bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Circulating and Local Uteroplacental Angiotensin II in Rat Pregnancy
Authors: Hering Lydia , Herse Florian , Geusens Nele , Verlohren Stefan , Wenzel Katrin , Staff Anne C. , Brosnihan K. Bridget , Huppertz Berthold , Luft Friedrich C. , Muller Dominik N. , Pijnenborg Robert , Cartwright Judith E. , Dechend Ralf
Published: June 2010

The renin-angiotensin (Ang) system is important during placental development. Dysregulation of the renin-Ang system is important in preeclampsia (PE). Female rats transgenic for the human angiotensinogen gene crossed with males transgenic for the human renin gene develop the PE syndrome, whereas those of the opposite cross do not. We used this model to study the role of Ang II in trophoblast invasion, which is shallow in human PE but deeper in this model. We investigated the following groups: PE rats, opposite-cross rats, Ang II–infused rats (1000 ng/kg per day), and control rats. Ang II infusion increased only circulating Ang II levels (267.82 pg/mL), opposite cross influenced only uteroplacental Ang II (13.52 fmol/mg of protein), and PE increased both circulating (251.09 pg/mL) and uteroplacental (19.24 fmol/mg of protein) Ang II. Blood pressure and albuminuria occurred in the models with high circulating Ang II but not in the other models. Trophoblast invasion increased in PE and opposite-cross rats but not in Ang II–infused rats. Correspondingly, uterine artery resistance index increased in Ang II–infused rats but decreased in PE rats. We then studied human trophoblasts and villous explants from first-trimester pregnancies with time-lapse microscopy. Local Ang II dose-dependently increased migration by 75%, invasion by 58%, and motility by 282%. The data suggest that local tissue Ang II stimulates trophoblast invasion in vivo in the rat and in vitro in human cells, a hitherto fore unrecognized function. Conceivably, upregulation of tissue Ang II in the maternal part of the placenta represents an important growth factor for trophoblast invasion and migration.
Association of Reduced Zinc Status With Angiographically Severe Coronary Atherosclerosis: A Pilot Study
Authors: Giannoglou George D. , Konstantinou Dimitris M. , Kovatsi Leda , Chatzizisis Yiannis S. , Mikhailidis Dimitri P.
Published: June 2010

In vitro studies attribute antiatherogenic and insulin-like properties to zinc (Zn). However, only a few conflicting clinical data exist concerning the relationship between Zn and coronary artery disease (CAD) as well as glycemic indices. We studied 72 patients without prior history of myocardial infarction or revascularization procedures, who underwent coronary angiography for evaluation of chest pain. Coronary artery disease severity was estimated using 3 angiographic scores. Zn in serum and 24-hour urine, as well as serum Zn/24-hour urine Zn ratio were determined. Serum Zn was not associated with CAD prevalence and severity. However, urinary Zn loss was significantly higher among patients with CAD and showed a positive association with CAD severity. Serum Zn/24-hour urine Zn ratio was inversely associated with CAD, as well as with diabetes mellitus prevalence, fasting glucose, and glycated hemoglobin levels. Low serum Zn/24-hour urine Zn ratio is associated with angiographically severe atherosclerosis and impaired glucose homeostasis.
Where Is the Café? The Challenge of Making Retail Uses Viable in Mixed-use Suburban Developments
Authors: Grant Jill , Perrott Katherine
Published: June 2010

Contemporary planners see mixing residential, retail and other compatible uses as an essential planning principle. This paper explores the challenges that planners, developers and municipal councillors encounter in trying to implement retail uses as part of the mix in suburban areas in three Canadian cities. The study finds that planners employ evolutionary theories of urban development to naturalise their normative visions of walkable and sociable communities. By contrast, developers point to consumer behaviour to explain why planners’ ideas on mix do not work. In a society where people shop at big-box outlets, making the local café or pub commercially viable proves increasingly challenging.
Bicycle Use in Germany: Explaining Differences between Municipalities with Social Network Effects
Authors: Goetzke Frank , Rave Tilmann
Published: June 2010

This paper aims to account for important factors influencing bicycle use and focuses in particular on differences between 20 selected German municipalities with considerable variation in their bicycle mode share. Using data from the nation-wide survey Mobility in Germany 2002, a mode choice model for bicycling is developed. In an extension to previous research, social network or spillover effects as a measure of the city’s bicycling culture are also taken into account. These effects are modelled using an instrumental variable approach. It is shown that social network effects increase the probability of cycling for shopping and recreational trip purposes, but not for school, work or errands. Furthermore, it is found that cycling infrastructure matters only for shopping and errand trips. Finally, commuting trips by bicycle seem to be largely independent of any policy variables.
Measuring and Explaining Competitiveness in the Context of Small Island Destinations
Authors: Croes Robertico
Published: June 2010

This study measures and explains competitiveness among small island destinations. Current measures of competitiveness do not respond to the special needs of small island destinations. An alternative measurement suggests a more suitable Tourism Competitiveness Index (TCI), and through the application of panel regression analysis, tracks the most important factors affecting competitiveness among island destinations. The findings imply likelihood that more expensive destinations obtain a larger share of regional tourism revenues. The study concludes that providing a high-quality product may allow destinations to become and remain competitive.
“My Mother’s Keeper”: The Effects of Parentification on Black Female College Students
Authors: Gilford Tawanna T. , Reynolds Amy
Published: June 2010

This qualitative study examined the parentification of eight Black American college females and its impact on their college experiences. Two 90-minute focus groups were conducted in order to gain insight about how these women overcame personal and family challenges while being away from their families of origin. Results highlight the push-pull factors experienced by the participants from both school and their family of origin and how they dealt with barriers to successful college completion.
Effect of the addition of cattle slurry plus different types of livestock litter to an acid soil and on the production of grass and corn crops
Authors: Fernández-Sanjurjo María J , Alvarez Rodríguez Esperanza , Corti Giuseppe
Published: June 2010

The aim of the present study was to determine how the addition of cattle slurry (S), cattle slurry mixed with sawdust and lime (SL) or cattle slurry mixed with sawdust and crushed (2-4 mm) mussel shells (SM), coming from livestock litter affected the chemical properties of an acid soil and the production in a grass/corn rotation. Bulk and rhizospheric soil were analysed. With respect to the not-treated soil, all the treatments increased pH, exchangeable cations and ECEC, and decreased total N, organic C and exchangeable Al. The lowest variations were observed in S treated plots, while considerable variations occurred in the corn plots treated with SM. In this case, the soil pH reached values up to 6.7, in contrast with the S treated plots that reached pH 5.9. An increase in the concentrations of Ca, Mg and K was also observed. These effects were more evident in the rhizosphere than in the bulk. The addition of both lime and crushed shells increased production and quality of the yield. In SL and SM treated plots the total production of grass was 3.5 to 4-fold the production obtained in S plots. The total production of corn increased by 1095 kg ha -1 in the SL-treated plots and 2559 kg ha- 1 in SM plots; almost all these increments of production were due to the augmented production of cob. We concluded that the use of crushed mussel shells can be recommended as livestock litter suitable to be distributed in acid soils.
Psychosocial Factors Associated With Recent Alcohol Use Among Hispanic Youth
Authors: King Keith A. , Vidourek Rebecca A.
Published: June 2010

A total of 946 Hispanic students in 7th to 12th grade in Greater Cincinnati schools ( N = 133) completed a survey assessing factors associated with recent alcohol use. Results indicated that 24.5% used alcohol in the past month. Males were more likely than females to recently use alcohol. A series of odds ratios revealed that frequent church attendance, making good grades, and having parents/teachers frequently talk and set/enforce rules regarding alcohol use were associated with decreased recent alcohol use. Frequent participation in risky behaviors was directly related to recent alcohol use. Ongoing parent, teacher, and school communication and the consistent setting and enforcement of rules should be encouraged. Findings may be beneficial to prevention specialists developing programs targeting Hispanic youth. Future studies should seek to identify specific activities within the family, school, and community that help deter alcohol use among this population.
Chloroform-induced oxidative stress in rat liver: Implication of metallothionein
Authors: Abbassi Riadh , Chamkhia Naoufel , Sakly Mohsen
Published: June 2010

Current studies evaluated the effect of acute and subacute exposure to chloroform (CHCl3) on rat liver and the implication of oxidative stress. For this purpose, different doses of CHCl3(150, 300 and 450 mg/kg bw) were administered intraperitoneally (ip) to male Wistar rats. Malondialdehyde (MDA), glutathione (GSH), reduced cytochrome c and metallothioneins (MTs) levels as well as the activities of catalase (CAT) and glutathione peroxidase (GPx) and the activities of the biochemical markers of hepatic injury (alanine transaminase [ALT] and aspartate transaminase [AST]) were determined. CHCl3did not cause a significant increase in hepatic lipid peroxidation. However, dose-dependant and/or time dependant effects of CHCl3were demonstrated on most of the oxidative stress parameters measured, namely the GSH depletion and the superoxide anion production. Acute exposure CHCl3increased the aminotransferase and GPx activities and reduced cytochrome c levels in a dose-dependant pattern. A well-combined dose-dependent and time-dependent effect of CHCl3on MT levels after acute and subacute exposure was noticed. Moreover, the increase of MT levels seems to be associated with the GSH depletion, indicating a possible role of the latter in MT synthesis. In conclusion, the superoxide anion production and the GSH depletion could be implicated in the mechanism of hepatotoxity of CHCl3and MTs seem to be a part of the antioxidant defense system against the oxidative damage caused by CHCl3in liver.
The Role of Auditing in Small, Private Family Firms: Is It About Quality and Credibility?
Authors: Niskanen Mervi , Karjalainen Jukka , Niskanen Jyrki
Published: June 2010

The authors present empirical evidence of how family ownership and control affect the demand for audit quality measured by audit firm size in a sample of small private firms. The results indicate that family-held or -controlled firms are less likely to use Big 4 auditors than nonfamily firms and that an increase in family ownership decreases the likelihood of a Big 4 audit. The results imply that the less concentrated family ownership is, the more need there is for outside control mechanisms because of higher agency costs. The results imply that family influence increases firms’ incentives to employ Big 4 audit firms, thereby increasing the credibility of their financial statements vis-à-vis outside stakeholders.
Devastatingly Human: An Analysis of Registered Nurses’ Medication Error Accounts
Authors: Treiber Linda A. , Jones Jackie H.
Published: June 2010

Despite many safeguards, nurses make the majority of medication administration errors. The purpose of our research was to investigate the perceived causes for such errors and to better understand how nurses deal with them. We performed an interpretive analysis of 158 accounts by nurses who made self-identified medication errors. We found common themes among these accounts. First, although nurses admitted responsibility for errors, they simultaneously identified a variety of external contributing factors. Second, nurses’ accounts were often framed in terms of “being new,” with the underlying background expectancy of inexperience. Third, emotionally devastating visceral responses to errors were common and often incongruent with error severity. Fourth, nurses had to deal with fear. Fifth, nurses voiced frustrations with technologies and regulations. Sixth, embedded within many of the accounts was a “lessons learned” theme, through which nurses developed “personal rules” as a result of an error. We conclude with suggestions for additional research.
Effects of High Glucose and Ketosis (Acetoacetate, ß-Hydroxybutyrate) on PAI-1 Secretion in Human Umbilical Vascular Endothelial Cells
Authors: Velusamy Thirunavukkarasu , Jain Sushil. K.
Published: June 2010

Plasminogen activator inhibitor 1 (PAI-1) is a known contributor of thrombus formation and cardiovascular diseases. Type 1 diabetes is associated with elevated levels of blood PAI-1 and cardiovascular disease (CVD) incidence. However, type 1 diabetic patients have elevated blood levels of ketone bodies acetoacetate (AA) and 3-β-hydroxybutyrate (BHB). This study examined the hypothesis that hyperketonemia (ketosis) contributes to increased secretion of PAI-1 from the cells that form the vascular endothelium. Human umbilical vein endothelial cells (HUVEC) were treated with different concentrations of AA or BHB in the presence or absence of high glucose (HG) and the amount of PAI-1 protein secreted by these cells into conditioned media was determined. Levels of PAI-1 secreted into conditioned media by these treated cells did not change significantly when compared to controls. High glucose induced a significant increase in PAI-1 secretion, but combination with AA or BHB did not cause significant effects on PAI-1 secretion caused by HG. These results indicate that hyperglycemia but not hyperketonemia is a significant contributor to increased blood levels of PAI-1 associated with type 1 diabetes.
Congenital Thrombophilia and Central Venous Catheter-Related Thrombosis in Patients With Cancer
Authors: Boersma Rinske S. , Hamulyak Karly , Hugo Ten Cate  , Schouten Harry C.
Published: June 2010

Central venous catheter (CVC)-related thrombosis is a frequently occurring complication and may cause significant morbidity in patients with cancer. The aim of this review is to discuss the main studies that examined whether a state of thrombophilia increases the risk of CVC-related thrombosis in patients with cancer. The studies were retrieved by an extensive Medline search. Patients with cancer with a CVC and a factor V Leiden mutation have a higher risk of developing CVC-related thrombosis than patients with cancer having a CVC without the mutation. The scarce information available suggests hyperhomocysteinemia to be a risk factor for CVC-related thrombosis. For other congenital thrombophilia factors, the available data are too limited to allow for any definitive conclusions to be made. Because the clinical implications of all these findings remain to be clarified, routine screening of patients with cancer having a CVC for thrombophilia cannot yet be recommended on the basis of the studies discussed.
Optimal design and analysis of phase I/II clinical trials in multiple sclerosis with gadolinium-enhanced lesions as the endpoint
Authors: Healy Brian C , Ikle David , Macklin Eric A , Cutter Gary
Published: June 2010

Many phase I/II clinical trials in multiple sclerosis use gadolinium-enhanced lesions as the outcome measure. The best scanning interval and analysis for this outcome has not been determined. The objective of this study was to compare timing schemes and analysis techniques in terms of power for phase I/II clinical trials. Data were simulated under four scenarios assuming a negative binomial distribution for the number of new lesions and an exponential distribution for the duration of enhancement. The first scenario assumed an immediate treatment effect on the number of new lesions, while the second scenario assumed a delayed treatment effect. The third scenario assumed a higher proportion of patients had no new lesions, and the final scenario assumed an immediate treatment effect on the duration of enhancement. For each scenario, power for a six-month trial with 100 patients per arm was calculated using 10 analysis strategies. The scanning intervals tested were monthly scans, bimonthly scans and a single end-of-study scan. In addition, cost-effectiveness of each trial design and analysis was compared. Negative binomial regression models for the total number of new lesions were the most powerful analyses under an immediate treatment effect, and repeated measures models with a categorical time effect were the most powerful analyses under a delayed treatment effect. Although monthly scans generally provided most power, this design was also most costly. Designs with fewer scans per patient provide similar power and are more cost-effective. Negative binomial regression models are more powerful than non-parametric approaches.
Drag Queens and Drag Kings: The Difference Gender Makes
Authors: Rupp Leila J. , Taylor Verta , Shapiro Eve Ilana
Published: June 2010

In this article, we use case studies of two different drag performance collectives, the 801 Girls, a drag queen troupe in Key West, Florida, and the Disposable Boy Toys, a political feminist collective in Santa Barbara, California, to explore the differences between drag queens and drag kings. We argue that, despite their divergent routes to performing drag and the different contexts and styles of their shows, a similar critique of hegemonic gender and heteronormativity emerges from their performances. As the first systematic comparison of drag queens and drag kings, this article enhances our understanding of the gendered dynamics of drag.
Sexual Ethics and Young Women’s Accounts of Heterosexual Casual Sex
Authors: Beres Melanie A. , Farvid Panteá
Published: June 2010

Drawing on Foucault’s work on sexuality and ethics we explore young women’s accounts of heterosexual casual sex experiences in Canada and New Zealand. We focus on what Foucault calls ‘ rapport à soi ’ (the relationship one has with one’s self) to explore reports of implied ethical (and less than ethical) practices of casual sex. To do this we conducted a theoretical thematic analysis of the women’s accounts to identify accounts of ‘ care for the self ’, ‘ self-reflection’, and ‘ care for the other’. In our analysis we draw on previous feminist theorizing on heterosexuality to demonstrate how gendered heteronormative discourses are implicated in, and at times impede, an ‘ethics of casual sex’. We argue that women’s expressions of sexual ethics are particularly constrained considering gendered power relations as they relate to heternormative sexual practices. We suggest that the cultivation of ethical sexual subjectivities offer radical potential for the subversion of dominant heterosexual discourses.
Structural health monitoring of a dragline cluster using the hot spot stress method
Authors: Joshi Suraj , Mashiri Fidelis R , Dayawansa Daya P , Zhao X-L. , Price John WH
Published: June 2010

‘Hot spot stress’ is an approach often used to consider fatigue loadings in heavily welded tubular joints. This article reports the determination of hot spot stresses in mining dragline booms, which are often ≥100 m in length, using strain gage measurements and finite element analysis (FEA) modeling as part of a structural health monitoring concept. Strain gages were installed on a typical A11 cluster for estimating hot spot stresses, as recommended in the existing fatigue design guidelines by the International Institute of Welding (IIW) and the International Committee for the Development and Study of Tubular Construction (CIDECT). The results from the experimental measurements and the FEA were found to be comparable to a large measure. It was concluded that while hot spot stresses were high enough at the weld toes to cause cracking, they could not explain the cracking that occurs at the welds in the main chords on their own. Issues in comparing theoretical and experimental measurements are discussed.
Practitioner-Recommended Policies and Procedures for Children Exposed to Domestic Violence
Authors: Black Sally , Dempsey Sandra H. , Davis Martha B.
Published: June 2010

Children exposed to domestic violence experience higher rates of psychosocial, behavioral, and physical problems. Current policy recommendations are that health care providers offer regular screening and treatment for childhood exposure to domestic violence (CEDV). However, screening recommendations have been slow to take hold. The purpose of this study was to identify recommended practices of CEDV, as reported by practitioners. Interviews were held with 24 experienced service providers from 14 agencies. Respondents provided practical suggestions for CEDV screening and intervention. Suggestions included refinement of screening tools for maximum validity and reliability, improved integration of DV education into medical training and practice, on-site DV resources in pediatric settings, and establishment of formal partnerships between human service organizations that promoted ongoing collaborative activities. Next steps are to evaluate outcomes for evidence-based practice.
Needlescopy-assisted resection of pulmonary nodule after dual localisation
Authors: Kang D-Y. , Kim H.K. , Kim Y.K. , Yong H.S. , Kang E-Y. , Choi Y.H.
Published: June 2010

The aim of this study was to evaluate the feasibility of dual localisation with hookwire and lipiodol before needlescopy-assisted resection for pulmonary nodule.

Computed tomography-guided dual marking was performed on 36 pulmonary nodules of 32 patients and needlescopy-assisted resection was performed monitored by C-arm fluoroscopy.

The mean age of the patients was 58±12 (range 12–77) yrs. The mean size of the nodules was 7.5±3.7 (3–17) mm. Their mean distance from the pleural surface was 7.3±7.5 (0–35) mm. There were nine pure ground-glass opacity lesions, five semi-solid lesions and 22 solid lesions. The time of the dual localisation procedure was 13.1±4.8 (7–23) min. Complications of the marking were pneumothorax in nine patients, and intrapulmonary bleeding in three. One hookwire dislodged during the operation. All nodules were successfully resected under needlescopy without conversion to a conventional thoracoscopy (5 mm or 10 mm thoracoscopy) or a minithoracotomy. There was no complication related to needlescopy-assisted resection.

Dual marking with hookwire and lipiodol is a safe and none time consuming procedure, and needlescopy-assisted lung resection for small nodules is technically feasible and useful for histological diagnosis and treatment.
Asthma Control Questionnaire in children: validation, measurement properties, interpretation
Authors: Juniper E.F. , Gruffydd-Jones K. , Ward S. , Svensson K.
Published: June 2010

The Asthma Control Questionnaire (ACQ) has been validated in adults to measure the primary goal of management (minimisation of symptoms, activity limitations, short-acting β2-agonist use and airway narrowing). The present study evaluated the validity, measurement properties and interpretability of the ACQ in children aged 6–16 yrs.

35 children attended clinic on three occasions (0, 1 and 4 weeks) and completed the ACQ, Mini Paediatric Asthma Quality of Life Questionnaire and the Royal College of Physicians’ “Three Questions”. Parents completed the Paediatric Asthma Caregiver’s Quality of Life Questionnaire. Between visits, children completed the Asthma Control Diary and measured peak expiratory flow. At weeks 1 and 4, clinicians and parents completed Global Rating of Change Questionnaires.

All patients completed the study. 19 children were stable between two assessments and provided evidence of good test–retest reliability (intraclass correlation coefficient 0.79). The ACQ was responsive to change in asthma control (p = 0.026) and the mean±sdMinimal Important Difference was 0.52±0.45. Both cross-sectional and longitudinal correlations between the ACQ and the other outcomes were close to predicted and provided evidence that the ACQ measures asthma control in children.

The ACQ has strong measurement properties and is valid for use in children aged 6–16 yrs. In children aged 6–10 yrs, it must be administered by a trained interviewer.
Enhancement of tolerance development to morphine in rats prenatally exposed to morphine, methadone, and buprenorphine
Authors: Chiang Yao-Chang , Hung Tsai-Wei , Lee Cynthia Wei-Sheng , Yan Jia-Ying , Ho Ing-Kang
Published: June 2010

Background

Abuse of addictive substances is a serious problem that has a significant impact on areas such as health, the economy, and public safety. Heroin use among young women of reproductive age has drawn much attention around the world. However, there is a lack of information on effects of prenatal exposure to opioids on their offspring. In this study, an animal model was established to study effects of prenatal exposure to opioids on offspring.

Methods

Female pregnant Sprague-Dawley rats were sub-grouped to receive (1) vehicle, (2) 2-4 mg/kg morphine (1 mg/kg increment per week), (3) 7 mg/kg methadone, and (4) 3 mg/kg buprenorphine, subcutaneously, once or twice a day from E3 to E20. The experiments were conducted on animals 8-12 weeks old and with body weight between 250 and 350 g.

Results

Results showed that prenatal exposure to buprenorphine caused higher mortality than other tested substance groups. Although we observed a significantly lower increase in body weight in all of the opioid-administered dams, the birth weight of the offspring was not altered in all treated groups. Moreover, no obvious behavioral abnormality or body-weight difference was noted during the growing period (8-12 weeks) in all offspring. When the male offspring received morphine injection twice a day for 4 days, the prenatally opioid-exposed rats more quickly developed a tolerance to morphine (as shown by the tail-flick tests), most notably the prenatally buprenorphine-exposed offspring. However, the tolerance development to methadone or buprenorphine was not different in offspring exposed prenatally to methadone or buprenorphine, respectively, when compared with that of the vehicle controlled group. Similar results were also obtained in the female animals.

Conclusions

Animals prenatally exposed to morphine, methadone, or buprenorphine developed tolerance to morphine faster than their controlled mates. In our animal model, prenatal exposure to buprenorphine also resulted in higher mortality and much less sensitivity to morphine-induced antinociception than prenatal exposure to morphine or methadone. This indicates that buprenorphine in higher doses may not be an ideal maintenance drug for treating pregnant women. This study provides a reference in selecting doses for clinical usage in treating pregnant heroin addicts.
Postnatal development of collagen structure in ovine articular cartilage
Authors: van Turnhout Mark C , Schipper Henk , Engel Bas , Buist Willem , Kranenbarg Sander , van Leeuwen Johan L
Published: June 2010

Background

Articular cartilage (AC) is the layer of tissue that covers the articulating ends of the bones in diarthrodial joints. Across species, adult AC shows an arcade-like structure with collagen predominantly perpendicular to the subchondral bone near the bone, and collagen predominantly parallel to the articular surface near the articular surface. Recent studies into collagen fibre orientation in stillborn and juvenile animals showed that this structure is absent at birth. Since the collagen structure is an important factor for AC mechanics, the absence of the adult Benninghoff structure has implications for perinatal AC mechanobiology. The current objective is to quantify the dynamics of collagen network development in a model animal from birth to maturity. We further aim to show the presence or absence of zonal differentiation at birth, and to assess differences in collagen network development between different anatomical sites of a single joint surface. We use quantitative polarised light microscopy to investigate properties of the collagen network and we use the sheep (Ovis aries) as our model animal.

Results

Predominant collagen orientation is parallel to the articular surface throughout the tissue depth for perinatal cartilage. This remodels to the Benninghoff structure before the sheep reach sexual maturity. Remodelling of predominant collagen orientation starts at a depth just below the future transitional zone. Tissue retardance shows a minimum near the articular surface at all ages, which indicates the presence of zonal differentiation at all ages. The absolute position of this minimum does change between birth and maturity. Between different anatomical sites, we find differences in the dynamics of collagen remodelling, but no differences in adult collagen structure.

Conclusions

The collagen network in articular cartilage remodels between birth and sexual maturity from a network with predominant orientation parallel to the articular surface to a Benninghoff network. The retardance minimum near, but not at, the articular surface at all ages shows that a zonal differentiation is already present in the perinatal animals. In these animals, the zonal differentiation can not be correlated to the collagen network orientation. We find no difference in adult collagen structure in the nearly congruent metacarpophalangeal joint, but we do find differences in the dynamics of collagen network remodelling.
Genotype and expression analysis of two inbred mouse strains and two derived congenic strains suggest that most gene expression is trans regulated and sensitive to genetic background
Authors: Noyes Harry A , Agaba Morris , Anderson Susan , Archibald Alan L , Brass Andy , Gibson John , Hall Laurence , Hulme Helen , Oh Sung Jong , Kemp Stephen
Published: June 2010

Background

Differences in gene expression may be caused by nearby DNA polymorphisms (cis regulation) or by interactions of gene control regions with polymorphic transcription factors (trans regulation). Trans acting loci are much harder to detect than cis acting loci and their effects are much more sensitive to genetic background.

Results

To quantify cis and trans regulation we correlated haplotype data with gene expression in two inbred mouse strains and two derived congenic lines. Upstream haplotype differences between the parental strains suggested that 30-43% of differentially expressed genes were differentially expressed because of cis haplotype differences. These cis regulated genes displayed consistent and relatively tissue-independent differential expression. We independently estimated from the congenic mice that 71-85% of genes were trans regulated. Cis regulated genes were associated with low p values (p < 0.005) for differential expression, whereas trans regulated genes were associated with values 0.005 < p < 0.05. The genes differentially expressed between congenics and controls were not a subset of those that were differentially expressed between the founder lines, showing that these were dependent on genetic background. For example, the cholesterol synthesis pathway was strongly differentially expressed in the congenic mice by indirect trans regulation but this was not observable in the parental mice.

Conclusions

The evidence that most gene regulation is trans and strongly influenced by genetic background, suggests that pathways that are modified by an allelic variant, may only exhibit differential expression in the specific genetic backgrounds in which they were identified. This has significant implications for the interpretation of any QTL mapping study.
Resistance loci affecting distinct stages of fungal pathogenesis: use of introgression lines for QTL mapping and characterization in the maize - Setosphaeria turcicapathosystem
Authors: Chung Chia-Lin , Longfellow Joy M , Walsh Ellie K , Kerdieh Zura , Van Esbroeck George , Balint-Kurti Peter , Nelson Rebecca J
Published: June 2010

Background

Studies on host-pathogen interactions in a range of pathosystems have revealed an array of mechanisms by which plants reduce the efficiency of pathogenesis. While R-gene mediated resistance confers highly effective defense responses against pathogen invasion, quantitative resistance is associated with intermediate levels of resistance that reduces disease progress. To test the hypothesis that specific loci affect distinct stages of fungal pathogenesis, a set of maize introgression lines was used for mapping and characterization of quantitative trait loci (QTL) conditioning resistance to Setosphaeria turcica, the causal agent of northern leaf blight (NLB). To better understand the nature of quantitative resistance, the identified QTL were further tested for three secondary hypotheses: (1) that disease QTL differ by host developmental stage; (2) that their performance changes across environments; and (3) that they condition broad-spectrum resistance.

Results

Among a set of 82 introgression lines, seven lines were confirmed as more resistant or susceptible than B73. Two NLB QTL were validated in BC4F2 segregating populations and advanced introgression lines. These loci, designated qNLB1.02 and qNLB1.06, were investigated in detail by comparing the introgression lines with B73 for a series of macroscopic and microscopic disease components targeting different stages of NLB development. Repeated greenhouse and field trials revealed that qNLB1.06

Tx303
(the Tx303 allele at bin 1.06) reduces the efficiency of fungal penetration, while qNLB1.02

B73
(the B73 allele at bin 1.02) enhances the accumulation of callose and phenolics surrounding infection sites, reduces hyphal growth into the vascular bundle and impairs the subsequent necrotrophic colonization in the leaves. The QTL were equally effective in both juvenile and adult plants; qNLB1.06

Tx303
showed greater effectiveness in the field than in the greenhouse. In addition to NLB resistance, qNLB1.02

B73
was associated with resistance to Stewart's wilt and common rust, while qNLB1.06

Tx303
conferred resistance to Stewart's wilt. The non-specific resistance may be attributed to pleiotropy or linkage.

Conclusions

Our research has led to successful identification of two reliably-expressed QTL that can potentially be utilized to protect maize from S. turcica in different environments. This approach to identifying and dissecting quantitative resistance in plants will facilitate the application of quantitative resistance in crop protection.
Combined effect of regulatory polymorphisms on transcription of UGT1A1 as a cause of Gilbert syndrome
Authors: Matsui Katsuyuki , Maruo Yoshihiro , Sato Hiroshi , Takeuchi Yoshihiro
Published: June 2010

Background

Gilbert syndrome is caused by defects in bilirubin UDP-glucuronosyltransferase (UGT1A1). The most common variation believed to be involved is A(TA)7TAA. Although several polymorphisms have been found to link with A(TA)7TAA, the combined effect of regulatory polymorphisms in the development of Gilbert syndrome remains unclear.

Methods

In an analysis of 15 patients and 60 normal subjects, we detected 14 polymorphisms and nine haplotypes in the regulatory region. We classified the 4-kbp regulatory region of the patients into: the TATA box including A(TA)7TAA; a phenobarbital responsive enhancer module including c.-3275T>G; and a region including other ten linked polymorphisms. The effect on transcription of these polymorphisms was studied.

Results

All haplotypes with A(TA)7TAA had c.-3275T>G and additional polymorphisms. In an in-vitro expression study of the 4-kbp regulatory region, A(TA)7TAA alone did not significantly reduce transcription. In contrast, c.-3275T>G reduced transcription to 69% of that of wild type, and the linked polymorphisms reduced transcription to 88% of wild type. Transcription of the typical regulatory region of the patients was 56% of wild type. Co-expression of constitutive androstane receptor (CAR) increased the transcription of wild type by a factor of 4.3. Each polymorphism by itself did not reduce transcription to the level of the patients, however, even in the presence of CAR.

Conclusions

These results imply that co-operation of A(TA)7TAA, c.-3275T>G and the linked polymorphisms is necessary in causing Gilbert syndrome.
Nosocomial methicillin-resistant Staphylococcus aureus (MRSA) bacteremia in Taiwan: Mortality analyses and the impact of vancomycin, MIC = 2 mg/L, by the broth microdilution method
Authors: Wang Jiun-Ling , Wang Jann-Tay , Sheng Wang-Huei , Chen Yee-Chun , Chang Shan-Chwen
Published: June 2010

Background

Previous studies regarding the prognosis of patients infected with MRSA isolates characterized by a high minimum inhibitory concentration (MIC) for vancomycin have generally used a commercial Etest. Little research has been conducted on determining the vancomycin susceptibility of MRSA using a reference microdilution. Additionally, there is discordance between the MIC result from an Etest and the value determined using the reference microdilution method.

Methods

Using a reference microdilution method, we determined the MIC of vancomycin for isolates from 123 consecutive patients with nosocomial MRSA bacteremia. The clinical features and outcome for these patients were recorded and the MRSA isolates were genotyped.

Results

Among the 123 non-duplicated isolates, 21.1% had a MIC = 2 mg/L, 76.4% had a MIC = 1 mg/L and 2.4% had MIC = 0.5 mg/L. Patients with MRSA bacteremia in the ICU or those who had been hospitalized for a long time were more likely to be infected with strains of high vancomycin MIC MRSA (MIC = 2 mg/L; p < 0.05). Cox regression analysis demonstrated that the high MIC group had a significantly higher 30-day mortality than the low MIC group (HR: 2.39; 95% CI: 1.20-4.79; p = 0.014). Multivariate analyses indicated that the presence of high MIC isolates, pneumonia, post-cardiothoracic surgery and a high Charlson comorbidity index were all independent predictors of a 30-day mortality. Genotyping of these high vancomycin MIC isolates demonstrated that SCCmec III, spa type037, was the predominant strain (> 80%). The rates of resistance to trimethoprim/sulfamethoxazole, gentamicin, levofloxacin, rifampin and tetracycline were also higher in the high MIC group than in the isolates belonging to low MIC group (p < 0.05).

Conclusions

In a high vancomycin MIC group in Taiwan, SCCmec III, spa type t037, was the predominant strain of MRSA identified. Patients with MRSA bacteremia in the ICU or who had prolonged hospitalization were more likely to be infected with S. aureus strains with high vancomycin MICs. The mortality rate was higher among patients infected with these strains compared to patients infected with low MIC strains.
High-throughput miRNA profiling of human melanoma blood samples
Authors: Leidinger Petra , Keller Andreas , Borries Anne , Reichrath Jörg , Rass Knuth , Jager Sven U , Lenhof Hans-Peter , Meese Eckart
Published: June 2010

Background

MicroRNA (miRNA) signatures are not only found in cancer tissue but also in blood of cancer patients. Specifically, miRNA detection in blood offers the prospect of a non-invasive analysis tool.

Methods

Using a microarray based approach we screened almost 900 human miRNAs to detect miRNAs that are deregulated in their expression in blood cells of melanoma patients. We analyzed 55 blood samples, including 20 samples of healthy individuals, 24 samples of melanoma patients as test set, and 11 samples of melanoma patients as independent validation set.

Results

A hypothesis test based approch detected 51 differentially regulated miRNAs, including 21 miRNAs that were downregulated in blood cells of melanoma patients and 30 miRNAs that were upregulated in blood cells of melanoma patients as compared to blood cells of healthy controls. The tets set and the independent validation set of the melanoma samples showed a high correlation of fold changes (0.81). Applying hierarchical clustering and principal component analysis we found that blood samples of melanoma patients and healthy individuals can be well differentiated from each other based on miRNA expression analysis. Using a subset of 16 significant deregulated miRNAs, we were able to reach a classification accuracy of 97.4%, a specificity of 95% and a sensitivity of 98.9% by supervised analysis. MiRNA microarray data were validated by qRT-PCR.

Conclusions

Our study provides strong evidence for miRNA expression signatures of blood cells as useful biomarkers for melanoma.
Methylthioadenosine (MTA) inhibits melanoma cell proliferation and in vivotumor growth
Authors: Andreu-Pérez Pedro , Hernandez-Losa Javier , Moliné Teresa , Gil Rosa , Grueso Judit , Pujol Anna , Cortés Javier , Avila Matias A , Recio Juan A
Published: June 2010

Background

Melanoma is the most deadly form of skin cancer without effective treatment. Methylthioadenosine (MTA) is a naturally occurring nucleoside with differential effects on normal and transformed cells. MTA has been widely demonstrated to promote anti-proliferative and pro-apoptotic responses in different cell types. In this study we have assessed the therapeutic potential of MTA in melanoma treatment.

Methods

To investigate the therapeutic potential of MTA we performed in vitro proliferation and viability assays using six different mouse and human melanoma cell lines wild type for RAS and BRAF or harboring different mutations in RAS pathway. We also have tested its therapeutic capabilities in vivo in a xenograft mouse melanoma model and using variety of molecular techniques and tissue culture we investigated its anti-proliferative and pro-apoptotic properties.

Results

In vitro experiments showed that MTA treatment inhibited melanoma cell proliferation and viability in a dose dependent manner, where BRAF mutant melanoma cell lines appear to be more sensitive. Importantly, MTA was effective inhibiting in vivo tumor growth. The molecular analysis of tumor samples and in vitro experiments indicated that MTA induces cytostatic rather than pro-apoptotic effects inhibiting the phosphorylation of Akt and S6 ribosomal protein and inducing the down-regulation of cyclin D1.

Conclusions

MTA inhibits melanoma cell proliferation and in vivo tumor growth particularly in BRAF mutant melanoma cells. These data reveal a naturally occurring drug potentially useful for melanoma treatment.
Insulin resistance and its association with the components of the metabolic syndrome among obese children and adolescents
Authors: Juárez-López Carlos , Klünder-Klünder Miguel , Medina-Bravo Patricia , Madrigal-Azcárate Adrián , Mass-Díaz Eliezer , Flores-Huerta Samuel
Published: June 2010

Background

Insulin resistance is the primary metabolic disorder associated with obesity; yet little is known about its role as a determinant of the metabolic syndrome in obese children. The aim of this study is to assess the association between the degree of insulin resistance and the different components of the metabolic syndrome among obese children and adolescents.

Methods

An analytical, cross-sectional and population-based study was performed in forty-four public primary schools in Campeche City, Mexico. A total of 466 obese children and adolescents between 11-13 years of age were recruited. Fasting glucose and insulin concentrations, high density lipoprotein cholesterol, triglycerides, waist circumference, systolic and diastolic blood pressures were measured; insulin resistance and metabolic syndrome were also evaluated.

Results

Out of the total population studied, 69% presented low values of high density lipoprotein cholesterol, 49% suffered from abdominal obesity, 29% had hypertriglyceridemia, 8% presented high systolic and 13% high diastolic blood pressure, 4% showed impaired fasting glucose, 51% presented insulin resistance and 20% metabolic syndrome. In spite of being obese, 13% of the investigated population did not present any metabolic disorder. For each one of the components of the metabolic syndrome, when insulin resistance increased so did odds ratios as cardiometabolic risk factors.

Conclusions

Regardless of age and gender an increased degree of insulin resistance is associated with a higher prevalence of disorders in each of the components of the metabolic syndrome and with a heightened risk of suffering metabolic syndrome among obese children and adolescents.
Insights into the oral health beliefs and practices of mothers from a north London Orthodox Jewish community
Authors: Scambler Sasha , Klass Charlotte , Wright Desmond , Gallagher Jennifer E
Published: June 2010

Background

The objective of this study was to explore oral health knowledge and beliefs and access to dental care in a culturally distinct Orthodox Jewish community in North London, with a view to informing local health policy.

Methods

A dual method qualitative approach to data collection was adopted in this study utilising semi-structured face to face interviews and focus groups with women from this North London orthodox Jewish community. In total nine interviews and four focus groups were conducted with a purposive sample of thirty three mothers from the community aged 21-58 years. The data were transcribed and analysed using Framework Methodology

Results

Cultural influences, competing pressures and perceptions of hereditary influences, together with a lack of contemporary oral health knowledge are the main factors affecting oral health knowledge and beliefs. This supported an overall perspective of disempowerment or a perceived lack of control over oral health behaviours, both for mothers and their children. Community signposting pointed mothers to dental services, whilst family pressures together with inadequate capacity and capability and generic barriers such as fear and cost acted as barriers. Mothers from this community welcomed community development initiatives from the NHS.

Conclusions

The results of this study provide insight into the challenges of a culturally isolated community who would welcome community support through schools and expanded culturally appropriate opening hours to improve access to dental care.