bluuebunny/crossref_metadata_2025 huggingface dataset:
Maximum-parsimony haplotype frequencies inference based on a joint constrained sparse representation of pooled DNA
Authors: Jajamovich Guido H , Iliadis Alexandros , Anastassiou Dimitris , Wang Xiaodong
Published: September 2013

Background

DNA pooling constitutes a cost effective alternative in genome wide association studies. In DNA pooling, equimolar amounts of DNA from different individuals are mixed into one sample and the frequency of each allele in each position is observed in a single genotype experiment. The identification of haplotype frequencies from pooled data in addition to single locus analysis is of separate interest within these studies as haplotypes could increase statistical power and provide additional insight.

Results

We developed a method for maximum-parsimony haplotype frequency estimation from pooled DNA data based on the sparse representation of the DNA pools in a dictionary of haplotypes. Extensions to scenarios where data is noisy or even missing are also presented. The resulting method is first applied to simulated data based on the haplotypes and their associated frequencies of the AGT gene. We further evaluate our methodology on datasets consisting of SNPs from the first 7Mb of the HapMap CEU population. Noise and missing data were further introduced in the datasets in order to test the extensions of the proposed method. Both HIPPO and HAPLOPOOL were also applied to these datasets to compare performances.

Conclusions

We evaluate our methodology on scenarios where pooling is more efficient relative to individual genotyping; that is, in datasets that contain pools with a small number of individuals. We show that in such scenarios our methodology outperforms state-of-the-art methods such as HIPPO and HAPLOPOOL.
L_RNA_scaffolder: scaffolding genomes with transcripts
Authors: Xue Wei , Li Jiong-Tang , Zhu Ya-Ping , Hou Guang-Yuan , Kong Xiang-Fei , Kuang You-Yi , Sun Xiao-Wen
Published: September 2013

Background

Generation of large mate-pair libraries is necessary for de novo genome assembly but the procedure is complex and time-consuming. Furthermore, in some complex genomes, it is hard to increase the N50 length even with large mate-pair libraries, which leads to low transcript coverage. Thus, it is necessary to develop other simple scaffolding approaches, to at least solve the elongation of transcribed fragments.

Results

We describe L_RNA_scaffolder, a novel genome scaffolding method that uses long transcriptome reads to order, orient and combine genomic fragments into larger sequences. To demonstrate the accuracy of the method, the zebrafish genome was scaffolded. With expanded human transcriptome data, the N50 of human genome was doubled and L_RNA_scaffolder out-performed most scaffolding results by existing scaffolders which employ mate-pair libraries. In these two examples, the transcript coverage was almost complete, especially for long transcripts. We applied L_RNA_scaffolder to the highly polymorphic pearl oyster draft genome and the gene model length significantly increased.

Conclusions

The simplicity and high-throughput of RNA-seq data makes this approach suitable for genome scaffolding. L_RNA_scaffolder is available at http://www.fishbrowser.org/software/L_RNA_scaffolder.
Predicting whole genome protein interaction networks from primary sequence data in model and non-model organisms using ENTS
Authors: Rodgers-Melnick Eli , Culp Mark , DiFazio Stephen P
Published: September 2013

Background

The large-scale identification of physical protein-protein interactions (PPIs) is an important step toward understanding how biological networks evolve and generate emergent phenotypes. However, experimental identification of PPIs is a laborious and error-prone process, and current methods of PPI prediction tend to be highly conservative or require large amounts of functional data that may not be available for newly-sequenced organisms.

Results

In this study we demonstrate a random-forest based technique, ENTS, for the computational prediction of protein-protein interactions based only on primary sequence data. Our approach is able to efficiently predict interactions on a whole-genome scale for any eukaryotic organism, using pairwise combinations of conserved domains and predicted subcellular localization of proteins as input features. We present the first predicted interactome for the forest tree Populus trichocarpa in addition to the predicted interactomes for Saccharomyces cerevisiae, Homo sapiens, Mus musculus, and Arabidopsis thaliana. Comparing our approach to other PPI predictors, we find that ENTS performs comparably to or better than a number of existing approaches, including several that utilize a variety of functional information for their predictions. We also find that the predicted interactions are biologically meaningful, as indicated by similarity in functional annotations and enrichment of co-expressed genes in public microarray datasets. Furthermore, we demonstrate some of the biological insights that can be gained from these predicted interaction networks. We show that the predicted interactions yield informative groupings of P. trichocarpa metabolic pathways, literature-supported associations among human disease states, and theory-supported insight into the evolutionary dynamics of duplicated genes in paleopolyploid plants.

Conclusion

We conclude that the ENTS classifier will be a valuable tool for the de novo annotation of genome sequences, providing initial clues about regulatory and metabolic network topology, and revealing relationships that are not immediately obvious from traditional homology-based annotations.
The St. Louis African American health-heart study: methodology for the study of cardiovascular disease and depression in young-old African Americans
Authors: Bruchas Robin R , de las Fuentes Lisa , Carney Robert M , Reagan Joann L , Bernal-Mizrachi Carlos , Riek Amy E , Gu Chi Charles , Bierhals Andrew , Schootman Mario , Malmstrom Theodore K , Burroughs Thomas E , Stein Phyllis K , Miller Douglas K , Dávila-Román Victor G
Published: September 2013

Background

Coronary artery disease (CAD) is a major cause of death and disability worldwide. Depression has complex bidirectional adverse associations with CAD, although the mechanisms mediating these relationships remain unclear. Compared to European Americans, African Americans (AAs) have higher rates of morbidity and mortality from CAD. Although depression is common in AAs, its role in the development and features of CAD in this group has not been well examined. This project hypothesizes that the relationships between depression and CAD can be explained by common physiological pathways and gene-environment interactions. Thus, the primary aims of this ongoing project are to: a) determine the prevalence of CAD and depression phenotypes in a population-based sample of community-dwelling older AAs; b) examine the relationships between CAD and depression phenotypes in this population; and c) evaluate genetic variants from serotoninP and inflammatory pathways to discover potential gene-depression interactions that contribute significantly to the presence of CAD in AAs.

Methods/design

The St. Louis African American Health (AAH) cohort is a population-based panel study of community-dwelling AAs born in 1936–1950 (inclusive) who have been followed from 2000/2001 through 2010. The AAH-Heart study group is a subset of AAH participants recruited in 2009–11 to examine the inter-relationships between depression and CAD in this population. State-of-the-art CAD phenotyping is based on cardiovascular characterizations (coronary artery calcium, carotid intima-media thickness, cardiac structure and function, and autonomic function). Depression phenotyping is based on standardized questionnaires and detailed interviews. Single nucleotide polymorphisms of selected genes in inflammatory and serotonin-signaling pathways are being examined to provide information for investigating potential gene-depression interactions as modifiers of CAD traits. Information from the parent AAH study is being used to provide population-based prevalence estimates. Inflammatory and other biomarkers provide information about potential pathways.

Discussion

This population-based investigation will provide valuable information on the prevalence of both depression and CAD phenotypes in this population. The study will examine interactions between depression and genetic variants as modulators of CAD, with the intent of detecting mechanistic pathways linking these diseases to identify potential therapeutic targets. Analytic results will be reported as they become available.
Meta-analysis of randomized controlled trials on the efficacy and safety of intracoronary administration of tirofiban for no-reflow phenomenon
Authors: Qin Tao , Xie Lu , Chen Meng-Hua
Published: September 2013

Background

Currently, there is still a lack of an optimal treatment for no-reflow phenomenon (NR). The aim of this simple meta-analysis was to evaluate the efficacy and safety of intracoronary (IC) administration of tirofiban compared with other conventional drugs during percutaneous coronary intervention (PCI) for NR.

Methods

Systematic literature search was done from PubMed, EMBASE, Google Scholar, EBSCO, Springer and CNKI databases without language or time limitation. Randomized controlled trials were enrolled for analyzing if they investigated the treatment of IC administration of tirofiban versus other conventional drugs for NR.

Results

Ten studies with 702 patients were included. Significantly, the treatment of tirofiban was more effective in improving the thrombolysis in myocardial infarction (TIMI) flow (OR 0.24, 95% CI 0.15-0.37, P < 0.00001) and reducing major adverse cardiovascular events (MACE) (OR 0.09, 95% CI 0.05-0.18, P < 0.00001). There was a trend to increase the risk of bleeding, but the data of the result did not reach the statistical significance (OR 1.44, 95% CI 0.69-3.00, P = 0.32).

Conclusions

Tirofiban is more effective than conventional drugs for NR during PCI, but the potential risk of bleeding complication induced by tirofiban shouldn’t be ignored during clinical practices.
Genotypic and phenotypic analysis of diarrheagenic Escherichia coli strains isolated from Brazilian children living in low socioeconomic level communities
Authors: Lozer Diego M , Souza Tamara B , Monfardini Mariane V , Vicentini Fernando , Kitagawa Sônia S , Scaletsky Isabel C A , Spano Liliana C
Published: September 2013

Background

Childhood diarrheal diseases remain highly endemic in developing areas of Brazil. The importance of Escherichia coli among children with diarrhea in these areas was unknown. This study determined the prevalence of different E. coli categories in symptomatic and asymptomatic children from low socioeconomic level rural communities in southeastern Brazil.

Methods

A total of 560 stool samples were collected from 141 children with diarrhea (< 10 years) and 419 apparently healthy controls who resided in 23 communities. E. coli isolates (n = 1943) were subjected to two multiplex PCRs developed for the detection of enteropathogenic E. coli (EPEC), enteroaggregative E. coli (EAEC), diffusely adherent E. coli (DAEC), enterotoxigenic E. coli (ETEC), enteroinvasive E. coli (EIEC), and Shiga toxin-producing E. coli (STEC). Strains were also examined for the presence of EPEC, EAEC, and DAEC by assays of adhesion to HEp-2 cells and by hybridization with specific DNA probes.

Results

Diarrheagenic E. coli strains were isolated from 253 (45.2%) children, and were associated with diarrhea in children aged < 5 years (p < 0.001). EAEC (20.9%), DAEC (11.6%), EPEC (9.3%) were the most frequent pathotypes, followed by ETEC (2.7%), EIEC (0.5%), and STEC (0.2%). Depending of the assay, EPEC, EAEC, and DAEC (collectively termed enteroadherent E. coli) strains were isolated in 45% to 56% of diarrhea cases, a significantly higher incidence than in controls (P < 0.05). Individually, only DAEC showed significant association with diarrhea (p < 0.05), particularly in children aged 2–5 years.

Conclusion

This study indicates that enteroadherent E. coli is an important cause of diarrhea in children living in low socioeconomic level communities in southeastern Brazil. Our results reveal that the PCR1 assay is an excellent tool for the identification of EAEC and DAEC.
The development of a combined mathematical model to forecast the incidence of hepatitis E in Shanghai, China
Authors: Ren Hong , Li Jian , Yuan Zheng-An , Hu Jia-Yu , Yu Yan , Lu Yi-Han
Published: September 2013

Background

Sporadic hepatitis E has become an important public health concern in China. Accurate forecasting of the incidence of hepatitis E is needed to better plan future medical needs. Few mathematical models can be used because hepatitis E morbidity data has both linear and nonlinear patterns. We developed a combined mathematical model using an autoregressive integrated moving average model (ARIMA) and a back propagation neural network (BPNN) to forecast the incidence of hepatitis E.

Methods

The morbidity data of hepatitis E in Shanghai from 2000 to 2012 were retrieved from the China Information System for Disease Control and Prevention. The ARIMA-BPNN combined model was trained with 144 months of morbidity data from January 2000 to December 2011, validated with 12 months of data January 2012 to December 2012, and then employed to forecast hepatitis E incidence January 2013 to December 2013 in Shanghai. Residual analysis, Root Mean Square Error (RMSE), normalized Bayesian Information Criterion (BIC), and stationary R square methods were used to compare the goodness-of-fit among ARIMA models. The Bayesian regularization back-propagation algorithm was used to train the network. The mean error rate (MER) was used to assess the validity of the combined model.

Results

A total of 7,489 hepatitis E cases was reported in Shanghai from 2000 to 2012. Goodness-of-fit (stationary R2=0.531, BIC= −4.768, Ljung-Box Q statistics=15.59,P=0.482) and parameter estimates were used to determine the best-fitting model as ARIMA (0,1,1)×(0,1,1)12. Predicted morbidity values in 2012 from best-fitting ARIMA model and actual morbidity data from 2000 to 2011 were used to further construct the combined model. The MER of the ARIMA model and the ARIMA-BPNN combined model were 0.250 and 0.176, respectively. The forecasted incidence of hepatitis E in 2013 was 0.095 to 0.372 per 100,000 population. There was a seasonal variation with a peak during January-March and a nadir during August-October.

Conclusions

Time series analysis suggested a seasonal pattern of hepatitis E morbidity in Shanghai, China. An ARIMA-BPNN combined model was used to fit the linear and nonlinear patterns of time series data, and accurately forecast hepatitis E infections.
Characterizing the syphilis epidemic among men who have sex with men in Lima, Peru to identify new treatment and control strategies
Authors: Deiss Robert G , Leon Segundo R , Konda Kelika A , Brown Brandon , Segura Eddy R , Galea Jerome T , Caceres Carlos F , Klausner Jeffrey D
Published: September 2013

Background

Syphilis is an important sexually transmitted infection (STI) with serious public health consequences. Among men who have sex with men (MSM) in Lima, the prevalence and incidence are extraordinarily high. Current syndromic approaches, however, fail to identify asymptomatic cases, and in settings where large proportions of individuals test positive again after treatment, it is frequently difficult to distinguish treatment failure from re-infection. Thus, new approaches are needed to improve treatment strategies and public health control efforts.

Methods/Design

Study participants will undergo baseline testing for syphilis infection along with a behavioral survey covering demographics, sexual behavior, drug and alcohol abuse and health-care seeking behavior. The cohort will be followed for 18 months at three-month intervals. Blood and earlobe scrapings will also be collected for T. pallidum DNA testing, to create molecular markers for subtyping. We will also perform cytokine testing on collected samples in order to create host immunologic profiles associated with recurrence, re-infection, treatment failure and success.

Discussion

Advances in social epidemiology, molecular typing and characterization of host immune responses will offer promise in developing new understandings of syphilis management. We will share our findings with the Peruvian Ministry of Health and other public health organizations, to identify new approaches of case detection and successful treatment.
Driver self-regulation and depressive symptoms in cataract patients awaiting surgery: a cross-sectional study
Authors: Fraser Michelle L , Meuleners Lynn B , Ng Jonathon Q , Morlet Nigel
Published: September 2013

Background

Cataract is an extremely common visual condition of ageing. Evidence suggests that visual impairment influences driving patterns and self-regulatory behavior among older drivers. However, little is known about the psychological effects of driver self-regulation among older drivers. Therefore, this study aimed to describe driver self-regulation practices among older bilateral cataract patients and to determine the association between self-regulation and depressive symptoms.

Methods

Ninety-nine older drivers with bilateral cataract were assessed the week before first eye cataract surgery. Driver self-regulation was measured via the Driving Habits Questionnaire. Depressive symptoms were assessed using the 20-item Center for Epidemiological Studies Depression Scale. Visual, demographic and cognitive data were also collected. Differences between self-regulators and non self-regulators were described and linear regression modeling used to determine the association between driver self-regulation and depressive symptoms score.

Results

Among cataract patients, 48% reported self-regulating their driving to avoid at least one challenging situation. The situations most commonly avoided were driving at night (40%), on the freeway (12%), in the rain (9%) and parallel parking (8%). Self-regulators had significantly poorer contrast sensitivity in their worse eye than non self-regulators (p = 0.027). Driver self-regulation was significantly associated with increased depressive symptoms after controlling for potential confounding factors (p = 0.002).

Conclusions

Driver self-regulation was associated with increased depressive symptoms among cataract patients. Further research should investigate this association among the general older population. Self-regulation programs aimed at older drivers may need to incorporate mental health elements to counteract unintended psychological effects.
Impact of atypical long-acting injectable versus oral antipsychotics on rehospitalization rates and emergency room visits among relapsed schizophrenia patients: a retrospective database analysis
Authors: Lafeuille Marie-Hélène , Laliberté-Auger François , Lefebvre Patrick , Frois Christian , Fastenau John , Duh Mei Sheng
Published: September 2013

Background

Among schizophrenia patients relapsed on an oral antipsychotic (AP), this study compared the impact of switching to atypical AP long-acting injectable therapy (LAT) versus continuing oral APs on hospitalization and emergency room (ER) visit recurrence.

Methods

Electronic records from the Premier Hospital Database (2006-2010) were analyzed. Adult patients receiving oral APs during a schizophrenia-related hospitalization were identified and, upon relapse (i.e., rehospitalization for schizophrenia), were stratified into (a) patients switching to atypical LAT and (b) patients continuing with oral APs. Atypical LAT relapse patients were matched 1:3 with oral AP relapse patients, using a propensity score model. Andersen-Gill Cox proportional hazards models assessed the impact of atypical LAT versus oral AP on time to multiple recurrences of all-cause hospitalizations and ER visits. No adjustment was made for multiplicity.

Results

Atypical LAT (N = 1032) and oral AP (N = 2796) patients were matched and well-balanced with respect to demographic (mean age: 42.1 vs 42.4 years, p = .5622; gender: 43.6% vs 44.6% female, p = .5345), clinical, and hospital characteristics. Over a mean 30-month follow-up period, atypical LATs were associated with significantly lower mean number of rehospitalizations (1.25 vs 1.61, p < .0001) and ER visits (2.33 vs 2.67, p = .0158) compared with oral APs, as well as fewer days in hospital (mean days: 13.46 vs. 15.69, p = .0081). Rehospitalization (HR 0.81, 95% CI 0.76–0.87, p < .0001) and ER visit (HR 0.88, 95% CI 0.87–0.93, p < .0001) rates were significantly lower for patients receiving atypical LAT versus oral APs.

Conclusions

This hospital database analysis found that in relapsed schizophrenia patients, atypical LATs were associated with lower rehospitalization and ER visit rates than oral APs.
Levels of autistic traits in anorexia nervosa: a comparative psychometric study
Authors: Courty Annaig , Maria Anne Solène , Lalanne Christophe , Ringuenet Damien , Vindreau Christine , Chevallier Coralie , Pouga Lydia , Pinabel François , Philippe Anne , Adrien Jean-Louis , Barry Caroline , Berthoz Sylvie
Published: September 2013

Background

A number of characteristics associated with Autism Spectrum Disorders (ASD) are over-represented among patients with Anorexia Nervosa (AN) as well as among relatives of these patients. Yet the co-occurrence of autistic traits in AN has not been fully explored and no previous study has directly compared self-reported evaluations of cognitive and socio-affective skills in AN and ASD.

Methods

We aimed to determine the degree of overlap between AN and ASD from scores on questionnaires classically used to measure ASD impairments. Fifteen AN participants, 15 ASD participants and two groups of matched controls completed a battery of self-reports measuring: autistic traits (Autism-Spectrum Quotient), empathy (Empathy Quotient-short and Interpersonal Reactivity Index), systemizing (Systemizing Quotient-short) and alexithymia (Bermond-Vorst Alexithymia Questionnaire-B). Univariate comparisons of mean totalled scores were performed on each measure (patients vs. controls, and AN vs. ASD), and a Principal Component Analysis was used to study subject proximities in a reduced-factor space constructed from AQ, BVAQ-B and IRI subscales.

Results

These analyses revealed similarities in a few cognitive domains (Attention Switching, Perspective Taking and Fantasy, lack of emotional introspection) and in some nonspecific affective dimensions (depression and feelings of distress), but also marked dissimilarities in social skills (the ability to communicate emotions to others, empathizing).

Conclusion

The AN and ASD participants reported similar needs for sameness, and similar difficulties understanding their emotions and taking the perspective of another, but contrasting abilities to feel concerned in interpersonal situations. Our mixed findings encourage further exploration of transdiagnostic similarities and associations between these disorders.
Factors associated with parental smoking in the presence of school-aged children: a cross-sectional study
Authors: Liao Yuan-Mei , Chen Yu-Ting , Kuo Liang-Chun , Chen Ping-Ling
Published: September 2013

Background

In 2009, the Tobacco Hazards Prevention Act (Taiwan) was amended to more effectively restrict smoking in indoor public places and workplaces in Taiwan. However, the lack of prohibitions for smoking in private homes may place family members at increased risk for exposure to environmental tobacco smoke (ETS). The aim of our study was to determine the factors associated with parental smoking in the presence of children at home.

Methods

In 2010, we performed a cross-sectional study of factors associated with parental smoking in the presence of children at home in Taiwan using self-administered questionnaires. Quota sampling was used to select five primary schools from four different regions of Taiwan. Parents were surveyed to identify parental smokers and 307 parental smokers were selected for participation in our study. Questionnaire data regarding parental smoking in the presence of children at home and related interactions among family members were analyzed. Hierarchical logistic regression was used to determine the best-fit model for examining the relationships among the variables related to parental smoking in the presence of children at home.

Results

Two-thirds of parents who smoked reported smoking in the presence of their children. The results of the hierarchical logistic regression analysis identified the smokers’ compliance with their family’s antismoking responses, mutual agreement with smoking bans, daily smoking, smoking more than 20 cigarettes per day, the education level of the parental smoker, and the annual family income as determinants of smoking in the presence of children at home.

Conclusions

Households with smoking parents should be targeted for interventions to encourage the adoption and enforcement of home smoking bans. Educational interventions that promote smoke-free homes for children and provide support to help parents stop smoking are critical factors in reducing the frequency of children’s ETS exposure in the home.
The atraumatic restorative treatment (ART) strategy in Mexico: two-years follow up of ART sealants and restorations
Authors: Luengas-Quintero Elisa , Frencken Jo E , Muñúzuri-Hernández Jorge Alejandro , Mulder Jan
Published: September 2013

Background

The massive use of preventive measures in Mexico has resulted in a large decline in dental caries over the past two decades. There does however remain a largely unmet need for restorative treatment. This paper describes the steps leading up to the adoption of a strategy, as part of general health policy, to use Atraumatic Restorative Treatment (ART) within the Mexican public health service as a means of addressing this. The objective was to evaluate ART restorations and sealants placed in primary and permanent teeth in schoolchildren from deprived areas over a period of 2 years.

Methods

18 Dentists from 13 municipalities in 6 states with the lowest human development index treated 304, 6- to 13-year-old schoolchildren with ART sealants and ART restorations (single-surfaces) on the school compounds. Ketac Molar Easymix was the filling material used. ART procedures were evaluated according to the ART assessment criteria after 1 and 2 years, by 7 calibrated evaluators. Survival rates were estimated, using the PHREG Model with frailty correction.

Results

The 2-year cumulative survival rates of fully and partially retained ART sealants were 73.1% (primary teeth) and 48.8% (permanent teeth). The dentine carious lesion failure rates of ART sealants in primary and permanent teeth over the 2-year period were 0% and 2.5%, respectively. The 2-year cumulative survival rates of single-surface ART restorations in primary and permanent teeth were 74% and 80.9%, respectively. Secondary carious lesion development occurred in 6 restored primary teeth (2.1%) and in one restored permanent tooth (1.3%). All restorations placed in primary teeth in one state survived, whilst those in one of the 5 remaining states failed statistically significantly more than those in the other 4.

Conclusions

The ART procedures were of substantial quality and had prevented to a large extent the development of new dentine carious lesions in these children from socio-economically deprived areas.
Xiao-Qing-Long-Tang shows preventive effect of asthma in an allergic asthma mouse model through neurotrophin regulation
Authors: Chang Ren-Shiu , Wang Shulhn-Der , Wang Yu-Chin , Lin Li-Jen , Kao Shung-Te , Wang Jiu-Yao
Published: September 2013

Background

This study investigates the effect of Xiao-Qing-Long-Tang (XQLT) on neurotrophin in an established mouse model of Dermatophagoides pteronyssinus (Der p)-induced acute allergic asthma and in a LA4 cell line model of lung adenoma. The effects of XQLT on the regulation of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), airway hyper-responsiveness (AHR) and immunoglobulin E were measured.

Methods

LA4 cells were stimulated with 100 μg/ml Der p 24 h and the supernatant was collected for ELISA analysis. Der p-stimulated LA4 cells with either XQLT pre-treatment or XQLT co-treatment were used to evaluate the XQLT effect on neurotrophin.

Balb/c mice were sensitized on days 0 and 7 with a base-tail injection of 50 μg Dermatophagoides pteronyssinus (Der p) that was emulsified in 50 μl incomplete Freund’s adjuvant (IFA). On day 14, mice received an intra-tracheal challenge of 50 μl Der p (2 mg/ml). XQLT (1g/Kg) was administered orally to mice either on days 2, 4, 6, 8, 10 and 12 as a preventive strategy or on day 15 as a therapeutic strategy.

Results

XQLT inhibited expression of those NGF, BDNF and thymus-and activation-regulated cytokine (TARC) in LA4 cells that were subjected to a Der p allergen. Both preventive and therapeutic treatments with XQLT in mice reduced AHR. Preventive treatment with XQLT markedly decreased NGF in broncho-alveolar lavage fluids (BALF) and BDNF in serum, whereas therapeutic treatment reduced only serum BDNF level. The reduced NGF levels corresponded to a decrease in AHR by XQLT treatment. Reduced BALF NGF and TARC and serum BDNF levels may have been responsible for decreased eosinophil infiltration into lung tissue. Immunohistochemistry showed that p75NTR and TrkA levels were reduced in the lungs of mice under both XQLT treatment protocols, and this reduction may have been correlated with the prevention of the asthmatic reaction by XQLT.

Conclusion

XQLT alleviated allergic inflammation including AHR, IgE elevation and eosinophil infiltration in Der p stimulated mice by regulating neurotrophin and reducing TARC. These results revealed the potential pharmacological targets on which the XQLT decotion exerts preventive and therapeutic effects in an allergic asthma mouse model.
On the usage of health records for the design of virtual patients: a systematic review
Authors: Bloice Marcus D , Simonic Klaus-Martin , Holzinger Andreas
Published: September 2013

Background

The process of creating and designing Virtual Patients for teaching students of medicine is an expensive and time-consuming task. In order to explore potential methods of mitigating these costs, our group began exploring the possibility of creating Virtual Patients based on electronic health records. This review assesses the usage of electronic health records in the creation of interactive Virtual Patients for teaching clinical decision-making.

Methods

The PubMed database was accessed programmatically to find papers relating to Virtual Patients. The returned citations were classified and the relevant full text articles were reviewed to find Virtual Patient systems that used electronic health records to create learning modalities.

Results

A total of n = 362 citations were found on PubMed and subsequently classified, of which n = 28 full-text articles were reviewed. Few articles used unformatted electronic health records other than patient CT or MRI scans. The use of patient data, extracted from electronic health records or otherwise, is widespread. The use of unformatted electronic health records in their raw form is less frequent. Patient data use is broad and spans several areas, such as teaching, training, 3D visualisation, and assessment.

Conclusions

Virtual Patients that are based on real patient data are widespread, yet the use of unformatted electronic health records, abundant in hospital information systems, is reported less often. The majority of teaching systems use reformatted patient data gathered from electronic health records, and do not use these electronic health records directly. Furthermore, many systems were found that used patient data in the form of CT or MRI scans. Much potential research exists regarding the use of unformatted electronic health records for the creation of Virtual Patients.
Assessing the safety attitudes questionnaire (SAQ), German language version in Swiss university hospitals - a validation study
Authors: Zimmermann Natalie , Küng Kaspar , Sereika Susan M , Engberg Sandra , Sexton Bryan , Schwendimann René
Published: September 2013

Background

Improving patient safety has become a major focus of clinical care and research over the past two decades. An institution’s patient safety climate represents an essential component of ensuring a safe environment and thereby can be vital to the prevention of adverse events. Covering six patient safety related factors, the Safety Attitudes Questionnaire (SAQ) is a validated and widely used instrument to measure the patient safety climate in clinical areas. The objective of this study was to assess the psychometric properties of the German language version of the SAQ.

Methods

A survey was carried out in two University Hospitals in Switzerland in autumn 2009 where the SAQ was distributed to a sample of 406 nurses and physicians in medical and surgical wards. Following the American Educational Research Association guidelines, we tested the questionnaire validity by levels of evidence: content validity, internal structure and relations to other variables. Confirmatory factor analysis was used to examine factor structure. Cronbach’s alphas and inter-item correlations were calculated to examine internal consistency reliability.

Results

A total of 319 questionnaires were completed representing an overall response rate of 78.6%. For three items, the item content validity index was <0.75. Confirmatory factor analysis showed acceptable model fit (RMSEA = 0.045; CFI = 0.944) for the six-factor model. Additional exploratory factor analysis could not identify a better factor model. SAQ factor scores showed positive correlations with the Safety Organizing Scale (r = .56 - .72). The SAQ German version showed moderate to strong internal consistency reliability indices (Cronbach alpha = .65 - .83).

Conclusions

The German language version of the SAQ demonstrated acceptable to good psychometric properties and therefore shows promise to be a sound instrument to measure patient safety climate in Swiss hospital wards. However, the low item content validity and large number of missing responses for several items suggest that improvements and adaptations in translation are required for select items, especially within the perception of management scale. Following these revisions, psychometric properties should reassessed in a randomly selected sample and hospitals and departments prior to use in Swiss hospital settings.
Engineered fungal polyketide biosynthesis in Pichia pastoris: a potential excellent host for polyketide production
Authors: Gao Limei , Cai Menghao , Shen Wei , Xiao Siwei , Zhou Xiangshan , Zhang Yuanxing
Published: September 2013

Background

Polyketides are one of the most important classes of secondary metabolites and usually make good drugs. Currently, heterologous production of fungal polyketides for developing a high potential industrial application system with high production capacity and pharmacutical feasibility was still at its infancy. Pichia pastoris is a highly successful system for the high production of a variety of heterologous proteins. In this work, we aim to develop a P. pastoris based in vivo fungal polyketide production system for first time and evaluate its feasibility for future industrial application.

Results

A recombinant P. pastoris GS115-NpgA-ATX with Aspergillus nidulans phosphopantetheinyl transferase (PPtase) gene npgA and Aspergillus terrus 6-methylsalicylic acid (6-MSA) synthase (6-MSAS) gene atX was constructed. A specific compound was isolated and idenified as 6-MSA by HPLC, LC-MS and NMR. Transcription of both genes were detected. In 5-L bioreactor, the GS115-NpgA-ATX grew well and produced 6-MSA quickly until reached a high value of 2.2 g/L by methanol induction for 20 hours. Thereafter, the cells turned to death ascribing to high concentration of antimicrobial 6-MSA. The distribution of 6-MSA changed that during early and late induction phase it existed more in supernatant while during intermediate stage it mainly located intracellular. Different from 6-MSA production strain, recombinant M. purpureus pksCT expression strains for citrinin intermediate production, no matter PksCT located in cytoplasm or in peroxisomes, did not produce any specfic compound. However, both npgA and pksCT transcripted effectively in cells and western blot analysis proved the expression of PPtase. Then the PPTase was expressed and purified, marked by fluorescent probes, and reacted with purified ACP domain and its mutant ACPm of PksCT. Fluoresence was only observed in ACP but not ACPm, indicating that the PPTase worked well with ACP to make it bioactive holo-ACP. Thus, some other factors may affect polyketide synthesis that include activities of the individual catalytic domains and release of the product from the synthase of PksCT.

Conclusions

An efficient P. pastoris expression system of fungal polyketides was successfully constructed. It produced a high production of 6-MSA and holds potential for future industrial application of 6-MSA and other fungal polyketides.
MTA2 promotes gastric cancer cells invasion and is transcriptionally regulated by Sp1
Authors: Zhou Chenfei , Ji Jun , Cai Qu , Shi Min , Chen Xuehua , Yu Yingyan , Liu Bingya , Zhu Zhenggang , Zhang Jun
Published: September 2013

Background

MTA2 gene belongs to metastasis associated family, and is highly expressed in some solid tumors, including gastric cancer. Its biological function in gastric cancer is currently undefined.

Methods

Metastasis-associated tumor gene family 2 (MTA2) and transcription factor specificity protein 1 (Sp1) expression were detected in 127 gastric cancer samples by immunohistochemistry staining. SGC-7901 and AGS gastric cancer cell lines transfected by MTA2 shRNA was used for biological function investigation. Binding and regulation activities of Sp1 on MTA2 promoter were investigated by chromatin immunoprecipitation and luciferase reporter gene.

Results

The expression rate of MTA2 in gastric cancer tissues was 55.9% (71/127), and its expression was closely related to the depth of tumor invasion, lymph nodes metastasis, and TNM staging. MTA2 knockdown in human SGC-7901 and AGS gastric cancer cells significantly inhibited migration and invasion in vitro, and disrupted structure of cytoskeleton. MTA2 knockdown also attenuated xenografts growth and lung metastasis in nude mice model. MTA2 expression was positively correlated with transcription factor Sp1 in gastric cancer tissues (r = 0.326, P < 0.001). Sp1 bound to human MTA2 gene promoter at region from -1043 bp to -843 bp. Transcriptional activity of MTA2 promoter could be enhanced by Sp1 overexpression.

Conclusions

MTA2 knockdown impairs invasion and metastasis of gastric cancer cells, and attenuates xenografts growth in vivo. Sp1 regulates MTA2 expression at transcriptional level.
Green material: ecological importance of imperative and sensitive chemi-sensor based on Ag/Ag2O3/ZnO composite nanorods
Authors: Asiri Abdullah M , Khan Sher Bahadar , Rahman Mohammed M , Al-Sehemi Abdullah G , Al-Sayari Saleh A , Al-Assiri Mohammad Sultan
Published: September 2013

In this report, we illustrate a simple, easy, and low-temperature growth of Ag/Ag2O3/ZnO composite nanorods with high purity and crystallinity. The composite nanorods were structurally characterized by field emission scanning electron microscopy, X-ray powder diffraction, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy which confirmed that synthesized product have rod-like morphology having an average cross section of approximately 300 nm. Nanorods are made of silver, silver oxide, and zinc oxide and are optically active having absorption band at 375 nm. The composite nanorods exhibited high sensitivity (1.5823 μA.cm−2.mM−1) and lower limit of detection (0.5 μM) when applied for the recognition of phenyl hydrazine utilizing I-V technique. Thus, Ag/Ag2O3/ZnO composite nanorods can be utilized as a redox mediator for the development of highly proficient phenyl hydrazine sensor.
Existence and uniqueness of positive solutions to fractional boundary value problems with nonlinear boundary conditions
Authors: Nyamoradi Nemat , Baleanu Dumitru , Agarwal Ravi P
Published: September 2013

In this manuscript, we consider two problems of boundary value problems for a fractional differential equation. A fixed point theorem in partially ordered sets and a contraction mapping principle are applied to prove the existence of at least one positive solution for both fractional boundary value problems.

MSC:47H10, 26A33, 34A08.
Bacterial artificial chromosome derived simian varicella virus is pathogenic in vivo
Authors: Meyer Christine , Dewane Jesse , Haberthur Kristen , Engelmann Flora , Arnold Nicole , Gray Wayne , Messaoudi Ilhem
Published: September 2013

Background

Varicella zoster virus (VZV) is a neurotropic alphaherpesvirus that infects humans and results in chickenpox and herpes zoster. A number of VZV genes remain functionally uncharacterized and since VZV is an obligate human pathogen, rigorous evaluation of VZV mutants in vivo remains challenging. Simian varicella virus (SVV) is homologous to VZV and SVV infection of rhesus macaques (RM) closely mimics VZV infection of humans. Recently the SVV genome was cloned as a bacterial artificial chromosome (BAC) and BAC-derived SVV displayed similar replication kinetics as wild-type (WT) SVV in vitro.

Methods

RMs were infected with BAC-derived SVV or WT SVV at 4x105 PFU intrabronchially (N=8, 4 per group, sex and age matched). We collected whole blood (PBMC) and bronchoalveolar lavage (BAL) at various days post-infection (dpi) and sensory ganglia during latent infection (>84 dpi) at necropsy and compared disease progression, viral replication, immune response and the establishment of latency.

Results

Viral replication kinetics and magnitude in bronchoalveolar lavage cells and whole blood as well as rash severity and duration were similar in RMs infected with SVV BAC or WT SVV. Moreover, SVV-specific B and T cell responses were comparable between BAC and WT-infected animals. Lastly, we measured viral DNA in sensory ganglia from both cohorts of infected RMs during latent infection.

Conclusions

SVV BAC is as pathogenic and immunogenic as WT SVV in vivo. Thus, the SVV BAC genetic system combined with the rhesus macaque animal model can further our understanding of viral ORFs important for VZV pathogenesis and the development of second-generation vaccines.
Sex Differences in Opioid Analgesia and Addiction: Interactions among Opioid Receptors and Estrogen Receptors
Authors: Lee Cynthia Wei-Sheng , Ho Ing-Kang
Published: September 2013

Opioids are widely used as the pain reliever and also notorious for being addictive drugs. Sex differences in the opioid analgesia and addiction have been reported and investigated in human subjects and animal models. Yet, the molecular mechanism underlying the differences between males and females is still unclear. Here, we reviewed the literature describing the sex differences in analgesic responses and addiction liabilities to clinically relevant opioids. The reported interactions among opioids, estrogens, opioid receptors, and estrogen receptors are also evaluated. We postulate that the sex differences partly originated from the crosstalk among the estrogen and opioid receptors when stimulated by the exogenous opioids, possibly through common secondary messengers and the downstream gene transcriptional regulators.
Roles of Phosphotase 2A in Nociceptive Signal Processing
Authors: Wang Yun , Lei Yongzhong , Fang Li , Mu Yonggao , Wu Jing , Zhang Xuan
Published: September 2013

Multiple protein kinases affect the responses of dorsal horn neurons through phosphorylation of synaptic receptors and proteins involved in intracellular signal transduction pathways, and the consequences of this modulation may be spinal central sensitization. In contrast, the phosphatases catalyze an opposing reaction of de-phosphorylation, which may also modulate the functions of crucial proteins in signaling nociception. This is an important mechanism in the regulation of intracellular signal transduction pathways in nociceptive neurons. Accumulated evidence has shown that phosphatase 2A (PP2A), a serine/threonine specific phosphatase, is implicated in synaptic plasticity of the central nervous system and central sensitization of nociception. Therefore, targeting protein phosphotase 2A may provide an effective and novel strategy for the treatment of clinical pain. This review will characterize the structure and functional regulation of neuronal PP2A and bring together recent advances on the modulation of PP2A in targeted downstream substrates and relevant multiple nociceptive signaling molecules.
Sigma-1 Receptor Expression in Sensory Neurons and the Effect of Painful Peripheral Nerve Injury
Authors: Bangaru Madhavi L , Weihrauch Dorothee , Tang Qing-Bo , Zoga Vasiliki , Hogan Quinn , Wu Hsiang-en
Published: September 2013

Background

The sigma-1 receptor (σ1R), an endoplasmic reticulum chaperone protein, is widely distributed and regulates numerous intracellular processes in neurons. Nerve injury alters the structure and function of axotomized dorsal root ganglion (DRG) neurons, contributing to the development of pain. The σ1R is enriched in the spinal cord and modulates pain after peripheral nerve injury. However, σ1R expression in the DRG has not been studied. We therefore characterized σ1R expression in DRGs at baseline and following spinal nerve ligation (SNL) in rats.

Results

Immunohistochemical (IHC) studies in DRG sections show σ1R in both neuronal somata and satellite glial cells. The punctate distribution of σ1R in the neuronal cytoplasm suggests expression in the endoplasmic reticulum. When classified by neuronal size, large neurons (>1300 μm) showed higher levels of σ1R staining than other groups (700–1300 μm, <700 μm). Comparing σ1R expression in neuronal groups characterized by expression of calcitonin gene-related peptide (CGRP), isolectin-B4 (IB4) and neurofilament-200 (NF-200), we found σ1R expression in all three neuronal subpopulations, with highest levels of σ1R expression in the NF-200 group. After SNL, lysates from L5 DRGs that contains axotomized neurons showed decreased σ1R protein but unaffected transcript level, compared with Control DRGs. IHC images also showed decreased σ1R protein expression, in SNL L5 DRGs, and to a lesser extent in the neighboring SNL L4 DRGs. Neurons labeled by CGRP and NF-200 showed decreased σ1R expression in L5 and, to a lesser extent, L4 DRGs. In IB4-labeled neurons, σ1R expression decreased only in axotomized L5 DRGs. Satellite cells also showed decreased σ1R expression in L5 DRGs after SNL.

Conclusions

Our data show that σ1R is present in both sensory neurons and satellite cells in rat DRGs. Expression of σ1R is down-regulated in axotomized neurons as well as in their accompanying satellite glial cells, while neighboring uninjured neurons show a lesser down-regulation. Therefore, elevated σ1R expression in neuropathic pain is not an explanation for pain relief after σ1R blockade. This implies that increased levels of endogenous σ1R agonists may play a role, and diminished neuroprotection from loss of glial σ1R may be a contributing factor.