EFSA Guidance Document for evaluating laboratory and field dissipation studies to obtain DegT50 values of active substances of plant protection products and transformation products of these active substances in soil

EFSA was asked by the European Commission to prepare a Guidance of EFSA for evaluating laboratory and field dissipation studies to obtain degradation rate parameters (DegT50matrix values) of active substances of plant protection products and transformation products of these active substances in soil. This EFSA Guidance Document provides guidance for users on how to obtain DegT50matrix values when performing risk assessments according to Regulation EC No 1107/2009 of the European Parliament and the Council. In addition, this document provides guidance on adsorption parameter (Koc) selection and new Crop Interception values

Effects of Muscle Fatigue, Creep, and Musculoskeletal Pain on Neuromuscular Responses to Unexpected Perturbation of the Trunk: A Systematic Review

Introduction: Trunk neuromuscular responses have been shown to adapt under the influence of muscle fatigue, as well as spinal tissue creep or even with the presence of low back pain (LBP). Despite a large number of studies exploring how these external perturbations affect the spinal stability, characteristics of such adaptations remains unclear. Aim: The purpose of this systematic review was to assess the quality of evidence of studies investigating trunk neuromuscular responses to unexpected trunk perturbation. More specifically, the targeted neuromuscular responses were trunk muscle activity reflex and trunk kinematics under the influence of muscle fatigue, spinal creep, and musculoskeletal pain. Methods: A research of the literature was conducted in Pubmed, Embase, and Sport-Discus databases using terms related to trunk neuromuscular reflex responses, measured by electromyography (baseline activity, reflex latency, and reflex amplitude) and/or trunk kinematic, in context of unexpected external perturbation. Moreover, independent variables must be either trunk muscle fatigue or spinal tissue creep or LBP. All included articles were scored for their electromyography methodology based on the “Surface Electromyography for the Non-Invasive Assessment of Muscles (SENIAM)” and the “International Society of Electrophysiology and Kinesiology (ISEK)” recommendations whereas overall quality of articles was scored using a specific quality checklist modified from the Quality Index. Meta-analysis was performed on reflex latency variable. Results: A final set of 29 articles underwent quality assessments. The mean quality score was 79%. No effect of muscle fatigue on erector spinae reflex latency following an unexpected perturbation, nor any other distinctive effects was found for back muscle fatigue and reflex parameters. As for spinal tissue creep effects, no alteration was found for any of the trunk reflex variables. Finally, the meta-analysis revealed an increased erector spinae reflex latency in patients with chronic LBP in comparison with healthy controls following an unexpected trunk perturbation. Conclusion: The literature provides some evidence with regard to trunk adaptions in a context of spinal instability. However, most of the evidence was inconclusive due to a high methodological heterogeneity between the studies

E119D Neuraminidase Mutation Conferring Pan-Resistance to Neuraminidase Inhibitors in an A(H1N1)pdm09 Isolate From a Stem-Cell Transplant Recipient

Background. An influenza A(H1N1)pdm09 infection was diagnosed in a hematopoietic stem cell transplant recipient during conditioning regimen. He was treated with oral oseltamivir, later combined with intravenous zanamivir. The H275Y neuraminidase (NA) mutation was first detected, and an E119D NA mutation was identified during zanamivir therapy. Methods. Recombinant wild-type (WT) E119D and E119D/H275Y A(H1N1)pdm09 NA variants were generated by reverse genetics. Susceptibility to NA inhibitors (NAIs) was evaluated with a fluorometric assay using the 2′-(4-methylumbelliferyl)-α-d-N-acetylneuraminic acid (MUNANA) substrate. Susceptibility to favipiravir (T-705) was assessed using plaque reduction assays. The NA affinity and velocity values were determined with NA enzymatic studies. Results. We identified an influenza A(H1N1)pdm09 E119D mutant that exhibited a marked increase in the 50% inhibitory concentrations against all tested NAIs (827-, 25-, 286-, and 702-fold for zanamivir, oseltamivir, peramivir, and laninamivir, respectively). The double E119D/H275Y mutation further increased oseltamivir and peramivir 50% inhibitory concentrations by 790- and >5000-fold, respectively, compared with the WT. The mutant viruses remained susceptible to favipiravir. The NA affinity and velocity values of the E119D variant decreased by 8.1-fold and 4.5-fold, respectively, compared with the WT. Conclusions. The actual emergence of a single NA mutation conferring pan-NAI resistance in the clinical setting reinforces the pressing need to develop new anti-influenza strategie

Glutathione peroxidase 3 is a potential biomarker for konzo.

Konzo is a neglected paralytic neurological disease associated with food (cassava) poisoning that affects the worlds poorest children and women of childbearing ages across regions of sub-Saharan Africa. Despite understanding the dietary factors that lead to konzo, the molecular markers and mechanisms that trigger this disease remain unknown. To identify potential protein biomarkers associated with a disease status, plasma was collected from two independent Congolese cohorts, a discovery cohort (n = 60) and validation cohort (n = 204), sampled 10 years apart and subjected to multiple high-throughput assays. We identified that Glutathione Peroxidase 3 (GPx3), a critical plasma-based antioxidant enzyme, was the sole protein examined that was both significantly and differentially abundant between affected and non-affected participants in both cohorts, with large reductions observed in those affected with konzo. Our findings raise the notion that reductions in key antioxidant mechanisms may be the biological risk factor for the development of konzo, particularly those mediated through pathways involving the glutathione peroxidase family

Scientific Opinion about the Guidance of the Chemical Regulation Directorate (UK) on how aged sorption studies for pesticides should be conducted, analysed and used in regulatory assessments

Abstract The EFSA Panel on Plant Protection Products and their Residues reviewed the guidance on how aged sorption studies for pesticides should be conducted, analysed and used in regulatory assessment. The inclusion of aged sorption is a higher tier in the groundwater leaching assessment. The Panel based its review on a test with three substances taken from a data set provided by the European Crop Protection Association. Particular points of attention were the quality of the data provided, the proposed fitting procedure of aged sorption experiments and the proposed method for combining results obtained from aged sorption studies and lower‐tier studies on degradation and adsorption. Aged sorption was a relevant process in all cases studied. The test revealed that the guidance could generally be well applied and resulted in robust and plausible results. The Panel considers the guidance suitable for use in the groundwater leaching assessment after the recommendations in this Scientific Opinion have been implemented, with the exception of the use of field data to derive aged sorption parameters. The Panel noted that the draft guidance could only be used by experienced users because there is no software tool that fully supports the work flow in the guidance document. It is therefore recommended that a user‐friendly software tool be developed. Aged sorption lowered the predicted concentration in groundwater. However, because aged sorption experiments may be conducted in different soils than lower‐tier degradation and adsorption experiments, it cannot be guaranteed that the higher tier predicts lower concentrations than the lower tier, while lower tiers should be more conservative than higher tiers. To mitigate this problem, the Panel recommends using all available higher‐ and lower‐tier data in the leaching assessment. The Panel further recommends that aged sorption parameters for metabolites be derived only from metabolite‐dosed studies. The formation fraction can be derived from parent‐dosed degradation studies, provided that the parent and metabolite are fitted with the best‐fit model, which is the double first‐order in parallel model in the case of aged sorption

Pleiotropic Effects of DDT Resistance on Male Size and Behaviour

Understanding the evolution and spread of insecticide resistance requires knowing the relative fitness of resistant organisms. In the absence of insecticides, resistance is predicted to be costly. The Drosophila melanogaster DDT resistance allele (DDT-R) is associated with a male mating cost. This could be because resistant males are generally smaller, but DDT-R may also alter courtship behaviours. Here we tested for body size and courtship effects of DDT-R on mating success in competitive and non-competitive mating trials respectively. We also assessed relative aggression in resistant and susceptible males because aggression can also influence mating success. While the effect of DDT-R on male size partly contributed to reduced mating success, resistant males also had lower rates of courtship and were less aggressive than susceptible males. These differences contribute to the observed DDT-R mating costs. Additionally, these pleiotropic effects of DDT-R are consistent with the history and spread of resistance alleles in nature

Invasion is a community affair: clandestine followers in the bacterial community associated to green algae, Caulerpa racemosa, track the invasion source

Biological invasions rank amongst the most deleterious components of global change inducing alterations from genes to ecosystems. The genetic characteristics of introduced pools of individuals greatly influence the capacity of introduced species to establish and expand. The recently demonstrated heritability of microbial communities associated to individual genotypes of primary producers makes them a potentially essential element of the evolution and adaptability of their hosts. Here, we characterized the bacterial communities associated to native and non-native populations of the marine green macroalga Caulerpa racemosa through pyrosequencing, and explored their potential role on the strikingly invasive trajectory of their host in the Mediterranean. The similarity of endophytic bacterial communities from the native Australian range and several Mediterranean locations confirmed the origin of invasion and revealed distinct communities associated to a second Mediterranean variety of C. racemosa long reported in the Mediterranean. Comparative analysis of these two groups demonstrated the stability of the composition of bacterial communities through the successive steps of introduction and invasion and suggested the vertical transmission of some major bacterial OTUs. Indirect inferences on the taxonomic identity and associated metabolism of bacterial lineages showed a striking consistency with sediment upheaval conditions associated to the expansion of their invasive host and to the decline of native species. These results demonstrate that bacterial communities can be an effective tracer of the origin of invasion and support their potential role in their eukaryotic host’s adaptation to new environments. They put forward the critical need to consider the 'meta-organism' encompassing both the host and associated micro-organisms, to unravel the origins, causes and mechanisms underlying biological invasions

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Environmental risk assessment of pesticides: state of the art and prospective improvement from science

International audiencePesticide risk assessment in the European regulatory framework is mandatory performed for active substances (pesticides) and the plant protection products they are constituents of. The aim is to guarantee that safe use can be achieved for the intended use of the product. This paper provides a feedback on the regulatory environmental risk assessment performed for pesticide registration at the EU and member state levels. The different steps of pesticide registration are addressed considering both exposure and hazard. In this paper, we focus on the environmental fate and behaviour in surface water together with the aquatic ecotoxicity of the substances to illustrate pesticide regulatory risk assessment performed for aquatic organisms. Current methodologies are presented along with highlights on potential improvements. For instance, as regards exposure aspects, moving from field based to landscape risk assessments is promising. Regarding ecotoxicology, ecological models may be valuable tools when applied to chemical risk assessment. In addition, interest and further developments to better take into account mitigation measures in risk assessment and management are also presented

Disponibilité spatio-temporelle et transfert des pesticides dans le sol

Dans les sols, les pesticides présents sous une forme disponible peuvent être transférés par l'eau mobile et contaminer les eaux. Le travail mené consiste à caractériser le comportement de différents couples sol- pesticides du laboratoire au champ, et de la minute à la saison climatique, afin d'évaluer la pertinence des paramètres déterminés. La disponibilité immédiate d'une molécule est régie par les processus d'adsorption/désorption. Des expérimentations d'adsorption en séries avec 13 sols variés ont permis une classification de cinq molécules: Kf trifluraline >> Kf 2,4-0 > Kf isoproturon > Kf atrazine > Kf bentazone. Le pH naturel des sols influence significativement l'adsorption de la bentazone alors que la composante organique des sols influence l'adsorption des quatre autres molécules. La sorption et la désorption sont des processus dynamiques qui interagissent avec la dégradation du composé. Dans les sols, les résidus présents à un temps donné peuvent être sous une forme extractible ou non. La diffusion de la bentazone, liée à sa solubilité, entraîne son piégeage dans la matrice organo-minérale des sols, alors que l'importante minéralisation du 2,4-D limite sa disponibilité. Au champ, l'hydrodynamique des sols gouverne le devenir des pesticides appliqués. Le suivi des quantités exportées par les eaux de drainage met en évidence des variations intra- et inter-saisons liées aux propriétés physico-chimiques des sols et des molécules. Les paramètres déterminés au laboratoire sont insuffisants pour aborder la complexité des processus in situ. Les simulations du transfert des produits réalisées par le modèle mécanistique, stochastique AgriFlux[copyright] ont fourni des résultats cohérents.NANCY/VANDOEUVRE-INPL (545472102) / SudocSudocFranceF