bluuebunny/crossref_metadata_2025 huggingface dataset:
Brief Report: Etanercept Inhibits the Tumor Necrosis Factor α–Driven Shift of Th17 Lymphocytes Toward a Nonclassic Th1 Phenotype in Juvenile Idiopathic Arthritis
Authors: Maggi Laura , Cimaz Rolando , Capone Manuela , Santarlasci Veronica , Querci Valentina , Simonini Gabriele , Nencini Francesca , Liotta Francesco , Romagnani Sergio , Maggi Enrico , Annunziato Francesco , Cosmi Lorenzo
Published: January 2014

Objective

To evaluate the effects of etanercept on the phenotype of CD4+ T helper lymphocytes from patients with juvenile idiopathic arthritis (JIA).

Methods

We compared the proportions of various Th cell subsets in peripheral blood (PB) from etanercept‐treated and untreated JIA patients. An in vitro study was performed on PB mononuclear cells (PBMCs) from 15 children with untreated JIA, in which we evaluated the proliferative response of these cells, as well as their cytokine production profile, in the presence of various stimuli with or without etanercept.

Results

We found lower proportions of CD4+ CD161+ (nonclassic) Th1 lymphocytes in the PB of patients treated with etanercept than in untreated patients. In vitro, etanercept inhibited the proliferative response induced by either polyclonal or recall antigen stimulation of PBMCs. Moreover, etanercept increased the proportion of CD4+CD161+ Th17/Th1 and Th17 cells in vitro while decreasing the proportions of nonclassic Th1 cell subsets, leaving CD4+CD161− (classic) Th1 cells unaffected. We also found that tumor necrosis factor α (TNFα) was able to induce transition of Th17 lymphocytes toward the nonclassic Th1 phenotype in vitro, probably due to the high expression of TNF receptor type II observed in Th17 cells.

Conclusion

We have previously demonstrated the occurrence of a shifting of CD4+CD161+ Th17 cells to the nonclassic Th1 phenotype in children with JIA. The present findings suggest that etanercept can exert its disease‐modifying action by interfering with this shifting.
Early Response of Mouse Joint Tissue to Noninvasive Knee Injury Suggests Treatment Targets
Authors: Wu P. , Holguin N. , Silva M. J. , Fu M. , Liao W. , Sandell L. J.
Published: January 2014

Objective

Joint trauma can lead to a spectrum of acute lesions, including cartilage degradation, ligament or meniscus tears, and synovitis, all potentially associated with osteoarthritis (OA). This study was undertaken to generate and validate a murine model of knee joint trauma following noninvasive controlled injurious compression in vivo.

Methods

The right knees of 8‐week‐old mice were placed in a hyperflexed position and subjected to compressive joint loading at 1 of 3 peak forces (3N, 6N, or 9N) for 60 cycles in a single loading period and harvested on days 5, 9, and 14 after loading (n = 3–5 for each time point and for each loading). The left knees were not loaded and were used as the contralateral control. Histologic, immunohistochemical, and enzyme‐linked immunosorbent assay analyses were performed to evaluate acute pathologic features in chondrocyte viability, cartilage matrix metabolism, synovial reaction, and serum cartilage oligomeric matrix protein (COMP) levels.

Results

Acute joint pathology was associated with increased injurious loads. All loading regimens induced chondrocyte apoptosis, cartilage matrix degradation, disruption of cartilage collagen fibril arrangement, and increased levels of serum COMP. We also observed that 6N loading induced mild synovitis by day 5, whereas at 9N, with tearing of the anterior cruciate ligament, severe posttraumatic synovitis and ectopic cartilage formation were observed.

Conclusion

We have established a murine model of knee joint trauma with different degrees of overloading in vivo. Our results suggest that immediate therapies particularly targeted to apoptosis and synovial cell proliferation could affect the acute posttraumatic reaction to potentially limit chronic consequences and OA.
Cyclin‐Dependent Kinase 9 Inhibition Protects Cartilage From the Catabolic Effects of Proinflammatory Cytokines
Authors: Yik Jasper H. N. , Hu Zi'ang , Kumari Ratna , Christiansen Blaine A. , Haudenschild Dominik R.
Published: January 2014

Objective

Cyclin‐dependent kinase 9 (CDK‐9) controls the activation of primary inflammatory response genes. The purpose of this study was to determine whether CDK‐9 inhibition protects cartilage from the catabolic effects of proinflammatory cytokines.

Methods

Human chondrocytes were challenged with different proinflammatory stimuli (interleukin‐1β [IL‐1β], lipopolysaccharides, and tumor necrosis factor α) in the presence or absence of either the CDK‐9 inhibitor flavopiridol or small interfering RNA (siRNA). The expression of messenger RNA (mRNA) for inflammatory mediator genes, catabolic genes, and anabolic genes were determined by real‐time quantitative reverse transcription–polymerase chain reaction (qRT‐PCR) analysis. Cartilage explants were incubated for 6 days with IL‐1β in the presence or absence of flavopiridol. Cartilage matrix degradation was assessed by the release of glycosaminoglycan (GAG) and cleaved type II collagen (COL2A) peptides.

Results

CDK‐9 inhibition by flavopiridol or knockdown by siRNA effectively suppressed the induction of mRNA for inducible nitric oxide synthase by all 3 proinflammatory stimuli. Results from NF‐κB–targeted PCR array analysis showed that flavopiridol suppressed IL‐1β induction of a broad range of inflammatory mediator genes (59 of 67 tested). CDK‐9 inhibition also suppressed the induction of catabolic genes (matrix metalloproteinase 1 [MMP‐1], MMP‐3, MMP‐9, MMP‐13, ADAMTS‐4, and ADAMTS‐5), but did not affect the basal expression of anabolic genes (COL2A, aggrecan, and cartilage oligomeric matrix protein) and housekeeping genes. Flavopiridol had no apparent short‐term cytotoxicity, as assessed by G6PDH activity. Finally, in IL‐1β–treated cartilage explants, flavopiridol reduced the release of the matrix degradation product GAG and cleaved COL2A peptides, but did not affect long‐term chondrocyte viability.

Conclusion

CDK‐9 activity is required for the primary inflammatory response in chondrocytes. Flavopiridol suppresses the induction of inflammatory mediator genes and catabolic genes to protect cartilage from the deleterious effects of proinflammatory cytokines, without affecting cell viability and functions.
Cost-effectiveness and cost–utility of endovascularversusopen repair of ruptured abdominal aortic aneurysm in the Amsterdam Acute Aneurysm Trial
Authors: Kapma M R , Dijksman L M , Reimerink J J , de Groof A J , Zeebregts C J , Wisselink W , Balm R , Dijkgraaf M G W , Vahl A C
Published: January 2014

Background

Minimally invasive endovascular aneurysm repair (EVAR) could be a surgical technique that improves outcome of patients with ruptured abdominal aortic aneurysm (rAAA). The aim of this study was to analyse the cost-effectiveness and cost–utility of EVAR compared with standard open repair (OR) in the treatment of rAAA, with costs per 30-day and 6-month survivor as outcome parameters.

Methods

Resource use was determined from the Amsterdam Acute Aneurysm (AJAX) trial, a multicentre randomized trial comparing EVAR with OR in patients with rAAA. The analysis was performed from a provider perspective. All costs were calculated as if all patients had been treated in the same hospital (Onze Lieve Vrouwe Gasthuis, teaching hospital).

Results

A total of 116 patients were randomized. The 30-day mortality rate was 21 per cent after EVAR and 25 per cent for OR: absolute risk reduction (ARR) 4·4 (95 per cent confidence interval (c.i.) –11·0 to 19·7) per cent. At 6 months, the total mortality rate for EVAR was 28 per cent, compared with 31 per cent among those assigned to OR: ARR 2·4 (−14·2 to 19·0) per cent. The mean cost difference between EVAR and OR was €5306 (95 per cent c.i. –1854 to 12 659) at 30 days and €10 189 (−2477 to 24 506) at 6 months. The incremental cost-effectiveness ratio per prevented death was €120 591 at 30 days and €424 542 at 6 months. There was no significant difference in quality of life between EVAR and OR. Nor was EVAR superior regarding cost–utility.

Conclusion

EVAR may be more effective for rAAA, but its increased costs mean that it is unaffordable based on current standards of societal willingness-to-pay for health gains.
Expertise-based randomized clinical trial of laparoscopic versus small-incision open cholecystectomy (Br J Surg 2013; 100: 886–894)
Authors: Naraynsingh V , Singh Y , Dan D , Maharaj R
Published: January 2014

The Editors welcome topical correspondence from readers relating to articles published in the Journal. Responses should be sent electronically via the BJS website (www.bjs.co.uk). All letters will be reviewed and, if approved, appear on the website. A selection of these will be edited and published in the Journal. Letters must be no more than 250 words in length.
A phase II study of preoperative capecitabine in women with operable hormone receptor positive breast cancer
Authors: Tolaney Sara M. , Jeong Joon , Guo Hao , Brock Jane , Morganstern Daniel , Come Steven E. , Golshan Mehra , Bellon Jennifer , Winer Eric P. , Krop Ian E.
Published: January 2014

Conventional preoperative chemotherapy regimens have only limited efficacy in hormone receptor positive (HR+) breast cancer and new approaches are needed. We hypothesized that capecitabine, which is effective in metastatic breast cancer, may be an active preoperative treatment for HR+ breast cancer. Women with HR+, HER2‐negative operable breast cancer received capecitabine, 2000 mg/m2 daily in divided doses for 14 days, followed by a 7‐day rest period. Treatment was repeated every 21 days for a total of four cycles. The primary endpoint of the study was to determine the rate of pathological complete response (pCR). Because of slow accrual, the study was closed after 24 patients were enrolled. Three patients had a complete clinical response, and eight patients had a partial clinical response, for an overall clinical response rate of 45.8%. There were no cases of pCR. Of the 22 patients who had pathological response assessment by the Miller–Payne grading system, there were six grade 3 responses, and no grade 4 or 5 responses. Toxicity was manageable: the only grade 3 toxicities observed were one case each of diarrhea, palmar plantar erythrodysesthesia, hypokalemia, and mucositis. There was no association between baseline levels, or change in level from baseline to cycle 1, or from baseline to time of surgery, of thymidine phosphorylase (TYMP), thymidylate synthase (TYMS), dihydropyrimidine dehydrogenase (DPYD), or Ki67 and pathological, clinical, or radiographic response. Preoperative capecitabine is a well‐tolerated regimen, but appears not lead to pCR when used as monotherapy in HR+ breast cancer.
Targeting of tumor endothelial cells combining 2 Gy/day of X‐ray with Everolimus is the effective modality for overcoming clinically relevant radioresistant tumors
Authors: Kuwahara Yoshikazu , Mori Miyuki , Kitahara Shuji , Fukumoto Motoi , Ezaki Taichi , Mori Shiro , Echigo Seishi , Ohkubo Yasuhito , Fukumoto Manabu
Published: January 2014

Radiotherapy is widely used to treat cancer because it has the advantage of physically and functionally conserving the affected organ. To improve radiotherapy and investigate the molecular mechanisms of cellular radioresistance, we established a clinically relevant radioresistant (CRR) cell line, SAS‐R, from SAS cells. SAS‐R cells continue to proliferate when exposed to fractionated radiation (FR) of 2 Gy/day for more than 30 days in vitro. A xenograft tumor model of SAS‐R was also resistant to 2 Gy/day of X‐rays for 30 days. The density of blood vessels in SAS‐R tumors was higher than in SAS tumors. Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, sensitized microvascular endothelial cells to radiation, but failed to radiosensitize SAS and SAS‐R cells in vitro. Everolimus with FR markedly reduced SAS and SAS‐R tumor volumes. Additionally, the apoptosis of endothelial cells (ECs) increased in SAS‐R tumor tissues when both Everolimus and radiation were administered. Both CD34‐positive and tomato lectin‐positive blood vessel densities in SAS‐R tumor tissues decreased remarkably after the Everolimus and radiation treatment. Everolimus‐induced apoptosis of vascular ECs in response to radiation was also followed by thrombus formation that leads to tumor necrosis. We conclude that FR combined with Everolimus may be an effective modality to overcome radioresistant tumors via targeting tumor ECs.
Allergenicity prediction by artificial neural networks
Authors: Dimitrov Ivan , Naneva Lyudmila , Bangov Ivan , Doytchinova Irini
Published: January 2014

Two artificial neural network (ANN)‐based algorithms for allergenicity prediction were developed and tested. The first algorithm consists of three steps. Initially, the protein sequences are described by amino acid principal properties as hydrophobicity, size, relative abundance, helix and β‐strand forming propensities. Second, the generated strings of different length are converted into vectors with equal length by auto‐covariance and cross‐covariance (ACC). At the third step, ANN is applied to discriminate between allergens and non‐allergens. The second algorithm consists of four steps. It has one additional step before the final ANN modeling. At this step, the ACC vectors are transformed into binary fingerprints. The algorithms were applied to a set of 2427 known allergens and 2427 non‐allergens and compared in terms of predictive ability. The three‐step algorithm performed better than the four‐step one identifying 82% versus 76% of the allergens and non‐allergens. The ANN algorithms presented here are universal. They could be applied for any classification problem in computational biology. The amino acid descriptors are able to capture the main structural and physicochemical properties of amino acids building the proteins. The ACC transformation overcomes the main problem in the alignment‐based comparative studies arising from the different length of the aligned protein sequences. The uniform‐length vectors allow similarity search and classification by different computational methods. Optionally, the ACC vectors could be converted into binary descriptor fingerprints. The comparative study on several Web tools for allergenicity prediction showed that the usage of more than one predictor is reasonable and recommendable because some of the tools recognize better the allergens, some of them—the non‐allergens, but none of them—both. Copyright © 2014 John Wiley & Sons, Ltd.
Anticancer Potential of (Pentamethylcyclopentadienyl)chloridoiridium(III) Complexes Bearing κP and κP,κS‐Coordinated Ph2PCH2CH2CH2S(O)xPh (x=0–2) Ligands
Authors: Ludwig Gerd , Ranđelović Ivan , Maksimović‐Ivanić Danijela , Mijatović Sanja , Bulatović Mirna Z. , Miljković Djordje , Korb Marcus , Lang Heinrich , Steinborn Dirk , Kaluđerović Goran N.
Published: January 2014

Iridium(III) complexes of the type [Ir(η5‐C5Me5)Cl2{Ph2PCH2CH2CH2S(O)xPh‐κP}] (x=0–2; 1–3) and [Ir(η5‐C5Me5)Cl{Ph2PCH2CH2CH2S(O)xPh‐κP,κS}][PF6] (x=0–1; 4 and 5) with 3‐(diphenylphosphino)propyl phenyl sulfide, sulfoxide, and sulfone ligands Ph2PCH2CH2CH2S(O)xPh were designed, synthesized, and characterized fully, including X‐ray diffraction analyses for complexes 3 and 4. In vitro studies against human thyroid carcinoma (8505C), submandibular carcinoma (A253), breast adenocarcinoma (MCF‐7), colon adenocarcinoma (SW480), and melanoma (518A2) cell lines provided evidence for the high biological potential of the neutral and cationic iridium(III) complexes. Neutral iridium(III) complex 5 proved to be the most active, with IC50 values up to about 0.1 μM, representing activities of up to one order of magnitude higher than cisplatin. Using 8505C cells, apoptosis was shown to be the main mechanism through which complex 5 exerts its tumoricidal action. The described iridium(III) complexes represent potential leads in the search for novel metal‐based anticancer agents.
Encapsulated gadolinium and dysprosium ions within ultra‐short carbon nanotubes for MR microscopy at 11.75 and 21.1 T
Authors: Rosenberg Jens T. , Cisneros Brandon T. , Matson Michael , Sokoll Michelle , Sachi‐Kocher Afi , Bejarano Fabian Calixto , Wilson Lon J. , Grant Samuel C.
Published: January 2014

Single‐walled carbon nanotubes (SWNTs) have gained interest for their biocompatibility and multifunctional properties. Ultra‐short SWNTs (US‐tubes) have demonstrated high proton relaxivity when encapsulating gadolinium ions (Gd3+) at clinical field strengths. At higher field strengths, however, Gd3+ ions demonstrate decreased proton relaxation properties while chemically similar dysprosium ions (Dy3+) improve relaxation properties. This report investigates the first use of Gd3+ and Dy3+ ions within US‐tubes (GNTs and DNTs, respectively) at ultra‐high magnetic field (21.1 T). Both agents are compared in solution and as an intracellular contrast agent labeling a murine microglia cell line (Bv2) immobilized in a tissue‐mimicking agarose phantom using two high magnetic fields: 21.1 and 11.75 T. In solution at 21.1 T, results show excellent transverse relaxation; DNTs outperformed GNTs as a T2 agent with measured r2/r1 ratios of 247 and 47, respectively. Additionally, intracellular DNTs were shown to be a better T2 agent than GNTs with higher contrast percentages and contrast‐to‐noise ratios. As such, this study demonstrates the potential of DNTs at high magnetic fields for cellular labeling and future in vivo, MRI‐based cell tracking. Copyright © 2014 John Wiley & Sons, Ltd.
Spectral CT: a technology primer for contrast agent development
Authors: Schirra Carsten O. , Brendel Bernhard , Anastasio Mark A. , Roessl Ewald
Published: January 2014

Recent developments in spectral CT systems featuring binned photon‐counting detector technology have enabled an imaging concept on a pre‐clinical level that has been coined K‐edge imaging. This exciting concept allows the selective and quantitative imaging of contrast media by exploiting the K‐edge discontinuity in the photo‐electric component of X‐ray absorption. An ideal application for K‐edge imaging is CT imaging of target‐specific and conventional contrast agents that have been designed to be spectral‐CT‐visible. Current limitations in detector hardware, however, result in typically high noise levels that hamper the application of K‐edge imaging. In order to battle noise and assure sufficient sensitivity, the development of dedicated K‐edge contrast media in combination with advanced image processing techniques is imperative. This work attempts a comprehensive overview on how the concert of dedicated contrast media, optimized data acquisition and innovative data processing techniques improve sensitivity of K‐edge imaging which will foster clinical translation of the technology. Copyright © 2014 John Wiley & Sons, Ltd.
Iodinated AlIII‐Based Phthalocyanines are Promising Sensitizers for Dye‐Sensitized Solar Cells; A Theoretical Comparison Between ZnII, MgII, and AlIII‐Based Phthalocyanine Sensitizers
Authors: Yang Li‐Na , Sun Zhu‐Zhu , Chen Shi‐Lu , Li Ze‐Sheng
Published: January 2014

To design efficient dyes for dye‐sensitized solar cells (DSSCs), using a Zn‐coordinated phthalocyanine (TT7) as the prototype, a series of phthalocyanine dyes (Pcs) with different metal ions and peripheral/axial groups have been investigated by means of density functional theory (DFT) and time‐dependent DFT (TDDFT) methods. Computational results show that the iodinated Al‐based dye with a peripheral amino group (Al‐I‐NH2‐Pc) exhibits the largest redshift in the maximum absorbance (λmax). In addition, Al‐based dyes have appropriate energy‐level arrangements of frontier orbitals to keep excellent balance between electron injection and regeneration of oxidized dyes. Further, it has been found that the intermolecular π‐staking interaction in Al‐I‐Pc molecules is weaker than the other metal‐based Pcs, which may effectively reduce dye aggregation on the semi‐conductor surface. All these results suggest iodinated Al‐based Pcs (Al‐I‐Pcs) to be potentially promising sensitizers in DSSCs.
Peptide‐Nanofiber‐Supported Palladium Nanoparticles as an Efficient Catalyst for the Removal of N‐Terminus Protecting Groups
Authors: Maity Indrajit , Manna Manoj K. , Rasale Dnyaneshwar B. , Das Apurba K.
Published: January 2014

Sonication‐induced tryptophan‐ and tyrosine‐based peptide bolaamphiphile nanofibers have been used to synthesize and stabilize Pd nanoparticles under physiological conditions. The peptide bolaamphiphile self‐assembly process has been thoroughly studied by using several spectroscopic and microscopic techniques. The stiffness of the soft hydrogel matrix was measured by an oscillatory rheological experiment. FTIR and circular dichroism (CD) experiments revealed a hydrogen‐bonded β‐sheet conformation of peptide bolaamphiphile molecules in a gel‐phase medium. The π–π stacking interactions also played a crucial role in the self‐assembly process, which was confirmed by fluorescence spectroscopy. Electron (SEM and TEM) and atomic force microscopy (AFM) studies showed that the peptide bolaamphiphile molecules self‐assemble into nanofibrillar structures. Pd nanoparticles were synthesized in the hydrogel matrix in which redox‐active tryptophan and tyrosine residues reduce the metal ions to metal nanoparticles. The size of the Pd nanoparticles are in the range of 3–9 nm, and are stabilized by peptide nanofibers. The peptide‐nanofiber‐supported Pd nanoparticles have shown effective catalytic activity for the removal of N‐terminus protecting groups of amino acids and peptides.
Synthesis and Optical Properties of Imidazole‐Based Fluorophores having High Quantum Yields
Authors: Lessi Marco , Manzini Chiara , Minei Pierpaolo , Perego Luca A. , Bloino Julien , Egidi Franco , Barone Vincenzo , Pucci Andrea , Bellina Fabio
Published: January 2014

A series of 1,4‐phenylene‐spaced bis‐imidazoles with fluorescence quantum yields up to 0.90 and large Stokes shifts have been designed and synthesized using recently developed regioselective direct CH arylation protocols. All the fluorophores show a bright blue‐green emission that is well retained in the solid state. DFT calculations attributed their excellent luminescence properties to the significant planarization of the molecules in the equilibrium structures of their excited electronic states.
Preliminary Evidence for a Nexus between Rumination, Behavioural Avoidance, Motive Satisfaction and Depression
Authors: Brockmeyer Timo , Holtforth Martin Grosse , Krieger Tobias , Altenstein David , Doerig Nadja , Zimmermann Johannes , Backenstrass Matthias , Friederich Hans‐Christoph , Bents Hinrich
Published: January 2014

The present study tested a theoretically derived link between rumination and depressive symptoms through behavioural avoidance and reduced motive satisfaction as a key aspect of positive reinforcement. Rumination, behavioural avoidance, motive satisfaction and levels of depression were assessed via self‐report measures in a clinical sample of 160 patients with major depressive disorder. Path analysis‐based mediation analysis was used to estimate the direct and indirect effects as proposed by the theoretical model. Operating in serial, behavioural avoidance and motive satisfaction partially mediated the association between rumination and depressive symptoms, irrespective of gender, medication and co‐morbid anxiety disorders. This is the first study investigating the associations between behavioural avoidance, rumination and depression in a clinical sample of depressed patients. The findings are in line with an understanding of rumination in depression as also serving an avoidance function. Copyright © 2014 John Wiley & Sons, Ltd.

Key Practitioner Message

Rumination, avoidance, motive satisfaction and levels of depressive symptoms were examined in a clinical sample of 160 outpatients with major depressive disorder.

Path analysis‐based mediation analysis revealed that, operating in serial, avoidance and motive satisfaction partially mediated the link between rumination and levels of depressive symptoms.

Findings support an understanding of rumination in depression as serving an avoidance function.
Burden of diabetic foot disorders, guidelines for management and disparities in implementation in Europe: a systematic literature review
Authors: van Acker Kristien , Léger Philippe , Hartemann Agnes , Chawla Abhineet , Siddiqui Mohd Kashif
Published: January 2014

The study aimed to assess the economic and quality of life burden of diabetic foot disorders and to identify disparities in the recommendations from guidelines and the current clinical practice across the EU5 (Spain, Italy, France, UK and Germany) countries. Literature search of electronic databases (MEDLINE®, Embase® and Cochrane Database of Systematic Reviews) was undertaken. English language studies investigating economic and resource burden, quality of life and management of diabetic foot disease in the EU5 countries were included. Additionally, websites were screened for guidelines and current management practices in diabetic foot complication in EU5. Diabetic foot complications accounted for a total annual cost of €509m in the UK and €430 per diabetic patient in Germany, during 2001. The cost of diabetic foot complications increased with disease severity, with hospitalizations (41%) and amputation (9%) incurring 50% of the cost. Medical devices (orthopaedic shoes, shoe lifts and walking aids) were the most frequently utilized resources. Patients with diabetic foot complications experienced worsened quality of life, especially in those undergoing amputations and with non‐healed ulcers or recurrent ulcers. Although guidelines advocate the use of multidisciplinary foot care teams, the utilization of multidisciplinary foot care teams was suboptimal. We conclude that diabetic foot disorders demonstrated substantial economic burden and have detrimental effect on quality of life, with more impairment in physical domain. Implementation of the guidelines and set‐up of multidisciplinary clinics for holistic management of the diabetic foot disorders varies across Europe and remains suboptimal. Hence, guidelines need to be reinforced to prevent diabetic foot complications and to achieve limb salvage if complications are unpreventable. Copyright © 2014 John Wiley & Sons, Ltd.
CuII‐Templated Threading of a Bis‐amide‐tris‐amine Macrocycle by Substituted 2,2′‐Bipyridyl Derivatives Assisted by Strong π–π Stacking and Second‐Sphere H‐Bonding Interactions
Authors: Saha Subrata , Santra Saikat , Ghosh Pradyut
Published: January 2014

Derivatives of 5,5′‐substituted 2,2′‐bipyridine (BPy) ligands with bromo‐terminated aliphatic side chains with ester functionalities (BPy5Br), hydroxy‐terminated aliphatic side chains with amide functionalities (BPy5OH), and benzyl‐terminated side chains with amide functionalities (BPy5Bnz) were synthesized. The single‐crystal X‐ray structure analysis of the axle BPy5Br shows that it has a linear rodlike structure with a length of 15.75 Å. The above three ligands along with a methyl‐substituted BPy ligand (BPy5Me) are explored as axles for CuII‐templated threading of a bis‐amide‐tris‐amine macrocycle wheel (MC). High‐yield (70–80 %) syntheses of the [2]pseudorotaxanes PRT1, PRT2, PRT3, and PRT4 are obtained by reaction of MC with the axles BPy5Me, BPy5Br, BPy5OH, and BPy5Bnz, respectively, in the presence of CuII ions. These complexes were characterized by ESI‐MS, UV/Vis and EPR spectroscopy, and single‐crystal X‐ray diffraction studies. The solution‐state binding stoichiometry and the association constants for complex formation between MC–Cu2+ and the axles were studied by UV/Vis absorption titrations. Sigma‐fit curves indicate 1:1 stoichiometry, and the association constants range from 1.2 × 103 to 2.6 × 103 M–1. Single‐crystal X‐ray structure analysis of PRT1, PRT2, and PRT4 confirms the threading of MC by the respective axles, which are coordinated to the CuII center with Cu–N bond lengths of 1.992–2.203 Å. Interestingly, strong aromatic π–π stacking interactions between two parallel arene moieties of MC and the pyridyl unit of the axle with π–π interaction distances of 3.402–3.618 Å are observed in all three [2]pseudorotaxanes. However, for PRT4, a strong hydrogen‐bonding interaction is also operative between the carbonyl oxygen atom of BPy5Bnz and the amide proton of MC with a N–H···O distance of 2.200 Å. Thus, multiple template interactions such as metal coordination, π–π stacking, and second‐sphere hydrogen‐bonding interactions between MC and the axles play crucial roles for facile threading and high‐yield syntheses of [2]pseudorotaxanes.
Influence of carbon and metal oxide nanomaterials on aqueous concentrations of the munition constituents cyclotrimethylenetrinitramine (RDX) and tungsten
Authors: Brame Jonathon A. , Kennedy Alan J. , Lounds Christopher D. , Bednar Anthony J. , Alvarez Pedro J.J. , Scott Andrea M. , Stanley Jacob K.
Published: January 2014

There is an increasing likelihood of interactions between nanomaterials and munitions constituents in the environment resulting from the use of nanomaterials as additives to energetic formulations and potential contact in waste streams from production facilities and runoff from training ranges. The purpose of the present research was to determine the ability of nano-aluminum oxide (Al2O3) and multiwalled carbon nanotubes (MWCNTs) to adsorb the munitions constituents cyclotrimethylenetrinitramine (RDX) and tungsten (W) from aqueous solution as a first step in determining the long-term exposure, transport, and bioavailability implications of such interactions. The results indicate significant adsorption of RDX by MWCNTs and of W by nano-Al2O3 (but not between W and MWCNT or RDX and nano-Al2O3). Kinetic sorption and desorption investigations indicated that the most sorption occurs nearly instantaneously (<5 min), with a relatively slower, secondary binding leading to statistically significant but relatively smaller increases in adsorption over 30 d. The RDX sorption that occurred during the initial interaction was irreversible, with long-term, reversible sorption likely the result of a secondary interaction; as interaction time increased, however, the portion of W irreversibly sorbed onto nano-Al2O3 also increased. The present study shows that strong interactions between some munitions constituents and nanomaterials following environmental release are likely. Time-dependent binding has implications for the bioavailability, migration, transport, and fate of munitions constituents in the environment. Environ Toxicol Chem 2014;33:1035–1042. © 2014 SETAC
Ecotoxicological effects of perfluorooctanoic acid on freshwater microalgae Chlamydomonas reinhardtii and Scenedesmus obliquus
Authors: Hu Changwei , Luo Qi , Huang Qingguo
Published: January 2014

As a persistent bioaccumulative compound, perfluorooctanoic acid (PFOA) is found in various ecosystems and receives growing attention. The acute toxicity of PFOA was tested on 2 freshwater microalgae, Chlamydomonas reinhardtii and Scenedesmus obliquus. The 96-h concentration for 50% of maximal effect (EC50) values were measured, physiological responses of the algae were investigated, and uptake of PFOA by the algae was quantified. The EC50 values for C. reinhardtii and S. obliquus were 51.9 ± 1.0 mg/L and 44.0 ± 1.5 mg/L PFOA, respectively. After 8-d exposure to PFOA ranging from 10 mg/L to 40 mg/L, the growth of C. reinhardtii was significantly inhibited, whereas that of S. obliquus was only slightly suppressed. Increases in malonaldehyde and proline levels were observed in the 2 algae when exposed to PFOA at certain concentrations, for instance, 20 mg/L and 40 mg/L, which is indicative of the trigger of a defensive mechanism. The percentage of PFOA that was adsorbed by the algae after 8-d exposure at a dosage between 5 mg/L and 20 mg/L ranged from 5.5% to 7.5%, and the uptake of PFOA by the algae exceeded 10%. Environ Toxicol Chem 2014;33:1129–1134. © 2014 SETAC
Vestibular loss promotes procedural response during a spatial task in rats
Authors: Machado Marie‐Laure , Lelong‐Boulouard Véronique , Philoxene Bruno , Davis Audrey , Denise Pierre , Besnard Stéphane
Published: January 2014

Declarative memory refers to a spatial strategy using numerous sources of sensory input information in which visual and vestibular inputs are assimilated in the hippocampus. In contrast, procedural memory refers to a response strategy based on motor skills and familiar gestures and involves the striatum. Even if vestibular loss impairs hippocampal activity and spatial memory, vestibular‐lesioned rats remain able to find food rewards during complex spatial memory task. Since hippocampal lesions induce a switch from declarative memory to procedural memory, we hypothesize that vestibular‐lesioned rats use a strategy other than that of hippocampal spatial response to complete the task and to counterbalance the loss of vestibular information. We test, in a reverse T‐maze paradigm, the types of strategy vestibular‐lesioned rats preferentially uses in a spatial task. We clearly demonstrate that all vestibular‐lesioned rats shift to a response strategy to solve the spatial task, while control rats use spatial and response strategies equally. We conclude that the loss of vestibular informations leading to spatial learning impairments is not offset at the hippocampus level by integration process of other sense mainly visual informations; but favors a response strategy through procedural memory most likely involving the striatum, cerebellum, and motor learning. © 2014 Wiley Periodicals, Inc.
Infection, antibiotic therapy and risk of colorectal cancer: A nationwide nested case–control study in patients with Type 2 diabetes mellitus
Authors: Wang Jiun‐Ling , Chang Chia‐Hsuin , Lin Jou‐Wei , Wu Li‐Chiu , Chuang Lee‐Ming , Lai Mei‐Shu
Published: January 2014

Patients with Type 2 diabetes mellitus are at a higher risk of colorectal cancer (CRC). The objective of our study was to examine the inter‐relationship among infection sites, systemic antibiotic use and risk of CRC among patients with Type 2 diabetes mellitus. From a diabetic cohort from the Taiwan's National Health Insurance claims database, we identified 3,593 incident colon cancer cases, 1,979 rectal cancer cases and 22,288 controls and conducted a nested case–control study to examine the association between antibiotic use and CRC incidence. Logistic regression models were applied to estimate the odds ratio (OR) and the 95% confidence interval (95% CI) between infection sites, antibiotic use and CRC incidence. Patients with intra‐abdominal infection were significantly associated with increased risk for colon cancer (OR = 2.01, 95% CI = 1.73–2.35) and rectal cancer (OR = 1.59, 95% CI = 1.26–2.00). Any antianaerobic antibiotic use was associated with a higher risk of colon cancer (OR = 2.31, 95% CI = 2.12–2.52) and rectal cancer (OR = 1.69, 95% CI = 1.50–1.90) but without an obvious dose–response relationship for cumulative use. Antianaerobic antibiotics also increased the risks for those with nonintra‐abdominal infection. No association was found between antiaerobic agent use and the CRC risk. The results suggest intra‐abdominal infections and antianaerobic antibiotic use may be a marker for precancerous lesions or early CRC, although the possibility of antianaerobic antibiotics playing an additional role cannot be excluded. Further research examining the relationship between intra‐abdominal infection, antianaerobic antibiotics use and possible change of microbiota leading to colorectal carcinogenesis is warranted.
Men and Body Image: Current Issues and Counseling Implications
Authors: Burlew Larry D. , Shurts W. Matthew
Published: January 2014

Male adolescents and men may experience body image dissatisfaction/distress (BID), and their symptoms and behaviors may often go unrecognized or underdiagnosed. This lack of recognition occurs because the symptoms are often at the subclinical level on the continuum of BID, yet more men than ever before are experiencing BID. The authors describe BID and present an overview of BID symptoms, related diagnoses, and recommended prevention and intervention strategies for men experiencing BID.
Sleeping Beauty–baculovirus hybrid vectors for long‐term gene expression in the eye
Authors: Turunen Tytteli Anni Kaarina , Laakkonen Johanna Päivikki , Alasaarela Laura , Airenne Kari Juhani , Ylä‐Herttuala Seppo
Published: January 2014

Background

A baculovirus vector is capable of efficiently transducing many nondiving and diving cell types. However, the potential of baculovirus is restricted for many gene delivery applications as a result of the transient gene expression that it mediates. The plasmid‐based Sleeping Beauty (SB) transposon system integrates transgenes into target cell genome efficiently with a genomic integration pattern that is generally considered safer than the integration of many other integrating vectors; yet efficient delivery of therapeutic genes into cells of target tissues in vivo is a major challenge for nonviral gene therapy. In the present study, SB was introduced into baculovirus to obtain novel hybrid vectors that would combine the best features of the two vector systems (i.e. effective gene delivery and efficient integration into the genome), thus circumventing the major limitations of these vectors.

Methods

We constructed and optimized SB‐baculovirus hybrid vectors that bear either SB100x transposase or SB transposon in the forward or reverse orientations with respect to the viral backbone The functionality of the novel hybrid vectors was investigated in cell cultures and in a proof‐of‐concept study in the mouse eye.

Results

The hybrid vectors showed high and sustained transgene expression that remained stable and demonstrated no signs of decline during the 2 months follow‐up in vitro. These results were verified in the mouse eye where persistent transgene expression was detected two months after intravitreal injection.

Conclusions

Our results confirm that (i) SB‐baculovirus hybrid vectors mediate long‐term gene expression in vitro and in vivo, and (ii) the hybrid vectors are potential new tools for the treatment of ocular diseases. Copyright © 2014 John Wiley & Sons, Ltd.
Review of hepatopancreatoduodenectomy for biliary cancer: an extended radical approach of Japanese origin
Authors: Ebata Tomoki , Yokoyama Yukihiro , Igami Tsuyoshi , Sugawara Gen , Mizuno Takashi , Nagino Masato
Published: January 2014

Cholangiocarcinomas exhibit various modes of local extension, and some tumors can only be completely resected by hepatopancreatoduodenectomy (HPD), which is defined as the resection of the whole extrahepatic biliary system with the adjacent liver and pancreatoduodenum. Since Takasaki et al. introduced HPD for locally advanced gallbladder cancer in 1980, Japanese hepatobiliary surgeons have aggressively challenged this extended procedure for advanced biliary tumors. Early experiences with HPD were frequently associated with liver failure and sequential mortality, leading to an underestimation of the survival benefit of HPD. However, with improvements in surgical techniques and perioperative patient care, including portal vein embolization, over the last two decades, the mortality rate after HPD has gradually decreased. Recent studies have demonstrated a favorable survival in cholangiocarcinoma, provided that R0 resection is achieved. In contrast, HPD for gallbladder cancer remains controversial because of the extremely poor survival, although the study populations have been limited. HPD can be performed with low mortality and offers a better probability of long‐term survival in patients with cholangiocarcinoma. We should consider HPD to be a standard approach for laterally advanced cholangiocarcinomas that are otherwise unresectable.
Recent advances in 3D computed tomography techniques for simulation and navigation in hepatobiliary pancreatic surgery
Authors: Uchida Masafumi
Published: January 2014

A few years ago it could take several hours to complete a 3D image using a 3D workstation. Thanks to advances in computer science, obtaining results of interest now requires only a few minutes. Many recent 3D workstations or multimedia computers are equipped with onboard 3D virtual patient modeling software, which enables patient‐specific preoperative assessment and virtual planning, navigation, and tool positioning. Although medical 3D imaging can now be conducted using various modalities, including computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and ultrasonography (US) among others, the highest quality images are obtained using CT data, and CT images are now the most commonly used source of data for 3D simulation and navigation image. If the 2D source image is bad, no amount of 3D image manipulation in software will provide a quality 3D image. In this exhibition, the recent advances in CT imaging technique and 3D visualization of the hepatobiliary and pancreatic abnormalities are featured, including scan and image reconstruction technique, contrast‐enhanced techniques, new application of advanced CT scan techniques, and new virtual reality simulation and navigation imaging.
Analysis of aquatic‐phase natural organic matter by optimized LDI‐MS method
Authors: Wang Ren‐Qi , Druckenmüller Katharina , Elbers Gereon , Guenther Klaus , Croué Jean‐Philippe
Published: January 2014

The composition and physiochemical properties of aquatic‐phase natural organic matter (NOM) are most important problems for both environmental studies and water industry. Laser desorption/ionization (LDI) mass spectrometry facilitated successful examinations of NOM, as humic and fulvic acids in NOM are readily ionized by the nitrogen laser. In this study, hydrophobic NOMs (HPO NOMs) from river, reservoir and waste water were characterized by this technique. The effect of analytical variables like concentration, solvent composition and laser energy was investigated. The exact masses of small molecular NOM moieties in the range of 200–1200 m/z were determined in reflectron mode. In addition, spectra of post‐source‐decay experiments in this range showed that some compounds from different natural NOMs had the same fragmental ions. In the large mass range of 1200–15 000 Da, macromolecules and their aggregates were found in HPO NOMs from natural waters. Highly humic HPO exhibited mass peaks larger than 8000 Da. On the other hand, the waste water and reservoir water mainly had relatively smaller molecules of about 2000 Da. The LDI‐MS measurements indicated that highly humic river waters were able to form large aggregates and membrane foulants, while the HPO NOMs from waste water and reservoir water were unlikely to form large aggregates. Copyright © 2014 John Wiley & Sons, Ltd.
Synthesis and Characterization of Poly(phenylacetylene)s with Ru(II) Bis‐Terpyridine Complexes in the Side‐Chain
Authors: Breul Alexander M. , Kübel Joachim , Häupler Bernhard , Friebe Christian , Hager Martin D. , Winter Andreas , Dietzek Benjamin , Schubert Ulrich S.
Published: January 2014

An alkyne‐functionalized ruthenium(II) bis‐terpyridine complex is directly copolymerized with phenylacetylene by alkyne polymerization. The polymer is characterized by size‐exclusion chromatography (SEC), 1H NMR spectroscopy, cyclic voltammetry (CV) measurements, and thermal analysis. The photophysical properties of the polymer are studied by UV–vis absorption spectroscopy. In addition, spectro‐electrochemical measurements are carried out. Time‐resolved luminescence lifetime decay curves show an enhanced lifetime of the metal complex attached to the conjugated polymer backbone compared with the Ru(tpy)22+ model complex.

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Novel IRF6 mutations in families with Van Der Woude syndrome and popliteal pterygium syndrome from sub‐Saharan Africa
Authors: Butali Azeez , Mossey Peter A. , Adeyemo Wasiu L. , Eshete Mekonen A. , Gaines LauRen A. , Even Dee , Braimah Ramat O. , Aregbesola Babatunde S. , Rigdon Jennifer V. , Emeka Christian I. , James Olutayo , Ogunlewe Mobolanle O. , Ladeinde Akinola L. , Abate Fikre , Hailu Taye , Mohammed Ibrahim , Gravem Paul E. , Deribew Milliard , Gesses Mulualem , Adeyemo Adebowale A. , Murray Jeffrey C.
Published: January 2014

Orofacial clefts (OFC) are complex genetic traits that are often classified as syndromic or nonsyndromic clefts. Currently, there are over 500 types of syndromic clefts in the Online Mendelian Inheritance in Man (OMIM) database, of which Van der Woude syndrome (VWS) is one of the most common (accounting for 2% of all OFC). Popliteal pterygium syndrome (PPS) is considered to be a more severe form of VWS. Mutations in the IRF6 gene have been reported worldwide to cause VWS and PPS. Here, we report studies of families with VWS and PPS in sub‐Saharan Africa. We screened the DNA of eight families with VWS and one family with PPS from Nigeria and Ethiopia by Sanger sequencing of the most commonly affected exons in IRF6 (exons 3, 4, 7, and 9). For the VWS families, we found a novel nonsense variant in exon 4 (p.Lys66X), a novel splice‐site variant in exon 4 (p.Pro126Pro), a novel missense variant in exon 4 (p.Phe230Leu), a previously reported splice‐site variant in exon 7 that changes the acceptor splice site, and a known missense variant in exon 7 (p.Leu251Pro). A previously known missense variant was found in exon 4 (p.Arg84His) in the PPS family. All the mutations segregate in the families. Our data confirm the presence of IRF6‐related VWS and PPS in sub‐Saharan Africa and highlights the importance of screening for novel mutations in known genes when studying diverse global populations. This is important for counseling and prenatal diagnosis for high‐risk families.
Quantized output feedback control with multiplicative measurement noises
Authors: Wei Li , Fu Minyue , Zhang Huanshui
Published: January 2014

In this paper, we consider the problem of quantized quadratic performance control for a class of stochastic systems, which are subject to multiplicative noises in the measurement. A dynamic output feedback controller is designed to guarantee a given level of performance. By using the sector bound approach to characterize the quantization error, the existence of a solution for the quantized quadratic performance control problem is found by solving the so‐called guaranteed cost control problem of the associated system with a sector bounded uncertainty. We show that the latter problem can be solved using LMIs. Copyright © 2014 John Wiley & Sons, Ltd.
High‐impedance fault location using matching technique and wavelet transform for underground cable distribution network
Authors: Ali Mohd Syukri , Abu Bakar Ab Halim , Mokhlis Hazlie , Arof Hamzah , Azil Illias Hazlee
Published: January 2014

Locating the faulty section of a high‐impedance fault (HIF) is quite challenging for the underground distribution network of a power system. The complexity of the distribution network, such as branches, nonhomogenous lines, and HIF, contributes to the difficulties in locating the faulty section. In this paper, the shortest distance (SD) technique and a database approach have been proposed to determine the faulty section. A multiresolution analysis based on discrete wavelet transforms is chosen to extract the unique features from voltage signals during the HIF event. The output coefficients from the decomposition process is stored in a database and used as the input data for the SD algorithm. The first, second, and third level of detailed coefficients of the post‐disturbance voltage signal were utilized for the identification of the faulty section using the proposed method. A ranking analysis was created to provide a number of possibilities of faulty section. In this paper, a 38‐node underground distribution network system in a national grid in Malaysia was modeled using the PSCAD software. The proposed method was able to successfully determine the faulty section. © 2013 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.