In Vitro Effects of Budesonide on Eosinophil-Basophil Lineage Commitment

IL-5 is the primary cytokine that stimulates the production and survival of eosinophils and basophils from progenitor cells. The inhaled glucocorticoid, budesonide, has been shown to exert a therapeutic effect via suppression of eosinophil/basophil progenitors in vivo. Since various steroids have exhibited the ability to enhance eosinophil/basophil progenitor differentiation, we examined the effects of budesonide in vitro. Bone marrow and cord blood samples were obtained and cultured in the presence of IL-5 alone or IL-5 plus budesonide. Eosinophil/basophil colony-forming units were enumerated from cultured nonadherent mononuclear cells and from purified CD34+ cells. CD34+ cells with and without budesonide were also examined for up-regulation of ERK1/2, MAPK and GATA-1 using real time-PCR. Results: i) up-regulation of eosinophil/basophil colony-forming units is due to the direct effects of budesonide on IL-5-stimulated progenitors; ii) GATA-1 is likely involved in the early amplification of eosinophil/basophil progenitor commitment leading to increased differentiation. A potential transcriptional pathway has been identified which may mediate the effects of budesonide on eosinophil/basophil lineage commitment

Modelling human choices: MADeM and decision‑making

Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

Alcohol fixation of induced sputum samples for applications in rural communities

BACKGROUND: Sputum induction is a tool recommended for the assessment of airway inflammation and disease management. Currently, its use is limited because samples need to be processed within 3 h of induction (ie, while cells are viable); therefore, this procedure is unavailable to most clinicians

An Assessment of the Validity of an Audio-Video Method of Food Journaling for Dietary Quantity and Quality

Objective. To validate an audio-video (AV) method of food journaling, in a free-living scenario, compared to direct, weighed food assessment. Design and Setting. Data were collected in a cafeteria. Meals, selected by participants (n=30), were documented using the AV method: participants video-recorded their tray while audio-recording a description of their selected meal, after which the research team digitally weighed each food item and created an itemized diary record of the food. Variables Measured. Data from the AV method and from the weighed food diaries were transcribed and entered into a nutrition software analysis program (Nutribase Pro 10.0). Nutrient outputs were compared between the two methods including kilocalories, macronutrients, and selected micronutrients. Analyses. Using mean scores for each variable, Wilcoxon signed-rank test and Spearman’s correlation coefficients were conducted. Interclass correlation coefficient (ICC) was calculated for absolute agreement between the two methods to assess interrater reliability. Results. With the exception of Vitamin E and total weight, nutrient values were highly correlated between methods and were statistically significant given alpha = 0.05, power = 0.95, and effect size of 0.70. Conclusions. The AV method may be a meaningful alternative to diary recording in a free-living setting

Safety Culture: A Retrospective Analysis of Occupational Health and Safety Mining Reports

Background: In the mining industry, various methods of accident analysis have utilized official accident investigations to try and establish broader causation mechanisms. An emerging area of interest is identifying the extent to which cultural influences, such as safety culture, are acting as drivers in the reoccurrence of accidents. Thus, the overall objective of this study was to analyze occupational health and safety (OHS) reports in mining to investigate if/how safety culture has historically been framed in the mining industry, as it relates to accident causation. Methods: Using a computer-assisted qualitative data analysis software, 34 definitions of safety culture were analyzed to highlight key terms. Based on word count and contextual relevance, 26 key terms were captured. Ten OHS reports were then analyzed via an inductive thematic analysis, using the key terms. This analysis provided a concept map representing the 50-year data set and facilitated the use of text framing to highlight safety culture in the selected OHS mining reports. Results: Overall, 954 references and six themes, safety culture, attitude, competence, belief, patterns, and norms, were identified in the data set. Of the 26 key terms originally identified, 24 of them were captured within the text. The results made evident two distinct frames in which to interpret the data: the role of the individual and the role of the organization, in safety culture. Conclusion: Unless efforts are made to understand and alter cultural drivers and share these findings within and across industries, the same accidents are likely to continue to occur

Increased Levels of Airway Neutrophils Reduces the Inhibitory Effects of Inhaled Glucocorticosteroids on Allergen-Induced Airway Eosinophils

BACKGROUND: Treatment with inhaled glucocorticosteroids attenuates allergen-induced airway inflammation but is less effective in people with asthma who have noneosinophilic airway inflammation