bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiac valve replacement in patients with antiphospholipid syndrome
Authors: Erdozain José‐Gabriel , Ruiz‐Irastorza Guillermo , Segura Maria‐Isabel , Amigo Mary‐Carmen , Espinosa Gerard , Pomar Jose‐Luis , Perez‐Valero Ignacio , Ateka‐Barrutia Oier , Khamashta Munther A.
Published: March 2012

Objective

To analyze the results of cardiac valve replacement in a multicenter cohort of patients with antiphospholipid syndrome (APS) and to identify prognostic factors of poor outcome.

Methods

We performed a retrospective analysis of clinical manifestations (cardiac involvement and APS characteristics), operative and early postoperative courses, and long‐term followup. All of the patients fulfilled the Sapporo criteria for APS. Logistic regression analyses were performed to identify those variables associated with adverse outcomes.

Results

Between 1981 and 2008, 33 valvular replacements were carried out in 32 patients with APS. The mean ± SD age at the time of surgery was 43.09 ± 14.08 years. Thirty patients were women. Primary APS was present in 21 patients. The median followup time after surgery was 33.5 months (range 0–192 months). The mitral valve was the most frequently replaced (22 of 33). Mechanical valve replacement was performed in 23 patients (71.9%). The mortality rate was 12.5% (1 cardiogenic shock, 1 septic shock, 1 following renal transplantation, and 1 hemorrhagic stroke). Fourteen patients experienced 20 complications (8 major bleeding, 5 thrombotic events, 2 valvular deteriorations, 2 third‐degree atrioventricular block, 1 endocarditis, 1 cardiac tamponade, and 1 cardiac failure). Fifty percent of the patients had an uneventful outcome.

Conclusion

Morbidity and mortality were high in APS patients undergoing valve replacement surgery. Most complications were related to thrombosis and bleeding. Anticoagulation must be carefully monitored to prevent hemorrhagic and thrombotic complications.
Increased frequency of DRB1*11:01 in anti–hydroxymethylglutaryl‐coenzyme A reductase–associated autoimmune myopathy
Authors: Mammen Andrew L. , Gaudet Daniel , Brisson Diane , Christopher‐Stine Lisa , Lloyd Thomas E. , Leffell Mary S. , Zachary Andrea A.
Published: March 2012

Objective

To investigate the association of anti–hydroxymethylglutaryl‐coenzyme A reductase (anti‐HMGCR) myopathy with HLA class I and II antigens.

Methods

HLA antigens were determined in 1) 20 white and 8 African American anti‐HMGCR patients, 2) 487 white and 167 African American controls, and 3) 51 white subjects with mild self‐limited statin intolerance.

Results

White anti‐HMGCR patients had a higher frequency of the combination HLA–DR11, DQA5, and DQB7 than controls or statin‐intolerant subjects (70% versus 17%; odds ratio [OR] 11.7 [95% confidence interval (95% CI) 4.0–35.3], P = 4.1 × 10−7 and 70% versus 21%; OR 8.3 [95% CI 2.2–33.9], P = 5.4 × 10−4, respectively). This combination was not increased in African American anti‐HMGCR subjects compared to controls (13% versus 3%; OR 4.6 [95% CI 0.2–53.3], P = 0.2). However, DR11 was increased in African American anti‐HMGCR patients compared to controls (88% versus 21%; OR 26.4 [95% CI 3.1–590.3], P = 0.0002). High‐resolution mapping showed that 95% with DR11 had DRB1*11:01. DQA1 and DQB6 were less frequent in white anti‐HMGCR–positive patients compared to controls (25% versus 65%; OR 0.2 [95% CI 0.1–0.5], P = 5.5 × 10−4 and 0% versus 45%; OR 0.0 [95% CI 0.0–0.3], P = 2.1 × 10−5, respectively). DRB11 was not associated with particular disease features.

Conclusion

DRB1*11:01 is associated with an increased risk of anti‐HMGCR myopathy in whites and African Americans. These findings suggest a mechanistic link between statin exposure, increased HMGCR expression, and the possible presentation of HMGCR‐derived peptide(s) by DRB1*11:01.
Protein Adsorption Modes Determine Reversible Cell Attachment on Poly(N‐isopropyl acrylamide) Brushes
Authors: Xue Changying , Choi Byun‐Chan , Choi Sangwook , Braun Paul V. , Leckband Deborah E.
Published: March 2012

Protein adsorption and reversible cell attachment are investigated as a function of the grafting density of poly(N‐isopropyl acrylamide) (PNIPAM) brushes. Prior studies demonstrated that the thermally driven collapse of grafted PNIPAM above the lower critical solution temperature of 32 °C is not required for protein adsorption. Here, the dependence of reversible, protein‐mediated cell adhesion on the polymer chain density, above and below the lower critical solution temperature, is reported. Above 32 °C, protein adsorption on PNIPAM brushes grafted from a non‐adsorbing, oligo(ethylene oxide)‐coated surface exhibits a maximum with respect to the grafting density. Few cells attach to either dilute or densely grafted PNIPAM chains, independent of whether the polymer brush collapses above 32 °C. However, both cells and proteins adsorb reversibly at intermediate chain densities. This supports a model in which the proteins, which support reversible cell attachment, adsorb by penetrating the brushes at intermediate grafting densities, under poor solvent conditions. In this scenario, reversible protein adsorption to PNIPAM brushes is determined by the thermal modulation of relative protein‐segment attraction and osmotic repulsion.
Relationship of 2D:4D finger ratio with muscle strength, testosterone, and androgen receptor CAG repeat genotype
Authors: Folland Jonathan P. , Mc Cauley Tracey M. , Phypers Cherry , Hanson Beth , Mastana Sarabjit S.
Published: March 2012

This study aimed to examine the relationship between the ratio of the length of the second and fourth digits (2D:4D) and locomotor muscle strength. Furthermore, two putative mechanisms that might explain any relationship of 2D:4D with muscle strength, specifically serum total and free testosterone, and androgen receptor genotype CAG repeat number (AR CAGn) were investigated. Seventy‐seven healthy young Caucasian men completed a thorough assessment of isometric and isokinetic knee extensor strength, with unilateral measurements averaged across both legs and repeated on two occasions. The lengths of the second and fourth fingers of each hand were measured to calculate 2D:4D ratio. Serum total testosterone (TT) and serum hormone binding globulin (SHBG) were measured by ELISA and used to calculate free testosterone (FT). AR CAGn was determined by PCR and microchip electrophoresis. There was no association between mean, left or right hand 2D:4D and isometric or isokinetic knee extensor strength (all, R < 0.12, P > 0.32). TT and FT were unrelated to mean, left or right hand 2D:4D ratio (all, R < 0.12, P > 0.34). Finally AR CAGn was not associated with mean, right or left hand 2D:4D ratio (all, R < 0.20, P > 0.10). This study found no evidence of 2D:4D being related to locomotor muscle strength, TT, FT, or AR CAGn. The reported association of 2D:4D with sports performance does not seem to be explained by an influence on locomotor muscle strength, and could be due to an effect on motor or cognitive skills. Am J Phys Anthropol, 2012. © 2012 Wiley Periodicals, Inc.
Arine und Cyclohexin in der Naturstoffsynthese
Authors: Gampe Christian M. , Carreira Erick M.
Published: March 2012

Dieser Kurzaufsatz stellt neueste Fortschritte auf dem Gebiet der Arin‐ und Cyclohexinchemie vor, die es ermöglicht haben, die außergewöhnliche Reaktivität dieser Verbindungen in der Naturstoffsynthese nutzbar zu machen. Die vorgestellten Synthesen beruhen auf der Nutzung dieser reaktiven Spezies in chemoselektiven Umsetzungen, folgen noch nicht dagewesenen Synthesestrategien und sind daher inspririerend für die organische Synthesechemie.
The Art of Fluorescence Imaging with Chemical Sensors
Authors: Schäferling Michael
Published: March 2012

Fluorescence imaging techniques involving chemical sensors are essential tools in many fields of science and technology because they enable the visualization of parameters which exhibit no intrinsic color or fluorescence, for example, oxygen, pH value, CO2, H2O2, Ca2+, or temperature, to name just a few. This Review aims to highlight the state of the art of fluorescence sensing and imaging, starting from a comprehensive overview of the basic functional principles of fluorescent probes (or indicators) and the design of sensor materials. The focus is directed towards the progress made in the development of multiple sensors and methods for their signal read out. Imaging methods involving optical sensors are applied in quite diverse scientific areas, such as medical research, aerodynamics, and marine research.
Tailoring the ionic association and microstructure of ionomers with various metal salts
Authors: Gao Yan , Choudhury Namita Roy , Dutta Naba K.
Published: March 2012

In this work, we investigated the effects of metal stearate salts on the structure, morphology, and properties of poly(ethylene–acrylic acid) neutralized by zinc salts (PI). The samples were characterized in detail with spectroscopic [Fourier transform infrared (FTIR) spectroscopy], microscopic (hot‐stage optical microscopy), thermal [thermogravimetric analysis, modulated differential scanning calorimetry, and dynamic mechanical analysis], mechanical, and scattering (small‐angle neutron scattering and small‐angle X‐ray scattering) techniques. The melt rheological properties of the samples were also investigated. The structure of the ionic domains was determined by the type of cations and the salt proportion (FTIR). The predominant interaction was found to exist between the metal stearate and the ionic group. Na+ cation exhibited a unique behavior, whereas Zn2+ showed a coordinated structure and, hence, properties. The ionic groups in the Na and Zn stearate systems existed as multiplets and clusters, but multiplets were the main structure in the Al salt system. The salts acted as plasticizers above their melting points (mp's) but as fillers below their mp's. The melt flow properties of PI were significantly affected by the metal cation and salt proportion and were improved greatly by the introduction of the salts. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
Characterization of structure and properties of polylactic fiber
Authors: Du Zhaoqun , Xu Yun , Yu Weidong
Published: March 2012

Polylactic fiber (PLA) is a new environment‐friendly fiber and has been produced by different plants with wide application, while there are few studies on the difference of the structure and property of PLA fibers produced from these plants in China. The main content in present article is to conduct elementary analysis, gas chromatography mass spectrum, IR spectroscopy, ultraviolet, X‐ray, differential scanning calorimetry (DSC), TG, SEM, and tensile tests to obtain the common structure and properties of PLA fibers and to prove that there are no significant difference between the 13 kinds of PLA fibers made by 13 plants in China. The elementary analysis method is used to test the contents of C, H, and O elements, and it has good accordance with the theoretical results. Gas chromatography mass spectrum method proves that the functional groups of PLA fiber are lactide and acetaldehyde as well as 2,3‐pentanedione. IR spectroscopy depicts that significant absorbing peaks exist as CO, CO, OH within absorbing wavelength zones. There are no characteristic absorbing peaks of ultraviolet spectrum. Crystallinity and orientation degree in full wave at half maximum and in area are calculated based on X‐ray. The peak melting point and pyrogenation peak point are obtained by DSC and TG testings. The tensile property and the surface morphology by SEM are conducted and some typical faults in the surface are observed. In addition, the coefficient of variance of these experimental results between 13 kinds of PLA fibers show that their structure and properties are similar. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
Normalization of widespread hyperesthesia and facilitated spatial summation of deep‐tissue pain in knee osteoarthritis patients after knee replacement
Authors: Graven‐Nielsen T. , Wodehouse T. , Langford R. M. , Arendt‐Nielsen L. , Kidd B. L.
Published: March 2012

Objective

The modest association between radiographic joint damage and pain in osteoarthritis (OA) has led to the suggestion of facilitated central pain processing. This study evaluated the importance of ongoing tissue pathology in the maintenance of enhanced central pain processing.

Methods

Pain assessment was performed on 48 patients with symptomatic knee OA and 21 sex‐ and age‐matched pain‐free healthy control subjects. Twenty of the OA patients subsequently underwent total knee replacement surgery and were reassessed. Pressure–pain thresholds (PPTs) were recorded using a pressure algometer (both over and distant from the knee) and a double‐chamber inflatable cuff mounted around the calf. Spatial summation was assessed by relating PPTs using the dual‐ and single‐chamber cuff. Conditioned pain modulation (CPM) was assessed by recording the increase in PPT in response to experimental arm pain.

Results

PPTs at the knee and at sites away from the knee were reduced in OA patients as compared with healthy pain‐free control subjects (P < 0.0001). Cuff PPTs were decreased in OA patients as compared with the healthy controls (P < 0.05), who also exhibited a greater degree of spatial summation (P < 0.05). Whereas an elevation of PPTs was noted in the healthy controls in response to experimental arm pain (P < 0.0001), no such CPM was observed in the OA patients. Following joint replacement in the OA patients, there was a reduction in the widespread mechanical hyperesthesia, along with normalization of spatial summation ratios and restoration of CPM.

Conclusion

The widespread hyperesthesia and enhanced spatial summation observed in OA patients imply sensitized central pain mechanisms together with the loss of CPM. Normalization of the results following joint replacement implies that these central pain processes are maintained by peripheral input.
Detection of synovitis in the hands of patients with rheumatologic disorders: Diagnostic performance of optical imaging in comparison with magnetic resonance imaging
Authors: Meier Reinhard , Thürmel Klaus , Moog Philipp , Noël Peter B. , Ahari Carmen , Sievert Matti , Dorn Franziska , Waldt Simone , Schaeffeler Christoph , Golovko Daniel , Haller Bernhard , Ganter Carl , Weckbach Sabine , Woertler Klaus , Rummeny Ernst J.
Published: March 2012

Objective

To prospectively compare an indocyanine green (ICG)–enhanced optical imaging system with contrast‐enhanced magnetic resonance imaging (MRI) for the detection of synovitis in the hands of patients with rheumatologic disorders.

Methods

Forty‐five patients (30 women [67%], mean ± SD age 52.6 ± 13.4 years) in whom there was a clinical suspicion of an inflammatory arthropathy were examined with a commercially available device for ICG‐enhanced optical imaging as well as by contrast‐enhanced 3T MRI as the standard of reference. Three independent readers graded the degree of synovitis in the carpal, metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints of both hands (1,350 joints), using a 4‐point ordinate scale (0 = no synovitis, 1 = mild, 2 = moderate, 3 = severe). Statistical analyses were performed using a logistic generalized estimating equation approach. Agreement of optical imaging ratings made by the different readers was estimated with a weighted kappa coefficient.

Results

When MRI was used as the standard of reference, optical imaging showed a sensitivity of 39.6% (95% confidence interval [95% CI] 31.1–48.7%), a specificity of 85.2% (95% CI 79.5–89.5%), and accuracy of 67.0% (95% CI 61.4–72.1%) for the detection of synovitis in patients with arthritis. Diagnostic accuracy was especially limited in the setting of mild synovitis, while it was substantially better in patients with severely inflamed joints. Moderate interreader and intrareader agreement was observed.

Conclusion

The evaluated ICG‐enhanced optical imaging system showed limitations for the detection of inflamed joints of the hand in comparison with MRI.
Progressive multifocal leukoencephalopathy associated with immunosuppressive therapy in rheumatic diseases: Evolving role of biologic therapies
Authors: Molloy Eamonn S. , Calabrese Leonard H.
Published: March 2012

Objective

To evaluate the association of progressive multifocal leukoencephalopathy (PML) with immunosuppressive therapy for autoimmune rheumatic diseases (ARDs).

Methods

A Freedom of Information Act request was submitted for all cases of PML within the Food and Drug Administration Adverse Event Reporting System database. ARD cases were selected for further analysis.

Results

A total of 34 confirmed cases of PML in the setting of ARDs were identified: 17 had systemic lupus erythematosus, 10 had rheumatoid arthritis, 4 had vasculitis, and 3 had dermatomyositis. Fifteen of these patients were treated with one or more biologic agents: 14 received rituximab (RTX), 6 received anti–tumor necrosis factor (anti‐TNF) therapy (5 treated with anti‐TNF agent prior to RTX). Four RTX‐treated patients were not receiving additional immunosuppressive therapy at the time of PML onset, other than an antimalarial drug and/or low‐dose glucocorticoids; all others who were receiving a biologic agent were also receiving one or more synthetic disease‐modifying agents. All but 1 patient receiving a biologic agent had at least 1 potential confounding factor for the diagnosis of PML. The remaining 19 confirmed cases of PML among ARD patients were treated with synthetic disease‐modifying antirheumatic drugs only, 14 of whom had received an alkylating agent.

Conclusion

PML has been reported in patients with ARD treated with various immunosuppressive agents. The limitations of this study preclude definitive attribution of causality. While the paucity of confirmed cases recently exposed to anti‐TNF therapy suggests a causal relationship is unlikely, a specific signal is emerging with regard to rituximab and PML. Although this is a rare adverse event associated with RTX therapy, the devastating nature of PML mandates continued vigilance, particularly in patients with current or prior exposure to an alkylating agent.
Biomass recalcitrance. Part I: the chemical compositions and physical structures affecting the enzymatic hydrolysis of lignocellulose
Authors: Zhao Xuebing , Zhang Lihua , Liu Dehua
Published: March 2012

Lignocellulosic biomass is recalcitrant to biodegradation due to the rigid and compact structure of plant cell wall. The recalcitrance of biomass is mainly constructed by its chemical compositions that build a spatial network as a protective bulwark. Generally, the factors affecting the accessibility of biomass cellulose can be divided into direct and indirect factors. The direct factors refer to the accessible surface area, and the indirect factors include biomass structure‐relevant factors (pore size and volume, particle size, and specific surface area), chemical compositions (lignin, hemicelluloses, and acetyl group), and cellulose structure‐relevant factors (cellulose crystallinity and degree of polymerization). Pre‐treatment is actually the process to alter indirect factors and improve direct factors thus enhancing the accessibility of cellulose. In this review, we summarize the effects of chemical compositions and physical structures on the enzymatic digestibility of lignocellulosic biomass. We suggest that future work should be focused on but not limited to the molecular mechanisms of biomass recalcitrance by investigating the microscale and nanoscale features as well as hydrogen bonds network of lignocellulosic biomass. © 2012 Society of Chemical Industry and John Wiley & Sons, Ltd
Industry expectations regarding the transition toward a biobased economy
Authors: Vandermeulen Valerie , Van der Steen Marijke , Stevens Christian V. , Van Huylenbroeck Guido
Published: March 2012

The transition from a fossil‐input‐based economy toward a bio‐based economy is not an easy process. Although policy‐makers in the European Union (EU) advocate this transition, still most companies and economies in the EU rely on fossil fuels for the production of materials and goods. However, the transition will not only depend on policy but will also involve all stakeholders: consumers, firms, and supporting policy with industry playing a major role. This paper focuses on the perceptions and expectations of industry regarding a possible transition toward a bio‐based economy. Based on the multilevel perspective emphasized in transition theory, the opinions of Flemish captains of industry active in the bio‐based sector are analyzed. The case of Flanders is taken because it is a good example of a small European economy relying heavily on imported fossil inputs. Based on the views of the captains of industry combined with the multilevel transition perspective, we argue that the transition toward a bio‐based economy follows a typical sequence of pathways starting with a transformation pathway and evolving toward a technological substitution or de‐ and re‐‐alignment pathway. This theoretical transition perspective helps to define which issues related to market development, technology, research, science, and policy, can influence the transition toward a bio‐based economy which helps to describe some future directions for Flanders as well as other European regions. © 2012 Society of Chemical Industry and John Wiley & Sons, Ltd
Banding patterns in Drosophila melanogaster polytene chromosomes correlate with DNA‐binding protein occupancy
Authors: Zhimulev Igor F. , Belyaeva Elena S. , Vatolina Tatiana Yu , Demakov Sergey A.
Published: March 2012

The most enigmatic feature of polytene chromosomes is their banding pattern, the genetic organization of which has been a very attractive puzzle for many years. Recent genome‐wide protein mapping efforts have produced a wealth of data for the chromosome proteins of Drosophila cells. Based on their specific protein composition, the chromosomes comprise two types of bands, as well as interbands. These differ in terms of time of replication and specific types of proteins. The interbands are characterized by their association with “active” chromatin proteins, nucleosome remodeling, and origin recognition complexes, and so they have three functions: acting as binding sites for RNA pol II, initiation of replication and nucleosome remodeling of short fragments of DNA. The borders and organization of the same band and interband regions are largely identical, irrespective of the cell type studied. This demonstrates that the banding pattern is a universal principle of the organization of interphase polytene and non‐polytene chromosomes.

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Immune tolerance: Are regulatory T cell subsets needed to explain suppression of autoimmunity?
Authors: Tian Lei , Humblet‐Baron Stephanie , Liston Adrian
Published: March 2012

The potential for self‐reactive T cells to cause autoimmune disease is held in check by Foxp3+ regulatory T cells (Tregs), essential mediators of peripheral immunological tolerance. Tregs have the capacity to suppress multiple branches of the immune system, tightly controlling the different subsets of effector T cells across multiple different tissue environments. Recent genetic experiments have found mutations that disrupt specific Treg: effector T cell relationships, leading to the possibility that subsets of Tregs are required to suppress each subset of effector T cells. Here we review the environmental factors and mechanisms that allow Tregs to suppress specific subsets of effector T cells, and find that a parsimonious explanation of the genetic data can be made without invoking Treg subsets. Instead, Tregs show a functional and chemotactic plasticity based on microenvironmental influences that allows the common pool of cells to suppress multiple distinct immune responses.
Ascorbic acid, cognitive function, and Alzheimer's disease: A current review and future direction
Authors: Bowman Gene L.
Published: March 2012

This narrative review appraises the human and animal studies implicating ascorbic acid (AA) in normal cognitive function and Alzheimer's disease. A research framework for how nutrition affects brain aging is proposed with emphasis on AA intake, status, metabolism, and transport into brain tissue. A final synopsis highlights areas for future research regarding AA nourishment and healthy brain aging.
Mitochondrial pharmacology: Electron transport chain bypass as strategies to treat mitochondrial dysfunction
Authors: Atamna Hani , Mackey Jeanette , Dhahbi Joseph M.
Published: March 2012

Mitochondrial dysfunction (primary or secondary) is detrimental to intermediary metabolism. Therapeutic strategies to treat/prevent mitochondrial dysfunction could be valuable for managing metabolic and age‐related disorders. Here, we review strategies proposed to treat mitochondrial impairment. We then concentrate on redox‐active agents, with mild‐redox potential, who shuttle electrons among specific cytosolic or mitochondrial redox‐centers. We propose that specific redox agents with mild redox potential (−0.1 V; 0.1 V) improve mitochondrial function because they can readily donate or accept electrons in biological systems, thus they enhance metabolic activity and prevent reactive oxygen species (ROS) production. These agents are likely to lack toxic effects because they lack the risk of inhibiting electron transfer in redox centers. This is different from redox agents with strong negative (−0.4 V; −0.2 V) or positive (0.2 V; 0.4 V) redox potentials who alter the redox status of redox‐centers (i.e.,become permanently reduced or oxidized). This view has been demonstrated by testing the effect of several redox active agents on cellular senescence. Methylene blue (MB, redox potential ≅10 mV) appears to readily cycle between the oxidized and reduced forms using specific mitochondrial and cytosolic redox centers. MB is most effective in delaying cell senescence and enhancing mitochondrial functionin vivoandin vitro. Mild‐redox agents can alter the biochemical activity of specific mitochondrial components, which then in response alters the expression of nuclear and mitochondrial genes. We present the concept of mitochondrial electron‐carrier bypass as a potential result of mild‐redox agents, a method to prevent ROS production, improve mitochondrial function, and delay cellular aging. Thus, mild‐redox agents may prevent/delay mitochondria‐driven disorders.
Non‐native aggregation of recombinant human granulocyte‐colony stimulating factor under simulated process stress conditions
Authors: Roessl Ulrich , Wiesbauer Johanna , Leitgeb Stefan , Birner‐Gruenberger Ruth , Nidetzky Bernd
Published: March 2012

Effective inhibition of protein aggregation is a major goal in biopharmaceutical production processes optimized for product quality. To examine the characteristics of process‐stress‐dependent aggregation of human granulocyte colony‐stimulating factor (G‐CSF), we applied controlled stirring and bubble aeration to a recombinant non‐glycosylated preparation of the protein produced in Escherichia coli. We characterized the resulting denaturation in a time‐resolved manner using probes for G‐CSF conformation and size in both solution and the precipitate. G‐CSF was precipitated rapidly from solutions that were aerated or stirred; only small amounts of soluble aggregates were found. Exposed hydrophobic surfaces were a characteristic of both soluble and insoluble G‐CSF aggregates. Using confocal laser scanning microscopy, the aggregates presented mainly a circular shape. Their size varied according to incubation time and stress applied. The native intramolecular disulfide bonds in the insoluble G‐CSF aggregates were largely disrupted as shown by mass spectrometry. New disulfide bonds formed during aggregation. All involved Cys18, which is the only free cysteine in G‐CSF; one of them had an intermolecular Cys18(A)‐Cys18(B) crosslink. Stabilization strategies can involve external addition of thiols and extensive reduction of surface exposition during processing.
Role of non‐specific DNA in reducing coding DNA requirement for transient gene expression with CHO and HEK‐293E cells
Authors: Rajendra Yashas , Kiseljak Divor , Manoli Sagar , Baldi Lucia , Hacker David L. , Wurm Florian M.
Published: March 2012

Transient gene expression (TGE) is a rapid method for the production of recombinant proteins in mammalian cells. While the TGE volumetric productivity has improved significantly over the past decade, the amount of plasmid DNA (pDNA) needed for transfection remains very high. Here, we examined the use of non‐specific (filler) DNA to partially replace the transgene‐bearing plasmid DNA (coding pDNA) in transfections of Chinese hamster ovary (CHO) and human embryo kidney (HEK‐293E) cells. When the optimal amount of coding pDNA for either host was reduced by 67% and replaced with filler DNA, the recombinant protein yield decreased by only 25% relative to the yield in control transfections. Filler DNA did not affect the cellular uptake or intracellular stability of coding pDNA, but its presence lead to increases of the percentage of transfected cells and the steady‐state level of transgene mRNA compared to control transfections. Studies of the physicochemical properties of DNA–polyethyleneimine (PEI) complexes with or without filler DNA did not reveal any differences in their size or surface charge. The results suggest that filler DNA allows the coding pDNA to be distributed over a greater number of DNA–PEI complexes, leading to a higher percentage of transfected cells. The co‐assembly of filler DNA and coding pDNA within complexes may also allow the latter to be more efficiently utilized by the cell's transcription machinery, resulting in a higher level of transgene mRNA. Biotechnol. Bioeng. 2012;109: 2271–2278. © 2012 Wiley Periodicals, Inc.
Fed‐batch microbioreactor platform for scale down and analysis of a plasmid DNA production process
Authors: Bower Diana M. , Lee Kevin S. , Ram Rajeev J. , Prather Kristala L.J.
Published: March 2012

The rising costs of bioprocess research and development emphasize the need for high‐throughput, low‐cost alternatives to bench‐scale bioreactors for process development. In particular, there is a need for platforms that can go beyond simple batch growth of the organism of interest to include more advanced monitoring, control, and operation schemes such as fed‐batch or continuous. We have developed a 1‐mL microbioreactor capable of monitoring and control of dissolved oxygen, pH, and temperature. Optical density can also be measured online for continuous monitoring of cell growth. To test our microbioreactor platform, we used production of a plasmid DNA vaccine vector (pVAX1‐GFP) in Escherichia coli via a fed‐batch temperature‐inducible process as a model system. We demonstrated that our platform can accurately predict growth, glycerol and acetate concentrations, as well as plasmid copy number and quality obtained in a bench‐scale bioreactor. The predictive abilities of the micro‐scale system were robust over a range of feed rates as long as key process parameters, such as dissolved oxygen, were kept constant across scales. We have highlighted plasmid DNA production as a potential application for our microbioreactor, but the device has broad utility for microbial process development in other industries as well. Biotechnol. Bioeng. 2012; 109:1976–1986. © 2012 Wiley Periodicals, Inc.
Thy1‐hAPPLond/Swe+ mouse model of Alzheimer's disease displays broad behavioral deficits in sensorimotor, cognitive and social function
Authors: Faizi Mehrdad , Bader Patrick L. , Saw Nay , Nguyen Thuy‐Vi V. , Beraki Simret , Wyss‐Coray Tony , Longo Frank M. , Shamloo Mehrdad
Published: March 2012

Alzheimer’s disease (AD), the most common form of dementia, is an age‐dependent progressive neurodegenerative disorder. β‐amyloid, a metabolic product of the amyloid precursor protein (APP), plays an important role in the pathogenesis of AD. The Thy1‐hAPPLond/Swe+ (line 41) transgenic mouse overexpresses human APP751 and contains the London (V717I) and Swedish (K670M/N671L) mutations. Here, we used a battery of behavioral tests to evaluate general activity, cognition, and social behavior in six‐month‐old male Thy1‐hAPPLond/Swe+ mice. We found hyperactivity in a novel environment as well as significant deficits in spontaneous alternation behavior. In fear conditioning (FC), Thy1‐hAPPLond/Swe+ mice did not display deficits in acquisition or in memory retrieval in novel context of tone‐cued FC, but they showed significant memory retrieval impairment during contextual testing in an identical environment. Surprisingly, in a standard hidden platform water maze, no significant deficit was detected in mutant mice. However, a delayed‐matching‐to‐place paradigm revealed a significant deficit in Thy1‐hAPPLond/Swe+ mice. Lastly, in the social novelty session of a three‐chamber test, Thy1‐hAPPLond/Swe+ mice exhibited a significantly decreased interest in a novel versus a familiar stranger compared to control mice. This could possibly be explained by decreased social memory or discrimination and may parallel disturbances in social functioning in human AD patients. In conclusion, the Thy1‐hAPPLond/Swe+ mouse model of AD displayed a behavioral phenotype that resembles, in part, the cognitive and psychiatric symptoms experienced in AD patients.
Critical aortic stenosis in a patient with a large saccular abdominal aortic aneurysm
Authors: Drury‐Smith Mark , Garnham Andrew , Khogali Saib
Published: March 2012

Elderly patients with aortic stenosis are often deemed too high risk, and consequently turned down for conventional surgery. Transcatheter aortic valve implantation (TAVI) is a safe and an increasingly attractive option in this group of patients. Although TAVI has been shown to be successful and safe, the cardiovascular assessment of other co‐morbidities in this susceptible group of patients is critical to ensuring good clinical outcomes. The presence of a saccular abdominal aortic aneurysm (AAA) in our patient was an example of an important co‐morbidity which could have a significant impact on the outcome of TAVI, if not managed appropriately. The increased systolic pressure post successful TAVI will result in an increased strain within the wall of the saccular AAA with an increased risk of rupture. Therefore, a timely management strategy for the AAA was necessary. We believe that we report the first case of simultaneous TAVI and endovascular aneurysm repair (EVAR). The patient underwent uncomplicated transfemoral TAVI immediately followed by successful drive‐by percutaneous EVAR delivered over the same superstiff guidewire via the transfemoral route. Our case highlights the importance of a detailed assessment in all patients before consideration for TAVI, and the multi‐disciplinary team and a management strategy for both pathologies tailored to the patient. The case demonstrates the versatility of trans‐catheter techniques which has enabled the treatment of aortic stenosis and abdominal AAA in a single procedure. © 2012 Wiley Periodicals, Inc.
Early beneficial effects of drug‐eluting stents in vein grafts wane during long term follow‐up
Authors: Pasceri Vincenzo , Tarsia Giandomenico , Niccoli Giampaolo , Viceconte Nicola , Porto Italo , Leone Antonio Maria , Trani Carlo , Speciale Giulio , LIsanti Pasquale
Published: March 2012

Objectives

The aim of the study was to compare outcomes of drug‐eluting stents (DES) versus bare‐metal stents (BMS) in saphenous vein graft (SVG) interventions in a case–control study with a long‐term follow‐up.

Background

Safety and efficacy of DES in SVG interventions are still controversial.

Methods

We performed a multicenter registry assessing clinical outcomes with DES vs. BMS. We included 311 patients (239 men, age 68 ± 8 years) who underwent percutaneous coronary interventions (PCI) of SVG lesions with DES (n = 138) or BMS (n = 173) with a 2‐year follow‐up.

Results

The two groups were similar for age, sex, main risk factors, incidence of diabetes, use of IIb/IIIa antagonists, use of aspiration devices or filters, number of stents, and total stent length. Overall, at 9 months follow‐up incidence of major adverse cardiac events (MACE) and target vessel revascularization (TVR) were significantly lower in the DES group compared with the BMS group (10.9% vs. 22.0%, P = 0.014 and 8.7% vs. 19.1% in DES and BMS respectively, P = 0.015), while there was no significant difference in incidence of myocardial infarction (5.1% vs. 5.2%, P = 0.96) or death (2.2% vs. 4%, respectively, P = 0.54). However, at 24‐month follow‐up incidence of MACE was 29.7% in the DES group and 37.0% in BMS group (P = 0.29); incidence of TVR (23.2% vs. 28.9% P = 0.39), myocardial infarction (9.4% vs. 9.2%), death (7.2% vs. 6.9%) were also similar in the two groups.

Conclusions

Although DES appear safe, our findings suggest that the early benefit of DES in SVG may rapidly wane during long‐term follow‐up. © 2012 Wiley Periodicals, Inc.
Safety and efficacy of balloon pulmonary valvuloplasty
Authors: Holzer Ralf J. , Gauvreau Kimberlee , Kreutzer Jacqueline , Trucco Sara M. , Torres Alejandro , Shahanavaz Shabana , Bergersen Lisa
Published: March 2012

Background

Balloon pulmonary valvuloplasty (BPV) is the treatment of choice for patients with pulmonary valve stenosis (PS); however, safety and efficacy outcomes are lacking in the current era.

Methods

Demographic, procedural, and adverse event (AE) data were prospectively collected using a multicenter registry (C3PO) and cases performed between 02/07 and 06/10 at eight institutions. The registry was queried for cases of isolated BPV. Multivariable models were built to determine risk factors for procedure failure and adverse outcomes.

Results

211 cases were included (45%, <1 month). Procedural success was achieved in 91% procedures, being defined as one or more of the following: post‐BPV peak systolic valvar gradient to < 25 mm Hg (88%), decrease in gradient by 50% (79%), or reduction of RV/systemic pressure ratio by 50% (45%). Procedural success was more common in neonates, when compared to older patients (96% vs. 87%, P = 0.03). Risk factors for procedural failure included moderate or severe pulmonary valve thickening (OR 2.9, CI 1–8.3), and presence of supravalve PS (OR 9.6, CI 2.7–33.8). Low severity AEs (levels 1–2) occurred in 9% of patients and higher severity AEs (levels 3–5) occurred in 3% of patient; there were no deaths. Risk factors for any AE (levels 1–5) were age below 1 month (OR 3.5, CI 1.3–8.9), as well as operator experience of less than 10 years (OR 3.8, CI 1.5–9.9).

Conclusions

Procedural success is common and AEs, especially higher severity AEs, are rare for BPV in patients with isolated PS. Results have improved considerably when compared to historical data. © 2012 Wiley Periodicals Inc.
Right versus left transradial approach for coronary catheterization in octogenarian patients
Authors: Freixa Xavier , Trilla Marc , Feldman Matías , Jiménez Marcelo , Betriu Amadeo , Masotti Mónica
Published: March 2012

Objectives: The aim of the study was to evaluate if the left radial approach (LRA) confers any additional advantage compared to the right radial approach (RRA) in octogenarian patients who undergo a coronary diagnostic procedure. Background: Octogenarians, an increasing segment of patients in our society, present a higher risk of access‐site complications related to invasive coronary catheterization. Transradial approach has been shown to be an effective alternative to reduce vascular complications. Although some studies have suggested that elderly people might benefit from a LRA, the advantages of using the left or right radial access remain not clear. Methods: One hundred octogenarian patients undergoing a transradial coronary angiogram with normal Allen test and without previous history of coronary artery by‐pass grafting were randomized to either LRA (n = 50) or RRA (n = 50). The primary end‐points of the study were procedural and fluoroscopy times. Results: Mean age was 82.6 years (80–88) and 59% were males. Procedural and fluoroscopy times were similar among study groups. Crossover was required in two patients (4%) with RRA and five patients (10%) with LRA (P = 0.24). Subclavian tortuosity was more frequent in the right side (32% vs. 6% in the left side; P = 0.002) but this difference did not translate into longer procedural or fluoroscopy times or higher cross‐over, procedural difficulty or wire manipulation. Conclusions: In our series of octogenarian patients, the LRA was a valid alternative for diagnostic procedures but its usage was not associated with a significant reduction in procedural and fluoroscopy times compared to the RRA. © 2012 Wiley Periodicals, Inc.
Prevalence and echocardiographic features of iatrogenic atrial septal defect after catheter‐based mitral valve repair with the mitraclip system
Authors: Smith Thomas , McGinty Patrick , Bommer William , Low Reginald I. , Lim Scott , Fail Peter , Rogers Jason H.
Published: March 2012

Objectives: Review the prevalence, echocardiographic features and potential predictors of iatrogenic ASD (iASD) created with the MitraClip guiding catheter. Background: Catheter‐based repair of mitral regurgitation (MR) with the MitraClip device (Abbott Vascular, Menlo Park, CA), is performed through a 22‐French transseptal guiding catheter. The echocardiographic prevalence of iASDs after the MitraClip procedure has not been reported. Methods: Thirty subjects undergoing MitraClip repair during the roll‐in phase of the EVEREST II randomized trial who had baseline, 30 day, 6 and 12 month transthoracic echocardiograms (TTEs) available for review were included. Patients who underwent surgery for MR within the first 12 months were excluded. Residual iASD size, right ventricular (RV) size, left atrial (LA) volume, and tricuspid/MR grade were quantified. Results: iASDs were found at 12 months in 8 patients (27%) with a mean diameter of 6.6 ± 3.1 mm. Subjects with iASD at 12 months had more residual MR, increased TR and a trend toward larger LA volumes than non‐iASD patients. 83% of non‐ASD patients were free from MR > 2+ at 12 mos. vs. 38% of those with iASD (p=0.016). There were no other significant associations between clinical and echocardiographic variables and the persistence of iASD. Conclusions: After MitraClip repair, persistent iASDs occur at a rate comparable to reports after other transseptal interventional procedures and do not appear hemodynamically significant. Patients with persistent iASDs had less MR reduction at 12‐months and a trend toward larger LA volumes, suggesting that increased LA pressure may be a mechanism for persistent iASD. © 2012 Wiley Periodicals, Inc.
A multicenter randomized comparison of drug‐eluting balloon plus bare‐metal stent versus bare‐metal stent versus drug‐eluting stent in bifurcation lesions treated with a single‐stenting technique: Six‐month angiographic and 12‐month clinical results of the drug‐eluting balloon in bifurcations trial
Authors: Stella Pieter R. , Belkacemi Anouar , Dubois Christophe , Nathoe Hendrik , Dens Jo , Naber Christoph , Adriaenssens Tom , van Belle Eric , Doevendans Pieter , Agostoni Pierfrancesco
Published: March 2012

Background

Percutaneous treatment of coronary bifurcation lesions remains hampered by suboptimal results, mainly in the side branch (SB), even with the use of drug‐eluting stents (DES). Paclitaxel drug‐eluting balloons (DEB) could provide an attractive alternative to treat bifurcations in combination with a provisional T‐stenting technique in order to minimize SB restenosis. We compared angiographic and clinical outcomes of a provisional T‐stenting technique with a DEB plus bare‐metal stent (BMS) versus BMS versus paclitaxel DES.

Methods

In this randomized, international, multicenter, single‐blinded 3‐arm study, 117 patients with coronary bifurcation lesions underwent treatment with: (A) DEB in both main branch (MB) and SB and BMS in MB; (B) BMS in MB and regular balloon angioplasty in SB; or (C) paclitaxel DES in MB and regular balloon in SB. All patients underwent provisional T‐stenting with an identical stent platform in the MB. Paclitaxel was the drug for elution in groups A and C. The primary endpoint was 6‐month angiographic late luminal loss. Secondary end points were 6‐month binary restenosis and 12‐month major adverse cardiac events (MACE: death, myocardial infarction, target vessel revascularization).

Results

The procedure was successful in all cases. Late luminal loss, measured respectively in the proximal MB, distal MB and SB was 0.58 ± 0.65, 0.41 ± 0.60, and 0.19 ± 0.66 mm in group A; 0.60 ± 0.65, 0.49 ± 0.85, and 0.21 ± 0.57 mm in group B; and 0.13 ± 0.45, 0.19 ± 0.64, and 0.11 ± 0.43 mm in group C (P = 0.001). Binary restenosis rates per bifurcation and MACE rates were 24.2%, 28.6%, and 15% (P = 0.45) and 20%, 29.7%, and 17.5% (P = 0.40) in groups A, B, and C, respectively.

Conclusions

Pretreatment of both MB and SB with DEB failed to show angiographic and clinical superiority over conventional BMS, using a provisional T‐stenting technique. Moreover DES showed superior angiographic results than DEB and BMS. © 2012 Wiley Periodicals, Inc.
1H,89Y HMQC and Further NMR Spectroscopic and X‐ray Diffraction Investigations on Yttrium‐Containing Complexes Exhibiting Various Nuclearities
Authors: Löble Matthias W. , Casimiro María , Thielemann Dominique T. , Oña‐Burgos Pascual , Fernández Ignacio , Roesky Peter W. , Breher Frank
Published: March 2012

2D 1H,89Y heteronuclear shift correlation through scalar coupling has been applied to the chemical‐shift determination of a set of yttrium complexes with various nuclearities. This method allowed the determination of 89Y NMR data in a short period of time. Multinuclear NMR spectroscopy as function of temperature, PGSE NMR‐diffusion experiments, heteronuclear NOE measurements, and X‐ray crystallography were applied to determine the structures of [Y5(OH)5(L‐Val)4(Ph2acac)6] (1) (Ph2acac=dibenzoylmethanide, L‐Val=L‐valine), [Y(2)(OTf)3] (3), and [Y2(4)(OTf)5] (5) (2: [(S)P{N(Me)NC(H)Py}3], 4: [B{N(Me)NC(H)Py}4]−) in solution and in the solid state. The structures found in the solid state are retained in solution, where averaged structures were observed. NMR diffusion measurements helped us to understand the nuclearity of compounds 3 and 5 in solution. 1H,19F HOESY and 19F,19F EXSY data revealed that the anions are specifically located in particular regions of space, which nicely correlated with the geometries found in the X‐ray structures.
Calcium Carbonate–Gold Nanocluster Hybrid Spheres: Synthesis and Versatile Application in Immunoassays
Authors: Peng Juan , Feng Li‐Na , Zhang Kui , Li Xing‐Hua , Jiang Li‐Ping , Zhu Jun‐Jie
Published: March 2012

Fluorescent gold nanoclusters (AuNCs) were incorporated into porous calcium carbonate spheres through electrostatic interaction. The resulting CaCO3/AuNCs hybrid material exhibited interesting properties, such as porous structure, excellent biocompatibility, good water solubility, and degradability. These properties make the CaCO3/AuNCs hybrid material a promising template to assemble horseradish peroxidase/antibody conjugates (HRP‐Ab2). By using CaCO3/AuNCs/HRP‐Ab2 bioconjugates as probes, a versatile immunosensor was developed for fluorescent and electrochemical detection of the cancer biomarker neuron‐specific enolase (NSE). The detection limits of the sensor were 2.0 and 0.1 pg mL−1 for fluorescent and electrochemical detection, respectively. The immunosensor shows high sensitivity and offers an alternative strategy for the detection of other proteins and DNA.