Αρχειοθήκη ιστολογίου

Κυριακή 6 Δεκεμβρίου 2015

Immersion liquid techniques in solid particle characterization: A review

Publication date: 1 March 2016
Source:Talanta, Volume 149
Author(s): Ilpo Niskanen, Kenichi Hibino, Jukka Räty
Chemical, physical and optical properties of small solid particles are widely utilized in our everyday merchandises. For example, tailored particles embedded in paper or cosmetics improve the visual appearance of the products substantially. As a consequence of the small size of particles, one particle characterization tool is a microscope. It may provide e.g. the particle size, shape and the refractive index. The determination of the refractive index, using the microscope, typically exploited the so-called immersion liquid method. In this review, we provide an overview of non-imaging immersion matching techniques including immersion liquid set, the temperature, the wavelength, the double variation and the liquid evaporation methods. The basic features, benefits and limitations of each technique have been described followed by examples of potential applications in a quality monitoring of particle suspensions and colloids in industry.

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Fabrication of an ionic liquid-based macroporous polymer monolithic column via atom transfer radical polymerization for the separation of small molecules

Publication date: 1 March 2016
Source:Talanta, Volume 149
Author(s): Hang Zhang, Ligai Bai, Zhen Wei, Sha Liu, Haiyan Liu, Hongyuan Yan
A polymer monolithic column was prepared in a stainless steel column (50×4.6mm i.d.) via atom transfer radical polymerization technique using triallyl isocyanurate and ionic liquid (1-allyl-3-methylimidazolium chloride) as co-monomers, ethylene dimethacrylate as cross linking agent, polyethylene glycol 200, 1,4-butanediol, and N, N- dimethylformamide as porogen system, CCl4 as initiator, and FeCl2 as catalyst. The optimized polymer columns were characterized by scanning electron microscope, nitrogen adsorption-desorption instrument, mercury intrusion porosimetry, infrared spectrometer, and thermogravimetric analysis technique. Respectively, all of these factors above could illustrate that the optimized columns had relative uniform macroporous structure and high thermal stability. A series of basic and acidic small molecules, isomers, and homologues were used to evaluate the performance of these monoliths and enhanced column efficiency was obtained.

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Study of consumer fireworks post-blast residues by ATR-FTIR

Publication date: 1 March 2016
Source:Talanta, Volume 149
Author(s): Carlos Martín-Alberca, Félix Zapata, Héctor Carrascosa, Fernando E. Ortega-Ojeda, Carmen García-Ruiz
Specific analytical procedures are requested for the forensic analysis of pre- and post-blast consumer firework samples, which present significant challenges. Up to date, vibrational spectroscopic techniques such as Fourier transform infrared spectroscopy (FTIR) have not been tested for the analysis of post-blast residues in spite of their interesting strengths for the forensic field. Therefore, this work proposes a simple and fast procedure for the sampling and analysis of consumer firework post-blast residues by a portable FTIR instrument with an Attenuated Total Reflection (ATR) accessory. In addition, the post-blast residues spectra of several consumer fireworks were studied in order to achieve the identification of their original chemical compositions. Hence, this work analysed 22 standard reagents usually employed to make consumer fireworks, or because they are related to their combustion products. Then, 5 different consumer fireworks were exploded, and their residues were sampled with dry cotton swabs and directly analysed by ATR-FTIR. In addition, their pre-blast fuses and charges were also analysed in order to stablish a proper comparison. As a result, the identification of the original chemical compositions of the post-blast samples was obtained. Some of the compounds found were potassium chlorate, barium nitrate, potassium nitrate, potassium perchlorate or charcoal. An additional study involving chemometric tools found that the results might greatly depend on the swab head type used for the sampling, and its sampling efficiency. The proposed procedure could be used as a complementary technique for the analysis of consumer fireworks post-blast residues.

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Ultrasonic frequency analysis for estimating pH in albumin-rich biofluids

Publication date: 1 March 2016
Source:Talanta, Volume 149
Author(s): Andrien A. Rackov, David H. Burns
Ultrasound is known as a non-invasive imaging modality capable of propagating through highly scattering media such as tissue, blood, and other biological fluids, yet currently provides little chemical information. We have developed a straightforward and rapid methodology for estimating pH in albumin-rich biofluids based on analysis of ultrasonic frequencies. Albumin is the most abundant protein in serum and undergoes conformational changes with pH. It was shown that when ultrasound propagated through albumin solutions, the attenuation of collected ultrasound signals increased with pH. By measuring the ultrasound frequency spectra at several albumin concentrations and pH values, the pH of the solutions could be determined by multilinear regression. Differences in absolute protein content contributed to signal differences in the frequency profiles and were minimized through normalization of each spectrum by the sum of all its frequency intensities. This strategy was applied to human serum samples from multiple donors, for which a multilinear regression model was developed with a coefficient of determination (R2) of 0.93 and a standard error of estimate (SEE) of 0.08 pH units. The use of albumin as a pH indicator opens the doors for estimations in other albumin-rich media, such as amniotic fluid and cerebrospinal fluid.



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Ultrasound-assisted extraction of azadirachtin from dried entire fruits of Azadirachta indica A. Juss. (Meliaceae) and its determination by a validated HPLC-PDA method

Publication date: 1 March 2016
Source:Talanta, Volume 149
Author(s): Joelma Abadia Marciano de Paula, Lucas Ferreira Brito, Karen Lorena Ferreira Neves Caetano, Mariana Cristina de Morais Rodrigues, Leonardo Luiz Borges, Edemilson Cardoso da Conceição
Azadirachta indica A. Juss., also known as neem, is a Meliaceae family tree from India. It is globally known for the insecticidal properties of its limonoid tetranortriterpenoid derivatives, such as azadirachtin. This work aimed to optimize the azadirachtin ultrasound-assisted extraction (UAE) and validate the HPLC-PDA analytical method for the measurement of this marker in neem dried fruit extracts. Box–Behnken design and response surface methodology (RSM) were used to investigate the effect of process variables on the UAE. Three independent variables, including ethanol concentration (%, w/w), temperature (°C), and material-to-solvent ratio (gmL−1), were studied. The azadirachtin content (µgmL−1), i.e., dependent variable, was quantified by the HPLC-PDA analytical method. Isocratic reversed-phase chromatography was performed using acetonitrile/water (40:60), a flow of 1.0mLmin−1, detection at 214nm, and C18 column (250×4.6mm2, 5µm). The primary validation parameters were determined according to ICH guidelines and Brazilian legislation. The results demonstrated that the optimal UAE condition was obtained with ethanol concentration range of 75–80% (w/w), temperature of 30°C, and material-to-solvent ratio of 0.55gmL−1. The HPLC-PDA analytical method proved to be simple, selective, linear, precise, accurate and robust. The experimental values of azadirachtin content under optimal UAE conditions were in good agreement with the RSM predicted values and were superior to the azadirachtin content of percolated extract. Such findings suggest that UAE is a more efficient extractive process in addition to being simple, fast, and inexpensive.

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Utilization of deep eutectic solvents as novel mobile phase additives for improving the separation of bioactive quaternary alkaloids

Publication date: 1 March 2016
Source:Talanta, Volume 149
Author(s): Ting Tan, Mingliang Zhang, Yiqun Wan, Hongdeng Qiu
Deep eutectic solvents (DESs) were used as novel mobile phase additives to improve chromatographic separation of four quaternary alkaloids including coptisine chloride, sanguinarine, berberine chloride and chelerythrine on a C18 column. DESs as a new class of ionic liquids are renewably sourced, environmentally benign, low cost and easy to prepare. Seven DESs were obtained by mixing different hydrogen acceptors and hydrogen-bond donors. The effects of organic solvents, the concentration of DESs, the types of DESs and the pH values of the buffer solution on the separation of the analytes were investigated. The composition of acetonitrile and 1.0% deep eutectic solvents aqueous solution (pH 3.3, adjusted with hydrochloric acid) in a 32:68 (v/v) ratio was used as optimized mobile phase, with which four quaternary alkaloids were well separated. When a small amount of DESs was added in the mobile phase for the separation of alkaloids on the C18 column, noticeable improvements were distinctly observed such as decreasing peak tailing and improving resolution. The separation mechanism mediated by DESs as mobile phase additives can be attributed to combined effect of both hydrogen acceptors and hydrogen-bond donors. For example, choline chloride can effectively cover the residual silanols on silica surface and ethylene glycol can reduce the retention time of analytes. The proposed method has been applied to determine BerbC in Lanqin Chinese herbal oral solution and BerbC tablet. Utilization of DESs in mobile phase can efficiently improve separation and selectivity of analytes from complex samples.

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Development of Hf4+-immobilized polydopamine-coated magnetic graphene for highly selective enrichment of phosphopeptides

Publication date: 1 March 2016
Source:Talanta, Volume 149
Author(s): Haizhu Lin, Chunhui Deng
In this work, we first designed and synthesized an IMAC material with Hf4+ immobilized on polydopamine-coated magnetic graphene and applied it to phosphopeptides enrichment successfully. The newly prepared material gathered the advantages of large specific surface area of graphene, good hydrophilicity and biocompatibility of polydopamine and superparamagnetism of Fe3O4. We investigated the performance of Hf4+-immobilized polydopamine-coated magnetic graphene (denoted as magG@PDA-Hf4+) in phosphopeptides enrichment and the results showed high selectivity and sensitivity of the new material. Finally, we successfully applied magG@PDA-Hf4+ to phosphopeptides enrichment from non-fat milk digests and human serum, further demonstrating excellent performance of this new material in phosphopeptides enrichment.

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Cationic-perylene-G-quadruplex complex based fluorescent biosensor for label-free detection of Pb2+

Publication date: 1 March 2016
Source:Talanta, Volume 149
Author(s): Xu-Hua Zhao, Liang Gong, Yuan Wu, Xiao-Bing Zhang, Jun Xie
In this work we use a water-soluble cationic perylene derivative (compound 1) as the G-quadruplex (G4) structure fluorescence indicator to construct a fluorescent biosensor for simple, rapid and label-free detection of Pb2+. In the absence of Pb2+, strong electrostatic interactions between compound 1 and the G-rich DNA probe (PW17) induced the aggregation of compound 1 and resulted in the fluorescence quenching. In the presence of Pb2+, the PW17 formed Pb2+-stabilized G4 structure, which reduced the aggregation of compound 1 and gave rise to high fluorescence. This allowed us to use convenient "mix-and-detect" protocol for quantitative analysis of Pb2+. Since Pb2+ can specially induce PW17 to form compact DNA fold, our proposed biosensor displayed high selectivity for Pb2+. It also exhibited a high sensitivity to Pb2+, with a limit of detection of 5.0nM observed. Furthermore, the biosensor was applied for the detection of Pb2+ in urine and paint samples, and both showed satisfactory results.

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Development and evaluation of an ELIME assay to reveal the presence of Salmonella in irrigation water: Comparison with Real-Time PCR and the Standard Culture Method

Publication date: 1 March 2016
Source:Talanta, Volume 149
Author(s): G. Volpe, E. Delibato, L. Fabiani, E. Pucci, S. Piermarini, A. D'Angelo, F. Capuano, D. De Medici, G. Palleschi
A reliable, low-cost and easy-to-use ELIME (Enzyme-Linked-Immuno-Magnetic-Electrochemical) assay for detection of Salmonella enterica in irrigation water is presented. Magnetic beads (MBs), coupled to a strip of eight-magnetized screen-printed electrodes localized at the bottom of eight wells (8-well/SPE strip), effectively supported a sandwich immunological chain. Enzymatic by-product is quickly measured by chronoamperometry, using a portable instrument. With the goal of developing a method able to detect a wide range of Salmonella serotypes, including S. Napoli and S. Thompson strains responsible for various community alerts, different kinds of MBs, antibodies and blocking agents were tested. The final system employs MBs coated with a broad reactivity monoclonal antibody anti-salmonella and blocked with dry milk. For a simple and rapid assay these two steps were performed in a preliminary phase, while the two sequential incubations for the immuno-recognition events were merged in a single step of 1h. In parallel a Real-Time PCR (RTi-PCR) method, based on a specific locked nucleic acid (LNA) fluorescent probe and an internal amplification control (IAC), was carried out. The selectivity of the ELIME and RTi-PCR assays was proved by inclusivity and exclusivity tests performed analyzing different Salmonella serotypes and non-target microorganisms, most commonly isolated from environmental sources. Furthermore, both methods were applied to experimentally and not experimentally contaminated irrigation water samples. Results confirmed by the ISO culture method, demonstrated the effectiveness of ELIME and RTi-PCR assays to detect a low number of salmonella cells (1-10 CFU/L) reducing drastically the long analysis time usually required to reveal this pathogen.

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Quantitative analysis of dicamba residues in raw agricultural commodities with the use of ion-pairing reagents in LC–ESI–MS/MS

Publication date: 1 March 2016
Source:Talanta, Volume 149
Author(s): Hongyue Guo, Leah S Riter, Chad E Wujcik, Daniel W Armstrong
A sensitive and selective HPLC–MS/MS method was developed for the quantitative analysis of dicamba residues in raw agricultural commodities (RACs). Instead of analysis in the traditionally used negative electrospray ionization (ESI) mode, these anionic compounds were detected in positive ESI with the use of ion-pairing reagents. In this approach, only a small amount (60µM) of a commercially available dicationic ion-pairing reagent was introduced into the post-column sample stream. This method has been validated in six different types of RACs including corn grain, corn stover, cotton seed, soybean, soy forage and orange with satisfactory quantitative accuracy and precision. The limits of quantitation (LOQ) values for these analytes were 1.0 to 3.0µg/kg. The standard curves were linear over the range of the tested concentrations (3.0 to 500µg/kg), with correlation coefficient (r) values≥0.999. Evaluation of ionization effects in RAC matrix extracts using diluent blanks for comparison showed no significant matrix effects were present.

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Sensitive immunochemical approaches for quantitative (FPIA) and qualitative (lateral flow tests) determination of gentamicin in milk

Publication date: 1 March 2016
Source:Talanta, Volume 149
Author(s): N.V. Beloglazova, P.S. Shmelin, S.A. Eremin
Three kinds of immunoassays for the determination of gentamicin in milk samples were developed and validated. First, a fast and easily-performed fluorescence polarization immunoassay was used for characterization of the employed polyclonal antibody. The calculated Kaff were (1.9±0.4)×109М−1 and (6.0±0.2)×106М−1 for the high- and low-affinity fractions respectively. The assay was characterized with a good sensitivity, the limit of detection being 5μgkg−1. Two different kinds of detection labels, i.e. colloidal gold (CG) and quantum dots (QDs), were evaluated for use in lateral-flow format with respect to rapid visual on-site testing. The cut-off levels for both qualitative formats were selected based on the maximum level for gentamicin in milk established by the European Commission, 100μgkg−1, resulting in a 10μgkg−1 cut-off considering sample dilution. The intra-laboratory validation was performed with sterilized milk samples artificially spiked with gentamicin at concentrations less than, equal to, and greater than the cut-off level. It was shown that milk products could be analyzed without any sample preparation, except for dilution with the buffer solution. The rates of false-positive and false-negative results were below 5% for both labels. The different developed immunoassays were tested towards gentamicin determination in artificially-spiked and naturally contaminated milk samples.

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Association between p53 status, human papillomavirus infection, and overall survival in advanced oral cancer after resection and combination systemic treatment

Publication date: Available online 6 December 2015
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): Tommaso Cutilli, Pietro Leocata, Vincenza Dolo, Emma Altobelli
Our previous study on 75 cases of advanced oral squamous cell carcinomas (SCC) treated by neoadjuvant chemotherapy, radical surgery, and radiotherapy showed that overexpression of p53 of more than 50% indicated a strong probability of genetic mutation, and tumours that are characterised by this p53 pattern respond poorly to treatment and have a poor prognosis (p= 0.0001). We have studied the same cohort of patients retrospectively to investigate the incidence of human papillomavirus-16 (HPV16) infection, the relation to the overexpression or mutation of the p53 gene, and the association with overall survival. There were 57 men and 18 women, mean age 67 (range 57-72) years. HPV16 infectivity was found in 66 patients (88%) - 49/57 men (86%) and 17/18 women (94%). There was no significant difference between the sexes (p=0.32). The cumulative survival of the entire group after a follow-up of 38 months was 26% (SE 6.4). The log rank test indicated that the combination of HPV-16 infectivity and p53mutation was significantly related to prognosis (p=0.000). On the other hand HPV16 infectivity alone was not significantly related to prognosis (p=0.78) The incidence of HPV-16 infection decreased with increasing immune p53 expression (p=0.005), whereas that of the HPV16+p53mutation combination increased with increasing immune p53 expression (p=0.000). The results show the importance of the investigation of HPV and p53 expression to define prognosis in oral SCC.



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TWiV 366: Doctorates down under

Host: Vincent Racaniello

Guests: Carla Giles, Zoe Dyson, Brianna McLean, and Caitlin O'Brien

In Melbourne, Australia, Vincent speaks with four PhD students about their research projects and what...



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Friday Fun

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Effluent Tenascin-C Levels Reflect Peritoneal Deterioration in Peritoneal Dialysis: MAJOR IN PD Study

Peritoneal deterioration causing structural changes and functional decline is a major complication of peritoneal dialysis (PD). The aim of this study was to explore effluent biomarkers reflecting peritoneal deterioration. In an animal study, rats were intraperitoneally administered with PD fluids adding 20 mM methylglyoxal (MGO) or 20 mM formaldehyde (FA) every day for 21 days. In the MGO-treated rats, tenascin-C (TN-C) levels in the peritoneal effluents were remarkably high and a cluster of TN-C-positive mesothelial cells with epithelial-to-mesenchymal transition- (EMT-) like change excessively proliferated at the peritoneal surface, but not in the FA-treated rats. Effluent matrix metalloproteinase-2 (MMP-2) levels increased in both the MGO- and FA-treated rats. In a clinical study at 18 centers between 2006 and 2013, effluent TN-C and MMP-2 levels were quantified in 182 PD patients with end-stage renal disease. Peritoneal function was estimated using the peritoneal equilibration test (PET). From the PET results, the D/P Cr ratio was correlated with effluent levels of TN-C (ρ = 0.57, ) and MMP-2 (ρ = 0.73, ). We suggest that TN-C in the effluents may be a diagnostic marker for peritoneal deterioration with EMT-like change in mesothelial cells in PD.

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How to Have a Healthy Holiday Season

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SUNDAY, Dec. 6, 2015 -- You're at increased risk for colds and the flu over the holidays, but a few simple measures will help lower your chances of getting sick, an expert says. "With all the hustle and bustle of the holidays, we come into contact...

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Editorial Board

Publication date: 1 January 2016
Source:Acta Biomaterialia, Volume 29





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Preparation, characterization, in vitro drug release, and cellular interactions of tailored paclitaxel releasing polyethylene oxide films for drug-coated balloons

Publication date: 1 January 2016
Source:Acta Biomaterialia, Volume 29
Author(s): Jordan A. Anderson, Sujan Lamichhane, Tyler Remund, Patrick Kelly, Gopinath Mani
Drug-coated balloons (DCBs) are used to treat various cardiovascular diseases. Currently available DCBs carry drug on the balloon surface either solely or using different carriers. Several studies have shown that a significant amount of drug is lost in the blood stream during balloon tracking to deliver only a sub-therapeutic level of drug at the treatment site. This research is focused on developing paclitaxel (PAT) loaded polyethylene oxide (PEO) films (PAT–PEO) as a controlled drug delivery carrier for DCBs. An array of PAT–PEO films were developed in this study to provide tailored release of >90% of drug only at specific time intervals, which is the time frame required for carrying out balloon-based therapy. The characterizations of PAT–PEO films using SEM, FTIR, and DSC showed that the films developed were homogenous and the PAT was molecularly dispersed in the PEO matrix. Mechanical tests showed that most PAT–PEO films developed were flexible and ductile, with yield and tensile strengths not affected after PAT incorporation. The viability, proliferation, morphology, and phenotype of smooth muscle cells (SMCs) interacted with control-PEO and PAT–PEO films were investigated. All control-PEO and PAT–PEO films showed a significant inhibitory effect on the growth of SMCs, with the degree of inhibition strongly dependent on the w/v% of the polymer used. The PAT–PEO coating was produced on the balloons. The integrity of PAT–PEO coating was well maintained without any mechanical defects occurring during balloon inflation or deflation. The drug release studies showed that only 15% of the total PAT loaded was released from the balloons within the initial 1min (typical balloon tracking time), whereas 80% of the PAT was released between 1min and 4min (typical balloon treatment time). Thus, this study demonstrated the use of PEO as an alternate drug delivery system for the balloons.Statement of SignificanceAtherosclerosis is primarily responsible for cardiovascular diseases (CVDs) in millions of patients every year. Drug-coated balloons (DCBs) are commonly used to treat various CVDs. However, in several currently used DCBs, a significant amount of drug is lost in the blood stream during balloon tracking to deliver only a sub-therapeutic level of drug at the treatment site. In this study, paclitaxel containing polyethylene oxide (PEO) films were developed to provide unique advantages including drug release profiles specifically tailored for balloon-based therapy, homogeneous films with molecularly dispersed drug, flexible and ductile films, and exhibits significant inhibitory effect on smooth muscle cell growth. Thus, this study demonstrated the use of PEO as an alternate drug delivery platform for DCBs to improve its efficacy.

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Decellularized human placenta chorion matrix as a favorable source of small-diameter vascular grafts

Publication date: 1 January 2016
Source:Acta Biomaterialia, Volume 29
Author(s): Karl Heinrich Schneider, Petra Aigner, Wolfgang Holnthoner, Xavier Monforte, Sylvia Nürnberger, Dominik Rünzler, Heinz Redl, Andreas Herbert Teuschl
Biomaterials based on decellularized tissues are increasingly attracting attention as functional alternatives to other natural or synthetic materials. However, a source of non-cadaver human allograft material would be favorable. Here we establish a decellularization method of vascular tissue from cryopreserved human placenta chorionic plate starting with an initial freeze–thaw step followed by a series of chemical treatments applied with a custom-made perfusion system. This novel pulsatile perfusion set-up enabled us to successfully decellularize the vascular tissue with lower concentrations of chemicals and shorter exposure times compared to a non-perfusion process. The decellularization procedure described here lead to the preservation of the native extracellular matrix architecture and the removal of cells. Quantitative analysis revealed no significant changes in collagen content and a retained glycosaminoglycan content of approximately 29%. In strain-to-failure tests, the decellularized grafts showed similar mechanical behavior compared to native controls. In addition, the mechanical values for ultimate tensile strength and stiffness were in an acceptable range for in vivo applications. Furthermore, biocompatibility of the decellularized tissue and its recellularizationability to serve as an adequate substratum for upcoming recellularization strategies using primary human umbilical vein endothelial cells (HUVECs) was demonstrated. HUVECs cultured on the decellularized placenta vessel matrix performed endothelialization and maintained phenotypical characteristics and cell specific expression patterns. Overall, the decellularized human placenta vessels can be a versatile tool for experimental studies on vascularization and as potent graft material for future in vivo applications.Statement of significanceIn the US alone more than 1million vascular grafts are needed in clinical practice every year. Despite severe disadvantages, such as donor site morbidity, autologous grafting from the patient's own arteries or veins is regarded as the gold standard for vascular tissue repair. Besides, strategies based on synthetic or natural materials have shown limited success. Tissue engineering approaches based on decellularized tissues are regarded as a promising alternative to clinically used treatments to overcome the observed limitations. However, a source for supply of non-cadaver human allograft material would be favorable. Here, we established a decellularization method of vascular tissue from the human placenta chorionic plate, a suitable human tissue source of consistent quality. The decellularized human placenta vessels can be a potent graft material for future in vivo applications and furthermore might be a versatile tool for experimental studies on vascularization.

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A smart, phase transitional and injectable DOX/PLGA-Fe implant for magnetic-hyperthermia-induced synergistic tumor eradication

Publication date: 1 January 2016
Source:Acta Biomaterialia, Volume 29
Author(s): Wei Gao, Yuanyi Zheng, Ronghui Wang, Hangrong Chen, Xiaojun Cai, Guangming Lu, Lei Chu, Chunyan Xu, Nan Zhang, Zhigang Wang, Haitao Ran, Pan Li, Chunjiang Yang, Zhechuan Mei, Jinlin Song
Magnetic hyperthermia ablation is a new and minimally invasive modality for localized tumor removal. However, an inadequate ablation dosage can leave a residual tumor or cause a variety of complications. In addition, commonly used magnetic nanoparticles can easily escape from the tumor tissue, which present potential safety problems. In this study, a smart phase transitional and injectable implant based on biocompatible poly lactic-co-glycolic acid (PLGA) implant incorporating magnetic material (Fe powder) and anti-cancer drug (doxorubicin (DOX)) was developed. The magnetic-induced hyperthermia and release efficiency of DOX were evaluated in vitro. Drug release can be controlled under external alternating current magnetic field (AMF). The results of the in vivo tumor therapeutic efficacy showed that when exposed to external AMF, this smart injectable DOX/PLGA-Fe implant could converse magnetic energy into heat and accelerate the release of DOX, which leads to increasing the temperature to achieve tumor coagulative necrosis and accelerating the release of DOX to enhance residual tumor apoptosis. Furthermore, there was no leakage of magnetic material, as demonstrated using real-time ultrasound (US) and computerized tomography (CT) imaging, realizing the guidance and monitoring of tumor therapy. In conclusion, this smart phase transitional and injectable implant DOX/PLGA-Fe has the ability to improve the efficiency of this newly developed minimally invasive magnetic ablation of tumor treatment technique, and will provide a new avenue of developing minimally invasive synergistic tumor therapy.

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Inhibition of osteoclastogenesis through siRNA delivery with tunable mesoporous bioactive nanocarriers

Publication date: 1 January 2016
Source:Acta Biomaterialia, Volume 29
Author(s): Tae-Hyun Kim, Rajendra K. Singh, Min Sil Kang, Joong-Huyn Kim, Hae-Won Kim
Gene silencing through siRNA delivery has shown great promise for treating diseases and repairing damaged tissues, including bone. This report is the first to develop siRNA delivery system in the inhibition of osteoclastic functions which in turn can help turn-over bone mass increase in the diseases like osteoporosis. For this reason, biocompatible and degradable nanocarriers that can effectively load and deliver genetic molecules to target cells and tissues are being actively sought by researchers. In this study, mesoporous bioactive glass nanospheres (MBG), a novel unique biocompatible degradable inorganic nanocarrier, is introduced. Furthermore, siRNA was designed to function by inhibiting the expression of the receptor activator of nuclear factor kappa B (RANK) in order to suppress osteoclastogenesis. Amine-functionalized MBG were synthesized with tunable mesoporosities, showing a strong complexation with siRNA. An in vitro release profile indicated that the siRNA from the MBG was able to achieve a highly sustainable liberation for up to 4days, confirming a temporary delivery system can be designed to function for that period of time. The intracellular uptake capacity of the complex siRNA(RANK)-MBG was recorded to be around 70%. Furthermore, the RANK-expressing cell population declined down to 29% due to the delivery of siRNA(RANK)-MBG (vs. 86% in control). The expression of osteoclastogenesis-related genes, including c-fos, cathepsin-K, tartrate-resistant acid phosphatase (TRAP), and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), was substantially down-regulated by the siRNA delivery system. This study reports for the first time on the use of a novel MBG delivery system for siRNA that aims to suppress osteoclastic actions. MBGs may be a potential gene delivery platform for hard tissue repair and disease treatment due to the collective results which indicate a high loading capacity, temporary release kinetics, high intracellular uptake rate, and sufficient gene silencing effects, together with the intrinsic beneficial properties like bone-bioactivity and degradability.Statement of SignificanceThis report is the first to develop siRNA delivery system of biocompatible and degradable nanocarriers made from a unique composition, i.e., mesoporous bioactive glass that can effectively load and deliver genetic molecules to osteoclastic cells. We proved through a series of studies that the biocompatible nanocarriers are effective for the delivery of siRNA in the inhibition of osteoclastic functions which thus might be considered as a nanocarrier platform to help turn-over bone mass increase in the diseases like osteoporosis.

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The structure and mechanical properties of articular cartilage are highly resilient towards transient dehydration

Publication date: 1 January 2016
Source:Acta Biomaterialia, Volume 29
Author(s): K. Boettcher, S. Kienle, J. Nachtsheim, R. Burgkart, T. Hugel, O. Lieleg
Articular cartilage is a mechanically highly challenged material with very limited regenerative ability. In contrast to elastic cartilage, articular cartilage is exposed to recurring partial dehydration owing to ongoing compression but maintains its functionality over decades. To extend our current understanding of the material properties of articular cartilage, specifically the interaction between the fluid and solid phase, we here analyze the reversibility of tissue dehydration. We perform an artificial dehydration that extends beyond naturally occurring levels and quantify material recovery as a function of the ionic strength of the rehydration buffer. Mechanical (indentation, compression, shear, and friction) measurements are used to evaluate the influence of de- and rehydration on the viscoelastic properties of cartilage. The structure and composition of native and de/rehydrated cartilage are analyzed using histology, scanning electron microscopy, and atomic force microscopy along with a 1,9-dimethylmethylene blue (DMMB) assay. A broad range of mechanical and structural properties of cartilage can be restored after de- and rehydration provided that a physiological salt solution is used for rehydration. We detect only minor alterations in the microarchitecture of rehydrated cartilage in the superficial zone and find that these alterations do not interfere with the viscoelastic and tribological properties of the tissue.Statement of SignificanceWe here demonstrate the sturdiness of articular cartilage towards changes in fluid content and show that articular cartilage recovers a broad range of its material properties after dehydration. We analyze the reversibility of tissue dehydration to extend our current understanding of how the material properties of cartilage are established, focusing on the interaction between the fluid and solid phase. Our findings suggest that the high resilience of the tissue minimizes the risk of irreversible material failure and thus compensates, at least in part, its poor regenerative abilities. Tissue engineering approaches should thus not only reproduce the correct tissue mechanics but also its pronounced sturdiness to guarantee a similar longevity.

Graphical abstract

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Differential Expression of MUC12, MUC16, and MUC20 in Patients with Active and Remission Ulcerative Colitis

Background. Patients with UC have shown an important defect in the secretion and maintenance of the mucosal barrier as part of inadequate expression of mucin genes. The aim of the present study was to determine the expression of MUC12, MUC16, and MUC20 in colonic tissue from patients with UC in regard to their clinical outcomes. Methods. We included a total of 40 patients with UC and 30 normal controls. Mucin gene expression was performed by RT-PCR and protein expression was detected by immunohistochemistry. Results. Patients with active UC showed no significant expression of MUC12 gene in mucosa compared to the group of patients with UC in remission and the normal control group. MUC16 gene expression was significantly increased in the UC active and remission groups compared to the normal control group (). MUC20 gene expression was found significantly decreased in patients with active UC compared to both remission group () and normal controls (). Furthermore, an association was found between MUC20 gene expression and the presence of histological remission in patients with UC (, OR = 0.37). Conclusions. An increased gene expression of MUC16 and MUC20 was found in patients with remission UC.

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Synergistic Stimulation with Different TLR7 Ligands Modulates Gene Expression Patterns in the Human Plasmacytoid Dendritic Cell Line CAL-1

Objective. TLR7 ligation in plasmacytoid dendritic cells is promising for the treatment of cancer, allergy, and infectious diseases; however, high doses of ligands are required. We hypothesized that the combination of structurally different TLR7 ligands exponentiates the resulting immune response. Methods. CAL-1 (human pDC line) cells were incubated with the TLR7-specific adenine analog CL264 and single-stranded 9.2s RNA. Protein secretion was measured by ELISA. Microarray technique was used to detect modified gene expression patterns upon synergistic stimulation, revealing underlying functional groups and networks. Cell surface binding properties were studied using FACS analysis. Results. CL264 in combination with 9.2s RNA significantly enhanced cytokine and interferon secretion to supra-additive levels. This effect was due to a stronger stimulation of already regulated genes (by monostimulation) as well as to recruitment of thus far unregulated genes. Top scoring canonical pathways referred to immune-related processes. Network analysis revealed IL-1β, IL-6, TNF, and IFN-β as major regulatory nodes, while several minor regulatory nodes were also identified. Binding of CL264 to the cell surface was enhanced by 9.2s RNA. Conclusion. Structurally different TLR7 ligands act synergistically on gene expression patterns and on the resulting inflammatory response. These data could impact future strategies optimizing TLR7-targeted drug design.

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A Large Extragnathic Keratocystic Odontogenic Tumour

Odontogenic keratocysts (OKCs) are developmental cysts which occur typically in the jawbones. They present more commonly in the posterior mandible of young adults than the maxilla. OKCs have been reclassified under odontogenic tumours in 2005 by the WHO and have since been termed as keratocystic odontogenic tumours (KCOTs). Here we report a case of a recurrent buccal lesion in a 62-year-old man which was provisionally diagnosed as a space infection (buccal abscess) but surprisingly turned out to be a soft tissue KCOT in an unusual location on histopathologic examination.

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Editorial Board & Aims and Scope

Publication date: October 2015
Source:Nano Today, Volume 10, Issue 5





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Adipokines and Cysteinyl Leukotrienes in the Pathogenesis of Asthma

Background. The prevalence of obesity has increased dramatically over the last decades, and its association with asthma is being increasingly recognized. Aims. Our hypothesis is that increased leptin and decreased adiponectin levels in obese subjects play a direct role in regulating inflammation in asthmatics. We wanted to examine the hypothesis that cysteinyl leukotrienes (cys-LT), inflammatory mediators that are regulated by adipokines, are involved in the pathogenesis of asthma. Methods. We studied a population of asthmatics and nonasthmatics, who in turn were divided into obese and nonobese categories. We examined leptin and its ratio to adiponectin, in asthmatics and nonasthmatics, with and without obesity. In addition, we measured cys-LT levels in exhaled breath condensate (EBC) and in peripheral blood monocytes (PBM) in these groups. Results. Leptin levels were increased in obese asthmatics compared to obese nonasthmatics. The leptin/adiponectin (L/A) ratio was higher in obese asthmatics compared to obese nonasthmatics. EBC cys-LT levels were elevated in asthmatics compared to nonasthmatics. Discussion. Proinflammatory adipokines, released from adipose tissue, may promote an asthma phenotype through enhanced cys-LT production that may result in more prevalent and difficult to control airway disease.

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Autocrine Signaling and Quorum Sensing: Extreme Ends of a Common Spectrum

Publication date: Available online 5 December 2015
Source:Trends in Cell Biology
Author(s): Berkalp A. Doğaner, Lawrence K.Q. Yan, Hyun Youk
'Secrete-and-sense cells' can communicate by secreting a signaling molecule while also producing a receptor that detects the molecule. The cell can potentially 'talk' to itself ('self-communication') or talk to neighboring cells with the same receptor ('neighbor communication'). The predominant forms of secrete-and-sense cells are self-communicating 'autocrine cells', which are largely found in animals, and neighbor-communicating 'quorum sensing cells', which are mostly associated with bacteria. While assumed to function independently of one another, recent studies have discovered quorum-sensing organs and autocrine-signaling microbes. Moreover, similar types of genetic circuit control many autocrine and quorum-sensing cells. Here, we outline these recent findings and explain how autocrine and quorum sensing are two sides of a many-sided 'dice' created by the versatile secrete-and-sense cell.



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Experimental Analysis of the Mechanism of Hearing under Water

The mechanism of human hearing under water is debated. Some suggest it is by air conduction (AC), others by bone conduction (BC), and others by a combination of AC and BC. A clinical bone vibrator applied to soft tissue sites on the head, neck, and thorax also elicits hearing by a mechanism called soft tissue conduction (STC) or nonosseous BC. The present study was designed to test whether underwater hearing at low intensities is by AC or by osseous BC based on bone vibrations or by nonosseous BC (STC). Thresholds of normal hearing participants to bone vibrator stimulation with their forehead in air were recorded and again when forehead and bone vibrator were under water. A vibrometer detected vibrations of a dry human skull in all similar conditions (in air and under water) but not when water was the intermediary between the sound source and the skull forehead. Therefore, the intensities required to induce vibrations of the dry skull in water were significantly higher than the underwater hearing thresholds of the participants, under conditions when hearing by AC and osseous BC is not likely. The results support the hypothesis that hearing under water at low sound intensities may be attributed to nonosseous BC (STC).

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Proceedings Fifth ESWI Influenza Conference

Publication date: 8 December 2015
Source:Vaccine, Volume 33, Issue 49
Author(s): A.D.M.E. Osterhaus, Chris Vanlangendonck




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Editorial Board/Aims and Scope

Publication date: 8 December 2015
Source:Vaccine, Volume 33, Issue 49





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Influenza vaccines: Where do we stand? Where do we go?

Publication date: 8 December 2015
Source:Vaccine, Volume 33, Issue 49
Author(s): Guus Rimmelzwaan, Isabel Leroux-Roels, Sarah Gilbert, Angus Thomson




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Conclusions: From peer to peer communication to communicating with policy makers and the general public

Publication date: 8 December 2015
Source:Vaccine, Volume 33, Issue 49





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The confounded effects of age and exposure history in response to influenza vaccination

Publication date: Available online 5 December 2015
Source:Vaccine
Author(s): Ana Mosterín Höpping, Janet McElhaney, Judith M. Fonville, Douglas C. Powers, Walter E.P. Beyer, Derek J. Smith
Numerous studies have explored whether the antibody response to influenza vaccination in elderly adults is as strong as it is in young adults. Results vary, but tend to indicate lower post-vaccination titers (antibody levels) in the elderly, supporting the concept of immunosenescence—the weakening of the immunological response related to age. Because the elderly in such studies typically have been vaccinated against influenza before enrollment, a confounding of effects occurs between age, and previous exposures, as a potential extrinsic reason for immunosenescence.We conducted a four-year study of serial annual immunizations with inactivated trivalent influenza vaccines in 136 young adults (16 to 39 years) and 122 elderly adults (62 to 92 years). Compared to data sets of previously published studies, which were designed to investigate the effect of age, this detailed longitudinal study with multiple vaccinations allowed us to also study the effect of prior vaccination history on the response to a vaccine.In response to the first vaccination, young adults produced higher post-vaccination titers, accounting for pre-vaccination titers, than elderly adults. However, upon subsequent vaccinations the difference in response to vaccination between the young and elderly age groups declined rapidly. Although age is an important factor when modeling the outcome of the first vaccination, this term lost its relevance with successive vaccinations. In fact, when we examined the data with the assumption that the elderly group had received (on average) as few as two vaccinations prior to our study, the difference due to age disappeared.Our analyses therefore show that the initial difference between the two age groups in their response to vaccination may not be uniquely explained by immunosenescence due to ageing of the immune system, but could equally be the result of the different pre-study vaccination and infection histories in the elderly.



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Nasopharyngeal carriage of Streptococcus pneumoniae and other bacteria in the 7th year after implementation of the pneumococcal conjugate vaccine in the Netherlands

Publication date: Available online 5 December 2015
Source:Vaccine
Author(s): Astrid A.T.M. Bosch, Marlies A. van Houten, Jacob P. Bruin, Alienke J. Wijmenga-Monsuur, Krzysztof Trzciński, Debby Bogaert, Nynke Y. Rots, Elisabeth A.M. Sanders
After introduction of 7-valent pneumococcal conjugate vaccine (PCV7) in the infant national immunization program (NIP) in the Netherlands in 2006, Streptococcus pneumoniae strains of the non-vaccine serotype 19A became the dominant in carriage in children and their parents. Similar patterns were observed in other European countries and the United States. Increases in carriage rates of Staphylococcus aureus and non-typeable (NT) Haemophilus influenzae were also observed. After switching of PCV7 to 10-valent vaccine (PCV10) in 2011, a new carriage surveillance study was performed in the winter of 2012/2013. Nasopharyngeal carriage of S. pneumoniae, H. influenzae, S. aureus, and Moraxella catarrhalis was determined by conventional culture in 330 PCV10-vaccinated 11-month-old children, 330 PCV7-vaccinated 24-month-old children, and their parents. Carriage prevalence was compared with similar carriage studies conducted in 2005, 2009, and 2010/2011. Although serotype 19A remained the most frequently carried pneumococcal serotype in children, prevalence of 19A significantly declined in PCV7-vaccinated 24-month-old children (14% to 8%, p=0.01), but less in PCV10-vaccinated 11-month-old children (12% to 9%, p=0.31). Carriage of H. influenzae remained stable at an elevated level (65% in 11-month-olds and 69% in 24-month-olds), while the carriage of S. aureus returned to pre-PCV7 levels in 11-month-old children (14% in 2010/2011 to 7% in 2012/2013), but not in 24-month-olds (remained at 7%). Our results might indicate a new balance between replacing non-vaccine pneumococcal serotypes and other potential pathogenic bacteria in nasopharyngeal carriage. Carriage studies are valuable tools in assessing vaccine effects on pathogens circulating in the population, for evaluation of PCV impact, and in predicting changes in respiratory and invasive disease.



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National hospital data for intussusception: Data linkage and retrospective analysis to assess quality and use in vaccine safety surveillance

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Publication date: Available online 5 December 2015
Source:Vaccine
Author(s): Lamiya Samad, Mario Cortina-Borja, Alastair G. Sutcliffe, Sean Marven, J. Claire Cameron, Haitham El Bashir, Richard Lynn, Brent Taylor
ObjectivesTo assess the quality of national Hospital Episode Statistics (HES) data for intussusception, and evaluate this routinely collected database for rotavirus vaccine safety surveillance by estimating pre-vaccination trends in intussusception hospitalisation.MethodsData linkage was performed between HES and prospective intussusception data from the British Paediatric Surveillance Unit (BPSU), followed by capture–recapture analysis to verify HES data quality. Inclusion criteria were infants aged less than 12 months and admitted for intussusception to National Health Service (NHS) hospitals in England from March 2008 to March 2009. To estimate pre-vaccination incidence rates of intussusception, we performed a retrospective analysis of HES data. Infants aged less than 12 months and admitted for intussusception to NHS hospitals in England between 1995 and 2009 were included.ResultsData linkage between 254 cases of intussusception identified in HES data and 190 cases reported via the BPSU resulted in 163 cases common to both data sources. Of remaining 91 cases in HES, 37 had confirmed intussusception. HES data accuracy was 78.7% (200 confirmed/254 cases) and completeness for intussusception was 86% (163 matched/190 BPSU cases) compared to 81.5% (163 matched/200 HES cases) for BPSU. A total of 233 (95% CI: 227.4 to 238.8) intussusception cases were estimated for the infant population (2008 to 2009). For retrospective analysis, of 6462 intussusception admissions in HES data (1995 to 2009), 1594 (24.7%) were duplicate admissions. A declining trend in intussusception incidence was observed in the infant population, from 86/100,000 in 1997 to 34/100,000 in 2009 (60% reduction, P<0.001). Cosinor modelling showed an excess of cases among infants in winter and spring (P<0.001, n=4957, 1995 to 2009).ConclusionNational hospital data capture the majority of admissions for intussusception and should be considered for the post-implementation surveillance of rotavirus vaccine safety in England.



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Optimization of physiological properties of hydroxyapatite as a vaccine adjuvant

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Publication date: Available online 5 December 2015
Source:Vaccine
Author(s): Masayuki Hayashi, Taiki Aoshi, Yasumichi Kogai, Daisuke Nomi, Yasunari Haseda, Etsushi Kuroda, Kouji Kobiyama, Ken J. Ishii
Various particles such as Alum or silica are known to act as an adjuvant if co-administered with vaccine antigens. Several reports have demonstrated that the adjuvanticity is strongly affected by the physicochemical properties of particles such as the size, shape and surface charge, although the required properties and its relationship to the adjuvanticity are still controversial. Hydroxyapatite particle (HAp) composed of calcium phosphate has been shown to work as adjuvant in mice. However, the properties of HAp required for the adjuvanticity have not been fully characterized yet. In this study, we examined the role of size or shape of HAps in the antibody responses after immunization with antigen. HAps whose diameter ranging between 100 and 400nm provided significantly higher antibody responses than smaller or larger ones. By comparison between sphere and rod shaped HAps, rod shaped HAps induced stronger inflammasome-dependent IL-1β production than the sphere shaped ones in vitro. However, sphere- and rod-shaped HAp elicited comparable antibody response in WT mice. Vice versa, Nlrp3−/−, Asc−/− or Caspase1−/− mice provided comparable level of antibody responses to HAp adjuvanted vaccination. Collectively, our results demonstrated that the size rather than shape is a more critical property, and IL-1β production via NLRP3 inflammasome is dispensable for the adjuvanticity of HAps in mice.



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Scintilla : Interview with doeyens

Thank you team scintilla for my interview
=============
Scintilla presents: Interview with Doeyens category. To read more articles in this category, visit Scintilla Diaries.
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Akzelerierte Teilbrustbestrahlung mit interstitieller Multikatheter-Brachytherapie



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The combination of radiation therapy and immunotherapy for genitourinary cancer treatment: rationale, current evidence, and prospects

Abstract

Targeted immunotherapy has emerged as a potentially effective systemic treatment for metastatic cancer in the past decade. However, a significant fraction of patients will either not respond or develop resistance to immunotherapy due to the immune-evasive properties of cancer. Radiation therapy can augment immunotherapy to modulate the immune suppressive tumor microenvironment and promote specific tumor targeting by the adaptive immune system. In this review, we will discuss the rationale for combining radiation therapy with immunotherapy and describe clinical studies using this combination strategy to improve the treatment response by inducing synergistic and abscopal effects. We will discuss ongoing prospective clinical trials that employ the combination of radiation therapy and immunotherapy in the treatment of genitourinary malignancies. Further advances in these combination therapy strategies are expected to improve the clinical response and disease course while further providing insight to the complex interactions and regulations between the immune system and cancer cells. Multiple additional clinical trials will be required to find routine application of this concept to the clinic.



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Evaluation of the In Vivo and In Vitro Effects of Fructose on Respiratory Chain Complexes in Tissues of Young Rats

Hereditary fructose intolerance (HFI) is an autosomal-recessive disorder characterized by fructose and fructose-1-phosphate accumulation in tissues and biological fluids of patients. This disease results from a deficiency of aldolase B, which metabolizes fructose in the liver, kidney, and small intestine. We here investigated the effect of acute fructose administration on the activities of mitochondrial respiratory chain complexes, succinate dehydrogenase (SDH), and malate dehydrogenase (MDH) in cerebral cortex, liver, kidney, and skeletal muscle of male 30-day-old Wistar rats. The rats received subcutaneous injection of sodium chloride (0.9%; control group) or fructose solution (5 μmol/g; treated group). One hour later, the animals were euthanized and the cerebral cortex, liver, kidney, and skeletal muscle were isolated and homogenized for the investigations. Acute fructose administration increased complex I-III activity in liver. On the other hand, decreased complexes II and II-III activities in skeletal muscle and MDH in kidney were found. Interestingly, none of these parameters were affected in vitro. Our present data indicate that fructose administration elicits impairment of mitochondrial energy metabolism, which may contribute to the pathogenesis of the HFI patients.

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(english) Adherence to a Mediterranean diet and risk of myocardial infarction, heart failure and ischemic stroke



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EEG Derived Neuronal Dynamics during Meditation: Progress and Challenges

Meditation advances positivity but how these behavioral and psychological changes are brought can be explained by understanding neurophysiological effects of meditation. In this paper, a broad spectrum of neural mechanics under a variety of meditation styles has been reviewed. The overall aim of this study is to review existing scientific studies and future challenges on meditation effects based on changing EEG brainwave patterns. Albeit the existing researches evidenced the hold for efficacy of meditation in relieving anxiety and depression and producing psychological well-being, more rigorous studies are required with better design, considering client variables like personality characteristics to avoid negative effects, randomized controlled trials, and large sample sizes. A bigger number of clinical trials that concentrate on the use of meditation are required. Also, the controversial subject of epileptiform EEG changes and other adverse effects during meditation has been raised.

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Bilateral Sensorineural Hearing Loss and Polyneuropathy in a Patient with Sweet’s Syndrome

Sweet's syndrome is an inflammatory systemic disease which has been associated with various underlying causes. The disease can involve multiple areas of the body including the skin and neurological system. There have been only two cases which have described otological involvement. This report presents a patient who developed loss of hearing secondary to Sweet's syndrome after developing cutaneous involvement along with peripheral neuropathy. Despite the patient's skin and neuropathy noticing improvement with intravenous immunoglobulin and azathioprine, he required bilateral cochlear implants for partial recovery of his hearing loss. This case highlights the need to recognize Sweet's syndrome as a complicated disease process where the role of otolaryngologists is important in the multidisciplinary coordination of care in both diagnosis and treatment.

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Discordance between sonographic and cytological diagnoses of solid thyroid nodules: Retrospective Doppler U.S. examination is mandatory



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Clear cell hepatocellular carcinoma diagnosed by bile duct brushing cytology

Clear cell hepatocellular carcinoma (CCHCC) is an uncommon morphologic variant of HCC and rarely invades into the main bile ducts. Here we describe a case of CCHCC that was diagnosed by bile duct brushing cytology. Liquid-based preparation of brushing specimen showed clusters of atypical epithelial cells with abundant clear cytoplasm, round nuclei, and occasional intranuclear inclusions. The tumor cells were positive for HepPar-1 and arginase 1, suggestive of their hepatic origin. The overall morphologic and immunophenotypic features were consistent with CCHCC. The cytological diagnosis was confirmed by histopathologic examination of the resected tumor. Diagn. Cytopathol. 2015. © 2015 Wiley Periodicals, Inc.



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MR enterography–histology comparison in resected pediatric small bowel Crohn disease strictures: can imaging predict fibrosis?

Abstract

Background

Crohn disease is a chronic inflammatory condition that can lead to intestinal strictures. The presence of fibrosis within strictures alters optimal management but is not reliably detected by current imaging methods.

Objective

To correlate the MRI features of surgically resected small-bowel strictures in pediatric Crohn disease with histological inflammation and fibrosis scoring.

Materials and methods

We included children with Crohn disease who had symptomatic small-bowel strictures requiring surgical resection and had preoperative MR enterography (MRE) within 3 months of surgery (n = 20). Two blinded radiologists reviewed MRE examinations to document stricture-related findings. A pediatric pathologist scored stricture histological specimens for fibrosis (0–4) and inflammation (0–4). MRE findings were correlated with histological data using Spearman correlation (ρ) and exact logistic regression analysis.

Results

There was significant positive correlation between histological bowel wall fibrosis and inflammation in resected strictures (ρ = 0.55; P = 0.01). Confluent transmural histological fibrosis was associated with pre-stricture upstream small-bowel dilatation >3 cm at univariate (odds ratio [OR] = 51.7; 95% confidence interval [CI]: 7.6– > 999.9; P = 0.0002) and multivariate (OR = 43.4; 95% CI: 6.1– > 999.9; P = 0.0006, adjusted for age) analysis. The degree of bowel wall T2-weighted signal intensity failed to correlate with histological bowel wall fibrosis or inflammation (P-values >0.05). There were significant negative correlations between histological fibrosis score and patient age at resection (ρ = −0.48, P = 0.03), and time from diagnosis to surgery (ρ = −0.73, P = 0.0002).

Conclusion

Histological fibrosis and inflammation co-exist in symptomatic pediatric Crohn disease small-bowel strictures and are positively correlated. Pre-stenotic upstream small-bowel dilatation greater than 3 cm is significantly associated with confluent transmural fibrosis.



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Disk abnormality coexists with any degree of synovial and osseous abnormality in the temporomandibular joints of children with juvenile idiopathic arthritis

Abstract

Background

MRI manifestation of temporomandibular joint arthritis is frequently reported in children with juvenile idiopathic arthritis. However, little attention has been paid to temporomandibular joint disk abnormalities.

Objective

To assess combinations of MRI findings in the symptomatic temporomandibular joint in children with juvenile idiopathic arthritis with focus on disk abnormalities.

Materials and methods

This was a retrospective study of 46 patients with juvenile idiopathic arthritis, mean age 12 years (range: 5-17 years). Mean disease duration was 70 months (standard deviation: 61 months). MR images of 92 temporomandibular joints were scored for thickness of abnormally enhancing synovium (synovitis), joint effusion, bone marrow oedema, abnormal bone shape, bone erosion and disk abnormalities.

Results

The 92 temporomandibular joints were categorized as A: No synovitis and normal bone shape (30/92; 33%), B: Synovitis and normal bone shape (14/92: 15%), C: Synovitis and abnormal bone shape (38/92; 41%) and D: No synovitis but abnormal bone shape (10/92; 11%). Thirty-six of the 46 patients (78%) had synovitis and 33/46 (72%) had abnormal bone shape, most frequently in combination (30/46; 65%). Disk abnormalities (flat disk, fragmented disk, adherent disk and displaced disk) were found in 29/46 patients (63%). Disk abnormalities were found in all categories of juvenile idiopathic arthritis involved temporomandibular joints (B: 8/14 [57%]; C: 25/38 [66%] and D: 7/10 [70%]). Disk displacement was found in half of the joints (7/14) in category B. Synovitis was most pronounced in this category.

Conclusion

Disk abnormalities were frequent. Disk displacement also occurred in joints with early temporomandibular joint arthritis, i.e., with normal bone shape. Other disk abnormalities were found in joints with bone abnormalities. Attention should be paid to disk abnormalities both in early and long-standing temporomandibular joint arthritis in children with juvenile idiopathic arthritis.



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Tonsil ultrasound: technical approach and spectrum of pediatric peritonsillar infections

Abstract

Peritonsillar infections are one of the most common deep neck space infections, particularly in adolescents. Inaccurate diagnosis can lead to delay in management and potentially life-threatening complications. Contrast-enhanced computed tomography (CT) scan of the neck traditionally has been used to diagnose suspected peritonsillar abscess. With growing concern over radiation exposure, there has been increasing utilization of ultrasound (US) using intraoral and transcutaneous approaches. We chose the transcutaneous US technique due to its ease of performance in children. The purpose of this article is twofold: a) to describe our technique of performing transcutaneous US of the tonsil showing sonographic appearance of normal tonsil, highlighting pertinent anatomy and unique considerations for this modality in children, and b) to illustrate the sonographic findings in the spectrum of pediatric peritonsillar infections, which includes uncomplicated tonsillitis, peritonsillar cellulitis, small intratonsillar abscess and frank peritonsillar abscess. Parapharyngeal abscess can sometimes be detected.



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A Tumor Suppressor Function for Notch Signaling in Forebrain Tumor Subtypes

Publication date: Available online 5 December 2015
Source:Cancer Cell
Author(s): Claudio Giachino, Jean-Louis Boulay, Robert Ivanek, Alvaro Alvarado, Cristobal Tostado, Sebastian Lugert, Jan Tchorz, Mustafa Coban, Luigi Mariani, Bernhard Bettler, Justin Lathia, Stephan Frank, Stefan Pfister, Marcel Kool, Verdon Taylor
In the brain, Notch signaling maintains normal neural stem cells, but also brain cancer stem cells, indicating an oncogenic role. Here, we identify an unexpected tumor suppressor function for Notch in forebrain tumor subtypes. Genetic inactivation of RBP-Jκ, a key Notch mediator, or Notch1 and Notch2 receptors accelerates PDGF-driven glioma growth in mice. Conversely, genetic activation of the Notch pathway reduces glioma growth and increases survival. In humans, high Notch activity strongly correlates with distinct glioma subtypes, increased patient survival, and lower tumor grade. Additionally, simultaneous inactivation of RBP-Jκ and p53 induces primitive neuroectodermal-like tumors in mice. Hence, Notch signaling cooperates with p53 to restrict cell proliferation and tumor growth in mouse models of human brain tumors.

Graphical abstract

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Teaser

Notch signaling has been implicated in promoting brain tumor development. Giachino et al. now show that inactivating Notch signaling accelerates the growth of Trp53−/−, PDGF-driven gliomas in mice and that high Notch pathway activity correlates with better survival of patients with some subtypes of glioma.


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