bluuebunny/crossref_metadata_2025 huggingface dataset:
A common mechanism for adaptive scaling of reward and novelty
Authors: Bunzeck Nico , Dayan Peter , Dolan Raymond J. , Duzel Emrah
Published: January 2010

Declarative memory is remarkably adaptive in the way it maintains sensitivity to relative novelty in both unknown and highly familiar environments. However, the neural mechanisms underlying this contextual adaptation are poorly understood. On the basis of emerging links between novelty processing and reinforcement learning mechanisms, we hypothesized that responses to novelty will be adaptively scaled according to expected contextual probabilities of new and familiar events, in the same way that responses to prediction errors for rewards are scaled according to their expected range. Using functional magnetic resonance imaging in humans, we show that the influence of novelty and reward on memory formation in an incidental memory task is adaptively scaled and furthermore that the BOLD signal in orbital prefrontal and medial temporal cortices exhibits concomitant scaled adaptive coding. These findings demonstrate a new mechanism for adjusting gain and sensitivity in declarative memory in accordance with contextual probabilities and expectancies of future events. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.
The neural signature of phosphene perception
Authors: Taylor Paul C.J. , Walsh Vincent , Eimer Martin
Published: January 2010

Artificial percepts (phosphenes) can be induced by applying transcranial magnetic stimulation (TMS) over human visual cortex. Although phosphenes have been used to study visual awareness, the neural mechanisms generating them have not yet been delineated. We directly tested the two leading hypotheses of how phosphenes arise. These hypotheses correspond to the two competing views of the neural genesis of awareness: the early, feedforward view and the late, recurrent feedback model. We combined online TMS and EEG recordings to investigate whether the electrophysiological correlates of conscious phosphene perception are detectable early after TMS onset as an immediate local effect of TMS, or only at longer latencies, after interactions of TMS‐induced activity with other visual areas. Stimulation was applied at the intensity threshold at which participants saw a phosphene on half of the trials, and brain activity was recorded simultaneously with electroencephalography. Phosphene perception was associated with a differential pattern of TMS‐evoked brain potentials that started 160–200 ms after stimulation and encompassed a wide array of posterior areas. This pattern was differentiated from the TMS‐evoked potential after stimulation of a control site. These findings suggest that conscious phosphene perception is not a local phenomenon, but arises only after extensive recurrent processing. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.
Design, synthesis, and evaluation of unsymmetrical difluoro‐boron complexes with imidazoline as potential fungicides
Authors: Wang Kewei , Cui Jingnan , Xie Lijuan , Qian Xuhong
Published: January 2010

A series of unsymmetrical difluoro‐boron(BF2) complexes with pyridine and imidazoline were synthesized by reaction of new chelating ligands (arylmethyl‐imidazolidinylidene)‐pyridin‐2‐yl‐amine with boron trifluoride diethyl etherate. All the ligands and BF2 complexes were structurally characterized by IR, HRMS, 1H, 13C,11B, and 19F NMR, indicating the bidentate complexation of imidazoline nitrogen and the pyridine nitrogen to the boron center. Evaluation of agricultural bioactivities showed that some of the BF2 complexes exhibited moderate fungicidal activities, and most of the BF2 complexes exhibited higher activities than the none‐BF2 complexed substrates. © 2010 Wiley Periodicals, Inc. Heteroatom Chem 20:418–424, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20567
Usefulness of the combination of ultrasonography and 99mTc‐sestamibi scintigraphy in the preoperative evaluation of uremic secondary hyperparathyroidism
Authors: Vulpio Carlo , Bossola Maurizio , De Gaetano Annamaria , Maresca Giulia , Bruno Isabella , Fadda Guido , Morassi Francesca , Magalini Sabina C. , Giordano Alessandro , Castagneto Marco
Published: January 2010

Background.

The usefulness of the combination of technetium‐99m‐methoxyisobutylisonitrile (99mTc‐MIBI) parathyroid scintigraphy and ultrasonography to detect parathyroid glands (PTGs) in secondary hyperparathyroidism (SHPT) is still controversial.

Methods.

In all, 21 patients with SHPT underwent parathyroidectomy. The sensitivity and specificity of ultrasonography and scintigraphy related to site, size, hyperplasia type of PTG, concomitant thyroid disease, and the frequency of intraoperative frozen sections were determined.

Results.

The sensitivities of scintigraphy and ultrasonography were 62% and 55%, and the specificity was 95% for both procedures. The sensitivity of combined techniques was 73%. The scintigraphy detected 7/9 (78%) ectopic PTGs, whereas ultrasonography was always negative. A PTG maximum longitudinal diameter <8 mm, the presence of diffuse hyperplasia, the upper localization of glands, and the presence of concomitant thyroid disease reduced the sensitivity and specificity of imaging techniques. In cases of positive imaging, the rate of intraoperative frozen sections was significantly lower.

Conclusions.

The ultrasonography and sestamibi scintigraphy, which showed a higher sensitivity than that of either ultrasonography or scintigraphy alone, led to a reduction of intraoperative frozen sections and to preoperative diagnosis of ectopic (29%) or supernumerary PTGs (10%) and concomitant nodular thyroid disease (24%). © 2010 Wiley Periodicals, Inc. Head Neck, 2010
Optical and molecular techniques to identify tumor margins within the larynx
Authors: Hughes Owain R. , Stone Nicholas , Kraft Marcel , Arens Christoph , Birchall Martin A.
Published: January 2010

Failure to remove tumor cells from the larynx significantly increases the risk of local recurrence following surgical excision. Healthy tissue must be preserved to optimize long‐term vocal and swallowing function. It is essential to accurately distinguish between healthy mucosa, dysplasia, and invasive carcinoma. Optical and molecular examining technologies have been developed to improve tumor margin identification in vivo. We aimed to review the efficacy of these technologies. Published articles were identified using MEDLINE, EMBASE, and Cochrane central register of controlled trials (CENTRAL). Randomized clinical trials are required to establish the benefit to patients and cost to the health service of using 5‐aminolevulinic acid (ALA)–induced fluorescent imaging, contact endoscopy, and optical coherence tomography (OCT). Furthermore, primary research is required to validate other techniques, such as confocal endomicroscopy and Raman spectroscopy, and to develop their clinical applications in the larynx. © 2010 Wiley Periodicals, Inc. Head Neck, 2010
Usefulness of intraoperative parathyroid hormone measurements in patients with renal hyperparathyroidism
Authors: Freriks Kim , Hermus Ad R.M.M. , de Sévaux Ruud G.L. , Bonenkamp Han J. , Biert Jan , den Heijer Martin , Sweep Fred C.G.J. , van Hamersvelt Henk W.
Published: January 2010

Background

In renal hyperparathyroidism, it remains unclear whether intraoperative parathyroid hormone (PTH) measurements can predict postoperative outcome and guide the extent of surgical exploration.

Methods

In 42 parathyroidectomies for renal hyperparathyroidism, we analyzed the predictive value of the Miami Criterion of 50% intraoperative PTH decrease. We used receiver operating characteristic (ROC) curves to find the criterion with the best diagnostic performance. We also investigated whether the whole PTH assay improved accuracy.

Results

Twenty‐six operations (62%) resulted in normal postoperative PTH. With the Miami Criterion, cure was predicted with a sensitivity of 95% and specificity of only 8%. Specificity could be improved to 50% using a 70% PTH decrease as cut‐off level. The whole PTH assay did not improve accuracy.

Conclusion

Prediction of cure after parathyroidectomy for renal hyperparathyroidism might be improved with a criterion of 70% PTH decrease 10 minutes after excision of all parathyroid glands. Prospective analysis needs to validate this new criterion. © 2010 Wiley Periodicals, Inc. Head Neck, 2010
Predicting the pattern of regional metastases from cutaneous squamous cell carcinoma of the head and neck based on location of the primary
Authors: Ebrahimi Ardalan , Moncrieff Marc D. , Clark Jonathan R. , Shannon Kerwin F. , Gao Kan , Milross Christopher G. , O'Brien Christopher J.
Published: January 2010

Background

We aimed to analyze the distribution of regional nodal metastases according to primary tumor location in patients with cutaneous squamous cell carcinoma of the head and neck (SCCHN).

Methods

Analysis of 295 neck dissections performed for patients with clinically evident regional metastases from cutaneous SCCHN between 1987 and 2009.

Results

Level I involvement in the absence of level II or III only occurred in patients with facial primaries. In patients with clear nodes in level II–III, the risk of level IV–V involvement was 0.0% for external ear primaries, 2.7% for face and anterior scalp, and 15.8% for posterior scalp and neck.

Conclusion

In patients undergoing parotidectomy for metastatic cutaneous SCCHN with a clinically negative neck, the results of this study support selective neck dissection including level I–III for facial primaries, level II–III for anterior scalp and external ear primaries, and levels II–V for posterior scalp and neck primaries. © 2010 Wiley Periodicals, Inc. Head Neck, 2010
Proliferative activity and diagnostic delay in oral cancer
Authors: Seoane Juan , Pita‐Fernández Salvador , Gómez Iria , Vazquez Inés , López‐Cedrún José Luis , De Agustin Domingo , Varela‐Centelles Pablo
Published: January 2010

Background

Tumor stage may relate to the chronology of neoplasm growth and has been used as an outcome variable when studying diagnostic delay in oral cancer. However, tumor growth rate may act as a confounding factor.

Methods

We reviewed a total of 63 incident cases of oral cancer. The variables considered for the study included age, sex, smoking history, tumor site, TNM stage, Ki‐67 score, and diagnostic delay.

Results

Significant differences between survivors and exitus were found in terms of tumor stage at diagnosis (I–II vs III–IV), sex, and Ki‐67 scores. When the analysis was adjusted for tumor stage at diagnosis (I–II vs III–IV), proliferative activity resulted to be an independent prognostic factor for survival, whereas diagnostic delay did not influence survival.

Conclusion

These results seem to suggest that survival from oral cancer is affected more by the biology of the cancer (rapid tumor growth) than by diagnostic delay. © 2010 Wiley Periodicals, Inc. Head Neck, 2010
Additional ent‐Kaurane Diterpenoids from Rubus corchorifolius L. f.
Authors: Chen Xue‐Xiang , Zhou Shuang‐De , Ou Yang‐Wen , Xiao Su‐Yao , Lin Wang‐Huang , Cao Yong , Zhang Min , Zhao Li‐Chao , Li Long‐Fang
Published: January 2010

A further chemical investigation of the plant Rubus corchorifolius L. f., collected in Hunan Province, afforded three new ent‐kauranoids 3–5. Their structures were elucidated by various spectroscopic methods.
A Novel and Expedient Synthesis of 7‐Pyrimidinylpyrimido[4,5‐d]pyrimidinones
Authors: Mohammadizadeh Mohammad R. , Bahramzadeh Mojtaba , Mohammadi Ali A. , Karimi Ali R.
Published: January 2010

A novel and efficient procedure for the synthesis of new 7‐pyrimidinylpyrimido[4,5‐d]pyrimidinone derivatives was elaboratedviathe base‐promoted cyclodimerization reaction of 5‐[(dimethylamino)methylidene]‐6‐iminopyrimidine‐2,4(1H,3H)‐dione hydrochlorides. In an analogous manner, a 2‐thioxo analog was prepared starting with the corresponding 2‐thioxopyrimidin‐4‐one.
Two New Metabolites, Epoxydine A and B, from Phoma sp.
Authors: Qin Song , Hussain Hidayat , Schulz Barbara , Draeger Siegfried , Krohn Karsten
Published: January 2010

The new compounds, epoxydines A and B (1 and 2, resp.), along with the known and related metabolites, 3–6, were isolated from the fungal endophyte Phoma sp. The structures of the new compounds were elucidated by detailed spectroscopic analysis, and the relative configuration of 1 was confirmed by ROESY experiments. Preliminary studies indicated that compounds 2–5 possess good antibacterial, antifungal, and algicidal properties. Similarly, compound 1 showed antifungal and algicidal, and compound 6 antibacterial and algicidal properties.
Photoannelation Reactions of 3‐(Alk‐1‐ynyl)cyclohept‐2‐en‐1‐ones
Authors: Vallée M. Robert J. , Inhülsen Inga , Margaretha Paul
Published: January 2010

Irradiation (350 nm) of the newly synthesized 3‐(alk‐1‐ynyl)cyclohept‐2‐en‐1‐ones 1 and 2 leads to the selective formation of tricyclic head‐to‐head dimers. In the presence of 2,3‐dimethylbuta‐1,3‐diene, the (monocyclic) enone 1 affords trans‐fused 7‐alkynyl‐bicyclo[5.2.0]nonan‐2‐ones as major photoproducts, whereas photocycloaddition of benzocyclohept‐5‐en‐7‐one 2 to the same diene gives preferentially the eight‐membered cyclic allene 16 via ‘end‐to‐end’ cyclization of the intermediate allyl‐propargyl biradical 22. On contact with acid, cycloocta‐1,2,5‐triene 16 isomerizes to cycloocta‐1,3,5‐triene 18.
Neolignans from the Leaves of Casearia sylvestrisSwartz
Authors: Wang Wei , Ali Zulfiqar , Li Xing‐Cong , Khan Ikhlas A.
Published: January 2010

Six new neolignans, casearialignans A–F (1–6, resp.) and one known lignan syringaresinol‐β‐D‐glucoside were isolated from the leaves of Casearia sylvestris. Their structures were determined on the basis of 1D‐ and 2D‐NMR, and HR‐ESI‐MS analyses. The relative and absolute configurations were determined by the value of the coupling constants and CD spectral analysis, respectively.
Alternative Synthesis of 2‐Hydroxy‐3,5,5‐trimethylcyclopent‐2‐en‐1‐one
Authors: Chapuis Christian , Saint‐Léger Christine
Published: January 2010

The 2‐hydroxy‐3,5,5‐trimethylcyclopent‐2‐en‐1‐one (1) was synthesized in 42% yield by rearrangement of epoxy ketone 10 on treatment with BF3⋅Et2O under anhydrous conditions. Intermediate 10 was available from the known enone 8, either via direct epoxidation (60% H2O2, NaOH, MeOH; yield 50%), or via reduction to the corresponding allylic alcohol 14 (LiAlH4, THF), followed by epoxidation ([VO(acac)2], tBuOOH) and reoxidation under Swern conditions, in 37% total yield.
Experimental and Theoretical Conformational Analysis of 5‐Benzylimidazolidin‐4‐one Derivatives – a ‘Playground’ for Studying Dispersion Interactions and a ‘Windshield‐Wiper’ Effect in Organocatalysis
Authors: Seebach Dieter , Grošelj Uroš , Schweizer W. Bernd , Grimme Stefan , Mück‐Lichtenfeld Christian
Published: January 2010

The PF6 salts of 5‐benzyl‐1‐isopropylidene‐ and 5‐benzyl‐1‐cinnamylidene‐3‐methylimidazolidin‐4‐ones 1 (Scheme) with various substituents in the 2‐position have been prepared, and single crystals suitable for X‐ray structure determination have been obtained of 14 such compounds, i.e., 2–10 and 12–16 (Figs. 2–5). In nine of the structures, the Ph ring of the benzyl group resides above the heterocycle, in contact with the cis‐substituent at C(2) (staggered conformation A; Figs. 1–3); in three structures, the Ph ring lies above the iminium π‐plane (staggered conformation B; Figs. 1 and 4); in two structures, the benzylic CC bond has an eclipsing conformation (C; Figs. 1 and 5) which places the Ph ring simultaneously at a maximum distance with its neighbors, the CO group, the NC‐π‐system, and the cis‐substituent at C(2) of the heterocycle. It is suggested by a qualitative conformational analysis (Fig. 6) that the three staggered conformations of the benzylic CC bond are all subject to unfavorable steric interactions, so that the eclipsing conformation may be a kind of ‘escape’. State‐of‐the‐art quantum‐chemical methods, with large AO basic sets (near the limit) for the single‐point calculations, were used to compute the structures of seven of the 14 iminium ions, i.e., 3, 4/12, 5–7, 13, and 16 (Table) in the two staggered conformations, A and B, with the benzylic Ph group above the ring and above the iminium π‐system, respectively. In all cases, the more stable computed conformer (‘isolated‐molecule’ structure) corresponds to the one present in the crystal (overlay in Fig. 7). The energy differences are small (≤2 kcal/mol) which, together with the result of a potential‐curve calculation for the rotation around the benzylic CC bond of one of the structures, 16 (Fig. 8), suggests that the benzyl group is more or less freely rotating at ambident temperatures. The importance of intramolecular London dispersion (benzene ring in ‘contact’ with the cis‐substituent in conformation A) for DFT and other quantum‐chemical computations is demonstrated; the benzyl‐imidazolidinones 1 appear to be ideal systems for detecting dispersion contributions between a benzene ring and alkyl or aryl CH groups. Enylidene ions of the type studied herein are the reactive intermediates of enantioselective organocatalytic conjugate additions, Diels–Alder reactions, and many other transformations involving α,β‐unsaturated carbonyl compounds. Our experimental and theoretical results are discussed in view of the performance of 5‐benzyl‐imidazolidinones as enantioselective catalysts.
Applications of the Chiral Auxiliaries DIOZ and TRIOZ for Conjugate Additions and Comparison with Other Auxiliaries
Authors: Sprecher Hanspeter , Pletscher Stefan , Möri Manuel , Marti Roger , Gaul Christoph , Patora‐Komisarska Krystyna , Otchertianova Ekatarina , Beck Albert K. , Seebach Dieter
Published: January 2010

A number of N‐acryloyl‐, N‐crotonoyl‐, N‐(3,3,3‐trifluorocrotonoyl)‐, N‐cinnamoyl‐, and N‐(3‐nitroacryloyl)‐4‐isopropyl‐ or ‐4‐phenyl‐oxazolidin‐2‐ones with geminal diphenyl substitution, i.e., 7–15, have been prepared and used for conjugate additions of organocuprate reagents (Me, iPr, Ph, 4‐MeOPh) in the β‐carbonyl (Table 2) and in the α‐carbonyl position (NO2‐derivative 11 in Scheme 3). The yields and diastereoselectivities are compared with previously tested enoyl‐oxazolidinones (Table 2). Highest diastereoselectivities (>90%) are always observed with the 4‐Ph derivatives (Hruby effect). Nitroacryloyl‐oxazolidinones and a corresponding phenylmenthol ester undergo less diastereoselective additions (Scheme 3). A 3‐(1‐methylethyl)‐5,5‐diphenyloxazolidin‐2‐one (DIOZ)‐derived Li2‐enolate‐nitronate was also tested for α‐carbonyl alkylation (Scheme 4). The X‐ray crystal structures of three acryloyl‐oxazolidinones and of four adducts are described (Tables 1 and 3), and they serve for configurational assignments and description of the stereochemical courses of the additions and alkylation. Possible applications of the nitro compounds for the preparation of β2‐amino acids are discussed (Scheme 2).
Fibromyalgia: a complex syndrome requiring a multidisciplinary approach
Authors: Spaeth Michael , Briley Mike
Published: January 2010

Fibromyalgia is a pain syndrome which is not due to tissue damage or inflammation and is thus fundamentally different from rheumatic disorders and many other pain conditions. In addition to widespread pain it is associated with a range of other symptoms such as sleep disturbance, fatigue, cognitive disturbance, stiffness and depressive symptoms. A number of multidisciplinary therapeutic programmes involving education, exercise and cognitive therapy have been shown to be effective in bringing relief. The various medications that are currently being developed for the treatment of fibromyalgia are based on different mechanistic approaches. In particular, serotonin noradrenaline reuptake inhibitors (SNRI) such as duloxetine and milnacipran and α2‐δ receptor ligands such as pregabalin have been shown, in a variety of placebo‐controlled studies, to bring significant relief from pain and other symptoms. The complex symptomatology of fibromyalgia will, however, continue to require a multidisciplinary approach including education and exercise in addition to drug therapy to achieve the most efficient management of fibromyalgia. Copyright © 2009 John Wiley & Sons, Ltd.
Effect of a small molecule BCL‐2 inhibitor on immune function and use with a recombinant vaccine
Authors: Farsaci Benedetto , Sabzevari Helen , Higgins Jack P. , Di Bari Maria Giovanna , Takai Shinji , Schlom Jeffrey , Hodge James W.
Published: January 2010

Small molecule BCL‐2 inhibitors are being examined as monotherapy in phase I/II clinical trials for several types of tumors. However, few data are available about the effect of BCL‐2 inhibitors on immune function. The aims of our study were to investigate the effect of a small molecule BCL‐2 inhibitor on immune function and determine the most effective way of combining this inhibitor with a recombinant vaccine to treat tumors. The in vitro effect of the pan‐BCL‐2 inhibitor GX15‐070 was assessed in mouse CD8 T lymphocytes at 2 different stages of activation as well as regulatory T lymphocytes (Treg). The in vivo effect of GX15‐070 after recombinant vaccinia/fowlpox CEA‐TRICOM vaccination was analyzed in tumor‐infiltrating lymphocytes, and in splenocytes of mice bearing subcutaneous tumors. The therapeutic efficacy of such sequential therapy was measured as a reduction of pulmonary tumor nodules. Activated mature CD8 T lymphocytes were more resistant to GX15‐070 as compared to early‐activated cells. Treg function was significantly decreased after treatment with the BCL‐2 inhibitor. In vivo, GX15‐070 was given after vaccination so as to not negatively impact the induction of vaccine‐mediated immunity, resulting in increased intratumoral activated CD8:Treg ratio and significant reduction of pulmonary tumor nodules. Our study is the first to show the effect of a small molecule BCL‐2 inhibitor on the immune system and following a vaccine. It is also the first to demonstrate the efficacy of this sequence in reducing tumors in mouse models, providing a rationale for the design of combinational clinical studies.
Retracted: Aurora kinase inhibitor AZD1152 negatively affects the growth and survival of HTLV‐1‐infected T lymphocytes in vitro
Authors: Tomita Mariko , Tanaka Yuetsu , Mori Naoki
Published: January 2010

Retraction: The following article has been retracted through agreement between the first author and several coauthors, the journal Editor‐in‐Chief, Peter Lichter, and John Wiley & Sons, Ltd.: Tomita, M., Tanaka, Y. and Mori, N. (2010), Aurora kinase inhibitor AZD1152 negatively affects the growth and survival of HTLV‐1‐infected T lymphocytes in vitro. Int J Cancer, 127:1584–1594, published online on 20 JAN 2010 in Wiley Online Library (www.onlinelibrary.wiley.com). After an investigation the retraction has been agreed due to inappropriate duplication of images and overlap with other published work.
Macroscopic morphologic subtypes of laterally spreading colorectal tumors showing distinct molecular alterations
Authors: Sugimoto Takafumi , Ohta Miki , Ikenoue Tsuneo , Yamada Atsuo , Tada Motohisa , Fujishiro Mitsuhiro , Ogura Keiji , Yamaji Yutaka , Okamoto Makoto , Kanai Fumihiko , Kawabe Takao , Omata Masao
Published: January 2010

Recent advances in colonoscopic techniques have resulted in more frequent detection of superficial‐type colorectal tumors, that is, laterally spreading tumors (LSTs), although little is known about the characteristic clinical features and genetic alterations of LSTs. To elucidate the molecular characteristics of LSTs, genetic alterations in the KRAS, BRAF and PIK3CA genes and abnormal expression of the p53, β‐catenin and MYC proteins were analyzed using direct DNA sequencing and immunohistochemistry for 50 protruded‐type tumors (Protruded), 35 granular‐type LSTs (LST‐G) and 19 nongranular‐type LSTs (LST‐NG). In addition, loss of heterozygosity (LOH) close to the adenomatous polyposis coli (APC) gene (5q21) was examined in these tumors. In univariate analyses, significant differences were noted in the percentages with KRAS mutations (Protruded, LST‐G, LST‐NG = 30.0%, 54.3%, 21.1%, respectively, p = 0.0156), nuclear accumulation of β‐catenin (Protruded, LST‐G, LST‐NG = 50.0%, 37.1%, 68.4%, respectively, p = 0.0267), expression of MYC (Protruded, LST‐G, LST‐NG = 26.0%, 17.1%, 42.1%, respectively, p = 0.0456) and LOH at the APC gene locus (Protruded, LST‐G, LST‐NG = 22.0%, 20.0%, 47.4%, respectively, p = 0.0302). Multivariate analysis demonstrated that the macroscopic subtype of LST was significantly associated with KRAS mutation (for LST‐NG: odds ratio [OR] 0.23, 95% CI 0.06–0.90) and nuclear accumulation of β‐catenin (for LST‐NG: OR 4.05, 95% CI 1.11–14.8). Our data revealed that the 2 subtypes of LST have different molecular characteristics, suggesting that 2 or more different molecular mechanisms result in colorectal tumors with a similar growth pattern.
Determining the protein drug release characteristics and cell adhesion to a PLLA or PLGA biodegradable polymer membrane
Authors: Burns Sarah A. , Hard Robert , Hicks Wesley L. , Bright Frank V. , Cohan David , Sigurdson Lynn , Gardella Joseph A.
Published: January 2010

Biodegradable polymers are of interest for developing controlled protein drug delivery platforms. In this study, two poly (α‐hydroxy) esters were formulated with Aerosol‐OT, a surfactant stabilizer, to encapsulate the protein keratinocyte growth factor (KGF) for controlled release KGF is involved in a number of crucial biologic processes, most notably epithelial growth and repair. The concentration of KGF that caused a biological response in vitro was determined (optimally 10 ng/mL) and compared with the release of KGF from the two biodegradable polymer membrane formulations. Each polymer formulation released biologically relevant levels, 10 ng/mL of active KGF, although with different times release kinetics. The membrane composed of PLGA/AOT/KGF exhibited a faster release rate of KGF into solution after 120 h of degradation time than the release rate of the PLLA/AOT/KGF matrices. Cell seeding assays showed that both polymer matrices, when formulated with AOT, sustained cell growth. Time of Flight Secondary Ion Mass Spectrometry (ToF‐SIMS) was used to characterize the distribution of AOT and KGF through the polymer membrane. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Effects of parylene‐C photooxidation on serum‐assisted glial and neuronal patterning
Authors: Delivopoulos Evangelos , Murray Alan F. , Curtis John C.
Published: January 2010

The increasing use of patterned neural networks in multielectrode arrays and similar devices drives the constant development and evaluation of new biomaterials. Recently, we presented a promising technique to guide neurons and glia reliably and effectively. Parylene‐C, a common hydrophobic polymer, was photolithographically patterned on silicon oxide (SiO2) and subsequently activated via immersion in serum. In this article, we explore the effects of ultraviolet (UV)‐induced oxidation on parylene's ability to pattern neurons and glia. We exposed parylene‐C stripe patterns to increasing levels of UV radiation and found a dose‐dependent reduction in the total mass of patterned cells, as well as a gradual loss of glial and neuronal conformity to the patterns. In contrast, nonirradiated patterns had superior patterning results and increased presence of cells. The reduced cell adhesion and patterning after the formation of aldehyde and carboxyl groups on UV‐radiated parylene‐C supports our hypothesis that cell adhesion and growth on parylene is facilitated by hydrophobic adsorption of serum proteins. We conclude that unlike other cell patterning schemes, our technique does not rely on photooxidation of the polymer. Nonetheless, the precise control of oxygenated groups on parylene could pave the way for the differential binding of proteins and other molecules on the surface, aiding in the adhesion of alternative cell types. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
In vitroevaluation of cell proliferation and collagen synthesis on titanium following plasma electrolytic oxidation
Authors: Whiteside Paul , Matykina Endzhe , Gough Julie E. , Skeldon Peter , Thompson George E.
Published: January 2010

Titania‐based coatings produced by plasma electrolytic oxidation are being investigated as bioactive surfaces for titanium implants. In this study, plasma electrolytic oxidation was performed in calcium‐ and phosphorus‐based electrolytes under DC conditions, resulting in coatings of thickness of ∼8–15 μm. Coating morphologies, microstructures, and compositions were examined by scanning electron microscopy with energy‐dispersive X‐ray analysis, X‐ray diffraction, and electron probe microanalysis. The coatings revealed a cratered morphology, with incorporated calcium and phosphorus species. Proliferation rates of primary human osteoblasts cells on the coatings were up to ∼37% faster than those for uncoated titanium and 316L stainless steel reference materials. Further, the coatings assisted cell adhesion and generation and anchorage of collagen. The amount of collagen was upto ∼2.4 times greater than for the reference substrates. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Human osteoblast behavior on as‐synthesized SiO4 and B‐CO3 co‐substituted apatite
Authors: Landi Elena , Uggeri Jacopo , Sprio Simone , Tampieri Anna , Guizzardi Stefano
Published: January 2010

The functional behavior of synthetic apatite, commonly used as fillers or scaffolds, depends on physical and chemical parameters, which vary in response to chemical substitutions and to thermal treatments. The effect of silicon co‐substituting with carbonate ions in the apatite lattice on the properties of the as‐synthesized powder and finally on human osteoblast in vitro behavior was investigated. Dose‐response curves of Si‐free and Si‐substituted carbonated apatites (namely CHA and SiCHA‐1 and SiCHA‐2 with 0.88 and 0.55 wt % of Si, respectively) showed that SiCHA‐1 had toxic effect, whereas CHA and SiCHA‐2, at worst, hindered osteoblast proliferation, but no toxicity occurred. Subsequent experiments compared the effects of CHA and SiCHA‐2 used at the doses of 0.3 and 1 mg/mL. After 7 days of treatment, both the powders stimulated cell proliferation and protein content and inhibited alkaline phosphatase activity. However, SiCHA‐2 slightly stimulated osteoblast differentiation, as shown by higher calcium deposition, compared with CHA. The cell behaviors were linked to the peculiar powder characteristics. The as‐synthesized powder represents the most critical system in terms of reactivity toward cells and can inform on the limits for positively exploiting the characteristics of SiCHA powders in making bone fillers or scaffolds, using no thermal treatments. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Plasma mediated collagen‐I‐coating of metal implant materials to improve biocompatibility
Authors: Hauser Joerg , Koeller Manfred , Bensch Sebastian , Halfmann Helmut , Awakowicz Peter , Steinau Hans‐Ulrich , Esenwein Stefan
Published: January 2010

This study describes the collagen‐I coating of titanium and steel implants via cold low‐pressure gas plasma treatment. To analyze the coatings in terms of biocompatibility osteoblast‐like osteosarcoma cells and human leukocytes were cultivated on the metal surfaces. Two different implant materials were assessed (Ti6Al4V, X2CrNiMo18) and four different surface properties were evaluated: (a) plasma pretreated and collagen‐I coated implant materials; (b) collagen‐I dip‐coated without plasma pretreatment; (c) plasma treated but not collagen‐I coated; (d) standard implant materials served as control. The different coating characteristics were analyzed by scanning electron microscopy (SEM). For adhesion and viability tests calcein‐AM staining of the cells and Alamar blue assays were performed. The quantitative analysis was conducted by computer assisted microfluorophotography and spectrometer measurements. SEM analysis revealed that stable collagen‐I coatings could not be achieved on the dip‐coated steel and titanium alloys. Only due to pretreatment with low‐pressure gas plasma a robust deposition of collagen I on the surface could be achieved. The cell viability and cell attachment rate on the plasma pretreated, collagen coated surfaces was significantly (p < 0.017) increased compared to the non coated surfaces. Gas plasma treatment is a feasible method for the deposition of proteins on metal implant materials resulting in an improved biocompatibility in vitro. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Addition of nimesulide to small intestinal submucosa biomaterial inhibits postsurgical adhesiogenesis in rats
Authors: Suckow Mark A. , Hodde Jason P. , Wolter William R. , Wood Karl V. , Hiles Michael C. , Janis Abram D.
Published: January 2010

Adhesion formation is a common complication in abdominal surgery with incidence as high as 93% and small bowel obstruction a common complication. Because the extracellular matrix material, small intestinal submucosa (SIS), is commonly used in various surgical procedures, methods to inhibit adhesiogenesis are of great interest. This study was undertaken to determine if incorporation of nimesulide (NM), a selective cyclooxygenase (COX)‐2 inhibitor, could reduce the extent and tenacity of intraabdominal adhesion formation associated with SIS implantation. Female Sprague–Dawley rats underwent a cecal abrasion surgical procedure to induce adhesiogenesis. Rats were either left untreated or treated by direct application over the injured cecum with polypropylene mesh (PPM); SIS; SIS containing a low dose of NM; or SIS containing a high dose of NM. Rats were euthanized 21 days later, and adhesion extent and tenacity were evaluated using standard scales (0 = minimal adhesiogenesis; 4 = severe adhesiogenesis). Addition of NM to SIS resulted in a significant (p < 0.05) reduction in adhesion extent and in a similar reduction in adhesion tenacity for SIS containing a low dose of NM. Adhesions typically extended from the abraded cecal surface to the body wall and were characterized histologically by fibrous tissue adherent to the cecal wall. In conclusion, addition of the nonsteroidal anti‐inflammatory, COX‐2 selective drug, NM, to SIS attenuates adhesion extent and tenacity when compared with surgical placement of SIS or PPM alone. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010
The effect of static applied potential on the 24‐hour impedance behavior of commercially pure titanium in simulated biological conditions
Authors: Ehrensberger Mark T. , Gilbert Jeremy L.
Published: January 2010

Potential step impedance analysis was utilized to evaluate the electrochemical impedance of commercially pure titanium (cpTi) samples that were polarized to static potentials (range from −1000 mV to +1000 mV vs. Ag/AgCl) and immersed in physiologically relevant electrolytes [phosphate buffered saline (PBS) and cell culture medium with 10% fetal bovine serum (AMEM + FBS)] for 24 hrs. The cpTi impedance outcomes were a complex function of voltage, solution constituents, and immersion time. In the 0 mV to +1000 mV range, oxide growth was observed over 24 hr immersion in both solutions based on decreasing current density (∼10−6 A/cm2 to ∼10−8 A/cm2) and increasing Rp (200 kΩ cm2 to ∼10 MΩ cm2). Below 0 mV, the 24 hr Rp decreased with negative potential to ∼15 kΩ cm2. After 24 hr immersion, oxide dissolution and/or adsorption of organic species caused the capacitance to increase at −1000 mV (AMEM + FBS & PBS) and at −600 mV (AMEM + FBS only). Twenty‐four hours of immersion in AMEM + FBS at −1000 mV and −600 mV produced a surface coloration that is likely due to alteration of oxide valance state and/or doping level. This work shows that Ti surface oxide and its electrochemical behavior can be altered dramatically under sustained cathodic potentials. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010
Effect of curing mode on bond strength of self‐adhesive resin luting cements to dentin
Authors: Aguiar T. R. , Di Francescantonio M. , Ambrosano G. M. B. , Giannini M.
Published: January 2010

In this study, the in vitro bond strength of dual‐curing resin cements to indirect composite restorations when the cement was either light polymerized or allowed to only autopolymerize was evaluated. Occlusal dentin surfaces of 56 extracted human third molars were flattened to expose coronal dentin. Teeth were assigned to eight groups (n = 7) according to resin cement products and polymerization modes: conventional cement (Panavia F 2.0; Kuraray Medical) and self‐adhesive cements [RelyX Unicem (3M ESPE), BisCem (Bisco), and G‐Cem (GC Corp.)]. Cements were applied to prepolymerized resin discs (2‐mm‐thick Sinfony; 3M ESPE), which were subsequently bonded to the prepared dentin surfaces. The restored teeth were either light‐polymerized through the overlying composite according to manufacturers' instructions or were allowed to only self‐cure. After 24 h, the teeth and restorations were sectioned to obtain multiple bonded beams (1.0 mm2) and tested in tension at a crosshead speed of 0.5 mm/min until failure. Data (MPa) were analyzed by two‐way ANOVA and Tukey test (α = 0.05). Light activation of some cement systems (G‐Cem and Panavia F 2.0) increased the bond strength, while the curing mode did not affect the bond strength for some (RelyX Unicem and BisCem). The bond strength in the autopolymerized mode varied among products. In general, the use of self‐adhesive resin cements did not provide significantly higher bond strengths than that of a conventional material, and two self‐adhesive cements yielded significantly lower bond values (regardless of cure mode) than the other products. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010
Mechanical, permeability, and degradation properties of 3D designed poly(1,8 octanediol‐co‐citrate) scaffolds for soft tissue engineering
Authors: Jeong Claire G. , Hollister Scott J.
Published: January 2010

Poly(1,8‐octanediol‐co‐citric acid) (POC) is a synthetic biodegradable elastomer that can be processed into three‐dimensional (3D) scaffolds for tissue engineering. We investigated the effect of designed porosity on the mechanical properties, permeability, and degradation profiles of the POC scaffolds. For mechanical properties, scaffold compressive data were fitted to a one‐dimensional (1D) nonlinear elastic model, and solid tensile data were fitted to a Neohookean incompressible nonlinear elastic model. Chondrocytes were seeded on scaffolds to assess the biocompatibility of POC. Increased porosity was associated with increased degradation rate, increased permeability, and decreased mechanical stiffness, which also became less nonlinear. Scaffold characterization in this article will provide design guidance for POC scaffolds to meet the mechanical and biological parameters needed for engineering soft tissues such as cartilage. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010
Effect of artificial aging regimens on the performance of self‐etching adhesives
Authors: Ülker Mustafa , Özcan Mutlu , Şengün Abdulkadir , Özer Füsun , Belli Sema
Published: January 2010

This in vitro study was performed to compare the microtensile bond strengths (MTBS) of current self‐etching adhesives to dentin and to evaluate the effects of artificial aging [(thermocycling (TC) and/or mechanic loading (ML)] on MTBS and on nanoleakage of self‐etching adhesives. Two‐step (AdheSE Bond, Clearfil Protect Bond, Clearfil SE Bond, Optibond Self‐Etch) and one‐step (Hybrid Bond, G‐bond, Clearfil Tri‐S Bond, and Adper Prompt L‐Pop) self‐etching adhesives were tested. Resin composite build‐ups were created, and the specimens were subjected to 104 TC, 105 ML, and 104/105 TC/ML. Non‐aged specimens served as controls. In the control group, no significant differences were found among the MTBS of the one‐step self‐etching adhesives and among those of three two‐step self‐etching adhesives (AdheSE Bond, Clearfil Protect Bond, and Clearfil SE Bond) (p > 0.05). The MTBS of AdheSE Bond and Clearfil Protect Bond were higher than were those of all one‐step self‐etching adhesives and than those of Optibond Self‐Etch. The MTBS of Clearfil SE Bond was higher than were those of two one‐step self‐etching adhesives (Adper Prompt L‐Pop, G‐bond) (p < 0.05). Compared with the non‐aged controls, TC did not decrease (p > 0.05), but ML and TC/ML significantly decreased the MTBS of the adhesives tested (p < 0.05). Two‐step self‐etching adhesives tended to fail more cohesively in dentin. Transmission electron microscopy revealed different nanoleakage patterns in the adhesive and hybrid layers of all adhesives examined, and signs of additional silver‐filled water channels were more readily detectable after TC/ML. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010
Ceramic scaffolds produced by computer‐assisted 3D printing and sintering: Characterization and biocompatibility investigations
Authors: Warnke Patrick H. , Seitz Hermann , Warnke Frauke , Becker Stephan T. , Sivananthan Sureshan , Sherry Eugene , Liu Qin , Wiltfang Jörg , Douglas Timothy
Published: January 2010

Hydroxyapatite (HAP) and tricalcium phosphate (TCP) are two very common ceramic materials for bone replacement. However, in general HAP and TCP scaffolds are not tailored to the exact dimensions of the defect site and are mainly used as granules or beads. Some scaffolds are available as ordinary blocks, but cannot be customized for individual perfect fit. Using computer‐assisted 3D printing, an emerging rapid prototyping technique, individual three‐dimensional ceramic scaffolds can be built up from TCP or HAP powder layer by layer with subsequent sintering. These scaffolds have precise dimensions and highly defined and regular internal characteristics such as pore size. External shape and internal characteristics such as pore size can be fabricated using Computer Assisted Design (CAD) based on individual patient data. Thus, these scaffolds could be designed as perfect fit replacements to reconstruct the patient's skeleton. Before their use as bone replacement materials in vivo, in vitro testing of these scaffolds is necessary. In this study, the behavior of human osteoblasts on HAP and TCP scaffolds was investigated. The commonly used bone replacement material BioOss® served as control. Biocompatibility was assessed by scanning electron microscopy (SEM), fluorescence microscopy after staining for cell vitality with fluorescin diacetate (FDA) and propidium iodide (PI) and the MTT, LDH, and WST biocompatibility tests. Both versions were colonised by human osteoblasts, however more cells were seen on HAP scaffolds than TCP scaffolds. Cell vitality staining and MTT, LDH, and WST tests showed superior biocompatibility of HAP scaffolds to BioOss®, while BioOss® was more compatible than TCP. Further experiments are necessary to determine biocompatibility in vivo. Future modifications of 3D printed scaffolds offer advantageous features for Tissue Engineering. The integration of channels could allow for vascular and nerve ingrowth into the scaffold. Also the complex shapes of convex and concave articulating joint surfaces maybe realized with these rapid prototyping techniques. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010
Hyperosmolarity enhanced susceptibility to renal tubular fibrosis by modulating catabolism of type I transforming growth factor‐β receptors
Authors: Chiang Tai‐An , Yang Yu‐Lin , Yang Ya‐Ying , Hu Min‐Hsiu , Wu Pei‐Fen , Liu Shu‐Fen , Huang Ruay‐Ming , Liao Tung‐Nan , Hung Chien‐Ya , Hung Tsung‐Jen , Lee Tao‐Chen
Published: January 2010

Hyperosmolarity plays an essential role in the pathogenesis of diabetic tubular fibrosis. However, the mechanism of the involvement of hyperosmolarity remains unclear. In this study, mannitol was used to evaluate the effects of hyperosmolarity on a renal distal tubule cell line (MDCK). We investigated transforming growth factor‐β receptors and their downstream fibrogenic signal proteins. We show that hyperosmolarity significantly enhances the susceptibility to exogenous transforming growth factor (TGF)‐β1, as mannitol (27.5 mM) significantly enhanced the TGF‐β1‐induced increase in fibronectin levels compared with control experiments (5.5 mM). Specifically, hyperosmolarity induced tyrosine phosphorylation on TGF‐β RII at 336 residues in a time (0–24 h) and dose (5.5–38.5 mM) dependent manner. In addition, hyperosmolarity increased the level of TGF‐β RI in a dose‐ and time‐course dependent manner. These observations may be closely related to decreased catabolism of TGF‐β RI. Hyperosmolarity significantly downregulated the expression of an inhibitory Smad (Smad7), decreased the level of Smurf 1, and reduced ubiquitination of TGF‐β RI. In addition, through the use of cycloheximide and the proteasome inhibitor MG132, we showed that hyperosmolarity significantly increased the half‐life and inhibited the protein level of TGF‐β RI by polyubiquitination and proteasomal degradation. Taken together, our data suggest that hyperosmolarity enhances cellular susceptibility to renal tubular fibrosis by activating the Smad7 pathway and increasing the stability of type I TGF‐β receptors by retarding proteasomal degradation of TGF‐β RI. This study clarifies the mechanism underlying hyperosmotic‐induced renal fibrosis in renal distal tubule cells. J. Cell. Biochem. 109: 663–671, 2010. © 2010 Wiley‐Liss, Inc.
Giant cell tumor of a tendon sheath mimicking an axillary lymph node
Authors: Sohn Yu‐Mee , Kim Ah‐Hyun , Choi Junjeong , Kim Eun‐Kyung , Moon Hee Jung , Kim Min Jung , Park Young Nyun , Kwak Jin Young
Published: January 2010

A giant cell tumor of the tendon sheath (GCTTS) is 1 of the most common soft‐tissue tumors of the hand and wrist, while the 2nd most frequent site is the ankle‐foot complex. Although various solid tumors can develop in the axilla, GCTTS has not yet been reported. We describe the sonographic appearance of GCTTS in the axilla. © 2010 Wiley Periodicals, Inc. J Clin Ultrasound 2010
Diagnostic accuracy of real‐time 3D sonography in the diagnosis of congenital Mullerian anomalies in high‐risk patients with respect to the phase of the menstrual cycle
Authors: Caliskan Eray , Ozkan Sabiha , Cakiroglu Yigit , Sarisoy Hasan Tahsin , Corakci Aydin , Ozeren Semih
Published: January 2010

Purpose.

To compare the diagnostic accuracy of 2‐dimensional sonography (2DUS) and real‐time 3‐dimensional sonography (3DUS) in the diagnosis of congenital mullerian defects (CMD) with respect to the phase of the menstrual endometrium.

Method.

The accuracy of sonography was examined on 108 women by 2 gynecologists during the 1st 5 days after cessation of menstrual flow and then re‐examined at the cycle days 20–24. Entrance criteria for the patients enrolled in the study were as follows: women who were referred to our center with a suspected Mullerian anomaly at hysterosalpingography, and women who were suspected to have a uterine anomaly at our hospital during infertility, dysmenorrhea, and recurrent abortion workup. First, 1 of the gynecologists performed the 2DUS, and afterwards the 2nd gynecologist performed the real‐time 3DUS. Results from both examiners were compared and correlated with the definitive diagnosis obtained by MRI, laparoscopy, or hysteroscopy. The sensitivity and specificity values of 2DUS and real‐time 3DUS for the diagnosis of CMD were calculated at follicular and luteal phases.

Result.

Among the 108 cases suspected to have CMD, the sensitivity and specificity values of real‐time 3DUS were significantly higher in the follicular sensitivity, 94.7%, specificity, 75.0%, and luteal phases (sensitivity, 100%, specificity, 93.7%) when compared with 2DUS values (sensitivity of 30.2% and specificity of 78.1% in the follicular phase and sensitivity of 42.1% and specificity of 81.2% in the luteal phase).

Conclusion.

Real‐time 3DUS is an accurate method that can be used for the diagnosis of congenital mullerian defects. © 2010 Wiley Periodicals, Inc. J Clin Ultrasound 2010