bluuebunny/crossref_metadata_2025 huggingface dataset:
Posttraumatic Stress Symptoms in Children and Adolescents Referred for Child Welfare Investigation
Authors: Kolko David J. , Hurlburt Michael S. , Jinjin Zhang  , Barth Richard P. , Leslie Laurel K. , Burns Barbara J.
Published: June 2009

This study examines the prevalence and correlates of heightened posttraumatic stress (PTS) symptoms in a nationally representative sample of 1,848 children and adolescents (ages 8-14) who were referred to child welfare for investigation of abuse or neglect based on the National Survey of Child and Adolescent Well-Being. The severity of current PTS symptoms was assessed using the PTS subscale of the Trauma Symptom Checklist for Children, a standardized child-report scale evaluating common symptoms associated with trauma. The overall prevalence of clinically significant PTS symptoms was 11.7% (overall mean T score = 49.5). The prevalence was higher for cases that were placed in out-of-home care (19.2%) than those maintained at home (10.7%). Multivariate hierarchical regression identified four contributors to heightened PTS symptoms: younger child age, abuse by a nonbiological parent, violence in the home, and child depression. The authors discuss the modest but still lower than expected prevalence of self-reported, clinically significant PTS symptoms and the variables associated with greater risk for heightened PTS symptoms found among cases referred to child welfare services.
Reconceptualizing Evaluator Roles
Authors: Skolits Gary J. , Morrow Jennifer Ann , Burr Erin Mehalic
Published: June 2009

The current evaluation literature tends to conceptualize evaluator roles as a single, overarching orientation toward an evaluation, an orientation largely driven by evaluation methods, models, or stakeholder orientations. Roles identified range from a social transformer or a neutral social scientist to that of an educator or even a power merchant. We argue that these single, broadly construed role orientations do not reflect the multiple roles evaluators actually assume as they complete the activities encompassing an external evaluation. In contrast to the current literature, this article suggests that typical evaluation activities create functional demands on evaluators, and that evaluators respond to these demands through a limited number of specified evaluator roles. This depiction of a set of specific multiple evaluator roles, generated in response to particular evaluation activities and their associated demands, has implications regarding how evaluation is conceptualized, practiced, and studied. This article concludes with a discussion of these implications.
Using Mixed-Method Design and Network Analysis to Measure Development of Interagency Collaboration
Authors: Cross Jennifer Eileen , Dickmann Ellyn , Newman-Gonchar Rebecca , Fagan Jesse Michael
Published: June 2009

In recent years, there has been increasing attention to the importance of interagency collaboration for improving community well-being, environmental and public health, and educational outcomes. This article uses a mixed-methods approach including network analysis to examine the changes in interagency collaboration in one site funded by the Safe Schools/Healthy Students Initiative (SS/HS). Results of the evaluation demonstrated that although intraproject collaboration peaked in the middle of the grant and began to decline during the last year, interagency collaborations continued to grow during the last year of the grant. These results illustrate how network data can easily be collected and used to assess the development of interagency relationships.
High Water Barrier Nanobiocomposites of Methyl Cellulose and Chitosan for Film and Coating Applications
Authors: Lagarón J.M. , Fendler A.
Published: June 2009

Polysaccharides and protein biopolymers are of increasing interest for their use as sustainable film and coating materials. However, their main drawback in these applications is their inherent high water permeability and low water resistance at high relative humidity conditions. In this study, two specifically designed commercial fillers of different nature and aspect ratios were successfully incorporated into two polysaccharides: methyl cellulose and chitosan. The morphology study indicated that a good dispersion with intercalation of the fillers was observed in both matrices. The water barrier properties of the nanobiocomposites were found to be enhanced to a significant extent, particularly for the higher aspect ratio filler, as compared to the pure matrix materials, while the biodegradability of the composite materials was maintained.
Analysis of the Ten-Eleven Translocation 2 (TET2) gene in familial myeloproliferative neoplasms
Authors: Saint-Martin Cécile , Leroy Gwendoline , Delhommeau François , Panelatti Gérard , Dupont Sabrina , James Chloé , Plo Isabelle , Bordessoule Dominique , Chomienne Christine , Delannoy André , Devidas Alain , Gardembas-Pain Martine , Isnard Françoise , Plumelle Yves , Bernard Olivier , Vainchenker William , Najman Albert , Bellanné-Chantelot Christine ,   the French Group of Familial Myeloproliferative Disorders
Published: June 2009

The JAK2V617F mutation does not elucidate the phenotypic variability observed in myeloproliferative neoplasm (MPN) families. A putative tumor suppressor gene, TET2, was recently implicated in MPN and myelodysplastic syndromes through the identification of acquired mutations affecting hematopoietic stem cells. The present study analyzed the TET2 gene in 61 MPN cases from 42 families. Fifteen distinct mutations were identified in 12 (20%) JAK2V617F-positive or -negative patients. In a patient with 2 TET2 mutations, the analysis of 5 blood samples at different phases of her disease showed the sequential occurrence of JAK2V617F and TET2 mutations concomitantly to the disease evolution. Analysis of familial segregation confirmed that TET2 mutations were not inherited but somatically acquired. TET2 mutations were mainly observed (10 of 12) in patients with primary myelofibrosis or patients with polycythemia vera or essential thrombocythemia who secondarily evolved toward myelofibrosis or acute myeloid leukemia.
Adjunctive resectional lung surgery for extensively drug-resistant tuberculosis: Table 1—
Authors: Dravniece G. , Cain K. P. , Holtz T. H. , Riekstina V. , Leimane V. , Zaleskis R.
Published: June 2009

Extensively drug-resistant (XDR) tuberculosis (TB) poses significant management challenges as there are limited pharmacological treatment options for cure. Adjunctive resectional lung surgery decreases case-fatality rates for some patients with multidrug-resistant tuberculosis (MDR-TB), but its use has not been well documented for patients with XDR-TB.

We describe 17 XDR-TB patients treated with surgery as part of their case management in Latvia during 1999–2005. One patient had no previous TB treatment history, 10 were previously treated for drug-susceptible TB and six were previously treated for MDR-TB.Mycobacterium tuberculosisisolates from the 17 patients were resistant to a mean of 9.2 drugs. Due to failure of pharmacological therapy, one due to a large cavity and one due to pulmonary haemorrhage, 15 patients were treated with surgery. Despite failure of pharmacological treatment in 15 out of 17 patients, eight (47%) were cured with adjunctive surgical treatment. Surgery should be explored as a possible treatment option for patients with XDR-TB.
End-points and clinical trial design in pulmonary arterial hypertension: have we made progress?
Authors: Peacock A. J. , Naeije R. , Galiè N. , Rubin L.
Published: June 2009

There is enormous interest in the treatment of pulmonary arterial hypertension (PAH), so it is appropriate to consider the design of trials of new therapies and the end-points to be measured when trying to decide whether or not a therapy is effective.

In May 2003, the first meeting devoted solely to the discussion of end-points and trial design in PAH was held in Gleneagles, UK. At that time, most of the randomised controlled trials in PAH had used 6-min walking distance and/or resting haemodynamics as their primary end-points.

The present article considers the progress that has been made since 2003. It deals with aspects of clinical trial design (such as noninferiority, superiority and withdrawal trials), considers end-points used in previous and current studies (such as 6-min walking distance, time to clinical worsening, haemodynamics, imaging and plasma brain natriuretic peptide), and considers what end-points might be used in the future.

The second end-points meeting was held in Turnberry, UK, in June 2007. It had a similar format to the first meeting. Much of what is presented here is a summary of the workshops from that meeting. An attempt has been made to both summarise the current state of end-points and trial design and suggest new ways in which they could be improved. The present article forms one of a series being published in theEuropean Respiratory Journalon pulmonary hypertension.
Lymphoid follicles in (very) severe COPD: beneficial or harmful?
Authors: Brusselle G. G. , Demoor T. , Bracke K. R. , Brandsma C-A. , Timens W.
Published: June 2009

Inflammation is a main pathogenetic factor in the development and progression of chronic obstructive pulmonary disease (COPD). Recently, it has become clear that not only the innate, but also the specific immune response plays a role. A striking finding, in particular in lungs of patients with severe COPD, often with a predominant emphysema phenotype, is the presence of B-cell follicles. As seen in other tissues, these follicles are the result of lymphoid neogenesis. The finding of oligoclonality in B-cell follicles in COPD suggests that they play a role in local antigen specific immune responses. To date, it is not known which antigens may be involved; microbial antigens, cigarette smoke-derived antigens and antigens from extracellular matrix breakdown products have been suggested. Consequently, the pathogenetic role of this follicular B-cell response is not yet clear. It might be protective against microbial colonisation and infection of the lower respiratory tract and, therefore, beneficial, or it could be of a more harmful (autoimmune) nature, directed against lung tissue components. It is necessary to determine the specific antigen(s) and to explore the exact role of the COPD related B-cell response in order to include modulation of this response and develop therapeutic options.
Sleep, sleep-disordered breathing and metabolic consequences
Authors: Lévy P. , Bonsignore M. R. , Eckel J.
Published: June 2009

Sleep profoundly affects metabolic pathways. In healthy subjects, experimental sleep restriction caused insulin resistance (IR) and increased evening cortisol and sympathetic activation. Increased obesity in subjects reporting short sleep duration leads to speculation that, during recent decades, decreased sleeping time in the general population may have contributed to the increasing prevalence of obesity. Causal inference is difficult due to lack of control for confounders and inconsistent evidence of temporal sequence.

In the general population, obstructive sleep apnoea (OSA) is associated with glucose intolerance. OSA severity is also associated with the degree of IR. However, OSA at baseline does not seem to significantly predict the development of diabetes. Prevalence of the metabolic syndrome is higher in patients with OSA than in obese subjects without OSA. Treatment with continuous positive airway pressure seems to improve glucose metabolism both in diabetic and nondiabetic OSA but mainly in nonobese subjects.

The relative role of obesity and OSA in the pathogenesis of metabolic alterations is still unclear and is intensively studied in clinical and experimental models. In the intermittent hypoxia model in rodents, strong interactions are likely to occur between haemodynamic alterations, systemic inflammation and metabolic changes, modulated by genetic background. Molecular and cellular mechanisms are currently being investigated.
ERS/ESTS clinical guidelines on fitness for radical therapy in lung cancer patients (surgery and chemo-radiotherapy)
Authors: Brunelli A. , Charloux A. , Bolliger C. T. , Rocco G. , Sculier J-P. , Varela G. , Licker M. , Ferguson M. K. , Faivre-Finn C. , Huber R. M. , Clini E. M. , Win T. , De Ruysscher D. , Goldman L.
Published: June 2009

A collaboration of multidisciplinary experts on the functional evaluation of lung cancer patients has been facilitated by the European Respiratory Society (ERS) and the European Society of Thoracic Surgery (ESTS), in order to draw up recommendations and provide clinicians with clear, up-to-date guidelines on fitness for surgery and chemo-radiotherapy.

The subject was divided into different topics, which were then assigned to at least two experts. The authors searched the literature according to their own strategies, with no central literature review being performed. The draft reports written by the experts on each topic were reviewed, discussed and voted on by the entire expert panel. The evidence supporting each recommendation was summarised, and graded as described by the Scottish Intercollegiate Guidelines Network Grading Review Group. Clinical practice guidelines were generated and finalised in a functional algorithm for risk stratification of the lung resection candidates, emphasising cardiological evaluation, forced expiratory volume in 1 s, systematic carbon monoxide lung diffusion capacity and exercise testing.

Contrary to lung resection, for which the scientific evidences are more robust, we were unable to recommend any specific test, cut-off value, or algorithm before chemo-radiotherapy due to the lack of data. We recommend that lung cancer patients should be managed in specialised settings by multidisciplinary teams.
Current status of research on osteoporosis in COPD: a systematic review
Authors: Graat-Verboom L. , Wouters E. F. M. , Smeenk F. W. J. M. , van den Borne B. E. E. M. , Lunde R. , Spruit M. A.
Published: June 2009

Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of osteoporosis. However, the prevalence, correlates and effectiveness of treatment of osteoporosis in COPD patients remain unclear.

We performed a systematic review of the literature to answer three questions. 1) What is the prevalence of osteoporosis in COPD? 2) What are identified correlates of osteoporosis in COPD? 3) What are the effects of treatment of osteoporosis in COPD? A computerised literature search in MEDLINE/PubMed and the Cochrane database was carried out. In addition, reference lists were searched by hand and authors were contacted if necessary.

The prevalence of osteoporosis and osteopenia varied 9–69% and 27–67%, respectively. Prevalence of osteoporosis was generally higher than in healthy subjects and some other chronic lung diseases. Correlates of osteoporosis in COPD are mainly measures of body composition, disease severity and the use of corticosteroids, although causality has not been proven. Effects of treatment of osteoporosis have not been investigated in samples consisting of COPD patients only.

Longitudinal follow-up to assess determinants of osteoporosis in COPD and randomised placebo-controlled trials on the effects of treatment of osteoporosis in patients with COPD only are warranted.
ZAK negatively regulates RhoGDIβ-induced Rac1-mediated hypertrophic growth and cell migration
Authors: Huang Chih-Yang , Yang Li-Chiu , Liu Kuan-Yu , Chang I-Chang , Liao Pao-Hsin , Chou Janet Ing-Yuh , Chou Ming-Yung , Lin Wei-Wen , Yang Jaw-Ji
Published: June 2009

RhoGDIβ, a Rho GDP dissociation inhibitor, induced hypertrophic growth and cell migration in a cultured cardiomyoblast cell line, H9c2. We demonstrated that RhoGDIβ plays a previously undefined role in regulating Rac1 expression through transcription to induce hypertrophic growth and cell migration and that these functions are blocked by the expression of a dominant-negative form of Rac1. We also demonstrated that knockdown of RhoGDIβ expression by RNA interference blocked RhoGDIβ-induced Rac1 expression and cell migration. We demonstrated that the co-expression of ZAK and RhoGDIβ in cells resulted in an inhibition in the activity of ZAK to induce ANF expression. Knockdown of ZAK expression in ZAK-RhoGDIβ-expressing cells by ZAK-specific RNA interference restored the activities of RhoGDIβ.
geneCBR: a translational tool for multiple-microarray analysis and integrative information retrieval for aiding diagnosis in cancer research
Authors: Glez-Peña Daniel , Díaz Fernando , Hernández Jesús M , Corchado Juan M , Fdez-Riverola Florentino
Published: June 2009

Background

Bioinformatics and medical informatics are two research fields that serve the needs of different but related communities. Both domains share the common goal of providing new algorithms, methods and technological solutions to biomedical research, and contributing to the treatment and cure of diseases. Although different microarray techniques have been successfully used to investigate useful information for cancer diagnosis at the gene expression level, the true integration of existing methods into day-to-day clinical practice is still a long way off. Within this context, case-based reasoning emerges as a suitable paradigm specially intended for the development of biomedical informatics applications and decision support systems, given the support and collaboration involved in such a translational development. With the goals of removing barriers against multi-disciplinary collaboration and facilitating the dissemination and transfer of knowledge to real practice, case-based reasoning systems have the potential to be applied to translational research mainly because their computational reasoning paradigm is similar to the way clinicians gather, analyze and process information in their own practice of clinical medicine.

Results

In addressing the issue of bridging the existing gap between biomedical researchers and clinicians who work in the domain of cancer diagnosis, prognosis and treatment, we have developed and made accessible a common interactive framework. Our geneCBR system implements a freely available software tool that allows the use of combined techniques that can be applied to gene selection, clustering, knowledge extraction and prediction for aiding diagnosis in cancer research. For biomedical researches, geneCBR expert mode offers a core workbench for designing and testing new techniques and experiments. For pathologists or oncologists, geneCBR diagnostic mode implements an effective and reliable system that can diagnose cancer subtypes based on the analysis of microarray data using a CBR architecture. For programmers, geneCBR programming mode includes an advanced edition module for run-time modification of previous coded techniques.

Conclusion

geneCBR is a new translational tool that can effectively support the integrative work of programmers, biomedical researches and clinicians working together in a common framework. The code is freely available under the GPL license and can be obtained at http://www.genecbr.org.
DOTcvpSB, a software toolbox for dynamic optimization in systems biology
Authors: Hirmajer Tomáš , Balsa-Canto Eva , Banga Julio R
Published: June 2009

Background

Mathematical optimization aims to make a system or design as effective or functional as possible, computing the quality of the different alternatives using a mathematical model. Most models in systems biology have a dynamic nature, usually described by sets of differential equations. Dynamic optimization addresses this class of systems, seeking the computation of the optimal time-varying conditions (control variables) to minimize or maximize a certain performance index. Dynamic optimization can solve many important problems in systems biology, including optimal control for obtaining a desired biological performance, the analysis of network designs and computer aided design of biological units.

Results

Here, we present a software toolbox, DOTcvpSB, which uses a rich ensemble of state-of-the-art numerical methods for solving continuous and mixed-integer dynamic optimization (MIDO) problems. The toolbox has been written in MATLAB and provides an easy and user friendly environment, including a graphical user interface, while ensuring a good numerical performance. Problems are easily stated thanks to the compact input definition. The toolbox also offers the possibility of importing SBML models, thus enabling it as a powerful optimization companion to modelling packages in systems biology. It serves as a means of handling generic black-box models as well.

Conclusion

Here we illustrate the capabilities and performance of DOTcvpSB by solving several challenging optimization problems related with bioreactor optimization, optimal drug infusion to a patient and the minimization of intracellular oscillations. The results illustrate how the suite of solvers available allows the efficient solution of a wide class of dynamic optimization problems, including challenging multimodal ones. The toolbox is freely available for academic use.
A-MADMAN: Annotation-based microarray data meta-analysis tool
Authors: Bisognin Andrea , Coppe Alessandro , Ferrari Francesco , Risso Davide , Romualdi Chiara , Bicciato Silvio , Bortoluzzi Stefania
Published: June 2009

Background

Publicly available datasets of microarray gene expression signals represent an unprecedented opportunity for extracting genomic relevant information and validating biological hypotheses. However, the exploitation of this exceptionally rich mine of information is still hampered by the lack of appropriate computational tools, able to overcome the critical issues raised by meta-analysis.

Results

This work presents A-MADMAN, an open source web application which allows the retrieval, annotation, organization and meta-analysis of gene expression datasets obtained from Gene Expression Omnibus. A-MADMAN addresses and resolves several open issues in the meta-analysis of gene expression data.

Conclusion

A-MADMAN allows i) the batch retrieval from Gene Expression Omnibus and the local organization of raw data files and of any related meta-information, ii) the re-annotation of samples to fix incomplete, or otherwise inadequate, metadata and to create user-defined batches of data, iii) the integrative analysis of data obtained from different Affymetrix platforms through custom chip definition files and meta-normalization. Software and documentation are available on-line at http://compgen.bio.unipd.it/bioinfo/amadman/.
NLStradamus: a simple Hidden Markov Model for nuclear localization signal prediction
Authors: Nguyen Ba Alex N , Pogoutse Anastassia , Provart Nicholas , Moses Alan M
Published: June 2009

Background

Nuclear localization signals (NLSs) are stretches of residues within a protein that are important for the regulated nuclear import of the protein. Of the many import pathways that exist in yeast, the best characterized is termed the 'classical' NLS pathway. The classical NLS contains specific patterns of basic residues and computational methods have been designed to predict the location of these motifs on proteins. The consensus sequences, or patterns, for the other import pathways are less well-understood.

Results

In this paper, we present an analysis of characterized NLSs in yeast, and find, despite the large number of nuclear import pathways, that NLSs seem to show similar patterns of amino acid residues. We test current prediction methods and observe a low true positive rate. We therefore suggest an approach using hidden Markov models (HMMs) to predict novel NLSs in proteins. We show that our method is able to consistently find 37% of the NLSs with a low false positive rate and that our method retains its true positive rate outside of the yeast data set used for the training parameters.

Conclusion

Our implementation of this model, NLStradamus, is made available at: http://www.moseslab.csb.utoronto.ca/NLStradamus/
The pluripotency factor LIN28 marks undifferentiated spermatogonia in mouse
Authors: Zheng Ke , Wu Xin , Kaestner Klaus H , Wang Peijing Jeremy
Published: June 2009

Background

Life-long production of spermatozoa depends on spermatogonial stem cells. Spermatogonial stem cells exist among the most primitive population of germ cells – undifferentiated spermatogonia. Transplantation experiments have demonstrated the functional heterogeneity of undifferentiated spermatogonia. Although the undifferentiated spermatogonia can be topographically divided into As(single), Apr(paired), and Aal(aligned) spermatogonia, subdivision of this primitive cell population using cytological markers would greatly facilitate characterization of their functions.

Results

In the present study, we show that LIN28, a pluripotency factor, is specifically expressed in undifferentiated spermatogonia (As, Apr, and Aal) in mouse.Ngn3also specifically labels undifferentiated spermatogonia. We usedNgn3-GFP knockin mice, in which GFP expression is under the control of allNgn3transcription regulatory elements. Remarkably,Ngn3-GFP is only expressed in ~40% of LIN28-positive As(single) cells. The percentage ofNgn3-GFP-positive clusters increases dramatically with the chain length of interconnected spermatogonia.

Conclusion

Our study demonstrates that LIN28 specifically marks undifferentiated spermatogonia in mice. These data, together with previous studies, suggest that the LIN28-expressing undifferentiated spermatogonia exist as two subpopulations:Ngn3-GFP-negative (high stem cell potential) andNgn3-GFP-positive (high differentiation commitment). Furthermore,Ngn3-GFP-negative cells are found in chains ofNgn3-GFP-positive spermatogonia, suggesting that cells in the Aalspermatogonia could revert to a more primitive state.
Role of accelerated segment switch in exons to alter targeting (ASSET) in the molecular evolution of snake venom proteins
Authors: Doley Robin , Mackessy Stephen P , Kini R Manjunatha
Published: June 2009

Background

Snake venom toxins evolve more rapidly than other proteins through accelerated changes in the protein coding regions. Previously we have shown that accelerated segment switch in exons to alter targeting (ASSET) might play an important role in its functional evolution of viperid three-finger toxins. In this phenomenon, short sequences in exons are radically changed to unrelated sequences and hence affect the folding and functional properties of the toxins.

Results

Here we analyzed other snake venom protein families to elucidate the role of ASSET in their functional evolution. ASSET appears to be involved in the functional evolution of three-finger toxins to a greater extent than in several other venom protein families. ASSET leads to replacement of some of the critical amino acid residues that affect the biological function in three-finger toxins as well as change the conformation of the loop that is involved in binding to specific target sites.

Conclusion

ASSET could lead to novel functions in snake venom proteins. Among snake venom serine proteases, ASSET contributes to changes in three surface segments. One of these segments near the substrate binding region is known to affect substrate specificity, and its exchange may have significant implications for differences in isoform catalytic activity on specific target protein substrates. ASSET therefore plays an important role in functional diversification of snake venom proteins, in addition to accelerated point mutations in the protein coding regions. Accelerated point mutations lead to fine-tuning of target specificity, whereas ASSET leads to large-scale replacement of multiple functionally important residues, resulting in change or gain of functions.
Genome-wide transcriptomic profiling of Anopheles gambiae hemocytes reveals pathogen-specific signatures upon bacterial challenge and Plasmodium berghei infection
Authors: Baton Luke A , Robertson Anne , Warr Emma , Strand Michael R , Dimopoulos George
Published: June 2009

Background

The mosquito Anopheles gambiae is a major vector of human malaria. Increasing evidence indicates that blood cells (hemocytes) comprise an essential arm of the mosquito innate immune response against both bacteria and malaria parasites. To further characterize the role of hemocytes in mosquito immunity, we undertook the first genome-wide transcriptomic analyses of adult female An. gambiae hemocytes following infection by two species of bacteria and a malaria parasite.

Results

We identified 4047 genes expressed in hemocytes, using An. gambiae genome-wide microarrays. While 279 transcripts were significantly enriched in hemocytes relative to whole adult female mosquitoes, 959 transcripts exhibited immune challenge-related regulation. The global transcriptomic responses of hemocytes to challenge with different species of bacteria and/or different stages of malaria parasite infection revealed discrete, minimally overlapping, pathogen-specific signatures of infection-responsive gene expression; 105 of these represented putative immunity-related genes including anti-Plasmodium factors. Of particular interest was the specific co-regulation of various members of the Imd and JNK immune signaling pathways during malaria parasite invasion of the mosquito midgut epithelium.

Conclusion

Our genome-wide transcriptomic analysis of adult mosquito hemocytes reveals pathogen-specific signatures of gene regulation and identifies several novel candidate genes for future functional studies.
Calyx and dimorphic neurons of mouse Scarpa's ganglion express histamine H3 receptors
Authors: Tritto Simona , Botta Laura , Zampini Valeria , Zucca Gianpiero , Valli Paolo , Masetto Sergio
Published: June 2009

Background

Histamine-related drugs are commonly used in the treatment of vertigo and related vestibular disorders. The site of action of these drugs however has not been elucidated yet. Recent works on amphibians showed that histamine H3 receptor antagonists, e.g. betahistine, inhibit the afferent discharge recorded from the vestibular nerve. To assess the expression of H3 histamine receptors in vestibular neurons, we performed mRNA RT-PCR and immunofluorescence experiments in mouse Scarpa's ganglia.

Results

RT-PCR analysis showed the presence of H3 receptor mRNA in mouse ganglia tissue. H3 protein expression was found in vestibular neurons characterized by large and roundish soma, which labeled for calretinin and calbindin.

Conclusion

The present results are consistent with calyx and dimorphic, but not bouton, afferent vestibular neurons expressing H3 receptors. This study provides a molecular substrate for the effects of histamine-related antivertigo drugs acting on (or binding to) H3 receptors, and suggest a potential target for the treatment of vestibular disorders of peripheral origin.
Effect of questionnaire structure on recall of drug utilization in a population of university students
Authors: Gama Helena , Correia Sofia , Lunet Nuno
Published: June 2009

Background

Self-reported data are a common source of information about drug exposure. Modes of data collection differ considerably and the questionnaire's structure may affect prevalence estimates. We compared the recall of medication use evaluated by means of two questionnaires differing in structure and length.

Methods

Drug utilization was assessed by two alternative versions of a questionnaire (A – 4 pages, including specific questions for 12 indications/pharmacological groups and one question for "other medicines"; B – 1 page, including 1 open-ended question to cover overall drug consumption). Each of 32 classes in a private University in Maputo, Mozambique, was randomly assigned questionnaire A (233 participants) or B (276 participants). Logistic regression (allowing for clustering by classroom) was used to compare the two groups in terms of socio-demographic characteristics and medication used during the previous month.

Results

Overall, 67.4% of the subjects had used at least one drug during the previous month. The following prevalences were greater among participants completing questionnaire A: use of drugs from two or more pharmacological groups (60.5% vs. 34.4%, p < 0.001), use of two or more drugs (66.2% vs. 43.0%, p < 0.001), and use of antibiotics (14.6% vs. 6.9%, p = 0.001), antifungals (9.4% vs. 4.0%, p = 0.013), antiparasitics (5.6% vs. 1.8%, p = 0.031) and antacids (8.6% vs. 3.6%, p = 0.024). Information about duration of treatment and medical advice was more complete with version A.

Conclusion

The indication/drug-specific questions (questionnaire A) revealed a significantly higher prevalence of use of medicines – antibiotics, antifungals, antiparasitics and antacids – without compromising the completeness of the information.
Role of pathogenic oral flora in postoperative pneumonia following brain surgery
Authors: Bágyi Kinga , Haczku Angela , Márton Ildikó , Szabó Judit , Gáspár Attila , Andrási Melinda , Varga Imre , Tóth Judit , Klekner Almos
Published: June 2009

Background

Post-operative pulmonary infection often appears to result from aspiration of pathogens colonizing the oral cavity. It was hypothesized that impaired periodontal status and pathogenic oral bacteria significantly contribute to development of aspiration pneumonia following neurosurgical operations. Further, the prophylactic effects of a single dose preoperative cefazolin on the oral bacteria were investigated.

Methods

A matched cohort of 18 patients without postoperative lung complications was compared to 5 patients who developed pneumonia within 48 hours after brain surgery. Patients waiting for elective operation of a single brain tumor underwent dental examination and saliva collection before surgery. Bacteria from saliva cultures were isolated and periodontal disease was scored according to type and severity. Patients received 15 mg/kg cefazolin intravenously at the beginning of surgery. Serum, saliva and bronchial secretion were collected promptly after the operation. The minimal inhibitory concentrations of cefazolin regarding the isolated bacteria were determined. The actual antibiotic concentrations in serum, saliva and bronchial secretion were measured by capillary electrophoresis upon completion of surgery. Bacteria were isolated again from the sputum of postoperative pneumonia patients.

Results

The number and severity of coexisting periodontal diseases were significantly greater in patients with postoperative pneumonia in comparison to the control group (p = 0.031 and p = 0.002, respectively). The relative risk of developing postoperative pneumonia in high periodontal score patients was 3.5 greater than in patients who had low periodontal score (p < 0.0001). Cefazolin concentration in saliva and bronchial secretion remained below detectable levels in every patient.

Conclusion

Presence of multiple periodontal diseases and pathogenic bacteria in the saliva are important predisposing factors of postoperative aspiration pneumonia in patients after brain surgery. The low penetration rate of cefazolin into the saliva indicates that its prophylactic administration may not be sufficient to prevent postoperative aspiration pneumonia. Our study suggests that dental examination may be warranted in order to identify patients at high risk of developing postoperative respiratory infections.
Association study of SHANK3 gene polymorphisms with autism in Chinese Han population
Authors: Qin Jian , Jia Meixiang , Wang Lifang , Lu Tianlan , Ruan Yan , Liu Jing , Guo Yanqing , Zhang Jishui , Yang Xiaoling , Yue Weihua , Zhang Dai
Published: June 2009

Background

Autism, a heterogeneous disease, is described as a genetic psychiatry disorder. Recently, abnormalities at the synapse are supposed to be important for the etiology of autism.SHANK3 (SH3 and multiple ankyrin repeat domains protein) gene encodes a master synaptic scaffolding protein at postsynaptic density (PSD) of excitatory synapse. Rare mutations and copy number variation (CNV) evidence suggested SHANK3 as a strong candidate gene for the pathogenesis of autism.

Methods

We performed an association study between SHANK3 gene polymorphisms and autism in Chinese Han population. We analyzed the association between five single nucleotide polymorphisms (SNPs) of the SHANK3 gene and autism in 305 Chinese Han trios, using the family based association test (FBAT). Linkage disequilibrium (LD) analysis showed the presence of LD between pairwise markers across the locus. We also performed mutation screening for the rare de novo mutations reported previously.

Results

No significant evidence between any SNPs of SHANK3 and autism was observed. We did not detect any mutations described previously in our cohort.

Conclusion

We suggest that SHANK3 might not represent a major susceptibility gene for autism in Chinese Han population.
Lack of association of TIM3polymorphisms and allergic phenotypes
Authors: Zhang Jian , Daley Denise , Akhabir Loubna , Stefanowicz Dorota , Chan-Yeung Moira , Becker Allan B , Laprise Catherine , Paré Peter D , Sandford Andrew J
Published: June 2009

Background

T-cell immunoglobulin mucin-3 (TIM3) is a TH1-specific type 1 membrane protein that regulates TH1 proliferation and the development of immunological tolerance. TIM3 and its genetic variants have been suggested to play a role in regulating allergic diseases. Polymorphisms in the TIM3 promoter region have been reported to be associated with allergic phenotypes in several populations. The aims of this study were to examine whether genetic variation in the promoter region of TIM3 influenced transcription of the gene and risk for allergic phenotypes.

Methods

We performed 5' rapid amplification of cDNA ends and reverse transcription-polymerase chain reaction. We screened for polymorphisms in the promoter region. Deletion analysis was used to localize the promoter region of TIM3. Genotyping was performed by TaqMan assays in three asthma/allergy population samples.

Results

We found two regions with promoter activity in TIM3. One region was from -214 bp to +58 bp and the other from -1.6 kb to -914 bp relative to the transcription start site. None of the single nucleotide polymorphisms (SNPs) or haplotypes affected the transcriptional activity in reporter gene assays. No association between the SNPs and any phenotype was observed in the study cohorts.

Conclusion

Our findings indicate that SNPs and haplotypes in the TIM3 promoter region do not have a functional effect in vitro and are not associated with allergic diseases. These data suggest that polymorphisms in the TIM3 promoter region are unlikely to play an important role in susceptibility to allergic diseases.
Age-related associations of hypertension and diabetes mellitus with chronic kidney disease
Authors: Islam Tareq M , Fox Caroline S , Mann Devin , Muntner Paul
Published: June 2009

Background

Studies suggest end-stage renal disease incidence and all-cause mortality rates among patients with chronic kidney disease (CKD) differ by age. The association of diabetes mellitus and hypertension with CKD across the adult lifespan is not well established.

Methods

Data from NHANES 1999–2004 were used to determine the association of risk factors for stage 3 or 4 CKD (n = 12,518) and albuminuria (n = 12,778) by age grouping (20 to 49, 50 to 69, and ≥70 years). Stage 3 or 4 CKD was defined as an estimated glomerular filtration rate of 15 to 59 ml/min/1.73 m2 and albuminuria as an albumin to creatinine ratio ≥30 mg/g.

Results

For adults 20 to 49, 50 to 69 and ≥70 years of age, the prevalence ratios (95% confidence interval) of stage 3 or 4 CKD associated with hypertension were 1.94 (0.86 – 4.35), 1.51 (1.09 – 2.07), 1.31 (1.15 – 1.49), respectively (p-trend = 0.038). The analogous prevalence ratios (95% confidence interval) were 3.01 (1.35 – 6.74), 1.61 (1.15 – 2.25), 1.40 (1.15 – 1.69), respectively, for diagnosed diabetes mellitus (p-trend = 0.067); and 2.67 (0.53 – 13.4), 1.35 (0.69 – 2.63), 1.08 (0.78 – 1.51), respectively, for undiagnosed diabetes mellitus (p-trend = 0.369). The prevalence ratios of albuminuria associated with hypertension and diagnosed and undiagnosed diabetes mellitus were lower at older age (each p < 0.05).

Conclusion

Among US adults, diabetes mellitus and hypertension are associated with CKD and albuminuria regardless of age. However, the associations were stronger at younger ages.
A simple method for co-segregation analysis to evaluate the pathogenicity of unclassified variants; BRCA1 and BRCA2 as an example
Authors: Mohammadi Leila , Vreeswijk Maaike P , Oldenburg Rogier , van den Ouweland Ans , Oosterwijk Jan C , van der Hout Annemarie H , Hoogerbrugge Nicoline , Ligtenberg Marjolijn , Ausems Margreet G , van der Luijt Rob B , Dommering Charlotte J , Gille Johan J , Verhoef Senno , Hogervorst Frans B , van Os Theo A , Gómez García Encarna , Blok Marinus J , Wijnen Juul T , Helmer Quinta , Devilee Peter , van Asperen Christi J , van Houwelingen Hans C
Published: June 2009

Background

Assessment of the clinical significance of unclassified variants (UVs) identified in BRCA1 and BRCA2 is very important for genetic counselling. The analysis of co-segregation of the variant with the disease in families is a powerful tool for the classification of these variants. Statistical methods have been described in literature but these methods are not always easy to apply in a diagnostic setting.

Methods

We have developed an easy to use method which calculates the likelihood ratio (LR) of an UV being deleterious, with penetrance as a function of age of onset, thereby avoiding the use of liability classes. The application of this algorithm is publicly available http://www.msbi.nl/cosegregation. It can easily be used in a diagnostic setting since it requires only information on gender, genotype, present age and/or age of onset for breast and/or ovarian cancer.

Results

We have used the algorithm to calculate the likelihood ratio in favour of causality for 3 UVs in BRCA1 (p.M18T, p.S1655F and p.R1699Q) and 5 in BRCA2 (p.E462G p.Y2660D, p.R2784Q, p.R3052W and p.R3052Q). Likelihood ratios varied from 0.097 (BRCA2, p.E462G) to 230.69 (BRCA2, p.Y2660D). Typing distantly related individuals with extreme phenotypes (i.e. very early onset cancer or old healthy individuals) are most informative and give the strongest likelihood ratios for or against causality.

Conclusion

Although co-segregation analysis on itself is in most cases insufficient to prove pathogenicity of an UV, this method simplifies the use of co-segregation as one of the key features in a multifactorial approach considerably.
The prosurvival role of autophagy in Resveratrol-induced cytotoxicity in human U251 glioma cells
Authors: Li Jun , Qin Zhenghong , Liang Zhongqin
Published: June 2009

Background

Previous study reported that resveratrol has anti-tumor activity. In this study, we investigated the involvement of autophagy in the resveratrol-induced apoptotic death of human U251 glioma cells.

Methods

The growth inhibition of U251 cells induced by resveratrol was assessed with methyl thiazolyl tetrazolium (MTT). The activation of autophagy and proapoptotic effect were characterized by monodansylcadaverine labeling and Hoechst stain, respectively. Mitochondrialtransmembrane potential (ΔΨm) was measured as a function of drug treatment using 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1). The role of autophagy and apoptosis in the resveratrol-induced death of U251 cells was assessed using autophagic and caspase inhibitors. Immunofluorescence, flow cytometry, and Western blot analysis were used to study the apoptotic and autophagic mechanisms.

Results

Methyl thiazolyl tetrazolium (MTT) assays indicated that resveratrol decreased the viability of U251 cells in a dose- and time-dependent manner. Flow cytometry analysis indicated that resveratrol increased cell population at sub-G1 phase, an index of apoptosis. Furthermore, resveratrol-induced cell death was associated with a collapse of the mitochondrial membrane potential. The pan-caspase inhibitor Z-VAD-fmk suppressed resveratrol-induced U251 cell death. Resveratrol stimulated autophagy was evidenced by punctuate monodansylcadaverine(MDC) staining and microtubule-associated protein light chain 3 (LC3) immunoreactivty. Resveratrol also increased protein levels of beclin 1 and membrane form LC3 (LC3-II). Autophagy inhibitors 3-methylademine (3-MA) and bafilomycin A1 sensitized the cytotoxicity of resveratrol.

Conclusion

Together, these findings indicate that resveratrol induces autophagy in human U251 glioma cells and autophagy suppressed resveratrol-induced apoptosis. This study thus suggests that autophagy inhibitors can increase the cytotoxicity of resveratrol to glioma cells.
High levels of multidrug resistant tuberculosis in new and treatment-failure patients from the Revised National Tuberculosis Control Programme in an urban metropolis (Mumbai) in Western India
Authors: D'souza Desiree TB , Mistry Nerges F , Vira Tina S , Dholakia Yatin , Hoffner Sven , Pasvol Geoffrey , Nicol Mark , Wilkinson Robert J
Published: June 2009

Background

India, China and Russia account for more than 62% of multidrug resistant tuberculosis (MDRTB) globally. Within India, locations like urban metropolitan Mumbai with its burgeoning population and high incidence of TB are suspected to be a focus for MDRTB. However apart from sporadic surveys at watched sites in the country, there has been no systematic attempt by the Revised National Tuberculosis Control Programme (RNTCP) of India to determine the extent of MDRTB in Mumbai that could feed into national estimates. Drug susceptibility testing (DST) is not routinely performed as a part of programme policy and public health laboratory infrastructure, is limited and poorly equipped to cope with large scale testing.

Methods

From April 2004 to January 2007 we determined the extent of drug resistance in 724 {493 newly diagnosed, previously untreated and 231 first line treatment failures (sputum-smear positive at the fifth month after commencement of therapy)} cases of pulmonary tuberculosis drawn from the RNTCP in four suboptimally performing municipal wards of Mumbai. The observations were obtained using a modified radiorespirometric Buddemeyer assay and validated by the Swedish Institute for Infectious Disease Control, Stockholm, a supranational reference laboratory. Data was analyzed utilizing SPSS 10.0 and Epi Info 2002.

Results

This study undertaken for the first time in RNTCP outpatients in Mumbai reveals a high proportion of MDRTB strains in both previously untreated (24%) and treatment-failure cases (41%). Amongst new cases, resistance to 3 or 4 drug combinations (amplified drug resistance) including isoniazid (H) and rifampicin (R), was greater (20%) than resistance to H and R alone (4%) at any point in time during the study. The trend for monoresistance was similar in both groups remaining highest to H and lowest to R. External quality control revealed good agreement for H and R resistance (k = 0.77 and 0.76 respectively).

Conclusion

Levels of MDRTB are much higher in both previously untreated and first line treatment-failure cases in the selected wards in Mumbai than those projected by national estimates. The finding of amplified drug resistance suggests the presence of a well entrenched MDRTB scenario. This study suggests that a wider set of surveillance sites are needed to obtain a more realistic view of the true MDRTB rates throughout the country. This would assist in the planning of an adequate response to the diagnosis and care of MDRTB.