bluuebunny/crossref_metadata_2025_split huggingface dataset:
The ecto‐nucleotidase NTPDase1 differentially regulates P2Y1 and P2Y2 receptor‐dependent vasorelaxation
Authors: Kauffenstein Gilles , Fürstenau Cristina Ribas , D'Orléans‐Juste Pedro , Sévigny Jean 
Published: January 2010

Background and purpose: Extracellular nucleotides produce vasodilatation through endothelial P2 receptor activation. As these autacoids are actively metabolized by the ecto‐nucleotidase nucleoside triphosphate diphosphohydrolase‐1 (NTPDase1), we studied the effects of this cell surface enzyme on nucleotide‐dependent vasodilatation.Experimental approach: Vascular NTPDase expression and activity were evaluated by immunohistochemistry and histochemistry. The vascular effects of nucleotides were testedin vivoby monitoring mean arterial pressure, andin vitrocomparing reactivity of aortic rings using wild‐type andEntpd1−/−(lacking NTPDase1) mice.Key results: The absence of NTPDase1 inEntpd1−/−mice led to a dramatic drop in endothelial nucleotidase activity. This deficit was associated with an exacerbated decrease in blood pressure after nucleotide injection. Following ATP injection, mean arterial pressure was decreased inEntpd1+/+andEntpd1−/−mice by 5.0 and 17%, respectively, and by 0.1 and 19% after UTP injection (10 nmole·kg−1both).In vitro, the concentration‐response curves of relaxation to ADP and ATP were shifted to the left, revealing a facilitation of endothelial P2Y1 and P2Y2 receptor activation inEntpd1−/−mice. EC50values inEntpd1+/+versusEntpd1−/−aortic rings were 14 µM versus 0.35 µM for ADP, and 29 µM versus 1 µM for ATP. InEntpd1−/−aortas, P2Y1 receptors were more extensively desensitized than P2Y2 receptors. Relaxations to the non‐hydrolysable analogues ADPβS (P2Y1) and ATPγS (P2Y2) were equivalent in both genotypes confirming the normal functionality of these P2Y receptors in mutant mice.Conclusions and implications: NTPDase1 controls endothelial P2Y receptor‐dependent relaxation, regulating both agonist level and P2 receptor reactivity.
The mixed‐lineage kinase 1–3 signalling pathway regulates stress response in cardiac myocytes via GATA‐4 and AP‐1 transcription factors
Authors: Ola A , Kerkelä R , Tokola H , Pikkarainen S , Skoumal R , Vuolteenaho O , Ruskoaho H 
Published: January 2010

Background and purpose: The mixed‐lineage kinases (MLKs) act upstream of mitogen‐activated protein kinases, but their role in cardiac biology and pathology is largely unknown.Experimental approach: We investigated the effect of a MLK1–3 inhibitor CEP‐11004 on G protein‐coupled receptor agonist‐induced stress response in neonatal rat cardiac myocytes in culture.Key results: CEP‐11004 administration dose‐dependently attenuated phenylephrine and endothelin‐1 (ET‐1)‐induced c‐Jun N‐terminal kinase activation. MLK inhibition also reduced ET‐1‐ and phenylephrine‐induced phosphorylation of p38 mitogen‐activated protein kinase. In contrast, phenylephrine‐induced extracellular signal‐regulated kinase phosphorylation was further up‐regulated by CEP‐11004. ET‐1 increased activator protein‐1 binding activity 3.5‐fold and GATA‐binding protein 4 (GATA‐4) binding activity 1.8‐fold, both of which were attenuated with CEP‐11004 administration by 59% and 63% respectively. Phenylephrine induced activator protein‐1 binding activity by 2.6‐fold, which was decreased by 81% with CEP‐11004 administration. Phenylephrine also induced a 3.7‐fold increase in the transcriptional activity of B‐type natriuretic peptide (BNP), which was attenuated by 41% with CEP‐11004 administration. In agreement, MLK inhibition also reduced hypertrophic agonist‐induced secretion of immunoreactive atrial natriuretic peptide and BNP.Conclusions and implications: These results showed that inhibition of the MLK1–3 signalling pathway was sufficient for suppressing the activity of key nuclear effectors (GATA‐4 and activator protein‐1 transcription factors) in cardiac hypertrophy, and attenuated the agonist‐induced atrial natriuretic peptide secretion and activation of BNP gene transcription.
Physical Frailty Is Associated with Incident Mild Cognitive Impairment in Community‐Based Older Persons
Authors: Boyle Patricia A. , Buchman Aron S. , Wilson Robert S. , Leurgans Sue E. , Bennett David A. 
Published: January 2010

OBJECTIVES:To test the hypothesis that physical frailty is associated with risk of mild cognitive impairment (MCI).DESIGN:Prospective, observational cohort study.SETTING:Approximately 40 retirement communities across the Chicago metropolitan area.PARTICIPANTS:More than 750 older persons without cognitive impairment at baseline.MEASUREMENTS:Physical frailty, based on four components (grip strength, timed walk, body composition, and fatigue), was assessed at baseline, and cognitive function was assessed annually. Proportional hazards models adjusted for age, sex, and education were used to examine the association between physical frailty and the risk of incident MCI, and mixed effect models were used to examine the association between frailty and the rate of change in cognition.RESULTS:During up to 12 years of annual follow‐up, 305 of 761 (40%) persons developed MCI. In a proportional hazards model adjusted for age, sex, and education, physical frailty was associated with a high risk of incident MCI, such that each one‐unit increase in physical frailty was associated with a 63% increase in the risk of MCI (hazard ratio=1.63; 95% confidence interval=1.27–2.08). This association persisted in analyses that required MCI to persist for at least 1 year and after controlling for depressive symptoms, disability, vascular risk factors, and vascular diseases. Furthermore, a higher level of physical frailty was associated with a faster rate of decline in global cognition and five cognitive systems (episodic memory, semantic memory, working memory, perceptual speed, and visuospatial abilities).CONCLUSION:Physical frailty is associated with risk of MCI and a rapid rate of cognitive decline in aging.
Monozygotic twins are discordant for chronic periodontitis: clinical and bacteriological findings
Authors: Torres de Heens Gaudy L. , Loos Bruno G. , Van Der Velden Ubele 
Published: January 2010

Torres de Heens GL, Loos BG, van der Velden U. Monozygotic twins are discordant for chronic periodontitis: clinical and bacteriological findings. J Clin Periodontol 2010; 37: 120–128. doi: 10.1111/j.1600‐051X.2009.01511.x.AbstractObjectives: The aim of this study was to assess, in monozygotic (MZ) and dizygotic (DZ) twin pairs in whom the proband of the twin pair was suffering from moderate to severe chronic periodontitis, the contribution of genetics, periodontal pathogens and lifestyle factors towards the clinical phenotype.Material and Methods: For this study, 18 adult twin pairs were selected on the basis of interproximal attachment loss (AL) 5 mm in 2 non‐adjacent teeth in one twin member. The study included 10 MZ and eight DZ twin pairs, in whom the periodontal condition, presence of periodontal pathogens, educational level, smoking behaviour and body mass index (BMI) were evaluated.Results: Both MZ and DZ twins were discordant regarding AL and alveolar bone loss. Discordance was greater in DZ compared with MZ twins. In MZ twins, the discordance could not be explained by education, smoking, BMI and periodontal pathogens. In DZ twins, 45.6% of the discordance could be explained by more pack‐years of the probands.Conclusion: The results confirm a possible role of genetic factors in periodontitis. However, the magnitude of the genetic effects on disease severity may have been overestimated previously.
Seasonal and diel patterns in the migrations of fishes between a river and a floodplain tributary
Authors: Nunn A. D. , Copp G. H. , Vilizzi L. , Carter M. G. 
Published: January 2010

Nunn AD, Copp GH, Vilizzi L, Carter MG. Seasonal and diel patterns in the migrations of fishes between a river and a floodplain tributary. Ecology of Freshwater Fish 2010: 19: 153–162. © 2009 John Wiley & Sons A/SAbstract –  The population behaviours associated with the migrations of fishes in lowland river ecosystems are amongst the most poorly‐understood dispersal mechanisms of temperate freshwater organisms. This study evaluated the influence of four environmental variables (light levels, river discharge, water temperature and water velocity) on the timing, intensity and direction of fish movements between the River Avon (Hampshire, England) and a small floodplain tributary, Ibsley Brook, over a 12‐month period. Using canonical correspondence analysis (CCA) to identify patterns of movement (by groups of species) and the relative strengths of explanatory variables in the data, the probability of fishes migrating between the river and tributary was determined using Bayesian modelling. The intensity and direction of fish movements between the river and tributary varied temporally, both on a diel and seasonal basis, and there were species‐ and age‐specific patterns in behaviour. Diel movements appeared to be triggered by changes in light intensity and brook water velocity, whereas seasonal movements were mostly driven by changes in river discharge and water temperature, particularly those associated with floods. This study emphasises the importance of connectivity in river systems, as fishes migrated in all conditions, but especially during rapidly‐rising discharge.
RESPONSE SURFACE MODELING OF LISTERIA MONOCYTOGENES INACTIVATION ON LETTUCE TREATED WITH ELECTROLYZED OXIDIZING WATER
Authors: DING TIAN , DONG QING‐LI , RAHMAN S. M. E. , OH DEOG‐HWAN 
Published: January 2010

ABSTRACTElectrolyzed oxidizing water has been estimated that it has strong bactericidal activity and has been widely used as a disinfectant for inactivating microbial organisms. The combined effects of temperature (15–35C), chlorine concentration of electrolyzed oxidizing water (30–70 ppm) and treatment time (1–5 min) on the reduction of Listeria monocytogenes in lettuce were investigated. Reductions of 1.39–2.79 log10 cfu/g were observed in different combinations of the three factors. Also, a quadratic equation for L. monocytogenes inactivation kinetic was developed by multiple regression analysis using response surface methodology. The predicted values were shown to be significantly in good agreement with experimental values because the adjusted determination coefficient () was 0.9578 and the level of significance was P < 0.0001. Besides, average mean deviation (E%), bias factor (Bf) and accuracy factor (Af), which are validation indicators of the model were 0.0218, 1.0003 and 1.0220, respectively. Thus, predicted model showed a good correlation between the experimental and predicted values, indicating success at providing reliable predictions of L. monocytogenes growth in lettuce.PRACTICAL APPLICATIONSElectrolyzed oxidizing water is an important sanitizer, and nowadays it has been widely used in food industry. Lettuce is regarded as a “healthier” food, which is one of the most popular vegetables consumed, whereas many outbreaks caused by L. monocytogenes have been reported until now. According to the model developed in this study, inactivation of L. monocytogenes in lettuce treated with EO water could be predicted by inputting a certain group of environmental factors.
Non‐Representational Approaches to Body–Landscape Relations
Authors: Macpherson Hannah 
Published: January 2010

AbstractThis short paper offers a critical summary of some of the key themes of non‐representational theory (NRT), with a particular focus on recent approaches to body‐landscape relations and the potential place of disability in these accounts. NRT in British human geography has encouraged an emphasis on the embodied, practiced and habitual qualities of embodied experience. Recent non‐representational work on landscape has developed these agendas to show how landscape may be thought of as a ‘process’ (Rose 2002) or ‘tension’ which potentially ‘animates’ the embodied subject (Rose and Wylie 2006). Here the body and the landscape are understood to be complimentary concepts that are useful to think through together – each in a constant process of ‘becoming’ through the other. This paper reflects on the methodological challenges of researching such non‐representational body‐landscape relations, showing how researchers have drawn on insights of disciplines as diverse as neuroscience and performance studies to address this challenge.
Validation of the INNO-LiPA HBV DR Assay (Version 2) in Monitoring Hepatitis B Virus-Infected Patients Receiving Nucleoside Analog Treatment
Authors: Niesters H. G. M. , Zoulim F. , Pichoud C. , Buti M. , Shapiro F. , D'Heuvaert N. , Celis L. , Doutreloigne J. , Sablon E. 
Published: January 2010

ABSTRACTHepatitis B virus (HBV) antiviral drug resistance mutations prevent successful outcome of treatment and lead to worsening of liver disease. Detection of its emergence permits opportune treatment with alternative drugs. Unfortunately, the use of newly approved antivirals, including adefovir dipivoxil, emtricitabine, and telbivudine, is also associated with the development of drug resistance, albeit to a lesser extent than the use of lamivudine. The objectives of this work were to assess the performance characteristics (sensitivity and accuracy) of an updated drug resistance test, the INNO-LiPA HBV DR v2, which includes detection of mutations associated with lamivudine, adefovir, emtricitabine, and telbivudine resistance, and to compare the results with consensus sequencing of serum samples from patients treated with HBV antivirals. Diagnostic sensitivity, defined as detection of a positive amplification line on the line probe assay (LiPA) strip, was 94.8% (95% confidence interval [CI], 89.7 to 97.9) after initial testing, increasing to 96.3% (95% CI, 91.6 to 98.8) after repeat test 1 and to 100% (95% CI, 97.3 to 100.0) after repeat test 2. In diagnostic accuracy determinations, full concordance was observed between sequencing and LiPA for 77.0% of the codons tested (620/805 codons [95% CI, 74.0 to 79.9]), whereas LiPA and sequencing were partially concordant 22% of the time (177/805 codons). In 167 out of 177 cases, LiPA detected a wild-type/mutant mixture whereas sequencing detected only one of the two results. Performance testing of the new LiPA test, the INNO-LiPA HBV DR v2, showed convincing diagnostic sensitivity and accuracy. The ability of the test to detect mixed infections and minority viral populations associated with resistance to the current generation of antivirals, including adefovir, emtricitabine, and telbivudine, makes it a useful tool for HBV therapy monitoring.
Surveillance and Correlation of Antibiotic Prescription and Resistance of Gram-Negative Bacteria in Singaporean Hospitals
Authors: Hsu Li-Yang , Tan Thean-Yen , Tam Vincent H. , Kwa Andrea , Fisher Dale Andrew , Koh Tse-Hsien 
Published: January 2010

ABSTRACTA surveillance study was performed in four Singapore public hospitals from 2006 to 2008 to determine the correlation between antibiotic prescription and Gram-negative bacterial antimicrobial resistance. Targeted organisms included ceftriaxone- and ciprofloxacin-resistantEscherichia coliandKlebsiella pneumoniae, as well as imipenem-resistantPseudomonas aeruginosaandAcinetobacterspp. Antibiotic prescription data were collated in the WHO anatomical therapeutic chemical (ATC)/defined daily dose (DDD) format, while antibiotic resistance was expressed as incidence density adjusted for total inpatient-days every quarter. Individual trends were determined by linear regression, while possible associations between antibiotic prescription and resistance were evaluated via cross-correlation analysis. Results over 3 years indicated significantly rising incidence densities of ceftriaxone- and ciprofloxacin-resistantE. coliand imipenem-resistantAcinetobacterspp. (blood isolates only). Antimicrobial-resistantKlebsiella pneumoniaerates declined. The prescription rates of piperacillin-tazobactam, ertapenem, meropenem, ciprofloxacin, and levofloxacin increased significantly, while imipenem and moxifloxacin prescription decreased. Cross-correlation analysis demonstrated possible associations between prescription of fluoroquinolones and ciprofloxacin-resistantE. coli(R2= 0.46), fluoroquinolones and ceftriaxone-resistantE. coli(R2= 0.47), and carbapenems and imipenem-resistantAcinetobacterspp. (R2= 0.48), all at zero time lag. Changes in meropenem prescription were associated with a similar trend in imipenem-resistantAcinetobacterblood isolates after a 3-month time lag. No correlation was found between cephalosporin use and resistance. In conclusion, our data demonstrated correlation between prescription of and Gram-negative bacterial resistance to several, but not all, key antimicrobial agents in Singapore hospitals. In areas where Gram-negative bacterial resistance is endemic and prescription of broad-spectrum antimicrobial agents is high, factors other than antimicrobial usage may be equally important in maintaining high resistance rates.
Amodiaquine Dosage and Tolerability for Intermittent Preventive Treatment To Prevent Malaria in Children
Authors: Cairns M. , Cisse B. , Sokhna C. , Cames C. , Simondon K. , Ba E. H. , Trape J.-F. , Gaye O. , Greenwood B. M. , Milligan P. J. M. 
Published: January 2010

ABSTRACT
Sulfadoxine-pyrimethamine with amodiaquine (SP-AQ) is a highly efficacious regimen for intermittent preventive treatment to prevent malaria in children (IPTc), but the amodiaquine component is not always well tolerated. We determined the association between amodiaquine dosage by body weight and mild adverse events (AEs) and investigated whether alternative age-based regimens could improve dosing accuracy and tolerability, using data from two trials of IPTc in Senegal, one in which AQ dose was determined by age and the other in which it was determined by weight category. Both dosage strategies resulted in some children receiving AQ doses above the recommended therapeutic range. The odds of vomiting increased with increasing amodiaquine dosage. In one study, incidence of fever also increased with increasing dosage. Anthropometric data from 1,956 children were used to predict the dosing accuracy of existing and optimal alternative regimens. Logistic regression models describing the probability of AEs by dosage were used to predict the potential reductions in mild AEs for each regimen. Simple amendments to current AQ dosing schedules based on the child's age could substantially increase dosing accuracy and thus improve the tolerability of IPTc using SP-amodiaquine in situations where weighing the child is impractical.
In Vitro
Sensitivities of
Plasmodium falciparum
to Different Antimalarial Drugs in Uganda
Authors: Nsobya Samuel L. , Kiggundu Moses , Nanyunja Sarah , Joloba Moses , Greenhouse Bryan , Rosenthal Philip J. 
Published: January 2010

ABSTRACT

The control of malaria is challenged by resistance of
Plasmodium falciparum
to multiple drugs. New combination regimens are now advocated for the treatment of uncomplicated falciparum malaria, but the extent of resistance to newer agents is incompletely understood. We measured the
in vitro
sensitivity of
P. falciparum
parasites cultured from children enrolled in a drug efficacy trial in Kampala, Uganda, from 2006 to 2008. Sensitivities were measured by comparing levels of histidine-rich protein-2 in parasites incubated with different concentrations of drugs with those in untreated controls. The cultured parasites exhibited a wide range of sensitivities to chloroquine (CQ); monodesethylamodiaquine (MDAQ), the major active metabolite of amodiaquine; and quinine (QN). Mean 50% inhibitory concentration (IC
50
) results were above standard cutoffs for resistance for CQ and MDAQ. Parasites were generally sensitive to dihydroartemisinin (DHA), lumefantrine (LM), and piperaquine (PQ). For CQ, MDAQ, and QN but not the other drugs, activities against individual strains were highly correlated. We also assessed known resistance-mediating polymorphisms in two putative transporters,
pfcrt
and
pfmdr1
. When parasites that were least and most sensitive to each drug were compared, the
pfmdr1
86Y mutation was significantly more common in parasites that were most resistant to CQ and MDAQ, and the
pfmdr1
D1246Y mutation was significantly more common in parasites that were most resistant to MDAQ and QN. In summary, we demonstrated in parasites from Kampala a range of sensitivities to older drugs; correlation of sensitivities to CQ, MDAQ, and QN; and good activity against nearly all strains for DHA, LM, and PQ.
Efficacy of Posaconazole as Treatment and Prophylaxis against
Fusarium solani
Authors: Wiederhold Nathan P. , Najvar Laura K. , Bocanegra Rosie , Graybill John R. , Patterson Thomas F. 
Published: January 2010

ABSTRACT

Invasive fusariosis is a highly aggressive fungal infection associated with high mortality in heavily immunocompromised patients. Although posaconazole is efficacious as salvage therapy against infections caused by
Fusarium
species, concerns remain regarding this agent in the setting of reduced potency. To evaluate the efficacy of posaconazole as treatment or prophylaxis against invasive fusariosis caused by
Fusarium solani
, we utilized a neutropenic murine model of disseminated disease. ICR mice were administered escalating doses of posaconazole (6.25, 12.5, 25, or 50 mg/kg of body weight twice daily [BID]) by oral gavage beginning 2 days prior to inoculation in the prophylaxis studies or beginning 12 h after inoculation as treatment. Therapy was continued until day 9 postinoculation, and animals were monitored off therapy until day 15 for survival. Fungal burden was assessed as CFU in the kidneys. A clear dose-response relationship was observed, as the highest dose of posaconazole (50 mg/kg) was the most effective in prolonging survival and reducing tissue fungal burden both as prophylaxis and as treatment. This dose response was associated with high posaconazole serum concentrations as measured by bioassay. However, the extent of efficacy was also dependent on the infecting inoculum, as greater increases in survival and reductions in fungal burden were observed with the lower inocula tested. In this model high dosages of posaconazole were effective as treatment and prophylaxis against disseminated fusariosis caused by
F. solani
.
Rifampin Combination Therapy for Nonmycobacterial Infections
Authors: Forrest Graeme N. , Tamura Kimberly 
Published: January 2010

SUMMARY

The increasing emergence of antimicrobial-resistant organisms, especially methicillin-resistant
Staphylococcus
aureus
(MRSA), has resulted in the increased use of rifampin combination therapy. The data supporting rifampin combination therapy in nonmycobacterial infections are limited by a lack of significantly controlled clinical studies. Therefore, its current use is based upon in vitro or in vivo data or retrospective case series, all with major limitations. A prominent observation from this review is that rifampin combination therapy appears to have improved treatment outcomes in cases in which there is a low organism burden, such as biofilm infections, but is less effective when effective surgery to obtain source control is not performed. The clinical data support rifampin combination therapy for the treatment of prosthetic joint infections due to methicillin-sensitive
S. aureus
(MSSA) after extensive debridement and for the treatment of prosthetic heart valve infections due to coagulase-negative staphylococci. Importantly, rifampin-vancomycin combination therapy has not shown any benefit over vancomycin monotherapy against MRSA infections either clinically or experimentally. Rifampin combination therapy with daptomycin, fusidic acid, and linezolid needs further exploration for these severe MRSA infections. Lastly, an assessment of the risk-benefits is needed before the addition of rifampin to other antimicrobials is considered to avoid drug interactions or other drug toxicities.