bluuebunny/crossref_metadata_2025 huggingface dataset:
Imaging Tumor Vasculature Noninvasively with Positron Emission Tomography and RGD Peptides Labeled with Copper 64 Using the Bifunctonal Chelates DOTA, Oxo-DO3A. and PCTA
Authors: Yapp Donald T.T. , Ferreira Cara L. , Gill Rajanvir K. , Boros Eszter , Wong May Q. , Mandel Derek , Jurek Paul , Kiefer Garry E.
Published: March 2018

Two novel bifunctional chelates, 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-3,6,9-triacetic acid (PCTA) and 1-oxa-4,7,10-triazacyclododecane-4,7,10-triacetic acid (Oxo-DO3A), were found to radiolabel antibodies with copper 64 (64Cu) well for positron emission tomography (PET). In this study, the same chelators were used to radiolabel peptides with 64Cu for PET imaging of angiogenesis. PCTA, Oxo-DO3A, and 1,4,7,10-tetraazacyclododecane-N,N‘,N“,N”’-tetraacetic acid (DOTA) were conjugated to cyclic-(RGDyK), and their binding affinities were confirmed. Conditions for 64Cu radiolabeling were optimized for maximum yield and specific activity. The in vitro stability of the radiolabeled compounds was challenged with serum incubation. PET studies were carried out in a non-αvβ3-expressing tumor model to evaluate the compounds' specificity for proliferating tumor vasculature and their in vivo pharmacokinetics. The PCTA and Oxo-DO3A bioconjugates were labeled with 64Cu at higher effective specific activity and radiochemical yield than the DOTA bioconjugate. In the imaging studies, all the 64Cu bioconjugates could be used to visualize the tumor and the radiotracer uptake was blocked with cyclic-(RGDyK). Target uptake of each bioconjugate was similar, but differences in other tissues were observed. 64Cu-PCTA-RGD showed the best clearance from nontarget tissue and the highest tumor to nontarget ratios. PCTA was the most promising bifunctional chelate for 64Cu peptide imaging and warrants further investigation.
Technetium 99m–Labeled VQ Peptide: A New Imaging Agent for the Early Detection of Tumors or Premalignancies
Authors: Shi Jiyun , Cui Liyang , Jia Bing , Liu Zhaofei , He Peng , Dong Chengyan , Jin Xiaona , Zhao Huiyun , Li Fang , Wang Fan
Published: March 2018

There is a critical need to develop diagnostic procedures enabling early detection of tumors while at a curable stage. Technetium 99m (99mTc)-labeled VQ peptide (99mTc-HYNIC-VQ) identified through screening phage display peptide libraries against fresh human colonic adenomas was prepared and evaluated for tumor detection. 99mTc-HYNIC-VQ was prepared by a non-SnCl2 method with more than 99% radiochemical purity. The biodistribution in the HT-29 tumor model showed that although the absolute tumor uptake values were relatively low (0.60 ± 0.09, 0.41 ± 0.09, 0.36 ± 0.18, and 0.19 ± 0.08 %ID/g at 0.5, 1, 2, and 4 hours postinjection, respectively), the tumor uptake was higher than that of any of the other organs except for the kidneys at any time point examined, which led to the high tumor to nontarget ratios. The tumors and inflammation were clearly visualized with high contrast. Although the mechanism of accumulation of radiolabeled VQ peptide in tumors and inflammation needs to be further investigated, 99mTc-HYNIC-VQ is a promising imaging agent for the early detection of tumors or premalignancies, at least for screening patients with a high risk of developing cancers.
In Vivo Demonstration of Cancer Molecular Imaging with Ultrasound Radiation Force and Buried-Ligand Microbubbles
Authors: Borden Mark A. , Streeter Jason E. , Sirsi Shashank R. , Dayton Paul A.
Published: March 2018

In designing targeted contrast agent materials for imaging, the need to present a targeting ligand for recognition and binding by the target is counterbalanced by the need to minimize interactions with plasma components and to avoid recognition by the immune system. We have previously reported on a microbubble imaging probe for ultrasound molecular imaging that uses a buried-ligand surface architecture to minimize unwanted interactions and immunogenicity. Here we examine for the first time the utility of this approach for in vivo molecular imaging. In accordance with previous results, we showed a threefold increase in circulation persistence through the tumor of a fibrosarcoma model in comparison with controls. The buried-ligand microbubbles were then activated for targeted adhesion through the application of noninvasive ultrasound radiation forces applied specifically to the tumor region. Using a clinical ultrasound scanner, microbubbles were activated, imaged, and silenced. The results showed visually conspicuous images of tumor neovasculature and a twofold increase in ultrasound radiation force enhancement of acoustic contrast intensity for buried-ligand microbubbles, whereas no such increase was found for exposed-ligand microbubbles. We therefore conclude that the use of acoustically active buried-ligand microbubbles for ultrasound molecular imaging bridges the demand for low immunogenicity with the necessity of maintaining targeting efficacy and imaging conspicuity in vivo.
NanoLuc Reporter for Dual Luciferase Imaging in Living Animals
Authors: Stacer Amanda C. , Nyati Shyam , Moudgil Pranav , Iyengar Rahul , Luker Kathryn E. , Rehemtulla Alnawaz , Luker Gary D.
Published: March 2018

Bioluminescence imaging is widely used for cell-based assays and animal imaging studies in biomedical research and drug development, capitalizing on the high signal to background of this technique. A relatively small number of luciferases are available for imaging studies, substantially limiting the ability to image multiple molecular and cellular events, as done commonly with fluorescence imaging. To advance dual reporter bioluminescence molecular imaging, we tested a recently developed, adenosine triphosphate–independent luciferase enzyme from Oplophorus gracilirostris (NanoLuc [NL]) as a reporter for animal imaging. We demonstrated that NL could be imaged in superficial and deep tissues in living mice, although the detection of NL in deep tissues was limited by emission of predominantly blue light by this enzyme. Changes in bioluminescence from NL over time could be used to quantify tumor growth, and secreted NL was detectable in small volumes of serum. We combined NL and firefly luciferase reporters to quantify two key steps in transforming growth factor β signaling in intact cells and living mice, establishing a novel dual luciferase imaging strategy for quantifying signal transduction and drug targeting. Our results establish NL as a new reporter for bioluminescence imaging studies in intact cells and living mice that will expand imaging of signal transduction in normal physiology, disease, and drug development.
Monitoring Steady Flow Effects on Cell Distribution in Engineered Valve Tissues by Magnetic Resonance Imaging
Authors: Martinez Catalina , Henao Angela , Rodriguez Jose E. , Padgett Kyle R. , Ramaswamy Sharan
Published: March 2018

In heart valve tissue engineering, assessment of cell migration under dynamic states can provide insights on the evolving tissue structure. We labeled human vascular smooth muscle (SMCs), endothelial (ECs), and bone marrow–derived mesenchymal stem cells (BMSCs) with superparamagnetic iron oxide (SPIO) microparticles and visualized them using magnetic resonance imaging (MRI) under steady flow. We determined that vascular cells were able to remain reasonably viable and proliferate well after being labeled with SPIO microparticles (200 μg/mL) for 48 hours. SPIO-labeled cells were successfully visualized using T2* contrast. When physiologically representative shear stresses (5–6 dynes/cm2) were applied to SMC-EC coculture–seeded scaffolds, hypointense regions seemed to have decreased after 2 weeks in some locations, whereas others revealed sustained levels of T2* contrast; similar observations were seen in the case of BMSC-seeded scaffolds. This could be attributable to increased out-of-plane cell migratory activity, which occurred from the fluid-induced mechanical cues received, which was not previously evidenced in static culture. Vascular cells and BMSCs were labeled with remarkably high concentrations of SPIO. Moreover, steady fluid flow enhanced intrascaffold cell migration of vascular SMCs and ECs as well as BMSCs, which, in turn, significantly improved construct cellularity and extracellular collagen content
Screening of a Novel Peptide Targeting the Proteoglycan-Like Region of Human Carbonic Anhydrase IX
Authors: Rana Shoaib , Nissen Felix , Lindner Thomas , Altmann Annette , Mier Walter , Debus Juergen , Haberkorn Uwe , Askoxylakis Vasileios
Published: March 2018

The extracellular domain of human carbonic anhydrase IX (CA IX) is extended by a proteoglycan-like region (PGLR). The aim of the present study was the development of novel molecules with specificity for PGLR, which may be used for tumor targeting and imaging. PGLR was chemically synthesized, and phage display biopanning was performed. The identified ligand PGLR-P1 was labeled with 125I and characterized for target binding and metabolic stability. In vitro characterization included kinetic, competition, and internalization studies on CA IX–positive renal cell carcinoma SKRC 52 cells. The CA IX–negative cell lines HEK293 wt and BxPC3 were used as negative controls. In vitro binding experiments revealed an increasing affinity of 125I-PGLR-P1 to SKRC 52 cells but not to negative control HEK293 wt and BxPC3 cells. Internalization studies indicated an exclusive cell membrane binding. Biodistribution analysis demonstrated a higher accumulation in SKRC 52 tumors than in most normal tissues after perfusion. In vivo blocking led to a significant decrease in tumor uptake. Our findings indicate that PGLR-P1 is a promising lead structure for the development of new peptide-based ligands targeting the PGLR of CA IX and reveal challenges that need to be considered for peptide-related molecular imaging.
In Vivo Imaging of Brain Aromatase in Female Baboons: [11C]Vorozole Kinetics and Effect of the Menstrual Cycle
Authors: Pareto Deborah , Biegon Anat , Alexoff David , Carter Pauline , Shea Coreen , Muench Lisa , Xu Youwen , Fowler Joanna S. , Kim Sunny W. , Logan Jean
Published: March 2018

The aim of this work was to quantify the brain distribution of the enzyme aromatase in the female baboon with positron emission tomography and the tracer [11C]vorozole using three different quantification methods for estimating the total distribution volume (VT): a graphical method, compartment modeling, and a tissue to plasma ratio. The graphical model and the compartment modeling gave similar estimates to the data and similar values (correlation R = .988; p = .0001). [11C]Vorozole shows a rapid uptake by the brain followed by a relatively constant accumulation, suggesting the possibility of using the tissue to plasma ratio as an estimate of VT. The highest uptake of [11C]vorozole in the baboon brain was measured in the amygdala, followed by the preoptic area and hypothalamus, basal ganglia, and cortical areas. Pretreatment studies with vorozole or letrozole showed a generalized decrease in brain accumulation and VT. The results suggested that the physiologic changes in gonadal hormone levels accompanying the menstrual cycle had a significant effect on brain aromatase VT.
Fluorescent Nanoparticle Imaging Allows Noninvasive Evaluation of Immune Cell Modulation in Esophageal Dysplasia
Authors: Habibollahi Peiman , Waldron Todd , Heidari Pedram , Cho Hoon Sung , Alcantara David , Josephson Lee , Wang Timothy C. , Rustgi Anil K. , Mahmood Umar
Published: March 2018

Esophageal tumors provide unique challenges and opportunities for developing and testing surveillance imaging technology for different tumor microenvironment components, including assessment of immune cell modulation, with the ultimate goal of promoting early detection and response evaluation. In this context, accessibility through the lumen using a minimally invasive approach provides a means for repetitive evaluation longitudinally by combining fluorescent endoscopic imaging technology with novel fluorescent nanoparticles that are phagocytized by immune cells in the microenvironment. The agent we developed for imaging is synthesized from Feraheme (ferumoxytol), a Food and Drug Administration-approved monocrystaline dextran-coated iron oxide nanoparticle, which we conjugated to a near-infrared fluorochrome, CyAL5.5. We demonstrate a high level of uptake of the fluorescent nanoparticles by myeloid-derived suppressor cells (MDSCs) in the esophagus and spleen of L2Cre;p120ctnflox/flox mice. These mice develop esophageal dysplasia leading to squamous cell carcinoma; we have previously demonstrated that dysplastic and neoplastic esophageal lesions in these mice have an immune cell infiltration that is dominated by MDSCs. In the L2Cre;p120ctnflox/flox mice, evaluation of the spleen reveals that nearly 80% of CD45+ leukocytes that phagocytized the nanoparticle were CD11b+Gr1+ MDSCs. After dexamethasone treatment, we observed concordant decreased fluorescent signal from esophageal lesions during fluorescent endoscopy and decreased CyAL5.5-fluorescent-positive immune cell infiltration in esophageal dysplastic lesions by fluorescence-activated cell sorting analysis. Our observations suggest that this translatable technology may be used for the early detection of dysplastic changes and the serial assessment of immunomodulatory therapy and to visualize changes in MDSCs in the esophageal tumor microenvironment.
Ex Vivo and in Vivo Administration of Fluorescent CNA35 Specifically Marks Cardiac Fibrosis
Authors: de Jong Sanne , van Middendorp Lars B. , Hermans Robin H.A. , de Bakker Jacques M.T. , Bierhuizen Marti F.A. , Prinzen Frits W. , van Rijen Harold V.M. , Losen Mario , Vos Marc A. , van Zandvoort Marc A.M.J.
Published: March 2018

Cardiac fibrosis is a major hallmark of cardiac diseases. For evaluation of cardiac fibrosis, the development of highly specific and preferably noninvasive methods is desired. Our aim was to evaluate CNA35, a protein known to specifically bind to collagen, as a specific marker of cardiac fibrosis. Fluorescently labeled CNA35 was applied ex vivo on tissue sections of fibrotic rat, mouse, and canine myocardium. After quantification of CNA35, sections were examined with picrosirius red (PSR) and compared to CNA35. Furthermore, fluorescently labeled CNA35 was administered in vivo in mice. Hearts were isolated, and CNA35 labeling was examined in tissue sections. Serial sections were histologically examined with PSR. Ex vivo application of CNA35 showed specific binding to collagen and a high correlation with PSR (Pearson r = .86 for mice/rats and r = .98 for canine; both p < .001). After in vivo administration, CNA35 labeling was observed around individual cardiomyocytes, indicating its ability to penetrate cardiac endothelium. High correlation was observed between CNA35 and PSR ( r = .91, p < .001). CNA35 specifically binds to cardiac collagen and can cross the endothelial barrier. Therefore, labeled CNA35 is useful to specifically detect collagen both ex vivo and in vivo and potentially can be converted to a noninvasive method to detect cardiac fibrosis.
Breast Cancer Imaging Using the Near-Infrared Fluorescent Agent, CLR1502
Authors: Korb Melissa L. , Warram Jason M. , Grudzinski Joseph , Weichert Jamey , Jeffery Justin , Rosenthal Eben L.
Published: March 2018

Positive margins after breast conservation surgery represent a significant problem in the treatment of breast cancer. The near-infrared fluorescence agent CLR1502 (Cellectar Biosciences, Madison, WI) was studied in a preclinical breast cancer model to determine imaging properties and ability to detect small islands of malignancy. Nude mice bearing human breast cancer flank xenografts were given a systemic injection of CLR1502, and imaging was performed using LUNA (Novadaq Technologies Inc., Richmond, BC) and Pearl Impulse (LI-COR Biosciences, Lincoln, NE) devices. Normal tissues were examined for fluorescence signal, and conventional and fluorescence histology was performed using the Odyssey scanner. Peak tumor to background ratio occurred 2 days after injection with CLR1502. The smallest amount of tumor that was imaged and detected using these devices was 1.9 mg, equivalent to 1.9 × 106 cells. The highest fluorescence signal was seen in tumor and normal lymph node tissue, and the lowest fluorescence signal was seen in muscle and plasma. Human breast cancer tumors can be imaged in vivo with multiple optical imaging platforms using CLR1502. This pilot study supports further investigations of this fluorescent agent for improving surgical resection of malignancies, with the goal of eventual clinical translation.
X-Ray Fluorescence Microscopy Demonstrates Preferential Accumulation of a Vanadium-Based Magnetic Resonance Imaging Contrast Agent in Murine Colonic Tumors
Authors: Mustafi Devkumar , Ward Jesse , Dougherty Urszula , Bissonnette Marc , Hart John , Vogt Stefan , Karczmar Gregory S.
Published: March 2018

Contrast agents that specifically enhance cancers on magnetic resonance imaging (MRI) will allow earlier detection. Vanadium-based chelates (VCs) selectively enhance rodent cancers on MRI, suggesting selective uptake of VCs by cancers. Here we report x-ray fluorescence microscopy (XFM) of VC uptake by murine colon cancer. Colonic tumors in mice treated with azoxymethane/dextran sulfate sodium were identified by MRI. Then a gadolinium-based contrast agent and a VC were injected intravenously; mice were sacrificed and colons sectioned. VC distribution was sampled at 120 minutes after injection to evaluate the long-term accumulation. Gadolinium distribution was sampled at 10 minutes after injection due to its rapid washout. XFM was performed on 72 regions of normal and cancerous colon from five normal mice and four cancer-bearing mice. XFM showed that all gadolinium was extracellular, with similar concentrations in colon cancers and normal colon. In contrast, the average VC concentration was twofold higher in cancers versus normal tissue ( p < .002). Cancers also contained numerous “hot spots” with intracellular VC concentrations sixfold higher than the concentration in normal colon ( p < .0001). No hot spots were detected in normal colon. This is the first direct demonstration that VCs selectively accumulate in cancer cells and thus may improve cancer detection.
Monoclonal Antibody–Conjugated Superparamagnetic Iron Oxide Nanoparticles for Imaging of Epidermal Growth Factor Receptor–Targeted Cells and Gliomas
Authors: Mu Ketao , Zhang Shun , Ai Tao , Jiang Jingjing , Yao Yihao , Jiang Lingyu , Zhou Qing , Xiang Hongbing , Zhu Yanhong , Yang Xiangliang , Zhu Wenzhen
Published: March 2018

The objective of this study was to successfully synthesize epidermal growth factor receptor monoclonal antibody–conjugated superparamagnetic iron oxide nanoparticles (EGFRmAb-SPIONs) and explore their biocompatibility and potential applications as a targeted magnetic resonance imaging (MRI) contrast agent for the EGFR-specific detection of brain glioma in vivo. After conjugation of EGFRmAb with SPIONs, the magnetic characteristics of EGFRmAb-SPIONs were investigated. Thereafter, the targeting abilities of EGFRmAb-SPIONs with MRI were qualitatively and quantitatively assessed in EGFR-positive C6 glioma cells in vitro and in a Wistar rat model bearing C6 glioma in vivo. Furthermore, the preliminary biocompatibility and toxicity of EGFRmAb-SPIONs were evaluated in normal rats through hematology assays and histopathologic analyses. Statistical analysis was performed using one-way analysis of variance and Student t-test, with a significance level of p < .05. From the results of EGFRmAb-SPION characterizations, the average particle size was 10.21 nm and the hydrodynamic diameter was 161.5 ± 2.12 nm. The saturation magnetization was 55 emu/g·Fe, and T2 relaxivity was 92.73 s−1mM−1 in distilled water. The preferential accumulation of the EGFRmAb-SPIONs within glioma and subsequent MRI contrast enhancement were demonstrated both in vitro in C6 cells and in vivo in rats bearing C6 glioma. After intravenous administration of EGFRmAb-SPIONs, T2-weighted MRI of the rat model with brain glioma exhibited an apparent hypointense region within glioma from 2 to 48 hours. The maximal image contrast was reached at 24 hours, where the signal intensity decreased and the R2 value increased by 30% compared to baseline. However, T2-weighted imaging of the rat model administered with SPIONs showed no visible signal changes within the tumor over the same time period. Moreover, no evident toxicities in vitro and in vivo with EGFRmAb-SPIONs were clearly identified based on the laboratory examinations. EGFRmAb-SPIONs could potentially be employed as a targeted contrast agent in the molecule-specific diagnosis of brain glioma in MRI.
Monitoring Disease Progression and Therapeutic Response in a Disseminated Tumor Model for Non-Hodgkin Lymphoma by Bioluminescence Imaging
Authors: Köberle Margarethe , Müller Kristin , Kamprad Manja , Horn Friedemann , Scholz Markus
Published: March 2018

Xenograft tumor models are widely studied in cancer research. Our aim was to establish and apply a model for aggressive CD20-positive B-cell non-Hodgkin lymphomas, enabling us to monitor tumor growth and shrinkage in a noninvasive manner. By stably transfecting a luciferase expression vector, we created two bioluminescent human non-Hodgkin lymphoma cell lines, Jeko1(luci) and OCI-Ly3(luci), that are CD20 positive, a prerequisite to studying rituximab, a chimeric anti-CD20 antibody. To investigate the therapy response in vivo, we established a disseminated xenograft tumor model injecting these cell lines in NOD/SCID mice. We observed a close correlation of bioluminescence intensity and tumor burden, allowing us to monitor therapy response in the living animal. Cyclophosphamide reduced tumor burden in mice injected with either cell line in a dose-dependent manner. Rituximab alone was effective in OCI-Ly3(luci)-injected mice and acted additively in combination with cyclophosphamide. In contrast, it improved the therapeutic outcome of Jeko1(luci)-injected mice only in combination with cyclophosphamide. We conclude that well-established bioluminescence imaging is a valuable tool in disseminated xenograft tumor models. Our model can be translated to other cell lines and used to examine new therapeutic agents and schedules.
In Vivo Imaging Study of Angiogenesis in a Channelized Porous Scaffold
Authors: Tamplenizza Margherita , Tocchio Alessandro , Gerges Irini , Martello Federico , Martelli Cristina , Ottobrini Luisa , Lucignani Giovanni , Milani Paolo , Lenardi Cristina
Published: March 2018

The main scientific issue hindering the development of tissue engineering technologies is the lack of proper vascularization. Among the various approaches developed for boosting vascularization, scaffold design has attracted increasing interest over the last few years. The aim of this article is to illustrate a scaffold design strategy for enhancing vascularization based on sacrificial microfabrication of embedded microchannels. This approach was combined with an innovative poly(ether urethane urea) (PEUtU) porous scaffold to provide an alternative graft substitute material for the treatment of tissue defects. Fluorescent and chemiluminescent imaging combined with computed tomography were used to study the behavior of the scaffold composition within living subjects by analyzing angiogenesis and inflammation processes and observing the variation in x-ray absorption, respectively. For this purpose, an IntegriSense 680 probe was used in vivo for the localization and quantification of integrin αvβ3, due to its critical involvement in angiogenesis, and a XenoLight RediJect Inflammation Probe for the study of the decline in inflammation progression during healing. Overall, the collected data suggest the advantages of embedding a synthetic vascular network into a PEUtU porous matrix to enhance in vivo tissue integration, maturation, and regeneration. Moreover, our imaging approach proved to be an efficient and versatile tool for scaffold in vivo testing.
Imaging Reporters for Proteasome Activity Identify Tumor- and Metastasis-Initiating Cells
Authors: Stacer Amanda C. , Wang Hanxiao , Fenner Joseph , Dosch Joseph S. , Salomonnson Anna , Luker Kathryn E. , Luker Gary D. , Rehemtulla Alnawaz , Ross Brian D.
Published: March 2018

Tumor-initiating cells, also designated as cancer stem cells, are proposed to constitute a subpopulation of malignant cells central to tumorigenesis, metastasis, and treatment resistance. We analyzed the activity of the proteasome, the primary organelle for targeted protein degradation, as a marker of tumor- and metastasis-initiating cells. Using human and mouse breast cancer cells expressing a validated fluorescent reporter, we found a small subpopulation of cells with low proteasome activity that divided asymmetrically to produce daughter cells with low or high proteasome activity. Breast cancer cells with low proteasome activity had greater local tumor formation and metastasis in immunocompromised and immunocompetent mice. To allow flexible labeling of cells, we also developed a new proteasome substrate based on HaloTag technology. Patient-derived glioblastoma cells with low proteasome activity measured by the HaloTag reporter show key phenotypes associated with tumor-initiating cells, including expression of a stem cell transcription factor, reconstitution of the original starting population, and enhanced neurosphere formation. We also show that patient-derived glioblastoma cells with low proteasome activity have higher frequency of tumor formation in mouse xenografts. These studies support proteasome function as a tool to investigate tumor- and metastasis-initiating cancer cells and a potential biomarker for outcomes in patients with several different cancers.
A Novel Endoscopic Cerenkov Luminescence Imaging System for Intraoperative Surgical Navigation
Authors: Song Tianming , Liu Xia , Qu Yawei , Liu Haixiao , Bao Chengpeng , Leng Chengcai , Hu Zhenhua , Wang Kun , Tian Jie
Published: March 2018

Cerenkov luminescence imaging is an emerging optical technique for imaging the distribution of radiopharmaceuticals in vivo. However, because of the light scattering effect, it cannot obtain optical information from deep internal organs. To overcome this challenge, we established a novel endoscopic Cerenkov luminescence imaging system that used a clinically approved laparoscope and an electron-multiplying charge-coupled device camera. We assessed the performance of the system through a series of in vitro and in vivo experiments. The results demonstrated superior superficial imaging resolution (0.1 mm), a large field of view (500 mm2 with 10 mm imaging distance), and superb imaging sensitivity (imaging 1 μCi) of our system. It captured the weak Cerenkov signal from internal organs successfully and was applied to intraoperative surgical navigation of tumor resection. It offered objective information of the tumor location and tumor residual during the surgical operation. This technique holds great potential for clinical translation.
Does Classification of Composites for Network Meta-analyses Lead to Erroneous Conclusions?
Authors: Schwendicke F , Blunck U , Tu Y-K , Göstemeyer G
Published: March 2018

Objectives: 

Composites can be classified differently, according to manufacturer information, filler particle size, resin-monomer base, or viscosity, for example. Using clinical trial data, network meta-analyses aim to rank different composite material classes. Dentists then use these ranks to decide whether to use specific materials. Alternatively, annual failure rates (AFRs) of materials can be assessed, not requiring any classification for synthesis. It is unclear whether different classification systems lead to different rankings of the same material (ie, erroneous conclusions). We aimed to evaluate the agreement of material rankings between different classification systems.

Methods: 

A systematic review was performed via MEDLINE, Cochrane Central Register of Controlled Trials, and EMBASE. Randomized controlled trials published from 2005-2015 that investigated composite restorations placed in load-bearing cavitated lesions in permanent teeth were included. Network meta-analyses were performed to rank combinations of composite classes (according to manufacturer, filler particle size, resin-monomers, viscosity) and adhesives. Material combinations were additionally ranked using AFRs.

Results: 

A total of 42 studies (6088 restorations, 2325 patients) were included. The ranking of most material class combinations showed significant agreement between classifications (R2 ranged between 0.03 and 0.56). Comparing material combinations using AFRs had low precision and agreement with other systems. AFRs were significantly correlated with follow-up periods of trials.

Conclusion: 

There was high agreement between rankings of identical materials in different classification systems. Such rankings thus allow cautious deductions as to the performance of a specific material. Syntheses based on AFRs might lead to erroneous results because AFRs are determined by follow-up periods and have low precision.
Effect of Toothpaste Use Against Mineral Loss Promoted by Dental Bleaching
Authors: Vieira-Junior WF , Ferraz LN , Pini NIP , Ambrosano GMB , Aguiar FHB , Tabchoury CPM , Lima DANL
Published: March 2018

Aim: To investigate the effect of different toothpaste formulations used prior to dental bleaching with 35% hydrogen peroxide (HP) on the mineral content and surface morphology of enamel. Methods: Seventy bovine enamel blocks (4×4×2 mm) were submitted to in vitro treatment protocols using a toothbrushing machine prior to dental bleaching or a placebo procedure (n=10) as proposed in the following groups: unbleached control (PLA), bleached control (HP), and brushing with differing toothpastes prior to HP bleaching, including: potassium nitrate toothpaste containing sodium fluoride (PN), sodium monofluorophosphate/MFP toothpaste (FT), arginine-carbonate (8% arginine) (PA) or arginine-carbonate (1.5% arginine) toothpaste (SAN), and toothpaste containing bioactive glass (NM). Phosphorus concentration in gel ([P]) was evaluated (μg of P/mg of gel), and the elemental levels (wt%) of Ca, P, and Na as well as the proportion between Ca and P and spectra graphics were determined using an energy-dispersive X-ray spectrometer (EDS). The surface morphology was assessed using scanning electron microscopy (SEM). The data were subjected to analysis of variance and the Tukey test (α=0.05). Results: HP demonstrated the greatest [P] values in gel, being statistically different from PLA. The [P] of NM was statistically similar to PLA. HP showed a significant decrease in the Ca% and Ca/P values when compared to PLA in EDS analysis. PA showed Ca/P values statistically different from HP. In accordance with SEM analysis, the PA, SAN, and NM groups presented a smooth and uniform enamel surface, while HP and FT demonstrated some alterations in morphology. Conclusion: The toothpastes containing bioactive glass or arginine carbonate used prior to dental bleaching were effective in protecting enamel against mineral loss promoted by the whitening procedure.
Combination of Acetaminophen/Codeine Analgesics Does Not Avoid Bleaching-Induced Tooth Sensitivity: A Randomized, Triple-Blind Two-Center Clinical Trial
Authors: Coppla FM , Rezende M , de Paula E , Farago PV , Loguercio AD , Kossatz S , Reis A
Published: March 2018

Bleaching-induced tooth sensitivity (TS) is highly prevalent. Objective: This study aimed to determine if the combination of opioids and nonopioids analgesics (Tylex) may provide a better analgesic effect. Method: A triple-blind, parallel, randomized two-center clinical trial was conducted with 105 healthy patients who received either a placebo or a combination of acetaminophen/codeine. The first dose of Tylex 30 mg (acetaminophen 500 mg/codeine 30 mg) or placebo was administered one hour before the in-office bleaching (35% hydrogen peroxide), and extra doses were administered every six hours for 48 hours. The TS was recorded using a visual analog scale of 0 to 10 and a numeric rating scale of 0 to 4 in different periods: during bleaching, one hour up to 24 hours, and 24 hours up to 48 hours postbleaching. The color was measured before and one month after dental bleaching with a visual shade guide (Vita Classical), Vita Bleachedguide 3D-MASTER, and the spectrophotometer Vita Easyshade. The absolute risk of TS was evaluated using the Fisher exact test. Data of TS intensity with numeric rating scale of the two groups were compared with the Mann-Whitney U-test and the Friedman test, while data from the visual analog scale were evaluated by two-way repeated measures analysis of variance and the Tukey test for pairwise comparison. The color changes between groups were compared using the Student t-test (α=0.05). Results: No significant differences between the groups were observed in the risk and intensity of TS. The overall absolute risk of TS was approximately 96%. No significant differences between groups were observed in terms of color change (p>0.05) for any scale. Conclusion: The use of an acetaminophen/codeine combination prior to in-office bleaching does not reduce the risk and intensity of bleaching-induced TS.
Degradation of Multimode Adhesive System Bond Strength to Artificial Caries-Affected Dentin Due to Water Storage
Authors: Follak AC , Miotti LL , Lenzi TL , Rocha RO , Soares FZM
Published: March 2018

The purpose of this study was to evaluate the influence of water storage on bond strength of multimode adhesive systems to artificially induced caries-affected dentin. One hundred twelve sound bovine incisors were randomly assigned to 16 groups (n=7) according to the dentin condition (sound; SND, artificially induced caries-affected dentin; CAD, cariogenic challenge by pH cycling for 14 days); the adhesive system (SU, Scotchbond Universal Adhesive; AB, All-Bond Universal; PB, Prime & Bond Elect; SB, Adper Single Bond 2; and CS, Clearfil SE Bond), and the etching strategy (etch-and-rinse and self-etch). All adhesive systems were applied under manufacturer's instructions to flat dentin surfaces, and a composite block was built up on each dentin surface. After 24 hours of water storage, the specimens were sectioned into stick-shaped specimens (0.8 mm2) and submitted to a microtensile test immediately (24 hours) or after six months of water storage. Bond strength data (MPa) were analyzed using three-way repeated-measures analysis of variance and post hoc Tukey test (α=5%), considering each substrate separately (SND and CAD). The etching strategy did not influence the bond strength of multimode adhesives, irrespective of the dentin condition. Water storage only reduced significantly the bond strength to CAD. The degradation of bond strength due to water storage was more pronounced in CAD, regardless of the etching strategy.
Minimizing the Network Overhead load for Virtual Desktop
Authors: Prashanth Tirumanapally
Published: March 2018

Over the past decade, cloud computing services become pervasive in the industrial field in order to enhance the efficiency and reduce the TCO (Total Cost of Ownership). Virtual desktop infrastructure (VDI) provides the computing environment to the client, where the host server delivers the video images encoded on the host server. The client decodes the video images and then displays them on the screen. However, this scheme causes the heavy traffic and increases an overhead on the host server due to the frequent memory access. In this paper, we propose a novel method for reducing the network traffic and decreasing an overhead on the host server through the cyclic redundancy check (CRC) comparison of each frame. Experimental result shows the feasibility of our proposal.
PEMANFAATAN KACANG KORO PEDANG (Canavalia ensiformis L) TERHADAP PEMBUATAN TAHU KACANG KORO BERDASARKAN PERBEDAAN KONSENTRASI KOAGULAN
Authors: Widiantara Tantan , Cahyadi WIsnu
Published: March 2018

Tahu adalah makanan semi padat yang terbuat dari susu kedelai dengan proses pengendapan protein pada titik isoelektrik, yang dipenelitian ini kacang koro sebagai bahan baku utama. Tujuan dari penelitian ini adalah untuk mengetahui dan mempelajari pengaruh konsentrasi koagulan terhadap karakteristik tahu koro pedang tanpa penambahan atau penggantian bahan lainnya. Penelitian ini terdiri dari dua tahapan yaitu penelitian pendahuluan dan penelitian utama, untuk tahap pendahuluan terdiri dari dua faktor yang menentukan jenis koagulan dan suhu yang dipilih, jenis koagulan adalah asam sitrat, asam asetat dan kalsium sulfat, yang menggunakan suhu 60 ° C, 70 ° C dan 80 ° C. Penelitian utama terdiri dari 1 faktor dengan jumlah taraf adalah 5 (variasi konsentrasi sebagai taraf ) yaitu ; 0,25%, 1%, 1,25%, 1,5%, 1,75% dengan temperatur pemasakan adalah 70 ° C. Metode eksperimen yang digunakan dalam penelitian ini adalah rancangan acak kelompok (RAK) dengan ulangan sebanyak 5 kali sehingga ada 25 satuan percobaan. Hasil penelitian pendahuluan menunjukkan bahwa kalsium sulfat adalah koagulan terpilih dengan pada suhu pemasakan 70°C, sedangkan penelitian utama menunjukkan bahwa kalsium sulfat koagulan pada konsentrasi 1,75% adalah perlakuan yang dipilih, berdasarkan respon kimia untuk mengetahui sebelum dan sesudah penggorengan yang mengandung kadar protein tinggi sebelum digoreng sebesar 26,41% dan 23,56% setelah penggorengan, Tingkat HCN sebelum digoreng pada 43,87 ppm dan 29,25 ppm setelah digoreng, kadar karbohidrat sebelum digoreng sebesar 26,06% dan 21,15% setelah menggoreng, menggoreng kandungan lemak 2% sebelum dan setelah menggoreng sampai 21% kadar air sebelum menggoreng sebesar 76, 92 % dan 36% setelah penggorengan, dan total mikroba sebelum menggoreng 5.45x105 cfu / ml, 5,32 x 103 cfu / ml.
Analysis of Species in Meat Products in Bandung City using Multiplex PCR
Authors: Yelliantty Yelliantty , Rohima Ira Endah
Published: March 2018

Cases concerning the substitution of meat raw material also occur in Indonesia and are quite common. Therefore, careful monitoring and control that needs to be done on the meat products. Screening or sampling products on the market should be conducted periodically to ensure the safety of consumers and society in general. Such screening should be done accurately. This study aimed to analyze the composition of meat in processed products in traditional markets in Bandung using PCR method. This study was using four specific primers to detect four different species. Screening is done on samples of meatballs from several markets. The results showed the presence of several samples that contain meat of some species. based it can be concluded that the substitution of raw materials processed meat products also occurs in the traditional market in the city of Bandung, and the PCR method referred to can be used as the basis for the development of detection methods of food security in Indonesia.
Troya y Roma en algunas Odas de Horacio: traducciones endecasilábicas
Authors: Rollié Emilio
Published: March 2018

El metro elegido para la traducción es el endecasílabo, un metro que tiene amplia tradición en la poesía en español. En el caso de la poesía clásica, en donde la rima no existe, puede decirse que es completamente adecuado, ya que es el tipo de verso que más ha prescindido de ella, aquel en el que se ha producido la mayor cantidad de composiciones no rimadas (salvo, por supuesto, el verso no medido).
Assessment of the effects of diet and physical rehabilitation on radiographic findings and markers of synovial inflammation in dogs following tibial plateau leveling osteotomy
Authors: Verpaalen Valentine D. , Baltzer Wendy I. , Smith-Ostrin Sarah , Warnock Jennifer J. , Stang Bernadette , Ruaux Craig G.
Published: March 2018

OBJECTIVE To determine the effects of an omega-3 fatty acid and protein–enriched diet, physical rehabilitation, or both on radiographic findings and markers of synovial inflammation in dogs following tibial plateau leveling osteotomy and arthroscopic surgery for treatment of cranial cruciate ligament disease.

DESIGN Randomized, prospective clinical trial.

ANIMALS 48 dogs with unilateral cranial cruciate ligament disease.

PROCEDURES Dogs were randomly assigned to receive a dry omega-3 fatty acid and protein–enriched dog food formulated to support joint health (test food [TF]), a dry food formulated for adult canine maintenance (control food [CF]), TF plus rehabilitation, or CF plus rehabilitation after surgery. Synovial fluid prostaglandin (PG) E2 and interleukin-1β concentrations, radiographic osteoarthritis scores, osteotomy site healing, and patellar ligament thickness were assessed at predetermined time points up to 6 months after surgery.

RESULTS Dogs that received CF had significantly higher PGE2 concentrations over time following surgery than did dogs that received TF, regardless of rehabilitation status. Synovial fluid interleukin-1β concentrations did not change over time in any groups. Diet and rehabilitation were both associated with osteoarthritis scores, with significantly lower scores over time for dogs that received TF versus CF and for dogs that underwent rehabilitation versus those that did not. Proportions of dogs with complete osteotomy healing 8 and 24 weeks after surgery were significantly lower for dogs that received TF than for dogs that received CF, regardless of rehabilitation status.

CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that feeding the TF can result in lower synovial fluid PGE2 concentrations and that both the TF and rehabilitation can reduce progression of osteoarthritis in the 6 months following tibial plateau leveling osteotomy; clinical relevance of slower osteotomy healing in dogs fed the TF was unclear.
Outcome of ureteral stent placement for treatment of benign ureteral obstruction in dogs: 44 cases (2010–2013)
Authors: Pavia Philippa R. , Berent Allyson C. , Weisse Chick W. , Neiman Dana , Lamb Kenneth , Bagley Demetrius
Published: March 2018

OBJECTIVE To describe the technique and short- and long-term outcomes for dogs undergoing double-pigtail ureteral stent placement for treatment of benign ureteral obstruction.

DESIGN Retrospective case series.

ANIMALS 44 dogs (57 ureters).

PROCEDURES Medical records of dogs that underwent ureteral stenting for treatment of benign ureteral obstruction between 2010 and 2013 were reviewed. Signal-ment, history, pertinent diagnostic imaging results, endourologic and post-procedural details, duration of hospitalization, complications, and outcome (short term, 7 to 30 days; long term, > 30 days) were recorded. Ureteral stent placement was performed endoscopically, surgically, or both, with fluoroscopic guidance.

RESULTS 57 ureters (44 dogs) underwent stenting because of obstructive ureterolithiasis (n = 48 [84%]), stricture (5 [9%]), or both (4 [7%]). Endoscopic or surgical techniques were successful for stent placement in 45 of 55 and 12 of 12 ureters (34/42 and 10/10 dogs), respectively. Median hospitalization time was 1 day. Median creatinine concentration was 2 mg/dL prior to stenting and 1.3 mg/dL 3 months after the procedure. Urinary tract infections were present in 26 of 44 (59%) dogs prior to stenting and in 11 of 43 dogs (26%) after stenting. One of the 44 (2%) dogs died after undergoing stenting, but the cause of death was not related to the procedure. Median follow-up time was 1,158 days (range, 3 to > 1,555 days), with 30 of 44 dogs alive at the time of last follow-up.

CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that ureteral stenting may be a viable option for first-line treatment of dogs with benign ureteral obstruction. However, patients should be monitored for urinary tract infection following stenting.
Surgical and endoscopic treatment of bladder exstrophy-epispadias complex in a female dog
Authors: Jones Brittani , Berent Allyson C. , Weisse Chick W. , Hart Robert , Alvarez Leilani , Fischetti Anthony , Horn B. David , Canning Douglas
Published: March 2018

CASE DESCRIPTION A 14-week-old 7.7-kg (16.9-lb) sexually intact female Golden Retriever was evaluated because of urine dripping from the caudoventral aspect of the abdomen.

CLINICAL FINDINGS Ultrasonography, radiography, excretory CT urography, and vaginocystourethroscopy were performed. Results indicated eversion of the bladder through the ventral abdominal wall with exposure of the ureterovesicular junctions, pubic diastasis, and an open vulva and clitoral fossa. Clinical findings were suggestive of bladder exstrophy, a rare congenital anomaly.

TREATMENT AND OUTCOME The dog was anesthetized and bilateral ileal osteotomies were performed. Two ureteral catheters were passed retrograde into the renal pelves under fluoroscopic guidance. The lateral margins of the bladder, bladder neck, and urethra were surgically separated from the abdominal wall, and the bladder was closed, forming a hollow viscus. The symphysis pubis was closed on midline with horizontal mattress sutures. The defects in the vestibule and clitoral fossa were closed. Lastly, the iliac osteotomies were stabilized. The dog was initially incontinent with right hind limb sciatic neuropraxia and developed pyelonephritis. Over time, the dog became continent with full return to orthopedic and neurologic function, but had recurrent urinary tract infections, developed renal azotemia likely associated with chronic pyelonephritis, and ultimately was euthanized 3.5 years after surgery because of end-stage kidney disease.

CLINICAL RELEVANCE Bladder exstrophy and epispadias is a treatable but rare congenital abnormality. The procedure described could be considered for treatment of this condition, but care should be taken to monitor for urinary tract infections and ascending pyelonephritis.
Treatment of pyonephrosis with a subcutaneous ureteral bypass device in four cats
Authors: Cray Megan , Berent Allyson C. , Weisse Chick W. , Bagley Demetrius
Published: March 2018

CASE DESCRIPTION 4 cats were examined because of ureteral obstruction.

CLINICAL FINDINGS Clinical and clinicopathologic abnormalities were nonspecific and included anorexia, lethargy, weight loss, anemia, leukocytosis, neutrophilia, lymphopenia, and azotemia. A diagnosis of pyonephrosis was made in all cats. The presence of bacteriuria was confirmed by means of urinalysis in 2 cats, bacterial culture of a urine sample obtained by means of preoperative cystocentesis in 2 cats, and bacterial culture of samples obtained from the renal pelvis intraoperatively in 3 cats. Ureteral obstruction was caused by a urolith in 3 cats; ureteral stricture associated with a circumcaval ureter was identified in 1 cat.

TREATMENT AND OUTCOME All 4 cats underwent renal pelvis lavage and placement of a subcutaneous ureteral bypass (SUB) device for treatment of obstructive pyonephrosis. Postoperatively, the cystostomy tube became occluded with purulent material in 1 cat, requiring exchange. The procedure was successful in relieving the obstruction and pyonephrosis in all cats. Three of 4 cats had documented resolution of urinary tract infection. One cat had persistent bacteriuria without clinical signs 1 month after SUB device placement.

CLINICAL RELEVANCE Results of this small series suggested that renal pelvis lavage with placement of an SUB device may be a treatment option for cats with obstructive pyonephrosis.