Small-group,interactive education and the effect on asthma control by children and their families

Background

Effective approaches to education about asthma need to be identified. We evaluated the impact on asthma control by children and their caregivers of an intervention involving small-group, interactive education about asthma.

Methods

We randomly assigned children who visited an emergency department for an exacerbation of asthma (n = 398) to either of 2 groups. Children assigned to the control group followed the usual care recommended by their primary care physician. Those assigned to the intervention group participated in a small-group, interactive program of education about asthma. We examined changes in the number of visits to the emergency department during the year after the intervention.

Results

During the year after enrolment, children in the intervention group made significantly fewer visits to the emergency department (0.45 visits per child) compared with those in the control group (0.75 visits per child) (p = 0.004). The likelihood of a child in the intervention group requiring emergency care was reduced by 38% (relative risk [RR] 0.62, 95% confidence interval CI 0.48–0.81, p = 0.004). Fewer courses of oral corticosteroids (0.63 per child) were required by children in the intervention group than by those in the control group (0.85 per child) (p = 0.006). We observed significant improvements in the symptom domain of the questionnaire on pediatric asthma quality-of-life (p = 0.03) and the activity domain of the questionnaire on caregivers’ quality of life (p = 0.05). Parents of children in the intervention group missed less work because of their child’s asthma after participating in the educational program (p = 0.04). No impact on hospital admissions was observed.

Interpretation

Education about asthma, especially in a small-group, interactive format, improved clinically important outcomes and overall care of children with asthma.Management of asthma often focuses on “crisis intervention,” meaning that the disease is addressed only when a problem occurs. Shifting emphasis to a preventive health model, which includes guided self-management, has been shown to reduce costs related to hospital admissions and visits to emergency departments.¹ Education about asthma is an integral part of the recommendations of most guidelines for the management of asthma.^2–4There is no consensus on the best model for education about asthma. A review of publications from 1991 through 2004 showed that only half of the studies identified were randomized controlled trials and that many studies used patients as their own historic controls.⁴ Given that a regression to the mean is commonly observed in the data of such studies, with improvements in asthma over time, the use of historic controls is not an acceptable means of defining the impact of education. The studies reviewed also varied greatly in the demographic characteristics of the participants, the professional qualifications of the educators used, the nature of the interventions, the outcomes measured, the time frames for measurement and the inclusion of medical care and other services. These variations make it difficult to compare results and make firm recommendations.^5–15Programs of education about asthma are typically directed toward the learner and conducted using either a one-on-one, large-group or small-group format. The intervention may consist of self-directed educational material, lectures (i.e., a teacher-focused format) or group interaction (i.e., a learner-focused format). Effective change in behaviour occurs when learners actively interact with the content to be learned, with the teacher and with each other.¹⁶ Small groups of fewer than 10 members allow for an ideal level of interaction. Westberg and Jason¹⁷ cite several compelling reasons for using small groups to promote learning. Learners are more likely to take ownership of their education and may be more engaged with the material. They can learn from each other in a supportive, nonjudgmental environment. They can both give and receive peer-oriented feedback. They can practise skills that can be applied later in real-life situations. Learners retain and transfer knowledge more effectively when they are able to practise what they have learned.¹⁸ For children with asthma and their families, such a model would help facilitate memory retention and a higher comfort level with future decisions related to management of asthma.We conducted a randomized controlled trial to evaluate the impact on asthma control of an intervention involving small-group, interactive education of children with asthma and their caregivers.     

Diphenyl ethers as androgen receptor antagonists for the topical suppression of sebum production

A series of diphenyl ethers was prepared and evaluated for androgen receptor antagonist activity in human androgen receptor binding and cellular functional assays. Analogs with potent in vitro activities were evaluated for topical in vivo efficacy in the Golden Syrian Hamster ear model. Several compounds showed reduction in wax esters in this validated animal model.     

Sex-specific variation in the emphasis,inducibility and timing of the post-mating immune response in Drosophila melanogaster

Ecological immunology attempts to explain variation in immune function. Much of this work makes predictions about how potential hosts should invest in overall immunity. However, this ‘overall’ perspective under-emphasizes other critical aspects, such as the specificity, inducibility and timing of an immune response. Here, we investigate these aspects by examining gene regulation across several immune system components in both male and female Drosophila melanogaster prior to and after mating. To elucidate potentially important temporal dynamics, we also assayed several genes over time. We found that males and females emphasized different components of their immune system, however overall investment was similar. Specifically, the sexes emphasized different gene paralogues within major gene families, and males tended to invest more in gram-negative defence. By contrast, the inducibility of the immune response was both transient (lasting approx. 24 hours) and equal between the sexes. Furthermore, mating tended to induce humoral gene upregulation, while cell-mediated genes were unaffected. Within the humoral system, gram-negative bacterial defence genes exhibited a greater inducibility than those associated with fungal or gram-positive bacterial defence. Our results suggest that variation in the effectiveness of the immune response between the sexes may be driven by differences in emphasis rather than overall investment.     

A parallel stranded G‐quadruplex composed of threose nucleic acid (TNA)

G‐rich sequences can adopt four‐stranded helical structures, called G‐quadruplexes, that self‐assemble around monovalent cations like sodium (Na⁺) and potassium (K⁺). Whether similar structures can be formed from xeno‐nucleic acid (XNA) polymers with a shorter backbone repeat unit is an unanswered question with significant implications on the fold space of functional XNA polymers. Here, we examine the potential for TNA (α‐l ‐threofuranosyl nucleic acid) to adopt a four‐stranded helical structure based on a planar G‐quartet motif. Using native polyacrylamide gel electrophoresis (PAGE), circular dichroism (CD) and solution‐state nuclear magnetic resonance (NMR) spectroscopy, we show that despite a backbone repeat unit that is one atom shorter than the backbone repeat unit found in DNA and RNA, TNA can self‐assemble into stable G‐quadruplex structures that are similar in thermal stability to equivalent DNA structures. However, unlike DNA, TNA does not appear to discriminate between Na⁺ and K⁺ ions, as G‐quadruplex structures form equally well in the presence of either ion. Together, these findings demonstrate that despite a shorter backbone repeat unit, TNA is capable of self‐assembling into stable G‐quadruplex structures.     

Genetic variants in telomere‐maintenance genes are associated with ovarian cancer risk and outcome

Most ovarian cancer patients present at an advanced stage with poor prognosis. Telomeres play a critical role in protecting chromosomes stability. The associations of genetic variants in telomere maintenance genes and ovarian cancer risk and outcome are unclear. We genotyped 137 single nucleotide polymorphisms (SNPs) in telomere‐maintenance genes in 417 ovarian cancer cases and 417 matched healthy controls to evaluate their associations with cancer risk, survival and therapeutic response. False discovery rate Q‐value was calculated to account for multiple testing. Eleven SNPs from two genes showed nominally significant associations with the risks of ovarian cancer. The most significant SNP was TEP1: rs2228026 with participants carrying at least one variant allele exhibiting a 3.28‐fold (95% CI: 1.72‐6.29; P < 0.001, Q = 0.028) increased ovarian cancer risk, which remained significant after multiple testing adjusting. There was also suggested evidence for the associations of SNPs with outcome, although none of the associations had a Q < 0.05. Seven SNPs from two genes showed associations with ovarian cancer survival (P < 0.05). The strongest association was found in TNKS gene (rs10093972, hazard ratio = 1.88; 95% CI: 1.20‐2.92; P = 0.006, Q = 0.076). Five SNPs from four genes showed suggestive associations with therapeutic response (P < 0.05). In a survival tree analysis, TEP1:rs10143407 was the primary factor contributing to overall survival. Unfavourable genotype analysis showed a cumulative effect of significant SNPs on ovarian cancer risk, survival and therapeutic response. Genetic variations in telomere‐maintenance genes may be associated with ovarian cancer risk and outcome.     

Reconstructed historical distribution and phylogeography unravels non-steppic origin of <Emphasis Type="Italic">Caucasotachea vindobonensis</Emphasis> (Gastropoda: Helicidae)

Existing data on the phylogeography of European taxa of steppic provenance suggests that species were widely distributed during glacial periods but underwent range contraction and fragmentation during interglacials into “warm-stage refugia.” Among the steppe-related invertebrates that have been examined, the majority has been insects, but data on the phylogeography of snails is wholly missing. To begin to fill this gap, phylogeographic and niche modeling studies on the presumed steppic snail Caucasotachea vindobonensis were conducted. Surprisingly, reconstruction of ancestral areas suggests that extant C. vindobonensis probably originated in the Balkans and survived there during the Late Pleistocene glaciations, with a more recent colonization of the Carpatho-Pannonian and the Ponto-Caspian regions. In the Holocene, C. vindobonensis colonized between the Sudetes and the Carpathians to the north, where its recent and current distribution may have been facilitated by anthropogenic translocations. Together, these data suggest a possible non-steppic origin of C. vindobonensis. Further investigation may reveal the extent to which the steppic snail assemblages consist partly of Holocene newcomers.     

Variable gene family usage of protective and non‐protective anti‐Vibrio cholerae O1 LPS antibody heavy chains

Vibrio cholerae causes cholera, an enteric disease of humans that is a worldwide problem. The O1 serogroup of Vibrio cholerae contains two predominant serotypes (Inaba and Ogawa) of LPS, a proven protective antigen for humans and experimental animals. We generated B‐cell hybridomas from mice immunized with either: (i) two doses of purified Inaba LPS; (ii) two doses of an Inaba hexasaccharide conjugate (terminal six perosamine bound to a protein carrier), (iii) four doses of purified Inaba LPS; or (iv) a low dose of purified Inaba LPS followed by a booster with the Inaba conjugate. We showed previously that the first and third immunization protocols induce vibriocidal antibodies, as does the fourth; the second protocol induces antibodies that bind Inaba and Ogawa LPS but are not vibriocidal. Anti‐LPS mAbs derived from hybridomas resulting from each immunization protocol were characterized for binding to Inaba and Ogawa LPS, their vibriocidal or protective capacity, and the variable heavy chain family they expressed. LPS immunogens selected different LPS‐specific B cells expressing six different Vh chain families. Protective and non‐protective mAbs could express variable regions from the same family. One mAb was specific for Inaba LPS, the other mAbs were cross‐reactive with both LPS serotypes. Sequence comparison suggests that the pairing of a specific light chain, somatic mutation, or the specific VDJ recombination can modulate the protective capacity of mAbs that express a common variable heavy chain family member.     

Insight into ligand diversity and novel biological roles for family 32 carbohydrate-binding modules

Family 32 carbohydrate-binding modules (CBM32s) are found in a diverse group of microorganisms, including archea, eubacteria, and fungi. Significantly, many members of this family belong to plant and animal pathogens where they are likely to play a key role in enzyme toxin targeting and function. Indeed, ligand targets have been shown to range from insoluble plant cell wall polysaccharides to complex eukaryotic glycans. Besides a potential direct involvement in microbial pathogenesis, CBM32s also represent an important family for the study of CBM evolution due to the wide variety of complex protein architectures that they are associated with. This complexity ranges from independent lectin-like proteins through to large multimodular enzyme toxins where they can be present in multiple copies (multimodularity). Presented here is a rigorous analysis of the evolutionary relationships between available polypeptide sequences for family 32 CBMs within the carbohydrate active enzyme database. This approach is especially helpful for determining the roles of CBM32s that are present in multiple copies within an enzyme as each module tends to cluster into groups that are associated with distinct enzyme classes. For enzymes that contain multiple copies of CBM32s, however, there are differential clustering patterns as modules can either cluster together or in very distant sections of the tree. These data suggest that enzymes containing multiple copies possess complex mechanisms of ligand recognition. By applying this well-developed approach to the specific analysis of CBM relatedness, we have generated here a new platform for the prediction of CBM binding specificity and highlight significant new targets for biochemical and structural characterization.