bluuebunny/crossref_metadata_2025 huggingface dataset:
An investigation of the relationship between subjective sleep quality, loneliness and mood in an Australian sample: Can daily routine explain the links?
Authors: Smith Simon Squire , Kozak Nahum , Sullivan Karen Anne
Published: November 2010

Background: Loneliness and low mood are associated with significant negative health outcomes including poor sleep, but the strength of the evidence underlying these associations varies. There is strong evidence that poor sleep quality and low mood are linked, but only emerging evidence that loneliness and poor sleep are associated.

Aims: To independently replicate the finding that loneliness and poor subjective sleep quality are associated and to extend past research by investigating lifestyle regularity as a possible mediator of relationships, since lifestyle regularity has been linked to loneliness and poor sleep.

Methods: Using a cross-sectional design, 97 adults completed standardized measures of loneliness, lifestyle regularity, subjective sleep quality and mood.

Results: Loneliness was a significant predictor of sleep quality. Lifestyle regularity was not a predictor of, nor associated with, mood, sleep quality or loneliness.

Conclusions: This study provides an important independent replication of the association between poor sleep and loneliness. However, the mechanism underlying this link remains unclear. A theoretically plausible mechanism for this link, lifestyle regularity, does not explain the relationship between loneliness and poor sleep. The nexus between loneliness and poor sleep is unlikely to be broken by altering the social rhythm of patients who present with poor sleep and loneliness.
A Perspective on the Field of Organization Development and Change
Authors: Burke W. Warner
Published: November 2010

Essentially, and perhaps arguably, there has been no innovation in the social technology of organization development (OD) since appreciative inquiry originated in 1987. It is as if the creative work of OD is done. Moreover, it is as if the mission of OD—to loosen tightly coupled systems, think large bureaucracies—has largely been achieved. Decentralization, involvement, and autonomy on the job are commonplace in many organizations. There is a paradox, however. The need for expertise in organization change has never been greater, and OD has so much to contribute, yet the failure rate for organization change efforts is around 70%, and for mergers and acquisitions the failure rate is even larger. The premise of this article is that there is much work yet to be done. We who identify ourselves with the field of OD have unfinished business. As research on the Zeigarnik effect showed, we tend to remember things undone more than we remember things that have been completed. A purpose of this article is to create a Zeigarnik effect. Four domains of unfinished business in the field are identified and explored. There are no doubt many other domains, but these four definitely need attention. We need to know much more than we now know about how to (a) work with loosely coupled systems, (b) change the culture of an organization, (c) identify and deal with perceived resistance to change more effectively, and (d) get leadership development right—it is not about training.
Using a Cell Phone-Based Glucose Monitoring System for Adolescent Diabetes Management
Authors: Carroll Aaron E. , DiMeglio Linda A. , Stein Stephanie , Marrero David G.
Published: November 2010

Introduction

Mobile technology may be useful in addressing several issues in adolescent diabetes management.

Purpose

To assess the feasibility and acceptability of a cell phone glucose monitoring system for adolescents with type 1 diabetes and their parents.

Methods

The authors recruited patients with type 1 diabetes who had been diagnosed for at least 1 year. Each adolescent used the system for 6 months, filling out surveys every 3 months to measure their usability and satisfaction with the cell phone glucose monitoring system, as well as how use of the system might affect quality of family functioning and diabetes management.

Results

Adolescents reported positive feelings about the technology and the service, even though a concerning number of them had significant technical issues that affected continued use of the device. Nearly all thought that the clinic involvement in monitoring testing behavior was quite acceptable. The use of the Glucophone™ did not, however, significantly change the quality of life of the adolescents, their level of conflict with their parents, their reported self-management of diabetes, or their average glycemic control within the short time frame of the study.

Conclusions

As a feasibility study of the technology, this work was successful in demonstrating that cell phone glucose monitoring technology can be used in an adolescent population to track and assist in self-monitoring behavior. The authors speculate that explicitly attempting to change behavior, perhaps with the use of behavioral contracts, would enhance the technology’s ability to improve outcomes.
D-cycloserine, sarcosine and D-serine diminish the expression of cocaine-induced conditioned place preference
Authors: Yang Fu-Yung , Lee Yung-Shuan , Cherng Chianfang G , Cheng Ling-Yi , Chang Wan-Ting , Chuang Jia-Ying , Kao Gour-Shenq , Yu Lung
Published: November 2010

Reactivation of cocaine-associated memories plays a critical role in reinstating the cocaine-seeking behavior and causing relapse. Cocaine-induced conditioned place preference (CPP) was used as a behavioral paradigm indicative of cocaine-associated memory and repeated cocaine-free preference tests served as a behavioral procedure to retrieve such a memory in this study. Since D-cycloserine was reported to eradicate drug-associated memories, two other N-methyl-D-aspartate (NMDA) receptor agonists were assessed for their efficacy on facilitating the extinction of cocaine-induced CPP. Although D-cycloserine (30 mg/kg) abolished cocaine (10 mg/kg)-induced CPP, sarcosine (300 and 600 mg/kg) and D-serine (600 mg/kg) diminished the expression of such a cocaine memory. Sarcosine (600 mg/kg) and D-serine (600 mg/kg) did not affect the storage of this cocaine memory. It was of interest to note that D-cycloserine facilitated the extinction of cocaine-induced CPP in a fast and early-onset manner, while sarcosine and D-serine decreased cocaine-induced CPP expression in a delay-onset manner. D-cycloserine (30 mg/kg), D-serine (600 mg/kg) and sarcosine (600 mg/kg) did not affect the consolidation of cocaine (5 mg/kg)-induced CPP. Finally, sarcosine (at 600 mg/kg/day for 3 consecutive days) and D-serine (at 600 mg/kg/day for 3 consecutive days) did not produce observable aversive effect associated with their administration in a conditioned place aversion paradigm. Likewise, a similar dosing regimen of sarcosine or D-serine did not cause evident activity-impairing effect. In addition to D-cycloserine treatment, our results indicate that long-term treatment with D-serine and sarcosine may afford a therapeutic advance in suppressing the expression of cocaine-associated memory.
Corporate Social Responsibility in an Indian Public Sector Organization
Authors: Shah Shashank , Bhaskar A. Sudhir
Published: November 2010

The society and local community is the resource pool from which any organization gets its manpower and also so to say ‘the license to operate’. The society is the entity to which an organization owes its existence. The organization exists in the society because of the inputs received from it—material and human—and ultimately sells its products and services to it. Any organization must pay its due in various ways to this important constituency. In this article, the authors have used the case study of an Indian Public Sector Undertaking (PSU) like Bharat Petroleum Corporation Ltd to describe its Society and Local Community-related initiatives. Being a PSU and true to its mandate, BPCL has undertaken lot of innovative CSR initiatives in and around the areas of its functioning. An attempt has been made here to highlight the same. The data collection for the case has been done by the authors through personal interviews with top executives of the Company and supplemented through other information available in the public domain.
The Role of Greed in the Ongoing Global Financial Crisis
Authors: Smith Raymond D.
Published: November 2010

The author posits that greed and insensitivity to the needs of others are corrosive values that have engendered the global economic crisis. Examples are cited to support the thesis that it is primarily an ethics crisis that has resulted in the distortion of the US economy, such that the middle class is sliding into poverty while the wealthiest 1 per cent is ever more powerful and wealthy. The irony of the predatory capitalism (as distinct from stakeholderbased capitalism) being practised is that it is ultimately self-destructive to the practitioners. The unsustainability of the present system is discussed along with solutions, including stakeholder management, corporate and personal altruism and spiritual awakening.
Factors Influencing Help Seeking, Hearing Aid Uptake, Hearing Aid Use and Satisfaction With Hearing Aids: A Review of the Literature
Authors: Vestergaard Knudsen Line , Öberg Marie , Nielsen Claus , Naylor Graham , Kramer Sophia E.
Published: November 2010

Objectives: This descriptive summary of the literature provides an overview of the available studies (published between January 1980 and January 2009) on correlates of help-seeking behavior for hearing loss, hearing-aid uptake, hearing-aid use, and satisfaction with the device. Methods: Publications were identified by structured searches in Pubmed and Cinahl and by inspecting the reference lists of relevant articles. The articles covered different stages that a person with hearing impairment may go through: prior to hearing aid fitting, the period covering the fitting and the period post hearing aid fitting. Inclusion of articles occurred according to strict inclusion and exclusion criteria. Data were extracted by two independent researchers. Thirty-nine papers were included that identified 31 factors examined in relation to the four outcome measures. These covered personal factors (e.g., source of motivation, expectation, attitude), demographic factors (e.g., age, gender) and external factors (e.g., cost, counseling). Only two studies covered the actual fitting process. There was only one factor positively affecting all four outcome variables. This was self-reported hearing disability. The vast majority of studies showed no relationship of age and gender with any of the outcome domains. Discussion and conclusion: Whereas research of the last 28 years yielded valuable information regarding relevant and irrelevant factors in hearing aid health care, there are still many relevant issues that have never been investigated in controlled studies. These are discussed.
Utility and Importance of Hearing-Aid Features Assessed by Hearing-Aid Acousticians
Authors: Meister Hartmut , Grugel Linda , Walger Martin , von Wedel Hasso , Meis Markus
Published: November 2010

Modern hearing instruments include many features addressing situation-specific and user-related amplification. The main tasks of the acoustician are the appropriate choice of hearing instruments and fitting them to hearing impaired individuals. This study aims at investigating the utility and importance of several hearing-aid features as assessed by hearing-aid acousticians. For this purpose, eight different hearing-aid features with three levels each are addressed in a discrete-choice experiment. Preferences for systematically varied combinations of the features are assessed with 143 acousticians, using an adaptive conjoint analysis conducted via the Internet. Based on the preference data, utility and importance of the features are calculated. Highest utility and importance are found for noise cancellation and directional microphones. Outcome of these two features do not differ significantly. In contrast, data management functions, that is, self-learning options, show lowest importance. Though the acousticians’ professional experience reveal statistically significant influence on the assessment of some of the features’ utility and importance, a clear impact of sociodemographic or subject-specific factors on the outcome cannot be found. The study can be seen as a first approach to determine the estimation of basic hearing-aid features assessed by acousticians. Results show the outstanding utility and importance of features addressing speech perception in adverse listening situations. Furthermore, the outcome reveals reservations of the acousticians regarding self-learning options of the instruments.
Influence of Window Views on the Subjective Evaluation of Discomfort Glare
Authors: Geun Young Yun  , Ju Young Shin  , Jeong Tai Kim
Published: November 2010

A window is an indispensable element in a building and acts as a view-giving component that keeps occupants in touch with the outside. This study investigated the potential effect of different window views on the subjective assessment of discomfort glare from a simulated window that rendered blank, natural and man-made views from far to close distances. Forty-eight subjects (24 men, 24 women) participated in the experiments. The experimental results confirmed that the subjective evaluation of discomfort glare can vary with the type of window views presented. The results also indicated that there were noticeable variations in the subjective assessments of discomfort glare over the same visual stimuli. A preliminary criterion for classification of subjects’ sensitivity to glare was illustrated and the difference for the ‘‘glare-sensitive’’ and ‘‘glareinsensitive’’ people was statistically significant. This study found that the psychological factor such as window views could be an important factor in the subjective evaluation of discomfort glare. Widely used glare evaluation formulas such as unified glare rating and daylight glare index would not consider psychological factors. Thus, the finding from this study would contribute to a more realistic evaluation of discomfort glare for future design of glare control systems.
A Position Index Formula for Evaluation of Glare Source in the Visual Field
Authors: Kim Wonwoo , Jeong Tai Kim
Published: November 2010

The purpose of this study was to propose a formula of the position index for evaluation of the glare source in the whole visual field. The glare sensation was measured to create the formula in binocular and monocular vision. The results showed that there is not a big difference in the level of discomfort glare sensation between the left and right eyes while the lower visual field is more sensitive to the discomfort glare than the upper visual field. Based on the borderline between comfort and discomfort luminance distribution in the whole visual field obtained through a series of experiments, position index was created, which was then turned into a formula. When predicting or evaluating the discomfort glare generated from the indoor or outdoor lighting with a computer, this formula would be of great help in easily identifying a position index. The findings of this research would provide important basic data for the evaluation of discomfort glare.
Demographic, clinical, and outcome features of children with acute lymphoblastic leukemia and CRLF2 deregulation: results from the MRC ALL97 clinical trial
Authors: Ensor Hannah M. , Schwab Claire , Russell Lisa J. , Richards Sue M. , Morrison Heather , Masic Dino , Jones Lisa , Kinsey Sally E. , Vora Ajay J. , Mitchell Christopher D. , Harrison Christine J. , Moorman Anthony V.
Published: November 2010

Deregulated expression of CRLF2 (CRLF2-d) arises via its juxtaposition to the IGH@ enhancer or P2RY8 promoter. Among 865 BCP-ALL children treated on MRC ALL97, 52 (6%) had CRLF2-d, but it was more prevalent among Down syndrome patients (54%). P2RY8-CRLF2 (n = 43) was more frequent than IGH@-CRLF2 (n = 9). CRLF2-d was not associated with age, sex, or white cell count, but IGH@-CRLF2 patients were older than P2RY8-CRLF2 patients (median 8 vs 4 years, P = .0017). Patients with CRLF2-d were more likely to present with enlarged livers and spleens (38% vs 18%, P < .001). CRLF2-d was not seen in conjunction with established chromosomal translocations but 6 (12%) cases had high hyperdiploidy, and 5 (10%) had iAMP21. Univariate analysis suggested that CRLF2-d was associated with an inferior outcome: (event-free survival [EFS] hazard ratio 2.27 [95% confidence interval 1.48-3.47], P < .001; OS 3.69 [2.34-5.84], P < .001). However, multivariate analysis indicated that its effect was mediated by other risk factors such as cytogenetics and DS status (EFS 1.45 [0.88-2.39], P = .140; OS 1.90 [1.08-3.36], P = .027). Although the outcome of IGH@-CRLF2 patients appeared inferior compared with P2RY8-CRLF2 patients, the result was not significant (EFS 2.69 [1.15-6.31], P = .023; OS 2.86 [1.15-6.79], P = .021). Therefore, we concluded that patients with CRLF2-d should be classified into the intermediate cytogenetic risk group.
Rational engineering of L-asparaginase reveals importance of dual activity for cancer cell toxicity
Authors: Offman Marc N. , Krol Marcin , Patel Naina , Krishnan Shekhar , Liu JiZhong , Saha Vaskar , Bates Paul A.
Published: November 2010

Using proteins in a therapeutic context often requires engineering to modify functionality and enhance efficacy. We have previously reported that the therapeutic antileukemic protein macromolecule Escherichia coli L-asparaginase is degraded by leukemic lysosomal cysteine proteases. In the present study, we successfully engineered L-asparaginaseto resist proteolytic cleavage and at the same time improve activity. We employed a novel combination of mutant sampling using a genetic algorithm in tandem with flexibility studies using molecular dynamics to investigate the impact of lid-loop and mutations on drug activity. Applying these methods, we successfully predicted the more active L-asparaginase mutants N24T and N24A. For the latter, a unique hydrogen bond network contributes to higher activity. Furthermore, interface mutations controlling secondary glutaminase activity demonstrated the importance of this enzymatic activity for drug cytotoxicity. All selected mutants were expressed, purified, and tested for activity and for their ability to form the active tetrameric form. By introducing the N24A and N24A R195S mutations to the drug L-asparaginase, we are a step closer to individualized drug design.
Assessing the potential for AAV vector genotoxicity in a murine model
Authors: Li Hojun , Malani Nirav , Hamilton Shari R. , Schlachterman Alexander , Bussadori Giulio , Edmonson Shyrie E. , Shah Rachel , Arruda Valder R. , Mingozzi Federico , Fraser Wright J. , Bushman Frederic D. , High Katherine A.
Published: November 2010

Gene transfer using adeno-associated virus (AAV) vectors has great potential for treating human disease. Recently, questions have arisen about the safety of AAV vectors, specifically, whether integration of vector DNA in transduced cell genomes promotes tumor formation. This study addresses these questions with high-dose liver-directed AAV-mediated gene transfer in the adult mouse as a model (80 AAV-injected mice and 52 controls). After 18 months of follow-up, AAV-injected mice did not show a significantly higher rate of hepatocellular carcinoma compared with controls. Tumors in mice treated with AAV vectors did not have significantly different amounts of vector DNA compared with adjacent normal tissue. A novel high-throughput method for identifying AAV vector integration sites was developed and used to clone 1029 integrants. Integration patterns in tumor tissue and adjacent normal tissue were similar to each other, showing preferences for active genes, cytosine-phosphate-guanosine islands, and guanosine/cysteine-rich regions. Gene expression data showed that genes near integration sites did not show significant changes in expression patterns compared with genes more distal to integration sites. No integration events were identified as causing increased oncogene expression. Thus, we did not find evidence that AAV vectors cause insertional activation of oncogenes and subsequent tumor formation.
Autologous hematopoietic stem cell transplantation in chronic lymphocytic leukemia: results of European intergroup randomized trial comparing autografting versus observation
Authors: Michallet Mauricette , Dreger Peter , Sutton Laurent , Brand Ronald , Richards Sue , van Os Marleen , Sobh Mohamad , Choquet Sylvain , Corront Bernadette , Dearden Claire , Gratwohl Alois , Herr Wolfgang , Catovsky Daniel , Hallek Michael , de Witte Theo , Niederwieser Dietger , Leporrier Michel , Milligan Donald
Published: November 2010

We present results of a phase 3 randomized trial of autografting in chronic lymphocytic leukemia versus observation for responding patients after first- or second-line treatment. The primary objective was to demonstrate that autografting improves the 5-year event-free survival (EFS) from 30% to 50%. There were 223 enrolled patients, 72% men and 28% women, 83% after first and 17% after second-line treatment. Binet stages were progressive A 13%, B 67%, C 20%; at randomization, 59% were in complete remission, and 41% in less than complete remission. Patients were randomized between autografting (n = 112) and observation (n = 111). Median EFS was 24.4 months (range, 16.7-32 months) in the observation group and 51.2 months (39.8-62.5 months) in the autografting group; the 5-year EFS was 24% and 42%, respectively (P < .001). Accordingly, the 5-year relapse incidence was 76% versus 54% (P < .001). Median time to relapse requiring therapy or death was 40 months (25-56 months) in the observation arm and 65 months (59-71 months) after autografting (P = .002). Cox modeling confirmed that autografting significantly improved EFS (hazard ratio 0.44, 95% confidence interval 0.30-0.65; P < .001). At 5 years, the probability of OS was 85.5% and 84.3% for autografting and observation, respectively (P = .77). In chronic lymphocytic leukemia, consolidating autografting reduces the risk of progression by more than 50% but has no effect on overall survival.
Speeding up tandem mass spectrometry-based database searching by longest common prefix
Authors: Zhou Chen , Chi Hao , Wang Le-Heng , Li You , Wu Yan-Jie , Fu Yan , Sun Rui-Xiang , He Si-Min
Published: November 2010

Background

Tandem mass spectrometry-based database searching has become an important technology for peptide and protein identification. One of the key challenges in database searching is the remarkable increase in computational demand, brought about by the expansion of protein databases, semi- or non-specific enzymatic digestion, post-translational modifications and other factors. Some software tools choose peptide indexing to accelerate processing. However, peptide indexing requires a large amount of time and space for construction, especially for the non-specific digestion. Additionally, it is not flexible to use.

Results

We developed an algorithm based on the longest common prefix (ABLCP) to efficiently organize a protein sequence database. The longest common prefix is a data structure that is always coupled to the suffix array. It eliminates redundant candidate peptides in databases and reduces the corresponding peptide-spectrum matching times, thereby decreasing the identification time. This algorithm is based on the property of the longest common prefix. Even enzymatic digestion poses a challenge to this property, but some adjustments can be made to this algorithm to ensure that no candidate peptides are omitted. Compared with peptide indexing, ABLCP requires much less time and space for construction and is subject to fewer restrictions.

Conclusions

The ABLCP algorithm can help to improve data analysis efficiency. A software tool implementing this algorithm is available at http://pfind.ict.ac.cn/pfind2dot5/index.htm
Protogenin, a new member of the immunoglobulin superfamily, is implicated in the development of the mouse lower first molar
Authors: Takahashi Keiko F , Kiyoshima Tamotsu , Kobayashi Ieyoshi , Xie Ming , Yamaza Haruyoshi , Fujiwara Hiroaki , Ookuma Yukiko , Nagata Kengo , Wada Hiroko , Sakai Takako , Terada Yoshihiro , Sakai Hidetaka
Published: November 2010

Background

Protogenin (Prtg) has been identified as a gene which is highly expressed in the mouse mandible at embryonic day 10.5 (E10.5) by a cDNA subtraction method between mandibles at E10.5 and E12.0. Prtg is a new member of the deleted in colorectal carcinoma (DCC) family, which is composed of DCC, Neogenin, Punc and Nope. Although these members play an important role in the development of the embryonic central nervous system, recent research has also shed on the non-neuronal organization. However, very little is known regarding the fetal requirement of the non-neuronal organization for Prtg and how this may be associated with the tooth germ development. This study examined the functional implications of Prtg in the developing tooth germ of the mouse lower first molar.

Results

Ptrg is preferentially expressed in the early stage of organogenesis. Prtg mRNA and protein were widely expressed in the mesenchymal cells in the mandible at E10.5. The oral epithelial cells were also positive for Prtg. The expression intensity of Prtg after E12.0 was markedly reduced in the mesenchymal cells of the mandible, and was restricted to the area where the tooth bud was likely to be formed. Signals were also observed in the epithelial cells of the tooth germ. Weak signals were observed in the inner enamel epithelial cells at E16.0 and E18.0. An inhibition assay using a hemagglutinating virus of Japan-liposome containing Prtg antisense-phosphorothioated-oligodeoxynucleotide (AS-S-ODN) in cultured mandibles at E10.5 showed a significant growth inhibition in the tooth germ. The relationship between Prtg and the odontogenesis-related genes was examined in mouse E10.5 mandible, and we verified that the Bmp-4 expression had significantly been decreased in the mouse E10.5 mandible 24 hr after treatment with Prtg AS-S-ODN.

Conclusion

These results indicated that the Prtg might be related to the initial morphogenesis of the tooth germ leading to the differentiation of the inner enamel epithelial cells in the mouse lower first molar. A better understanding of the Prtg function might thus play a critical role in revealing a precious mechanism in tooth germ development.
Genetic constraints for thermal coadaptation in Drosophila subobscura
Authors: Dolgova Olga , Rego Carla , Calabria Gemma , Balanyà Joan , Pascual Marta , Rezende Enrico L , Santos Mauro
Published: November 2010

Background

Behaviour has been traditionally viewed as a driver of subsequent evolution because behavioural adjustments expose organisms to novel environments, which may result in a correlated evolution on other traits. InDrosophila subobscura, thermal preference and heat tolerance are linked to chromosomal inversion polymorphisms that show parallel latitudinal clines worldwide, such that "cold-climate" ("warm-climate") chromosome arrangements collectively favour a coherent response to colder (warmer) settings as flies carrying them prefer colder (warmer) conditions and have lower (higher) knock out temperatures. Yet, it is not clear whether a genetic correlation between thermal preference and heat tolerance can partially underlie such response.

Results

We have analyzed the genetic basis of thermal preference and heat tolerance using isochromosomal lines inD. subobscura. Chromosome arrangements on the O chromosome were known to have a biometrical effect on thermal preference in a laboratory temperature gradient, and also harbour several genes involved in the heat shock response; in particular, the genesHsp68andHsp70. Our results corroborate that arrangements on chromosome O affect adult thermal preference in a laboratory temperature gradient, with cold-climate Ostcarriers displaying a lower thermal preference than their warm-climate O3+4and O3+4+8counterparts. However, these chromosome arrangements did not have any effect on adult heat tolerance and, hence, we putatively discard a genetic covariance between both traits arising from linkage disequilibrium between genes affecting thermal preference and candidate genes for heat shock resistance. Nonetheless, a possible association of juvenile thermal preference and heat resistance warrants further analysis.

Conclusions

Thermal preference and heat tolerance in the isochromosomal lines ofD. subobscuraappear to be genetically independent, which might potentially prevent a coherent response of behaviour and physiology (i.e., coadaptation) to thermal selection. If this pattern is general to all chromosomes, then any correlation between thermal preference and heat resistance across latitudinal gradients would likely reflect a pattern of correlated selection rather than genetic correlation.
Genome sequence of adherent-invasive Escherichia coli and comparative genomic analysis with other E. coli pathotypes
Authors: Nash John HE , Villegas Andre , Kropinski Andrew M , Aguilar-Valenzuela Renan , Konczy Paulina , Mascarenhas Mariola , Ziebell Kim , Torres Alfredo G , Karmali Mohamed A , Coombes Brian K
Published: November 2010

Background

Adherent and invasive Escherichia coli (AIEC) are commonly found in ileal lesions of Crohn's Disease (CD) patients, where they adhere to intestinal epithelial cells and invade into and survive in epithelial cells and macrophages, thereby gaining access to a typically restricted host niche. Colonization leads to strong inflammatory responses in the gut suggesting that AIEC could play a role in CD immunopathology. Despite extensive investigation, the genetic determinants accounting for the AIEC phenotype remain poorly defined. To address this, we present the complete genome sequence of an AIEC, revealing the genetic blueprint for this disease-associated E. coli pathotype.

Results

We sequenced the complete genome of E. coli NRG857c (O83:H1), a clinical isolate of AIEC from the ileum of a Crohn's Disease patient. Our sequence data confirmed a phylogenetic linkage between AIEC and extraintestinal pathogenic E. coli causing urinary tract infections and neonatal meningitis. The comparison of the NRG857c AIEC genome with other pathogenic and commensal E. coli allowed for the identification of unique genetic features of the AIEC pathotype, including 41 genomic islands, and unique genes that are found only in strains exhibiting the adherent and invasive phenotype.

Conclusions

Up to now, the virulence-like features associated with AIEC are detectable only phenotypically. AIEC genome sequence data will facilitate the identification of genetic determinants implicated in invasion and intracellular growth, as well as enable functional genomic studies of AIEC gene expression during health and disease.
Novel Method of Monitoring Trace Cytokines and Activated STAT Molecules in the Paws of Arthritic Mice using Multiplex Bead Technology
Authors: Lu Lily D , Stump Kristine L , Seavey Matthew M
Published: November 2010

Background

The use of mouse models to study human disease provides useful data that can provide support for research projects or an existing drug discovery program. How well a model recapitulates the human condition and the ease and reproducibility of data collected will determine how much confidence a scientist can place on results obtained. Designing new treatments for rheumatic diseases, such as rheumatoid arthritis (RA), requires complex immunocompetent models that depend on intricate cytokine networks. Using local cytokines, signal transduction and transcription factor molecules as potential biomarkers to monitor disease and treatment efficacy is the best method to follow the progression of tissue damage and repair when testing an unknown compound or biologic. Described here in this report, a novel method for the non-enzymatic extraction and measurement of cytokines and signal transducers and activators of transcription (STAT) molecules using Luminex® bead array technology in two different mouse models for human RA - collagen antibody-dependent arthritis (CAIA) and collagen-induced arthritis (CIA).

Results

Dynamic expression of several pro-inflammatory cytokines responsible for promoting disease augmentation overtime were monitored, such as IL-1β, TNFα, IL-6 and IL-12, locally in the paws of affected animals directly ex vivo. Local cytokine responses could be matched with serum cytokine levels and joint pathology results. In addition, STAT1, 3, and 5a/b activation status could be monitored with confidence using specifically formulated extraction buffer that protected the phosphorylation site. STAT3 activation followed paw swelling and cytokine levels in both models and correlates of disease could be ablated upon treatment with dexamethasone. Here reported a novel method of extracting joint fluid from the paws of inflamed mice coupled with powerful multiplex bead technology allowing us to measure cytokine responses, pharmacodynamic markers such as STATs and pharmacokinetic analysis of dosed agent all from the same sample directly ex vivo.

Conclusions

This method is powerful in that it is applicable to multiple autoimmunity model types, streamlines ex vivo readouts in a high-throughput manner, and allows multiplexing providing the investigator with an array of options and possible analytes when developing preclinical animal models to support drug discovery efforts in the search for new treatments for rheumatic diseases.
Estimation of cancer incidence and mortality attributable to alcohol drinking in china
Authors: Liang Hao , Wang Jianbing , Xiao Huijuan , Wang Ding , Wei Wenqiang , Qiao Youlin , Boffetta Paolo
Published: November 2010

Background

Cancer constitutes a serious burden of disease worldwide and has become the second leading cause of death in China. Alcohol consumption is causally associated with the increased risk of certain cancers. Due to the current lack of data and the imperative need to guide policymakers on issues of cancer prevention and control, we aim to estimate the role of alcohol on the cancer burden in China in 2005.

Methods

We calculated the proportion of cancers attributable to alcohol use to estimate the burden of alcohol-related cancer. The population attributable fraction was calculated based on the assumption of no alcohol drinking. Data on alcohol drinking prevalence were from two large-scale national surveys of representative samples of the Chinese population. Data on relative risk were obtained from meta-analyses and large-scale studies.

Results

We found that a total of 78,881 cancer deaths were attributable to alcohol drinking in China in 2005, representing 4.40% of all cancers (6.69% in men, 0.42% in women). The corresponding figure for cancer incidence was 93,596 cases (3.63% of all cancer cases). Liver cancer was the main alcohol-related cancer, contributing more than 60% of alcohol-related cancers.

Conclusions

Particular attention needs to be paid to the harm of alcohol as well as its potential benefits when making public health recommendations on alcohol drinking.
Impact of air pollution on pulmonary function and respiratory symptoms in children. Longitudinal repeated-measures study
Authors: Linares Benigno , Guizar Juan M , Amador Norma , Garcia Alfonso , Miranda Victor , Perez Jose R , Chapela Rocío
Published: November 2010

Background

Salamanca, Mexico occupied fourth place nationally in contaminating emissions. The aim of the study was to determine the impact of air pollution on the frequency of pulmonary function alterations and respiratory symptoms in school-age children in a longitudinal repeated-measures study.

Methods

We recruited a cohort of 464 children from 6 to 14 years of age, from two schools differing in distance from the major stationary air pollution sources. Spirometry, respiratory symptoms and air pollutants (O3, SO2, NO, NO2, NOx, PM10,) were obtained for each season. Mixed models for continuous variables and multilevel logistic regression for respiratory symptoms were fitted taking into account seasonal variations in health effects according to air pollution levels.

Results

Abnormalities in lung function and frequency of respiratory symptoms were higher in the school closer to major stationary air pollution sources than in the distant school. However, in winter differences on health disappeared. The principal alteration in lung function was the obstructive type, which frequency was greater in those students with greater exposure (10.4% vs. 5.3%; OR = 1.95, 95% CI 1.0-3.7), followed by the mixed pattern also more frequent in the same students (4.1% vs. 0.9%; OR = 4.69, 95% CI, 1.0-21.1). PM10 levels were the most consistent factor with a negative relationship with FVC, FEV1 and PEF but with a positive relationship with FEV1/FVC coefficient according to its change per 3-month period.

Conclusions

Students from the school closer to major stationary air pollution sources had in general more respiratory symptoms than those from the distant school. However, in winter air pollution was generalized in this city and differences in health disappeared. PM10 levels were the most consistent factor related to pulmonary function according, to its change per 3-month period.
The Key Indicator Method for Manual Handling Operations (KIM-MHO) - evaluation of a new method for the assessment of working conditions within a cross-sectional study
Authors: Klussmann André , Steinberg Ulf , Liebers Falk , Gebhardt Hansjürgen , Rieger Monika A
Published: November 2010

Background

Upper extremity musculoskeletal symptoms and disorders are common in the working population. The economic and social impact of such disorders is considerable. Long-time, dynamic repetitive exposure of the hand-arm system during manual handling operations (MHO) alone or in combination with static and postural effort are recognised as causes of musculoskeletal symptoms and disorders. The assessment of these manual work tasks is crucial to estimate health risks of exposed employees. For these work tasks, a new method for the assessment of the working conditions was developed by the Federal Institute for Occupational Safety and Health (BAuA) and released as a draft in the year 2007. The draft of the so-called Key Indicator Method for Manual Handling Operations (KIM-MHO) was developed in analogy with the existing KIM for Lifting/Holding/Carrying (KIM-LHC) and Pulling/Pushing (KIM-PP) of loads. The KIM-MHO is designed to fill the gap existing in risk assessment of manual work processes, since the existing KIMs deal only with manual handling of loads.

This research project focused on the following:

- Examination of the validity of workplace assessment with the KIM-MHO comparing expert ratings with the results of the observations.

- Examination of the objectivity of workplace assessment with the KIM-MHO applied by different examiners.

- Examination of the criterion validity of the risk assessment provided by KIM-MHO with respect to the association between exposure and the occurrence and prevalence of health related outcomes.

Methods/Design

To determine the objectivity and validity of workplace assessment, the KIM-MHO is applied by occupational health and safety officers at different workplaces involving manual handling operations.

To determine the criterion validity of risk assessment, a survey of employees at different workplaces takes place with standardised questionnaires and interviews about symptoms in the neck and upper extremities. In addition, physical examinations of these employees following a standardised medical diagnostic procedure are also carried out.

Discussion

This research project will provide scientific evaluation of the new KIM-MHO and, if necessary, indicate areas for modification to improve this new method for assessment of the health risk of manual handling operations at diverse workplaces.
Inhibition of core gene of HCV 3a genotype using synthetic and vector derived siRNAs
Authors: Khaliq Saba , Jahan Shah , Ijaz Bushra , Ahmad Waqar , Asad Sultan , Pervaiz Asim , Samreen Baila , Khan Mahwish , Hassan Sajida
Published: November 2010

Background

Hepatitis C virus (HCV) is a major causative agent of liver associated diseases throughout the world, with genotype 3a responsible for most of the cases in Pakistan. Due to the limited efficiency of current therapy, RNA interference (RNAi) a novel regulatory and powerful silencing approach for molecular therapeutics through a sequence-specific RNA degradation process represents an alternative option.

Results

The current study was purposed to assess and explore the possibility of RNAi to silence the HCV-3a Core gene expression, which play complex role in regulation of cell growth and host genes expression essential for infectivity and disease progression. To identify the potent siRNA target sites, 5 small interfering RNAs (siRNAs) against Core gene were designed and in
vitro transcribed after consensus sequence analysis of different HCV-3a isolates. Antiviral effects of siRNAs showed upto 80% inhibition of Core gene expression by different siRNAs into Huh-7 cells as compared with Mock transfected and control siRNAs treated cells. For long lasting effect of siRNAs, vector based short hairpin siRNAs (shRNAs) were designed and tested against HCV-3a Core which resulted in a similar pattern of inhibition on RNA and protein expression of HCV Core as synthetic siRNAs. Furthermore, the efficacy of cell culture tested siRNA and shRNA, were evaluated for inhibition of HCV replication in HCV infected serum inoculated Huh-7 cells and a significant decrease in HCV viral copy number was observed.

Conclusions

Our results support the possibility of using consensus siRNA and shRNA-based molecular therapy as a promising strategy in effective inhibition of HCV-3a genotype.
Computed tomography imaging of subpleural lipoma in two men: two case reports
Authors: Karlo Christoph A , Stolzmann Paul , Frauenfelder Thomas , Donati Olivio F , Leschka Sebastian
Published: November 2010

Introduction

Subpleural lipomas are very rare pleural lesions and are often discovered incidentally in asymptomatic patients on conventional radiographs.

Case presentations

We report two cases of subpleural lipomas and describe their imaging characteristics on chest radiographs and computed tomography. We describe the cases of two Caucasian men, aged 77 and 62 years old.

Conclusions

For non-invasive diagnostic investigation, computed tomography enables the identification and quantification of these tumors due to their characteristic fat attenuation.
Increased vulnerability of rural children on antiretroviral therapy attending public health facilities in South Africa: a retrospective cohort study
Authors: Fatti Geoffrey , Bock Peter , Grimwood Ashraf , Eley Brian
Published: November 2010

Background

A large proportion of the 340,000 HIV‐positive children in South Africa live in rural areas, yet there is little sub‐Saharan data comparing rural paediatric antiretroviral therapy (ART) programme outcomes with urban facilities. We compared clinical, immunological and virological outcomes between children at seven rural and 37 urban facilities across four provinces in South Africa.

Methods

We conducted a retrospective cohort study of routine data of children enrolled on ART between November 2003 and March 2008 in three settings, namely: urban residence and facility attendance (urban group); rural residence and facility attendance (rural group); and rural residents attending urban facilities (rural/urban group). Outcome measures were: death, loss to follow up (LTFU), virological suppression, and changes in CD4 percentage and weight‐for‐age‐z (WAZ) scores. Kaplan‐Meier estimates, logrank tests, multivariable Cox regression and generalized estimating equation models were used to compare outcomes between groups.

Results

In total, 2332 ART‐naïve children were included, (1727, 228 and 377 children in the urban, rural and rural/urban groups, respectively). At presentation, rural group children were older (6.7 vs. 5.6 and 5.8 years), had lower CD4 cell percentages (10.0% vs. 12.8% and 12.7%), lower WAZ scores (‐2.06 vs. ‐1.46 and ‐1.41) and higher proportions with severe underweight (26% vs.15% and 15%) compared with the urban and rural/urban groups, respectively. Mortality was significantly higher in the rural group and LTFU significantly increased in the rural/urban group. After 24 months of ART, mortality probabilities were 3.4% (CI: 2.4‐4.8%), 7.7% (CI: 4.5‐13.0%) and 3.1% (CI: 1.7‐5.6%) p = 0.0137; LTFU probabilities were 11.5% (CI: 9.3‐14.0%), 8.8% (CI: 4.5‐16.9%) and 16.6% (CI: 12.4‐22.6%), p = 0.0028 in the urban, rural and rural/urban groups, respectively. The rural group had an increased adjusted mortality probability, adjusted hazards ratio 2.41 (CI: 1.25‐4.67) and the rural/urban group had an increased adjusted LTFU probability, aHR 2.85 (CI: 1.41‐5.79). The rural/urban group had a decreased adjusted probability of virological suppression compared with the urban group at any timepoint on treatment, adjusted odds ratio 0.67 (CI: 0.48‐0.93).

Conclusions

Rural HIV‐positive children are a vulnerable group, exhibiting delayed access to ART and an increased risk of poor outcomes while on ART. Expansion of rural paediatric ART programmes, with future research exploring improvements to rural health system effectiveness, is required.
Systematic detection of putative tumor suppressor genes through the combined use of exome and transcriptome sequencing
Authors: Zhao Qi , Kirkness Ewen F , Caballero Otavia L , Galante Pedro A , Parmigiani Raphael B , Edsall Lee , Kuan Samantha , Ye Zhen , Levy Samuel , Vasconcelos Ana Tereza R , Ren Bing , de Souza Sandro J , Camargo Anamaria A , Simpson Andrew JG , Strausberg Robert L
Published: November 2010

Background

To identify potential tumor suppressor genes, genome-wide data from exome and transcriptome sequencing were combined to search for genes with loss of heterozygosity and allele-specific expression. The analysis was conducted on the breast cancer cell line HCC1954, and a lymphoblast cell line from the same individual, HCC1954BL.

Results

By comparing exome sequences from the two cell lines, we identified loss of heterozygosity events at 403 genes in HCC1954 and at one gene in HCC1954BL. The combination of exome and transcriptome sequence data also revealed 86 and 50 genes with allele specific expression events in HCC1954 and HCC1954BL, which comprise 5.4% and 2.6% of genes surveyed, respectively. Many of these genes identified by loss of heterozygosity and allele-specific expression are known or putative tumor suppressor genes, such as BRCA1, MSH3 and SETX, which participate in DNA repair pathways.

Conclusions

Our results demonstrate that the combined application of high throughput sequencing to exome and allele-specific transcriptome analysis can reveal genes with known tumor suppressor characteristics, and a shortlist of novel candidates for the study of tumor suppressor activities.
Neutrophil IL-10 suppresses peritoneal inflammatory monocytes during polymicrobial sepsis
Authors: Ocuin Lee M , Bamboat Zubin M , Balachandran Vinod P , Cavnar Michael J , Obaid Hebroon , Plitas George , DeMatteo Ronald P
Published: November 2010

Septic peritonitis remains a major cause of death. Neutrophils and inflammatory monocytes are principal components of the innate immune system and are essential for defense against a range of microbial pathogens. Their role and interaction in polymicrobial sepsis have not been defined clearly. Using a murine model of CLP to induce moderate sepsis, we found that neutrophil depletion did not alter survival, whereas depletion of neutrophils and inflammatory monocytes markedly reduced survival. After neutrophil depletion, inflammatory monocytes had greater phagocytic capacity and oxidative burst, and increased expression of costimulatory molecules, TNF, and iNOS. Notably, peritoneal neutrophils produced IL-10 following CLP. Adoptive i.p. transfer of WT but not IL-10−/− neutrophils into septic mice reduced monocyte expression of TNF. In vitro experiments confirmed that monocyte suppression was mediated by neutrophil-derived IL-10. Thus, during septic peritonitis, neutrophils suppress peritoneal inflammatory monocytes through IL-10 and are dispensable for survival.