Effects of tank mixtures of plant protection products on honey bees and possible physiological interactions

Im Zuge der Nahrungssuche werden Bestäuber, wie Honig­bienen, unter Umständen einer Vielzahl von Pflanzenschutzmitteln (PSM) ausgesetzt. Während die Effekte einzelner PSM auf Bienen im Rahmen des Zulassungsprozesses umfangreich geprüft werden, erfolgt für Tank­mischungen eine routinemäßige Risikobewertung i.d.R. nur für Insektizide und bekannte potentiell synergistisch wirkende Mischungspartner. Aus ökonomischen und arbeits­wirtschaftlichen Gründen kommen Mischungen von PSM dennoch häufig zum Einsatz. In einigen Fällen führen Interaktionen zwischen den Mischungspartnern hierbei zu unerwünschten additiven oder synergistischen Effekten. Insbesondere für Pyrethroide und Neonikoti­noide in Mischung mit Ergosterol-Biosynthese-hemmenden Azolfungiziden ist das synergistische Potential der Mischtoxizität auf Honigbienen bekannt und wird regulatorisch bereits berücksichtigt. Diese Wirkungssteigerung resultiert aus der Hemmung des Hauptentgiftungsen­zyms P450 durch Azolfungizide, sodass das jeweilige Insek­tizid von den Bienen nicht mehr abgebaut werden kann. Erste Hinweise auf wirkungssteigernde Effekte liegen ebenfalls für Mischungen aus Insektiziden und Zusatzstoffen vor. Für eine realistische Risikobewertung ist ein besseres Verständnis von Mischungseffekten essen­tiell, das nur über weitere Forschung erreicht werden kann.During foraging bouts pollinators like honey bees may be exposed to multiple plant protection products (PPPs). In contrast to applications of single PPPs the effects of tank mixtures are not routinely evaluated in the risk assessment process of PPPs with the exception of known synergistic insecticides and mixing partners. Due to economical constraints and process efficiency PPP mixtures are commonly used in agricultural practices. However, sometimes interactions among agrochemicals lead to undesirable additive and synergistic effects. Especially mixtures of pyrethroids or neonicotinoids with azole fungicides, which inhibit sterol biosynthesis, have a synergistic poten­tial of negatively affecting honey bees. For such mixtures, regulatory restrictions are already in place. These synergistic effects are associated with azole fungicides inhibiting the main detoxification enzyme P450, which hinders the bee to detoxify the insecticide. Further studies provide first evidence for increased impacts of mixtures of insecticides with adjuvants on honey bees. More research is necessary to better understand mixture toxicity and to implement this knowledge in the risk assess­ment

3.13 Tank mixtures of insecticides and fungicides, adjuvants, additives, fertilizers and their effects on honey bees after contact exposure in a spray chamber

In agriculture honey bees may be exposed to multiple pesticides. In contrast to single applications of plant protection products (PPP), the effects of tank mixtures of two or more PPP on honey bees are not routinely assessed in the risk assessment of plant protection products. However, tank mixes are often common practice by farmers. Mixtures of practically non-toxic substances can lead to synergistic increase of toxic effects on honey bees, observed for the first time in 19921 in combinations of pyrethroids and azole fungicides. 2004 Iwasa et al. already reported that ergosterol-biosynthesis-inhibiting (EBI) fungicides strongly increase the toxicity of neonicotinoids in laboratory for the contact exposure route. Furthermore, in agricultural practice additives, adjuvants and fertilizers may be added to the spray solution. For these additives usually no informations on potential side effects on bees are available when mixed with plant protection products. Therefore, it is considered necessary to investigate possible additive or synergistic impacts and evaluate potentially critical combinations to ensure protection of bees. Here, we investigated the effects on bees of combinations of insecticides, fungicides and fertilizers under controlled laboratory conditions. A spray chamber was used to evaluate effects following contact exposure by typical field application rates. Subsequently, mortality and behaviour of bees were monitored for at least 48 h following the OECD acute contact toxicity test 2143. Dependencies of synergistic effects and the time intervals between the applications of the mixing partners were evaluated.In agriculture honey bees may be exposed to multiple pesticides. In contrast to single applications of plant protection products (PPP), the effects of tank mixtures of two or more PPP on honey bees are not routinely assessed in the risk assessment of plant protection products. However, tank mixes are often common practice by farmers. Mixtures of practically non-toxic substances can lead to synergistic increase of toxic effects on honey bees, observed for the first time in 19921 in combinations of pyrethroids and azole fungicides. 2004 Iwasa et al. already reported that ergosterol-biosynthesis-inhibiting (EBI) fungicides strongly increase the toxicity of neonicotinoids in laboratory for the contact exposure route. Furthermore, in agricultural practice additives, adjuvants and fertilizers may be added to the spray solution. For these additives usually no informations on potential side effects on bees are available when mixed with plant protection products. Therefore, it is considered necessary to investigate possible additive or synergistic impacts and evaluate potentially critical combinations to ensure protection of bees. Here, we investigated the effects on bees of combinations of insecticides, fungicides and fertilizers under controlled laboratory conditions. A spray chamber was used to evaluate effects following contact exposure by typical field application rates. Subsequently, mortality and behaviour of bees were monitored for at least 48 h following the OECD acute contact toxicity test 2143. Dependencies of synergistic effects and the time intervals between the applications of the mixing partners were evaluated

Influence of Sedation Level and Ventilation Status on the Diagnostic Validity of Delirium Screening Tools in the ICU—An International, Prospective, Bi-Center Observational Study (IDeAS)

Background and objectives: The use of delirium screening instruments (DSIs) is recommended in critical care practice for a timely detection of delirium. We hypothesize that the patient-related factors "level of sedation" and "mechanical ventilation" impact test validity of DSIs. Materials and Methods: This is a prospective, bi-center observational study (clinicaltrials.gov: NCT01720914). Critically ill patients were screened for delirium daily for up to seven days after enrollment using the Nursing Delirium Screening Scale (Nu-DESC), Intensive Care Delirium Screening Checklist (ICDSC), and Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Reference standard for delirium diagnosis was the neuropsychiatric examination using the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). Immediately before delirium assessment, ventilation status and sedation levels were documented. Results: 160 patients were enrolled and 151 patients went into final analysis. Delirium incidence was 23.2%. Nu-DESC showed a sensitivity and specificity of 88.5%, a positive predictive value (PPV) of 71.9%, and a negative predictive value (NPV) of 95.8%. ICDSC had a sensitivity of 62.5%, a specificity of 92.4%, a PPV of 71.4%, and a NPV of 89.0%. CAM-ICU showed a sensitivity of 75.0%, a specificity of 94.7%, a PPV of 85.7%, and a NPV of 90.0%. For Nu-DESC and ICDSC, test validity was significantly better for non-sedated patients (Richmond Agitation Sedation Scale (RASS) 0/-1), whereas test validity for CAM-ICU in a severity scale version showed no significant differences for different sedation levels. No DSI showed a significant difference in test validity between noninvasively and invasively ventilated patients. Conclusions: Test validities of DSIs were comparable to previous studies. The observational scores ICDSC and Nu-DESC showed a significantly better performance in awake and drowsy patients (RASS 0/-1) when compared with other sedation levels. Physicians should refrain from sedation whenever possible to avoid suboptimal performance of DSIs

Apheresis therapies for NMOSD attacks A retrospective study of 207 therapeutic interventions

Objective To analyze whether 1 of the 2 apheresis techniques, therapeutic plasma exchange (PE) or immunoadsorption (IA), is superior in treating neuromyelitis optica spectrum disorder (NMOSD) attacks and to identify predictive factors for complete remission (CR). Methods This retrospective cohort study was based on the registry of the German Neuromyelitis Optica Study Group, a nationwide network established in 2008. It recruited patients with neuromyelitis optica diagnosed according to the 2006 Wingerchuk criteria or with aquaporin-4 (AQP4-ab)-antibody-seropositive NMOSD treated at 6 regional hospitals and 16 tertiary referral centers until March 2013. Besides descriptive data analysis of patient and attack characteristics, generalized estimation equation (GEE) analyses were applied to compare the effectiveness of the 2 apheresis techniques. A GEE model was generated to assess predictors of outcome. Results Two hundred and seven attacks in 105 patients (87% AQP4-ab-antibody seropositive) were treated with at least 1 apheresis therapy. Neither PE nor IA was proven superior in the therapy of NMOSD attacks. CR was only achieved with early apheresis therapy. Strong predictors for CR were the use of apheresis therapy as first-line therapy (OR 12.27, 95% CI: 1.04-144.91, p = 0.047), time from onset of attack to start of therapy in days (OR 0.94, 95% CI: 0.89-0.99, p = 0.014), the presence of AQP4-abantibodies (OR 33.34, 95% CI: 1.76-631.17, p = 0.019), and monofocal attack manifestation (OR 4.71, 95% CI: 1.03-21.62, p = 0.046). Conclusion: s Our findings suggest early use of an apheresis therapy in NMOSD attacks, particularly in AQP4-ab-seropositive patients. No superiority was shown for one of the 2 apheresis techniques

Influence of female sex and fertile age on neuromyelitis optica spectrum disorders

Background: Gender and age at onset are important epidemiological factors influencing prevalence, clinical presentation, and treatment response in autoimmune diseases. Objective: To evaluate the impact of female sex and fertile age on aquaporin-4-antibody (AQP4-ab) status, attack localization, and response to attack treatment in patients with neuromyelitis optica (NMO) and its spectrum disorders (neuromyelitis optica spectrum disorder (NMOSD)). Methods: Female-to-male ratios, diagnosis at last visit (NMO vs NMOSD), attack localization, attack treatment, and outcome were compared according to sex and age at disease or attack onset. Results: A total of 186 NMO/SD patients (82% female) were included. In AQP4-ab-positive patients, female predominance was most pronounced during fertile age (female-to-male ratio 23:1). Female patients were more likely to be positive for AQP4-abs (92% vs 55%;p40years. Conclusion: Our data suggest an influence of sex and age on susceptibility to AQP4-ab-positive NMO/SD. Genetic and hormonal factors might contribute to pathophysiology of NMO/SD

Modelling human choices: MADeM and decision‑making

Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)