bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional and Radiological Evaluation of a Simple Intra Operative Technique to Avoid Limb Length Discrepancy in Total Hip Arthroplasty
Authors: Desai Aravind S , Connors Liz , Board Timothy N.
Published: April 2011

We aimed to assess the radiological and functional outcome of total hip arthroplasty performed using a simple technique for intra-operative leg length assessment. The comparative group was made up of patients receiving total hip arthroplasty prior to introduction of the technique. Fifty patients were studied in each group. The pre- and 3 month post-operative leg length difference (LLD) was measured radiologically along with pre- and 12 months post-operative Oxford hip scores (OHS) and University of California Los Angeles (UCLA) activity scores. There were no statistically significant differences in pre-operative parameters between the two groups. The mean LLD in the new technique group was 0.46mm which was significantly less than in the control group (p< 0.001). Post operative OHS values were worse when shortening or lengthening was >5mm in both groups. UCLA activity scores were significantly better in the new technique group than in the control group (p< 0.001). The overall radiological and functional outcome of the patients was better in the new technique group.

Functional outcome is related to small differences in leg length and our simple new technique can be used to control leg length intraoperatively.
Sexual Activity and Total Hip Arthroplasty: A Survey of Patients' and Surgeons' Perspectives
Authors: Wall Peter D.H. , Hossain Munier , Ganapathi Muthu , Andrew John G.
Published: April 2011

It is not clear if regaining sexual activity is important for patients undergoing total hip arthroplasty (THA) or whether hip surgeons are aware of and manage the concerns of their patients in this context. A questionnaire survey was conducted on 100 patients undergoing THA immediately before and six months after surgery. All members of the British Hip Society with a valid email address were surveyed.

86 patients responded. 71 were sexually active and of these, 55 (77%) believed their hip pathology had been limiting their sex lives. 39 (55%) would have preferred further information than was provided. 51 (72%) patients had recommenced sexual activity by six months post operation.

83 of 140 surgeons responded. 30 (36%) surgeons enquired preoperatively if symptoms were interfering with patients' sex lives and 32 (39%) provided written information about sexual activity following THA. 55 (66%) surgeons believed four weeks after surgery patients could resume sexual activity but only 21 (25%) surgeons regularly advised patients about an appropriate time to resume sexual activity. Sexual activity is adversely affected in many patients awaiting THA and regaining sexual function is important to these patients. Most surgeons do not discuss this with their patients and may not be aware of their patients' expectations in this respect.
Biomimetic Materials for Bone Tissue Engineering – State of the Art and Future Trends
Authors: Cordonnier Thomas , Sohier Jérôme , Rosset Philippe , Layrolle Pierre
Published: April 2011

Bone tissue engineering is extremely promising for regenerating large bone defects in orthopedic or maxillofacial surgery. It consists of harvesting, culturing and differentiating human mesenchymal stem cells in combination with scaffolds. Different cell sources, such as bone marrow or adipose tissue, have been studied. Biomaterials resembling bone extracellular matrix have been used for scaffolding cells. However, these macroporous calcium phosphate ceramics or biodegradable polymers are two dimensional structures at the cellular level and have low osteogenesis properties in vivo. In this paper, several biomimetic approaches involving hydrogels or particles for 3‐dimensional (3D) cell cultures are reviewed. High numbers of cells for low amounts of material induced abundant extracellular matrix formation in vitro and relatively large amounts of bone tissue formation in vivo. In addition, the 3D culture of several cell populations should make it easier for bone tissue constructs to vascularize, thus lifting the limits of current clinical applications.
A Printable Photopolymerizable Thermosensitive p(HPMAm‐lactate)‐PEG Hydrogel for Tissue Engineering
Authors: Censi Roberta , Schuurman Wouter , Malda Jos , di Dato Giorgio , Burgisser Petra E. , Dhert Wouter J. A. , van Nostrum Cornelus F. , di Martino Piera , Vermonden Tina , Hennink Wim E.
Published: April 2011

Bioprinting is a new technology in regenerative medicine that allows the engineering of tissues by specific placement of cells in biomaterials. Importantly, the porosity and the relatively small dimensions of the fibers allow rapid diffusion of nutrients and metabolites. This technology requires the availability of hydrogels that ensure viability of encapsulated cells and have adequate mechanical properties for the preparation of structurally stable and well‐defined three‐dimensional constructs. The aim of this study is to evaluate the suitability of a biodegradable, photopolymerizable and thermosensitive A–B–A triblock copolymer hydrogel as a synthetic extracellular matrix for engineering tissues by means of three dimensional fiber deposition. The polymer is composed of poly(N‐(2‐hydroxypropyl)methacrylamide lactate) A‐blocks, partly derivatized with methacrylate groups, and hydrophilic poly(ethylene glycol) B‐blocks of a molecular weight of 10 kDa. Gels are obtained by thermal gelation and stabilized with additional chemical cross‐links by photopolymerization of the methacrylate groups coupled to the polymer. A power law dependence of the storage plateau modulus of the studied hydrogels on polymer concentration is observed for both thermally and chemically cross‐linked hydrogels. The hydrogels demonstrated mechanical characteristics similar to natural semi‐flexible polymers, including collagen. Moreover, the hydrogel shows suitable mechanical properties for bioprinting, allowing subsequent layer‐by‐layer deposition of gel fibers to form stable constructs up to at least 0.6 cm (height) with different patterns and strand spacing. The resulting constructs have reproducible vertical porosity and the ability to maintain separate localization of encapsulated fluorescent microspheres. Moreover, the constructs show an elastic modulus of 119 kPa (25 wt% polymer content) and a degradation time of approximately 190 days. Furthermore, high viability is observed for encapsulated chondrocytes after 1 and 3 days of culture. In summary, we conclude that the evaluated hydrogel is an interesting candidate for bioprinting applications.
An Emerging Pore‐Making Strategy: Confined Swelling‐Induced Pore Generation in Block Copolymer Materials
Authors: Wang Yong , Li Fengbin
Published: April 2011

Block copolymers (BCPs) composed of two or more thermodynamically incompatible homopolymers self‐assemble into periodic microdomains. Exposing self‐assembled BCPs with solvents selective to one block causes a swelling of the domains composed of this block. Strong swelling in the confinement imposed by the matrix of the other glassy block leads to well‐defined porous structures via morphology reconstruction. This confined swelling‐induced pore‐making process has emerged recently as a new strategy to produce porous materials due to synergic advantages that include extreme simplicity, high pore regularity, involvement of no chemical reactions, no weight loss, reversibility of the pore forming process, etc. The mechanism, kinetics, morphology, and governing parameters of the confined swelling‐induced pore‐making process in BCP thin films are discussed, and the main applications of nanoporous thin films in the fields of template synthesis, surface patterning, and guidance for the areal arrangements of nanomaterials and biomolecules are summarized. Recent, promising results of extending this mechanism to produce BCP nanofibers or nanotubes and bulk materials with well‐defined porosity, which makes this strategy also attractive to researchers outside the nanocommunity, are also presented.
Investigating regional mobility in the southern hinterland of the Wari empire: Biogeochemistry at the site of Beringa, Peru
Authors: Knudson Kelly J. , Tung Tiffiny A.
Published: April 2011

Empires have transformed political, social, and environmental landscapes in the past and present. Although much research on archaeological empires focuses on large‐scale imperial processes, we use biogeochemistry and bioarchaeology to investigate how imperialism may have reshaped regional political organization and regional migration patterns in the Wari Empire of the Andean Middle Horizon (ca. AD 600–1000). Radiogenic strontium isotope analysis of human remains from the site of Beringa in the Majes Valley of southern Peru identified the geographic origins of individuals impacted by the Wari Empire. At Beringa, the combined archaeological human enamel and bone values range from 87Sr/86Sr = 0.70802 − 0.70960, with a mean 87Sr/86Sr = 0.70842 ± 0.00027 (1σ, n = 52). These data are consistent with radiogenic strontium isotope data from the local fauna in the Majes Valley and imply that most individuals were local inhabitants, rather than migrants from the Wari heartland or some other locale. There were two outliers at Beringa, and these “non‐local” individuals may have derived from other parts of the South Central Andes. This is consistent with our understanding of expansive trade networks and population movement in the Andean Middle Horizon, likely influenced by the policies of the Wari Empire. Although not a Wari colony, the incorporation of small sites like Beringa into the vast social and political networks of the Middle Horizon resulted in small numbers of migrants at Beringa. Am J Phys Anthropol, 2011. © 2011 Wiley‐Liss, Inc.
Female “dispersal” in hamadryas baboons: Transfer among social units in a multilevel society
Authors: Swedell Larissa , Saunders Julian , Schreier Amy , Davis Brittany , Tesfaye Teklu , Pines Mathew
Published: April 2011

Unlike most cercopithecines, hamadryas baboons (Papio hamadryas hamadryas) are characterized by female‐biased dispersal. To clarify this pattern within the context of their hierarchical social system (comprising one‐male units, clans, bands, and troops), we report here 7 years of data on female transfers among social units in wild hamadryas baboons in Ethiopia. Female tenure in one‐male units (OMUs) ranged from 1 to 2,556 days (N= 208) and survival analysis revealed a median tenure length of 1,217 days (40 months). Changes in OMU membership consisted almost exclusively of takeovers by males, not voluntary transfer. Of 130 takeovers, 67% occurred within the band and 33% across bands, and, of the 22 takeovers for which we have clan membership data, 77% occurred within, not between, clans. These results reinforce the notion that hamadryas female dispersal is not analogous to sex‐biased dispersal in other taxa, because (1) at least in Ethiopian populations, females do not disperse voluntarily but are transferred, often forcibly, by males; (2) only dispersal between bands will promote gene flow, whereas females are most often rearrangedwithinbands; (3) hamadryas females undergo social dispersal but not usually locational dispersal; and (4) while male hamadryas are far more philopatric than females, they have been observed to disperse. It thus appears that the ancestral baboon pattern of female philopatry and male dispersal has evolved into a system in which neither sex is motivated to disperse, but females are forcibly transferred by males, leading to female‐mediated gene flow, and males more rarely disperse to find females. Am J Phys Anthropol, 2011. © 2011 Wiley‐Liss, Inc.
An LC‐ESI‐MS method for the quantitative analysis of bile acids composition in fecal materials
Authors: Cai Xiaohan , Liu Yiding , Zhou Xiang , Navaneethan Udayakumar , Shen Bo , Guo Baochuan
Published: April 2011

In this work, a liquid chromatography coupled with electrospray ionization mass spectrometry (LC‐ESI‐MS) method was developed and validated for quantification of bile acids in fecal materials. Co‐eluting matrix impurities in fecal materials have been shown to greatly suppress the ionization of analytes in mass spectrometry, which is known as the matrix effect. To correct large quantitative errors caused by the matrix effect, we developed a scheme that combined the standard addition method with internal standard (SA‐IS). The fecal sample pretreatment involved a single step of extraction with ethanol. Bile acids were separated using a Luna C18 column (150 mm, 2 mm i.d., 5 µm) with gradient elution. The deprotonated analytes were detected in selective ion monitoring mode. Our results showed that, by using this method, the accuracy of quantification was significantly improved in comparison to the conventional internal standard method. The linearity, sensitivity, accuracy and precision of the method were within the range of 0.05–5 µmol/L. This SA‐IS method was successfully applied to the analysis of bile acids in the samples collected from patients diagnosed with inflammatory bowel disease. Copyright © 2011 John Wiley & Sons, Ltd.
Squaric Acid Monoamide Mannosides as Ligands for the Bacterial Lectin FimH: Covalent Inhibition or Not?
Authors: Grabosch Carsten , Hartmann Mirja , Schmidt‐Lassen Jörn , Lindhorst Thisbe K.
Published: April 2011

Bacteria use long proteinaceous appendages, called fimbriae or pili, to adhere to the surfaces of their host cells. Widely distributed among the Enterobacteriacae are type 1 fimbriae that mediate mannose‐specific bacterial adhesion through the lectin FimH, located at the fimbrial tips. It is possible to design synthetic mannosides such that they show high affinity for FimH and can thus inhibit mannose‐specific bacterial adhesion in a competitive manner. It has been found that mannosidic squaric acid monoamides serve especially well as inhibitors of type 1 fimbriae‐mediated bacterial adhesion, but it has remained unclear whether this effect is due to specific inhibition of the bacterial lectin FimH or to unspecific bioconjugation between the lectin's carbohydrate binding site and a squaric acid monoamide. A bioconjugation reaction would result in a covalently crosslinked squaric acid diamide. Here it is shown that covalent inhibition of FimH by mannosidic squaric acid derivatives is very unlikely and that compounds of this type serve rather as excellent specific candidates for low‐molecular‐weight inhibitors of bacterial adhesion. This has been verified by testing the properties of glycosidic squaric acid monoamides in diamide formation, by two different adhesion assays with a series of selected control compounds, and by molecular docking studies that further support the results obtained in the bioassays.
The First Total Synthesis of Ganglioside GalNAc‐GD1a, a Target Molecule for Autoantibodies in Guillain–Barré Syndrome
Authors: Fujikawa Kohki , Nakashima Shinya , Konishi Miku , Fuse Tomoaki , Komura Naoko , Ando Takayuki , Ando Hiromune , Yuki Nobuhiro , Ishida Hideharu , Kiso Makoto
Published: April 2011

The first synthesis of ganglioside GalNAc‐GD1a, featuring efficient glycan assembly and a cyclic glucosyl ceramide as a versatile unit for ganglioside synthesis is described. Although ganglioside GalNAc‐GD1a was first found as a brain ganglioside, IgG autoantibodies to GalNAc‐GD1a were subsequently found to be closely related to a human peripheral‐nerve disorder, Guillain–Barré syndrome, which is the commonest cause of acute flaccid paralysis worldwide. In this study, the characteristic hexasaccharide part carrying two sialic acid residues was synthesized efficiently by use of a readily accessible GM2‐core unit as a common unit. The potentially difficult coupling of the oligosaccharide and ceramide moieties was carried out by using a cyclic glucosyl ceramide as a coupling partner for the hexasaccharide part, thereby successfully providing the framework of the target compound. Global deprotection delivered the homogenous ganglioside GalNAc‐GD1a. An enzyme‐linked immunosorbent assay showed that sera from patients with Guillain–Barré syndrome reacted both with natural and with synthetic GalNAc‐GD1a.
Transglutaminase‐Mediated Synthesis of a DNA–(Enzyme)n Probe for Highly Sensitive DNA Detection
Authors: Kitaoka Momoko , Tsuruda Yukito , Tanaka Yukari , Goto Masahiro , Mitsumori Masayuki , Hayashi Kounosuke , Hiraishi Yoshiyuki , Miyawaki Katsuyuki , Noji Sumihare , Kamiya Noriho
Published: April 2011

A new synthetic strategy for DNA–enzyme conjugates with a novel architecture was explored using a natural cross‐linking catalyst, microbial transglutaminase (MTG). A glutamine‐donor substrate peptide of MTG was introduced at the 5‐position on the pyrimidine of deoxyuridine triphosphate to prepare a DNA strand with multiple glutamine‐donor sites by polymerase chain reaction (PCR). A substrate peptide that contained an MTG‐reactive lysine residue was fused to the N terminus of a thermostable alkaline phoshatase from Pyrococcus furiosus (PfuAP) by genetic engineering. By combining enzymatically the substrate moieties of MTG introduced to the DNA template and the recombinant enzyme, a DNA–(enzyme)n conjugate with 1:n stoichiometry was successfully obtained. The enzyme/DNA ratio of the conjugate increased as the benzyloxycarbonyl‐L‐glutaminylglycine (Z‐QG) moiety increased in the DNA template. The potential utility of the new conjugate decorated with signaling enzymes was validated in a dot blot hybridization assay. The DNA–(enzyme)n probe could clearly detect 104 copies of the target nucleic acid with the complementary sequence under harsh hybridization conditions, thereby enabling a simple detection procedure without cumbersome bound/free processes associated with a conventional hapten–antibody reaction‐based DNA‐detection system.
Revisiting the Lipase from Pseudomonas aeruginosa: Directed Evolution of Substrate Acceptance and Enantioselectivity Using Iterative Saturation Mutagenesis
Authors: Prasad Shreenath , Bocola Marco , Reetz Manfred T.
Published: April 2011

The most thoroughly studied enzyme in directed evolution is the lipase from Pseudomonas aeruginosa (PAL) as a catalyst in the hydrolytic kinetic resolution of 2‐methyldecanoic acid p‐nitrophenyl ester. Seminal studies utilized epPCR, saturation mutagenesis and DNA shuffling or combinations thereof. With current emphasis on efficacy in laboratory evolution, however, we recently applied our previously developed method, iterative saturation mutagenesis (ISM), to the same catalytic system, discovering that this approach is much more efficient than the original strategies. Herein, we consider PAL once more, this time testing ISM as a means to broaden the substrate scope of this lipase by studying bulky substrates of the type 2‐phenylalkanoic acid esters as substrates that are not accepted by the WT. Highly active and enantioselective (E up to 436) mutants were evolved, a process that required only small mutant libraries and thus a minimum of screening effort. A theoretical investigation using molecular dynamics simulations and docking experiments revealed the source of enhanced activity and stereoselectivity.
Invariant Oxidation State of Copper but not of Ruthenium in Complexes with Noninnocent N‐(2‐Methyl‐5,8‐dioxo‐5,8‐dihydroquinolin‐7‐yl)acetamide: A Combined Structural, Electrochemical and Spectroelectrochemical Investigation
Authors: Paretzki Alexa , Das Hari Sankar , Weisser Fritz , Scherer Thomas , Bubrin Denis , Fiedler Jan , Nycz Jacek E. , Sarkar Biprajit
Published: April 2011

The compounds [(dppf)Cu(L)](BF4) (1[BF4]) [dppf = 1,1′‐bis(diphenylphosphanylferrocene), L = N‐(2‐methyl‐5,8‐dioxo‐5,8‐dihydroquinolin‐7‐yl)acetamide] and [(acac)2Ru(L)] (2) (acac = acetylacetonato) were prepared from the reactions of [Cu(dppf)(CH3CN)2](BF4) or [Ru(acac)2(CH3CN)2], respectively with L. Structural characterization of 1[BF4] shows a distorted tetrahedral coordinated copper center. Both complexes show one‐electron reversible oxidation as well as reduction processes in their cyclic voltammogram. The first oxidation process of 1[BF4] leads to absorptions at around 900 nm in the UV/Vis/NIR spectrum and results in an EPR silent species up to 110 K thus indicating a dppf‐centered oxidation. The reduction processes of 1[BF4] show features in the UV/Vis/NIR, IR as well as EPR spectrum that are compatible with L‐centered redox processes. In contrast to this, the ruthenium complex 2 shows metal‐centered spin in both the one‐electron oxidized as well as reduced forms. These results show that the copper center does not participate in the redox processes in 1[BF4] whereas the ruthenium center participates strongly in the electron‐transfer processes in 2. Results obtained from electrochemistry as well as from UV/Vis/NIR, IR, and EPR spectroelectrochemistry are invoked to show the noninnocent nature of L in these complexes as well as the more relative importance of metal–L covalency in 2 as compared to 1[BF4].
Identification of a Δ4‐desaturase from the microalga Ostreococcus lucimarinus
Authors: Ahmann Katharina , Heilmann Mareike , Feussner Ivo
Published: April 2011

Very long chain PUFA (VLCPUFA) like DHA are essential and health‐beneficial components of the human diet. Due to a shortfall in VLCPUFA supply, research is ongoing to establish VLCPUFA production in heterologous systems like for example oilseed plants. For this purpose it is crucial to identify the required enzymes from primary producers of VLCPUFA. Here, we describe a cDNA from the microalga Ostreococcus lucimarinus coding for a Δ4‐fatty acid desaturase. It exhibits a cytochrome b5 domain fused to its amino terminus and three histidine boxes that are typically found in front‐end desaturases. Heterologous expression of the partly codon‐optimized version of the cDNA in yeast revealed that the encoded protein catalyzes the desaturation of (n‐3)‐ as well as (n‐6)‐substrates with a preference for VLCPUFA. In yeast it localized at the endoplasmic reticulum (ER) membrane and analysis of the product distribution into different lipid classes suggested that the enzyme most likely acts in a lipid‐dependent manner.

Practical applications: The identified Δ4‐desaturase may be useful for the production of DHA in transgenic oleaginous organisms like annual oilseed crops.
Direct Arylation of Pyrrole Derivatives in Ionic Liquids
Authors: Vakuliuk Olena , Gryko Daniel T.
Published: April 2011

An efficient methodology for the direct arylation of pyrrole derivatives has been developed. The reaction proceeds smoothly with a wide range of structurally diverse aryliodides. Derivatives bearing an N,N‐dimethylamino group at the 1‐position and an aryl substituent at the 2‐position were prepared for the first time. This protocol is more environmentally friendly than those previously reported because it is free of transition metals and utilizes ionic liquids rather than volatile organic solvents.
Total Synthesis of Lavendamycin by a [2+2+2] Cycloaddition
Authors: Nissen Felix , Detert Heiner
Published: April 2011

The total synthesis of the bacterial‐derived, pentacyclic, antitumor antibiotic lavendamycin has been achieved through a highly convergent strategy. The key step of this synthesis is a ruthenium‐catalyzed [2+2+2] cycloaddition of an electron‐deficient nitrile to an alkynyl‐ynamide to prepare the carboline scaffold. The elaborate cycloaddition substrate is obtained in few steps by an N‐ethynylation using alkynyliodonium salt chemistry and two palladium‐catalyzed cross‐coupling reactions. An efficient synthesis of a halogenated quinoline‐5,8‐dione building block starting from hydroquinone is presented.
Impact of the kind of ultraviolet light on the photocatalytic degradation kinetics of the TiO2/UV process
Authors: Cortés J.A. , Alarcón‐Herrera M.T. , Villicaña‐Méndez M. , González‐Hernández J. , Pérez‐Robles J.F.
Published: April 2011

Advanced oxidation processes have gained importance in the last decade because of their application in the treatment of wastewater containing toxic, recalcitrant, and/or colored compounds. The catalyst TiO2, activated with ultraviolet (UV) light, has been used for the degradation of different kinds of compounds, but its activation has been performed with different varieties of UV light without a clear reason for choosing any of the three wavelengths that can be generated with commercially available sources. This work evaluates the degradation speed of acid blue 9 dye through the activation of TiO2 with the different kinds of UV light (UV‐A, UV‐B, and UV‐C). The results indicate that the wavelength of the light used for photoactivation has an impact on the dye degradation speed; shorter wavelengths lead to faster degradation.

The analysis of the possible causes affecting the degradation speed was performed by superposing the emission bands of the used UV light with the absorption bands of the dye and catalyst. It is concluded that the interaction zone between the type of UV light and the catalyst notoriously impacts the degradation kinetics. © 2011 American Institute of Chemical Engineers Environ Prog, 2011.
Erosion rates and mechanisms of knickzone retreat inferred from 10Be measured across strong climate gradients on the northern and central Andes Western Escarpment
Authors: Abbühl Luca M. , Norton Kevin P. , Jansen John D. , Schlunegger Fritz , Aldahan Ala , Possnert Göran
Published: April 2011

A steep escarpment edge, deep gorges and distinct knickzones in river profiles characterize the landscape on the Western Escarpment of the Andes between ~5°S and ~18°S (northern Peru to northern Chile). Strong north–south and east–west precipitation gradients are exploited in order to determine how climate affects denudation rates in three river basins spanning an otherwise relatively uniform geologic and geomorphologic setting. Late Miocene tectonics uplifted the Meseta/Altiplano plateau (~3000 m a.s.l.), which is underlain by a series of Tertiary volcanic‐volcanoclastic rocks. Streams on this plateau remain graded to the Late Miocene base level. Below the rim of the Meseta, streams have responded to this ramp uplift by incising deeply into fractured Mesozoic rocks via a series of steep, headward retreating knickzones that grade to the present‐day base level defined by the Pacific Ocean.

It is found that the Tertiary units on the plateau function as cap‐rocks, which aid in the parallel retreat of the sharp escarpment edge and upper knickzone tips. 10Be‐derived catchment denudation rates of the Rio Piura (5°S), Rio Pisco (13°S) and Rio Lluta (18°S) average ~10 mm ky−1 on the Meseta/Altiplano, irrespective of precipitation rates; whereas, downstream of the escarpment edge, denudation rates range from 10 mm ky−1 to 250 mm ky−1 and correlate positively with precipitation rates, but show no strong correlation with hillslope angles or channel steepness. These relationships are explained by the presence of a cap‐rock and climate‐driven fluvial incision that steepens hillslopes to near‐threshold conditions.

Since escarpment retreat and the precipitation pattern were established at least in the Miocene, it is speculated that the present‐day distribution of morphology and denudation rates has probably remained largely unchanged during the past several millions of years as the knickzones have propagated headward into the plateau. Copyright © 2011 John Wiley & Sons, Ltd.
Selective neck dissection as an early salvage intervention for clinically persistent nodal disease following chemoradiation
Authors: Dhiwakar Muthuswamy , Robbins K. Thomas , Vieira Francisco , Rao Krishna , Malone James
Published: April 2011

Background

The aim of this study was to determine the efficacy of selective neck dissection (SND) performed for persistent nodal disease after chemoradiation.

Methods

Patients treated with definitive chemoradiation for squamous cell carcinoma of the head and neck who subsequently underwent SND for early salvage of clinically persistent nodal disease were evaluated. The primary outcome measure was regional disease control.

Results

A total of 62 patients underwent 69 SND procedures. The median time interval between completion of chemoradiation and neck dissection was 10 weeks. There was evidence of residual tumor in 32 neck dissection specimens (46%). Forty patients (65%) remained free of disease, whereas the remaining 22 patients (35%) developed a recurrence, among which 4 were regional. Of these, 3 occurred in the contralateral neck and only 1 occurred in the targeted (ipsilateral) neck.

Conclusions

SND is an effective early salvage intervention for persistent nodal disease in patients treated with chemoradiation. © 2011 Wiley Periodicals, Inc. Head Neck, 2012
Association of polymorphisms and haplotypes of the NBN gene with laryngeal cancer and multiple primary tumors of the head and neck
Authors: Ziółkowska–Suchanek Iwona , Mosor Maria , Wierzbicka Małgorzata , Fichna Marta , Rydzanicz Małgorzata , Nowak Jerzy
Published: April 2011

Background

We investigated whether genetic polymorphisms of the DNA repair gene NBN are associated with head and neck cancer risk.

Methods

We analyzed 6 polymorphisms in 175 patients with a single laryngeal tumor, 104 with multiple primary tumors but 1 malignancy (primary/second) localized in the larynx, 60 patients with multiple primary tumors localized in the head or neck, and 275 controls.

Results

Although frequencies of single nucleotide polymorphism alleles did not show marked differences, we found significant differences in haplotype frequencies between patients and controls. Haplotypes GGTTAA and ACCCGT were associated with an increased risk of laryngeal cancer (p < .0001, p = .002) and haplotypes GGCCAA and GCCCGT with an increased risk of multiple primary tumors (p < .0001, p = .039).

Conclusion

Specific haplotypes of the NBN gene may be related to increased susceptibility to laryngeal cancer and second primary tumors localized in the head and neck. © 2011 Wiley Periodicals, Inc. Head Neck, 2012
Metastatic head and neck cutaneous squamous cell carcinoma: Defining a low‐risk patient
Authors: Ebrahimi Ardalan , Clark Jonathan R. , Lorincz Balazs B. , Milross Christopher G. , Veness Michael J.
Published: April 2011

Background

The purpose of this study was to determine whether there is a “low‐risk” subset of patients with regional metastatic head and neck cutaneous squamous cell carcinoma (SCC) suitable for treatment with surgery alone and omission of adjuvant radiotherapy.

Methods

We conducted a retrospective analysis of 168 patients with a single parotid gland or neck nodal metastasis ≤3 cm in size from cutaneous SCC treated with curative intent by surgery ± adjuvant radiotherapy.

Results

Disease‐specific survival for the 33 patients treated with surgery alone was 97% at 5 years. In the subset of 19 patients without extracapsular nodal spread (ECS), there was 1 regional recurrence which was successfully salvaged yielding a 5‐year disease‐specific survival of 100%.

Conclusion

In head and neck cutaneous SCC, the subset with a single node ≤3 cm in size without ECS are at low risk of regional failure and death from cutaneous cancer. These patients may be suitable for single‐modality therapy with surgery alone. © 2011 Wiley Periodicals, Inc. Head Neck, 2012
Effects of E‐cadherin (CDH1) gene promoter polymorphisms on the risk and clinicopathologic development of oral cancer
Authors: Chien Ming‐Hsien , Chou Lin Shih‐Shen , Chung Tsung‐Te , Lin Chien‐Huang , Chou Ming‐Yung , Weng Meng‐Shih , Yang Shun‐Fa , Chen Mu‐Kuan
Published: April 2011

Background

This study investigates the association between polymorphism in the E‐cadherin/CDH1 promoter region and the risk and progression of oral cancer.

Methods

Genetic polymorphisms of CDH1‐160 and ‐347 were analyzed by polymerase chain reaction–restriction fragment length polymorphism (PCR‐RFLP) in 347 noncancer controls and in 251 patients with oral cancer.

Results

The statistical analysis showed that subjects with at least 1 varied GA allele of CDH1‐347 polymorphic genotypes or combinations of the CDH1‐160 CA/‐347 GGA, CDH1‐160 CC/‐347 GGA, or CDH1‐160 CC/‐347 GAGA genotypes had a significantly higher risk, whereas subjects with CDH1‐160 C/A or A/A had a significantly lower risk of developing oral cancer than those with wild‐type genotypes. Furthermore, elderly patients with the CDH1‐347 G/GA or GA/GA genotype were associated with a higher incidence in lymph node metastasis than were those with the G/G genotype.

Conclusions

These results suggest that CDH1‐347 polymorphisms are associated with increased risks of oral cancer, and may be a predictive factor for tumor lymph node metastasis. © 2011 Wiley Periodicals, Inc. Head Neck, 2012
Non‐invasive in vivo imaging of vessel calibre in orthotopic prostate tumour xenografts
Authors: Walker‐Samuel Simon , Boult Jessica K.R. , McPhail Lesley D. , Box Gary , Eccles Suzanne A. , Robinson Simon P.
Published: April 2011

Susceptibility contrast magnetic resonance imaging (MRI), utilising ultrasmall superparamagnetic iron oxide (USPIO) particles, was evaluated for the quantitation of vessel size index (Rv, μm), a weighted average measure of tumour blood vessel calibre, and fractional tumour blood volume (fBV, %), in orthotopically propagated murine PC3 prostate tumour xenografts. Tumour vascular architecture was assessed in vivo by MRI prior to and 24 hr after treatment with 200 mg/kg of the vascular disrupting agent ZD6126. A Bayesian hierarchical model (BHM) was used to reduce the uncertainty associated with quantitation of Rv and fBV. Quantitative histological analyses of the uptake of Hoechst 33342 for perfused vasculature, and haematoxylin and eosin staining for necrosis, were also performed to qualify the MRI data. A relatively large median Rv of 40.3 μm (90% confidence interval (CI90) = 37.4, 44.0 μm) and a high fBV of 5.4% (CI90 = 5.3, 5.5%) were determined in control tumours, which agreed with histologically determined vessel size index. Treatment with ZD6126 significantly (p < 0.01) reduced tumour Rv (34.2μm, CI90 = 31.2, 38.0 μm) and fBV (3.9%, CI90 = 3.8, 4.1%), which were validated against histologically determined significant reductions in perfusion and vessel size, and increased necrosis. Together these data (i) highlight the use of a BHM to optimise the inferential power available from susceptibility contrast MRI data, (ii) provide strong evaluation and qualification of Rv and fBV as non‐invasive imaging biomarkers of tumour vascular morphology, (iii) reveal the presence of a different vascular phenotype and (iv) demonstrate that ZD6126 exhibits good anti‐vascular activity against orthotopic prostate tumours.
Peroxotitanate‐ and monosodium metal‐titanate compounds as inhibitors of bacterial growth
Authors: Chung Whasun O. , Wataha John C. , Hobbs David T. , An Jonathan , Wong Jacqueline J. , Park Christine H. , Dogan Sami , Elvington Mark C. , Rutherford R. Bruce
Published: April 2011

Sodium titanates are ion‐exchange materials that effectively bind a variety of metal ions over a wide pH range. Sodium titanates alone have no known adverse biological effects but metal‐exchanged titanates (or metal titanates) can deliver metal ions to mammalian cells to alter cell processes in vitro. In this work, we test a hypothesis that metal‐titanate compounds inhibit bacterial growth; demonstration of this principle is one prerequisite to developing metal‐based, titanate‐delivered antibacterial agents. Focusing initially on oral diseases, we exposed five species of oral bacteria to titanates for 24 h, with or without loading of Au(III), Pd(II), Pt(II), and Pt(IV), and measuring bacterial growth in planktonic assays through increases in optical density. In each experiment, bacterial growth was compared with control cultures of titanates or bacteria alone. We observed no suppression of bacterial growth by the sodium titanates alone, but significant (p < 0.05, two‐sided t‐tests) suppression was observed with metal‐titanate compounds, particularly Au(III)‐titanates, but with other metal titanates as well. Growth inhibition ranged from 15 to 100% depending on the metal ion and bacterial species involved. Furthermore, in specific cases, the titanates inhibited bacterial growth 5‐ to 375‐fold versus metal ions alone, suggesting that titanates enhanced metal–bacteria interactions. This work supports further development of metal titanates as a novel class of antibacterials. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
Performance of six functionals (LDA, PBE, PBESOL, B3LYP, PBE0, and WC1LYP) in the simulation of vibrational and dielectric properties of crystalline compounds. The case of forsterite Mg2SiO4
Authors: De La Pierre M. , Orlando R. , Maschio L. , Doll K. , Ugliengo P. , Dovesi R.
Published: April 2011

The performance of six different density functionals (LDA, PBE, PBESOL, B3LYP, PBE0, and WC1LYP) in describing the infrared spectrum of forsterite, a crystalline periodic system with orthorhombic unit cell (28 atoms in the primitive cell, Pbmn space group), is investigated by using the periodic ab initio CRYSTAL09 code and an all‐electron Gaussian‐type basis set. The transverse optical (TO) branches of the 35 IR active modes are evaluated at the equilibrium geometry together with the oscillator strengths and the high‐frequency dielectric tensor ϵ∞. These quantities are essential to compute the dielectric function ϵ(ν), and then the reflectance spectrum R(ν), which is compared with experiment. It turns out that hybrid functionals perform better than LDA and GGA, in general; that B3LYP overperforms WC1LYP and, in turn, PBE0; that PBESOL is better than PBE; that LDA is the worst performing functional among the six under study. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Role of bridging water molecules in GSK3β‐inhibitor complexes: Insights from QM/MM, MD, and molecular docking studies
Authors: Lu Shao‐Yong , Jiang Yong‐Jun , Lv Jing , Zou Jian‐Wei , Wu Tian‐Xing
Published: April 2011

The role of water molecules is increasingly gaining interest in drug design, and several studies have highlighted their paramount contributions to the specificity and the affinity of ligand binding. In this study, we employ the two‐layer ONIOM‐based quantum mechanics/molecular mechanics (QM/MM) calculations, molecular dynamics (MD) simulations, and molecular docking studies to investigate the effect of bridging water molecules at the GSK3β‐inhibitors interfaces. The results obtained from the ONIOM geometry optimization and AIM analysis corroborated the presence of bridging water molecules that form hydrogen bonds with protein side chain of Thr138 and/or backbone of Gln185, and mediate interactions with inhibitors in the 10 selected GSK3β‐inhibitor complexes. Subsequently, MD simulations carried out on a representative system of 1R0E demonstrated that the bridging water molecule is stable at the GSK3β‐inhibitor interface and appears to contribute to the stability of the protein–inhibitor interactions. Furthermore, molecular docking studies of GSK3β‐inhibitor complexes indicated that the inhibitors can increase binding affinities and the better docked conformation of inhibitors can be obtained by inclusion of the bridging water molecules, especially for the flexible inhibitors, in docking experiments into individual protein conformations. Our results elucidate the importance of bridging water molecules at the GSK3β‐inhibitor interfaces and suggest that they might prove useful in rational drug design. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Homocysteine mediated decrease in bone blood flow and remodeling: Role of folic acid
Authors: Tyagi Neetu , Kandel Madhavi , Munjal Charu , Qipshidze Natia , Vacek Jonathan C. , Pushpakumar Sathnur B. , Metreveli Naria , Tyagi Suresh C.
Published: April 2011

Deficiencies in folate lead to increased serum concentrations of homocysteine (Hcy), which is known as hyperhomocysteinemia (HHcy), is associated with bone disorders. Although, Hcy accumulates collagen in bone and contribute to decrease in bone strength. The mechanism of Hcy induced bone loss and remodeling is unclear. Therefore, the present study was aimed to determine the role of folic acid (FA) in genetically HHcy‐associated decrease in bone blood flow and remodeling. Wild type (WT) and cystathionine‐β‐synthase heterozygous (CBS+/−) mice were used in this study and supplemented with or without FA (300 mg/kg, Hcy reducing agent) in drinking water for 6 weeks. The tibial bone blood flow was measured by laser Doppler and ultrasonic flow probe method. The tibial bone density (BD) was assessed by dual energy X‐ray absorptiometry. The bone homogenates were analyzed for oxidative stress, NOX‐4 as oxidative marker and thioredoxin‐1 (Trx‐1) as anti‐oxidant marker, bone remodeling (MMP‐9) and bio‐availability of nitric oxide (eNOS/iNOS/NO) by Western blot method. The results suggested that there was decrease in tibial blood flow in CBS+/− mice. The BD was also reduced in CBS+/− mice. There was an increase in NOX‐4, iNOS, MMP‐9 protein as well as MMP‐9 activity in CBS+/− mice and decrease in Trx‐1, eNOS protein levels, in part by decreasing NO bio‐availability in CBS+/− mice. Interestingly, these effects were ameliorated by FA and suggested that FA supplementation may have therapeutic potential against genetically HHcy induced bone loss. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29: 1511–1516, 2011
Backbone‐Thermoresponsive Hyperbranched Polyglycerol by Random Copolymerization of Glycidol and 3‐Methyl‐3‐(hydroxymethyl)oxetane
Authors: Xia Yumin , Wang Yimin , Wang Yanping , Wang Dali , Deng Hongping , Zhuang Yuanyuan , Yan Deyue , Zhu Bangshang , Zhu Xinyuan
Published: April 2011

The hyperbranched polyglycerol analog, hyperbranched poly[glycerol‐co‐3‐methyl‐3‐(hydroxymethyl)oxetane] [HP(G‐co‐M)], was synthesized in one‐step by random copolymerization of glycidol and 3‐methyl‐3‐(hydroxymethyl)oxetane (MHO). The obtained polymer exhibited a thermoresponsive behavior in an aqueous solution, and the corresponding lower critical solution temperature (LCST) could be readily adjusted by changing the feed ratio of glycidol to MHO. The MTT assay against COS‐7 cells demonstrated that HP(G‐co‐M) had low cytotoxicity. Moreover, the existence of numerous hydroxyl terminals of HP(G‐co‐M) facilitated their further modification and functionalization. All of these characteristics suggest that this novel backbone‐thermoresponsive hyperbranched polyglycerol is a promising functional material for biomedical applications.

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Rapid UV Light‐Triggered Macromolecular Click Conjugations via the Use of o‐Quinodimethanes
Authors: Gruendling Till , Oehlenschlaeger Kim K. , Frick Elena , Glassner Mathias , Schmid Christina , Barner‐Kowollik Christopher
Published: April 2011

Shining a light on click chemistry: The use of UV‐radiation as trigger signal provides a facile means to obtain spatial and temporal control over polymer conjugation reactions in addition to providing a further means of achieving orthogonality in click transformations. In the current contribution, UV‐radiation was employed to induce a highly efficient Diels–Alder conjugation of polymeric building blocks via the photo‐induced in situ formation of highly reactive cis‐dienes from a 2‐methylbenzophenone precursor.

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PREPARED: Comparison of prolonged and immediate release ropinirole in advanced Parkinson's disease
Authors: Stocchi Fabrizio , Giorgi Luigi , Hunter Brian , Schapira Anthony HV
Published: April 2011

Background: PREPARED was a randomized, parallel‐group, double‐blind, multicenter study to evaluate the efficacy of adjunctive ropinirole prolonged release (PR) versus immediate release (IR) in patients with advanced Parkinson's disease (PD). Methods: Patients received once‐daily PR (2–24 mg/d; n = 177) or three‐times‐daily IR (0.75–24 mg/d; n = 173) for 24 weeks. The primary endpoint was the proportion of patients maintaining ≥20% reduction from baseline in “off” time over two consecutive visits at Week 24 last observation carried forward (LOCF). Results: At Week 24 LOCF, PR significantly increased the proportion of patients maintaining ≥20% reduction in “off” time versus IR (adjusted odds ratio: 1.82; 95% CI: 1.16, 2.86; P = 0.009). Mean (SD) doses at Week 24 LOCF were: PR, 18.6 (6.5) mg/d; IR, 10.4 (6.4) mg/d; mean (SD) reductions from baseline in levodopa (L‐dopa) dose were –162 (226) mg and –113 (138) mg, respectively. Adverse events (AEs) were reported by 72% of patients in the PR group and 61% in the IR group; 12% and 9% of patients, respectively, withdrew from the study due to an AE, and 6% and 5%, respectively, reported serious AEs. Conclusions: Adjunctive PR provided a significantly greater improvement in symptom control in terms of the odds of achieving ≥20% maintained reduction in time spent “off” compared with IR. Interpretation may be confounded by the higher doses of PR versus IR that were achieved, in combination with lower doses of L‐dopa by the study end. Despite dosing differences, the PR titration regimen was generally well tolerated, with an AE profile similar to that of IR. © 2011 Movement Disorder Society
Comparison of subthalamic nucleus deep brain stimulation and Duodopa in the treatment of advanced Parkinson's disease
Authors: Merola Aristide , Zibetti Maurizio , Angrisano Serena , Rizzi Laura , Lanotte Michele , Lopiano Leonardo
Published: April 2011

Background:

Subthalamic nucleus deep brain stimulation (STN‐DBS) and levodopa/carbidopa enteral (Duodopa) infusion are two effective therapeutic options for the treatment of advanced Parkinson's disease (PD).

Methods:

Retrospectively, this study compared the two procedures, evaluating 40 PD patients who underwent either STN‐DBS or a percutaneous gastrostomy (PEG) for Duodopa infusion. Duodopa group comprised 20 patients, with a mean follow‐up of ∼15 months, treated by Duodopa infusion rather than STN‐DBS because of the presence of neurosurgical contraindications, age > 70 years‐old, moderate cognitive impairment or patient's unwillingness to undergo neurosurgery. The STN‐DBS group comprised 20 consecutive patients similar to the patients of the Duodopa group for age at the disease onset, age at the procedure, follow‐up, and duration of motor complications. The only difference concerned neuropsychological functions, which were more impaired in the group of Duodopa patients. Clinical and neuropsychological data were compared at baseline and at follow‐up for the two procedures.

Results:

Both procedures showed a significant improvement in UPDRS‐II, UPDRS‐III, and UPDRS‐IV and a considerable reduction in the percentage of waking day spent in “off,” whereas only the STN‐DBS group showed a significant improvement in dyskinesias duration and disability. STN‐DBS was associated to a significant drop in the phonemic verbal fluency score, whereas Duodopa patients showed a milder worsening in this task. The procedure‐related complications occurred more frequently with Duodopa.

Conclusion:

STN‐DBS and Duodopa showed a significant efficacy on motor symptoms, activities of daily living, and motor complications. The group of Duodopa‐treated patients developed more procedure‐related complications. © 2011 Movement Disorder Society