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Hexabromocyclododecane (HBCD) is a ubiquitous environmental contaminant of current concern despite its global ban in 2013 due to its characteristics as a persistent organic pollutant. While the toxicity of HBDC in vertebrates has been extensively studied, the specific molecular mechanisms underlying its toxicity in fish are not fully understood to date. Therefore, the aim of this work was to determine the in vitro cytotoxicity of HBCD in the fathead minnow (Pimephales promelas) using liver explants, and to investigate the molecular mechanisms underlying these effects. Explants were incubated with nine different concentrations of HBCD (0.00032, 0.0016, 0.008, 0.04, 0.2, 1, 5, 25 and 125 mg HBCD/L) for 6 and 24 h, and cytotoxicity was tested by using the Lactate Dehydrogenase (LDH) assay. The expression of genes with a key role in the regulation of apoptosis, oxidative stress, cryoprotective responses to reactive oxygen species (ROS), and xenobiotic metabolism was also measured in liver explants after exposure st all HBCD concentrations tested after 6 h but remained unaltered after 24 h. Overall, we demonstrated that the cytotoxic effect of HBCD in fathead minnow liver explant was not proportional to its concentration in the culture media. Cytotoxicity was highly dynamic and did not follow a typical concentration-response pattern, complicating its toxicological characterization.Antimicrobial resistance is a worldwide issue whereby a more prudent use of medications is needed, especially for those antimicrobials (AM) classified as 'highest priority critically important antimicrobials' (HPCIAs) which are likely contributors to the development of resistance. So far, data on antimicrobial use (AMU) in EU are mainly reported at sales level while information on real use, mostly in beef production, is poor. The most reliable indicator to measure AMU is the treatment incidence (TI100) calculated by using the Defined Daily Dose Animal (DDDA) as stated by the European Medicines Agency (EMA). Although Italy ranks second among EU countries with regard to the AM sales in livestock production, data on AMU of the Italian beef production is still lacking, whereby the aim of this study was to provide information on the current scenario of AMU in Italian beef cattle. Data were collected from January 2016 to April 2019 from specialized beef fattening farms located in the north of Italy yielding a finaltion of HPCIAs use. This shows how overall knowledge on where efforts need to be optimized is important to develop targeted strategies for a more responsible AM stewardship. Results of the current study may also contribute to define national and EU benchmark criteria for AMU, as a comparison with studies carried out in other countries or on other food-producing sectors is still challenging to achieve.Although attentional impairments (particularly cognitive slowing) are frequent in Parkinson's disease (PD), the mechanisms underlying these phenomena have not been fully characterized. The MRI-compatible version of the Symbol Digit Modalities Test (SDMT) has been applied to healthy individuals but not previously to patients with PD. We sought to assess functional changes in brain activation patterns associated with cognitive slowing in PD. Eighteen patients with PD and 11 matched healthy controls (HCs) were enrolled. High-resolution three-dimensional T1-weighted images and blood-oxygen-level-dependent images were acquired during the SDMT. SDMT-related brain networks for the HC and PD groups were extracted from one-sample T-test maps. In each hemisphere, correlated regions were identified by selecting 120 voxels around the peak of each significant cluster (puncorrected less then 0.001). Regions of interest were then analyzed. When performing the SDMT, both groups displayed activation in the frontal, parietal and occipital regions known to be involved in attention. In the PD group, activation was lower in several parts of the cerebellum, left and right occipital cortices, and right supramarginal gyrus. In eight of these regions, fMRI activation was positively correlated with performance in the SDMT task. Our results suggest that the right supramarginal gyrus (an important interface for information integration), the cerebellum, and the left and right occipital cortices are involved in cognitive slowing in PD. A lower level of brain activation was associated with greater cognitive impairment.The purpose of this study was to investigate the effects of (-)-stepholidine (SPD), a compound with dopamine D1 partial agonist and D2/D3 antagonist properties, on the development and expression of cocaine conditioned place preference (CPP). Subjects (N = 65; male Long Evans rats) were tested using a CPP procedure consisting of 3 phases (1) a 15-min pre-exposure session where animals could explore each compartment freely, (2) eight 30-min conditioning sessions where animals were restricted to one side or the other with cocaine (10 mg/kg) or saline, respectively, on alternating days and (3) a 15-minute preference test session where animals could explore each compartment freely. To test the effects of SPD on expression of cocaine CPP, rats were administered vehicle (distilled water with 20 % DMSO), 10, 15 or 20 mg/kg SPD (intraperitoneally) 30 min prior to the test session. We found that 20 mg/kg of SPD significantly blocked the expression of cocaine CPP. To test the effects of SPD on the development of CPP, 0 (vehicle), 10, 15 or 20mg/kg SPD were administered 30 min prior to each cocaine conditioning session and vehicle before each saline conditioning session; no treatment was given prior to the test session. A preference test showed that each SPD group maintained a CPP similar to the vehicle group. click here These data indicate that SPD can block the expression of a cocaine CPP but has no effect on its development, suggesting that it inhibits the effects of cocaine cues on cocaine incentive motivated behavior. These results suggest that SPD may be a potential treatment for cue-driven aspects of cocaine use disorder.Spinal cord injury (SCI) causes loss of locomotor function and chronic neuropathic pain (NeP). Hematogenous macrophages and activated microglia are key monocytic lineage cell types in the response to SCI, and each has M1- and M2-phenotypes. To understand the roles of these cells in neuronal regeneration and chronic NeP after SCI, differences in distribution and phenotypes of activated microglia and infiltrated macrophages after SCI were examined at the injured site and the lumbar enlargement, as a remote region. Chimeric mice were used for differentiating activated microglia from hematogenous macrophages. The prevalences of activated microglia and infiltrating macrophages increased at day 14 after SCI, at the time of most severe pain hypersensitivity, with mainly M1-type hematogenous macrophages at the injured site and M2-type activated microglia at the lumbar enlargement. Peak expression of TNF-α, an M1-induced cytokine, occurred on day 4 post-SCI at the injured site, but not until day 14 at the lumbar enlargement.