Serum amyloid A activates the NLRP3 inflammasome and promotes Th17 allergic asthma in mice.

IL-1ß is a cytokine critical to several inflammatory diseases in which pathogenic Th17 responses are implicated. Activation of the NLRP3 inflammasome by microbial and environmental stimuli can enable the caspase-1-dependent processing and secretion of IL-1ß. The acute-phase protein serum amyloid A (SAA) is highly induced during inflammatory responses, wherein it participates in systemic modulation of innate and adaptive immune responses. Elevated levels of IL-1ß, SAA, and IL-17 are present in subjects with severe allergic asthma, yet the mechanistic relationship among these mediators has yet to be identified. In this study, we demonstrate that Saa3 is expressed in the lungs of mice exposed to several mixed Th2/Th17-polarizing allergic sensitization regimens. SAA instillation into the lungs elicits robust TLR2-, MyD88-, and IL-1-dependent pulmonary neutrophilic inflammation. Furthermore, SAA drives production of IL-1α, IL-1ß, IL-6, IL-23, and PGE(2), causes dendritic cell (DC) maturation, and requires TLR2, MyD88, and the NLRP3 inflammasome for secretion of IL-1ß by DCs and macrophages. CD4(+) T cells polyclonally stimulated in the presence of conditioned media from SAA-exposed DCs produced IL-17, and the capacity of polyclonally stimulated splenocytes to secrete IL-17 is dependent upon IL-1, TLR2, and the NLRP3 inflammasome. Additionally, in a model of allergic airway inflammation, administration of SAA to the lungs functions as an adjuvant to sensitize mice to inhaled OVA, resulting in leukocyte influx after Ag challenge and a predominance of IL-17 production from restimulated splenocytes that is dependent upon IL-1R signaling.

Monozygotic twins discordant for congenital adrenal hyperplasia due to mosaicism.

INTRODUCTION: Genotype-phenotype discordance occurs occasionally in congenital adrenal hyperplasia (CAH). Its causes are largely unknown. We describe a case of monochorionic, diamniotic twins with discordant clinical presentations of CAH, and show evidence for this being due to mosaicism resulting from a postzygotic full gene deletion of CYP21A2 prior to twinning. CASE DESCRIPTION: A 7-day-old 36-week gestation female infant (Twin A) presented to the emergency department with elevated 17-hydroxyprogesterone (17-OHP). Her identical twin (Twin B) had normal 17-OHP on newborn screening. Both twins showed signs of virilization, more pronounced in Twin B. Molecular genetic testing of both twins and their parents showed a WT paternally-inherited CYP21A2 and a maternally-inherited copy containing the c.293-13C>G mutation. Both twins were also found to have a 5'-CYP21A1P/CYP21A2-3' hybrid (product of the common 30-kb deletion), derived from the deletion of the paternally-inherited CYP21A2. Neither mother nor father carried the deletion. CONCLUSIONS: The genetic findings are consistent with mosaicism for two CYP21A2 cell lines in both twins. The first cell line is expected, based on parental results, while the second line is due to a postzygotic full gene deletion of the paternally-inherited WT CYP21A2. The resultant genotype, compound heterozygosity for c.293-13C>G and a CYP21A2 full gene deletion, is consistent with a salt-wasting CAH phenotype. Differential distribution of the second cell line between the twins is most likely the cause for their discrepant phenotypes. We believe this is the first report of somatic CYP21A2 mosaicism, and represents a novel cause for discrepant CAH phenotypes in monozygotic twins.

Impact of Body Mass Index on Postconcussion Symptoms in Teenagers Aged 13 to 18 Years.

CONTEXT: Adolescent obesity and sports-related concussion are rising in prevalence, yet there is minimal research exploring the relationship between these two conditions. OBJECTIVE: To assess the impact of body mass index (BMI) percentile on duration of recovery and reported symptoms after sports-related concussion in adolescents. DESIGN: Retrospective chart review at a regional concussion program located at an academic medical center. Medical records of all patients aged 13 to 18 years treated from March 2006 through January 2012 were reviewed. Two hundred fifty-two patients met the inclusion criteria of sports-related concussion and having BMI data. MAIN OUTCOME MEASURES: Outcome variables included reported emotional symptoms, sleep-related symptoms, physical symptoms (headache), and time to recovery after a concussion. Explanatory variables in this analysis were BMI percentile and sex. RESULTS: More male patients were obese and overweight than were females (42% vs 27%, p = 0.02). There was no statistically significant difference in recovery time between obese and overweight patients and others. Obese and overweight patients were more likely than healthy-weight patients to report symptoms of irritability (p = 0.05) and impulsivity (p = 0.01), and less likely to report headache (p = 0.03). CONCLUSION: After concussion, irritability and impulsivity may be more likely than headaches in overweight and obese patients. There was no difference in recovery time between obese and healthy-weight teens. These findings may have importance in the evaluation, treatment, and anticipatory guidance of patients with concussions.

The fruits of lifelong learning. Environments rich in continuing education ripen staff development, morale, and retention.

Implementation of a mandatory internal continuing education program changed acute care for the better at Wausau Hospital, a 321-bed not-for-profit facility in central Wisconsin.