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Progressive myoclonus epilepsy type 1 (EPM1) is an autosomal recessively inherited childhood-adolescence onset neurodegenerative disease caused by mutations in the cystatin B ( CSTB gene). The key clinical manifestation in EPM1 is progressive, stimulus-sensitive, in particular action-induced myoclonus. The cystatin B-deficient mouse model, Cstb -/- , has been described to present with myoclonic seizures and progressive ataxia. Here we describe results from in-depth behavioral phenotyping of the Cstb -/- mouse model in pure isogenic 129S2/SvHsd background covering ages from 1.5 to 6 months. We developed a method for software-assisted detection of myoclonus from video recordings of the Cstb -/- mice. Additionally, we observed that the mice were hyperactive and showed reduced startle response, problems in motor coordination and lack of inhibition. We were, however, not able to demonstrate an ataxic phenotype in them. This detailed behavioral phenotyping of the Cstb -/- mice reveals new aspects of this mouse model. The nature of the motor problems in the Cstb -/- mice seems to be more complex and more resembling the human phenotype than initially described., Competing Interests: EP, HB, and AH are employees of Orion Pharma Corporation. RK has received speaker’s or consultancy fees from Angelini Pharma, Eisai, Jazz Pharma, Orion, UCB Pharma, and Takeda. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pollari, Tegelberg, Björklund, Kälviäinen, Lehesjoki and Haapalinna.)

This study describes antibiotic use by small-scale freshwater aquaculture farmers in the upper Mekong Delta in southwestern Vietnam and the knowledge and practices surrounding the cause and prevention of aquaculture disease in that region. Forty five farmers were included in the study, of which 19 (42%) cultivated tilapia Oreochromis spp., 13 (29%) Striped Catfish Pangasianodon hypophthalmus and 13 (29%) giant river prawns Macrobrachium rosenbergii. Antibiotics were used by farmers of tilapia and Striped Catfish (84% and 69% of farmers, respectively), but not by any of the prawn farmers. Most farmers (72%) used antibiotics for around 3 d when treating diseases, depending on the farmers' economic means and whether the fish recovered, as judged by the farmer. If farmers perceived that the antibiotic treatment had failed, the most common response was to change to another type of antibiotic. Some farmers also used antibiotics in the absence of clinical symptoms as a preventive measure. In the absence of rapid, cost-effective diagnostics, the likelihood for the incorrect use of antibiotics is high, which has implications for antibiotic resistance. Moreover, the sequential use of different antibiotics following therapeutic failure is a risk factor for the emergence of resistance. All farmers that were surveyed were aware of the risks associated with antibiotic use. This may lead to successful intervention toward reduced antibiotic use in freshwater fish farming in Vietnam., (© 2019 The Authors. Journal of Aquatic Animal Health published by Wiley Periodicals, Inc. on behalf of American Fisheries Society.)

Intraguild (IG) predation and interspecific competition may affect the settlement and success of species in their habitats. Using data on forest-dwelling hawks from Finland, we addressed the impact of an IG predator, the northern goshawk Accipiter gentilis (goshawk), on the breeding of an IG prey, the common buzzard Buteo buteo. We hypothesized that the subordinate common buzzard avoids breeding in the proximity of goshawks and that interspecific competitors, mainly Strix owls, may also disturb common buzzards by competing for nests and food. Our results show that common buzzards more frequently occupied territories with a low IG predation threat and with no interspecific competitors. We also observed that common buzzards avoided territories with high levels of grouse, the main food of goshawks, possibly due to a risk of IG predation since abundant grouse can attract goshawks. High levels of small rodents attracted interspecific competitors to common buzzard territories and created a situation where there was not only an abundance of food but also an abundance of competitors for the food. These results suggest interplay between top-down and bottom-up processes which influence the interactions between avian predator species. We conclude that the common buzzard needs to balance the risks of IG predation and interference competition with the availability of its own resources. The presence of other predators associated with high food levels may impede a subordinate predator taking full advantage of the available food. Based on our results, it appears that interspecific interactions with dominant predators have the potential to influence the distribution pattern of subordinate predators.

Habitat loss causes population declines, but the mechanisms are rarely known. In the European Boreal Zone, loss of old forest due to intensive forestry is suspected to cause declines in forest-dwelling raptors by reducing their breeding performance. We studied the boreal breeding habitat and habitat-associated breeding performance of the northern goshawk (Accipiter gentilis), common buzzard (Buteo buteo) and European honey buzzard (Pernis apivorus). We combined long-term Finnish bird-of-prey data with multi-source national forest inventory data at various distances (100-4000 m) around the hawk nests. We found that breeding success of the goshawk was best explained by the habitat within a 2000-m radius around the nests; breeding was more successful with increasing proportions of old spruce forest and water, and decreasing proportions of young thinning forest. None of the habitat variables affected significantly the breeding success of the common buzzard or the honey buzzard, or the brood size of any of the species. The amount of old spruce forest decreased both around goshawk and common buzzard nests and throughout southern Finland in 1992-2010. In contrast, the area of young forest increased in southern Finland but not around hawk nests. We emphasize the importance of studying habitats at several spatial and temporal scales to determine the relevant species-specific scale and to detect environmental changes. Further effort is needed to reconcile the socioeconomic and ecological functions of forests and habitat requirements of old forest specialists.

Background: In vitro findings have indicated that the novel anxiolytic drug, deramciclane, is an inhibitor of the cytochrome P(450) (CYP) 2D6 enzyme and co-administration of deramciclane and the CYP2D6 probe drug desipramine is possible in clinical practice., Objective: To evaluate the effects of deramciclane on CYP2D6 activity as measured by desipramine pharmacokinetics and pharmacodynamics using paroxetine as a positive control for CYP2D6 inhibition., Methods: Fifteen healthy subjects received either 60 mg deramciclane, 20 mg paroxetine or matched placebo for 8 days in randomized order in this double-blind, cross-over study. On day 8 of each study phase, the subjects received a 100-mg single dose of desipramine. Desipramine and its CYP2D6-dependent metabolite, 2-OH-desipramine, concentrations were measured for 240 h. Measurement of secretion of saliva, Visual Analogue Scale assessment of dryness of mouth and tiredness were carried out on day 7 and day 8 to assess the pharmacodynamic consequences of deramciclane or paroxetine co-administration with desipramine., Results: Repeated administration of deramciclane doubled the AUC of desipramine ( P<0.001), while paroxetine caused a 4.8-fold increase in the AUC of desipramine ( P<0.001). Significant correlations were observed with paroxetine (r(s)=0.84, P<0.001) and deramciclane (r(s)=0.51, P=0.0498) concentrations and the magnitude of increase of desipramine AUC. Both deramciclane and paroxetine decreased the formation of 2-OH-desipramine in the first-pass phase. The AUC ratio of 2-OH-desipramine/desipramine was decreased by 39% ( P<0.001) by deramciclane and by 74% ( P<0.001) by paroxetine. There were no changes in the secretion of saliva during co-administration of desipramine with deramciclane compared with placebo., Conclusion: Although deramciclane seems to be a weaker inhibitor of CYP2D6 than paroxetine, dose adjustment of drugs metabolized by CYP2D6 may be needed when used concomitantly with deramciclane.