257 research outputs found
Genotoxicological Characterization of (+/-)cis-4,4 '-DMAR and (+/-)trans-4,4 '-DMAR and Their Association
The novel psychoactive substance (NPS) 4-Methyl-5-(4-methylphenyl)-4,5-dihydroxazol-2-amine (4,4'-DMAR) shows psychostimulant activity. Data on the acute toxicity of 4,4'-DMAR are becoming increasingly available, yet the long-term effects are still almost unknown. In particular, no data on genotoxicity are available. Therefore, the aim of the present study was to evaluate its genotoxic potential using the "In Vitro Mammalian Cell Micronucleus Test" (MNvit) on (+/-)cis-4,4'-DMAR and (+/-)trans-4,4'-DMAR and their associations. The analyses were conducted in vitro on human TK6 cells. To select suitable concentrations for MNvit, we preliminarily evaluated cytotoxicity and apoptosis. All endpoints were analysed by flow cytometry. The results reveal the two racemates' opposite behaviours: (+/-)cis-4,4'-DMAR shows a statistically significant increase in micronuclei (MNi) frequency that (+/-)trans-4,4'-DMAR is completely incapable of. This contrast confirms the well-known possibility of observing opposite biological effects of the cis- and trans- isomers of a compound, and it highlights the importance of testing single NPSs that show even small differences in structure or conformation. The genotoxic capacity demonstrated stresses an additional alarming toxicological concern related to this NPS. Moreover, the co-treatments indicate that consuming both racemates will magnify the genotoxic effect, an aspect to consider given the unpredictability of illicit drug composition
Machine-learning blends of geomorphic descriptors: value and limitations for flood hazard assessment across large floodplains
Recent literature shows several examples of simplified approaches that perform flood hazard (FH) assessment and mapping across large geographical areas on the basis of fast-computing geomorphic descriptors. These approaches may consider a single index (univariate) or use a set of indices simultaneously (multivariate). What is the potential and accuracy of multivariate approaches relative to univariate ones? Can we effectively use these methods for extrapolation purposes, i.e., FH assessment outside the region used for setting up the model? Our study addresses these open problems by considering two separate issues: (1) mapping flood-prone areas and (2) predicting the expected water depth for a given inundation scenario. We blend seven geomorphic descriptors through decision tree models trained on target FH maps, referring to a large study area (⌠105 km2). We discuss the potential of multivariate approaches relative to the performance of a selected univariate model and on the basis of multiple extrapolation experiments, where models are tested outside their training region. Our results show that multivariate approaches may (a) significantly enhance flood-prone area delineation (accuracy: 92%) relative to univariate ones (accuracy: 84%), (b) provide accurate predictions of expected inundation depths (determination coefficient âŒ0.7), and (c) produce encouraging results in extrapolation
Mindsets and Failures : Neural Differences in Reactions to Mistakes among 2nd Grade Finnish Girls
Mindsets have been identified as an important factor in explaining learning differences among students. Growth mindset students have been shown to recover from mistakes easier than fixed mindset students, and recent neuroscientific research has shown differences in the brainâs event-related potentials to errors in fixed and growth mindset participants. The purpose of this study was to examine and evaluate these differences in the Finnish elementary school context. To achieve this, event-related potentials of five fixed and five growth mindset 8-9-year-old female students were recorded during a go/no-go task. Differences between the two groups emerged, however, they were different from the results of some previous studies in the field. These findings are discussed in the light of earlier neuroscientific research related to mindsets, including limitations and suggestions for future research in the field.Peer reviewe
Comprehensive evaluation of the pharmacological and toxicological effects of Îł-valerolactone as compared to Îł-hydroxybutyric acid: Insights from in vivo and in silico models
Î-valerolactone (GVL), marketed online as "Tranquilli-G" and "excellent Valium", is used as a legal substitute for Îł-hydroxybutyric acid (GHB); however, until now, GVL has only been connected to one Drug-Facilitated Sexual Assault (DFSA) case. Moreover, the pharmaco-toxicological effects of GVL are poorly studied. The aim of this study was to investigate the 1) in vivo effects of gavage administration of GVL (100-3000âmg/kg) on neurological (myoclonia, convulsions), sensorimotor (visual, acoustic, and overall tactile) responses, righting reflex, thermoregulation, motor activity (bar, drag, and accelerod test) and cardiorespiratory changes (heart rate, breath rate, oxygen saturation, and pulse distension) in CD-1 male mice and the 2) in silico ADMET profile of GVL in comparison to GHB and the open active form Îł-hydroxyvaleric acid (GHV). The present study demonstrates that GVL inhibits, in a dose-dependent manner, sensorimotor and motor responses and induces cardiorespiratory depression (at a dose of 3000âmg/kg) in mice. The determination of the ED50 in sensorimotor and motor responses revealed that GVL is about 4-5 times less potent than GHB. In silico prediction of ADMET profiles revealed toxicokinetic similarities between GHB and GHV, and differences with GVL. These results suggest that GVL could be used as a substitute for GHB and should be added to forensic toxicology screenings
Effectiveness of Golimumab as Second Anti-TNFα Drug in Patients with Rheumatoid Arthritis, Psoriatic Arthritis and Axial Spondyloarthritis in Italy: GO-BEYOND, a Prospective Real-World Observational Study
In this prospective observational study, data were collected from 34 rheumatology clinics in Italy in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) who started golimumab (GLM) as a second anti-TNFα drug. The primary objective was to evaluate the effectiveness of GLM after 6 months. Changes in quality of life using the EQ-5D-5L were also assessed. A total of 194 patients aged 53.2 ± 12 years started GLM as a second anti-TNF drug: 39 (20.1%) with RA, 91 (46.9%) with PsA and 64 (32.9%) with axSpA. After 6 months of GLM treatment, 68% of RA patients achieved low disease activity (LDA; DAS28-CRP †3.2), 31.9% of PsA patients achieved minimal disease activity and 32.5% of axSpA patients achieved LDA (ASDAS-CRP < 2.1). Good/moderate EULAR response was achieved in 61.9% and 73.8% of patients with RA and PsA, respectively, and 16% of axSpA patients achieved a 50% improvement in BASDAI. Across all indications, improvements in disease activity measures and EQ-5D-5L domains were observed over 6 months. The main reasons for GLM interruption were lack/loss of efficacy (7.2%) or adverse events (2%). This study confirms the effectiveness of GLM as a second-line anti-TNF for the treatment of RA, PsA and axSpA in a real-world setting in Italy
NEMA NU 4-2008 and in vivo imaging performance of RAYCAN trans-PET/CT X5 small animal imaging system
The RAYCAN Trans-PET/CT X5 is a preclinical positron emission tomography and computed tomography (PET/CT) system intended for in vivo imaging of rats and mice, featuring all-digital readout electronics for PET data acquisition.The National Electrical Manufacturers Association (NEMA) NU 4-2008 performance evaluation was conducted on the RAYCAN Trans-PET/CT X5 in addition to assessing in vivo imaging performance of the system on live animals. The performance characteristics of the system were evaluated, including system spatial resolution, count rate performance, sensitivity and image quality. The system imaging performance is assessed in dynamic in vivo PET imaging.The system resolution defined as full width half maximum (FWHM) was 2.07 mm, 2.11 mm and 1.31 mm for the tangential, radial and axial resolution, respectively, at the center of the field of view. The peak noise equivalent count rate (NECR) values measured were 61 kcps at 0.19 MBq ml(-1) for the rat size phantom and 126 kcps at 1.53 MBq ml(-1) for the mouse size phantom. Scatter fractions were 24% and 14% for the rat and mouse phantom. The measured peak sensitivity of the system was 1.70%. Image quality in static imaging was deemed sufficient based on the image quality phantom study, with average activity concentration of 155 +/- 8.6 kBq ml(-1) and image uniformity of 5.57% when using two-dimensional filtered backprojection algorithm (2D-FBP). Rods in the image quality phantom were visualized easily up to 2 mm in size. In dynamic in vivo PET imaging, time-activity-curves from several regions were successfully measured, characterizing the radioactivity distribution in myocardial blood pool, liver, left ventricle and the lung.In conclusion, the RAYCAN Trans-PET/CT X5 system can be considered a suitable option for basic imaging needs in preclinical imaging
The invisible plan: how English teachers develop their expertise and the special place of adapting the skills of lesson planning
This paper analyses how English teachers learn to become expert designers of learning and why sharing that expertise is increasingly vital. Its conceptual framework is the widely recognised, empirically tested, five-stage developmental Dreyfus model of skill acquisition, exemplifying the development of teacher expertise, constituted by the âmilestoneâ [m] and âtransitoryâ [t] phases connecting with the five stages of: Novice [m], Advanced Beginner [t], Competent [m], Proficient [t] and Expert [m]. Teacher planning is analysed as one key tacit or non-tangible component of developing expertise. Focusing specifically on English teachers as key participants in this pioneer teacher cognition study, the defining characteristics of milestone stages of expertise development are explored with specific attention to the remarkably under-researched area of planning. We introduce three new categories, defining modes of planning: (i) visible practical planning, (ii) external reflective planning and (iii) internal reflective planning, demonstrating their role in teacher development through the Dreyfus five stages. English is a subject which suffers from frequent disruptive changes to curriculum and assessment: new learning designs are constantly demanded, making planning an ongoing challenge. The implications for practice include the importance of an explicit understanding of how teachersâ planning moves through the three phases from the very âvisibleâ novice phase to the internal relatively âautomaticâ competent teacher and finally the seemingly âinvisibleâ expert phase. Further research is needed to explore how English teachers can share planning expertise between the three phases to improve teachersâ skills and student learning
Representations and concepts of professional ethos among Swiss religious education teacher trainers
Over the past two decades, the organisation of religious education classes in Switzerland has undergone profound reforms. Amid the increasing secularisation and pluralisation of the religious landscape, many cantons have introduced a compulsory course that falls under the responsibility of the state and is aimed at teaching basic knowledge about a variety of religions. These reforms have enabled a harmonisation of the syllabi for religious education across the country and have prompted the adaptation of teacher training programmes. Because of the many diverse social expectations surrounding these new courses and the diverse academic tra- ditions in the field of religious education, however, a unified conception of these courses is still absent. In this article, we discuss the ongoing construction of religious education teachersâ professional ethos within this fluid context. In particular, we discuss the perspective of teacher trainers on pragmatic questions concerning religious plurality and the place of teachersâ and pupilsâ personal (religious) experiences in the classroom, and pay attention to different representations of âreligionâ and distinct ideas regarding the purpose of these courses as they have a major impact on the professional attitudes expected from teachers.
Keywords: professional ethos; teacher trainers; Switzerland; concepts of religion; impartialit
Pharmaco-toxicological effects of the novel tryptamine hallucinogen 5-MeO-MiPT on motor, sensorimotor, physiological, and cardiorespiratory parameters in miceâfrom a human poisoning case to the preclinical evidence
Rationale: The 5-methoxy-N-methyl-N-isopropyltryptamine (5-MeO-MiPT, known online as âMoxyâ) is a new psychedelic tryptamine first identified on Italian national territory in 2014. Its hallucinogen effects are broadly well-known; however, only few information is available regarding its pharmaco-toxicological effects. Objectives: Following the seizure of this new psychoactive substances by the Arm of Carabinieri and the occurrence of a human intoxication case, in the current study we had the aim to characterize the in vivo acute effects of systemic administration of 5-MeO-MiPT (0.01â30Â mg/kg i.p.) on sensorimotor (visual, acoustic, and overall tactile) responses, thermoregulation, and stimulated motor activity (drag and accelerod test) in CD-1 male mice. We also evaluated variation on sensory gating (PPI, prepulse inhibition; 0.01â10Â mg/kg i.p.) and on cardiorespiratory parameters (MouseOx and BP-2000; 30Â mg/kg i.p.). Lastly, we investigated the in silico ADMET (absorption, distribution, metabolism, excretion, toxicity) profile of 5-MeO-MiPT compared to 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) and N,N-dimethyltryptamine (DMT). Results: This study demonstrates that 5-MeO-MiPT dose-dependently inhibits sensorimotor and PPI responses and, at high doses, induces impairment of the stimulated motor activity and cardiorespiratory changes in mice. In silico prediction shows that the 5-MeO-MiPT toxicokinetic profile shares similarities with 5-MeO-DIPT and DMT and highlights a cytochrome risk associated with this compound. Conclusions: Consumption of 5-MeO-MiPT can affect the ability to perform activities and pose a risk to human health status, as the correspondence between the effects induced in mice and the symptoms occurred in the intoxication case suggests. However, our findings suggest that 5-MeO-MiPT should not be excluded from research in the psychiatric therapy field
- âŠ