Responsiveness and construct validity of a symptom scale for acute otitis media

BACKGROUND:: Because resolution of symptoms is a primary goal of antimicrobial therapy in children with acute otitis media (AOM), measurement of symptoms in studies of antimicrobial effectiveness in such children is important. We have developed a scale for measuring symptoms of AOM in young children (AOM-SOS), and we present data on its construct validity and responsiveness. METHODS:: We followed children 3 months to 3 years of age with AOM, who were receiving antimicrobial treatment, using the AOM-SOS scale. The scale was administered at the enrollment visit, as a twice-a-day diary measure, and at the follow-up visit (days 5-7). To evaluate construct validity, we examined the correlation, at entry, between AOM-SOS scores and scores on other measures of pain and functional status. To evaluate the scale's responsiveness, we examined the change in scale scores from entry to follow-up. We also examined the levels of agreement between the scale scores and overall assessments of the children by parents. RESULTS:: We enrolled 70 children (mean age 12.5 months) of whom 57 returned for follow-up. The magnitude of the correlations between the AOM-SOS scale scores and other measures of pain and functional status ranged from 0.56 to 0.84. The responsiveness of the AOM-SOS, as measured by the standardized response mean was 1.20. CONCLUSIONS:: These data support the validity and responsiveness of the AOM-SOS; the scale seems to measure effectively both pain and overall functional status in young children with AOM. Changes in score over the first few days of illness were substantial and generally matched the assessments both of parents and of clinicians. The AOM-SOS promises to be useful as an outcome measure in clinical studies of AOM

MultiMetEval: comparative and multi-objective analysis of genome-scale metabolic models

Comparative metabolic modelling is emerging as a novel field, supported by the development of reliable and standardized approaches for constructing genome-scale metabolic models in high throughput. New software solutions are needed to allow efficient comparative analysis of multiple models in the context of multiple cellular objectives. Here, we present the user-friendly software framework Multi-Metabolic Evaluator (MultiMetEval), built upon SurreyFBA, which allows the user to compose collections of metabolic models that together can be subjected to flux balance analysis. Additionally, MultiMetEval implements functionalities for multi-objective analysis by calculating the Pareto front between two cellular objectives. Using a previously generated dataset of 38 actinobacterial genome-scale metabolic models, we show how these approaches can lead to exciting novel insights. Firstly, after incorporating several pathways for the biosynthesis of natural products into each of these models, comparative flux balance analysis predicted that species like Streptomyces that harbour the highest diversity of secondary metabolite biosynthetic gene clusters in their genomes do not necessarily have the metabolic network topology most suitable for compound overproduction. Secondly, multi-objective analysis of biomass production and natural product biosynthesis in these actinobacteria shows that the well-studied occurrence of discrete metabolic switches during the change of cellular objectives is inherent to their metabolic network architecture. Comparative and multi-objective modelling can lead to insights that could not be obtained by normal flux balance analyses. MultiMetEval provides a powerful platform that makes these analyses straightforward for biologists. Sources and binaries of MultiMetEval are freely available from https://github.com/PiotrZakrzewski/MetEv​al/downloads

Mechanical strain-mediated reduction in RANKL expression is associated with RUNX2 and BRD2

Mechanical loading-related strains trigger bone formation by osteoblasts while suppressing resorption by osteoclasts, uncoupling the processes of formation and resorption. Osteocytes may orchestrate this process in part by secreting sclerostin (SOST), which inhibits osteoblasts, and expressing receptor activator of nuclear factor-κB ligand (RANKL/TNFSF11) which recruits osteoclasts. Both SOST and RANKL are targets of the master osteoblastic transcription factor RUNX2. Subjecting human osteoblastic Saos-2 cells to strain by four point bending down-regulates their expression of SOST and RANKL without altering RUNX2 expression. RUNX2 knockdown increases basal SOST expression, but does not alter SOST down-regulation following strain. Conversely, RUNX2 knockdown does not alter basal RANKL expression, but prevents its down-regulation by strain. Chromatin immunoprecipitation revealed RUNX2 occupies a region of the RANKL promoter containing a consensus RUNX2 binding site and its occupancy of this site decreases following strain. The expression of epigenetic acetyl and methyl writers and readers was quantified by RT-qPCR to investigate potential epigenetic bases for this change. Strain and RUNX2 knockdown both down-regulate expression of the bromodomain acetyl reader BRD2. BRD2 and RUNX2 co-immunoprecipitate, suggesting interaction within regulatory complexes, and BRD2 was confirmed to interact with the RUNX2 promoter. BRD2 also occupies the RANKL promoter and its occupancy was reduced following exposure to strain. Thus, RUNX2 may contribute to bone remodeling by suppressing basal SOST expression, while facilitating the acute strain-induced down-regulation of RANKL through a mechanosensitive epigenetic loop involving BRD2

Teaching: Natural or Cultural?

In this chapter I argue that teaching, as we now understand the term, is historically and cross-culturally very rare. It appears to be unnecessary to transmit culture or to socialize children. Children are, on the other hand, primed by evolution to be avid observers, imitators, players and helpers—roles that reveal the profoundly autonomous and self-directed nature of culture acquisition (Lancy in press a). And yet, teaching is ubiquitous throughout the modern world—at least among the middle to upper class segment of the population. This ubiquity has led numerous scholars to argue for the universality and uniqueness of teaching as a characteristically human behavior. The theme of this chapter is that this proposition is unsustainable. Teaching is largely a result of recent cultural changes and the emergence of modern economies, not evolution

Pneumococcal resistance and serotype 19a in Pittsburgh-area children with acute otitis media before and after introduction of 7-valent Pneumococcal polysaccharide vaccine

Methods: Before and after introduction of pneumococcal conjugate vaccine (PCV7), the authors obtained nasopharyngeal (NP) specimens from 3 groups of children aged 6 to 23 months with acute otitis media (AOM): group 1 (pre-PCV7), group 2 (early post-PCV7), and group 3 (late post-PCV7). Results: Of the Streptococcus pneumoniae isolates, the proportion that were vaccine serotypes (VTs) declined progressively (60.4% vs 48.6% vs 5.2% in groups 1, 2, and 3, respectively; P 0.1 μg/mL; 26.7% vs 37.8% vs. 38.5%; P =.12); the proportion of isolates that were serotype 19A (4.0% vs 0% vs 25.9%; P <.001); and the proportion of 19A isolates that were penicillin-nonsusceptible (0% in group 1, 68.6% in group 3; P =.004). Conclusion: Shifts in pneumococcal serotype distribution and increases in penicillin nonsusceptibility among pneumococcal isolates from children with AOM underscore the need for continuing bacteriological surveillance for future vaccine development. © The Author(s) 2011

Avaliação do impacto da adenotonsilectomia sobre a qualidade de vida em crianças com hipertrofia das tonsilas palatinas e faríngeas Assessing the impact adenotonsilectomy has on the lives of children with hypertrophy of palatine and pharyngeal tonsils

A hipertrofia das tonsilas palatinas e faríngeas é extremamente comum na infância, sendo um dos problemas mais freqüentes do consultório do otorrinolaringologista, podendo prejudicar a qualidade de vida das crianças. OBJETIVO: Avaliar o impacto da adenotonsilectomia sobre a qualidade de vida das crianças que apresentam aumento do volume das tonsilas. MATERIAL E MÉTODOS: Estudo de coorte contemporâneo longitudinal. Foi aplicado a setenta e cinco pais ou responsáveis por crianças submetidas a adenotonsilectomia um questionário específico para a avaliação da qualidade de vida, OSD-6, antes do procedimento cirúrgico e trinta dias após. RESULTADOS: A adenotonsilectomia proporcionou significativa diminuição na pontuação obtida no questionário. DISCUSSÃO: Ronco e a obstrução nasal foram os sintomas responsáveis pelas maiores pontuações nos questionários. Existe grande preocupação dos pais com o ronco das crianças e pobre correlação estatística entre o grau de obstrução e a pior qualidade de vida. CONCLUSÃO: A adenotonsilectomia apresenta impacto relevante na qualidade de vida das crianças com hipertrofia das tonsilas.<br>The hypertrophy of the palatine and pharyngeal tonsils is extremely common in children, being one of the most frequent causes of visits to otolaryngologists and such problem can impair the child's quality of life. AIM: to evaluate the impact of adenotonsillectomy on the lives of children with hypertrophied tonsils. MATERIALS AND METHODS: Contemporary longitudinal cohort study. A specific questionnaire used to evaluate the quality of life - OSD-6, was given to seventy five parents or guardians of children previously submitted to adenotonsillectomy, before the surgery and thirty days afterwards. RESULTS: The adenotonsillectomy provided a significant reduction in the questionnaire score. DISCUSSION: Snoring and nasal obstruction were the symptoms with the highest scores. There is a great concern from the parents with the snoring of the children and a poor statistic correlation between the degree of obstruction degree and a worse quality of life. CONCLUSION: Adenotonsillectomy causes a relevant impact in the quality of life of children with tonsil hypertrophy