Background: Some oxysterols are identified in atheromatous plaques and in plasma of atherosclerotic patients. We asked whether they might modulate cytokine secretion on human monocytic cells. In healthy and atherosclerotic subjects, we also investigated the relationships between circulating levels of C‐reactive protein (CRP), conventional markers of hyperlipidemia, some oxysterols (7β‐hydroxycholesterol, 7‐ketocholesterol, and 25‐hydroxycholesterol), and various cytokines. Methods: Different flow cytometric bead‐based assays were used to quantify some cytokines (IL‐1β, IL‐2, IL‐4, IL‐5, IL‐6, IL‐7, IL‐8, IL‐10, IL‐12, IL‐13, IL‐17, G‐CSF, GM‐CSF, IFN‐γ, MCP‐1, MIP‐1β, or TNF‐α) in the culture media of oxysterol‐treated U937 and THP‐1 cells, and in the sera of healthy and atherosclerotic subjects. CRP and markers of hyperlipidemia were determined with routine analytical methods. Oxysterols were quantified by gas chromatography/mass spectrometry. Flow cytometric and biochemical methods were used to measure IL‐8 mRNA levels, intracellular IL‐8 content, and protein phosphorylation in the mitogenic extracellular kinase/extracellular signal‐regulated kinase1/2 (MEK/ERK1/2) signaling pathway. Results: All oxysterols investigated are potent in vitro inducers of MCP‐1, MIP‐1β, TNF‐α, and/or IL‐8 secretion, the latter involving the MEK/ERK1/2 cell signaling pathway. In healthy and atherosclerotic subjects, no relationships were found between cytokines (IL‐8, IL‐1β, IL‐6, IL‐10, TNF‐α, IL‐12, and MCP‐1), CRP, conventional markers of hyperlipidemia, and oxysterols. However, in patients with arterial disorders of the lower limbs, small but statistically significant differences in the circulating levels of CRP, TNF‐α, and IL‐10 were observed comparatively to healthy subjects and according to the atherosclerotic stage considered. Conclusions: Flow cytometric bead‐based assays are well adapted to measure variations of cytokine secretion in the culture media of oxysterol‐treated cells and in the sera of healthy and atherosclerotic subjects. They underline the in vitro proinflammatory properties of oxysterols and may permit to distinguish healthy and atherosclerotic subjects, as well as various atherosclerotic stages. © 2006 International Society for Analytical Cytology

These findings suggest that the deficit in functional brain organization underlying dyslexia can be reversed after sufficiently intense intervention lasting as little as 2 months, and are consistent with current proposals that reading difficulties in many children represent a variation of normal development that can be altered by intensive intervention.

The authors conducted the largest study to date of survival in cystic fibrosis. The study cohort consisted of all patients with cystic fibrosis seen at Cystic Fibrosis Foundation-accredited care centers in the United States between 1988 and 1992 (n = 21,047), or approximately 85% of all US patients diagnosed with cystic fibrosis. Cox proportional hazards regression analysis was used to compare the age-specific mortality rates of males and females and to identify risk factors serving as potential explanatory variables for the gender-related difference in survival. Among the subjects 1-20 years of age, females were 60% more likely to die than males (relative risk = 1.6, 95% confidence interval 1.4-1.8). Outside this age range, male and female survival rates were not significantly different. The median survival for females was 25.3 years and for males was 28.4 years. Nutritional status, pulmonary function, and airway microbiology at a given age were strong predictors of mortality at subsequent ages. Nonetheless, differences between the genders in these parameters, as well as pancreatic insufficiency, age at diagnosis, mode of presentation, and race, could not account for the poorer survival among females. Even after adjustment for all these potential risk factors, females in the age range 1-20 years remained at greater risk for death (relative risk = 1.6, 95% confidence interval 1.2-2.1). The authors concluded that in 1- to 20-year-old individuals with cystic fibrosis, survival in females was poorer than in males. This "gender gap" was not explained by a wide variety of potential risk factors.

Severe chronic neutropenia (SCN) is defined as an absolute neutrophil (ANC) of less than

Depression in late adolescence is associated with later obesity, but only among girls. Future studies should address reasons for these age and sex differences and the potential for intervention to reduce the risk for adult obesity in depressed older adolescent girls.