Maternal immunity enhances systemic recall immune responses upon oral immunization of piglets with F4 fimbriae

F4 enterotoxigenic Escherichia coli (ETEC) cause diarrhoea and mortality in piglets leading to severe economic losses. Oral immunization of piglets with F4 fimbriae induces a protective intestinal immune response evidenced by an F4-specific serum and intestinal IgA response. However, successful oral immunization of pigs with F4 fimbriae in the presence of maternal immunity has not been demonstrated yet. In the present study we aimed to evaluate the effect of maternal immunity on the induction of a systemic immune response upon oral immunization of piglets. Whereas F4-specific IgG and IgA could be induced by oral immunization of pigs without maternal antibodies and by intramuscular immunization of pigs with maternal antibodies, no such response was seen in the orally immunized animals with maternal antibodies. Since maternal antibodies can mask an antibody response, we also looked by ELIspot assays for circulating F4-specific antibody secreting cells (ASCs). Enumerating the F4-specific ASCs within the circulating peripheral blood mononuclear cells, and the number of F4-specific IgA ASCs within the circulating IgA+ B-cells revealed an F4-specific immune response in the orally immunized animals with maternal antibodies. Interestingly, results suggest a more robust IgA booster response by oral immunization of pigs with than without maternal antibodies. These results demonstrate that oral immunization of piglets with F4-specific maternal antibodies is feasible and that these maternal antibodies seem to enhance the secondary systemic immune response. Furthermore, our ELIspot assay on enriched IgA+ B-cells could be used as a screening procedure to optimize mucosal immunization protocols in pigs with maternal immunity

Weekends affect mortality risk and chance of discharge in critically ill patients: a retrospective study in the Austrian registry for intensive care.

BACKGROUND: In this study, we primarily investigated whether ICU admission or ICU stay at weekends (Saturday and Sunday) is associated with a different risk of ICU mortality or chance of ICU discharge than ICU admission or ICU stay on weekdays (Monday to Friday). Secondarily, we analysed whether weekend ICU admission or ICU stay influences risk of hospital mortality or chance of hospital discharge. METHODS: A retrospective study was performed for all adult patients admitted to 119 ICUs participating in the benchmarking project of the Austrian Centre for Documentation and Quality Assurance in Intensive Care (ASDI) between 2012 and 2015. Readmissions to the ICU during the same hospital stay were excluded. RESULTS: In a multivariable competing risk analysis, a strong weekend effect was observed. Patients admitted to ICUs on Saturday or Sunday had a higher mortality risk after adjustment for severity of illness by Simplified Acute Physiology Score (SAPS) 3, year, month of the year, type of admission, ICU, and weekday of death or discharge. Hazard ratios (95% confidence interval) for death in the ICU following admission on a Saturday or Sunday compared with Wednesday were 1.15 (1.08-1.23) and 1.11 (1.03-1.18), respectively. Lower hazard ratios were observed for dying on a Saturday (0.93 (0.87-1.00)) or Sunday (0.85 (0.80-0.91)) compared with Wednesday. This is probably related to the reduced chance of being discharged from the ICU at the weekend (0.63 (0.62-064) for Saturday and 0.56 (0.55-0.57) for Sunday). Similar results were found for hospital mortality and hospital discharge following ICU admission. CONCLUSIONS: Patients admitted to ICUs at weekends are at increased risk of death in both the ICU and the hospital even after rigorous adjustment for severity of illness. Conversely, death in the ICU and discharge from the ICU are significantly less likely at weekends

Staat van de ambtelijke dienst 2015 De overheid in tijden van verandering

bookHervorming Sociale Regelgevin

Interactions between Glucocorticoid Treatment and Cis-Regulatory Polymorphisms Contribute to Cellular Response Phenotypes

Glucocorticoids (GCs) mediate physiological responses to environmental stress and are commonly used as pharmaceuticals. GCs act primarily through the GC receptor (GR, a transcription factor). Despite their clear biomedical importance, little is known about the genetic architecture of variation in GC response. Here we provide an initial assessment of variability in the cellular response to GC treatment by profiling gene expression and protein secretion in 114 EBV-transformed B lymphocytes of African and European ancestry. We found that genetic variation affects the response of nearby genes and exhibits distinctive patterns of genotype-treatment interactions, with genotypic effects evident in either only GC-treated or only control-treated conditions. Using a novel statistical framework, we identified interactions that influence the expression of 26 genes known to play central roles in GC-related pathways (e.g. NQO1, AIRE, and SGK1) and that influence the secretion of IL6

Difficult tracheal intubation in neonates and infants. NEonate and Children audiT of Anaesthesia pRactice IN Europe (NECTARINE): a prospective European multicentre observational study

Background: Neonates and infants are susceptible to hypoxaemia in the perioperative period. The aim of this study was to analyse interventions related to anaesthesia tracheal intubations in this European cohort and identify their clinical consequences. Methods: We performed a secondary analysis of tracheal intubations of the European multicentre observational trial (NEonate and Children audiT of Anaesthesia pRactice IN Europe [NECTARINE]) in neonates and small infants with difficult tracheal intubation. The primary endpoint was the incidence of difficult intubation and the related complications. The secondary endpoints were the risk factors for severe hypoxaemia attributed to difficult airway management, and 30 and 90 day outcomes. Results: Tracheal intubation was planned in 4683 procedures. Difficult tracheal intubation, defined as two failed attempts of direct laryngoscopy, occurred in 266 children (271 procedures) with an incidence (95% confidence interval [CI]) of 5.8% (95% CI, 5.1e6.5). Bradycardia occurred in 8% of the cases with difficult intubation, whereas a significant decrease in oxygen saturation (SpO2<90% for 60 s) was reported in 40%. No associated risk factors could be identified among comorbidities, surgical, or anaesthesia management. Using propensity scoring to adjust for confounders, difficult anaesthesia tracheal intubation did not lead to an increase in 30 and 90 day morbidity or mortality. Conclusions: The results of the present study demonstrate a high incidence of difficult tracheal intubation in children less than 60 weeks post-conceptual age commonly resulting in severe hypoxaemia. Reassuringly, the morbidity and mortality at 30 and 90 days was not increased by the occurrence of a difficult intubation event. Clinical trial registration: NCT02350348