bluuebunny/crossref_metadata_2025 huggingface dataset:
Allergen-induced airway remodelling
Authors: Lloyd C. M. , Robinson D. S.
Published: April 2007

Airway remodelling is associated with chronic asthma but it remains unclear whether it results from airway inflammation in response to allergens or immune-mediated events such as viral infections. Although the acute inflammation associated with asthma has been modelled extensively bothin vitroandin vivo, the structural changes occurring in the lung have only recently been investigated. Thesein vitro,in vivoandin silicosystems have been designed to examine the pathways leading to allergen-induced airway remodelling and have enabled investigators to draw conclusions about the participation of key cells and molecules in the development of allergen-induced airway remodelling. However, fundamental questions remain regarding the genesis of remodelling as well as the relationship between functional symptoms and pathological changes that occur. In this review the key questions relating allergen exposure to development of remodelling are discussed, as well as the steps that are being undertaken to investigate them.
Genomic analysis of human lung fibroblasts exposed to vanadium pentoxide to identify candidate genes for occupational bronchitis
Authors: Ingram Jennifer L , Antao-Menezes Aurita , Turpin Elizabeth A , Wallace Duncan G , Mangum James B , Pluta Linda J , Thomas Russell S , Bonner James C
Published: April 2007

Background

Exposure to vanadium pentoxide (V2O5) is a cause of occupational bronchitis. We evaluated gene expression profiles in cultured human lung fibroblasts exposed to V2O5
in vitro in order to identify candidate genes that could play a role in inflammation, fibrosis, and repair during the pathogenesis of V2O5-induced bronchitis.

Methods

Normal human lung fibroblasts were exposed to V2O5 in a time course experiment. Gene expression was measured at various time points over a 24 hr period using the Affymetrix Human Genome U133A 2.0 Array. Selected genes that were significantly changed in the microarray experiment were validated by RT-PCR.

Results

V2O5 altered more than 1,400 genes, of which ~300 were induced while >1,100 genes were suppressed. Gene ontology categories (GO) categories unique to induced genes included inflammatory response and immune response, while GO catogories unique to suppressed genes included ubiquitin cycle and cell cycle. A dozen genes were validated by RT-PCR, including growth factors (HBEGF, VEGF, CTGF), chemokines (IL8, CXCL9, CXCL10), oxidative stress response genes (SOD2, PIPOX, OXR1), and DNA-binding proteins (GAS1, STAT1).

Conclusion

Our study identified a variety of genes that could play pivotal roles in inflammation, fibrosis and repair during V2O5-induced bronchitis. The induction of genes that mediate inflammation and immune responses, as well as suppression of genes involved in growth arrest appear to be important to the lung fibrotic reaction to V2O5.
Continuous in situ measurements of volcanic gases with a diode-laser-based spectrometer: CO2 and H2O concentration and soil degassing at Vulcano (Aeolian islands: Italy)
Authors: De Rosa Maurizio , Gagliardi Gianluca , Rocco Alessandra , Somma Renato , De Natale Paolo , De Natale Giuseppe
Published: April 2007

We report on a continuous-measurement campaign carried out in Vulcano (Aeolian islands, Sicily), devoted to the simultaneous monitoring of CO2 and H2O concentrations. The measurements were performed with an absorption spectrometer based on a semiconductor laser source emitting around a 2-μm wavelength. The emitted radiation was selectively absorbed by two molecular ro-vibrational transitions specific of the investigated species. Data for CO2 and H2O concentrations, and CO2 soil diffusive flux using an accumulation chamber configuration, were collected at several interesting sampling points on the island (Porto Levante beach- PLB, Fossa Grande Crater – FOG- and Valley of Palizzi, PAL). CO2/H2O values, measured on the ground, are very similar (around 0.019 (± 0.006)) and comparable to the previous discrete detected values of 0.213 (Fumarole F5-La Fossa crater rim) and 0.012 (Fumarole VFS – Baia Levante beach) obtaid during the 1977–1993 heating phase of the crater fumaroles.

In this work much more homogeneous values are found in different points of the three sites investigated. The field work, although carried out in a limited time window (25th–28th August 2004), pointed out the new apparatus is suitable for continuous gas monitoring of the two species and their ratios, which are important geochemical indicators of volcanic activity, for which other reliable continuous monitoring systems are not yet available.
Selective prediction of interaction sites in protein structures with THEMATICS
Authors: Wei Ying , Ko Jaeju , Murga Leonel F , Ondrechen Mary Jo
Published: April 2007

Background

Methods are now available for the prediction of interaction sites in protein 3D structures. While many of these methods report high success rates for site prediction, often these predictions are not very selective and have low precision. Precision in site prediction is addressed using Theoretical Microscopic Titration Curves (THEMATICS), a simple computational method for the identification of active sites in enzymes. Recall and precision are measured and compared with other methods for the prediction of catalytic sites.

Results

Using a test set of 169 enzymes from the original Catalytic Residue Dataset (CatRes) it is shown that THEMATICS can deliver precise, localised site predictions. Furthermore, adjustment of the cut-off criteria can improve the recall rates for catalytic residues with only a small sacrifice in precision. Recall rates for CatRes/CSA annotated catalytic residues are 41.1%, 50.4%, and 54.2% for Z score cut-off values of 1.00, 0.99, and 0.98, respectively. The corresponding precision rates are 19.4%, 17.9%, and 16.4%. The success rate for catalytic sites is higher, with correct or partially correct predictions for 77.5%, 85.8%, and 88.2% of the enzymes in the test set, corresponding to the same respective Z score cut-offs, if only the CatRes annotations are used as the reference set. Incorporation of additional literature annotations into the reference set gives total success rates of 89.9%, 92.9%, and 94.1%, again for corresponding cut-off values of 1.00, 0.99, and 0.98. False positive rates for a 75-protein test set are 1.95%, 2.60%, and 3.12% for Z score cut-offs of 1.00, 0.99, and 0.98, respectively.

Conclusion

With a preferred cut-off value of 0.99, THEMATICS achieves a high success rate of interaction site prediction, about 86% correct or partially correct using CatRes/CSA annotations only and about 93% with an expanded reference set. Success rates for catalytic residue prediction are similar to those of other structure-based methods, but with substantially better precision and lower false positive rates. THEMATICS performs well across the spectrum of E.C. classes. The method requires only the structure of the query protein as input. THEMATICS predictions may be obtained via the web from structures in PDB format at: http://pfweb.chem.neu.edu/thematics/submit.html
TagSmart: analysis and visualization for yeast mutant fitness data measured by tag microarrays
Authors: Kim Chulyun , Kim Sangkyum , Dorer Russell , Xie Dan , Han Jiawei , Zhong Sheng
Published: April 2007

Background

A nearly complete collection of gene-deletion mutants (96% of annotated open reading frames) of the yeast Saccharomyces cerevisiae has been systematically constructed. Tag microarrays are widely used to measure the fitness of each mutant in a mutant mixture. The tag array experiments can have a complex experimental design, such as time course measurements and drug treatment with multiple dosages.

Results

TagSmart is a web application for analysis and visualization of Saccharomyces cerevisiae mutant fitness data measured by tag microarrays. It implements a robust statistical approach to assess the concentration differences among S. cerevisiae mutant strains. It also provides an interactive environment for data analysis and visualization. TagSmart has the following advantages over previously described analysis procedures: 1) it is user-friendly software rather than merely a description of analytical procedure; 2) It can handle complicated experimental designs, such as multiple time points and treatment with multiple dosages; 3) it has higher sensitivity and specificity; 4) It allows users to mask out "bad" tags in the analysis.

Two biological tests were performed to illustrate the performance of TagSmart. First, we generated titration mixtures of mutant strains, in which the relative concentration of each strain was controlled. We used tag microarrays to measure the numbers of tag copies in each titration mixture. The data was analyzed with TagSmart and the result showed high precision and recall. Second, TagSmart was applied to a dataset in which heterozygous deletion strain mixture pools were treated with a new drug, Cincreasin. TagSmart identified 53 mutant strains as sensitive to Cincreasin treatment. We individually tested each identified mutant, and found 52 out of the 53 predicted mutants were indeed sensitive to Cincreasin.

Conclusion

TagSmart is provided "as is" to analyze tag array data produced by Affymetrix and Agilent arrays. TagSmart web application is assessable by Windows, Mac, and Linux users. It also has a downloadable version for execution on PCs running Windows. TagSmart is available for academic use at: http://biocomp.bioen.uiuc.edu/tagsmart
The lin-35/ Rb and RNAi pathways cooperate to regulate a key cell cycle transition in C. elegans
Authors: Ouellet Jimmy , Roy Richard
Published: April 2007

Background

The Retinoblastoma gene product (Rb) has been shown to regulate the transcription of key genes involved in cell growth and proliferation. Consistent with this, mutations in Rb are associated with numerous types of cancer making it a critical tumour suppressor gene. Its function is conferred through a large multiprotein complex that exhibits a dual function in both activation and repression of gene targets. In C. elegans, the Rb orthologue lin-35 functions redundantly with other transcriptional regulators to appropriately specify both vulval and pharyngeal cell fates.

Results

In C. elegans the intestinal cells must alter their cell cycle from the mitotic cell divisions typical of embryogenesis to karyokinesis and then endoreplication, which facilitates growth during larval development. While screening for genes that affect the ability of the intestinal cells to appropriately make this cell cycle transition during post-embryonic development, we isolated mutants that either compromise this switch and remain mononucleate, or cause these cells to undergo multiple rounds of nuclear division. Among these mutants we identified a novel allele of lin-35/Rb, while we also found that the components of the synMuv B complex, which are involved in vulval specification, are also required to properly regulate the developmentally-controlled cell cycle transition typical of these intestinal cells during larval development. More importantly, our work uncovered a role for certain members of the pathways involved in RNAi in mediating the efficient transition between these cell cycle programs, suggesting that lin-35/Rb cooperates with these RNAi components. Furthermore, our findings suggest that met-2, a methyltransferase as well as hpl-1 and hpl-2, two C. elegans homologues of the heterochromatin protein HP1 are also required for this transition.

Conclusion

Our findings are consistent with lin-35/Rb, synMuv and RNAi components cooperating, probably through their additive effects on chromatin modification, to appropriately modulate the expression of genes that are required to switch from the karyokinesis cell cycle to endoreplication; a highly specified growth pathway in the intestinal epithelium. The lin-35/Rb repressor complex may be required to initiate this process, while components of the RNAi machinery positively reinforce this repression.
Gain and loss of polyadenylation signals during evolution of green algae
Authors: Wodniok Sabina , Simon Andreas , Glöckner Gernot , Becker Burkhard
Published: April 2007

Background

The Viridiplantae (green algae and land plants) consist of two monophyletic lineages: the Chlorophyta and the Streptophyta. Most green algae belong to the Chlorophyta, while the Streptophyta include all land plants and a small group of freshwater algae known as Charophyceae. Eukaryotes attach a poly-A tail to the 3' ends of most nuclear-encoded mRNAs. In embryophytes, animals and fungi, the signal for polyadenylation contains an A-rich sequence (often AAUAAA or related sequence) 13 to 30 nucleotides upstream from the cleavage site, which is commonly referred to as the near upstream element (NUE). However, it has been reported that the pentanucleotide UGUAA is used as polyadenylation signal for some genes in volvocalean algae.

Results

We set out to investigate polyadenylation signal differences between streptophytes and chlorophytes that may have emerged shortly after the evolutionary split between Streptophyta and Chlorophyta. We therefore analyzed expressed genes (ESTs) from three streptophyte algae, Mesostigma viride, Klebsormidium subtile and Coleochaete scutata, and from two early-branching chlorophytes, Pyramimonas parkeae and Scherffelia dubia. In addition, to extend the database, our analyses included ESTs from six other chlorophytes (Acetabularia acetabulum, Chlamydomonas reinhardtii, Helicosporidium sp. ex Simulium jonesii, Prototheca wickerhamii, Scenedesmus obliquus and Ulva linza) and one streptophyte (Closterium peracerosum). Our results indicate that polyadenylation signals in green algae vary widely. The UGUAA motif is confined to late-branching Chlorophyta. Most streptophyte algae do not have an A-rich sequence motif like that in embryophytes, animals and fungi. We observed polyadenylation signals similar to those of Arabidopsis and other land plants only in Mesostigma.

Conclusion

Polyadenylation signals in green algae show considerable variation. A new NUE (UGUAA) was invented in derived chlorophytes and replaced not only the A-rich NUE but the complete poly(A) signal in all chlorophytes investigated except Scherffelia (only NUE replaced) and Pyramimonas (UGUAA completely missing). The UGUAA element is completely absent from streptophytes. However, the structure of the poly(A) signal was often modified in streptophyte algae. In most species investigated, an A-rich NUE is missing; instead, these species seem to rely mainly on U-rich elements.
An insight into the sialome of the oriental rat flea, Xenopsylla cheopis (Rots)
Authors: Andersen John F , Hinnebusch B Joseph , Lucas David A , Conrads Thomas P , Veenstra Timothy D , Pham Van M , Ribeiro José MC
Published: April 2007

Background

The salivary glands of hematophagous animals contain a complex cocktail that interferes with the host hemostasis and inflammation pathways, thus increasing feeding success. Fleas represent a relatively recent group of insects that evolved hematophagy independently of other insect orders.

Results

Analysis of the salivary transcriptome of the flea Xenopsylla cheopis, the vector of human plague, indicates that gene duplication events have led to a large expansion of a family of acidic phosphatases that are probably inactive, and to the expansion of the FS family of peptides that are unique to fleas. Several other unique polypeptides were also uncovered. Additionally, an apyrase-coding transcript of the CD39 family appears as the candidate for the salivary nucleotide hydrolysing activity in X.cheopis, the first time this family of proteins is found in any arthropod salivary transcriptome.

Conclusion

Analysis of the salivary transcriptome of the flea X. cheopis revealed the unique pathways taken in the evolution of the salivary cocktail of fleas. Gene duplication events appear as an important driving force in the creation of salivary cocktails of blood feeding arthropods, as was observed with ticks and mosquitoes. Only five other flea salivary sequences exist at this time at NCBI, all from the cat flea C. felis. This work accordingly represents the only relatively extensive sialome description of any flea species. Sialotranscriptomes of additional flea genera will reveal the extent that these novel polypeptide families are common throughout the Siphonaptera.
diArk – a resource for eukaryotic genome research
Authors: Odronitz Florian , Hellkamp Marcel , Kollmar Martin
Published: April 2007

Background

The number of completed eukaryotic genome sequences and cDNA projects has increased exponentially in the past few years although most of them have not been published yet. In addition, many microarray analyses yielded thousands of sequenced EST and cDNA clones. For the researcher interested in single gene analyses (from a phylogenetic, a structural biology or other perspective) it is therefore important to have up-to-date knowledge about the various resources providing primary data.

Description

The database is built around 3 central tables: species, sequencing projects and publications. The species table contains commonly and alternatively used scientific names, common names and the complete taxonomic information. For projects the sequence type and links to species project web-sites and species homepages are stored. All publications are linked to projects. The web-interface provides comprehensive search modules with detailed options and three different views of the selected data. We have especially focused on developing an elaborate taxonomic tree search tool that allows the user to instantaneously identify e.g. the closest relative to the organism of interest.

Conclusion

We have developed a database, called diArk, to store, organize, and present the most relevant information about completed genome projects and EST/cDNA data from eukaryotes. Currently, diArk provides information about 415 eukaryotes, 823 sequencing projects, and 248 publications.
Use of suppression subtractive hybridisation to extend our knowledge of genome diversity in Campylobacter jejuni
Authors: Hepworth Philip J , Leatherbarrow Howard , Hart C Anthony , Winstanley Craig
Published: April 2007

Background

Previous studies have sought to identify a link between the distribution of variable genes amongst isolates of Campylobacter jejuni and particular host preferences. The genomic sequence data available currently was obtained using only isolates from human or chicken hosts. In order to identify variable genes present in isolates from alternative host species, five subtractions between C. jejuni isolates from different sources (rabbit, cattle, wild bird) were carried out, designed to assess genomic variability within and between common multilocus sequence type (MLST) clonal complexes (ST-21, ST-42, ST-45 and ST-61).

Results

The vast majority (97%) of the 195 subtracted sequences identified had a best BLASTX match with a Campylobacter protein. However, there was considerable variation within and between the four clonal complexes included in the subtractions. The distributions of eight variable sequences, including four with putative roles in the use of alternative terminal electron acceptors, amongst a panel of C. jejuni isolates representing diverse sources and STs, were determined.

Conclusion

There was a clear correlation between clonal complex and the distribution of the metabolic genes. In contrast, there was no evidence to support the hypothesis that the distribution of such genes may be related to host preference. The other variable genes studied were also generally distributed according to MLST type. Thus, we found little evidence for widespread horizontal gene transfer between clonal complexes involving these genes.
Assessing the reliability of eBURST using simulated populations with known ancestry
Authors: Turner Katherine ME , Hanage William P , Fraser Christophe , Connor Thomas R , Spratt Brian G
Published: April 2007

Background

The program eBURST uses multilocus sequence typing data to divide bacterial populations into groups of closely related strains (clonal complexes), predicts the founding genotype of each group, and displays the patterns of recent evolutionary descent of all other strains in the group from the founder. The reliability of eBURST was evaluated using populations simulated with different levels of recombination in which the ancestry of all strains was known.

Results

For strictly clonal simulations, where all allelic change is due to point mutation, the groups of related strains identified by eBURST were very similar to those expected from the true ancestry and most of the true ancestor-descendant relationships (90–98%) were identified by eBURST. Populations simulated with low or moderate levels of recombination showed similarly high performance but the reliability of eBURST declined with increasing recombination to mutation ratio. Populations simulated under a high recombination to mutation ratio were dominated by a single large straggly eBURST group, which resulted from the incorrect linking of unrelated groups of strains into the same eBURST group. The reliability of the ancestor-descendant links in eBURST diagrams was related to the proportion of strains in the largest eBURST group, which provides a useful guide to when eBURST is likely to be unreliable.

Conclusion

Examination of eBURST groups within populations of a range of bacterial species showed that most were within the range in which eBURST is reliable, and only a small number (e.g. Burkholderia pseudomallei and Enterococcus faecium) appeared to have such high rates of recombination that eBURST is likely to be unreliable. The study also demonstrates how three simple tests in eBURST v3 can be used to detect unreliable eBURST performance and recognise populations in which there appears to be a high rate of recombination relative to mutation.
Cross-sectional validation of the Aging Perceptions Questionnaire: a multidimensional instrument for assessing self-perceptions of aging
Authors: Barker Maja , O'Hanlon Ann , McGee Hannah M , Hickey Anne , Conroy Ronan M
Published: April 2007

Background

Self-perceptions of aging have been implicated as independent predictors of functional disability and mortality in older adults. In spite of this, research on self-perceptions of aging is limited. One reason for this is the absence of adequate measures. Specifically, there is a need to develop a measure that is theoretically-derived, has good psychometric properties, and is multidimensional in nature. The present research seeks to address this need by adopting the Self-Regulation Model as a framework and using it to develop a comprehensive, multi-dimensional instrument for assessing self-perceptions of aging. This study describes the validation of this newly-developed instrument, the Aging Perceptions Questionnaire (APQ).

Methods

Participants were 2,033 randomly selected community-dwelling older (+65 yrs) Irish adults who completed the APQ alongside measures of physical and psychological health. The APQ assesses self-perceptions of aging along eight distinct domains or subscales; seven of these examine views about own aging, these are: timeline chronic, timeline cyclical, consequences positive, consequences negative, control positive, control negative, and emotional representations; the eighth domain is the identity domain and this examines the experience of health-related changes.

Results

Mokken scale analysis showed that the majority of items within the views about aging subscales were strongly scalable. Confirmatory factor analysis also indicated that the model provided a good fit for the data. Overall, subscales had good internal reliabilities. Hierarchical linear regression was conducted to investigate the independent contribution of APQ subscales to physical and psychological health and in doing so determine the construct validity of the APQ. Results showed that self-perceptions of aging were independently related to physical and psychological health. Mediation testing also supported a role for self-perceptions of aging as partial mediators in the relationship between indices of physical functioning and physical and psychological health outcomes.

Conclusion

Findings support the complex and multifaceted nature of the aging experience. The good internal reliability and construct validity of the subscales suggests that the APQ is a promising instrument that can enable a theoretically informed, multidimensional assessment of self-perceptions of aging. The potential role of self-perceptions of aging in facilitating physical and psychological health in later life is also highlighted.
Role of previous hospitalization in clinically-significant MRSA infection among HIV-infected inpatients: results of a case-control study
Authors: Drapeau Cecilia MJ , Angeletti Claudio , Festa Anna , Petrosillo Nicola
Published: April 2007

Background

HIV-infected subjects have high incidence rates of Staphylococcus aureus infections, with both methicillin-susceptible and methicillin-resistant (MRSA) strains. Possible explanations could include the high burden of colonization, the behavioral risk factors, and the frequent exposures to health care facilities of HIV-infected patients. The purpose of the study was to assess the risk factors for clinically- significant methicillin-resistant Staphylococcus aureus (CS-MRSA) infections in HIV-infected patients admitted to Infectious Diseases Units.

Methods

From January 1, 2002 to December 31, 2005, we conducted a retrospective case-control (1:2) study. We identified all the cases of CS-MRSA infections in HIV-infected patients admitted to the National Institute for Infectious Diseases (INMI) "Lazzaro Spallanzani" in the 4-year study period. A conditional logistic regression model was used to identify risk factors for CS-MRSA infection.

Results

We found 27 CS-MRSA infections, i.e. 0.9 CS-MRSA infections per 100 HIV-infected individuals cared for in our Institute. At multivariate analysis, independent predictors of CS-MRSA infection were cumulative hospital stay, invasive procedures in the previous year, and low CD4 cell count. Particularly, the risk for CS-MRSA increased by 14% per an increase of 5 days hospitalization in the previous year. Finally, we identified a low frequency of community-acquired MRSA infections (only 1 of 27; 3.7%) among HIV-infected patients.

Conclusion

Clinicians should be aware of the risk for CS-MRSA infection in the clinical management of HIV-infected patients, especially in those patients with a low CD4 cell count, longer previous hospital stay, and previous invasive procedures.
Sequence, "subtle" alternative splicing and expression of the CYYR1 (cysteine/tyrosine-rich 1) mRNA in human neuroendocrine tumors
Authors: Vitale Lorenza , Frabetti Flavia , Huntsman Shane A , Canaider Silvia , Casadei Raffaella , Lenzi Luca , Facchin Federica , Carinci Paolo , Zannotti Maria , Coppola Domenico , Strippoli Pierluigi
Published: April 2007

Background

CYYR1 is a recently identified gene located on human chromosome 21 whose product has no similarity to any known protein and is of unknown function. Analysis of expressed sequence tags (ESTs) have revealed high human CYYR1 expression in cells belonging to the diffuse neuroendocrine system (DNES). These cells may be the origin of neuroendocrine (NE) tumors. The aim of this study was to conduct an initial analysis of sequence, splicing and expression of the CYYR1 mRNA in human NE tumors.

Methods

The CYYR1 mRNA coding sequence (CDS) was studied in 32 NE tumors by RT-PCR and sequence analysis. A subtle alternative splicing was identified generating two isoforms of CYYR1 mRNA differing in terms of the absence (CAG- isoform, the first described mRNA for CYYR1 locus) or the presence (CAG+ isoform) of a CAG codon. When present, this specific codon determines the presence of an alanine residue, at the exon 3/exon 4 junction of the CYYR1 mRNA. The two mRNA isoform amounts were determined by quantitative relative RT-PCR in 29 NE tumors, 2 non-neuroendocrine tumors and 10 normal tissues. A bioinformatic analysis was performed to search for the existence of the two CYYR1 isoforms in other species.

Results

The CYYR1 CDS did not show differences compared to the reference sequence in any of the samples, with the exception of an NE tumor arising in the neck region. Sequence analysis of this tumor identified a change in the CDS 333 position (T instead of C), leading to the amino acid mutation P111S. NE tumor samples showed no significant difference in either CYYR1 CAG- or CAG+ isoform expression compared to control tissues. CYYR1 CAG- isoform was significantly more expressed than CAG+ isoform in NE tumors as well as in control samples investigated. Bioinformatic analysis revealed that only the genomic sequence of Pan troglodytes CYYR1 is consistent with the possible existence of the two described mRNA isoforms.

Conclusion

A new "subtle" splicing isoform (CAG+) of CYYR1 mRNA, the sequence and the expression of this gene were defined in a large series of NE tumors.
Thiazolidinedione induced thyroid associated orbitopathy
Authors: Lee Seongmu , Tsirbas Angelo , Goldberg Robert A , McCann John D
Published: April 2007

Background

To describe an episode of thyroid associated orbitopathy (TAO) following the initiation of thiazolidinedione (TZD).

Case presentation

We report a female patient with a history of Graves' disease and stabilised thyroid associated orbitopathy for 2.5 years, who experienced rapid progression of TAO after the initiation of thiazolidinedione for glycemic control. Following the discontinuation of TZD, the patient experienced subsequent stabilisation of disease and normalization of vision. The medical history, ophthalmic findings, and clinical course are discussed.

Conclusion

Thiazolidinediones may exacerbate TAO, and this should be taken into consideration when selecting treatment for diabetic patients with a history of autoimmune thyroid disorders.
Smoking among pregnant women in Cantabria (Spain): trend and determinants of smoking cessation
Authors: Palma Silvia , Pérez-Iglesias Rocio , Pardo-Crespo Rosa , Llorca Javier , Mariscal Marcial , Delgado-Rodríguez Miguel
Published: April 2007

Background

Cantabria (Spain) has one of the highest prevalence of smoking among women of the European Union. The objectives are to assess the trend of smoking during pregnancy in a five-year period and the determinants of smoking cessation during pregnancy in Cantabria.

Methods

A 1/6 random sample of all women delivering at the reference hospital of the region for the period 1998–2002 was drawn, 1559 women. Information was obtained from personal interview, clinical chart, and prenatal care records. In the analysis relative risks and 95% confidence intervals were estimated. Multivariable analysis was carried out using stepwise logistic regression.

Results

Smoking prior to pregnancy decreased from 53.6% in 1998 to 39.4% in 2002. A decrease in smoking cessation among women smoking at the beginning of pregnancy was observed, from 37.3% in 1998 to 20.6% in 2002. The mean number of cigarettes/day (cig/d) before pregnancy remained constant, around 16 cig/d, whereas a slight trend to increase over time was seen, from 7.7 to 8.9 cig/d. In univariate analysis two variables favoured significantly smoking cessation, although they were not included in the stepwise logistic regression analysis, a higher education level and to be married. The logistic regression model included five significant predictors (also significant in univariate analysis): intensity of smoking, number of previous pregnancies, partner's smoking status, calendar year of study period (these four variables favoured smoking continuation), and adequate prenatal care (which increased smoking cessation).

Conclusion

The frequency of smoking among pregnant women is very high in Cantabria. As smoking cessation rate has decreased over time, a change in prenatal care programme on smoking counseling is needed. Several determinants of smoking cessation, such as smoking before pregnancy and partner's smoking, should be also addressed by community programmes.
Amelioration of galactosamine-induced nephrotoxicity by a protein isolated from the leaves of the herb, Cajanus indicus L
Authors: Sinha Mahua , Manna Prasenjit , Sil Parames C
Published: April 2007

Background

Galactosamine (GalN), an established experimental toxin, mainly causes liver injury via the generation of free radicals and depletion of UTP nucleotides. Renal failure is often associated with end stage liver damage. GalN intoxication also induces renal dysfunction in connection with hepatic disorders. Present study was designed to find out the effect of a protein isolated from the leaves of the herb Cajanus indicus against GalN induced renal damage.

Methods

Both preventive as well as curative effect of the protein was investigated in the study. GalN was administered intraperitoneally at a dose of 800 mg/kg body weight for 3 days pre and post to protein treatment at an intraperitoneal dose of 2 mg/kg body weight for 4 days. The activities of antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) and glutathione-S-transferase (GST), levels of cellular metabolites, reduced glutathione (GSH), total thiols, oxidized glutathione (GSSG) and lipid peroxidation end products were determined to estimate the status of the antioxidative defense system. In addition, serum creatinine and urea nitrogen (UN) levels were also measured as a marker of nephrotoxicity.

Results

Results showed that GalN treatment significantly increased the serum creatinine and UN levels compared to the normal group of mice. The extent of lipid peroxidation and the level of GSSG were also enhanced by the GalN intoxication whereas the activities of antioxidant enzymes SOD, CAT, GR and GST as well as the levels of total thiols and GSH were decreased in the kidney tissue homogenates. Protein treatment both prior and post to the toxin administration successfully altered the effects in the experimental mice.

Conclusion

Our study revealed that GalN caused a severe oxidative insult in the kidney. Protein treatment both pre and post to the GalN intoxication could protect the kidney tissue against GalN induced oxidative stress. As GalN induced severe hepatotoxicity followed by renal failure, the protective role of the protein against GalN induced renal damages is likely to be an indirect effect. Since the protein possess hepatoprotective activity, it may first ameliorate GalN-induced liver damage and consequently the renal disorders are reduced. To the best of our knowledge, this is probably the first report describing GalN-induced oxidative stress in renal damages and the protective role of a plant protein molecule against it.
Cultural diversity teaching and issues of uncertainty: the findings of a qualitative study
Authors: Dogra Nisha , Giordano James , France Nicholas
Published: April 2007

Background

There is considerable ambiguity in the subjective dimensions that comprise much of the relational dynamic of the clinical encounter. Comfort with this ambiguity, and recognition of the potential uncertainty of particular domains of medicine (e.g. – cultural factors of illness expression, value bias in diagnoses, etc) is an important facet of medical education. This paper begins by defining ambiguity and uncertainty as relevant to clinical practice. Studies have shown differing patterns of students' tolerance for ambiguity and uncertainty that appear to reflect extant attitudinal predispositions toward technology, objectivity, culture, value- and theory-ladeness, and the need for self-examination. This paper reports on those findings specifically related to the theme of uncertainty as relevant to teaching about cultural diversity. Its focus is to identify how and where the theme of certainty arose in the teaching and learning of cultural diversity, what were the attitudes toward this theme and topic, and how these attitudes and responses reflect and inform this area of medical pedagogy.

Methods

A semi-structured interview was undertaken with 61 stakeholders (including policymakers, diversity teachers, students and users). The data were analysed and themes identified.

Results

There were diverse views about what the term cultural diversity means and what should constitute the cultural diversity curriculum. There was a need to provide certainty in teaching cultural diversity with diversity teachers feeling under considerable pressure to provide information. Students discomfort with uncertainty was felt to drive cultural diversity teaching towards factual emphasis rather than reflection or taking a patient centred approach.

Conclusion

Students and faculty may feel that cultural diversity teaching is more about how to avoid professional, medico-legal pitfalls, rather than improving the patient experience or the patient-physician relationship. There may be pressure to imbue cultural diversity issues with levels of objectivity and certainty representative of other aspects of the medical curriculum (e.g. – biochemistry). This may reflect a particular selection bias for students with a technocentric orientation. Inadvertently, medical education may enhance this bias through training effects, and accommodate disregard for subjectivity, over-reliance upon technology and thereby foster incorrect assumptions of objective certainty. We opine that it is important to teach students that technology cannot guarantee certainty, and that dealing with subjectivity, diversity, ambiguity and uncertainty is inseparable from the personal dimension of medicine as moral enterprise. Uncertainty is inherent in cultural diversity so this part of the curriculum provides an opportunity to address the issue as it relates to pateint care.
Investigating health system performance: An application of data envelopment analysis to Zambian hospitals
Authors: Masiye Felix
Published: April 2007

Background

Zambia has recently articulated an ambitious national health program designed to meeting health-related MDGs. Public expectations are high and Zambia continues to receive significant resources from global and bilateral donors to support its health agenda. Although the lack of adequate resources presents the most important constraint, the efficiency with which available resources are being utilised is another challenge that cannot be overlooked. Inefficiency in producing health care undermines the service coverage potential of the health system. This paper estimates the technical efficiency of a sample of hospitals in Zambia.

Methods

Efficiency is measured using a DEA model. Vectors of hospital inputs and outputs, representing hospital expended resources and output profiles respectively, were specified and measured. The data were gathered from a sample of 30 hospitals throughout Zambia. The model estimates an efficiency score for each hospital. A decomposition of technical efficiency into scale and congestion is also provided.

Results

Results show that overall Zambian hospitals are operating at 67% level of efficiency, implying that significant resources are being wasted. Only 40% of hospitals were efficient in relative terms. The study further reveals that the size of hospitals is a major source of inefficiency. Input congestion is also found to be a source of hospital inefficiency.

Conclusion

This study has demonstrated that inefficiency of resource use in hospitals is significant. Policy attention is drawn to unsuitable hospital scale of operation and low productivity of some inputs as factors that reinforce each other to make Zambian hospitals technically inefficient at producing and delivering services. It is argued that such evidence of substantial inefficiency would undermine Zambia's prospects of achieving its health goals.
Exploring the effect of changes to service provision on the use of unscheduled care in England: population surveys
Authors: O'Cathain Alicia , Knowles Emma , Munro James , Nicholl Jon
Published: April 2007

Background

Unscheduled care is defined here as when someone seeks treatment or advice for a health problem without arranging to do so more than a day in advance. Recent health policy initiatives in England have focused on introducing new services such as NHS Direct and walk in centres into the unscheduled care system. This study used population surveys to explore the effect of these new services on the use of traditional providers of unscheduled care, and to improve understanding of help seeking behaviour within the system of unscheduled care.

Methods

Cross-sectional population postal surveys were undertaken annually over the five year period 1998 to 2002 in two geographical areas in England. Each year questionnaires were sent to 5000 members of the general population in each area.

Results

The response rate was 69% (33,602/48,883). Over the five year period 16% (5223/33602) 95%CI (15.9 to 16.1) of respondents had an unscheduled episode in the previous four weeks and this remained stable over time (p = 0.170). There was an increased use of telephone help lines over the five years, reflecting the change in service provision (p = 0.008). However, there was no change in use of traditional services over this time period. Respondents were most likely to seek help from general practitioners (GPs), family and friends, and pharmacists, used by 9.0%, 7.2% and 6.3% respectively of the 5815 respondents in 2002. Most episodes involved contact with a single service only: 7.0% (2363/33,602) of the population had one contact and 2% (662/33602) had three or more contacts per episode. GPs were the most frequent point of first contact with services.

Conclusion

Introducing new services to the provision of unscheduled care did not affect the use of traditional services. A large majority of the population continued to turn to their GP for unscheduled health care.
Individual differences in the use of the response scale determine valuations of hypothetical health states: an empirical study
Authors: Essink-Bot Marie-Louise , Stuifbergen Marja C , Meerding Willem-Jan , Looman Caspar WN , Bonsel Gouke J ,   the VOTE group
Published: April 2007

Background

The effects of socio-demographic characteristics of the respondent, including age, on valuation scores of hypothetical health states remain inconclusive. Therefore, we analyzed data from a study designed to discriminate between the effects of respondents' age and time preference on valuations of health states to gain insight in the contribution of individual response patterns to the variance in valuation scores.

Methods

A total of 212 respondents from three age groups valued the same six hypothetical health states using three different methods: a Visual Analogue Scale (VAS) and two variants of the Time trade-off (TTO). Analyses included a generalizability study, principal components analysis, and cluster analysis.

Results

Valuation scores differed significantly, but not systematically, between valuation methods. A total of 36.8% of variance was explained by health states, 1.6% by the elicitation method, and 0.2% by age group. Individual differences in the use of the response scales (e.g. a tendency to give either high or low TTO scores, or a high or low scoring tendency on the VAS) were the main source of remaining variance. These response patterns were not related to age or other identifiable respondent characteristics.

Conclusion

Individual response patterns in this study were more important determinants of TTO or VAS valuations of health states than age or other respondent characteristics measured. Further valuation research should focus on explaining individual response patterns as a possible key to understanding the determinants of health state valuations.
Considering the case for an antidepressant drug trial involving temporary deception: a qualitative enquiry of potential participants
Authors: Dowrick Christopher F , Hughes John G , Hiscock Julia J , Wigglesworth Mark , Walley Thomas J
Published: April 2007

Background

Systematic reviews of randomised placebo controlled trials of antidepressant medication show small and decreasing differences between pharmacological and placebo arms. In part this finding may relate to methodological problems with conventional trial designs, including their assumption of additivity between drug and placebo trial arms. Balanced placebo designs, which include elements of deception, may address the additivity question, but pose substantial ethical and pragmatic problems. This study aimed to ascertain views of potential study participants of the ethics and pragmatics of various balanced placebo designs, in order to inform the design of future antidepressant drug trials.

Methods

A qualitative approach was employed to explore the perspectives of general practitioners, psychiatrists, and patients with experience of depression. The doctors were chosen via purposive sampling, while patients were recruited through participating general practitioners. Three focus groups and 12 in-depth interviews were conducted. A vignette-based topic guide invited views on three deceptive strategies: post hoc, authorised and minimised deception. The focus groups and interviews were tape-recorded and transcribed. Transcripts were analysed thematically using Framework.

Results

Deception in non-research situations was typically perceived as acceptable within specific parameters. All participants could see the potential utility of introducing deception into trial designs, however views on the acceptability of deception within antidepressant drug trials varied substantially. Authorized deception was the most commonly accepted strategy, though some thought this would reduce the effectiveness of the design because participants would correctly guess the deceptive element. The major issues that affected views about the acceptability of deception studies were the welfare and capacity of patients, practicalities of trial design, and the question of trust.

Conclusion

There is a trade-off between pragmatic and ethical responses to the question of whether, and under what circumstances, elements of deception could be introduced into antidepressant drug trials. Ensuring adequate ethical safeguards within balanced placebo designs is likely to diminish their ability to address the crucial issue of additivity. The balanced placebo designs considered in this study are unlikely to be feasible in future trials of antidepressant medication. However there remains an urgent need to improve the quality of antidepressant drug trials.