bluuebunny/crossref_metadata_2025 huggingface dataset:
Using web-based screening to enhance efficiency of HMO clinical trial recruitment in women aged forty and older
Authors: Smith K Sabina , Eubanks Donna , Petrik Amanda , Stevens Victor J
Published: February 2007

Background Screening potential participants for clinical trials can be labor-intensive, particularly when using long questionnaires administered by telephone.

Purpose This report describes the development and use of an interactive recruitment website as a supplemental screening strategy for a study using telephone screening interviews.

Methods Female HMO members, aged 40 and older, were recruited for a study testing dietary change interventions. Cohorts of potential participants were identified from electronic membership records every two to four weeks; they were sent a letter describing the study and then contacted by telephone. Those interested in the study were asked to complete a 27-question screening interview focused on dietary habits. After 14 cohorts of women were recruited by this method ( n = 4246), a recruitment website was added and an additional 12 cohorts ( n = 3000) were contacted. The modified recruitment letter for these later screening cohorts included the website address and a personal password for each woman. The website contained study information, and those who were interested could complete eligibility screening on-line.

Results Proactive participant response (women actively seeking study participation/screening) to the recruitment mailing was 9.5% (95% confidence interval (CI), 8.6–10.4%) in the cohorts without the website option and 11.5% (CI, 10.4–12.7%) after addition of the website option ( P = 0.004). About half of women screened were ineligible for the study, a proportion that did not statistically differ by recruitment method.

Limitations The study population was limited to middle-aged and older female members of a non-profit health plan, so the generalizability of these findings to other populations is unknown. The pre-post design used in this study does not control for possible temporal changes unrelated to the study methods.

Conclusions The addition of the website screening option was associated with a relative 22% increase in recruitment combined with reduced staff time required for screening, thereby increasing screening efficiency. Web-based options for clinical trial recruitment and screening in targeted populations may increase response rates while also reducing staff time.
Innovative approaches to cohort retention in a community-based HIV/STI prevention trial for socially marginalized Peruvian young adults
Authors: Villacorta Victoria , Kegeles Susan , Galea Jerome , Konda Kelika A , Cuba José Pajuelo , Palacios Carlos F Cáceres , Coates Thomas J ,   NIMH Collaborative HIV/STD Prevention Trial Group
Published: February 2007

Background The conduct of longitudinal clinical trials must involve effective strategies to retain study participants in order to ensure internal validity, adequate statistical power and generalizability of results.

Purpose In a large trial in Peru, we implemented various retention strategies to maintain high participation rates over time.

Methods Novel participant retention strategies were used to follow highly marginalized populations for two years because traditional locator information, such as telephone numbers and official identification (eg, passport, driver's license, the local equivalent of a social security number) were often unreliable or unavailable. These strategies included detailed preliminary ethnographic research to identify the behaviours of key target groups, approaches to develop strong informal bonds between project staff and participants outside of study settings, and methods to enhance positive participant attitudes towards the study.

Results The overall study retention rate after two years was 84%, even though only 26% of the study populations supplied complete locator information (telephone, address and the names of two friends).

Limitations The retention strategies used were labour intensive and iterative, which could prove difficult to replicate.

Conclusions The two-year retention rate in this study was sufficient to maintain required sample sizes. The methods used to maintain contact with the populations were labour intensive, low tech and adequate for these populations and could be used to retain study participants in other marginalized, urban, low-income areas.
Authority to Teach in Classical Anglicanism
Authors: Sixtus Bernhard
Published: February 2007

Anglicanism currently finds itself embroiled in a variety of ‘controversies of Faith’ that individually and together threaten to split the Communion - and most of these concern questions of teaching and authority: who within Anglicanism has authority to teach what, and why? In this situation one naturally looks back on the tradition to seek how an understanding of the past may inform the present. The following paper does so by considering the concept of authority in the foundational period of ‘Anglicanism’, namely from the Thirty-nine Articles of the Church of England to the denominational ‘invention’ of Anglicanism after 1829. It discovers there three interrelated principles of an Anglican understanding of authority, which are briefly summarized after some remarks about how to use conclusions of papers such as this - and how not to.
Appreciating the ‘work’ of discourse: occupational identity and difference as organizing mechanisms in the case of commercial airline pilots
Authors: Ashcraft Karen Lee
Published: February 2007

This article pursues two central goals. First, I seek to advance the sustained study of occupational identity as a pivotal mechanism for organizing work and, thus, as a productive means of integrating the aims of two scholarly movements: 1) the ‘dislocation’ of organization (i.e. beyond container metaphors of site) and 2) the renewed emphasis on work (i.e. ‘bringing work back’) in organization studies. Specifically, I propose the study of evolving relations between occupational image discourse and role communication, and my analysis of US commercial airline pilots enacts the potential of such research. The analysis demonstrates how contemporary pilots draw on the deliberate historical construction of airline pilots as elite, fatherly professionals to make sense of their work, explicitly invoking gender discourse as a rational and emotional warrant for their labor and, in so doing, implicitly articulating sexuality, race, and class discourses. Accordingly, the second major goal of the article is to promote inquiry into how discourses of difference function to organize occupational identity and, thus, to (re)produce the division and hierarchy of labor. With this move, I seek to bring a more constitutive view of discourse and communication, as well as a focus on intersection and interplay among discourses of difference, to the study of occupational identity and segregation.
Gendered discourses on the ‘problem’ of ageing: consumerized solutions
Authors: Coupland Justine
Published: February 2007

Contemporary consumer culture sees the body as the crucial indicator of the self and apparent bodily ageing as problematic. All bodies age, but how is evidence of ageing culturally interpreted? This article develops a critical-pragmatic analysis of consumerized body discourses, with particular focus on the semiotics of the visibly ageing face, in the context of lifestyle magazine features and advertisements on skin care. Such texts work to equate ageing with the look of ageing, problematize ageing appearance, and offer marketized solutions to the ‘problem’ of ageing, using markedly gendered strategies. Texts aimed at a female market project skin care as a serious issue, pathologize the look of ageing, offer highly technologized solutions, and naturalize surgical intervention. The (newer) male market is being discursively engaged by strategies designed to normalize male investment in products and processes traditionally seen as in the domain of female bodily grooming. Consumerized male narcissism is enabled by ironic, ‘uncommitted’ discourses, the use of highly masculinized images and text, and, more recently, discourses which draw attention to the salience of the female appraising gaze.
Citizens, consumers and the citizen-consumer: articulating the citizen interest in media and communications regulation
Authors: Livingstone Sonia , Lunt Peter , Miller Laura
Published: February 2007

The Office of Communications (Ofcom), established by an Act of Parliament in 2003, is a new sector wide regulator in the UK, required to further the interests of what has been termed the ‘citizen-consumer’. Using a critical discursive approach, this article charts the unfolding debate among stakeholders in the new regulatory environment as they attempt to define the interests of citizens, consumers and the citizen-consumer. Ofcom has preferred to align the terms ‘citizen’ and ‘consumer’ so that the interests of both may be met, as far as possible, through an economic agenda of market regulation. Among civil society groups, there is growing concern that the citizen interest is becoming marginalized as the consumer discourse becomes more widespread. We conclude by advocating the development of a positive definition of the citizen interests, distinct from the consumer interests, for the media and communications environment.
Legitimation in discourse and communication
Authors: Van Leeuwen Theo
Published: February 2007

The article sets out a framework for analysing the way discourses construct legitimation for social practices in public communication as well as in everyday interaction. Four key categories of legitimation are distinguished: 1) ‘authorization’, legitimation by reference to the authority of tradition, custom and law, and of persons in whom institutional authority is vested; 2) ‘moral evaluation’, legitimation by reference to discourses of value; 3) rationalization, legitimation by reference to the goals and uses of institutionalized social action, and to the social knowledges that endow them with cognitive validity; and 4) mythopoesis, legitimation conveyed through narratives whose outcomes reward legitimate actions and punish non-legitimate actions. Examples are drawn from texts legitimating or de-legitimating compulsory education, including children’s books, brochures for parents, teacher training texts, and media texts.
Resolution of Arterial Stenosis in a Patient With Periarterial Neurocysticercosis Treated With Oral Prednisone
Authors: Bouldin Anthony , Pinter Joseph D.
Published: February 2007

Neurocysticercosis is the most common parasitic infection of the central nervous system. Neurovascular complications have been recognized as a frequent complication, with up to 10% of strokes in endemic areas being secondary to neurocysticercosis. We report a case of acute transient left hemichorea in an 11-year-old boy with cerebral cysticercosis involving the right middle cerebral artery. Brain magnetic resonance imaging (MRI) revealed T2-weighted hyperintensity and gadolinium enhancement in the area surrounding the M1 segment of the right middle cerebral artery. Magnetic resonance angiography showed severe narrowing of the vessel at this site acutely. After treatment with a 1-month course of oral prednisone and initiation of aspirin, our patient had no recurrence of abnormal movements and follow-up magnetic resonance angiography and transcranial Doppler ultrasonography showed resolution of stenosis of the M1 segment.
Interrater Reliability of Modified Ashworth Scale and Modified Tardieu Scale in Children With Spastic Cerebral Palsy
Authors: Yam Winnie Ka Ling , Leung Milan So Mei
Published: February 2007

Resistance to passive movement in children with spastic cerebral palsy was assessed by two raters using the Modified Ashworth Scale and the Modified Tardieu Scale. Four muscle groups in the lower limbs were tested using a standardized procedure. Interrater reliability of the scales was evaluated by the intraclass correlation coefficient. Seventeen children, with a mean age of 7 years 9 months, were included. Two children were rated twice. The intraclass correlation coefficients of both scales were low and did not reach the acceptable limit of 0.75. Caution should be used when these scales are applied.
Botulinum Toxin A Injection for Spasticity in Diplegic-Type Cerebral Palsy
Authors: El Ozlem , Peker Ozlen , Kosay Can , Iyilikci Leyla , Bozan Ozgur , Berk Haluk
Published: February 2007

Botulinum toxin type A can be both safe and effective in relieving spasticity in pediatric patients with cerebral palsy. In our prospective study, we evaluated the functional effect of botulinum toxin A in spastic diplegic-type cerebral palsy. Patients were examined on enrollment and at 1, 3, and 6 months after injection. Passive dorsiflexion of the ankle joint was measured using a goniometer as an angle of possible maximal dorsiflexion with the knee extended and flexed. Spasticity was graded using the Modified Ashworth Scale. Selective motor control at the ankle was assessed, and observational gait analysis was done. The functional status of the patients was determined by using the gross motor classification system. Botulinum toxin A was injected into the gastrocnemius muscle in all patients, and in four patients with concomitant jump knee gait, a hamstring muscle injection was added. Fourteen patients were included in the study. The mean age was 58.81 6 15.34 months. Following injection, spasticity was clinically decreased and statistically significant improvement was noticed in all clinical parameters after 1, 3, and 6 months of injection. The improvement in the clinical parameters decreased after 6 months but not to the baseline. One patient was Level II, four patients were Level III, and six patients were Level IV according to the Gross Motor Function Classification System at baseline. Improvement in the gross motor classification system is continued after 6 months in 12 children. The main goal of spasticity treatment in cerebral palsy is functional improvement. In our study, most of our patients had functional improvement according to the gross motor function classification system and did not change at 6 months.
De Novo Duplication of Chromosome 13(q32-q34) in a Child With Developmental Delay
Authors: Milani Donatella , D'Arrigo Stefano , Guerneri Silvana , Selicorni Angelo , Riva Daria , Pantaleoni Chiara
Published: February 2007

We report the case of a child affected by a duplication of chromosome 13(q32-q34). This cytogenetic abnormality is rarely described in the literature. The description of our patient's characteristics might contribute to a better phenotype definition.
Fragile X Syndrome and Cerebral Perfusion Abnormalities: Single-Photon Emission Computed Tomographic Study
Authors: Kabakus Nimet , Aydin Mustafa , Akin Haluk , Balci Tansel Ansal , Kurt Abdullah , Kekilli Ersoy
Published: February 2007

Fragile X syndrome is an inherited disorder caused by a defective gene on the X chromosome. It is associated with developmental or behavioral symptoms and various degrees of mental retardation. Morphologic abnormalities and altered perfusion of various brain areas can underlie these functional disturbances. The aim of this study was to investigate the cerebral perfusion state in patients with fragile X syndrome using single-photon emission computed tomography (SPECT). Structural and functional assessment was also performed by magnetic resonance imaging (MRI) and electroencephalography (EEG). Eight boys with cytogenetically confirmed fragile X syndrome (mean age 8.8 ± 4.4 years, range 5–18 years), were included. All patients had mental retardation, with a mean IQ of 58.9 ± 8.8 (range 40–68), and additional neurobehavioral symptoms. SPECT revealed cerebral perfusion abnormalities in six patients (75%), most commonly in the frontoparietotemporal area and prominent in the right hemisphere. The SPECT and EEG findings were concordant: hypoperfused areas in SPECT corresponded to regions of persistent slow-wave paroxysms on EEG. On the other hand, cranial MRI was abnormal qualitatively only in two patients (25%) showing cerebellar and vermal hypoplasia and cerebral hemispheric asymmetry. Our results indicate that cerebral perfusion abnormalities, which are correlated with electrophysiologic findings but not necessarily with anatomic abnormalities, can underlie the pathogenesis of the clinical findings observed in fragile X syndrome.
Clinical and Biochemical Studies on Chinese Patients With Methylmalonic Aciduria
Authors: Yang Yanling , Sun Fang , Song Jinqing , Hasegawa Yuki , Yamaguchi Seiji , Zhang Yuehua , Jiang Yuwu , Qin Jiong , Wu Xiru
Published: February 2007

Methylmalonic aciduria is a common organic aciduria disease. Recently, gas chromatography–mass spectrometry has been used to diagnose methylmalonic aciduria in China. Often, however, the diagnosis of methylmalonic aciduria is delayed because of a lack of technical expertise and the limited experience of general clinicians in China. In this study, the natural history, clinical features, and outcome of 77 Chinese patients with methylmalonic aciduria were investigated. Of the 77 patients, 31 (40.3%) had isolated methylmalonic aciduria and 46 (59.7%) had methylmalonic aciduria combined with homocystinemia. Thus, we observed a higher rate of the combined disease than studies conducted in other countries, suggesting that it might be more common in China. Total plasma homocysteine measurement might enable differential diagnoses of methylmalonic aciduria to be distinguished. The clinical spectrum of these 77 patients with methylmalonic aciduria ranged from neonatal death and severe symptoms to benign asymptomatic organic aciduria. Neonatal and infantile onset, which was a characteristic of the majority of cases, was associated with a greater severity relative to later-onset cases. Among the 17 cases who had onset after 3 years of age, only 1 patient had isolated methylmalonic aciduria and 16 had combined methylmalonic aciduria and homocystinemia. Nine of the patients with combined methylmalonic aciduria and homocystinemia completely recovered and exhibited normal intelligence, whereas seven improved, with a mild handicap.
Meningoencephalitis as a Presentation of Kawasaki Disease
Authors: Husain Entesar , Hoque Enamul
Published: February 2007

We describe an 11-year-old boy who presented with meningoencephalitis and was found later to have Kawasaki disease. The neurologic outcome of this patient was excellent, with full recovery without any neurologic deficit. The case report is followed by a review of the neurologic associations and complications of Kawasaki disease.
Saccadic Adaptation in Children
Authors: Salman Michael S. , Sharpe James A. , Eizenman Moshe , Lillakas Linda , To Teresa , Westall Carol , Dennis Maureen , Steinbach Martin J.
Published: February 2007

Saccades are fast-orienting eye movements. Saccadic adaptation, a form of motor learning, is a corrective change in the amplitude of saccades in response to error. The aim of the study was to ascertain whether saccadic adaptation occurs in typically developing children. We recorded saccades with an infrared eye tracker in 39 children, aged 8 to 19 years, at baseline to 12-degree horizontal target steps and after an adaptive task. During the adaptive task, a saccadic hypometric error was induced. This task consisted of 200 12-degree target steps that stepped backward 3 degrees during the initial saccade and without the participants' awareness. The initial saccade triggered the back-step. This paradigm required a corrective reduction of the amplitude of the initial saccades in response to the induced error. Saccadic adaptation was achieved in 26 participants, whose mean saccadic amplitudes decreased by 13% ( P < .05). Saccadic adaptation was not influenced by age. We conclude that children as young as 8 years old have established functions of the neural circuits responsible for the motor learning required for saccadic adaptation.
Sleep, Sleepiness, and Behavior Problems in Children With Headache
Authors: Bursztein Cendrine , Steinberg Tamar , Sadeh Avi
Published: February 2007

The purpose of this study was to assess sleep, daytime sleepiness, and behavior problems in children suffering from headaches and in controls, with a special focus on the role of gender. A clinical group of 28 children with persistent headache complaints and a control group of 108 healthy children were included. Sleep was assessed by actigraphy and diaries. Behavior problems were assessed by parental reports. In comparison with the control group, the sleep quality of the clinical group was poorer and they complained more about excessive daytime sleepiness. Children suffering from headache showed higher levels of internalizing behavior problems. Gender was found to be a moderating factor for the relationships between headache and sleep. Compared with control girls, girls suffering from headaches had poorer sleep quality, whereas the opposite was true for the boys. The results highlight the importance of assessing sleep, daytime sleepiness, and psychologic adjustment in children complaining about headaches as an integral part of their routine assessment.
Anomalous Inhibitory Circuits in Cortical Tubers of Human Tuberous Sclerosis Complex Associated With Refractory Epilepsy: Aberrant Expression of Parvalbumin and Calbindin-D28k in Dysplastic Cortex
Authors: Valencia Ignacio , Legido Agustin , Yelin Karina , Khurana Divya , Kothare Sanjeev V. , Katsetos Christos D.
Published: February 2007

Damage or loss of inhibitory cortical γ-aminobutyric acid (GABA)ergic interneurons is associated with impaired inhibitory control of neocortical pyramidal cells, leading to hyperexcitability and epileptogenesis. The calcium binding proteins parvalbumin and calbindin-D28k are expressed in subpopulations of GABAergic local circuit neurons in the neocortex and can serve as neuronotypic markers. Parvalbumin and calbindin-D28k facilitate the neuron's ability to sustain firing and provide neuroprotection. The goal of this study was to assess the hitherto unknown status of inhibitory interneurons in cortical tubers of human tuberous sclerosis complex. Surgically excised cortical tubers from three patients with tuberous sclerosis complex were evaluated immunohistochemically with antibodies to parvalbumin and calbindin-D28k. Cortical specimens from young patients with intractable seizures, including microdysgenesis (n = 3), postischemic cortical scarring (n = 1), porencephaly (n = 1), postictal gliosis (n = 3), and low-grade neuronal or glial tumors (n = 5), were also examined for comparison. In cortical tubers, calcium binding protein immunoreactivities (calbindin-D28k > parvalbumin) were present in medium or large-size dysplastic neurons, whereas giant or ballooned cells were parvalbumin or calbindin-D28k negative. In microdysgenesis, a nearly normal number of parvalbumin-positive neurons and a decreased number of calbindin-D28k-positive neurons were present. In peritumoral but more so in gliotic cortex, a coordinate decrease of parvalbumin and calbindin-D28k immunoreactivities was present. Our findings indicate that the expression of parvalbumin or calbindin-D28k by subpopulations of dysplastic neurons in cortical tubers is aberrant and denotes dysfunctional inhibitory circuits inept for excitoprotection.
Huntington Disease in a 9-Year-Old Boy: Clinical Course and Neuropathologic Examination
Authors: Wojaczyńska-Stanek Katarzyna , Adamek Dariusz , Marszał Elżbieta , Hoffman-Zacharska Dorota
Published: February 2007

Huntington disease is a dominantly inherited, neurodegenerative disorder, usually with onset in the fourth to fifth decade of life but in a small proportion of patients before the age of 20 years. The early-onset form, juvenile Huntington disease, is clinically different from that of more common adult-onset forms and includes cognitive decline, parkinsonism, myoclonus, and seizures. We report a case of a boy with juvenile Huntington disease with a very early age at disease onset (3 years). The suspected clinical diagnosis was confirmed by DNA analysis, which revealed (CAG)n expansion into the range characteristic of juvenile Huntington disease (95 repeats). The clinical course of the disease was typical for the juvenile form of Huntington disease, but the diagnosis was not so obvious because there was no history of any neurodegenerative disorder in the family. The child died at the age of 11 years. The detailed neuropathologic investigations performed postmortem showed the characteristic features of Huntington disease. As the patient's de novo mutation was very unlikely to occur, genetic counseling and the possibility of predictive testing were proposed to the family. Indirect molecular data indicate the familial character of the disease, with strong anticipation of transmission.
Minimus: a fast, lightweight genome assembler
Authors: Sommer Daniel D , Delcher Arthur L , Salzberg Steven L , Pop Mihai
Published: February 2007

Background

Genome assemblers have grown very large and complex in response to the need for algorithms to handle the challenges of large whole-genome sequencing projects. Many of the most common uses of assemblers, however, are best served by a simpler type of assembler that requires fewer software components, uses less memory, and is far easier to install and run.

Results

We have developed the Minimus assembler to address these issues, and tested it on a range of assembly problems. We show that Minimus performs well on several small assembly tasks, including the assembly of viral genomes, individual genes, and BAC clones. In addition, we evaluate Minimus' performance in assembling bacterial genomes in order to assess its suitability as a component of a larger assembly pipeline. We show that, unlike other software currently used for these tasks, Minimus produces significantly fewer assembly errors, at the cost of generating a more fragmented assembly.

Conclusion

We find that for small genomes and other small assembly tasks, Minimus is faster and far more flexible than existing tools. Due to its small size and modular design Minimus is perfectly suited to be a component of complex assembly pipelines. Minimus is released as an open-source software project and the code is available as part of the AMOS project at Sourceforge.
Detection of the inferred interaction network in hepatocellular carcinoma from EHCO (E ncyclopedia of H epatocellular C arcinoma genes O nline)
Authors: Hsu Chun-Nan , Lai Jin-Mei , Liu Chia-Hung , Tseng Huei-Hun , Lin Chih-Yun , Lin Kuan-Ting , Yeh Hsu-Hua , Sung Ting-Yi , Hsu Wen-Lian , Su Li-Jen , Lee Sheng-An , Chen Chang-Han , Lee Gen-Cher , Lee DT , Shiue Yow-Ling , Yeh Chang-Wei , Chang Chao-Hui , Kao Cheng-Yan , Huang Chi-Ying F
Published: February 2007

Background

The significant advances in microarray and proteomics analyses have resulted in an exponential increase in potential new targets and have promised to shed light on the identification of disease markers and cellular pathways. We aim to collect and decipher the HCC-related genes at the systems level.

Results

Here, we build an integrative platform, theEncyclopedia ofHepatocellularCarcinoma genesOnline, dubbed EHCOhttp://ehco.iis.sinica.edu.tw, to systematically collect, organize and compare the pileup of unsorted HCC-related studies by using natural language processing and softbots. Among the eight gene set collections, ranging across PubMed, SAGE, microarray, and proteomics data, there are 2,906 genes in total; however, more than 77% genes are only included once, suggesting that tremendous efforts need to be exerted to characterize the relationship between HCC and these genes. Of these HCC inventories, protein binding represents the largest proportion (~25%) from Gene Ontology analysis. In fact, many differentially expressed gene sets in EHCO could form interaction networks (e.g. HBV-associated HCC network) by using available human protein-protein interaction datasets. To further highlight the potential new targets in the inferred network from EHCO, we combine comparative genomics and interactomics approaches to analyze 120 evolutionary conserved and overexpressed genes in HCC. 47 out of 120 queries can form a highly interactive network with 18 queries serving as hubs.

Conclusion

This architectural map may represent the first step toward the attempt to decipher the hepatocarcinogenesis at the systems level. Targeting hubs and/or disruption of the network formation might reveal novel strategy for HCC treatment.
Full Length Bid is sufficient to induce apoptosis of cultured rat hippocampal neurons
Authors: König Hans-Georg , Rehm Markus , Gudorf Daniel , Krajewski Stan , Gross Atan , Ward Manus W , Prehn Jochen HM
Published: February 2007

Background

Bcl-2 homology domain (BH) 3-only proteins are pro-apoptotic proteins of the Bcl-2 family that couple stress signals to the mitochondrial cell death pathways. The BH3-only protein Bid can be activated in response to death receptor activation via caspase 8-mediated cleavage into a truncated protein (tBid), which subsequently translocates to mitochondria and induces the release of cytochrome-C. Using a single-cell imaging approach of Bid cleavage and translocation during apoptosis, we have recently demonstrated that, in contrast to death receptor-induced apoptosis, caspase-independent excitotoxic apoptosis involves a translocation of full length Bid (FL-Bid) from the cytosol to mitochondria. We induced a delayed excitotoxic cell death in cultured rat hippocampal neurons by a 5-min exposure to the glutamate receptor agonist N-methyl-D-aspartate (NMDA; 300 μM).

Results

Western blot experiments confirmed a translocation of FL-Bid to the mitochondria during excitotoxic apoptosis that was associated with the release of cytochrome-C from mitochondria. These results were confirmed by immunofluorescence analysis of Bid translocation during excitotoxic cell death using an antibody raised against the amino acids 1–58 of mouse Bid that is not able to detect tBid. Finally, inducible overexpression of FL-Bid or a Bid mutant that can not be cleaved by caspase-8 was sufficient to induce apoptosis in the hippocampal neuron cultures.

Conclusion

Our data suggest that translocation of FL-Bid is sufficient for the activation of mitochondrial cell death pathways in response to glutamate receptor overactivation.
The evolutionary history of Cytochrome P450 genes in four filamentous Ascomycetes
Authors: Deng Jixin , Carbone Ignazio , Dean Ralph A
Published: February 2007

Background

The Cytochrome P450 system is important in fungal evolution for adapting to novel ecological niches. To elucidate the evolutionary process of cytochrome P450 genes in fungi with different life styles, we studied the patterns of gene gains and losses in the genomes of four filamentous Ascomycetes, including two saprotrophs (Aspergillus nidulans (AN) and Neurospora crassa (NC)) and two plant pathogens (Fusarium graminearum (FG) and Magnaporthe grisea (MG)).

Results

A total of 376 P450 genes were assigned to 168 families according to standard nomenclature. On average, only 1 to 2 genes per family were in each genome. To resolve conflicting results between different clustering analyses and standard family designation, a higher order relationship was formulated. 376 genes were clustered into 115 clans. Subsequently a novel approach based on parsimony was developed to build the evolutionary models. Based on these analyses, a core of 30 distinct clans of P450s was defined. The core clans experienced contraction in all four fungal lineages while new clans expanded in all with exception of NC. MG experienced more genes and clans gains compared to the other fungi. Parsimonious analyses unanimously supported one species topology for the four fungi.

Conclusion

The four studied fungi exhibit unprecedented diversity in their P450omes in terms of coding sequence, intron-exon structures and genome locations, suggesting a complicated evolutionary history of P450s in filamentous Ascomycetes. Clan classification and a novel strategy were developed to study evolutionary history. Contraction of core clans and expansion of novel clans were identified. The exception was the NC lineage, which exhibited pure P450 gene loss.
No association between the PREP gene and lithium responsive bipolar disorder
Authors: Mamdani Firoza , Sequeira Adolfo , Alda Martin , Grof Paul , Rouleau Guy , Turecki Gustavo
Published: February 2007

Background

Bipolar disorder (BD) is a major psychiatric condition that commonly requires prophylactic and episodic treatment. Lithium (Li) has been used for over 40 years now as an effective prophylactic agent. Response to Li treatment seems to be, at least in part, genetically determined. Although we ignore how Li specifically prevents mood episodes, it has previously been suggested that Li exerts an effect on the phosphoinositide pathway, and more recently, it has been proposed that Li may modulate prolyl endopeptidase (PREP).

Methods

In this study we carried out an association study looking at the PREP gene, located on ch 6q22. Five intronic single nucleotide polymorphisms (SNP), three coding SNPs and one SNP in the 5' UTR were investigated for their frequency in a BD sample of 180 excellent Li responders, 69 Li nonresponders and 126 controls. Genotyping was carried out using the SNaPshot reaction from Applied Biosystems, which is a modified fluorescent single base pair extension procedure.

Results

Following correction for multiple testing, no significant genotypic, allelic or estimated haplotypic differences were found between responders and nonresponders or between BD patients and controls.

Conclusion

PREP is an interesting candidate gene to investigate in genetic studies of BD, but our findings do not support the hypothesis that genetic variation in this gene plays a major role in the etiology of BD or Li response.
The links between health-related behaviors and life satisfaction in elderly individuals who prefer institutional living
Authors: Inal Serap , Subasi Feryal , Ay Serap M , Hayran Osman
Published: February 2007

Background

Life satisfaction among residents of institutions is becoming an important issue in a rapidly aging population. The aim of this cross-sectional study was to investigate the links between life satisfaction and health-related behaviors amongst functionally independent elderly people who prefer institutional living in İstanbul, Turkey.

Methods

The socio-demographic characteristics, health-related behaviors, leisure-time activities and fall histories of 133 residents of an institution in Istanbul were assessed by a structured questionnaire during face-to-face interviews. A validated life-satisfaction index questionnaire (LSI-A) was completed.

Results

The mean age of the study group was 73.9 ± 8.0 (range 60–90 years). Within the group, 22.6% had never married and 14.3% had university degrees. The majority (71.4%) were in the low income bracket. The overall mean LSI-A score was 20.3 ± 5.9. Participants who declared moderate/high income levels had a significantly higher mean LSI-A score than those in the low-income bracket (p = 0.009). Multivariate analysis of the data suggested that leisure-time activities and participation in regular physical activities are significant predictors of LSI-A scores (R2: 0.112; p = 0.005 and p = 0.02, respectively).

Conclusion

The findings imply that regular physical activity and leisure-time activities are significantly related to life satisfaction among residents in institutions. Participation in physical activity and leisure-time activity programs may help to improve the life satisfaction of elderly people living in institutions.
Evaluation of the reach and impact of the 100% Jeune youth social marketing program in Cameroon: findings from three cross-sectional surveys
Authors: Plautz Andrea , Meekers Dominique
Published: February 2007

Background

The 100% Jeune youth social marketing program in Cameroon aims to address the high STI/HIV prevalence rates and the high levels of unwanted pregnancy. This study evaluates the 100% Jeune program, analyzing its reach and impact on condom use, level of sexual activity, and predictors of condom use.

Methods

This analysis uses data from three waves of the Cameroon Adolescent Reproductive Health Survey, implemented at 18-month intervals between 2000 and 2003. The sample is restricted to unmarried youth aged 15–24; sample sizes are 1,956 youth in 2000, 3,237 in 2002, and 3,370 in 2003. Logistic regression analyses determine trends in reproductive health behavior and their predictors, as well as estimate the effect of program exposure on these variables. All regression analyses control for differences in sample characteristics.

Results

A comparison of trends over the 36-month study period shows that substantial positive changes occurred among youth. Results of dose response analyses indicate that some of these positive changes in condom use and predictors of use can be attributed to the 100% Jeune youth social marketing program. The program contributed to substantial increases in condom use, including consistent use with regular partners among youth of both sexes. Among males, it also contributed to consistent use with casual partners. While condom use increased with both regular and casual partners, levels of use are higher with the latter. Observed secular trends indicate that factors besides the 100% Jeune program also contributed to the observed improvements. Despite efforts to promote abstinence, the 100% Jeune program had no effect on levels of sexual activity or number of sexual partners. Likewise, there is no evidence that reproductive health programs for youth lead to increased sexual activity.

Conclusion

Results show that 100% Jeune successfully used a variety of mass media and interpersonal communication channels to reach a high proportion of youth throughout the intervention period. In a context in which a variety of governmental and nongovernmental partners are increasing youth-focused reproductive health programming, the 100% Jeune program reached a higher proportion of youth than did other programs. Collective efforts of multiple organizations over time can lead to improvements in adolescent reproductive health. Resources should be allocated to identify and understand predictors of abstinence and partner reduction to inform future programming decisions.
The effects of DNA methylation and histone deacetylase inhibitors on human papillomavirus early gene expression in cervical cancer, an in vitro and clinical study
Authors: de la Cruz-Hernández Erick , Pérez-Cárdenas Enrique , Contreras-Paredes Adriana , Cantú David , Mohar Alejandro , Lizano Marcela , Dueñas-González Alfonso
Published: February 2007

Background

The methylation status at the human papilloma virus (HPV) genome found in pre-invasive and invasive cervical lesions suggests that neoplastic transformation can be suppressed by gene hypermethylation, whereas hypomethylation accompanies or causes cancer progression; hence, epigenetic therapy aimed at reactivating cellular suppressor-gene expression has the potential to act as a tumor promoter by enhancing HPV oncoprotein expression in HPV-related malignancies. The objective of this study was to determine the influence of hydralazine and valproate on HPV oncogene expression in cervical cancer cell lines and the primary tumors of patients undergoing treatment with hydralazine and valproate.

Results

Overall, hydralazine and valproate either alone or combined exerted a growth inhibitory effect on cervical cancer cell lines. A cell line-specific up-regulating effect was observed on E6/E7 gene expression, which in general correlated with DNA hypomethylation and histone acetylation at the long control region (LCR). Nonetheless, E6/E7 expression was unchanged or decreased in the majority of patients with cervical cancer treated with hydralazine, valproate, or both. In some cervical cancer cell lines, these drugs led to increased transcription of p53, and increased its stabilization due to acetylation at lysines 273 and 282, which allowed a higher bax-protein transactivating effect.

Conclusion

The results of this study demonstrate that hydralazine and valproate can be safely administered to HPV-related malignancies such as cervical cancer because they do not increase viral oncoprotein expression. Most importantly, the antitumor effect of hydralazine and valproate in cervical cancer may at least partially depend on an up-regulating effect on p53 gene and on the valproate-induced hyperacetylation of p53 protein, protecting it from degradation by E6.
Pathogeneses of respiratory infections with virulent and attenuated vaccinia viruses
Authors: Hayasaka Daisuke , Ennis Francis A , Terajima Masanori
Published: February 2007

Background

Respiratory infection with the neurovirulent vaccinia virus (VV) strain Western Reserve (WR) results in an acute infection of the lung followed by dissemination of the virus to other organs and causes lethality in mice. The mechanisms of lethality are not well-understood. In this study, we analyzed virus replication and host immune responses after intranasal infection with lethal and non-lethal doses of VV using the WR strain and the less virulent Wyeth strain.

Results

The WR strain replicated more vigorously in the lung and in the brain than the Wyeth strain. There were, however, no differences between the virus titers in the brains of mice infected with the higher lethal dose and the lower non-lethal dose of WR strain, suggesting that the amount of virus replication in the brain is unlikely to be the sole determining factor of lethality. The WR strain grew better in primary mouse lung cells than the Wyeth strain. Lethal infection with WR strain was associated with a reduced number of lymphocytes and an altered phenotype of the T cells in the lung compared to non-lethal infections with the WR or Wyeth strains. Severe thymus atrophy with a reduction of CD4 and CD8 double positive T cells was also observed in the lethal infection.

Conclusion

These results suggest that the lethality induced by intranasal infection with a high dose of the WR strain is caused by the higher replication of virus in lung cells and immune suppression during the early phase of the infection, resulting in uncontrolled virus replication in the lung.
Patients with early rheumatoid arthritis exhibit elevated autoantibody titers against mildly oxidized low-density lipoprotein and exhibit decreased activity of the lipoprotein-associated phospholipase A2
Authors: Lourida Evangelia S , Georgiadis Athanasios N , Papavasiliou Eleni C , Papathanasiou Athanasios I , Drosos Alexandros A , Tselepis Alexandros D
Published: February 2007

Rheumatoid arthritis is a chronic inflammatory disease, associated with an excess of cardiovascular morbidity and mortality due to accelerated atherosclerosis. Oxidized low-density lipoprotein (oxLDL), the antibodies against oxLDL and the lipoprotein-associated phospholipase A2 (Lp-PLA2) may play important roles in inflammation and atherosclerosis. We investigated the plasma levels of oxLDL and Lp-PLA2 activity as well as the autoantibody titers against mildly oxLDL in patients with early rheumatoid arthritis (ERA). The long-term effects of immunointervention on these parameters in patients with active disease were also determined. Fifty-eight ERA patients who met the American College of Rheumatology criteria were included in the study. Patients were treated with methotrexate and prednisone. Sixty-three apparently healthy volunteers also participated in the study and served as controls. Three different types of mildly oxLDL were prepared at the end of the lag, propagation and decomposition phases of oxidation. The serum autoantibody titers of the IgG type against all types of oxLDL were determined by an ELISA method. The plasma levels of oxLDL and the Lp-PLA2 activity were determined by an ELISA method and by the trichloroacetic acid precipitation procedure, respectively. At baseline, ERA patients exhibited elevated autoantibody titers against all types of mildly oxLDL as well as low activity of the total plasma Lp-PLA2 and the Lp-PLA2 associated with the high-density lipoprotein, compared with controls. Multivariate regression analysis showed that the elevated autoantibody titers towards oxLDL at the end of the decomposition phase of oxidation and the low plasma Lp-PLA2 activity are independently associated with ERA. After immunointervention autoantibody titers against all types of oxLDL were decreased in parallel to the increase in high-density lipoprotein-cholesterol and high-density lipoprotein-Lp-PLA2 activity. We conclude that elevated autoantibody titers against oxLDL at the end of the decomposition phase of oxidation and low plasma Lp-PLA2 activity are feature characteristics of patients with ERA, suggesting an important role of these parameters in the pathophysiology of ERA as well as in the accelerated atherosclerosis observed in these patients.
Extracellular localization of galectin-3 has a deleterious role in joint tissues
Authors: Janelle-Montcalm Audrée , Boileau Christelle , Poirier Françoise , Pelletier Jean-Pierre , Guévremont Mélanie , Duval Nicolas , Martel-Pelletier Johanne , Reboul Pascal
Published: February 2007

In this study we examine the extracellular role of galectin-3 (gal-3) in joint tissues. Following intra-articular injection of gal-3 or vehicle in knee joints of mice, histological evaluation of articular cartilage and subchondral bone was performed. Further studies were then performed using human osteoarthritic (OA) chondrocytes and subchondral bone osteoblasts, in which the effect of gal-3 (0 to 10 μg/ml) was analyzed. Osteoblasts were incubated in the presence of vitamin D3 (50 nM), which is an inducer of osteocalcin, encoded by an osteoblast terminal differentiation gene. Genes of interest mainly expressed in either chondrocytes or osteoblasts were analyzed with real-time RT-PCR and enzyme immunoassays. Signalling pathways regulating osteocalcin were analyzed in the presence of gal-3. Intra-articular injection of gal-3 induced knee swelling and lesions in both cartilage and subchondral bone. On human OA chondrocytes, gal-3 at 1 μg/ml stimulated ADAMTS-5 expression in chondrocytes and, at higher concentrations (5 and 10 μg/ml), matrix metalloproteinase-3 expression. Experiments performed with osteoblasts showed a weak but bipolar effect on alkaline phosphatase expression: stimulation at 1 μg/ml or inhibition at 10 μg/ml. In the absence of vitamin D3, type I collagen alpha 1 chain expression was inhibited by 10 μg/ml of gal-3. The vitamin D3induced osteocalcin was strongly inhibited in a dose-dependent manner in the presence of gal-3, at both the mRNA and protein levels. This inhibition was mainly mediated by phosphatidylinositol-3-kinase. These findings indicate that high levels of extracellular gal-3, which could be encountered locally during the inflammatory process, have deleterious effects in both cartilage and subchondral bone tissues.
Quantifying similarity between motifs
Authors: Gupta Shobhit , Stamatoyannopoulos John A , Bailey Timothy L , Noble William Stafford
Published: February 2007

A common question within the context of de novo motif discovery is whether a newly discovered, putative motif resembles any previously discovered motif in an existing database. To answer this question, we define a statistical measure of motif-motif similarity, and we describe an algorithm, called Tomtom, for searching a database of motifs with a given query motif. Experimental simulations demonstrate the accuracy of Tomtom's E values and its effectiveness in finding similar motifs.