Nitrous oxide and hypnotherapy in paediatric dentistry.

AIM: Patient compliance is of paramount importance for proper dental treatment, which can be difficult to achieve in children due to anxiety and fear, hindering the therapeutic procedure. In addition to well-known sedation methods (pharmacological and nitrous oxide), further methods of approach are being tested, such as hypnotherapy. MATERIALS: The sample consisted of 150 children (90 males, 60 females). Paper questionnaires, frequency meter, nitrous oxide dispenser in association with the use of the television were exploited. At the end of treatment, subjective pain was assessed using the VAS scale, while objective pain was assessed using the FLACC scale and heart rate. This made it possible to compare two experimental groups, one treated with nitrous oxide, and the other with hypnotherapy. The control group was treated with classic behavioural approach techniques. The results obtained were analysed by SPSS Software (Statistical Package for Social Science, version 27) and the inferences between the results were calculated for confirmation. CONCLUSION: Hypnotherapy can be a valid substitute for nitrous oxide in paediatric dentistry.

Dim artificial light at night alters gene expression rhythms and growth in a key seagrass species (Posidonia oceanica).

Artificial light at night (ALAN) is a globally spreading anthropogenic stressor, affecting more than 20% of coastal habitats. The alteration of the natural light/darkness cycle is expected to impact the physiology of organisms by acting on the complex circuits termed as circadian rhythms. Our understanding of the impact of ALAN on marine organisms is lagging behind that of terrestrial ones, and effects on marine primary producers are almost unexplored. Here, we investigated the molecular and physiological response of the Mediterranean seagrass, Posidonia oceanica (L.) Delile, as model to evaluate the effect of ALAN on seagrass populations established in shallow waters, by taking advantage of a decreasing gradient of dim nocturnal light intensity (from < 0.01 to 4 lx) along the NW Mediterranean coastline. We first monitored the fluctuations of putative circadian-clock genes over a period of 24 h along the ALAN gradient. We then investigated whether key physiological processes, known to be synchronized with day length by the circadian rhythm, were also affected by ALAN. ALAN influenced the light signalling at dusk/night in P. oceanica, including that of shorter blue wavelengths, through the ELF3-LUX1-ZTL regulatory network, and suggested that the daily perturbation of internal clock orthologs in seagrass might have caused the recruitment of PoSEND33 and PoPSBS genes to mitigate the repercussions of a nocturnal stress on photosynthesis during the day. A long-lasting impairment of gene fluctuations in sites characterised by ALAN could explain the reduced growth of the seagrass leaves when these were transferred into controlled conditions and without lighting during the night. Our results highlight the potential contribution of ALAN to the global loss of seagrass meadows, posing questions about key interactions with a variety of other human-related stressors in urban areas, in order to develop more efficient strategies to globally preserve these coastal foundation species.

The connection between diverticulosis and colonic superficial neoplastic lesions in patients who underwent screening colonoscopy.

PURPOSE: If could be a potential pathophysiological connection between colonic diverticula and colonic superficial neoplastic lesions, beyond the shared risk factors, has been a subject of debate in the last years. This study tries to evaluate the association between diverticulosis and colonic neoplastic lesions. METHODS: This is a cross-sectional study including asymptomatic patients who underwent a screening colonoscopy (patients with a positive fecal occult blood test under the regional program of colorectal cancer (CRC) screening), surveillance after polypectomy resection, or familiarity (first-degree relatives) between 2020 and 2021 to evaluate the association between diverticula and colonic polyps. A multivariate analysis with multiple logistic regression and odds ratio (OR) to study the independent association between adenomas and adenocarcinomas was performed. RESULTS: One thousand five hundred one patients were included. A statistically significant association between adenomas or CRC alone and colonic diverticula was found (p = 0.045). On a multivariate analysis of demographic (age, gender) and clinical parameters (familiarity for diverticula and adenoma/CRC), only age was significantly associated with the development of colorectal adenomas or cancer (OR 1.05, 95% CI 1.03-1.07, p < 0.0001). CONCLUSIONS: This study showed a statistically significant association between diverticula and colonic adenomas. However, it is impossible to establish a cause-effect relationship due to the intrinsic characteristics of this study design. A study with a prospective design including both patients with diverticulosis and without colonic diverticula aimed at establishing the incidence of adenoma and CRC could help to answer this relevant clinical question, since a potential association could indicate the need for closer endoscopic surveillance.

Clowntherapy in paediatric dentistry: The psychological approach to the paediatric patient.

AIM: Anxiety towards dental treatments and visits in children are often cause for the avoidance and/or failure of the treatment itself, as well as a reason for stress in both the patient and the orthodontist. The aim of the research is to understand if the use of clown therapy in dental waiting rooms is efficient in bringing down the level of preoperative anxiety in paediatric dental patients. METHODS: Two psychometric tests were used: CFSS-DS (Dental Subscale of the Children's Fear Survey Schedule) and FIS (Facial Image Scale), after the translation of the original versions, to both the patients and their parents. The CFSS-DS is the most used instrument in order to assess dental fear in children, it is composed by 15 questions that outline situations which children and adolescents will have to face while on the dental chair. The FIS is a visual analogical scale that uses faces as indicators of anxiety. CONCLUSION: Clowntherapy proves to be an efficient non-pharmacological method to reduce anxiety and dental fear in paediatric patients, offeringa valid and practical support for paediatric dentists.

Hydrothermal carbonization of the wet fraction from mixed municipal solid waste: Hydrochar characteristics and energy balance.

Mixed municipal solid waste (MSW) may be pre-treated in a mechanical-biological treatment (MBT) plant to produce an exiting stream with improved combustible characteristics. The process also produces a second waste stream, which is generally separated on a size basis by industrial sieving equipment. It contains fractions with a high moisture content such as residual food waste, soiled paper and cardboard, and small fragments of other materials. Samples of this stream, collected at an existing plant, were characterized and processed by hydrothermal carbonization (HTC) at laboratory scale, at various temperatures (180, 200 and 220 °C), reaction times (1, 4 and 8 h) and solid to water ratios (0.15 and 0.07). The primary energy balance, on a hypothetical industrial scale, was performed. In brief, the results confirmed that the produced hydrochar was a brittle, hydrophobic, solid carbonaceous product which gave a better combustion performance as the residence time of the HTC process was increased. Moreover, the dewaterability of the carbonized waste was greatly improved when compared to raw, wet samples. The results of the primary energy balance confirmed that the energy contained in the produced hydrochar was higher than the energy consumption for the process itself, under all the HTC working conditions. The energy consumed in the process was in the range of 40-70 % of the energy content of the produced hydrochar.

Environmental Life Cycle Assessment of Hydrothermal Carbonization of Sewage Sludge and Its Products Valorization Pathways.

Abstract: This study is aimed at evaluating through Life Cycle Assessment (LCA) the environmental performances of an integrated system of an existing Water Resources Recovery Facility (WRRF) and a hypothetical hydrothermal carbonization (HTC) plant applied to the generated sewage sludge (SS). Beside the valorisation of the solid product (hydrochar, HC) as a fuel substituting lignite, the possibility to valorize also the liquid fraction (process water, PW) derived by the HTC, by anaerobic digestion to produce biogas, is here proposed and analysed. Additionally, phosphorus recovery from HC, prior its use, by acid leaching with nitric acid is also suggested and evaluated. Thus, four integrated scenarios, based on SS carbonization, are proposed and compared with the current SS treatment, based on composting outside of the WRRF (Benchmark scenario). The proposed scenarios, based on HTC, show improved performances with respect to the benchmark one, for thirteen of sixteen considered impact indicators. For the Climate Change (CC) indicator, the two HTC scenarios are able to reduce the impacts up to - 98%, with respect to the Benchmark. Further, the introduction of anaerobic digestion of PW proves to reduce impacts more than other configurations in eleven on sixteen impact categories. On the contrary, the introduction of phosphorus recovery process negatively affects the values for most of indicators. Thus, possible solutions to improve the integration of this process are outlined (e.g., the use of sulfuric acid instead of nitric one, or the application of a different ratio between solid and acidified solution during acid leaching of HC to recover phosphorus). Supplementary Information: The online version contains supplementary material available at 10.1007/s12649-022-01821-x.

Aspergillus fumigatus and aspergillosis: From basics to clinics.

The airborne fungus Aspergillus fumigatus poses a serious health threat to humans by causing numerous invasive infections and a notable mortality in humans, especially in immunocompromised patients. Mould-active azoles are the frontline therapeutics employed to treat aspergillosis. The global emergence of azole-resistant A. fumigatus isolates in clinic and environment, however, notoriously limits the therapeutic options of mould-active antifungals and potentially can be attributed to a mortality rate reaching up to 100 %. Although specific mutations in CYP 51A are the main cause of azole resistance, there is a new wave of azole-resistant isolates with wild-type CYP 51A genotype challenging the efficacy of the current diagnostic tools. Therefore, applications of whole-genome sequencing are increasingly gaining popularity to overcome such challenges. Prominent echinocandin tolerance, as well as liver and kidney toxicity posed by amphotericin B, necessitate a continuous quest for novel antifungal drugs to combat emerging azole-resistant A. fumigatus isolates. Animal models and the tools used for genetic engineering require further refinement to facilitate a better understanding about the resistance mechanisms, virulence, and immune reactions orchestrated against A. fumigatus. This review paper comprehensively discusses the current clinical challenges caused by A. fumigatus and provides insights on how to address them.

The Hannes hand prosthesis replicates the key biological properties of the human hand.

Replacing the human hand with artificial devices of equal capability and effectiveness is a long-standing challenge. Even the most advanced hand prostheses, which have several active degrees of freedom controlled by the electrical signals of the stump's residual muscles, do not achieve the complexity, dexterity, and adaptability of the human hand. Thus, prosthesis abandonment rate remains high due to poor embodiment. Here, we report a prosthetic hand called Hannes that incorporates key biomimetic properties that make this prosthesis uniquely similar to a human hand. By means of an holistic design approach and through extensive codevelopment work involving researchers, patients, orthopaedists, and industrial designers, our proposed device simultaneously achieves accurate anthropomorphism, biomimetic performance, and human-like grasping behavior that outperform what is required in the execution of activities of daily living (ADLs). To evaluate the effectiveness and usability of Hannes, pilot trials on amputees were performed. Tests and questionnaires were used before and after a period of about 2 weeks, in which amputees could autonomously use Hannes domestically to perform ADLs. Last, experiments were conducted to validate Hannes's high performance and the human likeness of its grasping behavior. Although Hannes's speed is still lower than that achieved by the human hand, our experiments showed improved performance compared with existing research or commercial devices.

Is the inferior occlusal plane a reliable anatomic landmark for inferior alveolar nerve block? A study on dry mandibles of Brazilian adults.

PURPOSE: To investigate the relationship between the mandibular foramen (MF) and the inferior occlusal plane (IOP) of anatomic specimens, in order to guide clinicians in the inferior alveolar nerve block (IANB). METHOD: Eighty-two dry mandibles (totally or partially toothed) of Brazilian adults were selected, totalizing 66 left and 66 right antimeres. A flat plate of rigid PVC plastic was placed on the occlusal surfaces of posterior teeth and pressure was then manually applied to simulate the IOP. Following, the perpendicular distance from the IOP to the lowest point of the MF was measured by the use of a digital caliper, adopting negative values inferiorly and positive values superiorly. RESULTS: Regarding the antimeres, the majority of the lowest limits of the MF was below the IOP (right: 86.4%, left: 81.8%) with a mean of -4.2mm (±4.8) in the right and -4.1mm (±4.8) in the left ones, without any statistical significance. Considering both sexes, no statistically significant difference was obtained between them. CONCLUSION: The IOP seems not to be a good anatomical landmark to localize the MF and, its turn, to guide clinicians during the IANB for Brazilian adults, given the marked topographic variations.

Waste to energy efficiency improvements: Integration with solar thermal energy.

Hybridisation of waste to energy with solar facility can take competing energy technologies and make them complementary. However, realising the benefits of solar integration requires careful consideration of the technical feasibility as well as the economic and environmental benefits of a proposed system. In this work, a solar-integrated waste-to-energy plant scheme is proposed and analysed from an energy, environmental and economic point of view. The new system integrates a traditional waste-to-energy plant with a concentrated solar power plant, by superheating the steam produced by the waste-to-energy flue gas boiler in the solar facility. The original waste-to-energy plant - that is, the base case before introducing the integration with concentrated solar power - has a thermal power input of 50 MW and operates with superheated steam at 40 bar and 400 °C; net power output is 10.7 MW, and the net energy efficiency is equal to 21.65%. By combining waste-to-energy plant with the solar facility, the power plant could provide higher net efficiency (from 1.4 to 3.7 p.p. higher), lower specific CO2 emissions (from 69 to 180 kg MWh-1 lower) and lower levellised cost of electricity (from 13.4 to 42.3 EUR MWh-1 lower) comparing with the standalone waste to energy case. The study shows that: (i) in the integrated case and for the increasing steam parameters energy, economic and ecological performances are improved; (ii) increasing the solar contribution could be an efficient way to improve the process and system performances. In general, we can conclude that concentrated solar-power technology holds significant promise for extending and developing the waste to energy systems.

Tests of a novel imaging algorithm to localize hidden objects or cavities with muon radiography.

A novel algorithm developed within muon radiography to localize objects or cavities hidden inside large material volumes was recently proposed by some of the authors (Bonechi et al. 2015 J. Instrum. 10, P02003 (doi:10.1088/1748-0221/10/02/P02003)). The algorithm, based on muon back projection, helps to estimate the three-dimensional position and the transverse extension of detected objects without the need for measurements from different points of view, which would be required to make a triangulation. This algorithm can now be tested owing to the availability of real data collected both in laboratory tests and from real-world measurements. The methodology and some test results are presented in this paper.This article is part of the Theo Murphy meeting issue 'Cosmic-ray muography'.

Polymicrobial antibiofilm activity of the membranotropic peptide gH625 and its analogue.

This work illustrates a new role for the membranotropic peptide gH625 and its derivative gH625-GCGKKK in impairing formation of polymicrobial biofilms. Mixed biofilms composed of Candida and bacterial species cause frequently infections and failure of medical silicone devices and also show a major drug resistance than single-species biofilms. Inhibition and eradication of biofilms were evaluated by complementary methods: XTT-reduction, and crystal violet staining (CV). Our results indicate that gH625-GCGKKKK, better than the native peptide, strongly inhibited formation of mixed biofilms of clinical isolates of C. tropicalis/S. marcescens and C. tropicalis/S. aureus and reduced the biofilm architecture, interfering with cell adhesion and polymeric matrix, as well as eradicated the long-term polymicrobial biofilms on silicone surface.

Short versus mid-long-term outcome of transanal irrigation in children with spina bifida and anorectal malformations.

PURPOSE: We assessed short- and mid-long-term clinical efficacy of transanal irrigation (TAI) and its effect on the quality of life of children with spina bifida (SB) and anorectal malformations (ARM). METHODS: Seventy-four pediatric patients (age 6-17 years) with SB and ARM with neurogenic bowel dysfunction were enrolled for a prospective and multicentric study. Patients were evaluated before the beginning of TAI (T0), after 3 months (T1) and after at least 2 years (range 24-32 months) (T2) using a questionnaire assessing bowel function, the Bristol scale, and two validated questionnaires on quality of life: the CHQ-PF50 questionnaire for the parents of patients aged 6-11 years and the SF36 questionnaires for patients aged between 12 and 18 years. RESULTS: Seventy-two patients completed TAI program in T1, and 67 continued into T2. Bowel outcomes (constipation and fecal incontinence) improved in both the SB and the ARM groups in the short and mid-long term. In both groups at T1 and T2, parents and children reported an improvement in quality of life and there was a significant increase of stool form types 4 and 5 as described by the Bristol scale. Common adverse effects during the study were similar at T1 and T2 without serious complications. CONCLUSIONS: We observed a sustained improvement in bowel management and quality of life in SB and ARM children during the study, more significant in the short term than in mid-long term. To maintain success rates in the mid-long term and to reduce the dropout rate, we propose patient training and careful follow-ups.

Autosomal-dominant myopia associated to a novel P4HA2 missense variant and defective collagen hydroxylation.

We recently described a complex multisystem syndrome in which mild-moderate myopia segregated as an independent trait. A plethora of genes has been related to sporadic and familial myopia. More recently, in Chinese patients severe myopia (MYP25, OMIM:617238) has been linked to mutations in P4HA2 gene. Seven family members complaining of reduced distance vision especially at dusk underwent complete ophthalmological examination. Whole-exome sequencing was performed to identify the gene responsible for myopia in the pedigree. Moderate myopia was diagnosed in the family which was associated to the novel missense variant c.1147A > G p.(Lys383Glu) in the prolyl 4-hydroxylase,alpha-polypeptide 2 (P4HA2) gene, which catalyzes the formation of 4-hydroxyproline residues in the collagen strands. In vitro studies demonstrated P4HA2 mRNA and protein reduced expression level as well as decreased collagen hydroxylation and deposition in mutated fibroblast primary cultures compared to healthy cell lines. This study suggests that P4HA2 mutations may lead to myopic axial elongation of eyeball as a consequence of quantitative and structural alterations of collagen. This is the first confirmatory study which associates a novel dominant missense variant in P4HA2 with myopia in Caucasian patients. Further studies in larger cohorts are advisable to fully clarify genotype-phenotype correlations.

Flat Panel Angiography in the Cross-Sectional Imaging of the Temporal Bone: Assessment of Image Quality and Radiation Dose Compared with a 64-Section Multisection CT Scanner.

BACKGROUND AND PURPOSE: Cross-sectional imaging of the temporal bone is challenging because of the complexity and small dimensions of the anatomic structures. We evaluated the role of flat panel angiography in the cross-sectional imaging of the temporal bone by comparing its image quality and radiation dose with a 64-section multisection CT scanner. MATERIALS AND METHODS: We retrospectively collected 29 multisection CT and 29 flat panel angiography images of normal whole-head temporal bones. Image quality was assessed by 2 neuroradiologists, who rated the visualization of 30 anatomic structures with a 3-point ordinal scale. The radiation dose was assessed with an anthropomorphic phantom. RESULTS: Flat panel angiography showed better image quality than multisection CT in depicting the anterior and posterior crura of the stapes, the footplate of the stapes, the stapedius muscle, and the anterior ligament of the malleus (P < .05). In contrast, multisection CT showed better image quality than flat panel angiography in assessing the tympanic membrane, the bone marrow of the malleus and incus, the tendon of the tensor tympani, the interscalar septum, and the modiolus of the cochlea (P < .05). Flat panel angiography had a significantly higher overall image quality rating than multisection CT (P = .035). A reduction of the effective dose of approximately 40% was demonstrated for flat panel angiography compared with multisection CT. CONCLUSIONS: Flat panel angiography shows strengths and weaknesses compared with multisection CT. It is more susceptible to artifacts, but due to the higher spatial resolution, it shows equal or higher image quality in assessing some bony structures of diagnostic interest. The lower radiation dose is an additional advantage of flat panel angiography.

Experimental evaluation of two different types of reactors for CO2 removal from gaseous stream by bottom ash accelerated carbonation.

Low methane content landfill gas may be enriched by removing carbon dioxide. An innovative process, based on carbon dioxide capture and storage by means of accelerated carbonation of bottom ash is proposed and studied for the above purpose. Within this research framework we devoted a preliminary research activity to investigate the possibility of improving the way the contact between bottom ash and landfill gas takes place: this is the scope of the work reported in this paper. Two different types of reactors - fixed bed and rotating drum - were designed and constructed for this purpose. The process was investigated at laboratory scale. As the aim of this phase was the comparison of the performances of the two different reactors, we used a pure stream of CO2 to preliminarily evaluate the reactor behaviors in the most favorable condition for the process (i.e. maximum CO2 partial pressure at ambient condition). With respect to the simple fixed bed reactor concept, some modifications were proposed, consisting of separating the ash bed in three layers. With the three layer configuration we would like to reduce the possibility for the gas to follow preferential paths through the ash bed. However, the results showed that the process performances are not significantly influenced by the multiple layer arrangement. As an alternative to the fixed bed reactor, the rotating drum concept was selected in order to provide continuous mixing of the solids. Two operating parameters were considered and varied during the tests: the filling ratio and the rotating speed. Better performances were observed for lower filling ratio while the rotating speed showed minor importance. Finally the performances of the two reactors were compared. The rotating drum reactor is able to provide improved carbon dioxide removal with respect to the fixed bed one, especially when the rotating reactor is operated at low filling ratio values and slow rotating speed values. Comparing the carbon dioxide specific removal obtained by using the rotating reactor (35-37g/kgBA), in the best operating conditions, with that measured for the fixed bed reactor (21-23g/kgBA), an increase of about 61-66% is observed.

Solid recovered fuel: An experiment on classification and potential applications.

The residual urban waste of Prato district (Italy) is characterized by a high calorific value that would make it suitable for direct combustion in waste-to-energy plants. Since the area of central Italy lacks this kind of plant, residual municipal waste is quite often allocated to mechanical treatment plants in order to recover recyclable materials (such as metals) and energy content, sending the dry fractions to waste-to-energy plants outside the region. With the previous Italian legislation concerning Refuse Derived Fuels, only the dry stream produced as output by the study case plant, considered in this study, could be allocated to energy recovery, while the other output flows were landfilled. The most recent Italian regulation, introduced a new classification for the fuel streams recovered from waste following the criteria of the European standard (EN 15359:2011), defining the Solid Recovered Fuel (SRF). In this framework, the aim of this study was to check whether the different streams produced as output by the study case plant could be classified as SRF. For this reason, a sampling and analysis campaign was carried out with the purpose of characterizing every single output stream that can be obtained from the study case mechanical treatment plant, when operating it in different ways. The results showed that all the output flows from the study case mechanical treatment plant were classified as SRF, although with a wide quality range. In particular, few streams, of rather poor quality, could be fed to waste-to-energy plants, compatibly with the plant feeding systems. Other streams, with very high quality, were suitable for non-dedicated facilities, such as cement plants or power plants, as a substitute for coal. The implementation of the new legislation has hence the potential for a significant reduction of landfilling, contributing to lowering the overall environmental impact by avoiding the direct impacts of landfilling and by exploiting the beneficial effects of energy recovery from waste.

Peristeen(®) transanal irrigation in paediatric patients with anorectal malformations and spinal cord lesions: a multicentre Italian study.

AIM: In paediatric and adult patients with neurogenic bowel, transanal irrigation (TAI) of the colon has gained popularity due to the introduction of a specifically designed device. The aim of this pilot study was to present the results of TAI using the Peristeen(®) TAI system in a group of paediatric patients with anorectal malformation (ARM) and congenital or acquired spinal cord lesions (SCLs). METHOD: Eight Italian paediatric surgery and spina bifida centres participated in the study. The inclusion criteria were age between 6 and 17 years, weight above 20 kg and unsatisfactory bowel management. Patients with chronic inflammatory bowel disease, mental disability and surgery within the previous 3 months were excluded. At the beginning of treatment (T0) and after 3 months (T1) the Bristol scale, a questionnaire assessing bowel function, and two questionnaires on quality of life (QoL) for patients aged 6-11 years (CHQ-pf50) and 12-17 years (SF36) were administered. RESULTS: Eighty-three patients were enrolled, and seventy-eight completed the study (41 ARMs, 37 SCLs). At T1, constipation was reduced in ARMs from 69% to 25.6% and in SCLs from 92.7% to 41.5%, faecal incontinence in ARMs from 50% to 18.6% and in SCLs from 39% to 9.8% and flatus incontinence in ARMs from 20.9% to 9.8% and in SCLs from 31.7% to 10%. At T0, the Bristol Stool Scale types were 1-2 in 45% of ARMs and 77.5% of SCL patients, whereas at T1 types 1-2 were recorded in only 2.5% of SCL patients. QoL improved in both groups. In the younger group, a significant improvement in QoL was recorded in ARM patients for eight of nine variables and in SCL patients for seven of nine variables. CONCLUSION: This study showed that Peristeen TAI resulted in a significant time reduction in colonic cleansing, increased independence from the carer and improved QoL in paediatric patients with ARMs and SCLs.

Metalloproteinase-9 contributes to inflammatory glia activation and nigro-striatal pathway degeneration in both mouse and monkey models of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism.

Inflammation is a predominant aspect of neurodegenerative diseases, manifested by glia activation and expression of pro-inflammatory mediators. Studies on animal models of Parkinson's disease (PD) suggest that sustained neuroinflammation exacerbates degeneration of the dopaminergic (DA) nigro-striatal pathway. Therefore, insights into the inflammatory mechanisms of PD may help the development of novel therapeutic strategies against this disease. As extracellular matrix metalloproteinases (MMPs) could be major players in the progression of Parkinsonism, we investigated, in the substantia nigra and striatum of mice acutely injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), changes in mRNA expression, protein levels, and cell localization of MMP-9. This protease is mainly neuronal, but early after MPTP injection its mRNA and protein levels, as well as the number of MMP-9-expressing microglia and astrocytes, increase concomitantly to a prominent inflammation. Neuroinflammation and MMP-9(+) glia begin to decline within 2 weeks, although protein levels remain higher than control, in association with a partial recovery of DA nigro-striatal circuit. Comparable quantitative studies on MMP-9 knock-out mice, show a significant decrease in both glia activation and loss of DA neurons and fibers, with respect to wild-type. Moreover, in a parallel study on chronically MPTP-injected macaques, we observed that perpetuation of inflammation and high levels of MMP-9 are associated to DA neuron loss. Our data suggest that MMP-9 released by injured neurons favors glia activation; glial cells in turn reinforce their reactive state via autocrine MMP-9 release, contributing to nigro-striatal pathway degeneration. Specific modulation of MMP-9 activity may, therefore, be a strategy to ameliorate harmful inflammatory outcomes in Parkinsonism.