bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact and cost-effectiveness of strategies to detect drug-resistant tuberculosis
Authors: Oxlade O. , Falzon D. , Menzies D.
Published: August 2011

Drug-resistant tuberculosis (TB) is a serious emerging problem in many low-resource countries. TB control programmes are uncertain of which drug susceptibility tests (DSTs) to use and when to test patients. We predicted the potential cost-effectiveness of different DST strategies, in settings with varying prevalence of drug resistance.

Using decision analysis, we assessed the cost-effectiveness of conventional and rapid DSTs for previously diagnosed smear-positive TB cases. Five different time-points were considered for administering DSTs. Different initial drug resistance and HIV scenarios were also considered.

All DST scenarios in the wide range of settings considered were found to be cost-effective. The strategy of performing a rapid DST that detects any form of isoniazid (INH) and rifampicin (RIF) resistance for all patients before the initiation of treatment was predicted to be the most cost-effective strategy. In a setting with moderate drug resistance, the cost per disability-adjusted life year gained was as low as US$744.

Our findings support the roll-out of rapid drug susceptibility testing at the moment of diagnosis to detect any form of INH and RIF resistance in all countries with moderate or greater burdens of drug-resistant TB.
WHO guidelines for the programmatic management of drug-resistant tuberculosis: 2011 update
Authors: Falzon D. , Jaramillo E. , Schünemann H.J. , Arentz M. , Bauer M. , Bayona J. , Blanc L. , Caminero J.A. , Daley C.L. , Duncombe C. , Fitzpatrick C. , Gebhard A. , Getahun H. , Henkens M. , Holtz T.H. , Keravec J. , Keshavjee S. , Khan A.J. , Kulier R. , Leimane V. , Lienhardt C. , Lu C. , Mariandyshev A. , Migliori G.B. , Mirzayev F. , Mitnick C.D. , Nunn P. , Nwagboniwe G. , Oxlade O. , Palmero D. , Pavlinac P. , Quelapio M.I. , Raviglione M.C. , Rich M.L. , Royce S. , Rüsch-Gerdes S. , Salakaia A. , Sarin R. , Sculier D. , Varaine F. , Vitoria M. , Walson J.L. , Wares F. , Weyer K. , White R.A. , Zignol M.
Published: August 2011

The production of guidelines for the management of drug-resistant tuberculosis (TB) fits the mandate of the World Health Organization (WHO) to support countries in the reinforcement of patient care.

WHO commissioned external reviews to summarise evidence on priority questions regarding case-finding, treatment regimens for multidrug-resistant TB (MDR-TB), monitoring the response to MDR-TB treatment, and models of care. A multidisciplinary expert panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations.

The recommendations support the wider use of rapid drug susceptibility testing for isoniazid and rifampicin or rifampicin alone using molecular techniques. Monitoring by sputum culture is important for early detection of failure during treatment. Regimens lasting ≥20 months and containing pyrazinamide, a fluoroquinolone, a second-line injectable drug, ethionamide (or prothionamide), and either cycloserine orp-aminosalicylic acid are recommended. The guidelines promote the early use of antiretroviral agents for TB patients with HIV on second-line drug regimens. Systems that primarily employ ambulatory models of care are recommended over others based mainly on hospitalisation.

Scientific and medical associations should promote the recommendations among practitioners and public health decision makers involved in MDR-TB care. Controlled trials are needed to improve the quality of existing evidence, particularly on the optimal composition and duration of MDR-TB treatment regimens.
Initial management of pneumonia and sepsis: factors associated with improved outcome
Authors: Menéndez R. , Torres A. , Reyes S. , Zalacain R. , Capelastegui A. , Aspa J. , Borderías L. , Martín-Villasclaras J.J. , Bello S. , Alfageme I. , de Castro F.R. , Rello J. , Molinos L. , Ruiz-Manzano J.
Published: August 2011

Processes of care and adherence to guidelines have been associated with improved survival in community-acquired pneumonia (CAP). In sepsis, bundles of processes of care have also increased survival. We aimed to audit compliance with guideline-recommended processes of care and its impact on outcome in hospitalised CAP patients with sepsis.

We prospectively studied 4,137 patients hospitalised with CAP in 13 hospitals. The processes of care evaluated were adherence to antibiotic prescription guidelines, first dose within 6 h and oxygen assessment. Outcome measures were mortality and length of stay (LOS).

Oxygen assessment was measured in 3,745 (90.5%) patients; 3,024 (73.1%) patients received antibiotics according to guidelines and 3,053 (73.8%) received antibiotics within 6 h. In CAP patients with sepsis, the strongest independent factor for survival was antibiotic adherence (OR 0.4). In severe sepsis, only compliance to antibiotic adherence plus first dose within 6 h was associated with lower mortality (OR 0.60), adjusted for fine prognostic scale and hospital. Antibiotic adherence was related to shorter hospital stay.

In sepsis, antibiotic adherence is the strongest protective factor of care associated with survival and LOS. In severe sepsis, combined antibiotic adherence and first dose within 6 h may reduce mortality.
Nasal lavage natural killer cell function is suppressed in smokers after live attenuated influenza virus
Authors: Horvath Katherine M , Herbst Margaret , Zhou Haibo , Zhang Hongtao , Noah Terry L , Jaspers Ilona
Published: August 2011

Background

Modified function of immune cells in nasal secretions may play a role in the enhanced susceptibility to respiratory viruses that is seen in smokers. Innate immune cells in nasal secretions have largely been characterized by cellular differentials using morphologic criteria alone, which have successfully identified neutrophils as a significant cell population within nasal lavage fluid (NLF) cells. However, flow cytometry may be a superior method to fully characterize NLF immune cells. We therefore characterized immune cells in NLF by flow cytometry, determined the effects of live attenuated influenza virus (LAIV) on NLF and peripheral blood immune cells, and compared responses in samples obtained from smokers and nonsmokers.

Methods

In a prospective observational study, we characterized immune cells in NLF of nonsmokers at baseline using flow cytometry and immunohistochemistry. Nonsmokers and smokers were inoculated with LAIV on day 0 and serial nasal lavages were collected on days 1-4 and day 9 post-LAIV. LAIV-induced changes of NLF cells were characterized using flow cytometry. Cell-free NLF was analyzed for immune mediators by bioassay. Peripheral blood natural killer (NK) cells from nonsmokers and smokers at baseline were stimulatedin vitrowith LAIV followed by flow cytometric and mediator analyses.

Results

CD45(+)CD56(-)CD16(+) neutrophils and CD45(+)CD56(+) NK cells comprised median 4.62% (range 0.33-14.52) and 23.27% (18.29-33.97), respectively, of non-squamous NLF cells in nonsmokers at baseline. LAIV did not induce changes in total NK cell or neutrophil percentages in either nonsmokers or smokers. Following LAIV inoculation, CD16(+) NK cell percentages and granzyme B levels increased in nonsmokers, and these effects were suppressed in smokers. LAIV inoculation enhanced expression of activating receptor NKG2D and chemokine receptor CXCR3 on peripheral blood NK cells from both nonsmokers and smokersin vitrobut did not induce changes in CD16(+) NK cells or granzyme B activity in either group.

Conclusions

These data are the first to identify NK cells as a major immune cell type in the NLF cell population and demonstrate that mucosal NK cell cytotoxic function is suppressed in smokers following LAIV. Altered NK cell function in smokers suggests a potential mechanism that may enhance susceptibility to respiratory viruses.
Pseudomonas aeruginosa toxin ExoU induces a PAF-dependent impairment of alveolar fibrin turnover secondary to enhanced activation of coagulation and increased expression of plasminogen activator inhibitor-1 in the course of mice pneumosepsis
Authors: Machado Gloria-Beatriz , de Oliveira Albanita V , Saliba Alessandra M , de Lima Carolina D Mallet , Suassuna José HR , Plotkowski Maria-Cristina
Published: August 2011

Background

ExoU, a Pseudomonas aeruginosa cytotoxin with phospholipase A2 activity, was shown to induce vascular hyperpermeability and thrombus formation in a murine model of pneumosepsis. In this study, we investigated the toxin ability to induce alterations in pulmonary fibrinolysis and the contribution of the platelet activating factor (PAF) in the ExoU-induced overexpression of plasminogen activator inhibitor-1 (PAI-1).

Methods

Mice were intratracheally instilled with the ExoU producing PA103 P. aeruginosa or its mutant with deletion of the exoU gene. After 24 h, animal bronchoalveolar lavage fluids (BALF) were analyzed and lung sections were submitted to fibrin and PAI-1 immunohistochemical localization. Supernatants from A549 airway epithelial cells and THP-1 macrophage cultures infected with both bacterial strains were also analyzed at 24 h post-infection.

Results

In PA103-infected mice, but not in control animals or in mice infected with the bacterial mutant, extensive fibrin deposition was detected in lung parenchyma and microvasculature whereas mice BALF exhibited elevated tissue factor-dependent procoagulant activity and PAI-1 concentration. ExoU-triggered PAI-1 overexpression was confirmed by immunohistochemistry. In in vitro assays, PA103-infected A549 cells exhibited overexpression of PAI-1 mRNA. Increased concentration of PAI-1 protein was detected in both A549 and THP-1 culture supernatants. Mice treatment with a PAF antagonist prior to PA103 infection reduced significantly PAI-1 concentrations in mice BALF. Similarly, A549 cell treatment with an antibody against PAF receptor significantly reduced PAI-1 mRNA expression and PAI-1 concentrations in cell supernatants, respectively.

Conclusion

ExoU was shown to induce disturbed fibrin turnover, secondary to enhanced procoagulant and antifibrinolytic activity during P. aeruginosa pneumosepsis, by a PAF-dependent mechanism. Besides its possible pathophysiological relevance, in vitro detection of exoU gene in bacterial clinical isolates warrants investigation as a predictor of outcome of patients with P. aeruginosa pneumonia/sepsis and as a marker to guide treatment strategies.
The volatile compound BinBase mass spectral database
Authors: Skogerson Kirsten , Wohlgemuth Gert , Barupal Dinesh K , Fiehn Oliver
Published: August 2011

Background

Volatile compounds comprise diverse chemical groups with wide-ranging sources and functions. These compounds originate from major pathways of secondary metabolism in many organisms and play essential roles in chemical ecology in both plant and animal kingdoms. In past decades, sampling methods and instrumentation for the analysis of complex volatile mixtures have improved; however, design and implementation of database tools to process and store the complex datasets have lagged behind.

Description

The volatile compound BinBase (vocBinBase) is an automated peak annotation and database system developed for the analysis of GC-TOF-MS data derived from complex volatile mixtures. The vocBinBase DB is an extension of the previously reported metabolite BinBase software developed to track and identify derivatized metabolites. The BinBase algorithm uses deconvoluted spectra and peak metadata (retention index, unique ion, spectral similarity, peak signal-to-noise ratio, and peak purity) from the Leco ChromaTOF software, and annotates peaks using a multi-tiered filtering system with stringent thresholds. The vocBinBase algorithm assigns the identity of compounds existing in the database. Volatile compound assignments are supported by the Adams mass spectral-retention index library, which contains over 2,000 plant-derived volatile compounds. Novel molecules that are not found within vocBinBase are automatically added using strict mass spectral and experimental criteria. Users obtain fully annotated data sheets with quantitative information for all volatile compounds for studies that may consist of thousands of chromatograms. The vocBinBase database may also be queried across different studies, comprising currently 1,537 unique mass spectra generated from 1.7 million deconvoluted mass spectra of 3,435 samples (18 species). Mass spectra with retention indices and volatile profiles are available as free download under the CC-BY agreement (http://vocbinbase.fiehnlab.ucdavis.edu).

Conclusions

The BinBase database algorithms have been successfully modified to allow for tracking and identification of volatile compounds in complex mixtures. The database is capable of annotating large datasets (hundreds to thousands of samples) and is well-suited for between-study comparisons such as chemotaxonomy investigations. This novel volatile compound database tool is applicable to research fields spanning chemical ecology to human health. The BinBase source code is freely available at http://binbase.sourceforge.net/ under the LGPL 2.0 license agreement.
Strategies for aggregating gene expression data: The collapseRows R function
Authors: Miller Jeremy A , Cai Chaochao , Langfelder Peter , Geschwind Daniel H , Kurian Sunil M , Salomon Daniel R , Horvath Steve
Published: August 2011

Background

Genomic and other high dimensional analyses often require one to summarize multiple related variables by a single representative. This task is also variously referred to as collapsing, combining, reducing, or aggregating variables. Examples include summarizing several probe measurements corresponding to a single gene, representing the expression profiles of a co-expression module by a single expression profile, and aggregating cell-type marker information to de-convolute expression data. Several standard statistical summary techniques can be used, but network methods also provide useful alternative methods to find representatives. Currently few collapsing functions are developed and widely applied.

Results

We introduce the R function collapseRows that implements several collapsing methods and evaluate its performance in three applications. First, we study a crucial step of the meta-analysis of microarray data: the merging of independent gene expression data sets, which may have been measured on different platforms. Toward this end, we collapse multiple microarray probes for a single gene and then merge the data by gene identifier. We find that choosing the probe with the highest average expression leads to best between-study consistency. Second, we study methods for summarizing the gene expression profiles of a co-expression module. Several gene co-expression network analysis applications show that the optimal collapsing strategy depends on the analysis goal. Third, we study aggregating the information of cell type marker genes when the aim is to predict the abundance of cell types in a tissue sample based on gene expression data ("expression deconvolution"). We apply different collapsing methods to predict cell type abundances in peripheral human blood and in mixtures of blood cell lines. Interestingly, the most accurate prediction method involves choosing the most highly connected "hub" marker gene. Finally, to facilitate biological interpretation of collapsed gene lists, we introduce the function userListEnrichment, which assesses the enrichment of gene lists for known brain and blood cell type markers, and for other published biological pathways.

Conclusions

The R function collapseRows implements several standard and network-based collapsing methods. In various genomic applications we provide evidence that both types of methods are robust and biologically relevant tools.
RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome
Authors: Li Bo , Dewey Colin N
Published: August 2011

Background

RNA-Seq is revolutionizing the way transcript abundances are measured. A key challenge in transcript quantification from RNA-Seq data is the handling of reads that map to multiple genes or isoforms. This issue is particularly important for quantification with de novo transcriptome assemblies in the absence of sequenced genomes, as it is difficult to determine which transcripts are isoforms of the same gene. A second significant issue is the design of RNA-Seq experiments, in terms of the number of reads, read length, and whether reads come from one or both ends of cDNA fragments.

Results

We present RSEM, an user-friendly software package for quantifying gene and isoform abundances from single-end or paired-end RNA-Seq data. RSEM outputs abundance estimates, 95% credibility intervals, and visualization files and can also simulate RNA-Seq data. In contrast to other existing tools, the software does not require a reference genome. Thus, in combination with a de novo transcriptome assembler, RSEM enables accurate transcript quantification for species without sequenced genomes. On simulated and real data sets, RSEM has superior or comparable performance to quantification methods that rely on a reference genome. Taking advantage of RSEM's ability to effectively use ambiguously-mapping reads, we show that accurate gene-level abundance estimates are best obtained with large numbers of short single-end reads. On the other hand, estimates of the relative frequencies of isoforms within single genes may be improved through the use of paired-end reads, depending on the number of possible splice forms for each gene.

Conclusions

RSEM is an accurate and user-friendly software tool for quantifying transcript abundances from RNA-Seq data. As it does not rely on the existence of a reference genome, it is particularly useful for quantification with de novo transcriptome assemblies. In addition, RSEM has enabled valuable guidance for cost-efficient design of quantification experiments with RNA-Seq, which is currently relatively expensive.
rapmad: Robust analysis of peptide microarray data
Authors: Renard Bernhard Y , Löwer Martin , Kühne Yvonne , Reimer Ulf , Rothermel Andrée , Türeci Özlem , Castle John C , Sahin Ugur
Published: August 2011

Background

Peptide microarrays offer an enormous potential as a screening tool for peptidomics experiments and have recently seen an increased field of application ranging from immunological studies to systems biology. By allowing the parallel analysis of thousands of peptides in a single run they are suitable for high-throughput settings. Since data characteristics of peptide microarrays differ from DNA oligonucleotide microarrays, computational methods need to be tailored to these specifications to allow a robust and automated data analysis. While follow-up experiments can ensure the specificity of results, sensitivity cannot be recovered in later steps. Providing sensitivity is thus a primary goal of data analysis procedures. To this end we created rapmad (Robust Alignment of Peptide MicroArray Data), a novel computational tool implemented in R.

Results

We evaluated rapmad in antibody reactivity experiments for several thousand peptide spots and compared it to two existing algorithms for the analysis of peptide microarrays. rapmad displays competitive and superior behavior to existing software solutions. Particularly, it shows substantially improved sensitivity for low intensity settings without sacrificing specificity. It thereby contributes to increasing the effectiveness of high throughput screening experiments.

Conclusions

rapmad allows the robust and sensitive, automated analysis of high-throughput peptide array data. The rapmad R-package as well as the data sets are available from http://www.tron-mz.de/compmed.
Complete genome sequence of Brachyspira intermedia reveals unique genomic features in Brachyspira species and phage-mediated horizontal gene transfer
Authors: Håfström Therese , Jansson Désirée S , Segerman Bo
Published: August 2011

Background

Brachyspira spp. colonize the intestines of some mammalian and avian species and show different degrees of enteropathogenicity. Brachyspira intermedia can cause production losses in chickens and strain PWS/AT now becomes the fourth genome to be completed in the genus Brachyspira.

Results

15 classes of unique and shared genes were analyzed in B. intermedia, B. murdochii, B. hyodysenteriae and B. pilosicoli. The largest number of unique genes was found in B. intermedia and B. murdochii. This indicates the presence of larger pan-genomes. In general, hypothetical protein annotations are overrepresented among the unique genes. A 3.2 kb plasmid was found in B. intermedia strain PWS/AT. The plasmid was also present in the B. murdochii strain but not in nine other Brachyspira isolates. Within the Brachyspira genomes, genes had been translocated and also frequently switched between leading and lagging strands, a process that can be followed by different AT-skews in the third positions of synonymous codons. We also found evidence that bacteriophages were being remodeled and genes incorporated into them.

Conclusions

The accessory gene pool shapes species-specific traits. It is also influenced by reductive genome evolution and horizontal gene transfer. Gene-transfer events can cross both species and genus boundaries and bacteriophages appear to play an important role in this process. A mechanism for horizontal gene transfer appears to be gene translocations leading to remodeling of bacteriophages in combination with broad tropism.
Syntenic relationships between cucumber (Cucumis sativus L.) and melon (C. melo L.) chromosomes as revealed by comparative genetic mapping
Authors: Li Dawei , Cuevas Hugo E , Yang Luming , Li Yuhong , Garcia-Mas Jordi , Zalapa Juan , Staub Jack E , Luan Feishi , Reddy Umesh , He Xiaoming , Gong Zhenhui , Weng Yiqun
Published: August 2011

Background

Cucumber,Cucumis sativusL. (2n = 2 × = 14) and melon,C. meloL. (2n = 2 × = 24) are two important vegetable species in the genusCucumis(family Cucurbitaceae). Both species have an Asian origin that diverged approximately nine million years ago. Cucumber is believed to have evolved from melon through chromosome fusion, but the details of this process are largely unknown. In this study, comparative genetic mapping between cucumber and melon was conducted to examine syntenic relationships of their chromosomes.

Results

Using two melon mapping populations, 154 and 127 cucumber SSR markers were added onto previously reported F2- and RIL-based genetic maps, respectively. A consensus melon linkage map was developed through map integration, which contained 401 co-dominant markers in 12 linkage groups including 199 markers derived from the cucumber genome. Syntenic relationships between melon and cucumber chromosomes were inferred based on associations between markers on the consensus melon map and cucumber draft genome scaffolds. It was determined that cucumber Chromosome 7 was syntenic to melon Chromosome I. Cucumber Chromosomes 2 and 6 each contained genomic regions that were syntenic with melon chromosomes III+V+XI and III+VIII+XI, respectively. Likewise, cucumber Chromosomes 1, 3, 4, and 5 each was syntenic with genomic regions of two melon chromosomes previously designated as II+XII, IV+VI, VII+VIII, and IX+X, respectively. However, the marker orders in several syntenic blocks on these consensus linkage maps were not co-linear suggesting that more complicated structural changes beyond simple chromosome fusion events have occurred during the evolution of cucumber.

Conclusions

Comparative mapping conducted herein supported the hypothesis that cucumber chromosomes may be the result of chromosome fusion from a 24-chromosome progenitor species. Except for a possible inversion, cucumber Chromosome 7 has largely remained intact in the past nine million years since its divergence from melon. Meanwhile, many structural changes may have occurred during the evolution of the remaining six cucumber chromosomes. Further characterization of the genomic nature ofCucumisspecies closely related to cucumber and melon might provide a better understanding of the evolutionary history leading to modern cucumber.
Bifidobacterium pseudolongum are efficient indicators of animal fecal contamination in raw milk cheese industry
Authors: Delcenserie Véronique , Gavini Françoise , China Bernard , Daube Georges
Published: August 2011

Background

The contamination of raw milk cheeses (St-Marcellin and Brie) from two plants in France was studied at several steps of production (raw milk, after addition of rennet - St-Marcellin - or after second maturation - Brie -, after removal from the mold and during ripening) using bifidobacteria as indicators of fecal contamination.

Results

Bifidobacterium semi-quantitative counts were compared using PCR-RFLP and real-time PCR. B. pseudolongum were detected in 77% (PCR-RFLP; 1.75 to 2.29 log cfu ml-1) and 68% (real-time PCR; 2.19 to 2.73 log cfu ml-1) of St-Marcellin samples and in 87% (PCR-RFLP; 1.17 to 2.40 log cfu ml-1) of Brie cheeses samples. Mean counts of B. pseudolongum remained stable along both processes. Two other populations of bifidobacteria were detected during the ripening stage of St-Marcellin, respectively in 61% and 18% of the samples (PCR-RFLP). The presence of these populations explains the increase in total bifidobacteria observed during ripening. Further characterization of these populations is currently under process. Forty-eight percents (St-Marcellin) and 70% (Brie) of the samples were B. pseudolongum positive/E. coli negative while only 10% (St-Marcellin) and 3% (Brie) were B. pseudolongum negative/E. coli positive.

Conclusions

The increase of total bifidobacteria during ripening in Marcellin's process does not allow their use as fecal indicator. The presence of B. pseudolongum along the processes defined a contamination from animal origin since this species is predominant in cow dung and has never been isolated in human feces. B. pseudolongum was more sensitive as an indicator than E. coli along the two different cheese processes. B. pseudolongum should be used as fecal indicator rather than E. coli to assess the quality of raw milk and raw milk cheeses.
A galU mutant of francisella tularensisis attenuated for virulence in a murine pulmonary model of tularemia
Authors: Jayakar Himangi R , Parvathareddy Jyothi , Fitzpatrick Elizabeth A , Bina Xiaowen R , Bina James E , Re Fabio , Emery Felicia D , Miller Mark A
Published: August 2011

Background

A number of studies have revealed thatFrancisella tularensis(FT) suppresses innate immune responses such as chemokine/cytokine production and neutrophil recruitment in the lungs following pulmonary infection via an unidentified mechanism. The ability of FT to evade early innate immune responses could be a very important virulence mechanism for this highly infectious bacterial pathogen.

Results

Here we describe the characterization of agalUmutant strain of FT live vaccine strain (LVS). We show that thegalUmutant was highly attenuated in a murine model of tularemia and elicited more robust innate immune responses than the wild-type (WT) strain. These studies document that the kinetics of chemokine expression and neutrophil recruitment into the lungs of mice challenged with thegalUmutant strain are significantly more rapid than observed with WT FT, despite the fact that there were no observed differences in TLR2 or TLR4 signaling or replication/dissemination kinetics during the early stages of infection. We also show that thegalUmutant had a hypercytotoxic phenotype and more rapidly induced the production of IL-1β following infection eitherin vitroorin vivo, indicating that attenuation of thegalUmutant strain may be due (in part) to more rapid activation of the inflammasome and/or earlier death of FT infected cells. Furthermore, we show that infection of mice with thegalUmutant strain elicits protective immunity to subsequent challenge with WT FT.

Conclusions

Disruption of thegalUgene of FTLVS has little (if any) effect onin vivoinfectivity, replication, or dissemination characteristics, but is highly attenuating for virulence. The attenuated phenotype of this mutant strain of FT appears to be related to its increased ability to induce innate inflammatory responsiveness, resulting in more rapid recruitment of neutrophils to the lungs following pneumonic infection, and/or to its ability to kill infected cells in an accelerated fashion. These results have identified two potentially important virulence mechanisms used by FT. These findings could also have implications for design of a live attenuated vaccine strain of FT because sublethal infection of mice with thegalUmutant strain of FTLVS promoted development of protective immunity to WT FTLVS.
The direction of research into visual disability and quality of life in glaucoma
Authors: Glen Fiona C , Crabb David P , Garway-Heath David F
Published: August 2011

Background

Glaucoma will undoubtedly impact on a person's ability to function as they go about their day-to-day life. The purpose of this study is to investigate the amount of published knowledge in quality of life (QoL) and visual disability studies for glaucoma, and make comparisons with similar research in other chronic conditions.

Methods

A systematic literature search of the Global Health, EMBASE Psychiatry and MEDLINE databases. Title searches for glaucoma and six other example chronic diseases were entered alongside a selection of keywords chosen to capture studies focusing on QoL and everyday task ability. These results were further filtered during a manual search of resulting abstracts. Outcomes were the number of publications per year for each disease, number relating to QoL and type of glaucoma QoL research.

Results

Fifteen years ago there were no published studies relating to the impact of glaucoma on QoL but by 2009 this had risen to 1.2% of all glaucoma articles. The number of papers relating to QoL as a proportion of all papers in glaucoma in the past 10 years (0.6%) is smaller than for AMD and some other disabling chronic diseases. Most QoL studies in glaucoma (82%) involve questionnaires.

Conclusion

QoL studies in glaucoma are increasing in number but represent a tiny minority of the total publications in glaucoma research. There are fewer QoL articles in glaucoma compared to some other disabling chronic conditions. The majority of QoL articles in glaucoma research use questionnaires; performance-based measures of visual disability may offer an additional method of determining how the disease impacts on QoL.
Behaviour patterns preceding a railway suicide: Explorative study of German Federal Police officers' experiences
Authors: Lukaschek Karoline , Baumert Jens , Ladwig Karl-Heinz
Published: August 2011

Background

Constant high-level numbers of railway suicides indicate that prevention strategies against railway suicides are urgently needed. The main question of the present study was whether pre-crash railway suicide behaviour can be identified, using German Federal Police officers experience with suicidal events in railway related environments.

Methods

To collect information on pre-crash railway suicide behaviour, a questionnaire was used and made available on the German Federal Police intranet. A total of 202 subjects (mean age: 41 years, sex: 84.9% male) were included in the analysis. Multivariate logistic regression analyses were performed to predict the prevention of suicide (first model) or demand for counselling (second model) as outcomes. Sex, age, years of service, number of experienced suicides, suicides personally observed, information on suicides obtained from witnesses and finally either counselling/debriefing (first model) or whether officers had prevented a suicide (second model) were used as predictors.

Results

A considerable proportion of police officers reported behavioural patterns preceding a suicide. Half of them observed the dropping or leaving behind of personal belongings or the avoidance of eye contact, more than a third erratic gesture, mimic or movement. Erratic communication patterns and general confusion were each reported by about one quarter. One fifth indicated the influence of alcohol. Less frequently observed behaviour was aimlessly wandering (14.3%) and out of the ordinary clothing (4%). About one third of all railway suicide victims committed suicide in stations. Of those, 70% had chosen an eminent spot. The multivariate logistic regression model using prevented suicides as the outcome identified the number of suicides experienced, counselling/debriefing and having personally observed a suicide as variables with significant impact. The model using counselling/debriefing as the outcome identified age and having prevented a suicide as variables with a significant association.

Conclusions

Our results provide evidence that railway suicides are preceded by identifiable behavioural patterns. This emphasizes the importance of educational efforts, taking into account the knowledge and skills of experienced police officers.
Awareness of health risks related to body art practices among youth in Naples, Italy: a descriptive convenience sample study
Authors: Gallè Francesca , Mancusi Caterina , Onofrio Valeria Di , Visciano Aniello , Alfano Vincenza , Mastronuzzi Roberto , Guida Marco , Liguori Giorgio
Published: August 2011

Background

Body art practices have emerged as common activities among youth, yet few studies have investigated awareness in different age groups of possible health complications associated with piercing and tattooing.

Methods

We investigated perceptions of and knowledge about health risks. To highlight differences among age groups, we gathered data from students at high schools and universities in the province of Naples.

Results

Of 9,322 adolescents, 31.3% were pierced and 11.3% were tattooed. Of 3,610 undergraduates, 33% were pierced and 24.5% were tattooed (p < 0.05). A higher number of females were pierced in both samples, but there were no gender differences among tattooed students. Among high school students, 79.4% knew about infectious risks and 46% about non-infectious risks; the respective numbers among university students were 87.2% and 59.1%. Only 3.5% of students in high school and 15% of university undergraduates acknowledged the risk of viral disease transmission; 2% and 3% knew about allergic risks. Among adolescents and young adults, 6.9% and 15.3%, respectively, provided signed informed consent; the former were less knowledgeable about health risks (24.7% vs. 57.1%) (p < 0.05). Seventy-three percent of the high school students and 33.5% of the university students had body art done at unauthorized facilities. Approximately 7% of both samples reported complications from their purchased body art.

Conclusions

Results indicate a need for adequate information on health risks associated with body art among students in Naples, mainly among high school students. Therefore, adolescents should be targeted for public health education programs.
Alcohol misuse, drinking contexts and intimate partner violence in St. Petersburg, Russia: results from a cross-sectional study
Authors: Zhan Weihai , Shaboltas Alla V , Skochilov Roman V , Kozlov Andrei P , Krasnoselskikh Tatiana V , Abdala Nadia
Published: August 2011

Background

Alcohol misuse has been linked to intimate partner violence (IPV). However, this association is not usually examined in Russia. Moreover, more investigation is required as to whether specific drinking contexts are also associated with IPV. The objectives of this study are: to investigate whether alcohol misuse is associated with IPV and to further examine whether specific drinking contexts among drinkers are associated with IPV.

Methods

A questionnaire was used to collect information on demographics, health status, alcohol use, and violence involving sexual partners among 440 participants who were recruited from an STI (sexually transmitted infection) clinic center in St. Petersburg, Russia for a cross-sectional study from 2008 to 2009. Multivariate logistic regression was used for analysis.

Results

Overall, 47.0% participants were classified as misusing alcohol and 7.2% participants perpetrated IPV in the past three months. Participants with alcohol misuse were 3.28 times (OR: 3.28; 95% CI: 1.34-8.04) as likely as those without alcohol misuse to perpetrate IPV. Among participants who had consumed alcohol in the past three months, those who usually drank on the streets or in parks (OR: 5.62; 95% CI: 1.67-18.90) were more likely to perpetrate IPV.

Conclusions

Both alcohol misuse and certain drinking contexts (e.g., drinking on the streets or at parks) were associated with IPV. The association between drinking contexts and IPV needs further investigation, as do the underlying mechanisms for this association. IPV prevention initiatives might benefit from reducing alcohol misuse. Drinking contexts such as drinking on the streets or at parks as well as the factors related to the use of alcohol in these contexts may also need to be addressed.
Effectiveness of the back school and mckenzie techniques in patients with chronic non-specific low back pain: a protocol of a randomised controlled trial
Authors: Garcia Alessandra N , Gondo Francine LB , Costa Renata A , Cyrillo Fábio N , Silva Tatiane M , Costa Luciola CM , Costa Leonardo OP
Published: August 2011

Background

Chronic low back pain is a highly prevalent condition, which is associated with high direct and indirect costs to the society. Although this condition is highly prevalent, it is still extremely difficult to treat. Two potentially useful treatments for patients with chronic low back pain are called the McKenzie and Back School treatment programs. These programs have good biological plausibility, are widely available and have a modest cost. Although these treatments are already available for patients, the evidence that supports their use is largely based on low quality methodological studies. Therefore, a high-quality randomised controlled trial is required to compare, for the first time, the effectiveness of these treatments in patients with chronic low back pain.

Methods/design

One hundred and forty-eight patients will be randomly allocated to a four-week treatment program based upon the McKenzie or Back School principles. Clinical outcomes (pain intensity, disability, quality of life, and trunk flexion range of motion) will be obtained at follow-up appointments at 1, 3 and 6 months after randomisation. The data will be collected by an assessor who will be blinded to the group allocation.

Discussion

This will be the first study aimed to compare the McKenzie and Back School approaches in patients with chronic low back pain. The results of this trial may help in the decision-making process of allied health providers for the treatment of chronic low back pain and reduce the health-related costs of this condition.

Trial Registration

ACTRN12610000435088
Overproduction of Bacillus amyloliquefaciens extracellular glutamyl-endopeptidase as a result of ectopic multi-copy insertion of an efficiently-expressed mpr gene into the Bacillus subtilis chromosome
Authors: Yomantas Yurgis AV , Abalakina Elena G , Golubeva Lyubov I , Gorbacheva Lyubov Y , Mashko Sergey V
Published: August 2011

Background

Plasmid-less, engineeredBacillusstrains have several advantages over plasmid-carrier variants. Specifically, their stability and potential ecological safety make them of use in industrial applications. As a rule, however, it is necessary to incorporate many copies of a key gene into a chromosome to achieve strain performance that is comparable to that of cells carrying multiple copies of a recombinant plasmid.

Results

A plasmid-lessB. subtilisJE852-based strain secreting glutamyl-specific protease (GSP-the protein product of themprgene fromB. amyloliquefaciens) was constructed that exhibits decreased levels of other extracellular proteases. Ten copies of anmprB.amycassette in which the GSP gene was placed between the promoter of theB. amyloliquefaciens rplU-rpmAgenes and the Rho-independent transcription terminator were ectopically inserted into designated (3 copies) and random (7 copies) points in the recipient chromosome. The resulting strain produced approximately 0.5 g/L of secreted GSP after bacterial cultivation in flasks with starch-containing media, and its performance was comparable to an analogous strain in which themprB.amycassette was carried on a multi-copy plasmid.

Conclusion

A novel strategy for ectopically integrating a cassette into multiple random locations in theB. subtilischromosome was developed. This new method is based on the construction of DNA fragments in which the desired gene, marked by antibiotic resistance, is sandwiched between "front" and "back" portions of random chromosomal DNA restriction fragments. These fragments were subsequently inserted into the targeted sites of the chromosome using double-cross recombination. The construction of a marker-free strain was achieved by gene conversion between the integrated marked gene and a marker-less variant carried by plasmid DNA, which was later removed from the cells.
Preventing malaria in pregnancy through community-directed interventions: evidence from Akwa Ibom State, Nigeria
Authors: Okeibunor Joseph C , Orji Bright C , Brieger William , Ishola Gbenga , Otolorin Emmanuel 'Dipo , Rawlins Barbara , Ndekhedehe Enobong U , Onyeneho Nkechi , Fink Günther
Published: August 2011

Background

Despite massive anti-malaria campaigns across the subcontinent, effective access to intermittent preventive treatment (IPTp) and insecticide-treated nets (ITNs) among pregnant women remain low in large parts of sub-Saharan Africa. The slow uptake of malaria prevention products appears to reflect lack of knowledge and resistance to behavioural change, as well as poor access to resources, and limited support of programmes by local communities and authorities.

Methods

A recent community-based programme in Akwa Ibom State, Nigeria, is analysed to determine the degree to which community-directed interventions can improve access to malaria prevention in pregnancy. Six local government areas in Southern Nigeria were selected for a malaria in pregnancy prevention intervention. Three of these local government areas were selected for a complementary community-directed intervention (CDI) programme. Under the CDI programme, volunteer community-directed distributors (CDDs) were appointed by each village and kindred in the treatment areas and trained to deliver ITNs and IPTp drugs as well as basic counseling services to pregnant women.

Findings

Relative to women in the control area, an additional 7.4 percent of women slept under a net during pregnancy in the treatment areas (95% CI [0.035, 0.115], p-value < 0.01), and an additional 8.5 percent of women slept under an ITN after delivery and prior to the interview (95% CI [0.045, 0.122], p-value < 0.001). The effects of the CDI programme were largest for IPTp adherence, increasing the fraction of pregnant women taking at least two SP doses during pregnancy by 35.3 percentage points [95% CI: 0.280, 0.425], p-value < 0.001) relative to the control group. No effects on antenatal care attendance were found.

Conclusion

The presented results suggest that the inclusion of community-based programmes can substantially increase effective access to malaria prevention, and also increase access to formal health care access in general, and antenatal care attendance in particular in combination with supply side interventions. Given the relatively modest financial commitments they require, community-directed programmes appear to be a cost-effective way to improve malaria prevention; the participatory approach underlying CDI programmes also promises to strengthen ties between the formal health sector and local communities.
Antibody cross-linking and target elution protocols used for immunoprecipitation significantly modulate signal-to noise ratio in downstream 2D-PAGE analysis
Authors: Sousa Mirta ML , Steen Kristian W , Hagen Lars , Slupphaug Geir
Published: August 2011

Background

Immunoprecipitation and subsequent 2D-PAGE/mass spectrometry are powerful tools to study post-translational protein modifications. Often disregarded in this workflow is the impact of the chemical cross-linker upon antibody affinity, as well as incomplete elution of primary target protein in buffers commonly used in 2D-PAGE. This may impede detection of non-abundant protein isoforms.

Results

Here we have compared cross-linking of antibodies to Dynabeads® Protein A by using DMP or BS3, as well as the efficiency of various target elution buffers prior to 2D-PAGE separation. BS3 cross-linking generally resulted in less non-specific binding than DMP, whereas DMP cross-linking gave overall higher yield of target protein. Regardless of the cross-linker used, incomplete elution of target protein was observed with conventional glycine- or urea-based buffers. Conversely, complete elution was obtained with 2% hot SDS and subsequent dilution in urea buffer containing 4% CHAPS, to 0.2% final SDS yielded perfectly focused gels suitable for mass spectrometry analysis.

Conclusion

Careful choice of Ig cross-linker as well as efficient elution of target protein in SDS prior to downstream 2D-PAGE may be key factors to analyze low-abundance proteins enriched by magnetic bead immunoprecipitation.
Epidemiologic application of verbal autopsy to investigate the high occurrence of cancer along Huai River Basin, China
Authors: Wan Xia , Zhou Maigeng , Tao Zhuang , Ding Ding , Yang Gonghuan
Published: August 2011

Background

In 2004, the media repeatedly reported water pollution and "cancer villages" along the Huai River in China. Due to the lack of death records for more than 30 years, a retrospective survey of causes of death using verbal autopsy was carried out to investigate cancer rates in this area.

Methods

An epidemiologic study was designed to compare numbers of deaths and causes of death between the study areas with water pollution and the control areas without water pollution in S County and Y District in 2005. The study areas were selected based on the distribution of the Huai River and its tributaries. Verbal autopsy was used to assist cause of death (COD) diagnoses and to verify mortality rates. The standard mortality rates (SMRs) of cancer in the study area were compared with those in the control areas. In order to verify the difference between mortality rates due to cancers in the study and the control areas, patients who reported having cancer in the survey received a second diagnosis by national and provincial oncologists with pathological and laboratory examinations. Comparisons were made to determine if differential cancer prevalence rates in the study and control areas were similar to the difference in mortality due to cancer in these study and control areas. Mortality rates of cancers in study and control areas were also compared with national statistics for the rural population of China.

Results

Over five years, 3,301 deaths were identified, including 1,158 cancer deaths. The annual average SMRs of cancer in the study areas of S County and Y District were 277.8/100,000 and 223.6/100,000, respectively, which is three to four times higher than those in the control areas. In addition, a total of 626 cases of cancer in the study and control areas were confirmed. The prevalence rates of cancer were 545/100,000 and 128.1/100,000 per year in the study and control areas in S County, respectively, and 440.9/100,000 and 200/100,000 per year in the study and control areas in Y District, respectively. The mortality and prevalence rates of digestive cancers were higher in the study areas than the control areas. In 2000, the SMR for cancer in rural areas nationwide was 120.9/100,000, and in study areas in S County and Y District, the excess rates of deaths were 184/100,000 and 138.8/100,000, respectively.

Conclusions

The death rates of digestive cancers were much higher in the study areas of S County and Y District. The patterns for between-area differences in prevalence and mortality rates of cancer were similar. Verbal autopsy is shown to be a useful tool in retrospective mortality surveys in low-resource areas with limited access to health care.