The osmotic effectiveness of a large molecular weight glucose polymer fraction (Icodextrin) as a novel "colloid" osmotic agent in peritoneal dialysis was established, but the long-term safety remained undetermined. A randomized, controlled multicenter investigation of Icodextrin in ambulatory peritoneal dialysis (MIDAS) was undertaken to evaluate the long-term safety and efficacy by comparing daily overnight (8 to 12 hr dwell) use of isosmolar Icodextrin (282 mOsm/kg) with conventional 1.36% (346 mOsm/kg) and 3.86% (484 mOsm/kg) glucose exchanges over six months. Two hundred and nine patients were randomized from 11 centers, with 106 allocated to receive Icodextrin (D) and 103 to remain on glucose (control group; C); 138 patients completed the six month study (71 C, 67 D). All patients were divided into weak (1.36%) or strong (3.86%) subgroups based on their use of glucose solutions overnight during the pretreatment baseline period. The mean (+/- SEM) overnight ultrafiltration (UF) with D was 3.5 times greater than 1.36% glucose at eight hours [527 +/- 36 vs. 150 +/- 47 ml; 95% confidence interval (CI) for the difference +257 to +497 ml; P < 0.0001] and 5.5 times greater at 12 hours (561 +/- 44 vs. 101 +/- 48 ml, 95% CI for the difference +329 to +590; P < 0.0001) and no different from that of 3.86% glucose at eight hours (510 +/- 48 vs. 448 +/- 60 ml, 95% CI for the difference -102 to +226 ml; P = 0.44) and at 12 hours (552 +/- 44 vs. 414 +/- 78 ml, 95% CI for the difference -47 to +325 ml; P = 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)

Identifying risk factors for impaired oral rotavirus vaccine (ORV) efficacy in low-income countries may lead to improvements in vaccine design and delivery. In this prospective cohort study, we measure maternal rotavirus antibodies, environmental enteric dysfunction (EED), and bacterial gut microbiota development among infants receiving two doses of Rotarix in India (n = 307), Malawi (n = 119), and the UK (n = 60), using standardised methods across cohorts. We observe ORV shedding and seroconversion rates to be significantly lower in Malawi and India than the UK. Maternal rotavirus-specific antibodies in serum and breastmilk are negatively correlated with ORV response in India and Malawi, mediated partly by a reduction in ORV shedding. In the UK, ORV shedding is not inhibited despite comparable maternal antibody levels to the other cohorts. In both India and Malawi, increased microbiota diversity is negatively correlated with ORV immunogenicity, suggesting that high early-life microbial exposure may contribute to impaired vaccine efficacy.

NCT00261118.

Background. Neutrophils are the predominant cell in the lung inflammatory infiltrate of infants with respiratory syncytial virus (RSV) bronchiolitis. Although it has previously been shown that neutrophils from both blood and bronchoalveolar lavage (BAL) are activated, little is understood about their role in response to RSV infection. This study investigated whether RSV proteins and mRNA are present in neutrophils from blood and BAL of infected infants.Methods. We obtained blood and BAL samples from 20 infants with severe RSV bronchiolitis and 8 healthy control infants. Neutrophil RSV F, G, and N proteins, RSV N genomic RNA, and messenger RNA (mRNA) were quantified.Results. RSV proteins were found in BAL and blood neutrophils in infants with RSV disease but not in neutrophils from healthy infants. BAL and blood neutrophils from infants with RSV disease, but not those from healthy infants, expressed RSV N genomic RNA, indicating uptake of whole virus; 17 of 20 BAL and 8 of 9 blood neutrophils from patients expressed RSV N mRNA.Conclusions. This work shows, for the first time, the presence of RSV proteins and mRNA transcripts within BAL and blood neutrophils from infants with severe RSV bronchiolitis.

BackgroundThe mechanisms regulating antibody expression within the human lung during airway infection are largely unknown. In this study, our objectives were to determine if infection with respiratory syncytial virus (RSV) upregulates expression of the B cell differentiation factors A proliferation inducing ligand (APRIL) and B cell activating factor of the TNF family (BAFF), if this is a common feature of viral airway infection, and how this is regulated in human airway epithelial cells. Methods We measured BAFF and APRIL protein expression in bronchoalveolar lavage (BAL) fluid from infants with severe RSV disease, and healthy control children, and in nasopharyngeal aspirates from preschool children with other single respiratory viral infections. We also measured mRNA expression in bronchial brushings from RSV-infected infants, and in RSV-infected paediatric primary airway epithelial cell cultures ( pAEC). Beas-2B cell cultures were used to examine mechanisms regulating BAFF expression.