Breeding for grapevine downy mildew resistance via gene editing

Downy mildew (DM) caused by the oomycete Plasmopara viticola ranks in the top diseases affecting grapevine (Vitis vinifera L.) cultivation and its control requires every year a large use of fungicides. The Farm to Fork strategy newly promoted by the EU aims to accelerate the transition to a sustainable food system and has set very ambitious targets including the reduction by 50% of the use and risk of pesticides by 2030. The introduction of disease-tolerant grapevine varieties or clones clearly represents a step forward to reach this goal. The recent advent of new breeding tools such as genome editing and cis-genesis offers a great opportunity to obtain resistant plants with higher precision and speed than by conventional breeding, either by knocking down susceptibility genes or by introducing known resistance-genes in commercial cultivars. Based on reports in other crops, the family of Downy Mildew Resistant 6 (DMR6) and DMR6-like oxygenases (DLOs) are candidate susceptibility genes for the control of DM resistance in V. vinifera. Deep-sequencing the putative susceptibility genes in 190 genetically diverse grapevine genotypes identified several Single Nucleotide Polymorphisms then screened for their impact on protein structure/function and association with DM resistant genotypes. Gene expression and gene network analysis suggested that grapevine DMR6 and DLO genes have distinct functions, and that VviDMR6-1 is co-regulated with several Pathogenesis-related genes. Based on this evidence, we generated a large collection of DMR6-1 and DMR6-2 single and double knock-out mutants in multiple grapevine cultivars and evaluated their resistance to DM. Phenotypic resistance data upon artificial infection are being collected and will be presented here. In parallel, we also developed a new DNA-free gene editing methodology and obtained non-transgenic and non-chimeric edited grapevine plants regenerated from a single cell

Opname van nicotine door kippen en overdracht naar eieren bij toepassing van nicotine tegen bloedluis

Uit onderzoek van de AID blijkt nicotine gebruikt te worden voor de bestrijding van bloedluis bij kippen. Dit levert mogelijk gezondheidsrisico's op voor de consument van het kippenvlees of de eieren. Omdat niet duidelijk is of het nicotine na de bestrijding van bloedluis in het vlees of eieren achterblijft is, in opdracht van LNV/VD, een verkennende overdrachtstudie gedaan om na te gaan in hoeverre nicotine en twee bekende metabolieten, cotinine en 3-hydroxycotinine, worden overgedragen naar eieren, organen en weefsels van de ki

Recovery of cefazolin and clindamycin in in vitro pediatric CPB systems

Cardiopulmonary bypass (CPB) is often necessary for congenital cardiac surgery, but CPB can alter drug pharmacokinetic parameters resulting in underdosing. Inadequate plasma levels of antibiotics could lead to postoperative infections with increased morbidity. The influence of pediatric CPB systems on cefazolin and clindamycin plasma levels is not kn

In Vitro Recovery of Sufentanil, Midazolam, Propofol, and Methylprednisolone in Pediatric Cardiopulmonary Bypass Systems

Objectives: To evaluate in vitro drug recovery in cardiopulmonary bypass (CPB) systems used for pediatric cardiac surgery. Design: Observational in vitro study. Setting: Single-center university hospital. Participants: In vitro CPB systems used for pediatric cardiac surgery. Interventions: Three full neonatal, infant, and pediatric CPB systems were primed according to hospital protocol and kept running for 6 hours. Midazolam, propofol, sufentanil, and methylprednisolone were added to the venous side of the systems in doses commonly used for induction of general anesthesia. Blood samples were taken from the postoxygenator side of the circuit immediately after injection of the drugs and after 2, 5, 7, 10, 30, 60, 180, and 300 minutes. Measurements and Main Results: Linear mixed model analyses were performed to assess the relationship between log-transformed drug concentration (dependent variable) and type of CPB system and sample time point (independent variables). The mean percentage of drug recovery after 60 and 180 minutes compared with T1 was 41.7% (95% confidence interval [CI] 35.9-47.4) and 23.0% (95% CI 9.2-36.8) for sufentanil, 87.3% (95% CI 64.9-109.7) and 82.0% (95% CI 64.6-99.4) for midazolam, 41.3% (95% CI 15.5-67.2) and 25.0% (95% CI 4.7-45.3) for propofol, and 119.3% (95% CI 101.89-136.78) and 162.0% (95% CI 114.09-209.91) for methylprednisolone, respectively. Conclusions: The present in vitro experiment with neonatal, infant, and pediatric CPB systems shows a variable recovery of routinely used drugs with significant differences between drugs, but not between system categories (with the exception of propofol). The decreased recovery of mainly sufentanil and propofol could lead to suboptimal dosing of patients during cardiac surgery with CPB

Approaches to mixture risk assessment of PFASs in the European population based on human hazard and biomonitoring data

Per- and polyfluoroalkyl substances (PFASs) are a highly persistent, mobile, and bioaccumulative class of chemicals, of which emissions into the environment result in long-lasting contamination with high probability for causing adverse effects to human health and the environment. Within the European Biomonitoring Initiative HBM4EU, samples and data were collected in a harmonized way from human biomonitoring (HBM) studies in Europe to derive current exposure data across a geographic spread. We performed mixture risk assessments based on recent internal exposure data of PFASs in European teenagers generated in the HBM4EU Aligned Studies (dataset with N = 1957, sampling years 2014-2021). Mixture risk assessments were performed based on three hazard-based approaches: the Hazard Index (HI) approach, the sum value approach as used by the European Food Safety Authority (EFSA) and the Relative Potency Factor (RPF) approach. The HI approach resulted in the highest risk estimates, followed by the RPF approach and the sum value approach. The assessments indicate that PFAS exposure may result in a health risk in a considerable fraction of individuals in the HBM4EU teenager study sample, thereby confirming the conclusion drawn in the recent EFSA scientific opinion. This study underlines that HBM data are of added value in assessing the health risks of aggregate and cumulative exposure to PFASs, as such data are able to reflect exposure from different sources and via different routes.This work was supported by the European Union’s Horizon 2020 research and innovation programme under Grant agreement No 733032 HBM4EU (www.HBM4EU.eu), and received co-funding from the au thors’ organizations. The Norwegian Institute of Public Health (NIPH) has contributed to funding of the Norwegian Environmental Biobank (NEB), and the laboratory measurements have partly been funded by the Research Council of Norway through research projects (275903 and 268465). The PCB cohort (follow-up) received additional funding from the Ministry of Health of the Slovak Republic (program 07B0103).S

Intravenous morphine versus intravenous paracetamol after cardiac surgery in neonates and infants

Background: Morphine is worldwide the analgesic of first choice after cardiac surgery in children. Morphine has unwanted hemodynamic and respiratory side effects. Therefore, post-cardiac surgery patients may potentially benefit from a non-opioid drug for pain relief. A previous study has shown that intravenous (IV) paracetamol is effective and opioid-sparing in children after major non-cardiac surgery. The aim of the study is to test the hypothesis that intermittent IV paracetamol administration in children after cardiac surgery will result in a reduction of at least 30% of the cumulative morphine requirement. Methods: This is a prospective, multi-center, randomized controlled trial at four level-3 pediatric intensive care units (ICUs) in the Netherlands and Belgium. Children who are 0-36months old will be randomly assigned to receive either intermittent IV paracetamol or continuous IV morphine up to 48h post-operatively. Morphine will be available as rescue medication for both groups. Validated pain and sedation assessment tools will be used to monitor patients. The sample size (n=208, 104 per arm) was calculated in order to detect a 30% reduction in morphine dose; two-sided significance level was 5% and power was 95%. Discussion: This study will focus on the reduction, or replacement, of morphine by IV paracetamol in children (0-36months old) after cardiac surgery. The results of this study will form the basis of a new pain management algorithm and will be implemented at the participating ICUs, resulting in an evidence-based guideline on post-operative pain after cardiac surgery in infants who are 0-36months old