinical illness. This is the first published case description in the current literature of the association of an aggressive subphenotype of JDM and life-threatening pediatric SCLS. This report opens the Pandora's Box to explore the genetic and pathomechanisms of both disorders.

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Edgar adrian and patrick merton: Names blurred with the passage of time

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Kalyan B Bhattacharyya

Annals of Indian Academy of Neurology 2018 21(1):19-23

Edgar Douglas Adrian and Patrick Anthony Merton are two supreme neurophysiologists from England in the last century whose names are almost forgotten these days. Adrian's work on all-or-none phenomenon in nerve and muscle excitability ushered in a new era and Merton's servo theory of muscular movement and muscle fatigue added a new dimension to the understanding of stretch reflex and deep tendon reflexes. Both of them trained and worked at Trinity College, Cambridge and both were elected as Fellow of the Royal Society and Adrian in addition, was awarded the Nobel Prize in 1932 along with Charles Scott Sherrington.

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Cysts in White Matter: A Novel Neuroimaging Finding in Infantile GM1 Gangliosidosis

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Mahesh Kamate

Annals of Indian Academy of Neurology 2018 21(1):82-83



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Evaluation of various movement disorders in patients of genetically proven spinocerebellar ataxia: A study from a Tertiary Care Center in Northern India

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Divya M Radhakrishnan, Vinay Goyal, Achal Kumar Srivastava, Garima Shukla, Madhuri Behari

Annals of Indian Academy of Neurology 2018 21(1):24-28

Background: Movement disorders are one of the prominent nonataxic symptoms in patients of spinocerebellar ataxia (SCA). The type of movement disorder may provide clinical clue to the type of SCA. Objective: The objective of this study is to evaluate various movement disorders in patients of genetically proven SCAs and to establish a probable clinico-genetic correlation. Methods: Ninety-Five patients of genetically proven SCAs were assessed for the presence of various movement disorders. Results: Patients with SCA (75.8% males) with at least one movement disorder contributed 43.16%. Age for onset of movement disorder was 43.39 ± 13.43 years. SCA-12 (38.95%) was the most common subtype. Among the patients with at least one movement disorder, action tremor of hands contributed majority (90.2%). Dystonia and parkinsonism were present in 17.07% and 12.2% of patients (with movement disorder), respectively. Action tremor of hands was present in 34 patients with SCA-12 (91.89%), and 20 patients (54.05%) had onset of hand tremor preceding the onset of ataxia. Majority of patients with SCA-12 (81%) were of the same ethnic origin belonging to Agrawal community. Patients with movement disorder had a later onset (45 ± 13.88 years) of ataxic symptoms compared to those without a movement disorder (32.8 ± 11.92) (P = <0.0005). There was no significant association between severity of ataxia and presence of movement disorder. Conclusion: Movement disorders are present in about 43% of patients with SCA and can precede or succeed the onset of ataxia. Tremor onset SCA predicted SCA-12, especially in Agrawal community.

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Unilateral limb thinning –Thinking out of the box

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Chandramouleeswaran Venkatraman, Shubha Subramanian, Daniel Sweetson Abraham, Kannan Vellaichamy

Annals of Indian Academy of Neurology 2018 21(1):74-76

We report an unusual presentation in a 9-year-old girl with unilateral circumferential thinning of the entire right upper limb without any other neurological deficit, with normal nerve conduction and electromyography initially thought of as a neurodegenerative disorder based on clinical presentation. Magnetic resonance imaging of the upper limb showed partial lipoatrophy with normal glucose metabolism and lipid profile and negativity for HIV and autoimmune disease (panniculitis) with no family history of similar disorder. Remember to think out of box before labeling neurodegenerative disease.

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The Spectrum of Autonomic Dysfunction in Myasthenic Crisis

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Rohit Ninan Benjamin, Sanjith Aaron, Ajith Sivadasan, Suresh Devasahayam, Amalan Sebastin, Mathew Alexander

Annals of Indian Academy of Neurology 2018 21(1):42-48

Background: Autoimmune autonomic dysfunction is described in Myasthenia Gravis. In myasthenic crisis, the spectrum of autonomic dysfunction is hitherto uncharacterized. Objective: The objective of this study is to describe the spectrum of autonomic dysfunction in myasthenic crises using the composite autonomic symptom scale 31 (COMPASS 31) autonomic symptom questionnaire and power spectral analysis of heart rate variability (HRV), which is a simple way of estimating general autonomic dysfunction. Methods: Adult patients with myasthenic crisis from January 1, 2014 to March 15, 2015, were prospectively included in this study. The COMPASS 31 questionnaire for symptoms of autonomic dysfunction and power spectral analysis of HRV were assessed. These were compared with the patient's demographic and clinical parameters and with previous literature. IRB approval was obtained. Results: Sixteen patients were included (M:F 3:1). 15/16 patents (93%) had autonomic dysfunction on COMPASS 31 questionnaire. The domains of involvement were gastrointestinal (80%), orthostatic (67.7%), pupillomotor (67.7%); sudomotor (33.3%), and vasomotor (13.3%). Parasympathetic dysfunction predominance was suggested by the symptom profile. HRV analysis showed a low frequency (LF) spectral shift suggesting slowed parasympathetic responsiveness (LF normalized unit (nu): high frequency [HF] nu mean 8.35, standard deviation ± 5.4, 95% confidence interval 2.2–12.5), which significantly exceeded the mean LF nu: HF nu ratios of the majority of previously reported noncrises myasthenic populations. Conclusions: Myasthenic crisis has autonomic dysfunction involving multiple organ systems. Increased latency of parasympathetic reflexes is suggested. A comprehensive management protocol addressing different autonomic domains is required for holistic patient care.

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Uncommon anatomical variant – Types artery of percheron infarcts: Clinical-radiological correlations

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T Harisuthan, Anirudh Vilas Kulkarni, Gigy Varkey Kuruttukulam

Annals of Indian Academy of Neurology 2018 21(1):80-81



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Pseudo-subarachnoid hemorrhage sign

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Ramnath Santosh Ramanathan

Annals of Indian Academy of Neurology 2018 21(1):83-84



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Phrenic nerve conduction study in the early stage of guillain–barre syndrome as a predictor of respiratory failure

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Barun Kumar Sen, Alak Pandit

Annals of Indian Academy of Neurology 2018 21(1):57-61

Background: Guillain-Barré syndrome (GBS) has unpredictable clinical course with severe complication of respiratory failure. Objective: To identify clinical profiles and electrophysiological study particularly non-invasive Phrenic nerve conduction study in patients of early GBS to predict respiratory failure. Methods: 64 adult (age≥18yrs) patients of early GBS (onset ≤ 14 days) during the study period from January 2014 to October 2015 were evaluated by clinical profiles of age, gender, antecedent infection, time to peak disability, single breath counts, cranial nerve involvement, autonomic dysfunction and non-invasive Phrenic nerve conduction study. Patients with predisposition factors of polyneuropathy like diabetes mellitus, hypothyroidism, vitamin deficiency, renal failure were excluded. Results: Among 64 patients abnormal phrenic nerve conduction study was seen in 65.62% cases (42/64) and 45.23% (19/42) of them developed respiratory failure. Phrenic nerve sum latency, amplitude, duration and area were abnormal in those who developed respiratory failure and they had sum of phrenic nerve latency >28 msec, sum of CMAP amplitude <300 μV, sum of CMAP duration >50 msec and sum of area < 4 mVmS. None with normal phrenic nerve study developed respiratory failure. It was found that age, gender, preceding infection, autonomic involvement and types of GB syndrome had no influence on development of respiratory failure (p>0.05). Rapid disease progression to peak disability, more severe disease, shorter single breath counts and cranial nerve involvement were seen more often in patients with respiratory failure. Conclusion: Abnormal Phrenic nerve conduction study in the early Guillain-Barré syndrome might be of great value independently in predicting impending respiratory failure.

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An Exodus of Bedside Nurses.

Author: W., Cynthia via Facebook
Page: 10


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An Exodus of Bedside Nurses.

Author: F., Stephanie via ajnoffthecharts.com
Page: 10


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An Exodus of Bedside Nurses.

Author: R., Susan via Facebook
Page: 10


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Short-Term Medical Missions: Toward an Ethical Approach.

Author: Matlick, Garrett Logan BSN, RN
Page: 11


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HHS Division to Enforce 'Conscience and Religious Freedom'.

Author: Sofer, Dalia
Page: 12


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Mandatory Parental Counseling Reduces Vaccine Exemptions.

Author: Zolot, Joan PA
Page: 13


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NewsCAP: Updated guidelines for treating nausea and vomiting during pregnancy.

Author:
Page: 13


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Among Other Industrialized Countries, the United States Has Highest Childhood Mortality Rate.

Author: Stockwell, Serena
Page: 14


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NewsCAP: DEA gives NPs the authority to treat opioid use disorder.

Author:
Page: 14


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Duration of Postoperative Opioid Use Predicts Misuse More Than Dosage.

Author: Mechcatie, Elizabeth MA, BSN
Page: 15


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NewsCAP: On the horizon: a blood test for identifying solid organ tumors and their origin.

Author:
Page: 15


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NewsCAP: The best age for one-time HIV screening is 25 years.

Author:
Page: 15


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Hysterectomy Associated with Long-Term Health Risks.

Author: Potera, Carol
Page: 16


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The Value of Simulation in Nursing Education.

Author: Sofer, Dalia
Page: 17-18


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AJN On the Cover.

Author: Szulecki, Diane Editor
Page: 19


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Particulate matter on two Prunus spp. decreases survival and performance of the folivorous beetle Gonioctena quinquepunctata

Abstract

Woody plants growing along streets and construction sites play an important role in removing harmful particulate matter (PM). Researchers rarely consider the impact of different types and size fractions of PM deposited on the leaves on insect folivores. We determined differences in the accumulation of cement and roadside PM on the leaves of two Prunus species (P. padus and P. serotina) with different leaf surface structures. We also determined the effect of PM on the beetle Gonioctena quinquepunctata, the main pest of these plants. Saplings were artificially dusted in greenhouses and leaves were utilised for larval and adult insect stages feeding in laboratory conditions. Road PM accumulated in greater amounts than did cement PM, regardless of plant species. For both PM sources, P. padus accumulated twofold more than did P. serotina. Insect survival was negatively affected by PM pollution; however, neither Prunus species nor PM source variant significantly affected masses of larvae and pupae, duration of larval and pupal development or relative growth rates. The experiment showed strong negative influences of PM were noted only for adult insects, due to the grazing period being longer than that in larvae. The mass of adult insects and the efficiency of conversion of ingested food (ECI) were lower for insects exposed to PM than those for control insects. Insects compensated for lower ECI by eating a greater total amount of food (TFE). Adult insects gained significantly higher mass when fed with P. serotina than with P. padus. The effect of PM on analysed plant metabolites was insignificant. Only Prunus sp. and date of collection affected the level of condensed tannins and total phenols. Our results indicate that, when investigating the effect of the host plant on folivore performance, the accumulation of PM, as well as its type and quantity, should be taken into account.



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Cardiotoxic effects of chemotherapy: A review of both cytotoxic and molecular targeted oncology therapies and their effect on the cardiovascular system

Publication date: Available online 29 March 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Hani M Babiker, Ali McBride, Michael Newton, Leigh M. Boehmer, Adrienne Goeller Drucker, Mollie Gowan, Manouchkathe Cassagnol, Todd D. Camenisch, Faiz Anwer, James M. Hollands
Cardiotoxic effects of chemotherapy and targeted drugs are ubiquitous and challenging in the field of oncology therapeutics. The broad spectrum of toxicities ranging from ischemic, hypertensive, cardiomyopathic, and arrhythmic complications can present as a significant challenge for clinicians treating cancer patients. If early diagnosis and intervention of cardiotoxic complications is missed, this can lead to delay or abrogation of planned treatment, which can potentially culminate to significant morbidity due to not only the cardiotoxic complications but also the progression of cancer. Hence, full knowledge of cardiovascular complications of chemotherapeutic agents, essential diagnostics tests to order, and appropriate management is paramount to oncologist, oncology pharmacists, and scientific clinical investigators. The aforementioned is particularly true in the current oncology era of plenteous early clinical trials studying several pathway/molecular-targeting agents with an increased cardiotoxic potential and the rapid expedited approval of those drugs by the FDA. Herein, we present a review discussing cardiotoxic effects of drugs and guidelines for management of the toxicities to assist the medical field in general managing patients with cancer.



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A Low-Cost Solution for Quantification of Movement during DBS Surgery

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Publication date: Available online 29 March 2018
Source:Journal of Neuroscience Methods
Author(s): Erin L. Schaeffer, Daniel Y. Liu, Julie Guerin, Minkyu Ahn, Shane Lee, Wael F. Asaad
BackgroundDuring the deep brain stimulation (DBS) electrode implantation operation with microelectrode recordings (MER) in awake patients, somatotopic testing and test stimulation are performed to improve electrode placement and provide the most beneficial symptom reduction possible, while minimizing side effects. As this procedure is commonly used to alleviate abnormal movements associated with Parkinson's disease (PD) and Essential Tremor (ET), intraoperative assessment of a patient's movements is critical to optimizing surgical benefit. However, despite its importance, movement assessment is typically subjective and qualitative.New MethodHere, we present a detailed description of a low-cost, open-source system as a solution.ResultsThe described system measures movements intraoperatively and in synchrony with neurophysiological recordings for both online visualization and offline analysis.Comparison with Existing Method(s)Few movement quantification systems are designed to interface with intraoperative neurophysiological recordings; the widespread application of such systems may be limited by their cost and proprietary, closed-source nature. The system presented provides a low-cost, open-source alternative.ConclusionsThe system outlined in this work may improve the DBS procedure by adding valuable objectivity in movement quantification.



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EpiTools, A software suite for presurgical brain mapping in epilepsy: Intracerebral EEG.

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Publication date: Available online 29 March 2018
Source:Journal of Neuroscience Methods
Author(s): S. Medina Villalon, R. Paz, N. Roehri, S. Lagarde, F. Pizzo, B. Colombet, F. Bartolomei, R. Carron, C.-G. Bénar
BackgroundIn pharmacoresistant epilepsy, exploration with depth electrodes can be needed to precisely define the epileptogenic zone. Accurate location of these electrodes is thus essential for the interpretation of Stereotaxic EEG (SEEG) signals. As SEEG analysis increasingly relies on signal processing, it is crucial to make a link between these results and patient's anatomy.Our aims were thus to develop a suite of software tools, called "EpiTools", able to i) precisely and automatically localize the position of each SEEG contact and ii) display the results of signal analysis in each patient's anatomy.New MethodThe first tool, GARDEL (GUI for Automatic Registration and Depth Electrode Localization), is able to automatically localize SEEG contacts and to label each contact according to a pre-specified nomenclature (for instance that of FreeSurfer or MarsAtlas). The second tool, 3Dviewer, enables to visualize in the 3D anatomy of the patient the origin of signal processing results such as rate of biomarkers, connectivity graphs or Epileptogenicity Index.ResultsGARDEL was validated in 30 patients by clinicians and proved to be highly reliable to determine within the patient's individual anatomy the actual location of contacts.Comparison with Existing MethodsGARDEL is a fully automatic electrode localization tool needing limited user interaction (only for electrode naming or contact correction). The 3Dviewer is able to read signal processing results and to display them in link with patient's anatomy.ConclusionEpiTools can help speeding up the interpretation of SEEG data and improving its precision.



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Genome Sequencing Analysis of Liver Cancer for Precision Medicine

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Publication date: Available online 29 March 2018
Source:Seminars in Cancer Biology
Author(s): Hidewaki Nakagawa, Masashi Fujita, Akihiro Fujimoto
Liver cancer is the third leading cause of cancer-related death worldwide. Some thousands of liver cancer genome have been sequenced globally so far and most of driver genes/mutations with high frequency are established in liver cancer, including Wnt/β-catenin pathway, TP53/cell-cycle pathways, telomere maintenance, and chromatin regulators. HBV integration into cancer-related genes is also a driver event in hepatocarcinogenesis. These genes are affected by structural variants, copy-number alterations and virus integrations as well as point mutations. Etiological factors of liver cancer is most understood among common cancers, such as hepatitis, aflatoxin, alcohol, and metabolic diseases, and mutational signatures of liver cancer can provide evidence of the association between specific etiological factors and mutational signatures. Molecular classifications based on somatic mutations profiles, RNA expression profiles, and DNA methylation profiles are related with patient prognosis. For precision medicine, several actionable mutations with solid evidence such as targets of multi-kinase inhibitors is observed in liver cancer, but there is few molecular target therapy so far. It is possible that rare actionable mutations in liver cancer can guide other specific molecular therapy and immune therapy



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Optimization of photo-Fenton process for the treatment of prednisolone

Abstract

Prednisolone is a widely prescribed synthetic glucocorticoid and stated to be toxic to a number of non-target aquatic organisms. Its extensive consumption generates environmental concern due to its detection in wastewater samples at concentrations ranged from ng/L to μg/L that requests the application of suitable degradation processes. Regarding the actual treatment options, advanced oxidation processes (AOPs) are presented as a viable alternative. In this work, the comparison in terms of pollutant removal and energetic efficiencies, between different AOPs such as Fenton (F), photo-Fenton (UV/F), photolysis (UV), and hydrogen peroxide/photolysis (UV/H2O2), was carried out. Light diode emission (LED) was the selected source to provide the UV radiation. The UV/F process revealed the best performance, reaching high levels of both degradation and mineralization with low energy consumption. Its optimization was conducted and the operational parameters were iron and H2O2 concentrations and the working volume. Using the response surface methodology with the Box-Behnken design, the effect of independent variables and their interactions on the process response were effectively evaluated. Different responses were analyzed taking into account the prednisolone removal (TOC and drug abatements) and the energy consumptions associated. The obtained model showed an improvement of the UV/F process when treating smaller volumes and when adding high concentrations of H2O2 and Fe2+. The validation of this model was successfully carried out, having only 5% of discrepancy between the model and the experimental results. Finally, the performance of the process when having a real wastewater matrix was also tested, achieving complete mineralization and detoxification after 8 h. In addition, prednisolone degradation products were identified. Finally, the obtained low energy permitted to confirm the viability of the process.



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Perfusión tejido-músculo evaluada mediante protocolo de un día de gammagrafía reposo-dipiramidol con 99mTc-MIBI en pacientes no diabéticos y diabéticos

Publication date: Available online 28 March 2018
Source:Revista Española de Medicina Nuclear e Imagen Molecular
Author(s): N. Manevska, S. Stojanoski, D. Pop Gjorceva, L. Todorovska, M. Vavlukis, V. Majstorov
ObjetivoDeterminar la reserva de perfusión en miembros inferiores utilizando el método de gammagrafía de perfusión (protocolo de un día) con 99mTc-MIBI (reposo-dipiridamol) en la evaluación diagnóstica de la enfermedad arterial periférica (EAP) en pacientes con y sin diabetes mellitus (DM).Material y métodosRealizamos gammagrafía de perfusión tejido-músculo (TMPS) de miembros inferiores, mediante el protocolo de un día de reposo-dipiridamol con 99mTc-MIBI en 24 pacientes, divididos en dos grupos, según la presencia de diabetes: pacientes con DM (Dp) 13/24 (54%), 2 varones y 9 mujeres, de edad 63±13 años, y pacientes sin DM (NDp) 11/24 (46%), 3 varones y 10 mujeres, de edad 61±14 años.ResultadosEn la fase dinámica del estudio en reposo, el tiempo de actividad máxima (Tmax), en la fase arterial temprana, de la región de la pantorrilla, estaba significativamente retrasado en Dp con respecto a NDp, con menor acumulación de radiotrazador en el 1er minuto (85-87% en Dp vs. 89-90% en NDp, ns). 4/11 pacientes de NDp (36,4%) y 7/13 de Dp (53,8%) registraron un valor patológico del índice inter-extremidad de la pantorrilla en el estudio de estrés. La reserva de perfusión (RP) de los muslos (MI, MD) y las pantorrillas (PI, PD) calculada mediante la fórmula «(ROI estrés-ROI reposo) x 100%/ROI reposo», fue significativamente menor en Dp: MI: 28±19% vs. 43±24% en NDp, p<0,05; MD: 27±17% vs. 40±25% en NDp, p<0,05; PI: 22±15% vs. 36±15% en NDp, p<0,01; PD: 25±15% vs. 38±14% in NDp, p<0,01.ConclusiónEste protocolo de un día (reposo-dipiridamol con 99mTc-MIBI) de gammagrafía de perfusión de miembros inferiores se considera un procedimiento útil para la valoración de los pacientes con EAP, especialmente en su forma asintomática. La TMPS de miembros inferiores en nuestro estudio indicó que la reserva de perfusión en pacientes con DM fue significativamente menor, en comparación con los pacientes sin diabetes.AimTo determine the perfusion reserve of the lower limbs using the method 99mTc-MIBI (rest-dipyridamole) perfusion scintigraphy (one-day protocol) in the diagnostic evaluation of peripheral artery disease (PAD) in patients with and without diabetes mellitus (DM).Material and methodsWe performed tissue-muscle perfusion scintigraphy (TMPS) of the lower limbs, through one-day rest-dipyridamole protocol with 99mTc-MIBI in 24 patients, divided in two groups according to the presence of diabetes – patients with DM (Dp) 13/24 (54%), 2 males and 9 female patients, age 63±13 years and patients without DM (NDp) 11/24 (46%), 3 males and 10 females, age 61±14 years.ResultsIn the dynamic phase of the rest study, the time of maximum activity (Tmax), in the early arterial phase, of the calf region was significantly prolonged in Dp compared to NDp, with lower accumulation of the radiotracer in the 1st minute (85%/87% in Dp vs. 89%/90% in NDp, ns). 4/11 of NDp (36.4%) and 7/13 of Dp (53.8%) registered pathological value of the inter-extremity index of the calves in the stress study. Perfusion reserve (PR) of the thighs (LT, RT) and calves (LC, RC) calculated with the formula "(ROI stress−ROI rest)×100%/ROI rest", was significantly lower in Dp: LT: 28±19% vs. 43±24% in NDp, p<0.05; RT: 27±17% vs. 40±25% in NDp, p<0.05; LC: 22±15% vs. 36±15% in NDp, p<0.01; RC: 25±15% vs. 38±14% in NDp, p<0.01.ConclusionThis one-day protocol (rest-dipyridamole with 99mTc-MIBI) of perfusion scintigraphy of lower limbs is considered as a useful procedure in PAD assessment, especially the asymptomatic form. TMPS of the lower limbs in our study indicated that perfusion reserve in patients with DM was significantly lower, compared to the patients without diabetes.



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99mTc-HMPAO SPECT cerebral en la monitorización de la terapia de vasculitis

Publication date: Available online 28 March 2018
Source:Revista Española de Medicina Nuclear e Imagen Molecular
Author(s): V. Frantellizzi, M. Morreale, M. Pontico, A. Francia, F.M. Drudi, A. Farcomeni, M. Liberatore
ObjetivoEl sistema nervioso central (SNC) puede estar afectado en una variedad de enfermedades inflamatorias de los vasos sanguíneos, generalmente conocidas como vasculitis. El diagnóstico clínico de dicha afectación en etapas tempranas es difícil, ya que un leve deterioro cognitivo puede ser el único síntoma. Se planteó la hipótesis de que la SPECT de perfusion cerebral podría mostrar la afectación del SNC y podría servir para controlar el curso de la enfermedad. El propósito de este estudio fue evaluar si y cuándo una mejora de la perfusión cerebral puede ser registrada por SPECT durante el seguimiento de estas enfermedades.Material y métodosDieciocho pacientes afectados por Lupus eritematoso sistémico (LES), 22 por vasculitis indiferenciada (VI), 5 por la enfermedad de Behcet (EB) y 5 por el síndrome de Sjogren Primario (SSp) se incluyeron en este estudio prospectivo. Se realizó una SPECT de perfusión cerebral con 99mTc-HMPAO antes del tratamiento, y se repitió durante el seguimiento a diferentes intervalos de tiempo. El análisis de imagen se realizó en 10 áreas cerebrales utilizando un software específico.ResultadosEn los pacientes con LES no se encontró una mejora significativa de la perfusión cerebral. Por el contrario, en la VI la captación cerebral del trazador comenzó a mejorar significativamente desde el vigésimo cuarto mes (18/22 pacientes). Los pacientes con EB mostraron una mejora de los hallazgos gammagráficos (5/5 pacientes), mientras que sólo se obtuvo un resultado similar en dos de los pacientes con SSp.ConclusionesEn conclusión, el SPECT cerebral parece ser capaz de monitorizar la enfermedad en VI, evaluando cuándo se puede registrar una mejoría de la perfusión cerebral. En los pacientes con LES, esta técnica gammagráfica no ha encontrado una mejoría significativa en la perfusión del SNC.ObjectiveThe central nervous system (CNS) may be involved in a variety of inflammatory diseases of the blood vessels, generally known as vasculitis. The clinical diagnosis of such involvement in early stages is difficult, since a mild cognitive impairment can be the only symptom. It was hypothesized that brain-perfusion SPECT would be able to reveal CNS involvement and to monitor the course of the disease. The purpose of this study was assess if and when an improvement of cerebral perfusion can be registered by SPECT during the follow-up of these diseases.Material and methodsEighteen patients affected by Systemic Lupus Erythematosus (SLE), 22 by undifferentiated vasculitis (UV), 5 by Behcet's disease (BD) and 5 by primary Sjogren's Syndrome (pSS) were enrolled in this prospective study. A 99mTc-HMPAO brain perfusion SPECT was performed before the treatment and was repeated during the follow-up at different time intervals. Image analysis was performed on 10 cerebral areas using a specific software.ResultsIn the SLE patients, no significant improvement of brain perfusion was found. On the contrary, in the UV the cerebral uptake of the tracer significantly improved from the twenty-fourth month (18/22 patients). Patients with BD showed an improvement of scintigraphic findings (5/5 patients), while a similar result was obtained only in 2 of the patients with pSS.ConclusionsIn conclusion, brain SPECT seems to be able to monitor the disease in UV, indicating the moment when an improvement of the cerebral perfusion is achieved. In SLE patients this scintigraphic technique did not show a significant improvement in CNS perfusion.



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Spectral fitting approach for the determination of enrichment and contamination factors in mining sediments using laser-induced breakdown spectroscopy

Abstract

Monitoring of pollution index values in sediments is crucial in assessing the environmental impacts of toxic metals in a given location. These indices are typically acquired using elaborate and tedious calibration curve-dependent techniques such as (inductively coupled plasma – optical emission spectroscopy) ICP-OES and (atomic absorption spectroscopy) AAS. In this study, laser-induced breakdown spectroscopy (LIBS) was used as a simple and fast alternative method for estimating enrichment factor (EF) and contamination factor (CF) of the sediment samples obtained from selected mining sites. Quantitative analyses of three metal targets (Cd, Pb, and Zn) were done using a calibration-free LIBS method based on the Boltzmann population distribution. Both the EF and CF values calculated from classical ICP-OES method provided significantly high correspondence with the respective EF (R2 = 0.8862–0.9770, p < 0.01–0.05) and CF (R2 = 0.9454–0.9714, p < 0.01) obtained from the developed LIBS method. The intensity-based LIBS approach identified samples AC2 and CCC as the ones with the highest and lowest pollution index values, respectively. The same observation was seen using the concentration-based ICP-OES technique which showed good correlation between the two methods. The correlation results showed the potential of the curve-fitting LIBS analysis in evaluating the level of metal contamination in an area without the preparation of matrix-matched calibration curves.



https://ift.tt/2uvOwwL

A comparative evaluation of spectrophotometric intracutaneous analysis and laser doppler imaging in the assessment of adult and paediatric burn injuries

Clinical assessment of mid dermal burns can be challenging. Currently, Laser Doppler Imaging is the gold standard adjunct in the assessment of burn injuries. Whilst Laser Doppler Imaging has demonstrated reliable accuracy, it poses various limitations in everyday use including cost and ease of use. In comparison, Spectrophotometric Intracutaneous Analysis is a relatively cheaper technique which can be carried out using a modified digital camera which enables easy image acquisition. We aim to compare the accuracy of the two modalities in the assessment of mid-dermal burn injuries.

https://ift.tt/2GjoL8r

Tissue expansion in cranioplasty - a collaborative approach for all involved for improved outcomes?

The use of tissue expanders is well established in plastic surgery. However, there are currently no clear indications for tissue expansion as an adjunct to cranioplasty. We present a series of nine patients who underwent tissue expansion prior to cranioplasty after removal of an infected bone flap and/or radiotherapy. Family members of 8 patients were taught how to undertake expansion at home. Two patients experienced exposure and infection of the expander. Post-operatively two patients developed an infection of their cranioplasty implant which was removed.

https://ift.tt/2uvOd55

Editorial Board and Contents

Publication date: April 2018
Source:Trends in Immunology, Volume 39, Issue 4





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Neutrophils and redox stress in the pathogenesis of autoimmune disease

Publication date: Available online 29 March 2018
Source:Free Radical Biology and Medicine
Author(s): Laurence Glennon-Alty, Angela P Hackett, Elinor A Chapman, Helen L Wright
Polymorphonuclear leukocytes, or neutrophils, are specialist phagocytic cells of the innate immune system. Their primary role is host defence against micro-organisms, which they kill via phagocytosis, followed by release of reactive oxygen species (ROS) and proteolytic enzymes within the phagosome. ROS are generated via the action of the NADPH oxidase (also known as NOX2), in a process termed the 'Respiratory Burst'. This process consumes large amounts of oxygen, which is converted into the highly-reactive superoxide radical O2- and H2O2. Subsequent activation of myeloperoxidase (MPO) generates secondary oxidants and chloroamines that are highly microbiocidal in nature, which together with proteases such as elastase and gelatinase provide a toxic intra-phagosomal environment able to kill a broad range of micro-organisms. However, under certain circumstances such as during an auto-immune response, neutrophils can be triggered to release ROS and proteases extracellularly causing damage to host tissues, modification of host proteins, lipids and DNA and dysregulation of oxidative homeostasis. This review describes the range of ROS species produced by human neutrophils with a focus on the implications of neutrophil redox products in autoimmune inflammation.

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Redox regulation of cell proliferation: Bioinformatics and redox proteomics approaches to identify redox-sensitive cell cycle regulators

Publication date: Available online 29 March 2018
Source:Free Radical Biology and Medicine
Author(s): Christine H. Foyer, Michael Wilson, Megan Wright
Plant stem cells are the foundation of plant growth and development. The balance of quiescence and division is highly regulated, while ensuring that proliferating cells are protected from the adverse effects of environment fluctuations that may damage the genome. Redox regulation is important in both the activation of proliferation and arrest of the cell cycle upon perception of environmental stress. Within this context, reactive oxygen species serve as 'pro-life' signals with positive roles in the regulation of the cell cycle and survival. However, very little is known about the metabolic mechanisms and redox-sensitive proteins that influence cell cycle progression. We have identified cysteine residues on known cell cycle regulators in Arabidopsis that are potentially accessible, and could play a role in redox regulation, based on secondary structure and solvent accessibility likelihoods for each protein. We propose that redox regulation may function alongside other known posttranslational modifications to control the functions of core cell cycle regulators such as the retinoblastoma protein. Since our current understanding of how redox regulation is involved in cell cycle control is hindered by a lack of knowledge regarding both which residues are important and how modification of those residues alters protein function, we discuss how critical redox modifications can be mapped at the molecular level.

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Apathy in Alzheimer’s disease and frontotemporal dementia: Distinct clinical profiles and neural correlates

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Publication date: Available online 29 March 2018
Source:Cortex
Author(s): Fiona Kumfor, Alice Zhen, John R. Hodges, Olivier Piguet, Muireann Irish
ObjectiveApathy is the most prevalent and disabling non-cognitive symptom of dementia and affects 90% of patients across the disease course. Despite its pervasiveness, how apathy manifests across dementia syndromes and the neurobiological mechanisms driving these symptoms are poorly understood. Here, we applied the multidimensional ABC model of apathy, which recognizes Affective, Behavioural and Cognitive apathy, in Alzheimer's disease (AD) and behavioural-variant frontotemporal dementia (bvFTD).MethodsOne hundred and twenty-two patients (53 AD; 69 bvFTD) were included. Informants completed the Neuropsychiatric Inventory (NPI), Cambridge Behavioral Inventory and Disability and Dementia scale to quantify Affective, Behavioural and Cognitive apathy. All patients underwent structural MRI and voxel-based morphometry was employed to identify brain regions correlated with increased Affective, Behavioural and Cognitive apathy.ResultsOn the NPI, 60% of AD and 84% of bvFTD patients had some degree of apathy, but bvFTD had more severe and more frequent symptoms than AD. Using the multidimensional ABC model, bvFTD patients had higher affective and cognitive apathy whereas AD had higher cognitive apathy only. Neuroimaging analyses revealed that affective apathy was associated with the ventral prefrontal cortex; behavioural apathy with the basal ganglia; and cognitive apathy with the dorsomedial prefrontal cortex. Finally, affective and behavioural apathy significantly predicted carer burden.ConclusionsOur results support the notion that apathy is multidimensional and manifests differently across dementia syndromes. Thus, novel interventions which target these divergent mechanisms will be necessary to improve motivation and goal-directed behaviour in people with dementia.



http://bit.ly/2IdPAHE

Attenuation of TNF-induced neutrophil adhesion by simvastatin is associated with the inhibition of Rho-GTPase activity, p50 activity and morphological changes

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Publication date: May 2018
Source:International Immunopharmacology, Volume 58
Author(s): Angélica Aparecida Antoniellis Silveira, Venina Marcela Dominical, Daiana Morelli Vital, Wilson Alves Ferreira, Fabio Trindade Maranhão Costa, Claudio C. Werneck, Fernando Ferreira Costa, Nicola Conran
Neutrophil adhesion to the vasculature in response to potent inflammatory stimuli, such as TNF-α (TNF), can contribute to atheroprogression amongst other pathophysiological mechanisms. Previous studies have shown that simvastatin, a statin with known pleiotropic anti-inflammatory properties, can partially abrogate the effects of TNF-induced neutrophil adhesion, in association with the modulation of β2-integrin expression. We aimed to further characterize the effects of this statin on neutrophil and leukocyte adhesive mechanisms in vitro and in vivo. A microfluidic assay confirmed the ability of simvastatin to inhibit TNF-induced human neutrophil adhesion to fibronectin ligand under conditions of shear stress, while intravital imaging microscopy demonstrated an abrogation of leukocyte recruitment by simvastatin in the microvasculature of mice that had received a TNF stimulus. This inhibition of neutrophil adhesion was accompanied by the inhibition of TNF-induced RhoA activity in human neutrophils, and alterations in cell morphology and β2-integrin activity. Additionally, TNF augmented the activity of the p50 NFκB subunit in human neutrophils and TNF-induced neutrophil adhesion and β2-integrin activity could be abolished using pharmacological inhibitors of NFκB translocation, BAY11-7082 and SC514. Accordingly, the TNF-induced elevation of neutrophil p50 activity was abolished by simvastatin. In conclusion, our data provide further evidence of the ability of simvastatin to inhibit neutrophil adhesive interactions in response to inflammatory stimuli, both in vivo and in vitro. Simvastatin appears to inhibit neutrophil adhesion by interfering in TNF-induced cytoskeletal rearrangements, in association with the inhibition of Rho A activity, NFκB translocation and, consequently, β2-integrin activity.



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Editorial Board

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Publication date: April 2018
Source:Autoimmunity Reviews, Volume 17, Issue 4





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Patterns in Health Care Access and Affordability Among Cancer Survivors

This population-based study analyzes cancer survivors' ability to access and afford health care during implementation of the US Affordable Care Act using data from the 2010 to 2016 National Health Interview Survey.

https://ift.tt/2GDV8hh

Adding Cetuximab to Definitive Chemoradiation for Esophageal Cancer—Reply

In Reply We read with interest the Letters to the Editor from Liu and Yue as well as Adenis and Lordick, and we appreciate the opportunity to provide a response. We agree with Liu and Yue that this phase 3 trial was not designed or powered to assess the primary end point within the histology subsets. The Statistical Considerations section of the article describes the rationale for stratifying patients based on histologic type. In addition, it describes the required clinical complete response rate that would have to be achieved in order to continue to accrue patients with a specific histologic type. The Results section provides the outcome for patients with adenocarcinoma. The failure to meet the required end point of a 12% improvement in clinical complete response rate led to the mandated cessation of accruing patients with adenocarcinoma histologic type. The subsequent decision to discontinue accruing patients with squamous cell carcinoma histologic type and close the trial early came as a result of the publication of the United Kingdom SCOPE1 trial in January 2013, which failed to document a benefit of the addition of cetuximab to chemoradiation therapy in a similar cohort. Again, this is described in the Results section of the article. We did not perform toxicity, survival, or local failure analyses between treatment arms within histology subsets because these were not considered part of the primary end point of the trial and, therefore, not appropriate for this article. We note that the results of the phase 2 multi-institutional trial mentioned by the authors describe a clinical complete response rate of 64%, which is consistent with the findings of the control arm of RTOG 0436, and does not provide level 1 evidence to support a benefit associated with the addition of cetuximab. We look forward to the publication of the results of their phase 3 trial (NCT02858206).

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Genetic Alterations and Response to EGFR Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer

This cohort study examines the association of concomitant genetics alterations with response to treatment with epidermal growth factor receptor tyrosine kinase inhibitors among patients with EGFR-mutant advanced non–small cell lung cancer.

https://ift.tt/2GGGNB2

Rituximab Maintenance Therapy After Induction Chemoimmunotherapy for Follicular Lymphoma

This synopsis summarizes the prospective randomized clinical trials that examined the use of rituximab maintenance therapy in treatment-naive patients with follicular lymphoma after first-line induction chemoimmunotherapy.

https://ift.tt/2GjbWHe

Adding Cetuximab to Definitive Chemoradiation for Esophageal Cancer

To the Editor We read with interest the article by Suntharalingam et al demonstrating that the addition of cetuximab to concurrent chemoradiation therapy did not improve overall survival in the nonoperative treatment of patients with esophageal cancer. Although the study stratified patients according to tumor histologic type, it was not powered to assess with certainty the benefit of cetuximab therapy in each of the 2 main histological variants of this disease.

https://ift.tt/2GGKdU6

CSF Biomarkers of CNS Injury and Neurocognitive Outcomes in Children With Acute Lymphoblastic Leukemia

This cohort study evaluates the association of cerebrospinal fluid biomarkers of brain injury with short- and long-term outcomes and genetic polymorphisms in children receiving chemotherapy for acute lymphoblastic leukemia.

https://ift.tt/2E567Ls

Adding Cetuximab to Definitive Chemoradiation for Esophageal Cancer

To the Editor In a recent issue of JAMA Oncology, Suntharalingam et al reported that the addition of cetuximab to concurrent chemoradiation therapy (CRT) with paclitaxel and cisplatin failed to improve the survival of patients undergoing nonoperative treatment of esophageal cancer. They concluded that RTOG 0436 had negative results and suggested focusing future trials on patients with actionable molecular targets. Surprisingly, Suntharalingam et al also stated that because of the toxic effects observed in both experimental and control treatment arms, they were inclined to recommend a systemic therapy that uses a platinum-taxane combination rather than fluorouracil.

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Assessment of Tumor Sequencing to Screen for Lynch Syndrome in Colorectal Cancer

This genetic sequencing study explores whether up-front tumor sequencing can replace the prevailing paradigm for universal tumor screening for Lynch syndrome, which includes a sequence of several screening tests.

https://ift.tt/2GmaKCW

Intraoperative Radiation Therapy for Accelerated Partial Breast Irradiation

This Viewpoint examines the evidence supporting the efficacy of intraoperative radiation therapy compared with other treatment modalities for patients with early-stage breast cancer.

https://ift.tt/2GGKeYf

Motors of influenza vaccination uptake and vaccination advocacy in healthcare workers: A comparative study in six European countries

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Publication date: Available online 28 March 2018
Source:Vaccine
Author(s): George Kassianos, Ernest Kuchar, Aneta Nitsch-Osuch, Jan Kyncl, Andrey Galev, Isme Humolli, Oana Falup-Pecurariu, Angus Thomson, Christina Klein, Gaëlle Vallée-Tourangeau
BackgroundAnnual vaccination is the most effective way to prevent and control the health and economic burden caused by seasonal influenza. Healthcare workers (HCWs) play a crucial role in vaccine acceptance and advocacy for their patients. This study explored the drivers of HCWs' vaccine acceptance and advocacy in six European countries.MethodsHealthcare workers (mainly general practitioners, specialist physicians, and nurses) voluntarily completed a questionnaire in Bulgaria (N = 485), Czech Republic (N = 518), Kosovo (N = 466), Poland (N = 772), Romania (N = 155), and the United Kingdom (N = 80). Twelve-item scales were used to analyse sentiment clusters for influenza vaccination acceptance and engagement with vaccination advocacy. Past vaccination behaviour and patient recommendation were also evaluated. All data were included in a single analysis.ResultsFor vaccination acceptance, the main cluster (engaged sentiment: 68%) showed strong positive attitudes for influenza vaccination. A second cluster (hesitant sentiment: 32%) showed more neutral attitudes. Cluster membership was predicted by country of origin and age. The odds ratio for past vaccination in the engaged cluster was 39.6 (95% CI 12.21–128.56) although this varied between countries. For vaccination advocacy, the main cluster (confident sentiment: 73%) showed strong positive attitudes towards advocacy; a second cluster (diffident sentiment: 27%) showed neutral attitudes. Cluster membership was predicted by country of origin, age and profession, with specialist physicians being the least likely to belong to the confident sentiment cluster. HCWs characterised by confident advocacy sentiments were also more likely recommend flu vaccination. Again, this association was moderated by country of origin.ConclusionsThese data show that there is room to improve both vaccination acceptance and advocacy rates in European HCWs, which would be expected to lead to higher rates of HCW vaccination. Benefits that could be expected from such an outcome are improved advocacy and better control of morbidity and mortality related to seasonal influenza infection.



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The N6-adenine methylation in yeast genome profiled by single-molecule technology

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Publication date: Available online 28 March 2018
Source:Journal of Genetics and Genomics
Author(s): Zhe Liang, Guoliang Yu, Jingrong Liu, Yuke Geng, Jinghui Mao, Depeng Wang, Jiapeng Zhou, Xiaofeng Gu




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Dermocosmetics for Use in Rosacea: Guideline of the Society for Dermopharmacy

Rosacea is a widespread inflammatory skin disease that is chronically recurrent and affects predominately the central parts of the face. Affected individuals typically react to numerous cosmetics with redness, burning, and/or worsening of the complexion. Consequently, there is a high demand for dermocosmetics that do not provoke such reactions and are suitable for use in rosacea. The present guideline of the Society for Dermopharmacy describes the requirements that dermocosmetics for use in rosacea should meet. They include, inter alia, methods to prove the efficacy of and tolerance to these cosmetics, as well as the product documentation that the manufacturer or the distributing company should make available to professionals, like dermatologists and pharmacists, counseling patients with rosacea.
Skin Pharmacol Physiol 2018;31:147–154

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Vaginal spindle cell epithelioma: A first complete MRI and histopathologic description

Publication date: July–August 2018
Source:Clinical Imaging, Volume 50
Author(s): Michael T. Johnson, Kristin C. Smith, Leo L. Tsai
Spindle cell epithelioma of the vagina is a benign entity with fewer than sixty cases described in the literature, and only two with limited imaging findings, since the early 1950s. Early pathology literature suggested the lesions were mixed tumors of myoepithelial origin, but subsequent studies have found relatively few immunohistochemical characteristics in common with other mixed cell tumors. More recently, Mullerian, urogenital sinus epithelial, and pluripotential cell origins have been proposed. Given lesion rarity and a typical lack of imaging before excision, the imaging appearance of vaginal spindle cell epitheliomas has not been fully described in the radiology literature, and without comprehensive pathology correlation. The authors describe a case of spindle cell epithelioma in a 54-year-old woman which was incidentally discovered on MRI performed for uterine fibroid embolization planning. Pathology and immunohistochemistry confirmed the diagnosis.



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A Novel Mechanism to Drive Castration-Resistant Prostate Cancer

Publication date: Available online 28 March 2018
Source:Trends in Endocrinology & Metabolism
Author(s): Salma Kaochar, Nicholas Mitsiades
Androgen receptor signaling is critical for prostate adenocarcinoma, even after androgen deprivation therapy. Persistence of intratumoral androgens has been found in castration-resistant prostate cancer and attributed to increased in situ synthesis. Recently, Sharifi and colleagues reported an additional mechanism that can enhance local androgenic exposure: downregulation of an androgen-inactivating enzyme.



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High-throughput non-invasive prenatal testing for fetal rhesus D status in RhD-negative women not known to be sensitised to the RhD antigen: a systematic review and economic evaluation.

Non-invasive prenatal testing for fetal rhesus D could substantially reduce unnecessary use of antenatal anti-D, though with a small increase in risk of sensitisation, and may be cost saving.

https://ift.tt/2pPmfvv

Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Women: An Evidence Review for the U.S. Preventive Services Task Force [Internet].

Hormone therapy plays an important role in the clinical management of menopausal symptoms. Because of an increased risk of harms, hormone therapy is currently not recommended for the primary prevention of chronic conditions.

https://ift.tt/2J3qL2l

Motivational Interviewing as a Method to Facilitate Return to Work: A Systematic Review [Internet].

The Norwegian Labour and Welfare Administration (NAV) strives to include as many people as possible in employment. Motivational Interviewing (MI) is suggested to be a suitable method to achieve this goal. Training in MI is already widespread within NAV, despite the lack of solid research evidence about its effects on employment, wherefore NAV commissioned this systematic review.

https://ift.tt/2pTCJmy

Effectiveness of Tapering from Methadone or Buprenorphine Maintenance Treatment Compared to Traditional Maintenance Treatment for People with Opiate Addiction: Systematic Review [Internet].

In Norway we offer opioid maintenance treatment with methadone or buprenorphine for people with opioid dependence. For most people who use methadone or buprenorphine the maintenance treatment has a lifelong perspective. We summarized the research on the effect of tapering the dosage of methadone or buprenorphine compared with continued opioid assisted maintenance treatment.

https://ift.tt/2IZaTOp

Depth of Muscularis Propria Invasion Does Not Prognosticate Survival in T2 Esophageal Adenocarcinoma

Aim: Although tumor depth of invasion is strongly associated with risk of lymph node metastasis and long-term survival in patients with esophageal adenocarcinoma, the significance of differential T2 invasion (inner circular layer versus outer longitudinal layer) is unknown. The current study was undertaken to explore the hypothesis that greater T2-specific depth of invasion is associated with inferior long-term outcomes in patients with esophageal adenocarcinoma treated with esophagectomy. Patients and Methods: Demographic, treatment, and outcome data were collected for patients with resected pT2N0-3M0 esophageal adenocarcinoma treated between 2005 and 2015 pooled from four U.S. academic medical centers. Two blinded pathologists evaluated depth of muscularis propria tumor invasion. Univariate and Cox proportional hazard regression analyses were performed to identify prognostic factors for overall (OS) and disease-free (DFS) survival, and Kaplan–Meier analysis to compare survival differences specific to prognostic factors. Results: A total of 84 patients were identified for analysis (53 with circular invasion; 31 with longitudinal invasion), with a median age of 66 years. Sixty percent of patients (50/84) received induction therapy prior to esophagectomy. The median OS and DFS was 58 months (95% confidence interval(CI)=42 months-not reached) and 27 months (95% CI=13.7-66 months) respectively. Depth of muscularis propria invasion did not correlate with OS or DFS on univariate (p=0.42; and p=0.34, respectively) or multivariate (p=0.15 and p=0.21, respectively) analysis after adjustment for age, nodal status, perineural invasion, and tumor grade. These findings did not vary by induction therapy status. Conclusion: Depth of muscularis propria invasion does not appear to correlate with survival in patients with esophageal adenocarcinoma.



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Clinicopathological Analysis of Ultrasound-guided Vacuum-assisted Breast Biopsy for the Diagnosis and Treatment of Breast Disease

Background/Aim: To evaluate the usefulness and safety of vacuum-assisted breast biopsy (VABB) for breast lesion diagnosis and treatment. Patients and Methods: Clinical and histopathological data of 8,748 patients, who underwent 11,221 VABB procedures were analyzed. Results: Most patients (58.2%) were <40 years old. Most lesions (39.6%) were 0.6-1.0 cm in diameter while 3.2% were ≥3.0 cm; fibroadenomas were the most common (46.6%). Eight (14% of 57) cases of atypical ductal hyperplasia were underestimated. The positive predictive values (PPVs) of breast imaging reporting and data system (BI-RADS) ultrasound category were 0.6%, 3.4%, 34.8%, 66.2%, and 93.8% for category 3, 4a, 4b, 4c, and 5 lesions, respectively. The mean number of core specimens was 9.5±8.8; the mean procedure time was 3.4±2.7 min. No residual lesions were found in 94.4% of the 7,480 patients. Conclusion: VABB could replace ultrasound-guided core biopsy and surgical excisional biopsy for the diagnosis of breast disease and the treatment of benign breast lesions.



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Effectiveness and Safety of Tissue Expander for Adjuvant Helical Tomotherapy in Curatively Resected Retroperitoneal Sarcoma

Background/Aim: We investigated the effectiveness and safety of using a tissue expander (TE) for adjuvant helical tomotherapy (HT) for curatively resected retroperitoneal sarcoma (RPS). Materials and Methods: This study was conducted with 60 RPS patients who underwent curative resection with or without TE insertion followed by HT from June 2009 to December 2016. Among the patients, TE was inserted in 37 (61.7%). The quality of TE insertion was evaluated. Median follow-up after surgery was 19.4 months (range=4.5-93.2 months). Results: A higher biologically-equivalent dose (α/β=10) was used with patients who had TE insertion (median, 72.0 gray [Gy] vs. 67.1 Gy, p=0.02). The quality of TE insertion was excellent in 18 patients (48.6%), good in 10 (27.0%), fair in seven (18.9%), and poor in two (5.4%). Toxicity was not significantly different according to TE insertion. Local recurrence-free survival (LRFS) was 78.2%, and overall survival was 95.6% at 3 years. TE insertion was not a significant factor for LRFS (91.1% in TE vs. 62.9% in non-TE group at 3 years, p=0.62). In the subgroup of patients with R1 or unknown tumor margin status, however, LRFS was marginally higher in the TE insertion group (100.0% in TE vs. 62.9% non-TE group at 3 years, p=0.05). Conclusion: HT with TE insertion as adjuvant RT for curatively resected RPS was feasible with acceptable toxicity. In the patients with R1 or unknown tumor margin status, LRFS was marginally higher in the TE insertion group after HT.



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ABSTRACTS OF THE 28th ANNUAL MEETING OF THE ITALIAN SOCIETY OF URO-ONCOLOGY (SIUrO): URO-ONCOLOGIA: MULTIDISCIPLINARIETA E REALTA CLINICA



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Natural History of Squamous Intraepithelial Lesions in Pregnancy and Mode of Delivery

Background: Numerous studies have addressed the impact of mode of delivery on the natural history of squamous intraepithelial lesions (SIL) in pregnant women. However, the literature is still contradictory. Patients and Methods: In the course of a retrospective analysis, data of 63 pregnant women with abnormal cervical smears who were referred to our Outpatient Department for pre-invasive lesions of the cervix were analyzed. The study was conducted at the General Hospital in Vienna, Austria, between 2010 and 2015. Data collection included demographics, delivery route and diagnostic results of cervical lesions by cytology, colposcopy, human papilloma virus (HPV) testing, histological report of punch biopsy and, if applicable, cone biopsy. Results: Among 63 women who met the inclusion criteria, 40 (63%) delivered vaginally and 23 (37%) underwent caesarean section. Postpartum regression of cervical dysplasia was documented in 15 women delivering vaginally and in 10 who had a caesarean section (p=0.641). Among those women who delivered vaginally, three had progression and in 22 women the lesions persisted postpartum. In the group of women with caesarean section, one had progression and the lesions of 12 women persisted after delivery. No woman had progression to invasive disease. Conclusion: The mode of delivery does not significantly influence the natural history of cervical dysplastic lesions in pregnant women. The numbers of spontaneous regressions to normal cervical cytology during pregnancy were similar in both groups.



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Clinicopathological Profiling of LC3B, an Autophagy Marker, and ESRRA (Estrogen-related Receptor-alpha) in Muscle-invasive Bladder Cancer

Background/Aim: Microtubule-associated protein 1 light chain 3B (LC3B), an autophagy marker, has been used as a promising marker in various cancer types. However, the expression of LC3B in muscle-invasive bladder cancer (MIBC) and its prognostic significance have not been investigated. Recent studies pointed to the involvement of ESRRA in regulating autophagy via both transcriptional and post-translational control. In the current study, prognostic importance of LC3B and ESRRA in MIBC was investigated. Patients and Methods: We immunohistochemically studied the expression of LC3B and ESRRA in 56 MIBC samples. Results: LC3B was stained high in 16 patients (28.6%) and low or negative in 40 patients (71.4%). ESRRA expression was high for 20 patients (35.7%) and low for 36 patients (64.3%). Both LC3B (p=0.003) and ESRRA (p=0.026) expression correlated significantly with disease-free survival rates. Double-positive LC3B and ESRRA correlated with poor overall survival (p=0.007) and disease-free survival (p=0.001) in MIBC patients. Conclusion: LC3B and ESRRA might be a useful prognostic factor in patients with MIBC. The co-expression of LC3B and ESRRA might be a prognostic and therapeutic target for patients with bladder cancer.



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