bluuebunny/crossref_metadata_2025 huggingface dataset:
The combination of the biomarkers urinary C‐terminal telopeptide of type II collagen, serum cartilage oligomeric matrix protein, and serum chondroitin sulfate 846 reflects cartilage damage in hemophilic arthropathy
Authors: Jansen Nathalie W. D. , Roosendaal Goris , Lundin Björn , Heijnen Lily , Mauser‐Bunschoten Evelien , Bijlsma Johannes W. J. , Theobald Matthias , Lafeber Floris P. J. G.
Published: December 2008

Objective

Hemophilic arthropathy, with characteristics of inflammatory (rheumatoid arthritis) and degenerative (osteoarthritis) joint damage, occurs at an early age, is associated with minor comorbidity, and is restricted to 3 pairs of large joints. The aim of this study was to determine whether commonly used serum and/or urinary biomarkers of cartilage and bone turnover for which assay kits are commercially available are associated with the severity of joint damage in patients with various degrees of hemophilic arthropathy and, thus, whether this disease could be useful in the identification and evaluation of such biomarkers.

Methods

Blood and urine samples were collected from 36 patients with various degrees of hemophilic arthropathy. Commercially available assays for the most frequently investigated serum and urine biomarkers were performed: urinary C‐terminal telopeptide of type I collagen (CTX‐I), urinary CTX‐II, serum CTX‐I, serum CTX‐II, serum cartilage oligomeric matrix protein (COMP), serum cartilage cleavage products C1,2C and C2C, and serum chondroitin sulfate 846 (CS‐846). Radiographs of the ankles, knees, and elbows in all patients were evaluated for the degree of joint damage according to the Pettersson score, which is based on cartilage and periarticular bone changes and is specific for hemophilic arthropathy.

Results

Urinary CTX‐II, serum C1,2C, and serum CS‐846 levels correlated with the overall Pettersson score and with the joint space narrowing component. Regression analysis showed that combined indexes of different markers increased the degree of correlation for the combination of urinary CTX‐II, serum COMP, and serum CS‐846. Bone‐specific markers (urinary/serum CTX‐I and serum C1,2C) did not correlate with specific bone‐related items of the Pettersson score (osteoporosis and erosions).

Conclusion

These results support the idea that a combination of biomarkers relates significantly better to the severity of joint damage than do individual biomarkers. The combination of urinary CTX‐II, serum COMP, and serum CS‐846 correlated best with the degree of arthropathy. Because of its specific characteristics and restricted involvement, hemophilic arthropathy may prove useful in the screening of newly developed biomarkers of joint damage.
Patient‐reported outcomes in a randomized trial comparing four different treatment strategies in recent‐onset rheumatoid arthritis
Authors: van der Kooij S. M. , de Vries‐Bouwstra J. K. , Goekoop‐Ruiterman Y. P. M. , Ewals J. A. P. M. , Han K. H. , Hazes J. M. W. , Kerstens P. J. S. M. , Peeters A. J. , van Zeben D. , Breedveld F. C. , Huizinga T. W. J. , Dijkmans B. A. C. , Allaart C. F.
Published: December 2008

Objective

To investigate the effectiveness of 4 different treatment strategies for recent‐onset rheumatoid arthritis (RA) on 2‐year patient‐reported outcomes, including functioning and quality of life.

Methods

A total of 508 patients with recent‐onset RA were randomly assigned to 1) sequential monotherapy, 2) step‐up combination therapy, both starting with methotrexate, 3) initial combination therapy, including a tapered high‐dose prednisone, or 4) initial combination therapy with methotrexate and infliximab. Treatment was adjusted every 3 months if the Disease Activity Score (DAS) remained >2.4. The McMaster Toronto Arthritis Patient Preference Disability Questionnaire, the Short Form 36 (SF‐36), and scores for pain, global health, and disease activity measured on a 100‐mm visual analog scale (VAS) were compared between groups at baseline and every 3 months thereafter for 2 years.

Results

After 2 years, all patient‐reported outcomes had improved significantly from baseline, irrespective of the treatment strategy. SF‐36 subscale scores approached population norms for 3 physical components, and achieved population norms (P > 0.05) for bodily pain and 4 mental components. Improvement in functioning, VAS scores, and physical items of the SF‐36 occurred significantly earlier in patients treated with initial combination therapies (all comparisons after 3 months: overall P < 0.001; P < 0.05 for groups 1 and 2 versus groups 3 and 4).

Conclusion

All 4 DAS‐driven treatment strategies resulted in substantial improvements in functional ability, quality of life, and self‐assessed VAS scores after 2 years. Initial combination therapy led to significantly faster improvement in all patient‐reported measures.
Development and testing of a decision board to help clinicians present treatment options to lupus nephritis patients in Brazil
Authors: De Abreu Mirhelen Mendes , Gafni Amiran , Ferraz Marcos Bosi
Published: December 2008

Objective

Decision boards (DBs) help clinicians present options and include patients in the decision‐making process. Our objective was to describe the steps to develop a DB to support shared decision making and assess reliability and construct validity.

Methods

Systemic lupus erythematosus (SLE) scenarios were designed with the support of experts for disease severity, potential side effects, and outcomes. The DB comprised clinical information, 2 different treatment options (oral and intravenous), a description of the potential to control SLE within 5 years, and a list of potential side effects. Patients selected what they thought would be the 3 worst side effects and were informed of the probability that these would occur. We presented the DB to 172 patients who were asked to select and justify 1 treatment option. Reliability was assessed by kappa statistics. Construct validity was tested by an a priori hypothesis, analyzing the correlation between treatment decision and side effects selected, self‐assessment score, educational level, and clinical aspects.

Results

Patients favored oral medication, and side effects most often listed were iatrogenic cancer (44.2%), hair loss (21.6%), and severe infection (19.1%). Justifications were risk (48.9%), practicality (36.6%), effectiveness (12.2%), and risk‐benefit tradeoff (2.3%). Reliability was similar to that found in the test phase (κ = 0.689, P < 0.001). Validity was tested by prediction of treatment decision based on the undesirable side effects selected (P = 0.047). DB content was clear and easy for all patients to understand (P = 0.05). Immunosuppressive drugs influenced patient decisions (P = 0.006).

Conclusion

DB is a reliable and valid instrument to assess SLE patient preference.
How to evaluate and improve the reliability of power Doppler ultrasonography for assessing enthesitis in spondylarthritis
Authors: D'agostino Maria Antonietta , Aegerter Philippe , Jousse‐Joulin Sandrine , Chary‐Valckenaere Isabelle , Lecoq Bertrand , Gaudin Philippe , Brault Isabelle , Schmitz Jérôme , Dehaut François‐Xavier , Le Parc Jean‐marie , Breban Maxime , Landais Paul
Published: December 2008

Objective

To evaluate and improve the reliability of power Doppler ultrasonography (PDUS) for detecting and scoring enthesitis in patients with spondylarthitis, using a 3‐step procedure.

Methods

In the first step, we evaluated the reliability of 5 sonographers by bilaterally scanning 5 entheses twice in 5 patients. In the second step, starting from disagreements observed during the first step, we established consensus guidelines. The sonographers' implementation was further evaluated in 2 reliability exercises: one on 60 PDUS enthesitis images and the other by scanning 5 new patients. In the third step, we performed a final reliability evaluation of 5 additional patients after 1 year. Kappa coefficients (κ) as well as variance component analysis (VCA) and generalizability theory (GT) were used to assess reliability.

Results

The initial intra‐ and interobserver reliability were poor, especially for detecting and scoring Doppler signal. VCA and GT showed that most variability was accounted for by interaction between sonographer and enthesis. Implementation of consensus guidelines was associated with a significant improvement in Doppler reliability between the first and second steps (mean interobserver κ increased from 0.13 to 0.51 for binary Doppler scoring in patients; P < 0.005), which persisted in the third step (mean interobserver κ = 0.57). The high GT coefficients reached in the last steps supported such improvement.

Conclusion

The 3‐step procedure used in this study to standardize PDUS technique was associated with a significant improvement in interobserver reliability for detecting enthesitis in spondylarthritis patients. Such an approach can be useful to standardize PDUS assessment of musculoskeletal disorders.
Effectiveness of treatment of calcific tendinitis of the shoulder by disodium EDTA
Authors: Cacchio Angelo , De Blasis Elisabetta , Desiati Piergiorgio , Spacca Giorgio , Santilli Valter , De Paulis Fosco
Published: December 2008

Objective

To evaluate the effectiveness of disodium EDTA administration in the treatment of calcific tendinitis of the shoulder.

Methods

Eighty patients with radiographically verified calcific tendinitis of the shoulder were enrolled between September 2001 and October 2003. Patients were randomly assigned to either a study group (n = 40) or a control group (n = 40). Pain and functional level were evaluated before and after treatment and at 1‐year followup. Radiographic modifications in calcifications were evaluated before and after treatment. Disodium EDTA was administered through single needle mesotherapy and 15 minutes of pulsed‐mode 1 MHz‐ultrasound.

Results

The study group displayed improvement in all of the parameters analyzed after treatment and at the 1‐year followup. Calcifications disappeared completely in 62.5% of the patients in the study group and partially in 22.5%; calcifications partially disappeared in only 15% of the patients in the control group, and none displayed a complete disappearance.

Conclusion

Our results suggest that the use of disodium EDTA for the management of calcific tendinitis of the shoulder is safe and effective, leading to a significant reduction in pain, improvement in shoulder function, and disappearance of calcifications after 4 weeks, without adverse effects.
(Mis)understanding in patient‐health care provider communication about total knee replacement
Authors: Street Richard L. , Richardson Marsha N. , Cox Vanessa , Suarez‐Almazor Maria E.
Published: December 2008

Objective

To examine whether communication factors affect health care provider and patient agreement on the need for, risks of, and benefits of joint replacement, and also whether degree of agreement predicts patient satisfaction and intent to follow treatment recommendations.

Methods

Health care providers (n = 27) and patients (n = 74) with severe osteoarthritis (OA) were recruited from clinics in Houston, Texas. Patients completed a baseline survey prior to the consultation. After the visit, patients and providers completed measures of the severity of the patient's OA, the expected benefits of total knee replacement (TKR), and concern about surgical complications. Patients also completed satisfaction and intent to adhere measures. Provider communication and patient participation were measured by patient self‐report and by observers' codings of audiorecordings of the consultations.

Results

Provider‐patient agreement was modest to poor regarding severity of the patient's OA and the expected benefits and risks of TKR. Providers and patients were more aligned on the patient's OA severity when providers used more partnership building but spent less time simply giving information. Differences between providers' and patients' concerns about surgery were greater when patients were less participatory, African American, or expressed lower trust in their doctors. Patient satisfaction and intent to adhere were predicted by provider‐patient agreement on the benefits of TKR.

Conclusion

Patients and providers often differ in their beliefs about the need for, risks of, and benefits of TKR, and these differences can affect patient satisfaction and commitment to treatment. Facilitating active patient participation might contribute to greater physician–patient agreement on the patient's concerns about OA and surgical interventions.
Bio‐Inspired Silicification on Patterned Surfaces Generated by Microcontact Printing and Layer‐by‐Layer Self‐Assembly
Authors: Yang Sung Ho , Choi Insung S.
Published: December 2008

Micropatterns of silica were generated under biocompatible conditions by a combination of microcontact printing (μCP), layer‐by‐layer (LbL) self‐assembly, and biomimetic silicification. Quaternary amine‐containing poly(diallyl dimethyl ammonium chloride) induced polycondensation of silicic acid, resulting in spatioselective formation of silica micropatterns. Scale bar: 10 μm.

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The onset of autism: patterns of symptom emergence in the first years of life
Authors: Ozonoff Sally , Heung Kelly , Byrd Robert , Hansen Robin , Hertz‐Picciotto Irva
Published: December 2008

Previous conceptualizations of autism have suggested that symptoms are evident either early in the first year of life or later in the second year, after a loss of previously acquired skills. New research suggests, however, that these two patterns do not capture all the different ways autism can emerge. For example, some children show a developmental plateau marked by failure to progress, while other children display mixed features, with both early delays and later losses evident. This article reviews the literature on autism onset, discusses problems with the traditional ways in which onset has been conceptualized, and provides recommendations for future research. We suggest that onset is better thought of as a dimensional process rather than dichotomous categories.
Evidence that the pattern of visuomotor sequence learning is altered in children with autism
Authors: Gidley Larson Jennifer C. , Mostofsky Stewart H.
Published: December 2008

Motor deficits are commonly reported in autism, with one of the most consistent findings being impaired execution of skilled movements and gestures. Given the developmental nature of autism, it is possible that deficits in motor/procedural learning contribute to impaired acquisition of motor skills. Thus, careful examination of mechanisms underlying learning and memory may be critical to understanding the neural basis of autism. A previous study reported impaired motor learning in children with high‐functioning autism (HFA); however, it is unclear whether the observed deficits in motor learning are due, in part, to impaired motor execution and whether these deficits are specific to autism. In order to examine these questions, 153 children (52 with HFA, 39 with attention‐deficit/hyperactivity disorder (ADHD) and 62 typically developing (TD) children) participated in two independent experiments using a Rotary Pursuit task, with change in performance across blocks as a measure of learning. For both tasks, children with HFA demonstrated significantly less change in performance than did TD children, even when differences in motor execution were minimized. Differences in learning were not seen between ADHD and TD groups on either experiment. Analyses of the pattern of findings revealed that compared with both ADHD and TD children, children with HFA showed a similar degree of improvement in performance; however, they showed significantly less decrement in performance when presented with an alternate (“interference”) pattern. The findings suggest that mechanisms underlying acquisition of novel movement patterns may differ in children with autism. These findings may help explain impaired skill development in children with autism and help to guide approaches for helping children learn novel motor, social and communicative skills.
Enhanced Cellular Uptake and Cytotoxicity Studies of Organometallic Bioconjugates of the NLS Peptide in Hep G2 Cells
Authors: Noor Fozia , Kinscherf Ralf , Bonaterra Gabriel A. , Walczak Steffen , Wölfl Stefan , Metzler‐Nolte Nils
Published: December 2008

Space invaders: Organometallic fragments such as the ferrocenyl group (shown in red in the picture) help to enhance cellular entry of NLS peptides. Eventually, these nontoxic conjugates find their way to the cellular nucleus as shown by fluorescence microscopy studies in this work.

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Intracellular delivery to biomolecular targets is still a major challenge in molecular and cell biology. We recently found that attaching an organometallic group, namely the cobaltocenium cation, to the SV 40 large T antigen nuclear localisation signal (NLS) greatly enhances cellular uptake of the conjugate (Noor et al., Angew. Chem. Int. Ed. 2005, 45, 2429). In addition, nuclear localisation of the conjugate was observed. In this work, we present a thorough investigation of this novel cellular delivery system with respect to the nature of the metal complex and the peptide sequence. A number of ferrocene ((FeII), neutral metal complex) and cobaltocenium ((CoIII), cationic metal complex) bioconjugates with both the NLS wild‐type sequence PKKKRKV and a scrambled sequence (NLSscr, KKVKPKR) were prepared by solid‐phase peptide synthesis (SPPS). Cellular and nuclear uptake of these bioconjugates was studied by fluorescence microscopy on living Hep G2 cells. In addition, cytotoxicity screening on the conjugates was carried out, as the toxic effects of several simple metallocenes have been noted previously. Rapid cellular uptake as well as nuclear localisation was observed for the metal–NLS conjugates, but not for any dipeptide controls, the metal–NLSscr conjugates or any metal‐free conjugates. It thus appears that the presence of a metallocene, but not its charge, and the correct NLS sequence is essential for cellular uptake. Fluorescence microscopy co‐localisation studies did not reveal a significant endosomal entrapment of the conjugates. The metallocene not only provides a hydrophobic handle for membrane translocation but also facilitates the localisation and distribution of the conjugate in the cytoplasm. The NLS peptide on the other hand is responsible for the nuclear localisation of the bioconjugate. Finally, none of the conjugates were found to be toxic up to the highest concentrations that was tested (1 mM) against the Hep G2 cells that were used in this study. In conclusion, this work supports metallocene–NLS bioconjugates, in particular with the very robust cobaltocenium group, as a simple but potent, nontoxic system for cellular uptake and nuclear delivery. Concurrently, our finding is relevant to the still‐unresolved question of cytotoxicity of metallocenes because it excludes binding and/or damage to the DNA as a mechanism of metallocene cytotoxicity. This finding is confirmed by a combined yeast cytotoxicity/genotoxicity assay, which also shows very little toxic effects for all organometal–NLS conjugates that were tested.
Identification, Quantification, and Determination of the Absolute Configuration of the Bacterial Quorum‐Sensing Signal Autoinducer‐2 by Gas Chromatography–Mass Spectrometry
Authors: Thiel Verena , Vilchez Ramiro , Sztajer Helena , Wagner‐Döbler Irene , Schulz Stefan
Published: December 2008

Sensing the signal: A gas chromatography–mass spectrometry (GC–MS) method for the analysis of the quorum‐sensing autoinducer‐2 is described. It allows, for the first time, the direct analysis and accurate determination of this highly water soluble signaling compound, which exists in complex equilibria. The application on the caries‐causing bacterium Streptococcus mutans is described.

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Autoinducer‐2 (AI‐2) is an important, small extracellular signaling molecule that is used by many bacteria. It is part of the AI‐2 pool, a group of equilibrium‐connected compounds derived from (S)‐4,5‐dihydroxy‐2,3‐pentanedione [(S)‐DPD, 1]. Currently, these compounds are analyzed by indirect methods relying on the luminescence of sensor strains, the fluorescence of receptor proteins modified with fluorophores, or by isolation procedures not practical for quantitative analysis. Herein, we report a direct analytical procedure that allows for the unambiguous identification and quantification of molecular species by mass spectrometry. Phenylenediamine reacts readily and quantitatively with 1 to form the quinoxalinediol 12 under aqueous conditions. The extraction and silylation of this compound results in the formation of a silyl ether (13), which is amenable for analysis by gas chromatography–mass spectrometry. The use of an isotopically labeled variant (16) of 12 as an internal standard opens the possibility for the accurate quantification of samples containing AI‐2 or its equilibrium products. The analysis of cell‐free culture supernatants of Vibrio harveyi and Streptococcus mutans allowed for the accurate quantification of the AI‐2 concentration above the limit of detection (0.7 ng mL−1). No compounds were detected in mutants lacking the capability to produce AI‐2. In addition, the absolute configuration of 1 can be analyzed using the derivative 13 by chiral gas chromatography.
Magnetic Interactions and Magnetic Anisotropy in Exchange Coupled 4f–3d Systems: A Case Study of a Heterodinuclear Ce3+–Fe3+ Cyanide‐Bridged Complex
Authors: Sorace Lorenzo , Sangregorio Claudio , Figuerola Albert , Benelli Cristiano , Gatteschi Dante
Published: December 2008

We report here a detailed single‐crystal EPR and magnetic study of a homologous series of complexes of the type Ln–M (Ln=LaIII, CeIII; M=FeIII, CoIII). We were able to obtain a detailed picture of the low‐lying levels of CeIII and FeIII centres through the combined use of single‐crystal EPR and magnetic susceptibility data. We show that classical ligand field theory can be of great help in rationalising the energies of the low‐lying levels of both the transition‐metal and rare‐earth ions. The combined analysis of single‐crystal EPR and magnetic data of the coupled system Ce–Fe confirmed the great complexity of the interactions involving rare‐earth elements. With little uncertainty, it turned out clearly that the description of the interaction involving the lowest lying spin levels requires the introduction of the isotropic, anisotropic and antisymmetric terms.
MALDI‐TOF Mass‐Spectrometry‐Based Versatile Method for the Characterization of Protein Kinases
Authors: Kondo Noriyasu , Nishimura Shin‐Ichiro
Published: December 2008

We describe a MALDI‐TOF mass‐spectrometry‐based method that is rapid and versatile for the characterization of protein kinases and their inhibitors. We have designed new kinase substrates by the modification of common synthetic peptides, such as kemptide (LRRALSG), CaMKII substrate (KRQQSFDLF), erktide (ATGPLSPGPFGRR), abltide (EAIYAAPFAKKK), srctide (AEEEIYGEFEAKKKK), neurogranin (AAAKIQASFRGHMARKK), and casein kinase I (CKI) substrate (RRKDLHDDEEDEAMSITA). There are two fundamental points on which the proposed method is based to improve the mass‐spectrometric response: 1) mass tag technology by N‐derivatization through stable isotope labeling and 2) C‐terminal conjugation with tryptophanylarginine (WR). It was suggested that C‐terminal conjugation with the WR moiety enhances the ionization potency of these new substrates 1.5–13.7 times as much as those of the original peptides. We demonstrated, by using modified abltide (Ac‐EAIYAAPFAKKKWR‐NH2), that WR conjugation at the C‐terminus in combination with stable‐isotope labeling at the N‐terminus allowed the quantitative assay of recombinant c‐Abl kinase in the presence of adenosine 5′‐triphosphate (ATP; KM,ATP=18.6 μM and Vmax=642 pmol min−1 μg−1). The present protocol made a simple and reliable inhibition assay of recombinant c‐Abl kinase by imatinib possible (IC50(recombinant)=291 nM; STI571, Gleevec; Novartis Pharma). Moreover, it was also demonstrated that this ATP noncompetitive inhibitor differentiates between two conformers of c‐Abl kinases: the phosphorylated active and dephosphorylated inactive forms (IC50(active form)=1049 nM and IC50(inactive form)=54 nM). The merit of this approach is evident because the present protocol can be applied to the direct monitoring of the activities of living cell kinases by using cancer‐cell lines, such as mouse B16 melanoma cells and human lung cancer K562 cells. A multiple‐kinase assay that uses K562 cell lysate in the presence of seven new synthetic substrates made high‐throughput inhibitor profiling possible. It should be emphasized that this radioactive isotope‐free quantitative kinase assay will greatly accelerate the discovery of a new generation of potential kinase inhibitors that exhibit highly selective or unique inhibitory profiles.
Osmotically Shrunken LIPOCEST Agents: An Innovative Class of Magnetic Resonance Imaging Contrast Media Based on Chemical Exchange Saturation Transfer
Authors: Terreno Enzo , Delli Castelli Daniela , Violante Elisabetta , Sanders Honorius M. H. F. , Sommerdijk Nico A. J. M. , Aime Silvio
Published: December 2008

The peculiar properties of osmotically shrunken liposomes acting as magnetic resonance imaging–chemical exchange saturation transfer (MRI–CEST) contrast agents have been investigated. Attention has been primarily devoted to assessing the contribution arising from encapsulated and incorporated paramagnetic lanthanide(III)‐based shift reagents in determining the chemical shift of the intraliposomal water protons, which is a relevant factor for generating the CEST contrast. It is demonstrated that a highly shifted resonance for the encapsulated water can be attained by increasing the percentage of the amphiphilic shift reagent incorporated in the liposome bilayer. It is also demonstrated that the shift contribution arising from the bulk magnetic susceptibility can be optimized through the modulation of the osmotic shrinkage. In terms of sensitivity, it is shown that the saturation transfer efficiency can be significantly improved by increasing the size of the vesicle, thus allowing a high number of exchangeable protons to be saturated. In addition, the role played by the intensity of the saturating radiofrequency field has also been highlighted.
Regio‐ and Chemoselective Metalation of Chloropyrimidine Derivatives with TMPMgCl⋅LiCl and TMP2Zn⋅2 MgCl2⋅2 LiCl
Authors: Mosrin Marc , Knochel Paul
Published: December 2008

Efficient zincation and magnesiation of chlorinated pyrimidines can be performed at convenient temperatures (e.g., 25 and 55 °C) by using TMPMgCl⋅LiCl and TMP2Zn⋅2 MgCl2⋅2 LiCl (TMP=2,2,6,6‐tetramethylpiperidyl) as effective bases. Quenching of the resulting zincated or magnesiated pyrimidines with various electrophiles furnishes highly functionalized pyrimidines in 51–93 % yield. Oxidative aminations were carried out, thus leading to aminated pyrimidines. By using this methodology, we have also prepared pharmaceutically relevant pyrazolopyrimidines and the fungicide Mepanipyrim.
Solid‐State Gas Sensors Developed from Functional Difluoroboradiazaindacene Dyes
Authors: Ziessel Raymond , Ulrich Gilles , Harriman Anthony , Alamiry Mohammed A. H. , Stewart Beverly , Retailleau Pascal
Published: December 2008

This article describes the synthesis and characterization of several new difluoroboradiazaindacene (BODIPY™) dyes functionalized at the central 8‐position by a phenyliodo, phenylheptynoate or phenylheptynoic fragment and at the 3‐ or 3/5‐position(s) by 4‐dimethylaminophenylstyryl residue(s). Single‐crystal structural determinations confirm the planarity of the dyes, while the absorption and fluorescence spectroscopic properties are highly sensitive to the state of protonation (or alkylation) of the terminal anilino donor group(s). Reversible color tuning from green to blue for absorption and from colorless (i.e., near‐IR region) to red for fluorescence is obtained on successive addition of acid and base. The difunctionalized derivative is especially interesting in this respect and shows two well‐resolved pKa values of 5.10 and 3.04 in acetonitrile. Addition of the first proton causes only small spectral changes and deactivates the molecule towards addition of the second proton. It is this latter step that accommodates the large change in absorption and emission properties, due to the reversible extinction of the intramolecular charge‐transfer character inherent to this type of dye. The main focus of the work is the covalent anchoring of the dyes to inert, porous polyacrylate beads so as to form a solid‐state sensor suitable for analysis of gases or flowing liquids. The final material is highly stable—its performance is undiminished after more than one year—and fully reversible over many cycles. The sensitivity is such that reactions can be followed by the naked eye and the detection limit is about 600 ppb for HCl and about 80 ppb for ammonia. Trace amounts of diphosgene can be detected, as can alkylating agents. The sensing action is indiscriminate and also operates when the beads are dispersed in aqueous media.
FeNCN and Fe(NCNH)2: Synthesis, Structure, and Magnetic Properties of a Nitrogen‐Based Pseudo‐oxide and ‐hydroxide of Divalent Iron
Authors: Liu Xiaohui , Stork Ludwig , Speldrich Manfred , Lueken Heiko , Dronskowski Richard
Published: December 2008

Iron man challenge: Iron carbodiimide, FeNCN, and its precursor iron (bis)monohydrocyanamide, Fe(NCNH)2, have been synthesized and physically characterized. Both FeNCN and Fe(NCNH)2 exhibit nitrogen‐mediated antiferromagnetic superexchange interactions with reduced magnetic moments very similar, but not identical, to the correlated 3d oxides.

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No Abstract
Morphology and deactivation behaviour of Co–Ru/γ‐Al2O3 Fischer–Tropsch synthesis catalyst
Authors: Tavasoli Ahmad , Irani Mohammad , Abbaslou Reza M. Malek , Trépanier Mariane , Dalai Ajay K.
Published: December 2008

Deactivation of Co–Ru/γ‐Al2O3 Fischer–Tropsch (FT) synthesis catalyst along the catalytic bed over 850 h of time‐on‐stream (TOS) was investigated. Catalytic bed was divided into four parts and structural changes of the spent catalysts collected from each catalytic bed after FT synthesis were studied using BET, ICP, XRD, TPR, carbon determination, H2 chemisorption and oxygen titration techniques. Rapid deactivation was observed during first 200 h of FT synthesis. In this case, the deactivation rate was not dependent on the number of the catalyst active sites. It was zero order to CO conversion and independent of the size of active sites. Beyond the TOS of 200 h, the deactivation could be simulated with a power law expression: $- {\rm d}X_{{\rm CO}} /{\rm d}t = kX_{{\rm CO}}^{28.5}$. The physical properties of the catalyst charged in 1st half of the reactor did not change significantly. Interaction of cobalt with alumina and formation of mixed oxides of the form xCoO·yAl2O3 and CoAl2O4 was increased along the catalytic bed. Percentage reducibility and dispersion decreased by 2.4–25.5% and 0.5–8.8% for the catalyst in the beds 1 and 4, respectively. Particle diameter increased by 0.8–6.1% for the catalyst in the beds 1 and 4 respectively suggesting higher rate of sintering at last catalytic bed. The amount of coke formation in the 4th catalytic bed was 6 times more than that of in bed 1.
Properties of uniaxially stretched polypropylene films
Authors: Sadeghi Farhad , Carreau Pierre J.
Published: December 2008

Polypropylene (PP) films have been prepared through two different cast extrusion processes: one using a machine direction orientation (MDO) unit and the other stretching the films at the die under high cooling conditions (lab unit). Films for two PP resins different in molecular structure have been prepared using both processing techniques. The effect of the resin structure and the processing conditions on the film properties has been examined. It was found that the MDO unit generated a highly oriented fibrillar crystalline structure with a distribution of elongated thick fibrils while extrusion under high cooling conditions generated an oriented row nucleated lamellar structure. The films showed distinctive tensile responses in stretching, with a strong solid‐elastic response for the oriented MDO films and a steady strain hardening after yielding for the sample obtained from lab unit cast extrusion. It was found that the strength in the transverse direction (TD) was particularly very low for the oriented MDO films made of the bimodal PP. The oxygen permeability was reduced with increasing draw ratio (DR) for the MDO films. The haze property for the MDO samples reduced to a plateau for DR up to 5 while clarity improved continuously with DR.
The influence of distributor structure on the solids distribution and flow development in circulating fluidized beds
Authors: Yan Aijie , Huang Weixing , Zhu Jesse (Jingxu)
Published: December 2008

The influence of distributor structure on solids distribution is studied in two riser circulating fluidized bed reactors with different distributor structures but similar diameters. Optic fibre probes were used for the measurement of local solids distribution. The axial and radial distribution of solids holdup in the riser with a multi‐tube distributor is more uniform than that with a multi‐orifice distributor. The radial profiles of particle velocity in the riser with the multi‐tube distributor are also more uniform than that with the multi‐orifice distributor. In the riser with the multi‐tube distributor, both gas and particles are distributed more uniformly across the section, so that the flow acceleration is much more uniform and faster. The flow development is much faster and the fully developed region is reached early for the riser with the multi‐tube distributor. The distributor design is an important factor for the design of circulating fluidized bed reactor.
Assembly properties of the Bacillus subtilis actin, MreB
Authors: Mayer Joshua A. , Amann Kurt J.
Published: December 2008

The bacterial actin MreB has been implicated in a variety of cellular roles including cell shape determination, cell wall synthesis, chromosome condensation and segregation, and the establishment and maintenance of cell polarity. Toward elucidating a clearer understanding of how MreB functions inside the bacterial cell, we investigated biochemically the polymerization of MreB from Bacillus subtilis. Light scattering and sedimentation assays revealed pH‐, ionic‐, cationic‐, and temperature‐dependent behavior. B. subtilis MreB polymerizes in the presence of millimolar divalent cations in a protein concentration‐dependent manner. Polymerization is favored by decreasing pH and inhibited by monovalent salts and low temperatures. Although B. subtilis MreB binds and hydrolyzes both ATP and GTP, it does not require a bound nucleotide for assembly and polymerizes indistinguishably regardless of the nucleotide species bound, with a critical concentration of ∼900 nM. A number of the presently reported properties of B. subtilis MreB differ significantly from those of T. maritima MreB1 (Bean and Amann [2008]: Biochemistry 47: 826–835), including the nucleotide requirements and temperature and ionic effects on polymerization state. These observations collectively suggest that additional factors interact with MreB to account for its complex dynamic behavior in cells. Cell Motil. Cytoskeleton 2009. © 2008 Wiley‐Liss, Inc.
A selective cyclooxygenase‐2 inhibitor prevents inflammation‐related squamous cell carcinogenesis of the forestomach via duodenogastric reflux in rats
Authors: Oba Masaru , Miwa Koichi , Fujimura Takashi , Harada Shinichi , Sasaki Shozo , Oyama Katsunobu , Ohta Tetsuo , Hattori Takanori
Published: December 2008

BACKGROUND:

Duodenal reflux causes inflammation‐related squamous cell carcinogenesis in the forestomach of rats without any carcinogens. The aim of this study was to investigate the efficacy of a selective cyclooxygenase (COX)‐2 inhibitor, meloxicam, in preventing this carcinogenesis.

METHODS:

A series of 188 rats underwent a surgical duodenogastric reflux procedure and were divided into 2 groups. One group was given commercial chow (control group), and the other was given experimental chow containing meloxicam (0.3 mg/kg body weight/day) (meloxicam group). The animals were sequentially sacrificed at Weeks 20, 30, 40, 50, and 60 after surgery. The forestomach was examined for the presence of carcinoma, the incidence of reflux‐related morphological changes, COX‐2 expression, and its activity.

RESULTS:

At Week 60, squamous cell carcinoma developed in 8 of 21 animals (38%) in the control group, but none of 20 (0%) in the meloxicam group (P < .05). In addition, basal cell dysplasia developed in 19 of 21 (90%) animals in the control group, but only 4 of 20 (20%) in the meloxicam group (P < .01). COX‐2 immunoreactivity was predominantly detected in macrophages in the epithelial stroma. Compared with nonsurgical rats, RNA expression of COX‐2 in the epithelium was up‐regulated, reaching peak at an early stage of Week 20 in both groups (P < .005). The expression of microsomal prostaglandin E synthase‐1 was lower in the meloxicam group than in the control group. PGE2 production was significantly suppressed throughout the experiment in the meloxicam group compared with the control group (P < .005).

CONCLUSIONS:

Meloxicam was effective in preventing reflux‐induced squamous cell carcinogenesis via an inflamed squamous epithelium. Cancer 2009. © 2009 American Cancer Society.
Mental health, treatment preferences, advance care planning, location, and quality of death in advanced cancer patients with dependent children
Authors: Nilsson Matthew E. , Maciejewski Paul K. , Zhang Baohui , Wright Alexi A. , Trice Elizabeth D. , Muriel Anna C. , Friedlander Robert J. , Fasciano Karen M. , Block Susan D. , Prigerson Holly G.
Published: December 2008

BACKGROUND:

Clinicians observe that advanced cancer patients with dependent children agonize over the impact their death will have on their children. The objective of this study was to determine empirically whether advanced cancer patients with and without dependent children differ in treatment preferences, mental health, and end‐of‐life (EOL) outcomes.

METHODS:

Coping with Cancer is a National Cancer Institute/National Institute of Mental Health‐funded, multi‐institutional, prospective cohort study of 668 patients with advanced cancer. Patients with and without dependent children were compared on rates of psychiatric disorders, advance care planning (ACP), EOL care, quality of their last week of life, and location of death.

RESULTS:

In adjusted analyses, patients with advanced cancer who had dependent children were more likely to meet panic disorder criteria (adjusted odds ratio [AOR], 5.41; 95% confidence interval [95% CI], 2.13–13.69), more likely to be worried (mean difference in standard deviations [δ], 0.09; P = .006), and more likely to prefer aggressive treatment over palliative care (AOR, 1.77; 95% CI, 1.07–2.93). Patients with dependent children were less likely to engage in ACP (eg, do not resuscitate orders: AOR, 0.44; 95% CI, 0.26–0.75) and had a worse quality of life in the last week of life (δ, 0.15; P = .007). Among spousal caregivers, those with dependent children were more likely to meet criteria for major depressive disorder (AOR, 4.53; 95% CI, 1.47–14) and generalized anxiety disorder (AOR, 3.95; 95% CI, 1.29–12.16).

CONCLUSIONS:

Patients with dependent children were more anxious, were less likely to engage in ACP, and were more likely to have a worse quality of life in their last week of life. Advanced cancer patients and spousal caregivers with dependent children represent a particularly distressed group that warrants further clinical attention, research, and support. Cancer 2009. © 2009 American Cancer Society.
Consideration of hereditary nonpolyposis colorectal cancer in BRCA mutation‐negative familial ovarian cancers
Authors: South Stacey A. , Vance Heidi , Farrell Carolyn , DiCioccio Richard A. , Fahey Cathy , Piver M. Steven , Rodabaugh Kerry J.
Published: December 2008

BACKGROUND:

Inherited mutations account for approximately 10% of all epithelial ovarian cancers. Breast cancer (BRCA1 and BRACA2) gene mutations are responsible for up to 85% of inherited breast and/or ovarian cancer. Another condition that has been associated with ovarian cancer is hereditary nonpolyposis colorectal cancer syndrome (HNPCC), which carries a lifetime risk of up to 13% for ovarian cancer. The objective of this study was to determine the incidence of HNPCC‐related gene mutations in patients with familial ovarian cancer who previously tested negative for BRCA1 and BRCA2 gene mutations.

METHODS:

Seventy‐seven probands were identified who had familial ovarian cancer and negative BRCA gene mutation testing. Their pedigrees were analyzed for HNPCC syndrome. DNA samples underwent gene sequencing and Southern blot analysis for mutations in the 3 most common HNPCC‐associated genes: mutL homolog 1 (MLH1) and mutS homolog 2 (MSH2) with reflex testing for MSH6 if tests for the first 2 genes were negative.

RESULTS:

None of the probands met Amsterdam criteria for the clinical diagnosis of HNPCC. DNA testing revealed 2 patients (2.6%) with deleterious mutations in the MSH2 gene. An additional 8 patients (10.4%) had substitutions in either the MLH1 gene or the MSH2 gene that were classified as variants of uncertain significance. If Amsterdam criteria were expanded to include ovarian cancer, then 15 of 77 patients (19.5%) would have met these expanded criteria. One deleterious mutation was noted in this group, yielding a mutation incidence of 6.7%. This percentage may be even higher if any of the identified variants of uncertain significance are confirmed to be deleterious.

CONCLUSIONS:

HNPCC should be considered when evaluating patients with suspected hereditary ovarian cancer who have had negative BRCA mutation testing. Cancer 2009. © 2009 American Cancer Society.
Bacterial artificial chromosome array‐based comparative genomic hybridization using paired formalin‐fixed, paraffin‐embedded and fresh frozen tissue specimens in multiple myeloma
Authors: Lennon Patrick A. , Zhuang Yi , Pierson Diane , Zhang Xiang , Williams Chris , Perez Cintia , Lin Pei
Published: December 2008

BACKGROUND:

Multiple myeloma (MM) is a neoplasm of malignant plasma cells that often harbors many chromosomal aberrations. Currently, fresh frozen tissues (FT) are considered the most reliable for molecular genetic analysis; however, formalin‐fixed, paraffin‐embedded (FFPE) tissues are easily retrievable. Compared with conventional cytogenetics, bacterial artificial chromosome (BAC) array‐comparative genomic hybridization (CGH) allows more sensitive detection of chromosomal abnormalities.

METHODS:

The authors analyzed 7 paired FT and FFPE samples of bone marrow aspirate materials obtained from patients with MM in parallel to determine the efficacy of BAC array‐CGH using FFPE.

RESULTS:

Thirty‐four aberrations were identified, including 29 that were observed in both sample types, yielding 85% concordance. Nonrandom anomalies, including gains on 7q, 9q, 15q, and 19p and losses on 8p and 13q, were observed in paired samples from at least 2 patients. To verify these results, fluorescence in situ hybridization (FISH) was performed using probes specific for 7q and 15q, and gains were observed in the 4 samples that were examined. Furthermore, 1 of 3 samples from patients who had monoclonal gammopathy of undetermined significance that were tested also carried gain on 7q, suggesting that this aberration may be an early transforming event.

CONCLUSIONS:

The current results indicated that BAC array‐CGH can be effective using FFPE samples and is a sensitive method for the identification of nonrandom chromosomal aberrations in MM. Cancer 2009. © 2009 American Cancer Society.
Galactomannan serves as a surrogate endpoint for outcome of pulmonary invasive aspergillosis in neutropenic hematology patients
Authors: Maertens Johan , Buvé Kristel , Theunissen Koen , Meersseman Wouter , Verbeken Eric , Verhoef Gregor , Van Eldere Johan , Lagrou Katrien
Published: December 2008

BACKGROUND:

A noninvasive, objective, reproducible, and quantitative Aspergillus‐specific surrogate marker is needed for a more accurate assessment of the outcome of invasive aspergillosis (IA) in patients with a hematologic disorder. The quantitative serum galactomannan index (GMI) assay seems to fulfill the requirements of surrogacy for outcome evaluation.

METHODS:

Kappa statistics were used to determine the strength of correlation between GMI outcome and clinical outcome (survival or death), autopsy data, and response outcome of IA in 70 adults with prolonged neutropenia. All patients underwent serial GMI monitoring until discharge or death.

RESULTS:

The overall correlation between GMI and clinical outcome was good at 6 weeks (κ = 0.5882; 95% confidence interval [95% CI], 0.4023‐0.7741) and was excellent at 12 weeks (κ = 0.8857; 95% CI, 0.7766‐0.9948). Concordance with autopsy findings was perfect (κ = 1). At 6 weeks, the correlation between GMI and response outcome (favorable or unfavorable) was excellent (κ = 0.7523; 95% CI, 0.5803‐0.9243). Survival was significantly better in patients who became GMI‐negative (P < .0001).

CONCLUSIONS:

In neutropenic patients with seropositive IA, serum galactomannan index outcome strongly correlates with survival, autopsy findings, and response outcome. This finding may have implications for patient management and for clinical trial design. Cancer 2009. © 2009 American Cancer Society.
Hyperthermia‐treated mesenchymal stem cells exert antitumor effects on human carcinoma cell line
Authors: Cho Jung Ah , Park Ho , Kim Hee Kyung , Lim Eun Hye , Seo Sang Won , Choi Joong Sub , Lee Kyo Won
Published: December 2008

BACKGROUND:

Mesenchymal stem cells (MSCs) possess the potential for differentiation into multilineages. MSCs have been reported to play a role as precursors for tumor stroma in providing a favorable environment for tumor progression. Hyperthermia destroys cancer cells by raising the temperature of tumor‐loaded tissue to 40°C to 43°C and causes indirect sensitizing effects when combined with chemo‐ and/or radiotherapy. However, how hyperthermia affects the tumor‐supportive stroma is unknown. Here, the authors investigated the effects of hyperthermia‐treated MSCs, from different sources, on the human ovarian cancer cell line SK‐OV‐3.

METHODS:

MSCs from adipose tissue and amniotic fluid were untreated or heat‐treated (HS‐MSCs). The culture supernatant of each treatment group was collected and transferred to the SK‐OV‐3 cells.

RESULTS:

The morphological analysis and cell proliferation assay showed a reduced viability of the tumor cells in the conditioned medium with the HS‐MSCs. Further investigations revealed that the conditioned medium of the HS‐MSCs induced a higher nuclear condensation and a greater number of sub‐G1 cells among the tumor cells. Analysis of the mRNA expression demonstrated that the conditioned medium of the HS‐MSCs induced up‐regulation or down‐regulation of several tumor‐associated molecules. Finally, the cytokine array of each conditioned medium showed that angiogenin, insulin‐like growth factor binding protein 4, neurotrophin 3, and chemokine (C‐C motif) ligand 18 are involved as main factors.

CONCLUSIONS:

This study showed that the conditioned medium of the HS‐MSCs exerted a suppressive effect on tumor progression and malignancy, suggesting that hyperthermia enables tumor stromal cells to provide a sensitizing environment for tumor cells to undergo cell death. Cancer 2009. © 2009 American Cancer Society.