bluuebunny/crossref_metadata_2025 huggingface dataset:
Acceptance of health information technology in health professionals: An application of the revised technology acceptance model
Authors: Ketikidis Panayiotis , Dimitrovski Tomislav , Lazuras Lambros , Bath Peter A.
Published: June 2012

The response of health professionals to the use of health information technology (HIT) is an important research topic that can partly explain the success or failure of any HIT application. The present study applied a modified version of the revised technology acceptance model (TAM) to assess the relevant beliefs and acceptance of HIT systems in a sample of health professionals (n = 133). Structured anonymous questionnaires were used and a cross-sectional design was employed. The main outcome measure was the intention to use HIT systems. ANOVA was employed to examine differences in TAM-related variables between nurses and medical doctors, and no significant differences were found. Multiple linear regression analysis was used to assess the predictors of HIT usage intentions. The findings showed that perceived ease of use, but not usefulness, relevance and subjective norms directly predicted HIT usage intentions. The present findings suggest that a modification of the original TAM approach is needed to better understand health professionals’ support and endorsement of HIT. Perceived ease of use, relevance of HIT to the medical and nursing professions, as well as social influences, should be tapped by information campaigns aiming to enhance support for HIT in healthcare settings.
An analysis of electronic document management in oncology care
Authors: Poulter Thomas , Gannon Brian , Bath Peter A.
Published: June 2012

In this research in progress, a reference model for the use of electronic patient record (EPR) systems in oncology is described. The model, termed CICERO, comprises technical and functional components, and emphasises usability, clinical safety and user acceptance. One of the functional components of the model—an electronic document and records management (EDRM) system—is monitored in the course of its deployment at a leading oncology centre in the UK. Specifically, the user requirements and design of the EDRM solution are described.The study is interpretative and forms part a wider research programme to define and validate the CICERO model. Preliminary conclusions confirm the importance of a socio-technical perspective in Onco-EPR system design.
Health information literacy in everyday life: A study of Finns aged 65–79 years
Authors: Eriksson-Backa Kristina , Ek Stefan , Niemelä Raimo , Huotari Maija-Leena
Published: June 2012

This article examines the health information literacy of elderly Finns. The results are based on a survey conducted in January 2011. The questionnaire was distributed to 1000 persons that were randomly drawn from the Finnish Population Register. The respondents were aged 65–79 years (mean age 70 years) and lived in the Turku region in Finland. A total of 281 questionnaires (28%) were returned. χ2 analyses were used to find possible relationships between demographic factors, as well as interest, seeking activity, current self-rated health and different dimensions of health information literacy, including needs, seeking and use of health-related information. Significant relationships were found between education level, interest in health information, seeking activity, self-rated current health and dimensions of health information literacy. Some categories of elderly people are more vulnerable regarding obtaining and use of health information: those with lower levels of education, those with poor health, and those who are not interested in and active at seeking information. For people who are found in any of these categories, it is important that available health-related information is understandable and can be accessed without too much effort—something that information providers should take into account.
What constitutes the field of health information systems? Fostering a systematic framework and research agenda
Authors: Mettler Tobias , Raptis Dimitri Aristotle
Published: June 2012

The main aim of this article is to present a research agenda and systematic framework of what the field of health information systems is about, namely its central topics and connecting areas. In doing so, we try to provide a cohesive ‘big picture’ for academics and professionals that are interested in conducting research in this broad area. By using a large number of disparate data sources, we identified 3 major research fields and 18 sub-fields. As this discipline is quite new and heterogeneous in terms of themes and the educational backgrounds of its researchers, we see our conceptualisation as a first step in obtaining a collective understanding of this field, as well as being a common starting point for discussing future directions.
Inpatient management of patients with diabetes and chronic kidney disease undergoing elective surgery in a large nephrology centre
Authors: Suckling Rebecca J , Andrews Peter A
Published: June 2012

The objective of this study was to evaluate current practice in the management of glycaemia in patients with diabetes undergoing elective surgical procedures in a single renal unit. We performed an audit of the hospital records of 83 patients undergoing elective surgical procedures at a regional renal unit between January and March 2011. Of these patients 22 had diabetes: four with type 1 diabetes and 18 with type 2 diabetes. During their hospitalisation, glucose control was suboptimal with good diabetic days accounting for 52% of the hospital admission. There was over-reliance on variable rate intravenous insulin, which was prescribed in 59% of patients, of which the majority were deemed inappropriate. Prescription errors were more common when insulin was used, with 67% of prescription charts having at least one dose of insulin omitted or not signed. Oral agents were prescribed and administered accurately in 87% of patients. A hypoglycaemic event was experienced by 22% of patients. In conclusion, patients with diabetes and chronic kidney disease are at risk of suboptimal glycaemic management during hospitalisation for elective surgery. These findings have led to improved pre-operative planning, blood glucose management protocols and targeted education programmes.
Diabetes and frailty: an emerging issue. Part 1: Sarcopaenia and factors affecting lower limb function
Authors: Atiénzar Pilar , Abizanda Pedro , Guppy Andrew , Sinclair Alan J
Published: June 2012

Frailty and sarcopaenia are commonly used terms in the medical management of older people but their relationship to those with diabetes has not been explored in great detail. In this review, we hypothesise that diabetes and frailty are related conditions, and we attempt to explain the nature of this relationship, and consider the possibility that sarcopaenia is an intermediate step.
The ageing pancreas
Authors: Brown James E
Published: June 2012

Type 2 diabetes is historically associated with older adults, and glucose tolerance is known to decline with advancing age. During the course of natural ageing, changes in many peripheral tissues contribute to this deterioration of glucose homeostasis. Included in this process are changes to the structure and function of the pancreatic islets, which undergo deviation in endocrine responses to glycaemic challenge. Current knowledge about the changes seen in the ageing pancreas is reviewed here.
Disability in older people with diabetes: issues for the clinician
Authors: Bourdel-Marchasson Isabelle , Dugaret Elodie , Regueme Sophie
Published: June 2012

Diabetes may become a disabling disease due to diverse mechanisms. Many patients have evidence of physical or cognitive impairments that can markedly influence their ability to diabetes self manage and adversely affect possible outcomes of diabetes care. A screening process for impairment is therefore needed and in frail patients a comprehensive gerontological assessment should be used to improve the efficiency of care. A diabetes educational programme adapted to this population, which has involved the main care-giver has shown its efficacy to improve risk factor control and quality of life in a safer way. The experience of case-managers according to a model of heart failure may be promising for the future.
Familial hypercholesterolaemia and dyslipidaemias: new international guidelines for clinical practice
Authors: Sell Craig , Van Heyningen Charles
Published: June 2012

Familial hypercholesterolaemia (FH) presents a significant risk for early cardiovascular morbidity and mortality. Several new international guidelines on FH have been published in the last year and similarities and differences between them are described and summarised in this review. New European guidelines discuss other familial dyslipidaemias as well as FH. These guidelines should improve the quality and cost effectiveness of care provided.
Diabetes and frailty: an emerging issue. Part 2: Linking factors
Authors: Atiénzar Pilar , Abizanda Pedro , Guppy Andrew , Sinclair Alan J
Published: June 2012

Diabetes and frailty may be causally related and operate through each of the key components of the frailty phenotype or via the associated medical co-morbidities. The presence of frailty in a setting of diabetes increases the level of disability and leads to poorer clinical outcomes. The vascular complications of diabetes (both macro- and microvascular) are implicated in this aetiopathogenesis of frailty and any associated mood disturbance or cognitive impairments worsen the outcome. Research into exploring this relationship further is needed and this may lead to more effective interventional strategies.
Rituximab therapy in pulmonary alveolar proteinosis improves alveolar macrophage lipid homeostasis
Authors: Malur Anagha , Kavuru Mani S , Marshall Irene , Barna Barbara P , Huizar Isham , Karnekar Reema , Thomassen Mary Jane
Published: June 2012

Rationale

Pulmonary Alveolar Proteinosis (PAP) patients exhibit an acquired deficiency of biologically active granulocyte-macrophage colony stimulating factor (GM-CSF) attributable to GM-CSF specific autoantibodies. PAP alveolar macrophages are foamy, lipid-filled cells with impaired surfactant clearance and markedly reduced expression of the transcription factor peroxisome proliferator-activated receptor gamma (PPARγ) and the PPARγ-regulated ATP binding cassette (ABC) lipid transporter, ABCG1. An open label proof of concept Phase II clinical trial was conducted in PAP patients using rituximab, a chimeric murine-human monoclonal antibody directed against B lymphocyte specific antigen CD20. Rituximab treatment decreased anti-GM-CSF antibody levels in bronchoalveolar lavage (BAL) fluid, and 7/9 patients completing the trial demonstrated clinical improvement as measured by arterial blood oxygenation.

Objectives

This study sought to determine whether rituximab therapy would restore lipid metabolism in PAP alveolar macrophages.

Methods

BAL samples were collected from patients pre- and 6-months post-rituximab infusion for evaluation of mRNA and lipid changes.

Results

Mean PPARγ and ABCG1 mRNA expression increased 2.8 and 5.3-fold respectively (p ≤ 0.05) after treatment. Lysosomal phospholipase A2 (LPLA2) (a key enzyme in surfactant degradation) mRNA expression was severely deficient in PAP patients pre-treatment but increased 2.8-fold post-treatment. In supplemental animal studies, LPLA2 deficiency was verified in GM-CSF KO mice but was not present in macrophage-specific PPARγ KO mice compared to wild-type controls. Oil Red O intensity of PAP alveolar macrophages decreased after treatment, indicating reduced intracellular lipid while extracellular free cholesterol increased in BAL fluid. Furthermore, total protein and Surfactant protein A were significantly decreased in the BAL fluid post therapy.

Conclusions

Reduction in GM-CSF autoantibodies by rituximab therapy improves alveolar macrophage lipid metabolism by increasing lipid transport and surfactant catabolism. Mechanisms may involve GM-CSF stimulation of alveolar macrophage ABCG1 and LPLA2 activities by distinct pathways.
Gene regulatory network modeling via global optimization of high-order dynamic Bayesian network
Authors: Xuan Vinh Nguyen , Chetty Madhu , Coppel Ross , Wangikar Pramod P
Published: June 2012

Background

Dynamic Bayesian network (DBN) is among the mainstream approaches for modeling various biological networks, including the gene regulatory network (GRN). Most current methods for learning DBN employ either local search such as hill-climbing, or a meta stochastic global optimization framework such as genetic algorithm or simulated annealing, which are only able to locate sub-optimal solutions. Further, current DBN applications have essentially been limited to small sized networks.

Results

To overcome the above difficulties, we introduce here a deterministic global optimization based DBN approach for reverse engineering genetic networks from time course gene expression data. For such DBN models that consist only of inter time slice arcs, we show that there exists a polynomial time algorithm for learning the globally optimal network structure. The proposed approach, named GlobalMIT+, employs the recently proposed information theoretic scoring metric named mutual information test (MIT). GlobalMIT+ is able to learn high-order time delayed genetic interactions, which are common to most biological systems. Evaluation of the approach using both synthetic and real data sets, including a 733 cyanobacterial gene expression data set, shows significantly improved performance over other techniques.

Conclusions

Our studies demonstrate that deterministic global optimization approaches can infer large scale genetic networks.
Comprehensive analysis of CCCH zinc finger family in poplar (Populus trichocarpa)
Authors: Chai Guohua , Hu Ruibo , Zhang Dongyuan , Qi Guang , Zuo Ran , Cao Yingping , Chen Peng , Kong Yingzhen , Zhou Gongke
Published: June 2012

Background

CCCH zinc finger proteins contain a typical motif of three cysteines and one histidine residues and serve regulatory functions at all stages of mRNA metabolism. In plants, CCCH type zinc finger proteins comprise a large gene family represented by 68 members in Arabidopsis and 67 in rice. These CCCH proteins have been shown to play diverse roles in plant developmental processes and environmental responses. However, this family has not been studied in the model tree species Populus to date.

Results

In the present study, a comprehensive analysis of the genes encoding CCCH zinc finger family in Populus was performed. Using a thorough annotation approach, a total of 91 full-length CCCH genes were identified in Populus, of which most contained more than one CCCH motif and a type of non-conventional C-X11-C-X6-C-X3-H motif was unique for Populus. All of the Populus CCCH genes were phylogeneticly clustered into 13 distinct subfamilies. In each subfamily, the gene structure and motif composition were relatively conserved. Chromosomal localization of these genes revealed that most of the CCCHs (81 of 90, 90 %) are physically distributed on the duplicated blocks. Thirty-four paralogous pairs were identified in Populus, of which 22 pairs (64.7 %) might be created by the whole genome segment duplication, whereas 4 pairs seem to be resulted from tandem duplications. In 91 CCCH proteins, we also identified 63 putative nucleon-cytoplasm shuttling proteins and 3 typical RNA-binding proteins. The expression profiles of all Populus CCCH genes have been digitally analyzed in six tissues across different developmental stages, and under various drought stress conditions. A variety of expression patterns of CCCH genes were observed during Populus development, of which 34 genes highly express in root and 22 genes show the highest level of transcript abundance in differentiating xylem. Quantitative real-time RT-PCR (RT-qPCR) was further performed to confirm the tissue-specific expression and responses to drought stress treatment of 12 selected Populus CCCH genes.

Conclusions

This study provides the first systematic analysis of the Populus CCCH proteins. Comprehensive genomic analyses suggested that segmental duplications contribute significantly to the expansion of Populus CCCH gene family. Transcriptome profiling provides first insights into the functional divergences among members of Populus CCCH gene family. Particularly, some CCCH genes may be involved in wood development while others in drought tolerance regulation. Our results presented here may provide a starting point for the functional dissection of this family of potential RNA-binding proteins.
On the effect of protein conformation diversity in discriminating among neutral and disease related single amino acid substitutions
Authors: Juritz Ezequiel , Fornasari Maria Silvina , Martelli Pier Luigi , Fariselli Piero , Casadio Rita , Parisi Gustavo
Published: June 2012

Background

Non-synonymous coding SNPs (nsSNPs) that are associated to disease can also be related with alterations in protein stability. Computational methods are available to predict the effect of single amino acid substitutions (SASs) on protein stability based on a single folded structure. However, the native state of a protein is not unique and it is better represented by the ensemble of its conformers in dynamic equilibrium. The maintenance of the ensemble is essential for protein function. In this work we investigated how protein conformational diversity can affect the discrimination of neutral and disease related SASs based on protein stability estimations. For this purpose, we used 119 proteins with 803 associated SASs, 60% of which are disease related. Each protein was associated with its corresponding set of available conformers as found in the Protein Conformational Database (PCDB). Our dataset contains proteins with different extensions of conformational diversity summing up a total number of 1023 conformers.

Results

The existence of different conformers for a given protein introduces great variability in the estimation of the protein stability (ΔΔG) after a single amino acid substitution (SAS) as computed with FoldX. Indeed, in 35% of our protein set at least one SAS can be described as stabilizing, destabilizing or neutral when a cutoff value of ±2 kcal/mol is adopted for discriminating neutral from perturbing SASs. However, when the ΔΔG variability among conformers is taken into account, the correlation among the perturbation of protein stability and the corresponding disease or neutral phenotype increases as compared with the same analysis on single protein structures. At the conformer level, we also found that the different conformers correlate in a different way to the corresponding phenotype.

Conclusions

Our results suggest that the consideration of conformational diversity can improve the discrimination of neutral and disease related protein SASs based on the evaluation of the corresponding Gibbs free energy change.
Domain landscapes of somatic mutations in cancer
Authors: Nehrt Nathan L , Peterson Thomas A , Park DoHwan , Kann Maricel G
Published: June 2012

Background

Large-scale tumor sequencing projects are now underway to identify genetic mutations that drive tumor initiation and development. Most studies take a gene-based approach to identifying driver mutations, highlighting genes mutated in a large percentage of tumor samples as those likely to contain driver mutations. However, this gene-based approach usually does not consider the position of the mutation within the gene or the functional context the position of the mutation provides. Here we introduce a novel method for mapping mutations to distinct protein domains, not just individual genes, in which they occur, thus providing the functional context for how the mutation contributes to disease. Furthermore, aggregating mutations from all genes containing a specific protein domain enables the identification of mutations that are rare at the gene level, but that occur frequently within the specified domain. These highly mutated domains potentially reveal disruptions of protein function necessary for cancer development.

Results

We mapped somatic mutations from the protein coding regions of 100 colon adenocarcinoma tumor samples to the genes and protein domains in which they occurred, and constructed topographical maps to depict the “mutational landscapes” of gene and domain mutation frequencies. We found significant mutation frequency in a number of genes previously known to be somatically mutated in colon cancer patients including APC, TP53 and KRAS. In addition, we found significant mutation frequency within specific domains located in these genes, as well as within other domains contained in genes having low mutation frequencies. These domain “peaks” were enriched with functions important to cancer development including kinase activity, DNA binding and repair, and signal transduction.

Conclusions

Using our method to create the domain landscapes of mutations in colon cancer, we were able to identify somatic mutations with high potential to drive cancer development. Interestingly, the majority of the genes involved have a low mutation frequency. Therefore, themethod shows good potential for identifying rare driver mutations in current, large-scale tumor sequencing projects. In addition, mapping mutations to specific domains provides the necessary functional context for understanding how the mutations contribute to the disease, and may reveal novel or more refined gene and domain target regions for drug development.
Matrix metalloproteinase 9 contributes to gut microbe homeostasis in a model of infectious colitis
Authors: Rodrigues David M , Sousa Andrew J , Hawley Steve P , Vong Linda , Gareau Melanie G , Kumar Sachin A , Johnson-Henry Kathene C , Sherman Philip M
Published: June 2012

Background

Inflammatory bowel diseases are associated with increased expression of zinc-dependent Matrix Metalloproteinase 9 (MMP-9). A stark dysregulation of intestinal mucosal homeostasis has been observed in patients with chronic inflammatory bowel diseases. We therefore sought to determine the contribution of MMP-9 to the pathogenesis of Citrobacter rodentium-induced colitis and its effects on gut microbiome homeostasis.

Results

Wild-type and MMP-9−/− mice aged 5–6 weeks were challenged with C. rodentium by orogastric gavage and sacrificed either 10 or 30 days post-infection. Disease severity was assessed by histological analysis of colonic epithelial hyperplasia and by using an in vivo intestinal permeability assay. Changes in the inflammatory responses were measured by using qPCR, and the composition of the fecal microbiome evaluated with both qPCR and terminal restriction fragment length polymorphism. Activation and localization of MMP-9 to the apical surface of the colonic epithelium in response to C. rodentium infection was demonstrated by both zymography and immunocytochemistry. The pro-inflammatory response to infection, including colonic epithelial cell hyperplasia and barrier dysfunction, was similar, irrespective of genotype. Nonmetric multidimensional scaling of terminal restriction fragments revealed a different fecal microbiome composition and C. rodentium colonization pattern between genotypes, with MMP-9−/− having elevated levels of protective segmented filamentous bacteria and interleukin-17, and lower levels of C. rodentium. MMP-9−/− but not wild-type mice were also protected from reductions in fecal microbial diversity in response to the bacterial enteric infection.

Conclusions

These results demonstrate that MMP-9 expression in the colon causes alterations in the fecal microbiome and has an impact on the pathogenesis of bacterial-induced colitis in mice.
High speed coding for velocity by archerfish retinal ganglion cells
Authors: Kretschmer Viola , Kretschmer Friedrich , Ahlers Malte T , Ammermüller Josef
Published: June 2012

Background

Archerfish show very short behavioural latencies in response to falling prey. This raises the question, which response parameters of retinal ganglion cells to moving stimuli are best suited for fast coding of stimulus speed and direction.

Results

We compared stimulus reconstruction quality based on the ganglion cell response parameters latency, first interspike interval, and rate. For stimulus reconstruction of moving stimuli using latency was superior to using the other stimulus parameters. This was true for absolute latency, with respect to stimulus onset, as well as for relative latency, with respect to population response onset. Iteratively increasing the number of cells used for reconstruction decreased the calculated error close to zero.

Conclusions

Latency is the fastest response parameter available to the brain. Therefore, latency coding is best suited for high speed coding of moving objects. The quantitative data of this study are in good accordance with previously published behavioural response latencies.
The impact of preceding noise on the frequency tuning of rat auditory cortex neurons
Authors: Peng Yinting , Xing Pengpeng , He Juan , Sun Xinde , Zhang Jiping
Published: June 2012

Background

In a natural environment, contextual noise frequently occurs with a signal sound for detection or discrimination in a temporal relation. However, the representation of sound frequency by auditory cortical neurons in a noisy environment is not fully understood. Therefore, the purpose of this study was to explore the impact of contextual noise on the cortical tuning to signal sound frequency in order to better understand the mechanism of cortical frequency coding in a complex acoustical environment.

Results

We compared the excitatory frequency-level receptive fields (FLRFs) of neurons in the rat primary auditory cortex determined under both quiet and preceding noise conditions. Based on the changes of minimum threshold and the extent of FLRF of auditory cortical neurons, we found that the FLRFs of a cortical neuron were modulated dynamically by a varying preceding noise. When the interstimulus interval between noise and the probe tone was constant, the modulation of the FLRF increased as the level of noise was increased. If the preceding noise level was constant, the modulation decreased when the interstimulus interval was increased. Preceding noise sharpened the bandwidth of the FLRFs of 47.6% tested neurons. Moreover, preceding noise shifted the CFs of 47.6% neurons by more than 0.25 octaves, while the CFs of the rest of the neurons remained relatively unchanged.

Conclusions

The results indicate that the cortical representation of sound frequency is dynamically modulated by contextual acoustical environment, and that there are cortical neurons whose characteristic frequencies were resistant to the interference of contextual noise.
Association mapping in sunflower for sclerotinia head rot resistance
Authors: Fusari Corina M , Di Rienzo Julio A , Troglia Carolina , Nishinakamasu Verónica , Moreno María Valeria , Maringolo Carla , Quiroz Facundo , Álvarez Daniel , Escande Alberto , Hopp Esteban , Heinz Ruth , Lia Verónica V , Paniego Norma B
Published: June 2012

Background

Sclerotinia Head Rot (SHR) is one of the most damaging diseases of sunflower in Europe, Argentina, and USA, causing average yield reductions of 10 to 20 %, but leading to total production loss under favorable environmental conditions for the pathogen. Association Mapping (AM) is a promising choice for Quantitative Trait Locus (QTL) mapping, as it detects relationships between phenotypic variation and gene polymorphisms in existing germplasm without development of mapping populations. This article reports the identification of QTL for resistance to SHR based on candidate gene AM.

Results

A collection of 94 sunflower inbred lines were tested for SHR under field conditions using assisted inoculation with the fungal pathogen Sclerotinia sclerotiorum. Given that no biological mechanisms or biochemical pathways have been clearly identified for SHR, 43 candidate genes were selected based on previous transcript profiling studies in sunflower and Brassica napus infected with S. sclerotiorum. Associations among SHR incidence and haplotype polymorphisms in 16 candidate genes were tested using Mixed Linear Models (MLM) that account for population structure and kinship relationships. This approach allowed detection of a significant association between the candidate gene HaRIC_B and SHR incidence (P < 0.01), accounting for a SHR incidence reduction of about 20 %.

Conclusions

These results suggest that AM will be useful in dissecting other complex traits in sunflower, thus providing a valuable tool to assist in crop breeding.
Swedish Child Health Care nurses conceptions of overweight in children: a qualitative study
Authors: Isma Gabriella E , Bramhagen Ann-Cathrine , Ahlstrom Gerd , Östman Margareta , Dykes Anna-Karin
Published: June 2012

Background

Registered Sick Children’s Nurses and District Nurses employed at Child Health Care centres are in a position to help prevent childhood overweight and obesity. Prevention of this challenging public health threat could be improved through having a better understanding of how this group of nurses perceives childhood obesity. The aim of this study was to elucidate the conceptions of childhood overweight, including obesity, among nurses working in Child Health Care.

Method

A qualitative study using a phenomenographic approach, based on open-ended interviews with 18 Child Health Care nurses (CHC-nurses) strategically selected from 17 Child Health Care Centres in the southern part of Sweden.

Results

Four categories of description emerged from the data: Perception of childhood overweight changes, Overweight in younger children a neglected concern, Overweight a delicate issue and Importance of family lifestyle. The participating CHC-nurses conceived overweight in children, primarily obesity in children to be an extensive and serious problem which affects children, families and the surrounding society. Overweight in children was further perceived as a consequence of their parent’s lifestyle and their awareness of the problem, which was considered by the CHC-nurses as a sensitive and a provoking issue. It was also perceived that overweight in children is not taken seriously during the pre-school period and that concerns regarding overweight in younger children were mainly about the appearance and not the health of the child. The CHC-nurses perceived that the proportion of overweight children has increased, which Swedish society and the CHC-nurses have adapted to. This adaptation makes it difficult for CHC-nurses to define those children who are overweight.

Conclusion

CHC-nurses provide a comprehensive and complex picture of childhood overweight, which includes several difficulties dealing with this issue. Attention to CHC-nurse’s conceptions of overweight in children is important since it can affect the parent-nurse relationship and thereby the nurse’s, as well as the parent’s efforts to influence the children’s weight. It is suggested that CHC- nurses should work with person centered counseling and empowerment concerning parent to child relations in cases involving overweight.
Anticonvulsant and neuroprotective effects of Pimpinella anisum in rat brain
Authors: Karimzadeh Fariba , Hosseini Mahmoud , Mangeng Diana , Alavi Hassan , Hassanzadeh Gholam Reza , Bayat Mohamad , Jafarian Maryam , Kazemi Hadi , Gorji Ali
Published: June 2012

Background

Essential oil of Pimpinella anisum L. Apiaceae (anise oil) has been widely used in traditional Persian medicine to treat a variety of diseases, including some neurological disorders. This study was aimed to test the possible anti-seizure and anti-hypoxia effects of anise oil.

Methods

The effects of different concentrations of anise oil were tested on seizure attacks induced by pentylenetetrazol (PTZ) injection and neuronal hypoxia induced by oxygen withdrawal as well as on production of dark neurons and induction of long-term potentiation (LTP) in in vivo and in vitro experimental models of rat brain.

Results

Anise oil significantly prolonged the latency of seizure attacks and reduced the amplitude and duration of epileptiform burst discharges induced by injection of intraperitoneal PTZ. In addition, anise oil significantly inhibited production of dark neurons in different regions of the brain in epileptic rats. Anise oil also significantly enhanced the duration of the appearance of anoxic terminal negativity induced by oxygen withdrawal and inhibited induction of LTP in hippocampal slices.

Conclusions

Our data indicate the anticonvulsant and neuroprotective effects of anise oil, likely via inhibition of synaptic plasticity. Further evaluation of anise oil to use in the treatment of neurological disorders is suggested.
Identification of shared genetic susceptibility locus for coronary artery disease, type 2 diabetes and obesity: a meta-analysis of genome-wide studies
Authors: Wu Chaoneng , Gong Yunguo , Yuan Jie , Gong Hui , Zou Yunzeng , Ge Junbo
Published: June 2012

Type 2 diabetes (2DM), obesity, and coronary artery disease (CAD) are frequently coexisted being as key components of metabolic syndrome. Whether there is shared genetic background underlying these diseases remained unclear. We performed a meta-analysis of 35 genome screens for 2DM, 36 for obesity or body mass index (BMI)-defined obesity, and 21 for CAD using genome search meta-analysis (GSMA), which combines linkage results to identify regions with only weak evidence and provide genetic interactions among different diseases. For each study, 120 genomic bins of approximately 30 cM were defined and ranked according to the best linkage evidence within each bin. For each disease, bin 6.2 achieved genomic significanct evidence, and bin 9.3, 10.5, 16.3 reached suggestive level for 2DM. Bin 11.2 and 16.3, and bin 10.5 and 9.3, reached suggestive evidence for obesity and CAD respectively. In pooled all three diseases, bin 9.3 and 6.5 reached genomic significant and suggestive evidence respectively, being relatively much weaker for 2DM/CAD or 2DM/obesity or CAD/obesity. Further, genomewide significant evidence was observed of bin 16.3 and 4.5 for 2DM/obesity, which is decreased when CAD was added. These findings indicated that bin 9.3 and 6.5 are most likely to be shared by 2DM, obesity and CAD. And bin 16.3 and 4.5 are potentially common regions to 2DM and obesity only. The observed shared susceptibility regions imply a partly overlapping genetic aspects of disease development. Fine scanning of these regions will definitely identify more susceptibility genes and causal variants.
Insulin resistance predicts progression of de novo atherosclerotic plaques in patients with coronary heart disease: a one-year follow-up study
Authors: An Xuanqi , Yu Dong , Zhang Ruiyan , Zhu Jinzhou , Du Run , Shi Yuhang , Xiong Xiaowei
Published: June 2012

Background

The aim of our study was to explore and evaluate the relationship between insulin resistance and progression of coronary atherosclerotic plaques. With the great burden coronary heart disease is imposing on individuals, healthcare professionals have already embarked on determining its potential modifiable risk factors in the light of preventive medicine. Insulin resistance has been generally recognized as a novel risk factor based on epidemiological studies; however, few researches have focused on its effect on coronary atherosclerotic plaque progression.

Methods

From June 7, 2007 to December 30, 2011, 366 patients received their index coronary angiogram and were subsequently found to have coronary atherosclerotic plaques or normal angiograms were consecutively enrolled in the study by the department of cardiology at the Ruijin Hospital, which is affiliated to the Shanghai Jiaotong University School of Medicine. All patients had follow-up angiograms after the 1-year period for evaluating the progression of the coronary lesions. The modified Gensini score was adopted for assessing coronary lesions while the HOMA-IR method was utilized for determining the state of their insulin resistance. Baseline characteristics and laboratory test results were described and the binomial regression analysis was conducted to investigate the relationship between insulin resistance and coronary atherosclerotic plaque progression.

Results

Index and follow-up Gensini scores were similar between the higher insulin lower insulin resistant groups (9.09 ± 14.33 vs 9.44 ± 12.88, p = 0.813 and 17.21 ± 18.46 vs 14.09 ± 14.18, p =0.358). However the Gensini score assessing coronary lesion progression between both visits was significantly elevated in the higher insulin resistant group (8.13 ± 11.83 versus 4.65 ± 7.58, p = 0.019). Multivariate logistic binomial regression analysis revealed that insulin resistance (HOMA-IR > 3.4583) was an independent predictor for coronary arterial plaque progression (OR = 4.969, p = 0.011). We also divided all the participants into a diabetic (n = 136) and a non-diabetic group (n = 230), and HOMA-IR remained an independent predictor for atherosclerosis plaque progression.

Conclusions

Insulin resistance is an independent predictor of atherosclerosis plaque progression in patients with coronary heart disease in both the diabetic and non-diabetic population.
Fatty acid-binding protein 4 impairs the insulin-dependent nitric oxide pathway in vascular endothelial cells
Authors: Aragonès Gemma , Saavedra Paula , Heras Mercedes , Cabré Anna , Girona Josefa , Masana Lluís
Published: June 2012

Background

Recent studies have shown that fatty acid-binding protein 4 (FABP4) plasma levels are associated with impaired endothelial function in type 2 diabetes (T2D). In this work, we analysed the effect of FABP4 on the insulin-mediated nitric oxide (NO) production by endothelial cells in vitro.

Methods

In human umbilical vascular endothelial cells (HUVECs), we measured the effects of FABP4 on the insulin-mediated endothelial nitric oxide synthase (eNOS) expression and activation and on NO production. We also explored the impact of exogenous FABP4 on the insulin-signalling pathway (insulin receptor substrate 1 (IRS1) and Akt).

Results

We found that eNOS expression and activation and NO production are significantly inhibited by exogenous FABP4 in HUVECs. FABP4 induced an alteration of the insulin-mediated eNOS pathway by inhibiting IRS1 and Akt activation. These results suggest that FABP4 induces endothelial dysfunction by inhibiting the activation of the insulin-signalling pathway resulting in decreased eNOS activation and NO production.

Conclusion

These findings provide a mechanistic linkage between FABP4 and impaired endothelial function in diabetes, which leads to an increased cardiovascular risk.
Engineering of daidzein 3’-hydroxylase P450 enzyme into catalytically self-sufficient cytochrome P450
Authors: Choi Kwon-Young , Jung EunOk , Jung Da-Hye , An Byeo-Ri , Pandey Bishnu Prasad , Yun Hyungdon , Sung Changmin , Park Hyung-Yeon , Kim Byung-Gee
Published: June 2012

A cytochrome P450 (CYP) enzyme, 3’-daidzein hydroxylase, CYP105D7 (3’-DH), responsible for daidzein hydroxylation at the 3’-position, was recently reported. CYP105D7 (3’-DH) is a class I type of CYP that requires electrons provided through electron transfer proteins such as ferredoxin and ferredoxin reductase. Presently, we constructed an artificial CYP in order to develop a reaction host for the production of a hydroxylated product. Fusion-mediated construction with the reductase domain from self-sufficient CYP102D1 was done to increase electron transfer efficiency and coupling with the oxidative process. An artificial self-sufficient daidzein hydroxylase (3’-ASDH) displayed distinct spectral properties of both flavoprotein and CYP. The fusion enzyme catalyzed hydroxylation of daidzein more efficiently, with akcat/Kmvalue of 16.8 μM-1 min-1, which was about 24-fold higher than that of the 3’-DH-camA/B reconstituted enzyme. Finally, a recombinantStreptomyces avermitilishost for the expression of 3’-ASDH and production of the hydroxylated product was developed. The conversion that was attained (34.6%) was 5.2-fold higher than that of the wild-type.
Expression of osteoprotegerin, receptor activator of nuclear factor kappa-B ligand, tumor necrosis factor-related apoptosis-inducing ligand, stromal cell-derived factor-1 and their receptors in epithelial metastatic breast cancer cell lines
Authors: Labovsky Vivian , Vallone Valeria B Fernández , Martinez Leandro M , Otaegui Julian , Chasseing Norma A
Published: June 2012

Background

While breast cancer (BC) is the major cause of death among women worldwide, there is no guarantee of better patient survival because many of these patients develop primarily metastases, despite efforts to detect it in its early stages. Bone metastasis is a common complication that occurs in 65-80 % of patients with disseminated disease, but the molecular basis underlyingdormancy,dissemination and establishment of metastasis is not understood. Our objective has been to evaluate simultaneously osteoprotegerin (OPG), receptor activator of nuclear factor kappa B ligand (RANKL), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), stromal cell-derived factor-1 (SDF-1), and their receptors (R) in 2 human BC cell lines, MDA-MB-231 and MCF-7.

Methods

OPG, RANKL, TRAIL and SDF-1 expression and release, in addition to the expression of their receptors has been investigated using immunofluorescence, immunocytochemistry and ELISA analyses.

Results

MCF-7 cells released higher levels of OPG in conditioned media (CM) than MDA-MB-231 cells; 100 % of both types of cell expressed OPG, RANKL, TRAIL and SDF-1. Moreover, 100 % in both lines expressed membrane RANKL and RANK, whereas only 50 % expressed CXCR4. Furthermore, 100 % expressed TRAIL-R1 and R4, 30-50 % TRAIL-R2, and 40-55 % TRAIL-R3.

Conclusions

MCF-7 and MDA-MB-231 cells not only released OPG, but expressed RANKL, TRAIL and SDF-1. The majority of the cells also expressed RANK, CXCR4 and TRAIL-R. Since these ligands and their receptors are implicated in the regulation of proliferation, survival, migration and future bone metastasis during breast tumor progression, assessment of these molecules in tumor biopsies of BC patients could be useful in identifying patients with more aggressive tumors that are also at risk of bone metastasis, which may thus improve the available options for therapeutic intervention.
Knockdown of PLC-gamma-2 and calmodulin 1 genes sensitizes human cervical adenocarcinoma cells to doxorubicin and paclitaxel
Authors: Stanislaus Anthony , Bakhtiar Athirah , Salleh Diyana , Tiash Snigdha , Fatemian Tahereh , Hossain Sharif , Akaike Toshihiro , Chowdhury Ezharul Hoque
Published: June 2012

Background

RNA interference (RNAi) is a powerful approach in functional genomics to selectively silence messenger mRNA (mRNA) expression and can be employed to rapidly develop potential novel drugs against a complex disease like cancer. However, naked siRNA being anionic is unable to cross the anionic cell membrane through passive diffusion and therefore, delivery of siRNA remains a major hurdle to overcome before the potential of siRNA technology can fully be exploited in cancer. pH-sensitive carbonate apatite has recently been developed as an efficient tool to deliver siRNA into the mammalian cells by virtue of its high affinity interaction with the siRNA and the desirable size distribution of the resulting siRNA-apatite complex for effective cellular endocytosis. Moreover, internalized siRNA was found to escape from the endosomes in a time-dependent manner and efficiently silence gene expression.

Results

Here we show that carbonate apatite-mediated delivery of siRNA against PLC-gamma-2 (PLCG2) and calmodulin 1 (CALM1) genes has led to the sensitization of a human cervical cancer cell line to doxorubicin- and paclitaxel depending on the dosage of the individual drug whereas no such enhancement in cell death was observed with cisplatin irrespective of the dosage following intracellular delivery of the siRNAs.

Conclusion

Thus, PLCG2 and CALM1 genes are two potential targets for gene knockdown in doxorubicin and paclitaxel-based chemotherapy of cervical cancer.
Gene expression changes as markers of early lapatinib response in a panel of breast cancer cell lines
Authors: O’Neill Fiona , Madden Stephen F , Aherne Sinead T , Clynes Martin , Crown John , Doolan Padraig , O’Connor Robert
Published: June 2012

Background

Lapatinib, a tyrosine kinase inhibitor of HER2 and EGFR and is approved, in combination with capecitabine, for the treatment of trastuzumab-refractory metastatic breast cancer. In order to establish a possible gene expression response to lapatinib, a panel of breast cancer cell lines with varying sensitivity to lapatinib were analysed using a combination of microarray and qPCR profiling.

Methods

Co-inertia analysis (CIA), a data integration technique, was used to identify transcription factors associated with the lapatinib response on a previously published dataset of 96 microarrays. RNA was extracted from BT474, SKBR3, EFM192A, HCC1954, MDAMB453 and MDAMB231 breast cancer cell lines displaying a range of lapatinib sensitivities and HER2 expression treated with 1 μM of lapatinib for 12 hours and quantified using Taqman RT-PCR. A fold change ≥ ± 2 was considered significant.

Results

A list of 421 differentially-expressed genes and 8 transcription factors (TFs) whose potential regulatory impact was inferred in silico, were identified as associated with lapatinib response. From this group, a panel of 27 genes (including the 8 TFs) were selected for qPCR validation. 5 genes were determined to be significantly differentially expressed following the 12 hr treatment of 1 μM lapatinib across all six cell lines. Furthermore, the expression of 4 of these genes (RB1CC1, FOXO3A, NR3C1 and ERBB3) was directly correlated with the degree of sensitivity of the cell line to lapatinib and their expression was observed to “switch” from up-regulated to down-regulated when the cell lines were arranged in a lapatinib-sensitive to insensitive order. These included the novel lapatinib response-associated genes RB1CC1 and NR3C1. Additionally, Cyclin D1 (CCND1), a common regulator of the other four proteins, was also demonstrated to observe a proportional response to lapatinib exposure.

Conclusions

A panel of 5 genes were determined to be differentially expressed in response to lapatinib at the 12 hour time point examined. The expression of these 5 genes correlated directly with lapatinib sensitivity. We propose that the gene expression profile may represent both an early measure of the likelihood of sensitivity and the level of response to lapatinib and may therefore have application in early response detection.
Effects of UVB-induced oxidative stress on protein expression and specific protein oxidation in normal human epithelial keratinocytes: a proteomic approach
Authors: Perluigi Marzia , Di Domenico Fabio , Blarzino Carla , Foppoli Cesira , Cini Chiara , Giorgi Alessandra , Grillo Caterina , De Marco Federico , Butterfield David A , Schininà Maria E , Coccia Raffaella
Published: June 2012

Background

The UVB component of solar ultraviolet irradiation is one of the major risk factors for the development of skin cancer in humans. UVB exposure elicits an increased generation of reactive oxygen species (ROS), which are responsible for oxidative damage to proteins, DNA, RNA and lipids. In order to examine the biological impact of UVB irradiation on skin cells, we used a parallel proteomics approach to analyze the protein expression profile and to identify oxidatively modified proteins in normal human epithelial keratinocytes.

Results

The expression levels of fifteen proteins - involved in maintaining the cytoskeleton integrity, removal of damaged proteins and heat shock response - were differentially regulated in UVB-exposed cells, indicating that an appropriate response is developed in order to counteract/neutralize the toxic effects of UVB-raised ROS. On the other side, the redox proteomics approach revealed that seven proteins - involved in cellular adhesion, cell-cell interaction and protein folding - were selectively oxidized.

Conclusions

Despite a wide and well orchestrated cellular response, a relevant oxidation of specific proteins concomitantly occurs in UVB-irradiated human epithelial Keratinocytes. These modified (i.e. likely dysfunctional) proteins might result in cell homeostasis impairment and therefore eventually promote cellular degeneration, senescence or carcinogenesis.