bluuebunny/crossref_metadata_2025_split huggingface dataset:
How to develop a program to increase influenza vaccine uptake among workers in health care settings?
Authors: Looijmans-van den Akker Ingrid , Hulscher Marlies E , Verheij Theo JM , Riphagen-Dalhuisen Josien , van Delden Johan JM , Hak Eelko 
Published: May 2011

Abstract

Background
Apart from direct protection and reduced productivity loss during epidemics, the main reason to immunize healthcare workers (HCWs) against influenza is to provide indirect protection of frail patients through reduced transmission in healthcare settings. Because the vaccine uptake among HCWs remains far below the health objectives, systematic programs are needed to take full advantage of such vaccination. In an earlier report, we showed a mean 9% increase of vaccine uptake among HCWs in nursing homes that implemented a systematic program compared with control homes, with higher rates in those homes that implemented more program elements. Here, we report in detail the process of the development of the implementation program to enable researchers and practitioners to develop intervention programs tailored to their setting.

Methods
We applied the intervention mapping (IM) method to develop a theory- and evidence-based intervention program to change vaccination behaviour among HCWs in nursing homes.

Results
After a comprehensive needs assessment, we were able to specify proximal program objectives and selected methods and strategies for inducing behavioural change. By consensus, we decided on planning of three main program components, i.e., an outreach visit to all nursing homes, plenary information meetings, and the appointment of a program coordinator -- preferably a physician -- in each home. Finally, we planned program adoption, implementation, and evaluation.

Conclusion
The IM methodology resulted in a systematic, comprehensive, and transparent procedure of program development. A potentially effective intervention program to change influenza vaccination behaviour among HCWs was developed, and its impact was assessed in a clustered randomised controlled trial.
Management outcomes in pubic diastasis: our experience with 19 patients
Authors: Aggarwal Sameer , Bali Kamal , Krishnan Vibhu , Kumar Vishal , Meena Dharm , Sen Ramesh K 
Published: May 2011

Abstract

Background
Pubic diastasis, a result of high energy antero-posterior compression (APC) injury, has been managed based on the Young and Burguess classification system. The mode of fixation in APC II injury has, however, been a subject of controversy and some authors have proposed a need to address the issue of partial breach of the posterior pelvic ring elements in these injuries.

Methods
The study included a total of 19 patients with pubic diastasis managed by us from May 2006 to December 2007. There was a single patient with type I APC injury who treated conservatively. Type II APC injuries (13 patients) were treated surgically with symphyseal plating using single anterior/superior plates or double perpendicularly placed plates. Type III injuries (5 patients) in addition underwent posterior fixation using plates or percutaneous sacro-iliac screws. The outcome was assessed clinically (Majeed score) and radiologically.

Results
The mean follow-up was for 2.9 years (6 months to 4.5 years). Among the 13 patients with APC II injuries, the clinical scores were excellent in one (7.6%), good in 6 (46.15%), fair in 4 (30.76%) and poor in 2 (15.38%). Radiological scores were excellent in 2 (15.38%), good in 8 (61.53%), fair in 2 (15.38%) and poor in one patient (7.6%). Among the 5 patients with APC III injuries, there were 2 patients each with good (50%) and fair (50%) clinical scores while one patient was lost on long term follow up. The radiological outcomes were also similar in these. Complications included implant failure in 3 patients, postoperative infection in 2 patients, deep venous thrombosis in one patient and bladder herniation in one of the patients with implant failure.

Conclusions
There is no observed dissimilarity in outcomes between isolated anterior and combined symphyseal (perpendicular) plating techniques in APC II injuries. Single anterior symphyseal plating along with posterior stabilisation provides a stable fixation in type III APC injuries. Limited dissection ensuring adequate intactness of rectus sheath is important to avoid long term post-operative complications.
Neuroprotective effects of ginsenosides Rh1 and Rg2 on neuronal cells
Authors: Li Xiao-Fan , Lui Cathy Nga-Ping , Jiang Zhi-Hong , Ken Yung Kin-Lam 
Published: May 2011

AbstractBackgroundThe present study investigates the effects of ginsenosides Rh1and Rg2against 6-hydroxydopamine (6-OHDA), a neurotoxin on SH-SY5Y cells and PC-12 cells. The effects of these two ginsenosides on neuronal differentiation are also examined.MethodsLDH assay was used to measure cell viability after exposure to 6-OHDA and ginsenosides. Neuronal differentiation was evaluated by changes in cell morphology and density of neurite outgrowths. Western blotting was used to determine the ginsenosides' effects on activation of extracellular signal-regulated protein kinases (ERKs).ResultsRh1and Rg2attenuated 6-OHDA toxicity in SH-SY5Y cells and induced neurite outgrowths in PC-12 cells. 6-OHDA-induced ERK phosphorylation was decreased by Rh1and Rg2. 20(R)-form and 20(S)-form of the ginsenosides exerted similar effects in inducing neurite outgrowths in PC-12 cells.ConclusionThe present study demonstrates neuroprotective effects of ginsenosides Rh1and Rg2on neuronal cell lines. These results suggest potential Chinese medicine treatment for neurodegenerative disorders (egParkinson's disease).
Parental risk factors and anorectal malformations: systematic review and meta-analysis
Authors: Zwink Nadine , Jenetzky Ekkehart , Brenner Hermann 
Published: May 2011

AbstractBackgroundAnorectal malformations (ARM) are rare forms of congenital uro-rectal anomalies with largely unknown causes. Besides genetic factors, prenatal exposures of the parents to nicotine, alcohol, caffeine, illicit drugs, occupational hazards, overweight/obesity and diabetes mellitus are suspected as environmental risk factors.MethodsRelevant studies published until August 2010 were identified through systematic search in PubMed, EMBASE, ISI Web of Knowledge and the Cochrane Library databases. Furthermore, related and cross-referencing publications were reviewed. Pooled odds ratios (95% confidence intervals) were determined to quantify associations of maternal and paternal smoking, maternal alcohol consumption, underweight (body mass index [BMI] < 18.5), overweight (BMI 25-29.9), obesity (BMI ≥30) and maternal diabetes mellitus with ARM using meta-analyses.Results22 studies that reported on the association between prenatal environmental risk factors and infants born with ARM were included in this review. These were conducted in the United States of America (n = 12), Spain (n = 2), Sweden (n = 2), the Netherlands (n = 2), Japan (n = 1), France (n = 1), Germany (n = 1) and Hungary (n = 1). However, only few of these studies reported on the same risk factors. Studies were heterogeneous with respect to case numbers, control types and adjustment for covariates. Consistently increased risks were observed for paternal smoking and maternal overweight, obesity and diabetes, but not for maternal smoking and alcohol consumption. In meta-analyses, pooled odds ratios (95% confidence intervals) for paternal smoking, maternal overweight, obesity, pre-gestational and gestational diabetes were 1.53 (1.04-2.26), 1.25 (1.07-1.47), 1.64 (1.35-2.00), 4.51 (2.55-7.97) and 1.81 (1.23-2.65), respectively.ConclusionEvidence on risk factors for ARM from epidemiological studies is still very limited. Nevertheless, the few available studies indicate paternal smoking and maternal overweight, obesity and diabetes to be associated with increased risks. Further, ideally large-scale multicentre and register-based studies are needed to clarify the role of key risk factors for the development of ARM.
PGC-1alpha downstream transcription factors NRF-1 and TFAM are genetic modifiers of Huntington disease
Authors: Taherzadeh-Fard Elahe , Saft Carsten , Akkad Denis A , Wieczorek Stefan , Haghikia Aiden , Chan Andrew , Epplen Jörg T , Arning Larissa 
Published: May 2011

Abstract

Background
Huntington disease (HD) is an inherited neurodegenerative disease caused by an abnormal expansion of a CAG repeat in the huntingtin HTT (HD) gene. The primary genetic determinant of the age at onset (AO) is the length of the HTT CAG repeat; however, the remaining genetic contribution to the AO of HD has largely not been elucidated. Recent studies showed that impaired functioning of the peroxisome proliferator-activated receptor gamma coactivator 1a (PGC-1alpha) contributes to mitochondrial dysfunction and appears to play an important role in HD pathogenesis. Further genetic evidence for involvement of PGC-1alpha in HD pathogenesis was generated by the findings that sequence variations in the PPARGC1A gene encoding PGC-1alpha exert modifying effects on the AO in HD. In this study, we hypothesised that polymorphisms in PGC-1alpha downstream targets might also contribute to the variation in the AO.

Results
In over 400 German HD patients, polymorphisms in the nuclear respiratory factor 1 gene, NRF-1, and the mitochondrial transcription factor A, encoded by TFAM showed nominally significant association with AO of HD. When combining these results with the previously described modifiers rs7665116 in PPARGC1A and C7028T in the cytochrome c oxidase subunit I (CO1, mt haplogroup H) in a multivariable model, a substantial proportion of the variation in AO can be explained by the joint effect of significant modifiers and their interactions, respectively.

Conclusions
These results underscore that impairment of mitochondrial function plays a critical role in the pathogenesis of HD and that upstream transcriptional activators of PGC-1alpha may be useful targets in the treatment of HD.
Rheumatoid arthritis-associated polymorphisms are not protective against Alzheimer's disease
Authors: Simmons Christopher R , Zou Fanggeng , Younkin Steven G , Estus Steven 
Published: May 2011

Abstract

Background
Rheumatoid arthritis (RA) and Alzheimer's disease (AD) are inversely associated. To test the hypothesis that genetic elements associated with increased RA risk are associated with decreased AD risk, we evaluated RA genetic risk factors recently identified in genome-wide association studies (GWAS) for their association with AD in a two-stage, case-control analysis.

Results
In our Stage 1 analysis of ~800 AD and ~1,200 non-AD individuals, three of seventeen RA-associated SNPs were nominally associated with AD (p < 0.05) with one SNP, rs2837960, retaining significance after correction for multiple testing (p = 0.03). The rs2837960_G (minor) allele, which is associated with increased RA risk, was associated with increased AD risk. Analysis of these three SNPs in a Stage 2 population, consisting of ~1,100 AD and ~2,600 non-AD individuals, did not confirm their association with AD. Analysis of Stage 1 and 2 combined suggested that rs2837960 shows a trend for association with AD. When the Stage 2 population was age-matched for the Stage 1 population, rs2837960 exhibited a non-significant trend with AD. Combined analysis of Stage 1 and the age-matched Stage 2 subset showed a significant association of rs2837960 with AD (p = 0.002, OR 1.24) that retained significance following correction for age, sex and APOE (p = 0.02, OR = 1.20). Rs2837960 is near BACE2, which encodes an aspartic protease capable of processing the AD-associated amyloid precursor protein. Testing for an association between rs2837960 and the expression of BACE2 isoforms in human brain, we observed a trend between rs2837960 and the total expression of BACE2 and the expression of a BACE2 transcript lacking exon 7 (p = 0.07 and 0.10, respectively).

Conclusions
RA-associated SNPs are generally not associated with AD. Moreover, rs2837960_G is associated with increased risk of both RA and, in individuals less than 80 years of age, with AD. Overall, these results contest the hypothesis that genetic variants associated with RA confer protection against AD. Further investigation of rs2837960 is necessary to elucidate the mechanism by which rs2837960 contributes to both AD and RA risk, likely via modulation of BACE2 expression.
Oxidation of the cysteine-rich regions of parkin perturbs its E3 ligase activity and contributes to protein aggregation
Authors: Meng Fanjun , Yao Dongdong , Shi Yang , Kabakoff Jonathan , Wu Wei , Reicher Joshua , Ma Yuliang , Moosmann Bernd , Masliah Eliezer , Lipton Stuart A , Gu Zezong 
Published: May 2011

Abstract

Background
Accumulation of aberrant proteins to form Lewy bodies (LBs) is a hallmark of Parkinson's disease (PD). Ubiquitination-mediated degradation of aberrant, misfolded proteins is critical for maintaining normal cell function. Emerging evidence suggests that oxidative/nitrosative stress compromises the precisely-regulated network of ubiquitination in PD, particularly affecting parkin E3 ligase activity, and contributes to the accumulation of toxic proteins and neuronal cell death.

Results
To gain insight into the mechanism whereby cell stress alters parkin-mediated ubiquitination and LB formation, we investigated the effect of oxidative stress. We found significant increases in oxidation (sulfonation) and subsequent aggregation of parkin in SH-SY5Y cells exposed to the mitochondrial complex I inhibitor 1-methyl-4-phenlypyridinium (MPP
+
), representing an in vitro cell-based PD model. Exposure of these cells to direct oxidation via pathological doses of H2O2 induced a vicious cycle of increased followed by decreased parkin E3 ligase activity, similar to that previously reported following S-nitrosylation of parkin. Pre-incubation with catalase attenuated H2O2 accumulation, parkin sulfonation, and parkin aggregation. Mass spectrometry (MS) analysis revealed that H2O2 reacted with specific cysteine residues of parkin, resulting in sulfination/sulfonation in regions of the protein similar to those affected by parkin mutations in hereditary forms of PD. Immunohistochemistry or gel electrophoresis revealed an increase in aggregated parkin in rats and primates exposed to mitochondrial complex I inhibitors, as well as in postmortem human brain from patients with PD with LBs.

Conclusion
These findings show that oxidative stress alters parkin E3 ligase activity, leading to dysfunction of the ubiquitin-proteasome system and potentially contributing to LB formation.
Changes in thermal nociceptive responses in dairy cows following experimentally induced Escherichia coli mastitis
Authors: Rasmussen Ditte B , Fogsgaard Katrine , Røntved Christine M , Klaas Ilka C , Herskin Mette S 
Published: May 2011

AbstractBackgroundMastitis is a high incidence disease in dairy cows. The acute stage is considered painful and inflammation can lead to hyperalgesia and thereby contribute to decreased welfare. The aim of this study was to examine changes in nociceptive responses toward cutaneous nociceptive laser stimulation (NLS) in dairy cows with experimentally inducedEscherichia colimastitis, and correlate behavioral changes in nociceptive responses to clinical and paraclinical variables.MethodsSeven Danish Holstein-Friesian cows were kept in tie-stalls, where theE. coliassociated mastitis was induced and laser stimulations were conducted. Measurements of rectal temperature, somatic cell counts, white blood cell counts andE. colicounts were conducted. Furthermore, scores were given for anorexia, local udder inflammation and milk appearance to quantify the local and systemic disease response. In order to quantify the nociceptive threshold, behavioral responses toward cutaneous NLS applied to six skin areas at the tarsus/metatarsus and udder hind quarters were registered at evening milking on day 0 (control) and days 1, 2, 3, 6 and 10 after experimental induction of mastitis.ResultsAll clinical and paraclinical variables were affected by the induced mastitis. All cows were clinically ill on days 1 and 2. The cows responded behaviorally toward the NLS. For hind leg stimulation, the proportion of cows responding by stepping was higher on day 0 than days 3 and 6, and the frequency of leg movements after laser stimulation tended to decrease on day 1 compared to the other days. After udder stimulation, the proportion of cows responding by stepping was higher on day 1 than on all other days of testing. Significant correlations between the clinical and paraclinical variables of disease and the behavioral responses toward nociceptive stimulation were found.ConclusionsChanges in behavioral responses coincide with peaks in local and systemic signs of E. coli mastitis. During the acute stage of E. coli mastitis nociceptive thermal stimulation on hind leg and mammary glands results in decreased behavioral responses toward nociceptive stimulation, which might be interpreted as hypoalgesia.
Expanding a dynamic flux balance model of yeast fermentation to genome-scale
Authors: Vargas Felipe A , Pizarro Francisco , Pérez-Correa J Ricardo , Agosin Eduardo 
Published: May 2011

AbstractBackgroundYeast is considered to be a workhorse of the biotechnology industry for the production of many value-added chemicals, alcoholic beverages and biofuels. Optimization of the fermentation is a challenging task that greatly benefits from dynamic models able to accurately describe and predict the fermentation profile and resulting products under different genetic and environmental conditions. In this article, we developed and validated a genome-scale dynamic flux balance model, using experimentally determined kinetic constraints.ResultsAppropriate equations for maintenance, biomass composition, anaerobic metabolism and nutrient uptake are key to improve model performance, especially for predicting glycerol and ethanol synthesis. Prediction profiles of synthesis and consumption of the main metabolites involved in alcoholic fermentation closely agreed with experimental data obtained from numerous lab and industrial fermentations under different environmental conditions. Finally, fermentation simulations of genetically engineered yeasts closely reproduced previously reported experimental results regarding final concentrations of the main fermentation products such as ethanol and glycerol.ConclusionA useful tool to describe, understand and predict metabolite production in batch yeast cultures was developed. The resulting model, if used wisely, could help to search for new metabolic engineering strategies to manage ethanol content in batch fermentations.
Modeling microRNA-mRNA Interactions Using PLS Regression in Human Colon Cancer
Authors: Li Xiaohong , Gill Ryan , Cooper Nigel GF , Yoo Jae Keun , Datta Susmita 
Published: May 2011

Abstract

Background
Changes in microRNA (miRNA) expression patterns have been extensively characterized in several cancers, including human colon cancer. However, how these miRNAs and their putative mRNA targets contribute to the etiology of cancer is poorly understood. In this work, a bioinformatics computational approach with miRNA and mRNA expression data was used to identify the putative targets of miRNAs and to construct association networks between miRNAs and mRNAs to gain some insights into the underlined molecular mechanisms of human colon cancer.

Method
The miRNA and mRNA microarray expression profiles from the same tissues including 7 human colon tumor tissues and 4 normal tissues, collected by the Broad Institute, were used to identify significant associations between miRNA and mRNA. We applied the partial least square (PLS) regression method and bootstrap based statistical tests to the joint expression profiles of differentially expressed miRNAs and mRNAs. From this analysis, we predicted putative miRNA targets and association networks between miRNAs and mRNAs. Pathway analysis was employed to identify biological processes related to these miRNAs and their associated predicted mRNA targets.

Results
Most significantly associated up-regulated mRNAs with a down-regulated miRNA identified by the proposed methodology were considered to be the miRNA targets. On average, approximately 16.5% and 11.0% of targets predicted by this approach were also predicted as targets by the common prediction algorithms TargetScan and miRanda, respectively. We demonstrated that our method detects more targets than a simple correlation based association. Integrative mRNA:miRNA predictive networks from our analysis were constructed with the aid of Cytoscape software. Pathway analysis validated the miRNAs through their predicted targets that may be involved in cancer-associated biological networks.

Conclusion
We have identified an alternative bioinformatics approach for predicting miRNA targets in human colon cancer and for reverse engineering the miRNA:mRNA network using inversely related mRNA and miRNA joint expression profiles. We demonstrated the superiority of our predictive method compared to the correlation based target prediction algorithm through a simulation study. We anticipate that the unique miRNA targets predicted by the proposed method will advance the understanding of the molecular mechanism of colon cancer and will suggest novel therapeutic targets after further experimental validations.
Monitoring resistance of Plasmdium vivax: Point mutations in dihydrofolate reductase gene in isolates from Central China
Authors: Huang Fang , Zhou Shuisen , Zhang Shaosen , Li Weidong , Zhang Hongwei 
Published: May 2011

Abstract

Background
Malaria still represents a significant public health problem in China, and the cases dramatically increased in Central China after 2001. Antifolate resistance in Plasmodium vivax is caused by point mutations in genes encoding dihydrofolate reductase (pvdhfr) and dihydropteroate synthase (pvdhps). In this study, we used direct sequencing to investigate genetic variation in pvdhfr of malaria patients' samples from Central China.

Results
Among all the samples, 21.4% were wild-type, whereas mutations were detected at three codons (58, 61 and 117) including single mutant (34.6%) and double mutants (43.8%). The most prevalent mutant allele was the one with double mutation at codons 58 and 117 (24.6%). Three types of single mutation (S58R, T61M and S117N) were found in 2.1%, 11.8% and 20.9% of parasite isolates, respectively. The four P. vivax parasite populations in Central China also differed in pvdhfr allele frequencies.

Conclusions
This study suggested that P. vivax in Central China may be relatively susceptible to pyrimethamine. And it also highlights genotyping in the pvdhfr genes remains a useful tool to monitor the emergence and spread of P. vivax pyrimethamine resistance.