bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms promoting tree species co‐existence: Experimental evidence with saplings of subtropical forest ecosystems of China
Authors: Lang Anne C. , Härdtle Werner , Baruffol Martin , Böhnke Martin , Bruelheide Helge , Schmid Bernhard , von Wehrden Henrik , von Oheimb Goddert 
Published: March 2012

AbstractQuestionsThe maintenance of a diverse sapling pool is of particular importance for the regeneration and persistance of species‐rich forest ecosystems. However, the mechanisms of co‐existence of saplings have rarely been studied experimentally. Do species richness, species composition, species identity and stand density affect the co‐existence, growth patterns and crown architecture of tree saplings?LocationJiangxi Province, southeast China.MethodsIn a field experiment, we manipulated the local neighbourhood of saplings of four early‐successional subtropical species (Schima superba,Elaeocarpus decipiens,Quercus serrataandCastanea henryi) with regard to species richness (one, two and four species), species composition (monocultures, six‐two‐species combinations and one‐four‐species combination) and stand density (low, intermediate and high). We tested for treatment effects and impact of species identity on growth variables, biomass allocation, crown architectural traits and branch demography.ResultsSpecies richness was a poor predictor of all response variables, but enhanced pruning and branch turnover. In contrast, species composition proved to be of great importance for growth, biomass allocation, crown architecture and branch demography. Local neighbourhood interactions of saplings were characterized by complementary or facilitative, as well as by competitive mechanisms. Intra‐specific competition was higher than inter‐specific competition for two species (C. henryi,Q. serrata) depending on the respective species combination. To a high degree, the competitive ability of species can be explained by species identity. Competition for light likely played a major role in our experiment, as evidenced by the strong response of crown architecture and branch demography to the manipulated predictor variables.ConclusionsEffects of species composition and species identity on growth rates and crown architecture variables of tree saplings point to niche separation as a mechanism of species co‐existence, while effects of species richness were not yet prominent at the sapling life stage.
A cross‐sectional analysis of the prevalence of dental anxiety and its relation to the oral health‐related quality of life in patients with dental treatment needs at a university clinic in Switzerland
Authors: Gisler Vanessa , Bassetti Renzo , Mericske‐Stern Regina , Bayer Stefan , Enkling Norbert 
Published: March 2012

doi: 10.1111/j.1741‐2358.2011.00465.xA cross‐sectional analysis of the prevalence of dental anxiety and its relation to the oral health‐related quality of life in patients with dental treatment needs at a university clinic in SwitzerlandObjectives:  The aim of this observational, cross‐sectional study was to analyse the relationship between dental anxiety (DA) and health‐related quality of life aspects associated with oral conditions of a population with dental treatment needs in Switzerland.Methods:  The measurements of DA were collected by means of two questionnaires, the Dental Anxiety Scale (DAS) and a Visual Analogue Scale (VAS). Oral health‐related quality of life (OHRQoL) was assessed with the Oral Health Impact Profile (OHIP). The sample included 223 patients enrolled at a university clinic which specialises in oral prosthetic rehabilitation and temporomandibular disorders. Of them, 78.9% were at or above the age of 50.Results:  No gender or age dependencies were observed. A comparison of answers regarding OHRQoL and DA revealed a significant interdependence (p = 0.0118); highly anxious patients were 3.55 times more likely to suffer from poor quality of life compared with less anxious ones.Conclusion:  This cross‐sectional study of mostly elderly patients seeking dental treatment in Switzerland found that increased DA was associated with an impaired OHRQoL. The average DA was slightly higher than the results of other industrialised countries and the average OHRQoL was reduced.
Effect of Imidafenacin before Sleeping on Nocturia
Authors: KADEKAWA Katsumi , ONAGA Tomohiro , SHIMABUKURO Shuichi , SHIMABUKURO Hiroichi , SAKUMOTO Misao , ASHITOMI Katsuhiro , NISHIJIMA Saori , SUGAYA Kimio 
Published: March 2012

Objectives: Clinical efficacy, influence on quality of life (QOL), and safety of imidafenacin before sleeping were assessed in patients with overactive bladder (OAB) who suffered from nocturia.Methods: A total of 60 OAB patients with a mean age of 74 years (45 men and 15 women) who mainly complained of nocturia were enrolled. Imidafenacin (0.1 mg) was administered once daily before sleeping for four weeks. Then the patients were divided into two groups, “a stable‐dose group” with sufficient efficacy who remained on 0.1 mg of imidafenacin daily, and “a dose‐escalation group” with insufficient efficacy in whom the daily dose of imidafenacin was increased to 0.2 mg before sleeping. Lower urinary tract symptoms and postvoid residual volume (PVR) were examined before treatment and after 4 and 8 weeks of imidafenacin therapy.Results: In the stable‐dose group, nighttime frequency decreased significantly from 3.4 ± 1.1 to 2.3 ± 1.1 and 2.6 ± 2.0 times after four and eight weeks, respectively. In the dose‐escalation group, nighttime frequency did not change significantly (from 3.8 ± 1.5 to 3.6 ± 1.8 times) at four weeks, but decreased significantly to 2.8 ± 1.4 times at eight weeks. Daytime frequency, OAB symptom score, and IPSS‐QOL index score were significantly improved in both groups at four and/or eight weeks. There was no increase of PVR and no serious adverse events.Conclusion: Administration of imidafenacin at 0.1–0.2 mg once daily before sleeping was safe and effective for the treatment of OAB with the main symptom of nocturia.
Use of A Public Telephone Hotline to Detect Urban Plague Cases
Authors: Malberg J. A. , Pape W. J. , Lezotte D. , Hill A. E. 
Published: March 2012

SummaryCurrent methods for vector‐borne disease surveillance are limited by time and cost. To avoid human infections from emerging zoonotic diseases, it is important that the United States develop cost‐effective surveillance systems for these diseases. This study examines the methodology used in the surveillance of a plague epizootic involving tree squirrels (Sciurus niger) in Denver Colorado, during the summer of 2007. A call‐in centre for the public to report dead squirrels was used to direct animal carcass sampling. Staff used these reports to collect squirrel carcasses for the analysis of Yersinia pestis infection. This sampling protocol was analysed at the census tract level using Poisson regression to determine the relationship between higher call volumes in a census tract and the risk of a carcass in that tract testing positive for plague. Over‐sampling owing to call volume‐directed collection was accounted for by including the number of animals collected as the denominator in the model. The risk of finding an additional plague‐positive animal increased as the call volume per census tract increased. The risk in the census tracts with >3 calls a month was significantly higher than that with three or less calls in a month. For tracts with 4–5 calls, the relative risk (RR) of an additional plague‐positive carcass was 10.08 (95% CI 5.46–18.61); for tracts with 6–8 calls, the RR = 5.20 (2.93–9.20); for tracts with 9–11 calls, the RR = 12.80 (5.85–28.03) and tracts with >11 calls had RR = 35.41 (18.60–67.40). Overall, the call‐in centre directed sampling increased the probability of locating plague‐infected carcasses in the known Denver epizootic. Further studies are needed to determine the effectiveness of this methodology at monitoring large‐scale zoonotic disease occurrence in the absence of a recognized epizootic.
Inadequate Efficacy of a New Formulation of Fosmidomycin-Clindamycin Combination in Mozambican Children Less than Three Years Old with Uncomplicated Plasmodium falciparum Malaria
Authors: Lanaspa Miguel , Moraleda Cinta , Machevo Sónia , González Raquel , Serrano Beatriz , Macete Eusebio , Cisteró Pau , Mayor Alfredo , Hutchinson David , Kremsner Peter G. , Alonso Pedro , Menéndez Clara , Bassat Quique 
Published: March 2012

ABSTRACT

The combination of fosmidomycin and clindamycin (F/C) is effective in adults and older children for the treatment of malaria and could be an important alternative to existing artemisinin-based combinations (ACTs) if proven to work in younger children. We conducted an open-label clinical trial to assess the efficacy, safety, and tolerability of F/C for the treatment of uncomplicated
P. falciparum
malaria in Mozambican children <3 years of age. Aqueous solutions of the drugs were given for 3 days, and the children were followed up for 28 days. The primary outcome was the PCR-corrected adequate clinical and parasitological response at day 28. Secondary outcomes included day 7 and 28 uncorrected cure rates and fever (FCT) and parasite (PCT) clearance times. Fifty-two children were recruited, but only 37 patients were evaluable for the primary outcome. Day 7 cure rates were high (94.6%; 35/37), but the day 28 PCR-corrected cure rate was 45.9% (17/37). The FCT was short (median, 12 h), but the PCT was longer (median, 72 h) than in previous studies. Tolerability was good, and most common adverse events were related to the recurrence of malaria. The poor efficacy observed for the F/C combination may be a consequence of the new formulations used, differential bioavailability in younger children, naturally occurring variations in parasite sensitivity to the drugs, or an insufficient enhancement of their effects by naturally acquired immunity in young children. Additional studies should be conducted to respond to the many uncertainties arising from this trial, which should not discourage further evaluation of this promising combination.
In Vitro
Antimalarial Activity and Drug Interactions of Fenofibric Acid
Authors: Wong Rina P. M. , Davis Timothy M. E. 
Published: March 2012

ABSTRACT

Plasmodium falciparum
has developed resistance to most available treatments, underscoring the need for novel antimalarial drugs. Fibrates are lipid-modifying agents used to reduce morbidity and mortality associated with cardiovascular disease. They may have antimalarial activity through modulation of P-glycoprotein and ATP-binding cassette subfamily A member (ABC-1)-mediated nutrient transport and/or via a putative peroxisome proliferator-activated receptor alpha-like protein. We therefore examined
in vitro
antimalarial activities of fibrates and their interactions with chloroquine and dihydroartemisinin in chloroquine-sensitive (3D7) and chloroquine-resistant (W2mef) strains of
P. falciparum
using the conventional isotopic assay microtechnique. A bioassay was used to assess inhibition activities of human plasma after therapeutic fenofibrate doses. Fenofibric acid, the main metabolite of fenofibrate, was the most potent of the fibrates tested, with mean 50% inhibitory concentrations of 152 nM and 1,120 nM for chloroquine-sensitive and -resistant strains, respectively. No synergistic interaction between fibrates and chloroquine or dihydroartemisinin was observed. Plasma fenofibric acid concentrations, quantified by high-performance liquid chromatography in seven healthy volunteers after treatment (mean, 15.3 mg/liter, or 48 μM), inhibited
P. falciparum
. BLAST analysis revealed the likely presence of an ABC-1 transporter homolog in
P. falciparum
. Our findings demonstrate that fenofibric acid has activity similar to the activities of conventional antimalarial drugs at concentrations well below those achieved after therapeutic doses. It may inhibit
P. falciparum
growth by inhibiting intracellular lipid transport.
Integrated Population Pharmacokinetic Analysis of Voriconazole in Children, Adolescents, and Adults
Authors: Friberg Lena E. , Ravva Patanjali , Karlsson Mats O. , Liu Ping 
Published: March 2012

ABSTRACT

To further optimize the voriconazole dosing in the pediatric population, a population pharmacokinetic analysis was conducted on pooled data from 112 immunocompromised children (2 to <12 years), 26 immunocompromised adolescents (12 to <17 years), and 35 healthy adults. Different maintenance doses (i.e., 3, 4, 6, 7, and 8 mg/kg of body weight intravenously [i.v.] every 12 h [q12h]; 4 mg/kg, 6 mg/kg, and 200 mg orally q12h) were evaluated in these children. The adult dosing regimens (6 mg/kg i.v. q12h on day 1, followed by 4 mg/kg i.v. q12h, and 300 mg orally q12h) were evaluated in the adolescents. A two-compartment model with first-order absorption and mixed linear and nonlinear (Michaelis-Menten) elimination adequately described the voriconazole data. Larger interindividual variability was observed in pediatric subjects than in adults. Deterministic simulations based on individual parameter estimates from the final model revealed the following. The predicted total exposure (area under the concentration-time curve from 0 to 12 h [AUC
0-12
]) in children following a 9-mg/kg i.v. loading dose was comparable to that in adults following a 6-mg/kg i.v. loading dose. The predicted AUC
0-12
s in children following 4 and 8 mg/kg i.v. q12h were comparable to those in adults following 3 and 4 mg/kg i.v. q12h, respectively. The predicted AUC
0-12
in children following 9 mg/kg (maximum, 350 mg) orally q12h was comparable to that in adults following 200 mg orally q12h. To achieve voriconazole exposures comparable to those of adults, dosing in 12- to 14-year-old adolescents depends on their weight: they should be dosed like children if their weight is <50 kg and dosed like adults if their weight is ≥50 kg. Other adolescents should be dosed like adults.
Pharmacokinetics and Pulmonary Disposition of Tedizolid and Linezolid in a Murine Pneumonia Model under Variable Conditions
Authors: Keel Rebecca A. , Crandon Jared L. , Nicolau David P. 
Published: March 2012

ABSTRACT

In vivo
pharmacokinetics are often evaluated in only one variation of an infection model, and the resulting exposures are assumed to be similar in each model. We evaluated and compared the effect of lung infection and immune status on the murine pharmacokinetics and pulmonary disposition of tedizolid and linezolid. Both factors resulted in differing blood and pulmonary exposure profiles, with similar trends for tedizolid and linezolid. These data highlight the importance of pharmacokinetic confirmation in each model.
Phase II Dose-Ranging Trial of the Early Bactericidal Activity of PA-824
Authors: Diacon Andreas H. , Dawson Rodney , du Bois Jeannine , Narunsky Kim , Venter Amour , Donald Peter R. , van Niekerk Christo , Erondu Ngozi , Ginsberg Ann M. , Becker Piet , Spigelman Melvin K. 
Published: March 2012

ABSTRACT

PA-824 is a novel nitroimidazo-oxazine under evaluation as an antituberculosis agent. A dose-ranging randomized study was conducted to evaluate the safety, tolerability, pharmacokinetics, and early bactericidal activity of PA-824 in drug-sensitive, sputum smear-positive adult pulmonary-tuberculosis patients to find the lowest dose giving optimal bactericidal activity (EBA). Fifteen patients per cohort received oral PA-824 in doses of 50 mg, 100 mg, 150 mg, or 200 mg per kg body weight per day for 14 days. Eight subjects received once-daily standard antituberculosis treatment with isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) as a positive control. The primary efficacy endpoint was the mean rate of decline in log CFU of
Mycobacterium tuberculosis
in sputum incubated on agar plates from serial overnight sputum collections, expressed as log
10
CFU/day/ml sputum (± standard deviation). The mean 14-day EBA of HRZE was consistent with previous studies (0.177 ± 0.042), and that of PA-824 at 50 mg, 100 mg, 150 mg, and 200 mg was 0.063 ± 0.058, 0.091 ± 0.073, 0.078 ± 0.074, and 0.112 ± 0.070, respectively. Although the study was not powered for testing the difference between arms, there was a trend toward significance, indicating a lower EBA at the 50-mg dose. Serum PA-824 levels were approximately dose proportional with respect to the area under the time-concentration curve. All doses were safe and well tolerated with no dose-limiting adverse events or clinically significant QTc changes. A dose of 100 mg to 200 mg PA-824 daily appears to be safe and efficacious and will be further evaluated as a component of novel antituberculosis regimens for drug-sensitive and drug-resistant tuberculosis.
Pegylation of Antimicrobial Peptides Maintains the Active Peptide Conformation, Model Membrane Interactions, and Antimicrobial Activity while Improving Lung Tissue Biocompatibility following Airway Delivery
Authors: Morris Christopher J. , Beck Konrad , Fox Marc A. , Ulaeto David , Clark Graeme C. , Gumbleton Mark 
Published: March 2012

ABSTRACT

Antimicrobial peptides (AMPs) have therapeutic potential, particularly for localized infections such as those of the lung. Here we show that airway administration of a pegylated AMP minimizes lung tissue toxicity while nevertheless maintaining antimicrobial activity. CaLL, a potent synthetic AMP (KWKLFKKIFKRIVQRIKDFLR) comprising fragments of LL-37 and cecropin A peptides, was N-terminally pegylated (PEG-CaLL). PEG-CaLL derivatives retained significant antimicrobial activity (50% inhibitory concentrations [IC
50
s] 2- to 3-fold higher than those of CaLL) against bacterial lung pathogens even in the presence of lung lining fluid. Circular dichroism and fluorescence spectroscopy confirmed that conformational changes associated with the binding of CaLL to model microbial membranes were not disrupted by pegylation. Pegylation of CaLL reduced AMP-elicited cell toxicity as measured using
in vitro
lung epithelial primary cell cultures. Further, in a fully intact
ex vivo
isolated perfused rat lung (IPRL) model, airway-administered PEG-CaLL did not result in disruption of the pulmonary epithelial barrier, whereas CaLL caused an immediate loss of membrane integrity leading to pulmonary edema. All AMPs (CaLL, PEG-CaLL, LL-37, cecropin A) delivered to the lung by airway administration showed limited (<3%) pulmonary absorption in the IPRL with extensive AMP accumulation in lung tissue itself, a characteristic anticipated to be beneficial for the treatment of pulmonary infections. We conclude that pegylation may present a means of improving the lung biocompatibility of AMPs designed for the treatment of pulmonary infections.
Association of ITPA Gene Polymorphisms and the Risk of Ribavirin-Induced Anemia in HIV/Hepatitis C Virus (HCV)-Coinfected Patients Receiving HCV Combination Therapy
Authors: Domingo Pere , Guardiola Josep M. , Salazar Juliana , Torres Ferran , Mateo M. Gracia , Pacho Cristina , del Mar Gutierrez M. , Lamarca Karuna , Fontanet Angels , Martin Jordi , Muñoz Jessica , Vidal Francesc , Baiget Montserrat 
Published: March 2012

ABSTRACT

Polymorphisms of the ITPA gene have been associated with anemia during combination therapy in hepatitis C virus (HCV)-monoinfected patients. Our aim was to confirm this association in HIV/HCV-coinfected patients. In this prospective, observational study, 73 HIV/HCV-coinfected patients treated with pegylated interferon plus ribavirin (RBV) were enrolled. Two single nucleotide polymorphisms within or adjacent to the ITPA gene (rs1127354 and rs7270101) were genotyped. The associations between the ITPA genotype and anemia or treatment outcome were examined. Fifty-nine patients (80.8%) had CC at rs1127354, whereas 14 (19.2%) had a CA/AA ITPA genotype. Percent decreases from baseline hemoglobin level were significantly greater in patients with the CC genotype than in those with the CA/AA genotype at week 4 (
P
= 0.0003), week 12 (
P
< 0.0001), and week 36 (
P
= 0.0102) but not at the end of treatment. RBV dose reduction was more often needed in patients with the CC genotype than in those with the CA/AA genotype (odds ratio [OR] = 11.81; 95% confidence interval [CI] = 1.45 to 256.17;
P
= 0.0039), as was erythropoietin therapy (OR = 8.28; 95% CI = 1.04 to 371.12;
P
= 0.0057). Risk factors independently associated with percent hemoglobin nadir decrease were RBV dose reduction (OR = 11.72; 95% CI = 6.82 to 16.63;
P
< 0.001), baseline hemoglobin (OR = 1.69; 95% CI = 0.23 to 3.15;
P
= 0.024), and body mass index (OR = −0.7; 95% CI = −1.43 to 0.03;
P
= 0.061). ITPA polymorphism was not an independent predictor of sustained virological response. Polymorphisms at rs1127354 in the ITPA gene influence hemoglobin levels during combination HCV therapy and the need for RBV dose reduction and erythropoietin use in HIV/HCV-coinfected patients.
Mycobacterium tuberculosis Lacking All Mycolic Acid Cyclopropanation Is Viable but Highly Attenuated and Hyperinflammatory in Mice
Authors: Barkan Daniel , Hedhli Dorsaf , Yan Han-Guang , Huygen Kris , Glickman Michael S. 
Published: March 2012

ABSTRACTMycolic acids, the major lipid of theMycobacterium tuberculosiscell wall, are modified by cyclopropane rings, methyl branches, and oxygenation through the action of eightS-adenosylmethionine (SAM)-dependent mycolic acid methyltransferases (MAMTs), encoded at four genetic loci. Mycolic acid modification has been shown to be important forM. tuberculosispathogenesis, in part through effects on the inflammatory activity of trehalose dimycolate (cord factor). Studies using the MAMT inhibitor dioctylamine have suggested that the MAMT enzyme class is essential forM. tuberculosisviability. However, it is unknown whether a cyclopropane-deficient strain ofM. tuberculosiswould be viable and what the effect of cyclopropane deficiency on virulence would be. We addressed these questions by creating and characterizingM. tuberculosisstrains lacking all functional MAMTs. Our results show thatM. tuberculosisis viable either without cyclopropanation or without cyclopropanation and any oxygenated mycolates. Characterization of these strains revealed that MAMTs are required for acid fastness and resistance to detergent stress. Complete lack of cyclopropanation confers severe attenuation during the first week after aerosol infection of the mouse, whereas complete loss of MAMTs confers attenuation in the second week of infection. Characterization of immune responses to the cyclopropane- and MAMT-deficient strains indicated that the net effect of mycolate cyclopropanation is to dampen host immunity. Taken together, our findings establish the immunomodulatory function of the mycolic acid modification pathway in pathogenesis and buttress this enzyme class as an attractive target for antimycobacterial drug development.
Receptor-Dependent and -Independent Immunomodulatory Effects of Phenol-Soluble Modulin Peptides from Staphylococcus aureus on Human Neutrophils Are Abrogated through Peptide Inactivation by Reactive Oxygen Species
Authors: Forsman Huamei , Christenson Karin , Bylund Johan , Dahlgren Claes 
Published: March 2012

ABSTRACTThe virulence and pathogenesis mechanisms of community-associated methicillin-resistantStaphylococcus aureus(CA-MRSA) strains depend on a newly described group of phenol-soluble modulin (PSM) peptides (the PSMα peptides) with cytolytic activity. These toxins are α-helical peptides with a formyl group at the N terminus, and they activate neutrophils through formyl peptide receptor 2 (FPR2), a function closely correlated to the capacity of staphylococcal species to cause invasive infections. The effects of two synthetic PSMα peptides were investigated, and we show that they utilize FPR2 and promote neutrophils to produce reactive oxygen species (ROS) which in turn trigger inactivation of the peptides. Independently of FPR2, the PSMα peptides also downregulate the neutrophil response to other stimuli and exert a cytolytic effect to which apoptotic neutrophils are more sensitive than viable cells. The novel immunomodulatory functions of the PSMα peptides were sensitive to ROS generated by the neutrophil myeloperoxidase (MPO)-H2O2system, suggesting a role for this enzyme system in counteracting bacterial virulence.