bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiplex Analyses of Antibodies Against Citrullinated Peptides in Individuals Prior to Development of Rheumatoid Arthritis
Authors: Brink Mikael , Hansson Monika , Mathsson Linda , Jakobsson Per‐Johan , Holmdahl Rikard , Hallmans Göran , Stenlund Hans , Rönnelid Johan , Klareskog Lars , Rantapää‐Dahlqvist Solbritt
Published: January 2013

Objective

The presence of antibodies against cyclic citrullinated peptides has been demonstrated to precede the onset of symptoms of rheumatoid arthritis (RA) by several years. The aim of this study was to analyze antibodies against 10 citrullinated autoantigen‐derived peptides for reactivity before the onset of RA symptoms.

Methods

A case–control study was conducted within the Medical Biobank of Northern Sweden. The study was performed in 409 individuals, 386 of whom donated 717 blood samples before the onset of symptoms of RA (pre‐patients). The median period of time predating the onset of RA was 7.4 years. A total of 1,305 population‐based control subjects were also studied. Antibodies to 10 citrullinated peptides, fibrinogen α573 (Fibα573), Fibα591, Fibβ36–52, Fibβ72, Fibβ74, α‐enolase (citrullinated α‐enolase peptide 1 [CEP‐1]), triple‐helical type II collagen peptide C1 (citC1III), filaggrin, vimentin 2–17 (Vim2–17), and Vim60–75, were analyzed using a microarray system.

Results

The fluorescence intensity of antibodies against Fibβ36–52, Fibβ74, CEP‐1, citC1III, and filaggrin was significantly increased in pre‐patients compared with controls (P < 0.001). The levels of the earliest‐detectable antibodies (Fibα591 and Vim60–75) fluctuated over time, with only a slight increase after the onset of disease. The frequency of antibodies against Fibβ36–52, CEP‐1, and filaggrin increased gradually, reaching the highest levels before symptom onset. The frequency of a cluster of antibodies, citC1III, Fibα573, and Fibβ74, increased only slightly before the onset of symptoms but increased prominently after disease onset. The odds ratio for the development of RA in individuals expressing both CEP‐1 and Fibβ36–52 antibodies (using data from samples obtained <3.35 years predating symptom onset) was 40.4 (95% confidence interval 19.8–82.3) compared with having either antibody alone.

Conclusion

Development of an immune response toward citrullinated peptides is initially restricted but expands with time to induce a more specific response, with levels, particularly those of antibodies against CEP‐1, Fibβ36–52, and filaggrin, increasing during the predating time period closer to the onset of symptoms.
Seeking information for a middle school history project: The concept of implicit knowledge in the students' transition from Kuhlthau's Stage 3 to Stage 4
Authors: Cole Charles , Behesthi Jamshid , Large Andrew , Lamoureux Isabelle , Abuhimed Dhary , AlGhamdi Mohammed
Published: January 2013

The article reports the findings of a content analysis study of 16 student‐group proposals for a grade eight history project. The students listed their topic and thesis in the proposal, and information in support of their thesis. The study's focus is this topic‐to‐thesis transition. The study's conceptual framework is Kuhlthau's six stage ISP Model's transition from exploring information in Stage 3 to formulating a focus or personal perspective on the assignment topic in Stage 4. Our study coding scheme identifies elements of the students' implicit knowledge in the 16 proposals. To validate implicit knowledge as a predictor of successful student performance, implicit knowledge was coded, scored, and then the correlation coefficient was established between the score and the students' instructors' marks. In Part 2 of the study we found strong and significant association between the McGill coding scores and the instructors' marks for the 16 proposals. This study is a first step in identifying, operationalizing, and testing user‐centered implicit knowledge elements for future implementation in interactive information systems designed for middle school students researching a thesis‐objective history assignment.
ETA: Robust software for determination of cell specific rates from extracellular time courses
Authors: Murphy Taylor A. , Young Jamey D.
Published: January 2013

Accurate quantification of cell specific rates and their uncertainties is of critical importance for assessing metabolic phenotypes of cultured cells. We applied two different methods of regression and error analysis to estimate specific metabolic rates from time‐course measurements obtained in exponentially growing cell cultures. Using simulated data sets to compute specific rates of growth, glucose uptake, and lactate excretion, we found that Gaussian error propagation from prime variables to the final calculated rates was the most accurate method for estimating parameter uncertainty. We incorporated this method into a MATLAB‐based software package called Extracellular Time‐Course Analysis (ETA), which automates the analysis workflow required to (i) compute cell specific metabolic rates and their uncertainties; (ii) test the goodness‐of‐fit of the experimental data to the regression model; and (iii) rapidly compare the results across multiple experiments. ETA was used to estimate the uptake or excretion rate of glucose, lactate, and 18 different amino acids in a B‐cell model of c‐Myc‐driven cancer. We found that P493‐6 cells with High Myc expression increased their specific uptake of glutamine, arginine, serine, lysine, and branched‐chain amino acids by two‐ to threefold in comparison to low Myc cells, but exhibited only modest increases in glucose uptake and lactate excretion. By making the ETA software package freely available to the scientific community, we expect that it will become an important tool for rigorous estimation of specific rates required for metabolic flux analysis and other quantitative metabolic studies. Biotechnol. Bioeng. 2013; 110: 1748–1758. © 2013 Wiley Periodicals, Inc.
Bis(phosphite) Ligands with Distal Regulation: Application in Rhodium‐mediated Asymmetric Hydroformylations
Authors: Mon Ignasi , Jose D. Amilan , Vidal‐Ferran Anton
Published: January 2013

Small amounts of achiral polyether binders are employed to enhance the enantioselectivity of the hydroformylation of an array of diversely substituted substrates (increase of up to 62 % ee for vinyl acetate) mediated by chiral rhodium complexes derived from the α,ω‐bis(phosphite)–polyether ligands 1. To the best of our knowledge, this study represents an unprecedented successful example of the positive regulation of enantioselectivity in hydroformylations.
Synchronous bilateral Wilms tumor
Authors: Indolfi Paolo , Jenkner Alessandro , Terenziani Monica , Crocoli Alessandro , Serra Annalisa , Collini Paola , Biasoni Davide , Gandola Lorenza , Bisogno Gianni , Cecchetto Giovanni , Di Martino Martina , D'Angelo Paolo , Bianchi Maurizio , Conte Massimo , Inserra Alessandro , Pession Andrea , Spreafico Filippo ,   on behalf of the AIEOP Wilms Tumor Working Group
Published: January 2013

BACKGROUND:

The optimal management of bilateral Wilms tumor (BWT) is challenging, and their survival is lower than for unilateral tumors. This report discusses a large series of BWTs treated in Italy in the last 2 decades.

METHODS:

This analysis concerns patients with synchronous BWT registered at Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) centers between 1990 and 2011; details on their treatment and outcome are presented and discussed.

RESULTS:

Ninety BWTs were registered in the AIEOP Wilms tumor database. Preoperative chemotherapy was given for a median 12 weeks before definitive tumor resection was attempted. Forty‐eight percent of the patients had preservation of bilateral renal parenchyma. The proportion of bilateral nephron‐sparing surgeries was not higher in the 37 patients initially given doxorubicin/vincristine/actinomycin D (32%) than in the 43 children receiving vincristine/actinomycin D alone (58%). The 4‐year disease‐free survival rate was 66.5% ± 5% and overall survival was 80% ± 5% for the cohort as a whole. The 4‐year disease‐free survival (overall survival) for 18 children with diffuse anaplasia or postchemotherapy blastemal‐type tumors was 51% ± 13% (62% ± 13%), as opposed to 72% ± 3% (88% ± 4%) for 68 children with a favorable histology (log‐rank P = .04 [P = .007]).

CONCLUSIONS:

These results provide further evidence that the optimal duration and choice of drugs for preoperative chemotherapy remain an open question. Outcome remained significantly worse for BWT than for unilateral Wilms tumor. To enable the conservative treatment of as many affected kidneys as possible, only centers with experience in BWT should manage such cases. Cancer 2013. © 2013 American Cancer Society.
Microwave Spectroscopic and Atoms in Molecules Theoretical Investigations on the Ar⋅⋅⋅Propargyl Alcohol Complex: Ar⋅⋅⋅HO, Ar⋅⋅⋅π, and Ar⋅⋅⋅C Interactions
Authors: Mani Devendra , Arunan Elangannan
Published: January 2013

The structure of the Ar⋅⋅⋅propargyl alcohol (Ar⋅⋅⋅PA) complex is determined from the rotational spectra of the parent complex and its two deuterated isotopologues, namely Ar⋅⋅⋅PA‐D(OD) and Ar⋅⋅⋅PA‐D(CD). The spectra confirm a geometry in which PA exists in the gauche form with Ar located in between OH and CCH groups. All a, b and c types of transitions show small splitting due to some large‐amplitude motion dominated by COH torsion, as in the monomer. Splittings in a‐ and b‐type transitions are of the order of a few kilohertz, whereas splitting in the c‐type transitions is relatively larger (0.9–2.6 MHz) and decreases in the order Ar⋅⋅⋅PA>Ar⋅⋅⋅PA‐D(CD)>Ar⋅⋅⋅PA‐D(OD). The assignments are well supported by ab initio calculations. Atoms in molecules (AIM) and electrostatic potential calculations are used to explore the nature of the interactions in this complex. AIM calculations not only reveal the expected OH⋅⋅⋅Ar and π⋅⋅⋅Ar interactions in the Ar⋅⋅⋅gauche‐PA complex, but also novel C⋅⋅⋅Ar (of CH2OH group) and OH⋅⋅⋅Ar interactions in the Ar⋅⋅⋅trans‐PA complex. Similar interactions are also present in the Ar⋅⋅⋅methanol complex.
Kinetics of luminescence of CsI single crystals scavenged by Y3+
Authors: Cherginets V. L. , Rebrova T. P. , Datsko Yu. N. , Ponomarenko T. V. , Yavetsky R. P. , Pedash V. Yu.
Published: January 2013

CsI single crystals were grown from the melt scavenged by Y3+ (YCl3) addition in 6.7·10−4–6.7·10−3 mol·kg−1 range. The addition of the scavenger amounts comparable with the total concentration of the oxygen‐containing admixtures in molten CsI results in complete destruction of the latter. Because of this, the intensity of the band with a maximum at 2.8 eV in radioluminescence spectra caused by the oxygen‐containing admixtures (anion vacancies) considerably decreases, and the fraction of the slow 2μs‐component corresponding to these admixtures becomes lower than 0.01 (0.007). The addition of larger quantities of YCl3 leads to the appearance of a wide band with a maximum at 2.8 eV caused by cation vacancies, and the intensity of the slow 2μs‐component increases to 0.02. The maximum ratio of two faster components with the decay constants equal to 7 and 30 ns reaches 0.65:0.33 at Y3+ concentration in CsI melt equal to 6.7·10‐3 mol·kg‐1, the effective luminescence time of fastest components is ca 14 ns. The dependence of the ‘Fast/Total ratio’ on Y3+ concentration passes through its maximum (0.81) corresponding to the equivalence of Y3+ and O2− concentrations in the growth CsI melt.
Developments in the Coordination Chemistry of Phosphinines
Authors: Müller Christian , Broeckx Leen E. E. , de Krom Iris , Weemers Jarno J. M.
Published: January 2013

Invited for this month's cover is the group of Christian Müller at the Freie Universität Berlin. The image shows the most recent developments in the coordination chemistry of functionalized, π‐accepting phosphinines.
Fast Inline Roll‐to‐Roll Printing for Indium‐Tin‐Oxide‐Free Polymer Solar Cells Using Automatic Registration
Authors: Hösel Markus , Søndergaard Roar R. , Jørgensen Mikkel , Krebs Frederik C.
Published: January 2013

Fast inline roll‐to‐roll printing and coating on polyethylene terephthalate (PET) and barrier foil was demonstrated under ambient conditions at web speeds of 10 m min−1 for the manufacture of indium‐tin‐oxide‐free (ITO‐free) polymer solar cells comprising a 6‐layer stack: silver‐grid/PEDOT:PSS/ZnO/P3HT:PCBM/PEDOT:PSS/silver‐grid. The first and second layers were printed at the same time using inline processing at a web speed of 10 m min−1 where flexographic printing of a hexagonal silver grid comprises the first layer followed by rotary‐screen printing of a PEDOT:PSS electrode as the second layer. The third and fourth layers were slot‐die coated at the same time again using inline processing at a web speed of 10 m min−1 of firstly zinc oxide as the electron transport layer followed by P3HT:PCBM as the active layer. The first three layers (silver‐grid/PEDOT:PSS/ZnO) comprise a generally applicable ITO‐free, semitransparent, electron‐selective front electrode for inverted polymer solar cells. This electrode shows a low sheet resistance (∼10 Ω/□) and good optical transmission in the visible range (∼60 %). The solar cell stack was completed by rotary‐screen printing of a hole‐collecting PEDOT:PSS layer at 2 m min−1 and a comb‐patterned silver‐grid back electrode at the same speed. The solar cells were post processed by using fast roll‐to‐roll switching to a functional state.
Use of the ecosystem services concept in landscape management in the Netherlands
Authors: van Wensem Joke
Published: January 2013

Increasing reference to the ecosystem services (ES) concept is made in publications on the need to use natural resources sustainably, to protect and enhance biodiversity, and to alleviate poverty in developing countries. To examine the significance of the concept in densely populated industrialized countries, this case study investigates its use in several sustainable landscape management projects in the Netherlands. Guidance by the Economics of Ecosystems and Biodiversity project (TEEB) for local and regional policy and management serves as a reference. The projects studied show that the ES concept is seen as a tool for enhancing biodiversity, creating more sustainable regional development plans, supporting better spatial-planning decisions on soil sealing, and, most importantly, for getting the involvement of much broader stakeholder groups—not just to make better decisions, but also to attract more funding for the plans. Not only does the Netherlands have a high demand for various ecosystem services and a desire for multifunctional land use, it also has a long tradition of consensus-seeking. As a result, “Dutch practice” is complex and involves many different stakeholders. Because of increasing recognition of the role ecosystem services play in enhancing the visibility of natural resources in decision making, the ES concept seems to be gaining a foothold. However, the number of projects is still limited, and neither the use of the methods nor the results are monitored. So far, this has made it impossible to say whether the approach leads to more sustainable decisions—in other words, to the better protection and management of natural resources. Integr Environ Assess Manag 2013; 9: 237–242. © 2013 SETAC
A Spanish Version of the Sociocultural Attitudes Towards Appearance Questionnaire‐3 (SATAQ‐3): Translation and Psychometric Evaluation
Authors: Llorente Enrique , Warren Cortney S. , de Eulate Lourdes Pérez , Gleaves David H.
Published: January 2013

Objective

The goal of this study was to translate the Sociocultural Attitudes Towards Appearance Questionnaire‐3 (SATAQ‐3; Thompson, van den Berg, Roehrig, Guarda, & Heinberg, 2004) into Spanish and psychometrically evaluate the comparability of the Spanish translation to the original English version.

Method

638 female college students from Spain and the United States completed the SATAQ‐3 in Spanish and English, respectively.

Results

Internal consistency was high in both languages. Tests of factor equivalence suggested that the four pre‐established factors of the SATAQ‐3 (i.e., knowledge, perceived pressure, thin‐ideal internalization, athletic‐ideal internalization) were relatively similar between the two groups. Differences that emerged between groups (on items 6 and 20) were in the expected direction and appeared to be influenced by reverse‐scoring or item wording.

Conclusions

Results support the psychometric properties of this Spanish translation of the SATAQ‐3 and support its use to measure endorsement of Western values and ideals of appearance in adult women.
In vivo gene transfer using pDNA/chitosan/chondroitin sulfate ternary complexes: influence of chondroitin sulfate on the stability of freeze‐dried complexes and transgene expression in vivo
Authors: Hagiwara Kenji , Kishimoto Satoko , Ishihara Masayuki , Koyama Yoshiyuki , Mazda Osam , Sato Toshinori
Published: January 2013

Background

Chitosan has been investigated as a promising nonviral vector. However, several problems still remain, such as a relatively low transfection efficiency and instability under physiological conditions. We previously demonstrated that a chondroitin sulfate (CS) coating enhanced the transfection efficiency and physicochemical stability of plasmid DNA (pDNA)/chitosan complexes in vitro. In the present study, the effects of coating pDNA/chitosan complexes with CS on the stability in freeze–dry rehydration processes and gene expression in vivo were investigated.

Methods

Freeze‐drying storage at –20 °C, 4 °C, or room temperature, freezing storage at –20 °C, or liquid storage at 4 °C or room temperature, were examined for preservation conditions of pDNA/chitosan/CS ternary complexes by a gel retardation assay, measurements of sizes and zeta potentials, and a luciferase assay. Moreover, to determine the transfection efficiency of the ternary complexes in vivo, suicide gene therapy was carried out in Huh‐7‐implanted mice using herpes simplex virus thymidine kinase coding pDNA and ganciclovir.

Results

The freeze‐dried pDNA/chitosan/CS ternary complexes showed sufficient cell transfection ability in vitro and in vivo. In addition, ternary complexes were associated with a significant suppression of tumor growth and a histopathologically high anti‐tumor effect by intratumoral injection to tumor‐bearing mice.

Conclusions

The CS coating enhanced the preservation stability of the pDNA/chitosan complexes after freeze‐drying–rehydration and their transgene expression in vivo. Copyright © 2013 John Wiley & Sons, Ltd.
A comparative study on the mode of interaction of different nanoparticles during MALDI‐MS of bacterial cells
Authors: Gopal Judy , Manikandan M. , Hasan Nazim , Lee Chia‐Hsun , Wu Hui‐Fen
Published: January 2013

We propose the benefits of preincubation during nanoparticle‐assisted bacterial analysis, where the bacteria are grown along with the nanoparticles. We were able to obtain a two to ten fold enhancement of bacterial signals in 3 h compared to the generally used methodology followed in previous literature. The previous literature method required a long time (18 h) to obtain such an enhancement. We probe the interactions of two bacteria, Staphylococcus aureus and Pseudomonas aeruginosa, with Ag, NiO, Pt TiO2 and ZnO nanoparticles via transmission electron microscopy, ultraviolet spectroscopy and matrix‐assisted laser desorption/ionization (MALDI) mass spectrometry (MS). Based on these results, we propose a mechanism for interaction of these five nanoparticles with bacteria. Two mechanisms were observed for the interactions: (1) Mechanism A is proposed for the Pt and NiO NPs which functioned based on affinity for bacterial cells. (2) Mechanism B was proposed for the bactericidal NPs such as TiO2, ZnO and Ag NPs. The results indicate that the success of the unmodified NPs in MALDI‐MS bacterial studies lies in following the ideal protocol for incubation at the ideal concentrations. Copyright © 2013 John Wiley & Sons, Ltd.
Flow‐through immobilized enzyme reactors based on monoliths: I. Preparation of heterogeneous biocatalysts
Authors: Vlakh Evgenia G. , Tennikova Tatiana B.
Published: January 2013

The application of monoliths for realization of solid‐phase biocatalytic processes was dramatically extended since the beginning of new century. Different enzyme immobilization techniques regarding these modern stationary phases have been developed, adapted, and optimized within last decade. The choice of enzyme immobilization method depends on material nature and monolith manufacturing. The present review collected, analyzed, and discussed the accessible published data on existing approaches and specialties of preparation of flow‐through enzyme reactors based on monoliths.
Chromatographic and mass spectrometric characterization of essential oils and extracts from Lippia (Verbenaceae) aromatic plants
Authors: Stashenko Elena E. , Martínez Jairo R. , Cala Mónica P. , Durán Diego C. , Caballero Deyanira
Published: January 2013

Analytical methodologies based on GC and HPLC were developed for the separation and quantification of carnosic acid, ursolic acid, caffeic acid, p‐coumaric acid, rosmarinic acid, apigenin, luteolin, quercetin, kaempferol, naringenin, and pinocembrin. These methods were used to characterize essential oils and extracts obtained by solvent (methanol) and by supercritical fluid (CO2) extraction from stems and leaves of Lippia (Verbenaceae family) aromatic plants (Lippia alba, Lippia origanoides, Lippia micromera, Lippia americana, Lippia graveolens, and Lippia citriodora). Supercritical CO2 extraction isolated solely pinocembrin and narigenin from three L. origanoides chemotypes. Solvent extracts possessed a more varied composition that additionally included apigenin, quercetin, and luteolin. Solvent extraction afforded higher overall flavonoid yields from all species in comparison with supercritical CO2 extraction. Pinocembrin was determined in L. origanoides extract at a concentration of 30 mg/g of plant material, which is more than ten times higher than the amount at which polyphenols are regularly found in aromatic plant extracts.
HPLC separation of enantiomers of chiral arylpropionic acid derivatives using polysaccharide‐based chiral columns and normal‐phase eluents with emphasis on elution order
Authors: Matarashvili Iza , Chankvetadze Lali , Fanali Salvatore , Farkas Tivadar , Chankvetadze Bezhan
Published: January 2013

The separation of enantiomers of ten chiral arylpropionic acid derivatives was studied on six different polysaccharide‐based chiral HPLC columns with various normal‐phase eluents. Along with the successful separation of analyte enantiomers, the emphasis of this study was on the effect of the chiral selector and mobile phase composition as well as of the separation temperature on the elution order of enantiomers. The interesting phenomena of reversal of enantiomer elution order function of the polysaccharide backbone (cellulose or amylose), type of derivative (carbamate or benzoate), nature and position of the substituent(s) in the phenylcarbamate moiety, the polar modifier of the mobile phase (ethanol or 2‐propanol), its content in the mobile phase, and separation temperature were investigated. In addition, an unusual increase in retention with increasing temperature was observed for some arylpropionic acid derivatives.
Pharmacokinetic study of schisandrin, schisandrol B, schisantherin A, deoxyschisandrin, and schisandrin B in rat plasma after oral administration of Shengmaisan formula by UPLC‐MS
Authors: Sun Hui , Wu Fangfang , Zhang Aihua , Wei Wenfeng , Han Ying , Wang Xijun
Published: January 2013

Shengmaisan (SMS) is a traditional Chinese medicine prescription widely used for the treatment of cardiovascular diseases in Asia. Its lignans are major components responsible for therapeutic action. A rapid and specific UPLC‐Q‐TOF/MS has been developed and validated for simultaneous quantification of the five main bioactive components, i.e. schisandrin, schisandrol B, schisantherin A, deoxyschisandrin, and schisandrin B, in rat plasma after oral administration of SMS. All calibration curves showed excellent linearity within the test ranges. Validation proved the repeatability of the method was good and recovery was satisfactory. The separation of these compounds was carried out on a Waters ACQUITY HSS T3 column (2.1 × 100 mm, 1.8 μm) by linear gradient elution using a mobile phase consisting of 0.01% formic acid in water and ACN containing 0.01% formic acid. In this work, plasma pharmacokinetic characteristics of lignans components after oral administration SMS were investigated using UPLC‐Q‐TOF/MS method. MS was performed on a Waters Micromass high‐definition technology with an ESI source. Data were analyzed and estimated by compartmental methods and pharmacokinetic parameters calculated using WinNonlin Professional version 6.1. Results demonstrated that the proposed UPLC‐Q‐TOF/MS method was successfully applied to pharmacokinetic study of all components in rat plasma after oral administration of the SMS.
Does Innovativeness Drive Environmentally Conscious Consumer Behavior?
Authors: Englis Basil G. , Phillips Diane M.
Published: January 2013

This study seeks to improve the predictive utility of the attitude–behavior link within the realm of environmentally responsible consumption by examining the role of consumer innovativeness as a mediator. A sample of over 1400 American consumers provided data regarding their attitudes about the environment, receptiveness to new and innovative ideas, propensity to adopt new products early, and likelihood of performing a variety of green behaviors. The evidence suggests that one dimension of consumer innovativeness mediates the link between environmentally conscious attitudes and behaviors: the general affinity for new ideas. Managerial implications of these findings are discussed.
The Marketers’ Prismatic Palette: A Review of Color Research and Future Directions
Authors: Labrecque Lauren I. , Patrick Vanessa M. , Milne George R.
Published: January 2013

Color carries meaning and can influence consumers’ thoughts, feelings, and behaviors. Many disciplines, such as neuroscience, psychophysics, visual cognition, and biology have used new technologies to gain insights in understanding the complexities of color perception, yet there exists relatively little research in the field of marketing. This paper aims to reestablish the importance of color research in marketing, draw attention to the complex nature of this research, and to fuel further investigation and the development of new insights about color as it relates to marketing. The authors offer an integrated conceptual framework centered on the embodied and referential meanings of color and highlight the complexities and nuances that researchers must consider in order to develop this area. Insights from and gaps in the extant literature are highlighted to present a set of questions and propositions for future research in this area of investigation.
Reliability and spatial specificity of rat brain sensorimotor functional connectivity networks are superior under sedation compared with general anesthesia
Authors: Kalthoff Daniel , Po Chrystelle , Wiedermann Dirk , Hoehn Mathias
Published: January 2013

Functional connectivity networks derived from resting‐state functional MRI (rsfMRI) have received increasing interest to further our understanding of brain function. The anesthesia in rodent models may influence the interpretation and comparison of results from functional connectivity MRI (fcMRI). More research is required on this aspect. In this study, we investigated rat brain connectivity networks under 1.5% isoflurane anesthesia in comparison with medetomidine sedation. rsfMRI data were acquired under both anesthesia conditions within one imaging session. Male Wistar rats (n = 17) were scanned at 11.7 T with focus on the sensorimotor system. The data underwent a per‐subject independent component analysis (ICA), after which individual components were grouped using hierarchical clustering. Consistent and reliable networks were identified under medetomidine in sensorimotor cortex (three networks) and striatum (two networks). The incidence of these networks was drastically reduced under isoflurane. Seed correlation analysis confirmed these results and revealed globally elevated correlations with low topical specificity under isoflurane, stemming from low‐frequency global signal fluctuations. Global signal removal thus enhanced slightly regional specificity under isoflurane and showed anti‐correlations of cortico‐striatal connections in both anesthesia regimes. Functional connectivity networks are thus reliably detected in medetomidine‐sedated animals on an individual basis using ICA. Their occurrence, however, is heavily compromised under isoflurane as a result of global signal fluctuations potentially stemming from burst‐suppression‐like neural activity. Anesthesia and pharmacologically induced modulations may provide insight into network mechanisms in the future. As an agent for fcMRI in brain disease studies, light sedation using medetomidine preserves connectivity networks in a greater level of detail, and may therefore be considered superior to standard isoflurane anesthesia. Copyright © 2013 John Wiley & Sons, Ltd.
Differential regulation of HIF‐mediated pathways increases mitochondrial metabolism and ATP production in hypoxic osteoclasts
Authors: Morten Karl J , Badder Luned , Knowles Helen J
Published: January 2013

Inappropriate osteoclast activity instigates pathological bone loss in rheumatoid arthritis. We have investigated how osteoclasts generate sufficient ATP for the energy‐intensive process of bone resorption in the hypoxic microenvironment associated with this rheumatic condition. We show that in human osteoclasts differentiated from CD14+ monocytes, hypoxia (24 h, 2% O2): (a) increases ATP production and mitochondrial electron transport chain activity (Alamar blue, O2 consumption); (b) increases glycolytic flux (glucose consumption, lactate production); and (c) increases glutamine consumption. We demonstrate that glucose, rather than glutamine, is necessary for the hypoxic increase in ATP production and also for cell survival in hypoxia. Using siRNA targeting specific isoforms of the hypoxia‐inducible transcription factor HIF (HIF‐1α, HIF‐2α), we show that employment of selected components of the HIF‐1α‐mediated metabolic switch to anaerobic respiration enables osteoclasts to rapidly increase ATP production in hypoxia, while at the same time compromising long‐term survival. We propose this atypical HIF‐driven metabolic pathway to be an adaptive mechanism to permit rapid bone resorption in the short term while ensuring curtailment of the process in the absence of re‐oxygenation. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Evaluation of Dosing and Clinical Outcomes in Patients Undergoing Conversion of Insulin Glargine to Insulin Detemir
Authors: Bryant Ginelle A. , McDanel Deanna L. , Horner Kathleen E. , Farris Karen B. , Newkirk Erin N.
Published: January 2013

Study Objectives

To evaluate the dose and frequency of insulin detemir for patients with diabetes mellitus undergoing conversion from insulin glargine to insulin detemir, and to assess glycemic control, weight gain, and risk of hypoglycemia after converting to insulin detemir.

Design

Retrospective medical record review.

Setting

Large academic medical center.

Patients

Thirty‐one patients with type 1 (10 patients) or type 2 (21 patients) diabetes who were converted from insulin glargine to insulin detemir by usual practice between January 1, 2006, and March 3, 2007, after an Iowa Medicaid formulary switch.

Measurement and Main Results

Data were collected for 12 months after conversion from insulin glargine to insulin detemir. No significant change in mean basal insulin dose was noted in patients with type 1 diabetes at the end of 12 months (insulin detemir 31.1 units/day vs baseline insulin glargine 32.0 units/day, p=0.89; insulin detemir 0.41 unit/kg/day vs baseline insulin glargine 0.42 unit/kg/day, p=0.91). In patients with type 2 diabetes, however, the mean basal insulin dose was significantly higher with insulin detemir compared with baseline insulin glargine (74.2 vs 55.8 units/day, p=0.002; 0.68 vs 0.48 unit/kg/day, p=0.001) at the end of 12 months. Twice‐daily administration was required in a higher proportion of patients receiving insulin detemir (15 patients [48%]) at 12 months compared with insulin glargine (4 patients [13%]) at baseline (p=0.043). A significant change in hemoglobin A1c was not observed in patients with type 1 diabetes (9.7% with insulin detemir vs 9.3% with insulin glargine, p=0.41) or type 2 diabetes (9.4% with insulin detemir vs 9.7% with insulin glargine at baseline, p=0.57) despite the use of higher insulin detemir doses in patients with type 2 diabetes. No significant differences in weight or frequency of hypoglycemia were noted.

Conclusion

Treatment with insulin detemir appears to require more frequent administration and higher insulin doses compared with insulin glargine in patients with type 2 diabetes, with 33% higher doses, on average, observed in this study. These findings suggest that a unit‐for‐unit conversion from insulin glargine to insulin detemir, as suggested by the manufacturer of insulin detemir, may not be adequate in patients with type 2 diabetes.
In situ Cu(0)‐mediated single electron transfer living radical polymerization of methyl methacrylate using nickel powder
Authors: Liu Xiao‐Hui , Yu Yun‐Hai , Jia Di , Cheng Bo‐Wen , Zhang Fei‐Jun , Li Hui‐Na , Chen Peng , Xie Shan
Published: January 2013

Single electron transfer living radical polymerization of methyl methacrylate catalyzed by the in situ prepared Cu(0) at ambient temperature was first examined using various metallic powders, including Zn(0), Ni(0), Mg(0), and Fe(0). Importantly, the polymerization initiated with Ni(0)/EBiB/CuBr2/PMDETA system exhibited optimal living/controlled nature and generated polymers with polydispersity index as low as 1.04 for 75.27% conversion and controlled molecular weights close to theoretical ones. A wide of range of Cu(II) salts were also investigated as catalyst sources instead of CuBr2. The recycling of Ni(0) was very convenient due to its magnetic property, which enables its extensive application. © 2013 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013
Meta‐analysis of randomised trials with a continuous outcome according to baseline imbalance and availability of individual participant data
Authors: Riley Richard D. , Kauser Iram , Bland Martin , Thijs Lutgarde , Staessen Jan A. , Wang Jiguang , Gueyffier Francois , Deeks Jonathan J.
Published: January 2013

We describe methods for meta‐analysis of randomised trials where a continuous outcome is of interest, such as blood pressure, recorded at both baseline (pre treatment) and follow‐up (post treatment). We used four examples for illustration, covering situations with and without individual participant data (IPD) and with and without baseline imbalance between treatment groups in each trial.

Given IPD, meta‐analysts can choose to synthesise treatment effect estimates derived using analysis of covariance (ANCOVA), a regression of just final scores, or a regression of the change scores. When there is baseline balance in each trial, treatment effect estimates derived using ANCOVA are more precise and thus preferred. However, we show that meta‐analysis results for the summary treatment effect are similar regardless of the approach taken. Thus, without IPD, if trials are balanced, reviewers can happily utilise treatment effect estimates derived from any of the approaches.

However, when some trials have baseline imbalance, meta‐analysts should use treatment effect estimates derived from ANCOVA, as this adjusts for imbalance and accounts for the correlation between baseline and follow‐up; we show that the other approaches can give substantially different meta‐analysis results. Without IPD and with unavailable ANCOVA estimates, reviewers should limit meta‐analyses to those trials with baseline balance. Trowman's method to adjust for baseline imbalance without IPD performs poorly in our examples and so is not recommended.

Finally, we extend the ANCOVA model to estimate the interaction between treatment effect and baseline values and compare options for estimating this interaction given only aggregate data. Copyright © 2013 John Wiley & Sons, Ltd.
Multistage Vectored siRNA Targeting Ataxia‐Telangiectasia Mutated for Breast Cancer Therapy
Authors: Xu Rong , Huang Yi , Mai Junhua , Zhang Guodong , Guo Xiaojing , Xia Xiaojun , Koay Eugene J. , Qin Guoting , Erm Donald R. , Li Qingpo , Liu Xuewu , Ferrari Mauro , Shen Haifa
Published: January 2013

The ataxia‐telangiectasia mutated (ATM) protein plays a central role in DNA damage response and cell cycle checkpoints, and may be a promising target for cancer therapy if normal tissue toxicity could be avoided. The strategy presented here to target ATM for breast cancer therapy involves the use of liposomal‐encapsulated, gene‐specific ATM siRNA delivered with a well‐characterized porous silicon‐based multistage vector (MSV) delivery system (MSV/ATM). Biweekly treatment of MSV/ATM suppressed ATM expression in tumor tissues, and consequently inhibited growth of MDA‐MB‐231 orthotopic tumor in nude mice. At the therapeutic dosage, neither free liposomal ATM siRNA nor MSV/ATM triggered an acute immune response in BALB/c mice, including changes in serum cytokines, chemokines or colony‐stimulating factors. Weekly treatments of mice with free liposomal ATM siRNA or MSV/ATM for 4 weeks did not cause significant changes in body weight, hematology, blood biochemistry, or major organ histology. These results indicate that MSV/ATM is biocompatible and efficacious in inhibiting tumor growth, and that further preclinical evaluation is warranted for the development of MSV/ATM as a potential therapeutic agent.
Targeted Delivery of siRNA‐Generating DNA Nanocassettes Using Multifunctional Nanoparticles
Authors: Cho Young‐Seok , Lee Gee Young , Sajja Hari Krishna , Qian Weiping , Cao Zehong , He Weiling , Karna Prasanthi , Chen Xiaoyuan , Mao Hui , Wang Y. Andrew , Yang Lily
Published: January 2013

Molecular therapy using a small interfering RNA (siRNA) has shown promise in the development of novel therapeutics. Various formulations have been used for in vivo delivery of siRNAs. However, the stability of short double‐stranded RNA molecules in the blood and efficiency of siRNA delivery into target organs or tissues following systemic administration have been the major issues that limit applications of siRNA in human patients. In this study, multifunctional siRNA delivery nanoparticles are developed that combine imaging capability of nanoparticles with urokinase plasminogen activator receptor‐targeted delivery of siRNA expressing DNA nanocassettes. This theranostic nanoparticle platform consists of a nanoparticle conjugated with targeting ligands and double‐stranded DNA nanocassettes containing a U6 promoter and a shRNA gene for in vivo siRNA expression. Targeted delivery and gene silencing efficiency of firefly luciferase siRNA nanogenerators are demonstrated in tumor cells and in animal tumor models. Delivery of survivin siRNA expressing nanocassettes into tumor cells induces apoptotic cell death and sensitizes cells to chemotherapy drugs. The ability of expression of siRNAs from multiple nanocassettes conjugated to a single nanoparticle following receptor‐mediated internalization should enhance the therapeutic effect of the siRNA‐mediated cancer therapy.
Plasmon‐Mediated Synthesis of Silver Cubes with Unusual Twinning Structures Using Short Wavelength Excitation
Authors: Personick Michelle L. , Langille Mark R. , Zhang Jian , Wu Jinsong , Li Shuyou , Mirkin Chad A.
Published: January 2013

The plasmon‐mediated synthesis of silver nanoparticles is a versatile synthetic method which leverages the localized surface plasmon resonance (LSPR) of nanoscale silver to generate particles with non‐spherical shapes and control over dimensions. Herein, a method is reported for controlling the twinning structure of silver nanoparticles, and consequently their shape, via the plasmon‐mediated synthesis, solely by varying the excitation wavelength between 400, 450, and 500 nm, which modulates the rate of Ag+ reduction. Shorter, higher energy excitation wavelengths lead to faster rates of reaction, which in turn yield structures containing a greater number of twin boundaries. With this method, silver cubes can be synthesized using 450 nm excitation, which represents the first time this shape has been realized by a plasmon‐mediated synthetic approach. In addition, these cubes contain an unusual twinning structure composed of two intersecting twin boundaries or multiple parallel twin boundaries. With respect to their twinning structure, these cubes fall between planar‐twinned and multiply twinned nanoparticles, which are synthesized using 500 and 400 nm excitation, respectively.
Polyethylene Glycol and Polyethylenimine Dual‐Functionalized Nano‐Graphene Oxide for Photothermally Enhanced Gene Delivery
Authors: Feng Liangzhu , Yang Xianzhu , Shi Xiaoze , Tan Xiaofang , Peng Rui , Wang Jun , Liu Zhuang
Published: January 2013

Graphene oxide (GO) has been extensively explored in nanomedicine for its excellent physiochemical, electrical, and optical properties. Here, polyethylene glycol (PEG) and polyethylenimine (PEI) are covalently conjugated to GO via amide bonds, obtaining a physiologically stable dual‐polymer‐functionalized nano‐GO conjugate (NGO‐PEG‐PEI) with ultra‐small size. Compared with free PEI and the GO‐PEI conjugate without PEGylation, NGO‐PEG‐PEI shows superior gene transfection efficiency without serum interference, as well as reduced cytotoxicity. Utilizing the NIR optical absorbance of NGO, the cellular uptake of NGO‐PEG‐PEI is shown to be enhanced under a low power NIR laser irradiation, owing to the mild photothermal heating that increases the cell membrane permeability without significantly damaging cells. As the results, remarkably enhanced plasmid DNA transfection efficiencies induced by the NIR laser are achieved using NGO‐PEG‐PEI as the light‐responsive gene carrier. More importantly, it is shown that our NGO‐PEG‐PEI is able to deliver small interfering RNA (siRNA) into cells under the control of NIR light, resulting in obvious down‐regulation of the target gene, Polo‐like kinase 1 (Plk1), in the presence of laser irradiation. This study is the first to use photothermally enhanced intracellular trafficking of nanocarriers for light‐controllable gene delivery. This work also encourages further explorations of functionalized nano‐GO as a photocontrollable nanovector for combined photothermal and gene therapies.
Hierarchical Metal/Semiconductor Nanostructure for Efficient Water Splitting
Authors: Thiyagarajan Pradheep , Ahn Hyo‐Jin , Lee Jung‐Soo , Yoon Jong‐Chul , Jang Ji‐Hyun
Published: January 2013

A hierarchically patterned metal/semiconductor (gold nanoparticles/ZnO nanowires) nanostructure with maximized photon trapping effects is fabricated via interference lithography (IL) for plasmon enhanced photo‐electrochemical water splitting in the visible region of light. Compared with unpatterned (plain) gold nanoparticles‐coated ZnO NWs (Au NPs/ZnO NWs), the hierarchically patterned Au NPs/ZnO NWs hybrid structures demonstrate higher and wider absorption bands of light leading to increased surface enhanced Raman scattering due to the light trapping effects achieved by the combination of two different nanostructure dimensions; furthermore, pronounced plasmonic enhancement of water splitting is verified in the hierarchically patterned Au NPs/ZnO NWs structures in the visible region. The excellent performance of the hierarchically patterned Au NPs/ZnO NWs indicates that the combination of pre‐determined two different dimensions has great potential for application in solar energy conversion, light emitting diodes, as well as SERS substrates and photoelectrodes for water splitting.
TG13 management bundles for acute cholangitis and cholecystitis
Authors: Okamoto Kohji , Takada Tadahiro , Strasberg Steven M. , Solomkin Joseph S. , Pitt Henry A. , Garden O. James , Büchler Markus W. , Yoshida Masahiro , Miura Fumihiko , Kimura Yasutoshi , Higuchi Ryota , Yamashita Yuichi , Mayumi Toshihiko , Gomi Harumi , Kusachi Shinya , Kiriyama Seiki , Yokoe Masamichi , Lau Wan‐Yee , Kim Myung‐Hwan
Published: January 2013

Bundles that define mandatory items or procedures to be performed in clinical practice have been increasingly used in guidelines in recent years. Observance of bundles enables improvement of the prognosis of target diseases as well as guideline preparation. There were no bundles adopted in the Tokyo Guidelines 2007, but the updated Tokyo Guidelines 2013 (TG13) have adopted this useful tool. Items or procedures strongly recommended in clinical practice have been prepared in the practical guidelines and presented as management bundles. TG13 defined the mandatory items for the management of acute cholangitis and acute cholecystitis. Critical parts of the bundles in TG13 include diagnostic process, severity assessment, transfer of patients if necessary, therapeutic approach, and time course. Their observance should improve the prognosis of acute cholangitis and cholecystitis. When utilizing TG13 management bundles, further clinical research needs to be conducted to evaluate the effectiveness and outcomes of the bundles. It is also expected that the present report will lead to evidence construction and contribute to further updating of the Tokyo Guidelines.
TG13 diagnostic criteria and severity grading of acute cholecystitis (with videos)
Authors: Yokoe Masamichi , Takada Tadahiro , Strasberg Steven M. , Solomkin Joseph S. , Mayumi Toshihiko , Gomi Harumi , Pitt Henry A. , Garden O. James , Kiriyama Seiki , Hata Jiro , Gabata Toshifumi , Yoshida Masahiro , Miura Fumihiko , Okamoto Kohji , Tsuyuguchi Toshio , Itoi Takao , Yamashita Yuichi , Dervenis Christos , Chan Angus C.W. , Lau Wan‐Yee , Supe Avinash N. , Belli Giulio , Hilvano Serafin C. , Liau Kui‐Hin , Kim Myung‐Hwan , Kim Sun‐Whe , Ker Chen‐Guo
Published: January 2013

Since its publication in 2007, the Tokyo Guidelines for the management of acute cholangitis and cholecystitis (TG07) have been widely adopted. The validation of TG07 conducted in terms of clinical practice has shown that the diagnostic criteria for acute cholecystitis are highly reliable but that the definition of definite diagnosis is ambiguous. Discussion by the Tokyo Guidelines Revision Committee concluded that acute cholecystitis should be suspected when Murphy's sign, local inflammatory findings in the gallbladder such as right upper quadrant abdominal pain and tenderness, and fever and systemic inflammatory reaction findings detected by blood tests are present but that definite diagnosis of acute cholecystitis can be made only on the basis of the imaging of ultrasonography, computed tomography or scintigraphy (HIDA scan). These proposed diagnostic criteria provided better specificity and accuracy rates than the TG07 diagnostic criteria. As for the severity assessment criteria in TG07, there is evidence that TG07 resulted in clarification of the concept of severe acute cholecystitis. Furthermore, there is evidence that severity assessment in TG07 has led to a reduction in the mean duration of hospital stay. As for the factors used to establish a moderate grade of acute cholecystitis, such as leukocytosis, ALP, old age, diabetes, being male, and delay in admission, no new strong evidence has been detected indicating that a change in the criteria used in TG07 is needed. Therefore, it was judged that the severity assessment criteria of TG07 could be applied in the updated Tokyo Guidelines (TG13) with minor changes. TG13 presents new standards for the diagnosis, severity grading and management of acute cholecystitis.