Enhancing ventilation in homes of children with asthma: pragmatic randomised controlled trial

Background

Few robust studies have tested whether enhancing housing also improves health.

Aim

To evaluate the effectiveness of installing ventilation systems, and central heating where necessary, in the homes of children with moderate or severe asthma.

Design and setting

Pragmatic randomised controlled trial (RCT) in homes within Wrexham County Borough, Wales, UK.

Method

A pragmatic RCT was carried out, of a tailored package of housing improvements providing adequate ventilation and temperature, following inspection by a housing officer. One hundred and ninety-two children with asthma aged 5 to 14 years, identified from general practice registers, were randomised to receive this package, either immediately or a year after recruitment. At baseline, and after 4 and 12 months, parents reported their child''s asthma-specific and generic quality of life, and days off school.

Results

The package improved parent-reported asthma-specific quality of life significantly at both 4 and 12 months. At 12 months, this showed an adjusted mean difference between groups of 7.1 points (95% confidence interval [CI] = 2.8 to 11.4, P= 0.001): a moderate standardised effect size of 0.42. The generic quality-of-life scale showed reported physical problems were significantly reduced at 4 months, but not quite at 12 months, when the mean difference was 4.5 (95% CI = -0.2 to 9.1, P= 0.061). The improvement in psychosocial quality of life at 12 months was not significant, with a mean difference of 2.2 (95% CI = -1.9 to 6.4, P= 0.292). Parent-reported school attendance improved, but not significantly

Conclusion

This novel and pragmatic trial, with integrated economic evaluation, found that tailored improvement of the housing of children with moderate to severe asthma significantly increases parent-reported asthma-related quality of life and reduces physical problems. Collaborative housing initiatives have potential to improve health.     

Analysis of 81 genes from 64 plastid genomes resolves relationships in angiosperms and identifies genome-scale evolutionary patterns

Angiosperms are the largest and most successful clade of land plants with >250,000 species distributed in nearly every terrestrial habitat. Many phylogenetic studies have been based on DNA sequences of one to several genes, but, despite decades of intensive efforts, relationships among early diverging lineages and several of the major clades remain either incompletely resolved or weakly supported. We performed phylogenetic analyses of 81 plastid genes in 64 sequenced genomes, including 13 new genomes, to estimate relationships among the major angiosperm clades, and the resulting trees are used to examine the evolution of gene and intron content. Phylogenetic trees from multiple methods, including model-based approaches, provide strong support for the position of Amborella as the earliest diverging lineage of flowering plants, followed by Nymphaeales and Austrobaileyales. The plastid genome trees also provide strong support for a sister relationship between eudicots and monocots, and this group is sister to a clade that includes Chloranthales and magnoliids. Resolution of relationships among the major clades of angiosperms provides the necessary framework for addressing numerous evolutionary questions regarding the rapid diversification of angiosperms. Gene and intron content are highly conserved among the early diverging angiosperms and basal eudicots, but 62 independent gene and intron losses are limited to the more derived monocot and eudicot clades. Moreover, a lineage-specific correlation was detected between rates of nucleotide substitutions, indels, and genomic rearrangements.     

Validity of electronically monitored medication adherence and conventional adherence measures in schizophrenia

OBJECTIVE: This study evaluated the validity of prescriber, patient, and research assistant ratings of adherence to prescribed oral antipsychotic medication among outpatients with schizophrenia or schizoaffective disorder in comparison with electronic monitoring. METHODS: Adult outpatients with schizophrenia (N=35) or schizoaffective disorder (N=26) received adherence assessments via electronically monitored medication vial caps as well as by monthly prescriber, patient, and research assistant report for up to six months. RESULTS: Electronic monitoring detected greater nonadherence rates (57%) than either prescribers (7%) or patients (5%), though the research assistant ratings were 54%. No directional bias was found between electronic monitoring and assignment of adherence by research assistants, although disagreement occurred in 36% of cases. CONCLUSIONS: Both patients and prescribers grossly overestimated medication adherence, which may interfere with or reduce the effectiveness of diligent medication management.     

Branched-Chain Amino Acids Are Required for the Survival and Virulence of Actinobacillus pleuropneumoniae in Swine

In Actinobacillus pleuropneumoniae, which causes porcine pleuropneumonia, ilvI was identified as an in vivo-induced (ivi) gene and encodes the enzyme acetohydroxyacid synthase (AHAS) required for branched-chain amino acid (BCAA) biosynthesis. ilvI and 7 of 32 additional ivi promoters were upregulated in vitro when grown in chemically defined medium (CDM) lacking BCAA. Based on these observations, we hypothesized that BCAA would be found at limiting concentrations in pulmonary secretions and that A. pleuropneumoniae mutants unable to synthesize BCAA would be attenuated in a porcine infection model. Quantitation of free amino acids in porcine pulmonary epithelial lining fluid showed concentrations of BCAA ranging from 8 to 30 μmol/liter, which is 10 to 17% of the concentration in plasma. The expression of both ilvI and lrp, a global regulator that is required for ilvI expression, was strongly upregulated in CDM containing concentrations of BCAA similar to those found in pulmonary secretions. Deletion-disruption mutants of ilvI and lrp were both auxotrophic for BCAA in CDM and attenuated compared to wild-type A. pleuropneumoniae in competitive index experiments in a pig infection model. Wild-type A. pleuropneumoniae grew in CDM+BCAA but not in CDM−BCAA in the presence of sulfonylurea AHAS inhibitors. These results clearly demonstrate that BCAA availability is limited in the lungs and support the hypothesis that A. pleuropneumoniae, and potentially other pulmonary pathogens, uses limitation of BCAA as a cue to regulate the expression of genes required for survival and virulence. These results further suggest a potential role for AHAS inhibitors as antimicrobial agents against pulmonary pathogens.Actinobacillus pleuropneumoniae is the causative agent of porcine pleuropneumonia, a disease of significant economic importance throughout the swine-raising areas of the world (6, 48). This pathogen possesses several well-studied virulence factors, including Apx toxins (20), capsular polysaccharides (57, 58), lipopolysaccharide (1, 17, 41), fimbriae (63), and iron-scavenging proteins (13, 50), which aid in the pathogenesis of acute pleuropneumonia marked by edema, hemorrhage, and necrosis (6, 26). In a search for additional virulence factors of this pathogen, we developed an in vivo expression technology (IVET) system and used this genetic tool to identify A. pleuropneumoniae gene promoters that are upregulated in vivo in the swine lung during infection compared to growth on laboratory media (22, 55).One of the A. pleuropneumoniae in vivo-induced (ivi) promoters that we identified drives the ilvIH operon, which encodes both large and small subunits of acetohydroxy acid synthase isozyme III (AHAS) (55). AHAS enzymes catalyze pivotal steps in the biosynthesis of the branched-chain amino acids (BCAA) isoleucine, leucine, and valine (31). In a survey of IVET, signature-tagged mutagenesis, and microarray studies of other pathogens, we observed that genes involved in BCAA biosynthesis were frequently identified in studies of pathogens that cause pneumonia, meningitis, or septicemia but not in pathogens of the gastrointestinal tract (55). This observation suggests that the ability to synthesize BCAA is critical for pathogens of the respiratory tract but not for gastrointestinal pathogens. BCAA are essential amino acids that must be acquired from ingested food for most mammals, including humans and pigs, and it is possible that fluids in “clean” body sites such as the lungs have only limited supplies of BCAA compared to the digestive tract.To test whether limitation of BCAA affects the expression of A. pleuropneumoniae genes that are induced in vivo, we compared expression from the A. pleuropneumoniae ivi promoters in a chemically defined medium (CDM) containing or lacking BCAA (55). We found that 25% (8 of 32) of the ivi promoters were upregulated during growth in CDM lacking BCAA compared to complete CDM. These included the ilvI promoter, as well as promoters for other genes potentially involved in survival within the host and virulence, such as hfq, a global regulator that binds sRNAs and mRNA and affects expression of virulence-associated genes in many pathogens (9, 49). These results strongly suggest that the environmental conditions encountered by A. pleuropneumoniae during infection of the swine lung include limitation of BCAA.The goals of the present study were to quantify free BCAA in porcine pulmonary secretions, to evaluate the effect of these concentrations of BCAA on expression of genes required for BCAA biosynthesis, and to test whether A. pleuropneumoniae mutants that cannot synthesize BCAA were attenuated. A. pleuropneumoniae deletion-disruption mutants of the ilvI biosynthetic gene and the lrp gene, which encodes a global regulator required for expression of several genes involved in BCAA biosynthesis, were constructed and shown to be attenuated in a porcine infection model. The low levels of available BCAA in pulmonary secretions and the attenuation of these mutants led us to examine the effect of small molecule inhibitors of AHAS on growth of A. pleuropneumoniae in vitro. Several AHAS inhibitors were shown to prevent growth in CDM lacking BCAA but not complete CDM. These results demonstrate that A. pleuropneumoniae, and likely other bacterial pathogens of the respiratory tracts of other mammals, encounter conditions where BCAA are available only in limited supply during infection, that these low levels of BCAA can affect bacterial gene expression, and that these pathogens must be able to synthesize BCAA to survive and cause disease in the lung.     

The role of topical growth factors in chronic wounds

Chronic wounds display aberrant wound healing or wound healing that deviates from normal. The term 'chronic wounds', implies that these wounds do not heal in a timely fashion. They are often predisposed to infection, and not uncommonly result in amputation. Growth factors and cytokines play a pivotal role in cutaneous wound healing. It has been noted that some growth factors are deficient in chronic wounds, therefore it has been suggested that local or topical application of these factors may compensate for any deficiency and allow normal wound healing to progress. This paper reviews current work on the application of topical growth factors to wounds. Some potential problems are identified and suggestions are made for future areas where research may improve the effectiveness of this form of therapy.