bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Weight Maintenance on Symptoms of Knee Osteoarthritis in Obese Patients: A Twelve‐Month Randomized Controlled Trial
Authors: Christensen Robin , Henriksen Marius , Leeds Anthony R. , Gudbergsen Henrik , Christensen Pia , Sørensen Tina J. , Bartels Else M. , Riecke Birgit F. , Aaboe Jens , Frederiksen Rikke , Boesen Mikael , Lohmander L. Stefan , Astrup Arne , Bliddal Henning
Published: November 2014

Objective

To compare results of obese patients with knee osteoarthritis (OA) who, after an intensive weight loss regimen, received 1 year of either dietary support (D), a knee‐exercise program (E), or “no attention” (C; control group).

Methods

We conducted a randomized, 2‐phase, parallel‐group trial. A total of 192 obese participants with knee OA were enrolled; the mean age was 62.5 years and 81% were women with a mean entry weight of 103.2 kg. In phase 1, all participants were randomly assigned to 1 of 3 groups and began a dietary regimen of 400–810 and 1,250 kcal/day for 16 weeks (2 8‐week phases) to achieve a major weight loss. Phase 2 consisted of 52 weeks' maintenance in either group D, E, or C. Outcomes were changes from randomization in pain on a 100‐mm visual analog scale, weight, and response according to the Outcome Measures in Rheumatology‐Osteoarthritis Research Society International criteria.

Results

Mean weight loss for phase 1 was 12.8 kg. After 1 year on maintenance therapy, the D group sustained a lower weight (11.0 kg, 95% confidence interval [95% CI] 9.0, 12.8 kg) than those in the E (6.2, 95% CI 4.4, 8.1 kg) and C (8.2, 95% CI 6.4, 10.1 kg) groups (P = 0.002 by analysis of covariance [ANCOVA]). Adherence was low in the E group. All groups had statistically significant pain reduction (D: 6.1; E: 5.6; and C: 5.5 mm) with no difference between groups (P = 0.98 by ANCOVA). In each group 32 (50%), 26 (41%), and 33 (52%) participants responded to treatment in the D, E, and C groups, respectively, with no statistically significant difference in the number of responders (P = 0.41).

Conclusion

A significant weight reduction with a 1‐year maintenance program improves knee OA symptoms irrespective of maintenance program.
Measures of Arthritis Activity Associated With Patient‐Reported Improvement in Rheumatoid Arthritis When Assessed Prospectively Versus Retrospectively
Authors: Ward Michael M. , Guthrie Lori C. , Alba Maria I.
Published: November 2014

Objective

The patient global assessment (PGA) is intended to provide an integrated summary of all symptoms of arthritis, but it is not clear which disease features most impact patients' assessments of changes in their overall status. We investigated what aspects of rheumatoid arthritis (RA) activity correlated best with prospectively measured changes in the PGA and with patients’ retrospective judgments of improvement.

Methods

We studied 250 patients with active RA in a prospective longitudinal study. Disease activity measures were collected before and after treatment escalation. Prospectively measured changes in PGA and patients' judgments of improvement or worsening at the followup visit were tested for correlations with changes in patient‐reported measures of symptoms and functioning, joint counts, and laboratory tests.

Results

Patients improved during the study, with the mean ± SD PGA decreasing from 55.6 ± 25.2 to 37.6 ± 24.0. At the followup visit, 167 patients (66.8%) reported improvement in overall arthritis status. Changes in pain severity, stiffness severity, and fatigue were the only significant correlates of changes in PGA. In contrast, changes in the Health Assessment Questionnaire, tender joint count or Disease Activity Score in 28 joints (DAS28), and stiffness severity were associated with retrospective judgments of improvement.

Conclusion

Prospectively measured changes in PGA in RA were related solely to other patient‐reported measures, but patients’ retrospective judgments of improvement were related to functional limitations, tender joint count, and DAS28. Patients' subjective judgments of improvement reflect aspects of RA different from the PGA and may be a simple complementary measure of treatment efficacy.
Iron(III) Chloride Catalyzed Synthesis of Highly Substituted Indolyl‐Tetrahydroquinoline Derivatives by Using Indolylnitroalkene as Dienophiles and Its Application to the Synthesis of Indolo‐Benzonaphthyridine Derivatives
Authors: Zanwar Manoj R. , Gawande Sachin D. , Kavala Veerababurao , Kuo Chun‐Wei , Yao Ching‐Fa
Published: November 2014

An efficient iron(III) chloride catalyzed synthesis of highly substituted indolyltetrahydroquinoline derivatives from easily available starting materials, including indolylnitroalkenes, substituted anilines and various aldehydes is reported. The reaction utilized strong electron deficient dienophiles like indolylnitroalkene via a Povarov approach.

The methodology shows good functional group tolerance and can be used to prepare fused indolo‐benzonaphthyridine derivatives.

magnified image
Phase II study of methotrexate, vincristine, pegylated‐asparaginase, and dexamethasone (MOpAD) in patients with relapsed/refractory acute lymphoblastic leukemia
Authors: Kadia Tapan M. , Kantarjian Hagop M. , Thomas Deborah A. , O'Brien Susan , Estrov Zeev , Ravandi Farhad , Jabbour Elias , Pemmaraju Naveen , Daver Naval , Wang Xuemei , Jain Preetesh , Pierce Sherry , Brandt Mark , Garcia‐Manero Guillermo , Cortes Jorge , Borthakur Gautam
Published: November 2014

Newer approaches are needed for the treatment of relapsed and refractory acute lymphoblastic leukemia (ALL). Asparaginase‐based regimens are active in the treatment of pediatric ALL and may be important in salvage therapy for adult patients. We conducted a pilot trial combining methotrexate, vincristine, PEGylated‐asparaginase, and dexamethasone (MOpAD) in adults with relapsed or refractory ALL. We added tyrosine kinase inhibitors in patients with Philadelphia chromosome positive (Ph+) ALL and rituximab in patients with CD20 positive B‐cell ALL. Among 37 patients treated (median age 42 years; median 2 prior therapies), the complete remission (CR) rate was 28% and an overall response rate (ORR) was 39%. The median CR duration was 4.3 months. Patients with Ph+ ALL had CR and ORR of 50% and 67%, respectively and the CR and ORR in patients with T‐cell leukemia were 45% and 56%, respectively. The median survival in patients with CR/CRp was 10.4 versus 3.4 months in nonresponders (P = 0.02). The most common grade 3 or 4 nonhematologic toxicities were elevations in bilirubin and transaminases, nausea, peripheral neuropathy, and hyperglycemia, which were managed with supportive care, dose adjustments, and interruptions. Am. J. Hematol. 90:120–124, 2015. © 2014 Wiley Periodicals, Inc.
Development, validation, and use of a semi‐quantitative food frequency questionnaire for assessing protein intake in Papua New Guinean Highlanders
Authors: Morita Ayako , Natsuhara Kazumi , Tomitsuka Eriko , Odani Shingo , Baba Jun , Tadokoro Kiyoshi , Igai Katsura , Greenhill Andrew R. , Horwood Paul F. , Soli Kevin W. , Phuanukoonnon Suparat , Siba Peter M. , Umezaki Masahiro
Published: November 2014

Objectives

The aim of this article was to develop a semi‐quantitative food frequency questionnaire (FFQ) and evaluate its validity to estimate habitual protein intake, and investigate current dietary protein intakes of Papua New Guinea (PNG) Highlanders.

Methods

A 32‐item FFQ was developed and tested among 135 healthy male and female volunteers. The FFQ‐estimated daily total and animal protein intakes were compared with biomarkers and 3‐day Weighed Food Records (WFR) by correlation analyses, Bland–Altman plot analyses and joint classification analyses.

Results

The FFQ‐estimated total protein intake significantly correlated with urinary nitrogen in the first morning void after adjusting urinary creatinine concentration (r = 0.28, P < 0.01) and the FFQ‐estimated animal protein intake significantly correlated with the hair δ15N (Spearman's r = 0.34, P < 0.001). The limits of agreement were ±2.39 Z‐score residuals for total protein intake and ±2.19 Z‐score for animal protein intake, and intra‐individual differences increased as protein intake increased. The classification into the same and adjacent quartiles was 66.0% for total protein intake and 73.6% for animal protein intake. Median daily total and animal protein intake estimates from the FFQ and the 3‐day WFR showed a good agreement with differences of 0.2 and 4.9 g, respectively. None of the studied communities in the PNG Highlands met the biologically required protein intake; although the community closer to an urban center showed higher protein intake than the more remote communities.

Conclusions

The newly developed 32‐item FFQ for PNG Highlanders is applicable for evaluation of protein intake at the individual level. Am. J. Hum. Biol. 27:349–357, 2015. © 2014 Wiley Periodicals, Inc.
A Perylene‐Bridged Switchable [3]Rotaxane Molecular Shuttle with a Fluorescence Output
Authors: Cao Zhan‐Qi , Li Hong , Yao Jian , Zou Lei , Qu Da‐Hui , Tian He
Published: November 2014

A bistable bis‐branched [3]rotaxane with a perylene bisimide (PBI) chromophore that separates two mechanically interlocked [2]rotaxane arms including a diferrocene‐functionalized dibenzo‐24‐crown‐8 ring, was designed, prepared, and characterized by 1H NMR and 13C NMR spectroscopy and HR‐ESI mass spectrometry. The uniform relative shuttling movement of target [3]rotaxane in response to external acid‐base stimuli was confirmed by 1H NMR spectroscopy. Furthermore, the shuttling motion of the macrocycles in the system was accompanied by a remarkably visual fluorescence change due to the distance‐dependent photoinduced electron transfer process from the ferrocene units to the PBI fluorophore. This kind of rotaxane has important potential for designing more sophisticated mechanically interlocked molecules with controllable functions.
Two‐Coordinate Iron(I) Complex [Fe{N(SiMe3)2}2]−: Synthesis, Properties, and Redox Activity
Authors: Werncke C. Gunnar , Bunting Philip C. , Duhayon Carine , Long Jeffrey R. , Bontemps Sébastien , Sabo‐Etienne Sylviane
Published: November 2014

First‐row two‐coordinate complexes are attracting much interest. Herein, we report the high‐yield isolation of the linear two‐coordinate iron(I) complex salt [K(L)][Fe{N(SiMe3)2}2] (L=18‐crown‐6 or crypt‐222) through the reduction of either [Fe{N(SiMe3)2}2] or its three‐coordinate phosphine adduct [Fe{N(SiMe3)2}2(PCy3)]. Detailed characterization is gained through X‐ray diffraction, variable‐temperature NMR spectroscopy, and magnetic susceptibility studies. One‐ and two‐electron oxidation through reaction with I2 is further found to afford the corresponding iodo iron(II) and diiodo iron(III) complexes.
Sonocrystallization Yields Monoclinic Paracetamol with Significantly Improved Compaction Behavior
Authors: Bučar Dejan‐Krešimir , Elliott James A. , Eddleston Mark D. , Cockcroft Jeremy K. , Jones William
Published: November 2014

Ultrasound‐assisted crystallization (sonocrystallization) was used to prepare a mixture of nano‐ and micrometer‐sized crystals of the monoclinic form of paracetamol—a widely used analgesic known for its particularly problematic mechanical behavior under compression (i.e. poor tabletability). The nano‐ and micrometer‐sized crystals yielded a powder which exhibits elastic moduli and bulk cohesions that are significantly higher than those observed in samples consisting of macrometer‐sized crystals, thus leading to enhanced tabletability without the use of excipients, particle coating, salt, or cocrystal formation. Experimental compaction and finite element analysis were utilized to rationalize the significantly improved compaction behavior of the monoclinic form of paracetamol.
Rational Design of Heterodimeric Protein using Domain Swapping for Myoglobin
Authors: Lin Ying‐Wu , Nagao Satoshi , Zhang Mohan , Shomura Yasuhito , Higuchi Yoshiki , Hirota Shun
Published: November 2014

Protein design is a useful method to create novel artificial proteins. A rational approach to design a heterodimeric protein using domain swapping for horse myoglobin (Mb) was developed. As confirmed by X‐ray crystallographic analysis, a heterodimeric Mb with two different active sites was produced efficiently from two surface mutants of Mb, in which the charges of two amino acids involved in the dimer salt bridges were reversed in each mutant individually, with the active site of one mutant modified. This study shows that the method of constructing heterodimeric Mb with domain swapping is useful for designing artificial multiheme proteins.
Entrapping an Ionic Liquid with Nanocarbon: The Formation of a Tailorable and Functional Surface
Authors: Ding Yuxiao , Sun Xiaoyan , Zhang Liyun , Mao Shanjun , Xie Zailai , Liu Zhong‐Wen , Su Dang Sheng
Published: November 2014

An interface microenvironment between nanocarbon and ionic liquids (ILs) is presented. By an entrapping effect, a few layers of ILs can be finely deposited on the surface of nanocarbon, endowing amazingly tailorable surface properties. The entrapped IL layer, which was believed to be unable to be charred under pyrolysis conditions alone, can be further carbonized to a functional carbon layer. C, B, and N were confirmed to share the same hexagonal ring in the resultant layer, which provides more designable electronic properties.
Adsorption and desorption properties of modified feather and feather/PP melt‐blown filter cartridge of lead ion (Pb2+)
Authors: Wang Hong , Jin Xiang‐Yu , Wu Hai‐Bo
Published: November 2014

Duck and chicken feather fibers are waste products of the poultry industry, creating a serious solid waste problem around the world. Previous works showed that feather fibers can be reused to adsorb heavy metal ions from water. To improve the adsorption capacity of feather fibers, sodium pyrosulfite (Na2S2O5) was used in this article to modify the feather fiber in order to improve its Pb2+ adsorption capacity. Scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) quantified chemical and structural changes of Na2S2O5 modified feather fibers. In addition, Na2S2O5 modified feather fibers were processed into feather/polypropylene (PP) melt‐blown filter cartridges and their dynamic Pb2+ adsorption properties were investigated. Finally, the desorption effects of NaOH and sodium sulfide nonahydrate (Na2S·9H2O) aqueous solutions on the feather fiber adsorbed with Pb2+ were studied. It is found that Pb2+ adsorption capacity of the feather fiber increased after being modified by Na2S2O5. Modified feather/PP filter cartridge exhibited higher Pb2+ adsorption capacity than feather/PP filter cartridge and pure PP filter cartridge in the whole dynamic adsorption process. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41555.
Functional Implications of Variation in Tooth Spacing and Crown Size in Pinnipedimorpha (Mammalia: Carnivora)
Authors: Churchill Morgan , Clementz Mark T.
Published: November 2014

Pinnipeds (seals, sea lions, and walruses) show variation in tooth morphology that relates to ecology. However, crown size and spacing are two aspects of morphology that have not been quantified in prior studies. We measured these characters for nearly all extant pinnipeds and three fossil taxa and then determined the principal sources of variation in tooth size and spacing using principal components (PCAs) and hierarchical cluster analysis (HCA). PCA and HCA showed that species sorted into three groups: taxa with small crowns and large diastemata, taxa with large crowns and small diastemata, and taxa that fell between these two extremes. We then performed discriminant function analysis (DFA) to determine if tooth morphology correlated with foraging strategy or diet. DFA results indicated weak correlation with diet, and stronger correlation with prey capture strategies. Tooth size and spacing were most strongly correlated with the importance of teeth in prey acquisition, with tooth size decreasing and tooth spacing increasing as teeth become less necessary in capturing food items. Taxa which relied on teeth for filtering prey from the water column or processing larger or tougher food items generally had larger crowns and smaller tooth spacing then taxa which swallowed prey whole. We found the fossil taxa Desmatophoca and Enaliarctos were most similar in tooth morphology to extant otariids, suggesting that both taxa were generalist feeders. This study established the relationship between tooth size and feeding behavior, and provides a new tool to explore the paleoecology of fossil pinnipeds and other aquatic tetrapods. Anat Rec, 298:878–902, 2015. © 2014 Wiley Periodicals, Inc.
Aspirin‐Triggered Lipoxin Prevents Antiphospholipid Antibody Effects on Human Trophoblast Migration and Endothelial Cell Interactions
Authors: Alvarez Angela M. , Mulla Melissa J. , Chamley Lawrence W. , Cadavid Angela P. , Abrahams Vikki M.
Published: November 2014

Objective

Antiphospholipid antibodies (aPL) interfere with several physiologic functions of human trophoblasts, including reducing their ability to migrate, decreasing their production of angiogenic factors, and inducing an inflammatory response. This may provide the underlying mechanism by which aPL responses lead to recurrent pregnancy loss or preeclampsia in women with obstetric antiphospholipid syndrome (APS). Although treatment with heparin may reduce the rate of recurrent pregnancy loss, the risk of preeclampsia remains high. Therefore, alternative treatments are needed for the management of pregnant patients with APS. Since aspirin‐triggered lipoxins (ATLs) have immune and angiogenic modulatory properties, the objective of this study was to determine the effects of the ATL 15‐epi‐lipoxin A4 on the function of aPL‐altered human trophoblasts in the first trimester of pregnancy.

Methods

A first‐trimester human trophoblast cell line (HTR8) was treated with mouse anti‐human β2‐glycoprotein I monoclonal antibodies (aPL) in the presence or absence of the ATL 15‐epi‐lipoxin A4. Trophoblast migration and interactions with endometrial endothelial cells were measured using Transwell and coculture assays. Trophoblast secretion of cytokines and angiogenic factors was measured by enzyme‐linked immunosorbent assay.

Results

Treatment of HTR8 cells with ATL reversed the aPL‐induced decrease in trophoblast migration, an effect that appeared to be regulated through restoration of interleukin‐6 production. Using a model of spiral artery transformation, aPL and sera from APS patients with pregnancy morbidity disrupted trophoblast–endothelial cell interactions, and treatment with ATL restored the stability of the cocultures. In contrast, ATL treatment did not resolve the proinflammatory and antiangiogenic responses of trophoblasts induced by aPL.

Conclusion

These findings indicate that ATLs may have some benefits in terms of preventing the effects of aPL on trophoblast function, which raises the possibility of the use of ATLs as an adjuvant therapy in women with aPL.
Power and Color Doppler Ultrasound Settings for Inflammatory Flow: Impact on Scoring of Disease Activity in Patients With Rheumatoid Arthritis
Authors: Torp‐Pedersen Søren , Christensen Robin , Szkudlarek Marcin , Ellegaard Karen , D'Agostino Maria Antonietta , Iagnocco Annamaria , Naredo Esperanza , Balint Peter , Wakefield Richard J. , Torp‐Pedersen Arendse , Terslev Lene
Published: November 2014

Objective

To determine how settings for power and color Doppler ultrasound sensitivity vary on different high‐ and intermediate‐range ultrasound machines and to evaluate the impact of these changes on Doppler scoring of inflamed joints.

Methods

Six different types of ultrasound machines were used. On each machine, the factory setting for superficial musculoskeletal scanning was used unchanged for both color and power Doppler modalities. The settings were then adjusted for increased Doppler sensitivity, and these settings were designated study settings. Eleven patients with rheumatoid arthritis (RA) with wrist involvement were scanned on the 6 machines, each with 4 settings, generating 264 Doppler images for scoring and color quantification. Doppler sensitivity was measured with a quantitative assessment of Doppler activity: color fraction. Higher color fraction indicated higher sensitivity.

Results

Power Doppler was more sensitive on half of the machines, whereas color Doppler was more sensitive on the other half, using both factory settings and study settings. There was an average increase in Doppler sensitivity, despite modality, of 78% when study settings were applied. Over the 6 machines, 2 Doppler modalities, and 2 settings, the grades for each of 7 of the patients varied between 0 and 3, while the grades for each of the other 4 patients varied between 0 and 2.

Conclusion

The effect of using different machines, Doppler modalities, and settings has a considerable influence on the quantification of inflammation by ultrasound in RA patients, and this must be taken into account in multicenter studies.
Cardiomyopathy in Murine Models of Systemic Sclerosis
Authors: Venalis Paulius , Kumánovics Gábor , Schulze‐Koops Hendrik , Distler Alfiya , Dees Clara , Zerr Pawel , Palumbo‐Zerr Katrin , Czirják László , Mackevic Zygmunt , Lundberg Ingrid E. , Distler Oliver , Schett Georg , Distler Jörg H. W.
Published: November 2014

Objective

Cardiomyopathy has emerged as a leading cause of death in patients with systemic sclerosis (SSc). However, the pathogenesis of SSc‐related cardiomyopathy is poorly understood, and new therapies as well as platforms for testing are needed. The aim of this study was to characterize the histopathologic features of cardiomyopathy in patients with SSc and in common mouse models of SSc.

Methods

The histopathologic features of myocardial tissue specimens obtained at autopsy from 5 subjects with SSc and 5 control subjects matched for sex, age, and cardiovascular risk factors were evaluated and compared with those of myocardial tissue specimens obtained from 3 common mouse models of SSc with systemic manifestations: Fra‐2–transgenic mice, mice with sclerodermatous chronic graft‐versus‐host disease (GVHD), and TSK‐1 mice.

Results

Myocardial tissue from autopsy subjects with SSc and no clinically manifest cardiac involvement showed endothelial cell apoptosis with reduced capillary density, perivascular inflammation, myofibroblast differentiation, and accumulation of collagen. Only selected features of SSc‐related cardiomyopathy were observed in the mice with chronic GVHD and TSK‐1 mice. However, the myocardial tissue of Fra‐2–transgenic mice mimicked all features of SSc‐related cardiomyopathy and also demonstrated comparable vascular, inflammatory, and fibrotic manifestations. Of note, the expression of Fra‐2 was also increased in the myocardium of autopsy subjects with SSc.

Conclusion

We demonstrate that all typical manifestations of SSc‐related cardiomyopathy are mimicked in Fra‐2–transgenic mice. Moreover, overexpression of Fra‐2 in the myocardium of autopsy subjects with SSc may suggest similar underlying pathogenic mechanisms. Thus, Fra‐2–transgenic mice might be a suitable preclinical model with which to study the mechanisms of and therapeutic approaches to myocardial involvement in SSc.
Fluorescence techniques used to measure interactions between hydroxyapatite nanoparticles and epidermal growth factor receptors
Authors: Kathawala Mustafa H. , Khoo Stella P. K. , Sudhaharan Thankiah , Zhao Xinxin , Say Chye Loo Joachim , Ahmed Sohail , Woei Ng Kee
Published: November 2014

The potential applications of nanomaterials in therapeutics are immense and to fully explore this potential, it is important to understand the interaction of nanoparticles with cellular components. To examine the interaction between nanoparticles and cell membrane receptors, this report describes the use of advanced fluorescence techniques to measure interactions between hydroxyapatite (HA) nanoparticles and epidermal growth factor receptors (EGFRs), as a model system. FITC‐labelled HA nanoparticles and monomeric red fluorescent protein (mRFP)‐conjugated EGFRs expressed in Chinese hamster ovary cells (CHO‐K1) were generated and their interaction measured using acceptor photobleaching‐fluorescence resonance energy transfer (AP‐FRET) and fluorescence lifetime imaging microscopy‐fluorescence resonance energy transfer (FLIM‐FRET). Results confirmed that hydroxyapatite nanoparticles not only interacted with EGFR but also attenuated downstream EGFR signalling, possibly by hindering normal dimerization of EGFR. Furthermore, the extent of signal attenuation suggested correlation with specific surface area of the nanoparticles, whereby greater specific surface area resulted in greater downstream signal attenuation. This novel demonstration establishes fluorescence techniques as a viable method to study nanoparticle interactions with proteins such as cell surface receptors. The approach described herein can be extended to study interactions between any fluorescently labelled nanoparticle‐biomolecule pair.
Xylan degradation improved by a combination of monolithic columns bearing immobilized recombinant β‐xylosidase from Aspergillus awamori X‐100 and Grindamyl H121 β‐xylanase
Authors: Volokitina Maria V. , Bobrov Kirill S. , Piens Kathleen , Eneyskaya Elena V. , Tennikova Tatiana B. , Vlakh Evgenia G. , Kulminskaya Anna A.
Published: November 2014

Synergistic action of exo‐ and endohydrolazes is preferred for effective destruction of biopolymers. The main purpose of the present work was to develop an efficient tool for degradation of xylan. Macroporous lab‐made monolithic columns and commercial CIM‐Epoxy disk were used to immobilize the recombinant β‐xylosidase from Aspergillus awamori and Grindamyl β‐xylanase. The efficiency of xylan degradation using the low‐loaded β‐xylosidase column appeared to be four times higher than for the in‐solution process and about six times higher than for the high‐loaded bioreactor. Disk bioreactor with the Grindamil β‐xylanase operated in a recirculation mode has shown noticeable advantages over the column design. Additionally, a system comprised of two immobilized enzyme reactors (IMERs) was tested to accelerate the biopolymer hydrolysis, yielding total xylan conversion into xylose within 20 min. Fast online monitoring HPLC procedure was developed where an analytical DEAE CIM disk was added to the two‐enzyme system in a conjoint mode. A loss of activity of immobilized enzymes did not exceed 7% after 5 months of the bioreactor usage. We can therefore conclude that the bioreactors developed exhibit high efficiency and remarkable long‐term stability.
Synchronized mammalian cell culture: Part II—population ensemble modeling and analysis for development of reproducible processes
Authors: Jandt Uwe , Platas Barradas Oscar , Pörtner Ralf , Zeng An‐Ping
Published: November 2014

The consideration of inherent population inhomogeneities of mammalian cell cultures becomes increasingly important for systems biology study and for developing more stable and efficient processes. However, variations of cellular properties belonging to different sub‐populations and their potential effects on cellular physiology and kinetics of culture productivity under bioproduction conditions have not yet been much in the focus of research. Culture heterogeneity is strongly determined by the advance of the cell cycle. The assignment of cell‐cycle specific cellular variations to large‐scale process conditions can be optimally determined based on the combination of (partially) synchronized cultivation under otherwise physiological conditions and subsequent population‐resolved model adaptation. The first step has been achieved using the physical selection method of countercurrent flow centrifugal elutriation, recently established in our group for different mammalian cell lines which is presented in Part I of this paper series. In this second part, we demonstrate the successful adaptation and application of a cell‐cycle dependent population balance ensemble model to describe and understand synchronized bioreactor cultivations performed with two model mammalian cell lines, AGE1.HNAAT and CHO‐K1. Numerical adaptation of the model to experimental data allows for detection of phase‐specific parameters and for determination of significant variations between different phases and different cell lines. It shows that special care must be taken with regard to the sampling frequency in such oscillation cultures to minimize phase shift (jitter) artifacts. Based on predictions of long‐term oscillation behavior of a culture depending on its start conditions, optimal elutriation setup trade‐offs between high cell yields and high synchronization efficiency are proposed. © 2014 American Institute of Chemical Engineers Biotechnol. Prog., 31:175–185, 2015
Inhibition of the hyaluronan oligosaccharides inflammatory response: reduction of adenosine 2A receptor activation by EPAC and PKA
Authors: Campo Giuseppe M. , Avenoso Angela , D'Ascola Angela , Scuruchi Michele , Nastasi Giancarlo , Calatroni Alberto , Campo Salvatore
Published: November 2014

The aim of this study was to investigate the involvement of exchange proteins directly activated by cyclic adenosine (ADO) monophosphate (EPAC) in 4‐mer hyaluronan (HA) oligosaccharide‐induced inflammatory response in mouse normal synovial fibroblasts (NSF).

Treatment of NSF with 4‐mer HA increased Toll‐like receptor‐4, TNF‐alpha and IL‐1beta mRNA expression and of the related proteins, as well as nuclear factor kappaB (NF‐kB) activation. Addition to NSF, previously stimulated with 4‐mer HA oligosaccharides, of ADO significantly reduced NF‐kB activation, TNF‐alpha and IL‐1beta expression. The pre‐treatment of NSF with cyclic ADO monophosphate and/or PKA and/or EPAC‐specific inhibitors significantly inhibited the anti‐inflammatory effect exerted by ADO. In particular, the EPAC inhibitor reduced the ADO effect to a major extent than the PKA inhibitor.

These results mean that both PKA and EPAC pathways are involved in ADO‐induced NF‐kB inhibition although EPAC seems to be more involved than PKA. Copyright © 2014 John Wiley & Sons, Ltd.
Optimal use of left ventriculography at the time of cardiac catheterization: A consensus statement from the society for cardiovascular angiography and interventions
Authors: Gigliotti Osvaldo S. , Babb Joseph D. , Dieter Robert S. , Feldman Dmitriy N. , Islam Ashequl M. , Marmagkiolis Konstantinos , Moore Phillip , Sorajja Paul , Blankenship James C.
Published: November 2014

The rationale to perform left ventriculography at the time of cardiac catheterization has been little studied. The technique and frequency of use of left ventriculography vary by geographic regions, institutions, and individuals. Despite the recent publication of guidelines and appropriate use criteria for coronary angiography, revascularization, and noninvasive imaging, to date there have been no specific guidelines on the performance of left ventriculography. When left ventriculography is performed, proper technique must be used to generate high quality data which can direct patient management. The decision to perform left ventriculography in place of, or in addition to, other forms of ventricular assessment should be made taking into account the clinical context and the type of information each study provides. This paper attempts to show the role of left ventriculography at the time of coronary angiography or left heart catheterization. The recommendations in this document are not formal guidelines but are based on the consensus of this writing group. These recommendations should be tested through clinical research studies. Until such studies are performed, the writing group believes that adoption of these recommendations will lead to a more standardized application of ventriculography and improve the quality of care provided to cardiac patients. © 2014 Wiley Periodicals, Inc.
Gender‐related clinical and echocardiographic outcomes at 30‐day and 12‐month follow up after MitraClip implantation in the GRASP registry
Authors: Attizzani Guilherme F. , Ohno Yohei , Capodanno Davide , Cannata Stefano , Dipasqua Fabio , Immé Sebastiano , Mangiafico Sarah , Barbanti Marco , Ministeri Margherita , Cageggi Anna , Pistritto Anna Maria , Giaquinta Sandra , Farruggio Silvia , Chiarandà Marta , Ronsivalle Giuseppe , Scandura Salvatore , Tamburino Corrado , Capranzano Piera , Grasso Carmelo
Published: November 2014

Objectives

To assess the influence of patients' gender on the outcomes of percutaneous edge‐to‐edge mitral valve repair (PMVR) using the MitraClip system.

Background

Although gender‐related differences have been extensively documented in patients who undergo surgery for moderate‐to‐severe (3+) and severe (4+) mitral regurgitation (MR), studies assessing whether these differences exist after PMVR are lacking.

Methods

Clinical and echocardiographic data through 12‐month follow up from 171 consecutive patients whom underwent MitraClip implantation and were dichotomized by the gender (106 males and 65 females) were obtained. The primary safety endpoint was the incidence of major adverse events at 30 days and the primary efficacy endpoint was freedom from death, surgery for mitral valve dysfunction, or grade ≥ 3+ MR at 12‐month follow up.

Results

The primary safety endpoint was observed in four males (3.8%) and four females (6.2%) (P = 0.358). Remarkable reduction in MR postprocedure was revealed in both groups, and these results were mostly sustained. Furthermore, left ventricle reverse remodeling and New York Heart Association (NYHA) functional class improvement were revealed in both groups, but females tended to demonstrate worse results over time (P = 0.083). The primary efficacy endpoint obtained by Kaplan‐Meier estimates was observed in 76.3 and 70.2%, respectively (log rank P = 0.231).

Conclusions

MitraClip implantation in patients with 3+ and 4+ MR is safe and efficacious until mid‐term follow up, regardless of patients' gender. Despite improvement in NYHA functional class in both groups, female gender demonstrated a trend toward poorer results. Further validation of our findings is warranted. © 2014 Wiley Periodicals, Inc.
Comparison of acute elastic recoil between the SAPIEN‐XT and SAPIEN valves in transfemoral–transcatheter aortic valve replacement
Authors: Garg Aatish , Parashar Akhil , Agarwal Shikhar , Aksoy Olcay , Hammadah Muhammad , Poddar Kanhaiya Lal , Puri Rishi , Svensson Lars G. , Krishnaswamy Amar , Tuzcu E. Murat , Kapadia Samir R.
Published: November 2014

Background

The SAPIEN‐XT is a newer generation balloon‐expandable valve created of cobalt chromium frame, as opposed to the stainless steel frame used in the older generation SAPIEN valve. We sought to determine if there was difference in acute recoil between the two valves.

Methods

All patients who underwent transfemoral–transcatheter aortic valve replacement using the SAPIEN‐XT valve at the Cleveland Clinic were included. Recoil was measured using biplane cine‐angiographic image analysis of valve deployment. Acute recoil was defined as [(valve diameter at maximal balloon inflation) − (valve diameter after deflation)]/valve diameter at maximal balloon inflation (reported as percentage). Patients undergoing SAPIEN valve implantation were used as the comparison group.

Results

Among the 23 mm valves, the mean (standard deviation—SD) acute recoil was 2.77% (1.14) for the SAPIEN valve as compared to 3.75% (1.52) for the SAPIEN XT valve (P = 0.04). Among the 26 mm valves, the mean (SD) acute recoil was 2.85% (1.4) for the SAPIEN valve as compared to 4.32% (1.63) for the SAPIEN XT valve (P = 0.01). Multivariable linear regression analysis demonstrated significantly greater adjusted recoil in the SAPIEN XT valves as compared to the SAPIEN valves by 1.43% [(95% CI: 0.69–2.17), P < 0.001]. However, the residual peak gradient was less for SAPIEN XT compared to SAPIEN valves [18.86 mm Hg versus 23.53 mm Hg (P = 0.01)]. Additionally, no difference in paravalvular leak was noted between the two valve types (P = 0.78).

Conclusions

The SAPIEN XT valves had significantly greater acute recoil after deployment compared to the SAPIEN valves. Implications of this difference in acute recoil on valve performance need to be investigated in future studies. © 2014 Wiley Periodicals, Inc.
Increasing the Electrolyte Capacity of Alkaline Zn–Air Fuel Cells by Scavenging Zincate with Ca(OH)2
Authors: Zhu Aaron L. , Duch Darek , Roberts Gregory A. , Li Sasha X. X. , Wang Haijiang , Duch Konrad , Bae Eunjoo , Jung Kwang S. , Wilkinson David , Kulinich Sergei A.
Published: November 2014

The use of calcium hydroxide for scavenging zincate species is demonstrated to be a highly effective approach for increasing the electrolyte capacity and improving the performance of the zinc–air fuel cell system. A fundamental approach is established in this study to quantify the formation of calcium zincate as the product of scavenging and the amount of water compensation necessary for optimal performance. The good agreement between predicted and experimental results proves the validity of the proposed theoretical approach. By applying the results of theoretical predictions, both the electrolyte capacity and the cell longevity have been increased by more than 40 %. It is also found that, using Ca(OH)2 to scavenge zincate species in concentrated KOH solutions, affects mostly the removal of zincate, rather than ZnO, from the electrolyte, whereas the presence of excess, free, mobile H2O plays a key role in dissolving ZnO and forming zincate. The results obtained in this study demonstrate that the proposed approach can widely and effectively be applied to all zinc–air cell systems during their discharge cycle.
Electrochemical Conversion of CO2 into Negative Electrode Materials for Li‐Ion Batteries
Authors: Ge Jianbang , Hu Liwen , Wang Wei , Jiao Handong , Jiao Shuqiang
Published: November 2014

The capture and electrochemical conversion of CO2 in molten LiCl–Li2CO3 salt is proposed. By using an inert platinum anode and a tungsten cathode, the CO32− could be easily converted into carbon and oxygen gas, as well as O2−. The released O2− was responsible for the further capture of CO2. Also, CO2 could be effectively absorbed in such chloride melts with a low content of oxygen ion dissolved. In addition, the produced carbon displayed good performance as a negative electrode material for Li‐ion batteries, suggesting that the process is an environmentally friendly way to convert CO2 into energy‐storage materials.
Strongly Coupled Cyclometalated Ruthenium–Triarylamine Hybrids: Tuning Electrochemical Properties, Intervalence Charge Transfer, and Spin Distribution by Substituent Effects
Authors: Yao Chang‐Jiang , Nie Hai‐Jing , Yang Wen‐Wen , Shao Jiang‐Yang , Yao Jiannian , Zhong Yu‐Wu
Published: November 2014

Nine cyclometalated ruthenium complexes with a redox‐active diphenylamine unit in the para position to the RuC bond were prepared. MeO, Me, and Cl substituents on the diphenylamine unit and three types of auxiliary ligands—bis(N‐methylbenzimidazolyl)pyridine (Mebip), 2,2′:6′,2′′‐terpyridine (tpy), and trimethyl‐4,4′,4′′‐tricarboxylate‐2,2′:6′,2′′‐terpyridine (Me3tctpy)—were used to vary the electronic properties of these complexes. The derivative with an MeO‐substituted amine unit and Me3tctpy ligand was studied by single‐crystal X‐ray analysis. All complexes display two well‐separated redox waves in the potential region of +0.1 to +1.0 V versus Ag/AgCl, and the potential splitting ranges from 360 to 510 mV. Spectroelectrochemical measurements show that these complexes display electrochromism at low potentials and intense near‐infrared (NIR) absorptions. In the one‐electron oxidized form, the complex with the Cl‐substituted amine unit and Mebip ligand shows a moderate ligand‐to‐metal charge transfer at 800 nm. The other eight complexes show asymmetric, narrow, and intense intervalence charge‐transfer transitions in the NIR region, which are independent of the polarity of the solvent. The Mebip‐containing complexes display rhombic or broad isotropic EPR signals, whereas the other seven complexes show relatively narrow isotropic EPR signals. In addition, DFT and time‐dependent DFT studies were performed to gain insights into the spin distributions and NIR absorptions.
Chemically and Biologically Harmless versus Harmful Ferritin/Copper–Metallothionein Couples
Authors: Carmona Fernando , Mendoza Daniela , Kord Scheghajegh , Asperti Michela , Arosio Paolo , Atrian Sílvia , Capdevila Mercè , Dominguez‐Vera Jose M.
Published: November 2014

The simultaneous measurement of the decrease of available FeII ions and the increase of available FeIII ions allowed the analysis of the ferroxidase activity of two distinct apoferritins. Although recombinant human apoferritin (HuFtH) rapidly oxidizes FeII to FeIII, this iron is not properly stored in the ferritin cavity, as otherwise occurs in horse‐spleen H/L‐apoferritin (HsFt; H=heavy subunit, L=light subunit). Iron storage in these apoferritins was also studied in the presence of two copper‐loaded mammalian metallothioneins (MT2 and MT3), a scenario that occurs in different brain‐cell types. For HuFtH, unstored FeIII ions trigger the oxidation of Cu–MT2 with concomitant CuI release. In contrast, there is no reaction with Cu–MT2 in the case of HsFt. Similarly, Cu–MT3 does not react during either HuFtH or HsFt iron reconstitution. Significantly, the combination of ferritin and metallothionein isoforms reported in glia and neuronal cells are precisely those combinations that avoid a harmful release of FeII and CuI ions.
Insights into the Crystallisation Process from Anhydrous, Hydrated and Solvated Crystal Forms of Diatrizoic Acid
Authors: Fucke Katharina , McIntyre Garry J. , Lemée‐Cailleau Marie‐Hélène , Wilkinson Clive , Edwards Alison J. , Howard Judith A. K. , Steed Jonathan W.
Published: November 2014

Diatrizoic acid (DTA), a clinically used X‐ray contrast agent, crystallises in two hydrated, three anhydrous and nine solvated solid forms, all of which have been characterised by X‐ray crystallography. Single‐crystal neutron structures of DTA dihydrate and monosodium DTA tetrahydrate have been determined. All of the solid‐state structures have been analysed using partial atomic charges and hardness algorithm (PACHA) calculations. Even though in general all DTA crystal forms reveal similar intermolecular interactions, the overall crystal packing differs considerably from form to form. The water of the dihydrate is encapsulated between a pair of host molecules, which calculations reveal to be an extraordinarily stable motif. DTA presents functionalities that enable hydrogen and halogen bonding, and whilst an extended hydrogen‐bonding network is realised in all crystal forms, halogen bonding is not present in the hydrated crystal forms. This is due to the formation of a hydrogen‐bonding network based on individual enclosed water squares, which is not amenable to the concomitant formation of halogen bonds. The main interaction in the solvates involves the carboxylic acid, which corroborates the hypothesis that this strong interaction is the last one to be broken during the crystal desolvation and nucleation process.
Hexane Cracking over Steamed Phosphated Zeolite H‐ZSM‐5: Promotional Effect on Catalyst Performance and Stability
Authors: van der Bij Hendrik E. , Meirer Florian , Kalirai Sam , Wang Jian , Weckhuysen Bert M.
Published: November 2014

The nature behind the promotional effect of phosphorus on the catalytic performance and hydrothermal stability of zeolite H‐ZSM‐5 has been studied using a combination of 27Al and 31P MAS NMR spectroscopy, soft X‐ray absorption tomography and n‐hexane catalytic cracking, complemented with NH3 temperature‐programmed desorption and N2 physisorption. Phosphated H‐ZSM‐5 retains more acid sites and catalytic cracking activity after steam treatment than its non‐phosphated counterpart, while the selectivity towards propylene is improved. It was established that the stabilization effect is twofold. First, the local framework silico‐aluminophosphate (SAPO) interfaces, which form after phosphatation, are not affected by steam and hold aluminum atoms fixed in the zeolite lattice, preserving the pore structure of zeolite H‐ZSM‐5. Second, the four‐coordinate framework aluminum can be forced into a reversible sixfold coordination by phosphate. These species remain stationary in the framework under hydrothermal conditions as well. Removal of physically coordinated phosphate after steam‐treatment leads to an increase in the number of strong acid sites and increased catalytic activity. We propose that the improved selectivity towards propylene during catalytic cracking can be attributed to local SAPO interfaces located at channel intersections, where they act as impediments in the formation of bulky carbenium ions and therefore suppress the bimolecular cracking mechanism.
Synthesis, Properties, and Redox Behavior of 1,1,4,4‐Tetracyano‐2‐ferrocenyl‐1,3‐butadienes Connected by Aryl, Biaryl, and Teraryl Spacers
Authors: Shoji Taku , Maruyama Akifumi , Yaku Chisa , Kamata Natsumi , Ito Shunji , Okujima Tetsuo , Toyota Kozo
Published: November 2014

Aryl‐substituted 1,1,4,4‐tetracyano‐1,3‐butadienes (FcTCBDs) and bis(1,1,4,4‐tetracyanobutadiene)s (bis‐FcTCBDs), possessing a ferrocenyl group on each terminal, were prepared by the reaction of a variety of alkynes with tetracyanoethylene (TCNE) in a [2+2] cycloaddition reaction, followed by retro‐electrocyclization of the initially formed [2+2] cycloadducts (i.e., cyclobutene derivatives). The characteristic intramolecular charge transfer (ICT) between the donor (ferrocene) and acceptor (TCBD) moieties were investigated by using UV/Vis spectroscopy. The redox behaviors of FcTCBDs and bis‐FcTCBDs were examined by cyclic voltammetry (CV) and differential pulse voltammetry (DPV), which revealed their properties of multi‐electron transfer depending on the number of ferrocene and TCBD moieties. Moreover, significant color changes were observed by visible spectroscopy under the electrochemical reduction conditions.
Dual Photo‐ and pH‐Responsive Supramolecular Nanocarriers Based on Water‐Soluble Pillar[6]arene and Different Azobenzene Derivatives for Intracellular Anticancer Drug Delivery
Authors: Hu Xiao‐Yu , Jia Keke , Cao Yu , Li Yan , Qin Shan , Zhou Fan , Lin Chen , Zhang Dongmei , Wang Leyong
Published: November 2014

Two novel types of supramolecular nanocarriers fabricated by the amphiphilic host–guest inclusion complex formed from water‐soluble pillar[6]arene (WP6) and azobenzene derivatives G1 or G2 have been developed, in which G1 is structurally similar to G2 but has an extra phenoxy group in its hydrophobic region. Supramolecular micelles can be initially formed by WP6 with G1, which gradually transform into layered structures with liquid‐crystalline properties, whereas stable supramolecular vesicles are obtained from WP6 and G2, which exhibit dual photo‐ and pH‐responsiveness. Notably, the resulting WP6⊃G2 vesicles can efficiently encapsulate anticancer drug mitoxantrone (MTZ) to achieve MTZ‐loaded vesicles, which maintain good stability in a simulated normal physiological environment, whereas in an acid environment similar to that of tumor cells or with external UV irradiation, the encapsulated drug is promptly released. More importantly, cytotoxicity assay indicates that such vesicles have good biocompatibility and the MTZ‐loaded vesicles exhibit comparable anticancer activity to free MTZ, especially with additional UV stimulus, whereas its cytotoxicity for normal cells was remarkably reduced. Flow cytometric analysis further confirms that the cancer cell death caused by MTZ‐loaded vesicles is associated with apoptosis. Therefore, the dual pH‐ and UV‐responsive supramolecular vesicles are a potential platform for controlled release and targeted anticancer drug delivery.