bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nursing Implementation Science: How Evidence‐Based Nursing Requires Evidence‐Based Implementation
Authors: Van Achterberg Theo , Schoonhoven Lisette , Grol Richard 
Published: November 2008

Purpose: Evidence is not always used in practice, and many examples of problematic implementation of research into practice exist. The aim of this paper is to provide an introduction and overview of current developments in implementation science and to apply these to nursing.
Methods: We discuss a framework for implementation, describe common implementation determinants, and provide a rationale for choosing implementation strategies using the available evidence from nursing research and general health services research.
Findings: Common determinants for implementation relate to knowledge, cognitions, attitudes, routines, social influence, organization, and resources. Determinants are often specific for innovation, context, and target groups. Strategies focused on individual professionals and voluntary approaches currently dominate implementation research. Strategies such as reminders, decision support, use of information and communication technology (ICT), rewards, and combined strategies are often effective in encouraging implementation of evidence and innovations. Linking determinants to theory‐based strategies, however, can facilitate optimal implementation plans.
Conclusions: An analytical, deliberate process of clarifying implementation determinants and choosing strategies is needed to improve situations where suboptimal care exists. Use of theory and evidence from implementation science can facilitate evidence‐based implementation. More research, especially in the area of nursing, is needed. This research should be focused on the effectiveness of innovative strategies directed to patients, individual professionals, teams, healthcare organizations, and finances.
Clinical Relevance: Implementation of evidence‐based interventions is crucial to professional nursing and the quality and safety of patient care.
Development of a Self‐Report Instrument to Measure Patient Safety Attitudes, Skills, and Knowledge
Authors: Schnall Rebecca , Stone Patricia , Currie Leanne , Desjardins Karen , John Rita Marie , Bakken Suzanne 
Published: November 2008

Purpose: To describe the development and psychometric testing of the Patient Safety Attitudes, Skills and Knowledge Scale (PS‐ASK).
Methods: Content validity of a 35‐item instrument was established by a panel of experts. The instrument was pilot tested on 285 nursing students. Principal components analysis (PCA) with varimax rotation was conducted, and Cronbach's alphas were examined. Paired samples t‐tests were used to show responsiveness of the scales pre‐ and post‐patient safety curriculum.
Results: The final instrument consists of 26 items and three separate scales: attitudes, skills, and knowledge. The attitudes and skills scales each had a three‐factor solution. The knowledge items had a one‐factor solution. Both skills and knowledge were significantly increased at Time 2 (p<0.001).
Conclusions: The skills and knowledge subscales had satisfactory internal consistency reliability, evidence for construct validity, and responsiveness for use as independent scales in future studies. The attitudes subscale needs further refinement before implementation. Comparison with other measures of patient safety skills (e.g., observation) and knowledge are warranted.
Clinical Relevance: A tool to measure clinicians' attitudes, skills, and knowledge about patient safety might be useful to evaluate nurses and other clinicians during educational preparation and in practice.
Combination of an EGFR blocker and a COX‐2 inhibitor for the treatment of advanced cutaneous squamous cell carcinoma
Authors: Jalili Ahmad , Pinc Alice , Pieczkowski Friederike , Karlhofer Franz M. , Stingl Georg , Wagner Stephan N. 
Published: November 2008

SummaryCutaneous squamous cell carcinoma (SCC) is one of the most common cancers worldwide. Epidermal growth factor receptor (EGFR) is expressed at the cell surface by more than 90% of SCCs and its activation is responsible for cell cycle progression, proliferation, survival, angiogenesis and metastasis. Cyclooxygenase‐2 (COX‐2) is an enzyme up‐regulated through EGFR signaling and responsible for some of the EGFR‐dependent biological effects. An 88‐year‐old man presented with a recurrent, locoregionally meta‐static SCC of the right parietal region, which was resistant to radiotherapy. With a combination therapy of an EGFR blocker (cetuximab) and a COX‐2 inhibitor (celecoxib), the tumor regressed partially and the patient's Karnofsky index improved. We speculate that the combined use of cetuxi‐mab and COX‐2 inhibitors can be a new and effective therapy for advanced and recurrent cutaneous SCCs.
Gravitational unloading inhibits the regenerative potential of atrophied soleus muscle in mice
Authors: Matsuba Y. , Goto K. , Morioka S. , Naito T. , Akema T. , Hashimoto N. , Sugiura T. , Ohira Y. , Beppu M. , Yoshioka T. 
Published: November 2008

AbstractAim:  The present study was performed to investigate the influence of unloading on the regeneration of atrophied and injured skeletal muscle.Methods:  Male mice (C57BL/6J), aged 8 weeks, were used. Cardiotoxin (CTX) was injected into soleus muscles bilaterally. Gravitational unloading on soleus muscle was performed by hind limb suspension for 2 weeks before and additionally 6 weeks after CTX injection in one group. Soleus muscles in the remaining groups were loaded keeping the mice in the cages and were dissected 14, 28 and 42 days after the injection.Results:  Recovery of the wet weight and protein content of soleus in the CTX‐injected group was inhibited by unloading. Increase in satellite cell number, induced by CTX injection and loading, was also inhibited by unloading. Disappearance of infiltration of mononucleated cells into the necrotic area was also delayed. This phenomenon suggests that regeneration, which is indicated by the appearance of fibres with central nuclei, was inhibited by unloading.Conclusion:  Results suggested that loading plays an important role in the activation of the regenerating potential of injured skeletal muscle.
Effects of ischemic postconditioning on reperfusion injury in rat liver grafts after orthotopic liver transplantation
Authors: Wang Nan , Lu Jian G. , He Xian L. , Li Na , Qiao Qing , Yin Ji K. , Ma Qing J. 
Published: November 2008

Aim:  The effects of ischemic postconditioning (IPostC) on ischemia reperfusion (IR) injury of liver grafts was examined in rats after orthotopic liver transplantation (OLT).Methods:  Male Wistar rats were used as donors and recipients to establish a liver transplantation model. The animals were randomly divided into four groups: sham‐operated (SO, n = 6), IR (n = 6), IPostC1 (n = 6) and IPostC2 (n = 6). IPostC was achieved by several intermittent interruptions of blood flow in the early phase of reperfusion. Several parameters of hepatic damage, oxidative stress, neutrophil infiltration and the expression of TNF‐α and MIP‐2 were detected as well as microscopic examination. Nitric oxide release and liver NO synthases (endothelial NO synthase and inducible NO synthase) expression were also measured.Results:  We observed that a significant reduction in alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase values in two IPostC groups when compared with IR group. The increases in hepatic malondialdehyde, and decreases in superoxide dismutase and reduced glutathione levels after orthotopic liver transplantation were significantly inhibited by IPostC. IR induced increase in hepatic myeloperoxidase content, TNF‐α and MIP‐2 expression were also lowered by IPostC. The increases in NO content and NOS protein expression were much more prominent in IPostC treated groups. Animals treated with IPostC presented minimal hemorrhage and reduced signs of liver injury. There was no significant difference between two IPostC treated groups.Conclusions:  IPostC provided significant protection against IR injury to liver grafts. The protective effect of IPostC is closely related to the NO production following the increase in endothelial and inducible NO synthases expression and the suppression of tumor necrosis factor‐α and macrophage inflammatory protein‐2 overproduction.
Analysis of hepatic genes involved in the metabolism of fatty acids and iron in nonalcoholic fatty liver disease
Authors: Mitsuyoshi Hironori , Yasui Kohichiroh , Harano Yuichi , Endo Mio , Tsuji Kazuhiro , Minami Masahito , Itoh Yoshito , Okanoue Takeshi , Yoshikawa Toshikazu 
Published: November 2008

Aims:  Hepatic steatosis and iron cause oxidative stress, thereby progressing steatosis to steatohepatitis. We quantified the expression of genes involved in the metabolism of fatty acids and iron in patients with nonalcoholic fatty liver disease (NAFLD).Methods:  The levels of transcripts for the following genes were quantified from biopsy specimens of 74 patients with NAFLD: thioredoxin (Trx), fatty acid transport protein 5 (FATP5), sterol regulatory element‐binding protein 1c (SREBP1c), fatty acid synthase (FASN), acetyl‐coenzyme A carboxylase (ACAC), peroxisome proliferative activated receptor α (PPARα), cytochrome P‐450 2E1 (CYP2E1), acyl‐coenzyme A dehydrogenase (ACADM), acyl‐coenzyme A oxidase (ACOX), microsomal triglyceride transfer protein (MTP), transferrin receptor 1 (TfR1), transferrin receptor 2 (TfR2) and hepcidin. Twelve samples of human liver RNA were used as controls. Histological evaluation followed the methods of Brunt.Results:  The levels of all genes were significantly higher in the NAFLD patients than in controls. The Trx level increased as the stage progressed. The levels of FATP5, SREBP1c, ACAC, PPARα, CYP2E1, ACADM and MTP significantly decreased as the stage and grade progressed (P < 0.05). Hepatic iron score (HIS) increased as the stage progressed. The TfR1 level significantly increased as the stage progressed (P < 0.05), whereas TfR2 level significantly decreased (P < 0.05). The ratio of hepcidin mRNA/ferritin (P < 0.001) or hepcidin mRNA/HIS (P < 0.01) was significantly lower in NASH patients than simple steatosis patients.Conclusions:  Steatosis‐related metabolism is attenuated as NAFLD progresses, whereas iron‐related metabolism is exacerbated. Appropriate therapies should be considered on the basis of metabolic changes.
Intrapulmonary Pharmacokinetics and Pharmacodynamics of Posaconazole at Steady State in Healthy Subjects
Authors: Conte John E. , Golden Jeffrey A. , Krishna Gopal , McIver Marina , Little Emily , Zurlinden Elisabeth 
Published: November 2008

ABSTRACT

We evaluated the pharmacokinetics (PK) and pharmacodynamics (PD) of posaconazole (POS) in a prospective, open-label study. Twenty-five healthy adults received 14 doses of POS oral suspension (400 mg twice daily) with a high-fat meal over 8 days. Pulmonary epithelial lining fluid (ELF) and alveolar cell (AC) samples were obtained via bronchoalveolar lavage, and blood samples were collected during the 24 h after the last dose. POS concentrations were determined using liquid chromatography with tandem mass spectrometry parameters. The maximum concentrations (
C
max
) (mean ± standard deviation) in plasma, ELF, and ACs were 2.08 ± 0.93, 1.86 ± 1.30, and 87.7 ± 65.0 μg/ml. The POS concentrations in plasma, ELF, and ACs did not decrease significantly, indicating slow elimination after multiple dosing. The mean concentrations of POS in plasma, ELF, and ACs were above the MIC
90
(0.5 μg/ml) for
Aspergillus
spp. over the 12-h dosing interval and for 24 h following the last dose. Area under the curve from 0 to 12 h (AUC
0-12
) ratios for ELF/plasma and AC/plasma were 0.84 and 33. AUC
0-24
/MIC
90
ratios in plasma, ELF, and AC were 87.6, 73.2, and 2,860. Nine (36%) of 25 subjects had treatment-related adverse events during the course of the study, which were all mild or moderate. We conclude that a dose of 400 mg twice daily resulted in sustained plasma, ELF, and AC concentrations above the MIC
90
for
Aspergillus
spp. during the dosing interval. The intrapulmonary PK/PD of POS are favorable for treatment or prevention of aspergillosis, and oral POS was well tolerated in healthy adults.
Molecular Evidence for Spread of Two Major Methicillin-Resistant
Staphylococcus aureus
Clones with a Unique Geographic Distribution in Chinese Hospitals
Authors: Liu Yudong , Wang Hui , Du Na , Shen Enhua , Chen Hongbin , Niu Junqi , Ye Huifen , Chen Minjun 
Published: November 2008

ABSTRACT

Methicillin (meticillin)-resistant
Staphylococcus aureus
(MRSA) is a serious problem worldwide. To investigate the molecular epidemiology of MRSA isolates in China, a total of 702 MRSA isolates collected from 18 teaching hospitals in 14 cities between 2005 and 2006 were characterized by antibiogram analysis, pulsed-field gel electrophoresis (PFGE), staphylococcal cassette chromosome
mec
(SCC
mec
) typing, and
spa
typing; and 102 isolates were selected for multilocus sequence typing (MLST). Overall, SCC
mec
type III was the most popular type and was found in 541 isolates (77.1%), followed by SCC
mec
type II (109/702; 15.5%). Twenty-four PFGE types were obtained among 395 isolates collected in 2005, and 18
spa
types were obtained among 702 isolates.
spa
type t030, which corresponded to PFEG types A to E, constituted 52.0% (365/702) of all isolates, and isolates of this type were present in all 14 cities;
spa
type t037, which corresponded to PFGE types F and G, accounted for 25.5% (179/702) of all isolates, and isolates of this type were identified in 12 cities. The two
spa
genotypes belonged to sequence type 239 (ST239) and carried SCC
mec
type III.
spa
type t002, which included isolates of PFGE types L to T, made up 16.0% (112/702) of the isolates that belonged to ST5 and SCC
mec
type II, and isolates of this type were distributed in 12 cities. The distribution of
spa
types varied among the regions.
spa
type t002 was the most common in Dalian (53.4%) and Shenyang (44.4%);
spa
type t037 was predominant in Shanghai (74.8%), whereas
spa
type t030 was the most common in the other cities. Two isolates from Guangzhou that harbored SCC
mec
type IVa with ST59 and ST88 were identified as community-associated MRSA. The prevalence of the Panton-Valentine leukocidin gene was 2.3%. The data documented two major epidemic MRSA clones, ST239-MRSA-SCC
mec
type III and ST5-MRSA-SCC
mec
type II, with unique geographic distributions across China.
First Report on a Hyperepidemic Clone of KPC-3-Producing
Klebsiella pneumoniae
in Israel Genetically Related to a Strain Causing Outbreaks in the United States
Authors: Navon-Venezia Shiri , Leavitt Azita , Schwaber Mitchell J. , Rasheed J. Kamile , Srinivasan Arjun , Patel Jean B. , Carmeli Yehuda 
Published: November 2008

ABSTRACT

A highly epidemic carbapenem-resistant clone of KPC-3-producing
Klebsiella pneumoniae
emerged in Israel in 2006, causing a nationwide outbreak. This clone was genetically related to outbreak strains from the United States isolated in 2000 but differed in KPC-carrying plasmids. The threat of the global spread of hyperepidemic, extensively drug-resistant bacterial strains should be recognized and confronted.
qnrD
, a Novel Gene Conferring Transferable Quinolone Resistance in
Salmonella enterica
Serovar Kentucky and Bovismorbificans Strains of Human Origin
Authors: Cavaco L. M. , Hasman H. , Xia S. , Aarestrup F. M. 
Published: November 2008

ABSTRACT

In a previous study, four
Salmonella
isolates from humans in the Henan province of China showed reduced susceptibility to ciprofloxacin (MIC, 0.125 to 0.25 μg/ml) but were susceptible to nalidixic acid (MIC, 4 to 8 μg/ml). All isolates were negative for known
qnr
genes (A, B, and S),
aac(6′)Ib-cr
, and mutations in
gyrA
and
parC
. Plasmid DNA was extracted from all four isolates and transformed into
Escherichia coli
TG1 and DH10B cells by electroporation, and transformants were selected on 0.06 μg/ml ciprofloxacin containing brain heart infusion agar plates. Resistance to ciprofloxacin could be transferred by electroporation, and a similar 4,270-bp plasmid was found in all transformants. By sequence analysis, the plasmid was found to carry an open reading frame that had similarities to other
qnr
genes and that encoded a 214-amino-acid pentapeptide repeat protein. This gene, designated
qnrD
, showed 48% similarity to
qnrA1
, 61% similarity to
qnrB1
, and 41% similarity to
qnrS1
. Further subcloning of the
qnrD
coding region into the constitutively expressed
tetA
gene of vector pBR322 showed that the gene conferred an increase in the MIC of ciprofloxacin by a factor of 32 (from an MIC of 0.002 to an MIC of 0.06 μg/ml). For comparison,
qnrA1
and
qnrS1
were also subcloned into pBR322 and transformed into DH10B cells, conferring MICs of 0.125 and 0.5 μg/ml, respectively. A phylogenetic analysis of all known
qnr
sequences was performed and showed that
qnrD
was more closely related to the
qnrB
variants but formed an independent cluster. To our knowledge, this is the first description of this
qnrD
gene.
Comprehensive In Vitro Analysis of Voriconazole Inhibition of Eight Cytochrome P450 (CYP) Enzymes: Major Effect on CYPs 2B6, 2C9, 2C19, and 3A
Authors: Jeong Seongwook , Nguyen Phuong D. , Desta Zeruesenay 
Published: November 2008

ABSTRACTVoriconazole is an effective antifungal drug, but adverse drug-drug interactions associated with its use are of major clinical concern. To identify the mechanisms of these interactions, we tested the inhibitory potency of voriconazole with eight human cytochrome P450 (CYP) enzymes. Isoform-specific probes were incubated with human liver microsomes (HLMs) (or expressed CYPs) and cofactors in the absence and the presence of voriconazole. Preincubation experiments were performed to test mechanism-based inactivation. In pilot experiments, voriconazole showed inhibition of CYP2B6, CYP2C9, CYP2C19, and CYP3A (half-maximal [50%] inhibitory concentrations, <6 μM); its effect on CYP1A2, CYP2A6, CYP2C8, and CYP2D6 was marginal (<25% inhibition at 100 μM voriconazole). Further detailed experiments with HLMs showed that voriconazole is a potent competitive inhibitor of CYP2B6 (Ki< 0.5), CYP2C9 (Ki= 2.79 μM), and CYP2C19 (Ki= 5.1 μM). The inhibition of CYP3A by voriconazole was explained by noncompetitive (Ki= 2.97 μM) and competitive (Ki= 0.66 μM) modes of inhibition. Prediction of the in vivo interaction of voriconazole from these in vitro data suggests that voriconazole would substantially increase the exposure of drugs metabolized by CYP2B6, CYP2C9, CYP2C19, and CYP3A. Clinicians should be aware of these interactions and monitor patients for adverse effects or failure of therapy.
In Vitro and In Vivo Studies To Characterize the Clearance Mechanism and Potential Cytochrome P450 Interactions of Anidulafungin
Authors: Damle Bharat D. , Dowell James A. , Walsky Robert L. , Weber Gregory L. , Stogniew Martin , Inskeep Philip B. 
Published: November 2008

ABSTRACTAnidulafungin is a novel semisynthetic echinocandin with potent activity againstCandida(including azole-resistant isolates) andAspergillusspp. and is used for serious systemic fungal infections. The purpose of these studies was to characterize the clearance mechanism and potential for drug interactions of anidulafungin. Experiments included in vitro degradation of anidulafungin in buffer and human plasma, a bioassay for antifungal activity, in vitro human cytochrome P450 inhibition studies, in vitro incubation with rat and human hepatocytes, and mass balance studies in rats and humans. Clearance of anidulafungin appeared to be primarily due to slow chemical degradation, with no evidence of hepatic-mediated metabolism (phase 1 or 2). Under physiological conditions, further degradation of the primary degradant appears to take place. The primary degradation product does not retain antifungal activity. Anidulafungin was not an inhibitor of cytochrome P450 enzymes commonly involved in drug metabolism. Mass balance studies showed that anidulafungin was eliminated in the feces predominantly as degradation products, with only a small fraction (10%) eliminated as unchanged drug; fecal elimination likely occurred via biliary excretion. Only negligible renal involvement in the drug's elimination was observed. In conclusion, the primary biotransformation of anidulafungin is mediated by slow chemical degradation, with no evidence for hepatic enzymatic metabolism or renal elimination.
Local and Systemic Responses in Matrix Metalloproteinase 8-Deficient Mice duringPorphyromonas gingivalis-Induced Periodontitis
Authors: Kuula Heidi , Salo Tuula , Pirilä Emma , Tuomainen Anita M. , Jauhiainen Matti , Uitto Veli-Jukka , Tjäderhane Leo , Pussinen Pirkko J. , Sorsa Timo 
Published: November 2008

ABSTRACTPeriodontitis is a bacterium-induced chronic inflammation that destroys tissues that attach teeth to jaw bone. Pathologically excessive matrix metalloproteinase 8 (MMP-8) is among the key players in periodontal destruction by initiating type I collagen degradation. We studied MMP-8 inPorphyromonas gingivalis-induced periodontitis by using MMP-8-deficient (MMP8−/−) and wild-type (WT) mice. Alveolar bone loss, inflammatory mediator expression, serum immunoglobulin, and lipoprotein responses were investigated to clarify the role of MMP-8 in periodontitis and systemic inflammatory responses.P. gingivalisinfection induced accelerated site-specific alveolar bone loss in bothMMP8−/−and WT mice relative to uninfected mice. The most extensive bone degradation took place in theP. gingivalis-infectedMMP8−/−group. Surprisingly, MMP-8 significantly attenuated (P< 0.05)P. gingivalis-induced site-specific alveolar bone loss. Increased alveolar bone loss inP. gingivalis-infectedMMP8−/−and WT mice was associated with increase in gingival neutrophil elastase production. Serum lipoprotein analysis demonstrated changes in the distribution of high-density lipoprotein (HDL) and very-low-density lipoprotein (VLDL) particles; unlike the WT mice, theMMP8−/−mice underwent a shift toward a smaller HDL/VLDL particle sizes.P. gingivalisinfection increased the HDL/VLDL particle size in theMMP8−/−mice, which is an indicator of lipoprotein responses during systemic inflammation. Serum total lipopolysaccharide activity and the immunoglobulin G-class antibody level in response toP. gingivaliswere significantly elevated in both infected mice groups. Thus, MMP-8 appears to act in a protective manner inhibiting the development of bacterium-induced periodontal tissue destruction, possibly through the processing anti-inflammatory cytokines and chemokines. Bacterium-induced periodontitis, especially inMMP8−/−mice, is associated with systemic inflammatory and lipoprotein changes that are likely involved in early atherosclerosis.
Discontinuities due to Joining Precipitation Station Observations in Canada
Authors: Vincent Lucie A. , Mekis Eva 
Published: November 2008

Abstract
When a climatological station is relocated or is closing, it is often possible to join the climate observations of a nearby site to create a longer time series. However, joining climate observations can sometimes introduce artificial discontinuity that affects the trend. A procedure to detect discontinuities at the joining dates for precipitation station observations is described. It is based on standardized ratios between a tested station and a neighbor, and the t test is used to determine whether the means before and after the joining dates are statistically significantly different. The procedure is applied to 234 climatological stations across Canada to identify steps in rainfall and snowfall. The results indicate that joining precipitation station observations creates steps of different magnitude for rain and snow. It is concluded that about 35% of the stations need adjustment for rain whereas 58% of the stations need adjustment for snow. The magnitude of the adjustments varies from 0.75 to 1.25 for rain and from 0.65 to 1.60 for snow. The annual and seasonal trends before and after adjustments are also examined for 1930–2007. The results show that the trends computed from the adjusted data present a more consistent regional pattern than do trends computed from the unadjusted observations.