bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased Frequency and Costs of Ambulatory Medical Care Utilization Prior to the Diagnosis of Rheumatoid Arthritis: A National Population‐Based Study
Authors: Lai Ning‐Sheng , Tsai Tzung‐Yi , Li Chung‐Yi , Koo Malcolm , Yu Chia‐Li , Lu Ming‐Chi
Published: August 2013

Objective

To investigate the frequency and costs associated with ambulatory medical care utilization over an 8‐year period in patients prior to the diagnosis of rheumatoid arthritis (RA).

Methods

We used Taiwan's National Health Insurance Research Database to identify 691 newly diagnosed RA cases between 2005 and 2010. We selected 1,382 controls without RA, frequency matched by sex, age, and the catastrophic illness certificate application year of the cases. The frequency and costs of ambulatory medical care utilization between the RA patients and controls were compared using the 2‐sample Kolmogorov‐Smirnov test.

Results

The median frequency of ambulatory medical care utilization was significantly higher in RA patients compared with controls (29 versus 13; P < 0.001) in the year before diagnosis. The differences remained significant throughout all 8 annual periods before diagnosis. Similarly, the inflation‐adjusted costs of ambulatory medical care utilization in RA patients increased annually over the study period, from a median of $212 eight years preceding diagnosis to $798 one year preceding diagnosis. Frequency of ambulatory medical care utilization due to diseases of the musculoskeletal system and connective tissue (P < 0.001), acute respiratory infections (P < 0.001), diseases of the upper respiratory tract (P = 0.01), and diseases of the upper gastrointestinal tract (P = 0.04) were higher among RA patients in the 2‐year period preceding diagnosis.

Conclusion

We found increased frequency and costs of ambulatory care utilization among RA patients in Taiwan preceding diagnosis of RA.
Transcutaneous Electrical Nerve Stimulation as an Adjunct to Education and Exercise for Knee Osteoarthritis: A Randomized Controlled Trial
Authors: Palmer Shea , Domaille Melissa , Cramp Fiona , Walsh Nicola , Pollock Jon , Kirwan John , Johnson Mark I.
Published: August 2013

Objective

To determine the additional effects of transcutaneous electrical nerve stimulation (TENS) for knee osteoarthritis (OA) when combined with a group education and exercise program (knee group).

Methods

The study was a randomized, sham‐controlled clinical trial. Patients referred for physiotherapy with suspected knee OA (confirmed using the American College of Rheumatology clinical criteria) were invited. Exclusion criteria included comorbidities preventing exercise, previous TENS experience, and TENS contraindications. Prospective sample size calculations required 67 participants in each trial arm. A total of 224 participants (mean age 61 years, 37% men) were randomized to 3 arms: TENS and knee group (n = 73), sham TENS and knee group (n = 74), and knee group (n = 77). All patients entered an evidence‐based 6‐week group education and exercise program (knee group). Active TENS produced a “strong but comfortable” paraesthesia within the painful area and was used as much as needed during the 6‐week period. Sham TENS used dummy devices with no electrical output. Blinded assessment took place at baseline and 3, 6, 12, and 24 weeks. The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function subscale at 6 weeks. Secondary outcomes included WOMAC pain, stiffness, and total scores; extensor muscle torque; global assessment of change; exercise adherence; and exercise self‐efficacy. Data analysis was by intent to treat.

Results

All outcomes improved over time (P < 0.05), but there were no differences between trial arms (P > 0.05). All improvements were maintained at 24‐week followup.

Conclusion

There were no additional benefits of TENS, failing to support its use as a treatment adjunct within this context.
Carbon‐Based Anodes for Lithium Sulfur Full Cells with High Cycle Stability
Authors: Brückner Jan , Thieme Sören , Böttger‐Hiller Falko , Bauer Ingolf , Grossmann Hannah Tamara , Strubel Patrick , Althues Holger , Spange Stefan , Kaskel Stefan
Published: August 2013

The lithium sulfur battery system has been studied since the late 1970s and has seen renewed interest in recent years. However, even after three decades of intensive research, prolonged cycling can only be achieved when a large excess of electrolyte and lithium is used. Here, for the first time, a balanced and stable lithium sulfur full cell is demonstrated with silicon–carbon as well as all‐carbon anodes. More than 1000 cycles, a specific capacity up to 1470 mAh g−1
sulfur (720 mAh g−1
cathode), and a high coulombic efficiency of over 99% even with a low amount of electrolyte are achieved. The alternative anodes do not suffer from electrolyte depletion, which is found to be the main cause of cell failure when using metallic lithium anodes.
MRI‐Visual Order–Disorder Micellar Nanostructures for Smart Cancer Theranostics
Authors: Patra Hirak K. , Khaliq Nisar Ul , Romu Thobias , Wiechec Emilia , Borga Magnus , Turner Anthony P. F. , Tiwari Ashutosh
Published: August 2013

The development of MRI‐visual order–disorder structures for cancer nanomedicine explores a pH‐triggered mechanism for theragnosis of tumor hallmark functions. Superparamagnetic iron oxide nanoparticles (SPIONs) stabilized with amphiphilic poly(styrene)‐b‐poly(acrylic acid)‐doxorubicin with folic acid (FA) surfacing are employed as a multi‐functional approach to specifically target, diagnose, and deliver drugs via a single nanoscopic platform for cancer therapy. The functional aspects of the micellar nanocomposite is investigated in vitro using human breast SkBr3 and colon cancer HCT116 cell lines for the delivery, release, localization, and anticancer activity of the drug. For the first time, concentration‐dependent T2‐weighted MRI contrast for a monolayer of clustered cancer cells is shown. The pH tunable order–disorder transition of the core–shell structure induces the relative changes in MRI contrast. The outcomes elucidate the potential of this material for smart cancer theranostics by delivering non‐invasive real‐time diagnosis, targeted therapy, and monitoring the course and response of the action before, during, and after the treatment regimen.
Theory of Sliding‐Mode Triboelectric Nanogenerators
Authors: Niu Simiao , Liu Ying , Wang Sihong , Lin Long , Zhou Yu Sheng , Hu Youfan , Wang Zhong Lin
Published: August 2013

The triboelectric nanogenerator (TENG) is a powerful approach toward new energy technology, especially for portable electronics. A theoretical model for the sliding‐mode TENG is presented in this work. The finite element method was utilized to characterize the distributions of electric potential, electric field, and charges on the metal electrodes of the TENG. Based on the FEM calculation, the semi‐analytical results from the interpolation method and the analytical V‐Q‐x relationship are built to study the sliding‐mode TENG. The analytical V‐Q‐x equation is validated through comparison with the semi‐analytical results. Furthermore, based on the analytical V‐Q‐x equation, dynamic output performance of sliding‐mode TENG is calculated with arbitrary load resistance, and good agreement with experimental data is achieved. The theory presented here is a milestone work for in‐depth understanding of the working mechanism of the sliding‐mode TENG, and provides a theoretical basis for further enhancement of the sliding‐mode TENG for both energy scavenging and self‐powered sensor applications.
The interconversion of the radial motional modes of an ion in a Penning trap mass spectrometer by 4n‐polar external radio frequency fields (n = 1,2,3,4)
Authors: Kretzschmar Martin
Published: August 2013

In Penning trap mass spectrometry ion masses are determined by measuring the free cyclotron frequency via the resonant conversion of the magnetron into the cyclotron motional mode, induced by the interaction with an external radio‐frequency field. With octupolar rf‐fields of frequency the mass resolution has been improved by more than an order of magnitude as compared to conventional quadrupolar fields of frequency and with the same pulse duration. This result raises the question what one might expect from using 12‐polar rf‐fields with frequency or even 16‐polar rf‐fields with frequency .

In this paper the theoretical model for the interconversion of the radial modes by quadrupolar and octupolar rf‐fields is generalized to general 4n‐polar fields. As in the earlier work the complex amplitudes of the cyclotron and magnetron oscillators are used as dynamical variables and the Hamiltonian equations of motion are reformulated in terms of Bloch vector components. The resulting non‐linear differential equations can be solved numerically.

Results are presented on excitation functions (conversion at the exact resonance frequency) and on conversion line shapes (dependence of conversion on the detuning parameter). The most important observation is the decrease of the resonance width by a factor of 2 × 103 as one passes from quadrupolar () to 12‐polar () and 16‐polar () excitation.
Brief Report: Fibrosis Caused by Loss of PTEN Expression in Mouse Fibroblasts Is Crucially Dependent on CCN2
Authors: Liu Shangxi , Parapuram Sunil K. , Leask Andrew
Published: August 2013

Objective

Protein phosphatase and tensin homolog (PTEN) expression is reduced in dermal fibroblasts isolated from patients with diffuse cutaneous systemic sclerosis, a fibrotic autoimmune disease. In support of this finding, deletion of the PTEN gene in the dermal fibroblasts of mice has been shown to result in skin fibrosis and in vivo overexpression of connective tissue growth factor (CTGF; CCN2), a proadhesive matricellular protein; however, whether CCN2 is required for the fibrosis caused by loss of PTEN is unclear. This study was undertaken to investigate the role of CCN2 in fibrosis caused by reduced PTEN expression.

Methods

We generated conditional knockout mice in which PTEN was deleted in fibroblasts, either alone or in combination with CCN2. Skin samples were collected for histologic examination, immunohistochemical analysis, and collagen assay.

Results

Loss of CCN2 resulted in resistance to the increases in collagen production and myofibroblast recruitment that are caused by loss of PTEN. CCN2 deficiency did not impair Akt phosphorylation or the increases in the intensity of proliferating cell nuclear antigen staining that were caused by loss of PTEN.

Conclusion

These data are consistent with the notion that CCN2 is required for particular aspects of the fibroproliferative response; therapeutic strategies blocking CCN2 may be of clinical benefit in combating fibrotic disease.
Association of Bone Morphogenetic Protein 6 With Exocrine Gland Dysfunction in Patients With Sjögren's Syndrome and in Mice
Authors: Yin Hongen , Cabrera‐Perez Javier , Lai Zhenan , Michael Drew , Weller Melodie , Swaim William D. , Liu Xibao , Catalán Marcelo A. , Rocha Eduardo M. , Ismail Nevien , Afione Sandra , Rana Noreen A. , Di Pasquale Giovanni , Alevizos Ilias , Ambudkar Indu , Illei Gabor G. , Chiorini John A.
Published: August 2013

Objective

Primary Sjögren's syndrome (SS) is characterized by autoimmune activation and loss of function in secretory epithelia. The present study was undertaken to investigate and characterize changes in the epithelia associated with the loss of gland function in primary SS.

Methods

To identify changes in epithelial gene expression, custom microarrays were probed with complementary RNA (cRNA) isolated from minor salivary glands (MSGs) of female patients with primary SS who had low focus scores and low salivary flow rates, and the results were compared with those obtained using cRNA from the MSGs of sex‐matched healthy volunteers. The effect of bone morphogenetic protein 6 (BMP‐6) on salivary gland function was tested using adeno‐associated virus–mediated gene transfer to the salivary glands of C57BL/6 mice.

Results

A significant increase in expression of BMP‐6 was observed in RNA isolated from SS patients compared with healthy volunteers. Overexpression of BMP‐6 locally in the salivary or lacrimal glands of mice resulted in the loss of fluid secretion as well as changes in the connective tissue of the salivary gland. Assessment of the fluid movement in either isolated acinar cells from mice overexpressing BMP‐6 or a human salivary gland cell line cultured with BMP‐6 revealed a loss in volume regulation in these cells. Lymphocytic infiltration in the submandibular gland of BMP‐6 vector–treated mice was increased. No significant changes in the production of proinflammatory cytokines or autoantibodies associated with SS (anti‐Ro/SSA and anti‐La/SSB) were found after BMP‐6 overexpression.

Conclusion

In addition to identifying BMP‐6 expression in association with xerostomia and xerophthalmia in primary SS, the present results suggest that BMP‐6–induced salivary and lacrimal gland dysfunction in primary SS is independent of the autoantibodies and immune activation associated with the disease.
Lipopolysaccharide Increases the Incidence of Collagen‐Induced Arthritis in Mice Through Induction of Protease HTRA‐1 Expression
Authors: Hou Yuzhu , Lin Haijiang , Zhu Linnan , Liu Zhaoting , Hu Fanlei , Shi Jianfeng , Yang Tao , Shi Xiaoyun , Zhu Mingzhao , Godley Bernard F. , Wang Qiang , Li Zhanguo , Zhao Yong
Published: August 2013

Objective

The protease HTRA‐1 is closely associated with rheumatoid arthritis (RA). The molecular mechanisms that control HTRA‐1 expression are currently unknown. This study was undertaken to determine the regulatory role of Toll‐like receptors (TLRs) on HTRA‐1 expression in mice with collagen‐induced arthritis (CIA) and in synovial cells from RA patients.

Methods

HTRA‐1 messenger RNA and protein production in mouse fibroblasts, mouse macrophages, and freshly isolated RA patient synovial cells treated with TLR ligands were detected by real‐time polymerase chain reaction and enzyme‐linked immunosorbent assay, respectively. Arthritis incidence and severity were determined using clinical scores and histopathologic analysis. Involvement of HTRA‐1 in lipopolysaccharide (LPS)–increased arthritis incidence and severity in mice was determined using anti–HTRA‐1 monoclonal antibody. The signal pathways involved in HTRA‐1 expression were accessed by specific inhibitors, RNA interference, dual‐luciferase reporter, and chromatin immunoprecipitation methods.

Results

LPS and tenascin‐C, but not the other TLR ligands tested, strongly induced HTRA‐1 expression. LPS significantly increased HTRA‐1 expression in the joint tissue as well as arthritis incidence and severity in mice with CIA. Blocking HTRA‐1 by antibody significantly decreased LPS‐promoted CIA severity. Inhibiting NF‐κB significantly decreased LPS‐induced HTRA‐1 expression in mouse and human cells. Dual‐luciferase reporter assay and ChIP analysis showed that p65 directly binds to HTRA‐1 promoter (amino acid 347).

Conclusion

Our findings indicate that TLR‐4 activation increases HTRA‐1 expression through the NF‐κB pathway in fibroblasts and macrophages. HTRA‐1 expression is involved in the enhancing effects of LPS on CIA. This study offers new insights into the regulation of HTRA‐1 expression via LPS/TLR‐4 and the role of HTRA‐1 in RA pathogenesis.
Genome‐Wide Association Study of Dermatomyositis Reveals Genetic Overlap With Other Autoimmune Disorders
Authors: Miller Frederick W. , Cooper Robert G. , Vencovský Jiří , Rider Lisa G. , Danko Katalin , Wedderburn Lucy R. , Lundberg Ingrid E. , Pachman Lauren M. , Reed Ann M. , Ytterberg Steven R. , Padyukov Leonid , Selva‐O'Callaghan Albert , Radstake Timothy R. D. J. , Isenberg David A. , Chinoy Hector , Ollier William E. R. , O'Hanlon Terrance P. , Peng Bo , Lee Annette , Lamb Janine A. , Chen Wei , Amos Christopher I. , Gregersen Peter K. ,   with the Myositis Genetics Consortium
Published: August 2013

Objective

To identify new genetic associations with juvenile and adult dermatomyositis (DM).

Methods

We performed a genome‐wide association study (GWAS) of adult and juvenile DM patients of European ancestry (n = 1,178) and controls (n = 4,724). To assess genetic overlap with other autoimmune disorders, we examined whether 141 single‐nucleotide polymorphisms (SNPs) outside the major histocompatibility complex (MHC) locus, and previously associated with autoimmune diseases, predispose to DM.

Results

Compared to controls, patients with DM had a strong signal in the MHC region consisting of GWAS‐level significance (P < 5 × 10–8) at 80 genotyped SNPs. An analysis of 141 non‐MHC SNPs previously associated with autoimmune diseases showed that 3 SNPs linked with 3 genes were associated with DM, with a false discovery rate (FDR) of <0.05. These genes were phospholipase C–like 1 (PLCL1; rs6738825, FDR = 0.00089), B lymphoid tyrosine kinase (BLK; rs2736340, FDR = 0.0031), and chemokine (C‐C motif) ligand 21 (CCL21; rs951005, FDR = 0.0076). None of these genes was previously reported to be associated with DM.

Conclusion

Our findings confirm the MHC as the major genetic region associated with DM and indicate that DM shares non‐MHC genetic features with other autoimmune diseases, suggesting the presence of additional novel risk loci. This first identification of autoimmune disease genetic predispositions shared with DM may lead to enhanced understanding of pathogenesis and novel diagnostic and therapeutic approaches.
Progressing Toward, and Recovering From, Knee Replacement Surgery: A Five‐Year Cohort Study
Authors: Riddle Daniel L. , Perera Robert A. , Stratford Paul W. , Jiranek William A. , Dumenci Levent
Published: August 2013

Objective

To determine the trajectories of preoperative worsening and postoperative recovery for both the index knee and the contralateral knee of patients undergoing knee replacement surgery.

Methods

Of the 4,796 subjects in the Osteoarthritis Initiative cohort study database, we examined 5‐year data from 177 patients who underwent isolated unilateral knee replacement surgery and no other joint replacement surgery. Patient‐reported outcomes captured domains defined by the International Classification of Functioning, Disability, and Health. Domains of knee structure and function, activity limitation, and participation restriction were examined using growth‐curve modeling over 5‐year periods prior to and following surgery.

Results

Preoperative worsening of the index knee was substantial in all domains of knee impairment, activity limitation, and societal participation. Pain intensity worsened only slightly from 5 years to 2.5 years prior to surgery, but worsened by ∼2 points (0–10‐point scale) during the 2.5 years prior to surgery. Trajectories of improvement following surgery varied depending on the outcome measure. The contralateral knee also changed over time, such that by ∼2 years following surgery, pain was worse and by 3 years, activity limitation was worse in the contralateral knee as compared to the index knee.

Conclusion

Patients who elect to undergo knee replacement surgery demonstrate perioperative trajectories of change that influence most health domains for both the index knee and the contralateral knee. After a period of no change, escalation of pain and worsening functioning in the index knee begins ∼2.5 years prior to surgery, which may be a key trigger for surgery.
Automated docking studies provide insights into molecular determinants of ligand recognition by N‐acetyl‐1‐d‐myo‐inosityl‐2‐amino‐2‐deoxy‐α‐d‐glucopyranoside deacetylase (MshB)
Authors: Huang Xinyi , Hernick Marcy
Published: August 2013

The metal‐dependent deacetylase N‐acetyl‐1‐d‐myo‐inosityl‐2‐amino‐2‐deoxy‐α‐d‐glucopyranoside deacetylase (MshB) catalyzes the deacetylation of N‐acetyl‐1‐d‐myo‐inosityl‐2‐amino‐2‐deoxy‐α‐d‐glucopyranoside (GlcNAc‐Ins), the committed step in mycothiol (MSH) biosynthesis. MSH is the thiol redox buffer used by mycobacteria to protect against oxidative damage and is involved in the detoxification of xenobiotics. As such, MshB is a target for the discovery of new drugs to treat tuberculosis (TB). While MshB substrate specificity and inhibitor activity have been probed extensively using enzyme kinetics, information regarding the molecular basis for the observed differences in substrate specificity and inhibitor activity is lacking. Herein we begin to examine the molecular determinants of MshB substrate specificity using automated docking studies with a set of known MshB substrates. Results from these studies offer insights into molecular recognition by MshB via identification of side chains and dynamic loops that may play roles in ligand binding. Additionally, results from these studies suggest that a hydrophobic cavity adjacent to the active site may be one important determinant of MshB substrate specificity. Importantly, this hydrophobic cavity may be advantageous for the design of MshB inhibitors with high affinity and specificity as potential TB drugs. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 406–417, 2014.
Effect of substituting arginine and lysine with alanine on antimicrobial activity and the mechanism of action of a cationic dodecapeptide (CL(14‐25)), a partial sequence of cyanate lyase from rice
Authors: Taniguchi Masayuki , Takahashi Nobuteru , Takayanagi Tomohiro , Ikeda Atsuo , Ishiyama Yohei , Saitoh Eiichi , Kato Tetsuo , Ochiai Akihito , Tanaka Takaaki
Published: August 2013

The antimicrobial activity of analogs obtained by substituting arginine and lysine in CL(14‐25), a cationic α‐helical dodecapeptide, with alanine against Porphyromonas gingivalis, a periodontal pathogen, varied significantly depending on the number and position of cationic amino acids. The alanine‐substituted analogs had no hemolytic activity, even at a concentration of 1 mM. The antimicrobial activities of CL(K20A) and CL(K20A, K25A) were 3.8‐fold and 9.1‐fold higher, respectively, than that of CL(14‐25). The antimicrobial activity of CL(R15A) was slightly lower than that of CL(14‐25), suggesting that arginine at position 15 is not essential but is important for the antimicrobial activity. The experiments in which the alanine‐substituted analogs bearing the replacement of arginine at position 24 and/or lysine at position 25 were used showed that arginine at position 24 was crucial for the antimicrobial activity whenever lysine at position 25 was substituted with alanine. Helical wheel projections of the alanine‐substituted analogs indicate that the hydrophobicity in the vicinity of leucine at position 16 and alanines at positions 18 and/or 21 increased by substituting lysine at positions 20 and 25 with alanine, respectively. The degrees of diSC3‐5 release from P. gingivalis cells and disruption of GUVs induced by the alanine‐substituted analogs with different positive charges were not closely related to their antimicrobial activities. The enhanced antimicrobial activities of the alanine‐substituted analogs appear to be mainly attributable to the changes in properties such as hydrophobicity and amphipathic propensity due to alanine substitution and not to their extents of positive charge (cationicity). © 2013 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 102: 58–68, 2014.
Stability of human telomere quadruplexes at high DNA concentrations
Authors: Kejnovská Iva , Vorlíčková Michaela , Brázdová Marie , Sagi Janos
Published: August 2013

For mimicking macromolecular crowding of DNA quadruplexes, various crowding agents have been used, typically PEG, with quadruplexes of micromolar strand concentrations. Thermal and thermodynamic stabilities of these quadruplexes increased with the concentration of the agents, the rise depended on the crowder used. A different phenomenon was observed, and is presented in this article, when the crowder was the quadruplex itself. With DNA strand concentrations ranging from 3 µM to 9 mM, the thermostability did not change up to ∼2 mM, above which it increased, indicating that the unfolding quadruplex units were not monomolecular above ∼2 mM. The results are explained by self‐association of the G‐quadruplexes above this concentration. The ΔGo37 values, evaluated only below 2 mM, did not become more negative, as with the non‐DNA crowders, instead, slightly increased. Folding topology changed from antiparallel to hybrid above 2 mM, and then to parallel quadruplexes at high, 6–9 mM strand concentrations. In this range, the concentration of the DNA phosphate anions approached the concentration of the K+ counterions used. Volume exclusion is assumed to promote the topological changes of quadruplexes toward the parallel, and the decreased screening of anions could affect their stability. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 428–438, 2014.
Subclavian transectional stent fracture and migration to the aortic carrefour: A case description of retrieval by snare system
Authors: Grasso Carmelo , Costanzo Luca , Tamburino Corrado
Published: August 2013

Percutaneous transluminal angioplasty with or without stent has become the treatment of choice for stenotic lesion in subclavian arteries. However, there is a growing concern following many reports of stent fractures, a serious complication of endovascular therapy. We report for the first time a case of delayed left subclavian stent fracture with transection of the protruding ostial part and migration into the aortic carrefour that was retrieved by a snare device. © 2013 Wiley Periodicals, Inc.
Catheterization laboratory activation during mechanical cardiopulmonary resuscitation: When should we say “No?”
Authors: Kalra Ankur , Maharaj Valmiki , Johannsen Ronald A. , Hollenberg Steven M.
Published: August 2013

Sudden cardiac arrest is a devastating manifestation of coronary artery disease and a leading cause of death in the western world. Early and effective cardiopulmonary resuscitation is essential for return of spontaneous circulation. If manual compression is ongoing and return of spontaneous circulation has not been achieved, the prognosis is poor, and the logistics of performing cardiac catheterization are forbidding. With the advent of mechanical chest compression, however, this clinical scenario has become much more complex. Coronary angiography and percutaneous coronary intervention, although still cumbersome, has been established as feasible with ongoing mechanical chest compression. This article discusses the strengths and pitfalls of mechanical cardiopulmonary resuscitation, our experience, and current evidence behind activation of the catheterization laboratory with ongoing mechanical chest compression. © 2013 Wiley Periodicals, Inc.
Removal of Impella® 2.5 while maintaining vascular access: A solution to a vascular quandary
Authors: Kim Michael S. , Clegg Stacey , Messenger John C.
Published: August 2013

Cardiogenic shock (CS) in the setting of acute myocardial infarction is associated with high in‐hospital mortality rates. Society guidelines provide a Class Ib recommendation for the use of hemodynamic support devices in patients with CS following ST‐elevation myocardial infarction. Exchanging of hemodynamic support devices is often complicated by inability to maintain percutaneous vascular access upon device removal in the setting of anticoagulation. This report highlights one potential solution to the dilemma of maintaining vascular access following removal of an Impella® 2.5 mechanical support device to allow safe transition to a TandemHeart system in a patient with refractory CS. © 2013 Wiley Periodicals, Inc.
Sequential moderate coronary artery fistula and moderate coronary artery stenosis causing ischemia demonstrated by fractional flow reserve and relieved following percutaneous coronary intervention
Authors: Hollenbeck Ryan D. , Salloum Joseph G.
Published: August 2013

Coronary artery fistulae are rare anomalous connections arising from the coronary circulation. We report a case of anterior wall myocardial ischemia caused by the combination of sequential coronary‐to‐pulmonary artery fistula and moderate (50–60%) stenosis of the left anterior descending coronary artery. Ischemia was demonstrated by myocardial stress perfusion imaging as well as fractional flow reserve. Percutaneous coronary intervention of the lesion resulted in resolution of ischemia. © 2013 Wiley Periodicals, Inc.
Study of Carbon Dioxide Transport in a Samaria Aerogel Catalyst by High Field Diffusion NMR
Authors: Müller Robert , Zhang Suihua , Neumann Björn , Bäumer Marcus , Vasenkov Sergey
Published: August 2013

Pulsed field gradient (PFG) NMR employing a high magnetic field of 17.6 T was used to study self‐diffusion of carbon dioxide in alumina stabilized samaria aerogel, a promising porous catalyst for gas‐phase reactions. Such rare‐earth aerogels exhibit high porosity and surface area with active sites directly integrated into the pore framework. In the reported diffusion NMR studies, application of a high magnetic field was essential for obtaining sufficiently high signal‐to‐noise ratios under conditions of relatively low CO2 densities in the primarily mesoporous catalyst particles. The diffusion studies were performed with the catalyst that was formed into the following two types of samples: macroscopic monoliths and beds of particles with sizes around 200 μm. The sorbate diffusivity inside the monolith was compared with the corresponding diffusivity in the bed under conditions of fast exchange of CO2 between the particles and the interparticle voids of the bed. The two‐domain exchange model proposed by Kärger for zeolites was used to describe the latter diffusivity. The reported results are expected to be useful for elucidating an influence of possible transport limitations under reaction conditions in aerogel catalysts.
Use of High‐Sensitivity Troponin Assays Predicts Mortality in Patients With Normal Conventional Troponin Assays on Admission—Insights From a Meta‐Analysis
Authors: Chatterjee Saurav , Kim Jiwon , Dahhan Ali , Choudhary Gaurav , Sharma Satish , Wu Wen‐Chih
Published: August 2013

Background

Use of high‐sensitivity troponin (hs‐Tn) assays can detect small levels of myocardial damage previously undetectable with conventional troponin (c‐Tn) assays. However, prognostic utility of these hs‐Tn assays in prediction of mortality remains unclear in the presence of nonelevated c‐Tn levels on admission. A systematic review and meta‐analysis was performed to assess mortality risk of patients with hs‐Tn elevations in the setting of normal c‐Tn levels.

Hypothesis

Patients with hs‐Tn elevations with normal c‐Tn levels on admission blood samples, drawn to rule out acute coronary syndrome (ACS), have a higher mortality risk than those without hs‐Tn or c‐Tn elevations.

Methods

A search was made of the PubMed, CENTRAL, EMBASE, CINAHL, EBSCO, and Web of Science databases. Studies evaluating patients with suspected ACS that reported mortality rates for those with elevated hs‐Tn levels but normal c‐Tn levels on admission were included. A random‐effects model was used to pool event rates, and data were reported in odds ratios (95% confidence interval).

Results

Four studies (N = 2033, mean age 64–75 years, 49%–70% male) revealed that nearly 32% of suspected ACS patients with normal c‐Tn levels on admission had elevated hs‐Tn levels. Elevated hs‐Tn levels conferred a significantly higher risk of all‐cause mortality vs normal hs‐Tn levels (odds ratio: 4.35, 95% confidence interval: 2.81‐6.73, P < 0.01), with negligible heterogeneity (I2 = 0%).

Conclusions

Elevation of hs‐Tn levels predicted a higher risk of mortality in patients with suspected ACS and may aid in the early identification of higher‐risk patients in this setting. Future studies are needed to investigate further optimal management strategies.
Bosentan Treatment Is Associated With Improvement of Right Ventricular Function and Remodeling in Chronic Thromboembolic Pulmonary Hypertension
Authors: Surie Sulaiman , Reesink Herre J. , Marcus J. Tim , van der Plas Mart N. , Kloek Jaap J. , Vonk‐Noordegraaf Anton , Bresser Paul
Published: August 2013

Background

Medical pretreatment before pulmonary endarterectomy (PEA) can optimize right ventricular (RV) function and may improve postoperative outcome in high‐risk patients. Using cardiac magnetic resonance imaging (cMRI), we determined whether the dual endothelin‐1 antagonist bosentan improves RV function and remodeling in patients with chronic thromboembolic pulmonary hypertension (CTEPH) who waited for PEA.

Hypothesis

We hypothesized that medical therapy prior to PEA will be associated with improvements in RV remodeling and function.

Methods

In this pilot study, 15 operable CTEPH patients were randomly assigned to either bosentan (n = 8) or no bosentan (n = 7, control) for 16 weeks, next to “best standard of care.” Both before and after treatment, RV stroke volume index (RVSVI), RV ejection fraction (RVEF), RV mass, RV isovolumic relaxation time (rIVRT), leftward ventricular septal bowing (LVSB), and left ventricular ejection fraction (LVEF) were determined using cMRI.

Results

After 16 weeks, the change (Δ) from baseline (median [range]) in the studied cMRI parameters differed significantly between the bosentan group and the controls: Δ RVSVI: 6 [−4–11] vs 1 [−6–3] mL/m−2; Δ RVEF: 8 [−10–15] vs −4 [−7–5]%; Δ RV mass: −3 [−6–−2] vs 2 [−1–3] g/m−2; Δ rIVRT: −30 [−130–20] vs 10 [−30–30] msec; Δ LVSB: 0.03 [−0.03–0.13] vs −0.03[−0.08–0.04] cm−1; and Δ LVEF: 8 [−5–17] vs −2 [−14–2]% (all P < 0.05). The change from baseline in mean pulmonary artery pressure (−11 [−17–11] vs 5 [−6–21] mm Hg, P < 0.05) and 6‐minute walk distance (20 [3–88] vs −4 [−40–40] m, P < 0.05) also differed significantly.

Conclusions

In CTEPH, compared with control, treatment with bosentan for 16 weeks was associated with a significant improvement in cMRI parameters of RV function and remodelling.
Efficacy of Short‐Term High‐Dose Atorvastatin Pretreatment in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: A Meta‐analysis of Nine Randomized Controlled Trials
Authors: Liu Yangchun , Su Qiang , Li Lang
Published: August 2013

Background

The efficacy of short‐term high‐dose atorvastatin pretreatment in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) remains unclear. This meta‐analysis was undertaken to assess the efficacy of short‐term high‐dose atorvastatin pretreatment in patients with ACS undergoing PCI.

Hypothesis

Short‐term high‐dose atorvastatin pretreatment may be beneficial in reducing major adverse cardiac events (MACEs) and improving myocardial blood flow in patients with ACS undergoing PCI.

Methods

MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were systematically reviewed for randomized controlled trials (RCTs) published up to March 2013, in which short‐term high‐dose atorvastatin pretreatment was compared with control for patients with ACS undergoing PCI. The primary outcome measure was the incidence of MACEs at 30 days. The meta‐analysis was performed with the fixed effect model or random‐effects model according to the heterogeneity. Meta‐analysis was performed by RevMan 5.0 software (Cochrane Collaboration, Copenhagen, Denmark).

Results

Nine RCTs incorporating 952 patients met the inclusion criteria and were included in this meta‐analysis. Short‐term high‐dose atorvastatin pretreatment significantly reduced the incidence of MACEs at 30‐day follow‐up (risk ratio [RR] 0.39, 95% confidence interval [Cl]: 0.25 to 0.61, P < 0.001) and improved the final Thrombolysis in Myocardial Infarction (TIMI) flow grade (RR 1.08, 95% Cl: 1.02 to 1.14, P = 0.01) compared with controls. There were no significant differences in peak creatine kinase‐myocardial band and high‐sensitivity C‐reactive protein level post‐PCI between the 2 groups, though there were favorable trends related to statin use. As to the safety end points, no significant difference was observed in elevated liver aminotransferase level between short‐term high‐dose atorvastatin pretreatment and control groups (RR 1.36, 95% Cl: 0.67 to 2.74).

Conclusions

The use of short‐term high‐dose atorvastatin pretreatment is safe and significantly improves the final TIMI flow grade as well as reduces the 30‐day MACEs in ACS patients post‐PCI. This finding encourages the use of short‐term high‐dose atorvastatin pretreatment as an alternative for ACS patients undergoing PCI, but more high‐quality randomized clinical trials are still needed to confirm the long‐term efficacy and safety.
Functionalized Porphyrins as Red Fluorescent Probes for Metal Cations: Spectroscopic, MALDI‐TOF Spectrometry, and Doped‐Polymer Studies
Authors: Moura Nuno M. M. , Núñez Cristina , Santos Sérgio M. , Faustino M. Amparo F. , Cavaleiro José A. S. , Neves M. Graça P. M. S. , Capelo José Luis , Lodeiro Carlos
Published: August 2013

Invited for this month’s cover are groups from the University of Aveiro and the University NOVA of Lisbon/Bioscope. The cover picture of the lighthouses of Barra (Aveiro) and Cabo Espichel (Lisbon) in Portugal represents the remarkable sensing ability of benzoporphyrin derivatives for Hg2+ metal ions. These systems have high potential for use as chromogenic and fluorogenic sensors. Read the full text of the article on page 1230.
QoS‐driven jointly optimal subcarrier pairing and power allocation for OFDM amplify‐and‐forward relay systems
Authors: Huang Gaofei , Tu Wanqing , Luo Liping , Zhang Ping , Zhang Guangchi , Qin Jiayin
Published: August 2013

In this paper, we investigate the quality‐of‐service (QoS) driven subcarrier pairing and power allocation for two‐hop amplify‐and‐forward OFDM relay systems. By integrating the concept of effective capacity, our goal is to maximize the system throughput subject to a given delay QoS constraint. We propose a jointly optimal subcarrier pairing and power allocation scheme, which can be implemented with two separate steps. First, pair the subcarriers over the source‐relay channel and relay‐destination channel by the descending order of the subcarriers’ channel gains. Second, by making use of the derived equivalent end‐to‐end channel gains of the subcarrier pairs, optimally allocate power over the subcarrier pairs, and then optimally partition the power of the subcarrier pairs between the source and the relay. The simulation results show that our proposed scheme can efficiently provide different levels of delay QoS guarantees, even if under stringent delay QoS constraints. The simulation results also verify that our proposed scheme shows significant superiorities over the other existing schemes. Copyright © 2013 John Wiley & Sons, Ltd.
Surface Mineralization of Cellulose by Metal Chloride – an Original Pathway for the Synthesis of Hierarchical Urchin and Needle Carpetlike TiO2 Superstructures
Authors: Nair G. Ranjith , Samdarshi Sanjoy K. , Boury Bruno
Published: August 2013

A new pathway has been developed for the preparation of hierarchical TiO2 structures obtained “with‐and‐from” the surface of cotton. By reaction with TiCl4 under anhydrous conditions, mineralization of the outer part of the cotton fiber produces hierarchical TiO2 superstructures: at the nanoscale, anatase needles are made of nanorod assemblies and these needles are assembled into urchins and carpets at the submicrometer scale. This one‐step cotton fiber cellulose mineralization process differs from a simple deposition from inorganic sol; here, cellulose acts as both a reacting oxygen donor and also as a biotemplate. The material has high‐temperature crystal stability, and its photocatalytic activity in the UV range, without any doping, is higher than that of titania standard P25. The high photoactivity is ascribed to efficient light harvesting by hierarchical superstructures, efficient charge separation with reduced recombination in the crystalline material, and efficient sorption ability. From a general standpoint, our findings could be adapted to other metal oxides and pave the way to a number of solar‐cell, energy‐storage, and photonic‐sensor applications.
Biotechnology for the functional improvement of cereal‐based materials enriched with PUFA and pigments
Authors: Čertík Milan , Klempová Tatiana , Guothová Lucia , Mihálik Daniel , Kraic Ján
Published: August 2013

Cereals as the major food supply are deficient in essential nutrients, such as PUFA and pigments. Biotechnological techniques based on solid state fermentation (SSF) and genetic engineering have been developed to naturally prepare functional cereals enriched with PUFAs and carotenoids. SSF represents a promising approach where the selected fungi (Zygomycetes) effectively utilize and transform raw cereal substrates to cereal‐based bioproducts containing high amounts of valuable PUFAs and carotenoids. Depending on the strain, types of cereal substrates, and cultivation conditions, a range of cereal‐based bioproducts enriched with PUFAs (up to 2.4% GLA, 4.2% AA, 2.1% dihomo‐gamma/linolenic acid, 2.3% eicosapentaenoic acid) and pigments (8.5 mg beta‐carotene/kg prefermented cereals) have been prepared. In addition, cereals (barley, wheat) consisting of gamma‐linolenic and stearidonic acids have been prepared by genetic transformation of the fungal fatty acid Δ6‐desaturase gene. Such functional prefermented cereal‐based bioproducts are characterized by the acceptable nutritive, functional, and flavor values, the improved antioxidant, radical‐scavenging, and thermal oxidation properties as well as the enhanced safety; therefore they may find applications in the food/feed fields.

Practical applications: Cereals lack a number of nutrients, such as PUFAs and pigments which are essential for human well‐being due to their healthy, dietary, and functional properties. However, cereals could be considered as challenging sources of these compounds if they are naturally modified with the aim to contain PUFAs and pigments. Therefore the biotechnological preparation of cereals enriched with PUFAs and carotene pigments by fungal SSF has been developed. This natural technique is promising for the application of prefermented “bioproducts” in various fields and such cereal materials enriched with PUFAs and carotenoids might be considered as new types of inexpensive functional cereal‐based food and feed supplements.
A Second‐Generation Tandem Ring‐Closing Metathesis Cleavable Linker for Solid‐Phase Oligosaccharide Synthesis
Authors: de Jong Ana R. , Volbeda Anne G. , Hagen Bas , van den Elst Hans , Overkleeft Herman S. , van der Marel Gijsbert A. , Codée Jeroen D. C.
Published: August 2013

A tandem ring‐closing metathesis cleavable linker system for solid‐phase oligosaccharide synthesis has been developed. The acid‐ and base‐stable linker can be readily cleaved with Grubbs second‐generation catalyst without the use of alkene additives to liberate the assembled oligosaccharides from the solid support. Application of the linker was shown in three solid‐phase oligosaccharide synthesis campaigns. Two frame‐shifted hyaluronic acid fragments were prepared, and we also report the synthesis of a trimeric β‐1,3‐glucan fragment, in which, next to the linker, our recently reported 4‐azido‐2,2‐dimethylbutanoyl (AzDMB) protective group was applied.
Fabrication of an Electrochemical L‐Cysteine Sensor Based on Graphene Nanosheets Decorated Manganese Oxide Nanocomposite Modified Glassy Carbon Electrode
Authors: Majd Samira Mansouri , Teymourian Hazhir , Salimi Abdollah
Published: August 2013

The graphene nanosheets/manganese oxide nanoparticles modified glassy carbon electrode (GC/GNSs/MnOx) was simply prepared by casting a thin film of GNSs on the GC electrode surface, followed by performing electrodeposition of MnOx at applied constant potential. The GC/GNSs/MnOx modified electrode shows high catalytic activity toward oxidation of L‐cysteine. Hydrodynamic amperometry determination of L‐cysteine gave linear responses over a concentration range up to 120 µM with a detection limit of 75 nM and sensitivity of 27 nA µM−1. The GC/GNSs/MnOx electrode appears to be a highly efficient platform for the development of sensitive, stable and reproducible L‐cysteine electrochemical sensors.
1,4‐Michael Addition – The Analytical Way for Quantitative Sensing of Neurotransmitter at Bare Gold Electrode in Physiological Solution in the Presence of Interfering Biogenic Compounds
Authors: Łuczak Teresa
Published: August 2013

Electrooxidation of norepinephrine in the presence a nucleophile was investigated on a bare gold electrode. Electrochemically produced norepinephrinequinone undergoes an attack by morpholine as nucleophile via 1,4‐Michael addition. The reaction products were identified by electrospray ionization mass spectrometry. The procedure used was suitable for quantitative norepinephrine determination in the concentration range from 1×10−9 M to 8×10−4 M with a detection limit of 8.7×10−10 M in a samples containing an excess of ascorbic and uric acids. The proposed method is simple, green which means that it does not require the use of toxic compounds and solvents and thus is promising for detection of norepinephrine in physiological environment.
Surface functionalized thiol‐ene waveguides for fluorescence biosensing in microfluidic devices
Authors: Feidenhans'l Nikolaj A. , Lafleur Josiane P. , Jensen Thomas G. , Kutter Jörg P.
Published: August 2013

Thiol‐ene polymers possess physical, optical, and chemical characteristics that make them ideal substrates for the fabrication of optofluidic devices. In this work, thiol‐ene polymers are used to simultaneously create microfluidic channels and optical waveguides in one simple moulding step. The reactive functional groups present at the surface of the thiol‐ene polymer are subsequently used for the rapid, one step, site‐specific functionalization of the waveguide with biological recognition molecules. It was found that while the bulk properties and chemical surface properties of thiol‐ene materials vary considerably with variations in stoichiometric composition, their optical properties remain mostly unchanged with an average refractive index value of 1.566 ± 0.008 for thiol‐ene substrates encompassing a range from 150% excess ene to 90% excess thiol. Microfluidic chips featuring thiol‐ene waveguides were fabricated from 40% excess thiol thiol‐ene to ensure the presence of thiol functional groups at the surface of the waveguide. Biotin alkyne was photografted at specific locations using a photomask, directly at the interface between the microfluidic channel and the thiol‐ene waveguide prior to conjugation with fluorescently labeled streptavidin. Fluorescence excitation was achieved by launching light through the thiol‐ene waveguide, revealing bright fluorescent patterns along the channel/waveguide interface.
Targeting the androgen receptor with siRNA promotes prostate cancer metastasis through enhanced macrophage recruitment via CCL2/CCR2‐induced STAT3 activation
Authors: Izumi Kouji , Fang Lei‐Ya , Mizokami Atsushi , Namiki Mikio , Li Lei , Lin Wen‐Jye , Chang Chawnshang
Published: August 2013

Increased CCL2 expression in prostate cancer (PCa) cells enhanced metastasis via macrophage recruitment. However, its linkage to androgen receptor (AR)‐mediated PCa progression remains unclear. Here, we identified a previously unrecognized regulation: targeting AR with siRNA in PCa cells increased macrophage recruitment via CCL2 up‐regulation, which might then result in enhancing PCa invasiveness. Molecular mechanism dissection revealed that targeting PCa AR with siRNA promoted PCa cell migration/invasion via CCL2‐dependent STAT3 activation and epithelial–mesenchymal transition (EMT) pathways. Importantly, pharmacologic interruption of the CCL2/CCR2‐STAT3 axis suppressed EMT and PCa cell migration, providing a new mechanism linking CCL2 and EMT. Simultaneously targeting PCa AR with siRNA and the CCL2/CCR2‐STAT3 axis resulted in better suppression of PCa growth and metastasis in a xenograft PCa mouse model. Human PCa tissue microarray analysis suggests that increased CCL2 expression may be potentially associated with poor prognosis of PCa patients. Together, these results may provide a novel therapeutic approach to better battle PCa progression and metastasis at the castration resistant stage via the combination of targeting AR with siRNA and anti‐CCL2/CCR2‐STAT3 signalling.