Frequency of Euroglyphus maynei sensitization in respiratory allergies: a real-life study with bioinformatic analysis and geographical exploration of allergen prevalence.

BACKGROUND: Dermatophagoides pteronyssinus and Dermatophagoides farinae belong to the family Pyroglyphidae (subfamily: "Dermatophagoidinae") and have the respective allergenic proteins of Der p1, Der p2, and Der p23 and Der f1 and Der f2. Euroglyphus maynei, belongs to the family Pyroglyphidae (subfamily: "Pyroglyphinae") and its main allergenic protein is Eur m1, a source of sensitization. Sensitization to D. pteronyssinus and D. farinae is assessed through skin tests, while sensitization to E. maynei is assessed less frequently. OBJECTIVE: This experimental work aims to analyze the prevalence of sensitization to E. maynei in patients with respiratory allergies treated at M. Albanesi Allergy and Immunology Unit in Bari, Italy, and the sequence homology of major allergenic proteins of E. maynei with D. farinae and D. pteronyssinus was analyzed. METHODS: In this real-life study, 65 patients were enrolled. In particular, patients with respiratory allergy were subjected to skin prick tests for common respiratory allergens, including Euroglyphus maynei. The sequence homology analysis was performed between the major allergenic proteins of E. maynei and those of D. pteronyssinus and D. farinae. RESULTS: Sensitization to E. maynei accounts for 41.5% of patients. All patients with E. maynei sensitization had concomitant sensitization to D. farinae and D. pteronyssinus. The analysis of sequence homology of Der p1 and Der f1 proteins with the sequence of Eur m1 protein demonstrated an identity of 84.4% and 86%, respectively. CONCLUSIONS: Nearly 50% of house dust mites-sensitized patients have a concomitant sensitization to E. maynei. The cross-sensitization could be due to Der f1, Der p1, and Eur m1 similarity.

Hypoxia upregulates neutrophil degranulation and potential for tissue injury.

BACKGROUND: The inflamed bronchial mucosal surface is a profoundly hypoxic environment. Neutrophilic airway inflammation and neutrophil-derived proteases have been linked to disease progression in conditions such as COPD and cystic fibrosis, but the effects of hypoxia on potentially harmful neutrophil functional responses such as degranulation are unknown. METHODS AND RESULTS: Following exposure to hypoxia (0.8% oxygen, 3 kPa for 4 h), neutrophils stimulated with inflammatory agonists (granulocyte-macrophage colony stimulating factor or platelet-activating factor and formylated peptide) displayed a markedly augmented (twofold to sixfold) release of azurophilic (neutrophil elastase, myeloperoxidase), specific (lactoferrin) and gelatinase (matrix metalloproteinase-9) granule contents. Neutrophil supernatants derived under hypoxic but not normoxic conditions induced extensive airway epithelial cell detachment and death, which was prevented by coincubation with the antiprotease α-1 antitrypsin; both normoxic and hypoxic supernatants impaired ciliary function. Surprisingly, the hypoxic upregulation of neutrophil degranulation was not dependent on hypoxia-inducible factor (HIF), nor was it fully reversed by inhibition of phospholipase C signalling. Hypoxia augmented the resting and cytokine-stimulated phosphorylation of AKT, and inhibition of phosphoinositide 3-kinase (PI3K)γ (but not other PI3K isoforms) prevented the hypoxic upregulation of neutrophil elastase release. CONCLUSION: Hypoxia augments neutrophil degranulation and confers enhanced potential for damage to respiratory airway epithelial cells in a HIF-independent but PI3Kγ-dependent fashion.

The influence of gender on heart rhythm disease.

This paper deals with cardiac arrhythmias, focusing on differences between genders. We sought to examine the potential effect of gonadal hormones on heart rhythm disorders, and sex-related differences in incidence and clinical course of arrhythmias--differences that may require specific approaches to detection and management of heart rhythm disease.

Expression of microRNAs in diffuse large B cell lymphoma is associated with immunophenotype, survival and transformation from follicular lymphoma.

MicroRNAs are naturally occurring small RNA species that regulate gene expression and are frequently abnormally expressed in cancers. However, the role of microRNAs in lymphoma is poorly understood. Therefore, we undertook a comprehensive study of microRNA expression in two of the most common lymphomas: diffuse large B-cell lymphoma (DLBCL) (n = 80) and follicular lymphoma (FCL) (n = 18) using microarrays containing probes for 464 human microRNAs. Unsupervised cluster analysis revealed distinct expression patterns between these two lymphomas and specific microRNA signatures (including members of the miR-17-92 cluster) were derived that correctly predicted lymphoma type in >95% of cases. Furthermore, we identified microRNAs in de novo DLBCL (n = 64) associated with germinal centre-like and non-germinal centre-like immunophenotypes, international prognostic index status and event-free survival in CHOP and rituximab (R)-CHOP treated patients. Despite the indolent nature of FCL a significant proportion of cases undergo high-grade transformation to more aggressive DLBCL. In order to see if transformation is associated with changes in microRNA expression we compared transformed DLBCL cases (n = 16) with de novo DLBCL, as well as FCL cases that underwent subsequent transformation (n = 7) with FCL cases that had not transformed at a median follow-up of 60 months (n = 11). Differential expression of 12 microRNAs correctly predicted >85% of transformed versus de novo DLBCL cases; six microRNAs (miR-223, 217, 222, 221 and let-7i and 7b) were found which could similarly predict or transformation in FCL (P < 0.05). These data suggest that microRNAs have potential as diagnostic and prognostic markers in these lymphomas and may be used to identify FCL patients at risk of high-grade transformation.

Ventilation strategies in burn intensive care: A retrospective observational study.

Consensus regarding optimal burns intensive care (BICU) patient management is lacking. This study aimed to assess whether ventilation strategies, cardiovascular support and sedation in BICU patients have changed over time, and whether this affects outcome. A retrospective observational study comparing two 12-patient BICU cohorts (2005/06 and 2010/11) was undertaken. Demographic and admission characteristics, ventilation parameters, sedation, fluid resuscitation, cardiovascular support and outcome (length of stay, mortality) data were collected from patient notes. Data was analysed using T-tests, Fisher's exact and Mann-Whitney U tests. In our study cohort groups were equivalent in demographic and admission parameters. There were equal ventilator-free days in the two cohorts 10 ± 12.7 vs. 13.3 ± 12.2 ventilator free days; P = 0.447). The 2005/06 cohort were mechanically ventilated more often than in 2010/11 cohort (568 ventilator days/1000 patient BICU days vs. 206 ventilator days/1000 patient BICU days; P = 0.001). The 2005/06 cohort were ventilated less commonly in tracheostomy group/endotracheal tube spontaneous (17.8% vs. 26%; P = 0.001) and volume-controlled modes (34.4% vs. 40.8%; P = 0.001). Patients in 2010/11 cohort were more heavily sedated (P = 0.001) with more long-acting sedative drug use (P = 0.001) than the 2005/06 cohort, fluid administration was equivalent. Patient outcome did not vary. Inhalational injury patients were ventilated in volume-controlled (44.5% vs. 28.1%; P = 0.001) and pressure-controlled modes (18.2% vs. 9.5%; P = 0.001) more frequently than those without. Outcome did not vary. This study showed there has been shift away from mechanical ventilation, with increased use of tracheostomy/tracheal tube airway spontaneous ventilation. Inhalation injury patients require more ventilatory support though patient outcomes do not differ. Prospective trials are required to establish which strategies confer benefit.

MicroRNA expression distinguishes between germinal center B cell-like and activated B cell-like subtypes of diffuse large B cell lymphoma.

Diffuse large B cell lymphoma (DLBCL) is an aggressive malignancy that accounts for nearly 40% of all lymphoid tumors. This heterogeneous disease can be divided into germinal center B cell-like (GCB) and activated B cell-like (ABC) subtypes by gene expression and immunohistochemical profiling. Using microarray analysis on prototypic cell lines, we identified microRNAs (miR-155, miR-21 and miR-221) that were more highly expressed in ABC-type than GCB-type cell lines. These microRNAs were over-expressed in de novo DLBCL (n = 35), transformed DLBCL (n = 14) and follicular center lymphoma cases (n = 27) compared to normal B cells. Consistent with the cell line model, expression levels were higher in DLBCL cases with an ABC-type immunophenotype than those that were GCB-type (p < 0.05). Moreover, using multivariate analysis we found that expression of miR-21 was an independent prognostic indicator in de novo DLBCL (p < 0.05). Interestingly, expression levels of both miR-155 and miR-21 were also higher in nonmalignant ABC than in GCB cells. As we also demonstrate that expression of microRNAs can be measured reliably from routine paraffin-embedded biopsies of more than 8-years-old (p < 0.001), we suggest that microRNAs could be clinically useful molecular markers for DLBCL as well as other cancers.