bluuebunny/crossref_metadata_2025 huggingface dataset:
S100A7 overexpression is a predictive marker for high risk of malignant transformation in oral dysplasia
Authors: Kaur Jatinder , Matta Ajay , Kak Ipshita , Srivastava Gunjan , Assi Jasmeet , Leong Iona , Witterick Ian , Colgan Terence J. , MacMillan Christina , Siu K.W. Michael , Walfish Paul G. , Ralhan Ranju
Published: October 2013

Early detection of oral lesions (OLs) at high risk of cancer development is of utmost importance for intervention. There is an urgent unmet clinical need for biomarkers that allow identification of high‐risk OLs. Recently, we identified and verified a panel of five candidate protein biomarkers namely S100A7, prothymosin alpha, 14‐3‐3ζ, 14‐3‐3σ and heterogeneous nuclear ribonucleoprotein K using proteomics to distinguish OLs with dysplasia and oral cancers from normal oral tissues. The objective of our study was to evaluate the potential of these candidate protein biomarkers for identification of oral dysplastic lesions at high risk of cancer development. Using immunohistochemistry, we analyzed expressions of these five candidate protein biomarkers in 110 patients with biopsy‐proven oral dysplasia and known clinical outcome and determined their correlations with p16 expression and HPV 16/18 status. Kaplan–Meier survival analysis showed reduced oral cancer‐free survival (OCFS) of 68.6 months (p = 0.007) in patients showing cytoplasmic S100A7 overexpression when compared to patients with weak or no S100A7 immunostaining in cytoplasm (mean OCFS = 122.8 months). Multivariate Cox regression analysis revealed cytoplasmic S100A7 overexpression as the most significant candidate marker associated with cancer development in dysplastic lesions (p = 0.041, hazard ratio = 2.36). In conclusion, our study suggested the potential of S100A7 overexpression in identifying OLs with dysplasia at high risk of cancer development.
Obesity induced a leptin‐Notch signaling axis in breast cancer
Authors: Battle Monica , Gillespie Corey , Quarshie Alexander , Lanier Viola , Harmon Tia , Wilson Kaamilah , Torroella‐Kouri Marta , Gonzalez‐Perez Ruben R.
Published: October 2013

To investigate whether obesity induces a leptin‐Notch signaling axis in breast cancer (BC), leptin‐induced Notch was determined in human MCF‐7 and MDA‐MB231 and mouse E0771 cells and in E0771‐BC hosted by syngeneic lean and diet‐induced obesity (DIO) C57BL/6J female mice. Lean and DIO mice were treated for 3 weeks with leptin inhibitor (PEG‐LPrA2) 1 week after the inoculation of E0771 cells. Leptin induced Notch1, 3 and 4 in BC cells, but Notch2 expression showed opposite pattern in MCF‐7 compared to MDA‐MB231 cells. Notch loss‐of‐function (DAPT and dominant negative [R218H] RBP‐Jk [CSL/CBF1]) showed that a functional leptin‐Notch signaling axis was involved in the proliferation and migration of E0771 cells. E0771‐BC onset was affected by obesity (lean mice7/10 [70%] vs. DIO mice: 11/12 [92%]; Pearson χ2: p = 0.06]). PEG‐LPrA2 significantly reduced BC growth (untreated: 19/42; [45%] vs. treated: 8/42 [19%]; Pearson χ2: p = 0.008). PEG‐LPrA2 did not influence the caloric intake of mice but increased carcass and/or body weights of lean and DIO mice inoculated with E0771 cells, which could be related to the improvement of health conditions (less aggressive disease). Importantly, BC from obese mice had higher levels of Notch3, JAG1 and survivin than lean mice. Inhibition of leptin signaling reduced protein levels of Notch (NICD1, NICD4, Notch3, JAG1 and survivin) and significantly decreased mRNA expression of Notch receptors, ligands and targets. PEG‐LPrA's effects were more prominent in DIO mice. Present data suggest that leptin induces Notch, which could be involved in the reported higher incidence and aggressiveness and, poor prognosis of BC in obese patients.
New frontiers in circulating tumor cell analysis: A reference guide for biomolecular profiling toward translational clinical use
Authors: Becker Therese M. , Caixeiro Nicole J. , Lim Stephanie H. , Tognela Annette , Kienzle Norbert , Scott Kieran F. , Spring Kevin J. , de Souza Paul
Published: October 2013

Circulating tumor cells (CTCs) are now routinely isolated from blood, and measurement of CTC concentrations appears to correlate well with survival in patients with cancer. Interrogation of the molecular profile of CTCs for expression of protein biomarkers, genetic variants and gene expression provides opportunities to use this information to guide personalized treatment, monitor therapy and detect emerging resistance. However, successful application of profiling techniques requires analyses that deliver a reliable and clinically relevant representation of a patient's cancer as it changes with time. Here, we comprehensively review the current knowledge of therapeutically relevant biomarkers in isolated CTCs obtained by fluorescence imaging and genomic profiling approaches. The reviewed data support the notion that molecular profiling of CTCs will provide a reliable representation or surrogate index of tumor burden. Large‐scale translational trials, many currently in progress, will provide critical data to progress CTC analysis toward wider clinical use in personalized treatment.
LE RESPECT DES DROITS D'EAU LORS DE LA REHABILITATION DES PERIMETRES TRADITIONNELS AU MAROC
Authors: Plusquellec Herve , Bachri Mohammed
Published: October 2013

Traditional irrigation sector covering about 300,000 hectares accounts for about 20 percent of the total irrigated area in Morocco. Traditional irrigation schemes developed since immemorial times, although of rustic appearance, are managed according to sophisticated rules of water allocation and distribution. This paper discusses these rules which depend on the nature of water resources (springs, perennial flows and floods), crops and traditional water rights. The paper then presents the actions taken to improve performance of about 80 schemes including physical improvements and intensive training of user associations, while conserving traditional water rights. These works were carried out under the Irrigated Fruit‐tree (PAF) Project financed by the Millenium Challenge Corporation (MCC), of which the original approach is the improvement of the value‐chains of olive trees and palm‐trees from the productivity of the trees to marketing. The project covers a total irrigated area of 53,000 ha of which 20,000 ha in oasis areas and 33,000 ha in areas of small and medium‐scale irrigation. Studies and works were carried out in very diverse area where each scheme has its own characteristics and the social environment responds to specific traditional rules. Copyright © 2013 John Wiley & Sons, Ltd.
NONLINEAR FORECASTING OF THE GOLD MINER SPREAD: AN APPLICATION OF CORRELATION FILTERS
Authors: Dunis Christian L. , Laws Jason , Middleton Peter W. , Karathanasopoulos Andreas
Published: October 2013

This paper models and forecasts the Gold Miner Spread from 23 May 2006 to 30 June 2011. The Gold Miner Spread acts as a suitable performance indicator for the relationship between physical gold and US gold equity.

The contribution of this investigation is twofold. First, the accuracy of each model is evaluated from a statistical perspective. Second, various forecasting methodologies are then applied to trade the spread. Trading models include an ARMA (12,12) model, a cointegration model, a multilayer perceptron neural network (NN), a particle swarm optimization radial basis function NN and a genetic programming algorithm (GPA).

Results obtained from an out‐of‐sample trading simulation validate the in‐sample back test as the GPA model produced the highest risk‐adjusted returns. Correlation filters are also applied to enhance performance and, as a consequence, volatility is reduced by 5%, on average, while returns are improved between 2.54% and 8.11% across five of the six models. Copyright © 2013 John Wiley & Sons, Ltd.
A SIMULATION ANALYSIS OF HERDING AND UNIFRACTAL SCALING BEHAVIOUR
Authors: Phelps Steve , Ng Wing Lon
Published: October 2013

We model the financial market using a class of agent‐based models in which agents’ expectations are driven by heuristic forecasting rules (in contrast to the rational expectations models used in traditional theories of financial markets). We show that, within this framework, we can reproduce unifractal scaling with respect to three well‐known power laws relating (i) moments of the absolute price change to the time‐scale over which they are measured, (ii) magnitude of returns with respect to their probability and (iii) the autocorrelation of absolute returns with respect to lag. In contrast to previous studies, we systematically analyse all three power laws simultaneously using the same underlying model by making observations at different time‐scales and higher moments. We show that the first two scaling laws are remarkably robust to the time‐scale over which observations are made, irrespective of the model configuration. However, in contrast to previous studies, we show that herding may explain why long memory is observed at all frequencies. Copyright © 2013 John Wiley & Sons, Ltd.
Catastrophizing mediates the relationship between fear of pain and preference for elective caesarean section
Authors: Dehghani M. , Sharpe L. , Khatibi A.
Published: October 2013

Background

Fear of childbirth is associated with preference for an elective caesarean section (ECS); however, the role of fear of pain and pain catastrophizing (the tendency to predict the worst case scenario) have not been investigated. The aim of current study was to investigate whether fear of pain and catastrophizing were independent predictors of preference for ECS. We hypothesized that pain catastrophizing and negative affectivity would mediate the relationship between fear of pain and preference for ECS.

Methods

Three hundred pregnant women between 4 and 36 weeks of gestation were asked to indicate whether they would prefer to deliver their baby through an ECS or a vaginal delivery. They were also asked to complete a battery of questionnaires assessing demographic details, mood, fear of childbirth, fear of pain and catastrophizing. Consistent with cultural norms, more than half of the women preferred an ECS (58%).

Results

Women who chose ECS were more likely to seek private obstetric care, have had a previous caesarean section and have higher levels of fear of childbirth, fear of pain, more catastrophic cognitions and lower mood. Catastrophizing, but not negative affectivity, mediated the relationship between fear of pain and preference for ECS, as predicted.

Conclusions

Fear of both childbirth and pain were both independent predictors of preference for ECS. Catastrophizing mediated the relationship between fear of pain and preference for ECS. Interventions that target these factors may reduce the trend towards increasing numbers of ECS internationally.
The effects of goal setting, contingent reward, and instruction on writing skills
Authors: Hansen Blake D. , Wills Howard P.
Published: October 2013

Writing is one of the primary skills that children learn in school. Interventions that address performance deficits and skill deficits have been shown to improve aspects of elementary school children's writing. This study demonstrates performance‐based interventions (goal setting, feedback, and contingent reward) and a skill‐based intervention (instruction) on the writing skills of a 10‐year‐old child. Results indicated that the performance intervention increased the number of correctly spelled words, and the combination of performance and instructional intervention increased the number of complete sentences.
ESTIMATING PERSON‐CENTERED TREATMENT (PeT) EFFECTS USING INSTRUMENTAL VARIABLES: AN APPLICATION TO EVALUATING PROSTATE CANCER TREATMENTS
Authors: Basu Anirban
Published: October 2013

This paper builds on the methods of local instrumental variables developed by Heckman and Vytlacil (1999, 2001, 2005) to estimate person‐centered treatment (PeT) effects that are conditioned on the person's observed characteristics and averaged over the potential conditional distribution of unobserved characteristics that lead them to their observed treatment choices. PeT effects are more individualized than conditional treatment effects from a randomized setting with the same observed characteristics. PeT effects can be easily aggregated to construct any of the mean treatment effect parameters and, more importantly, are well suited to comprehend individual‐level treatment effect heterogeneity. The paper presents the theory behind PeT effects, and applies it to study the variation in individual‐level comparative effects of prostate cancer treatments on overall survival and costs. Copyright © 2013 John Wiley & Sons, Ltd.
Towards an integrated in vitro strategy for estrogenicity testing
Authors: Wang Si , Aarts Jac M. M. J. G. , de Haan Laura H. J. , Argyriou Dimitrios , Peijnenburg Ad A. C. M. , Rietjens Ivonne M. C. M. , Bovee Toine F. H.
Published: October 2013

In order to define an in vitro integrated testing strategy (ITS) for estrogenicity, a set of 23 reference compounds representing diverse chemical classes were tested in a series of in vitro assays including proliferation and reporter gene assays. Outcomes of these assays were combined with published results for estrogen receptor (ER) binding assays and the OECD validated BG1Luc ER transcriptional activation (TA) assay and compared with the outcomes of the in vivo uterotrophic assay to investigate which assays most accurately predict the in vivo uterotrophic effect and to identify discrepancies between the in vitro assays and the in vivo uterotrophic assay. All in vitro assays used revealed a reasonable to good correlation (R2 = 0.62–0.87) with the in vivo uterotrophic assay but the combination of the yeast estrogen bioassay with the U2OS ERα‐CALUX assay seems most promising for an ITS for in vitro estrogenicity testing. The main outliers identified when correlating data from the different in vitro assays and the in vivo uterotrophic assay were 4‐hydroxytamoxifen, testosterone and to a lesser extent apigenin, tamoxifen and kepone. Based on the modes of action possibly underlying these discrepancies it becomes evident that to further improve the ITS and ultimately replace animal testing for (anti‐)estrogenic effects, the selected bioassays have to be combined with other types of in vitro assays, including for instance in vitro models for digestion, bioavailability and metabolism of the compounds under investigation. Copyright © 2013 John Wiley & Sons, Ltd.
Comparison of toxicity of different nanorod‐type TiO2 polymorphs in vivo and in vitro
Authors: Park Eun‐Jung , Lee Gwang‐Hee , Shim Hyun‐Woo , Kim Jae‐Ho , Cho Myung‐Haing , Kim Dong‐Wan
Published: October 2013

It is predicted that the toxicity of nanoparticles may be different depending on the properties of the nanoparticles and biological system being tested. However, the factors that influence the toxicity of nanoparticles have not been adequately investigated. In this study, we characterized two types of TiO2 nanorods, anatase (ATO) and brookite (BTO), and compared their toxicity in vivo and in vitro. ATO and BTO differed from each other most notably in their surface areas. Treatment with the two TiO2 nanorods (10 µg ml–1) produced similar effects on the cell cycle in eight cell lines which are derived from potential target organs of nanoparticles, with the BTO eliciting stronger responses than ATO in all cell lines, among the cell lines, H9C2 showed the maximal change. Similarly, when mice were exposed to two TiO2 nanorods (1 mg kg–1), BTO induced clearer histopathological lesions and triggered a more robust secretion of inflammatory cytokines than ATO. Furthermore, we compared the cellular response of both TiO2 nanorods using BEAS‐2B cells, the human bronchial epithelial cell line. Both nanorods induced cell death by increasing the formation of autophagosome‐like vacuoles. The mitochondrial calcium concentration decreased by exposure of both types, but the distribution of lysosome and endoplasmic reticulum (ER) showed a clear difference between the two nanorods. Thus, we conclude that the surface area acts as an important factor which depends on toxicity of nanorod type‐TiO2 nanoparticles. Furthermore, the toxicity of nanoparticles varies according to the type of cells tested, and that the assembly of autophagosome‐like vacuoles is a critical part of the cellular response to nanoparticle exposure. Copyright © 2013 John Wiley & Sons, Ltd.
Histopathological findings on Carassius auratus hepatopancreas upon exposure to acrylamide: correlation with genotoxicity and metabolic alterations
Authors: Larguinho Miguel , Costa Pedro M. , Sousa Gonçalo , Costa Maria H. , Diniz Mário S. , Baptista Pedro V.
Published: October 2013

Acrylamide is an amide used in several industrial applications making it easily discharged to aquatic ecosystems. The toxicity of acrylamide to aquatic organisms is scarcely known, although previous studies with murine models provided evidence for deleterious effects. To assess the effects of acrylamide to freshwater fish, goldfish (Carassius auratus L.) were exposed to several concentrations of waterborne acrylamide and analysed for genotoxic damage, alterations to detoxifying enzymes and histopathology. Results revealed a dose‐dependent increase in total DNA strand breakage, the formation of erythrocytic nuclear abnormalities and in the levels of hepatic cytochrome P4501A (CYP1A) and glutathione S‐transferase (GST) activity. In addition, acrylamide induced more histopathological changes to pancreatic acini than to the hepatic parenchyma, regardless of exposure concentration, whereas hepatic tissue only endured significant alterations at higher concentrations of exposure. Thus, results confirm the genotoxic potential of acrylamide to fish and its ability to induce CYP1A, probably as a direct primary defence mechanism. This strongly suggests the substance's pro‐mutagenic potential in fish, similarly to what is known for rodents. However, the deleterious effects observed in the pancreatic acini, more severe than in the liver, could indicate a specific, albeit unknown toxic mechanism of acrylamide to fish that overran the organism's metabolic defences against a chemical agent rather than causing a general systemic failure. Copyright © 2013 John Wiley & Sons, Ltd.
A catch‐up validation study of an in vitro skin irritation test method using reconstructed human epidermis LabCyte EPI‐MODEL24
Authors: Kojima Hajime , Katoh Masakazu , Shinoda Shinsuke , Hagiwara Saori , Suzuki Tamie , Izumi Runa , Yamaguchi Yoshihiro , Nakamura Maki , Kasahawa Toshihiko , Shibai Aya
Published: October 2013

Three validation studies were conducted by the Japanese Society for Alternatives to Animal Experiments in order to assess the performance of a skin irritation assay using reconstructed human epidermis (RhE) LabCyte EPI‐MODEL24 (LabCyte EPI‐MODEL24 SIT) developed by the Japan Tissue Engineering Co., Ltd. (J‐TEC), and the results of these studies were submitted to the Organisation for Economic Co‐operation and Development (OECD) for the creation of a Test Guideline (TG). In the summary review report from the OECD, the peer review panel indicated the need to resolve an issue regarding the misclassification of 1‐bromohexane. To this end, a rinsing operation intended to remove exposed chemicals was reviewed and the standard operating procedure (SOP) revised by J‐TEC. Thereafter, in order to confirm general versatility of the revised SOP, a new validation management team was organized by the Japanese Center for the Validation of Alternative Methods (JaCVAM) to undertake a catch‐up validation study that would compare the revised assay with similar in vitro skin irritation assays, per OECD TG No. 439 (2010). The catch‐up validation and supplementary studies for LabCyte EPI‐MODEL24 SIT using the revised SOPs were conducted at three laboratories. These results showed that the revised SOP of LabCyte EPI‐MODEL24 SIT conformed more accurately to the classifications for skin irritation under the United Nations Globally Harmonised System of Classification and Labelling of Chemicals (UN GHS), thereby highlighting the importance of an optimized rinsing operation for the removal of exposed chemicals in obtaining consistent results from in vitro skin irritation assays. Copyright © 2013 John Wiley & Sons, Ltd.
Fabrication and characterization of biomimetic multichanneled crosslinked‐urethane‐doped polyester tissue engineered nerve guides
Authors: Tran Richard T. , Choy Wai Man , Cao Hung , Qattan Ibrahim , Chiao Jung‐Chih , Ip Wing Yuk , Yeung Kelvin Wai Kwok , Yang Jian
Published: October 2013

Biomimetic scaffolds that replicate the native architecture and mechanical properties of target tissues have been recently shown to be a very promising strategy to guide cellular growth and facilitate tissue regeneration. In this study, porous, soft, and elastic crosslinked urethane‐doped polyester (CUPE) tissue engineered nerve guides were fabricated with multiple longitudinally oriented channels and an external non‐porous sheath to mimic the native endoneurial microtubular and epineurium structure, respectively. The fabrication technique described herein is highly adaptable and allows for fine control over the resulting nerve guide architecture in terms of channel number, channel diameter, porosity, and mechanical properties. Biomimetic multichanneled CUPE guides were fabricated with various channel numbers and displayed an ultimate peak stress of 1.38 ± 0.22 MPa with a corresponding elongation at break of 122.76 ± 42.17%, which were comparable to that of native nerve tissue. The CUPE nerve guides were also evaluated in vivo for the repair of a 1 cm rat sciatic nerve defect. Although histological evaluations revealed collapse of the inner structure from CUPE TENGs, the CUPE nerve guides displayed fiber populations and densities comparable with nerve autograft controls after 8 weeks of implantation. These studies are the first report of a CUPE‐based biomimetic multichanneled nerve guide and warrant future studies towards optimization of the channel geometry for use in neural tissue engineering. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 2793–2804, 2014.
Biological behavior of neurally differentiated periodontal ligament stem cells on different titanium implant surfaces
Authors: Xiaojie Li , Dapeng Liao , Ping Gong , Yan Dong , Gang Sun
Published: October 2013

We investigated the biological behavior of periodontal ligament stem cells (PDLSCs) induced to differentiate into Schwann cells (SCs) on the surfaces of titanium discs. Two types of titanium surfaces, sand blasted and acid etched (SA) and smooth polished, were prepared on titanium discs, and the behavior of SC‐like cells on these discs was investigated. Cell morphology was examined by scanning electron microscopy, and cell proliferation was assessed using assays for methylthiazol tetrazolium metabolism and total protein content. Real‐time polymerase chain reaction and Western blotting analyses were used to determine the gene and protein expression, respectively, of SC markers by PDLSCs. Differentiated PDLSCs could adhere, proliferate, differentiate, and express SC marker genes and proteins on the prepared titanium surfaces, and the highest levels of SC marker protein expression were observed in PDLSCs on SA titanium surfaces. SA titanium surfaces show good biocompatibility for the SC‐like cells, which is important for the application of these cells in peri‐implant nerve tissue engineering, through which they are expected to improve the osseoperception of dental implants. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 2805–2812, 2014.
Cross‐reactivity of cell‐selective CRRETAWAC peptide with human and porcine endothelial cells
Authors: Dudash Lynn A. , Kligman Faina L. , Bastijanic Jennifer M. , Kottke‐Marchant Kandice , Marchant Roger E.
Published: October 2013

We report on the cross‐reactivity of the cell adhesive peptide CRRETAWAC between human and porcine endothelial cells (ECs). CRRETAWAC is a phage display derived peptide which has been shown to bind the α5β1 receptor on human ECs, but does not bind platelets and thus could be incorporated into a coating for cardiovascular biomaterials that resists platelet adhesion and thrombosis, while allowing for endothelialization. To determine the cross‐reactivity of the peptide, attachment and growth of human and porcine ECs on CRRETAWAC fluorosurfactant polymer (FSP) coated surfaces was explored. CRRETAWAC FSP was synthesized and characterized by mass spectrometry, NMR, and IR spectroscopy. pEC attachment and growth on CRRETAWAC FSP was similar to the positive controls, human fibronectin and RGD FSP, achieving confluence in 72 h. Initial adhesion on CRRETAWAC FSP was also similar for porcine and human ECs. Blocking with soluble CRRETAWAC peptide reduced adhesion to CRRETAWAC coated surfaces by over 50%, indicating that the pECs specifically bind CRRETAWAC peptide. With this study, we have demonstrated that CRRETAWAC peptide coated surfaces are capable of binding porcine ECs in a specific manner and supporting a confluent layer of pECs. In vitro validation of the porcine model was critical for ensuring the best chance of success for the in vivo testing of CRRETAWAC coated ePTFE vascular grafts. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 2857–2863, 2014.
Dyeing and antibacterial activation with methylene blue of a cyclodextrin modified polyester vascular graft
Authors: Kacem I. , Laurent T. , Blanchemain N. , Neut C. , Chai F. , Haulon S. , Hildebrand H. F. , Martel B.
Published: October 2013

The aim of this study was to develop an antiseptic and blue dyed polyester (PET) vascular graft in order to reach two distinct properties: (i) the prevention of postoperative infections, (ii) the improvement of the graft compatibility with the coelioscopy surgical technique. This work consisted of dyeing a vascular prosthesis with methylene blue (MB) which is known as a cationic dye with antiseptic properties. Therefore, the functionalization of the PET fibers of the prosthesis with a cyclodextrin–citric acid polymer (PolyCD) was achieved in order to improve its sorption capacity. The NMR experiments demonstrated that a 1:2 complex occurred between hydroxypropyl β‐cyclodextrin (HP‐βCD) and MB. Kinetic and sorption isotherm studies showed that an impregnation of the polyCD modified prosthesis (PET‐CD) in a 1 g L−1 of MB solution for 150 min was sufficient to reach the saturation of the device. Results proved that the adsorption mechanism followed the Langmuir model and a maximum of 20 mg g−1 of MB on the graft. A sustained release of MB in batch tests was observed in PBS and in vitro microbiological assays displayed a prolongation of the bactericidal effect of PET‐CD whose extent varied with the amount of MB preliminarily adsorbed onto the PET‐CD. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 2942–2951, 2014.
Surface reconstruction and hemocompatibility improvement of a phosphorylcholine end‐capped poly(butylene succinate) coating
Authors: Hao Ni , Wang Yan‐Bing , Zhang Shi‐Ping , Shi Su‐Qing , Nakashima Kenichi , Gong Yong‐Kuan
Published: October 2013

Control over cell–material surface interactions is the key to many new and improved biomedical devices. In this study, we present a simple yet effective surface modification method that allows for the surface reconstruction and formation of cell outer membrane mimetic structure on coatings that have significantly increased hemocompatibility. To achieve this, a phosphorylcholine end‐capped poly(butylene succinate) (PBS‐PC) was synthesized and dip‐coated on coverslips. The surface structure of the amphiphilic PBS‐PC film was reconstructed by heating in a vacuum oven to obtain the less hydrophilic surface and by immersing in hot water to obtain the more hydrophilic surface. Significant changes in the surface element concentration were observed by X‐ray photoelectron spectroscopy analysis and changes in surface wettability were measured by sensitive dynamic contact angle technique. Scanning electron microscope images showed different morphologies of the reconstructed surfaces. Interestingly, the reconstruction between the less hydrophilic and more hydrophilic surfaces is reversible. More importantly, both the reconstructed surfaces are stable in room condition for more than 6 months, and both the surfaces show significant improvement in hemocompatibility as revealed by protein adsorption and platelet adhesion measurements. This reversible surface reconstruction strategy and the interesting results may be significant for fabricating stable and hemocompatible surfaces on differently shaped biomedical devices. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 2972–2981, 2014.
Immature muscular tissue differentiation into bone‐like tissue by bone morphogenetic proteins in vitro, with ossification potential in vivo
Authors: Hayashi Tatsuhide , Kobayashi Syuichiro , Asakura Masaki , Kawase Mayu , Ueno Atsuko , Uematsu Yasuaki , Kawai Tatsushi
Published: October 2013

The objective of this study was to induce bone formation from immature muscular tissue (IMT) in vitro, using bone morphogenetic proteins (BMPs) as a cytokine source and an expanded polytetrafluoroethylene (ePTFE) scaffold. In addition, cultured IMTs were implanted subcutaneously into Sprague‐Dawley (SD) rats to determine their in vivo ossification potential. BMPs, extracted from bovine cortical bones, were applied to embryonic SD rat IMT cultures, before 2 weeks culture on ePTFE scaffolds. Osteoblast‐like cells and osteoid tissues were partially identified by hematoxylin–eosin staining 2 weeks after culture. Collagen type I (Col‐I), osteopontin (OP), and osteocalcin (OC) were detected in the osteoid tissues by immunohistochemical staining. OC gene expression remained low, but OP and Col‐I were upregulated during the culture period. In vivo implanted IMTs showed slight radiopacity 1 week after implantation and strong radiopacity 2 and 3 weeks after implantation. One week after implantation, migration of numerous capillaries was observed and ossification was detected after 2 weeks by histological observation. These results suggest that IMTs are able to differentiate into bone‐like tissue in vitro, with an ossification potential after implantation in vivo. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 3112–3121, 2014.
Acceleration of bone formation during fracture healing by injectable collagen powder and human basic fibroblast growth factor containing a collagen‐binding domain from Clostridium histolyticum collagenase
Authors: Saito Wataru , Uchida Kentaro , Ueno Masaki , Matsushita Osamu , Inoue Gen , Nishi Nozomu , Ogura Takayuki , Hattori Shunji , Fujimaki Hisako , Tanaka Keisuke , Takaso Masashi
Published: October 2013

Growth factor delivered with implantable biomaterials has been used to both accelerate and ensure healing of open fractures in human patients. However, a major limitation of implantable biomaterials is the requirement for open surgical placement. Here, we developed an injectable collagen material‐based bone formation system consisting of injectable collagen powder with fibril morphology and collagen triple helix conformation, and basic fibroblast growth factor (bFGF) fused to the collagen‐binding domain (CBD) of Clostridium histolyticum collagenase. The affinity of the CBD towards collagen was confirmed by the results of collagen‐binding assays. Moreover, the combination of the collagen binding‐bFGF fusion protein (CB‐bFGF) with injectable collagen powder induced bone formation at protein concentrations lower than those required for bFGF alone in mice fracture models. Taken together, these properties suggest that the CB‐bFGF/collagen powder composite is a promising injectable material for bone repair in the clinical setting. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 3049–3055, 2014.
Enhanced osteoconductivity of titanium implant by polarization‐induced surface charges
Authors: Nozaki Kosuke , Wang Wei , Horiuchi Naohiro , Nakamura Miho , Takakuda Kazuo , Yamashita Kimihiro , Nagai Akiko
Published: October 2013

This study introduces the application of method for electrically polarizing titanium implants coated with anatase TiO2 using microarc oxidation. It also describes the features of the electrically polarized titanium implants, on which surface charges are generated by the dipole moment of the TiO2, and describes how the surface charges affect the implants' in vivo bone–implant integration capability. A comprehensive assessment using biomechanical, histomorphological, and radiographic analyses in a rabbit model was performed on polarized and nonpolarized implants. The electrically polarized surfaces accelerated the establishment of implant biomechanical fixation, compared with the nonpolarized surfaces. The percentage of the bone–implant contact ratio was higher using polarized implants than using nonpolarized implants. In contrast, the bone volume around the implants was not affected by polarization. Thus, using the polarized implant, this study identified that controlled surface charges have a significant effect on the properties of titanium implants. The application of the electrical polarization process and the polarization‐enhanced osteoinductivity, which resulted in greater bone–implant integration, was clearly demonstrated. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 3077–3086, 2014.
Self‐assembled apatite on multiwalled carbon nanotubes substrates support osteogenic cell function
Authors: Emohare Osa , Rushton Neil
Published: October 2013

The properties of multiwalled carbon nanotubes (MWCNT) make them attractive for use in biological matrices, especially in the development of bone‐like materials. However, their inherent hydrophobicity is a factor that has impeded broader use. A simple, novel method for coating MWCNT in apatite was developed and evaluated to enable their use in tissue engineering. This apatite coating was deposited on the nanotubes (which had been embedded in high‐density polyethylene) and facilitated the growth and differentiation of osteoblasts in a manner comparable to that of traditional tissue culture surfaces. Different levels of MWCNT purity (>90 and >95%) and chemical functionalization (carboxylation) were found to be amenable to deposition of an apatite coating and subsequent cell culture. The modalities evaluated were cell metabolic activity (MTS assay), cell proliferation (CyQuant assay), and cell differentiation (alkaline phosphatase assay); release of lactate dehydrogenase provided an indication of cytotoxicity. Although broadly comparable to traditional tissue culture surfaces, the carboxyl‐functionalized surfaces were associated with lower levels of growth and differentiation. The noncarboxylated surfaces proved to be broadly comparable to tissue culture plastic in terms of cell function. Therefore, apatite‐coated MWCNT provide a surface capable of supporting osteogenic cells. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 543–550, 2014.
Hydrothermal fabrication of ZSM‐5 zeolites: Biocompatibility, drug delivery property, and bactericidal property
Authors: Guo Ya‐Ping , Long Teng , Song Zhen‐Fu , Zhu Zhen‐An
Published: October 2013

The bone graft‐associated infection is widely considered in orthopedic surgery, which may lead to implant failure, extensive bone debridement, and increased patient morbidity. In this study, we fabricated ZSM‐5 zeolites for drug delivery systems by hydrothermal method. The structure, morphology, biocompatibility, drug delivery property, and bactericidal property of the ZSM‐5 zeolites were investigated. The ZSM‐5 zeolites have mordenite framework inverted‐type structure and exhibit the disk‐like shape with the diameter of ∼350 nm and thickness of ∼165 nm. The biocompatibility tests indicate that human bone marrow stromal cells spread out well on the surfaces of the ZSM‐5 zeolites and proliferate significantly with increasing culture time. As compared with the conventional hydroxyapatite particles, the ZSM‐5 zeolites possess greater drug loading efficiency and drug sustained release property because of the ordered micropores, large Brunauer‐Emmett‐Teller (BET) surface areas, and functional groups. For the gentamicin‐loaded ZSM‐5 zeolites, the sustained release of gentamicin minimizes significantly bacterial adhesion and prevents biofilm formation against Staphylococcus epidermidis. The excellent biocompatibility, drug delivery property, and bactericidal property of the ZSM‐5 zeolites suggest that they have great application potentials for treating implant‐associated infections. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 583–591, 2014.
CLCN7 and TCIRG1 Mutations Differentially Affect Bone Matrix Mineralization in Osteopetrotic Individuals
Authors: Barvencik Florian , Kurth Ingo , Koehne Till , Stauber Tobias , Zustin Jozef , Tsiakas Konstantinos , Ludwig Carmen F , Beil F Timo , Pestka Jan M , Hahn Michael , Santer Rene , Supanchart Chayarop , Kornak Uwe , Fattore Andrea Del , Jentsch Thomas J , Teti Anna , Schulz Ansgar , Schinke Thorsten , Amling Michael
Published: October 2013

Osteopetrosis is an inherited disorder of impaired bone resorption, with the most commonly affected genes being CLCN7 and TCIRG1, encoding the Cl−/H+ exchanger CLC-7 and the a3 subunit of the vacuolar H+-ATPase, respectively. We and others have previously shown that the disease is frequently accompanied by osteomalacia, and that this additional pathology is also found in Tcirg1-deficient oc/oc mice. The remaining question was whether osteoid enrichment is specifically associated with TCIRG1 inactivation, or whether CLCN7 mutations would also cause skeletal mineralization defects. Here we describe a complete osteologic assessment of one family carrying a novel mutation in CLCN7 (D145G), which impairs the activation and relaxation kinetics of the CLC-7 ion transporter. The two siblings carrying the mutation in the homozygous state displayed high bone mass, increased serum levels of bone formation markers, but no impairment of calcium homeostasis when compared to the other family members. Most importantly, however, undecalcified processing of an iliac crest biopsy from one of the affected children clearly demonstrated a pathological increase of trabecular bone mass, but no signs of osteomalacia. Given the potential relevance of these findings we additionally performed undecalcified histology of iliac crest biopsies from seven additional cases with osteopetrosis caused by a mutation in TNFRSF11A (n = 1), CLCN7 (n = 3), or TCIRG1 (n = 3). Here we observed that all cases with TCIRG1-dependent osteopetrosis displayed severe osteoid accumulation and decreased calcium content within the mineralized matrix. In contrast, there was no detectable bone mineralization defect in the cases with TNFRSF11A-dependent or CLCN7-dependent osteopetrosis. Taken together, our analysis demonstrates that CLCN7 and TCIRG1 mutations differentially affect bone matrix mineralization, and that there is a need to modify the current classification of osteopetrosis. © 2014 American Society for Bone and Mineral Research.
Risedronate Slows or Partly Reverses Cortical and Trabecular Microarchitectural Deterioration in Postmenopausal Women
Authors: Bala Yohann , Chapurlat Roland , Cheung Angela M , Felsenberg Dieter , LaRoche Michel , Morris Edward , Reeve Jonathan , Thomas Thierry , Zanchetta Jose , Bock Oliver , Ghasem-Zadeh Ali , Djoumessi Roger Martin Zebaze , Seeman Ego , Rizzoli René
Published: October 2013

During early menopause, steady-state bone remodeling is perturbed; the number of basic multicellular units (BMUs) excavating cavities upon the endosteal surface exceeds the number (generated before menopause) concurrently refilling. Later in menopause, steady-state is restored; the many BMUs generated in early menopause refill as similarly large numbers of BMUs concurrently excavate new cavities. We hypothesized that risedronate reduces the number of cavities excavated. However, in younger postmenopausal women, the fewer cavities excavated will still exceed the fewer BMUs now refilling, so net porosity increases, but less than in controls. In older postmenopausal women, the fewer cavities excavated during treatment will be less than the many (generated during early menopause) now refilling, so net porosity decreases and trabecular volumetric bone mineral density (vBMD) increases. We recruited 324 postmenopausal women in two similarly designed double-blind placebo-controlled studies that included 161 younger (Group 1, ≤ 55 years) and 163 older (Group 2, ≥ 55 years) women randomized 2:1 to risedronate 35 mg/week or placebo. High-resolution peripheral computed tomography was used to image the distal radius and tibia. Cortical porosity was quantified using the StrAx1.0 software. Risedronate reduced serum carboxyterminal cross-linking telopeptide of type 1 bone collagen (CTX-1) and serum amino-terminal propeptide of type 1 procollagen (P1NP) by ∼50%. In the younger group, distal radius compact-appearing cortex porosity increased by 4.2% ± 1.6% (p = 0.01) in controls. This was prevented by risedronate. Trabecular vBMD decreased by 3.6% ± 1.4% (p = 0.02) in controls and decreased by 1.6% ± 0.6% (p = 0.005) in the risedronate-treated group. In the older group, changes did not achieve significance apart from a reduction in compact-appearing cortex porosity in the risedronate-treated group (0.9% ± 0.4%, p = 0.047). No between-group differences reached significance. Results were comparable at the distal tibia. Between-group differences were significant for compact-appearing cortex porosity (p = 0.005). Risedronate slows microstructural deterioration in younger and partly reverses it in older postmenopausal women, features likely to contribute to antifracture efficacy. © 2014 American Society for Bone and Mineral Research.
Assessment of Bone Microarchitecture in Postmenopausal Women on Long-Term Bisphosphonate Therapy With Atypical Fractures of the Femur
Authors: Zanchetta Maria Belen , Diehl Maria , Buttazzoni Mirena , Galich Ana , Silveira Fernando , Bogado Cesar E , Zanchetta Jose Rubén
Published: October 2013

Reports of atypical femoral fractures (AFFs) in patients receiving long- term bisphosphonate therapy have raised concerns regarding the genesis of this rare event. Using high-resolution peripheral quantitative computed tomography (HR-pQCT), we conducted a study to evaluate bone microarchitecture in patients who had suffered an AFF during long-term bisphosphonate treatment. The aim of our study was to evaluate if bone microarchitecture assessment could help explain the pathophysiology of these fractures. We compared bone volumetric density and microarchitectural parameters measured by HR-pQCT in the radius and tibia in 20 patients with AFFs with 35 postmenopausal women who had also received long-term bisphosphonate treatment but had not experienced AFFs, and with 54 treatment-naive postmenopausal women. Control groups were similar in age, body mass index (BMI), and bone mineral density (BMD). Mean age of the 20 patients with AFFs was 71 years, mean lumbar spine T-score was −2.2, and mean femoral neck T-score was −2. Mean time on bisphosphonate treatment was 10.9 years (range, 5–20 years). None of the patients had other conditions associated with AFFs such as rheumatoid arthritis, diabetes or glucocorticoid use. There were no statistically significant differences in any of the parameters measured by HR-pQCT between postmenopausal women with or without treatment history and with or without history of atypical fractures. We could not find any distinctive microarchitecture features in the peripheral skeleton of women who had suffered an atypical fracture of the femur while receiving bisphosphonate treatment. This suggests that risk of developing an atypical fracture is not related to bone microarchitecture deterioration. Our results indicate that there may be other individual factors predisposing to atypical fractures in patients treated with bisphosphonates, and that those are independent of bone microarchitecture. In the future, identification of those factors could help prevent and understand the complex physiopathology of these rare events. © 2014 American Society for Bone and Mineral Research.
Plaque regression and progenitor cell mobilization with intensive lipid elimination regimen (PREMIER) trial design
Authors: Banerjee Subhash , Abu Fadel Mazen , Sarode Ravi , Terada Lance , Moritz Thomas , Luo Ping , Hastings Jeffrey , Brilakis Emmanouil S. , Reda Domenic
Published: October 2013

Progression of lipid rich necrotic core elements of atherosclerotic vulnerable plaque (VP) or its rupture leads to a majority of cardiovascular events. Endothelial progenitor cells (EPC) contribute to vascular healing and play a crucial role in repair following ischemic injury primarily by endothelialization of VP and neovascularization of ischemic myocardium. We present the rationale and design of the Plaque Regression and Progenitor Cell Mobilization with Intensive Lipid Elimination Regimen or the PREMIER Trial, which is designed to address the question for the very first time whether a highly intensive low‐density lipoprotein (LDL)‐lowering therapy with LDL‐apheresis could lead to a more rapid and detectable reduction in coronary atheroma volume, along with a robust mobilization of EPC compared to standard statin therapy, in patients selected for percutaneous coronary intervention for an acute coronary syndrome. J. Clin. Apheresis 29:97–106, 2014. © 2013 Wiley Periodicals, Inc.
Seasonal distribution of severe ADAMTS13 deficient idiopathic thrombotic thrombocytopenic purpura
Authors: Raval Jay S. , Harm Sarah K. , Rollins‐Raval Marian A. , Kiss Joseph E.
Published: October 2013

Background: Idiopathic thrombotic thrombocytopenic purpura (TTP) is a rare yet potentially fatal thrombotic microangiopathy. Severe deficiency of ADAMTS13 activity via autoantibody formation has been associated with idiopathic TTP; however, specific triggers are poorly defined. Previous studies have reported seasonal associations of TTP, with warm‐weather seasons appearing to have the strongest predilection. We characterized the seasonal distribution of severe ADAMTS13 deficient idiopathic TTP at our multi‐hospital institution. Methods: Apheresis records from 2005–2012 were queried for patients with a clinical diagnosis of TTP, accompanying pre‐plasmapheresis ADAMTS13 activity <10%, and no other explanations for thrombotic microangiopathy. Date of admission and ADAMTS13 activity were collected. Both initial episodes and relapses in patients whose initial episodes occurred since 2005 were included in the analysis. Goodness‐of‐fit chi‐square analysis was performed and statistical significance was defined as p<0.05. Results: Of 237 consecutive new patients with a suspected clinical diagnosis of TTP, 73 patients met inclusion criteria and had a total of 110 unique presentations for either initial TTP episodes or TTP relapses. Sixteen patients had 37 relapses of their idiopathic TTP (range 1–7). No statistically significant seasonal or monthly associations were identified with either initial or any TTP episodes. Conclusion: A seasonal association of severe ADAMTS13 deficient idiopathic TTP was not observed. Unknown variables may explain previous observations of seasonal associations of idiopathic TTP in other regions of the United States. Thus, individual institutions should characterize their own seasonal distributions of idiopathic TTP as part of the exploration of possible disease triggers in their respective areas. J. Clin. Apheresis 29:113–119, 2014. © 2013 Wiley Periodicals, Inc.