bluuebunny/crossref_metadata_2025 huggingface dataset:
A systematic review of the effectiveness of interventions in the management of infection in the diabetic foot
Authors: Peters E. J. G. , Lipsky B. A. , Berendt A. R. , Embil J. M. , Lavery L. A. , Senneville E. , Urbančič‐Rovan V. , Bakker K. , Jeffcoate W. J.
Published: January 2012

The International Working Group on the Diabetic Foot expert panel on infection conducted a systematic review of the published evidence relating to treatment of foot infection in diabetes. Our search of the literature published prior to August 2010 identified 7517 articles, 29 of which fulfilled predefined criteria for detailed data extraction. Four additional eligible papers were identified from other sources. Of the total of 33 studies, 29 were randomized controlled trials, and four were cohort studies.

Among 12 studies comparing different antibiotic regimens in the management of skin and soft‐tissue infection, none reported a better response with any particular regimen. Of seven studies that compared antibiotic regimens in patients with infection involving both soft tissue and bone, one reported a better clinical outcome in those treated with cefoxitin compared with ampicillin/sulbactam, but the others reported no differences between treatment regimens. In two health economic analyses, there was a small saving using one regimen versus another. No published data support the superiority of any particular route of delivery of systemic antibiotics or clarify the optimal duration of antibiotic therapy in either soft‐tissue infection or osteomyelitis. In one non‐randomized cohort study, the outcome of treatment of osteomyelitis was better when the antibiotic choice was based on culture of bone specimens as opposed to wound swabs, but this study was not randomized, and the results may have been affected by confounding factors.

Results from two studies suggested that early surgical intervention was associated with a significant reduction in major amputation, but the methodological quality of both was low. In two studies, the use of superoxidized water was associated with a better outcome than soap or povidone iodine, but both had a high risk of bias. Studies using granulocyte‐colony stimulating factor reported mixed results. There was no improvement in infection outcomes associated with hyperbaric oxygen therapy. No benefit has been reported with any other intervention, and, overall, there are currently no trial data to justify the adoption of any particular therapeutic approach in diabetic patients with infection of either soft tissue or bone of the foot. Copyright © 2012 John Wiley & Sons, Ltd.
A systematic review of the effectiveness of revascularization of the ulcerated foot in patients with diabetes and peripheral arterial disease
Authors: Hinchliffe R. J. , Andros G. , Apelqvist J. , Bakker K. , Fiedrichs S. , Lammer J. , Lepantalo M. , Mills J. L. , Reekers J. , Shearman C. P. , Valk G. , Zierler R. E. , Schaper N. C.
Published: January 2012

In several large recent observational studies, peripheral arterial disease (PAD) was present in up to 50% of the patients with a diabetic foot ulcer and was an independent risk factor for amputation. The International Working Group on the Diabetic Foot therefore established a multidisciplinary working group to evaluate the effectiveness of revascularization of the ulcerated foot in patients with diabetes and PAD. A systematic search was performed for therapies to revascularize the ulcerated foot in patients with diabetes and PAD from 1980–June 2010. Only clinically relevant outcomes were assessed. The research conformed to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines, and the Scottish Intercollegiate Guidelines Network methodological scores were assigned. A total of 49 papers were eligible for full text review. There were no randomized controlled trials, but there were three nonrandomized studies with a control group. The major outcomes following endovascular or open bypass surgery were broadly similar among the studies. Following open surgery, the 1‐year limb salvage rates were a median of 85% (interquartile range of 80–90%), and following endovascular revascularization, these rates were 78% (70.5–85.5%). At 1‐year follow‐up, 60% or more of ulcers had healed following revascularization with either open bypass surgery or endovascular revascularization. Studies appeared to demonstrate improved rates of limb salvage associated with revascularization compared with the results of medically treated patients in the literature. There were insufficient data to recommend one method of revascularization over another. There is a real need for standardized reporting of baseline demographic data, severity of disease and outcome reporting in this group of patients. Copyright © 2012 John Wiley & Sons, Ltd.
The development of global consensus guidelines on the management and prevention of the diabetic foot 2011
Authors: Bakker K. , Schaper N. C. ,   on behalf of the International Working Group on the Diabetic Foot Editorial Board
Published: January 2012

Diabetic foot ulcers are the source of major suffering and very large costs for both the patient and the health‐care system, and every 30 s, a leg is lost somewhere in the world. Investing in a diabetic foot care guideline can therefore be one of the most cost‐effective forms of health‐care expenditure, provided the guideline is goal focused and properly implemented. The objective of the International Working Group on the Diabetic Foot (IWGDF) is to develop guidelines that will reduce the effect of diabetic foot disease through cost‐effective and quality health care, based on the principles of evidence‐based medicine. These guidelines are produced by working groups of experts in the field and are endorsed by the more than 100 country representatives of the IWGDF. In 2009, the IWGDF invited again three working groups to write consensus guidelines on peripheral arterial disease, infection, and wound healing. New texts were produced according to a systematic review of the literature in order to inform protocols for routine care and to highlight areas that should be considered for further study. During a meeting of the members of the IWGDF in May 2011, the new set of guidelines was approved and is published in this journal. Copyright © 2012 John Wiley & Sons, Ltd.
Diagnosis and treatment of peripheral arterial disease in diabetic patients with a foot ulcer. A progress report of the International Working Group on the Diabetic Foot
Authors: Schaper N. C. , Andros G. , Apelqvist J. , Bakker K. , Lammer J. , Lepantalo M. , Mills J. L. , Reekers J. , Shearman C. P. , Zierler R. E. , Hinchliffe R. J.
Published: January 2012

The International Working Group on the Diabetic Foot (IWDGF) has produced in 2011 a guideline on the diagnosis and treatment of peripheral arterial disease in patients with diabetes and a foot ulcer. This document, together with a systematic review that provided the background information on management, was produced by a multidisciplinary working group of experts in the field and was endorsed by the IWDGF. This progress report is based on these two documents and earlier consensus texts of the IWDGF on the diagnosis and management of diabetic foot ulcers. Its aim is to give the clinician clear guidance on when and how to diagnose peripheral arterial disease in patients with diabetes and a foot ulcer and when and which treatment modalities should be considered, taking both risks and benefits into account. Copyright © 2012 John Wiley & Sons, Ltd.
Hyperbaric oxygen therapy as treatment of diabetic foot ulcers
Authors: Löndahl Magnus
Published: January 2012

Hyperbaric oxygen therapy (HBO) could be described as a short‐term, high‐dose oxygen inhalation and diffusion therapy, delivered systemically through airways and blood, achieved by having the patient breathing concentrated oxygen at a pressure higher than 1 absolute atmosphere. In clinical practice, monoplace or multiplace hyperbaric chambers are used to achieve this. Treatment is usually given as daily 90‐ to 120‐min‐long HBO sessions at pressures between 2.0 and 2.5 absolute atmosphere, aiming for 30–40 treatment sessions.

The use of HBO as treatment of diabetic foot ulcers has been founded on weak scientific ground, although the outcomes from previous studies are in concert with the conclusions from preclinical studies and supports the theoretical framework of HBO reversing hypoxia‐induced pathology. Two well‐designed randomized double‐blind trials have put HBO on firmer ground and may justify adjunctive HBO treatment to a selected group of patients with nonhealing diabetic foot ulcers.

Some health economic studies suggest potential cost effectiveness, but these studies are limited by deficient primary clinical data and should be interpreted with caution.

Several issues remain to be addressed, such as developing robust criteria to improve treatment protocols, determining which patients are likely to benefit, and when to start and stop treatment. Copyright © 2012 John Wiley & Sons, Ltd.
The ulcerated leg: when to revascularize
Authors: Apelqvist J. A. P. , Lepäntalo M. J. A.
Published: January 2012

The role of peripheral arterial disease in ulcerated diabetic feet has long been underestimated. Progressive claudication, rest pain and the extent of irreversible tissue loss have frequently been indications for revascularization for neuroischaemic ulcers in diabetic patients. These typical ischaemic symptoms are warning signs that are less frequent in diabetic individuals with ischaemia than those without diabetes. Consequently, 30–50% of individuals with diabetes and foot ulcers already have gangrene at admission and are therefore often considered unsuitable for revascularization. Furthermore, the healing of a neuroischaemic ulcer is worsened by microvascular dysfunction, causing arteriovenous shunting, capillary ischaemia, leakage and venous pooling. Therefore, the threshold of revascularizing neuroischaemic ulcers should be lower than that of purely ischaemic ulcers. Comorbidity, ulcer characteristics and infection affect the decision as to when to intervene, as do the severity and extent of occlusive arterial lesions. The window of opportunity for vascular intervention in the neuroischaemic diabetic foot should not be missed, and the need for early vascular intervention as an integrated part of a strategy to achieve healing should be emphasized. Noninvasive vascular testing should be performed on all individuals with an ulcerated diabetic foot. The arterial tree should be imaged if noninvasive tests indicate ischaemia or when mild or questionable ischaemia is diagnosed and conservative treatment does not promote ulcer healing in 6 weeks. Revascularization should be performed whenever feasible to repair distal perfusion to achieve ulcer healing. Copyright © 2012 John Wiley & Sons, Ltd.
Lessons from Eurodiale
Authors: Schaper N. C.
Published: January 2012

The European Study Group on Diabetes and the Lower Extremity is a collaborative, multi‐disciplinary network of 14 centres from ten countries. In 2003–2004, all patients treated in the participating centres because of a new diabetic foot ulcer (n = 1232) were included in a prospective observational study. Subjects attended follow‐up visits on a monthly basis until final outcome: healing of the foot, lower‐leg amputation, death or non‐healing after 1 year. During all visits, data were recorded on standardized case record forms by investigators who were trained during several plenary meetings and on‐site visits. Unique aspects of the study were its size, the pan‐European scope and the integrated/holistic approach for a multi‐organ disease. In this review, the main findings of the study and its implications for diabetic foot care are discussed. Copyright © 2012 John Wiley & Sons, Ltd.
Neogenin regulates sonic hedgehog pathway activity during digit patterning
Authors: Hong Mingi , Schachter Karen A. , Jiang Guoying , Krauss Robert S.
Published: January 2012

Background: Digit patterning integrates signaling by the Sonic Hedgehog (SHH), fibroblast growth factor (FGF), and bone morphogenetic protein (BMP) pathways. GLI3, a component of the SHH pathway, is a major regulator of digit number and identity. Neogenin (encoded by Neo1) is a cell surface protein that serves to transduce signals from several ligands, including BMPs, in various developmental contexts. Although neogenin is implicated in BMP signaling, it has not been linked to SHH signaling and its role in digit patterning is unknown. Results: We report that Neo1 mutant mice have preaxial polydactyly with low penetrance. Expression of SHH target genes, but not BMP target genes, is altered in Neo1 mutant limb buds. Analysis of mice carrying mutations in both Neo1 and Gli3 reveals that, although neogenin plays a role in constraint of digit numbers, suppressing polydactyly, it is also required for the severe polydactyly caused by loss of GLI3. Furthermore, embryo fibroblasts from Neo1 mutant mice are sensitized to SHH pathway activation in vitro. Conclusions: Our findings indicate that neogenin regulates SHH signaling in the limb bud to achieve proper digit patterning. Developmental Dynamics 241:627–637, 2012. © 2012 Wiley Periodicals Inc.
Accuracy of self‐reported energy intake in weight‐restored patients with anorexia nervosa compared with obese and normal weight individuals
Authors: Schebendach Janet E. , Porter Kathleen J. , Wolper Carla , Walsh B. Timothy , Mayer Laurel E.S.
Published: January 2012

Objective:

To compare self‐reported and measured energy intake in weight‐restored patients with anorexia nervosa (AN), weight‐stable obese individuals (OB), and normal weight controls (NC).

Method:

Forty participants (18 AN, 10 OB, and 12 NC) in a laboratory meal study simultaneously completed a prospective food record.

Results:

AN patients significantly (p = .018) over‐reported energy intake (16%, 50 kcal) and Bland‐Altman (B‐A) analysis indicated bias toward over‐reporting at increasing levels of intake. OB participants significantly (p = .016) under‐reported intake (19%, 160 kcal) and B‐A analysis indicated bias toward under‐reporting at increasing levels of intake. In NC participants, NS (p = .752) difference between reported and measured intake was found and B‐A analysis indicated good agreement between methods at all intake levels.

Discussion:

Self‐reported intake should be cautiously interpreted in AN and OB. Future studies are warranted to determine if over‐reporting is related to poor outcome and relapse in AN, or under‐reporting interferes with weight loss efforts in OB. © 2012 by Wiley Periodicals, Inc. (Int J Eat Disord 2012)
Association between the serotonin transporter triallelic genotype and eating problems is moderated by the experience of childhood trauma in women
Authors: Stoltenberg Scott F. , Anderson Cynthia , Nag Parthasarathi , Anagnopoulos Cheryl
Published: January 2012

Objective:

This study investigated a potential interaction between the triallelic polymorphism of the serotonin transporter gene (SLC6A4) promoter and the experience of childhood trauma on the number of problem eating behaviors.

Method:

The study sample was comprised of 439 (64.7% female) Caucasian college students (mean age = 22.49, SD = 6.12). Participants completed questionnaires that assessed eating problems and experience of trauma in childhood (ages 0–12) and donated cheek cells for 5‐HTTLPR and rs25531 genotyping.

Results:

Women carrying a lower expressing allele (i.e., LG or S) who were exposed to higher levels of childhood trauma reported significantly higher mean numbers of eating problems (gender × genotype × trauma interaction, p = .006).

Discussion:

These results are consistent with findings that the lower expressing alleles of the SLC6A4 promoter are associated with increased sensitivity to the negative impact of childhood stressors on adult behavioral outcomes. © 2012 by Wiley Periodicals, Inc. (Int J Eat Disord 2012)
Minimizing and treating chronicity in the eating disorders: A clinical overview
Authors: Wonderlich Stephen , Mitchell James E. , Crosby Ross D. , Myers Tricia Cook , Kadlec Kelly , LaHaise Kim , Swan‐Kremeier Lorraine , Dokken Julie , Lange Marnie , Dinkel Janna , Jorgensen Michelle , Schander Linda
Published: January 2012

Objective:

The purpose of this article is to review the available literature regarding treatment and management of eating disorder patients who fail to change over protracted periods of time.

Method:

Literature was reviewed pertaining to approaches to promoting change in treatment‐resistant cases and the treatment of chronic eating disordered individuals.

Results:

Although there are a number of clinical perspectives on the treatment of chronic eating disorder patients, fundamental studies defining the concept of “chronicity” and standardized treatment approaches do not exist. Empirical studies of chronic cases are needed, given the absence of investigation of maintenance factors in chronic eating disorders and evidence‐based approaches for treatment. An integrative and practical clinical protocol is provided.

Discussion:

The results of this review suggest that a significant number of eating disorder patients display a chronic course, which is poorly understood. Treatments for these individuals are not based on evidence‐based findings. © 2012 by Wiley Periodicals, Inc. (Int J Eat Disord 2012)
Color feature extraction of regions by means of GA for scenery image retrieval
Authors: Mitsukura Yasue , Sakamoto Koji , Fukai Hironobu , Yoshimori Seiki , Ito Seiji , Fukumi Minoru
Published: January 2012

Keyword image retrieval is now widely studied. By using such technologies, we can obtain images with the corresponding keywords easily. In the case of conventional image search systems, we basically search according to file names. However, the file names given are frequently incorrect. To resolve this problem, we propose an automatic keyword addition method for scenery images. In this paper, there are two important points. One is the image segmentation method using the maximum distance algorithm (MDA). The other is automatic keyword addition using the color features of regions. In the image segmentation method, we propose an automatic decision method for the parameters of the MDA. For this purpose, we investigate the relation between the optimal parameters and the features of regions. For the color feature extraction of regions, we propose a genetic algorithm (GA). Moreover, in order to show the effectiveness of the proposed method, we provide simulation examples. The results of simulations demonstrate the effectiveness of keyword addition for scenery images. © 2012 Wiley Periodicals, Inc. Electron Comm Jpn, 95(2): 39–49, 2012; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/ecj.10364
A method for cooperation support between discussion space and activity space in collaborative learning and its experimental evaluation
Authors: Tilwaldi Dilmurat , Kaneko Shigeto , Hosomura Tsukasa , Dasai Takashi , Mitsui Hiroyasu , Koizumi Hisao
Published: January 2012

This paper describes a prototype and the experimental evaluation of a chat system that offers cooperation support between a discussion space and an activity space in collaborative learning. In collaborative learning in the proposed system, the students are divided into groups, carry out discussions on a study topic through chats, and create online reports in a cooperative manner. The proposed cooperation support method aims at improving the level of cooperation among students and the effectiveness of learning by making group members aware of other members' learning circumstances through cooperation support in group member utterances and report creation. We use a Wiki as a tool for collaborative work in this research. Cooperation support displays the Wiki's update time and contents on the chat system with activity cooperation support, offering a space for distance collaborative learning and allowing each student to become aware of the other students' situations. In addition, the number of chat utterances is displayed, and other students' situation is easily grasped. © 2012 Wiley Periodicals, Inc. Electron Comm Jpn, 95(2): 25–38, 2012; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/ecj.10366
Genetic algorithm sampling the solution space selectively depending on difficulty of power distribution network restoration
Authors: Kato Yoshifumi , Hamagami Tomoki
Published: January 2012

A new genetic algorithm for a multiagent‐based autonomous power distribution network restoration system is proposed. The state of the art of this study is to realize a new genetic algorithm using selective sampling for improving the restoration performance. The proposed method realizes the selective sampling by a virtual accident selecting algorithm that changes the probability of selecting the virtual accident area. The virtual accident selecting algorithm consists of a weight table and an area‐value list. The weight table represents the difficulty of restoration in each accident area. The area‐value list represents the difficulty of restoration in the latest generation, and affects the weight table in the next generation. This architecture enables the system to alter the probability of changing each virtual accident area autonomously from restoration simulation. The simulation results show that the proposed method is capable of improving performance. © 2012 Wiley Periodicals, Inc. Electron Comm Jpn, 95(2): 16–24, 2012; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/ecj.10389
Improvement of accuracy of the measurement of electric field distributions using the Kerr electrooptic effect and computed tomography
Authors: Masuichi Naoya , Fujii Masaharu , Ihori Haruo
Published: January 2012

Computed tomography (CT) has been used for industrial application as well as its principal development in the medical field. We have investigated the measurement of nonuniform electric field vector distributions in liquid dielectrics using an original method based on the electrooptic Kerr effect and the CT method. In applying the CT method to the reconstruction of the electric field, a principle of the CT method has been faithfully observed, which has been one cause of error. Specifically, the region passed through by the light in the measurements was not equal to the reconstructed region and the electric field was reconstructed without consideration of the value of cells outside the region for reconstruction. To solve these problems, we suggest an improved algorithm for reconstruction using the concepts which we called “actual region projection data” and “extension of region for reconstruction.” Simulations and experiments were used to investigate the usefulness of the improved method. © 2012 Wiley Periodicals, Inc. Electron Comm Jpn, 95(2): 8–15, 2012; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/ecj.10404
Speed control of general‐purpose engine with electronic governor
Authors: Sawut Umerujan , Tohti Gheyret , Takigawa Buso , Tsuji Teruo
Published: January 2012

This paper presents a general‐purpose engine speed control system with an electronic governor in order to improve the current system with a mechanical governor, which shows unstable characteristics as a result of a change in mechanical friction or the A/F ratio (air–fuel ratio). The control system above has the problems that the feedback signal is only the crank angle because of cost, and the controlled object is a general‐purpose engine, which is strongly nonlinear. In order to overcome these problems, a system model is presented for dynamic estimation of the amount of air flow, and a robust controller is designed. In concrete terms, the proposed system includes a robust sliding‐mode controller using the feedback signal of only the crank angle, with a genetic algorithm applied to the controller design. Simulations and experiments performed using Matlab/Simulink show the effectiveness of our proposal. © 2012 Wiley Periodicals, Inc. Electr Eng Jpn, 179(2): 64–71, 2012; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/eej.21130
First plasma experiment on spherical tokamak device UTST
Authors: Imazawa Ryota , Nakagawa Makoto , Kamio Shuji , Hihara Ryuma , Yamada Takuma , Inomoto Michiaki , Takase Yuichi , Ono Yasushi
Published: January 2012

The UTST (University of Tokyo Spherical Tokamak) device was constructed for the purpose of exploring the formation of ultrahigh‐beta ST (spherical tokamak) plasma using the double null plasma merging method. When two plasmas merge together to form a single plasma, magnetic field lines reconnect, and magnetic field energy is converted to plasma kinetic energy, increasing the plasma beta. Merging start‐up has been demonstrated in the TS‐3/4, START, and MAST devices using coils inside the vacuum vessel, and the TS‐3 plasma obtained a 50% beta. In order to demonstrate start‐up in a more reactor‐relevant situation, UTST has all poloidal field (PF) coils outside the vacuum vessel. The first plasma experiment on the UTST was begun in December 2007. In the results, the plasma obtained 10 kA by using only the outer PF coils and a single ST was generated in the lower area (z = –0.3 to –1.0 m) close to a washer gun. This result suggests that another washer gun on the top of the UTST can allow the generation of ST in the upper area and merging start‐up by using outer PF coils. © 2012 Wiley Periodicals, Inc. Electr Eng Jpn, 179(2): 20–26, 2012; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/eej.21216
Effect of heat treatment on tolerance characteristic for electrical degradation of ZnO varistors with added Sb2O3
Authors: Takada Masayuki , Sato Yuuki , Yoshikado Shinzo
Published: January 2012

The effects of the heat treatment of ZnO varistors with added Bi‐Mn‐Co‐Sb on their electrical degradation were investigated. Before heat treatment, the degree of the tolerance characteristics of varistors for electrical degradation was smallest for the sample with 0.12 mole‐% of added Sb2O3. After heat treatment, the electrical degradation tolerance characteristic was markedly improved. It was found that the tolerance characteristics for electrical degradation after heat treatment strongly depend on the amount of added Sb2O3. For the samples with added Sb2O3, the tolerance characteristic for electrical degradation upon heat treatment is not affected by the intensity of the X‐ray diffraction peak of the (004) plane for ZnO. For samples with 0.12 mole‐% or less of added Sb2O3, the value of the nonlinearity index α of the voltage–current (V–I) characteristic after electrical degradation was proportional to the full width at half maximum (FWHM) of the X‐ray diffraction peak at 29.4° for Zn2.33Sb0.67O4 spinel particles in samples subjected to heat treatment under various conditions. Therefore, it is speculated that the increase in the FWHM for the spinel particles is due to the existence of fine spinel particles at grain boundaries or triple points of ZnO grains. Furthermore, it is speculated that the improvement of the electrical degradation tolerance characteristics is due to a decrease in the ion mobility of O2– ions or Zn2+ ions due to their blocking by uniformly dispersed fine spinel particles at grain boundaries. © 2012 Wiley Periodicals, Inc. Electr Eng Jpn, 179(2): 1–10, 2012; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/eej.21229
A method for determining pseudo‐measurement state values for topology observability of state estimation in power systems
Authors: Urano Shoichi , Mori Hiroyuki
Published: January 2012

This paper proposes a new technique for determining state values in power systems. Recently, it has been useful for carrying out state estimation with PMU (Phasor Measurement Unit) data. The authors have developed a method for determining state values with an artificial neural network (ANN) considering topology observability in power systems. The ANN has the advantage of approximating nonlinear functions with high precision. The method evaluates pseudo‐measurement state values of data which are lost in power systems. The method has been successfully applied to the IEEE 14‐bus system. © 2012 Wiley Periodicals, Inc. Electr Eng Jpn, 179(2): 27–34, 2012; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/eej.21235
The Nature of Spin Crossover and Coordination Core Distortion in a Family of Binuclear Iron(II) Complexes with Bipyridyl‐Like Bridging Ligands
Authors: Matouzenko Galina S. , Jeanneau Erwann , Verat Alexander Yu. , de Gaetano Yannick
Published: January 2012

The synthesis and characterization of two new binuclear compounds [{Fe(dpia)(NCS)2}2(bpac)]·nCH3OH [n = 0 (1) and 2 (2), dpia = bis(2‐picolyl)amine, bpac = 1,2‐bis(4‐pyridyl)ethyne] are reported. The magnetic susceptibility measurements of the compounds revealed different types of magnetic behavior. Complex 1 displays a two‐step spin crossover (SCO) that suggests the occurrence of a mixed [HS–LS] (HS = high spin, LS = low spin) pair at the plateau temperature (145 K), at which about 50 % of the complexes undergo a thermal spin conversion. The high‐temperature step is very gradual, whereas the low‐temperature step shows a first‐order spin transition with a hysteresis width equal to 17 K. Compound 2 manifests a relatively abrupt one‐step spin change with a narrow hysteresis of 4 K. The single‐crystal X‐ray structure of 1 was solved for the [HS–HS] complex at room temperature. Compound 2 was structurally characterized in both [HS–HS] and [LS–LS] spin states at 290 and 110 K. The magnetic and structural characteristics of 1 and 2 were compared with previously reported related binuclear compounds with 4,4′‐bipyridine and 1,2‐bis(4‐pyridyl)ethene spacer ligands. This analysis confirms a recently proposed idea about the key role of the [FeN6] core structural distortions, which are caused by crystal packing and strain effects of terminal and/or bridging ligands, in the spin‐crossover behavior of binuclear complexes. This study also revealed the predominant role of inter‐ vs. intramolecular interactions in the spin transition cooperativity.
Fish oil sensory properties can be predicted using key oxidative volatiles
Authors: Sullivan Jenna C. , Budge Suzanne M.
Published: January 2012

The high level of PUFA in fish oil, primarily eicosapentaenoic acid (EPA) and DHA result in rapid oxidation of the oil. Current methods used to assess oxidation have little correlation with sensory properties of fish oils. Here we describe an alternative method using solid phase microextraction (SPME) combined with GC‐MS to monitor volatile oxidation products. Stepwise discriminant function analysis (DFA) was used to classify oils characterized as acceptable or unacceptable based on sensory analysis; a cross‐validated success rate of 100% was achieved with the function. The classification function was also successfully validated with tasted samples that were not used to create the method. A total of 14 variables, primarily aldehydes and ketones, were identified as significant discriminators in the classification function. This method will be useful as a quality control method for fish oil manufacturers.

Practical applications: This paper describes an analytical method that can be used by fish oil manufacturers for quality control purposes. Solid phase microextraction and GC‐MS were used to monitor volatile oxidation products in fish oil. These data, combined with results of analyses by a sensory panel, were used to create a function that classified fish oil samples as acceptable or unacceptable. The volatile oxidation products used to in the function were primarily aldehydes and ketones. This method can be used by fish oil manufacturers as an alternative to expensive sensory panels.
A Spot of Turbulence
Authors: Czarske Jürgen W.
Published: January 2012

Measuring technique: An innovative technique enables non‐intrusive, high‐precision measurements of microscopic and macroscopic fluid flows. The laser Doppler velocity profile sensor has huge potential for applications in science and technology.
What Causes Itching Sensations?
Authors: Novak Natalija
Published: January 2012

Neurodermatitis is one of the most common and agonising skin diseases. The emergence and course of this chronic disease are affected by a number of factors. Molecular mechanisms that interlock like the pieces of a jigsaw puzzle are of particular importance.
A Confident Look Beyond
Authors: Kleiner Matthias
Published: January 2012

The finale of the Excellence Initiative has just begun — yet the scientific community must already contemplate the future of top‐level research funding. We need productive and constructive dialogue with policymakers. The key issues are obvious.
The Turtle Code
Authors: Unterstell Rembert
Published: January 2012

When the specific illuminates the general: Palaeontologist Walter Joyce uses spectacular finds to look deep into the history of evolution and the Earth / From Yale to Tübingen
Empire of the Ibex
Authors: Klimscha Florian , Siegel Ulrike , Eichmann Ricardo , Schmidt Klaus
Published: January 2012

Far from the well‐known excavation sites in Egypt and Mesopotamia, an international team of archaeologists are excavating the remains of a Chalcolithic settlement in Jordan at Tall Hujayr al‐Ghuzlan near modern Aqaba. Their finds are full of surprises — they demonstrate how social and technological innovations radiated out from the centres to the periphery.
Microglia are required for astroglial toll‐like receptor 4 response and for optimal TLR2 and TLR3 response
Authors: Holm Thomas H. , Draeby Dina , Owens Trevor
Published: January 2012

Within the central nervous system, astrocytes and microglia are the primary responders to endogenous ligands released upon injury and stress, as well as to infectious pathogens. Toll‐like receptors (TLRs) are implicated in recognition of both types of stimulus. Whether astrocytes respond as strongly as microglia to TLR agonists remains contentious. In this study, we have rigorously purified astrocytes to determine their capacity for autonomous TLR response, in absence of microglia. We used flow cytometry and differential adhesion as well as a myeloid lineage‐specific suicide gene to purify astrocytes from mixed glial cultures and measured their response to TLR agonists. Our results show that the response of astrocytes to TLR2 and TLR3 agonists is greatly enhanced by, and response to TLR4 agonists is completely dependent on, the presence of functional microglia. In the case of the TLR4 response to lipopolysaccharide, microglia exert their effect on astrocytes at least partially through release of soluble mediators that directly activate or facilitate astrocyte responses. Our findings underline the contribution of glial crosstalk in CNS responses to injury or inflammation. © 2012 Wiley Periodicals, Inc.
Nonalcoholic fatty liver disease is associated with coronary artery calcification
Authors: Kim Donghee , Choi Su-Yeon , Park Eun Ha , Lee Whal , Kang Jin Hwa , Kim Won , Kim Yoon Jun , Yoon Jung-Hwan , Jeong Sook Hyang , Lee Dong Ho , Lee Hyo-suk , Larson Joseph , Therneau Terry M. , Kim Ray W.
Published: January 2012

Nonalcoholic fatty liver disease (NAFLD) is related to risk factors of coronary artery disease, such as dyslipidemia, diabetes, and metabolic syndrome, which are closely linked with visceral adiposity. The aim of this study was to investigate whether NAFLD was associated with coronary artery calcification (CAC), which is used as a surrogate marker for coronary atherosclerosis independent of computed tomography (CT)-measured visceral adiposity. Out of 5,648 subjects who visited one of our health screening centers between 2003 and 2008, we enrolled 4,023 subjects (mean age, 56.9 ± 9.4 years; 60.7% males) without known liver disease or a history of ischemic heart disease. CAC score was evaluated using the Agatston method. On univariate analysis, the presence of CAC (score >0) was significantly associated with age, sex, body mass index, aspartate aminotransferase, alanine aminotransferase, high-density lipoprotein cholesterol, triglycerides, and increased risk of diabetes, hypertension, smoking, and NAFLD. Increasing CAC scores (0, <10, 10-100, ≥100) were associated with higher prevalence of NAFLD (odds ratio [OR], 1.84; 95% confidence interval [CI], 1.61-2.10;

P

<0.001). Multivariable ordinal regression analysis was adjusted for traditional risk factors, and CT-measured visceral adipose tissue area in a subgroup of subjects showed that the increased CAC scores were significantly associated with the presence of NAFLD (OR, 1.28, 95% CI, 1.04-1.59;

P

= 0.023) independent of visceral adiposity.

Conclusion:

Patients with NAFLD are at increased risk for coronary atherosclerosis independent of classical coronary risk factors, including visceral adiposity. These data suggest that NAFLD might be an independent risk factor for coronary artery disease. (HEPATOLOGY 2012)
Transcriptional regulation of methionine adenosyltransferase 2A by peroxisome proliferator-activated receptors in rat hepatic stellate cells
Authors: Ramani Komal , Tomasi Maria Lauda
Published: January 2012

Methionine adenosyltransferases (MATs) are critical enzymes that catalyze the formation of the methyl donor

S
-adenosyl methionine (SAM). The MAT2A gene, which encodes the catalytic subunit α2, is induced in dedifferentiated liver. We previously demonstrated that MAT2A expression is enhanced in activated hepatic stellate cells (HSCs) and that silencing this gene reduces HSC activation. In this study, we examined the molecular mechanisms responsible for the transcriptional regulation of the MAT2A gene in HSCs. We identified peroxisome proliferator-activated receptor (PPAR) response elements (PPREs) in the rat MAT2A promoter. The PPARγ agonist rosiglitazone (RSG) promoted quiescence in the activated rat HSC cell line (BSC) or culture-activated primary rat HSCs, decreased MAT2A expression and promoter activity, and enhanced PPARγ binding to MAT2A PPREs.

In vivo

HSC activation in bile duct–ligated rats lowered PPARγ interaction with MAT2A PPREs. Silencing PPARγ increased MAT2A transcription, whereas overexpressing it had the opposite effect, demonstrating that PPARγ negatively controls this gene. Site-directed mutagenesis of PPREs abolished PPARγ recruitment to the MAT2A promoter and its inhibitory effect on MAT2A transcription in quiescent HSCs. PPRE mutations decreased the basal promoter activity of MAT2A in activated HSCs independent of PPARγ, indicating that other factors might be involved in PPRE interaction. We identified PPARβ binding to wild-type but not to mutated PPREs in activated cells. Furthermore, silencing PPARβ inhibited MAT2A expression and promoter activity. Forced expression of MAT2A in RSG-treated HSCs lowered PPARγ and enhanced PPARβ expression, thereby promoting an activated phenotype.

Conclusion:

We identified PPARγ as a negative regulator of MAT2A in quiescent HSCs. A switch from quiescence to activation abolishes this control and allows PPARβ to up-regulate MAT2A transcription.
Histological diversity in cholangiocellular carcinoma reflects the different cholangiocyte phenotypes
Authors: Komuta Mina , Govaere Olivier , Vandecaveye Vincent , Akiba Jun , Van Steenbergen Werner , Verslype Chris , Laleman Wim , Pirenne Jacques , Aerts Raymond , Yano Hirohisa , Nevens Frederik , Topal Baki , Roskams Tania
Published: January 2012

Cholangiocellular carcinoma (CC) originates from topographically heterogeneous cholangiocytes. The cylindrical mucin-producing cholangiocytes are located in large bile ducts and the cuboidal non–mucin-producing cholangiocytes are located in ductules containing bipotential hepatic progenitor cells (HPCs). We investigated the clinicopathological and molecular features of 85 resected CCs (14 hilar CCs [so-called Klatskin tumor], 71 intrahepatic CCs [ICCs] including 20 cholangiolocellular carcinomas [CLCs], which are thought to originate from HPCs]) and compared these with the different cholangiocyte phenotypes, including HPCs. Immunohistochemistry was performed with biliary/HPC and hepatocytic markers. Gene expression profiling was performed in different tumors and compared with nonneoplastic different cholangiocyte phenotypes obtained by laser microdissection. Invasion and cell proliferation assay were assessed using different types of CC cell lines: KMC-1, KMCH-1, and KMCH-2. Among 51 ICCs, 31 (60.8%) contained only mucin-producing CC features (muc-ICCs), whereas 39.2% displayed histological diversity: focal hepatocytic differentiation and ductular areas (mixed-ICCs). Clinicopathologically, muc-ICCs and hilar CCs showed a predominantly (peri-)hilar location, smaller tumor size, and more lymphatic and perineural invasion compared with mixed-ICCs and CLCs (predominantly peripheral location, larger tumor size, and less lymphatic and perineural invasion). Immunoreactivity was similar in muc-ICCs and hilar CCs and in mixed-ICCs and CLCs.

S100P

and

MUC1

were significantly up-regulated in hilar CCs and muc-ICCs compared with mixed-ICCs and CLCs, whereas

NCAM1

and

ALB

tended to be up-regulated in mixed-ICCs and CLCs compared with other tumors. KMC-1 showed significantly higher invasiveness than KMCH-1 and KMCH-2.

Conclusion:

Muc-ICCs had a clinicopathological, immunohistochemical, and molecular profile similar to that of hilar CCs (from mucin-producing cholangiocytes), whereas mixed-ICCs had a profile similar to that of CLCs (thought to be of HPC origin), possibly reflecting their respective cells of origin.
Cyclin G1–mediated epithelial-mesenchymal transition via phosphoinositide 3-kinase/Akt signaling facilitates liver cancer progression
Authors: Wen Wen , Ding Jin , Sun Wen , Fu Jing , Chen Yao , Wu Kun , Ning Beifang , Han Tao , Huang Lei , Chen Cheng , Xie Dong , Li Zhong , Feng Gensheng , Wu Mengchao , Xie Weifen , Wang Hongyang
Published: January 2012

Cyclin G1 deficiency is associated with reduced incidence of carcinogen-induced hepatocellular carcinoma (HCC), but its function in HCC progression remains obscure. We report a critical role of cyclin G1 in HCC metastasis. Elevated expression of cyclin G1 was detected in HCCs (60.6%), and its expression levels were even higher in portal vein tumor thrombus. Clinicopathological analysis revealed a close correlation of cyclin G1 expression with distant metastasis and poor prognosis of HCC. Forced expression of cyclin G1 promoted epithelial-mesenchymal transition (EMT) and metastasis of HCC cells

in vitro

and

in vivo
. Cyclin G1 overexpression enhanced Akt activation through interaction with p85 (regulatory subunit of phosphoinositide 3-kinase [PI3K]), which led to subsequent phosphorylation of glycogen synthase kinase-3β (GSK-3β) and stabilization of Snail, a critical EMT mediator. These results suggest that elevated cyclin G1 facilitates HCC metastasis by promoting EMT via PI3K/Akt/GSK-3β/Snail-dependent pathway. Consistently, we have observed a significant correlation between cyclin G1 expression and p-Akt levels in a cohort of HCC patients, and found that combination of these two parameters is a more powerful predictor of poor prognosis.

Conclusions:

Cyclin G1 plays a pivotal role in HCC metastasis and may serve as a novel prognostic biomarker and therapeutic target.
Absence of adipose triglyceride lipase protects from hepatic endoplasmic reticulum stress in mice
Authors: Fuchs Claudia D. , Claudel Thierry , Kumari Pooja , Haemmerle Guenter , Pollheimer Marion J. , Stojakovic Tatjana , Scharnagl Hubert , Halilbasic Emina , Gumhold Judith , Silbert Dagmar , Koefeler Harald , Trauner Michael
Published: January 2012

Nonalcoholic fatty liver disease (NAFLD) is characterized by triglyceride (TG) accumulation and endoplasmic reticulum (ER) stress. Because fatty acids (FAs) may trigger ER stress, we hypothesized that the absence of adipose triglyceride lipase (ATGL/PNPLA2)–the main enzyme for intracellular lipolysis, releasing FAs, and closest homolog to adiponutrin (PNPLA3) recently implicated in the pathogenesis of NAFLD–protects against hepatic ER stress. Wild-type (WT) and ATGL knockout (KO) mice were challenged with tunicamycin (TM) to induce ER stress. Serum biochemistry, hepatic TG and FA profiles, liver histology, and gene expression for markers of hepatic lipid metabolism, ER stress, and inflammation were explored. Moreover, cell-culture experiments were performed in Hepa1.6 cells after the knockdown of ATGL before FA and TM treatment. TM increased hepatic TG accumulation in ATGL KO, but not in WT, mice. Lipogenesis and β-oxidation were repressed at the gene-expression level (sterol regulatory element-binding transcription factor 1c, fatty acid synthase, acetyl coenzyme A carboxylase 2, and carnitine palmitoyltransferase 1 alpha) in both WT and ATGL KO mice. Genes for very-low-density lipoprotein (VLDL) synthesis (microsomal triglyceride transfer protein and apolipoprotein B) were down-regulated by TM in WT and even more in ATGL KO mice, which displayed strongly reduced serum VLDL cholesterol levels. Notably, ER stress markers glucose-regulated protein, C/EBP homolog protein, spliced X-box-binding protein, endoplasmic-reticulum–localized DnaJ homolog 4, and inflammatory markers Tnfα and iNos were induced exclusively in TM-treated WT, but not ATGL KO, mice. Total hepatic FA profiling revealed a higher palmitic acid/oleic acid (PA/OA) ratio in WT mice, compared to ATGL KO mice, at baseline. Phosphoinositide-3-kinase inhibitor–known to be involved in FA-derived ER stress and blocked by OA–was increased in TM-treated WT mice only. In line with this, in vitro OA protected hepatocytes from TM-induced ER stress. Conclusions: Lack of ATGL may protect from hepatic ER stress through alterations in FA composition. ATGL could constitute a new therapeutic strategy to target ER stress in NAFLD. (HEPATOLOGY 2012;56:270–280 )
The inhibitors of nucleotide biosynthesis leflunomide, FK778, and mycophenolic acid activate hepatitis B virus replication in vitro
Authors: Hoppe-Seyler Karin , Sauer Peter , Lohrey Claudia , Hoppe-Seyler Felix
Published: January 2012

The inhibitors of pyrimidine synthesis, leflunomide and FK778, have been reported to exert broad antiviral effects, in addition to their immunosuppressive activities. Their possible therapeutic benefit for transplantation medicine is currently discussed, because they also block the replication of human cytomegalovirus and human polyomavirus BK, which both cause important complications in transplant recipients. Here, we show that leflunomide and FK778 strongly enhance hepatitis B virus (HBV) replication in vitro. This activity is shared by mycophenolic acid (MPA), an inhibitor of purine biosynthesis. Stimulation of HBV replication by these agents was linked to their inhibitory effects on de novo nucleotide biosynthesis because it could be efficiently counteracted by external nucleoside supply. Mechanistically, we found that mitogen-activated protein kinase p38 played a key role for the enhancement of HBV replication by leflunomide, FK778, and MPA. All three HBV-activating compounds increased p38 phosphorylation, in contrast to the HBV inhibitors, telbivudine and cyclosporine A. Moreover, silencing of p38 expression through RNA interference efficiently counteracted the stimulatory effect of leflunomide, FK778, and MPA on HBV replication. Conclusion: Our data indicate that, in contrast to their reported inhibitory effects on other viruses, both leflunomide and FK778 can augment HBV replication. Treatment with leflunomide, FK778, or MPA may bear the risk to enhance HBV replication in infected patients. (HEPATOLOGY 2012;56:9–16)