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Treatment with L-3,4-dihydroxyphenylalanine (L-Dopa) compensates for decreased striatal dopamine (DA) levels and reduces Parkinson's disease (PD) symptoms. However, during disease progression, L-Dopa-induced dyskinesia (LID) develops virtually in all PD patients, making the control of PD symptoms difficult. Thus, understanding the mechanisms underlying LID and the control of these motor abnormalities is a major issue in the care of PD patients. From experimental and clinical studies, a complex cascade of molecular and cellular events emerges, but the primary determinants of LID are still unclear. Here, with a translational approach, including four animal models and a wide cohort of PD patients, we show that striatal DA denervation is the major causal factor for the emergence of LID, while α-synuclein aggregates do not seem to play a significant role. Our data also support the concept that maladaptive basal ganglia plasticity is the main pathophysiological mechanism underlying LID., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Real lindane landfill leachate (HCH-LL) is characterised by high chlorinated organic compounds concentrations (primarily hexachlorocyclohexane (HCH) isomers and degradation products generated during more than 40 years of ageing), posing environmental and human health risks. In this work, the co-treatment of real HCH-LL (pre-treated via electro-oxidation (EO)) and urban wastewater using an activated sludge process operated in an anoxic/oxic sequencing batch (A/O-SBR) mode was investigated. EO tests were conducted employing either a boron-doped diamond (BDD) anode or a dimensionally stable anode (DSA), resulting in effective HCH isomers removal (>93 % after 20 Ah/L). Chloride-derived by-products (CDBPs) such as free chlorine (up to 828 mg Cl 2 /L), chlorate (up to 972 mg/L) (formed with EO (DSA)) and perchlorate (up to 1830 mg/L) (with EO (BDD)) persisted after the treatment. EO (DSA) resulted in inhibitory effects (up to 100 % respiration inhibition) on the biological process. Conversely, EO (BDD) negligibly affected biological respiration (up to 20 % less than without pre-treatment), while perchlorate bio-reduction by A/O-SBR was poor (28 %). Acetate addition in pre-treated HCH-LL for perchlorate bio-reduction allowed to achieve simultaneous contaminants removal (> 99 %) and CDBPs reduction (up to 100 %). Biodegradation and bio-adsorption tests without pre-treatment showed partial HCH isomers removal (about 40 %) and poor bio-adsorption., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The effects of solar photo-Fenton (SPF) process mediated by the iron chelate Fe 3+ imminodisuccinic acid (Fe:IDS) on both the inactivation of seven relevant pathogens and the potential for antibiotic resistance transfer (degradation of antibiotic resistance genes (ARGs) and after treatment regrowth), in real secondary treated urban wastewater, were investigated for the first time. A comparison with results obtained by sunlight/H 2 O 2 process and Fe 3+ ethylenediaminedisuccinic acid (Fe:EDDS) SPF was also carried out. ARGs were quantified by polymerase chain reaction (PCR) in samples before and after (3 h) the treatment. The persistence of the selected pathogens and ARGs was also evaluated in regrowth tests (72 h) under environmentally mimicking conditions. Fe:IDS SPF resulted to be more effective (from 1.4 log removal for Staphylococcus spp. to 4.3 log removal for Escherichia coli) than Fe:EDDS SPF (from 0.8 log removal for Pseudomonas aeruginosa to 2.0 log removal for Total coliphages) and sunlight/H 2 O 2 (from 1.2 log removal for Clostridium perfringens to 3.3 log removal for E. coli) processes for the seven pathogens investigated. Potential pathogens regrowth was also severely affected, as no substantial regrowth was observed, both in presence and absence of catalase. A similar trend was observed for ARGs removal too (until 0.001 fold change expression for qnrS after 3 h). However, a poor effect and a slight increase in fold change was observed after treatment especially for gyrA, mefA and intl1. Overall, the effect of the investigated processes on ARGs was found to be ARG dependent. Noteworthy, coliphages can regrow after sunlight/H 2 O 2 treatment unlike SPF processes, increasing the risk of antibiotic resistance transfer by transduction mechanism. In conclusion, Fe:IDS SPF is an attractive solution for tertiary treatment of urban wastewater in small wastewater treatment plants as it can provide effective disinfection and a higher protection against antibiotic resistance transfer than the other investigated processes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Excessive glutamatergic transmission in the striatum is implicated in Parkinson's disease (PD) progression. Astrocytes maintain glutamate homeostasis, protecting from excitotoxicity through the glutamate-aspartate transporter (GLAST), whose alterations have been reported in PD. Noninvasive brain stimulation using intermittent theta-burst stimulation (iTBS) acts on striatal neurons and glia, inducing neuromodulatory effects and functional recovery in experimental parkinsonism., Objective: Because PD is associated with altered astrocyte function, we hypothesized that acute iTBS, known to rescue striatal glutamatergic transmission, exerts regional- and cell-specific effects through modulation of glial functions., Methods: 6-Hydroxydopamine-lesioned rats were exposed to acute iTBS, and the areas predicted to be more responsive by a biophysical, hyper-realistic computational model that faithfully reconstructs the experimental setting were analyzed. The effects of iTBS on glial cells and motor behavior were evaluated by molecular and morphological analyses, and CatWalk and Stepping test, respectively., Results: As predicted by the model, the hippocampus, cerebellum, and striatum displayed a marked c-FOS activation after iTBS, with the striatum showing specific morphological and molecular changes in the astrocytes, decreased phospho-CREB levels, and recovery of GLAST. Striatal-dependent motor performances were also significantly improved., Conclusion: These data uncover an unknown iTBS effect on astrocytes, advancing the understanding of the complex mechanisms involved in TMS-mediated functional recovery. Data on numerical dosimetry, obtained with a degree of anatomical details never before considered and validated by the biological findings, provide a framework to predict the electric-field induced in different specific brain areas and associate it with functional and molecular changes. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Landfill leachate (LL) represents a very complex effluent difficult to treat and to manage which usually requires a chemical pre-treatment. In this study, response surface methodology (RSM) was used to identify the optimum operating conditions of the Fenton process as a pre-treatment of LL in order to reduce the high organic content and simultaneously optimize the BOD 5 :TN:TP ratio. The dosages of Fenton process reagents, namely Fe 2+ and H 2 O 2 , were used as variables for the implementation of RSM. Chemical oxygen demand (COD), five-days biochemical oxygen demand (BOD 5 ), total nitrogen (TN), total phosphorus (TP) removals (and simultaneously BOD 5 :TN:TP ratio), sludge-to-iron ratio (SIR) and organic removal-to-sludge ratio (ORSR) were selected as target responses. This approach considered the SIR and ORSR parameters which are a useful tool for assessing sludge formation during the process along with organic matter removal. The variables (H 2 O 2 and Fe 2+ concentrations) significantly affected the responses, as the role of oxidation mechanism is dominant with respect to coagulation one. The pH for the process was fixed to 2.8 while the treatment time was set to 2 h. The optimum operational conditions obtained by perturbation and 3D surface plot, were found to be 4262 mg/L and 5104 mg/L for Fe 2+ and H 2 O 2 , respectively (H 2 O 2 /Fe 2+ molar ratio = 2) with COD, BOD 5 , TN and TP removals of 70%, 67%, 84% and 96% respectively, while SIR and ORSR final values were 1.15 L/mol and 33.79 g/L respectively, in accordance with models-predicted values. Moreover, the initial unbalanced BOD 5 :TN:TP ratio (9:1:1) was significantly improved (100:6:1), making the effluent suitable for a subsequent biological treatment. The investigated approach allowed to optimize the removal of organic load and nutrients as well as to minimize the sludge formation in Fenton process, providing a useful tool for the operation and management of LL pre-treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Intensive physical activity improves motor functions in patients with Parkinson's disease (PD) at early stages. However, the mechanisms underlying the beneficial effects of exercise on PD-associated neuronal alterations have not been fully clarified yet. Here, we tested the hypothesis that an intensive treadmill training program rescues alterations in striatal plasticity and early motor and cognitive deficits in rats receiving an intrastriatal injection of alpha-synuclein (α-syn) preformed fibrils. Improved motor control and visuospatial learning in active animals were associated with a recovery of dendritic spine density alterations and a lasting rescue of a physiological corticostriatal long-term potentiation (LTP). Pharmacological analyses of LTP show that modulations of N -methyl-d-aspartate receptors bearing GluN2B subunits and tropomyosin receptor kinase B, the main brain-derived neurotrophic factor receptor, are involved in these beneficial effects. We demonstrate that intensive exercise training has effects on the early plastic alterations induced by α-syn aggregates and reduces the spread of toxic α-syn species to other vulnerable brain areas.

The sustainable and green treatment of landfill leachate (LL), produced by municipal solid waste, represents one of the most relevant challenges in the integrated waste management systems. Accordingly, in this work a green solution was investigated by coupling an innovative hybrid constructed wetland (HCW) to a solar photo-Fenton (SPF) process. A multiple layers HCW pilot plant including different medium substrates (sand, solid compost and carriers) and plant species (Phragmites australis, Arundo donax and A. plinii) was designed. The HCW was functionalised with compost tea solution to simultaneously provide high nutrient content for plants and increase the microorganism biodiversity. Process efficiency was investigated using different real LLs (young and mature) in terms of chemical oxygen demand (COD), nitrogen compounds, chlorides and metals. Removals in the range 75-95% were observed for all the parameters after ten days of leachate recirculation in the pilot plant. Subsequently, the SPF process was carried out in a raceway pond reactor (RPR) as polishing step, significantly improving COD removal (further 49%). HCW combined with SPF in RPR would allow to meet the corresponding limits according to the final use/fate of the effluent by modulating the main parameters of the process., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The impact of Fenton oxidation (FO) and Air stripping (AS) pre-treatments on the bacterial community of a biological activated sludge (B-AS) process for the co-treatment of mature landfill leachate (MLL) and urban wastewater (UWW) was assessed. In this work high-throughput sequencing was used to identify changes in the composition of the bacterial communities when exposed to different landfill leachate's pre-treatments. The combination of FO and AS to increase biodegradability (BOD 5 /COD) and reduce ammonia concentration (NH 3 ) respectively, allowed to successfully operate the B-AS and effectively treat MLL. In particular, BOD 5 /COD resulted to be the key factor for bacterial community shifting. The microbiological community of the B-AS, mainly composed by the phylum Bacteroidota (Saprospiraceae, PHOS-HE51, Chitinophagaceae) after FO pre-treatment, shifted to Pseudomonadota (Caulobacteraceae and Hyphomicrobiaceae) when FO was not used. At the same time a drastic reduction in BOD 5 removal was observed (90%-58%). On the other hand, high NH 3 concentration affected the abundance of the family Saprospiraceae, known to play a key role in the degradation of complex organic compounds in B-AS. The results obtained suggest that a suitable combination of pre-treatments can reduce the negative effect of MLL on the B-AS process, reducing the pressure on autochthonous bacteria and therefore the acclimatization time of the biological process., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

S100B is an astrocytic protein behaving at high concentration as a damage-associated molecular pattern molecule. A direct correlation between the increased amount of S100B and inflammatory processes has been demonstrated, and in particular, the inhibitor of S100B activity pentamidine has been shown to ameliorate clinical scores and neuropathologic-biomolecular parameters in the relapsing-remitting experimental autoimmune encephalomyelitis mouse model of multiple sclerosis. This study investigates the effect of arundic acid (AA), a known inhibitor of astrocytic S100B synthesis, in the chronic experimental autoimmune encephalomyelitis, which is another mouse model of multiple sclerosis usually studied. By the daily evaluation of clinical scores and neuropathologic-molecular analysis performed in the spinal cord, we observed that the AA-treated group showed lower severity compared to the vehicle-treated mice, particularly in the early phase of disease onset. We also observed a significant reduction of astrocytosis, demyelination, immune infiltrates, proinflammatory cytokines expression and enzymatic oxidative reactivity in the AA-treated group. Overall, our results reinforce the involvement of S100B in the development of animal models of multiple sclerosis and propose AA targeting the S100B protein as a focused potential drug to be considered for multiple sclerosis treatment.

The efficiency of a new Advanced Oxidation Process (AOP), namely the photo Fenton like process UV-C/H 2 O 2 /IDS-Cu, in removing determinants of antibiotic resistance and pathogenic bacteria was compared to a consolidated AOP (namely UV-C/H 2 O 2 ) in a secondary treated municipal WasteWater (WW). A reductionist experimental laboratory-based approach was applied on real WW and the parameters were collected by an alternative integrated approach using (i) flow cytometry to enumerate bacteria and test for the fitness of the bacterial communities and (ii) molecular analyses to define the community composition (16S rRNA amplicon sequencing) and the abundances of Antibiotic Resistance Genes (ARGs) and of the class 1 integron (intI1 gene) (by quantitative PCR). The same approach was applied also to post-treatment regrowth tests (24 h) to define the potential persistence of the tested parameters. These experiments were performed in both, human pathogens favorable conditions (HPC, in rich medium and 37°C) and in environmental mimicking conditions (EMC, original WW and 20°C). UV-C/H 2 O 2 /IDS-Cu process resulted to be more effective than the UV-C/H 2 O 2 in inactivating bacterial cells in the EMC post-treatment regrowth experiments. Both AOPs were efficiently abating potential human pathogenic bacteria and ARGs in the HPC regrowth experiments, although this trend could not be detected in the measurements taken immediately after the disinfection. In comparison with the UV-C/H 2 O 2 , the UV-C/H 2 O 2 /IDS-Cu process did not apparently offer significant improvements in the abatement of the tested parameters in the WW effluent but, by evaluating the results of the regrowth experiments it was possible to extrapolate more complex trends, suggesting contrasting efficiencies visible only after a few hours. This study offers a detailed view on the abatement efficiency of microbiological/genetic parameters for the UV-C/H 2 O 2 /IDS-Cu process, calling for technical adjustments for this very promising technology. At the same time, our results clearly demonstrated the inadequacy of currently applied methodologies in the evaluation of specific parameters (e.g. determinants of antibiotic resistance and pathogenic bacteria) in WW., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interest. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)