bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacokinetics and Antibody Responses to the CD3 Antibody Otelixizumab Used in the Treatment of Type 1 Diabetes
Authors: Hale Geoff , Rebello Peppy , Al Bakir Ibrahim , Bolam Emma , Wiczling Pawel , Jusko William J. , Vandemeulebroucke Evy , Keymeulen Bart , Mathieu Chantal , Ziegler Annette‐G , Chatenoud Lucienne , Waldmann Herman
Published: February 2010

Otelixizumab is a chimeric CD3 antibody that has been genetically engineered to remove the glycosylation site in the Fc domain. This limits its ability to bind to complement or Fc receptors and reduces the risk of adverse clinical reactions due to cytokine release. In a trial for treatment of type 1 diabetes, a short treatment with otelixizumab resulted in a reduced requirement for insulin lasting at least 18 months. In the course of this trial, the blood concentrations of the antibody were measured by flow cytometry to determine its pharmacokinetic profile. Dose‐dependent accumulation of otelixizumab was demonstrated and modeling of the data indicated that the terminal half‐life was approximately 1.5 days. Antibody responses to otelixizumab were measured by 2 methods: a bridging enzyme‐linked immunosorbent assay and surface plasmon resonance. The surface plasmon resonance method had a greater sensitivity and was able to detect responses in all patients, starting at 8 days after the commencement of therapy. Neutralizing antibodies were detected in a significant proportion of patients by days 22 to 29. Although no adverse clinical effects were associated with these antibody responses and they did not appear to affect the clearance of the drug, they might have important implications for possible retreatment of the patients.
What Triggers Social Responses to Flattering Computers? Experimental Tests of Anthropomorphism and Mindlessness Explanations
Authors: Lee Eun-Ju
Published: February 2010

The present research evaluated two explanations for the computers are social actors (CASA) paradigm: anthropomorphism and mindlessness. Using flattery effects as an example of social responses, two experiments examined how humanlikeness of the interface, individuals’ rationality, and cognitive busyness moderate the extent to which people apply social attributes to computers. In Experiment 1, anthropomorphic cartoon characters elicited more positive overall evaluations of the computer, but they significantly reduced low rationals’ self-confidence, suggesting social facilitation effects. Moreover, low rationals were less likely to accept the computer’s suggestions when flattered, whereas high rationals showed no corresponding tendency. In Experiment 2, although participants attributed greater social attractiveness to the flattering than generic-comment computer, they became more suspicious about the validity of its claims and more likely to dismiss its answer. Such negative effects, however, disappeared when they simultaneously engaged in a secondary task. Theoretical implications for CASA are discussed.
Explaining Global Box-Office Tastes in Hollywood Films: Homogenization of National Audiences’ Movie Selections
Authors: Fu W. Wayne , Govindaraju Achikannoo
Published: February 2010

This study examines the cross-country homogeneity of audience tastes in theatrical consumption of Hollywood films. It constructs empirical schemes to measure and explain similarities between national cinema audiences in box-office acceptance of common sets of Hollywood movies, using annual 2002-2007 panel data of ticket-sales receipts worldwide at the country-by-film level. The results show that countries more culturally like the United States tend to have box-office tastes more closely resembling those of American audiences for the same Hollywood titles than other countries do. The similarity in movie taste is also positively related to an importing country’s cinema market size. Moreover, the tastes of individual countries have converged with those of American audiences over the years. Also, correlational statistics calculated from the country-by-film cross-tabulations of box-office sales uncover the trend that the world’s tastes have become increasingly homogeneous.
Predicting Emotions and Meta-Emotions at the Movies: The Role of the Need for Affect in Audiences’ Experience of Horror and Drama
Authors: Bartsch Anne , Appel Markus , Storch Dennis
Published: February 2010

Audiences are attracted to dramas and horror movies even though negative and ambivalent emotions are likely to be experienced. Research into the seemingly paradoxical enjoyment of this kind of media entertainment has typically focused on gender- and genre-specific needs and viewing motivations. Extending this line of research, the authors focus the role of the need for affect as a more general, gender- and genre-independent predictor of individual differences in the experience of emotions and meta-emotions (i.e., evaluative thoughts and feelings about one’s emotions). The article discusses a field study of moviegoers who attended the regular screening of a drama or a horror film. Results support the assumption that individuals high in need for affect experience higher levels of negative and ambivalent emotions and evaluate their emotions more positively on the level of meta-emotions. Controlling for the Big Five personality factors does not alter these effects. The results are discussed within an extended meta-emotion framework.
Review: Escitalopram—translating molecular properties into clinical benefit: reviewing the evidence in major depression
Authors: Leonard Brian , Taylor David
Published: February 2010

The majority of currently marketed drugs contain a mixture of enantiomers; however, recent evidence suggests that individual enantiomers can have pharmacological properties that differ importantly from enantiomer mixtures. Escitalopram, the S-enantiomer of citalopram, displays markedly different pharmacological activity to the R-enantiomer. This review aims to evaluate whether these differences confer any significant clinical advantage for escitalopram over either citalopram or other frequently used antidepressants. Searches were conducted using PubMed and EMBASE (up to January 2009). Abstracts of the retrieved studies were reviewed independently by both authors for inclusion. Only those studies relating to depression or major depressive disorder were included. The search identified over 250 citations, of which 21 studies and 18 pooled or meta-analyses studies were deemed suitable for inclusion. These studies reveal that escitalopram has some efficacy advantage over citalopram and paroxetine, but no consistent advantage over other selective serotonin reuptake inhibitors. Escitalopram has at least comparable efficacy to available serotonin-norepinephrine reuptake inhibitors, venlafaxine XR and duloxetine, and may offer some tolerability advantages over these agents. This review suggests that the mechanistic advantages of escitalopram over citalopram translate into clinical efficacy advantages. Escitalopram may have a favourable benefit-risk ratio compared with citalopram and possibly with several other antidepressant agents.
Reactivity to smoking- and food-related cues in currently dieting and non-dieting young women smokers
Authors: Jenks Rebecca A , Higgs Suzanne
Published: February 2010

There is some evidence to suggest that young women dieters who smoke experience greater cigarette cravings in the presence of food-related related cues. The aim of this experiment was to examine reactivity to both smoking-related and water cues by dieting and non-dieting women smokers in the presence or absence of food cues. Eighteen female undergraduates attended two sessions (food present and food absent). At each session, participants were presented with a cigarette and water cue in a counterbalanced order. Pre- and post-cue measures included the brief version of the Questionnaire for Smoking Urges, heart rate and self-reported mood. All smokers showed enhanced reactivity (increased craving and heart rate) to smoking versus water cues. For dieters there was a larger increase in cigarette craving and heart rate in response to the smoking-related cues in the presence of food compared with the absence of food, whereas for non-dieters there was a smaller increase in cigarette craving and heart rate in response to the smoking-related cues in the presence of food compared with the absence of food. Mood and appetite ratings were not significantly affected by either cue type or session. The results suggest that cue reactivity to smoking-related cues is modulated by the presence of incentive stimuli relevant to the individual.
Perceived Needs of Grandmothers of Children With Disabilities
Authors: Gallagher Peggy A. , Kresak Karen , Rhodes Cheryl A.
Published: February 2010

This study investigated the perceptions of 20 grandmother caregivers related to their concerns and needs in caring for their grandchildren with disabilities. The research focused on grandmother caregivers who had a grandchild with a disability between the ages of 3 and 12 years. Almost all the grandmothers reported they were involved in the planning or implementation of the grandchild’s Individualized Education Program. Grandmothers responded that they needed information or help with behavior issues such as aggression or skill development in areas such as communication. Grandmothers also talked about how hard and challenging it is to raise a child with disabilities. On the positive side, several grandmothers noted that once they understood what to do, things got easier, and that they’d seen improvement for the child. Several also mentioned their joy in raising the grandchild and hope that they were doing the right thing.
Nonprofits and Public Administration
Authors: Rathgeb Smith Steven
Published: February 2010

Nonprofit organizations receiving government contracts are now central to the provision of a host of public services, including community care, workforce development, substance abuse treatment, and early childhood education. Government’s increased dependence on nonprofits has in turn prompted more intensive efforts to hold nonprofit service organizations accountable for the expenditure of public funds, especially through greater regulation such as performance-based contracting. Overall, these regulatory strategies do not directly address the governance of nonprofits or their engagement with the community and citizens; instead, the focus of performance management is on government programmatic priorities. The central argument of this article is that the inattention to governance and citizen engagement can undermine good performance and program sustainability. Consequently, this article offers a framework for government and nonprofit managers to integrate performance management and citizen engagement. This approach requires a more inclusive performance management strategy that emphasizes programmatic goals as well as sound governance and ongoing support for citizen participation. Indeed, only by close attention to community and citizenship, broadly defined, can the promise of innovation and performance by nonprofits be effectively realized.
Eosinophilic Airway Inflammation in a Cynomolgus Monkey
Authors: Shirai N. , Geoly F. J.
Published: February 2010

The present article describes an occurrence of eosinophilic airway inflammation of a 4-year-old female cynomolgus monkey in a vehicle control group of a routine toxicology study. Histologically, the airway lesion was characterized by prominent eosinophilic infiltrates, accompanied by mast cells, lymphocytes, and plasmacytes. The eosinophilic infiltrates were distributed throughout the airway: from trachea through respiratory bronchioles in the lung. The morphological feature of the lesion was indicative of an allergic airway disorder that can occur in humans with asthma. The present case is remarkable in that there is a paucity of reports on naturally occurring allergic airway disorders in nonhuman primates.
Rebalancing Fixed and Variable Pay in a Sales Organization: A Business Cycle Perspective
Authors: Madhani Pankaj M.
Published: February 2010

The business cycle has a significant impact on the revenue and profitability of sales organizations and directly influences sales compensation costs. Operating leverage is a key variable affecting business performance during different stages of business cycle. Rebalancing fixed and variable pay in the compensation structure helps organizations in the effective management of operating leverage in business cycle stages. This article provides a framework for properly designing pay structure and determining how much pay should be fixed or variable, according to different stages of business cycle. It also explains the relationship between job challenges and compensation structures. By synchronizing sales force compensation structure with the business cycle, organizations can design optimal compensation strategies.
Prevalence and Correlates of Functional Status in an Older Community— Representative Sample in Brazil
Authors: Fillenbaum Gerda G. , Blay Sergio L. , Andreoli Sergio B. , Gastal Fábio L.
Published: February 2010

Objective: Information on dependency level of elderly in rapidly aging developing countries is limited, but this is needed to ascertain the extent of need for help with activities of daily living (ADLs). Method: In-person information was obtained in 1995 from a statewide survey of representative community residents ≥60 years of age in the state of Rio Grande do Sul, Brazil ( N = 7,040), on demographic characteristics, health conditions, social ties, health behaviors, and ADL performance. Results: Nearly 40% needed help with one or more ADLs. In controlled analyses, need for help approximately doubled with each succeeding decade. Increased education and income and regular physical activity reduced risk. Selected health conditions (stroke, depression, poor self-rated health) were consistently associated with need for help. Discussion: A large proportion of noninstitutionalized elderly have ADL problems. In addition to health care, interventions promoting equity of access to education and economic opportunity could reduce ADL dependency in coming generations.
When Does Teamwork Translate Into Improved Team Performance? A Resource Allocation Perspective
Authors: Porter Christopher O. L. H. , Itir Gogus Celile , Yu Race Chien-Feng
Published: February 2010

Drawing on resource allocation theory, the authors examined boundary conditions for the positive effects of two aspects of teamwork (backing up behavior and performance monitoring) on team performance. Participants were 276 undergraduate business students who were organized into 69 teams and who worked on a computer simulation across multiple performance episodes. Approximately half the teams experienced a workload distribution problem. Results indicated that performance monitoring had positive effects on team performance when teams experienced a workload distribution problem. Backing up behavior had positive effects only when teams had both a workload distribution problem and during early performance episodes. The findings of this study suggest that resource allocation theory can provide insights regarding when members should devote and coordinate their own individual resources to assist others in teams. The implications of these findings for future theory and practice regarding teamwork are discussed.
Coinheritance of Severe von Willebrand Disease With Glanzmann Thrombasthenia
Authors: Ahmad Firdos , Kannan Meganathan , Kishor Kamal , Saxena Renu
Published: February 2010

A 35-years old male patient presented severe bleeding was diagnosed to have type 3 von Willebrand disease (VWD) and carrier for Glanzmann thrombasthenia (GT). Propositus and family members were studied through basic coagulation tests and genomic DNA analysis. Two offspring of the family were diagnosed to have GT through platelet aggregation along with VWD carrier. The patient with VWD was found positive for homozygous truncating mutation R1659X in VWF gene, and all offspring were heterozygous carriers of null allele. Hence, propositus was a carrier of GT with severe type 3 VWD and wife was a carrier of GT. Thus, it is concluded that there is importance of careful studies of patients even from nonconsanguineous families to exclude unusual coinheritance of congenital hemostatic disorders. If single replacement therapy in patient not responding well then probably co-expression of coagulopathies required and multiple replacement therapy should be given according to clinical and laboratory features.
Evaluation of the Siblings of Physically Abused Children: A Comparison of Child Protective Services Caseworkers and Child Abuse Physicians
Authors: Vitale Melissa A. , Squires Janet , Zuckerbraun Noel S. , Berger Rachel P.
Published: February 2010

Current theories suggest that all children in a home are at risk for physical abuse, when one child is abused. However, little evidence exists to guide decisions regarding the medical management of siblings of physically abused children (contact children [CC]). This study sought to compare child protective services (CPS) caseworkers’ and child abuse physicians’ (CAP) recommendations regarding the need for medical evaluation of CC in case scenarios of unequivocal physical abuse. In all cases, caseworkers and physicians disagreed on which CC warranted a medical evaluation. In addition, 25% of caseworkers did not think that physicians should make recommendations on the need for medical evaluation of CC. The findings of the authors suggest that the home visit is a critical part of the decision-making process for caseworkers and that it often acts as a substitute for a medical evaluation. Caseworkers indicated that visible injury to the contact child and severity of injury to the index child were among the most important factors in deciding which CC need a medical evaluation. Although caseworkers and physicians disagree on certain issues related to the evaluation of CC, it is clear that limited resources should be directed at CC at highest risk for physical abuse.
Incidence and predictors of cetuximab hypersensitivity reactions in a North Carolina academic medical center
Authors: Hansen Nicole L , Chandiramani Divya V , Morse Michael A , Wei David , Hedrick Nancy E , Hansen Richard A
Published: February 2010

Objectives. Previous research has indicated a high incidence of cetuximab hypersensitivity reactions in the southern US. This study documents the incidence of hypersensitivity reactions in North Carolina, and explores whether factors such as patient demographics, allergy history, premedications, and cancer type are potential predictors for cetuximab reactions.

Methods. This retrospective chart review consisted of 72 consecutively treated patients from Duke University’s Morris Oncology treatment center between September 2005 and August 2007. Data regarding stage of malignancy, premedications, and hypersensitivity reactions were collected from electronic databases. The number and type of reactions were characterized. Patients with and without hypersensitivity reactions were compared using bivariate statistics and multivariate logistic regression.

Results. Of the 72 patients, 21 (29%) experienced hypersensitivity reactions. The majority of reactions (62%) were grades III or IV. Of the 21 patients having a reaction, 9 (43%) were sent to the emergency room and 5 (24%) had an overnight hospitalization. Three hospitalized patients were admitted to the intensive care unit. Both male gender (p = 0.039) and head/neck cancer (p = 0.014) were related to an increased likelihood of hypersensitivity reaction in bivariate analyses. In multivariate analyses, controlling for demographics, allergy history, premedications, and cancer type/stage, only type of cancer was predictive of hypersensitivity reaction (colon vs head/neck OR = 0.177; 95% CI 0.036—0.858).

Conclusion. This study confirms a high rate of cetuximab hypersensitivity reactions in a southern region of the US. Patients with head/neck cancers were significantly more likely to have hypersensitivity reactions than patients with colon cancers. J Oncol Pharm Practice (2011) 17: 125—130.
Short-Term Hearing Aid Benefit in a Large Group
Authors: Ivory Peter J. , Hendricks Bryan L. , Van Vliet Dennis , Beyer Cynthia M. , Abrams Harvey B.
Published: February 2010

Short-term benefit in a very large group ( N = 4,584) following hearing aid treatment was estimated using a revised version of the Self-Assessment of Communication (SAC-Hx). A total of 4,584 veterans with adult-onset hearing loss and mean audiometric findings consistent with a mild to severe, sloping, symmetrical, sensorineural hearing impairment were fitted with hearing aids. Responses to the SAC-Hx were gathered prior to and then 6 weeks following hearing aid fitting. Benefit was defined as the difference between the baseline and the posttreatment SAC-Hx scores. Hearing aid treatment resulted in robust and statistically significant benefit in each category of self-perceived communication consequences. Prior experience influenced benefit: New hearing aid users demonstrated the greatest magnitude of benefit, but even previously satisfied and dissatisfied users obtained significant benefit after new hearing aid fitting. Duration of experience did not have a remarkable effect on the magnitude of benefit: All groups with various durations of experience obtained comparable benefit. Severity of the baseline scores paralleled degree of hearing impairment when impairment was defined using a better ear pure tone average at 1,000, 2,000, 3,000, and 4,000 Hz. Also, severity of perceived communication consequences paralleled poorer monosyllabic word recognition. Hearing aid treatment provided a functional, robust, and statistically significant benefit to individuals in all categories of hearing impairment (normal, mild, moderate, severe, and profound). This report demonstrates the feasibility of the SAC-Hx as a tool to efficiently assess outcome domains in hearing aid fitting.
Achieving Developmental Synchrony in Young Children With Hearing Loss
Authors: Mellon Nancy K. , Ouellette Meredith , Greer Tracy , Gates-Ulanet Patricia
Published: February 2010

Children with hearing loss, with early and appropriate amplification and intervention, demonstrate gains in speech, language, and literacy skills. Despite these improvements many children continue to exhibit disturbances in cognitive, behavioral, and emotional control, self-regulation, and aspects of executive function. Given the complexity of developmental learning, educational settings should provide services that foster the growth of skills across multiple dimensions. Transdisciplinary intervention services that target the domains of language, communication, psychosocial functioning, motor, and cognitive development can promote academic and social success. Educational programs must provide children with access to the full range of basic skills necessary for academic and social achievement. In addition to an integrated curriculum that nurtures speech, language, and literacy development, innovations in the areas of auditory perception, social emotional learning, motor development, and vestibular function can enhance student outcomes. Through ongoing evaluation and modification, clearly articulated curricular approaches can serve as a model for early intervention and special education programs. The purpose of this article is to propose an intervention model that combines best practices from a variety of disciplines that affect developmental outcomes for young children with hearing loss, along with specific strategies and approaches that may help to promote optimal development across domains. Access to typically developing peers who model age-appropriate skills in language and behavior, small class sizes, a co-teaching model, and a social constructivist perspective of teaching and learning, are among the key elements of the model.
The Impact of Intergovernmental Incentives on Student Disability Rates
Authors: Kwak Sally
Published: February 2010

Measured disability rates among school-age children and the associated spending on special education programs have risen steeply over the past thirty years. Currently, about 15 percent of U.S. school children are classified as "disabled." Many observers note that the special education funding programs established by state and federal governments create an incentive for local school districts to drive up disability rates, potentially accounting for some of the rise in measured disability rates. I use the experiences following a major reform of the special education funding system in California to examine this issue. Between 1996 and 1998, the state converted from a system that awarded funds based on the number of students classified as disabled in a district (with funding rates that varied across districts) to one based on total enrollment. This reform induced changes in the total funding awarded to different districts and also reduced the marginal revenue from classifying an additional student as disabled to zero. Consistent with standard models, I find that the California reform creates both "income" and "substitution" effects on the number of students classified as disabled.
‘I’ve just taken you to see the man with the CD on his head’: the experience and management of recurrent sore throat in children
Authors: Lock Catherine , Baker Rachel , Brittain Katie
Published: February 2010

Tonsillectomies for children with recurrent sore throat are common. There is a perception amongst medical professionals that parents are eager for surgical intervention but the parent/child perspective is overlooked in the literature. This study aimed to identify parent/child experience of recurrent sore throat. The study was qualitative, using grounded theory approach to data collection/analysis. Semi-structured, in-depth, interviews were conducted with 12 dyads of children (aged 4—16) and their parents, attending two Ear, Nose and Throat outpatient clinics held at a hospital in North East England, referred by their General Practitioner for recurrent sore throats. Analysis revealed recurrent sore throats significantly affected the families’ quality of life. Families felt the need for antibiotics and tonsillectomies although parent and child were not always in agreement over their choice of treatment. Families felt empowered when the health care system showed some flexibility, such as allowing self re-referral, giving families greater choice in the way they managed the condition. Policy makers need to be aware of the consequences of recurrent sore throats in children and the needs of families in managing this chronic condition. More flexible approaches to health care, such as self re-referral and use of waiting list to review symptoms, may be needed if the number of tonsillectomies is to be reduced.
The influence of fathers’ socioeconomic status and paternity leave on breastfeeding duration: A population-based cohort study
Authors: Flacking Renée , Dykes Fiona , Ewald Uwe
Published: February 2010

Aim: The propensity to breastfeed is a matter of public concern because of the favourable effects for infants. However, very few studies have described the influence of paternal variables upon duration of breastfeeding. The aim of this study was to describe the effects of fathers’ socioeconomic status and their use of paternity leave on breastfeeding duration for infants up to 1 year of age. Methods: A prospective population-based cohort study was undertaken. Data on breastfeeding, registered in databases in two Swedish counties for 1993—2001, were matched with data on socioeconomic status and paternity leave obtained from Statistics Sweden. Fathers of 51,671 infants were identified and included. Results: Infants whose fathers had a lower level of education, were receiving unemployment benefit and/or had a lower equivalent disposable household income were significantly less likely to be breastfed at 2, 4, 6, 9, and 12 months of age. Infants whose fathers did not take paternity leave during the infant’s first year were significantly less likely to be breastfed at 2 (p < 0.001), 4 (p < 0.001), and 6 months (p < 0.001). Conclusions: This paper shows that an enabling of an increased involvement from fathers during the infants’ first year of life, such as by paid paternity leave, may have beneficial effects on breastfeeding up to 6 months of age. A more systematic approach to supporting fathers’ involvement may be particularly valuable to those infants whose fathers have a lower socioeconomic status.
Counting Congress In: Patterns of Success in Judicial Nomination Requests by Members of Congress to Presidents Eisenhower and Ford
Authors: Rottinghaus Brandon , Nicholson Chris
Published: February 2010

The power to nominate and confirm federal judges is shared by Congress and the president, yet few works explicitly address the role that Congress plays in shaping the preselection pool for judicial nominees. In this article, we illuminate this debate by exploring judicial nomination requests from Members of Congress to the Eisenhower and Ford Administrations. In explaining who is nominated, the characteristics of the nominee matter more than the characteristics of the nominator, with the party affiliation of a nominee being the strongest predictive factor. Institutional characteristics are more prevalent at the confirmation stage, where the Senate relied more heavily on its members and the judicial experience of nominees than did presidents in nominating them. Given our results, partisanship appears to have mattered earlier than presumed in judicial nominations, with even ostensibly nonpartisan presidents such as Eisenhower understanding the importance of appointing like-minded individuals to lifetime positions on the bench.
Breaking barriers
Authors: Woolfrey Ann
Published: February 2010

It is difficult to imagine a greater challenge to the transplantation of haploidentical cells than thalassemia.
LINNAEUS: A species name identification system for biomedical literature
Authors: Gerner Martin , Nenadic Goran , Bergman Casey M
Published: February 2010

Background

The task of recognizing and identifying species names in biomedical literature has recently been regarded as critical for a number of applications in text and data mining, including gene name recognition, species-specific document retrieval, and semantic enrichment of biomedical articles.

Results

In this paper we describe an open-source species name recognition and normalization software system, LINNAEUS, and evaluate its performance relative to several automatically generated biomedical corpora, as well as a novel corpus of full-text documents manually annotated for species mentions. LINNAEUS uses a dictionary-based approach (implemented as an efficient deterministic finite-state automaton) to identify species names and a set of heuristics to resolve ambiguous mentions. When compared against our manually annotated corpus, LINNAEUS performs with 94% recall and 97% precision at the mention level, and 98% recall and 90% precision at the document level. Our system successfully solves the problem of disambiguating uncertain species mentions, with 97% of all mentions in PubMed Central full-text documents resolved to unambiguous NCBI taxonomy identifiers.

Conclusions

LINNAEUS is an open source, stand-alone software system capable of recognizing and normalizing species name mentions with speed and accuracy, and can therefore be integrated into a range of bioinformatics and text-mining applications. The software and manually annotated corpus can be downloaded freely at http://linnaeus.sourceforge.net/.
Identification of genes involved in the mutualistic colonization of the nematode Heterorhabditis bacteriophora by the bacterium Photorhabdus luminescens
Authors: Easom Catherine A , Joyce Susan A , Clarke David J
Published: February 2010

Background

Photorhabdus are Gram negative entomopathogenic bacteria that also have a mutualistic association with nematodes from the family Heterorhabditis. An essential part of this symbiosis is the ability of the bacterium to colonize the gut of the freeliving form of the nematode called the infective juvenile (IJ). Although the colonization process (also called transmission) has been described phenomonologically very little is known about the underlying molecular mechanisms. Therefore, in this study, we were interested in identifying genes in Photorhabdus that are important for IJ colonization.

Results

In this work we genetically tagged P. luminescens TT01 with gfp and constructed a library containing over 3200 mutants using the suicide vector, pUT-Km2. Using a combination of in vitro symbiosis assays and fluorescent microscopy we screened this library for mutants that were affected in their ability to colonize the IJ i.e. with decreased transmission frequencies. In total 8 mutants were identified with transmission frequencies of ≤ 30% compared to wild-type. These mutants were mapped to 6 different genetic loci; the pbgPE operon, galE, galU, proQ, asmA and hdfR. The pbgPE, galE and galU mutants were all predicted to be involved in LPS biosynthesis and, in support of this, we have shown that these mutants are avirulent and sensitive to the cationic antimicriobial peptide, polymyxin B. On the other hand the proQ, asmA and hdfR mutants were not affected in virulence and were either as resistant (proQ) or slightly more sensitive (asmA, hdfR) to polymyxin B than the wild-type (WT).

Conclusions

This is the first report describing the outcome of a comprehensive screen looking for transmission mutants in Photorhabdus. In total 6 genetic loci were identified and we present evidence that all of these loci are involved in the assembly and/or maintenance of LPS and other factors associated with the cell surface. Interestingly several, but not all, of the transmission mutants identified were also avirulent suggesting that there is a significant, but not complete, genetic overlap between pathogenicity and mutualism. Therefore, this study highlights the importance of the cell surface in mediating the symbiotic and pathogenic interactions of Photorhabdus.
Training of patient and consumer representatives in the basic competencies of evidence-based medicine: a feasibility study
Authors: Berger Bettina , Steckelberg Anke , Meyer Gabriele , Kasper Jürgen , Mühlhauser Ingrid
Published: February 2010

Background

Evidence-based medicine (EBM) has become standard approach in medicine. Patients and health authorities increasingly claim active patient roles in decision making. Education to cope with these roles might be useful. We investigated the feasibility, acceptability and possible impact of EBM training courses for patient and consumer representatives.

Methods

We designed a generic one-week EBM course based on previous experience with EBM courses for non-medical health professionals. A course specific competence test has been developed and validated to measure EBM skills. Formative and summative evaluation of the course comprised: 1) EBM skills; 2) individual learning goals; 3) self-reported implementation after six months using semi-structured interviews; 4) group-based feedback by content analysis. EBM skills' achievement was compared to results gathered by a group of undergraduate University students of Health Sciences and Education who had attended a comparable EBM seminar.

Results

Fourteen EBM courses were conducted including 161 participants without previous EBM training (n = 54 self-help group representatives, n = 64 professional counsellors, n = 36 patient advocates, n = 7 others); 71% had a higher education degree; all but five finished the course. Most participants stated personal learning goals explicitly related to practicing EBM such as acquisition of critical appraisal skills (n = 130) or research competencies (n = 67). They rated the respective relevance of the course on average with 80% (SD 4) on a visual analogue scale ranging from 0 to 100%.

Participants passed the competence test with a mean score of 14.7 (SD 3.0, n = 123) out of 19.5 points. The comparison group of students achieved a mean score of 14.4 (SD 3.3, n = 43). Group-based feedback revealed increases of self confidence, empowerment through EBM methodology and statistical literacy, and acquisition of new concepts of patient information and counselling. Implementation of EBM skills was reported by 84 of the 129 (65%) participants available for follow-up interviews. Barriers included lack of further support, limited possibilities to exchange experiences, and feeling discouraged by negative reactions of health professionals.

Conclusions

Training in basic EBM competencies for selected patient and consumer representatives is feasible and accepted and may affect counselling and advocacy activities. Implementation of EBM skills needs support beyond the training course.
Flow cytometry for the evaluation of anti-plasmodial activity of drugs on Plasmodium falciparum gametocytes
Authors: Chevalley Séverine , Coste Agnès , Lopez Alexandrine , Pipy Bernard , Valentin Alexis
Published: February 2010

Background

The activity of promising anti-malarial drugs against Plasmodium gametocytes is hard to evaluate even in vitro. This is because visual examination of stained smears, which is commonly used, is not totally convenient. In the current study, flow cytometry has been used to study the effect of established anti-malarial drugs against sexual stages obtained from W2 strain of Plasmodium falciparum. Gametocytes were treated for 48 h with different drug concentrations and the gametocytaemia was then determined by flow cytometry and compared with visual estimation by microscopy.

Results and conclusions

Initially gametocytaemia was evaluated either using light microscopy or flow cytometry. A direct correlation (r2 = 0.9986) was obtained. Two distinct peaks were observed on cytometry histograms and were attributed to gametocyte populations. The activities of established anti-malarial compounds were then measured by flow cytometry and the results were equivalent to those obtained using light microscopy. Primaquine and artemisinin had IC50 of 17.6 μM and 1.0 μM, respectively.

Gametocyte sex was apparently distinguishable by flow cytometry as evaluated after induction of exflagellation by xanthurenic acid. These data form the basis of further studies for developing new methods in drug discovery to decrease malaria transmission.
Leukotriene B4, administered via intracerebroventricular injection, attenuates the antigen-induced asthmatic response in sensitized guinea pigs
Authors: Zhu Yi-Liang , Zhang Shui-Jun , Deng Yang-Mei , Dong Xin-Wei , Jiang Jun-Xia , Xie Qiang-Min
Published: February 2010

Background

Despite intensive studies focused on the pathophysiology of asthmatic inflammation, little is known about how cross-talk between neuroendocrine and immune systems regulates the inflammatory response during an asthmatic attack. We recently showed corresponding changes of cytokines and leukotriene B4 (LTB4) in brain and lung tissues of antigen-challenged asthmatic rats. Here, we investigated how LTB4 interacts with the neuroendocrine-immune system in regulating antigen-induced asthmatic responses in sensitized guinea pigs.

Methods

Ovalbumin-sensitized guinea pigs were challenged by inhalation of antigen. Vehicle, LTB4 or U75302 (a selective LTB4 BLT1 receptor inhibitor) was given via intracerebroventricular injection (i.c.v.) 30 min before challenge. Airway contraction response was evaluated using Penh values before and after antigen challenge. The inflammatory response in lung tissue was evaluated 24 h after challenge. The LTB4 content of lung and brain homogenate preparations was detected by reversed phase high-performance liquid chromatography (RP-HPLC). Plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were measured using ELISA kits.

Results

Antigen challenge impaired pulmonary function and increased inflammatory cell infiltration in lung tissue. These responses could be significantly suppressed by LTB4, 30 ng i.c.v., in ovalbumin-sensitized guinea pigs. LTB4 content of lung and brain homogenates from antigen-challenged guinea pigs was significantly increased. In addition, administration of LTB4 via i.c.v. markedly increased CORT and ACTH level in plasma before antigen challenge, and there were further increases in CORT and ACTH levels in plasma after antigen challenge. U75302, 100 ng i.c.v., completely blocked the effects of LTB4. In addition, U75302, 100 ng via i.c.v. injection, markedly decreased LTB4 content in lung homogenates, but not in brain homogenates.

Conclusions

Increased LTB4 levels in brain during asthmatic attacks down-regulates airway contraction response and inflammation through the BLT1 receptor. Stimulation of the hypothalamic-pituitary-adrenal axis by LTB4 may result in an increase in systemic glucocorticoids which, in turn, would feed back to suppress the asthmatic response.
Is Duhuo Jisheng Tang containing Xixin safe? A four-week safety study
Authors: Hsieh Shu-Ching , Lai Jung-Nien , Chen Pau-Chung , Chen Chao-Chung , Chen Huey-Jen , Wang Jung-Der
Published: February 2010

Background

Though the nephrotoxicity and carcinogenicity of aristolochic acid (AA) are known, its safety in clinical usage is not clear. This study aims to evaluate the safety of Duhuo Jisheng Tang (DJT) in a four-week study to treat osteoarthritis (OA) of the knee.

Methods

A qualitative and quantitative investigations on DJT were conducted. A list of adverse events (AEs), complete blood counts, and liver and kidney function tests were measured for participants with knee OA at their scheduled hospital visits. Each detected AEs was independently assessed for severity and causality by site investigators (Chinese medical doctors) and study nurses.

Results

A total of 71 eligible subjects were included in the clinical study where 287 AEs were reported. DJT did not contain detectable aristolochic acid (AA) under thin-layer chromatography (TLC) analysis and gas chromatography coupled with mass spectrometry (GC-MS). There were no significant changes in liver or kidney functions.

Conclusion

In four-week use of DJT, no renal tubular damage, no severe incidences of AEs and adverse drug reactions (ADRs) were observed. The present study obtained safety data from active surveillance of DJT.
Decreased response inhibition in middle-aged male patients with type 2 diabetes
Authors: Ishizawa Kaya T , Kumano Hiroaki , Sato Atsushi , Sakura Hiroshi , Iwamoto Yasuhiko
Published: February 2010

Background

This study was performed to examine whether patients with type 2 diabetes have cognitive deficits associated with the prefrontal cortex (PFC).

Methods

Twenty-seven middle-aged patients with newly diagnosed type 2 diabetes and 27 healthy controls underwent physical measurements and neuropsychological tasks. Response inhibition, reward prediction, and executive function were assessed by the Go/NoGo task, the reversal and extinction tasks, and the Wisconsin Card Sorting Test (WCST). To examine the interactions of being overweight with diabetes on cognitive performance, performance data were analysed by two-way ANCOVA with diabetes and overweight as factors and age as a covariate.

Results

Patients with type 2 diabetes showed significantly decreased response inhibition in the Go/NoGo task (discriminability index:P= 0.001). There was an interaction of being overweight with diabetes on reaction time in the Go trials of the Go/NoGo task (P= 0.009). Being overweight was related to retained responses to the presentiment of reward in the extinction task (P= 0.029). The four groups showed normal cognitive performance in the WCST.

Conclusions

Our results showed that middle-aged, newly diagnosed and medication-free patients with type 2 diabetes have a particular neuropsychological deficit in inhibitory control of impulsive response, which is an independent effect of diabetes apart from being overweight.
Comparative kinetic analysis of two fungal β-glucosidases
Authors: Chauve Marie , Mathis Hugues , Huc Delphine , Casanave Dominique , Monot Frédéric , Lopes Ferreira Nicolas
Published: February 2010

Background

The enzymatic hydrolysis of cellulose is still considered as one of the main limiting steps of the biological production of biofuels from lignocellulosic biomass. It is a complex multistep process, and various kinetic models have been proposed. The cellulase enzymatic cocktail secreted by Trichoderma reesei has been intensively investigated. β-glucosidases are one of a number of cellulolytic enzymes, and catalyze the last step releasing glucose from the inhibitory cellobiose. β-glucosidase (BGL1) is very poorly secreted by Trichoderma reesei strains, and complete hydrolysis of cellulose often requires supplementation with a commercial β-glucosidase preparation such as that from Aspergillus niger (Novozymes SP188). Surprisingly, kinetic modeling of β-glucosidases lacks reliable data, and the possible differences between native T. reesei and supplemented β-glucosidases are not taken into consideration, possibly because of the difficulty of purifying BGL1.

Results

A comparative kinetic analysis of β-glucosidase from Aspergillus niger and BGL1 from Trichoderma reesei, purified using a new and efficient fast protein liquid chromatography protocol, was performed. This purification is characterized by two major steps, including the adsorption of the major cellulases onto crystalline cellulose, and a final purification factor of 53. Quantitative analysis of the resulting β-glucosidase fraction from T. reesei showed it to be 95% pure. Kinetic parameters were determined using cellobiose and a chromogenic artificial substrate. A new method allowing easy and rapid determination of the kinetic parameters was also developed. β-Glucosidase SP188 (Km = 0.57 mM; Kp = 2.70 mM) has a lower specific activity than BGL1 (Km = 0.38 mM; Kp = 3.25 mM) and is also more sensitive to glucose inhibition. A Michaelis-Menten model integrating competitive inhibition by the product (glucose) has been validated and is able to predict the β-glucosidase activity of both enzymes.

Conclusions

This article provides a useful comparison between the activity of β-glucosidases from two different fungi, and shows the importance of fully characterizing both enzymes. A Michaelis-Menten model was developed, including glucose inhibition and kinetic parameters, which were accurately determined and compared. This model can be further integrated into a cellulose hydrolysis model dissociating β-glucosidase activity from that of other cellulases. It can also help to define the optimal enzymatic cocktails for new β-glucosidase activities.