bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrophysiological Characteristics of Localized Reentrant Atrial Tachycardia Occurring After Catheter Ablation of Long‐Lasting Persistent Atrial Fibrillation
Authors: TAKAHASHI YOSHIHIDE , TAKAHASHI ATSUSHI , MIYAZAKI SHINSUKE , KUWAHARA TAISHI , TAKEI ASUMI , FUJINO TADASHI , FUJII AKIRA , KUSA SHIGEKI , YAGISHITA ATSUHIKO , NOZATO TOSHIHIRO , HIKITA HIROYUKI , SATO AKIRA , HIRAO KENZO , ISOBE MITSUAKI
Published: January 2009

Background: Mapping of recurrent atrial tachycardia (AT) after extensive ablation for long‐lasting persistent atrial fibrillation (AF) is complex. We sought to describe the electrophysiological characteristics of localized reentry occurring after ablation of long‐lasting persistent AF.

Methods: Out of 70 patients undergoing catheter ablation of long‐lasting persistent AF, 9 patients (13%, 55 ± 8 years, 8 males) in whom localized reentry was demonstrated in a repeat ablation were studied. Localized reentry was defined as reentry in which the circuit was localized to a small area and did not have a central obstacle. The mechanism of AT was determined by electroanatomical and entrainment mapping.

Results: Nine localized reentries with cycle length of 243 ± 41 ms were mapped in 9 patients. The location of AT was the left atrial appendage in 4 patients, anterior left atrium in 2, left septum in 2, and mitral isthmus in 1. In all ATs, a critical isthmus of <10 mm in width was identified in the vicinity of the prior linear lesions or ostia of isolated pulmonary veins. Ablation of the critical isthmus, which was characterized by continuous low‐voltage activity (median voltage: 0.15 mV, mean duration: 117 ± 31 ms), terminated AT and rendered it noninducible. Additionally, ablation was performed for all of inducible ATs. At 11 ± 7 months after the procedure, 8 of 9 patients (89%) were free from any arrhythmias.

Conclusions: After ablation of long‐lasting persistent AF, localized reentry may arise from a site in the vicinity of the prior ablation lesions. Ablation of the critical isthmus eliminates the arrhythmia.
Is This Atrial Fibrillation?
Authors: Jadidi Amir S. , Sunthorn Henri , Burri Haran , Gentil‐Baron Pascale , Shah Dipen
Published: January 2009

A 19‐year‐old girl was referred to our cardiology department for catheter ablation (isolation of the pulmonary veins) of paroxysmal atrial fibrillation (AF). The diagnosis was made upon a 12‐lead ECG of the arrhythmia documented in the emergency room. The ECG showed an irregular tachycardia without wide QRS complexes. Careful assessment revealed the irregularity of the rhythm was a sweep artifact due to a mechanic failure of the ECG‐machine to advance the article smoothly. During EP study a concealed anteroseptal accessory pathway causing an orthodromic AV reentrant tachycardia was eliminated by radio‐frequency ablation. This example emphasizes the need for careful assessment of an ECG tracing, including printed legends and technical data.
Detailed ECG Analysis of Atrial Repolarization in Humans
Authors: Holmqvist Fredrik , Carlson Jonas , Platonov Pyotr G.
Published: January 2009

Introduction: Data on human atrial repolarization are scarce since the QRS complex normally obscures its ECG trace. In the present study, consecutive patients with third‐degree AV block were studied to better describe the human Ta wave.

Methods and Results: Forty patients (mean age 75 years, 17 men) were included. All anti‐arrhythmic drugs were discontinued before ECG recording. Standard 12‐lead ECGs were recorded, transformed to orthogonal leads and studied using signal‐averaged P wave analysis. The average P wave duration was 124 ± 16 ms. The PTa duration was 449 ± 55 ms (corrected PTa 512 ± 60 ms) and the Ta duration (P wave end to Ta wave end) was 323 ± 56 ms. The polarity of the Ta wave was opposite to that of the P wave in all leads. The Ta peaks were located at 196 ± 55 ms in Lead Y, 216 ± 50 ms in Lead X, and 335 ± 92 in Lead Z. No correlation was found between P wave duration and Ta duration, or between Ta peak amplitude and Ta duration. The morphology of the Ta wave was similar regardless of the interatrial conduction.

Conclusions: The Ta wave has the opposite polarity, and the duration is generally two to three times that, of the P wave. Although the Ta peak may occasionally be located in the PQ interval during normal AV conduction, it is unlikely that enough information can be obtained from analysis of this segment to differentiate normal from abnormal atrial repolarization. Hence, an algorithm for QRST cancellation during sinus rhythm is needed to further improve analysis.
Added Value of a Resting ECG Neural Network That Predicts Cardiovascular Mortality
Authors: Perez Marco V. , Dewey Frederick E. , Tan Swee Y. , Myers Jonathan , Froelicher Victor F.
Published: January 2009

Background: The resting 12‐lead electrocardiogram (ECG) remains the most commonly used test in evaluating patients with suspected cardiovascular disease. Prognostic values of individual findings on the ECG have been reported but may be of limited use.

Methods: The characteristics of 45,855 ECGs ordered by physician's discretion were first recorded and analyzed using a computerized system. Ninety percent of these ECGs were used to train an artifical neural network (ANN) to predict cardiovascular mortality (CVM) based on 132 ECG and four demographic characteristics. The ANN generated a Resting ECG Neural Network (RENN) score that was then tested in the remaining ECGs. The RENN score was finally assessed in a cohort of 2189 patients who underwent exercise treadmill testing and were followed for CVM.

Results: The RENN score was able to better predict CVM compared to individual ECG markers or a traditional Cox regression model in the testing cohort. Over a mean of 8.6 years, there were 156 cardiovascular deaths in the treadmill cohort. Among the patients who were classified as intermediate risk by Duke Treadmill Scoring (DTS), the third tertile of the RENN score demonstrated an adjusted Cox hazard ratio of 5.4 (95% CI 2.0–15.2) compared to the first RENN tertile. The 10‐year CVM was 2.8%, 8.6% and 22% in the first, second and third RENN tertiles, respectively.

Conclusions: An ANN that uses the resting ECG and demographic variables to predict CVM was created. The RENN score can further risk stratify patients deemed at moderate risk on exercise treadmill testing.
QT Variability during Rest and Exercise in Patients with Implantable Cardioverter Defibrillators and Healthy Controls
Authors: Haigney Mark C. , Kop Willem J. , Alam Shama , Krantz David S. , Karasik Pamela , DelNegro Albert A. , Gottdiener John S.
Published: January 2009

Background: Increased QT Variability (QTVI) is predictive of life threatening arrhythmias in vulnerable patients. The predictive value of QTVI is based on resting ECGs, and little is known about the effect of acute exercise on QTVI. The relation between QTVI and arrhythmic vulnerability markers such as T‐wave alternans (TWA) has also not been studied. This study examined the effects of exercise on QTVI and TWA in patients with arrhythmic vulnerability.

Methods: Digitized ECGs were obtained from 47 ICD patients (43 males; age 60.9 ± 10.1) and 23 healthy controls (18 males; age 59.7 ± 9.5) during rest and bicycle exercise. QTVI was assessed using a previously validated algorithm and TWA was measured as both a continuous and a categorical variable based on a priori diagnostic criteria.

Results: QTVI increased with exercise in ICD patients (−0.79 ± 0.11 to 0.36 ± 0.08, P < 0.001) and controls (−1.50 ± 0.07 to −0.19 ± 0.12, P < 0.001), and QTVI levels were consistently higher in ICD patients than controls during rest and exercise (P < 0.001). The magnitude of QTVI increase from baseline levels was not larger among ICD patients versus controls (P > 0.20). Among ICD patients, elevated exercise QTVI was related to lower LV ejection fraction and inducibility of ischemia (P < 0.05). QTVI at rest correlated with exercise TWA (r = 0.54, P = 0.0004).

Conclusions: QT variability increases significantly with exercise, and exercise QTVI is related to other well‐documented markers of arrhythmic vulnerability, including low ejection fraction, inducible ischemia, and TWA. Resting QTVI may be useful in the risk stratification of individuals incapable of performing standard exercise protocols.
L'emploi informel: deux questions de politique controversées
Authors: KUCERA David , RONCOLATO Leanne
Published: January 2009

Cet article traite de deux questions controversées, importantes en termes de politiques: les effets de la réglementation du travail sur l'emploi informel, et ce qu'il est convenu d'appeler l'emploi informel «volontaire». Les auteurs exposent brièvement les théories sur le sujet et présentent les résultats d'analyses empiriques des effets de la réglementation du travail sur l'emploi informel. Ils concluent par des commentaires sur la pertinence des quatre objectifs du travail décent de l'OIT pour l'emploi informel et le développement économique, en mettant l'accent sur l'organisation des travailleurs de l'économie informelle.
RCT of the effects of block absence for outreach placements on dental students’ finals grades
Authors: Smith M. , Lennon M. A. , Robinson P. G.
Published: January 2009

Undergraduate dental curricula are being supplemented with primary care placements requiring periods away from the dental school. These absences may impact negatively on students’ other studies.

Objective:  To compare the effect of outreach placement and traditional hospital‐based training alone on students’ final examination scores. Existing primary care placements in northern England about one year from students’ qualification.

Subjects and Methods:  Analysis of secondary outcomes in a randomised controlled trial with students’ final examination marks being compared on qualification. To reduce Type I error only 4 of 24 available scores were considered and multiple testing correction applied. Five‐week block outreach placements for 25 of 49 students. Honours awarded and examination scores for children’s dentistry, overall clinical work and theory.

Results:  Groups’ final exam scores were similar: children’s dentistry – outreach 64.9 (SD 2.1), hospital‐based 65.0 (3.0); overall clinical work 58.3 (3.4) cf 60.7 (4.8) and theory 54.6 (3.5) cf 56.5 (4.0). The numbers of students awarded honours (outreach 1, hospital 4) showed no significant difference (Fisher’s exact text P = 0.19).

Conclusion:  Dental outreach training involving several weeks’ absence from the school had no negative impact on students’ finals scores.
Perceived sources of stress amongst Indian dental students
Authors: Kumar S. , Dagli R. J. , Mathur A. , Jain M. , Prabu D. , Kulkarni S.
Published: January 2009

Introduction:  Dental students have to face the additional stress of their studies in addition to the stresses related to dentistry as a profession. Furthermore, increasing stress may result in declining student performance. The aim of the present study was to assess perceived sources of stress amongst dental undergraduate students at a private dental institution in India.

Materials and methods:  A modified dental environment stress (DES) questionnaire which consisted of 38 questions was used to assess the levels of stress.

Results:  The first major stressor for all the students was examination and grades with a mean score of 2.86 (SD 1.06) followed by full working day, receiving criticism from supervisors about academic or clinical work, amount of cheating in dental faculty, rules and regulations of the faculty and fear of unemployment after graduation. Amongst the six highest stressors in each year, at least three were dental faculty related. There was a significant difference in stress perception between genders with a predilection for males. Twelve of the 38 questionnaire items had significant differences across the year groups including clinical DES items.

Conclusion:  The primary sources of stress as perceived by nearly 275 students at one private dental school in India were examinations and grades followed by full working day and receiving criticism from supervisors about academic or clinical work. It appears there is a need for the establishment of student advisors and counsellors combined with a faculty advising system in addition to student‐oriented programmes.
The European computer driving licence and the use of computers by dental students
Authors: Antonarakis G. S.
Published: January 2009

The use of computers within the dental curriculum for students is vital for many aspects of their studies. The aim of this study was to assess how dental students who had obtained the European computer driving licence (ECDL) qualification (an internationally‐recognised standard of competence) through taught courses, felt about the qualification, and how it changed their habits vis‐à‐vis computers, and information and communication technology. This study was carried out as a descriptive, one‐off, cross‐sectional survey. A questionnaire was distributed to 100 students who had successfully completed the course, with questions pertaining to the use of email, word processing and Internet for course‐works, Medline for research, computer based learning, online lecture notes, and online communication with members of staff, both before and after ECDL qualification. Scaled responses were given. The attitudes of students towards the course were also assessed. The frequencies and percentage distributions of the responses to each question were analysed. It was found that dental students who follow ECDL teaching and successfully complete its requirements, seem to increase the frequency with which they use email, word processing and Internet for course works, Medline for research purposes, computer based learning, online lecture notes, and online communication with staff. Opinions about the ECDL course varied, many dental students finding the course easy, enjoying it only a little, but admitting that it improved their computer skills.
Validity of caries detection on occlusal surfaces and treatment decisions based on results from multiple caries‐detection methods
Authors: Pereira Antonio Carlos , Eggertsson Hafsteinn , Martinez‐Mier Esperanza Angeles , Mialhe Fábio Luiz , Eckert George Joseph , Zero Domenick Thomas
Published: January 2009

The aim of this in vitro study was to evaluate whether having results available from multiple detection methods influences dentist’s treatment decisions for incipient caries lesions on occlusal surfaces. The occlusal surface of 96 extracted permanent molars without frank cavitation was examined by three examiners initially by visual examination alone, following which they chose one of three treatment options: (i) no treatment, (ii) preventive or non‐invasive treatment (sealants), and (iii) invasive treatment. Four weeks later the examiners again selected one of the three treatment options for the surfaces, but this time were able to refer to the results from additional caries‐detection methods [bitewing radiographs, electric conductance measurement (ECM), quantitative light fluorescence (QLF), and DIAGNOdent] that had been performed in the interim time. Stereomicroscopy was used to evaluate sensitivity, specificity, accuracy, and area under the Receiver Operating Characteristic (ROC) curve (AUC) for the detection methods at the D1 diagnostic threshold. Slight improvement was obtained in the percentage of sites correctly diagnosed, and in the AUC, when referring to the results obtained from all detection methods compared with visual examination alone. However, a drastic effect on the selection of treatment options was observed by having results available from multiple methods, with the choice of invasive treatment increasing substantially. In conclusion, having data available from multiple methods did not improve the accuracy of examiners in detecting early occlusal caries lesions, but it had a great influence on the number of surfaces indicated for operative treatment. The potential decrease in overall specificity while using multiple methods of detection may be of concern in populations with a low prevalence of occlusal caries lesions.
Interindividual differences in the perception of dental stimulation and related brain activity
Authors: Ettlin D. A. , Brügger M. , Keller T. , Luechinger R. , Jäncke L. , Palla S. , Barlow A. , Gallo L. M. , Lutz K.
Published: January 2009

For identical diagnoses in the trigeminal innervation territory, individual differences have been clinically observed among the symptoms reported, such as dysesthesia and pain. Different subjective perceptions of unpleasantness and pain intensity may have different cortical substrates. The aim of this study was to identify brain areas in which activation depends on the subjective perception (intensity and unpleasantness) of electric dental stimulation. Electrical stimuli of increasing intensity were applied to maxillary canines in 14 healthy volunteers. Ratings for stimulus intensity and unpleasantness perceived across the stimulation session were reported postscan on 11‐point numerical scales. The rating values were then included as covariates in the functional magnetic resonance imaging (fMRI) group analysis. Interindividual differences of intensity ratings were reflected in differential activity of the following brain areas: superior parietal lobule, superior temporal gyrus/anterior insula, inferior and middle temporal gyrus, lingual gyrus, anterior cingulate, and caudate nucleus. Differences related to unpleasantness ratings were reflected in the lingual gyrus. In conclusion, differences of perceived intensity between individuals are reflected in the differential activity of a set of brain areas distinct from those regions, reflecting rating differences of unpleasantness.
2‐Hydroxyethyl methacrylate as an inhibitor of matrix metalloproteinase‐2
Authors: Carvalho Rodrigo V. , Ogliari Fabrício A. , De Souza Ana P. , Silva Adriana F. , Petzhold Cesar L. , Line Sergio R. P. , Piva Evandro , Etges Adriana
Published: January 2009

This study evaluated the effect of different concentrations of 2‐hydroxyethyl methacrylate (HEMA) on the inhibition of matrix metalloproteinase‐2 (MMP‐2) in vitro. Mouse gingival explants were cultured overnight in Dulbecco’s modified Eagle’s minimal essential medium, following which the expression of secreted enzymes was analyzed by gelatin zymography and the effects of different amounts of HEMA on enzyme activity were investigated. The gelatinolytic proteinases present in the conditioned media were characterized as being matrix metalloproteinases (MMPs) by means of specific chemical inhibition. The MMPs present in the conditioned media were identified, using immunoprecipitation, as MMP‐2. Three major bands were detected in the zymographic assays and were characterized, according to their respective molecular weights, into the following forms of MMP‐2: zymogene (72 kDa), intermediate (66 kDa), and active (62 kDa). All forms of MMP‐2 were inhibited by HEMA in a dose‐dependent manner, implying that MMP‐2 may be inhibited by HEMA in vivo.
Long‐term release of monomers from modern dental‐composite materials
Authors: Polydorou Olga , König Armin , Hellwig Elmar , Kümmerer Klaus
Published: January 2009

The elution of monomers from composite materials influences the biocompatibility of dental restorations. The purpose of the present study was to investigate the elution of monomers [bisphenol A glycidyl methacrylate (BisGMA), triethylene glycol dimethacrylate (TEGDMA), urethane dimethacrylate (UDMA), and bisphenol A (BPA)] from two light‐cured materials (nanohybrid and ormocer) and from a chemically cured composite material, after different curing times (0, 20, 40 and 80 s) and different storage periods (24 h, 7 d, 28 d, and 1 yr after curing). Each specimen was stored in 1 ml of 75% ethanol. This medium was renewed after 24 h, 7 d, 28 d, and 1 yr. The ethanol samples were analyzed using liquid chromatography tandem mass spectrometry (LC–MS/MS). The amount of monomers released from the nanohybrid and the chemically cured composite was significantly higher than released from the ormocer. The curing time exerted a significant effect on the release of monomers. For the nanohybrid, less monomer was released after increasing the curing time. For the ormocer, 80 s of curing resulted in a higher degree of monomer release. The effect of storage differed between the monomers. Although the elution of TEGDMA was significantly decreased after storage for 28 d and 1 yr, a similar amount of BisGMA was released at each storage time‐point analyzed, even after 1 yr. The present study showed that ormocer released a very small amount of monomers compared with the other materials.
Is self‐reported alcohol consumption associated with osteoporotic mandibular bone loss in women?
Authors: Nackaerts Olivia , Horner Keith , Jacobs Reinhilde , Karayianni Kety , Mitsea Anastasia , Berkas Leonidas , Mastoris Michael , Lindh Christina , Van Der Stelt Paul F. , Marjanovic Elizabeth , Adams Judith E. , Pavitt Susan , Devlin Hugh
Published: January 2009

The aim of this study was to determine whether alcohol consumption would predict mandibular bone quality and quantity in a large European female population. In total, 672 middle‐aged and elderly women (45–70 yr of age; standard deviation = 6) were recruited in the study. Alcohol consumption was recorded through a self‐reported questionnaire. Mandibular cortical width was measured, by five observers, in the mental foramen region on panoramic radiographs. Mandibular bone density, expressed as aluminium thickness, was recorded on intra‐oral radiographs. Alcohol consumption was associated with a reduction of mandibular bone density and cortical width. This association was higher in subjects with excessive alcohol consumption, defined in the present study as > 14 units consumed per week. This study showed reduced jaw‐bone quality in older individuals and in those with increased alcohol consumption.
Spectres of Duty. Silence in Ibsen’s Ghosts
Authors: Vardoulakis Dimitris
Published: January 2009

The article considers Ibsen’s Ghosts through the figure of duty. The two main characters embody different notions of duty. Pastor Manders’s position is a religious one and Mrs Alving’s a political one, but neither can stand on its own. They both infringe upon, and contaminate, each other. This process of self‐contamination, which silence sets in motion, leads to an alternative understanding of duty as well as of the political.
Crystal structure of a family 16 endoglucanase from the hyperthermophile Pyrococcus furiosus– structural basis of substrate recognition
Authors: Ilari Andrea , Fiorillo Annarita , Angelaccio Sebastiana , Florio Rita , Chiaraluce Roberta , van der Oost John , Consalvi Valerio
Published: January 2009

Bacterial and archaeal endo‐β‐1,3‐glucanases that belong to glycoside hydrolase family 16 share a β‐jelly‐roll fold, but differ significantly in sequence and in substrate specificity. The crystal structure of the laminarinase (EC 3.2.1.39) from the hyperthermophilic archaeon Pyrococcus furiosus (pfLamA) has been determined at 2.1 Å resolution by molecular replacement. The pfLamA structure reveals a kink of six residues (72–77) at the entrance of the catalytic cleft. This peptide is absent in the endoglucanases from alkaliphilic Nocardiopsis sp. strain F96 and Bacillus macerans, two proteins displaying an overall fold similar to that of pfLamA, but with different substrate specificity. A deletion mutant of pfLamA, lacking residues 72–75, hydrolyses the mixed‐linkage β‐1,3‐1,4‐glucan lichenan 10 times more efficiently than the wild‐type protein, indicating the importance of the kink in substrate preference.
Murine serum nucleases – contrasting effects of plasmin and heparin on the activities of DNase1 and DNase1‐like 3 (DNase1l3)
Authors: Napirei Markus , Ludwig Sebastian , Mezrhab Jamal , Klöckl Thomas , Mannherz Hans G.
Published: January 2009

DNase1 is regarded as the major serum nuclease; however, a systematic investigation into the presence of additional serum nuclease activities is lacking. We have demonstrated directly that serum contains DNase1‐like 3 (DNase1l3) in addition to DNase1 by an improved denaturing SDS‐PAGE zymography method and anti‐murine DNase1l3 immunoblotting. Using DNA degradation assays, we compared the activities of recombinant murine DNase1 and DNase1l3 (rmDNase1, rmDNase1l3) with the serum of wild‐type and DNase1 knockout mice. Serum and rmDNase1 degrade chromatin effectively only in cooperation with serine proteases, such as plasmin or thrombin, which remove DNA‐bound proteins. This can be mimicked by the addition of heparin, which displaces histones from chromatin. In contrast, serum and rmDNase1l3 degrade chromatin without proteolytic help and are directly inhibited by heparin and proteolysis by plasmin. In previous studies, serum DNase1l3 escaped detection because of its sensitivity to proteolysis by plasmin after activation of the plasminogen system in the DNA degradation assays. In contrast, DNase1 is resistant to plasmin, probably as a result of its di‐N‐glycosylation, which is lacking in DNase1l3. Our data demonstrate that secreted rmDNase1 and murine parotid DNase1 are mixtures of three different di‐N‐glycosylated molecules containing two high‐mannose, two complex N‐glycans or one high‐mannose and one complex N‐glycan moiety. In summary, serum contains two nucleases, DNase1 and DNase1l3, which may substitute or cooperate with each other during DNA degradation, providing effective clearance after exposure or release from dying cells.
Polyphosphates from Mycobacterium bovis– potent inhibitors of class III adenylate cyclases
Authors: Guo Ying Lan , Mayer Hermann , Vollmer Waldemar , Dittrich Dorothea , Sander Peter , Schultz Anita , Schultz Joachim E.
Published: January 2009

cAMP generation in bacteria is often stimulated by sudden, but lasting, changes in extracellular conditions, whereas intracellular cAMP concentrations quickly settle at new levels. As bacteria lack G‐proteins, it is unknown how bacterial adenylate cyclase (AC) activities are modulated. Mycobacterium tuberculosis has 15 class III AC genes; therefore, we examined whether mycobacteria contain a factor that may regulate AC activities. We identified mycobacterial polyphosphates with a mean chain length of 72 residues as highly potent inhibitors of dimeric class IIIa, class IIIb and class IIIc ACs from M. tuberculosis and other bacteria. The identity of the inhibitor was established by phosphatase degradation, 31P‐NMR, acid or base hydrolysis, PAGE and comparisons with commercial standards, and functional substitution by several polyphosphates. The data indicate that each AC dimer occupies 8–15 phosphate residues on a polyphosphate strand. Other polyionic polymers such as polyglutamate, polylysine and hyaluronic acid do not affect cyclase activity. Notably, the structurally unrelated class I AC Cya from Escherichia coli is unaffected. Bacterial polyphosphate metabolism is generally viewed in the context of stress‐related regulatory networks. Thus, regulation of bacterial class III ACs by polyphosphates could be a component of the bacterial stress response.
Unchanged thymidine triphosphate pools and thymidine metabolism in two lines of thymidine kinase 2‐mutated fibroblasts
Authors: Frangini Miriam , Rampazzo Chiara , Franzolin Elisa , Lara Mari‐Carmen , Vilà Maya R. , Martí Ramon , Bianchi Vera
Published: January 2009

Mitochondrial thymidine kinase (TK2) catalyzes the phosphorylation of thymidine in mitochondria. Its function becomes essential for dTTP synthesis in noncycling cells, where cytosolic dTTP synthesis via R1/R2 ribonucleotide reductase and thymidine kinase 1 is turned down. Mutations in the nuclear gene for TK2 cause a fatal mtDNA depletion syndrome. Only selected cell types are affected, suggesting that the other cells compensate for the TK2 deficiency by adapting the enzyme network that regulates dTTP synthesis outside S‐phase. Here we looked for such metabolic adaptation in quiescent cultures of fibroblasts from two TK2‐deficient patients with a slow‐progressing syndrome. In cell extracts, we measured the activities of TK2, deoxycytidine kinase, thymidine phosphorylase, deoxynucleotidases and the amounts of the three ribonucleotide reductase subunits. Patient cells contained 40% or 5% TK2 activity and unchanged activities of the other enzymes. However, their mitochondrial and cytosolic dTTP pools were unchanged, and also the overall composition of the dNTP pools was normal. TK2‐dependent phosphorylation of [3H]thymidine in intact cells and the turnover of the dTTP pool showed that even the fibroblasts with 5% residual TK2 activity synthesized dTTP at an almost normal rate. Normal fibroblasts apparently contain more TK2 than needed to maintain dTTP during quiescence, which would explain why TK2‐mutated fibroblasts do not manifest mtDNA depletion despite their reduced TK2 activity.
Transcription factor specificity protein 1 (SP1) and activating protein 2α (AP‐2α) regulate expression of human KCTD10 gene by binding to proximal region of promoter
Authors: Liu Rushi , Zhou Aidong , Ren Daolong , He Ailan , Hu Xiang , Zhang Wenfeng , Yang Liping , Liu Mingjun , Li Hong , Zhou Jianlin , Xiang Shuanglin , Zhang Jian
Published: January 2009

Potassium channel tetramerization domain‐containing 10 gene (KCTD10) belongs to the polymerase delta‐interacting protein 1 (PDIP1) gene family. Mouse KCTD10 was thought to interact with proliferating cell nuclear antigen and the small subunit of polymerase δ, and to have roles in DNA repair, DNA replication and cell‐cycle control. To better understand the regulatory mechanism of KCTD10 expression, we characterized the promoter of human KCTD10 containing a 639 bp fragment of the 5′‐flanking region (−609/+30). A primer extension assay identified the transcription start site as an A, 63 bp upstream of the start codon. The promoter region contains neither a TATA box nor a CCAAT box, but a CpG island was found near to the transcription start site. Deletion mutagenesis showed that the region from −108 to +30 was indispensable to the promoter activity, and site‐directed mutation analysis in this proximal promoter region of KCTD10 revealed two important transcription regulatory elements of specificity protein 1 (SP1) and activating protein‐2 (AP‐2). An in vivo chromatin immunoprecipitation assay further demonstrated that SP1 and AP‐2α could bind to this proximal promoter region. Moreover, using a luciferase reporter assay, quantitative real‐time RT‐PCR and western blot analysis, both overexpression and RNA interference of SP1 and AP‐2α indicated that the binding of SP1 to the proximal promoter region stimulated the promoter activity and endogenous KCTD10 expression, whereas binding of AP‐2α to this region showed opposite effects.
Consequences of a flawed presidential election
Authors: Abuya Edwin Odhiambo
Published: January 2009

This paper evaluates the impact of a substandard presidential election. Using Kenya as a case study, it reviews the 2007 vote. The paper contends that there is a link between free and fair elections and the enjoyment of human rights. It argues that in order for states in Africa to walk the (desired) democratic path, sitting governments must comply with internationally recognised standards. While focusing on the violence that rocked the country, the paper analyses the causes and implications of the much-disputed presidential poll. Also evaluated is the role the international community can play in resolving a crisis. The paper concludes by asserting that a rule of law culture must be embraced if human rights and democracy are to flourish in Africa.
Quenching of Singlet Oxygen by a Carotenoid–Cyclodextrin Complex: The Importance of Aggregate Formation
Authors: Kanofsky Jeffrey R. , Sima Paul D.
Published: January 2009

The Girard’s reagent P derivative of canthaxanthin ((GRP)2‐canthaxanthin), a dicationic carotenoid, forms a highly water‐dispersible complex with (2‐hydroxypropyl)‐γ‐cyclodextrin. The UV–visible light spectrum of the complex is consistent with some degree of aggregation, but the spectrum is independent of concentration from 7.5 to 750 μm. Stern‐Vomer plots for singlet‐oxygen quenching by the complex are linear over a concentration range of 0–20 μm. In the presence of 1 mm (2‐hydroxypropyl)‐γ‐cyclodextrin, the singlet‐oxygen quenching constant for the complex is 7.9 ± 0.9 × 108 m−1s−1. This is about an order of magnitude lower than the singlet‐oxygen quenching constants for (GRP)2‐canthaxanthin in various organic solvents. The properties of the complex are also compared with the properties of (GRP)2‐canthaxanthin solubilized in neat water and in water containing various detergents. The singlet‐oxygen quenching constant for (GRP)2‐canthaxanthin in micelles depends strongly on the specific detergent used, varying from 9.4 × 108 m−1s−1 for hexadecyltrimethylammonium bromide (CTAB) to 1.24 ± 0.4 × 1010 m−1s−1 for sodium dodecyl sulfate. The small quenching constant in CTAB micelles correlates with spectroscopic evidence for aggregation of the (GRP)2‐canthaxanthin in this detergent.
The Effects of Self‐Discordance, Self‐Concordance, and Implementation Intentions on Health Behavior
Authors: Chatzisarantis Nikos L. D. , Hagger Martin S. , Thøgersen‐Ntoumani Cecilie
Published: January 2009

Building upon previous research on implementation intentions, the present study hypothesized that implementation intentions would be beneficial for participants who endorsed self‐concordant and self‐discordant forms of motivation. Self‐concordance describes the extent to which goals are congruent with organismic needs for self‐determination, competence, and relatedness whereas self‐discordance describes the extent to which goals and behaviors are incongruent with these needs. Results showed that implementation intentions were beneficial for people who endorsed self‐discordant forms of motivation. In addition, a statistically nonsignificant trend was observed for implementation intentions to be beneficial among individuals who endorsed self‐concordant forms of motivation. It is concluded that implementation exercises are beneficial for individuals who endorse self‐discordant motivation.
Influence of Social Support, Work Overload, and Parity on Pregnant Career Women's Psychological Well‐Being
Authors: Adejumo Adebayo O.
Published: January 2009

The influence of social support, work overload, and parity on psychological well‐being of pregnant career women was investigated. Women executives (N200) attending antenatal clinics were selected. A 2 × 2 × 2 analysis of variance (ANOVA) revealed significant independent influence of social support (F(1, 199) = 26.51, p < 0.05) and work overload (F(1, 199) = 461.76, p < 0.05), and significant joint effect of social support and work overload. There was no significant effect of parity (F(1, 199) = 0.72, p > 0.05). Combinations of parity, social support, and work overload were also not significant (F(1, 199) = 0.80, p > 0.05). Social support and appropriate work incentives are helpful in assisting pregnant women executives in coping with psychological changes during pregnancy.
Isolation and characterization of 16 microsatellite loci in the humbug damselfish, Dascyllus aruanus (family Pomacentridae)
Authors: FAUVELOT C. , SMITH‐KEUNE C. , JERRY D. R. , BUSTON P. M. , PLANES S.
Published: January 2009

Here we report on 16 microsatellite loci designed for the damselfish Dascyllus aruanus. All loci were tested on 98 individuals and were polymorphic (seven to 35 alleles). Expected heterozygosity ranged from 0.705 to 0.942. Six loci showed Hardy‐Weinberg disequilibrium due to the occurrence of null alleles. Cross‐species amplifications conducted within the genus Dascyllus (D. carneus, D. strasburgi, D. trimaculatus) lead to polymorphic fragments in 32 out of 48 tests. These 16 loci will enable future research into the behavioural ecology and population ecology of Dascyllus aruanus throughout the Indo‐Pacific.
Isolation and characterization of microsatellite loci in Babylonia areolata and cross‐species amplification in Babylonia formosae habei
Authors: CHEN FEI , KE CAI‐HUAN , WANG DE‐XIANG , CHEN JUN , ZHAN XIN , LUO XUAN
Published: January 2009

Nine novel microsatellite primer pairs were presented for Babylonia areolata, representing the first microsatellite markers available for this genus. Levels of polymorphism were variable with 2 to 11 alleles per locus and expected heterozygosities ranging from 0.073 to 0.907 in 27 individuals of the population from which the loci were isolated. We found significant heterozygote deficit at one locus that might be attributable to null alleles. We were successful at cross‐amplifying six loci in the congeneric B. formosae habei. These markers are therefore potentially useful for conservation studies, population structure assessment, ecological analyses and linkage map construction.
Effect of interferon α‐2b plus ribavirin therapy on incidence of hepatocellular carcinoma in patients with chronic hepatitis
Authors: Kurokawa Mika , Hiramatsu Naoki , Oze Tsugiko , Mochizuki Kiyoshi , Yakushijin Takayuki , Kurashige Nao , Inoue Yuko , Igura Takumi , Imanaka Kazuho , Yamada Akira , Oshita Masahide , Hagiwara Hideki , Mita Eiji , Ito Toshifumi , Inui Yoshiaki , Hijioka Taizo , Yoshihara Harumasa , Inoue Atsuo , Imai Yasuharu , Kato Michio , Kiso Shinichi , Kanto Tatsuya , Takehara Tetsuo , Kasahara Akinori , Hayashi Norio
Published: January 2009

Aim:  The objective of this study was to elucidate the long‐term effects of interferon (IFN)α‐2b plus ribavirin combination therapy and to clarify whether this therapy can reduce the incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C.

Methods:  A total of 403 patients infected with hepatitis C virus (HCV) were enrolled in a multicenter trial. All patients were treated with a combination of IFN‐α‐2b plus ribavirin therapy. We examined the incidence of HCC after combination therapy and analyzed the risk factors for liver carcinogenesis.

Results:  A sustained virological response (SVR) was achieved by 139 (34%) of the patients. The cumulative rate of incidence of HCC was significantly lower in SVR patients than in non‐SVR patients (P = 0.03), while there was no difference in the cumulative incidence of HCC between the transient response (TR) group and the no response (NR) group. Cox's regression analysis indicated the following risk factors as independently significant in relation to the development of HCC: age being > 60 years (P = 0.006), advanced histological staging (P = 0.033), non‐SVR to IFN therapy (P = 0.044). The cumulative incidence rate of HCC was significantly lower in patients who had average serum alanine aminotransferase (ALT) levels of < 40 IU/L than in those who showed average serum ALT levels of ≧ 40 IU/L after the combination therapy (P = 0.021).

Conclusions:  These results suggest that the attainment of SVR or continuous normalization of ALT levels after IFN therapy can affect patients apart from HCC development.
The α‐glucosidase inhibitor acarbose prevents obesity and simple steatosis in sequestosome 1/A170/p62 deficient mice
Authors: Okada Kosuke , Yanagawa Toru , Warabi Eiji , Yamastu Keiko , Uwayama Junya , Takeda Koichi , Utsunomiya Hirotoshi , Yoshida Hiroshi , Shoda Junichi , Ishii Tetsuro
Published: January 2009

Aim:  Sequestosome 1 (SQSTM1)/A170/p62 plays an important role in membrane‐receptor mediated signal transduction and autophagic protein degradation. Although the mechanism involved is not clear, sqstm1 gene knockout (KO) mice develop mature‐onset obesity and insulin resistance, leading to type II diabetes. KO mice show accumulation of fat in white adipose tissue and the liver when fed a standard diet. Acarbose is an α‐glucosidase inhibitor that improves insulin sensitivity and decreases postprandial hyperglycemia, and it is used to treat type 2 diabetes. We examined whether or not dietary acarbose prevented obesity and simple steatosis in KO mice.

Methods:  Wild‐type (WT) and KO mice were fed a standard diet with or without acarbose (0.8% w/w) from 15–25 weeks of age. The body weight and the fat content of adipose tissue and the liver were measured, and changes of lipid metabolism in these tissues were assessed from gene expression.

Results:  Acarbose treatment suppressed weight gain and the development of hepatic steatosis in KO mice. Acarbose treatment up‐regulated hepatic expression of the pparα, ucp‐2, and abca1 genes, as well as srebp1c, pparα, and pparγ in adipose tissue. In WT mice, however, acarbose treatment had little influence on weight gain and gene expression.

Conclusions:  The results of this study suggest that long‐term administration of acarbose is effective for prevention of obesity and simple steatosis in SQSTM1‐KO mice.
Effectiveness of combination therapy of splenectomy and long‐term interferon in patients with hepatitis C virus‐related cirrhosis and thrombocytopenia
Authors: Morihara Daisuke , Kobayashi Masahiro , Ikeda Kenji , Kawamura Yusuke , Saneto Hiromi , Yatuji Hiromi , Hosaka Tetuya , Sezaki Hitomi , Akuta Norio , Suzuki Yoshiyuki , Suzuki Fumitaka , Kumada Hiromitu
Published: January 2009

Aim:  To elucidate the effectiveness of combination therapy of splenectomy and long‐term interferon (IFN) on survival and hepatocarcinogenesis, we retrospectively analyzed 180 patients with hepatitis C virus (HCV)‐related cirrhosis and thrombocytopenia.

Methods:  Group A consisted of 121 patients who received neither splenectomy nor IFN therapy. Group B consisted of 11 patients who underwent splenectomy only. Group C consisted of 32 patients who underwent IFN therapy only. Group D consisted of 16 patients who received the combination therapy splenectomy followed by IFN therapy.

Results:  The viral response in group D estimated at least 6 months after IFN therapy showed sustained viral response in four patients, biochemical response in one and no response in six. Multivariate analysis using time‐dependent variables showed significant improvement of survival rate in patients on the combination therapy,but no effect on the appearance rate of hepatocarcinogenesis relative to the findings in group A.

Conclusions:  In this study, the splenectomy did not directly improve the prognosis, but increased the ability for patients to undergo IFN. As a result, we considered that the combination therapy of splenectomy and long‐term IFN significantly improved survival rate in patients with advanced HCV‐related cirrhosis and thrombocytopenia.
Resveratrol amplifies profibrogenic effects of free fatty acids on human hepatic stellate cells
Authors: Bechmann Lars P. , Zahn Denis , Gieseler Robert K. , Fingas Christian D. , Marquitan Guido , Jochum Christoph , Gerken Guido , Friedman Scott L. , Canbay Ali
Published: January 2009

Aim:  To ascertain whether resveratrol affects the expression of free fatty acids (FFA)‐induced profibrogenic genes, death receptors, and/or apoptosis‐related molecules in human hepatic stellate cells, using the LX‐2 cell line.

Methods:  Cells were cultured in the presence of FFAs (2:1 oleate : palmitate) and subsequently treated with resveratrol. Gene expression rates were determined by quantitative real‐time PCR. The 50% lethal dose (LD50) of resveratrol in the presence of FFAs was assessed with the MTT viability test.

Results:  Compared to vehicle controls, incubation of LX‐2 cells with 0.5 mM FFAs induced profibrogenic genes (α‐SMA × 2.9; TGF‐β1 × 1.6; TIMP‐1 × 1.4), death receptors (CD95/Fas × 3.8; TNFR‐1 × 1.4), and anti‐apoptotic molecules (Bcl‐2 × 2.3; Mcl‐1 × 1.3). Subsequent addition of 15 µM resveratrol (LD50 = 23.2 µM) significantly (P < 0.05) upregulated further these genes (α‐SMA × 6.5; TGF‐β1 × 1.9; TIMP‐1 × 2.2; CD95/Fas × 13.1, TNFR‐1 × 2.1; Bcl‐2 × 3.6; Mcl‐1 × 1.9). Importantly, this effect was only observed in the presence of FFAs.

Conclusion:  Resveratrol amplifies the profibrogenic activation of human hepatic LX‐2 stellate cells. This finding raises the possibility that in obese patients with elevated FFAs reserveratrol could provoke hepatic fibrogenesis. In‐vivo studies are necessary to further validate this conclusion.
Drug‐induced liver injury in Japan: An analysis of 1676 cases between 1997 and 2006
Authors: Takikawa Hajime , Murata Yousuke , Horiike Norio , Fukui Hiroshi , Onji Morikazu
Published: January 2009

At the 44th Annual Meeting of the Japan Society of Hepatology, 1674 cases of drug‐induced liver injury (DILI), occurring between January 1997 and December 2006, were reviewed. Data were obtained by questionnaires completed by the 29 presenters of the special DILI session during the meeting. This article presents the review's findings, including the role of dietary supplements and Chinese herbal medicines in DILI.
Passive Manipulation of Separation-Bubble Transition Using Surface Modifications
Authors: McAuliffe Brian R. , Yaras Metin I.
Published: January 2009

Through experiments using two-dimensional particle-image velocimetry (PIV), this paper examines the nature of transition in a separation bubble and manipulations of the resultant breakdown to turbulence through passive means of control. An airfoil was used that provides minimal variation in the separation location over a wide operating range, with various two-dimensional modifications made to the surface for the purpose of manipulating the transition process. The study was conducted under low-freestream-turbulence conditions over a flow Reynolds number range of 28,000–101,000 based on airfoil chord. The spatial nature of the measurements has allowed identification of the dominant flow structures associated with transition in the separated shear layer and the manipulations introduced by the surface modifications. The Kelvin–Helmholtz (K-H) instability is identified as the dominant transition mechanism in the separated shear layer, leading to the roll-up of spanwise vorticity and subsequent breakdown into small-scale turbulence. Similarities with planar free-shear layers are noted, including the frequency of maximum amplification rate for the K-H instability and the vortex-pairing phenomenon initiated by a subharmonic instability. In some cases, secondary pairing events are observed and result in a laminar intervortex region consisting of freestream fluid entrained toward the surface due to the strong circulation of the large-scale vortices. Results of the surface-modification study show that different physical mechanisms can be manipulated to affect the separation, transition, and reattachment processes over the airfoil. These manipulations are also shown to affect the boundary-layer losses observed downstream of reattachment, with all surface-indentation configurations providing decreased losses at the three lowest Reynolds numbers and three of the five configurations providing decreased losses at the highest Reynolds number. The primary mechanisms that provide these manipulations include: suppression of the vortex-pairing phenomenon, which reduces both the shear-layer thickness and the levels of small-scale turbulence; the promotion of smaller-scale turbulence, resulting from the disturbances generated upstream of separation, which provides quicker transition and shorter separation bubbles; the elimination of the separation bubble with transition occurring in an attached boundary layer; and physical disturbance, downstream of separation, of the growing instability waves to manipulate the vortical structures and cause quicker reattachment.
Simulation of Turbine Blade Trailing Edge Cooling
Authors: Joo Jongwook , Durbin Paul
Published: January 2009

The cause of overprediction of cooling efficiency by unsteady Reynolds averaged simulations of turbine blade trailing edge cooling flow is investigated. This is due to the deficiency in the level of unsteady coherent energy very near to the wall. Farther from the wall, the Reynolds averaged simulation produces the correct level of mixing. Eddy simulations of the instantaneous turbulent eddying produce a close agreement to data on film effectiveness. In particular, they reproduce the reduction in cooling effectiveness toward the trailing edge that has been seen in experiments. The scale adaptive simulation model of Menter and Egorov (2005, “A Scale-Adaptive Simulation Modeling Using Two-Equation Models,” AIAA Paper No. 2005-1095) is invoked for the eddy simulations.