bluuebunny/crossref_metadata_2025 huggingface dataset:
Impaired epidermal wound healing in vivo upon inhibition or deletion of Rac1
Authors: Tscharntke Michael , Pofahl Ruth , Chrostek-Grashoff Anna , Smyth Neil , Niessen Carien , Niemann Catherin , Hartwig Benedikt , Herzog Volker , Klein Helmut W. , Krieg Thomas , Brakebusch Cord , Haase Ingo
Published: March 2007

To address the functions of Rac1 in keratinocytes of the basal epidermal layer and in the outer root sheath of hair follicles, we generated transgenic mice expressing a dominant inhibitory mutant of Rac, N17Rac1, under the control of the keratin 14 promoter. These mice do not exhibit an overt skin phenotype but show protracted skin wound re-epithelialization. Investigation into the underlying mechanisms revealed that in vivo both proliferation of wound-edge keratinocytes and centripetal migration of the neo-epidermis were impaired. Similar results were obtained in mice with an epidermis-specific deletion of Rac1. Primary epidermal keratinocytes that expressed the N17Rac1 transgene were less proliferative than control cells and showed reduced ERK1/2 phosphorylation upon growth factor stimulation. Adhesion, spreading, random migration and closure of scratch wounds in vitro were significantly inhibited on collagen I and, to a lesser extent, on fibronectin. Stroboscopic analysis of cell dynamics (SACED) of N17Rac1 transgenic and control keratinocytes identified decreased lamella-protrusion persistence in connection with increased ruffle frequency as a probable mechanism for the observed impairment of keratinocyte adhesion and migration. We conclude that Rac1 is functionally required for normal epidermal wound healing and, in this context, exerts a dual function – namely the regulation of keratinocyte proliferation and migration.
Bcr-Abl induces abnormal cytoskeleton remodeling, β1 integrin clustering and increased cell adhesion to fibronectin through the Abl interactor 1 pathway
Authors: Li Yingzhu , Clough Nancy , Sun Xiaolin , Yu Weidong , Abbott Brian L. , Hogan Christopher J. , Dai Zonghan
Published: March 2007

Hematopoietic cells isolated from patients with Bcr-Abl-positive leukemia exhibit multiple abnormalities of cytoskeletal and integrin function. These abnormalities are thought to play a role in the pathogenesis of leukemia; however, the molecular events leading to these abnormalities are not fully understood. We show here that the Abi1 pathway is required for Bcr-Abl to stimulate actin cytoskeleton remodeling, integrin clustering and cell adhesion. Expression of Bcr-Abl induces tyrosine phosphorylation of Abi1. This is accompanied by a subcellular translocation of Abi1/WAVE2 to a site adjacent to membrane, where an F-actin-enriched structure containing the adhesion molecules such as β1-integrin, paxillin and vinculin is assembled. Bcr-Abl-induced membrane translocation of Abi1/WAVE2 requires direct interaction between Abi1 and Bcr-Abl, but is independent of the phosphoinositide 3-kinase pathway. Formation of the F-actin-rich complex correlates with an increased cell adhesion to fibronectin. More importantly, disruption of the interaction between Bcr-Abl and Abi1 by mutations either in Bcr-Abl or Abi1 not only abolished tyrosine phosphorylation of Abi1 and membrane translocation of Abi1/WAVE2, but also inhibited Bcr-Abl-stimulated actin cytoskeleton remodeling, integrin clustering and cell adhesion to fibronectin. Together, these data define Abi1/WAVE2 as a downstream pathway that contributes to Bcr-Abl-induced abnormalities of cytoskeletal and integrin function.
V2O5·nH2O Crystalline Nanosheets: Hydrothermal Fabrication and Structure Evolution
Authors: Hu Xiao Kai , Ma De Kun , Liang Jian Bo , Xiong Sheng Lin , Li Jiang Ying , Qian Yi Tai
Published: March 2007

V2O5·nH2O nanosheets are fabricated hydrothermally with the acidified peroxovanadate solution at 200 °C for 12 h. The X-ray diffraction suggests that V2O5·nH2O nanosheets display lamellar ordering along c-axis direction. Transmission electron microscopy, field-emission scanning electron microscopy, and selected area electron diffraction indicate that V2O5·nH2O nanosheets are very thin in thickness and micron-sized in lateral dimension, and they are two-dimensional crystallites. X-ray photoelectron spectroscopy and thermogravimetric analysis are utilized to confirm the elemental composition of nanosheets. The formation process of nanosheets is also discussed in terms of time- and temperature-controlled experiments.
Electrochemistry of Self-assembled Ultra-thin Films Composed of Chloroperoxidase and Polyions
Authors: Lu Zhongqing , Hou Wenjing , Wu Xiaqin , Li Hexing , Chen Jun
Published: March 2007

Direct electron transfer between chloroperoxidase (CPO) from Caldariomyces fumago and gold electrode has been achieved by layer-by-layer adsorption of CPO and polydimethyldiallylammonium chloride (PDDA) monolayers on a gold electrode. QCM frequency shift demonstrated monolayer formed during each adsorption. Electrochemical characterization studies show thin layer properties of these PDDA–CPO–PDDA films. The PDDA–CPO–PDDA ultra-thin films were stable, up to 97% electrochemical activity remained after two days storage in phosphate buffer pH 5.
Patients’ experiences of Western-style acupuncture: The influence of acupuncture ‘dose’, self-care strategies and integration
Authors: Paterson Charlotte
Published: March 2007

Objectives

To investigate patients’ perspectives of the process and outcome of Western-style acupuncture for chronic health problems. To use these results to inform the provision of acupuncture in health services in the UK.

Methods

A purposive sample of 18 patients who were having Western-style acupuncture, for the first time, for a health problem of at least three months duration, were interviewed twice over a four-month period using semi-structured interviews. Using a constant comparative method, the data were analysed across cases and within cases.

Results

The interviewees complained of chronic pain and moderate or severe disability which was resistant to conventional treatment. Their experience of acupuncture was diverse and varied according to the ‘dosage’ of acupuncture received, the inclusion of self-care strategies, and their relationship with the practitioner. These three factors were interlinked and constituted individual styles of practice for each practitioner. The majority of patients benefited in terms of complete or partial relief of pain and disability, and reduction in conventional medication. However, some patients were disappointed by the treatment, distressed about ‘wasting people's time’, and about the lack of continuity of care. People who benefited most had good general health and a single problem.

Conclusions

Patients showed discerning judgement regarding the ‘dosage’ of acupuncture they required, and combined acupuncture with exercises to good effect. Publicly funded health services should provide an acupuncture service that provides the optimal ‘dosage’ and uses pain relief to promote self-care. Further research to investigate the benefits of a service that combines Western-style and traditional acupuncture is planned.
Socioeconomic inequality in small area use of elective total hip replacement in the English National Health Service in 1991 and 2001
Authors: Cookson Richard , Dusheiko Mark , Hardman Geoffrey
Published: March 2007

Objectives

To compare socioeconomic inequality in small area use of elective total hip replacement in the English National Health Service (NHS) in 1991 and 2001.

Methods

Hospital Episode Statistics and Census data were aggregated to a common geography of ‘frozen’ 1991 English electoral wards. The Townsend deprivation score was used as the primary indicator of socioeconomic status for each ward, and the sensitivity analysis used other Census indicators. Two main measures of inequality were examined: the indirectly age-sex standardized utilization rate ratio between most and least deprived quintile groups, and the concentration index of deprivation-related inequality in age-sex standardized utilization ratios between small areas. Each standardized utilization ratio is the observed use divided by the expected use, if each age and sex group in the study population had the same use rate as the national population.

Results

In both years, observed use was below expected use for the bottom third of areas by socioeconomic status. The standardized utilization rate ratio between top and bottom Townsend quintiles fell from 1.41 (95% confidence interval [CI] 1.36-1.47) in 1991 to 1.27 (95% CI 1.23-1.32) in 2001. The proportionate increase in use required to bring the bottom quintile to the level of top thus fell significantly from 41% to 27%. The Town-send-based concentration index also fell from 0.069 (95% CI 0.059-0.079) in 1991 to 0.060 (95% CI 0.050-0.071) in 2001, although this fall was not statistically significant (P=0.085). Other socioeconomic indicators yielded a similar pattern.

Conclusions

Socioeconomic small area inequality in use of total hip replacement appears to have fallen between 1991 and 2001. One possible explanation is that increased hip replacement rates in the 1990s may have lowered barriers to access, thus allowing this health technology to diffuse further among lower socio-economic groups.
Describing the impact of health services and policy research
Authors: Kuruvilla Shyama , Mays Nicholas , Walt Gill
Published: March 2007

Objectives

In an essentially applied area of research, there are particular pressures on health services and policy researchers to describe the impact of their work. However, specialized research impact assessments often require skills and resources beyond those available to individual researchers, and ad hoc accounts impose a considerable burden to generate. Further, these idiosyncratic accounts may not facilitate comparative analysis to inform research management, practice and assessment. This paper describes an initial attempt to develop a methodical approach to identify and describe research impact.

Methods

A Research Impact Framework was developed, drawing on the literature and interviews with researchers at the London School of Hygiene and Tropical Medicine, and was used to structure impact narratives of selected research projects. These narratives were based on semi-structured interviews with principal investigators and documentary analysis of the projects.

Results

Using the framework as a guide, researchers were relatively easily and methodically able to identify and present impacts of their work. Researchers’ narratives contained verifiable evidence and highlighted a wide range of areas in which health services and policy research has impact. The standardized structure of the narratives also facilitated analysis across projects. Factors thought to positively influence the impact of research included researchers’ continued involvement in research and policy networks, established track records in the field, and the ability to identify and use key influencing events, such as ‘policy windows’.

Conclusions

The framework helped develop research impact narratives and facilitated comparisons across projects, highlighting issues for research management and assessment.
Tied to the job: Affective and relational components of nurse retention
Authors: Barron David , West Elizabeth , Reeves Rachel
Published: March 2007

Objective

To investigate whether affective and relational components of nurses’ experience of work have a significant impact on their intentions to leave either the job or the nursing profession in models that control forother factors (sociodemographic, work conditions, perceptions of quality of care) that are known to affect career decisions.

Method

An exploratory, cross-sectional postal survey of 2880 nurses in grades A-I in 20 National Health Service (NHS) Hospital Trusts, 11 in inner London and nine in outer London, was carried out between January and July 2002, looking at nurses’ intention to leave their current job or the nursing profession. The data were analysed using logistic regression with robust standard errors.

Results

In models that controlled for known sources of job dissatisfaction, relationships with supervisors and managers were found to have a significant effect on respondents’ career intentions. Feeling valued by the Trust and by society was very important. Nurses seemed to distinguish between local problems that are the responsibility of the Trust and those, such as levels of pay, that could only be solved at the national level.

Conclusion

Nurses’ career intentions are complex and multifactorial. Feelings of being valued and listened to play a role, as well as the individual and job-related characteristics. The study highlights the role of supervisors and managers in retaining staff and suggests that investment in robust systems of communication, conflict resolution and security could slow nurse turnover. The NHS as an employer may be most interested in the role of pay in nurse retention, and the general public in how societal attitudes and verbal abuse shape nurses’ career decisions.
From Iron Cage to Iron Shield? How Bureaucracy Enables Temporal Flexibility for Professional Service Workers
Authors: Briscoe Forrest
Published: March 2007

This paper develops a model of how organizations influence the temporal flexibility of professional service workers. The model starts by identifying a key source of temporal inflexibility for these workers: an inability to hand clients off among one other. Hand-offs are impeded by high levels of client-to-worker specificity, stemming from three common characteristics of professional service work. The organizational processes that reduce that specificity, and therefore facilitate hand-offs, function by (a) reshaping client participation and expectations about the nature of their service interactions, (b) partly standardizing client-related work practices, and (c) facilitating the sharing of knowledge about clients between workers. The presence of these organizational processes represents greater bureaucracy—an interesting twist, given that they create more temporal flexibility for workers. The model is grounded in field research conducted with primary care physicians, and is also evaluated using a unique survey data set of physician organizations. Implications are drawn for the study of temporal flexibility across professional services in general, as well as for recent attempts to rethink the meaning of bureaucracy for workers.
Leveraging Knowledge Across Geographic Boundaries
Authors: Tallman Stephen , Phene Anupama
Published: March 2007

This paper examines knowledge flows within and across geographic boundaries of clusters and nations in the biotechnology industry. We hypothesize that these flows are characterized by various factors relating to the knowledge itself and by firm innovativeness and the presence of prior knowledge flows at the firm level. Surprisingly, our findings suggest that geographic proximity does not matter in some instances, while in others it has a decidedly nonlinear effect opposite to that hypothesized. The pattern of findings points to the greatest contrast in the comparison of between-cluster and between-country flows and presents an opportunity to reevaluate the role of geography and knowledge flows.
Continuous Learning: The Influence of National Institutional Logics on Training Attitudes
Authors: Luo Xiaowei
Published: March 2007

This research attempts to understand and test a core assumption in neoinstitutional theory, i.e., that institutional logics shape individual attitudes and preferences, by studying cross-national differences in people’s attitudes toward the continuous learning model of employee training—an increasingly popular model of training. I propose that national institutional logics regarding the individual’s role (empowered versus limited) can shape people’s preferences for the new model of training. By using a historically grounded typology of national polities depicting the organization of authority (statism) and society (corporateness), I suggest how these two dimensions carry distinct logics about the individual’s role and, in turn, shape people’s training orientation. Training attitudes of people in 16 European (EU) countries/regions are examined using data from the 1995 Eurobarometer Training Survey. Results from hierarchical models show that, beyond the influence of individual characteristics, people from nonstatist (i.e., collective authority is located in civil society rather than in the state) and noncorporatist (i.e., individuals are incorporated into the society as autonomous actors rather than members in collectives) countries are more likely to prefer the continuous learning model of training. By explicitly linking institutional logics with individual attitudes, this study contributes to the neoinstitutional perspective, studies on training attitudes, and cross-national research.
Business Model Design and the Performance of Entrepreneurial Firms
Authors: Zott Christoph , Amit Raphael
Published: March 2007

We focus on the design of an organization’s set of boundary-spanning transactions—business model design—and ask how business model design affects the performance of entrepreneurial firms. By extending and integrating theoretical perspectives that inform the study of boundary-spanning organization design, we propose hypotheses about the impact of efficiency-centered and novelty-centered business model design on the performance of entrepreneurial firms. To test these hypotheses, we developed and analyzed a unique data set of 190 entrepreneurial firms that were publicly listed on U.S. and European stock exchanges. The empirical results show that novelty-centered business model design matters to the performance of entrepreneurial firms. Our analysis also shows that this positive relationship is remarkably stable across time, even under varying environmental regimes. Additionally, we find indications of potential diseconomies of scope in design; that is, entrepreneurs’ attempts to incorporate both efficiency- and novelty-centered design elements into their business models may be counterproductive.
The Contingent Impact of Contextualization on Computer-Mediated Collaboration
Authors: Katz Adi , Te’eni Dov
Published: March 2007

Computer-mediated collaboration, a rapidly expanding form of work, introduces unique opportunities but problems as well. One of these problems is the higher risk of misunderstandings. Current communication theories suggest that misunderstanding may be reduced by contextualization, i.e., providing contextual information to explain a core message. However, we hypothesize that contextualization is beneficial in some situations but not in others. Treating contextualization as a form of adaptive behavior, we propose a model for understanding its contingent impact on performance in collaborative tasks. We explain the motivation for contextualization and argue that it can be predicted by the extent to which the perspectives of the collaborators are different or shared: A difference of perspectives between collaborators motivates them to contextualize to increase mutual understanding (MU) and thereby increase performance. Computer support should also motivate communicators to contextualize by making it easier for them to do so. A controlled experiment tests these relationships in a collaborative machine-assembly task performed by dyads. We manipulate the collaborators’ perspectives and the level of computer support, and we measure contextualization behavior, MU, and performance. Results show that contextualization is effective only for dyads with different perspectives and may be detrimental when perspectives are similar.
Incremental Organizational Learning from Multilevel Information Sources: Evidence for Cross-Level Interactions
Authors: Schwab Andreas
Published: March 2007

The availability of both direct performance feedback at the organization level and vicarious information at the industry level raises the question of their relative impact, as well as potential multilevel interactions. Prior research suggests that an organization’s own experience after adopting an innovative managerial practice tends to replace information collected by observing other organizations that implement the practice. The findings in this study show, however, that both organization-level performance feedback and population-level comparisons to other organizations affected incremental change of an innovative practice during its execution. The effects of these two information sources are not independent. Instead, results support a substitutional cross-level interaction. In addition, the study discovered that, when learning from their own experience, organizations engage in superstitious learning and do not let sufficient time pass before assessing the effects of prior changes. This study identifies principles that will promote a more integrated understanding of learning during the execution of innovative practices and contributes to the development of more fine-grained multilevel models of organizational learning.
STCS outlines key objectives
Authors: Towell Elaine
Published: March 2007

'To be successful, an organisation must have vision. It must understand clearly what it can and cannot influence, where it can make inroads and where effort and energy will bring the most success' – so says Sir Bruce Keogh, president of the Society for Cardiothoracic Surgery in Great Britain and Ireland (SCTS). To introduce a clear direction to the society during his two-year presidency, Professor Keogh, along with the society's executive committee, have agreed six key objectives to provide focus, continuity and momentum for the society.
A personal view of surgery
Authors: Kelly MJ
Published: March 2007

Close on 60, after some 36 years as a general surgical provider , my arthritic hip found itself on the wrong side of an orthopod' s knife. My last direct surgical experience, an appendicectomy, was 42 years ago, as a medical student. My wife, a long-retired senior orthopaedic ward sister, was systematically sceptical of my ability to be a good patient and issued dire warnings and prohibitions. I expected it to be very like boarding school – which was pretty accurate – although the hospital staff were rather kinder than the teachers.
Faculty development curriculum countdown day
Authors: Peyton Rodney , Thomas Bill , Alexander Francine
Published: March 2007

16 January 2007 was a memorable day for gales and transport disruptions. It was also a crucial day for those involved in faculty development to support the implementation of the intercollegiate surgical curriculum, as it was curriculum countdown day. Six months to implementation, how ready are surgeons for the change?
Diagnostic and treatment centres – implications for surgical training
Authors: Hobson J , Cruise A , Dhillon R
Published: March 2007

The Ear, Nose and Throat (ENT) senior house officer (SHO) position is a training post, and it is expected that the SHO will become proficient in various procedures during a six-month ENT post and ultimately by the end of basic surgical training (see http://www.entuk.org/career_advice). These 'index' procedures include grommet insertion, adenoidectomy and tonsillectomy. Anecdotally, it is felt that current ENT SHOs are not performing as many procedures as previously, with consequent negative effects on training. One of the reasons for this may be the creation of NHS diagnostic and treatment centres (DTCs) and independent sector treatment centres (ISTCs), purely elective hospitals, which take patients from the waiting lists of standard NHS hospitals.
Dronedarone: An Amiodarone Analog for the Treatment of Atrial Fibrillation and Atrial Flutter
Authors: Dale Krista M , White C Michael
Published: March 2007

Objective:

To review the pharmacology, pharmacokinetics, clinical efficacy, and safety profile of dronedarone for the treatment of atrial fibrillation.

Data Sources:

A literature search was conducted using the search terms dronedarone, SR 33589, atrial fibrillation, and antiarrhythmic medication in MEDLINE (1966–February 2007), International Pharmaceutical Abstracts (1970–February 2007), and EMBASE (1990–February 2007). References from the identified trials and selected review articles were evaluated. Additional information, including abstracts and posters, was obtained from Sanofi-Aventis.

Study Selection and Data Extraction:

Published studies and meeting abstracts evaluating the effects of dronedarone in humans and animals were reviewed.

Data Synthesis:

Dronedarone is a novel antiarrhythmic medication to treat atrial fibrillation. Dronedarone has a multifaceted mechanism of action similar to that of amiodarone. Dronedarone works by blocking potassium, sodium, and calcium channels and exhibits antiadrenergic properties. The drug has been evaluated at doses of 400, 600, and 800 mg twice daily. It prolonged the time to atrial fibrillation recurrence to 60–158 days compared with 5–59 days with placebo and decreased heart rate during atrial fibrillation by 12–25 beats/min in clinical trials. Major adverse events include gastrointestinal side effects and risk of proarrhythmia. Dronedarone may increase the risk of mortality in patients with congestive heart failure.

Conclusions:

Dronedarone is a new antiarrhythmic agent for the treatment of atrial fibrillation. Further studies are needed to better define dronedarone's safety profile and place in therapy.
Use of Atypical Antipsychotics in the Treatment of Autistic Disorder
Authors: Stachnik Joan M , Nunn-Thompson Cheryl
Published: March 2007

Objective:

To review clinical trials and reports describing the efficacy and safety of atypical antipsychotics (olanzapine, ziprasidone, quetiapine, aripiprazole) in the treatment of autistic or other pervasive developmental disorders.

Data Sources:

English-language publications from the MEDLINE database (1966–February 2007) including clinical trials, case reports, and retrospective series were reviewed.

Study Selection and Data Extraction:

Relevant data were extracted from studies of selected atypical antipsychotics in the treatment of autistic disorder in children, adolescents, and adults. Most literature found was in the form of case reports or case series; however, several open-label and double-blind trials were also identified.

Data Synthesis:

Autistic disorder is a chronic neurodevelopmental disorder with limited treatment options. Nonpharmacologic approaches may be the most beneficial, but pharmacologic agents are needed for some patients with significant behavioral manifestations of the disorder. The atypical antipsychotics (olanzapine, ziprasidone, quetiapine, aripiprazole) have shown some efficacy in improving certain behavioral symptoms of autistic disorder—primarily aggressiveness, hyperactivity, and self-injurious behavior. Efficacy was based on observation or changes from baseline in behavioral rating scores. Data appear to be strongest for olanzapine compared with quetiapine, with several open-label trials suggesting its efficacy. Weight gain and sedation were frequently reported adverse events with both agents. Aripiprazole has demonstrated efficacy in limited case series, with minimal adverse effects reported.

Conclusions:

Atypical antipsychotics represent a treatment option for symptoms associated with autistic disorder. However, these drugs do not affect the core symptoms of autistic disorder and are associated with potentially significant adverse effects. In addition, there is a lack of randomized controlled trials to determine the true efficacy and long-term safety of these agents in the pediatric population.
Rationale for Emphasis on Management over Treatment of Schizophrenia in Clinical Practice
Authors: Ahmed Mohiuddin , Osser David N , Boisvert Charles M , Albert Lawrence G , Aslam Masood
Published: March 2007

There is a need for clinicians to emphasize “management” over “treatment” in their pharmacologic approach to schizophrenia. Using the term “treatment” may set up unrealistic expectations for a fuller recovery to a premorbid level of functioning, with potential use of overmedication and polypharmacy as well as possible unwanted adverse effects. The “management” concept allows clinicians to work with the best current medication practice, taking into account the wide variability in the course of illness and response to treatment. Prescribing clinicians should work collaboratively with other caregivers to enhance adaptive behavior and functional outcome through psychosocial rehabilitative interventions, within the context of recovery.
The Role of Statin Therapy in Sepsis
Authors: Chua Doson , Tsang Ruth S , Kuo I Fan
Published: March 2007

Objective:

To systematically review the evidence evaluating the role of statin therapy in sepsis.

Data Sources:

MEDLINE, EMBASE, and PubMed were searched (1980–January 2007) for English-language clinical trials that evaluated the use of statins and the development and treatment of sepsis in human subjects. Search terms included statin, HMG-CoA reductase inhibitor, bacteremia, sepsis, septic shock, septicemia, and severe sepsis. In addition, pertinent references from identified articles were obtained.

Study Selection and Data Extraction:

Only clinical trials with primary efficacy outcomes of mortality, incidence of sepsis, and severe sepsis were included.

Data Synthesis:

Seven retrospective and 2 prospective cohort studies were included in this review. One was excluded because the patient population was not experiencing sepsis. Three studies demonstrated a reduced mortality with statin use while 2 other studies did not demonstrate this mortality benefit. One study suggested increased mortality with statin use in sepsis. Three studies showed a reduced incidence of development of sepsis or sepsis-related outcomes, while one study did not. The observational and retrospective nature of these studies and the higher rate of cardiovascular comorbidities in the statin groups may have allowed for a confounding influence. The conflicting results and heterogeneity between the studies makes the observed association between statin use and incidence of sepsis and sepsis-related mortality inconclusive. The clinical benefit of statin therapy in sepsis remains to be determined.

Conclusions:

There is an association between statin use and a lower incidence of sepsis and sepsis-related mortality. However, a causal relationship between stalin use and reduced sepsis-related mortality has not yet been established. Currently, statins cannot be recommended for sepsis prevention or treatment until controlled trials are performed.
Medicine Use Among 11- and 13-Year-Olds: Agreement Between Parents' Reports and Children's Self-Reports
Authors: Andersen Anette , Krølner Rikke , Holstein Bjørn E , Due Pernille , Hansen Ebba Holme
Published: March 2007

Background:

The validity of children's self-reports on medicine use has not been reported.

Objective:

To determine the agreement between parents' and children's reports of medicine use for 5 common complaints and to analyze predictors for disagreement.

Methods:

We used the child–parent validation survey from the research project Health Behaviour in School-Aged Children. Three hundred ninety-three 11- and 13-year-old Danish children and their parents responded to identical questionnaires. The main outcome measures were self-reported medicine use during the previous month for headache, stomachache, difficulties in falling asleep, nervousness, and asthma.

Results:

The percent agreement was lowest with medicine use for headache (64.6%), but was very high for the other 4 complaints (85.3–91.8%). The simple κ coefficients were moderate to good for medicine use for headaches, stomachache, and asthma (0.31–0.58) but poor for difficulties in falling asleep and nervousness. Children who had the specific complaint during the previous month were more likely than their parents to report more frequent medicine use.

Conclusions:

We have some confidence in young adolescents' self-reports of medicine use, as the results of this study are in keeping with other studies on the validity of children's reports of health-related behaviors. Furthermore, the findings suggest that such data can be used in epidemiologic studies that aim to categorize children into groups with and without medicine use.
Effect of Nesiritide Infusion Duration on Renal Function in Acutely Decompensated Heart Failure Patients
Authors: Chow Sheryl L , Peng Jessica T , Okamoto Mark P , Heywood J Thomas
Published: March 2007

Background:

Nesiritide, a synthetic B-type natriuretic peptide, is used for the treatment of patients with acutely decompensated heart failure. Although nesiritide has been reported to worsen renal function, as reflected by significant elevations in serum creatinine (SCr), the impact of infusion duration on renal function has not been evaluated.

Objective:

To investigate the effect of nesiritide infusion duration (<24 h vs ≥24 h) on worsening renal function in patients with acutely decompensated heart failure.

Methods:

Medical records of hospitalized patients receiving nesiritide were retrospectively reviewed, and 84 consecutive charts of patients with acute decompensated heart failure and available renal function tests were identified for the study. SCr and blood urea nitrogen (BUN) were documented at baseline and during infusion. Worsening renal function was defined as an increase in SCr of 0.5 mg/dL or more or BUN 10 mg/dL or more from baseline.

Results:

Univariate analysis showed a significant association between nesiritide infusion duration of 24 hours or more (26.1% vs 2.6%; p = 0.003), high diuretic doses (61.5% vs 32.4%; p = 0.045), and baseline SCr (2.0 ± 0.8 vs 1.5 ± 0.7 mg/dL; p = 0.04) with increases in SCr of 0.5 mg/dL or more. However, only infusion duration of 24 hours or more was statistically significant on multivariate analysis, after adjusting for baseline SCr (OR 10.46; 95% CI 1.26 to 86.72; p = 0.03). Longer duration of infusion was also a consistent variable in both univariate and multivariate analysis when elevated BUN was evaluated (34.8 vs 2.6%; p < 0.001 and OR 19.73; 95% CI 2.47 to 157.46; p = 0.005, respectively).

Conclusions:

Nesiritide infusion of 24 hours or more appears to be significantly associated with elevated markers of worsening renal function in patients with acutely decompensated heart failure compared with infusion of less than 24 hours; however, prospective studies are needed to corroborate this finding.
Pharmaceutical Care in Community Pharmacies: Practice and Research in Denmark
Authors: Herborg Hanne , Sørensen Ellen Westh , Frøkjær Bente
Published: March 2007

Objective:

To review the current status of Danish community pharmacy in both practice and research and discuss future trends.

Findings:

Denmark has a social welfare system that provides health care, social services, and pensions to its population. Medical care and surgery are free. Prescription medicines are reimbursed by an average of 56%. Community pharmacies are privately owned, but the health authorities regulate drug prices and the number of pharmacies. At present, Denmark has 322 pharmacies, corresponding to 1 pharmacy per 16 700 inhabitants. All pharmacies provide prescription and over-the-counter products, advice about medicine use, dose dispensing, generic substitutions, and administration of individual reimbursement registers. Except for very simple processes, compounding is centralized at 3 pharmacies. Many pharmacies offer measurement of blood glucose, blood pressure, and cholesterol, and 60% offer inhalation counseling, a reimbursed service. Research in pharmacy practice is well established and conducted primarily at universities and at Pharmakon A/S, which is owned by the Danish Pharmaceutical Association.

Discussion:

Extended services in clinical pharmacy are priorities for all Danish pharmacy organizations. Reimbursement is sought at the national level, as well as from payers in the new local authority structures in Denmark. The trend in research focuses on collaborative health care, on developing and documenting the value of community pharmacy services, and on optimizing services and strengthening implementation.

Conclusions:

Denmark has few, but large, community pharmacies and a long tradition of research and development resulting in several well-documented cognitive and clinical services. However, few services are reimbursed and implementation is still a challenge.
Critical Care: Multicenter Treatment and Outcome Evaluation of Aspiration Syndromes in Critically III Patients
Authors: Kane-Gill Sandra L , Olsen Keith M , Rebuck Jill A , Rea Rhonda S , Boatwright D Wesston , Smythe Maureen A , Walker Terrence R , Lager Stephanie L , Hodgman Tudy
Published: March 2007

Background:

Aspiration syndromes (pneumonia and pneumonitis) have significantly different processes. An evaluation of treatment and outcomes for these different syndromes has not been reported previously.

Objective:

To characterize and assess antimicrobial prescribing patterns for aspiration syndromes in intensive care unit (ICU) patients and describe outcomes of those patients.

Methods:

A retrospective, observational evaluation was conducted using a convenience sample of patients at 27 hospitals in North America; these patients were admitted to an adult ICU with a diagnosis of suspected/confirmed aspiration or had a suspected/confirmed aspiration while in the ICU. Hospital demographic, diagnosis, treatment, and clinical outcome data were collected.

Results:

Over a 12 month period, 187 patients were observed. Aspiration syndromes included suspected aspiration (31%; n = 58), aspiration pneumonitis (12%; n = 23), aspiration pneumonia (55%; n = 103), and diagnosis not available (1.6%; n = 3). Antimicrobial management for the aspiration syndromes was as follows: suspected aspiration: 59% single agent, 38% multiple agents, and 3% no therapy; aspiration pneumonitis; 48% single agent, 39% multiple agents, and 13% no therapy; aspiration pneumonia: 48% single agent. 52% multiple agents, and 0% no therapy. Antimicrobial therapy was prescribed in patients with suspected (97%) and confirmed (100%) aspiration. Antibiotic therapy duration was significantly longer for aspiration pneumonia (9.1 ± 7.5 days) than for aspiration pneumonitis (5.2 ± 3.6 days; p = 0.013). Length of ICU stay was similar across patient groups.

Conclusions:

Antimicrobial agents are frequently prescribed to treat aspiration syndromes despite the lack of demonstrated efficacy for aspiration pneumonitis. Outcomes between aspiration syndromes were similar with the exception of duration of antibiotic treatment.
Could Risk Assessment for Non-albicans Candida Improve Empiric Treatment for Invasive Candidiasis?
Authors: Drew Richard H
Published: March 2007

The changing epidemiology of invasive candidiasis, along with concerns for the emergence of drug resistance, necessitates the identification of patients at increased risk of non-albicans Candida (NAC) to optimize selection of antifungal therapy. The major findings of a study regarding the demographic characteristics, costs, and outcomes of nonneutropenic patients with candidemia due to NAC are discussed. Given available treatment options, such risk assessment is most relevant to initial empiric therapy in stable patients without neutropenia who might be candidates for initial therapy with an azole (eg, fluconazole). The study's investigators reinforce the need for timely antifungal therapy for patients with candidemia.
Characterisation of novel splicing variants of the tyrosine hydroxylase C-terminal domain in human neuroblastic tumours
Authors: Roma Josep , Saus Ester , Cuadros Marc , Reventós Jaume , Sánchez de Toledo Josep , Gallego Soledad
Published: March 2007

Alternative splicing of human tyrosine hydroxylase (hTH) transcripts appears to occur mainly in the N-terminal domain, giving rise to at least eight different isoforms. We recently reported the existence of hTH transcript variants resulting from splicing of exons 8 and 9, within a region previously thought to be constant. The mRNA distribution of these novel hTH isoforms in neuroblastic tumours and in foetal adrenal glands was analysed by conventional and real-time RT-PCR. The presence of the target protein was determined by Western blotting, immunoprecipitation and protein analysis. Transcripts lacking exons 8 and 9 were widely distributed in the tissues analysed. Characterisation of full-length mRNA revealed that splicing of exons 8 and 9 was always associated with splicing of exons 2 (hTH-Δ2,8,9) or 1b and 2 (hTH-Δ1b,2,8,9). In addition, one variant detected on Western blots in several tumours fits the predicted size (58 kDa) of the isoforms lacking exons 8 and 9. In conclusion, the two novel isoforms reported here (hTH-Δ2,8,9 and hTH-Δ1b,2,8,9) represent the first full-length isoforms with alternative splicing in the hTH C-terminal domain. These results demonstrate for the first time the existence of hTH isoforms Δ2,8,9 and Δ1b,2,8,9. Their general distribution in neuroblastoma and adrenal glands and translation into protein suggest a significant functional role for these novel hTH isoforms, which merit further study.
N.BspD6I DNA nickase strongly stimulates template-independent synthesis of non-palindromic repetitive DNA by Bst DNA polymerase
Authors: Zyrina Nadezhda V. , Zheleznaya Lyudmila A. , Dvoretsky Eugene V. , Vasiliev Victor D. , Chernov Andrei , Matvienko Nicholas I.
Published: March 2007

Highly efficient DNA synthesis without template and primer DNAs occurs when N.BspD6I DNA nickase is added to a reaction mixture containing deoxynucleoside triphosphates and the large fragment of Bst DNA polymerase. Over a period of 2 h, virtually all the deoxynucleoside triphosphates (dNTPs) become incorporated into DNA. Inactivation of N.BspD6I nickase by heating inhibits DNA synthesis. Optimal N.BspD6I activity is required to achieve high yields of synthesized DNA. Electron microscopy data revealed that the majority of DNA molecules have a branched structure. Cloning and sequencing of the fragments synthesized demonstrated that the DNA product mainly consists of multiple hexanucleotide non-palindromic tandem repeats containing nickase recognition sites. A possible mechanism is discussed that addresses template-independent DNA synthesis stimulated by N.BspD6I nickase.
Insulin-regulated aminopeptidase: analysis of peptide substrate and inhibitor binding to the catalytic domain
Authors: Ye Siying , Chai Siew Yeen , Lew Rebecca A. , Albiston Anthony L.
Published: March 2007

Peptide inhibitors of insulin-regulated aminopeptidase (IRAP) accelerate spatial learning and facilitate memory retention and retrieval by binding competitively to the catalytic site of the enzyme and inhibiting its catalytic activity. IRAP belongs to the M1 family of Zn2+-dependent aminopeptidases characterized by a catalytic domain that contains two conserved motifs, the HEXXH(X)18E Zn2+-binding motif and the GXMEN exopeptidase motif. To elucidate the role of GXMEN in binding peptide substrates and competitive inhibitors, site-directed mutagenesis was performed on the motif. Non-conserved mutations of residues G428, A429 and N432 resulted in mutant enzymes with altered catalytic activity, as well as divergent changes in kinetic properties towards the synthetic substrate leucine β-naphthalamide. The affinities of the IRAP inhibitors angiotensin IV, Nle1-angiotensin IV, and LVV-hemorphin-7 were selectively decreased. Substrate degradation studies using the in vitro substrates vasopressin and Leu-enkephalin showed that replacement of G428 by either D, E or Q selectively abolished the catalysis of Leu-enkephalin, while [A429G]IRAP and [N432A]IRAP mutants were incapable of cleaving both substrates. These mutational studies indicate that G428, A429 and N432 are important for binding of both peptide substrates and inhibitors, and confirm previous results demonstrating that peptide IRAP inhibitors competitively bind to its catalytic site.
HIRIP3 is a nuclear phosphoprotein interacting with and phosphorylated by the serine-threonine kinase CK2
Authors: Assrir Nadine , Filhol Odile , Galisson Frédéric , Lipinski Marc
Published: March 2007

The HIRIP3 protein had been identified from its interaction with the HIRA histone chaperone. Experiments using anti-peptide antisera indicated that this 556-aa protein is nuclear throughout the cell cycle and excluded from condensed chromatin during mitosis. Based on its electrophoretic migration and sensitivity to phosphatase treatment, endogenous HIRIP3 was found to be heavily phosphorylated. HIRIP3 can be phosphorylated in vitro by a recombinant form of the serine-threonine kinase CK2. Moreover, HIRIP3 protein was found to co-purify with a CK2 activity. Together, these data prompt us to propose HIRIP3 as a new member of the growing list of CK2 substrates with a possible role in chromatin metabolism.
Enzymatic properties of human kallikrein-related peptidase 12 (KLK12)
Authors: Memari Nader , Jiang Weiping , Diamandis Eleftherios P. , Luo Liu-Ying
Published: March 2007

Human kallikrein-related peptidase 12 (KLK12) is a new member of the human tissue kallikrein family. Preliminary studies suggest that KLK12 is differentially expressed in breast cancer and may have potential use as a cancer biomarker. It has been predicted that KLK12 is a secreted serine protease. However, the enzymatic properties of this protein have not been reported so far. Here, we report the production of recombinant KLK12 and analyses of its enzymatic characteristics, including zymogen activation, substrate specificity, and regulation of its activity. KLK12 is secreted as an inactive pro-enzyme, which is able to autoactivate to gain enzymatic activity. Through screening of a panel of fluorogenic and chromogenic peptide substrates, we establish that active KLK12 possesses trypsin-like activity, cleaving peptide bonds after both arginine and lysine. Active KLK12 quickly loses its activity due to autodegradation, and its activity can also be rapidly inhibited by zinc ions and by α2-antiplasmin through covalent complex formation. Furthermore, we demonstrate that KLK12 is able to activate KLK11 zymogen in vitro. Our results indicate that KLK12 may participate in enzymatic cascades involving other kallikreins.
Glutamic acid-141: a heme ‘bodyguard’ in anionic tobacco peroxidase
Authors: Hushpulian Dmitri M. , Poloznikov Andrew A. , Savitski Pavel A. , Rozhkova Alexandra M. , Chubar Tatyana A. , Fechina Victoria A. , Orlova Marina A. , Tishkov Vladimir I. , Gazaryan Irina G. , Lagrimini L. Mark
Published: March 2007

The role of the conserved glutamic acid residue in anionic plant peroxidases with regard to substrate specificity and stability was examined. A Glu141Phe substitution was generated in tobacco anionic peroxidase (TOP) to mimic neutral plant peroxidases such as horseradish peroxidase C (HRP C). The newly constructed enzyme was compared to wild-type recombinant TOP and HRP C expressed in E. coli. The Glu141Phe substitution supports heme entrapment during the refolding procedure and increases the reactivation yield to 30% compared to 7% for wild-type TOP. The mutation reduces the activity towards ABTS, o-phenylenediamine, guaiacol and ferrocyanide to 50% of the wild-type activity. No changes are observed with respect to activity for the lignin precursor substrates, coumaric and ferulic acid. The Glu141Phe mutation destabilizes the enzyme upon storage and against radical inactivation, mimicking inactivation in the reaction course. Structural alignment shows that Glu141 in TOP is likely to be hydrogen-bonded to Gln149, similar to the Glu143-Lys151 bond in Arabidopsis A2 peroxidase. Supposedly, the Glu141-Gln149 bond provides TOP with two different modes of stabilization: (1) it prevents heme dissociation, i.e., it ‘guards’ heme inside the active center; and (2) it constitutes a shield to protect the active center from solvent-derived radicals.