bluuebunny/crossref_metadata_2025 huggingface dataset:
Listening to Black Male Student Voices Using Web-Based Mentoring
Authors: Grant David G. , Dieker Lisa A.
Published: March 2010

The voices of Black male students labeled as having an emotionally disorder (ED) are seldom heard regarding their perspectives on education. By excluding their opinions, educators are missing an important aspect that could improve educational services for Black males with ED. This study was undertaken to determine the implications of web-based mentoring for Black male students with ED on factors that affected their behaviors and academic achievement. Mentoring through technology was used to engage students with ED and to provide a platform to share their thoughts. Using a case study approach, two Black males with ED in high school participated in web-based mentoring. Results of the study reveal that the participants’ behaviors and achievement were affected by negative school and home environments, but that web-based mentoring was a positive venue to support their needs.
Combining Ecobehavioral Assessment, Functional Assessment, and Response to Intervention to Promote More Effective Classroom Instruction
Authors: Watson Silvana M. R. , Gable Robert A. , Greenwood Charles R.
Published: March 2010

In this article, the authors discuss ways ecobehavioral assessment (EBA) has contributed to greater understanding of students’ response to instructional intervention and its relationship to academic learning and achievement. EBA represents a proven effective way to conduct a contextual analysis of the instructional environments, teacher and student interactions, student engagement, and specific teaching practices that promote learning. It mirrors much of the current thinking regarding functional assessment of academic behavior and response to intervention (RTI). With EBA, school personnel are able to examine various aspects of the classroom environment and instruction to determine how best to increase students’ positive response to instruction and, in turn, improve academic achievement. The authors argue that incorporating elements of EBA into the RTI model yields a more complete picture by allowing observers to identify the ecological and educational factors that promote or inhibit student academic gains. That knowledge can easily be incorporated into multitiered prevention and intervention programs in schools.
An Examination of Social Skills Instruction in the Context of Small-Group Reading
Authors: Miller Melissa A. , Fenty Nicole , Scott Terrance M. , Park Kristy Lee
Published: March 2010

Students who are socially competent are more likely to experience school success than those who are not. Students with social deficits experience frequent failures with both peers and adults and often require explicit social skills instruction. Because social skills instruction programs taught in isolation rarely result in successful skill generalization, many researchers have supported incorporating social instruction into the academic curriculum. This study evaluated the effects of providing social skills instruction during small-group guided reading instruction to three students identified as experiencing social skills deficits. Results showed positive changes in trend and level across all three students from baseline to intervention. Limitations, suggestions for teachers, and recommendations for future research are discussed.
Knowledge of Alzheimer’s Disease, Feelings of Shame, and Awareness of Services Among Korean American Elders
Authors: Yuri Jang  , Kim Giyeon , Chiriboga David
Published: March 2010

Objective: To explore predictors of knowledge of Alzheimer’s disease (AD), feelings of shame if a family member were to have AD, and awareness of AD-related services among Korean American elders. Method: Using data from 675 Korean American elders (mean age = 70.2, SD = 6.87), the study estimates hierarchical linear or logistic regression models. Results: Greater knowledge of AD is predicted by higher levels of education and acculturation. Feelings of shame associated with family members having AD are more likely to be reported by individuals with lower levels of education, acculturation, and knowledge of AD. Those who are married have greater levels of education and acculturation, and those who have a family member with AD are more aware of AD-related services. Discussion: The study findings underscore the pivotal role of education and acculturation in predicting knowledge of AD, feelings of shame, and awareness of AD-related services.
Effect of aqueous extract of Leonotis leonurus (L.) R. Br. leaves in male Wistar rats
Authors: Oyedemi SO , Yakubu MT , Afolayan AJ
Published: March 2010

The aqueous extract of the leaves of Leonotis leonurus (L.) R. Br. at the doses of 125, 250 and 500 mg/kg body weight was investigated for toxicity in male rats following administration on daily basis for 21 days. The extract did not significantly (p > .05) alter the levels of haemoglobin, packed cell volume, mean corpuscular volume, red cell distribution width, basophils, total protein, phosphorus, calcium and chloride ions of the animals. Whereas the levels of lymphocytes, eosinophils, monocytes, triacylglycerol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, atherogenic index, albumin as well as alkaline phosphatase and gamma glutamyl transferase activity were decreased by the extract, those of neutrophil, magnesium, total and conjugated bilirubin, alanine and aspartate aminotransferase as well as liver and kidney body weight ratios increased. There was decrease in the mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration and cholesterol only at the 500 mg/kg body weight of the extract, whereas the large unstained cells, sodium ions, white blood cells and uric acid increased only at 250 and 500 mg/kg body weight of the extract, respectively. The urea, creatinine and potassium increased only at 125 mg/kg body weight of the extract while the globulin content was elevated only at 500 mg/kg body weight of the extract. The doses did not produce any definite pattern of effect on the red blood cells and platelets. These alterations by the aqueous extract of L. leonurus leaves on the haematological together with the liver and kidney functional indices suggests parameter and dose-selective effects of the extract and will have consequential effects on the normal functioning of the blood system, kidney and liver of the animals. The extract is also unlikely to predispose the animals to cardiovascular risk when repeatedly consumed on daily basis at the doses investigated for 21 days. Therefore, the aqueous extract of L. leonurus leaves may not be ‘safe’ as oral remedy in male rats.
The Magical Mystery Four
Authors: Cowan Nelson
Published: March 2010

Working memory storage capacity is important because cognitive tasks can be completed only with sufficient ability to hold information as it is processed. The ability to repeat information depends on task demands but can be distinguished from a more constant, underlying mechanism: a central memory store limited to 3 to 5 meaningful items for young adults. I discuss why this central limit is important, how it can be observed, how it differs among individuals, and why it may exist.
The Darker Side of Social Anxiety
Authors: Kashdan Todd B. , McKnight Patrick E.
Published: March 2010

The majority of definitions, research studies, and treatment programs that focus on social anxiety characterize the prototypical person with the disorder as shy, submissive, inhibited, and risk averse. This stereotype, however, has been challenged recently. Specifically, a subset of people with social anxiety who are aggressive, impulsive novelty seekers deviate from that prototype. People with this atypical profile show greater functional impairment and are less likely to complete or fare well in treatment compared with inhibited socially anxious people. The difference between these two groups of people with social anxiety cannot be explained by the severity, type, or number of social fears, nor by co-occurring anxiety and mood disorders. Conclusions about the nature, course, and treatment of social anxiety may be compromised by not attending to diverse behaviors and self-regulatory styles. These concerns may be compounded in neurobiological and clinical studies of people with social anxiety problems that rely on smaller samples to make claims about brain patterns and the efficacy of particular treatments.
Ape and Human Cognition
Authors: Tomasello Michael , Herrmann Esther
Published: March 2010

Humans share the vast majority of their cognitive skills with other great apes. In addition, however, humans have also evolved a unique suite of cognitive skills and motivations—collectively referred to as shared intentionality—for living collaboratively, learning socially, and exchanging information in cultural groups.
The Neural Bases of Infant Attention
Authors: Richards John E. , Reynolds Greg D. , Courage Mary L.
Published: March 2010

The development of attention in the infant can be characterized by changes in overall arousal (attentiveness) and by changes in attention’s effect on specific cognitive processes (e.g., stimulus orienting, spatial selection, recognition memory). These attention systems can be identified using behavioral and psychophysiological methods. The development of infant attention is thought to be closely related to changes in the neural systems underlying attention control. The recent application of cortical source analysis of event-related potentials (ERP) and structural magnetic resonance imaging (MRI) has led to the identification of some of these the neural systems.
Focal and diffuse cortical degenerative changes in a marmoset model of multiple sclerosis
Authors: Pomeroy IM , Jordan EK , Frank JA , Matthews PM , Esiri MM
Published: March 2010

Background: Degenerative features, such as neuronal, glial, synaptic and axonal loss, have been identified in neocortical and other grey matter structures in patients with multiple sclerosis, but mechanisms for neurodegeneration are unclear. Cortical demyelinating lesions are a potential cause of this degeneration, but the pathological and clinical significance of these lesions is uncertain as they remain difficult to identify and study in vivo. In this study we aimed to describe and quantify cellular and subcellular pathology in the cortex of myelin oligodendrocyte glycoprotein-induced marmoset experimental autoimmune encephalomyelitis using quantitative immunohistochemical methods.

Results: We found evidence of diffuse axonal damage occurring throughout cortical grey matter with evidence for synaptic loss and gliosis and a 13.6% decrease in neuronal size and occurring in deep cortical layers. Evidence of additional axonal damage and a 29.6—36.5% loss of oligodendrocytes was found in demyelinated cortical lesions. Leucocortical lesions also showed neuronal loss of 22.2% and a 15.8% increase in oligodendrocyte size.

Conclusions: The marmoset experimental autoimmune encephalomyelitis model, therefore, shows both focal and generalized neurodegeneration. The generalized changes cannot be directly related to focal lesions, suggesting that they are either a consequence of diffusible inflammatory factors or secondary to remote lesions acting through trans-synaptic or retrograde degeneration.
Interleukin 7 receptor alpha polymorphism rs6897932 and susceptibility to multiple sclerosis in the Western Balkans
Authors: Stanković Aleksandra , Dinčić Evica , Ristić Smiljana , Lovrečić Luca , Starčević Cizmarević Nada , Djurić Tamara , Sepčić Juraj , Kapović Miljenko , Raičević Ranko , Peterlin Borut , Alavantić Dragan , Živković Maja
Published: March 2010

The interleukin 7 receptor alpha single nucleotide polymorphism rs6897932 was identified as a multiple sclerosis susceptibility-modifying polymorphism in genome-wide and gene scan studies, mainly in populations in western countries.

The aim of this study was to investigate the association of interleukin 7 receptor alpha rs6897932 with multiple sclerosis in populations from the Western Balkans: Serbia, Croatia, and Slovenia.

A total of 678 unrelated white patients and 597 unrelated, ethnically matched healthy controls were included in the study. Genotyping was performed by real-time polymerase chain reaction.

We found no significant difference in genotype or allele frequencies between controls and patients with multiple sclerosis either separately in Serbian, Croatian, and Slovenian populations or in the whole sample from the Western Balkans. The odds ratio for multiple sclerosis in this study was 1.04 (0.86—1.25) for the C allele.

It is known that demographic as well as environmental factors have a substantial role in multiple sclerosis development, as well as population genetic background. The results of this study indicate that other types of genome variants should be required for the development and/or progression of multiple sclerosis, which may vary among populations.
Early cognitive impairment in multiple sclerosis predicts disability outcome several years later
Authors: Deloire Mathilde , Ruet Aurélie , Hamel Delphine , Bonnet Melissa , Brochet Bruno
Published: March 2010

Cognition is frequently impaired in the early stages of multiple sclerosis (MS). The predictive value of cognitive impairment on disability is unknown. The objective of this study was to correlate cognitive impairment and the progression of disability over 7 years. Forty-five patients, recruited after MS diagnosis, were followed for 7 years by yearly Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC) evaluations and were classified as cognitively impaired (CI) or unimpaired (CU) according to neuropsychological testing at baseline. At baseline, 47.8% of patients were CI, with deficits in mainly memory and information processing speed (IPS). The baseline EDSS correlated significantly with one IPS test. The EDSS, but not the MSFC, deteriorated significantly over the 7 years in the whole group and the CI group, but not the CU group. A multivariate analysis showed correlations between the EDSS change over 5 and 7 years and two baseline tests evaluating IPS and verbal memory. The deterioration of the EDSS after 7 years was significantly correlated with verbal memory testing at baseline after adjustment for age and baseline EDSS. In conclusion, in this sample of MS patients early in the disease, the baseline IPS and verbal memory impairments predict the EDSS score 5 and 7 years later.
Accuracy of MRI criteria for dissemination in space for the diagnosis of multiple sclerosis in patients with clinically isolated syndromes
Authors: Díaz-Sánchez María , Mayra Gómez-Moreno S. , Asunción Morales-Otal M. , Ramos-González Ana , Benito-León Julián
Published: March 2010

The MRI Barkhof—Tintoré criteria have proved to be highly specific for predicting conversion to clinically definite multiple sclerosis in patients with clinically isolated syndromes (CIS), but lacked an optimal sensitivity. In order to improve the accuracy of early multiple sclerosis diagnosis, new imaging criteria have been proposed by Swanton et al. We aimed to evaluate the accuracy of both MRI criteria for dissemination in space to predict conversion from CIS to clinically definite multiple sclerosis. We studied 79 CIS patients with baseline MRI performed within the first 3 months after onset. The sensitivity and specificity of both MRI criteria to predict conversion to clinically definite multiple sclerosis were analysed. The time to develop clinically definite multiple sclerosis from CIS onset, according to each imaging criteria, was studied by Kaplan—Meier survival curves. The overall conversion rate was 75.7% with a median follow-up of 57 months. Barkhof— Tintoré’s criteria showed a sensitivity of 71.9% and a specificity of 77.2%. Swanton’s criteria had a sensitivity of 91.2% and a specificity of 68.1%. Both MRI criteria identified CIS patients with higher risk and faster conversion to clinically definite multiple sclerosis. Swanton’s criteria are simpler and more sensitive than Barkhof—Tintoré‘s criteria, with a slight decrease in specificity. These results reinforce their use in multiple sclerosis diagnosis.
Synergistic inhibitory effect of angiotensin II receptor blocker and thiazide diuretic on the tissue renin-angiotensin-aldosterone system
Authors: Yoshimura Michihiro , Kawai Makoto
Published: March 2010

ARBs are conceptually more potent in a high renin state than in a low renin state at blood pressure reduction and cardiovascular protection, whereas the potency of thiazide diuretics in the contrary. However, the additive effect of the agents when used in combination remains unclear. Thus, the goal of the present review was to analyse available data to explain the mechanistic actions of the ARB-thiazide diuretic combination. Although the circulating renin-angiotensin-aldosterone system (RAAS) has been well characterised in the context of cardiovascular disease, recent attention has also focused on the role of the tissue RAAS. For example, both angiotensin II and aldosterone are produced in small amounts within cardiac tissue, and the angiotensin II type 1 receptor is widely distributed and activated within cardiovascular tissues. Recent reports also suggest that the mineralocorticoid receptor is activated through Rac1 GTP-ase in high salt-intake rats. Thus, many components of the RAAS are activated in cardiovascular tissues under high salt-intake conditions, and a low salt diet or use of diuretics likely suppresses the tissue RAAS. Since ARBs can block the effect of both tissue angiotensin II and circulating angiotensin II, it follows that the combination of an ARB and a thiazide diuretic results in synergistic inhibition of the tissue RAAS.
Rational design of a fully active, long-acting PEGylated factor VIII for hemophilia A treatment
Authors: Mei Baisong , Pan Clark , Jiang Haiyan , Tjandra Hendri , Strauss Jonathan , Chen Yaoqi , Liu Tongyao , Zhang Xin , Severs Joanne , Newgren Jim , Chen Jianmin , Gu Jian-Ming , Subramanyam Babu , Fournel Michael A. , Pierce Glenn F. , Murphy John E.
Published: March 2010

A long-acting factor VIII (FVIII) as a replacement therapy for hemophilia A would significantly improve treatment options for patients with hemophilia A. To develop a FVIII with an extended circulating half-life, but without a reduction in activity, we have engineered 23 FVIII variants with introduced surface-exposed cysteines to which a polyethylene glycol (PEG) polymer was specifically conjugated. Screening of variant expression level, PEGylation yield, and functional assay identified several conjugates retaining full in vitro coagulation activity and von Willebrand factor (VWF) binding.PEGylated FVIII variants exhibited improved pharmacokinetics in hemophilic mice and rabbits. In addition, pharmacokinetic studies in VWF knockout mice indicated that larger molecular weight PEG may substitute for VWF in protecting PEGylated FVIII from clearance in vivo. In bleeding models of hemophilic mice, PEGylated FVIII not only exhibited prolonged efficacy that is consistent with the improved pharmacokinetics but also showed efficacy in stopping acute bleeds comparable with that of unmodified rFVIII. In summary site-specifically PEGylated FVIII has the potential to be a long-acting prophylactic treatment while being fully efficacious for on-demand treatment for patients with hemophilia A.
Whole genome analysis of p38 SAPK-mediated gene expression upon stress
Authors: Ferreiro Isabel , Joaquin Manel , Islam Abul , Gomez-Lopez Gonzalo , Barragan Montserrat , Lombardía Luís , Domínguez Orlando , Pisano David G , Lopez-Bigas Nuria , Nebreda Angel R , Posas Francesc
Published: March 2010

Background

Cells have the ability to respond and adapt to environmental changes through activation of stress-activated protein kinases (SAPKs). Although p38 SAPK signalling is known to participate in the regulation of gene expression little is known on the molecular mechanisms used by this SAPK to regulate stress-responsive genes and the overall set of genes regulated by p38 in response to different stimuli.

Results

Here, we report a whole genome expression analyses on mouse embryonic fibroblasts (MEFs) treated with three different p38 SAPK activating-stimuli, namely osmostress, the cytokine TNFα and the protein synthesis inhibitor anisomycin. We have found that the activation kinetics of p38α SAPK in response to these insults is different and also leads to a complex gene pattern response specific for a given stress with a restricted set of overlapping genes. In addition, we have analysed the contribution of p38α the major p38 family member present in MEFs, to the overall stress-induced transcriptional response by using both a chemical inhibitor (SB203580) and p38α deficient (p38α-/-) MEFs. We show here that p38 SAPK dependency ranged between 60% and 88% depending on the treatments and that there is a very good overlap between the inhibitor treatment and the ko cells. Furthermore, we have found that the dependency of SAPK varies depending on the time the cells are subjected to osmostress.

Conclusions

Our genome-wide transcriptional analyses shows a selective response to specific stimuli and a restricted common response of up to 20% of the stress up-regulated early genes that involves an important set of transcription factors, which might be critical for either cell adaptation or preparation for continuous extra-cellular changes. Interestingly, up to 85% of the up-regulated genes are under the transcriptional control of p38 SAPK. Thus, activation of p38 SAPK is critical to elicit the early gene expression program required for cell adaptation to stress.
Genome-wide transcription factor binding site/promoter databases for the analysis of gene sets and co-occurrence of transcription factor binding motifs
Authors: Veerla Srinivas , Ringnér Markus , Höglund Mattias
Published: March 2010

Background

The use of global gene expression profiling is a well established approach to understand biological processes. One of the major goals of these investigations is to identify sets of genes with similar expression patterns. Such gene signatures may be very informative and reveal new aspects of particular biological processes. A logical and systematic next step is to reduce the identified gene signatures to the regulatory components that induce the relevant gene expression changes. A central issue in this context is to identify transcription factors, or transcription factor binding sites (TFBS), likely to be of importance for the expression of the gene signatures.

Results

We develop a strategy that efficiently produces TFBS/promoter databases based on user-defined criteria. The resulting databases constitute all genes in the Santa Cruz database and the positions for all TFBS provided by the user as position weight matrices. These databases are then used for two purposes, to identify significant TFBS in the promoters in sets of genes and to identify clusters of co-occurring TFBS. We use two criteria for significance, significantly enriched TFBS in terms of total number of binding sites for the promoters, and significantly present TFBS in terms of the fraction of promoters with binding sites. Significant TFBS are identified by a re-sampling procedure in which the query gene set is compared with typically 105 gene lists of similar size randomly drawn from the TFBS/promoter database. We apply this strategy to a large number of published ChIP-Chip data sets and show that the proposed approach faithfully reproduces ChIP-Chip results. The strategy also identifies relevant TFBS when analyzing gene signatures obtained from the MSigDB database. In addition, we show that several TFBS are highly correlated and that co-occurring TFBS define functionally related sets of genes.

Conclusions

The presented approach of promoter analysis faithfully reproduces the results from several ChIP-Chip and MigDB derived gene sets and hence may prove to be an important method in the analysis of gene signatures obtained through ChIP-Chip or global gene expression experiments. We show that TFBS are organized in clusters of co-occurring TFBS that together define highly coherent sets of genes.
Validation of reference genes for gene expression analysis in chicory (Cichorium intybus) using quantitative real-time PCR
Authors: Maroufi Asad , Van Bockstaele Erik , De Loose Marc
Published: March 2010

Background

Quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) is a sensitive technique for quantifying gene expression levels. One or more appropriate reference genes must be selected to accurately compare mRNA transcripts across different samples and tissues. Thus far, only actin-2 has been used as a reference gene for qRT-PCR in chicory, and a full comparison of several candidate reference genes in chicory has not yet been reported.

Results

Seven candidate reference genes, including nicotinamide adenine dinucleotide dehydrogenase (NADHD), actin (ACT), β-tubulin (TUB), glyceraldehyde-3-phosphate-dehydrogenase (GADPH), histone H3 (H3), elongation factor 1-alpha (EF) and 18S rRNA (rRNA) were selected to study the expression stability for normalisation of gene expression in chicory. Primer specificity and amplification efficiency were verified for each gene. The expression stability of these genes was analysed across chicory root and leaf tissues using geNorm, NormFinder and BestKeeper software. ACT, EF, and rRNA were the most stable genes as identified by the three different analysis methods. In addition, the use of ACT, EF and GAPDH as reference genes was illustrated by analysing 1-FEHII (FEHII) expression in chicory root and leaf tissues. These analyses revealed the biological variation in FEHII transcript expression among the tissues studied, and between individual plants.

Conclusions

geNorm, NormFinder, and BestKeeper analyses indicated that ACT, EF and rRNA had the highest expression stability across leaf and root tissues, while GAPDH and NADHD showed relatively low expression stability. The results of this study emphasise the importance of validating reference genes for qRT-PCR analysis in chicory. The use of the most stable reference genes such as ACT and EF allows accurate normalisation of gene expression in chicory leaf and root tissues.
Genome-wide gene copy number and expression analysis of primary gastric tumors and gastric cancer cell lines
Authors: Junnila Siina , Kokkola Arto , Karjalainen-Lindsberg Marja-Liisa , Puolakkainen Pauli , Monni Outi
Published: March 2010

Background

Gastric cancer is one of the most common malignancies worldwide and the second most common cause of cancer related death. Gene copy number alterations play an important role in the development of gastric cancer and a change in gene copy number is one of the main mechanisms for a cancer cell to control the expression of potential oncogenes and tumor suppressor genes.

Methods

To highlight genes of potential biological and clinical relevance in gastric cancer, we carried out a systematic array-based survey of gene expression and copy number levels in primary gastric tumors and gastric cancer cell lines and validated the results using an affinity capture based transcript analysis (TRAC assay) and real-time qRT-PCR.

Results

Integrated microarray analysis revealed altogether 256 genes that were located in recurrent regions of gains or losses and had at least a 2-fold copy number- associated change in their gene expression. The expression levels of 13 of these genes, ALPK2, ASAP1, CEACAM5, CYP3A4, ENAH, ERBB2, HHIPL2, LTB4R, MMP9, PERLD1, PNMT, PTPRA, and OSMR, were validated in a total of 118 gastric samples using either the qRT-PCR or TRAC assay. All of these 13 genes were differentially expressed between cancerous samples and nonmalignant tissues (p < 0.05) and the association between copy number and gene expression changes was validated for nine (69.2%) of these genes (p < 0.05).

Conclusion

In conclusion, integrated gene expression and copy number microarray analysis highlighted genes that may be critically important for gastric carcinogenesis. TRAC and qRT-PCR analyses validated the microarray results and therefore the role of these genes as potential biomarkers for gastric cancer.
Hepatotoxicity and effectiveness of a Nevirapine-based antiretroviral therapy in HIV-infected patients with or without viral hepatitis B or C infection in Cameroon
Authors: Mbougua Jules B Tchatchueng , Laurent Christian , Kouanfack Charles , Bourgeois Anke , Ciaffi Laura , Calmy Alexandra , Gwet Henri , Koulla-Shiro Sinata , Ducos Jacques , Mpoudi-Ngolé Eitel , Molinari Nicolas , Delaporte Eric
Published: March 2010

Background

Coinfection with hepatitis B virus (HBV) or hepatitis C virus (HCV) in HIV-infected patients receiving a commonly used nevirapine-based antiretroviral therapy is a major concern for African clinicians owing to its high prevalence, the infrequent testing and treatment of viral hepatitis, and the impact of liver disease on the tolerability and effectiveness of anti-HIV treatment. We compared the hepatotoxicity and the immunological, virological and clinical effectiveness of a nevirapine-based antiretroviral therapy between patients infected with HIV only and patients coinfected with hepatitis B or C virus in Cameroon.

Methods

A retrospective cohort study was conducted among HIV-1-infected patients. Plasma HBV DNA and HCV RNA were tested in positive or indeterminate samples for HBsAg or HCV antibodies, respectively. All patients received nevirapine and lamivudine plus stavudine or zidovudine.

Results

Of 169 HIV-1-infected patients with a median baseline CD4 count of 135 cells/mm3(interquartile range [IQR] 67-218), 21% were coinfected with HBV or HCV. In coinfected patients, the median viral load was 2.47 × 107IU/mL for HBV (IQR 3680-1.59 × 108) and 928 000 IU/mL for HCV (IQR 178 400-2.06 × 106). Multivariate analyses showed that the risk of hepatotoxicity was 2-fold higher in coinfected patients (p< 0.01). The response to antiretroviral therapy was however comparable between monoinfected and coinfected patients in terms of CD4 cell count increase (p= 0.8), HIV-1 viral load below 400 copies/mL (p= 0.9), death (p= 0.3) and death or new AIDS-defining event (p= 0.1). Nevirapine was replaced by a protease inhibitor in 4 patients owing to hepatotoxicity.

Conclusion

This study suggests that the nevirapine-based antiretroviral therapy could be used safely as first-line treatment in patients with low CD4 cell count in Africa despite frequent coinfections with HBV or HCV and infrequent testing of these infections. Although testing for HBV and HCV should be systematically performed before initiating antiretroviral therapy, transaminases elevations at baseline or during treatment should be a decisive argument for testing when hepatitis status is unknown.
Anti-tumor therapy with macroencapsulated endostatin producer cells
Authors: Rodrigues Danielle B , Chammas Roger , Malavasi Natália V , da Costa Patrícia LN , Chura-Chambi Rosa M , Balduino Keli N , Morganti Ligia
Published: March 2010

Background

Theracyte is a polytetrafluoroethylene membrane macroencapsulation system designed to induce neovascularization at the tissue interface, protecting the cells from host's immune rejection, thereby circumventing the problem of limited half-life and variation in circulating levels. Endostatin is a potent inhibitor of angiogenesis and tumor growth. Continuous delivery of endostatin improves the efficacy and potency of the antitumoral therapy. The purpose of this study was to determine whether recombinant fibroblasts expressing endostatin encapsulated in Theracyte immunoisolation devices can be used for delivery of this therapeutic protein for treatment of mice bearing B16F10 melanoma and Ehrlich tumors.

Results

Mice were inoculated subcutaneously with melanoma (B16F10 cells) or Ehrlich tumor cells at the foot pads. Treatment began when tumor thickness had reached 0.5 mm, by subcutaneous implantation of 107 recombinant encapsulated or non-encapsulated endostatin producer cells. Similar melanoma growth inhibition was obtained for mice treated with encapsulated or non-encapsulated endostatin-expressing cells. The treatment of mice bearing melanoma tumor with encapsulated endostatin-expressing cells was decreased by 50.0%, whereas a decrease of 56.7% in tumor thickness was obtained for mice treated with non-encapsulated cells. Treatment of Ehrlich tumor-bearing mice with non-encapsulated endostatin-expressing cells reduced tumor thickness by 52.4%, whereas lower tumor growth inhibition was obtained for mice treated with encapsulated endostatin-expressing cells: 24.2%. Encapsulated endostatin-secreting fibroblasts failed to survive until the end of the treatment. However, endostatin release from the devices to the surrounding tissues was confirmed by immunostaining. Decrease in vascular structures, functional vessels and extension of the vascular area were observed in melanoma microenvironments.

Conclusions

This study indicates that immunoisolation devices containing endostatin-expressing cells are effective for the inhibition of the growth of melanoma and Ehrlich tumors.

Macroencapsulation of engineered cells is therefore a reliable platform for the refinement of innovative therapeutic strategies against tumors.
Acute variceal bleeding in a patient with idiopathic myelofibrosis successfully treated with endoscopic variceal band ligation and chemotherapy: a case report
Authors: Tamaki Kumiko , Otaka Michiro , Sakamoto Naoto , Matsumoto Kenshi , Yamashina Shunhei , Watanabe Sumio
Published: March 2010

Introduction

Idiopathic myelofibrosis is a chronic myeloproliferative disorder characterized by leukoerythroblastosis, massive splenomegaly, and increases in the reticular and collagen fibers in the bone marrow. Portal hypertension is observed in some patients with idiopathic myelofibrosis. Gastrointestinal hemorrhages, which are due mostly to the rupture of the esophageal varices, have been sporadically reported to be an infrequent complication of idiopathic myelofibrosis.

Case presentation

We report a case of a Japanese 63-year-old woman with myelofibrosis and variceal hemorrhage, with a background of concomitant portal and pulmonary hypertension. She was successfully treated through a combination of endoscopic variceal ligation and chemotherapy.

Conclusion

This is the first known report on the successful application of endoscopic variceal ligation and chemotherapy as the therapeutic procedure for an esophageal variceal hemorrhage in a patient with myelofibrosis.
Detecting variable (V), diversity (D) and joining (J) gene segment recombination using a two-colour fluorescence system
Authors: Scott Gina B , de Wynter Erika A , Cook Graham P
Published: March 2010

Background

Diversity of immunoglobulins and the T cell antigen receptors is achieved via the recombination activating gene (RAG)-mediated rearrangement of variable (V), diversity (D) and joining (J) gene segments, and this underpins the efficient recognition of a seemingly limitless array of antigens. Analysis of V(D)J recombination activity is typically performed using extrachromosomal recombination substrates that are recovered from transfected cells and selected using bacterial transformation. We have developed a two-colour fluorescence-based system that simplifies detection of both deletion and inversion joining events mediated by RAG proteins.

Results

This system employs two fluorescent reporter genes that differentially mark unrearranged substrates and those that have undergone RAG-mediated deletion or inversion events. The recombination products bear the hallmarks of true V(D)J recombination and activity can be detected using fluorescence microscopy or flow cytometry. Recombination events can be detected without the need for cytotoxic selection of recombination products and the system allows analysis of recombination activity using substrates integrated into the genome.

Conclusions

This system will be useful in the analysis and exploitation of the V(D)J recombination machinery and suggests that similar approaches could be used to replace expression of one gene with another during lymphocyte development.
The anti-cyclic citrullinated peptide response in tuberculosis patients is not citrulline-dependent and sensitive to treatment
Authors: Elkayam Ori , Segal Refael , Bendayan Daniele , van Uitert Robert , Onnekink Carla , Pruijn Ger JM
Published: March 2010

Introduction

Patients with tuberculosis (TB) frequently produce anti-citrullinated protein antibodies (ACPA). The objective of this study is to characterize the citrulline-dependence of the ACPA reactivity in sera of patients with mycobacterium infections.

Methods

Serum samples of 134 patients with untreated mycobacterium infections (122 TB, 12 nontuberculous mycobacterium) were tested for antibodies against both the citrullinated (Cit) and the non-citrullinated (Arg) form of 2 cyclic synthetic peptides. In 33 patients, a follow-up sample was tested six months after starting anti-mycobacterial drugs.

Results

A substantial proportion of patients with mycobacterial infections demonstrated antibodies against 0401Cit, 0401Arg, 0722Cit and 0722Arg. Fourteen patients demonstrated anti-0401Cit, 83 anti-0401Arg, 22 anti-0722Cit and 61 anti-0722Arg, while none of these antibodies were detected in the 20 healthy controls. All the patients but one, who were anti-0401Cit and anti-0722Cit positive, demonstrated reactivity against the respective Arg peptide. In the subset of 33 patients with a follow-up test six months after starting treatment, the mean levels of antibodies to 0401Cit, 0401Arg, 0722Cit and 0722Arg significantly decreased after treatment. All the patients who were anti-0401Cit and anti-0722Cit positive turned negative after treatment. The presence of anti-0401Cit/Arg and anti-0722Cit/Arg was found to be significantly correlated with the presence of HIV.

Conclusions

ACPA may be found in patients with TB. In most of the cases, the reactivity is citrulline independent. A positive cyclic citrullinated peptide (CCP) test in these patients should therefore be interpreted with care, and preferably followed by a control ELISA with a non-citrullinated antigen.
Anabolic and catabolic responses of human articular chondrocytes to varying oxygen percentages
Authors: Ströbel Simon , Loparic Marko , Wendt David , Schenk Andreas D , Candrian Christian , Lindberg Raija LP , Moldovan Florina , Barbero Andrea , Martin Ivan
Published: March 2010

Introduction

Oxygen is a critical parameter proposed to modulate the functions of chondrocytes ex-vivo as well as in damaged joints. This article investigates the effect of low (more physiological) oxygen percentage on the biosynthetic and catabolic activity of human articular chondrocytes (HAC) at different phases of in vitro culture.

Methods

HAC expanded in monolayer were cultured in pellets for two weeks (Phase I) or up to an additional two weeks (Phase II). In each Phase, cells were exposed to 19% or 5% oxygen. Resulting tissues and culture media were assessed to determine amounts of produced/released proteoglycans and collagens, metalloproteinases (MMPs), collagen degradation products and collagen fibril organization using biochemical, (immuno)-histochemical, gene expression and scanning electron microscopy analyses. In specific experiments, the hypoxia-inducible factor-1α (HIF-1α) inhibitor cadmium chloride was supplemented in the culture medium to assess the involvement of this pathway.

Results

Independent from the oxygen percentage during expansion, HAC cultured at 5% O2 (vs 19% O2) during Phase I accumulated higher amounts of glycosaminoglycans and type II collagen and expressed reduced levels of MMP-1 and MMP-13 mRNA and protein. Switching to 19% oxygen during Phase II resulted in reduced synthesis of proteoglycan and collagen, increased release of MMPs, accumulation of type II collagen fragments and higher branching of collagen fibrils. In contrast, reducing O2 during Phase II resulted in increased proteoglycan and type II collagen synthesis and reduced expression and release of MMP-13 mRNA and protein. Supplementation of cadmium chloride during differentiation culture at 5% O2 drastically reduced the up-regulation of type II collagen and the down-regulation of MMP-1 mRNA.

Conclusions

The application of more physiologic oxygen percentage during specific phases of differentiation culture enhanced the biosynthetic activity and reduced the activity of catabolic enzymes implicated in cartilage breakdown. Modulation of the oxygen percentage during HAC culture may be used to study pathophysiological events occurring in osteoarthritis and to enhance properties of in vitro engineered cartilaginous tissues.
Prolonged mechanical ventilation in a respiratory-care setting: a comparison of outcome between tracheostomized and translaryngeal intubated patients
Authors: Wu Yao-Kuang , Tsai Ying-Huang , Lan Chou-Chin , Huang Chun-Yao , Lee Chih-Hsin , Kao Kuo-Chin , Fu Jui-Ying
Published: March 2010

Introduction

Mechanical ventilation of patients may be accomplished by either translaryngeal intubation or tracheostomy. Although numerous intensive care unit (ICU) studies have compared various outcomes between the two techniques, no definitive consensus indicates that tracheostomy is superior. Comparable studies have not been performed in a respiratory care center (RCC) setting.

Methods

This was a retrospective observational study of 985 tracheostomy and 227 translaryngeal intubated patients who received treatment in a 24-bed RCC between November 1999 and December 2005. Treatment and mortality outcomes were compared between tracheostomized and translaryngeal intubated patients, and the factors associated with positive outcomes in all patients were determined.

Results

Duration of RCC (22 vs. 14 days) and total hospital stay (82 vs. 64 days) and total mechanical ventilation days (53 vs. 41 days) were significantly longer in tracheostomized patients (all P < 0.05). The rate of in-hospital mortality was significantly higher in the translaryngeal group (45% vs. 31%;P < 0.05). No significant differences were found in weaning success between the groups (both were >55%) or in RCC mortality. Because of significant baseline between-group heterogeneity, case-match analysis was performed. This analysis confirmed the whole cohort findings, except for the fact that a trend for in-hospital mortality was noted to be higher in the translaryngeal group (P = 0.08). Stepwise logistic regression revealed that patients with a lower median severity of disease (APACHE II score <18) who were properly nourished (albumin >2.5 g/dl) or had normal metabolism (BUN <40 mg/dl) were more likely to be successfully weaned and survive (all P < 0.05). Patients who were tracheostomized were also significantly more likely to survive (P < 0.05)

Conclusions

These findings suggest that the type of mechanical ventilation does not appear to be an important determinant of weaning success in an RCC setting. Focused care administered by experienced providers may be more important for facilitating weaning success than the ventilation method used. However, our findings do suggest that tracheostomy may increase the likelihood of patient survival.
Collaboratively charting the gene-to-phenotype network of human congenital heart defects
Authors: Barriot Roland , Breckpot Jeroen , Thienpont Bernard , Brohée Sylvain , Van Vooren Steven , Coessens Bert , Tranchevent Leon-Charles , Van Loo Peter , Gewillig Marc , Devriendt Koenraad , Moreau Yves
Published: March 2010

Background

How to efficiently integrate the daily practice of molecular biologists, geneticists, and clinicians with the emerging computational strategies from systems biology is still much of an open question.

Description

We built on the recent advances in Wiki-based technologies to develop a collaborative knowledge base and gene prioritization portal aimed at mapping genes and genomic regions, and untangling their relations with corresponding human phenotypes, congenital heart defects (CHDs). This portal is not only an evolving community repository of current knowledge on the genetic basis of CHDs, but also a collaborative environment for the study of candidate genes potentially implicated in CHDs - in particular by integrating recent strategies for the statistical prioritization of candidate genes. It thus serves and connects the broad community that is facing CHDs, ranging from the pediatric cardiologist and clinical geneticist to the basic investigator of cardiogenesis.

Conclusions

This study describes the first specialized portal to collaboratively annotate and analyze gene-phenotype networks. Of broad interest to the biological community, we argue that such portals will play a significant role in systems biology studies of numerous complex biological processes.

CHDWiki is accessible at http://www.esat.kuleuven.be/~bioiuser/chdwiki
Psychological Distress in Adult Survivors of Childhood Cancer: The Swiss Childhood Cancer Survivor Study
Authors: Michel Gisela , Rebholz Cornelia E. , von der Weid Nicolas X. , Bergstraesser Eva , Kuehni Claudia E.
Published: March 2010

Purpose

To evaluate the degree of psychological distress in adult childhood cancer survivors in Switzerland and to characterize survivors with significant distress.

Methods

Childhood cancer survivors who were age younger than 16 years when diagnosed between 1976 and 2003, had survived more than 5 years, and were currently age 20 years or older received a postal questionnaire. Psychological distress was assessed using the Brief Symptom Inventory (BSI). Raw scores were transformed into T scores according to the German norm sample, and the proportion of participants being at increased risk for psychological distress was calculated (case rule: T ≥ 63). t tests and univariable and multivariable logistic regressions were used for statistical analyses.

Results

One thousand seventy-six survivors (63.% of eligible survivors, 71.9% of contacted survivors) returned the questionnaire, 987 with complete data on BSI. Comparison with the norm populations showed lower T scores (T < 50) in the Global Severity Index (GSI; T = 46.2), somatization (T = 47.6), obsessive-compulsive tendencies (T = 46.9), and anxiety (T = 48.4). However, more childhood cancer survivors (especially women) had increased distress for GSI (14.4%), interpersonal sensitivity (16.5%), depression (13.4%), aggression (16.9%), and psychotic tendencies (15.6%) than the expected 10% from the norm population. Caseness was associated with female sex, being a single child, older age at study, and self-reported late effects, especially psychological problems.

Conclusion

Results show that childhood cancer survivors, on average, have less psychological distress than a norm population but that the proportion of survivors at risk for high psychological distress is disproportionally large. Monitoring psychological distress in childhood cancer survivors may be desirable during routine follow-up, and psychological support should be offered as needed.