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Δευτέρα 24 Ιουλίου 2017

A machine learning approach for real-time modelling of tissue deformation in image-guided neurosurgery

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Publication date: Available online 24 July 2017
Source:Artificial Intelligence in Medicine
Author(s): Michele Tonutti, Gauthier Gras, Guang-Zhong Yang
ObjectivesAccurate reconstruction and visualisation of soft tissue deformation in real time is crucial in image-guided surgery, particularly in augmented reality (AR) applications. Current deformation models are characterised by a trade-off between accuracy and computational speed. We propose an approach to derive a patient-specific deformation model for brain pathologies by combining the results of pre-computed finite element method (FEM) simulations with machine learning algorithms. The models can be computed instantaneously and offer an accuracy comparable to FEM models.MethodA brain tumour is used as the subject of the deformation model. Load-driven FEM simulations are performed on a tetrahedral brain mesh afflicted by a tumour. Forces of varying magnitudes, positions, and inclination angles are applied onto the brain's surface. Two machine learning algorithms—artificial neural networks (ANNs) and support vector regression (SVR)—are employed to derive a model that can predict the resulting deformation for each node in the tumour's mesh.ResultsThe tumour deformation can be predicted in real time given relevant information about the geometry of the anatomy and the load, all of which can be measured instantly during a surgical operation. The models can predict the position of the nodes with errors below 0.3mm, beyond the general threshold of surgical accuracy and suitable for high fidelity AR systems. The SVR models perform better than the ANN's, with positional errors for SVR models reaching under 0.2mm.ConclusionsThe results represent an improvement over existing deformation models for real time applications, providing smaller errors and high patient-specificity. The proposed approach addresses the current needs of image-guided surgical systems and has the potential to be employed to model the deformation of any type of soft tissue.



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A New Preprocessing Parameter Estimation based on Geodesic Active Contour Model for Automatic Vestibular Neuritis Diagnosis

Publication date: Available online 23 July 2017
Source:Artificial Intelligence in Medicine
Author(s): Amine Ben Slama, Aymen Mouelhi, Hanene Sahli, Sondes Manoubi, Chiraz Mbarek, Hedi Trabelsi, Farhat Fnaiech, Mounir Sayadi
The diagnostic of the vestibular neuritis (VN) presents many difficulties to traditional assessment methods This paper deals with a fully automatic VN diagnostic system based on nystagmus parameter estimation using a pupil detection algorithm. A geodesic active contour model is implemented to find an accurate segmentation region of the pupil. Hence, the novelty of the proposed algorithm is to speed up the standard segmentation by using a specific mask located on the region of interest. This allows a drastically computing time reduction and a great performance and accuracy of the obtained results. After using this fast segmentation algorithm, the obtained estimated parameters are represented in temporal and frequency settings. A useful principal component analysis (PCA) selection procedure is then applied to obtain a reduced number of estimated parameters which are used to train a multi neural network (MNN). Experimental results on 90 eye movement videos show the effectiveness and the accuracy of the proposed estimation algorithm versus previous work.

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Gaussian Process Classification of Superparamagnetic Relaxometry Data: Phantom Study

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Publication date: Available online 24 July 2017
Source:Artificial Intelligence in Medicine
Author(s): Javad Sovizi, Kelsey B. Mathieu, Sara L. Thrower, Wolfgang Stefan, John D. Hazle, David Fuentes
MotivationSuperparamagnetic relaxometry (SPMR) is an emerging technology that holds potential for use in early cancer detection. Measurement of the magnetic field after the excitation of cancer-bound superparamagnetic iron oxide nanoparticles (SPIONs) enables the reconstruction of SPIONs spatial distribution and hence tumor detection. However, image reconstruction often requires solving an ill-posed inverse problem that is computationally challenging and sensitive to measurement uncertainty. Moreover, an additional image processing module is required to automatically detect and localize the tumor in the reconstructed image.ObjectiveOur goal is to examine the use of data-driven machine learning technique to detect a weak signal induced by a small cluster of SPIONs (surrogate tumor) in presence of background signal and measurement uncertainty. We aim to investigate the performance of both data-driven and image reconstruction models to characterize situations that one can replace the computationally-challenging reconstruction technique by the data-driven model.MethodsWe utilize Gaussian process (GP) classification model and a physics-based image reconstruction method, tailored to SPMR datasets that are obtained from (i) in silico simulations designed based on mouse cancer models and (ii) phantom experiments using MagSense system (Imagion Biosystems, Inc.). We investigate the performance of the GP classifier against the reconstruction technique, for different levels of measurement noise, different scenarios of SPIONs distribution, and different concentrations of SPIONs at the surrogate tumor.ResultsIn our in silico source detection analysis, we were able to achieve high sensitivity results using GP model that outperformed the ImR model for various choices of SPIONs concentration at the surrogate tumor and measurement noise levels. Moreover, in our phantom studies we were able to detect the surrogate tumor phantoms with 5% and 7.3% of the total used SPIONs, surrounded by 9 low-concentration phantoms with accuracies of 87.5% and 96.4%, respectively.ConclusionsThe GP framework provides acceptable classification accuracies when dealing with in silico and phantom SPMR datasets and can outperform an image reconstruction method for binary classification of SPMR data.



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Cold-induced retrotransposition of fish LINEs

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Publication date: Available online 24 July 2017
Source:Journal of Genetics and Genomics
Author(s): Shue Chen, Mengchao Yu, Xu Chu, Wenhao Li, Xiujuan Yin, Liangbiao Chen
Classes of retrotransposons constitute a large portion of metazoan genome. There have been cases reported that genomic abundance of retrotransposons is correlated with the severity of low environmental temperatures. However, the molecular mechanisms underlying such correlation are unknown. We show here by cell transfection assays that retrotransposition of a long interspersed nuclear element (LINE) from an Antarctic notothenioid fish Dissostichus mawsoni (dmL1) could be activated by low temperature exposure, causing increased dmL1 copies in the host cell genome. The cold-induced dmL1 propagation was demonstrated to be mediated by the mitogen-activated protein kinases (MAPK)/p38 signalling pathway, which is activated by accumulation of reactive oxygen species (ROS) in cold-stressed conditions. Surprisingly, dmL1 transfected cells showed an increase in the number of viable cells after prolonged cold exposures than non-transfected cells. Features of cold inducibility of dmL1 were recapitulated in LINEs of zebrafish origin both in cultured cell lines and tissues, suggesting existence of a common cold-induced LINE amplification in fishes. The findings revealed an important function of LINEs in temperature adaptation and provided insights into the MAPK/p38 stress responsive pathway that shapes LINE composition in fishes facing cold stresses.



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Value of post-therapy 177Lu PSMA images for accurate interpretation of therapy response with 68Ga-PSMA PET/CT

Publication date: Available online 24 July 2017
Source:Revista Española de Medicina Nuclear e Imagen Molecular
Author(s): M. Tuncel, T. Telli
A 54-year-old man with progressive prostate cancer underwent a 68Ga-PSMA-PET/CT, which showed lymph node and bone metastases. After 2-cycles of 177Lu-PSMA therapy, the repeated 68Ga-PSMA PET/CT showed decreased radiotracer uptake in lymph node and bones metastases, but there were new lesions which may be compatible with progression or tumour sink-effect. A review of 177Lu-PSMA-therapy images revealed that new lesions in the second PET/CT were the metastatic lesions that progressed after the first PET/CT, and subsequently showed a good response. The patient received additional cycles of 177Lu-PSMA therapy, and the disease regressed further, with a PSA of 0.06ng/mL. Response evaluation of new therapeutic diagnostics (theranostic) agents needs a review of not only diagnostic PET/CT images, but also post-therapy images and laboratory results.



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Hallazgo incidental de captación focal del colon en estudios 18F-FDG PET/TC

Publication date: Available online 24 July 2017
Source:Revista Española de Medicina Nuclear e Imagen Molecular
Author(s): L. Servente, V. Gigirey, M. García Fontes, O. Alonso
ObjetivosEvaluar la frecuencia de la captación focal de colon como observación incidental en estudios 18F-FDG PET/TC. Correlacionar dicho hallazgo con resultados histopatológicos.Material y métodosSe analizaron de forma sistemática 30 estudios en los que se constató captación focal del colon de un total de 3.176 PET/TC con 18F-FDG. Se excluyeron pacientes con neoplasia colorrectal conocida. Se consignó el valor del SUV máximo (SUVm) y el hallazgo morfológico de la TC. Los estudios fueron informados por un médico radiólogo y un médico nuclear. Los hallazgos fueron correlacionados con la endoscopia y la anatomía patológica.ResultadosDe los 30 pacientes con lesiones focales hipermetabólicas del colon (0,94%), 15 eran hombres y 15 mujeres con edades comprendidas entre los 27 y 73 años (media 55 años). Los motivos de realización de la PET/TC fueron: cáncer broncopulmonar (4), cáncer de mama (4), tumor de origen desconocido (4), melanoma (3), carcinoma renal (3), neoplasia de cuello uterino (2), adenocarcinoma de ovario (2) y otros (8). Se realizaron 23 fibrocolonoscopias (FCC): 10 pacientes (43,4%) presentaron lesiones malignas, 6 pacientes (26,1%) lesiones premalignas y en 7 pacientes (30,4%) no se identificó ninguna lesión o esta fue benigna. En 7 pacientes no se hizo endoscopia por diversos motivos (rechazo del paciente para realizar el estudio, enfermedad oncológica avanzada). Se correlacionó con valores de SUVm y no se encontraron diferencias estadísticamente significativas entre lesiones malignas-premalignas y las lesiones benignas.ConclusionesLa captación focal en colon de 18F-FDG tiene relevancia clínica sobre todo asociada a lesión morfológica en TC, puede tratarse de un segundo tumor o una lesión premaligna. Se recomienda que todas las captaciones focales del colon sean valoradas con endoscopia, tengan o no alteraciones en TC.ObjectivesTo assess the frequency of focal colonic uptake as an incidental observation in 18F-FDG PET/CT studies, and to correlate this finding with histopathological results.Material and methodsOut of a total of 3,176 PET/CT studies with 18F-FDG systematic analysis was carried out on 30 studies in which colonic focal uptake was observed. Patients with known colorectal neoplasia were excluded. The maximum standardised uptake values (SUVm) and the morphological findings provided by the CT were recorded. The studies were reported by a radiologist and a nuclear medicine doctor. The findings were compared with endoscopy and pathology findings.ResultsOf the 30 patients with focal hypermetabolic lesions of the colon (0.94%), 15 were men and 15 were women with ages between 27 and 73 (mean 55 years). The reasons for PET/CT were bronchopulmonary cancer (4), breast cancer (4), tumour of unknown origin (4), melanoma (3), renal carcinoma (3), cervical neoplasia (2), adenocarcinoma of ovary (2), and others (8). Of the 23 colonoscopies performed, 10 patients (43.4%) had malignant lesions, 6 (26.1%) had pre-malignant lesions, and in 7 patients (30.4%) no lesion was identified or was benign. No endoscopy was performed on 7 patients for various reasons (patient refusal to perform the study, advanced oncological disease). An analysis was performed with the SUVm, with no statistically significant differences being found between malignant-premalignant lesions and benign lesions.ConclusionsFocal uptake in the colon of 18F-FDG has clinical relevance, and is mainly associated with morphological lesions in CT. It should be evaluated, as it may be a second tumour or a pre-malignant lesion. It is recommended that all focal uptakes of the colon be evaluated with endoscopy.



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Bioactive polysaccharide from edible Dictyophora spp.: Extraction, purification, structural features and bioactivities

Publication date: Available online 24 July 2017
Source:Bioactive Carbohydrates and Dietary Fibre
Author(s): Yuxiao Wang, Xiaodan Shi, Junyi Yin, Shaoping Nie
Dictyophora indusiata and many other Dictyophora mushrooms distribute widely around the world. They have long been used as edible mushroom in China. Owing to the outstanding healthy benefits, various bioactive substances from Dictyophora indusiata, including polysaccharide, amino acid, vitamin and protein, have been studied in recent years. Polysaccharide is one of the most important substances reported through out years. This review outlines recent progress on the extraction, purification, structural features and biological activities of polysaccharide from Dictyophora indusiata.



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Inter and intraexaminer reliability in identifying and classifying myofascial trigger points in shoulder muscles

Publication date: Available online 24 July 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): José Diego Sales do Nascimento, Francisco Alburquerque-Sendín, Lorena Passos Vigolvino, Wandemberg Fortunato de Oliveira, Catarina de Oliveira Sousa
ObjectiveTo determine inter and intraexaminer reliability of examiners without clinical experience in identifying and classifying MTPs in the shoulder muscles of subjects asymptomatic and symptomatic for unilateral SIS.DesignWithin-day inter and intraexaminer reliability study.SettingPhysical Therapy Department of a University.ParticipantsFifty-two subjects participated in the study, 26 symptomatic (SG) and 26 asymptomatic (AG) for unilateral SIS.InterventionsTwo examiners, without experience for assessment MTPs, independent and blind to the clinical conditions of the subjects, assessed bilaterally the presence of MTPs (present or absent) in six shoulder muscles and classified them (latent or active) on the affected side of the SG. Each examiner performed the same assessment twice in the same day.Main Outcome MeasuresThe reliability was calculated through Percentage Agreement (PA), Prevalence and Bias Adjusted Kappa Statistics (PABAK), and weighted Kappa (IKw).ResultsIntraexaminer reliability in identifying MTPs for the SG and AG was moderate to perfect (PABAK: 0.46-1 and 0.60-1, respectively). Interexaminer reliability was between moderate and almost perfect in the two groups (PABAK: 0.46-0.92), except for the muscles of the SG, which were below these values. With respect to MTP classification, intraexaminer reliability was moderate to high for the most muscles, but interexaminer reliability was moderate for only one muscle (IKw=0.45), and between weak and reasonable for the rest (IKw: 0.06 -0.31).ConclusionsIntraexaminer reliability is acceptable in clinical practice to identify and classify MTPs. However, interexaminer reliability proved to be reliable only to identify MTPs, with the symptomatic side exhibiting lower values of reliability.



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Modification of spastic stretch reflexes at the elbow by flexion synergy expression in individuals with chronic hemiparetic stroke

Publication date: Available online 24 July 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Jacob G. McPherson, Arno H.A. Stienen, Justin M. Drogos, Julius P.A. Dewald
ObjectiveTo systematically characterize the impact of flexion synergy expression on the manifestation of elbow flexor stretch reflexes post-stroke, and to relate these findings to elbow flexor stretch reflexes in individuals without neurological injury.DesignControlled cohort study.SettingAcademic medical center.ParticipantsTen individuals with chronic hemiparetic stroke and a convenience sample of 10 individuals without neurological or musculoskeletal injury.InterventionsParticipants with stroke were interfaced with a robotic device that precisely manipulated flexion synergy expression (by regulating shoulder abduction loading) while it delivered controlled elbow extension perturbations over a wide range of velocities. This device was also used to elicit elbow flexor stretch reflexes during volitional elbow flexor activation, both in the cohort of individuals with stroke and in a control cohort. In both cases, the amplitude of volitional elbow flexor pre-activation was matched to that generated involuntarily during flexion synergy expression.Outcome measuresThe amplitude of short and long latency stretch reflexes in the biceps brachii, assessed by electromyography, and expressed as a function of background muscle activation and stretch velocity.ResultsIncreased shoulder abduction loading potentiated elbow flexor stretch reflexes via flexion synergy expression in the paretic arm. Compared to stretch reflexes in individuals without neurological injury, paretic reflexes were larger at rest but were approximately equal to control muscles at matched levels of pre-activation.ConclusionsBecause flexion synergy expression modifies stretch reflexes in involved muscles, interventions that reduce flexion synergy expression may confer the added benefit of reducing spasticity during functional use of the arm.



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Robotic Gait Training For Indiviuals With Cerebral Palsy: A Systematic Review And Meta-Analysis

Publication date: Available online 24 July 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Igor da Silveira Carvalho, Sérgio Medeiros Pinto, Daniel das Virgens Chagas, Jomilto Luiz Praxedes dos Santos, Tainá de Sousa Oliveira, Luiz Alberto Batista
ObjectiveTo identify the effects of robotic gait training practices in individuals with cerebral palsy.Data SourcesThe search was performed in the following electronic databases: PubMed, EMBASE (Excerpta Medical), MEDLINE (OvidSP), CDSR (Cochrane database of systematic reviews), Web of Science, Scopus, Compendex, IEEE Xplore, ScienceDirect, Academic Search Premier, and PEDro.Study SelectionStudies were included if they fulfilled the following criteria: (1) they investigated the effects of robotic gait training, (2) they involved patients with cerebral palsy, and (3) they enrolled patients classified between levels I and IV using the Gross Motor Function Classification System.Data ExtractionThe information was extracted from the selected articles using the descriptive-analytical method. The "Critical Review Form for Quantitative Studies" was used to quantitate the presence of critical components in the articles. To perform the meta-analysis, the effects of the intervention were quantified by effect size (Cohen's d).Data SynthesisOf the 133 identified studies, 10 met the inclusion criteria. The meta-analysis showed positive effects on gait speed (0.21 [-0.09, 0.51]), endurance (0.21 [-0.06, 0.49]), and gross motor function in dimension D (0.18 [-0.10, 0.45]) and dimension E (0.12 [- 0.15, 0.40]).ConclusionThe results obtained suggest that this training benefits people with cerebral palsy, specifically by increasing walking speed and endurance and improving gross motor functions. For future studies, we suggest investigating device configuration parameters and conducting a large number of randomized controlled trials with larger sample sizes and individuals with homogeneous impairment.



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Prognostic role of Nectin-4 expression in luminal B (HER2 negative) breast cancer

Publication date: Available online 24 July 2017
Source:Pathology - Research and Practice
Author(s): Jasmina Rajc, Damir Gugić, Irena Fröhlich, Ksenija Marjanović, Boris Dumenčić
Nectins are Ca2+-independent immunoglobulin (Ig) superfamily proteins that participate in the organization of epithelial and endothelial junctions and regulate several cellular activities including the entry of some viruses. Nectin-4 has recently been shown as a metastasis-associated protein in several cancers. In the following study, we have evaluated the expression of Nectin-4 inthe luminal B HER2 negative subtype breast cancer. The study group consisted of 147 patients presenting with primary unilateral breast carcinoma with no evidence of distant metastases. Nectin-4 protein expression was assessed by immunohistochemistry and the results were correlated with the clinical data using Kaplan–Meier curves, univariate and multivariate stepwise proportional-hazard analysis (Cox model).Nectin-4 overexpression was significantly correlated with the tumour size (p<0.05; Fisher's Exact Test), also Nectin-4 expression was negatively associated with overall survival, disease free survival and distant relapse free survival with the same significance (p<0,001; Kaplan-Meier, Cox model). We did not find statistically significant correlation between Nectin-4 and age, ER, PR, age, lymph node metastasis, tumour differentiation, histologicalsubtype and Ki-67proliferation index.We suggest that Nectin-4 is a relevant prognostic factor and a therapeutic target in luminalB (HER2 negative) breast cancer.



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Editorial Board

Publication date: August 2017
Source:Pathology - Research and Practice, Volume 213, Issue 8





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Nuclear maspin expression: a biomarker for budding assessment in colorectal cancer specimens

Publication date: Available online 24 July 2017
Source:Pathology - Research and Practice
Author(s): Laura Banias, Simona Gurzu, Zsolt Kovacs, Tivadar Bara, Tivadar Bara, Ioan Jung
AimTo evaluate the maspin expression in colorectal carcinomas (CRC) and its possible role in quantification of the tumor budding.MethodsThe tumor budding was prospectively quantified in 49 consecutive cases of patients that underwent surgical resection for CRC. The cases were divided in two groups: group A (n=23) − low budding (<5 tumor buds per high microscopic field) and group B (n=26) − high budding CRCs (≥5 buds). Maspin expression was evaluated in the tumor core and the buds from the hot spot area in 44 of the microsatellite stable adenocarcinomas. Its expression was quantified as negative, cytoplasmic only, nuclear only or mixed expression (cytoplasm and nucleus).ResultsCompared with group A, a higher pT (p <0.0001) and pN stage (p=0.0001) and infiltrating aspect at macroscopic evaluation (p=0.0081) was identified in group B. No correlation between the maspin expression in the tumore core and the budding grade was noted (p=0.14). Compared with the tumor core, the cytoplasm to nuclear translocation of maspin was more frequently observed in cases from group B than A (n=0.0063).ConclusionFor the colorectal carcinomas, the infiltrative aspect at macroscopic evaluation and nuclear maspin in the buds might be used as indicators of risk for lymph node metastases. Maspin nuclear expression in the buds may be helpful for a proper budding assessment and may serve as a negative prognostic factor.



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Efficacy of new natural biomodification agents from Anacardiaceae extracts on dentin collagen cross-linking

Publication date: Available online 24 July 2017
Source:Dental Materials
Author(s): M.A. Moreira, N.O. Souza, R.S. Sousa, D.Q. Freitas, M.V. Lemos, D.M. De Paula, F.J.N. Maia, D. Lomonaco, S.E. Mazzetto, V.P. Feitosa
ObjectivesSeveral polyphenols from renewable sources were surveyed for dentin biomodification. However, phenols from cashew nut shell liquid (CNSL, Anacardium occidentale) and from Aroeira (Myracrodruon urundeuva) extract have never been evaluated. The present investigation aimed to compare the dentin collagen crosslinking (biomodification) effectiveness of polyphenols from Aroeira stem bark extract, proanthocyanidins (PACs) from grape-seed extract (Vitis vinifera), cardol and cardanol from CNSL after clinically relevant treatment for one minute.MethodsThree-point bending test was used to obtain the elastic modulus of fully demineralized dentin beams before and after biomodification, whilst color change and mass variation were evaluated after four weeks water biodegradation. Color aspect was assessed by optical images after biodegradation whereas collagen cross-linking was investigated by micro-Raman spectroscopy. Statistical analysis was performed with repeated-measures two way ANOVA and Tukey's test (p<0.05).ResultsThe increase in elastic modulus after biomodification was in the order cardol>cardanol>aroeira=PACs with cardol solution achieving mean 338.2% increase. The mass increase after biomodification followed the same order aforementioned. Nevertheless, after four weeks aging, more hydrophobic agent (cardanol) induced the highest resistance against water biodegradation. Aroeira and cardol attained intermediate outcomes whereas PACs provided the lower resistance. Tannin-based agents (Aroeira and PACs) stained the specimens in dark brown color. No color alteration was observed with cardol and cardanol treatments. All four agents achieved crosslinking in micro-Raman after one minute application.SignificanceIn conclusion, major components of CNSL yield overall best dentin biomodification outcomes when applied for one minute without staining the dentin collagen.

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The interrelationship of microstructure and hardness of human coronal dentin using reference point indentation technique and micro-Raman spectroscopy

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Publication date: Available online 24 July 2017
Source:Dental Materials
Author(s): Rasoul Seyedmahmoud, Jacob D. McGuire, Yong Wang, Ganesh Thiagarajan, Mary P. Walker
ObjectivesThe aim of this paper is to determine the interrelationship between the microstructure – in terms of chemical composition and crystallinity – to the microhardness of coronal dentin.MethodsDentin microhardness was tested by a novel reference point indenter and compared to the traditional Knoop hardness method. Micro-Raman spectroscopy was used to determine the chemical composition and crystallinity of dentin.ResultsFrom the occlusal groove to the border of the coronal pulp chamber, dentin hardness decreased from superficial dentin (SD) to deep dentin (DD). Mineral/organic matrix ratios (phosphate/CH and phosphate/amide I) also decreased from SD to DD; however, this change was significant (P<0.05) in the phosphate/amide I ratio only. The phosphate/carbonate ratio decreased significantly by varying position from SD to DD. The degree of the crystallinity, as measured by the full width at half maximum (FWHM) of the peak at 960cm−1, decreased significantly going from superficial to deep dentin.SignificanceFor the first time, the interrelationship between the microstructure and the mechanical properties of coronal dentin was determined by using the novel reference point indentation technique and micro-Raman spectroscopy. We hypothesize that the decrease in hardness from superficial to deep dentin can potentially be explained by decreased mineral content and increased carbonate content, which is also associated with decreased crystallinity. Collectively, there is a positive association between dentin hardness and mineral content and a negative association between dentin hardness and carbonate content.



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IFC(EDITORIAL BOARD)

Publication date: August 2017
Source:DNA Repair, Volume 56





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Naringenin Ameliorates Behavioral Dysfunction and Neurological Deficits in a d-Galactose-Induced Aging Mouse Model Through Activation of PI3K/Akt/Nrf2 Pathway

Rejuvenation Research , Vol. 0, No. 0.


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Physical Activity and Cognitive Function of Long-Distance Walkers: Studying Four Days Marches Participants

Rejuvenation Research , Vol. 0, No. 0.


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Genomic Medicine in Cardiovascular Fellowship Training.

Author: Aday, Aaron W. MD; MacRae, Calum A. MD, PhD
Page: 345-346


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Age-Related Autonomous Aldosteronism.

Author: Nanba, Kazutaka MD *; Vaidya, Anand MD, MMSc *; Williams, Gordon H. MD; Zheng, Isabel; Else, Tobias MD; Rainey, William E. PhD
Page: 347-355


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Aldosterone in Advancing Age: Don't Shoot the Messenger.

Author: Funder, John W. MD, PhD
Page: 356-358


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Effect of Rosuvastatin on Carotid Intima-Media Thickness in Children With Heterozygous Familial Hypercholesterolemia: The CHARON Study (Hypercholesterolemia in Children and Adolescents Taking Rosuvastatin Open Label).

Author: Braamskamp, Marjet J.A.M. MD, PhD; Langslet, Gisle MD; McCrindle, Brian W. MD, MPH; Cassiman, David MD, PhD; Francis, Gordon A. MD; Gagne, Claude MD; Gaudet, Daniel MD, PhD; Morrison, Katherine M. MD; Wiegman, Albert MD, PhD; Turner, Traci MD; Miller, Elinor AB, MD; Kusters, D. Meeike MD, PhD; Raichlen, Joel S. MD; Martin, Paul D. PhD; Stein, Evan A. MD, PhD; Kastelein, John J.P. MD, PhD; Hutten, Barbara A. PhD, MSc
Page: 359-366


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A Novel [alpha]-Calcitonin Gene-Related Peptide Analogue Protects Against End-Organ Damage in Experimental Hypertension, Cardiac Hypertrophy, and Heart Failure.

Author: Aubdool, Aisah A. BSc, MRes, PhD; Thakore, Pratish BSc, MSc; Argunhan, Fulye BSc, MSc; Smillie, Sarah-Jane BSc, PhD; Schnelle, Moritz MD, PhD; Srivastava, Salil BSc, MRes, PhD; Alawi, Khadija M. BSc, MSc, PhD; Wilde, Elena BSc; Mitchell, Jennifer BSc, MRes; Farrell-Dillon, Keith BSc, MSc; Richards, Daniel A. BSc, MRes, PhD; Maltese, Giuseppe MD; Siow, Richard C. BSc, PhD; Nandi, Manasi BSc, PhD; Clark, James E. BSc, PhD; Shah, Ajay M. MD, FMedSci; Sams, Anette MSc, PhD; Brain, Susan D. BSc, PhD
Page: 367-383


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Calcitonin Gene-Related Peptide Receptor Agonism: A Double-Edged Sword?.

Author: Danser, A. H. Jan PhD; MaassenVanDenBrink, Antoinette PhD
Page: 384-387


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Vascular CXCR4 Limits Atherosclerosis by Maintaining Arterial Integrity: Evidence From Mouse and Human Studies.

Author: Doring, Yvonne PhD *; Noels, Heidi PhD *; van der Vorst, Emiel P.C. PhD +; Neideck, Carlos MSc +; Egea, Virginia PhD; Drechsler, Maik PhD; Mandl, Manuela PhD; Pawig, Lukas PhD; Jansen, Yvonne BS; Schroder, Katrin PhD; Bidzhekov, Kiril PhD; Megens, Remco T.A. PhD; Theelen, Wendy PhD; Klinkhammer, Barbara M. PhD; Boor, Peter MD, PhD; Schurgers, Leon PhD; van Gorp, Rick MSc; Ries, Christian PhD; Kusters, Pascal J.H. MSc; van der Wal, Allard MD, PhD; Hackeng, Tilman M. PhD; Gabel, Gabor MD; Brandes, Ralf P. MD; Soehnlein, Oliver MD, PhD; Lutgens, Esther MD, PhD; Vestweber, Dietmar PhD; Teupser, Daniel MD; Holdt, Lesca M. MD; PhD; Rader, Daniel J. MD; Saleheen, Danish MD; Weber, Christian MD
Page: 388-403


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Transcatheter Therapy for Mitral Regurgitation Clinical Challenges and Potential Solutions.

Author: Sorajja, Paul MD; Leon, Martin B. MD; Adams, David H. MD; Webb, John G. MD; Farivar, R. Saeid MD, PhD
Page: 404-417


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Highlights From the Circulation Family of Journals.

Author:
Page: 418-423


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Health Resource Implications of Heart Failure Hospitalizations in Younger Patients Compared With Older Patients.

Author: McAlister, Finlay A. MD, MSc; Youngson, Erik MMath; Kaul, Padma PhD
Page: 424-427


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Letter by Smiseth and Nagueh et al Regarding Article, "Role of Diastolic Stress Testing in the Evaluation for Heart Failure With Preserved Ejection Fraction: A Simultaneous Invasive-Echocardiographic Study".

Author: Smiseth, Otto A. MD, PhD; Nagueh, Sherif F. MD; On behalf of the American Society of Echocardiography and European Association of Cardiovascular Imaging Diastology Writing Group
Page: 428-429


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Response by Obokata and Borlaug to Letter Regarding Article, "Role of Diastolic Stress Testing in the Evaluation for Heart Failure With Preserved Ejection Fraction: A Simultaneous Invasive-Echocardiographic Study".

Author: Obokata, Masaru MD, PhD; Borlaug, Barry A. MD
Page: 430-431


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Letter by Koh Regarding Article, "Genetic Obesity and the Risk of Atrial Fibrillation: Causal Estimates from Mendelian Randomization".

Author: Kon Koh, Kwang MD, PhD
Page: 432-433


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Response by Chatterjee et al to Letter Regarding Article, "Genetic Obesity and the Risk of Atrial Fibrillation: Causal Estimates From Mendelian Randomization".

Author: Chatterjee, Neal A. MD, MSc; Chasman, Daniel I. PhD; Albert, Christine M. MD, MPH
Page: 434-435


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Development of Palliative Care in China: A Tale of Three Cities

AbstractBackground.China is the most populous country in the world, but access to palliative care is extremely limited. A better understanding of the development of palliative care programs in China and how they overcome the barriers to provide services would inform how we can further integrate palliative care into oncology practices in China. Here, we describe the program development and infrastructure of the palliative care programs at three Chinese institutions, using these as examples to discuss strategies to accelerate palliative care access for cancer patients in China.Methods.Case study of three palliative care programs in Chengdu, Kunming, and Beijing.Results.The three examples of palliative care delivery in China ranged from a comprehensive program that includes all major branches of palliative care in Chengdu, a program that is predominantly inpatient‐based in Kunming, and a smaller program at an earlier stage of development in Beijing. Despite the numerous challenges related to the limited training opportunities, stigma on death and dying, and lack of resources and policies to support clinical practice, these programs were able to overcome many barriers to offer palliative care services to patients with advanced diseases and to advance this discipline in China through visionary leadership, collaboration with other countries to acquire palliative care expertise, committed staff members, and persistence.Conclusion.Palliative care is limited in China, although a few comprehensive programs exist. Our findings may inform palliative care program development in other Chinese hospitals.Implications for Practice.With a population of 1.3 billion, China is the most populous country in the world, and cancer is the leading cause of death. However, only 0.7% of hospitals offer palliative care services, which significantly limits palliative care access for Chinese cancer patients. Here, we describe the program development and infrastructure of three palliative care programs in China, using these as examples to discuss how they were able to overcome various barriers to implement palliative care. Lessons from these programs may help to accelerate the progress of palliative cancer care in China.

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The Harm in Kratom



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What's the Harm?



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Soft Tissue Sarcomas of the Extremities: Surgical Margins Can Be Close as Long as the Resected Tumor Has No Ink on It

AbstractBackground.Soft tissue sarcomas (STS) arising in the extremities pose a therapeutic challenge due to concerns of functional morbidity. Resections with negative margins are the mainstay of therapy, but the prognostic significance of surgical margins remains controversial. The purpose of this study was to determine the prognostic impact of surgical margins and clear margin widths in patients with STS of the extremities.Materials and Methods.We assessed the relationship between local recurrence‐free (LRFS), disease‐specific (DSS), and metastasis‐free survival (MFS) and potential prognostic factors retrospectively in a consecutive series of 643 patients treated at our institution between 1996 and 2016. Potential prognostic factors were assessed using univariate and multivariate analyses.Results.The median follow‐up time after primary diagnosis was 5.4 years (95% confidence interval [CI]: 4.8–6.0). The five‐year estimates of the DSS, LRFS, and MFS rates in the entire cohort were 85.3% (95% CI: 81.6–88.3), 65.3% (95% CI: 60.8–69.5) and 78.0% (95% CI: 74.1–81.4), respectively. Histological grade and the quality of surgical margins were independent prognostic factors of all three survival endpoints (LRFS, DSS, MFS) in multivariate analyses. Within the R0 subgroup, univariate and multivariate analyses of categorized (≤1 mm vs. 1–5 mm vs. >5 mm) and non‐categorized margin widths revealed that close and wide negative margins led to similar outcomes. Adjuvant radiation improved local control independently, but not DSS and MFS.Conclusion.Microscopically negative margins were associated with better LRFS, DSS, and MFS regardless of whether adjuvant radiation was applied. Here, surgical margins can be close as long as the resected tumor has no ink on it.Implications for Practice.In the present retrospective analysis of 643 patients with primary soft issue sarcomas of the extremities, surgical margins could be identified as independent predictors of local recurrence‐free, disease‐specific, and metastasis‐free survival. Given the diminished outcome of patients left with positive margins, surgical efforts should aim to achieve microscopically negative margins whenever feasible. It is noteworthy that only the quality of surgical margins, but not the negative margin width attained, had an influence on the prognosis. Our findings suggest that surgical margins can be close as long as the resected tumor has no ink on it.

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Acute toxicity of chlorpyrifos and carbosulfan to glochidia of the freshwater mussel Hyriopsis bialata Simpson, 1900

Abstract

The acute toxicity of carbosulfan and chlorpyrifos in formulated pesticides to glochidia (larvae) of the freshwater mussel (Hyriopsis bialata Simpson, 1900) was evaluated under static conditions in moderately hard dechlorinated tap water. Measured pesticide concentrations were 26 to 34% lower than nominal concentrations; therefore, all results are expressed in terms of measured active ingredient. Carbosulfan was relatively non-toxic to the mussel larvae with median effective concentrations (EC50) of carbosulfan at 24 and 48 h greater than 0.10 mg/L. The EC50s of chlorpyrifos at 24 and 48 h were 0.083 and 0.078 mg/L, respectively (measured concentrations). The 48-h EC50 of a combined exposure to a mixture of chlorpyrifos and carbosulfan at a constant ratio of 2.9:1 was 0.0142:0.049 mg CP:CB/L. In a separate experiment, the effect of water hardness on carbosulfan, chlorpyrifos, or a combined exposure was assessed using glochidia exposed to either soft, moderately hard, or hard reconstituted water. There was no effect of water hardness on the survival of glochidia after 24- or 48-h exposure to carbosulfan. The chlorpyrifos 48-h EC50s in soft water, moderately hard water, and hard water were 0.18, 0.11, and 0.16 mg/L, respectively. The data indicate that the lowest water hardness resulted in the highest survival of glochidia, whereas an increase to moderate water hardness resulted in significantly decreased survival of glochidia (F = 15.5, P < 0.05). The EC50s of a combined exposure at 48 h in soft water, moderately hard water, and hard water were 0.124:0.044, 0.132:0.047, and 0.064:0.022 mg CP:CB/L, respectively. The data indicate that the combined toxicity was lowest at low and moderate water hardness, whereas an increase to high water hardness resulted in a significantly decreased survival of glochidia. After 48 h, the toxicity of the combined chlorpyrifos and carbosulfan exposure in soft and hard water was greater than that of chlorpyrifos alone.



http://ift.tt/2v23Z70

Market segmentation and industry overcapacity considering input resources and environmental costs through the lens of governmental intervention

Abstract

The problems with China's regional industrial overcapacity are often influenced by local governments. This study constructs a framework that includes the resource and environmental costs to analyze overcapacity using the non-radial direction distance function and the price method to measure industrial capacity utilization and market segmentation in 29 provinces in China from 2002 to 2014. The empirical analysis of the spatial panel econometric model shows that (1) the industrial capacity utilization in China's provinces has a ladder-type distribution with a gradual decrease from east to west and there is a severe overcapacity in the traditional heavy industry areas; (2) local government intervention has serious negative effects on regional industry utilization and factor market segmentation more significantly inhibits the utilization rate of regional industry than commodity market segmentation; (3) economic openness improves the utilization rate of industrial capacity while the internet penetration rate and regional environmental management investment have no significant impact; and(4) a higher degree of openness and active private economic development have a positive spatial spillover effect, while there is a significant negative spatial spillover effect from local government intervention and industrial structure sophistication. This paper includes the impact of resources and the environment in overcapacity evaluations, which should guide sustainable development in emerging economies.



http://ift.tt/2vU78SP

Escherichia coli maltose-binding protein (MBP) activates mouse Th1 through TLR2-mediated MyD88-dependent pathway and TLR4-mediated TRIF-dependent pathway

Publication date: September 2017
Source:International Immunopharmacology, Volume 50
Author(s): GuoMu Liu, YiXin Zhang, NanNan Zhang, WeiHua Ni, Jing Jie, LiNa Jiang, GuiXiang Tai
MBP (maltose-binding protein) is a component of Escherichia coli. Our previous study found that MBP directly induces the activation of Th1 (T helper type 1), but the molecular mechanism remains unclear. In the present study, CD4+T cells were purified from the spleens of normal mice using antibody-coated immunomagnetic beads by negative selection. CD4+T cells activated with a CD3/CD28 antibody were stimulated with MBP. The results indicated that MBP elevated IFN-γ mRNA levels in activated CD4+T cells and promoted IFN-γ production from activated CD4+T cells. To explore TLR2/TLR4 signaling involved in the mechanism of MBP-induced activation of Th1, we further detected downstream molecules of TLR2/TLR4 signaling. We found that MBP increased the mRNA levels of MyD88, TRAF6, TRIF and TRAF3 expressed in CD4+T cells. The results suggested that downstream molecules of TLR2/TLR4 signaling may be involved in MBP-induced activation of CD4+T cells. Furthermore, MyD88, TRIF, TRAF3 and TRAF6 expressed in activated CD4+T cells blocked with anti-TLR2 antibody or anti-TLR4 antibody followed by treatment with MBP were detected via RT-PCR and western blotting, respectively. MBP decreased the production of IFN-γ in CD4+T cells in the presence of anti-TLR2, accompanied by the down-regulated expression of MyD88 and TRAF6. However, MBP increased the production of IFN-γ in CD4+T cells in the presence of anti-TLR4 antibody accompanied by the up-regulated expression of MyD88 and the down-regulated expression of TRIF, TRAF6 and TRAF3. The results suggested that the MyD88-dependent pathway of TLR2 and TRIF-dependent pathway are involved in the mechanism of Th1 activation induced by MBP. Our study has contributed to the clarification of the molecular mechanism of MBP-induced activation of CD4+T cells.



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Effects of BPF on steroid hormone homeostasis and gene expression in the hypothalamic–pituitary–gonadal axis of zebrafish

Abstract

Bisphenol F (BPF) has been frequently detected in various environmental compartments, and previous studies found that BPF exhibits similar estrogenic and anti-androgenic effects on the mammalian endocrine system to those of bisphenol A (BPA). However, the potential disrupting effects of BPF on aquatic organisms and the underling disrupting mechanisms have not been investigated. In this study, the potential disrupting mechanisms of BPF on the hypothalamic–pituitary–gonadal (HPG) axis and liver were probed by employing the OECD 21-day short-term fecundity assay in zebrafish. The results show that BPF exposure (1 mg/L) impaired the reproductive function of zebrafish, as exemplified by alterations to testicular and ovarian histology of the treated zebrafish. Homogenate testosterone (T) levels in male zebrafish decreased in a concentration-dependent manner, and 17β-estradiol (E2) levels increased significantly when fish were exposed to 0.1 and 1 mg/L BPF. The real-time polymerase chain reaction was performed to examine gene expression in the HPG axis and liver. Hepatic vitellogenin expression was significantly upregulated in males, suggesting that BPF possesses estrogenic activity. The disturbed hormone balance was enhanced by the significant changes in gene expression along the HPG axis. These alterations suggest that BPF leads to adverse effects on the endocrine system of teleost fish, and that these effects were more prominent in males than in females.



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Evaluation of colour temperatures in the cultivation of Dunaliella salina and Nannochloropsis oculata in the production of lipids and carbohydrates

Abstract

The production of biofuels from microalgae is a promising and sustainable alternative. Its production is determined by the content of lipids and carbohydrates, which is different for each microalgae species and is affected by environmental factors, being lighting one of the principal determining their biochemical composition. The colour temperature (electromagnetic radiation and light spectrum) is a determining factor for the production of lipids and carbohydrates in microalgae. The aim of this assay was to evaluate the effect of three colour temperatures (6500, 10,000 and 20,000 °K) on the biomass (cel mL−1), biomass production and productivity (g L−1 and g L−1 day−1), lipid and carbohydrate content (%), lipid and carbohydrate production and productivity (mg L−1 and mg L−1 day−1), composition and content of fatty acids (%) in two microalgae species: Dunaliella salina and Nannochloropsis oculata. The highest cell density was observed for N. oculata in stationary phase in the control (83.93 × 106 cel mL−1). However, higher lipid content was obtained in D. salina in stationary phase at 10,000 °K (80%), while N. oculata showed 67% at 6500 °K. The highest carbohydrate content was 25% in stationary phase for D. salina at 20,000 °K. Regarding the production of lipids, D. salina reached a maximum of 523 mg L−1 in exponential phase at 6500 and 10,000 °K. The highest carbohydrate production was 38 mg L−1 for D. salina in exponential phase at 20,000 °K. In both microalgae, 15 different fatty acids were identified; the most abundant was palmitic acid with 35.8% for N. oculata in stationary phase at 10,000 °K, while D. salina showed 67% of polyunsaturated fatty acids in exponential phase at 6500 °K. In conclusion, the ideal colour temperature for microalgae culture to obtain biofuels should be based on the biomolecule of interest, being necessary to individually evaluate for each species.



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Influence of orientation, glazing proportion and zone aspect ratio on the thermal performance of buildings during the winter period

Abstract

The objective of this study is to assess the effect of orientation, glazing proportion and aspect ratio of building zones on heat fluxes through their surfaces, under specific environmental conditions. The investigation is carried out for thermally-insulated building zones with a varying facade orientation corresponding to each cardinal point, during the winter period in the northern Greek region. For this purpose, three glazing-to-facade ratios (GR) are taken into account; along with the glazing ratio the influence of the glazing U value is also considered. Regarding the impact of the fenestration layout geometry, five different building aspect ratio profiles are examined. Thermal fluxes are assessed for two different indoor temperature settings, while the operation of the heating unit is assumed to be continuous. The transient thermal analysis with its mathematical formulation and solution are based on the thermal-network modelling approach, while the solar heat gain through glazing relies on the sunlit-pattern approach; in this way, the stricken by the solar rays glazing area is projected onto any interior surfaces to form the so called "sunlit" areas. As the orientation, glazing proportion and aspect ratio of the building zone vary, so do the sizes and shapes of the illuminated "sunlit" areas. Accordingly, the delivered into the zone direct solar energy and its diffused and ground reflected components can be determined. The adopted methodology provides a more accurate determination of solar heat gain with respect to glazing proportion and orientation as well as zone aspect ratio. With regard to surface orientation, glazing proportion and aspect ratio, computer results demonstrate the improvement of the thermal performance for a building zone with a south oriented glazing surface, as well as the deterioration for the other surface orientations; relative increases/decreases in the energy fluxes of a rectangular shaped building zone compared to a square-shaped building zone can reach up to 50%/100%.



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Geochemical fractionation and pollution assessment of Zn, Cu, and Fe in surface sediments from Shadegan Wildlife Refuge, southwest of Iran

Abstract

This research focuses on the fractionation and distribution patterns of heavy metals (Zn, Cu, and Fe) in surficial sediments collected from Shadegan Wildlife Refuge, the biggest wetland in southern part of Iran, to provide an overall classification for the sources of metals in the study area using a sequential extraction method. For this purpose, a four-step sequential extraction technique was applied to define the partitioning of the metals into different geochemical phases of the sediment. The results illustrated that the average total level of Zn, Cu, and Fe in surface sediments were 55.20 ± 16.04, 22.86 ± 5.68, and 25,979.01 ± 6917.91 μg/g dw, respectively. On the average, the chemical partitioning of all metals in most stations was in the order of residual >oxidizable-organic > acid-reducible > exchangeable. In the same way, the results of calculated geochemical indices revealed that Cu, Zn, and Fe concentrations are mainly influenced by lithogenic origins. Compared with consensus-based SQGs, Cu was likely to result in occasionally harmful biological effects on the biota.



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Pb-induced changes in roots of two cultivated rice cultivars grown in lead-contaminated soil mediated by smoke

Abstract

Nowadays, public concerns regarding deleterious effect of lead (Pb) is on rise due to its abundance and toxic effect on plants and other living organisms. In plants, it has no noticeable biological importance but can cause various morphological, physiological, and biochemical malfunctions. To evaluate the remediating potential of plant-derived smoke (Cymbopogon jwarancusa), a pot culture experiment was designed to investigate the physiological, biochemical, metabolic, and antioxidant parameters of roots in lead (0 (control), 500, 1000, and 1500 ppm)-contaminated soil. Under dark condition, seeds were primed in smoke solution with two dilutions (1:500 and 1:1000) for 24 h. With an increasing concentration of Pb stress, fresh and dry weight and total nitrogen and protein contents decreased significantly while an increase was observed in smoke-treated seed. With increasing Pb stress level, metabolites (i.e., proline, total soluble sugar, total soluble protein, glycine betaine), and antioxidants (i.e., superoxide dismutase, peroxidase, catalase, ascorbate peroxidase, malonyldialdehyde, and H2O2), contents of roots were increased in non-treated (without smoke treatment) samples, whereas comparatively, a low level of alteration in aforementioned metabolites and antioxidative parameters was observed in the seeds treated with smoke solution. These results suggest a positive role of smoke in alleviating lead-induced changes in roots of two cultivated cultivars of rice grown in Pb-contaminated soil.



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Short-duration hydrothermal fermentation of food waste: preparation of soil conditioner for amending organic-matter-impoverished arable soils

Abstract

Soil conditioners can be used to compensate for the insufficient soil nutrition and organic matter (OM) of arable soils. However, the traditional preparation method for soil conditioners is lengthy and requires facilities that occupy large tracts of land. In this study, a short-duration hydrothermal fermentation (SHF) method was developed for the preparation of soil conditioners from food waste. The SHF method required only 18 h to produce soil conditioners with physicochemical characteristics that were similar to those of soil conditioners obtained through traditional fermentation (TF), which takes 20 days to complete. Inoculation and dynamic SHF significantly affected the distribution of different molecular weight fractions in the prepared soil conditioners. The results of spectral analysis revealed that a large amount of soluble microbial byproducts and carbohydrate C formed in the SHF soil conditioner. This effect indicated that the SHF soil conditioner supplied not only immediately available nutrients, which can stimulate the growth of soil microbial communities, but also provided sustained-release nutrients for the long-term cultivation of crops on OM-impoverished soils. Cyanobacteria were present in the SHF soil conditioner at a relative abundance of 6.29%, which was 28.6 and 314.5 times those in the raw material and TF soil conditioner, respectively. Amending OM-impoverished soil with the SHF soil conditioner enhanced the carbon pool management index of the resulting SHF soil by 1.50 and 1.12 times those of unfertilized soil and TF soil, respectively. These results indicated that the SHF soil exhibited a high capacity to supply nutrients for crop growth.



http://ift.tt/2vCRJHb

Influence of pH, EDTA/Fe(II) ratio, and microbial culture on Fe(II)-mediated autotrophic denitrification

Abstract

Fe(II)-mediated autotrophic denitrification with four different microbial cultures under different pH and EDTA/Fe(II) conditions was investigated in batch bioassays. Initially, the highest nitrate removal (72%) was achieved with an activated sludge inoculum. The use of pure cultures of Pseudogulbenkiania strain 2002 and Thiobacillus denitrificans resulted in a 55 and 52% nitrate removal, respectively. No denitrification was observed for a mixed culture dominated by Thiobacillus thioparus and T. denitrificans. A longer enrichment on Fe(II) and the supplementation of thiosulfate as additional electron donor were needed to stimulate the denitrifying activity of the Thiobacillus-mixed culture. A second subculture on Fe(II) as sole electron donor resulted in higher denitrification efficiencies for all microbial cultures. In particular, nitrate removal reached up to 84% with a specific nitrate removal rate of 1.160 mM·(g VSS·day)−1 in the bioassays seeded with the Thiobacillus-mixed culture. All cultures were favored by decreasing the EDTA/Fe(II) molar ratio from 2.0 to 0.5. The most significant denitrification enhancement was observed for the Pseudogulbenkiania species, indicating a lower tolerance to EDTA. The two pure cultures effectively maintained denitrification at pH 7.0 and were more sensitive to a pH decrease. Conversely, the optimal pH was 6.0 for the Thiobacillus-mixed and activated sludge cultures.



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Is there still a place for skin graft in giant congenital melanocytic nevus?

Abstract

Background

Congenital melanocytic nevi (CMN) has an incidence of 1–2% in newborns. These lesions can be categorized according to size, namely small, medium, large, and giant. Complete surgical excision is the main line of treatment with reconstruction by serial excision, tissue expansion, local flaps, Integra with skin graft, and skin grafting. Other modalities include curettage, dermabrasion, and laser. The aim of this article was to express the versatility of skin grafts for management of giant nevus.

Methods

All cases with lesions that cannot be closed primarily were included. Patients were 12 females and 4 males. Their ages ranged between 4 months and 22 years. All cases were excised and covered with skin graft.

Results

Full-thickness skin graft was used in combination with split-thickness sheet graft in four cases. All these cases were in the face. The average area of excised nevus was 225.5 cm2. No signs of malignancy were observed in any of the excised nevi. No recurrence was observed in this series.

Conclusions

Surgical and nonsurgical modalities are variable tools for management of giant congenital nevus. No doubt, skin graft is a good option for management of giant nevus.

Level of Evidence: IV, therapeutic study.



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More on molar incisor hypomineralisation (MIH) and linear enamel hypoplasia (LEH) in archaeological human remains



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Eye gaze and pupillary response in Angelman syndrome

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Publication date: September 2017
Source:Research in Developmental Disabilities, Volume 68
Author(s): Michael P. Hong, Janna L. Guilfoyle, Lindsey N. Mooney, Logan K. Wink, Ernest V. Pedapati, Rebecca C. Shaffer, John A. Sweeney, Craig A. Erickson
BackgroundAngelman syndrome (AS) is a rare neurological disorder characterized by severe developmental disability, communication impairment, elevated seizure risk, and motor system abnormalities.AimsThe aims of this study were to determine the feasibility of social scene eye tracking and pupillometry measures in individuals with AS and to compare the performance of AS participants to individuals with idiopathic Autism Spectrum Disorder (ASD) and typically developing controls (TDC).Methods and proceduresIndividuals with AS and age- and gender- matched controls completed a social eye tracking paradigm. Neurobehavioral characterization of AS participants was completed via a battery of psychological testing and caregiver behavioral evaluations.Outcomes and resultsEight of seventeen recruited AS participants completed the eye tracking paradigm. Compared to TDC, AS subjects demonstrated significantly less preference for social scenes than geometric shapes. Additionally, AS subjects showed less pupil dilation, compared to TDC, when viewing social scenes versus geometric shapes. There was no statistically significant difference found between AS and ASD subjects in either social eye tracking or pupillometry.Conclusions and implicationsThe use of eye tracking and pupillometry may represent an innovative measure for quantifying AS-associated impairments in social salience.



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The Androgen Receptor Supports Tumor Progression After the Loss of Ovarian Function in a Preclinical Model of Obesity and Breast Cancer

Abstract

The androgen receptor (AR) has context-dependent roles in breast cancer growth and progression. Overall, high tumor AR levels predict a favorable patient outcome, but several studies have established a tumor promotional role for AR, particularly in supporting the growth of estrogen receptor positive (ER-positive) breast cancers after endocrine therapy. Our previous studies have demonstrated that obesity promotes mammary tumor progression after ovariectomy (OVX) in a rat model of postmenopausal breast cancer. Here, we investigated a potential role for AR in obesity-associated post-OVX mammary tumor progression following ovarian estrogen loss. In this model, we found that obese but not lean rats had nuclear localized AR in tumors that progressed 3 weeks after OVX, compared to those that regressed. AR nuclear localization is consistent with activation of AR-dependent transcription. Longer-term studies (8 weeks post-OVX) showed that AR nuclear localization and expression were maintained in tumors that had progressed, but AR expression was nearly lost in tumors that were regressing. The anti-androgen enzalutamide effectively blocked tumor progression in obese rats by promoting tumor necrosis and also prevented the formation of new tumors after OVX. Neither circulating nor mammary adipose tissue levels of the AR ligand testosterone were elevated in obese compared to lean rats; however, IL-6, which we previously reported to be higher in plasma from obese versus lean rats, sensitized breast cancer cells to low levels of testosterone. Our study demonstrates that, in the context of obesity, AR plays a role in driving ER-positive mammary tumor progression in an environment of low estrogen availability, and that circulating factors unique to the obese host, including IL-6, may influence how cancer cells respond to steroid hormones.



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Isolation of limonoid compound (Hamisonine) from endophytic fungi Penicillium oxalicum LA-1 (KX622790) of Limonia acidissima L. for its larvicidal efficacy against LF vector, Culex quinquefasciatus (Diptera: Culicidae )

Abstract

Upon screening for novel and potential biocompounds with larvicidal activities, we successfully isolated hamisonine (HMSN) a limonoid compound from endophytic fungi Penicillium oxalicum LA-1 of Limonia acidissima. The extracted compound structure was elucidated by spectral studies such as UV-vis spectroscopy, thin-layer chromatography, FTIR, LC-ESI-MS, 1H NMR, and 13C NMR upon comparing with the spectral data available in the literature. Further, the isolated HMSN was tested against III and IV instar Culex quinquefasciatus larvae. The outcome of this study clearly emphasize that the extracted compound HMSN possesses a stupendous larvicidal activity in a dose-dependent manner with the LC50 and LC90 values of 1.779 and 7.685 ppm against III instar larvae and 3.031 and 28.498 ppm against IV instar larvae of C. quinquefasciatus, respectively. Interestingly, the histological studies evidently showing the damage of peritrophic membrane and epithelial cells of testing mosquito larvae.



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A diagnostically difficult case of a cellular pleural fluid: Morphology, immunohistochemistry, and fluorescence in situ hybridization study

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Minhua Wang, Shabnam Samankan, Amarpreet Bhalla, N Paul Ohori, Nora K Frisch

CytoJournal 2017 14(1):18-18



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Interobserver reproducibility of the Paris system for reporting urinary cytology

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Theresa Long, Lester J Layfield, Magda Esebua, Shellaine R Frazier, D Tamar Giorgadze, Robert L Schmidt

CytoJournal 2017 14(1):17-17

Background: The Paris System for Reporting Urinary Cytology represents a significant improvement in classification of urinary specimens. The system acknowledges the difficulty in cytologically diagnosing low-grade urothelial carcinomas and has developed categories to deal with this issue. The system uses six categories: unsatisfactory, negative for high-grade urothelial carcinoma (NHGUC), atypical urothelial cells, suspicious for high-grade urothelial carcinoma, high-grade urothelial carcinoma, other malignancies and a seventh subcategory (low-grade urothelial neoplasm). Methods: Three hundred and fifty-seven urine specimens were independently reviewed by four cytopathologists unaware of the previous diagnoses. Each cytopathologist rendered a diagnosis according to the Paris System categories. Agreement was assessed using absolute agreement and weighted chance-corrected agreement (kappa). Disagreements were classified as low impact and high impact based on the potential impact of a misclassification on clinical management. Results: The average absolute agreement was 65% with an average expected agreement of 44%. The average chance-corrected agreement (kappa) was 0.32. Nine hundred and ninety-nine of 1902 comparisons between rater pairs were in agreement, but 12% of comparisons differed by two or more categories for the category NHGUC. Approximately 15% of the disagreements were classified as high clinical impact. Conclusions: Our findings indicated that the scheme recommended by the Paris System shows adequate precision for the category NHGUC, but the other categories demonstrated unacceptable interobserver variability. This low level of diagnostic precision may negatively impact the applicability of the Paris System for widespread clinical application.

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The Science of Selection: Using Best Practices From Industry to Improve Success in Surgery Training

Publication date: Available online 24 July 2017
Source:Journal of Surgical Education
Author(s): Aimee K. Gardner, Teodor Grantcharov, Brian J. Dunkin
BackgroundThe selection of high-quality applicants is critical to the future of surgery. However, it is unclear if current practices meet industry criteria of a successful selection system, as measured by administrative efficiency and performance and attrition of those selected.MethodsWe performed a modified systematic review process to gain an understanding of current selection processes, remediation practices, and attrition rates in surgery residency training programs in the United States. We also conducted semistructured interviews with local residency program directors and coordinators to obtain a specific snapshot of the amount of time and resources dedicated to these activities in various sized programs. The associated financial costs of these activities are also presented.ResultsThe administrative costs for current residency selection processes are substantial, ranging from $45,000 to $148,000 for each program per year. Approximately 30% of residents require at least 1 remediation intervention, costing programs $3400 to $5300 per episode, and typically involve concerns around nontechnical skills. Attrition rates range from 20% to 40%.ConclusionsThis review suggests that additional methodologies may allow surgery residency programs to identify best-fit candidates more efficiently and effectively, while also decreasing remediation and attrition rates. Possible solutions include incorporation of structured interviews, personality inventories, and situational judgment tests. Resources dedicated to current interview practices, remediation efforts, and attrition management can be redirected to support these methodologies. By applying the science of selection and assessment to the recruitment process, programs may be able to make more data-driven decisions to identify candidates who will be successful at their institution.



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Deal or no deal? The prevalence and nutritional quality of price promotions among U.S. food and beverage purchases

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Publication date: 1 October 2017
Source:Appetite, Volume 117
Author(s): Lindsey Smith Taillie, Shu Wen Ng, Ya Xue, Matthew Harding
ObjectiveThis study examines trends in the prevalence of price promotions among packaged food and beverage purchases, differences in prevalence by household race/ethnicity or income, and the association between price promotions and the nutritional profile of purchases.DesignThis cross-sectional study utilizes a dataset of 90 million purchases from 38,744 (2008) to 45,042 (2012) US households in 2008–2012. Chi-square tests were used to examine whether the proportion of purchases with price promotions changed over time or differed by household race/ethnicity or income. T-tests were used to compare purchased products' nutritional profiles.ResultsPrevalence of price promotions among packaged food and beverage purchases increased by 8% and 6%, respectively, from 2008 to 2012, with both reaching 34% by 2012. Higher-income households had greater proportions of purchases with price promotions than lower-income households. Asian households had the highest proportion of purchases with any price promotion, followed by non-Hispanic whites. While total price-promoted packaged food purchases had higher mean energy, total sugar, and saturated fat densities than purchases with no price promotions, absolute differences were small.ConclusionsPrevalence of price promotions among US household purchases increased from 2008 to 2012 and was greater for higher-income households. No clear associations emerged between presence of price promotions and nutritional quality of purchases.



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Patient-driven hand hygiene audit process at a regional cancer center

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Publication date: Available online 24 July 2017
Source:American Journal of Infection Control
Author(s): E.J. Bow, V. Bourrier, J. Trudel, N. Kostiuk, J.M. McLeod
A patient-driven hand hygiene compliance audit strategy was piloted in a Canadian provincial cancer agency during routine provision of cancer outpatient care by health care providers (physicians, nurses, and health care aides) under conditions where the deployment of an independent external auditor was not feasible. The results of the audit suggest the feasibility of this approach as a routine institutional performance metric.



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Characteristics of methicillin-resistant Staphylococcus aureus in patients on admission to a teaching hospital in Rio de Janeiro, Brazil

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Publication date: Available online 24 July 2017
Source:American Journal of Infection Control
Author(s): Fernanda Sampaio Cavalcante, Marcos Vinicius Pinheiro, Dennis de Carvalho Ferreira, Celina Vieira da Cunha Guedes Alvarenga, Ana Carolina Fonseca Guimarães, Simone Aranha Nouér, Kátia Regina Netto dos Santos
BackgroundInfections caused by methicillin-resistant Staphylococcus aureus (MRSA) are associated with greater mortality and morbidity; however, risk factors for community-acquired infections caused by MRSA have not been established. Therefore, community patients who are admitted to hospitals without the necessary contact precautions and are infected with community-acquired lineages eventually cause these lineages to spread to these settings. The aim of this study was to detect community-acquired lineages of MRSA in patients on admission to a Brazilian teaching hospital.MethodsThe antimicrobial susceptibility of the MRSA isolates from nasal swabs was evaluated as was the molecular characteristics of the staphylococcal cassette chromosome mec (SCCmec). The clonality was determined using pulsed-field gel electrophoresis and multilocus sequence type analysis.ResultsA total of 702 patients were evaluated between March 2012 and March 2013; 180 (25%) of them were colonized by S aureus, and 21 (3%) were MRSA. The SCCmec IV/USA1100/sequence type (ST) 30 was the predominant MRSA lineage (42.8%), followed by SCCmec IV/USA800/ST5 (23.8%).ConclusionsThe occurrence of MRSA colonization was very low, and only 1 patient from cardiac surgery developed an infection, which was caused by an SCCmec II/USA100/ST5 isolate. Screening for MRSA colonization on admission does not seem to be productive; however, for populations submitted to specific surgeries, active surveillance should be implemented.



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Risk factors of neurosurgical site infection after craniotomy: A systematic review and meta-analysis

Publication date: Available online 24 July 2017
Source:American Journal of Infection Control
Author(s): Chenyan Fang, Tao Zhu, Ping Zhang, Liang Xia, Caixing Sun
BackgroundNeurosurgical site infection (SSI) is a complication related to craniotomy, which may lead to severe morbidity and higher hospital costs during the postoperative period.MethodsRetrospective cohorts, case-control studies, or prospective investigations addressing risk factors of SSI updated until January 2017 were systematically searched in 2 databases (PubMed and Embase). The Newcastle-Ottawa Scale was used to evaluate quality of the included studies, heterogeneity was assessed by I2 tests, and a funnel plot and Egger test were used for the evaluation of publication bias.ResultsThere were 26 studies in total enrolled in this review. The results showed that the risk factors which had relation with SSI were other infection (odds ratio [OR], 5.42; 95% confidence interval [CI], 2.8-10.49), number of operations (>1) (OR, 2.352; 95% CI, 1.142-4.847), cerebrospinal fluid (CSF) leak (OR, 7.817; 95% CI, 2.573-23.751), CSF drainage (OR, 2.55; 95% CI, 1.58-4.11), duration of operation (>4 hours) (as for retrospective cohort studies) (OR, 1.766; 95% CI, 1.110-2.809), venous sinus entry (OR, 4.015; 95% CI, 1.468-10.982), American Society of Anesthesiologists score (>2) (OR, 1.398; 95% CI, 1.098-1.78), sex (male) (as for prospective investigations) (OR, 1.474; 95% CI, 1.013-2.145), and surgical reasons (nontraumatic) (OR, 2.137; 95% CI, 1.106-4.129).ConclusionsAccording to the current analysis, all the factors mentioned were the risk factors for SSI after craniotomy. Patients with these risk factors should be paid more attention to prevent SSI. More evidence provided by high-quality studies is still needed to further investigate the risk factors of SSI.



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Ezrin-Radixin-Moesin Binding Phosphoprotein 50 (EBP50) Suppresses the Metastasis of Breast Cancer and HeLa Cells by Inhibiting Matrix Metalloproteinase-2 Activity

Background: Expression of ezrin-radixin-moesin-binding phosphoprotein-50 (EBP50) is correlated with human breast and cervical cancer development, but its effects on the metastasis of breast and cervical cancer and the underlying mechanism are not fully understood. Materials and Methods: In this study, EBP50 was overexpressed in MDA-MB-231 breast cancer and HeLa cervical cancer cells; moreover, EBP50 was knocked-down in MCF-7 breast cancer cells and HeLa cells. Metastasis-related ability and matrix metalloproteinase-2 (MMP-2) activity of these cells were investigated. Results: Cell adhesion, wound-healing and invasion were significantly suppressed in EBP50-overexpressing cells. Contrarily, EBP50-knockdown promoted cell adhesion, wound healing and invasion. EBP50 overexpression inhibited MMP-2 activity, and the knockdown of EBP50 promoted the activity of MMP-2, suggesting that EBP50 inhibited cell metastasis via suppression of MMP-2 activity. Conclusion: Our work reveals the anti-metastatic effect and a new mechanism of EBP50 action in breast and cervical cancer cells.



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miR-141 Inhibits Proliferation and Migration of Colorectal Cancer SW480 Cells

Background: This study was designed to determine the molecular function of miR-141 and the underlying mechanisms in colorectal cancer (CRC). Materials and Methods: SW480 cells in which miR-141 was up- or down-regulated were established. Reverse transcription, quantitative polymerase chain reaction and Western blotting were used to examine the microRNA and protein expression. Cell-cycle progression was analyzed by flow cytometry. Proliferation marker Ki-67 was evaluated by immunofluorescence. Transwell assay was conducted to determine the migration rates of cells. Subcutaneous xenograft models were used to examine the effect of miR-141 on tumorigenicity. Human mitogen-activated protein kinase (MAPK) and receptor tyrosine kinase (RTK) pathway phosphorylation array assays were used to interrogate MAPK and RTK pathway activation. Results: miR-141 directly targeted zinc finger E-box-binding homeobox 1/2 (ZEB1/2). We first determined the expression levels of ZEB1 and ZEB2 in miR-141-expressing cells and miR-141-knockdown cells and found that inhibition of miR-141 significantly increased the expression of ZEB2. In vitro study revealed that miR-141 overexpression inhibited the expression of Ki-67. Furthermore, overexpression of miR-141 led to a significant reduction in the proliferation of SW480 cells via induction of cell-cycle arrest at the G1 stage. In contrast, inhibition of miR-141 markedly promoted the proliferation of SW480 cells by promoting cell-cycle progression. Moreover, overexpression of miR-141 significantly inhibited SW480 cell migration in vitro. In addition, overexpression of miR-141 significantly reduced tumor size and weight, and inhibited the growth of SW480 cell-derived tumor in nude mice. Notably, overexpression of miR-141 also suppressed the liver metastasis of SW480 cells in nude mice. Using RTK and MAPK arrays, we found increased phosphorylation of hepatocyte growth factor receptor (HGFR/c-MET) following inhibition of miR-141, but phosphorylation of P53, AKT, ERK1/2, P38 and mTOR, etc., in SW480 cells was not affected by miR-141. Conclusion: Our results suggest that miR-141 functions as a tumor suppressor through ZEB2 and HGFR in CRC cells.



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Phase II Study of the Efficacy and Safety of High-dose Pemetrexed in Combination with Cisplatin Versus Temozolomide for the Treatment of Non-small Cell Lung Cancer with Brain Metastases

The aim of this study was to explore the efficacy and safety of high-dose pemetrexed with cisplatin versus combination with temozolomide in patients with brain metastases (BM) of lung adenocarcinoma. After standard whole-brain radiotherapy (WBRT, 30 Gy/10 fractions), patients with BM of non-small cell lung cancer (NSCLC) were given high-dose pemetrexed (900 mg/m2) on day 1 of each cycle (3 weeks), and cisplatin was administered on days 1-3 in the cisplatin-treated group. The temozolomide-treated group was treated as follows: 75 mg/m2 temozolomide orally with concurrent WBRT followed by 150 mg/m2 temozolomide on days 1-5 with high-dose pemetrexed (900 mg/m2) on day 1 of each cycle (3 weeks). Six cycles later, high-dose pemetrexed (900 mg/m2) monotherapy or the best available supportive therapy was administered to both groups. An evaluation was carried out every 2-3 cycles. The primary end-points were objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Secondary end-points included safety and tolerability. Thirty-two patients in the pemetrexed plus cisplatin (PC) group and 28 patients in the pemetrexed plus temozolomide (PT) group were enrolled from November 2013 to October 2015. The ORR was 68.8% and 75%, in the PC and PT groups, respectively, and there was no statistically significant difference between the two groups (p=0.711). The median PFS rates of the PC and PT groups were 13.6 months and 16.9 months, respectively, and the median OS rates of the PC and PT groups were 18.9 months and 19.3 months, respectively. There were no differences in PFS and OS between the two groups. There were no grade 4 or higher side-effects in either group, but grade 3 side-effects such as leucopenia (2/32, 6.3%), nausea/vomiting (2/32, 6.3%), alopecia (1/32, 3.1%), rash (3/32, 9.4%) and renal insufficiency (1/32, 3.1%) were observed in the PC group, whereas the PT-group-only showed the following grade 3 side-effects: leucopenia (1/28, 3.6%) and nausea/vomiting (2/28, 7.1%). The data showed that the PT group achieved the same efficacy in PFS and OS as the PC group but with fewer toxicities. Therefore, high-dose pemetrexed plus temozolomide may be a better regimen for treating NSCLC with BM due to its better safety.



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Effect of Interventional Therapy on the Expression of Survivin mRNA in Cervical Cancer

Aim: To examine the expression of survivin mRNA in cervical squamous cancer at different time points during interventional therapy in order to find the optimal time point for continual treatment. Patients and Methods: Fifty patients with stage IB2-IIB cervical squamous cancer receiving transarterial infusion chemotherapy and chemoembolization were included in the present study. The expression of survivin mRNA in cancer samples before and after interventional therapy (on days 7, 14 and 21) were examined by reverse transcription-polymerase chain reaction. Results: The expression of survivin mRNA in cancer samples before the interventional therapy was significantly higher than that of any time point after the interventional therapy (p<0.05). After treatment, the expression of survivin mRNA decreased until day 14. Conclusion: The expression of survivin mRNA was inhibited by the interventional therapy. It seems that day 14 after interventional treatment is the right time point for continuation of treatment.



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Study of Preoperative Antiviral Treatment of Patients with HCC Negative for HBV-DNA

Aim: To study preoperative HBV-DNA negative HBV-related hepatocellular carcinoma (HCC) which was reactivated after surgery and could influence liver function and HCC recurrence. Patients and Methods: Patients were divided into two groups according to preoperative antiviral therapy status. The control group comprised of 102 preoperative HBV-DNA-negative patients who had not undergone antiviral therapy before surgery. In the treatment group, all HBV-DNA-negative patients (n=63) received entecavir 3-5 days before surgery and for 12 months after surgery. Patients were followed-up regularly, during the preoperative period, and at 1, 3, 6, 12, 18, 24, 30 and 36 months postoperatively. The data for the two groups were analyzed including the level of HBV-DNA and HBV-DNA activation; liver function; 1-, 2- and 3-year survival rate; cumulative survival time; and tumor recurrence. Results: Liver function in the treatment group was better than that of the control group12 months after surgery. Compared to the control group, total bilirubin in the treatment group was significantly better at 6 and 12 months after surgery (p<0.05 and p<0.001, respectively). Serum albumin, alanine aminotransferase and prothrombin time in the treatment group was significantly better than that of controls 12 months after surgery (p<0.001). In the treatment group, two cases (3.17%) had HBV-DNA activation while there were 13 cases (12.75%) with HBV-DNA activation in the control group (p<0.05). There were 51 cases with tumor recurrence in the control group, that was statistically significantly higher than recurrent cases in the treatment group (p<0.05). Postoperative 1-, 2- and 3-year cumulative overall survival rates were 94.12%, 81.37% and 52.94%, respectively, for the control group and 93.65%, 77.78% and 71.43%, respectively, for the treatment group (p=0.006). There was no statistically significant difference in disease-free survival between the two groups (p=0.231). Conclusion: Antiviral treatment of HBV-related HCC with negative HBV-DNA is beneficial to liver function, coagulation function, disease control, prevention of tumor recurrence, improvement of patient quality of life, reduces the death rate and prolongs survival duration.



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Independent Correlation Between Ki67 Index and Circulating Tumor Cells in the Diagnosis of Colorectal Cancer

Background: The Ki67 index is a biomarker of proliferation, while the circulating tumor cell (CTC) count acts as a metastasis-related biomarker. In this study, we analyzed the potential value of CTC count and Ki67 index in diagnosis of colorectal cancer (CRC). Materials and Methods: A total of 105 patients with CRC undergoing surgery were included in the study. Isolation and identification of CTCs were performed by negative enrichment and immuno-fluorescence in situ hybridization, respectively. Expression of Ki67 was assessed by immunohistochemistry. Results: Patients with CTC count ≥2 were defined as CTC-positive. Ki67 index ≥50% was regarded as highly proliferative. Overall, 71 cases were CTC-positive, while 82 cases displayed a high Ki67 index. CTC count and Ki67 index had no correlation with tumor size, tumor site, age, gender and TNM stages of the patients. CTC count was correlated with tumor size (p=0.018) and Ki67 index with level of differentiation (p<0.001). However, there was no relationship between CTC count and Ki67 index (p=0.198). Conclusion: Our results suggest that CTCs can act as a potent metastasis-related biomarker for the diagnosis of CRC, independently of the Ki67 index.



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Efficacy and Safety of Nab-Paclitaxel as Second-line Chemotherapy for Locally Advanced and Metastatic Non-small Cell Lung Cancer

Aim: To investigate the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) for locally advanced or metastatic non-small cell lung cancer (NSCLC) as second-line chemotherapy. Patients and Methods: We retrospectively reviewed the treatment of 34 patients with advanced NSCLC whose first-line treatment had failed. These patients received nab-paclitaxel 260 mg/m2 on day 1 and day 8 of a 21-day cycle from July 2014 to February 2016. One cycle of treatment lasted 3 weeks and all patients completed more than two cycles. All patients were assessed for adverse events related to treatment. Results: No patient achieved complete response (CR); 12 patients reached partial response (PR), 12 patients achieved stable disease (SD) and 10 patients progressive disease (PD). The overall response rate (ORR) was 35.3% and the disease control rate (DCR) 70.6 %. There was no significant difference in either ORR or DCR within the subgroups. The median progression-free survival (PFS) was 5.7 months (95% confidence interval (CI)=3.8-7.6) and the median overall survival (OS) was 9 months (95% CI=8.3-9.7). There was no statistical difference in OS (p=0.066), but subgroup analysis showed that patients with squamous carcinoma benefited more in PFS (the median PFS of squamous carcinoma vs. adenocarcinoma was 7.3 months vs. 5 months, p=0.001). Major adverse events included myelosuppression, gastrointestinal response, baldness, myalgia and neurotoxicity. Hypersensitivity reactions were not reported. Conclusion: Nab-paclitaxel is an effective chemotherapy for locally advanced and metastatic NSCLC as treatment and has a superior application prospect for squamous NSCLC. Toxicity is generally mild and manageable.



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Clinical Characteristics and Prognosis of Elderly Small Cell Lung Cancer Patients Complicated with Hyponatremia: A Retrospective Analysis

Aim: This study was designed to evaluate the clinical characteristics and prognosis of elderly small cell lung cancer (SCLC) patients complicated with hyponatremia, thus providing increased attention for appropriate intervention and improving outcomes in symptomatic subjects. Patients and Methods: The clinical data of 320 patients with SCLC in the Yuhuangding Hospital from March 1st, 2006, to March 1st, 2012, were studied retrospectively. The prognosis and possible association with hyponatremia was investigated. Results: The incidence rate of hyponatremia in SCLC was 46.56% (149/320). The mean survival time was 1.10±0.42 years in patients with normal values and 0.83±0.35 years in patients with subnormal serum sodium. In the hyponatremia group, the mean survival time of corrected hyponatremia patients was 0.91±0.42 years, which was significantly longer than uncorrected hyponatremia patients whose mean survival time was 0.68±0.26 years (t=2.75, p<0.05) after symptomatic treatment. The mean survival time of the normal group and the hyponatremia group in elderly patients had a tendency to decrease when compared to another group of patients younger than 60 years old. Hyponatremia at 1- and 3-year follow-up was associated with worse survival rates (p<0.05). Conclusion: The severity of hyponatremia has unfavorable prognostic impacts. Elderly SCLC patients with hyponatremia are difficult to cure and associated with significantly shorter survival, especially in the uncorrected group. It is important that the cause of the hyponatremia is diagnosed at an early stage and precise medical treatment is provided.



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Gastric Cancer Mortality Trends in China (2006-2013) Reveal Increasing Mortality in Young Subjects

Background/Aim: Although the advent of Helicobacter pylori eradication and global societal changes are widely assumed to impact on gastric cancer (GC)-related mortality, there is remarkable little quantitative and qualitative insight into the nature of its effects. Here, we exploited a nationwide reporting system to investigate the epidemiological features of GC-related mortality in China between 2006 and 2013. Patients and Methods: GC mortality data between 2006 and 2013 were obtained from the National Disease Surveillance System published by the China Center for Disease Control and Prevention (CDC). Results: GC mortality increased by 8.2% (from 18.87/100,000 to 20.41/100,000), while GC mortality standardized by the age scale of the population in 2010 decreased by 17.8% (from 21.87/100,000 to 17.98/100,000). Standardized GC mortality in males (25.66/100,000 to 33.89/100,000) was higher compared to females (10.72/100,000 to 14.79/100,000), while standardized GC mortality in rural areas (19.17/100,000 to 26.46/100,000) was higher than in urban areas (15.48/100,000 to 20.04/100,000). Both crude and standardized rates in the 0- to 29-year-old group increased by 22.3% and 16.2%, respectively; while these rates declined in the 30- to 59-year-old group and over 60-year-old group. The proportion of GC deaths that accounts for all cancer deaths declined from 15.99% (2006) to 13.6% (2013); however, the proportion in the 0- to 29-year-old group revealed an increasing trend from 2006 (3.20%) to 2013 (3.87%). Conclusion: Our results reveal a remarkable increase in GC-related mortality in subjects under the age of 30 calling for further measures to prevent the increase in the incidence of GC in young patients.



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Effects of Different Palliative Jaundice Reducing Methods on Immunologic Functions in Patients with Advanced Malignant Obstructive Jaundice

Background/Aim: This study aimed to investigate the effects of three treatment methods on the immunological function of patients with advanced malignant obstructive jaundice (MOJ). Patients and Methods: Patients with advanced MOJ were randomly divided into three groups according to biliary drainage methods. Detection of levels of multi-indices were investigated in different time periods. Results: After drainage, the levels of complement 3 (C3) and complement 4 (C4) were increased. Forteen days post-operation, the levels of immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM) in the group undergoing palliative surgery decreased significantly compared to those in both percutaneous transhepatic cholangio drainage (PTCD) and endoscopic retrograde biliary drainage (ERBD) groups. The level of serum endotoxin in the group undergoing palliative surgery decreased gradually. Conclusion: Palliative surgery for reducing jaundice is superior to PTCD and ERBD in improving immune function of patients with MOJ.



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Preoperative High Neutrophil-to-Lymphocyte Ratio Is Associated with High-grade Bladder Cancer

Aim: To evaluate the correlation between the neutrophil–to–lymphocyte ratio (NLR) and histopathological characteristics of bladder cancer. Materials and Methods: A retrospective analysis was performed on a cohort of patients (n=302) who were diagnosed with bladder cancer and underwent transurethral resection of bladder tumor or cystectomy between 2009 and 2016. The pathological outcomes were compared between patients with low NLR and those with high NLR with a cut-off value of 2.5, and a logistic regression analysis was performed to find potential predictors of pathological tumor outcomes. Results: Patients with high-grade disease had significantly higher NLRs compared to those with low-grade disease (median NLR=4.42 vs. 3.42, p<0.001). Univariate analysis suggested that age, neutrophil count and NLR, as a continuous or binary variable, were significantly associated with high-grade disease. Multivariate analysis suggested that age and NLR, as a continuous variable, were predictors of pathologically high-grade disease. Conclusion: Preoperative NLR was found to be associated with pathological tumor grading, but was not associated with pathological tumor staging in patients with bladder cancer.



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Predictors of Malignancy for Female Patients with Suspicious Nipple Discharge: A Retrospective Study

Background: Suspicious nipple discharge (ND) in females requires further treatment, including biopsy or selective duct excision. It is important to identify predictors of malignancy in female patients with suspicious ND. Materials and Methods: This retrospective study included patients with suspicious ND who underwent surgical treatment at our center between January 2007 and December 2014. Clinicopathological features were compared between patients with and without malignancy. We used a Chi-square test and a logistic regression model as the univariate and multivariate analysis for identification of predictors of malignancy. Results: A total of 334 patients were eligible and included. The median age of the study population was 45 (range=19-81) years; 18.0% (60/334) of the entire study population had breast cancer. The univariate analysis suggested that older age (p=0.002) and presence of suspicious lumps (p<0.001) were significantly associated with malignancy. In contrast, presence of bloody discharge was not significantly associated with malignancy (p=0.324). The multivariate analysis confirmed that older age (p=0.023) and presence of suspicious lumps (p<0.001) were independent predictors of malignancy. For patients without suspicious lumps, we did not observe any association between the presence of bloody discharge and malignancy. For patients with suspicious lumps, tumor size was significantly associated with malignancy (p<0.001). Conclusion: Our study suggests that older age and the presence of suspicious lumps are predictors of the presence of malignancy in females with suspicious ND.



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Clinical Study on Using 125I Seeds Articles Combined with Biliary Stent Implantation in the Treatment of Malignant Obstructive Jaundice

Aim: To study the feasibility and curative effect of 125I seeds articles combined with biliary stent implantation in the treatment of malignant obstructive jaundice. Patients and Methods: Fifty patients with malignant obstructive jaundice were included. Twenty-four were treated by biliary stent implantation combined with intraluminal brachytherapy by 125I seeds articles as the experimental group, while the remaining 26 were treated by biliary stent implantation only as the control group. The goal of this study was to evaluate total bilirubin, direct bilirubin and tumor markers (cancer antigen (CA)-199, CA-242 and carcinoembryonic antigen (CEA)), as well as biliary stent patency status and survival time before and after surgery. Results: Jaundice improved greatly in both groups. The decreases of CA-199 and CA-242 had statistical significance (p=0.003 and p=0.004) in the experimental group. The ratio of biliary stent patency was 83.3% (20/24) in the experimental group and 57.7% (15/26) in the control group (p=0.048). The biliary stent patency time in the experimental group was 1~15.5 (mean=9.84) months. The biliary stent patency time in the control group was 0.8~9 (mean=5.57) months, which was statistically significant (p=0.018). The median survival time was 10.2 months in the experimental group, while 5.4 months in control group (p<0.05). Conclusion: 125I seeds articles combined with biliary stent implantation significantly prolongs biliary stent patency time and survival time for patients with malignant obstructive jaundice possibly by inhibiting the proliferation of vascular endothelial cells and the growth of tumor.



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Relationship of Th17/Treg Cells and Radiation Pneumonia in Locally Advanced Esophageal Carcinoma

Background/Aim: Radiation pneumonia is a main side-effect that has limited the clinical usage of radiotherapy in locally advanced esophageal carcinoma. T helper cells 17 (Th 17) and T regulatory cells (Tregs) play an important role in inflammatory diseases. The balance between Treg and Th17 cells is a key factor in the progression of many inflammatory and autoimmune diseases. Whether Tregs and Th17 cells are predictive factors of radiation pneumonia has not yet been reported. In this study, we investigated the relationships of Treg/Th17 cells and radiation pneumonia in patients with locally advanced esophageal cancer who received radiotherapy. Patients and Methods: One hundred and forty-eight patients with locally advanced esophageal cancer who received radical and palliative radiotherapy were enrolled. The levels of Th17 and Treg cells in the blood of patients were detected using flow cytometry at the time point of pre-radiotherapy, 1st, 2nd, 3rd, 4th, 5th and 6th week from the start of radiation and 4 weeks after completion of radiotherapy. Radiation pneumonia was evaluated according to Radiation Therapy Oncology Group's acute radiation pneumonia standards, with the endpoint being grade 2 or above radiation pneumonia. Results: There were 24 cases of radiation pneumonia in 148 cases of locally advanced esophageal cancer patients who underwent radiotherapy. Th17 cells increased and, in contrast, Treg cells decreased in the radiation pneumonia group. The change in the ratio of Th17/Treg was more pronounced and the difference was statistically significant from the 5th week after irradiation compared to patients with no radiation pneumonia (p<0.05). There was no significant difference in dosimetric parameters, including V5, V20, V30 and mean lung dose (MLD) and clinical factors, such as gender, age, smoking history, history of surgery and chemotherapy. Conclusion: The ratio of Th17/Treg cells may be an effective predictive factor of radiation pneumonia.



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MR-guided Percutaneous Biopsy of Focal Hepatic Dome Lesions with Free-hand Combined with MR Fluoroscopy Using 1.0-T Open High-field Scanner

Aim: To prospectively estimate the safety, feasibility and accuracy of 1.0T open-magnetic resonance (MR)-guided percutaneous biopsy in free-hand of focal lesions located in the hepatic dome. Materials and Methods: All percutaneous MR-guided biopsies of the lesions were performed at the Shandong Medical Imaging Research Institute. Thirty-six patients with focal liver lesions located in the hepatic dome measuring 6-36 mm in the maximum diameter were included in this study. Lesions were divided into two groups on the basis of maximum nodule diameters: ≤1.5 cm (n=14) and >1.5 cm (n=22). Surgical pathology of nodules or clinical and imaging follow-up for at least 12 months were used to establish final diagnosis. Diagnostic accuracy, specificity, sensitivity, average procedure time and complications were recorded and analyzed. Results: All obtained samples were sufficient for diagnosis. Accuracy, sensitivity and specificity of MRI-guided percutaneous liver lesions biopsy in diagnosing malignant tumors were 97.2%, 96.7% and 100%, respectively. Accuracy, sensitivity and specificity were 92.9%, 90.9% and 100% for the lesions that were 1.5 cm or smaller in diameter and 100%, 100% and 100% for lesions larger than 1.5 cm in diameter, respectively. There was no significant difference between the two groups (p>0.05). The average procedure time for each pass of the needle from skin entry to the target lesion was 1.1 min and the total procedural time was 28.5 min. Biopsy-induced complications included peri-hepatic hemorrhage in 8.3% (3/36) of cases. No serious complications occurred. Conclusion: 1.0T open-MR-guided free-hand percutaneous biopsy is a safe, feasible and highly accurate diagnostic method for pathological diagnosis of focal liver lesions located in the hepatic dome.



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Exploration of the Radiotherapeutic Clinical Target Volume Delineation for Gastric Cancer from Lymph Node Metastases

Aim: To clarify the clinical target volume of regional lymph nodes (CTVn) delineation of gastric adenocarcinoma. Materials and Methods: The pattern of lymph node metastases (LNM) of a total of 1,473 patients with gastric cancer (GC) who had undergone gastrectomy and lymphadenectomy with more than 15 lymph nodes retrieved was retrospectively examined. Results: A univariate analysis showed that T stage (p<0.001), macroscopic type (p=0.001), tumor differentiation (p<0.001), maximum diameter of tumor (p<0.001) as well as cancer embolus (p<0.001) were closely associated with the rate of LNM. While by multivariate analysis, gender [odds ratio (OR=0.687, p<0.05], maximum diameter (OR=1.734, p<0.001), tumor differentiation (OR=1.584, p<0.001), T stage (OR=2.066, p<0.001) and cancer embolus (OR=4.912, p<0.001) were strongly associated with the rate of LNM. Conclusion: In conclusion, for male patients with GC with large, deeply invasive, poorly differentiated, diffusely infiltration and positive cancer embolus, the radiation fields should be enlarged appropriately.



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Comparison of Efficiency of Video Endoscopy and Open Inguinal Lymph Node Dissection

Aims: To compare the efficiency and complications of video endoscopy, inguinal lymphadenectomy and open inguinal lymph node dissection. Patients and Methods: Nineteen video endoscopy inguinal lymphadenectomies were performed on 16 patients from September 2014 to December 2015, and 21 open inguinal lymph node dissections were performed on 18 patients from September 2013 to September 2014. Surgical time, operative blood loss, incidence of complications, length of stay, lymph node harvest and suture removal time were compared between the two groups. Results: Operative time (135.5±45.52 vs. 169.8±55.19 min), lymph node harvest (10.78±5.22 vs. 12.60±5.53), and hospital stay (10.43±2.53 vs. 12.50±4.98 days) did not statistically differ between the two groups (p>0.05). However, operative blood loss (22.50±14.24 vs. 68.44±42.19 ml), drainage tube removal time (7.23±1.79 vs. 11.44±2.69 days), incidence of complications (21.05% vs. 61.9%), and suture removal time (7.52±1.24 vs. 12.81±2.04 min) were significantly reduced in the video endoscopy surgery group compared with the open surgery group (p<0.05). Conclusion: Compared with open surgery, video endoscopy surgery achieved the same efficiency, and had the advantage of reduction of complications, suture removal time and in-surgery blood loss.



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