High motility group box 1 (HMGB1) protein and its receptor for advanced glycation end products (RAGE) expression in chronic rhinosinusitis without nasal polyps

Introduction. Chronic rhinosinusitis (CRS) affects 14% of the world population. The high motility group box 1 (HMGB1) protein triggers inflammation, cell proliferation and cell survival through its receptor for advanced glycation end products (RAGE) upon release from stressed or necrotic cells. The aim of the study was to analyze the expression and function of HMGB1 and RAGE in CRS, providing more information about HMGB1 signaling pathway in CRS, to determine its potential clinical significance. Material and methods. Thirty-seven patients with CRS and 26 normal controls (NC) were enrolled in this study. Classification of disease severity using the SNOT-20 questionnaire, nasal endoscopy, CT scan, assessment of allergy status, microbiological and cytological analysis was performed in patients. Fresh sinus mucosa samples were obtained and analyzed by immunohistochemistry for HMGB1 and RAGE expression in epithelial cells. ELISA assay was performed to evaluate the concentration of HMGB1 in the patients’ sera. Results. No differences were found in HMGB1 immunoexpression between CRS patients and NC, however there was a highly significant difference in RAGE immunoexpression between both groups. There was a correlation between RAGE expression and number of tissue-infiltrating lymphocytes. Further, RAGE expression positively correlated with disease severity and a positive history for allergies. Conclusions. Interaction of HMGB1 and RAGE might be relevant to CRS pathomechanisms leading to sinus mucosa hyperproliferation. CRS pathogenesis might be especially related to the RAGE overexpression correlated with disease severity and allergy.

Changes over time in sex assignment for disorders of sex development

BACKGROUND AND OBJECTIVE: It is unclear whether the proportion of infants with a disorder of sex development who are raised as male or female has changed over time. The temporal trends in sex assignment of affected cases entered in the International Disorder of Sex Development (I-DSD) Registry were studied. METHODS: Cases of disorders of sex development reported as partial androgen insensitivity syndrome (PAIS; n = 118), disorder of gonadal development (DGD; n = 232), and disorder of androgen synthesis (DAS; n = 104) were divided into those who were born before 1990, 1990-1999, and after 1999. External appearance of the genitalia was described by the external masculinization score. RESULTS: The median (5th-95th percentile) external masculinization scores of those infants with PAIS, DGD, and DAS who were raised as boys were 6 (2-9), 6 (3-9), and 6 (1-12), respectively, and were significantly higher than in those raised as girls (2 [0-6], 2 [0-7], and 0 [0-5], respectively); this difference was maintained in the 3 temporal birth cohorts (P < .01). Of the 118 cases in the pre-1990 cohort, 41 (35%) were raised as boys; of the 148 cases in the 1990-1999 cohort, 60 (41%) were raised as boys; and of the 188 cases in the post-1999 cohort, 128 (68%) were raised as boys. CONCLUSIONS: Although there is an association between the external appearance of the genitalia and the choice of sex assignment, there are clear temporal trends in this practice pointing toward an increased likelihood of affected infants being raised as boys. The impact of this change in practice on long-term health outcomes requires additional focus