bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunomodulatory effects of HSV-2 infection on immature macaque dendritic cells modify innate and adaptive responses
Authors: Peretti Silvia , Shaw Andrew , Blanchard James , Bohm Rudolf , Morrow Gavin , Lifson Jeffrey D. , Gettie Agegnehu , Pope Melissa 
Published: April 2005

AbstractHerpes simplex viruses (HSV) infect human and murine dendritic cells (DCs) and interfere with their immunostimulatory functions in culture. HSV-2 infection increases human immunodeficiency virus (HIV) spread in patients, and DCs also promote HIV infection. We have studied these topics in rhesus macaque monocyte-derived DCs (moDCs) to set the stage for future studies of these issues in animals. We provide the first evidence that macaque DCs become infected by HSV-2. Structural viral proteins (ICP5 [infected cell protein 5], glycoprotein D [gD], envelope) were detected in the cell periphery, and a functional protein (infected cell protein 8 [ICP8]) was predominantly found in the nucleus after infection. Infectious HSV-2 induced apoptotic death, decreased expression of HLA-DR, CD40, CD80, CD83, and CD86, and increased release of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), macrophage inflammatory protein-1α (MIP-1α) (CCL3), and RANTES (regulated on activation normal T cells expressed and secreted) (CCL5) but not IL-12 or interferon-α (IFN-α) by macaque DCs. This coincided with HSV-2–infected DCs stimulating weak T-cell responses, including impaired SIV-specific responses. Comparable HSV-2 protein expression, DC apoptosis, as well as membrane immunophenotype and functional modifications were observed in HSV-2–exposed human moDCs. Such HSV-2–induced modifications of macaque and human DCs could augment DC-driven immunodeficiency virus infection. This work affords the basis for future macaque studies to explore how HSV-2 impacts the efficacy of strategies being developed to prevent HIV transmission.
BK DNA viral load in plasma: evidence for an association with hemorrhagic cystitis in allogeneic hematopoietic cell transplant recipients
Authors: Erard Veronique , Kim Hyung Woo , Corey Lawrence , Limaye Ajit , Huang Meei-Li , Myerson David , Davis Chris , Boeckh Michael 
Published: April 2005

AbstractWe performed a case-control study to determine the association of BK plasma viremia with hemorrhagic cystitis (HC) in hematopoietic cell transplant (HCT) recipients. Thirty cases of HC (14 of which occurred after platelet engraftment with documented BK viruria [BK-HC]) were compared with matched controls. Weekly plasma samples were tested for BK virus DNA by polymerase chain reaction (PCR). BK viremia detected before or during the disease was independently associated with HC (adjusted odds ratio = 30, P &lt; .001); BK viremia was even important before clinical symptoms of HC occurred (odds ratio = 11, P &lt; .001). Cases of HC and BK-HC had a significantly higher peak of BK plasma viral load than controls. BK virus was detected by in situ hybridization in bladder biopsies of 2 cases with severe HC and long-lasting BK viremia. BK virus seems to play a role in the development of HC and quantitative detection of BK DNA in plasma appears to be a marker of BK virus disease in HCT recipients.
Human physiologically based pharmacokinetic model for propofol
Authors: Levitt David G , Schnider Thomas W 
Published: April 2005

Abstract
Background
Propofol is widely used for both short-term anesthesia and long-term sedation. It has unusual pharmacokinetics because of its high lipid solubility. The standard approach to describing the pharmacokinetics is by a multi-compartmental model. This paper presents the first detailed human physiologically based pharmacokinetic (PBPK) model for propofol.

Methods
PKQuest, a freely distributed software routine http://www.pkquest.com, was used for all the calculations. The "standard human" PBPK parameters developed in previous applications is used. It is assumed that the blood and tissue binding is determined by simple partition into the tissue lipid, which is characterized by two previously determined set of parameters: 1) the value of the propofol oil/water partition coefficient; 2) the lipid fraction in the blood and tissues. The model was fit to the individual experimental data of Schnider et. al., Anesthesiology, 1998; 88:1170 in which an initial bolus dose was followed 60 minutes later by a one hour constant infusion.

Results
The PBPK model provides a good description of the experimental data over a large range of input dosage, subject age and fat fraction. Only one adjustable parameter (the liver clearance) is required to describe the constant infusion phase for each individual subject. In order to fit the bolus injection phase, for 10 or the 24 subjects it was necessary to assume that a fraction of the bolus dose was sequestered and then slowly released from the lungs (characterized by two additional parameters). The average weighted residual error (WRE) of the PBPK model fit to the both the bolus and infusion phases was 15%; similar to the WRE for just the constant infusion phase obtained by Schnider et. al. using a 6-parameter NONMEM compartmental model.

Conclusion
A PBPK model using standard human parameters and a simple description of tissue binding provides a good description of human propofol kinetics. The major advantage of a PBPK model is that it can be used to predict the changes in kinetics produced by variations in physiological parameters. As one example, the model simulation of the changes in pharmacokinetics for morbidly obese subjects is discussed.
Frequency of alcohol use and obesity in community medicine patients
Authors: Rohrer James E , Rohland Barbara M , Denison Anne , Way Anthony 
Published: April 2005

AbstractBackgroundObesity is an important public health problem. However, the effects of alcohol use on the risk for obesity have not been thoroughly explored. This study focuses on how frequency of alcohol use is related to the risk of obesity in a community medicine clinic population.MethodsThis study used a cross-sectional survey to test the hypothesis that obesity (BMI > 30) is associated with alcohol use. The convenience sample was drawn from three clinics that primarily serve low-income populations. Independent variables included frequency of alcohol use, frequency of binge drinking, demographic characteristics, health behaviors and health status.ResultsIn comparison to non-drinkers, people who consumed alcohol 3 or more days per month had lower odds of being obese (Adjusted Odds Ratio = .49, p < .04). As expected, there was a significant association between watching eight or more hours of television per day and obesity (AOR = 2.34, p < .01).ConclusionMore frequent drinking and less television time are independently associated with reduced odds of obesity in this sample of community medicine patients. Additional research is needed to isolate casual mechanisms.
Rationale, design and conduct of a comprehensive evaluation of a school-based peer-led anti-smoking intervention in the UK: the ASSIST cluster randomised trial [ISRCTN55572965]
Authors: Starkey Fenella , Moore Laurence , Campbell Rona , Sidaway Mark , Bloor Michael ,   ASSIST (A Stop Smoking In Schools Trial)
Published: April 2005

Abstract

Background
To date, no school-based intervention has been proven to be effective in preventing adolescent smoking, despite continuing concern about smoking levels amongst young people in the United Kingdom. Although formal teacher-led smoking prevention interventions are considered unlikely to be effective, peer-led approaches to reducing smoking have been proposed as potentially valuable.

Methods/design
ASSIST (A Stop Smoking in Schools Trial) is a comprehensive, large-scale evaluation to rigorously test whether peer supporters in Year 8 (age 11–12) can be recruited and trained to effect a reduction in smoking uptake among their fellow students. The evaluation is employing a cluster randomised controlled trial (RCT) design with secondary school as the unit of randomisation, and is being undertaken in 59 schools in South East Wales and the West of England. Embedded within the trial are an economic evaluation of the intervention costs, a process evaluation to provide detailed information on how the intervention was delivered and received, and an analysis of social networks to consider whether such a peer group intervention could work amongst schoolchildren in this age group.
Schools were randomised to either continue with normal smoking education (n = 29 schools, 5562 students), or to do so and additionally receive the ASSIST intervention (n = 30 schools, 5481 students). No schools withdrew once the trial had started, and the intervention was successfully implemented in all 30 schools, with excellent participation rates from the peer supporters. The primary outcome is regular (weekly) smoking, validated by salivary cotinine, and this outcome has been obtained for 94.4%, 91.0% and 95.6% of eligible students at baseline, immediate post-intervention, and one-year follow-up respectively.

Discussion
Comprehensive evaluations of complex public health interventions of this scale and nature are rare in the United Kingdom. This paper demonstrates the feasibility of conducting cluster RCTs of complex public health interventions in schools, and how the rigour of such designs can be maximised both by thorough implementation of the protocol and by broadening the scope of questions addressed in the trial by including additional evaluative components.
The effectiveness of extra corporeal shock wave therapy for plantar heel pain: a systematic review and meta-analysis
Authors: Thomson Colin E , Crawford Fay , Murray Gordon D 
Published: April 2005

Abstract

Background
There is considerable controversy regarding the effectiveness of extracorporeal shock wave therapy in the management of plantar heel pain. Our aim was to conduct a systematic review of randomised controlled trials to investigate the effectiveness of extracorporeal shock wave therapy and to produce a precise estimate of the likely benefits of this therapy.

Methods
We conducted a systematic review of all randomised controlled trials (RCTs) identified from the Cochrane Controlled trials register, MEDLINE, EMBASE and CINAHL from 1966 until September 2004. We included randomised trials which evaluated extracorporeal shock wave therapy used to treat plantar heel pain. Trials comparing extra corporeal shock wave therapy with placebo or different doses of extra corporeal shock wave therapy were considered for inclusion in the review. We independently applied the inclusion and exclusion criteria to each identified randomised controlled trial, extracted data and assessed the methodological quality of each trial.

Results
Six RCTs (n = 897) permitted a pooled estimate of effectiveness based on pain scores collected using 10 cm visual analogue scales for morning pain. The estimated weighted mean difference was 0.42 (95% confidence interval 0.02 to 0.83) representing less than 0.5 cm on a visual analogue scale. There was no evidence of heterogeneity and a fixed effects model was used.

Conclusion
A meta-analysis of data from six randomised-controlled trials that included a total of 897 patients was statistically significant in favour of extracorporeal shock wave therapy for the treatment of plantar heel pain but the effect size was very small. A sensitivity analysis including only high quality trials did not detect a statistically significant effect.
Reactions to treatment debriefing among the participants of a placebo controlled trial
Authors: Di Blasi Zelda , Crawford Fay , Bradley Colin , Kleijnen Jos 
Published: April 2005

Abstract
Background
A significant proportion of trial participants respond to placebos for a variety of conditions. Despite the common conduct of these trials and the strong emphasis placed on informed consent, very little is known about informing participants about their individual treatment allocation at trial closure. This study aims to address this gap in the literature by exploring treatment beliefs and reactions to feedback about treatment allocation in the participants of a placebo-controlled randomized clinical trial (RCT).

Methods
Survey of trial participants using a semi-structured questionnaire including close and open-ended questions administered as telephone interviews and postal questionnaires. Trial participants were enrolled in a double-blind placebo-controlled RCT evaluating the effectiveness of corticosteroid for heel pain (ISRCTN36539116). The trial had closed and participants remained blind to treatment allocation. We assessed treatment expectations, the percentage of participants who wanted to be informed about their treatment allocation, their ability to guess and reactions to debriefing.

Results
Forty-six (73%) contactable participants responded to our survey. Forty-two were eligible (four participants with bilateral disease were excluded as they had received both treatments). Most (79%) participants did not have any expectations prior to receiving treatment, but many 'hoped' that something would help. Reasons for not having high expectations included the experimental nature of their care and possibility that they may get a placebo. Participants were hopeful because their pain was so severe and because they trusted the staff and services. Most (83%) wanted to be informed about their treatment allocation and study results. Over half (55%) said they could not guess which treatment they had been randomized to, and many of those who attempted a guess were incorrect. Reactions to treatment debriefing were generally positive, including in placebo responders.

Conclusion
Our study suggests that most trial participants want to be informed about their treatment allocation and trial results. Further research is required to develop measure of hope and expectancy and to rigorously evaluate the effects of debriefing prospectively.
The Arabidopsis AtRaptor genes are essential for post-embryonic plant growth
Authors: Anderson Garrett H , Veit Bruce , Hanson Maureen R 
Published: April 2005

Abstract

Background

Flowering plant development is wholly reliant on growth from meristems, which contain totipotent cells that give rise to all post-embryonic organs in the plant. Plants are uniquely able to alter their development throughout their lifespan through the generation of new organs in response to external signals. To identify genes that regulate meristem-based growth, we considered homologues of Raptor proteins, which regulate cell growth in response to nutrients in yeast and metazoans as part of a signaling complex with the target of rapamycin (TOR) kinase.

Results

We identified AtRaptor1A and AtRaptor1B, two loci predicted to encode Raptor proteins in Arabidopsis. Disruption of AtRaptor1B yields plants with a wide range of developmental defects: roots are thick and grow slowly, leaf initiation and bolting are delayed and the shoot inflorescence shows reduced apical dominance. AtRaptor1A AtRaptor1B double mutants show normal embryonic development but are unable to maintain post-embryonic meristem-driven growth. AtRaptor transcripts accumulate in dividing and expanding cells and tissues.

Conclusion

The data implicate the TOR signaling pathway, a major regulator of cell growth in yeast and metazoans, in the maintenance of growth from the shoot apical meristem in plants. These results provide insights into the ways in which TOR/Raptor signaling has been adapted to regulate plant growth and development, and indicate that in plants, as in other eukaryotes, there is some Raptor-independent TOR activity.
Comparison of amplification enzymes for Hepatitis C Virus quasispecies analysis
Authors: Polyak Stephen J , Sullivan Daniel G , Austin Michael A , Dai James Y , Shuhart Margaret C , Lindsay Karen L , Bonkovsky Herbert L , Di Bisceglie Adrian M , Lee William M , Morishima Chihiro , Gretch David R ,   the HALT-C Trial Group
Published: April 2005

Abstract

Background
Hepatitis C virus (HCV) circulates as quasispecies (QS), whose evolution is associated with pathogenesis. Previous studies have suggested that the use of thermostable polymerases without proofreading function may contribute to inaccurate assessment of HCV QS. In this report, we compared non-proofreading (Taq) with proofreading (Advantage High Fidelity-2; HF-2) polymerases in the sensitivity, robustness, and HCV QS diversity and complexity in the second envelope glycoprotein gene hypervariable region 1 (E2-HVR1) on baseline specimens from 20 patients in the HALT-C trial and in a small cohort of 12 HCV/HIV co-infected patients. QS diversity and complexity were quantified using heteroduplex mobility assays (HMA).

Results
The sensitivities of both enzymes were comparable at 50 IU/ml, although HF-2 was more robust and slightly more sensitive than Taq. Both enzymes generated QS diversity and complexity scores that were correlated (r = 0.68; p < 0.0001, and r = 0.47; p < 0.01; Spearman's rank correlation). QS diversity was similar for both Taq and HF-2 enzymes, although there was a trend for higher diversity in samples amplified by Taq (p = 0.126). Taq amplified samples yielded complexity scores that were significantly higher than HF-2 samples (p = 0.033). HALT-C patients who were HCV positive or negative following 20 weeks of pegylated IFN plus ribavirin therapy had similar QS diversity scores for Taq and HF-2 samples, and there was a trend for higher complexity scores from Taq as compared with HF-2 samples. Among patients with HCV and HIV co-infection, HAART increased HCV QS diversity and complexity as compared with patients not receiving therapy, suggesting that immune reconstitution drives HCV QS evolution. However, diversity and complexity scores were similar for both HF-2 and Taq amplified specimens.

Conclusion
The data suggest that while Taq may overestimate HCV QS complexity, its use does not significantly affect results in cohort-based studies of HCV QS analyzed by HMA. However, the use of proofreading enzymes such as HF-2 is recommended for more accurate characterization of HCV QS in vivo.
Global health priorities – priorities of the wealthy?
Authors: Ollila Eeva 
Published: April 2005

AbstractHealth has gained importance on the global agenda. It has become recognized in forums where it was once not addressed. In this article three issues are considered: global health policy actors, global health priorities and the means of addressing the identified health priorities. I argue that the arenas for global health policy-making have shifted from the public spheres towards arenas that include the transnational for-profit sector. Global health policy has become increasingly fragmented and verticalized. Infectious diseases have gained ground as global health priorities, while non-communicable diseases and the broader issues of health systems development have been neglected. Approaches to tackling the health problems are increasingly influenced by trade and industrial interests with the emphasis on technological solutions.
Prenatal exposure to alcohol does not affect radial maze learning and hippocampal mossy fiber sizes in three inbred strains of mouse
Authors: Sluyter Frans , Jamot Laure , Bertholet Jean-Yves , Crusio Wim E 
Published: April 2005

Abstract

Background
The aim of this study was to investigate the effects of prenatal alcohol exposure on radial-maze learning and hippocampal neuroanatomy, particularly the sizes of the intra- and infrapyramidal mossy fiber (IIPMF) terminal fields, in three inbred strains of mice (C57BL/6J, BALB/cJ, and DBA/2J).

Results
Although we anticipated a modification of both learning and IIPMF sizes, no such effects were detected. Prenatal alcohol exposure did, however, interfere with reproduction in C57BL/6J animals and decrease body and brain weight (in interaction with the genotype) at adult age.

Conclusion
Prenatal alcohol exposure influenced neither radial maze performance nor the sizes of the IIPMF terminal fields. We believe that future research should be pointed either at different targets when using mouse models for Fetal Alcohol Syndrome (e.g. more complicated behavioral paradigms, different hippocampal substructures, or other brain structures) or involve different animal models.
TNF-α promotes a stop signal that inhibits neutrophil polarization and migration via a p38 MAPK pathway
Authors: Lokuta Mary A , Huttenlocher Anna 
Published: April 2005

AbstractNeutrophils are a major component of the inflammatory response in patients with asthma and other inflammatory conditions. Proinflammatory cytokines, such as tumor necrosis factor α (TNF-α), are increased in the airway of patients with severe asthma and have been implicated in the recruitment of neutrophils into areas of inflammation. Here, we show that TNF-α induces a stop signal that promotes firm neutrophil adhesion and inhibits neutrophil polarization and chemotaxis to chemoattractants including interleukin-8 and C5a. TNF-α treatment of neutrophils plated on a fibrinogen-coated surface promotes firm neutrophil adhesion and the formation of vinculin-containing focal complexes. TNF-α induces a more than tenfold increase in p38 mitogen-activated protein kinase (MAPK) but not extracellular signal-regulated kinase phosphorylation. Inhibition of p38 MAPK in neutrophils treated with TNF-α causes neutrophil polarization and motility. These findings suggest that TNF-α initiates a stop signal through a p38 MAPK pathway, which may promote the retention of neutrophils in inflammatory sites. Together, our data suggest that inhibition of p38 MAPK may be an attractive target to limit inflammatory responses that are mediated by TNF-α.
BALB/c mice have more CD4+CD25+ T regulatory cells and show greater susceptibility to suppression of their CD4+CD25− responder T cells than C57BL/6 mice
Authors: Chen Xin , Oppenheim Joost J , Howard O M Zack 
Published: April 2005

AbstractIncreasing evidence indicates that CD4+CD25+ T regulatory (Treg) cells control a wide spectrum of immune responses. The initial identification of CD4+CD25+ Treg cell as a “professional suppressor” was based on observations made in BALB/c mice. This mouse strain is well known to preferentially develop T helper cell type 2 responses, to be more susceptible to intracellular parasite infection, to have a higher tumor incidence, and to be more resistant to the induction of autoimmune diseases, as compared with C57BL/6 (B6) mice. We therefore decided to compare Treg cell function of B6 and BALB/c mice. We observed that the frequency of CD4+CD25+ T cells in the thymus and peripheral lymphoid organs of BALB/c mice was higher than in B6 mice. CD4+CD25+ Treg cells from both mouse strains shared similar phenotypic properties, including expression of characteristic immunological markers and hyporesponsiveness to T cell receptor cross-linking and in their capacity to suppress proliferation of BALB/c CD4+CD25− T responder (Tres) cells. However, CD4+CD25− Tres cells from B6 mice were notably less susceptible to suppression by CD4+CD25+ Treg cells from either mouse strain. Our data suggest that the number and the level of suppression of CD4+CD25+ Treg cells for CD4+CD25− Tres cells may be dictated by genetic background. Our data also suggest that differences in the CD4+CD25+ Treg cell number and the susceptibility of CD4+CD25− Tres cells may, at least in part, account for the differences in immune response between B6 and BALB/c strains of mice.