bluuebunny/crossref_metadata_2025 huggingface dataset:
SOCIAL WITHDRAWAL BEHAVIOR IN INSTITUTIONALIZED TODDLERS: INDIVIDUAL, EARLY FAMILY AND INSTITUTIONAL DETERMINANTS
Authors: Baptista Joana , Belsky Jay , Martins Carla , Silva Joana , Marques Sofia , Mesquita Ana , Soares Isabel
Published: October 2013

Eighty‐five Portuguese children, aged 12 to 30 months, placed in residential institutions were assessed to investigate the influence of variations in the institutionalization experience of social withdrawal behavior, after taking into account potentially confounding individual characteristics and pre‐admission experiences. In light of the limited attention in institutionalization research on social withdrawal, the determinants of the identified predictors of withdrawal symptoms also were examined. Current quality of care experienced in the institution, operationalized in terms of the absence (vs. presence) of a preferred attachment relationship, predicted social withdrawal, such that absence of such a relationship forecasted greater withdrawal. Moreover, existence of a preferred attachment relationship was itself predicted by better child socioemotional functioning, greater caregiver sensitive‐responsiveness, and better quality of individualized care provided by the staff.
ASSOCIATIONS BETWEEN MATERNAL INTERACTION BEHAVIOR, MATERNAL PERCEPTION OF INFANT TEMPERAMENT, AND INFANT SOCIAL WITHDRAWAL
Authors: Puura Kaija , Mäntymaa Mirjami , Leppänen Jukka , Peltola Mikko , Salmelin Raili , Luoma Ilona , Latva Reija , Tamminen Tuula
Published: October 2013

Infant social behavior develops in the context of early parent–infant interaction. Persisting withdrawal from social interaction is a sign of infant distress and is linked with the existence of risk factors. Impaired social behavior of the infant not only may be an indicator of pathology in the infant but the first sign of an effect of a psychosocial risk. In this study, we assessed 39 seven‐month‐old infants in videotaped interaction with their mothers and then compared the total score of the infant social behavior rated with the Alarm Distress Baby Scale (ADBB; A. Guedeney & A. Fermanian, ) with variables of mother–infant interaction rated with the Emotional Availability Scales, second edition (EAS 2; Z. Biringen, J. Robinson, & R.N. Emde, ). The ADBB total score had a strong negative correlation with maternal sensitivity in the EAS 2 (r = −0.75) and with the EAS 2 child variables of child involvement (r = 0.82) and child responsiveness (r = 0.85), indicating that the infants with more signs of social withdrawal had less sensitive mothers and were less involving and responsive in the interaction. Against our expectations, the ADBB total score had no correlation with maternal structuring. Our results give further support of the ability of the ADBB to screen for early signs of pathology in infant social behavior and problems in parent–infant interaction.
A comparison of reinforcement schedules to increase independent responding in individuals with intellectual disabilities
Authors: Hausman Nicole L. , Ingvarsson Einar T. , Kahng SungWoo
Published: October 2013

We compared the effects of varying reinforcement schedules on independent responding with 3 individuals with intellectual disabilities. Independent responding was always reinforced, and responding after a vocal response was either (a) always reinforced, (b) never reinforced, or (c) reinforced on a fixed‐ratio 3 schedule. Results showed that for 2 of the 3 participants, independent responding was higher when responding after the vocal prompt was never reinforced. These data suggest that altering the reinforcement schedule to favor independent responding may lead to increased independent responding.
Forecasting interest rates with shifting endpoints
Authors: van Dijk Dick , Koopman Siem Jan , van der Wel Michel , Wright Jonathan H.
Published: October 2013

We consider forecasting the term structure of interest rates with the assumption that factors driving the yield curve are stationary around a slowly time‐varying mean or ‘shifting endpoint’. The shifting endpoints are captured using either (i) time series methods (exponential smoothing) or (ii) long‐range survey forecasts of either interest rates or inflation and output growth, or (iii) exponentially smoothed realizations of these macro variables. Allowing for shifting endpoints in yield curve factors provides substantial and significant gains in out‐of‐sample predictive accuracy, relative to stationary and random walk benchmarks. Forecast improvements are largest for long‐maturity interest rates and for long‐horizon forecasts. Copyright © 2013 John Wiley & Sons, Ltd.
A sensitivity theory for the equilibrium boundary layer over land
Authors: Cronin Timothy W.
Published: October 2013

Key Points

We develop an analytic sensitivity theory for an idealized boundary layer model

The theory estimates how much the land surface warms due to drying

Our theory agrees well with simulation results from a more complex model
Long‐term maintenance of HepaRG cells in serum‐free conditions and application in a repeated dose study
Authors: Klein Sebastian , Mueller Daniel , Schevchenko Valery , Noor Fozia
Published: October 2013

Chronic repeated‐dose toxicity studies are still carried out on animals and often do not correlate with the effects in human beings mainly due to species‐specific differences in biotransformation. The human hepatoma cell line HepaRG has been used for human relevant toxicity assessment. However, HepaRG cells are commonly maintained in serum containing medium which limits their use in ’omics‘‐based toxicology. In this study, we compared the maintenance of HepaRG cells in standard serum‐supplemented and serum‐free conditions. Viability and Cytochrome P450 (CYP) activity during long‐term cultivation were assessed. Liver‐specific albumin and urea production was measured. The extracellular metabolome (amino acids, glucose, lactate and pyruvate) was measured to compare different cultivation conditions using metabolic flux analysis. Although metabolic flux analysis reveals differences in certain parts of the metabolism, e.g. production of urea, the overall metabolism of serum‐free and serum‐supplemented cultured HepaRG cells is similar. We conclude that HepaRG cells can be maintained in optimized serum‐free conditions for 30 days without viability change and with high CYP activity. We also tested the acute (24 h) and long‐term repeated‐dose (7 doses, every second day) toxicity of valproic acid. We calculated an EC50 value of 1.4 mM after repeated exposure which is close to the cmax value for valproic acid. Maintenance of HepaRG cells in serum‐free conditions opens up the opportunity for the use of these cells in human long‐term repeated‐dose hepatotoxicity studies and for application in systems toxicology. Copyright © 2013 John Wiley & Sons, Ltd.
Chrysin inhibits metastatic potential of human triple‐negative breast cancer cells by modulating matrix metalloproteinase‐10, epithelial to mesenchymal transition, and PI3K/Akt signaling pathway
Authors: Yang Bing , Huang Jing , Xiang Tingxiu , Yin Xuedong , Luo Xinrong , Huang Jianbo , Luo Fuling , Li Hongyuan , Li Hongzhong , Ren Guosheng
Published: October 2013

Chrysin, a naturally occurring flavone, has been shown to inhibit cell proliferation and induce cell apoptosis in various cancers. However, the effect and mechanisms of chrysin on cancer metastasis are still enigmatic. In this study, metastatic triple‐negative breast cancer (TNBC) cell lines were used to evaluate the antimetastatic activity of chrysin. The results showed that chrysin (5, 10 and 20 μM) significantly suppressed TNBC cell migration and invasion in a dose‐dependent manner. Human matrix metalloproteinase (MMP) antibody array demonstrated that MMP‐10 was downregulated by chrysin, which was further verified by Western blotting and ELISA. Moreover, it was shown that chrysin induced increased E‐cadherin expression and decreased expression of vimentin, snail and slug in TNBC cells, suggesting that chrysin had a reversal effect on epithelial–mesenchymal transition. More importantly, it was demonstrated that inhibiting the Akt signal pathway might play a central role in chrysin‐induced antimetastatic activity by regulating MMP‐10 and epithelial–mesenchymal transition. In conclusion, our study indicates that chrysin exerts antimetastatic activities in TNBC cells, which suggests that chrysin might be a potential therapeutic candidate for the treatment of advanced or metastatic breast cancer. Copyright © 2013 John Wiley & Sons, Ltd.
2‐photon excitation fluorescence microscopy enables deeper high‐resolution imaging of voltage and Ca2+ in intact mice, rat, and rabbit hearts
Authors: Ghouri Iffath A. , Kelly Allen , Burton Francis L. , Smith Godfrey L. , Kemi Ole Johan
Published: October 2013

We describe a novel two‐photon (2P) laser scanning microscopy (2PLSM) protocol that provides ratiometric transmural measurements of membrane voltage (Vm) via Di‐4‐ANEPPS in intact mouse, rat and rabbit hearts with subcellular resolution. The same cells were then imaged with Fura‐2/AM for intracellular Ca2+ recordings. Action potentials (APs) were accurately characterized by 2PLSM vs. microelectrodes, albeit fast events (<1 ms) were sub‐optimally acquired by 2PLSM due to limited sampling frequencies (2.6 kHz). The slower Ca2+ transient (CaT) time course (>1ms) could be accurately described by 2PLSM. In conclusion, Vm ‐ and Ca2+‐sensitive dyes can be 2P excited within the cardiac muscle wall to provide AP and Ca2+ signals to ∼400 µm. (© 2013 WILEY‐VCH Verlag GmbH &Co. KGaA, Weinheim)
Preparation and in vitro characterization of biomorphic silk fibroin scaffolds for bone tissue engineering
Authors: Qian Junmin , Suo Aili , Jin Xinxia , Xu Weijun , Xu Minghui
Published: October 2013

In bone tissue engineering, a qualified scaffold should provide a three‐dimensional porous structure mimicking the extracellular matrix of bone except good biological properties. In this study, biomorphic silk fibroin (SF) scaffolds were fabricated from cane by an innovative biotemplating‐negative mold process. The physicochemical properties, in vitro enzymatic degradation behavior and biocompatibility of the biomorphic SF scaffolds were investigated. The results showed that the scaffolds well inherited the original porous morphology of cane, and possessed good mechanical stability. The scaffolds had a compressive modulus of 1.56 ± 0.08 MPa and a porosity of 82.73%, and exhibited a bimodal pore size distribution (15 and 172 μm). The degradation ratio of the SF scaffolds increased with prolonging degradation time and reached 29% within 21 days when exposed to 1.0 U/mL collagenase IA. The in vitro cytocompatibility evaluation indicated that the scaffolds could support cell attachment, proliferation, and osteogenic differentiation of osteoblast‐like MC3T3‐E1 cells, as assessed by SEM, fluorescent staining, MTT, and ALP activity assays. The results indicated the potential of biomorphic SF scaffolds for bone tissue engineering. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 2961–2971, 2014.
Effect of geometry and microstructure of honeycomb TCP scaffolds on bone regeneration
Authors: Takabatake Kiyofumi , Yamachika Eiki , Tsujigiwa Hidetsugu , Takeda Yasushi , Kimura Mariko , Takagi Shin , Nagatsuka Hitoshi , Iida Seiji
Published: October 2013

In recent years, artificial biological materials have been commonly used for the treatment of bone tissue defects caused by trauma, tumors, or surgical stress. Although tricalcium phosphate (TCP) is a promising absorbent bone tissue reconstruction biomaterial, it has been reported that its biocompatibility and osteoconductivity depend on its preparation method and sintering temperature. In addition, although it is thought that the microenvironment produced by the extracellular matrix plays an important role in cell growth and differentiation, there have been few studies on how the geometric structure of artificial biological materials affects cells. In the present study, a new honeycomb TCP scaffold containing through‐holes with diameters of 300 µm has been developed. The influence of the sintering temperature on the crystal structure and material properties of the honeycomb TCP scaffold was investigated using scanning electron microscopy and X‐ray diffraction. Its biocompatibility and osteoconductivity were also evaluated by implantation into experimental animals. It was found that a β‐TCP scaffold sintered at 1200°C exhibited high biocompatibility and osteoconductivity, and when it was loaded with BMP‐2, it exhibited both osteoconductivity and osteoinductivity, promoting rapid bone formation in both ectopic and orthotopic areas. It is thus a highly promising bone reconstruction material that is expected to find clinical applications. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 2952–2960, 2014.
Two‐stage implantation of the skin‐ and bone‐integrated pylon seeded with autologous fibroblasts induced into osteoblast differentiation for direct skeletal attachment of limb prostheses
Authors: Shevtsov Maxim A. , Galibin Oleg V. , Yudintceva Nataliya M. , Blinova Miralda I. , Pinaev George P. , Ivanova Anna A. , Savchenko Olga N. , Suslov Dmitriy N. , Potokin Igor L. , Pitkin Emil , Raykhtsaum Grigory , Pitkin Mark R.
Published: October 2013

Angio‐ and osteogenesis following the two‐stage (TS) implantation of the skin‐ and bone‐integrated pylon seeded with autologous fibroblasts was evaluated. Two consecutive animal substudies were undertaken: intramedullary subcutaneous implantation (15 rabbits) and a TS transcutaneous implantation (12 rabbits). We observed enhanced osseointegrative properties of the intramedullary porous component seeded with fibroblasts induced into osteoblast differentiation, as compared to the untreated porous titanium pylon. The three‐phase scintigraphy and subsequent histological analysis showed that the level of osteogenesis was 1.5‐fold higher than in the control group, and significantly so (p < 0.05). The biocompatibility was further proved by the absence of inflammatory response or encapsulation and sequestration on the histology assay. Treatment of the transcutaneous component with autologous fibroblasts was associated with nearly a 2‐fold decrease in the period required for the ingrowth of dermal and subdermal soft tissues into the implant surface, as compared to the untreated porous titanium component. Direct dermal attachment to the transcutaneous implant prevented superficial and deep periprosthetic infections in rabbits in vivo. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 3033–3048, 2014.
Effect of UV‐irradiation intensity on graft polymerization of 2‐methacryloyloxyethyl phosphorylcholine on orthopedic bearing substrate
Authors: Kyomoto Masayuki , Moro Toru , Yamane Shihori , Hashimoto Masami , Takatori Yoshio , Ishihara Kazuhiko
Published: October 2013

Photoinduced grafting of 2‐methacryloyloxyethyl phosphorylcholine (MPC) onto cross‐linked polyethylene (CLPE) was investigated for its ability to reduce the wear of orthopedic bearings. We investigated the effect of UV‐irradiation intensity on the extent of poly(MPC) (PMPC) grafting, and found that it increased with increasing intensity up to 7.5 mW/cm2, and the remained fairly constant. It was found to be extremely important to carefully control the UV intensity, as at higher values, a PMPC gel formed via homopolymerization of the MPC, resulting in the formation of cracks at the interface of the PMPC layer and the CLPE substrate. When the CLPE was exposed to UV‐irradiation during the graft polymerization process, some of its physical and mechanical properties were slightly changed due to cross‐linking and scission effects in the surface region; however, the results of all of the tests exceed the lower limits of the ASTM standards. Modification of the CLPE surface with the hydrophilic PMPC layer increased lubrication to levels that match articular cartilage. The highly hydrated thin PMPC films mimicked the native cartilage extracellular matrix that covers synovial joint surface, acting as an extremely efficient lubricant, and providing high‐wear resistance. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 3012–3023, 2014.
A self‐healing biomaterial based on free‐radical polymerization
Authors: Dailey Mary M. Caruso , Silvia Alexander W. , McIntire Patrick J. , Wilson Gerald O. , Moore Jeffrey S. , White Scott R.
Published: October 2013

Self‐healing chemistry used for damage repair have not previously been demonstrated for free‐radical polymerization pathways. However, this chemistry is important for addition polymers such as poly(methyl methacrylate) used in bone cement and epoxy vinyl ester used in dental resins. Self‐healing biomaterials offer the potential for safer and longer lasting implants and restoratives by slowing or arresting crack damage. In the free‐radical self‐healing system reported here, the three components required for polymerization (free‐radical peroxide initiator, tertiary amine activator, and vinyl acrylate monomers) are compartmentalized into two separate microcapsules—one containing the peroxide initiator, and the other containing both monomer and activator. Crack damage ruptures the capsules so that the three components mix and react to form a new polymer that effectively rebonds the crack and restores approximately 75% of the original fracture toughness. Optimal healing is obtained by a systematic evaluation of the effect of monomer, initiator, and activator concentration on healing performance. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 3024–3032, 2014.
Hyaluronic acid‐based nanocomposite hydrogels for ocular drug delivery applications
Authors: Widjaja Leonardus Kresna , Bora Meghali , Chan Paul Ng Poh Huat , Lipik Vitali , Wong Tina T. L. , Venkatraman Subbu S.
Published: October 2013

Hyaluronic acid (HA) is a widely investigated biomaterial for many therapeutic applications owing to its unique properties of biocompatibility, biodegradation, and viscoelasticity. HA being a natural component of eye tissue with significant role in wound healing is a natural choice as a carrier for ocular drug delivery, provided the incorporated drugs are released in a sustained manner. However, localized sustained release of drugs inside eye has been difficult to achieve because of the inability to retain carriers for long periods in the eye. Using noncrosslinked (soluble) HA offers limited control over site retention of drugs. In order to obtain prolonged sustained delivery, two HA‐based composite hydrogels incorporating nanocarriers, have been synthesized and characterized for swelling, rheology, degradation, and in vitro release of latanoprost, a drug used to reduce intraocular pressure. The HA is first chemically modified, mixed with drug‐loaded liposomes, and then crosslinked to obtain nanocomposite hydrogels. In vitro release study shows longer sustained release of latanoprost from composite hydrogels as compared to liposomes or hydrogels alone indicating additional resistance to drug diffusion because of the incorporation of liposomes inside the hydrogels. It is believed that these nanocomposite hydrogels, with controlled degradation properties and sustained release, could serve as potential drug delivery systems for many ocular diseases. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 3056–3065, 2014.
Drying and storage effects on poly(ethylene glycol) hydrogel mechanical properties and bioactivity
Authors: Luong P. T. , Browning M. B. , Bixler R. S. , Cosgriff‐Hernandez E.
Published: October 2013

Hydrogels based on poly(ethylene glycol) (PEG) are increasingly used in biomedical applications because of their ability to control cell‐material interactions by tuning hydrogel physical and biological properties. Evaluation of stability after drying and storage are critical in creating an off‐the‐shelf biomaterial that functions in vivo according to original specifications. However, there has not been a study that systematically investigates the effects of different drying conditions on hydrogel compositional variables. In the first part of this study, PEG‐diacrylate hydrogels underwent common processing procedures (vacuum‐drying, lyophilizing, hydrating then vacuum‐drying), and the effect of this processing on the mechanical properties and swelling ratios was measured. Significant changes in compressive modulus, tensile modulus, and swelling ratio only occurred for select processed hydrogels. No consistent trends were observed after processing for any of the formulations tested. The effect of storage conditions on cell adhesion and spreading on collagen‐ and streptococcal collagen‐like protein (Scl2‐2)‐PEG‐diacrylamide hydrogels was then evaluated to characterize bioactivity retention after storage. Dry storage conditions preserved bioactivity after 6 weeks of storage; whereas, storage in PBS significantly reduced bioactivity. This loss of bioactivity was attributed to ester hydrolysis of the protein linker, acrylate‐PEG‐N‐hydroxysuccinimide. These studies demonstrate that these processing methods and dry storage conditions may be used to prepare bioactive PEG hydrogel scaffolds with recoverable functionality after storage. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 3066–3076, 2014.
Synthesis of SiO2 and CaO rich calcium silicate systems via sol‐gel process: Bioactivity, biocompatibility, and drug delivery tests
Authors: Catauro M. , Papale F. , Roviello G. , Ferone C. , Bollino F. , Trifuoggi M. , Aurilio C.
Published: October 2013

Silica and calcium silicate amorphous materials, mixed with sodium ampicillin, a broad‐spectrum antibiotic, have been synthesized by sol‐gel method. The amorphous nature of the gels was ascertained by X‐ray diffraction analysis. The bioactivity of the synthesized materials has been put into evidence by the appearance of a crystal of hydroxyapatite on the surface of the samples soaked in a fluid simulating the composition of the human blood plasma, as detected through FTIR measurements and SEM micrographs. The present work refers to a series of in‐vitro biocompatibility tests, which has been performed on silicate and CaO rich calcium silicate gel‐glasses, to study the cell behavior when seeded on 1 cm2 material fragments, introduced into an in‐vitro culture system. 3T3 cell lines have been used and the viability has been evaluated by WST‐8 test. The composition of the adopted glasses can be expressed by the following general formula: x CaO• (1 − x) SiO2 with x = 0.00; 0.30; 0.40; 0.50; 0.60. Subsequently, release kinetics in a simulate body fluid (SBF) has been investigated. The amount of sodium ampicillin released has been detected by UV‐Vis spectroscopy. The release kinetics has appeared to occur in more than one stage. All data have shown that those materials could be used as drug delivery bioactive systems. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 3087–3092, 2014.
Evaluation of a bioactive bone‐inducing material consisting of collagen scaffolds and collagen‐binding bone morphogenetic protein 2
Authors: Han Qianqian , Zhang Beibei , Chen Bing , Dai Jianwu , Xu Jianxia , Wang Chunren , Wang Zhaoxu
Published: October 2013

Bioactive bone‐inducing material (BBIM) is a collagen‐based scaffold composed of demineralized bone matrix and collagen‐binding domain bone morphogenetic protein 2 (BMP‐2). BBIM is regarded as a promising bone‐inducing scaffold to repair bone defects. In this work, we evaluated the biocompatibility and osteogenecity of BBIM. Using enzyme‐linked immunosorbent assay, the level of BMP‐2 on BBIM was detected and considered adequate. Kunming mice were used as the animal model to investigate the acute systemic toxicity, long‐term bone regeneration, ectopic bone formation, and chronic systemic toxicity. Results show that BBIM induced no serious inflammatory reaction or acute and chronic systemic toxicity. Our analyses also demonstrated significant homogeneous ectopic bone formation as well as significantly high numbers of erythrocytes in the BBIM groups in the chronic systemic toxicity study, a phenomenon which may provide indirect proof of the bone regeneration capacity of BBIM, which may be considered as a bioactivity indicator in future studies. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 3093–3101, 2014.
Mutant monocyte chemoattractant protein 1 protein attenuates migration of and inflammatory cytokine release by macrophages exposed to orthopedic implant wear particles
Authors: Yao Zhenyu , Keeney Michael , Lin Tzu‐Hua , Pajarinen Jukka , Barcay Katherine , Waters Heather , Egashira Kensuke , Yang Fan , Goodman Stuart
Published: October 2013

Wear particles generated from total joint replacements can stimulate macrophages to release chemokines, such as monocyte chemoattractant protein 1 (MCP‐1), which is the most important chemokine regulating systemic and local cell trafficking and infiltration of monocyte/macrophages in chronic inflammation. One possible strategy to curtail the adverse events associated with wear particles is to mitigate migration and activation of monocyte/macrophages. The purpose of this study is to modulate the adverse effects of particulate biomaterials and inflammatory stimuli such as endotoxin by interfering with the biological effects of the chemokine MCP‐1. In the current study, the function of MCP‐1 was inhibited by the mutant MCP‐1 protein called 7ND, which blocks its receptor, the C–C chemokine receptor type 2 (CCR2) on macrophages. Addition of 7ND decreased MCP‐1‐induced migration of THP‐1 cells in cell migration experiments in a dose‐dependent manner. Conditioned media from murine macrophages exposed to clinically relevant polymethylmethacrylate (PMMA) particles with/without endotoxin [lipopolysaccharide (LPS)] had a chemotactic effect on human macrophages, which was decreased dramatically by 7ND. 7ND demonstrated no adverse effects on the viability of macrophages, and the capability of mesenchymal stem cells (MSCs) to form bone at the doses tested. Finally, proinflammatory cytokine production was mitigated when macrophages were exposed to PMMA particles with/without LPS in the presence of 7ND. Our studies confirm that the MCP‐1 mutant protein 7ND can decrease macrophage migration and inflammatory cytokine release without adverse effects at the doses tested. Local delivery of 7ND at the implant site may provide a therapeutic strategy to diminish particle‐associated periprosthetic inflammation and osteolysis. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 3291–3297, 2014.
The effect of oxidation on the mechanical response and microstructure of porcine aortas
Authors: Stephen Elizabeth A. , Venkatasubramaniam Arundhathi , Good Theresa A. , Timmie Topoleski L. D.
Published: October 2013

Reactive oxygen species (ROS), a product of many cellular functions, has been implicated in many age‐related pathophysiological processes, including cardiovascular disease. The arterial proteins collagen and elastin may also undergo structural and functional changes due to damage caused by ROS. This study examined the effect of oxidation on the mechanical response of porcine aortas and aorta elastin and the associated changes in structural protein ultrastructure as a step in exploring the role of molecular changes in structural proteins with aging on elastic artery function. We examined the change in mechanical properties of aorta samples after various oxidation times as a first step in understanding how the oxidative environment associated with aging could impact mechanical properties of arterial structural proteins. We used confocal microscopy to visualize how the microstructure of isolated elastin changed with oxidation. We find that short term oxidation of elastin isolated from aortas leads to an increase in material stiffness, but also an increase in the fiber diameter, increase in void space in the matrix, and a decrease in the fiber orientation, possibly due to fiber cross‐linking. The short term effects of oxidation on arterial collagen is more complex, with increase in material stiffness seen in the collagen region of the stress stretch curve at low extents of oxidation, but not at high levels of oxidation. These results may provide insight into the relationship between oxidative damage to tissue associated with aging and disease, structure of the arterial proteins elastin and collagen, and arterial mechanical properties and function. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 3255–3262, 2014
Microstructural design of functionally graded coatings composed of suspension plasma sprayed hydroxyapatite and bioactive glass
Authors: Cattini Andrea , Bellucci Devis , Sola Antonella , Pawłowski Lech , Cannillo Valeria
Published: October 2013

Various bioactive glass/hydroxyapatite (HA) functional coatings were designed by the suspension plasma spraying (SPS) technique. Their microstructure, scratch resistance, and apatite‐forming ability in a simulated body fluid (SBF) were compared. The functional coatings design included: (i) composite coating, that is, randomly distributed constituent phases; (ii) duplex coating with glass top layer onto HA layer; and (iii) graded coating with a gradual changing composition starting from pure HA at the interface with the metal substrate up to pure glass on the surface. The SPS was a suitable coating technique to produce all the coating designs. The SBF tests revealed that the presence of a pure glass layer on the working surface significantly improved the reactivity of the duplex and graded coatings, but the duplex coating suffered a relatively low scratch resistance because of residual stresses. The graded coating therefore provided the best compromise between mechanical reliability and apatite‐forming ability in SBF. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 551–560, 2014.
The influence of polymeric component of bioactive glass‐based nanocomposite paste on its rheological behaviors and in vitro responses: Hyaluronic acid versus sodium alginate
Authors: Sohrabi Mehri , Hesaraki Saeed , Kazemzadeh Asghar
Published: October 2013

Different biocomposite pastes were prepared from a solid phase that was nanoparticles of sol‐gel‐derived bioactive glass and different liquid phases including 3% hyaluronic acid solution, sodium alginate solutions (3% and 10 %) or mixtures of hyaluronic acid and sodium alginate (3% or 10 %) solutions in 50:50 volume ratio. Rheological properties of the pastes were measured in both rotatory and oscillatory modes. The washout behavior and in vitro apatite formation of the pastes were determined by soaking them in simulated body fluid under dynamic situation for 14 days. The proliferation and alkaline phosphatase activity of MG‐63 osteoblastic cells were also determined using extracts of the pastes. All pastes could be easily injected from the standard syringes with different tip diameters. All pastes exhibited visco‐elastic character, but a nonthixotropic paste was obtained using hyaluronic acid in which the loss modulus was higher than the storage modulus. The thixotropy and storage modulus were increasingly improved by adding/using sodium alginate as mixing liquid. Moreover, the pastes in which the liquid phase was sodium alginate or mixture of hyaluronic acid and 10% sodium alginate solution revealed better apatite formation ability and washout resistance than that made of hyaluronic acid alone. No cytotoxicity effects were observed by extracts of the pastes on osteoblasts but better alkaline phosphatase activity was found for the pastes containing hyaluronic acid. Overall, injectable biocomposites can be produced by mixing bioactive glass nanoparticles and sodium alginate/hyaluronic acid polymers. They are potentially useful for hard and even soft tissues treatments. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 561–573, 2014.
Cytotoxicity of PVPAC‐treated bovine pericardium: A potential replacement for glutaraldehyde in biological heart valves
Authors: Galvão Barros Janaina Aline , Filippin‐Monteiro Fabiola Branco , de Oliveira Edson Mendes , Campa Ana , Catalani Luiz Henrique , de Nogueira Moraes Pitombo Ronaldo , Polakiewicz Bronislaw
Published: October 2013

Acellular biological tissues, including bovine pericardium (BP), have been proposed as biomaterial for tissue engineering. BP is usually modified chemically to improve mechanical and biological properties using glutaraldehyde, the standard reagent for preservation of fresh bioprosthetic materials. Glutaraldehyde‐fixed BP (Glut‐BP), the most widely used material in heart valve manufacture, has been associated with calcificationin vivo. In an attempt to reduce this issue and maintain its biocompatibility, this study assesses the physical properties and cytotoxicity of lyophilized BP treated with poly (vinylpyrrolidone‐co‐acrolein) (PVPAC‐BP), a novel copolymer, as a substitute for glutaraldehyde. For that, PVPAC‐BP surface ultrastructure, elastic function, water uptake and tissue calcification were evaluated. For the analysis of biocompatibility, fibroblasts (3T3‐L1) and endothelial cells (HUVEC) were cultured on PVPAC‐BP, Untreated‐BP and Glut‐BP. Nitric oxide (NO) release assay, fluorescence and SEM images of endothelial cells adhered on scaffolds were also performed. As results, the data show some advantages of PVPAC‐BP over the Glut‐BP. The PVPAC‐BP maintains partially the original ultrastructure and elastic properties, improves scaffold hydration, and presents less calcium phosphate deposits. The cells demonstrated strong attachment, high proliferation rate, and formation of a monolayer on PVPAC‐BP. Attached cells were also able to release NO de‐monstrating regular metabolism. In conclusion, PVPAC may be considered as a promising alternative to BP treatment improving the efficiency of cell attachment and proliferation and also avoid immunogenicity. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 574–582, 2014.
Hyaluronic acid colloidal gels as self‐assembling elastic biomaterials
Authors: Fakhari Amir , Phan Quang , Berkland Cory
Published: October 2013

Hyaluronic acid (HA) is a naturally occurring biodegradable polymer with a variety of applications in medicine. The use of HA as a filler or scaffold for regenerating tissues often requires improving the elastic properties of HA. This is conventionally accomplished via chemical crosslinking, which might require the generation of toxic free radicals. Although the mechanical properties of the resulting gel material can be tuned, these types of materials are static and susceptible to mechanical failure. The aim of this study was to develop a colloidal system for scaffold fabrication that is held together by physical interactions between HA nanoparticles. HA nanoparticles composed of 17 kDa HA suspended in water at different concentrations (15%, 30%, and 45% w/v, respectively) formed a stable three‐dimensional (3D) colloidal gel as a result of physical entanglement of free polymer chains on the surfaces of nanoparticles. The swelling ratio, shear moduli (G), compressive failure properties, and viscosity of colloidal gels were concentration dependent. The colloidal gels also were found to exhibit dynamic and recoverable properties, thus suggesting that these “self‐associating colloids” offer characteristics distinct arising from crosslinked polymers or high concentration colloids. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 612–618, 2014.
Is keratinized mucosa indispensable to maintain peri‐implant health? A systematic review of the literature
Authors: Brito Carlos , Tenenbaum Howard C. , Wong Benjamin K. C. , Schmitt Christian , Nogueira‐Filho Getulio
Published: October 2013

The significance of keratinized mucosa (KM) around dental implants is still not well explained and has been controversial. The aim of this systematic review was to evaluate the importance of KM around dental implants. The electronic databases Cochrane library, MEDLINE, EMBASE, and Virtual Health Library (VHL) databases were utilized to search original articles from 2006 to March 2013. The inclusion and exclusion criteria used to select the articles were: (1) Human studies published in the English language; (2) Study published in international peer‐viewed journals; (3) Studies evaluated the association between KM width and the peri‐implant tissue health; (4) Studies that have follow up of greater than 12 months; (5) Publication of studies not older than 10 years. The searches retrieved 285 citations. Seven articles fulfilled all of the inclusion criteria. Out of these, three studies were ranked as presenting high methodological quality, and four were judged to be of moderate quality. This systematic review concludes that the presence of an adequate zone of keratinized tissue may be necessary because it was shown to be related to better peri‐implant tissue health. Further randomized controlled trials are necessary to support this statement. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 643–650, 2014.
Vitamin D Supplementation After Parathyroidectomy: Effect on Bone Mineral Density—A Randomized Double-Blind Study
Authors: Norenstedt Sophie , Pernow Ylva , Zedenius Jan , Nordenström Jörgen , Sääf Maria , Granath Fredrik , Nilsson Inga-Lena
Published: October 2013

Patients with primary hyperparathyroidism (PHPT) have higher bone turnover, lower bone mineral density (BMD), and an increased risk of fractures. They also have a high incidence of low vitamin D levels (25-OH-vitamin D <50 nmol/L) that could worsen the negative effect on the bone. In this double-blinded clinical trial, 150 patients with PHPT were randomized, after successful parathyroidectomy (PTX), to 1-year daily treatment with either cholecalciferol 1600 IU and calcium carbonate 1000 mg (D +font-family:monospace or calcium carbonate alone (D–). BMD was measured in the lumbar spine, femoral neck, total hip, distal and 33% radius using dual-energy X-ray absorptiometry (DXA) before surgery and after 1 year of study medication. Median age was 60 (range 30–80) years and there were 119 (79%) women and 31 (21%) men; 76% had 25-OH-D <50 nmol/L before PTX and 50% had persistent elevated parathyroid hormone (PTH) 6 weeks after PTX. A similar increase in BMD in the lumbar spine, femoral neck, and total hip was observed in both groups (D + : 3.6%, 3.2%, and 2.7%, p < 0.001, respectively; and D–: 3.0%, 2.3%, and 2.1%, respectively, p < 0.001). Patients with vitamin D supplementation also increased their BMD in distal radius (median 2.0%; interquartile range, −1.7% to 5.4%; p = 0.013). The changes in BMD, especially in the hips, were correlated to the baseline concentrations of PTH, ionized calcium, and bone markers (p < 0.001). A benefit from vitamin D substitution was observed among patients with a persistent postoperative PTH elevation, who also improved their BMD at 33% radius and radius ultradistal (p < 0.05). In conclusion, except for a minor improvement of radius BMD, our data show no beneficial effect on BMD or bone turnover markers of vitamin D supplementation after PTX. Preoperative PTH seems to have the strongest association with improvement in BMD. © 2014 American Society for Bone and Mineral Research.
In Vivo Assessment of Bone Quality in Postmenopausal Women With Type 2 Diabetes
Authors: Farr Joshua N , Drake Matthew T , Amin Shreyasee , Melton L Joseph , McCready Louise K , Khosla Sundeep
Published: October 2013

Although patients with type 2 diabetes (T2D) are at significant risk for well-recognized diabetic complications, including macrovascular disease, retinopathy, nephropathy, and neuropathy, it is also clear that T2D patients are at increased risk for fragility fractures. Furthermore, fragility fractures in patients with T2D occur at higher bone mineral density (BMD) values compared to nondiabetic controls, suggesting abnormalities in bone material strength (BMS) and/or bone microarchitecture (bone “quality”). Thus, we performed in vivo microindentation testing of the tibia to directly measure BMS in 60 postmenopausal women (age range, 50–80 years) including 30 patients diagnosed with T2D for >10 years and 30 age-matched, nondiabetic controls. Regional BMD was measured by dual-energy X-ray absorptiometry (DXA); cortical and trabecular bone microarchitecture was assessed from high-resolution peripheral quantitative computed tomography (HRpQCT) images of the distal radius and tibia. Compared to controls, T2D patients had significantly lower BMS: unadjusted (−11.7%; p < 0.001); following adjustment for body mass index (BMI) (−10.5%; p < 0.001); and following additional adjustment for age, hypertension, nephropathy, neuropathy, retinopathy, and vascular disease (−9.2%; p = 0.022). By contrast, after adjustment for confounding by BMI, T2D patients had bone microarchitecture and BMD that were not significantly different than controls; however, radial cortical porosity tended to be higher in the T2D patients. In addition, patients with T2D had significantly reduced serum markers of bone turnover (all p < 0.001) compared to controls. Of note, in patients with T2D, the average glycated hemoglobin level over the previous 10 years was negatively correlated with BMS (r = −0.41; p = 0.026). In conclusion, these findings represent the first demonstration of compromised BMS in patients with T2D. Furthermore, our results confirm previous studies demonstrating low bone turnover in patients with T2D and highlight the potential detrimental effects of prolonged hyperglycemia on bone quality. Thus, the skeleton needs to be recognized as another important target tissue subject to diabetic complications. © 2014 American Society for Bone and Mineral Research.
NF-κB RelB Negatively Regulates Osteoblast Differentiation and Bone Formation
Authors: Yao Zhenqiang , Li Yanyun , Yin Xiaoxiang , Dong Yufeng , Xing Lianping , Boyce Brendan F
Published: October 2013

RelA-mediated NF-κB canonical signaling promotes mesenchymal progenitor cell (MPC) proliferation, but inhibits differentiation of mature osteoblasts (OBs) and thus negatively regulates bone formation. Previous studies suggest that NF-κB RelB may also negatively regulate bone formation through noncanonical signaling, but they involved a complex knockout mouse model, and the molecular mechanisms involved were not investigated. Here, we report that RelB−/− mice develop age-related increased trabecular bone mass associated with increased bone formation. RelB−/− bone marrow stromal cells expanded faster in vitro and have enhanced OB differentiation associated with increased expression of the osteoblastogenic transcription factor, Runt-related transcription factor 2 (Runx2). In addition, RelB directly targeted the Runx2 promoter to inhibit its activation. Importantly, RelB−/− bone-derived MPCs formed bone more rapidly than wild-type cells after they were injected into a murine tibial bone defect model. Our findings indicate that RelB negatively regulates bone mass as mice age and limits bone formation in healing bone defects, suggesting that inhibition of RelB could reduce age-related bone loss and enhance bone repair. © 2014 American Society for Bone and Mineral Research.
Calcific Periarthritis as the Only Clinical Manifestation of Hypophosphatasia in Middle-Aged Sisters
Authors: Guañabens Núria , Mumm Steven , Möller Ingrid , González-Roca Eva , Peris Pilar , Demertzis Jennifer L , Whyte Michael P
Published: October 2013

Hypophosphatasia (HPP) is the inborn error of metabolism that features low serum alkaline phosphatase (ALP) activity caused by loss-of-function mutation(s) within the gene for the tissue nonspecific isoenzyme of ALP (TNSALP). In HPP, extracellular accumulation of inorganic pyrophosphate (PPi), a TNSALP substrate and inhibitor of mineralization, leads frequently to premature tooth loss and often to rickets or osteomalacia. In affected adults, the excess PPi sometimes also causes calcium pyrophosphate dihydrate (CPPD) deposition, PPi arthropathy, or pseudogout, or seemingly paradoxical deposition of hydroxyapatite crystals in ligaments or around joints when the condition is called calcific periarthritis (CP). We report three middle-aged sisters with CP as the only clinical manifestation of HPP. Each presented during early adult life with recurrent episodes of pain principally around the shoulders, elbows, wrists, hips, or Achilles tendon. Otherwise, they were in good health, including no history of unusual dental disease, fractures, or pseudofractures. Calcific deposits were identified in symptomatic areas principally by ultrasonographic assessment but also confirmed radiographically. All three sisters had low serum levels of total and bone-specific ALP, hyperphosphatemia, and increased serum concentrations of the TNSALP substrate pyridoxal 5′-phosphate together characteristic of HPP. Mutation analysis revealed that each carried a single unique 18-bp duplication within TNSALP (c.188_205dup18, p.Gly63_Thr68dup) as did two of their healthy sons and their mother, who was without signs of CPPD deposition or CP but had knee osteoarthritis. We find that CP can be the only complication of HPP in adults. Thus, multiple juxta-articular deposits of hydroxyapatite causing CP may be a useful sign of HPP, especially when the CP is familial. © 2014 American Society for Bone and Mineral Research.
Raf Kinase Inhibitory Protein Role in the Molecular Subtyping of Breast Cancer
Authors: Al‐Mulla Fahd , Marafie Makia , Zea Tan Tuan , Paul Thiery Jean
Published: October 2013

In this study, we examined the association between the RKIP expression and the molecular subtypes of breast cancer. Microarray gene expression data of 2,333 human breast cancer from 26 different cohorts performed on Affymetrix U133A or U133Plus2 platforms were downloaded from Array Express and Gene Expression Omnibus and the molecular subtype of breast cancer for the samples was determined by single sample Gene Set Enrichment Analysis. Differences in recurrence‐free survival (RFS) were tested using the Log‐rank test in univariate analysis and displayed using Kaplan–Meier curves. Cox proportional‐hazards model was used to calculate the hazard ratio using univariate and multivariate analysis. Loss or reduced RKIP expression was associated with reduced RFS in breast cancer using univariate and multivariate analyses, which was independent of lymph node (LN) metastasis status. Basal‐like, Claudin‐low, and Her‐2‐enriched tumors had significantly lower RKIP levels compared to other subclasses (P < 0.0001). Conversely, the Luminal subclass exhibited the highest expression levels of RKIP (P < 0.0001 for Luminal A and P = 0.0005 for Luminal B subtype), while in normal‐like breast cancer subtype, RKIP expression was not informative. RKIP expression was prognostic in ER+ and ER− subgroups. RKIP expression had no significant prognostic power within Basal‐like, Claudine‐low, Luminal B, or Her‐2‐enriched breast cancer subtypes. However, its expression pinpointed excellent from intermediate‐poor Luminal A survivors, in both ER+ (P = 0.035) and ER− (P = 0.012) subgroups, especially in LN negative breast cancers. In conclusion, RKIP expression adds significant value to the molecular subclassification of breast cancer especially for the Luminal A subtype. J. Cell. Biochem. 115: 488–497, 2014. © 2013 Wiley Periodicals, Inc.