Wheeze in preschool age is associated with pulmonary bacterial infection and resolves after antibiotic therapy

Background

Neonates with airways colonized by Haemophilus influenzae, Streptococcus pneumoniae or Moraxella catarrhalis are at increased risk for recurrent wheeze which may resemble asthma early in life. It is not clear whether chronic colonization by these pathogens is causative for severe persistent wheeze in some preschool children and whether these children might benefit from antibiotic treatment. We assessed the relevance of bacterial colonization and chronic airway infection in preschool children with severe persistent wheezing and evaluated the outcome of long-time antibiotic treatment on the clinical course in such children.

Methodology/Principal Findings

Preschool children (n = 42) with severe persistent wheeze but no symptoms of acute pulmonary infection were investigated by bronchoscopy and bronchoalveolar lavage (BAL). Differential cell counts and microbiological and virological analyses were performed on BAL samples. Patients diagnosed with bacterial infection were treated with antibiotics for 2–16 weeks (n = 29). A modified ISAAC questionnaire was used for follow-up assessment of children at least 6 months after bronchoscopy. Of the 42 children with severe wheezing, 34 (81%) showed a neutrophilic inflammation and 20 (59%) of this subgroup had elevated bacterial counts (≥10⁴ colony forming units per milliliter) suggesting infection. Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis were the most frequently isolated species. After treatment with appropriate antibiotics 92% of patients showed a marked improvement of symptoms upon follow-up examination.

Conclusions/Significance

Chronic bacterial infections are relevant in a subgroup of preschool children with persistent wheezing and such children benefit significantly from antibiotic therapy.     

High-dose chemotherapy followed by autologous stem cell transplantation for metastatic rhabdomyosarcoma--a systematic review

Introduction

Patients with metastatic rhabdomyosarcoma (RMS) have a poor prognosis. The aim of this systematic review is to investigate whether high-dose chemotherapy (HDCT) followed by autologous hematopoietic stem cell transplantation (HSCT) in patients with metastatic RMS has additional benefit or harm compared to standard chemotherapy.

Methods

Systematic literature searches were performed in MEDLINE, EMBASE, and The Cochrane Library. All databases were searched from inception to February 2010. PubMed was searched in June 2010 for a last update. In addition to randomized and non-randomized controlled trials, case series and case reports were included to complement results from scant data. The primary outcome was overall survival. A meta-analysis was performed using the hazard ratio as primary effect measure, which was estimated from Cox proportional hazard models or from summary statistics of Kaplan Meier product-limit estimations.

Results

A total of 40 studies with 287 transplant patients with metastatic RMS (age range 0 to 32 years) were included in the assessment. We identified 3 non-randomized controlled trials. The 3-year overall survival ranged from 22% to 53% in the transplant groups vs. 18% to 55% in the control groups. Meta-analysis on overall survival in controlled trials showed no difference between treatments. Result of meta-analysis of pooled individual survival data of case series and case reports, and results from uncontrolled studies with aggregate data were in the range of those from controlled data. The risk of bias was high in all studies due to methodological flaws.

Conclusions

HDCT followed by autologous HSCT in patients with RMS remains an experimental treatment. At present, it does not appear justifiable to use this treatment except in appropriately designed controlled trials.     

Floating Ice-Algal Aggregates below Melting Arctic Sea Ice

During two consecutive cruises to the Eastern Central Arctic in late summer 2012, we observed floating algal aggregates in the melt-water layer below and between melting ice floes of first-year pack ice. The macroscopic (1-15 cm in diameter) aggregates had a mucous consistency and were dominated by typical ice-associated pennate diatoms embedded within the mucous matrix. Aggregates maintained buoyancy and accumulated just above a strong pycnocline that separated meltwater and seawater layers. We were able, for the first time, to obtain quantitative abundance and biomass estimates of these aggregates. Although their biomass and production on a square metre basis was small compared to ice-algal blooms, the floating ice-algal aggregates supported high levels of biological activity on the scale of the individual aggregate. In addition they constituted a food source for the ice-associated fauna as revealed by pigments indicative of zooplankton grazing, high abundance of naked ciliates, and ice amphipods associated with them. During the Arctic melt season, these floating aggregates likely play an important ecological role in an otherwise impoverished near-surface sea ice environment. Our findings provide important observations and measurements of a unique aggregate-based habitat during the 2012 record sea ice minimum year.     

MORPHOLOGICAL,TOXICOLOGICAL, AND GENETIC DIFFERENCES AMONG PSEUDO‐NITZSCHIA (BACILLARIOPHYCEAE) SPECIES IN INLAND EMBAYMENTS AND OUTER COASTAL WATERS OF WASHINGTON STATE,USA1

Plankton samples from three inland embayments and several outer coastal sites of Washington State were collected from 1997 through 1999 and were examined for the presence of diatoms of the genus Pseudo‐nitzschia and levels of the toxin, domoic acid (DA). Seven species were observed, including Pseudo‐nitzschia pungens (Grunow ex Cleve) Hasle, P. multiseries (Hasle) Hasle, P. australis Frenguelli, P. fraudulenta (Cleve) Hasle, P. cf. heimii Manguim, P. pseudodelicatissima (Hasle) Hasle, and P. delicatissima (Cleve) Heiden. The coastal Pseudo‐nitzschia species assemblages differed significantly from those observed within embayments. The dominant species observed at coastal sites were P. pseudodelicatissima and P. cf. heimii. Pseudo‐nitzschia assemblages found in embayments included one or more of the following species: P. pungens, P. multiseries, P. australis, P. pseudodelicatissima, and P. fraudulenta. The nuclear large subunit rRNA gene was sequenced for six of the seven species identified. This sequence revealed that P. multiseries, P. pungens, P. australis, and P. heimii were genetically similar to those found in California, whereas P. delicatissima and P. pseudodelicatissima were distinct from the California isolates. Although the concentrations of DA in razor clams along Washington State coasts have exceeded regulatory limits several times since 1991, levels of DA in shellfish from Washington State embayments have not yet exceeded regulatory limits. The widespread presence of toxin‐producing Pseudo‐nitzschia species suggests, however, that toxic blooms are likely to occur within embayments in the future. In conjunction with the monitoring of environmental conditions conducive to toxic bloom formation, the development of species‐specific probes for rapid and accurate detection of potentially toxic Pseudo‐nitzschia species in this region would enable the forecasting of a toxic event before DA accumulates in shellfish, thereby reducing the impacts to coastal communities.     

Iron acquisition by phytosiderophores contributes to cadmium tolerance

Based on the ability of phytosiderophores to chelate other heavy metals besides iron (Fe), phytosiderophores were suggested to prevent graminaceous plants from cadmium (Cd) toxicity. To assess interactions between Cd and phytosiderophore-mediated Fe acquisition, maize (Zea mays) plants were grown hydroponically under limiting Fe supply. Exposure to Cd decreased uptake rates of 59Fe(III)-phytosiderophores and enhanced the expression of the Fe-phytosiderophore transporter gene ZmYS1 in roots as well as the release of the phytosiderophore 2'-deoxymugineic acid (DMA) from roots under Fe deficiency. However, DMA hardly mobilized Cd from soil or from a Cd-loaded resin in comparison to the synthetic chelators diaminetriaminepentaacetic acid and HEDTA. While nano-electrospray-high resolution mass spectrometry revealed the formation of an intact Cd(II)-DMA complex in aqueous solutions, competition studies with Fe(III) and zinc(II) showed that the formed Cd(II)-DMA complex was weak. Unlike HEDTA, DMA did not protect yeast (Saccharomyces cerevisiae) cells from Cd toxicity but improved yeast growth in the presence of Cd when yeast cells expressed ZmYS1. When supplied with Fe-DMA as a Fe source, transgenic Arabidopsis (Arabidopsis thaliana) plants expressing a cauliflower mosaic virus 35S-ZmYS1 gene construct showed less growth depression than wild-type plants in response to Cd. These results indicate that inhibition of ZmYS1-mediated Fe-DMA transport by Cd is not related to Cd-DMA complex formation and that Cd-induced phytosiderophore release cannot protect maize plants from Cd toxicity. Instead, phytosiderophore-mediated Fe acquisition can improve Fe uptake in the presence of Cd and thereby provides an advantage under Cd stress relative to Fe acquisition via ferrous Fe.     

Halomonas alkaliantarctica sp. nov., isolated from saline lake Cape Russell in Antarctica, an alkalophilic moderately halophilic, exopolysaccharide-producing bacterium

The taxomony of strain CRSS (DSM 15686(T)=ATCC BAA-848(T)) isolated from Cape Russell in Antarctica (Ross Sea, 74 52.35 S 163 53.03 E) was investigated in a polyphasic approach. The morphological, physiological and genetic characteristics were compared with that of related species of the genus Halomonas. The isolate grew optimally at pH 9.0, 10% NaCl at 30 degrees C. The cells were Gram-negative aerobic rods able to produce exopolysaccharide. They accumulated glycine-betaine, as a major osmolyte, with minor components ectoine and glutamate. The strain CRSS biosynthetised alpha-glucosidase. The polar lipid profile consisted of phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol as major components. Ubiquinone with nine repetitive unities (Q9) was the only quinone found and the fatty acid composition was dominated by C18:1 (53%). The G+C content of DNA was 55.0mol% and its phylogenetic position was established by 16S rRNA gene sequencing as a member of the genus Halomonas. For physiological, chemotaxonomic and genetic features (DNA-DNA hybridisation) it is proposed to classify the isolate as a new species for which we propose the name Halomonas alkaliantarctica sp. nov.     

PIC1, an ancient permease in Arabidopsis chloroplasts, mediates iron transport

In chloroplasts, the transition metals iron and copper play an essential role in photosynthetic electron transport and act as cofactors for superoxide dismutases. Iron is essential for chlorophyll biosynthesis, and ferritin clusters in plastids store iron during germination, development, and iron stress. Thus, plastidic homeostasis of transition metals, in particular of iron, is crucial for chloroplast as well as plant development. However, very little is known about iron uptake by chloroplasts. Arabidopsis thaliana PERMEASE IN CHLOROPLASTS1 (PIC1), identified in a screen for metal transporters in plastids, contains four predicted alpha-helices, is targeted to the inner envelope, and displays homology with cyanobacterial permease-like proteins. Knockout mutants of PIC1 grew only heterotrophically and were characterized by a chlorotic and dwarfish phenotype reminiscent of iron-deficient plants. Ultrastructural analysis of plastids revealed severely impaired chloroplast development and a striking increase in ferritin clusters. Besides upregulation of ferritin, pic1 mutants showed differential regulation of genes and proteins related to iron stress or transport, photosynthesis, and Fe-S cluster biogenesis. Furthermore, PIC1 and its cyanobacterial homolog mediated iron accumulation in an iron uptake-defective yeast mutant. These observations suggest that PIC1 functions in iron transport across the inner envelope of chloroplasts and hence in cellular metal homeostasis.     

Pretreatment strategies for microbial valorization of bio‐oil fractions produced by fast pyrolysis of ash‐rich lignocellulosic biomass

This work evaluates a biorefinery approach for microbial valorization of bio‐oil fractions produced by fast pyrolysis of ash‐rich lignocellulosic biomass. Different methods are presented for the pretreatment of the low‐sugar complex bio‐oil consisting of organic condensate (OC) and aqueous condensate (AC) to overcome their strong inhibitory effects and unsuitability for common analytical methods. Growth of Pseudomonas putida KT2440, which was chosen as a reference system, on untreated bio‐oil fractions was only detectable using solid medium with OC as sole carbon source. Utilization of a pretreated OC which was filtered, autoclaved, neutralized and centrifuged enabled growth in liquid medium with significant remaining optical instability. By subjecting the pretreated fractions to solid phase extraction, more stable and less inhibitory bio‐oil fractions could be obtained enabling the appliance of common analytical methods. Furthermore, this pretreatment facilitated growth of the applied reference organism Pseudomonas putida KT2440. As there is currently no convincing strategy for reliable application of bio‐oil as a sole source of carbon in industrial biotechnology, the presented work depicts a first step toward establishing bio‐oil as a future sustainable feedstock for a bio‐based economy.     

Statistical modeling of nitrogen-dependent modulation of root system architecture in Arabidopsis thaliana

Plant root development is strongly affected by nutrient availability. Despite the importance of structure and function of roots in nutrient acquisition,statistical modeling approaches to evaluate dynamic and temporal modulations of root system architecture in response to nutrient availability have remained as widely open and exploratory areas in root biology. In this study,we developed a statistical modeling approach to investigate modulations of root system architecture in response to nitrogen availability. Mathematical models were designed for quantitative assessment of root growth and root branching phenotypes and their dynamic relationships based on hierarchical con figuration of primary and lateral roots formulating the fishbone-shaped root system architecture in Arabidopsis thaliana. Time-series datasets reporting dynamic changes in root developmental traits on different nitrate or ammonium concentrations were generated for statistical analyses. Regression analyses unraveled key parameters associated with:(i) inhibition of primary root growth under nitrogen limitation or on ammonium;(ii) rapid progression of lateral root emergence in response to ammonium; and(iii) inhibition of lateral root elongation in the presence of excess nitrate or ammonium. This study provides a statistical framework for interpreting dynamic modulation of root system architecture,supported by metaanalysis of datasets displaying morphological responses of roots to diverse nitrogen supplies.