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Σάββατο 14 Οκτωβρίου 2017

Kinetics of imidazolium-based ionic liquids degradation in aqueous solution by Fenton oxidation

Abstract

In the last few years, several works dealing with Fenton oxidation of ionic liquids (ILs) have proved the capability of this technology for their degradation, achieving complete ILs removal and non-toxic effluents. Nevertheless, very little is known about the kinetics of this process, crucial for its potential application. In this work, the effect of several operating conditions, including reaction temperature (50–90 °C), catalyst load (10–50 mg L−1 Fe3+), initial IL concentration (100–2000 mg L−1), and hydrogen peroxide dose (10–200% of the stoichiometric amount for the complete IL mineralization) on 1-butyl-3-methylimidazolium chloride ([C4mim]Cl) oxidation has been investigated. Under the optimum operating conditions (T = 90 °C; [Fe3+]0 = 50 mg L−1; [H2O2]0 = 100% of the stoichiometric amount), the complete removal of [C4mim]Cl (1000 mg L−1) was achieved at 1.5-min reaction time. From the experimental results, a potential kinetic model capable to describe the removal of imidazolium-based ILs by Fenton oxidation has been developed. By fitting the proposed model to the experimental data, the orders of the reaction with respect to IL initial concentration, Fe3+ amount and H2O2 dose were found to be close to 1, with an apparent activation energy of 43.3 kJ mol−1. The model resulted in a reasonable fit within the wide range of operating conditions tested in this work.



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Effect and mechanism of microwave-activated ultraviolet-advanced oxidation technology for adsorbent regeneration

Abstract

To decrease the secondary pollution of volatile organic compounds (VOCs) during adsorbent regeneration by microwave, electrodeless lamp was added in the microwave field to oxidize VOCs in the gas phase. Ultraviolet has a significant improvement on mineralization of VOCs generated from adsorbate during adsorbent regeneration. However, the mechanism and main influence factors on the degradation of VOCs are not clear. The effect of microwave power, regeneration time, airflow rate, and humidity content on the mineralization of adsorbed tetracycline during adsorbent regeneration was studied. Ozone concentration and ultraviolet irradiation intensity were also measured to analyze the mechanism of the microwave-ultraviolet adsorbent regeneration method. Although the electrodeless lamp adsorbed microwave and competed with the regenerated adsorbent, the mineralization percentage of tetracycline increased about 10% with the presence of electrodeless lamp at the same microwave power supply. Besides, humidity content also takes an important role on enhancing the mineralization of tetracycline. The mineralization of tetracycline in the microwave-ultraviolet field consists of three major parts: pyrolysis, ozone oxidation, and free radical oxidation. More than 50% adsorbed tetracycline can be oxidized into H2O and CO2 during regeneration in 5 min. These results support the potential use of electrodeless lamp to treat VOCs in the gas phase to decrease the risk of secondary pollution during adsorbent regeneration.



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Mosquito oviposition deterrents

Abstract

Mosquitoes are well-known vectors of disease and threaten the health of millions of people annually. While synthetic insecticides have been relied on to combat these diseases, insecticide resistance and environmental concerns have directed attention towards novel and more targeted mosquitocides derived from botanicals. Research on the activity of botanical derivatives has focused on mosquito larvae and adults with little attention given to their potential as oviposition deterrents against gravid female mosquitoes. This review explores the influence of chemical and biological factors on deterrence and examines issues relating to environmental persistence and non-target effects. With very few discoveries of new insecticide pathways, the answer to effective mosquito control may well reside within other ancient plant-based organisms that have co-resided and evolved with this ubiquitous pest.



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Macrophytes as potential biomonitors in peri-urban wetlands of the Middle Parana River (Argentina)

Abstract

The aims of this study were to measure the concentrations of nutrients and pollutants in peri-urban wetlands, to analyze the plant morphology of the most representative macrophyte species, and to determine their potential use as biomonitors. Four wetlands in the Middle Paraná River floodplain evidencing contamination or anthropogenic impact were studied. The studied species were Typha domingensis Pers., Eichhornia crassipes (Mart.) Solms., Alternanthera philoxeroides (Mart.) Griseb., and Pistia stratiotes L. Besides, the same plant species from an uncontaminated wetland considered as control were studied. A. philoxeroides showed the highest total phosphorus (TP) concentration in leaves throughout the study, while the other species showed a higher TP concentration in roots than in leaves. Since metal concentration in A. philoxeroides tissues was always higher than in sediment, further studies focused on its phytoremediation capacity should be carried out. T. domingensis exhibited the highest Zn concentrations in roots followed by Pb, and E. crassipes presented the highest values of Pb concentrations in roots. The aerial part height of the plants from peri-urban wetlands was significantly higher than that of the plants from the control, while the root length was significantly lower. The root length of P. stratiotes showed a negative correlation with soluble reactive phosphorus (SRP) concentration in water. All the root anatomical parameters of T. domingensis and E. crassipes showed a positive correlation with nitrate and ammonium concentrations in water. The studied macrophytes evidenced a high tolerance, enabling them to grow and survive in peri-urban wetlands that receive pollution from different sources. The use of aquatic and wetland plants as contaminant bioindicators and bioaccumulators in the Middle Paraná River floodplain is completely feasible.



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A bibliometric analysis of research on haze during 2000–2016

Abstract

As one of the bibliometric analysis tools, CiteSpace software was applied to quantitatively and visually evaluate global scientific documents of research on haze from 2000 to 2016. Five thousand six hundred six documents from the Science Citation Index Expanded (SCI-Expanded) and Social Science Citation Index (SSCI) of the Web of Science database were statistically analyzed and examined. The distributions on authorship, countries/territories, institutes, and keywords were generated. The amount of publications has increased nearly for the past 17 years. The most productive author was Li J. with 46 articles. The publications on haze research were primarily originated from the USA, China, Germany, and France. By synthetically analyzing the keywords, the dominant hot spots of haze research could be concluded as "aerosol," "atmosphere," "particle," "PM2.5,"and "air quality."



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Interaction mechanisms between polycyclic aromatic hydrocarbons (PAHs) and organic soil washing agents

Abstract

Understanding interaction mechanisms between polycyclic aromatic hydrocarbons (PAHs) and soil-washing agents can help in choosing efficient agents which are able to desorb and solubilize PAHs. This study investigated interaction mechanisms between pyrene and four washing agents including: two dissolved organic matters (DOM) F-DOM and CRC-DOM, and two commercial bio-based surfactants BBE-1000 and Supersolv using fluorescence spectroscopy combined with multivariate curve resolution alternating regression (MCR-AR). The efficiencies of these washing agents in removing PAHs from the soil were tested in a soil washing experiment. Pyrene showed π-π interactions with F-DOM and no interaction with CRC-DOM. This could be attributed to the more aromatic structures in F-DOM compared to CRC-DOM. The two DOMs were inefficient in soil washing which might be attributed to the relatively weak effect of π-π interactions in releasing PAHs from the soil. Interaction mechanisms between pyrene and the bio-based surfactants were elucidated with MCR-AR, which resolved three spectroscopically active species from pyrene emission spectra as a function of pyrene and bio-based surfactants concentrations. These species resembled pyrene emission in a polar and nonpolar microenvironment, respectively and of an excimer. Concentration profiles retrieved by the model for the three species showed that, below the critical micelle concentration (CMC), Supersolv created more nonpolar interactions with pyrene compared to BBE-1000. In soil washing, Supersolv showed the highest efficiency in extracting PAHs from the soil. This highlighted the importance of nonpolar interactions in desorbing PAHs from soils, which could then be solubilized in micelles. This study demonstrated the potential of fluorescence spectroscopy combined with the MCR-AR model for selecting efficient soil-washing agents.



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Periodontitis: from Infection to Inflammation

Abstract

Purpose of the Review

The purpose of this study is to discuss the current understanding of periodontitis causation.

Recent Findings

The understanding of periodontitis as a monocausal infection has hindered the investigation of other potential causes that influence periodontitis morbidity and does not reflect the complexity of periodontitis etiology. Still today, the periodontal literature frequently defines periodontitis as an infection, whereas other potential causes of periodontitis, like smoking, which seems to be causally related to periodontitis, are typically called modifying or susceptibility factors. Instead of addressing the complexity of periodontitis, the field has narrowed its focus trying to find the most important bacteria or gene. Distal causes of periodontitis and interaction between constellations of causes at multiple levels have been commonly neglected.

Summary

Understanding periodontitis as a group of signs and symptoms characterized by inflammatory destruction of the periodontium would provide a better frame for future etiological research.



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Imaging in Rheumatology: An Update

Publication date: September 2017
Source:Radiologic Clinics of North America, Volume 55, Issue 5
Author(s): Giuseppe Guglielmi




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Practical Pediatric Imaging

Publication date: July 2017
Source:Radiologic Clinics of North America, Volume 55, Issue 4
Author(s): Edward Y. Lee




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Copyright

Publication date: November 2017
Source:Radiologic Clinics of North America, Volume 55, Issue 6





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Computed Tomography and MR Imaging in Crystalline-Induced Arthropathies

Publication date: September 2017
Source:Radiologic Clinics of North America, Volume 55, Issue 5
Author(s): Constantinus Franciscus Buckens, Maaike P. Terra, Mario Maas

Teaser

Crystalline-induced arthropathies impose substantial morbidity but can be challenging to diagnose, especially in early phases. The most common crystalline arthropathies are gout (monosodium urate deposition), calcium pyrophosphate dihydrate deposition, and hydroxyapatite deposition disease. Computed tomography (CT) and MR imaging provide 3-dimensional information on osseous structures, periarticular soft tissue, and tophi with superior spatial resolution. Dual-source CT (dual-energy CT [DECT]) offers the further advantage of selectively identifying crystalline deposits. CT, MR imaging, and DECT can be of value in problematic cases and can potentially be used for disease monitoring. Further research is necessary to elucidate their added value.


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Contributors

Publication date: November 2017
Source:Radiologic Clinics of North America, Volume 55, Issue 6





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Contributors

Publication date: September 2017
Source:Radiologic Clinics of North America, Volume 55, Issue 5





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Contents

Publication date: November 2017
Source:Radiologic Clinics of North America, Volume 55, Issue 6





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Conventional Radiology in Crystal Arthritis

Publication date: September 2017
Source:Radiologic Clinics of North America, Volume 55, Issue 5
Author(s): Thibaut Jacques, Paul Michelin, Sammy Badr, Michelangelo Nasuto, Guillaume Lefebvre, Neal Larkman, Anne Cotten

Teaser

This article reviews the main radiographic features of crystal deposition diseases. Gout is linked to monosodium urate crystals. Classic radiographic features include subcutaneous tophi, large and well-circumscribed paraarticular bone erosions, and exuberant bone hyperostosis. Calcium pyrophosphate deposition (CPPD) can involve numerous structures, such as hyaline cartilages, fibrocartilages, or tendons. CPPD arthropathy involves joints usually spared by osteoarthritis. Basic calcium phosphate deposits are periarticular or intraarticular. Periarticular calcifications are amorphous, dense, and round or oval with well-limited borders, and most are asymptomatic. When resorbing, they become cloudy and less dense with an ill-defined shape and can migrate into adjacent structures.


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CME Accreditation Page

Publication date: November 2017
Source:Radiologic Clinics of North America, Volume 55, Issue 6





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Imaging and Cancer Screening

Publication date: November 2017
Source:Radiologic Clinics of North America, Volume 55, Issue 6
Author(s): Dushyant V. Sahani




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Imaging and Cancer Screening

Publication date: November 2017
Source:Radiologic Clinics of North America, Volume 55, Issue 6
Author(s): Dushyant V. Sahani




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CME Accreditation Page

Publication date: September 2017
Source:Radiologic Clinics of North America, Volume 55, Issue 5





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Screening for Breast Cancer

Publication date: November 2017
Source:Radiologic Clinics of North America, Volume 55, Issue 6
Author(s): Bethany L. Niell, Phoebe E. Freer, Robert Jared Weinfurtner, Elizabeth Kagan Arleo, Jennifer S. Drukteinis

Teaser

The goal of screening is to detect breast cancers when still curable to decrease breast cancer–specific mortality. Breast cancer screening in the United States is routinely performed with mammography, supplemental digital breast tomosynthesis, ultrasound, and/or MR imaging. This article aims to review the most commonly used breast imaging modalities for screening, discuss how often and when to begin screening with specific imaging modalities, and examine the pros and cons of screening. By the article's end, the reader will be better equipped to have informed discussions with patients and medical professionals regarding the benefits and disadvantages of breast cancer screening.


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Conventional Radiology in Rheumatoid Arthritis

Publication date: September 2017
Source:Radiologic Clinics of North America, Volume 55, Issue 5
Author(s): Eva Llopis, Herman M. Kroon, Jose Acosta, Johan L. Bloem

Teaser

In clinical practice, the conventional radiography is still the radiologic method for the diagnosis of rheumatoid arthritis (RA). Moreover, it provides a quick overview of the symptomatic joints to narrow the differential diagnosis and to evaluate progression. RA is a polyarticular disease with bilateral and symmetric involvement of the peripheral joints, especially small joints, and less frequently, the cervical spine. The radiologic features are soft tissue swelling, periarticular osteoporosis, erosions, loss of joint space, and in advanced disease, osteolysis and typical subluxations or deformities, such as ulnar deviation.


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Lung Cancer Screening

Publication date: November 2017
Source:Radiologic Clinics of North America, Volume 55, Issue 6
Author(s): Florian J. Fintelmann, Ravi V. Gottumukkala, Shaunagh McDermott, Matthew D. Gilman, Inga T. Lennes, Jo-Anne O. Shepard

Teaser

This article explains the rationale of lung cancer screening with low-dose computed tomography and provides a practical approach to all relevant aspects of a lung cancer screening program. Imaging protocols, patient eligibility criteria, facility readiness, and reimbursement criteria are addressed step by step. Diagnostic criteria and Lung-RADS (Lung Computed Tomography Screening Reporting and Data System) nodule management pathways are illustrated with examples. Pearls and pitfalls for interpretation of lung cancer screening low-dose chest computed tomography are discussed.


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Computed Tomography and MR Imaging in Rheumatoid Arthritis

Publication date: September 2017
Source:Radiologic Clinics of North America, Volume 55, Issue 5
Author(s): Antonio Barile, Francesco Arrigoni, Federico Bruno, Giuseppe Guglielmi, Marcello Zappia, Alfonso Reginelli, Piero Ruscitti, Paola Cipriani, Roberto Giacomelli, Luca Brunese, Carlo Masciocchi

Teaser

The clinical diagnosis of rheumatoid arthritis is supported by imaging findings. MR imaging, in particular, can allow an early diagnosis to determine a target therapy that can stop or at least slow the disease progression.


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Imaging and Screening for Colorectal Cancer with CT Colonography

Publication date: November 2017
Source:Radiologic Clinics of North America, Volume 55, Issue 6
Author(s): Perry J. Pickhardt

Teaser

Despite being readily preventable, colorectal cancer ranks second behind only lung cancer in overall mortality. However, this situation could be reversed if screening tests that effectively detect advanced adenomas and early cancers were broadly applied. Computed tomographic colonography (CTC) reflects an ideal balance of minimal invasiveness with high-level performance, assuming all facets of the examination are appropriately addressed. Unfortunately, this promising screening test remains grossly underused. This article details the technical and interpretive approaches used by one successful CTC screening program.


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Imaging of Myopathies

Publication date: September 2017
Source:Radiologic Clinics of North America, Volume 55, Issue 5
Author(s): Lukas Filli, Sebastian Winklhofer, Gustav Andreisek, Filippo Del Grande

Teaser

This article clarifies the current role of MR imaging in the assessment of myopathies. Typical MR imaging findings are discussed for different forms of myopathies, including idiopathic inflammatory myopathies, muscular dystrophies, and congenital myopathies. The last section deals with advanced MR imaging techniques and their potential role in further characterization of muscular disease.


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Economic and sustainable management of wastes from rice industry: combating the potential threats

Abstract

Rice is one of the imperative staple foods, particularly in the developing countries. The exponential boom in human population has resulted in the continuous expansion in the rice industry in order to meet the food demands. The various stages of paddy processing release huge quantity of solid wastes, mainly rice husk, rice husk ash and liquid wastes in the form of rice industry wastewater. The discharge of the rice industry wastewater imparts a substantial threat to the aquatic bodies and the nearby surrounding and, thus, consequently demands eco-benign treatment plan. As a result, different strategies are needed to enhance the effluent quality and minimize the operational cost of the treatment process. Therefore, efficient technological approach targeting the minimization of pollution as well as assuring the economic prosperity should be implemented. In this review article, several aspects related to the rice industry discussing the significant challenges involved in the generation of both solid and liquid wastes, mitigation experiments and future prospects have been meticulously elaborated. Furthermore, the article also focuses on the various processes utilized for reducing the pollution load and promoting the practice of reuse and recycle of waste rather than the discharge action for the sake of sustainability and the emergence of novel techniques for the generation of energy and value-added products.



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Biological and analytical techniques used for detection of polyaromatic hydrocarbons

Abstract

Polycyclic aromatic hydrocarbons contain two or more fused benzene rings that are considered as cosmo-pollutants ubiquitously found in the environment. The identification and monitoring of polycyclic aromatic hydrocarbons (PAHs) are of great interests for rapid and on-site detection. Therefore, many analytical and biological techniques have been proposed for the qualitative and quantitative assessments of PAHs. Non-biological analytical techniques such as infrared, Raman, and fluorescence spectroscopies are commonly exploited as non-destructive techniques while gas chromatography (GC) and high-performance liquid chromatography (HPLC) with multiple detectors are extensively employed for the separation and detection of an analyte. Even though spectroscopy and chromatography are more accurate, convenient, and feasible techniques, often, these methods are expensive and sophisticated which require high maintenance cost. On the other hand, biological approaches, i.e., immunoassay, PCR, and microarray, offer comprehensive high-throughput specificity and sensitivity for a similar analyte. Biosensor- and immunoassay-mediated detections of PAHs have opened up new avenues in terms of low cost, rapid determination, and higher sensitivity. In this review, we have discussed the strengths and limitations of biological and analytical techniques that were explored for precise evaluation and were trusted at both the legislation and research levels.



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Extending the service life of existing dental restorations with esthetic and functional limitations

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Publication date: Available online 14 October 2017
Source:The Journal of Prosthetic Dentistry
Author(s): Malin Strasding, Vincent Fehmer, Bjarni E. Pjetursson, Irena Sailer
Adhesive cementation is a useful procedure not only for cementing restorations onto teeth but also for attaching new ceramic restorations to existing restorations to improve their esthetics and/or function. This clinical report presents a technique for modifying an existing nonsatisfactory implant-supported fixed dental prosthesis by means of adhesively cemented veneers and onlays bonded to the pre-existing metal–ceramic surface with resin cement. This modification may avoid the replacement of the fixed dental prosthesis, reducing both treatment costs and time while fulfilling the patient's demands.



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Restoring masticatory function in a patient with severe microstomia using rapid prototyped mesh and a custom-made hinge and swing-lock prosthesis

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Publication date: Available online 14 October 2017
Source:The Journal of Prosthetic Dentistry
Author(s): Ibrahim Tulunoglu, Meng Huan Lee, Mohammed Louay Taifur, Ozlem Tulunoglu
This clinical report describes the use of rapid prototyped mesh in a complete swing-lock prosthesis to restore masticatory function in an edentulous patient with severe microstomia and perioral scar tissue after an industrial hot tar accident.



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Marginal discrepancy dimensions of single unit metal crowns fabricated by using CAD-CAM–milled acrylate resin polymer blocks or a conventional waxing technique

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Publication date: Available online 14 October 2017
Source:The Journal of Prosthetic Dentistry
Author(s): David Lalande, Jeffrey A. Hodd, John S. Brousseau, Van Ramos, Daniel Dunham, Frederick Rueggeberg
Statement of problemBecause crowns with open margins are a well-known problem and can lead to complications, it is important to assess the accuracy of margins resulting from the use of a new technique. Currently, data regarding the marginal fit of computer-aided design and computer-aided manufacturing (CAD-CAM) technology to fabricate a complete gold crown (CGC) from a castable acrylate resin polymer block are lacking.PurposeThe purpose of this in vitro study was to compare marginal discrepancy widths of CGCs fabricated by using either conventional hand waxing or acrylate resin polymer blocks generated by using CAD-CAM technology.Material and methodsA plastic model of a first mandibular molar was prepared by using a 1-mm, rounded chamfer margin on the entire circumference of the tooth. The master die was duplicated 30 times, and 15 wax patterns were fabricated by using a manual waxing technique, and 15 were fabricated by using CAD-CAM technology. All patterns were invested and cast, and resulting CGCs were cemented on their respective die by using resin-modified glass ionomer cement. The specimens were then embedded in acrylic resin and sectioned buccolingually. The buccal and lingual marginal discrepancies of each sectioned portion were measured by using microscopy at ×50 magnification. Data were subjected to repeated measures 2-way ANOVA, by using the Tukey post hoc pairwise comparison test (α=.05).ResultsThe factor of "technique" had no significant influence on marginal discrepancy measurement (P=.431), but a significant effect of "margin location" (P=.019) was noted. The confounding combination of factors was found to be significantly lower marginal discrepancy dimensions of the lingual margin discrepancy than on the buccal side by using CAD-CAM technology.ConclusionsThe marginal discrepancy of CAD-CAM acrylate resin crowns was not significantly different from those made with a conventional manual method; however, lingual margin discrepancies present from CAD-CAM–prepared crowns were significantly less than those measured on the respective buccal surface.



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Effect of thickness and surface modifications on flexural strength of monolithic zirconia

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Publication date: Available online 14 October 2017
Source:The Journal of Prosthetic Dentistry
Author(s): Fusun Ozer, Andrew Naden, Volkan Turp, Francis Mante, Deniz Sen, Markus B. Blatz
Statement of problemA recommended minimum thickness for monolithic zirconia restorations has not been reported. Assessing a proper thickness that has the necessary load-bearing capacity but also conserves dental hard tissues is essential.PurposeThe purpose of this in vitro study was to evaluate the effect of thickness and surface modifications on monolithic zirconia after simulated masticatory stresses.Material and methodsMonolithic zirconia disks (10 mm in diameter) were fabricated with 1.3 mm and 0.8 mm thicknesses. For each thickness, 21 disks were fabricated. The specimens of each group were further divided into 3 subgroups (n=7) according to the surface treatments applied: untreated (control), airborne-particle abrasion with 50-μm Al2O3 particles at a pressure of 400 kPa at 10 mm, and grinding with a diamond rotary instrument followed by polishing. The biaxial flexure strength was determined by using a piston-on-3-balls technique in a universal testing machine. Flexural loading was applied with a 1.4-mm diameter steel cylinder, centered on the disk, at a crosshead speed of 0.5 mm/min until fracture occurred. X-ray diffraction (XRD) and scanning electron microscopy (SEM) analyses were performed. The data were statistically analyzed with 2-way ANOVA, Tamhane T2, 1-way ANOVA, and Student t tests (α=.05).ResultsThe 1.3-mm specimens had significantly higher flexural strength than the 0.8-mm specimens (P<.05). Airborne-particle abrasion significantly increased the flexural strength (P<.05). Grinding and polishing did not affect the flexural strength of the specimens (P>.05).ConclusionsThe mean flexural strength of 0.8-mm and 1.3-mm thick monolithic zirconia was greater than reported masticatory forces. Airborne-particle abrasion increased the flexural strength of monolithic zirconia. Grinding did not affect flexural strength if subsequently polished.



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Outer Membrane Protein OmpB Methylation May Mediate Bacterial Virulence

Publication date: Available online 13 October 2017
Source:Trends in Biochemical Sciences
Author(s): David C.H. Yang, Amila H. Abeykoon, Bok-Eum Choi, Wei-Mei Ching, P. Boon Chock
Methylation of outer membrane proteins (OMPs) has been implicated in bacterial virulence. Lysine methylation in rickettsial OmpB is correlated with rickettsial virulence, and N- and O-methylations are also observed in virulence-relevant OMPs from several pathogenic bacteria that cause typhus, leptospirosis, tuberculosis, and anaplasmosis. We summarize recent findings on the structure of methylated OmpB, biochemical characterization, and crystal structures of OmpB methyltransferases. Native rickettsial OmpB purified from highly virulent strains contains multiple clusters of trimethyllysine, in contrast with mostly monomethyllysine, and no trimethyllysine is found in an avirulent strain. Crystal structure of the methyltransferases reveals mechanistic insights for catalysis, and a working model is discussed for this unusual post-translational modification.



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ATA 2017 Abstracts Available Online

We are pleased to provide complimentary access to the conference program and meeting abstracts for the 87th Annual Meeting of the American Thyroid Association, October 18-21, 2017 in Victoria, British Columbia. The Abstracts are available now on the Thyroid website:

87th Annual Meeting of the American Thyroid Association Abstracts
Abstract Author Index
Short Call Abstracts
Short Call Author Abstract Index

The post ATA 2017 Abstracts Available Online appeared first on American Thyroid Association.



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Five Year Results of Great Saphenous Vein Treatment: A Meta-analysis

Publication date: Available online 14 October 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Sterre A.S. Hamann, Jenny Giang, Marianne G.R. De Maeseneer, Tamar E.C. Nijsten, Renate R. van den Bos
ObjectivesThe most frequently used treatment options for great saphenous vein incompetence are high ligation with stripping (HL+S), endovenous thermal ablation (EVTA), mainly consisting of endovenous laser ablation (EVLA) or radiofrequency ablation, and ultrasound guided foam sclerotherapy (UGFS). The objective of this systematic review and meta-analysis was to compare the long-term efficacy of these different treatment modalities.MethodsA systematic literature search was performed. Randomised controlled trials (RCTs) with follow-up ≥ 5 years were included. Pooled proportions of anatomical success, which was the primary outcome, rate of recurrent reflux at the saphenofemoral junction (SFJ), and mean difference in venous clinical severity score (VCSS) were compared using a z test or Student t test. Quality of life data were assessed and described.ResultsThree RCTs and 10 follow-up studies of RCTs were included of which 12 were pooled in the meta-analysis. In total, 611 legs were treated with EVLA, 549 with HL+S, 121 with UGFS, and 114 with HL+EVLA. UGFS had significantly lower pooled anatomical success rates than HL+S, EVLA, and EVLA with high ligation: 34% (95% CI 26–44) versus 83% (95% CI 72–90), 88% (95% CI 82–92), and 88% (95% CI 17–100) respectively; p ≤ .001. The pooled recurrent reflux rate at the SFJ was significantly lower for HL+S than UGFS (12%, 95% CI 7–20, vs. 29%, 95% CI 21–38; p ≤ .001) and EVLA (12%, 95% CI 7–20, vs. 22%, 95% CI 14–32; p = .038). VCSS scores were pooled for EVLA and HL+S, which showed similar improvements.ConclusionEVLA and HL+S show higher success rates than UGFS 5 years after GSV treatment. Recurrent reflux rates at the SFJ were significantly lower in HL+S than UGFS and EVLA. VCSS scores were similar between EVLA and HL+S.



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Data on the chemical properties of commercial fish sauce products

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Publication date: Available online 14 October 2017
Source:Data in Brief
Author(s): Mitsutoshi Nakano, Yoshimasa Sagane, Ryosuke Koizumi, Yozo Nakazawa, Masao Yamazaki, Toshihiro Watanabe, Katsumi Takano, Hiroaki Sato
This data article reports on the chemical properties of commercial fish sauce products associated with the fish sauce taste and flavor. All products were analyzed in triplicate. Dried solid content was analyzed by moisture analyzer. Fish sauce salinity was determined by a salt meter. pH was measured using a pH meter. The acidity was determined using a titration assay. Amino nitrogen and total nitrogen were evaluated using a titration assay and Combustion-type nitrogen analyzer, respectively.The analyzed products originated from Japan, Thailand, Vietnam, China, the Philippines, and Italy. Data on the chemical properties of the products are provided in table format in the current article.



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Dataset on antioxidant metabolites and enzymes activities of freshly harvested sweet cherries (Prunus avium L.) of Campania accessions

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Publication date: Available online 14 October 2017
Source:Data in Brief
Author(s): Antonio Mirto, Federica Iannuzzi, Petronia Carillo, Loredana F. Ciarmiello, Pasqualina Woodrow, Amodio Fuggi
In this article, we reported the original data obtained by the study of metabolites and enzymes involved in sweet cherry antioxidant system. We measured hydrogen peroxide (H2O2) and malondialdehyde (MDA), which are indicator of oxidative stress. Moreover, we measured the concentration of reduced and oxidized ascorbate and glutathione that are involved in ROS detoxification together with phenolics, anthocyanins and tocopherols. Among antioxidant enzymes, we analyzed the activities of ascorbate peroxidase (APX; EC 1.11.1.11), and the soluble and bound forms of polyphenol oxidase (PPO; EC 1.10.3.1) and guaiacol peroxidase (POD; EC 1.11.1.7). The data reported in this paper are related to the research article "Metabolic characterization and antioxidant activity in sweet cherry (Prunus avium L.) Campania accessions", authored by Mirto et al. (2018) [1].



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The effects of add-on exenatide to insulin on glycemic variability and hypoglycemia in patients with type 1 diabetes mellitus

Abstract

Objective

To investigate the effect of add-on exenatide to insulin on glycemic excursion and the counter-regulatory hormone in response to hypoglycemia in patients with type 1 diabetes mellitus (T1DM).

Methods

30 patients with T1DM were recruited and randomly assigned to exenatide + insulin-treated group (group 1, n = 15) or insulin-only-treated group (group 2, n = 15) for 4 weeks. All patients had continuous glucose monitor system (CGMS) applied at before (week-0) and after (week-4) treatment to evaluate the glycemic variability. All patients had an arginine-stimulated test at before and after treatment. Six patients from each group also had hypoglycemic clamp test to assess counter-regulatory hormone level.

Results

Patients in the exenatide group had significant reductions in body weight, body mass index (BMI), total insulin dose, bolus insulin dose, fructosamine, and glycemic excursion after 4 weeks' treatment. Compared with patients in group 2, the mean amplitude of glycemic excursion (MAGE) and coefficient of variation (CV) of exenatide group decreased significantly. Similarly, a significant decrease of glucagon (GLC) in the arginine-stimulated test was found in group 1. No significant changes of GLC, growth hormone (GH), cortisol (COR), epinephrine (E), and norepinephrine (NE) were found in both groups during hypoglycemia clamp test. However, patients who had residual islet function in group 1 showed an upward trend of basic C-peptide (C-P) and GLC during the hypoglycemia period.

Conclusion

Although exenatide could inhibit glucagon secretion during euglycemia or hyperglycemia in patients with T1DM, it has no effect on GLC and counter-regulatory hormones during hypoglycemia clamp in patients with no functional residual islet test.



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The management of first-line biologic therapy failures in rheumatoid arthritis: Current practice and future perspectives

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Publication date: Available online 14 October 2017
Source:Autoimmunity Reviews
Author(s): Ennio Giulio Favalli, Maria Gabriella Raimondo, Andrea Becciolini, Chiara Crotti, Martina Biggioggero, Roberto Caporali
The introduction of biologic disease–modifying anti-rheumatic drugs (bDMARDs) has dramatically changed the management of rheumatoid arthritis (RA). However, in a real-life setting about 30–40%.of bDMARD treated patients experience drug discontinuation because of either inefficacy or adverse events. According to international recommendations, to date the best strategy for managing first-line bDMARD failures has not been defined yet and available data (especially on TNF inhibitors [TNFis]) seem to drive toward a personalized approach for the individual patient. Some TNFi partial responders may benefit from optimization of concomitant methotrexate therapy or from switching to a different concomitant sDMARD such as leflunomide. Conversely, apart from infliximab, TNFi dose escalation seems to be poor efficacious and poor cost-effective compared with alternative strategies. Albeit counterintuitive, the use of a second TNFi after the failure of the first-one (cycling strategy) is supported by clear evidences and has become widespread in the 2000s as the result of the limited alternative options till the introduction of bDMARDs with a mechanism of action other than TNF blockade. Nowadays, the use of abatacept, rituximab, tocilizumab, or JAK inhibitors as second-line agent (swapping strategy) is strongly supported by RCTs and real-life experiences. In the absence of head-to-head trials directly comparing these two strategies, meta-analyses of separated RCTs failed to find significant differences in favor of one or another choice. However, results from most observational studies, including well designed prospective pragmatic randomised analyses, demonstrated the superiority of swapping over cycling approach, whereas only few studies reported a comparable effectiveness. In this review, we aimed to critically analyze all the potential therapeutic options for the treatment of first-line bDMARD failures in order to provide a comprehensive overview of available strategies to be applied in clinical practice.



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HLA-DRB1 alleles and juvenile idiopathic arthritis: Diagnostic clues emerging from a meta-analysis

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Publication date: Available online 14 October 2017
Source:Autoimmunity Reviews
Author(s): Annalisa De Silvestri, Cristina Capittini, Dimitri Poddighe, Gian Luigi Marseglia, Luca Mascaretti, Elena Bevilacqua, Annamaria Pasi, Miryam Martinetti, Carmine Tinelli
Juvenile Idiopathic Arthritis (JIA) is characterized with a variable pattern of articular involvement and systemic symptoms and, thus, it has been classified in several subtypes. Genetic predisposition to JIA is mainly due to HLA class II molecules (HLA-DRB1, HLA-DPB1), although HLA class I molecules and non-HLA genes have been implicated, too. Here, we carried out a meta-analysis on selected studies designed to assess HLA genetic background of JIA patients, compared to healthy controls and, particularly, we focused our attention on HLA-DRB1. In summary, our meta-analysis showed four main findings regarding HLA-DRB1 locus as a genetic factor of JIA: i) HLA-DRB1*08 is a strong factor predisposing to JIA, both for oligo-articular and poly-articular forms (oJIA > pJIA); ii) HLA-DRB1*01 and HLA-DRB1*04 may be involved in the genetic predisposition of Rheumatoid Factor (RF) positive forms of JIA; iii) HLA-DRB1*11 was confirmed to be predisposing to oligo-articular JIA; iv) HLA-DRB1*04 was confirmed to have a role in systemic JIA. Importantly, the positivity for the RF seems to select the JIA clinical subset with the strongest immunogenetic similarities with the adult form of rheumatoid arthritis.



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New Insights in the Pathogenesis of Immunoglobulin A Vasculitis (Henoch-Schönlein Purpura)

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Publication date: Available online 14 October 2017
Source:Autoimmunity Reviews
Author(s): Marieke H. Heineke, Aranka V. Ballering, Agnès Jamin, Sanae Ben Mkaddem, Renato C. Monteiro, Marjolein Van Egmond
Immunoglobulin A vasculitis (IgAV), also referred to as Henoch-Schönlein purpura, is the most common form of childhood vasculitis. The pathogenesis of IgAV is still largely unknown. The disease is characterized by IgA1-immune deposits, complement factors and neutrophil infiltration, which is accompanied with vascular inflammation. Incidence of IgAV is twice as high during fall and winter, suggesting an environmental trigger associated to climate. Symptoms can resolve without intervention, but some patients develop glomerulonephritis with features similar to IgA nephropathy that include hematuria, proteinuria and IgA deposition in the glomerulus. Ultimately, this can lead to end-stage renal disease. In IgA nephropathy immune complexes containing galactose-deficient (Gd-)IgA1 are found and thought to play a role in pathogenesis. Although Gd-IgA1 complexes are also present in patients with IgAV with nephritis, their role in IgAV is disputed. Alternatively, it is has been proposed that in IgAV IgA1 antibodies are generated against endothelial cells. We anticipate that such IgA complexes can activate neutrophils via the IgA Fc receptor FcαRI (CD89), thereby inducing neutrophil migration and activation, which ultimately causes tissue damage in IgAV. In this Review, we discuss the putative role of IgA, IgA receptors, neutrophils and other factors such as infections, genetics and the complement system in the pathogenesis of IgA vasculitis.



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Inferential language use by youth with Down syndrome during narration

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Publication date: December 2017
Source:Research in Developmental Disabilities, Volume 71
Author(s): Shealyn A. Ashby, Marie Moore Channell, Leonard Abbeduto
We examined inferential language use by youth with Down syndrome (DS) in the context of narrative storytelling relative to younger typically developing (TD) children and same-aged peers with fragile X syndrome (FXS) matched on nonverbal cognitive ability level. Participants' narratives were coded for the use of different types of inferential language. Participants with DS used proportionately less inferential language overall relative to their counterparts with TD or FXS, although mean length of utterance accounted for group differences observed for the DS-TD group comparison only. Patterns of inferential language use varied across inferential subtypes and across participant groups, with mean length of utterance playing a significant role in group differences. These findings suggest potential syndrome specificity to the DS phenotype regarding impairments in inferential language use that can be partially explained by level of expressive syntactic ability and should be considered in future research. Clinical interventions within the DS population, therefore, should target to some extent the use of inferential language and complex sentence structure.



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Difference or delay? A comparison of Bayley-III Cognition item scores of young children with and without developmental disabilities

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Publication date: December 2017
Source:Research in Developmental Disabilities, Volume 71
Author(s): Linda Visser, Carla Vlaskamp, Cornelius Emde, Selma A.J. Ruiter, Marieke E. Timmerman
The "difference or delay paradigm" focuses on the question of whether children with developmental disabilities (DD) develop in a way that is only delayed, compared to typically developing children, or also qualitatively different. The current study aimed to examine whether qualitative differences exist in cognitive development of young children with and without DD on the basis of item scores on the Dutch Bayley-III Cognition scale. Differential item functioning was identified for 15 of the 91 items. The presence of DD was related to a higher number of Guttman errors, hinting at more deviation in the order of skill development. An interaction between group (i.e., with or without DD) and developmental quotient appeared to predict the number of Guttman errors. DD was related to a higher number of Guttman errors for the whole range of developmental quotients; children with DD with a small developmental quotient had the highest number. Combined, the results mean that qualitative differences in development are not to be excluded, especially in cases of severe developmental disabilities. When using the Bayley-III in daily practice, the possibility needs to be taken into account that the instruments' assumption of a fixed order in skill development does not hold.



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Adaptation of the MABC-2 Test (Age Band 2) for children with low vision

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Publication date: December 2017
Source:Research in Developmental Disabilities, Volume 71
Author(s): Hanne Alves Bakke, Silvia Wanick Sarinho, Maria Teresa Cattuzzo
BackgroundThe tools used to assess motor performance in children with low vision often have no validity and reliability data concerning this population and use non-standardized modifications. Adaptations of these tools could help to identify motor problems and mitigate their effects.AimTo assess aspects of validity and reliability in an adaptation of the Movement ABC-2 Test (MABC-2) for children with low vision.Methods and proceduresThe research was undertaken in two stages: 1) application of the original MABC-2 to 10 children with low vision, adaptation and pilot test; 2) administration and re-administration of the adapted MABC-2 in 30 children with low vision. Inter-rater reliability and test-retest reliability were assessed with an intraclass correlation coefficient and Kappa index; internal consistency was assessed with Cronbach's alpha.Outcomes and resultsSubstantial to almost perfect inter-rater reliability was found between the component standard scores and a reasonable to excellent concordance rate in the classification of movement difficulty. The adapted tool has moderate internal consistency.Conclusions and implicationsThe adapted MABC-2 Test has improved the assessment of motor performance in children with low vision.



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Data-driven heterogeneity in mathematical learning disabilities based on the triple code model

Publication date: December 2017
Source:Research in Developmental Disabilities, Volume 71
Author(s): Christian Peake, Juan E. Jiménez, Cristina Rodríguez
Many classifications of heterogeneity in mathematical learning disabilities (MLD) have been proposed over the past four decades, however no empirical research has been conducted until recently, and none of the classifications are derived from Triple Code Model (TCM) postulates. The TCM proposes MLD as a heterogeneous disorder, with two distinguishable profiles: a representational subtype and a verbal subtype. A sample of elementary school 3rd to 6th graders was divided into two age cohorts (3rd − 4th grades, and 5th − 6th grades). Using data-driven strategies, based on the cognitive classification variables predicted by the TCM, our sample of children with MLD clustered as expected: a group with representational deficits and a group with number-fact retrieval deficits. In the younger group, a spatial subtype also emerged, while in both cohorts a non-specific cluster was produced whose profile could not be explained by this theoretical approach.

Graphical abstract

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Novel genetic loci associated HLA-B*08:01 positive myasthenia gravis

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Publication date: Available online 14 October 2017
Source:Journal of Autoimmunity
Author(s): Jezabel Varade, Ning Wang, Che Kang Lim, Tao Zhang, Yuanwei Zhang, Xiaomin Liu, Fredrik Piehl, Ritva Matell, Hongzhi Cao, Xun Xu, Lennart Hammarström
ObjectiveTo identify potential causative markers involved in the development of early-onset myasthenia gravis (EOMG) in the MHC and non-MHC regions that may interact with the HLA-B*08:01 allele.MethodsWe analyzed 583 MG patients and identified 5 patients homozygous for the disease-associated ancestral haplotype 8.1 (HLA-A*01:01, B*08:01, DRB1*03:01, DQB1*02:01). We also analyzed more than 9000 controls and selected 24 for further investigation. We subsequently conducted a fine mapping analysis through high-throughput sequencing of the MHC region (from upstream of the GPα5 gene to downstream of the ZBTB9 gene). For the interaction analysis we analyzed a total of 150,090 SNPs equally distributed throughout the genome in the individuals that were homozygous for the main susceptibility HLA allele HLA-B*08:01 and investigated the expression of the genes located close to the observed susceptibility variants.ResultsThe overall coverage of the 4.79 Mb MHC region ranged between 96.57% and 97.41%. We identified 705 new variants in the MHC region (673 SNPs and 32 InDels). However, no significant differences were found between patients and controls within the MHC region of the ancestral 8.1 haplotype. As the susceptibility gene is considered to be located close to the HLA-B locus, complete sequencing of the surrounding 200 kb was carried out in the 5 patients and 24 controls. No significant differences where observed, suggesting that the HLA-B molecule itself is the susceptibility factor for EOMG.We also observed two new susceptibility loci specific for MG HLA*08:01 patients (P < 3.33 × 10−7). These loci map to an intronic OVCH1 variant (rs10492374; P = 1.90 × 10−8) and a 5′ downstream CNPY2 variant (rs10783780; P = 3.33 × 10−7) on chromosome 12. Individuals heterozygous for GA*rs10492374 showed an increased expression of the OVCH1 gene. The rs10783780 genotypes were not associated with CNPY2 mRNA levels, but the MG HLA*08:01 patients present a lower expression of this gene than the healthy controls.ConclusionOur results showed that when we control for the influence of the ancestral haplotype 8.1, no polymorphism was demonstrated to be associated with EOMG development within the MHC region suggesting that the HLA-B*08:01 allele is the unique genetic factor within the HLA region responsible for EOMG development in patients who carry the ancestral haplotype 8.1. Our study also identified two novel polymorphisms as risk factors for MG HLA-B*08:01 positive patients which regulate the expression of the OVCH1 and CNYP2 genes.



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Impaired anti-inflammatory activity of PPARγ in the salivary epithelia of Sjögren's syndrome patients imposed by intrinsic NF-κB activation

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Publication date: Available online 14 October 2017
Source:Journal of Autoimmunity
Author(s): Aigli G. Vakrakou, Alexandros Polyzos, Efstathia K. Kapsogeorgou, Dimitris Thanos, Menelaos N. Manoussakis
Sjögren's syndrome (SS) patients manifest inflammation in the salivary glands (SG) and evidence of persistent intrinsic activation of ductal SG epithelial cells (SGEC), demonstrable in non-neoplastic SGEC lines derived from patients (SS-SGEC). The peroxisome-proliferator-activated receptor-γ (PPARγ) mediates important anti-inflammatory activities in epithelial cells. Herein, the comparative analysis of SG biopsies and SGEC lines obtained from SS patients and controls had revealed constitutively reduced PPARγ expression, transcriptional activity and anti-inflammatory function in the ductal epithelia of SS patients that were associated with cell-autonomously activated NF-κB and IL-1β pathways. Transcriptome profiling analysis revealed several differentially expressed proinflammatory and metabolism-related gene sets in SS-SGEC lines. These aberrations largely correlated with the severity of histopathologic lesions, the disease activity and the occurrence of adverse manifestations in SS patients studied, a fact which corroborates the key role of the persistently-activated epithelia in the pathogenesis of both local and systemic features of this disease. The treatment of control SGEC lines with PPARγ agonists was found to diminish the NF-κB activation and apoptosis induced by proinflammatory agents. In addition, the in-vitro application of PPARγ agonists and pharmacologic inhibitors of IL-1β and NF-κB had significant beneficial effects on SS-SGEC lines, such as the restoration of PPARγ functions and the reduction of their intrinsic activation, a fact which may advocate the future clinical study of the above agents as therapeutic modalities for SS.



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Clinical Application of Contrast-Enhanced Ultrasound Using High-Frequency Linear Probe in the Detection of Small Colorectal Liver Metastases

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Publication date: Available online 14 October 2017
Source:Ultrasound in Medicine & Biology
Author(s): Si Qin, Yao Chen, Xiao-yin Liu, Wen-jie Cheng, Jun-li Yu, Wen-jing Zhang, Qing-ling Jiang, Yi-min Wang, Yan-ling Wen, Guang-jian Liu
To compare the performance of contrast-enhanced ultrasound (CEUS) using high-frequency linear and convex probes in the detection of small colorectal liver metastases (CRLMs). A total of 85 patients with 143 small CRLMs were evaluated. High-frequency ultrasound (US) and CEUS detected significantly more superficial lesions within 60 mm below the skin than a convex probe (p < 0.05). The detection rate decreased in the chemotherapy group, especially when using a convex probe for US (p < 0.05). By combining convex and linear probes, detection rates of US and CEUS were significantly higher than that of a convex or a linear probe alone (p < 0.05). High-frequency US and CEUS helped to improve detection of small CRLMs and reduce the influence of chemotherapy. For patients with a high risk of CRLMs and those after chemotherapy, we recommend first scanning the liver by using a convex probe and subsequently screening the surface area of the liver and suspicious small lesions by using a linear probe.



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Spatio-Temporal Flow and Wall Shear Stress Mapping Based on Incoherent Ensemble-Correlation of Ultrafast Contrast Enhanced Ultrasound Images

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Publication date: Available online 13 October 2017
Source:Ultrasound in Medicine & Biology
Author(s): Chee Hau Leow, Meng-Xing Tang
In this study, a technique for high-frame-rate ultrasound imaging velocimetry (UIV) is extended first to provide more robust quantitative flow velocity mapping using ensemble correlation of images without coherent compounding, and second to generate spatio-temporal wall shear stress (WSS) distribution. A simulation model, which couples the ultrasound simulator with analytical flow solution, was implemented to evaluate its accuracy. It is shown that the proposed approach can reduce errors in velocity estimation by up to 10-fold in comparison with the coherent correlation approach. Mean errors (ME) of 3.2% and 8.6% were estimated under a steady flow condition, while 3.0% and 10.6% were found under a pulsatile condition for the velocity and wall shear rate (WSR) measurement, respectively. Appropriate filter parameters were selected to constrain the velocity profiles before WSR estimations and the effects of incorrect wall tracking were quantified under a controlled environment. Although accurate wall tracking is found to be critical in WSR measurement (as a 200 µm deviation from the wall may yield up to a 60% error), this can be mitigated by HFR imaging (of up to 10 kHz) with contrast agents, which allow for improved differentiation of the wall-fluid boundaries. In vitro investigations on two carotid bifurcation phantoms, normal and diseased, were conducted, and their relative differences in terms of the flow patterns and WSR distribution were demonstrated. It is shown that high-frame-rate UIV technique can be a non-invasive tool to measure quantitatively the spatio-temporal velocity and WSS distribution.



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Reproductibilité de la mesure de la force et de l’endurance du quadriceps dans la BPCO

Publication date: Available online 13 October 2017
Source:Revue des Maladies Respiratoires
Author(s): M. Beaumont, G. Kerautret, L. Peran, R. Pichon, C. Le Ber, M. Cabillic
IntroductionLes patients atteints de BPCO ont fréquemment une altération de la force et de l'endurance des membres inférieurs et l'évaluation des quadriceps est recommandée dans cette pathologie. Le dynamomètre manuel est un instrument facile d'utilisation pour cette évaluation ; toutefois, la reproductibilité de ses mesures n'a pas été étudiée pour l'endurance. L'objectif de cette étude était d'évaluer la reproductibilité inter et intra-opérateur des mesures de force maximale volontaire et d'endurance des quadriceps avec un dynamomètre manuel chez des patients atteints de BPCO.MéthodeLes mesures de force maximale volontaire et d'endurance du quadriceps ont été effectuées en isométrique à l'aide d'un même dynamomètre manuel. Trois sessions de mesures séparées de 24 heures chacune ont été réalisées. Les reproductibilités intra- et interopérateurs ont été évaluées par le calcul du coefficient de corrélation intraclasse.RésultatsVingt et un patients ont été inclus. Les coefficients de corrélations intraclasses pour la force maximale volontaire en intra- et interopérateurs étaient compris entre 0,95 et 0,99. Concernant l'endurance, le coefficient pour la reproductibilité intra-opérateur était de 0,81. Les deux coefficients de corrélation intraclasse pour la reproductibilité interopérateurs étaient de 0,69 et 0,77.ConclusionLe dynamomètre permet une excellente reproductibilité de la force maximale volontaire et une reproductibilité correcte à excellente de l'endurance. Cet outil est utilisable pour l'évaluation en pratique courante du quadriceps dans la BPCO, en particulier au cours de la réhabilitation respiratoire.IntroductionPatients with COPD frequently have lower strength and endurance in their lower limbs compared to healthy subjects and evaluation of their quadriceps strength is recommended in practice. The handheld dynamometer has been validated and is easy to use for this measurement but its reproducibility has never been studied for endurance evaluation and only poorly for strength. The objective of this study was to estimate the inter and intra-operator reproducibility of maximal voluntary strength and endurance measurements of the quadriceps with a handheld dynamometer in patients with COPD.MethodsThe measurements of maximal voluntary strength and endurance were performed with a single handheld dynamometer using isometric contraction. Three measurement sessions were undertaken, separated by 24hours. The intra- and interoperator reproducibility were estimated by calculation of the intraclass correlation coefficient.ResultsOverall, 21 patients were included in the study. The intraclass correlation coefficient calculated for the maximal voluntary strength for intra and interoperator reliability ranged between 0.95 and 0.99. For endurance, the coefficient for intra-operator reliability was 0.81 and the two for interoperator reliability were 0.69 and 0.77.ConclusionThe handheld dynamometer allows an excellent inter and intra-operator reproducibility for the measurement of quadricipital maximal voluntary strength and a correct to excellent reproducibility for the measurement of quadricipital endurance. This tool may be used for the evaluation of quadriceps strength in clinical practice in COPD patients, particularly during rehabilitation.



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Le tatouage et le principe de dignité humaine

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Publication date: Available online 12 October 2017
Source:Médecine & Droit
Author(s): Chloé Mitaine
Le tatouage est une pratique qui devient de plus en plus populaire dans notre société. Il implique nécessairement la notion de corps et de protection du corps. En effet, il dénature le corps humain puisqu'il le modifie. Ce faisant, il semble contrevenir au principe du respect de la dignité humaine. Or, dans le même temps, il respecte le principe de la libre disposition de son corps lorsque cette modification du corps est un acte désiré par la personne elle-même. L'opposition entre ces deux grands principes amène à se poser la question du rapport entre la dignité et le tatouage. La réponse est nuancée puisque le tatouage ne peut pas être considéré comme indigne en lui-même, alors que l'utilisation qui en est faite peut l'être.Tattooing is a practice that is becoming more and more popular in our society. It necessarily implies the notion of body and protection of the body. Indeed, it denatures the human body since it modifies it. In so doing, it appears to contravene the principle of respect for human dignity. At the same time, it respects the right to treat one's body as one pleases when this modification of the body is an act desired by the person himself. The contrast between these two main principles leads to the question of the relationship between dignity and tattooing. The answer is nuanced since the tattoo cannot be considered unworthy in itself, whereas the use made of it can be so considered.



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The Development of a Novel Perfused Cadaver Model With Dynamic Vital Sign Regulation and Real-World Scenarios to Teach Surgical Skills and Error Management

Publication date: Available online 14 October 2017
Source:Journal of Surgical Education
Author(s): Michael Minneti, Craig J. Baker, Maura E. Sullivan
AbstractThe landscape of graduate medical education has changed dramatically over the past decade and the traditional apprenticeship model has undergone scrutiny and modifications. The mandate of the 80-hour work-week, the introduction of integrated residency programs, increased global awareness about patient safety along with financial constraints have spurred changes in graduate educational practices. In addition, new technologies, more complex procedures, and a host of external constraints have changed where and how we teach technical and procedural skills. Simulation-based training has been embraced by the surgical community and has quickly become an essential component of most residency programs as a method to add efficacy to the traditional learning model.The purpose of this paper is twofold: (1) to describe the development of a perfused cadaver model with dynamic vital sign regulation, and (2) to assess the impact of a curriculum using this model and real world scenarios to teach surgical skills and error management. By providing a realistic training environment our aim is to enhance the acquisition of surgical skills and provide a more thorough assessment of resident performance.Twenty-six learners participated in the scenarios. Qualitative data showed that participants felt that the simulation model was realistic, and that participating in the scenarios helped them gain new knowledge, learn new surgical techniques and increase their confidence performing the skill in a clinical setting. Identifying the importance of both technical and nontechnical skills in surgical education has hastened the need for more realistic simulators and environments in which they are placed. Team members should be able to interact in ways that allow for a global display of their skills thus helping to provide a more comprehensive assessment by faculty and learners.



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How Does Level and Type of Experience Affect Measurement of Joint Range of Motion?

Publication date: Available online 14 October 2017
Source:Journal of Surgical Education
Author(s): Russell R. Russo, Matthew B. Burn, Sabir K. Ismaily, Brayden J. Gerrie, Shuyang Han, Jerry Alexander, Christopher Lenherr, Philip C. Noble, Joshua D. Harris, Patrick C. McCulloch
ObjectivesComparison of range of motion measurements by 3 types of investigators with different levels and types of training using three different measurement techniques. The study hypothesis was that the accuracy and precision of range of motion measurements would vary based on (1) the level and type of experience of the investigator and (2) the measurement technique used.Design/SettingDescriptive laboratory study.ParticipantsTen fresh frozen cadavers (20 upper and 20 lower extremities).InterventionsShoulder, elbow, hip, and knee motion were measured using 3 different measurement techniques (digital photography, goniometry, and visual estimation) by 3 groups of investigators (attending orthopedic surgeons, physical therapists, and residents). Accuracy was defined by the difference from the reference standard (motion capture analysis), whereas precision was defined by the proportion of measurements within either 5° or 10° of the reference standard. Analysis of variance, t-tests, and chi-squared tests were used.ResultsStatistically significant (p < 0.05) differences in accuracy were found for hip flexion, abduction, internal rotation, external rotation, and knee flexion. However, none of these differences met the authors' defined clinical significance (maximum difference 3°). Precision was significantly (p < 0.05) different for elbow extension, hip flexion, abduction, internal rotation, external rotation, and knee flexion.ConclusionThis study found that clinically accurate measurements of shoulder, elbow, hip, and knee motion are obtained regardless of technique used or the investigators' level and type of experience. Precision was equivalent for all shoulder motions, elbow flexion, and knee extension, but varied by as much as 7% to 28% between groups for all other motions.



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Graduating Surgical Residents Lack Competence in Critical Care Ultrasound

Publication date: Available online 14 October 2017
Source:Journal of Surgical Education
Author(s): Renuka Tripu, Margaret H. Lauerman, Daniel Haase, Syeda Fatima, Jacob Glaser, Cassandra Cardarelli, Thomas M. Scalea, Sarah Murthi
ObjectiveUltrasound provides accessible imaging for bedside diagnostics and procedural guidance, but may lead to misdiagnosis in untrained users. The main objective of this study was to determine observed and self-perceived competence with critical care ultrasound in graduated general surgery residents.DesignThe design of this study was a retrospective review. Ultrasound training program records were reviewed for number of prior ultrasound examinations performed, self-perceived competence, observed competence on faculty examinations, and intended future use of individual critical care ultrasound examinations.SettingThis study was undertaken at the R Adams Cowley Shock Trauma Center, which is a tertiary care center in Baltimore, MD.ParticipantsGraduated general surgery residents were identified at the beginning of their surgical critical care fellowship at our institution, and were included if they participated in our critical care ultrasound education program. Fifteen graduated general surgery residents were included.ResultsPrior ultrasound experience ranged from 100% for focused assessment of sonography for trauma (FAST) to 13.3% for advanced cardiac assessment. Self-perceived competence ranged from 46.7% with FAST to 0% for advanced cardiac assessment. Observed competence ranged from 20.0% for FAST examinations to 0% for basic cardiac assessment, advanced cardiac assessment, and inferior vena cava (IVC) assessment. All participants intended to use ultrasound in the future for FAST, pneumothorax detection and basic cardiac assessment, and 86.7% for IVC assessment and advanced cardiac assessment. Of participants with self-perceived competence, 28.6% had observed competence with FAST, 0% with IVC assessment, and 100% with pneumothorax detection.ConclusionsGraduated general surgery residents are not competent in multiple critical care ultrasound examinations despite universally planning to use critical care ultrasound in future practice. Current exposure to ultrasound in residency may give a false sense of competency with ultrasound use. A standardized ultrasound curriculum is an urgent need for general surgery training.



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Validation of a Novel Inverted Peg Transfer Task: Advancing Beyond the Regular Peg Transfer Task for Surgical Simulation-Based Assessment

Publication date: Available online 14 October 2017
Source:Journal of Surgical Education
Author(s): Amro M. Abdelrahman, Denny Yu, Bethany R. Lowndes, EeeLN H. Buckarma, Becca L. Gas, David R. Farley, Juliane Bingener, M. Susan Hallbeck
ObjectiveTo evaluate the validity of a novel inverted peg transfer (iPT) task for assessing laparoscopic skills of novices and experts and compare iPT to the regular PT (rPT) task to ensure surgical trainee acquisition of an adequate advanced laparoscopic skills level for safe laparoscopic practice in the operating room.DesignProspective crossover study.SettingMultidisciplinary simulation center and motion analysis laboratory, Mayo Clinic.ParticipantsNovices were medical students and surgical interns without laparoscopic experience. Experts were surgeons with at least 3 years of experience in laparoscopic surgery.MethodsThis was the first exposure to iPT for both groups. Completion time and performance metrics were recorded. A scoring rubric was used to calculate a normalized performance score between 0 and 100. Wilcoxon rank sum and Mann-Whitney tests were performed with α = 0.05. Receiver-operating characteristic curves were graphed for the 2 task scores to assess the tasks' sensitivity and specificity in differentiating laparoscopic experience level.Main Outcome MeasuresPerformance measures of completion time, transferred triangles, dropped triangles (errors), and the overall performance score on both tasks between- and within-subjects (i.e., novices and experts).ResultsThirty-six novices and eight experts participated. Both experts and novices had longer completion time and lower scores during iPT than rPT (p < 0.05). Within iPT, novice completion times were 144 seconds longer (p = 0.04), and performance score was 35 points lower than experts (p < 0.01). No differences between novices and experts were observed for completion time or performance scores (p > 0.05) for rPT. The iPT scores had a higher sensitivity and specificity than the rPT (area under the receiver-operating characteristic curve: iPT = 0.91; rPT = 0.69).ConclusionsiPT is a valid assessment of advanced laparoscopic skills for surgical trainees with higher specificity and sensitivity than rPT. As advanced minimally invasive surgery becomes more common, it is important that tasks such as iPT be included in surgical simulation curricula and training assessment.



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Current Techniques of Teaching and Learning in Bariatric Surgical Procedures: A Systematic Review

Publication date: Available online 13 October 2017
Source:Journal of Surgical Education
Author(s): Mirjam Kaijser, Gabrielle van Ramshorst, Bart van Wagensveld, Jean-Pierre Pierie
ObjectiveThe gastric sleeve resection and gastric bypass are the 2 most commonly performed bariatric procedures. This article provides an overview of current teaching and learning methods of those techniques in resident and fellow training.DesignA database search was performed on Pubmed, Embase, and the Education Resources Information Center (ERIC) to identify the methods used to provide training in bariatric surgery worldwide. After exclusion based on titles and abstracts, full texts of the selected articles were assessed. Included articles were reviewed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.ResultsIn total, 2442 titles were identified and 14 full text articles met inclusion criteria. Four publications described an ex vivo training course, and 6 focused on at least 1 step of the gastric bypass procedure. Two randomized controlled trials (RCT) provided high-quality evidence on training aspects. Surgical coaching caused significant improvement of Bariatric Objective Structured Assessment of Technical Skills (BOSATS) scores (3.60 vs. 3.90, p = 0.017) and reduction of technical errors (18 vs. 10, p = 0.003). A preoperative warm-up increased global rating scales (GRS) scores on depth perception (p = 0.02), bimanual dexterity (p = 0.01), and efficiency of movements (p = 0.03).ConclusionStepwise education, surgical coaching, warming up, Internet-based knowledge modules, and ex vivo training courses are effective in relation to bariatric surgical training of residents and fellows, possibly shortening their learning curves.



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Resource Usage Implementing the Surgical Resident Prep Curriculum at a Single Institution

Publication date: Available online 14 October 2017
Source:Journal of Surgical Education
Author(s): Lily Owei, Chris Neylan, Rachel Kelz, Kristoffel R. Dumon, Steve R. Allen, Noel Williams, Daniel T. Dempsey, Carla Fisher
ObjectiveThe Resident Prep Curriculum (RPC), published in 2014 and developed as a collaboration of the American College of Surgeons, Association of Program Directors in Surgery, and the Association for Surgical Education, was designed to improve the quality and consistency of medical student preparation for surgical residency. We aim to assess the feasibility of and resource usage for implementation of this curriculum at our institution.DesignOur institution expanded upon a pre-existing 2-week surgical preparatory course, adding modules designed to meet the goals and objectives of the RPC. We performed an evaluation of the resources required for these additions, namely time, logistics and incremental cost.SettingThe course took place at the Perelman School of Medicine, which is a large, academic medical center affiliated with the Hospital of the University of Pennsylvania.ResultsOur course satisfied each of the six domains outlined in the RPC. In 2015, 22 students were enrolled in the course. It was run over a consecutive 4-week period in the spring of 2015, with 9 full and 9 half days. To meet the needs of the Curriculum, approximately 33 hours (38%) were spent in the classroom, 34 hours (39%) in a simulation center, and 20 hours (23%) in the anatomical laboratory. Seventy faculty-hours (from 5 disciplines) and 73 resident-hours (double-counting for cotaught modules) were required to support the course. Besides room availability, funding was required for certain aspects of the course such as cadavers, dedicated anatomy teaching, and the costs of supplies in the simulation center. There is also a cost associated with the use of the Penn Medicine Simulation Center. Taking these into account, the total cost of implementing the curriculum amounted to $30,627.10.ConclusionThe implementation of the RPC was feasible but relied heavily upon faculty/resident time. As a result of the success of this initiative, our medical school seeks to expand the idea across multiple specialties.



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Surgical Education Module Improves Operative Proficiency in Endoscopic Carpal Tunnel Release: A Blinded Randomized Controlled Trial of Trainees

Publication date: Available online 13 October 2017
Source:Journal of Surgical Education
Author(s): Steve J. Kempton, A. Neil Salyapongse, Jacqueline S. Israel, Benjamin A. Mandel
ObjectiveThe purpose of this study is to evaluate whether an interactive endoscopic carpal tunnel release (ECTR) surgical education module can improve knowledge of surgical indications and improve procedural competency.DesignAn ECTR education module was developed and trainees at various level of training were enrolled and randomized to surgical module and nonmodule (control) groups. Subjects were instructed that they would be the primary surgeon performing an ECTR. A written assessment was administered before and after module completion or independent case preparation to test comprehension of the procedure. The senior author evaluated each subject's intraoperative performance using a 5-point scoring system. Statistical analysis was performed using chi-square and paired t-tests.SettingThis study took place at a tertiary care hospital at the University of Wisconsin.ResultsIn all, 30 subjects were tested (15 surgical module and 15 nonmodule). There were no differences in prepreparation test scores between groups. Postpreparation test scores following use of the module were significantly higher compared to the nonmodule group. The average operation performance scores for the surgical module group and nonmodule group were 96% and 82%, respectively. The surgical module group performed significantly better on all operative steps except for dressing application. Surgical module subjects without prior ECTR experience (n = 7) had operative scores that were significantly higher than those for nonmodule subjects without previous ECTR experience (n = 8) (95% vs. 75%). There was no difference in operative scores between surgical module subjects with no prior experience (n = 7) and nonmodule subjects who had performed at least 1 prior case (n = 7) (95% vs. 89%).ConclusionsThe use of an ECTR surgical education module demonstrates a significant benefit in ECTR-naïve subjects. When compared to subjects with previous ECTR experience, ECTR-naïve subjects trained using the surgical module demonstrate better familiarity with the equipment and equivalent performance of the procedure.



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Comparison of two coarse-grained models of cis-polyisoprene with and without pressure correction

Publication date: 9 November 2017
Source:Polymer, Volume 130
Author(s): Takahiro Ohkuma, Kurt Kremer
We investigate two coarse-grained models of a cis-polyisoprene melt. The bonded interactions which are used in both models are derived by Boltzmann inversion of the probability distributions of the bonded variables in a single chain simulation. The non-bonded interactions are derived by an iterative Boltzmann inversion method in the melt state with pressure correction in a model and without in the other model. In our mapping rule, two or three carbons are grouped into coarse-grained beads. The trade-off relationship between pressure and compressibility is observed in the coarse-grained models. Since the relaxation dynamics of the coarse-grained models are accelerated by the smoothed potentials, single numerical factors are introduced to rescale the time scale of the coarse-grained models, respectively. The factors of the two models are in the same order but the model with pressure correction displays larger acceleration than the other. It is found that the stress relaxation function near equilibrium and the nonlinear viscosity under steady shear are essentially the same between the two coarse-grained models in the rescaled time scales despite of their different equilibrium pressures. We also study the dependency of the rescaling factors on the chain length of the polymer. The rescaling factors increase with increasing the chain length and exponentially saturates to certain values around 100 monomers in chains.

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Effect of monomer sequence distribution on the CO2-philicity of a well-defined ternary copolymer: Poly(vinyl acetate-co-vinyl butyrate-co-vinyl butyl ether)

Publication date: 9 November 2017
Source:Polymer, Volume 130
Author(s): Zewen Zhu, Yongfei Zhang, Wei Jiang, Lu Sun, Lixin Dai, Gang Zhang, Jun Tang
The work aims to interpret the phase behavior of multi-polymers in super critical CO2 via a spatially dependent structural parameter, the monomer sequence distribution, rather than traditional statistical factors. Well-defined statistical copolymers based on three CO2-philic monomers, vinyl acetate, vinyl butyrate and vinyl butyl ether, were synthesized with reversible addition-fragmentation chain transfer free-radical polymerization by combining their kinetic behaviors and pairwise reactivity ratios into the Alfrey–Goldfinger–Skeist model. The corresponding cloud point pressures become nonlinear with the polymer composition and possess upper critical solution pressure behavior. Additionally, their diad and triad monomer sequence distributions were calculated by simple theoretical arithmetic. While analyzing the cloud point pressure measurements, we found that both the differences in composition and symmetrical structure of the monomer triads could impact the CO2-philicity of triads, which were close to the properties of the products, and thus, the variations in the triad sequence distribution could reasonably predict the phase behavior of the products.

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Surface roughness and bacterial adhesion on root dentin treated with diode laser and conventional desensitizing agents

Abstract

The treatments for dentin hypersensitivity (DH) may change the surface roughness of the root dentin, which can lead to biofilm accumulation, increasing the risk of root caries. The aim was to compare the surface roughness of root dentin after different treatments of DH and the biofilm formation on those surfaces. After initial surface roughness (Sa) assessment, 50 bovine root fragments received the following treatments (n = 10): G 1—no treatment; G2—5% sodium fluoride varnish; G3—professional application of a desensitizing dentifrice; G4—toothbrushing with a desensitizing dentifrice; and G5—diode laser application (908 nm; 1.5 W, 20 s). The Sa was reevaluated after treatments. Afterward, all samples were incubated in a suspension of Streptococcus mutans at 37 °C for 24 h. The colony-forming units (CFU) were counted using a stereoscope, and the results were expressed in CFU/mL. The one-way ANOVA and the Tukey's tests compared the roughness data and the results obtained on the bacterial adhesion test (α = 5%). G2 (2.3 ± 1.67%) showed similar Sa variation than G1 (0.25 ± 0.41%) and G5 (5.69 ± 0.99%), but different from group G3 (9.05 ± 2.39%). Group 4 showed the highest Sa variation (30.02 ± 3.83%; p < 0.05). Bacterial adhesion was higher in G4 (2208 ± 211.9), suggesting that bacterial growth is greater on rougher surfaces. The diode laser and the conventional treatments for DH may change the surface roughness of the root dentin, but only brushing with desensitizing dentifrice induced a higher bacteria accumulation on root dentin surface.



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CD4+CD52lo T-cell expression contributes to the development of systemic lupus erythematosus

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Publication date: Available online 13 October 2017
Source:Clinical Immunology
Author(s): Masataka Umeda, Tomohiro Koga, Kunihiro Ichinose, Takashi Igawa, Tomohito Sato, Ayuko Takatani, Toshimasa Shimizu, Shoichi Fukui, Ayako Nishino, Yoshiro Horai, Yasuko Hirai, Shin-ya Kawashiri, Naoki Iwamoto, Toshiyuki Aramaki, Mami Tamai, Hideki Nakamura, Kazuo Yamamoto, Norio Abiru, Tomoki Origuchi, Yukitaka Ueki, Atsushi Kawakami
The cell-surface glycoprotein CD52 is widely expressed in lymphocytes. CD4+CD52hi T cells are functioning suppressor CD4+T cells. We investigated the role of the immune regulation of CD4+CD52 T cells in systemic lupus erythematosus (SLE). CD4+CD52lo T cells were increased in SLE patients, in positive correlation with SLEDAI, anti-ds-DNA antibody, and IgG concentration. Circulating follicular helper-like T cells (Tfh-like cells) were also increased in SLE, in positive correlation with CD4+CD52lo T cells. Chemokine receptor 8 (CCR8) expression in CD4+CD52lo T cells was increased. In vitro experiments using CD4 T cells of SLE patients showed that thymus and activation-regulated chemokine (TARC), a ligand of CCR8, contributed to the development of CD4+CD52hi T cells into CD4+CD52lo T cells. Our findings suggest that CD4+CD52lo T-cell upregulation is involved in the production of pathogens by autoantibodies, and TARC may contribute to the development of SLE through an aberrant induction of CD4+CD52lo T cells.



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Overexpression of Notch ligand Delta-like-1 by dendritic cells enhances their immunoregulatory capacity and exerts antiallergic effects on Th2-mediated allergic asthma in mice

Publication date: Available online 14 October 2017
Source:Clinical Immunology
Author(s): Chen-Chen Lee, Chu-Lun Lin, Sy-Jye Leu, Yueh-Lun Lee
Dendritic cells (DCs) are professional antigen-presenting cells, and Notch ligand Delta-like-1 (DLL1) on DCs was implicated in type 1T helper (Th1) differentiation. In this study, we produced genetically engineered bone marrow-derived DCs that expressed DLL1 (DLL1-DCs) by adenoviral transduction. DLL1-DCs exerted a fully mature phenotype, and had positive effects on expression levels of interleukin (IL)-12 and costimulatory molecules. Coculture of allogeneic T cells with ovalbumin (OVA)-pulsed DLL1-DCs enhanced T cell proliferative responses and promoted Th1 cell differentiation. Furthermore, adoptive transfer of OVA-stimulated DLL1-DCs into asthmatic mice alleviated the cardinal features of allergic asthma, including immunoglobulin E (IgE) production, airway hyperresponsiveness (AHR), airway inflammation, and production of Th2-type cytokines. Notably, enhanced levels of the Th1-biased IgG2a response and interferon (IFN)-γ production were observed in these mice. Taken together, these data indicate that DLL1-DCs promoted Th1 cell development to alter the Th1/Th2 ratio and ameliorate Th2-mediated allergic asthma in mice.

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Manipulation of the response of human endothelial colony-forming cells by focal adhesion assembly using gradient nanopattern plates

Publication date: Available online 14 October 2017
Source:Acta Biomaterialia
Author(s): Long-Hui Cui, Hyung Joon Joo, Dae Hwan Kim, Ha-Rim Seo, Jung Suk Kim, Seung-Cheol Choi, Li-Hua Huang, Ji Eun Na, I-Rang Lim, Jong-Ho Kim, Im Joo Rhyu, Soon Jun Hong, Kyu Back Lee, Do-Sun Lim
Nanotopography plays a pivotal role in the regulation of cellular responses. Nonetheless, little is known about how the gradient size of nanostructural stimuli alters the responses of endothelial progenitor cells without chemical factors. Herein, the fabrication of gradient nanopattern plates intended to mimic microenvironment nanotopography is described. The gradient nanopattern plates consist of nanopillars of increasing diameter ranges [120–200 nm (GP 120/200), 200–280 nm (GP 200/280), and 280–360 nm (GP 280/360)] that were used to screen the responses of human endothelial colony-forming cells (hECFCs). Nanopillars with a smaller nanopillar diameter caused the cell area and perimeter of hECFCs to decrease and their filopodial outgrowth to increase. The structure of vinculin (a focal adhesion marker in hECFCs) was also modulated by nanostructural stimuli of the gradient nanopattern plates. Moreover, Rho-associated protein kinase (ROCK) gene expression was significantly higher in hECFCs cultured on GP 120/200 than in those on flat plates (no nanopillars), and ROCK suppression impaired the nanostructural-stimuli-induced vinculin assembly. These results suggest that the gradient nanopattern plates generate size-specific nanostructural stimuli suitable for manipulation of the response of hECFCs, in a process dependent on ROCK signaling. This is the first evidence of size-specific nanostructure-sensing behavior of hECFCs.SignificanceNano feature surfaces are of growing interest as materials for a controlled response of various cells. In this study, we successfully fabricated gradient nanopattern plates to manipulate the response of blood-derived hECFCs without any chemical stimulation. Interestingly, we find that the sensitive nanopillar size for manipulation of hECFCs is range between 120 nm to 200 nm, which decreased the area and increased the filopodial outgrowth of hECFCs. Furthermore, we only modulate the nanopillar size to increase ROCK expression can be an attractive method for modulating the cytoskeletal integrity and focal adhesion of hECFCs.

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Gold nanocage decorated pH-sensitive micelle for highly effective photothermo-chemotherapy and photoacoustic imaging

Publication date: Available online 13 October 2017
Source:Acta Biomaterialia
Author(s): Guoyong Zhou, Hong Xiao, Xiaoxia Li, Yi Huang, Wei Song, Liang Song, Meiwan Chen, Du Cheng, Xintao Shuai
A pH-sensitive copolymer PAsp(DIP)-b-PAsp(MEA) (PDPM) was synthesized and self-assembled to micelle loading chemotherapeutic drug doxorubicin (DOX) and introducing a gold nanocage structure for photothermo-chemotherapy and photoacoustic imaging. After further surface modification with polyethylene glycol (PEG), the DOX-loaded pH-sensitive gold nanocage (D-PGNC) around 100 nm possessed a uniform spherical structure with a pH-sensitive core of PAsp(DIP) incorporating DOX, an interlayer crosslinked via disulfide bonds and decorated with discontinuous gold shell, and a PEG corona. The release of DOX from D-PGNC was turned off in bloodstream due to the cross-linking and gold decoration of interlayer but turned on inside tumor tissue by multiple stimulations including the low pH value of tumor tissue (≈ 6.8), the low lysosomal pH value of cancer cells (≈ 5.0) and near-infrared (NIR) irradiation. The gold nanocage receiving NIR irradiation could generate hyperthermia to ablate tumor cells. Moreover, the photoacoustic (PA) imaging and analysis of DOX fluorescence inside tumor tissue demonstrated that photothermal therapy based on the gold nanocage effectively drove DOX penetration inside tumor. Owing to the rapid intratumor release and deep tissue penetration of drug favorable for killing cancer cells survived the photothermal therapy, the combined therapy based on D-PGNC via NIR irradiation exhibited a synergistic treatment effect superior to either chemotherapy or NIR-induced photothermal therapy alone.Statement of SignificanceThe novelty of the manuscript is its multifunctional system which incorporated anticancer drug DOX in its pH-sensitive core and acted as a template to introduce a gold nanocage. This nanomedicine presents potentials of sequestrating drug molecules in blood circulation but releasing them inside tumor upon responding to the acidic microenvironment therein. Exposure to NIR laser further expedited the pH-sensitive DOX release and promoted DOX penetration into cancer tissues far away from the vasculature. Consequently, the combined photothermo-chemotherapy showed synergistic effects to inhibit tumor growth and prolong animal survival in nude mice bearing human SKOV-3 ovarian tumor. Moreover, owing to the decoration with gold nanocage, the tumor accumulation and intratumor diffusion of the micelles were easily trackable using photoacoustic imaging.

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Title: In situ depot formation of anti-HIV fusion-inhibitor peptide in recombinant protein polymer hydrogel

Publication date: Available online 14 October 2017
Source:Acta Biomaterialia
Author(s): Daisuke Asai, Taisei Kanamoto, Mitsuko Takenaga, Hideki Nakashima
Most peptide drugs have short half-lives, necessitating frequent injections that may induce skin sensitivity reactions; therefore, versatile prolonged-release delivery platforms are urgently needed. Here, we focused on an oxidatively and thermally responsive recombinant elastin-like polypeptide with periodic cysteine residues (cELP), which can rapidly and reversibly form a disulfide cross-linked network in which peptide can be physically incorporated. As a model for proof of concept, we used enfuvirtide, an antiretroviral fusion-inhibitor peptide approved for treatment of human immunodeficiency virus (HIV) infection. cELP was mixed with enfuvirtide and a small amount of hydrogen peroxide (to promote cross-linking), and the soluble mixture was injected subcutaneously. The oxidative cross-linking generates a network structure, causing the mixture to form a hydrogel in situ that serves as an enfuvirtide depot. We fabricated a series of enfuvirtide-containing hydrogels and examined their stability, enfuvirtide-releasing profile and anti-HIV potency in vitro. Among them, hydrophobic cELP hydrogel provided effective concentrations of enfuvirtide in blood of rats for up to 8 hr, and the initial concentration peak was suppressed compared with that after injection of enfuvirtide alone. cELP hydrogels should be readily adaptable as platforms to provide effective depot systems for delivery of other anti-HIV peptides besides enfuvirtide.Statement of SignificanceIn this paper, we present an anti-HIV peptide delivery system using oxidatively and thermally responsive polypeptides that contain multiple periodic cysteine residues as an injectable biomaterial capable of in situ self-gelation, and we demonstrate its utility as an injectable depot capable of sustained release of anti-HIV peptides. The novelty of this work stems from the platform employed to provide the depot encapsulating the peptide drugs (without chemical conjugation), which consists of rationally designed, genetically engineered polypeptides that enable the release rate of the peptide drugs to be precisely controlled.

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Overcoming Multiple Gastrointestinal Barriers by Bilayer Modified Hollow Mesoporous Silica Nanocarriers

Publication date: Available online 14 October 2017
Source:Acta Biomaterialia
Author(s): Ying Wang, Yating Zhao, Yu Cui, Qinfu Zhao, Qiang Zhang, Sara Musetti, Karina A Kinghorn, Siling Wang
Oral administration of nanocarriers remains a significant challenge in the pharmaceutical sciences. The nanocarriers must efficiently overcome multiple gastrointestinal barriers including the harsh gastrointestinal environment, the mucosal layer, and the epithelium. Neutral hydrophilic surfaces are reportedly necessary for mucus permeation, but hydrophobic and cationic surfaces are important for efficient epithelial absorption. To accommodate these conflicting surface property requirements, we developed a strategy to modify nanocarrier surfaces with cationic cell-penetrating peptides (CPP) concealed by a hydrophilic succinylated casein (SCN) layer. SCN is a mucus-inert natural material specifically degraded in the intestine, thus protecting nanocarriers from the harsh gastric environment, facilitating their mucus permeation, and inducing exposure of CPPs after degradation for further effective transepithelial transport. Quantum dots doped hollow silica nanoparticles (HSQN) with a diameter around 180 nm was used as the nanocarrier and demonstrated as high as 50% loading efficacy of paclitaxel, a model drug with poor solubility and permeability. The dual layer modification strategy prevented premature drug leakage in stomach and maintained high mucus permeation (the trajectory spanned 9-fold larger area than single CPP modification). After intestinal degradation of SCN by trypsin, these nanocarriers exhibited strong interaction with epithelial membranes and a 5-fold increase in cellular uptake. Significant transepithelial transport and intestinal distribution were also observed for this dual-modified formulation. A pharmacokinetics study on the paclitaxel-loaded nanocarrier found 40% absolute bioavailability and 7.8-fold higher AUC compared to oral Taxol®. Compared with single CPP modified nanocarriers, our formulation showed increased in vivo efficacy and tumor accumulation of the model drug with negligible intestinal toxicity. In summary, sequential modification with CPP and SCN layers on HSQN offers a potential strategy to overcome the multiple barriers of the gastrointestinal tract.Statement of significanceOral administration of nanocarriers remains a big challenge due to the multiple gastrointestinal barriers. In order to achieve both strong mucus permeation and efficient epithelial absorption, we modified the surface of silica nanoparticles with two layers: cell penetrating peptide (CPP) layer and succinylated casein (SCN) layer. The newly developed nanoformulations are demonstrated to have the following advantages: 1) versatile carrier with easy preparation, 2) high drug loading especially for poor soluble molecules, 3) reduced drug leakage in the stomach, 4) effective mucus penetration and transepithelial transport and 5) good biocompatibility, which in all indicate a great potential of this bilayer-modification strategy to facilitate the oral delivery of therapeutic agents.

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Hybrid-spheroids incorporating ECM like engineered fragmented fibers potentiate stem cell function by improved cell/cell and cell/ECM interactions

Publication date: Available online 14 October 2017
Source:Acta Biomaterialia
Author(s): Taufiq Ahmad, Jinkyu Lee, Young Min Shin, Hyeok Jun Shin, Sajeesh Kumar Madhurakat Perikamana, Sun Hwa Park, Sung Won Kim, Heungsoo Shin
Extracellular matrix (ECM) microenvironment is critical for the viability, stemness, and differentiation of stem cells. In this study, we developed hybrid-spheroids of human turbinate mesenchymal stem cells (hTMSCs) by using extracellular matrix (ECM) mimicking fragmented fibers (FFs) for improvement of the viability and functions of hTMSCs. We prepared FFs with average size of 68.26 µm by partial aminolysis of poly L-lactide (PLLA) fibrous sheet (FS), which was coated with polydopamine for improved cell adhesion. The proliferation of hTMSCs within the hybrid-spheroids mixed with fragmented fibers was significantly increased as compared to that from the cell-only group. Cells and fragmented fibers were homogenously distributed with the presence of pore like empty spaces in the structure. Lox-1 staining revealed that the hybrid-spheroids improved the cell viability, which was potentially due to enhanced transport of oxygen through void space generated by engineered ECM. Transmission electron microscopy (TEM) analysis confirmed that cells within the hybrid-spheroid formed strong cell junctions and contacts with fragmented fibers. The expression of cell junction proteins including connexin 43 and E-cadherin was significantly upregulated in hybrid-spheroids by 16.53 ± 0.04 and 28.26 ± 0.11 fold greater than that from cell-only group. Similarly, expression of integrin α2, α5, and β1 was significantly enhanced at the same group by 25.72 ± 0.13, 27.48 ± 0.49, and 592.78 ± 0.06 fold, respectively. In addition, stemness markers including Oct-4, Nanog, and Sox2 were significantly upregulated in hybrid-spheroids by 96.56 ± 0.06, 158.95 ± 0.06, and 115.46 ± 0.47 fold, respectively, relative to the cell-only group. Additionally, hTMSCs within the hybrid-spheroids showed significantly greater osteogenic differentiation under osteogenic media conditions. Taken together, our hybrid-spheroids can be an ideal approach for stem cell expansion and serve as a potential carrier for bone regeneration.Statement of SignificanceCells are spatially arranged within extracellular matrix (ECM) and cell/ECM interactions are crucial for cellular functions. Here, we developed a hybrid-spheroid system incorporating engineered ECM prepared from fragmented electrospun fibers to tune stem cell functions. Conventionally prepared cell spheroids with large diameters (> 200 µm) is often prone to hypoxia. In contrast, the hybrid-spheroids significantly enhanced viability and proliferation of human turbinate mesenchymal stem cells (hTMSCs) as compared to spheroid prepared from cell only. Under these conditions, the presence of fragmented fibers also improved maintenance of stemness of hTMSCs for longer time cultured in growth media and demonstrated significantly greater osteogenic differentiation under osteogenic media conditions. Thus, the hybrid-spheroids can be used as a delivery carrier for stem cell based therapy or a 3D culture model for in vitro assay.

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Gelatin promotes rapid restoration of the blood brain barrier after acute brain injury

Publication date: Available online 14 October 2017
Source:Acta Biomaterialia
Author(s): Lucas S. Kumosa, Valdemar Zetterberg, Jens Schouenborg
Gelatin coating of brain implants is known to provide considerable benefits in terms of reduced inflammatory sequalae and long-term neuroprotective effects. However, the mechanisms for gelatin's protective role in brain injury are still unknown. To address this question, cellular and molecular markers were studied with quantitative immunohistochemical microscopy at acute (<2 hours, 1, 3 days), intermediate (1-2 weeks) and long-term time points (6 weeks) after transient insertion of stainless steel needles into female rat cortex cerebri with or without gelatin coating. Compared to non-coated controls, injuries caused by gelatin coated needles showed a significantly faster resolution of post-stab bleeding/leakage and differential effects on different groups of microglia cells. While similar levels of matrix metalloproteinase (MMP-2 and MMP-9, two gelatinases) was found for coated and noncoated needle stabs during the first week, markedly increased levels of both MMPs was seen for gelatin-coated but not non-coated needle stabs after 2 weeks. Neuronal populations and activated astrocytes were largely unaffected. In conclusion, the beneficial effects of gelatin may be the combined results of faster healing of the blood brain barrier curtailing leakage of blood borne molecules/cells into brain parenchyma and to a modulation of the microglial population response favoring restitution of the injured tissue. These findings present an important therapeutic potential for gelatin coatings in various disease, injury and surgical conditions.Statement of SignificanceThe neural interfaces field holds great promise to enable elucidation of neural information processing and to develop new implantable devices for stimulation based therapy. Currently, this field is struggling to find solutions for reducing tissue reactions to implanted micro and nanotechnology. Prior studies have recently shown that gelatin coatings lower activation of digestive microglia and mitigate the ubiquitous loss of neurons adjacent to implanted probes, both of which impede implant function. The underlying mechanisms remain to be elucidated, however. Our findings demonstrate for the first time that gelatin has a significant effect on the BBB by promoting rapid restoration of integrity after injury. Moreover, gelatin alters microglia phenotypes and modulates gelatinase activity for up to 2 weeks favoring anti-inflammation and restoration of the tissue. Given the key importance of the BBB for normal brain functions, we believe our findings have substantial significance and will be highly interesting to researchers in the biomaterial field.

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