bluuebunny/crossref_metadata_2025 huggingface dataset:
Inactivation of Escherichia coli in Broth and Sausage by Combined High Pressure and Lactobacillus casei Cell Extract
Authors: Chung Hyun-Jung , Yousef Ahmed E.
Published: September 2010

The purpose of this study was to investigate the effect of combined high pressure and Lactobacillus casei cell extract (CE) on Escherichia coli O157 strains with variation in pressure resistance in broth and sausage. Pressure-resistant (O157:H7 and O157:H12) and -sensitive (O157-M1 and O157-M2) E. coli strains were used. Pressure treatment at 350 MPa for 20 min in broth caused 1.1-1.2 logs reduction in O157:H12 and O157:H7 and 4.1-5.5 logs reduction in the O157-M1 and O157-M2. When high pressure was treated in the presence of CE (32 CEAU/mL), the combination treatment caused a significant inactivation in the pressure-resistant O157:H7 strains resulting in the viability loss of 4.3-4.6 logs and the synergistic effect increased with increase in treatment time (p < 0.05). Similar result was observed in sausage. Differential scanning calorimetry thermogram showed that the presence of Lb. casei CE may cause considerable damage to cellular components of E. coli during the high pressure treatment. The synergy between high pressure processing and Lb. casei OSY-LB6A CE against pressure-resistant E. coli O157 strains suggests the feasibility of using this combination to minimize the risk of transmission of E. coli O157 by food.
Changes in Emotions Related to Medication Used to Treat ADHD. Part II: Clinical Approaches
Authors: Findling Robert L. , Brams Matthew , Childress Ann C. , López Frank A. , Manos Michael J. , Jensen Peter S.
Published: September 2010

ADHD is one of the most common neurobehavioral disorders of childhood, and FDA-approved medications offer an efficacious treatment option. However, case reports and anecdotal sources suggest that children can have emotional responses, both salutary and detrimental, to these agents. We have previously conducted a comprehensive literature review and found very few research studies systematically examining changes in emotional expression (EE) associated with ADHD medication use. In addition, no empirical data pertaining to the management of these responses could be found. Although few methodologically stringent data are available for changes in EE, such changes should be recognized and measured to determine appropriate responses by clinicians and to maximize treatment benefits and reduce side effects. In this companion report, we draw on available research evidence and clinical experience to explore typical clinical manifestations, differential diagnosis, scales for monitoring, and management approaches of EE observed with pharmacologic treatment of ADHD. In the future, controlled clinical trials of ADHD pharmacotherapy should employ standardized ratings of EE at baseline, during and after treatment. In addition, future research studies should examine various management approaches of these EE changes, to ensure maximal treatment benefits and minimal risks to patients with ADHD who are treated with medication. (J. of Att. Dis. 2011; 15(2) 113-121)
An information aid for newly diagnosed multiple sclerosis patients improves disease knowledge and satisfaction with care
Authors: Solari A. , Martinelli V , Trojano M , Lugaresi A , Granella F , Giordano A , Messmer Uccelli M , D'Alessandro R , Pucci E , Confalonieri P , Borreani C ,   SIMS-Trial group
Published: September 2010

Background: Patients report information deficits in the period surrounding diagnosis of multiple sclerosis (MS). We assessed the effectiveness of an add-on information aid for newly diagnosed MS patients.

Methods: We randomly assigned 120 newly diagnosed MS patients from five Italian centres to diagnosis disclosure (current practice at the centre) or current practice plus information aid (ISRCTN81072971). The information aid consisted of a personal interview with a physician using a navigable compact disc and a take-home booklet. The primary composite endpoint was score in the highest tertile of MS knowledge and satisfaction with care questionnaires. Other endpoints were safety; treatment adherence; extra contacts/consultations; switching of care centre; and changes in Hospital Anxiety and Depression Scale and Control Preference Scale scores.

Results: At 1 month, 30/60 intervention and 8/60 control patients achieved the primary endpoint (odds ratio [OR] 6.5, 95% CI 2.6—16.0; p < 0.001; number needed to treat [NNT] 3). Figures at 6 months were 26/60 intervention and 11/60 control patients (OR 3.4, 95% CI 1.5—7.8; p = 0.04; NNT 4). There were no adverse events. No significant treatment effects were seen on secondary outcomes.

Conclusion: The information aid was safe and significantly associated with attainment of the primary outcome at 1 and 6 months.
Individual budgets and adult safeguarding: Parallel or converging tracks? Further findings from the evaluation of the Individual Budget pilots
Authors: Manthorpe Jill , Stevens Martin , Rapaport Joan , Challis David , Jacobs Sally , Netten Ann , Jones Karen , Knapp Martin , Wilberforce Mark , Glendinning Caroline
Published: September 2010

• Summary: The transformation of adult social care in England is underway, with the aim of promoting greater control and choice among people eligible for publicly funded social care services. A key part of personalization is the policy move to promote personal budgets. This article aims to investigate the inter-relation of personal budgets with another policy goal, adult safeguarding. A pilot programme of the predecessors of personal budgets, individual budgets, took place 2005–2008 and was evaluated by an independent research team. This article presents findings from the team’s second round of interviews with adult safeguarding coordinators (ASCs) in the 13 pilot sites held early 2008 which are discussed in the context of proposed adult safeguarding reforms in England.

• Findings: This second round of interviews with ASCs revealed greater engagement with social care transformation than previously. However, their detailed expertise in adult safeguarding and their local intelligence and experiences were not regularly accessed. This may constitute a missed opportunity to address some of the tensions of personalization in practice.

• Application: The interviews reveal that the personalization of social care is often interpreted as relating to greater use of Direct Payments and has yet to consider other facets of this policy transformation that are central to social work practice, including safeguarding.
Ambulatory actigraphy correlates with apathy in mild Alzheimer’s disease
Authors: David Renaud , Rivet Alice , Robert Philippe H. , Mailland Veronique , Friedman Leah , Zeitzer Jamie M. , Yesavage Jerome
Published: September 2010

Aim: Apathy is one of the most common behavioral symptoms in Alzheimer’s disease (AD). The aim of our study was to assess the relationship between apathy and locomotor activity in mild Alzheimer’s disease (AD).

Methods: Thirty AD subjects and fifteen healthy controls were recruited from the Nice Memory Center. Apathy was assessed with the Apathy Inventory (AI). Patients with a score greater than three on the AI caregiver version are considered in this report as having apathy. Locomotor activity was assessed using a wrist-worn actigraph for 75 minutes, during which a neuropsychological and behavioral examination were performed (60 minutes) followed by 15 minutes of free activity. Results: AD patients shown lower motor activity than healthy subjects. AD patients with apathy had lower motor activity than AD patients without apathy. Apathy total score correlated negatively with mean motor activity. Most of the total score correlation was accounted for by correlations between the apathy dimensions lack of initiative and lack of interest, with mean motor activity.

Conclusion: Ambulatory actigraphy could be a simple technique to assess apathy objectively as part of routine assessment of AD patients.
Geometry-based spatial acoustic source location for spaced structures
Authors: Ozevin Didem
Published: September 2010

This study presents a new source localization methodology to identify the spatial location of active flaws on spaced structures using the acoustic emission (AE) method. The methodology uses the geometric boundaries and the local coordinate system to find the shortest direct paths from the acoustic source to the AE sensors. The structural elements are modeled as 1D so that the source location is determined using linear equations in the local coordinate system. The local source location is converted into the global coordinate system to determine the source location in space. The approach has been successfully demonstrated using computer and laboratory simulations. The use of linear equations to solve the spatial location of the acoustic source in multi-dimensional space reduces the computational load as compared to the conventional 2D and 3D location algorithms.
Review: Disruption of the Postsynaptic Density in Alzheimer’s Disease and Other Neurodegenerative Dementias
Authors: Yuesong Gong  , Lippa Carol F.
Published: September 2010

The most common causes of neurodegenerative dementia include Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD). We believe that, in all 3, aggregates of pathogenic proteins are pathological substrates which are associated with a loss of synaptic function/plasticity. The synaptic plasticity relies on the normal integration of glutamate receptors at the postsynaptic density (PSD). The PSD organizes synaptic proteins to mediate the functional and structural plasticity of the excitatory synapse and to maintain synaptic homeostasis. Here, we will discuss the relevant disruption of the protein network at the PSD in these dementias and the accumulation of the pathological changes at the PSD years before clinical symptoms. We suggest that the functional and structural plasticity changes of the PSD may contribute to the loss of molecular homeostasis within the synapse (and contribute to early symptoms) in these dementias.
Clinical and radiographic outcomes of Image-Based Computer-Assisted Total Knee Arthroplasty: An Evidence-based Evaluation
Authors: Tao Cheng  , Gouyou Zhang  , Xianlong Zhang
Published: September 2010

Conventional instrumentation systems have limited accuracy in determining the crucial landmarks needed for alignment in total knee arthroplasty (TKA). Given this, the image-based navigation system was introduced to improve the accuracy of implantation of components into the femur and tibia. PubMed, EMBASE, Web of Science, and Evidence-Based Medicine databases were electronically searched to identify eligible studies published until October 2008. A systematic review and meta-analysis of 6 randomized/quasi-randomized controlled trials that compared image-based navigation and conventional techniques was conducted. The operative time was longer in the navigation group in 3 studies. Moreover, there was a higher rate of achieving mechanical leg axis within the range of 3° deviation in patients undergoing navigated TKA. However, all studies between the 2 groups were similar in range of motion, knee scores, and postoperative complication rates at the last follow-up. Overall, these short-term follow-up trials show that there were similar early clinical outcomes between image-based navigation and conventional techniques.
Change You Can Believe In
Authors: Hill Patrick L. , Jackson Joshua J. , Roberts Brent W. , Lapsley Daniel K. , Brandenberger Jay W.
Published: September 2010

A widely held assumption is that changes in one’s goals and motives for life during emerging and young adulthood have lasting influences on well-being into adulthood. However, this claim has yet to receive rigorous empirical testing. The current study examined the effects of prosocial and occupational goal change during college on adult well-being in a 17-year study of goal setting ( N = 416). Using a latent growth model across three time points, both level and growth in goal setting predicted later well-being. Moreover, goal changes both during college and in young adulthood uniquely predicted adult well-being, controlling for goal levels entering college. These findings suggest that what matters for attaining adult well-being is both how you enter adulthood and how you change in response to it.
Membrane-type MMPs are indispensable for placental labyrinth formation and development
Authors: Szabova Ludmila , Son Mee-Young , Shi Joanne , Sramko Marek , Yamada Susan S. , Swaim William D. , Zerfas Patricia , Kahan Stacie , Holmbeck Kenn
Published: September 2010

The membrane-type matrix metalloproteinases (MT-MMPs) are essential for pericellular matrix remodeling in late stages of development, as well as in growth and tissue homeostasis in postnatal life. Although early morphogenesis is perceived to involve substantial tissue remodeling, the roles of MT-MMPs in these processes are only partially characterized. Here we explore the functions of 2 prominently expressed MT-MMPs, MT1-MMP and MT2-MMP, and describe their roles in the process of placental morphogenesis. The fetal portion of the placenta, in particular the labyrinth (LA), displays strong overlapping expression of MT1-MMP and MT2-MMP, which is critical for syncytiotrophoblast formation and in turn for fetal vessels. Disruption of trophoblast syncytium formation consequently leads to developmental arrest with only a few poorly branched fetal vessels entering the LA causing embryonic death at embryonic day 11.5. Through knockdown of MMP expression, we demonstrate that either MT1-MMP or MT2-MMP is crucial specifically during development of the LA. In contrast, knockdown of MT-MMP activity after LA formation is compatible with development to term and postnatal life. Taken together these data identify essential but interchangeable roles for MT1-MMP or MT2-MMP in placental vasculogenesis and provide the first example of selective temporal and spatial MMP activity required for development of the mouse embryo.
Clinically significant cardiac disease in patients with Hodgkin lymphoma treated with mediastinal irradiation
Authors: Galper Shira L. , Yu James B. , Mauch Peter M. , Strasser Jon F. , Silver Barbara , LaCasce Ann , Marcus Karen J. , Stevenson Mary Ann , Chen Ming Hui , Ng Andrea K.
Published: September 2010

This study assessed the cumulative incidence of clinically significant cardiac disease in 1279 Hodgkin lymphoma patients treated with mediastinal irradiation and quantified the standard incidence ratios (SIRs) and absolute excess risks of cardiac procedures compared with a normal matched population. Cox regression analysis was used to explore factors associated with cardiac complications. Poisson regression analysis of SIRs was used to estimate the excess risk of cardiac interventions from mediastinal irradiation. After a median follow-up of 14.7 years, 187 patients experienced 636 cardiac events and 89 patients required a cardiac procedure. 5-, 10-, 15-, and 20-year cumulative incidence rates of cardiac events were 2.2%, 4.5%, 9.6%, and 16%. SIRs for cardiac procedures were increased for coronary artery bypass graft (3.19), percutaneous intervention (1.55), implantable cardioverter defibrillator or pacemaker placement (1.9), valve surgery (9.19), and pericardial surgery (12.91). Absolute excess risks were 18.2, 19.3, 9.4, 14.1, and 4.7 per 10 000 person-years, respectively. Older age at diagnosis and male sex were predictors for cardiac events. However, younger age at diagnosis was associated with excess risk specifically from radiation therapy compared with the general population. These results may help guideline development for both the types and timing of cardiac surveillance in survivors of Hodgkin lymphoma.
FragViz: visualization of fragmented networks
Authors: Štajdohar Miha , Mramor Minca , Zupan Blaž , Demšar Janez
Published: September 2010

Background

Researchers in systems biology use network visualization to summarize the results of their analysis. Such networks often include unconnected components, which popular network alignment algorithms place arbitrarily with respect to the rest of the network. This can lead to misinterpretations due to the proximity of otherwise unrelated elements.

Results

We propose a new network layout optimization technique called FragViz which can incorporate additional information on relations between unconnected network components. It uses a two-step approach by first arranging the nodes within each of the components and then placing the components so that their proximity in the network corresponds to their relatedness. In the experimental study with the leukemia gene networks we demonstrate that FragViz can obtain network layouts which are more interpretable and hold additional information that could not be exposed using classical network layout optimization algorithms.

Conclusions

Network visualization relies on computational techniques for proper placement of objects under consideration. These algorithms need to be fast so that they can be incorporated in responsive interfaces required by the explorative data analysis environments. Our layout optimization technique FragViz meets these requirements and specifically addresses the visualization of fragmented networks, for which standard algorithms do not consider similarities between unconnected components. The experiments confirmed the claims on speed and accuracy of the proposed solution.
Duplicate dmbx1genes regulate progenitor cell cycle and differentiation during zebrafish midbrain and retinal development
Authors: Wong Loksum , Weadick Cameron J , Kuo Claire , Chang Belinda SW , Tropepe Vincent
Published: September 2010

Background

The Dmbx1 gene is important for the development of the midbrain and hindbrain, and mouse gene targeting experiments reveal that this gene is required for mediating postnatal and adult feeding behaviours. A single Dmbx1 gene exists in terrestrial vertebrate genomes, while teleost genomes have at least two paralogs. We compared the loss of function of the zebrafish dmbx1a and dmbx1b genes in order to gain insight into the molecular mechanism by which dmbx1 regulates neurogenesis, and to begin to understand why these duplicate genes have been retained in the zebrafish genome.

Results

Using gene knockdown experiments we examined the function of the dmbx1 gene paralogs in zebrafish, dmbx1a and dmbx1b in regulating neurogenesis in the developing retina and midbrain. Dose-dependent loss of dmbx1a and dmbx1b function causes a significant reduction in growth of the midbrain and retina that is evident between 48-72 hpf. We show that this phenotype is not due to patterning defects or persistent cell death, but rather a deficit in progenitor cell cycle exit and differentiation. Analyses of the morphant retina or anterior hindbrain indicate that paralogous function is partially diverged since loss of dmbx1a is more severe than loss of dmbx1b. Molecular evolutionary analyses of the Dmbx1 genes suggest that while this gene family is conservative in its evolution, there was a dramatic change in selective constraint after the duplication event that gave rise to the dmbx1a and dmbx1b gene families in teleost fish, suggestive of positive selection. Interestingly, in contrast to zebrafish dmbx1a, over expression of the mouse Dmbx1 gene does not functionally compensate for the zebrafish dmbx1a knockdown phenotype, while over expression of the dmbx1b gene only partially compensates for the dmbx1a knockdown phenotype.

Conclusion

Our data suggest that both zebrafish dmbx1a and dmbx1b genes are retained in the fish genome due to their requirement during midbrain and retinal neurogenesis, although their function is partially diverged. At the cellular level, Dmbx1 regulates cell cycle exit and differentiation of progenitor cells. The unexpected observation of putative post-duplication positive selection of teleost Dmbx1 genes, especially dmbx1a, and the differences in functionality between the mouse and zebrafish genes suggests that the teleost Dmbx1 genes may have evolved a diverged function in the regulation of neurogenesis.
Suppression subtractive hybridization identifies an autotransporter adhesin gene of E. coli IMT5155 specifically associated with avian pathogenic Escherichia coli (APEC)
Authors: Dai Jianjun , Wang Shaohui , Guerlebeck Doreen , Laturnus Claudia , Guenther Sebastian , Shi Zhenyu , Lu Chengping , Ewers Christa
Published: September 2010

Background

Extraintestinal pathogenic E. coli (ExPEC) represent a phylogenetically diverse group of bacteria which are implicated in a large range of infections in humans and animals. Although subgroups of different ExPEC pathotypes, including uropathogenic, newborn meningitis causing, and avian pathogenic E. coli (APEC) share a number of virulence features, there still might be factors specifically contributing to the pathogenesis of a certain subset of strains or a distinct pathotype. Thus, we made use of suppression subtractive hybridization and compared APEC strain IMT5155 (O2:K1:H5; sequence type complex 95) with human uropathogenic E. coli strain CFT073 (O6:K2:H5; sequence type complex 73) to identify factors which may complete the currently existing model of APEC pathogenicity and further elucidate the position of this avian pathoype within the whole ExPEC group.

Results

Twenty-eight different genomic loci were identified, which are present in IMT5155 but not in CFT073. One of these loci contained a gene encoding a putative autotransporter adhesin. The open reading frame of the gene spans a 3,498 bp region leading to a putative 124-kDa adhesive protein. A specific antibody was raised against this protein and expression of the adhesin was shown under laboratory conditions. Adherence and adherence inhibition assays demonstrated a role for the corresponding protein in adhesion to DF-1 chicken fibroblasts. Sequence analyses revealed that the flanking regions of the chromosomally located gene contained sequences of mobile genetic elements, indicating a probable spread among different strains by horizontal gene transfer. In accordance with this hypothesis, the adhesin was found to be present not only in different phylogenetic groups of extraintestinal pathogenic but also of commensal E. coli strains, yielding a significant association with strains of avian origin.

Conclusions

We identified a chromosomally located autotransporter gene in a highly virulent APEC strain which confers increased adherence of a non-fimbriated E. coli K-12 strain to a chicken fibroblast cell line. Even though flanked by mobile genetic elements and three different genetic regions upstream of the gene, most probably indicating horizontal gene transfer events, the adhesin gene was significantly linked with strains of avian origin. Due to the nucleotide sequence similarity of 98% to a recently published adhesin-related gene, located on plasmid pAPEC-O1-ColBM, the name aatA (APEC autotransporter adhesin A) was adopted from that study.

Our data substantiate that AatA might not only be of relevance in APEC pathogenicity but also in facilitating their reservoir life style in the chicken intestine, which might pave the way for future intestinal preventive strategies.
Mutant alleles of FAD2-1A and FAD2-1Bcombine to produce soybeans with the high oleic acid seed oil trait
Authors: Pham Anh-Tung , Lee Jeong-Dong , Shannon J Grover , Bilyeu Kristin D
Published: September 2010

Background

The alteration of fatty acid profiles in soybean [Glycine max (L.) Merr.] to improve soybean oil quality is an important and evolving theme in soybean research to meet nutritional needs and industrial criteria in the modern market. Soybean oil with elevated oleic acid is desirable because this monounsaturated fatty acid improves the nutrition and oxidative stability of the oil. Commodity soybean oil typically contains 20% oleic acid and the target for high oleic acid soybean oil is approximately 80% of the oil; previous conventional plant breeding research to raise the oleic acid level to just 50-60% of the oil was hindered by the genetic complexity and environmental instability of the trait. The objective of this work was to create the high oleic acid trait in soybeans by identifying and combining mutations in two delta-twelve fatty acid desaturase genes, FAD2-1A and FAD2-1B.

Results

Three polymorphisms found in the FAD2-1B alleles of two soybean lines resulted in missense mutations. For each of the two soybean lines, there was one unique amino acid change within a highly conserved region of the protein. The mutant FAD2-1B alleles were associated with an increase in oleic acid levels, although the FAD2-1B mutant alleles alone were not capable of producing a high oleic acid phenotype. When existing FAD2-1A mutations were combined with the novel mutant FAD2-1B alleles, a high oleic acid phenotype was recovered only for those lines which were homozygous for both of the mutant alleles.

Conclusions

We were able to produce conventional soybean lines with 80% oleic acid in the oil in two different ways, each requiring the contribution of only two genes. The high oleic acid soybean germplasm developed contained a desirable fatty acid profile, and it was stable in two production environments. The presumed causative sequence polymorphisms in the FAD2-1B alleles were developed into highly efficient molecular markers for tracking the mutant alleles. The resources described here for the creation of high oleic acid soybeans provide a framework to efficiently develop soybean varieties to meet changing market demands.
Distribution of polycyclic aromatic hydrocarbons in subcellular root tissues of ryegrass (Lolium multiflorumLam.)
Authors: Kang Fuxing , Chen Dongsheng , Gao Yanzheng , Zhang Yi
Published: September 2010

Background

Because of the increasing quantity and high toxicity to humans of polycyclic aromatic hydrocarbons (PAHs) in the environment, several bioremediation mechanisms and protocols have been investigated to restore PAH-contaminated sites. The transport of organic contaminants among plant cells via tissues and their partition in roots, stalks, and leaves resulting from transpiration and lipid content have been extensively investigated. However, information about PAH distributions in intracellular tissues is lacking, thus limiting the further development of a mechanism-based phytoremediation strategy to improve treatment efficiency.

Results

Pyrene exhibited higher uptake and was more recalcitrant to metabolism in ryegrass roots than was phenanthrene. The kinetic processes of uptake from ryegrass culture medium revealed that these two PAHs were first adsorbed onto root cell walls, and they then penetrated cell membranes and were distributed in intracellular organelle fractions. At the beginning of uptake (< 50 h), adsorption to cell walls dominated the subcellular partitioning of the PAHs. After 96 h of uptake, the subcellular partition of PAHs approached a stable state in the plant water system, with the proportion of PAH distributed in subcellular fractions being controlled by the lipid contents of each component. Phenanthrene and pyrene primarily accumulated in plant root cell walls and organelles, with about 45% of PAHs in each of these two fractions, and the remainder was retained in the dissolved fraction of the cells. Because of its higher lipophilicity, pyrene displayed greater accumulation factors in subcellular walls and organelle fractions than did phenanthrene.

Conclusions

Transpiration and the lipid content of root cell fractions are the main drivers of the subcellular partition of PAHs in roots. Initially, PAHs adsorb to plant cell walls, and they then gradually diffuse into subcellular fractions of tissues. The lipid content of intracellular components determines the accumulation of lipophilic compounds, and the diffusion rate is related to the concentration gradient established between cell walls and cell organelles. Our results offer insights into the transport mechanisms of PAHs in ryegrass roots and their diffusion in root cells.
Comparison of ELF, FibroTest and FibroScan for the non-invasive assessment of liver fibrosis
Authors: Friedrich-Rust Mireen , Rosenberg William , Parkes Julie , Herrmann Eva , Zeuzem Stefan , Sarrazin Christoph
Published: September 2010

Background

FibroTest (FT) is the most frequently used serum fibrosis marker and consists of an algorithm of five fibrosis markers (alfa2-macroglobulin, apolipoproteinA1, haptoglobin, GGT, bilirubin). The Enhanced Liver Fibrosis (ELF) test consists of an algorithm of three fibrosis markers (hyaluronic acid, amino-terminal propeptide-of-type-III-collagen, tissue-inhibitor of matrix-metaloproteinase-1). While a systematic review has shown comparable results for both individual markers, there has been no direct comparison of both markers.

Methods

In the present study, the ELF-test was analyzed retrospectively in patients with chronic liver disease, who received a liver biopsy, transient elastography (TE) and the FibroTest using histology as the reference method. Histology was classified according to METAVIR and the Ludwig's classification (F0-F4) for patients with chronic hepatitis C and B virus (HCV, HBV) infection and primary biliary cirrhosis (PBC), respectively.

Results

Seventy-four patients were analysed: 36 with HCV, 10 with HBV, and 28 with PBC. The accuracy (AUROC) for the diagnosis of significant fibrosis (F≥2) for ELF and FibroTest was 0.78 (95%CI:0.67-0.89) and 0.69 (95%-CI:0.57-0.82), respectively (difference not statistically significant, n.s.). The AUROC for the diagnosis of liver cirrhosis was 0.92 (95%CI:0.83-1,00), and 0.91 (95%CI:0.83-0.99), respectively (n.s.). For 66 patients with reliable TE measurements the AUROC for the diagnosis of significant fibrosis (cirrhosis) for TE, ELF and FT were 0.80 (0.94), 0.76 (0.92), and 0.67 (0.91), respectively (n.s.).

Conclusion

FibroTest and ELF can be performed with comparable diagnostic accuracy for the non-invasive staging of liver fibrosis. Serum tests are informative in a higher proportion of patients than transient elastography.
Expression of RNA interference triggers from an oncolytic herpes simplex virus results in specific silencing in tumour cells in vitro and tumours in vivo
Authors: Anesti Anna-Maria , Simpson Guy R , Price Toby , Pandha Hardev S , Coffin Robert S
Published: September 2010

Background

Delivery of small interfering RNA (siRNA) to tumours remains a major obstacle for the development of RNA interference (RNAi)-based therapeutics. Following the promising pre-clinical and clinical results with the oncolytic herpes simplex virus (HSV) OncoVEXGM-CSF, we aimed to express RNAi triggers from oncolytic HSV, which although has the potential to improve treatment by silencing tumour-related genes, was not considered possible due to the highly oncolytic properties of HSV.

Methods

To evaluate RNAi-mediated silencing from an oncolytic HSV backbone, we developed novel replicating HSV vectors expressing short-hairpin RNA (shRNA) or artificial microRNA (miRNA) against the reporter genes green fluorescent protein (eGFP) and β-galactosidase (lacZ). These vectors were tested in non-tumour cell linesin vitroand tumour cells that are moderately susceptible to HSV infection bothin vitroand in mice xenograftsin vivo. Silencing was assessed at the protein level by fluorescent microscopy, x-gal staining, enzyme activity assay, and western blotting.

Results

Our results demonstrate that it is possible to express shRNA and artificial miRNA from an oncolytic HSV backbone, which had not been previously investigated. Furthermore, oncolytic HSV-mediated delivery of RNAi triggers resulted in effective and specific silencing of targeted genes in tumour cellsin vitroand tumoursin vivo, with the viruses expressing artificial miRNA being comprehensibly more effective.

Conclusions

This preliminary data provide the first demonstration of oncolytic HSV-mediated expression of shRNA or artificial miRNA and silencing of targeted genes in tumour cellsin vitroandin vivo. The vectors developed in this study are being adapted to silence tumour-related genes in an ongoing study that aims to improve the effectiveness of oncolytic HSV treatment in tumours that are moderately susceptible to HSV infection and thus, potentially improve response rates seen in human clinical trials.
Irresponsiveness of two retinoblastoma cases to conservative therapy correlates with up- regulation of hERG1 channels and of the VEGF-A pathway
Authors: Fortunato Pina , Pillozzi Serena , Tamburini Angela , Pollazzi Liliana , Franchi Alessandro , La Torre Agostino , Arcangeli Annarosa
Published: September 2010

Background

Treatment strategies for Retinoblastoma (RB), the most common primary intraocular tumor in children, have evolved over the past few decades and chemoreduction is currently the most popular treatment strategy. Despite success, systemic chemotherapeutic treatment has relevant toxicity, especially in the pediatric population. Antiangiogenic therapy has thus been proposed as a valuable alternative for pediatric malignancies, in particolar RB. Indeed, it has been shown that vessel density correlates with both local invasive growth and presence of metastases in RB, suggesting that angiogenesis could play a pivotal role for both local and systemic invasive growth in RB. We present here two cases of sporadic, bilateral RB that did not benefit from the conservative treatment and we provide evidence that the VEGF-A pathway is significantly up-regulated in both RB cases along with an over expression of hERG1 K+ channels.

Case presentation

Two patients showed a sporadic, bilateral RB, classified at Stage II of the Reese-Elsworth Classification. Neither of them got benefits from conservative treatment, and the two eyes were enucleated. In samples from both RB cases we studied the VEGF-A pathway: VEGF-A showed high levels in the vitreous, the vegf-a, flt-1, kdr, and hif1-α transcripts were over-expressed. Moreover, both the transcripts and proteins of the hERG1 K+ channels turned out to be up-regulated in the two RB cases compared to the non cancerous retinal tissue.

Conclusions

We provide evidence that the VEGF-A pathway is up-regulated in two particular aggressive cases of bilateral RB, which did not experience any benefit from conservative treatment, showing the overexpression of the vegf-a, flt-1, kdr and hif1-α transcripts and the high secretion of VEGF-A. Moreover we also show for the first time that the herg1 gene transcripts and protein are over expressed in RB, as occurs in several aggressive tumors. These results further stress the relevance of the VEGF-A pathway in RB and the correlation with hERG1, making aggressive and recurrent RB cases good candidates for antiangiogenesis therapies based on the targeting of VEGF-A.
The evaluation of "Safe Motherhood" program on maternal care utilization in rural western China: a difference in difference approach
Authors: Liu Xiaoning , Yan Hong , Wang Duolao
Published: September 2010

Background

Maternal care is an important strategy for protection and promotion of maternal and children's health by reducing maternal mortality and improving the quality of birth. However, the status of maternal care is quite weak in the less developed rural areas in western China. It is found that the maternal mortality rates in some western areas of China were 5.8 times higher than those of their eastern costal counterparts. In order to reduce the maternal mortality rates and to improve maternal care in western rural areas of China, the Chinese Ministry of Health (MOH) and the United Nations Children's Fund (UNICEF) sponsored a program named "Safe Motherhood" in ten western provinces of China from 2001 through 2005. This study mainly aims to evaluate the effects of "Safe Motherhood" program on maternal care utilization.

Methods

32 counties were included in both surveys conducted in 2001 and 2005, respectively. Ten counties of which implemented comprehensive community-based intervention were used as intervention groups, while 22 counties were used as control groups. Stratified 3-stage probability-proportion-to-size sampling method was used to select participating women. Two cross-sectional surveys were conducted with questionnaires about the prenatal care utilization in 2001 and 2005, respectively. Difference in difference estimation was used to assess the effect of intervention on the maternal care utilization while controlling for socio-economic characteristics of women.

Results

After the intervention, the proportion of pregnant women who had their first prenatal visit in the first trimester was increased from 38.9% to 76.1%. The proportion of prenatal visits increased from 82.6% to 98.3%. The proportion of women mobilized to deliver in hospitals increased from 62.7% to 94.5%. Hospital delivery was improved greatly from 31.1% to 87.3%. The maternal mortality rate was lowered by 34.9% from 91.76 to 59.74 per 100,000 live births. The community-based intervention had increased prenatal visits rate by 5.2%, first prenatal visit in first trimester rate by 12.0% and hospital delivery rate by 22.5%, respectively. No effect was found on rate of women being mobilized to hospital delivery compared with that of the control group.

Conclusion

The intervention program seemed to have improved the prenatal care utilization in rural western China.
Completeness and timeliness of Salmonella notifications in Ireland in 2008: a cross sectional study
Authors: Nicolay Nathalie , Garvey Patricia , Delappe Niall , Cormican Martin , McKeown Paul
Published: September 2010

Background

In Ireland, salmonellosis is the second most common cause of bacterial gastroenteritis. A new electronic system for reporting (Computerised Infectious Disease Reporting - CIDR) ofSalmonellacases was established in 2004. It collates clinical (and/or laboratory) data on confirmed and probableSalmonellacases. The authors studied the completeness and the timeliness ofSalmonellanotifications in 2008.

Methods

This analysis was based upon laboratory confirmed cases of salmonella gastroenteritis. Using data contained in CIDR, we examined completeness for certain non-mandatory fields (country of infection, date of onset of illness, organism, outcome, patient type, and ethnicity). We matched the CIDR data with the dataset provided by the nationalSalmonellareference laboratory (NSRL) to which allSalmonellaspp. isolates are referred for definitive typing. We calculated the main median time intervals in the flow of events of the notification process.

Results

In total, 416 laboratory confirmedSalmonellacases were captured by the national surveillance system and the NSRL and were included in the analysis. Completeness of non mandatory fields varied considerably. Organism was the most complete field (98.8%), ethnicity the least (11%). The median time interval between sample collection (first contact of the patient with the healthcare professional) to the first notification to the regional Department of Public Health (either a clinical or a laboratory notification) was 6 days (Interquartile 4-7 days). The median total identification time interval, time between sample collections to availability of serotyping and phage-typing results on the system was 25 days (Interquartile 19-32 days). Timeliness varied with respect toSalmonellaspecies. Clinical notifications occurred more rapidly than laboratory notifications.

Conclusions

Further feedback and education should be given to health care professionals to improve completeness of reporting of non-mandatory fields. The efficiency of reporting was similar to that published elsewhere. Delays in the reporting system at present mean that although the system is of value in facilitating comprehensive reporting it is unlikely it can be relied upon for rapid detection of outbreaks at an early stage. Direct person-to-person, communication between clinical and reference laboratories and public health practitioners remains a critical element of the surveillance system for rapid outbreak detection.
Increased expression and local accumulation of the Prion Protein, Alzheimer Aβ peptides, superoxide dismutase 1, and Nitric oxide synthases 1 & 2 in muscle in a rabbit model of diabetes
Authors: Bitel Claudine L , Feng Yicheng , Souayah Nizar , Frederikse Peter H
Published: September 2010

Background

Muscle disease associated with different etiologies has been shown to produce localized accumulations of amyloid and oxidative stress-related proteins that are more commonly associated with neurodegeneration in the brain. In this study we examined changes in muscle tissue in a classic model of diabetes and hyperglycemia in rabbits to determine if similar dysregulation of Alzheimer Aβ peptides, the prion protein (PrP), and superoxide dismutase 1 (SOD1), as well as nitric oxide synthases is produced in muscle in diabetic animals. This wild-type rabbit model includes systemic physiological expression of human-like Alzheimer precursor proteins and Aβ peptides that are considered key in Alzheimer protein studies.

Results

Diabetes was produced in rabbits by injection of the toxic glucose analogue alloxan, which selectively enters pancreatic beta cells and irreversibly decreases insulin production, similar to streptozotocin. Quadriceps muscle from rabbits 16 wks after onset of diabetes and hyperglycemia were analyzed with biochemical andin situmethods. Immunoblots of whole muscle protein samples demonstrated increased PrP, SOD1, as well as neuronal and inducible Nitric oxide synthases (NOS1 and NOS2) in diabetic muscle. In contrast, we detected little change in Alzheimer Aβ precursor protein expression, or BACE1 and Presenilin 1 levels. However, Aβ peptides measured by ELISA increased several fold in diabetic muscle, suggesting a key role for Aβ cleavage in muscle similar to Alzheimer neurodegeneration in this diabetes model. Histological changes in diabetic muscle included localized accumulations of PrP, Aβ, NOS1 and 2, and SOD1, and evidence of increased central nuclei and cell infiltration.

Conclusions

The present study provides evidence that several classic amyloid and oxidative stress-related disease proteins coordinately increase in overall expression and form localized accumulations in diabetic muscle. The present study highlights the capacity of this wild-type animal model to produce an array of hallmark pathological features that have also been described in other muscle diseases.
Trop2 expression contributes to tumor pathogenesis by activating the ERK MAPK pathway
Authors: Cubas Rafael , Zhang Sheng , Li Min , Chen Changyi , Yao Qizhi
Published: September 2010

Background

Trop2 is a cell-surface glycoprotein overexpressed by a variety of epithelial carcinomas with reported low to restricted expression in normal tissues. Expression of Trop2 has been associated with increased tumor aggressiveness, metastasis and decreased patient survival, but the signaling mechanisms mediated by Trop2 are still unknown. Here, we studied the effects murine Trop2 (mTrop2) exerted on tumor cellular functions and some of the signaling mechanisms activated by this oncogene.

Results

mTrop2 expression significantly increased tumor cell proliferation at low serum concentration, migration, foci formation and anchorage-independent growth. These in vitro characteristics translated to increased tumor growth in both subcutaneous and orthotopic pancreatic cancer murine models and also led to increased liver metastasis. mTrop2 expression also increased the levels of phosphorylated ERK1/2 mediating cell cycle progression by increasing the levels of cyclin D1 and cyclin E as well as downregulating p27. The activation of ERK was also observed in human pancreatic ductal epithelial cells and colorectal adenocarcinoma cells overexpressing human Trop2.

Conclusions

These findings demonstrate some of the pathogenic effects mediated by mTrop2 expression on cancer cells and the importance of targeting this cell surface glycoprotein. This study also provides the first indication of a molecular signaling pathway activated by Trop2 which has important implications for cancer cell growth and survival.
Nymphs of the common bed bug (Cimex lectularius) produce anti-aphrodisiac defence against conspecific males
Authors: Harraca Vincent , Ryne Camilla , Ignell Rickard
Published: September 2010

Background

Abdominal wounding by traumatic insemination and the lack of a long distance attraction pheromone set the scene for unusual sexual signalling systems. Male bed bugs (Cimex lectularius) mount any large, newly fed individual in an attempt to mate. Last instar nymphs overlap in size with mature females, which make them a potential target for interested males. However, nymphs lack the female's specific mating adaptations and may be severely injured by the abdominal wounding. We, therefore, hypothesized that nymphs emit chemical deterrents that act as an honest status signal, which prevents nymph sexual harassment and indirectly reduces energy costs for males.

Results

Behavioural mating assays showed that males mount nymphs significantly shorter time compared to females, although initial mounting preference was the same. In support of our hypothesis, nymphs experienced the same percentage of mating with sperm transfer as females if they were unable to emit (E)-2-hexenal, (E)-2-octenal 4-oxo-(E)-2-hexenal and 4-oxo-(E)-2-octenal, from their dorsal abdominal glands. We report that the aldehydes and 4-oxo-(E)-2-hexenal are detected by olfactory receptor neurons housed in smooth and grooved peg sensilla, respectively, on the adult antennae, at biologically relevant concentrations. Behavioural experiments showed that application of 4-oxo-(E)-2-hexenal or the two aldehydes at a nymph-emitted ratio, to a male/female pair during mounting initiation, decreased mating frequency to a rate comparable to that of a male/nymph pair.

Conclusions

By combining behavioural and sensory studies, we show that the nymph-specific alarm pheromone plays an important role in intra-specific communication in the common bed bug. Alarm pheromones are commonly looked upon as a system in predator/prey communication, but here we show that alarm pheromones may be used as multipurpose signals such as decreasing the risk of nymphal mating by males.

See commentary:http://www.biomedcentral.com/1741-7007/8/117