bluuebunny/crossref_metadata_2025 huggingface dataset:
Determining factors in evidence‐based clinical practice among hospital and primary care nursing staff
Authors: De Pedro‐Gómez Joan , Morales‐Asencio José Miguel , Bennasar‐Veny Miquel , Artigues‐Vives Guillem , Perelló‐Campaner Catalina , Gómez‐Picard Patricia
Published: August 2011

de pedro‐gómez j., morales‐asencio j.m., bennasar‐veny m., artigues‐vives g., perelló‐campaner c. & gómez‐picard p. (2012) Determining factors in evidence‐based clinical practice among hospital and primary care nursing staff. Journal of Advanced Nursing 68(2), 452–459.

Aim.  The general aim of this study is to identify key factors perceived by nurses to influence evidence‐based clinical practice at different centres.

Background.  During the last decade, there has been an increased interest in the identification of factors that facilitate the transfer of knowledge into clinical practice, among health care professionals. Previous research states that a suitable organisational framework and practice environment seems to have influence on a greater use of scientific evidence by nurses, which can be directly observed in patient outcomes. In consequence, several authors suggest that strategies should be encouraged from managers and nurse executives to guarantee the existence of environments that avoid emotional exhaustion and improve satisfaction of nurses with their work, and at the same time, ensure the use of research‐guided nursing decisions.

Methods.  Following the Spanish validation of the Practice Environment Scale‐Nursing Work Index and Evidence Based Practice Questionnaire, a descriptive observational cross‐sectional study has been conceived, from 2010 to 2011, in order to identify determining factors in evidence‐based clinical practice at different centres. In a second phase, a qualitative study has been designed, using focus groups, to identify practice factors that can lead to a successful implementation of evidence‐based clinical practice.

Discussion.  Organisational and attitudinal interventions are needed in order to implement evidence‐based clinical practice that improves the quality of patient care.
Evidence‐based medicine and progress in the medical sciences
Authors: De Vreese Leen
Published: August 2011

The question what scientific progress means for a particular domain such as medicine seems importantly different from the question what scientific progress is in general. While the latter question received ample treatment in the philosophical literature, the former question is hardly discussed. I argue that it is nonetheless important to think about this question in view of the methodological choices we make. I raise specific questions that should be tackled regarding scientific progress in the medical sciences and demonstrate their importance by means of an analysis of what evidence‐based medicine (EBM) has, and has not, to offer in terms of progress. I show how critically thinking about EBM from the point of view of progress can help us in putting EBM and its favoured methodologies in the right perspective. My conclusion will be that blindly favouring certain methods because of their immediately tangible short‐term benefits implies that we parry the important question of how best to advance progress in the long run. This leads us to losing sight of our general goals in doing research in the medical sciences.
Strong differences in chemical recognition cues between two closely related species of ants from the genus Lasius (Hymenoptera: Formicidae)
Authors: MORRISON W. R. , WITTE V.
Published: August 2011

Cuticular hydrocarbons (CHCs) are increasingly recognized as important to insects and are used for constructing taxonomies. However, multiple parameters affect the expression of CHCs besides a genetic component. We propose that selection may act differently on the expression of CHCs, depending on the evolutionary context. To explore the influence of selection, the CHCs of two closely related ant species, Lasius niger and Lasius platythorax, were studied in a multidisciplinary approach. We characterized (i) CHCs and (ii) niches (through baiting, activity observations and foraging analysis). The species were distinct in both measures, although to a varying degree. Although they showed moderate niche partitioning along diet and environmental preferences, chemical differences were unexpectedly pronounced. This may be explained by divergent selection on mate recognition cues or by other influences on CHCs. Such striking chemical differences among closely related species may not be the rule and suggest that taxonomies based on CHCs should be interpreted cautiously; though, they remain useful tools for differentiating among cryptic species.
Comparative studies on temperature threshold for heat shock protein 70 induction in young and adult Murrah buffaloes
Authors: Haque N. , Ludri A. , Hossain S. A. , Ashutosh M.
Published: August 2011

To know the temperature threshold for heat shock protein 70 (HSP70) induction in lymphocytes and to assess physiological changes, if any, in relation to HSP70 induction in young and adult Murrah buffaloes, this study was divided into two parts: I. In vivo study: where assay of HSP70 was performed in blood samples collected from acutely exposed young and adult Murrah buffaloes (n = 6) inside a climatic chamber at 40, 42 and 45 °C for 4 h and thermoneutral temperature (22 °C). Physiological parameters viz., rectal temperature, respiratory rate, pulse rate and skin temperature of different body parts were monitored to assess magnitude of stress in the animals owing to thermal exposure II. For in vitro study, equal numbers of lymphocyte cells were separated from blood collected from young and adult buffaloes and were subjected to four temperature treatments (38, 40, 42 and 45 °C) for 4 h. A significant increase (p < 0.05) in all the physiological parameters in both young and adult buffaloes was observed after exposure to 40, 42 and 45 °C for 4 h as compared to 38 °C. The average plasma HSP70 concentrations (ng/ml) were significantly higher (p < 0.05) at 40, 42 and 45 °C as compared to 38 °C in both young and adult and were higher in young than adult buffaloes at 38 and 45 °C. Heat shock protein 70 level in lymphocyte lysate showed highest concentration after 3‐h exposure to all temperatures (40, 42 and 45 °C) in both young and adult buffaloes. The intensity of changes of all physiological parameters was more in young animals than in the adults indicating the greater susceptibility of younger animals to heat stress and was found to be changed at around 40 °C when animals were exposed to different temperatures, indicating the possibility that HSP70 production may be initiated at this temperature which is 2 or 3 °C higher than core body temperature.
Adipokines and thrombosis
Authors: Schäfer Katrin , Konstantinides Stavros
Published: August 2011

1. Obesity is a major risk factor for cardiovascular disease. An increased body mass index (BMI) is associated with venous thromboembolism, myocardial infarction, stroke and stent thrombosis after percutaneous interventions. Studies in mouse models of obesity and induced arterial or venous thrombosis have provided insights into the mechanisms involved.

2. In addition to elevated circulating levels of fibrinogen, factor VII and plasminogen activator inhibitor (PAI)‐1, changes in platelet biology and function may underlie the increased (athero) thrombotic risk in obesity. These include elevated platelet counts, an increase in mean platelet volume, an increased platelet aggregatory response to agonists and a reversible resistance to the anti‐aggregatory effects of nitric oxide and prostacyclin I2.

3. Specific adipokines mediate the prothrombotic state in obesity. Of these, leptin enhances both arterial and venous thrombosis by promoting platelet adhesion, activation and aggregation. Leptin also induces tissue factor expression by human neutrophils and other cells. C‐Reactive protein enhances the formation of monocyte–platelet aggregates and also promotes P‐selectin expression and platelet adhesion to endothelial cells. Further, the adipose tissue is a significant source of tissue factor and PAI‐1. Conversely, the circulating levels of adiponectin, a hormone that exerts vasculoprotective, anti‐atherosclerotic and antithrombotic effects, are reduced in obese individuals.

4. A better understanding of the interactions of the adipose tissue with circulating and vascular cells and the dissection of the mechanisms linking adipokines to arterial and venous thrombosis may identify obese individuals at particularly high cardiovascular risk and indicate promising vasculoprotective and therapeutic targets.
Aggressive behavior in patients with dementia: Correlates and management
Authors: Cipriani Gabriele , Vedovello Marcella , Nuti Angelo , Di Fiorino Mario
Published: August 2011

Aim: To consider the phenomenon of aggressive behavior perpetrated by people with dementia.

Methods: We searched electronic databases and key journals using the search terms: aggressive behavior; dementia; behavioral and psychological symptoms.

Results: Aggressive behavior (AB) is probably one of the principal problems in dementia. Aggression is linked to internal factors (depression, psychosis, pain) and external determinants (caregiver burden, social stimulation, quality of caregiver–patient relationship). It has been suggested that challenging behavior in people with dementia reflects their premorbid personality traits.

Conclusion: Over the course of the illness AB occurs in 30 to 50% of patients and causes extreme stress for caregivers. Careful identification of target symptoms and their consequences, non‐pharmacological approaches, and use of the least harmful medication for the shortest period of time should be the guiding principle of treatment.Geriatr Gerontol Int 2011; 11: 408–413.
Local Weighted Linear Combination
Authors: Malczewski Jacek
Published: August 2011

The article focuses on one of the most often used GIS‐based multicriteria analysis methods: the weighted linear combination (WLC). The WLC model has traditionally been used as a global approach based on the implicit assumption that its parameters do not vary as a function of geographical space. This assumption is often unrealistic in real‐world situations. The article proposes a new approach to GIS‐based multicriteria analysis. It develops a local form of the global WLC model. The range sensitivity principle is used as a central concept for developing the local WLC model. The principle postulates that the greater the range of criterion values is, the greater the weight assigned to that criterion should be. Consequently, the local criterion weight can be defined for each neighborhood within a study area as a function of the range of criterion values in a given neighborhood. The range of criterion values provides also the base for defining the local value function. The article presents the theory behind the local WLC modeling and illustrates an implementation of the model in a GIS environment.
Monitoring Residual Spatial Patterns using Bayesian Hierarchical Spatial Modelling for Exploring Unknown Risk Factors
Authors: Law Jane , Chan Ping W.
Published: August 2011

This article studies Bayesian hierarchical spatial modelling that monitors the changes of residual spatial pattern (structure) of the outcome variable for exploring unknown risk factors in small‐area analysis. Spatially structured random effects (SRE) and unstructured random effects (URE) terms added to the conventional logistic regression model take into account overdispersion and residual spatial structure, which if unaccounted for could cause incorrect identification of risk factors. Mapping and/or calculating the ratio of random effects that are spatially‐structured monitor the extent of residual spatial structure. The monitoring provides insights into identification of unknown covariates that have similar spatial structures to those of SRE. Adding such covariates to the model has the potential to diminish the residual spatial structure, until possibly all or most of the spatial structure can be explained. Risk factors identified are the added covariates that have statistically significant regression coefficients. We apply the methods to the analysis of domestic burglaries in Cambridgeshire, England. Small‐area analysis of crime where data often display apparent spatial structure would particularly benefit from the methodologies. We discuss the methodologies, their relevancy in our analysis of domestic burglaries, their limitations, and possible paths for future research.
Street‐level Spatial Interpolation Using Network‐based IDW and Ordinary Kriging
Authors: Shiode Narushige , Shiode Shino
Published: August 2011

This study proposes network‐based spatial interpolation methods to help predict unknown spatial values along networks more accurately. It expands on two of the commonly used spatial interpolation methods, IDW (inverse distance weighting) and OK (ordinary kriging), and applies them to analyze spatial data observed on a network. The study first provides the methodological framework, and it then examines the validity of the proposed methods by cross‐validating elevations from two contrasting patterns of street network and comparing the MSEs (Mean Squared Errors) of the predicted values measured with the two proposed network‐based methods and their conventional counterparts. The study suggests that both network‐based IDW and network‐based OK are generally more accurate than their existing counterparts, with network‐based OK constantly outperforming the other methods. The network‐based methods also turn out to be more sensitive to the edge effect, and their performance improves after edge correction. Furthermore, the MSEs of standard OK and network‐based OK improve as more sample locations are used, whereas those of standard IDW and network‐based IDW remain stable regardless of the number of sample locations. The two network‐based methods use a similar set of sample locations, and their performance is inherently affected by the difference in their weight distribution among sample locations.
My, your and our needs for safety and security: relatives’ reflections on using information and communication technology in dementia care
Authors: Olsson Annakarin , Engström Maria , Skovdahl Kirsti , Lampic Claudia
Published: August 2011

Scand J Caring Sci; 2012; 26; 104–112
 
My, your and our needs for safety and security: relatives’ reflections on using information and communication technology in dementia care

Aim:  The present paper reports on a study aimed at describing relatives′ reflections on different kinds of information and communication technology (ICT) devices that are used or can be used in the daily care of persons with dementia.

Background:  Many persons with dementia continue living in their own homes, which requires the support of their relatives. One way to meet the needs of relatives and persons with dementia is to use ICT.

Methods:  An interview study was conducted in Sweden (2007–2008) with a purposive sample of 14 spouses of a person with dementia. Qualitative content analysis was used to identify categories and themes in the data.

Findings:  Relatives′ reflections on the use of ICT were described as ICT – a support in daily life, ICT – internal and external conditions and ICT – the decision to use or not use. Based on these categories, a theme was revealed: shifting between different perspectives: my, your and our needs for safety and security.

Conclusion:  Relatives struggle to create a situation of safety and security in daily life for themselves and the persons with dementia. ICT devices with the right functionality and used at the right time are regarded as useful in solving everyday problems. In the decision to use or not use ICT, the opportunity to create a safe and secure environment overshadows potential ethical problems. Providing early information about ICT to persons with dementia and their relatives could facilitate joint decision‐making regarding use of ICT.
Characteristics of isolated lactic acid bacteria and their effectiveness to improve stylo (Stylosanthes guianensis Sw.) silage quality at various temperatures
Authors: LIU Qinhua , CHEN Mingxia , ZHANG Jianguo , SHI Shangli , CAI Yimin
Published: August 2011

Two lactic acid bacteria (LAB) strains, Pediococcus pentosaceus SC1 and Lactobacillus paraplantarum SC2 isolated from king grass silage, were characterized and their effectiveness to improve the silage fermentation quality of stylo (Stylosanthes guianensis Sw.) was studied. Strain SC1 was able to grow at a high temperature of 45°C, while SC2 did not. SC2 normally grew at a low pH of 4.0, while SC1 could not. These two strains and a commercial inoculant of LAB (L. plantarum, LP) were used as additives to stylo silage preparation at various temperatures (20°C, 30°C and 40°C). All LAB inoculants significantly (P < 0.05) reduced the pH value and ammonia‐N content, and increased the ratio of lactic acid to acetic acid and quality score compared with the control. In addition, inoculating LAB strains markedly (P < 0.05) reduced butyric acid content at the temperatures of 30°C and 40°C. Compared to SC2 and LP strains, strain SC1 was the most effective for improving stylo silage quality at 20°C, indicated by the increase in lactic acid, ratio of lactic acid to acetic acid and quality score. At 30°C and 40°C, there were no significant differences among SC1, SC2 and LP treatments in pH values, contents of acetic acid, butyric acid and ammonia‐N (P > 0.05).
Changes in the hydrological functioning of a playa‐lake complex under increasing agricultural pressures (Andalusia, Southern Spain)
Authors: Beltran M. , Moral F. , Rodríguez‐Rodríguez M.
Published: August 2011

The La‐Lantejuela playa‐lakes endorheic complex is a groundwater‐dependent ecosystem located within the Guadalquivir River Basin (Southern Spain) in an area mainly devoted to agriculture production with increasing groundwater extractions for irrigation from the Osuna‐La Lantejuela (O‐LL) aquifer. The O‐LL aquifer was hydrogeologically characterised in previous works made by the authors. New data and the combination of more field observations, together with the use of morphologic indexes of the playa lakes, has permitted to analyse the relationships between the aquifer and each one of the playa lakes in the complex, assessing whether their hydrological functioning would have been affected by the expansion of irrigated agriculture. Furthermore, the analysis of the results obtained has allowed establishing a hypothesis of the hydrological functioning of the whole system under natural conditions. This case study represents a useful example to understand how agriculture in semi‐arid environments can induce alterations on the wetlands hydrological functioning.
Efficacy of Human-Simulated Exposures of Tomopenem (Formerly CS-023) in a Murine Model of Pseudomonas aeruginosa and Methicillin-Resistant Staphylococcus aureus Infection
Authors: Sugihara Kiyoshi , Tateda Kazuhiro , Yamamura Naotoshi , Koga Tetsufumi , Sugihara Chika , Yamaguchi Keizo
Published: August 2011

Tomopenem (formerly CS-023) is a novel carbapenem with improved activity against diverse hospital pathogens, including
Pseudomonas aeruginosa
and methicillin-resistant
Staphylococcus aureus
(MRSA), and has a half-life about twice longer than the half-lives of other carbapenems such as imipenem and meropenem. Our objective in this study was to estimate the efficacy of tomopenem in humans by human-simulated exposures in a neutropenic murine thigh infection model against 9 clinical isolates of
P. aeruginosa
with MICs of 4 to 32 μg/ml and 9 clinical isolates of MRSA with MICs of 4 to 16 μg/ml. Human-simulated dosing regimens in neutropenic mice were designed to approximate the cumulative percentage of a 24-h period that the free drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (
f
%
T
MIC
) observed with tomopenem at 750 and 1,500 mg given as a 0.5-h infusion three times a day (TID) in humans. As reported previously, there was no difference between the target values of
P. aeruginosa
and MRSA required for efficacy (K. Sugihara et al., Antimicrob. Agents Chemother.
54:
5298-5302, 2010). Tomopenem at 750 mg showed bactericidal or bacteriostatic effects against 10 of 11 strains of
P. aeruginosa
and MRSA with MICs of ≤8 μg/ml (
f
%
T
MIC
≥ 41), and tomopenem at 1,500 mg showed bactericidal effects against 16 of 17 strains of
P. aeruginosa
and MRSA with MICs of ≤16 μg/ml (
f
%
T
MIC
≥ 43). Meropenem at 1,000 mg TID was tested for comparison purposes and showed bactericidal or bacteriostatic effects against 3 of 4 strains of
P. aeruginosa
with MICs of ≤4 μg/ml (
f
%
T
MIC
≥ 33). From these results, tomopenem is expected to be effective with an
f
%
T
MIC
of over 40 against
P. aeruginosa
and MRSA strains with MICs of ≤8 μg/ml at doses of 750 mg TID and strains with MICs of ≤16 μg/ml at doses of 1,500 mg TID.
Antibacterial Mechanism of Action of Arylamide Foldamers
Authors: Mensa Bruk , Kim Yong Ho , Choi Sungwook , Scott Richard , Caputo Gregory A. , DeGrado William F.
Published: August 2011

Small arylamide foldamers designed to mimic the amphiphilic nature of antimicrobial peptides (AMPs) have shown potent bactericidal activity against both Gram-negative and Gram-positive strains without many of the drawbacks of natural AMPs. These foldamers were shown to cause large changes in the permeability of the outer membrane of
Escherichia coli
. They cause more limited permeabilization of the inner membrane which reaches critical levels corresponding with the time required to bring about bacterial cell death. Transcriptional profiling of
E. coli
treated with sublethal concentrations of the arylamides showed induction of genes related to membrane and oxidative stresses, with some overlap with the effects observed for polymyxin B. Protein secretion into the periplasm and the outer membrane is also compromised, possibly contributing to the lethality of the arylamide compounds. The induction of membrane stress response regulons such as
rcs
coupled with morphological changes at the membrane observed by electron microscopy suggests that the activity of the arylamides at the membrane represents a significant contribution to their mechanism of action.
Interleukin-1 Receptor-Associated Kinase 4 Is Essential for Initial Host Control of Brucella abortus Infection
Authors: Oliveira Fernanda S. , Carvalho Natália B. , Brandão Ana Paula M. S. , Gomes Marco Túlio R. , de Almeida Leonardo A. , Oliveira Sérgio C.
Published: August 2011

Brucella abortus
is a facultative intracellular bacterial pathogen that causes abortion in domestic animals and undulant fever in humans. Recent studies have revealed that Toll-like receptor (TLR)-initiated immune response to
Brucella
spp. depends on myeloid differentiation factor 88 (MyD88) signaling. Therefore, we decided to study the role of the interleukin-1 receptor-associated kinase 4 (IRAK-4) in host innate immune response against
B. abortus
. After
Brucella
infection, it was shown that the number of CFU in IRAK-4
−/−
mice was high compared to that in IRAK-4
+/−
animals only at 1 week postinfection. At 3 and 6 weeks postinfection, IRAK-4
−/−
mice were able to control the infection similarly to heterozygous animals. Furthermore, the type 1 cytokine profile was evaluated. IRAK-4
−/−
mice showed lower production of systemic interleukin-12 (IL-12) and gamma interferon (IFN-γ). Additionally, a reduced percentage of CD4
+
and CD8
+
T cells expressing IFN-γ was observed compared to IRAK-4
+/−
. Further, the production of IL-12 and tumor necrosis factor alpha (TNF-α) by macrophages and dendritic cells from IRAK-4
−/−
mice was abolished at 24 h after stimulation with
B. abortus
. To investigate the role of IRAK-4 in mitogen-activated protein kinase (MAPK) and NF-κB signaling pathways, macrophages were stimulated with
B. abortus
, and the signaling components were analyzed by protein phosphorylation. Extracellular signal-regulated kinase 1 (ERK1) and ERK2 and p38 as well as p65 NF-κB phosphorylation was profoundly impaired in IRAK-4
−/−
and MyD88
−/−
macrophages activated by
Brucella
. In summary, the results shown in this study demonstrated that IRAK-4 is critical to trigger the initial immune response against
B. abortus
but not at later phases of infection.
The Phosphoinositide-3-Kinase–Akt Signaling Pathway Is Important for Staphylococcus aureus Internalization by Endothelial Cells
Authors: Oviedo-Boyso Javier , Cortés-Vieyra Ricarda , Huante-Mendoza Alejandro , Yu Hong B. , Valdez-Alarcón Juan J. , Bravo-Patiño Alejandro , Cajero-Juárez Marcos , Finlay B. Brett , Baizabal-Aguirre Víctor M.
Published: August 2011

Internalization of
Staphylococcus aureus
in bovine endothelial cells (BEC) is increased by tumor necrosis factor alpha stimulation and NF-κB activation. Because the phosphoinositide-3-kinase (PI3K)–Akt signaling pathway also modulates NF-κB activity, we considered whether the internalization of
S. aureus
by BEC is associated with the activity of PI3K and Akt. We found a time- and multiplicity of infection-dependent phosphorylation of Akt on Ser473 in BEC infected with
S. aureus
. This phosphorylation was inhibited by LY294002 (LY), indicating the participation of PI3K. Inhibition of either PI3K with LY or wortmannin, or Akt with SH-5, strongly reduced the internalization of
S. aureus
. Transfection of BEC with a dominant-negative form of the Akt gene significantly decreased
S. aureus
internalization, whereas transfection with the constitutively active mutant increased the number of internalized bacterium. Inhibition of PDK1 activity with OSU-03012 did not affect the level of
S. aureus
internalization, demonstrating that phosphorylation of Akt on Thr308 is not important for this process. Compared to the untreated control, the adherence of
S. aureus
to the surface of BEC was unaltered when cells were transfected or incubated with the pharmacological inhibitors. Furthermore, Akt activation by internalized
S. aureus
triggered a time-dependent phosphorylation of glycogen synthase kinase-3α (GSK-3α) on Ser21 and GSK-3β on Ser9 that was partially inhibited with SH-5. Finally, treatment of BEC with LY prior to
S. aureus
infection inhibited the NF-κB p65 subunit phosphorylation on Ser536, indicating the involvement of PI3K. These results suggest that PI3K-Akt activity is important for the internalization of
S. aureus
and phosphorylation of GSK-3α, GSK-3β, and NF-κB.
Proteomic Analysis of Anaplasma phagocytophilum during Infection of Human Myeloid Cells Identifies a Protein That Is Pronouncedly Upregulated on the Infectious Dense-Cored Cell
Authors: Troese Matthew J. , Kahlon Amandeep , Ragland Stephanie A. , Ottens Andrew K. , Ojogun Nore , Nelson Kristina T. , Walker Naomi J. , Borjesson Dori L. , Carlyon Jason A.
Published: August 2011

Anaplasma phagocytophilum
is an obligate intracellular bacterium that invades neutrophils to cause the emerging infectious disease human granulocytic anaplasmosis.
A. phagocytophilum
undergoes a biphasic developmental cycle, transitioning between an infectious dense-cored cell (DC) and a noninfectious reticulate cell (RC). To gain insights into the organism's biology and pathogenesis during human myeloid cell infection, we conducted proteomic analyses on
A. phagocytophilum
organisms purified from HL-60 cells. A total of 324 proteins were unambiguously identified, thereby verifying 23.7% of the predicted
A. phagocytophilum
proteome. Fifty-three identified proteins had been previously annotated as hypothetical or conserved hypothetical. The second most abundant gene product, after the well-studied major surface protein 2 (P44), was the hitherto hypothetical protein APH_1235. APH_1235 homologs are found in other
Anaplasma
and
Ehrlichia
species but not in other bacteria. The
aph
_
1235
RNA level is increased 70-fold in the DC form relative to that in the RC form. Transcriptional upregulation of and our ability to detect APH_1235 correlate with RC to DC transition, DC exit from host cells, and subsequent DC binding and entry during the next round of infection. Immunoelectron microscopy pronouncedly detects APH_1235 on DC organisms, while detection on RC bacteria minimally, at best, exceeds background. This work represents an extensive study of the
A. phagocytophilum
proteome, discerns the complement of proteins that is generated during survival within human myeloid cells, and identifies APH_1235 as the first known protein that is pronouncedly upregulated on the infectious DC form.
Construction and Antiapoptosis Activities of Recombinant Adenoviral Expression Vector Carrying EBV Latent Membrane Protein 2A
Authors: Liu Xishuang , Gao Yu , Luo Bing , Zhao Youan
Published: August 2011

To evaluate the possible effects of LMP2A (EBV latent membrane protein 2A) on human gastric cancer cell line SGC-7901, LMP2A coding gene was subcloned into shuttle plasmid pAdTrackCMV to form transfer plasmid pAdTrackCMV-2A, which was linearized with PmeI and cotransformed intoE.coliBJ5183 with adenovirus genomic plasmid of pAdeasy-1. The identified recombinant adenovirus plasmid DNA was digested with PacI and transfected into 293 cells to package recombinant adenovirus particles named vAd-2A. Then the expression and antiapoptosis activities of LMP2A on SGC-7901 infected with vAd-2A were analyzed. The vAd-2A was successfully constructed and identified by PCR, restriction digestion, and sequencing. LMP2A expression in SGC was identified by strong green fluorescence expression with fluorescence microscopic photograph and Southern blotting. The growth of LMP2A expressing SGC cells was apparently improved. Both cyclin E expression and S phase ratio in LMP2A expressing SGC cells were upregulated by cell cycle analysis and confocal microscopic analysis respectively. The replication-deficient recombinant adenovirus vector can express LMP2A antigen in SGC cells and inhibit their apoptosis. The results indicate that LMP2A might play an important role in pathogenesis of EBV-associated gastric cancer (EBVaGC). This study establishes a foundation for further study on EBVaGC and its gene therapy.
Restoration of Fertility after Removal of Extrauterine Mirena Coil: A Case Report and Review of the Literature
Authors: Bhatta Smriti R. C. , Faraj Radwan
Published: August 2011

We present the case of a 27-year-old lady who was seen in the infertility clinic with a history of secondary infertility of a one-year duration. She had a hysteroscopy and Mirena insertion for heavy periods. Coil strings were not found by the GP during first coil check six weeks after insertion. A pelvic ultrasound scan did not show any coil, and it was not investigated further with a possible diagnosis of coil expulsion made. One year following that, she was seen in the infertility clinic. Initial investigations revealed anovulation, and HSG located the coil to be extrauterine. Mirena was removed laparoscopically, and a month following the removal she conceived. She is currently pregnant. This case highlights the effect of extrauterine mirena coils on fertility by possibly causing higher plasma levels of levonorgesterol and resulting suppression of ovulation. Laparoscopic removal of mirena coil can help in restoration of fertility.
Functionalization and Area-Selective Deposition of Magnetic Carbon-Coated Iron Nanoparticles from Solution
Authors: Widenkvist Erika , Alm Oscar , Boman Mats , Jansson Ulf , Grennberg Helena
Published: August 2011

A route to area-selective deposition of carbon-coated iron nanoparticles, involving chemical modification of the surface of the particles, is described. Partial oxidative etching of the coating introduces carboxylic groups, which then are esterified. The functionalized particles can be selectively deposited on the Si areas of Si/SiO2substrates by a simple dipping procedure. Nanoparticles and nanoassemblies have been analyzed using SEM, TEM, and XPS.
Metabolic Imaging: A Link between Lactate Dehydrogenase A, Lactate, and Tumor Phenotype
Authors: Serganova Inna , Rizwan Asif , Ni Xiaohui , Thakur Sunitha B. , Vider Jelena , Russell James , Blasberg Ronald , Koutcher Jason A.
Published: August 2011

Purpose: We compared the metabolic profiles and the association between LDH-A expression and lactate production in two isogenic murine breast cancer cell lines and tumors (67NR and 4T1). These cell lines were derived from a single mammary tumor and have different growth and metabolic phenotypes.

Experimental Design: LDH-A expression, lactate concentration, glucose utilization, and oxygen consumption were measured in cells, and the potential relationship between tumor lactate levels [measured by magnetic resonance spectroscopic imaging (MRSI)] and tumor glucose utilization [measured by [18F]2-deoxy-2-fluoro-d-glucose positron emission tomography ([18F]FDG-PET)] was assessed in orthotopic breast tumors derived from these cell lines.

Results: We show a substantial difference in LDH-A expression between 67NR and 4T1 cells under normoxia and hypoxia. We also show that small orthotopic 4T1 tumors generate 10-fold more lactate than corresponding 67NR tumors. The high lactate levels in small primary 4T1 tumors are associated with intense pimonidazole staining (a hypoxia indicator). Less-intense hypoxia staining was observed in the larger 67NR tumors and is consistent with the gradual increase and plateau of lactate concentration in enlarging 67NR tumors.

Conclusions: Lactate-MRSI has a greater dynamic range than [18F]FDG-PET and may be a more sensitive measure with which to evaluate the aggressive and metastatic potential of primary breast tumors. Clin Cancer Res; 17(19); 6250–61. ©2011 AACR.
Adoptive Transfer of Autologous Natural Killer Cells Leads to High Levels of Circulating Natural Killer Cells but Does Not Mediate Tumor Regression
Authors: Parkhurst Maria R. , Riley John P. , Dudley Mark E. , Rosenberg Steven A.
Published: August 2011

Purpose: Adoptive transfer of tumor-infiltrating lymphocytes (TIL) can mediate regression of metastatic melanoma. However, many patients with cancer are ineligible for such treatment because their TIL do not expand sufficiently or because their tumors have lost expression of antigens and/or MHC molecules. Natural killer (NK) cells are large granular lymphocytes that lyse tumor cells in a non–MHC-restricted manner. Therefore, we initiated in a clinical trial to evaluate the efficacy of adoptively transferred autologous NK cells to treat patients with cancers who were ineligible for treatment with TIL.

Experimental Design: Patients with metastatic melanoma or renal cell carcinoma were treated with adoptively transferred in vitro activated autologous NK cells after the patients received a lymphodepleting but nonmyeloablative chemotherapy regimen. Clinical responses and persistence of the adoptively transferred cells were evaluated.

Results: Eight patients were treated with an average of 4.7 × 1010 (± 2.1 × 1010) NK cells. The infused cells exhibited high levels of lytic activity in vitro. Although no clinical responses were observed, the adoptively transferred NK cells seemed to persist in the peripheral circulation of patients for at least one week posttransfer and, in some patients, for several months. However, the persistent NK cells in the circulation expressed significantly lower levels of the key activating receptor NKG2D and could not lyse tumor cell targets in vitro unless reactivated with IL-2.

Conclusions: The persistent NK cells could mediate antibody-dependent cell-mediated cytotoxicity without cytokine reactivation in vitro, which suggests that coupling adoptive NK cell transfer with monoclonal antibody administration deserves evaluation. Clin Cancer Res; 17(19); 6287–97. ©2011 AACR.
Viruses That Cross Borders: Factors Responsible for Global Dissemination of Viral Infections
Authors: Furuse Yuki , Suzuki Akira , Kamigaki Taro , Mpolya Emmanuel Abraham , Khandaker Irona , Oshitani Hitoshi
Published: August 2011

Objective: Pandemic viral infections as emerging infectious diseases are of a great global concern. However, for some viruses, particular strains are endemic to specific areas and can be genetically distinguished from strains in other regions. In contrast, for some other viruses, genetically similar strains can spread and circulate all over the world. This study addresses global dissemination of various viral infections. Methods: We classified 34 viruses as per their ability to cross borders by review. We also described factors responsible for and the dynamics of global dissemination. We examined biological characteristics of viruses, manners or routes of transmission, host responses and epidemiological factors. Results: Factors required for viruses to cross borders include ‘non-blood infection’, ‘short incubation period’, ‘short infectious period’, ‘frequent re-infection’, ‘small basic reproductive number (R₀)’ and ‘high annual incidence’. Conclusion: Knowing the factors responsible for global dissemination of pathogens is useful for controlling and/or containing both classic and emerging infectious diseases.
Reference Renal Artery Diameter Is a Stronger Predictor of Contrast-Induced Nephropathy than Chronic Kidney Disease in Patients with High Cardiovascular Risk
Authors: Zanoli Luca , Rastelli Stefania , Marcantoni Carmelita , Blanco Julien , Capodanno Davide , Tamburino Corrado , Castellino Pietro
Published: August 2011

Introduction: The incidence of contrast-induced nephropathy (CIN) increases in high cardiovascular risk patients. Chronic kidney disease (CKD) is a known risk factor for CIN development. In a previous report, we demonstrated that the mean reference renal artery diameter (RVD) is an important determinant of CKD in patients undergoing coronary angiography for ischemic heart disease. However, RVD was never tested as a predictor of CIN. Aim: To look at the predictors of CIN. Methods: A total of 218 consecutive patients undergoing coronary and renal angiography were enrolled from the cohort of the RAS-CAD study (NCT 01173666). CIN was defined as a relative increase in baseline serum creatinine ≧25% within 1 week of contrast administration. Results: The incidence of CIN was 22%. In a fully adjusted model, contrast medium dose (20 ml increase, OR 1.12, 95% CI 1.06–1.19, p < 0.001), iso-osmolar contrast media (OR 0.28, 95% CI 0.09–0.99, p < 0.05), atherosclerotic renovascular disease (OR 2.69, 95% CI 1.32–5.48, p < 0.05), and RVD (1 mm/1.73 m2 increase, OR 0.59, 95% CI 0.41–0.86, p < 0.05) had the greatest effect on outcome and were identified as independent predictors of CIN. CKD was selected as a predictor of CIN only in a model without RVD. Conclusions: In patients undergoing coronary angiography for ischemic heart disease, RVD is a stronger predictor of CIN than CKD.
Role of Single-Dose Clostridiopeptidase A Collagenase in Peritoneal Adhesions
Authors: Aysan E. , Bektas H. , Ersoz F. , Behzat K.
Published: August 2011

Background: To evaluate the effect of clostridiopeptidase A collagenase (CAC) in a rat model of postoperative peritoneal adhesion (PPA). Methods: Forty rats were divided into four equal groups. In group 1, 1 g CAC was injected into the peritoneal cavity. In group 2, adhesions were generated. In group 3, adhesions were generated, and, 10 days later, the area with PPAs was covered with 1 g CAC. In group 4, adhesions were generated and the area was covered immediately with 1 g CAC. All rats were sacrificed on postoperative day 10, and adhesions were scored both macroscopically and microscopically. Results: Mean macroscopic adhesion scores in groups 1–4 were 0, 2.9 ± 0.21, 2.55 ± 0.16, and 1.3 ± 1, respectively (p = 0.0001). The mean macroscopic adhesion score in group 4 was lower than that in group 2 (p = 0.045). The mean macroscopic adhesion score in group 4 was lower than that in group 3, but the value was not statistically different (p = 0.098). Mean microscopic values were 0, 2.8 ± 0.42, 2.5 ± 0.52, and 1.3 ± 0.67, respectively (p< 0.0001). The group 4 score was lower than those of groups 2 (p = 0.01) and 3 (p = 0.025). Discussion: A single dose of CAC reduces PPA formation. CAC, however, is not effective on already formed PPAs.
Clinical and Economic Outcomes of Liberal Versus Selective Drug-Eluting Stent Use
Authors: Venkitachalam Lakshmi , Lei Yang , Stolker Joshua M. , Mahoney Elizabeth M. , Amin Amit P. , Lindsey Jason B. , Kennedy Kevin F. , Pencina Michael J. , Lopez John J. , Kleiman Neal S. , Cohen David J. ,   for the EVENT Registry Investigators
Published: August 2011

Background—

Although the benefits of drug-eluting stents (DES) for reducing restenosis after percutaneous coronary intervention are well established, the impact of alternative rates of DES use on population-level outcomes is unknown.

Methods and Results—

We used data from the Evaluation of Drug Eluting Stents and Ischemic Events (EVENT) registry to examine the clinical impact and cost-effectiveness of varying DES use rates in routine care. Between 2004 and 2007, 10 144 patients undergoing percutaneous coronary intervention were enrolled in the EVENT registry at 55 US centers. Clinical outcomes and cardiovascular-specific costs were assessed prospectively over 1 year of follow-up. Use of DES decreased from 92 in 2004 to 2006 (liberal use era; n=7587) to 68 in 2007 (selective use era; n=2557;
P
<0.001). One-year rates of death or myocardial infarction were similar in both eras. Over this time period, the incidence of target lesion revascularization increased from 4.1 to 5.1, an absolute increase of 1.0 (95 confidence interval, 0.1 to 1.9;
P
=0.03), whereas total cardiovascular costs per patient decreased by $401 (95 confidence interval, 131 to 671;
P
=0.004). The risk-adjusted incremental cost-effectiveness ratio for the liberal versus selective DES era was $16 000 per target lesion revascularization event avoided, $27 000 per repeat revascularization avoided, and $433 000 per quality-adjusted life-year gained.

Conclusions—

In this prospective registry, a temporal reduction in DES use was associated with a small increase in target lesion revascularization and a modest reduction in total cardiovascular costs. These findings suggest that although clinical outcomes are marginally better with unrestricted DES use, this approach represents a relatively inefficient use of healthcare resources relative to several common benchmarks for cost-effective care.
Risk of Constrictive Pericarditis After Acute Pericarditis
Authors: Imazio Massimo , Brucato Antonio , Maestroni Silvia , Cumetti Davide , Belli Riccardo , Trinchero Rita , Adler Yehuda
Published: August 2011

Background—

Constrictive pericarditis (CP) is considered a rare, dreaded possible complication of acute pericarditis. Nevertheless, there is a lack of prospective studies that have evaluated the specific risk according to different etiologies. The aim of this study is to evaluate the risk of CP after acute pericarditis in a prospective cohort study with long-term follow-up.

Methods and Results—

From January 2000 to December 2008, 500 consecutive cases with a first episode of acute pericarditis (age, 51±16 years; 270 men) were prospectively studied to evaluate the evolution toward CP. Etiologies were viral/idiopathic in 416 cases (83.2%), connective tissue disease/pericardial injury syndromes in 36 cases (7.2%), neoplastic pericarditis in 25 cases (5.0%), tuberculosis in 20 cases (4.0%), and purulent in 3 cases (0.6%). During a median follow-up of 72 months (range, 24 to 120 months), CP developed in 9 of 500 patients (1.8%): 2 of 416 patients with idiopathic/viral pericarditis (0.48%) versus 7 of 84 patients with a nonviral/nonidiopathic etiology (8.3%). The incidence rate of CP was 0.76 cases per 1000 person-years for idiopathic/viral pericarditis, 4.40 cases per 1000 person-years for connective tissue disease/pericardial injury syndrome, 6.33 cases per 1000 person-years for neoplastic pericarditis, 31.65 cases for 1000 person-years for tuberculous pericarditis, and 52.74 cases per 1000 person-years for purulent pericarditis.

Conclusions—

CP is a relatively rare complication of viral or idiopathic acute pericarditis (<0.5%) but, in contrast, is relatively frequent for specific etiologies, especially bacterial.
Effects of Renal Sympathetic Denervation on Blood Pressure, Sleep Apnea Course, and Glycemic Control in Patients With Resistant Hypertension and Sleep Apnea
Authors: Witkowski Adam , Prejbisz Aleksander , Florczak Elżbieta , Kądziela Jacek , Śliwiński Paweł , Bieleń Przemysław , Michałowska Ilona , Kabat Marek , Warchoł Ewa , Januszewicz Magdalena , Narkiewicz Krzysztof , Somers Virend K. , Sobotka Paul A. , Januszewicz Andrzej
Published: August 2011

Percutaneous renal sympathetic denervation by radiofrequency energy has been reported to reduce blood pressure (BP) by the reduction of renal sympathetic efferent and afferent signaling. We evaluated the effects of this procedure on BP and sleep apnea severity in patients with resistant hypertension and sleep apnea. We studied 10 patients with refractory hypertension and sleep apnea (7 men and 3 women; median age: 49.5 years) who underwent renal denervation and completed 3-month and 6-month follow-up evaluations, including polysomnography and selected blood chemistries, and BP measurements. Antihypertensive regimens were not changed during the 6 months of follow-up. Three and 6 months after the denervation, decreases in office systolic and diastolic BPs were observed (median: −34/−13 mm Hg for systolic and diastolic BPs at 6 months; both
P
<0.01). Significant decreases were also observed in plasma glucose concentration 2 hours after glucose administration (median: 7.0 versus 6.4 mmol/L;
P
=0.05) and in hemoglobin A1C level (median: 6.1% versus 5.6%;
P
<0.05) at 6 months, as well as a decrease in apnea-hypopnea index at 6 months after renal denervation (median: 16.3 versus 4.5 events per hour;
P
=0.059). In conclusion, catheter-based renal sympathetic denervation lowered BP in patients with refractory hypertension and obstructive sleep apnea, which was accompanied by improvement of sleep apnea severity. Interestingly, there are also accompanying improvements in glucose tolerance. Renal sympathetic denervation may conceivably be a potentially useful option for patients with comorbid refractory hypertension, glucose intolerance, and obstructive sleep apnea, although further studies are needed to confirm these proof-of-concept data.
Angiotensin II Upregulates Protein Phosphatase 2Cα and Inhibits AMP-Activated Protein Kinase Signaling and Energy Balance Leading to Skeletal Muscle Wasting
Authors: Tabony A. Michael , Yoshida Tadashi , Galvez Sarah , Higashi Yusuke , Sukhanov Sergiy , Chandrasekar Bysani , Mitch William E. , Delafontaine Patrice
Published: August 2011

Congestive heart failure and chronic kidney disease are characterized by chronically elevated angiotensin II (Ang II) and muscle wasting. Ang II causes skeletal muscle wasting by reducing appetite and by enhancing catabolism. The serine/threonine kinase AMP-activated protein kinase (AMPK) functions mainly as a sensor of cellular energy status. It is energy sparing and favors ATP generation. We hypothesized that Ang II induces muscle wasting in part by inhibiting AMPK signaling and altering cellular energy balance. Our results show that Ang II infusion in mice reduced gastrocnemius muscle weight by 26% and depleted ATP by 74%. In addition, Ang II upregulated protein phosphatase 2Cα by 2.6-fold and reduced AMPK phosphorylation and signaling in muscle. Importantly, the pharmacological AMPK activator 5-aminoimidazole-4-carboxamide ribonucleoside restored AMPK activity to levels of pair-fed controls and reversed Ang II–mediated ATP depletion and muscle wasting. Moreover, 5-aminoimidazole-4-carboxamide ribonucleoside activated Akt and inhibited Ang II–induced increases in E3 ubiquitin ligase expression. These novel results demonstrate critical roles for energy depletion and AMPK inhibition in Ang II–induced skeletal muscle wasting and suggest a therapeutic potential for AMPK activators in diseases characterized by muscle wasting.