Influence of damaging and wilting red clover on lipid metabolism during ensiling and in vitro rumen incubation

This paper describes the relationship between protein-bound phenols in red clover, induced by different degrees of damaging before wilting and varying wilting duration, and in silo lipid metabolism. The ultimate effect of these changes on rumen biohydrogenation is the second focus of this paper For this experiment, red clover, damaged to different degrees (not damaged (ND), crushing or frozen/thawing (FT)) before wilting (4 or 24 h) was ensiled. Different degrees of damaging and wilting duration lead to differences in polyphenol oxidase (PPO) activity, measured as increase in protein-bound phenols. Treatment effects on fatty acid (FA) content and composition, lipid fractions (free FAs, membrane lipids (ML) and neutral fraction) and lipolysis were further studied in the silage. In FT, red clover lipolysis was markedly lower in the first days after ensiling, but this largely disappeared after 60 days of ensiling, regardless of wilting duration. This suggests an inhibition of plant lipases in FT silages. After 60 days of ensiling no differences in lipid fractions could be found between any of the treatments and differences in lipolysis were caused by reduced FA proportions in ML of wilted FT red clover Fresh, wilted (24 h) after damaging (ND or FT) and ensiled (4 or 60 days; wilted 24 h; ND or FT) red clover were also incubated in rumen fluid to study the biohydrogenation of C18:3n-3 and C18:2n-6 in vitro. Silages (both 60 days and to a lower degree 4 days) showed a lower biohydrogenation compared with fresh and wilted forages, regardless of damaging. This suggests that lipids in ensiled red clover were more protected, but this protection was not enhanced by a higher amount of protein-bound phenols in wilted FT compared with ND red clover The reduction of rumen microbial biohydrogenation with duration of red clover ensiling seems in contrast to what is expected, namely a higher biohydrogenation when a higher amount of FFA is present. This merits further investigation in relation to strategies to activate PPO toward the embedding of lipids in phenol protein complexes

A reference frame for blood volume in children and adolescents

BACKGROUND: Our primary purpose was to determine the normal range and variability of blood volume (BV) in healthy children, in order to provide reference values during childhood and adolescence. Our secondary aim was to correlate these vascular volumes to body size parameters and pubertal stages, in order to determine the best normalisation parameter. METHODS: Plasma volume (PV) and red cell volume (RCV) were measured and F-cell ratio was calculated in 77 children with idiopathic nephrotic syndrome in drug-free remission (mean age, 9.8 ± 4.6 y). BV was calculated as the sum of PV and RCV. Due to the dependence of these values on age, size and sex, all data were normalised for body size parameters. RESULTS: BV normalised for lean body mass (LBM) did not differ significantly by sex (p < 0.376) or pubertal stage (p < 0.180), in contrast to normalisation for the other anthropometric parameters. There was no significant difference between reference values for children and adults. CONCLUSION: LBM was the anthropometric index most closely correlated to vascular fluid volumes, independent of age, gender and pubertal stage

Development and performance of the c4c national clinical trial networks for optimizing pediatric trial facilitation

Introduction:The high failure rate of industry-driven pediatric clinical trials leads to insufficient timely labeling of drugs in children and a lack of scientific evidence, resulting in the persistently high off-label drug use. National clinical trial networks can facilitate collaboration between sites, investigators, and experts, increasing the likelihood of successful trials. Within the conect4children (c4c) network, an Innovative Medicines Initiative 2-funded project, National Hubs hosted by National Clinical Trials Networks were set up across 21 European countries to facilitate the setup and execution of pediatric clinical trials. In this paper, we aim to present the performance metrics of the trial feasibility process as well as learnings and challenges encountered by the Belgian and Dutch Networks in working within the European c4c project.Method:The c4c National Hubs streamline pediatric clinical trials by initiating early country outreach, identifying overlapping studies, recommending quality trial sites, and supporting trial budgeting for both industry and academic settings. To show the impact of Pedmed-NL and Belgian Pediatric Clinical Research Network (BPCRN), internal metrics were collected from 2019 to 2022 on four industry-sponsored and three academic trials performed within the c4c network. Timelines and outcomes of the site identification were collected and analyzed for industry trials. A qualitative analysis was conducted through c4c platforms, sponsor interactions, and stakeholder engagement to evaluate the added value of a research network.Results:In industry-sponsored trials, full feasibility questionnaires were completed within 2 weeks (n = 48), and inclusion rates were up to 80% of clinical sites. Before committing to c4c, 14% of sites were contacted by industry, leading to communication burdens. Utilizing national infrastructure knowledge and therapeutic environment insights helped optimize trial timelines and address feasibility challenges. In addition, national adaptations, such as bilingual staff and site development, played a role in streamlining trial operations in both academic and industry settings. Performance and experiences were similar for both networks.Conclusion:The early-facilitation examples from the c4c trials demonstrated promising metrics for two National Hubs, including optimized start-up timelines and aiding site selection quality. The learnings and challenges of the Belgian and Dutch Networks provided insights for the development of clinical research networks

FCGG Renal Biopsy Network: first epidemiological report on pediatric renal disease in Flanders

FCGG Renal Biopsy Network: first epidemiological report on pediatric renal diseases Sevasti Karamaria1, Johan De Meester2, Amélie Dendooven3, Elena Levtchenko4, Noel Knops4, Koen Van Hoeck5, Dominique Trouet5, Reiner Mauel6, Ben Sprangers7, Wim Laurens8, Johan Vande Walle1, on behalf of the FCGG – NBVN working group 1 Department of Pediatrics, UZ Gent, Ghent; 2NBVN, Antwerp; 3Pathology Department, UZ Gent, Ghent; 4Department of Pediatrics, UZ Leuven, Leuven; 5Departement of Pediatrics, UZ Antwerpen, Antwerp; 6Department of Pediatrics, UZ Brussel, Brussels; 7Department of Nephrology, UZ Leuven, Leuven; 8Department of Nephrology, AZ Nikolaas, Sint-Niklaas. Objective: In 2016, a regional renal biopsy network was founded as a collaboration between renal pathologists and nephrologists in order to standardize diagnosis and therapy. Uniform renal biopsy request and renal biopsy report forms were introduced, together with a new comprehensive list of renal pathology diagnoses for coding. The 2017-2018 epidemiological data of the pediatric patients (age= 0-17 years) are presented. Methods: Following informed consent and in compliance with GDPR, data registration consists of basic patient and categorical renal data, semi-structured medical information of renal histopathology and the clinical renal disease. Results: In 2017-2018, 92 renal biopsies were reported in pediatric patients or 3.6 per 100,000 pediatric inhabitants per year. Three clinical patterns were equally represented: only proteinuria >1g/day; only hematuria; and combination of proteinuria and hematuria. Acute or chronic renal failure were rare. In the youngest age group (0-5 years; N=26) minimal change disease predominated, followed by Henoch-Schönlein nephritis. The middle age group (6-11 years; N=32) mainly presented with disease characterized by hematuria: IgA nephropathy, Henoch-Schönlein nephritis and Alport’s disease. A more diverse renal disease spectrum was present in the highest age group (12-18 years; N=34): IgA nephropathy, different forms of proliferative glomerulonephritis and of nephrotic syndrome of childhood. Patients with a Caucasian descent presented with IgA nephropathy, while a nephrotic syndrome was more common in those without a Caucasian descent. Alport’s disease was particularly diagnosed in female patients, IgA nephropathy in male patients, and the gender distribution was equal in minimal change disease. Conclusion: The FCGG network provides an better cross-talk between renal pathologists and nephrologists. For the first time, reliable estimates of pediatric renal diseases based on histology are available. Genetic analyses are not yet included. Efforts to coordinate clinical care of pediatric renal diseases are ongoing

Development and performance of the c4c national clinical trial networks for optimizing pediatric trial facilitation

IntroductionThe high failure rate of industry-driven pediatric clinical trials leads to insufficient timely labeling of drugs in children and a lack of scientific evidence, resulting in the persistently high off-label drug use. National clinical trial networks can facilitate collaboration between sites, investigators, and experts, increasing the likelihood of successful trials. Within the conect4children (c4c) network, an Innovative Medicines Initiative 2-funded project, National Hubs hosted by National Clinical Trials Networks were set up across 21 European countries to facilitate the setup and execution of pediatric clinical trials. In this paper, we aim to present the performance metrics of the trial feasibility process as well as learnings and challenges encountered by the Belgian and Dutch Networks in working within the European c4c project.MethodThe c4c National Hubs streamline pediatric clinical trials by initiating early country outreach, identifying overlapping studies, recommending quality trial sites, and supporting trial budgeting for both industry and academic settings. To show the impact of Pedmed-NL and Belgian Pediatric Clinical Research Network (BPCRN), internal metrics were collected from 2019 to 2022 on four industry-sponsored and three academic trials performed within the c4c network. Timelines and outcomes of the site identification were collected and analyzed for industry trials. A qualitative analysis was conducted through c4c platforms, sponsor interactions, and stakeholder engagement to evaluate the added value of a research network.ResultsIn industry-sponsored trials, full feasibility questionnaires were completed within 2 weeks (n = 48), and inclusion rates were up to 80% of clinical sites. Before committing to c4c, 14% of sites were contacted by industry, leading to communication burdens. Utilizing national infrastructure knowledge and therapeutic environment insights helped optimize trial timelines and address feasibility challenges. In addition, national adaptations, such as bilingual staff and site development, played a role in streamlining trial operations in both academic and industry settings. Performance and experiences were similar for both networks.ConclusionThe early-facilitation examples from the c4c trials demonstrated promising metrics for two National Hubs, including optimized start-up timelines and aiding site selection quality. The learnings and challenges of the Belgian and Dutch Networks provided insights for the development of clinical research networks

Coulomb excitation of 68^{68}Ni at safe energies

The $B(E2;0^+\to2^+)$ value in $^{68}$Ni has been measured using Coulomb excitation at safe energies. The $^{68}$Ni radioactive beam was post-accelerated at the ISOLDE facility (CERN) to 2.9 MeV/u. The emitted $\gamma$ rays were detected by the MINIBALL detector array. A kinematic particle reconstruction was performed in order to increase the measured c.m. angular range of the excitation cross section. The obtained value of 2.8$^{+1.2}_{-1.0}$ 10$^2$ e$^2$fm$^4$ is in good agreement with the value measured at intermediate energy Coulomb excitation, confirming the low $0^+\to2^+$ transition probability.Comment: 4 pages, 5 figure