Clinical validation of an evidence-based method to adjust Pancreatic Enzyme Replacement Therapy through a prospective interventional study in paediatric patients with Cystic Fibrosis

Background A method to adjust Pancreatic Enzyme Replacement Therapy in Cystic Fibrosis is not currently available. Objectives To assess the in vivo efficacy of a method to adjust the dose of enzymatic supplement in CF extrapolated from previous in vitro digestion studies (theoretical optimal dose, TOD). Secondly, to assess how individual patient characteristics influence the expected coefficient of fat absorption (CFA) and thus to identify an individual correction factor to improve TOD. Methods A prospective interventional study in 43 paediatric patients with CF from 5 European centres. They followed a 24h fixed diet with the theoretical optimal dose for each meal. Faecal collection was carried out between colorimetric markers in order to include all the faeces corresponding to the fixed diet. Beta regression models were applied to assess the associations of individual patient characteristics with the CFA. Results Median CFA was 90% (84, 94% 1st, 3rd Q.) with no significant differences among centres. Intestinal transit time was positively associated with CFA (p = 0.007), but no statistical associations were found with and age, gender, phenotype or BMI. Regression model showed no improvement of the in vitro predicted theoretical optimal dose when taking individual patient characteristics into account. Conclusion Strict adherence to the theoretical optimal dose of enzymatic supplement for a prescribed meal, led to median CFA levels at the clinical target of 90% with a low variability between patients. The proposed method can be considered as a first approach for an evidencebased method in PERT dosing based on food characteristics. Results have to be confirmed in free dietary settings

The European Solar Telescope

The European Solar Telescope (EST) is a project aimed at studying the magnetic connectivity of the solar atmosphere, from the deep photosphere to the upper chromosphere. Its design combines the knowledge and expertise gathered by the European solar physics community during the construction and operation of state-of-the-art solar telescopes operating in visible and near-infrared wavelengths: the Swedish 1m Solar Telescope, the German Vacuum Tower Telescope and GREGOR, the French Télescope Héliographique pour l'Étude du Magnétisme et des Instabilités Solaires, and the Dutch Open Telescope. With its 4.2 m primary mirror and an open configuration, EST will become the most powerful European ground-based facility to study the Sun in the coming decades in the visible and near-infrared bands. EST uses the most innovative technological advances: the first adaptive secondary mirror ever used in a solar telescope, a complex multi-conjugate adaptive optics with deformable mirrors that form part of the optical design in a natural way, a polarimetrically compensated telescope design that eliminates the complex temporal variation and wavelength dependence of the telescope Mueller matrix, and an instrument suite containing several (etalon-based) tunable imaging spectropolarimeters and several integral field unit spectropolarimeters. This publication summarises some fundamental science questions that can be addressed with the telescope, together with a complete description of its major subsystems

Significant reduction in processing time for Ca0.95Ce0.05MnO3 thermoelectric ceramics

Attrition-milling process has been applied to Ce-doped CaMnO3 precursors to obtain small grain-size powders. The use of Ce4+ as dopant instead a Rare Earth3+ has allowed decreasing by 50% the atomic proportion of dopant, to obtain equivalent charge carrier concentration, which is required for attaining promising properties for thermoelectric applications. An impressive decrease in thermal processing time was achieved, together with an increase in thermoelectric performances, when compared to classically prepared materials. XRD and SEM analysis have confirmed that the final material is nearly single phase. Moreover, grain sizes and density increase with the sintering duration. These microstructural differences are reflected in a significant decrease in electrical resistivity, when compared to the samples prepared from ball-milled precursors (used as reference), without drastically modifying the Seebeck coefficient values. On the other hand, despite of their high electrical conductivity, thermal conductivity is decreased for short time sintered materials, leading to the highest ZT values at 800 °C (∼0.27) in samples sintered for 1 h at 1310 °C. These values are among the best reported in the literature, but they have been obtained in very short time using a simple, and easily scalable process. The suggested approach presented in this work appears particularly promising for large-scale production of oxide-based thermoelectric modules for power generation

Development and evaluation of combined PCRs for detecting Salmonella in swine lymph nodes

Salmonellosis is one of the major zoonoses worldwide extended, frequently transmitted by subclinically infected pigs. Thus, EU health authorities have initiated salmonellosis control programs including prevalence studies in pigs by microbiological culture of lymph nodes (LN) following the ISO 6579 method. This method has some disadvantages that recommend the development of new diagnostic tools. The aim of this study was to develop and evaluate the usefulness of new PCRs for detecting Salmonella in LN pig samples, by amplifying 2 chromosomal (A and B) and 2 plasmidic (C and D) genes highly conserved in Salmonella. These PCRs were evaluated (i) in lab conditions; (ii) against 38 contaminants; (iii) against 132 Salmonella strains of 37 serotypes; and (iv) with 320 swine LN samples. Results shown that: (i) the four PCRs were specific for Salmonella; (ii) PCR-A and PCR-B had more sensitivity than PCR-C and PCR-D, unrelated to the serotype; (iii) PCR-A showed 94.4% SeR vs. the ISO method, while it was below 63.6% for the other genes; and (iv) best results of SeR was obtained by considering the 4 PCRs jointly, allowing to detect Salmonella in 26 ISO- samples, 17 (65.4%) of which resulted positive after a second culture. In conclusion, the combined PCRs showed higher diagnostic sensitivity, indicating its usefulness as a complementary or alternative method to the ISO

The extradomain A of fibronectin (EDA) combined with poly(I:C) enhances the immune response to HIV-1 p24 protein and the protection against recombinant Listeria monocytogenes-Gag infection in the mouse model

The development of effective vaccines against HIV-1 infection constitutes one of the major challenges in viral immunology. One of the protein candidates in vaccination against this virus is p24, since it is a conserved HIV antigen that has cytotoxic and helper T cell epitopes as well as B cell epitopes that may jointly confer enhanced protection against infection when used in immunization-challenge approaches. In this context, the adjuvant effect of EDA (used as EDAp24 fusion protein) and poly(I:C), as agonists of TLR4 and TLR3, respectively, was assessed in p24 immunizations using a recombinant Listeria monocytogenes HIV-1 Gag proteins (Lm-Gag, where p24 is the major antigen) for challenge in mice. Immunization with EDAp24 fusion protein together with poly(I:C) adjuvant induced a specific p24 IFN-γ production (Th1 profile) as well as protection against a Lm-Gag challenge, suggesting an additive or synergistic effect between both adjuvants. The combination of EDA (as a fusion protein with the antigen, which may favor antigen targeting to dendritic cells through TLR4) and poly(I:C) could thus be a good adjuvant candidate to enhance the immune response against HIV-1 proteins and its use may open new ways in vaccine investigations on this virus