56 results on '"De Girolamo, P."'
Search Results
2. Exploration of effects of galvanic vestibular stimulation on circadian rhythms and its associations with sleep and spatial memory in patients with breast cancer: The ICANSLEEP-2 protocol.
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Melvin Galin, Laura de Girolamo, Bénédicte Clarisse, Carine Segura-Djezzar, Franka Glöckner, Clara Elia, Stéphane Réhel, Patrice Clochon, Franck Doidy, Julien Chavant, Olivier Etard, Fausto Viader, Jean-Michel Grellard, Justine Lequesne, Florence Joly, Francis Eustache, Tristan Martin, Bénédicte Giffard, Gaëlle Quarck, and Joy Perrier
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Medicine ,Science - Abstract
BackgroundPatients with breast cancer (BC) exhibit circadian rhythm disruptions, mainly of rest-activity rhythm (RAR), of which sleep is an essential component, and cortisol rhythm. Sleep complaints such as insomnia and cognitive impairments are prevalent in BC. In general population, sleep is known to contribute greatly to cognition. Thus, improving RAR (and particularly sleep) could help limiting cognitive impairments in BC patients. It has recently been suggested that, in addition to its essential role in spatial memory, the vestibular system contributes to RAR synchronization. Its stimulation could therefore limit both sleep disturbances and spatial memory deficits in BC.ObjectivesThe main aim of the ICANSLEEP-2 study is to assess the effects of galvanic vestibular stimulation (GVS) on circadian rhythms. The secondary aim is to assess whether GVS improves sleep and spatial memory in BC patients.MethodsTwo groups with insomnia complaints (Insomnia Severity Index > 7) will be included: a patients' group with BC (n = 50) and a healthy control group without history of cancer (n = 25). There will be two assessment sessions, before and after 2 weeks of GVS. Patients will be randomly assigned to either a GVS group or a sham group (noneffective stimulation). Controls will receive GVS. GVS effects will be quantified and compared between groups. Assessments will include actigraphy, salivary cortisol, polysomnography, a cognitive test battery (including a computer-based task for spatial memory) and validated questionnaires (for psychological functioning and sleep complaints).DiscussionCurrent methods for improving sleep in BC have had controversial outcomes regarding sleep structure. We expect GVS to offer a new mean of directly targeting RAR disruptions in BC patients, with beneficial effects on sleep structure. Given the crucial impact of sleep on cognitive functioning, notably spatial memory, improving sleep of BC patients should enhance their cognitive functioning.Ethics and disseminationThis study received ethical approval from the Ile de France IV institutional review board on 19 April 2022 (no. ID-RCB: 2022-A00437-36). The findings yielded by this protocol will be presented at various conferences and in peer-reviewed journals.Clinicaltrials.gov registration numberNCT05414357.
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- 2024
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3. Metabolic Syndrome in people treated with Antipsychotics (RISKMet): A multimethod study protocol investigating genetic, behavioural, and environmental risk factors.
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Giovanni de Girolamo, Caterina La Cascia, Paolo Emidio Macchia, Maria Nobile, Stefano Calza, Laura Camillo, Maddalena Mauri, Marco Pozzi, Giada Tripoli, Claudia Vetrani, Elisa Caselani, and Marta Magno
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Medicine ,Science - Abstract
IntroductionThe RISKMet project aims to: (1) identify risk factors for metabolic syndrome (MetS) by comparing patients with and without MetS; (2) characterise patients treated with second-generation antipsychotics (SGAs) about MetS diagnosis; (3) study behavioural patterns, including physical activity (PA) and dietary habits, in patients and healthy individuals using a prospective cohort design.MethodThe RISKMet project investigates MetS in individuals treated with SGAs, focusing on both adult and paediatric populations. The study utilizes a case-control design to examine potential risk factors for MetS, categorizing participants as MetS+ considered as "Cases" and MetS- considered as "Controls" matched by sex and age. The evaluation of factors such as MetS, lifestyle habits, and environmental influences is conducted at two time points, T0 and T3, after 3 months. Subsequently, the project aims to assess body parameters, including physical examinations, and blood, and stool sample collection, to evaluate metabolic markers and the impact of SGAs. The analysis includes pharmacological treatment data and genetic variability. Behavioural markers related to lifestyle, eating behaviour, PA, and mood are assessed at both T0 and T3 using interviews, accelerometers, and a mobile app. The study aims to improve mental and physical well-being in SGA-treated individuals, establish a biobank for MetS research, build an evidence base for physical health programs, and develop preventive strategies for SGA-related comorbidities.ConclusionsThis project innovates MetS monitoring in psychiatry by using intensive digital phenotyping, identifying biochemical markers, assessing familial risks, and including genetically similar healthy controls.Study registration numberISRCTN18419418 at www.isrctn.com.
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- 2024
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4. Data repurposing from digital home cage monitoring enlightens new perspectives on mouse motor behaviour and reduction principle
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Sara Fuochi, Mara Rigamonti, Marcello Raspa, Ferdinando Scavizzi, Paolo de Girolamo, and Livia D’Angelo
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Medicine ,Science - Abstract
Abstract In this longitudinal study we compare between and within-strain variation in the home-cage spatial preference of three widely used and commercially available mice strains—C57BL/6NCrl, BALB/cAnNCrl and CRL:CD1(ICR)—starting from the first hour post cage-change until the next cage-change, for three consecutive intervals, to further profile the circadian home-cage behavioural phenotypes. Cage-change can be a stressful moment in the life of laboratory mice, since animals are disturbed during the sleeping hours and must then rapidly re-adapt to a pristine environment, leading to disruptions in normal motor patterns. The novelty of this study resides in characterizing new strain-specific biological phenomena, such as activity along the cage walls and frontality, using the vast data reserves generated by previous experimental data, thus introducing the potential and exploring the applicability of data repurposing to enhance Reduction principle when running in vivo studies. Our results, entirely obtained without the use of new animals, demonstrate that also when referring to space preference within the cage, C57BL/6NCrl has a high variability in the behavioural phenotypes from pre-puberty until early adulthood compared to BALB/cAnNCrl, which is confirmed to be socially disaggregated, and CRL:CD1(ICR) which is conversely highly active and socially aggregated. Our data also suggest that a strain-oriented approach is needed when defining frequency of cage-change as well as maximum allowed animal density, which should be revised, ideally under the EU regulatory framework as well, according to the physiological peculiarities of the strains, and always avoiding the “one size fits all” approach.
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- 2023
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5. Psychological well-being during the COVID-19 pandemic in Italy assessed in a four-waves survey
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Giovanni de Girolamo, Clarissa Ferrari, Valentina Candini, Chiara Buizza, Gemma Calamandrei, Marta Caserotti, Teresa Gavaruzzi, Paolo Girardi, Katrine Bach Habersaat, Lorella Lotto, Martha Scherzer, Fabrizio Starace, Alessandra Tasso, Manuel Zamparini, and Cristina Zarbo
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Medicine ,Science - Abstract
Abstract COVID-19 pandemic had a negative impact on the mental health and well-being (WB) of citizens. This cross-sectional study included 4 waves of data collection aimed at identifying profiles of individuals with different levels of WB. The study included a representative stratified sample of 10,013 respondents in Italy. The WHO 5-item well-being scale (WHO-5) was used for the assessment of WB. Different supervised machine learning approaches (multinomial logistic regression, partial least-square discriminant analysis—PLS-DA—, classification tree—CT—) were applied to identify individual characteristics with different WB scores, first in waves 1–2 and, subsequently, in waves 3 and 4. Forty-one percent of participants reported “Good WB”, 30% “Poor WB”, and 28% “Depression”. Findings carried out using multinomial logistic regression show that Resilience was the most important variable able for discriminating the WB across all waves. Through the PLS-DA, Increased Unhealthy Behaviours proved to be the more important feature in the first two waves, while Financial Situation gained most relevance in the last two. COVID-19 Perceived Risk was relevant, but less than the other variables, across all waves. Interestingly, using the CT we were able to establish a cut-off for Resilience (equal to 4.5) that discriminated good WB with a probability of 65% in wave 4. Concluding, we found that COVID-19 had negative implications for WB. Governments should support evidence-based strategies considering factors that influence WB (i.e., Resilience, Perceived Risk, Healthy Behaviours, and Financial Situation).
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- 2022
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6. Willingness to share contacts in case of COVID-19 positivity–predictors of collaboration resistance in a nation-wide Italian survey
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Boris Bikbov, Mauro Tettamanti, Alexander Bikbov, Barbara D’Avanzo, Alessia Antonella Galbussera, Alessandro Nobili, Gemma Calamandrei, Valentina Candini, Fabrizio Starace, Cristina Zarbo, and Giovanni de Girolamo
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Medicine ,Science - Abstract
Background The unwillingness to share contacts is one of the least explored aspects of the COVID-19 pandemic. Here we report the factors associated with resistance to collaborate on contact tracing, based on the results of a nation-wide survey conducted in Italy in January-March 2021. Methods and findings The repeated cross-sectional on-line survey was conducted among 7,513 respondents (mean age 45.7, 50.4% women) selected to represent the Italian adult population 18–70 years old. Two groups were defined based on the direct question response expressing (1) unwillingness or (2) willingness to share the names of individuals with whom respondents had contact. We selected 70% of participants (training data set) to produce several multivariable binomial generalized linear models and estimated the proportion of variation explained by the model by McFadden R2, and the model’s discriminatory ability by the index of concordance. Then, we have validated the regression models using the remaining 30% of respondents (testing data set), and identified the best performing model by removing the variables based on their impact on the Akaike information criterion and then evaluating the model predictive accuracy. We also performed a sensitivity analysis using principal component analysis. Overall, 5.5% of the respondents indicated that in case of positive SARS-CoV-2 test they would not share contacts. Of note, this percentage varied from 0.8% to 46.5% depending on the answers to other survey questions. From the 139 questions included in the multivariable analysis, the initial model proposed 20 independent factors that were reduced to the 6 factors with only modest changes in the model performance. The 6-variables model demonstrated good performance in the training (c-index 0.85 and McFadden R2 criteria 0.25) and in the testing data set (93.3% accuracy, AUC 0.78, sensitivity 30.4% and specificity 97.4%). The most influential factors related to unwillingness to share contacts were the lack of intention to perform the test in case of contact with a COVID-19 positive individual (OR 5.60, 95% CI 4.14 to 7.58, in a fully adjusted multivariable analysis), disagreement that the government should be allowed to force people into self-isolation (OR 1.79, 95% CI 1.12 to 2.84), disagreement with the national vaccination schedule (OR 2.63, 95% CI 1.86 to 3.69), not following to the preventive anti-COVID measures (OR 3.23, 95% CI 1.85 to 5.59), the absence of people in the immediate social environment who have been infected with COVID-19 (1.66, 95% CI 1.24 to 2.21), as well as difficulties in finding or understanding the information about the infection or related recommendations. A limitation of this study is the under-representation of persons not participating in internet-based surveys and some vulnerable groups like homeless people, persons with disabilities or migrants. Conclusions Our analysis revealed several groups that expressed unwillingness to collaborate on contact tracing. The identified patterns may play a principal role not only in the COVID-19 epidemic but also be important for possible future public health threats, and appropriate interventions for their correction should be developed and ready for the implementation.
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- 2022
7. Biopsychosocial Response to the COVID-19 Lockdown in People with Major Depressive Disorder and Multiple Sclerosis
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Sara Siddi, Iago Giné-Vázquez, Raquel Bailon, Faith Matcham, Femke Lamers, Spyridon Kontaxis, Estela Laporta, Esther Garcia, Belen Arranz, Gloria Dalla Costa, Ana Isabel Guerrero, Ana Zabalza, Mathias Due Buron, Giancarlo Comi, Letizia Leocani, Peter Annas, Matthew Hotopf, Brenda W. J. H. Penninx, Melinda Magyari, Per S. Sørensen, Xavier Montalban, Grace Lavelle, Alina Ivan, Carolin Oetzmann, Katie M. White, Sonia Difrancesco, Patrick Locatelli, David C. Mohr, Jordi Aguiló, Vaibhav Narayan, Amos Folarin, Richard J. B. Dobson, Judith Dineley, Daniel Leightley, Nicholas Cummins, Srinivasan Vairavan, Yathart Ranjan, Zulqarnain Rashid, Aki Rintala, Giovanni De Girolamo, Antonio Preti, Sara Simblett, Til Wykes, PAB Members, Inez Myin-Germeys, Josep Maria Haro, and on behalf of the RADAR-CNS Consortium
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COVID-19 ,SARS-CoV-2 ,major depressive disorder ,multiple sclerosis ,depression severity ,heart rate ,Medicine - Abstract
Background: Changes in lifestyle, finances and work status during COVID-19 lockdowns may have led to biopsychosocial changes in people with pre-existing vulnerabilities such as Major Depressive Disorders (MDDs) and Multiple Sclerosis (MS). Methods: Data were collected as a part of the RADAR-CNS (Remote Assessment of Disease and Relapse—Central Nervous System) program. We analyzed the following data from long-term participants in a decentralized multinational study: symptoms of depression, heart rate (HR) during the day and night; social activity; sedentary state, steps and physical activity of varying intensity. Linear mixed-effects regression analyses with repeated measures were fitted to assess the changes among three time periods (pre, during and post-lockdown) across the groups, adjusting for depression severity before the pandemic and gender. Results: Participants with MDDs (N = 255) and MS (N = 214) were included in the analyses. Overall, depressive symptoms remained stable across the three periods in both groups. A lower mean HR and HR variation were observed between pre and during lockdown during the day for MDDs and during the night for MS. HR variation during rest periods also decreased between pre- and post-lockdown in both clinical conditions. We observed a reduction in physical activity for MDDs and MS upon the introduction of lockdowns. The group with MDDs exhibited a net increase in social interaction via social network apps over the three periods. Conclusions: Behavioral responses to the lockdown measured by social activity, physical activity and HR may reflect changes in stress in people with MDDs and MS. Remote technology monitoring might promptly activate an early warning of physical and social alterations in these stressful situations. Future studies must explore how stress does or does not impact depression severity.
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- 2022
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8. Industrial-Scale Cleaning Solutions for the Reduction of Fusarium Toxins in Maize
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Michelangelo Pascale, Antonio F. Logrieco, Vincenzo Lippolis, Annalisa De Girolamo, Salvatore Cervellieri, Veronica M. T. Lattanzio, Biancamaria Ciasca, Anna Vega, Mareike Reichel, Matthias Graeber, and Katarina Slettengren
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maize ,deoxynivalenol ,zearalenone ,fumonisins ,remediation ,mechanical cleaning ,Medicine - Abstract
Grain cleaning is the most effective non-destructive post-harvest mitigation strategy to reduce high levels of mycotoxins on account of the removal of mold-infected grains and grain fractions with high mycotoxin content. In this study, the reduction in the concentration of some co-occurring Fusarium toxins in maize, namely deoxynivalenol (DON), zearalenone (ZEA) and fumonisins B1 and B2 (FBs), was evaluated at an industrial-scale level by mechanical removal (sieving and density separation) of dust, coarse, small, broken, shriveled and low-density kernels and/or optical sorting of defected kernels. Samples were dynamically collected according to the Commission Regulation No. 401/2006 along the entire process line. Mycotoxin analyses of water–slurry aggregate samples were performed by validated LC methods. Depending on the contamination levels in raw incoming maize, the overall reduction rates ranged from 36 to 67% for DON, from 67 to 87% for ZEA and from 27 to 67% for FBs. High levels of DON, ZEA and FBs were found in all rejected fractions with values, respectively, up to 3030%, 1510% and 2680%, compared to their content in uncleaned maize. Results showed that grain cleaning equipment based on mechanical and or optical sorting technologies can provide a significant reduction in Fusarium toxin contamination in maize.
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- 2022
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9. Childhood generalized specific phobia as an early marker of internalizing psychopathology across the lifespan: results from the World Mental Health Surveys
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Ymkje Anna de Vries, Ali Al-Hamzawi, Jordi Alonso, Guilherme Borges, Ronny Bruffaerts, Brendan Bunting, José Miguel Caldas-de-Almeida, Alfredo H. Cia, Giovanni De Girolamo, Rumyana V. Dinolova, Oluyomi Esan, Silvia Florescu, Oye Gureje, Josep Maria Haro, Chiyi Hu, Elie G. Karam, Aimee Karam, Norito Kawakami, Andrzej Kiejna, Viviane Kovess-Masfety, Sing Lee, Zeina Mneimneh, Fernando Navarro-Mateu, Marina Piazza, Kate Scott, Margreet ten Have, Yolanda Torres, Maria Carmen Viana, Ronald C. Kessler, Peter de Jonge, and on behalf of the WHO World Mental Health Survey Collaborators
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Specific phobia ,Internalizing disorders ,Early markers ,Comorbidity ,Suicidality ,Medicine - Abstract
Abstract Background Specific phobia (SP) is a relatively common disorder associated with high levels of psychiatric comorbidity. Because of its early onset, SP may be a useful early marker of internalizing psychopathology, especially if generalized to multiple situations. This study aimed to evaluate the association of childhood generalized SP with comorbid internalizing disorders. Methods We conducted retrospective analyses of the cross-sectional population-based World Mental Health Surveys using the Composite International Diagnostic Interview. Outcomes were lifetime prevalence, age of onset, and persistence of internalizing disorders; past-month disability; lifetime suicidality; and 12-month serious mental illness. Logistic and linear regressions were used to assess the association of these outcomes with the number of subtypes of childhood-onset (
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- 2019
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10. Overview of Recent Liquid Chromatography Mass Spectrometry-Based Methods for Natural Toxins Detection in Food Products
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Annalisa De Girolamo, Vincenzo Lippolis, and Michelangelo Pascale
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natural toxins ,food ,analytical methods ,liquid chromatography-mass spectrometry ,simultaneous detection ,Medicine - Abstract
Natural toxins include a wide range of toxic metabolites also occurring in food and products, thus representing a risk for consumer health. In the last few decades, several robust and sensitive analytical methods able to determine their occurrence in food have been developed. Liquid chromatography mass spectrometry is the most powerful tool for the simultaneous detection of these toxins due to its advantages in terms of sensitivity and selectivity. A comprehensive review on the most relevant papers on methods based on liquid chromatography mass spectrometry for the analysis of mycotoxins, alkaloids, marine toxins, glycoalkaloids, cyanogenic glycosides and furocoumarins in food is reported herein. Specifically, a literature search from 2011 to 2021 was carried out, selecting a total of 96 papers. Different approaches to sample preparation, chromatographic separation and detection mode are discussed. Particular attention is given to the analytical performance characteristics obtained in the validation process and the relevant application to real samples.
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- 2022
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11. Characterization of Microfragmented Adipose Tissue Architecture, Mesenchymal Stromal Cell Content and Release of Paracrine Mediators
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Enrico Ragni, Marco Viganò, Enrica Torretta, Carlotta Perucca Orfei, Alessandra Colombini, Carlo Tremolada, Cecilia Gelfi, and Laura de Girolamo
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osteoarthritis ,regenerative medicine ,adipose tissue ,lipoaspirate ,microfragmentation ,mesenchymal stromal cells ,Medicine - Abstract
The use of microfragmented adipose tissue (µFAT) for the treatment of musculoskeletal disorders, especially osteoarthritis (OA), is gaining popularity, following positive results reported in recent case series and clinical trials. Although these outcomes were postulated to rely on paracrine signals, to date, a thorough fingerprint of released molecules is largely missing. The purpose of this study was to first characterize both structure and cell content of unprocessed lipoaspirate (LA) and µFAT, and further identify and frame the array of signaling factors in the context of OA disease, by means of high throughput qRT-PCR for extracellular-vesicle (EV) embedded miRNAs and proteomics for tissue and secreted factors. Cell count showed reduction of blood cells in µFAT, confirmed by histological and flow cytometry analyses, that also showed a conserved presence of structural, endothelial and stromal components and pericytes. In the secretome, 376 and 381 EV-miRNAs in LA and µFAT, respectively, were identified. In particular, most abundant and µFAT upregulated EV-miRNAs were mainly recapitulating those already reported as ASC-EVs-specific, with crucial roles in cartilage protection and M2 macrophage polarization, while only a scarce presence of those related to blood cells emerged. Furthermore, secretome proteomic analysis revealed reduction in µFAT of acute phase factors driving OA progression. Taken together, these results suggest that processing of LA into µFAT allows for removal of blood elements and maintenance of tissue structure and stromal cell populations, and possibly the increase of OA-protective molecular features. Thus, microfragmentation represents a safe and efficient method for the application of adipose tissue properties in the frame of musculoskeletal disorders.
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- 2022
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12. Diagnosis of Primary Cardiac T-cell Lymphoma: Feasibility and Safety of Endomyocardial Biopsy Guided by Pre-acquired Cardiovascular Magnetic Resonance
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Andrea Avella, Carla Giordano, Vitaliano Buffa, Piergiuseppe De Girolamo, and Massimo Uguccioni
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cardiac tumour ,cardiac magnetic resonance ,right-sided catheterization ,endomyocardial biopsy ,Medicine - Abstract
Background: Multimodality imaging of a cardiac mass lesion may raise suspicion of a primitive cardiac lymphoma (PCL). However, a definitive diagnosis requires histopathological confirmation. Methods: This report describes the methodology we used to perform biopsy sampling of a cardiac mass lesion affecting a 45-year-old man. In order to increase endomyocardial biopsy diagnostic accuracy, we used pre-acquired cardiac magnetic resonance (CMR) images to guide the bioptome on a cardiac site overtly infiltrated by the suspected tumour. The right ventricular outflow tract was identified as the target site for biopsy sampling. To reduce the risk of the procedure, the biopsy was performed at a safe distance from the tip of a diagnostic quadripolar catheter positioned at the level of the pulmonary valve, previously identified by pacing manoeuvres. The reported approach demonstrated safety and diagnostic accuracy, allowing the identification of an extremely rare PCL subtype of T-cell origin. Conclusion: Biopsy sampling of a suspected tumour may be safely and accurately performed using pre-acquired CMR images to guide the bioptome on the target site.
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- 2021
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13. Autologous Microfragmented Adipose Tissue for the Treatment of Knee Osteoarthritis: Real-World Data at Two Years Follow-Up
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Daniele Screpis, Simone Natali, Luca Farinelli, Gianluca Piovan, Venanzio Iacono, Laura de Girolamo, Marco Viganò, and Claudio Zorzi
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osteoarthritis ,autologous microfragment adipose tissue ,orthobiologics ,knee ,adipose-derived mesenchymal stem cells ,Medicine - Abstract
The purpose of the present study was to assess, prospectively, the safety, clinical effectiveness, and feasibility of a single intra-articular injection of microfragmented adipose tissue in different stages of knee osteoarthritis (OA). The study included patients (aged 18–70 years), affected by OA (Kellgren–Lawrence I-IV). Unselected patients were evaluated before and prospectively after 6, 12, and 24 months from the injection. Visual analog scale (VAS) and knee injury and osteoarthritis outcome score (KOOS) were used for clinical evaluations. A total of 202 patients were eligible. The mean follow-up time in the cohort of patients was 24.5 ± 9.6 months. Total KOOS significantly improved from pre-operative baseline levels to 6-month follow-up (p < 0.001), and again between 6- and 12-month follow-ups (p < 0.001). The VAS showed a prompt reduction at 6 months (p < 0.001 vs. baseline), but then it increased again at 12 months compared to the 6-month assessment (p < 0.001), even though it remained lower than baseline (p < 0.001). At 24 months, patients with KL-IV demonstrated a lower improvement compared to baseline; patients that had undergone previous corticosteroid injections had a greater risk to further injection treatment. The collected clinical results suggest that MFAT may represent a safe and effective treatment for OA symptoms, offering a low-demanding and minimally invasive treatment.
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- 2022
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14. Validation of the Transition Readiness and Appropriateness Measure (TRAM) for the Managing the Link and Strengthening Transition from Child to Adult Mental Healthcare in Europe (MILESTONE) study
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Dieter Wolke, Jason Madan, Jatinder Singh, Federico Fiori, Paramala Santosh, Helena Tuomainen, Swaran Singh, Laura Adams, Mathilde Mastroianni, Natalie Heaney, Kate Lievesley, Ilyas Sagar-Ouriaghli, Giovanni Allibrio, Rebecca Appleton, Nikolina Davidović, Giovanni de Girolamo, Gwen Dieleman, Katarina Dodig-Ćurković, Tomislav Franić, Charlotte Gatherer, Suzanne Gerritsen, Elisa Gheza, Lidia Manenti, Athanasios Maras, Francesco Margari, Adriana Pastore, Moli Paul, Diane Purper-Ouakil, Francesco Rinaldi, Vehbi Sakar, Ulrike Schulze, Giulia Signorini, Cathy Street, Priya Tah, Sabine Tremmery, Amanda Tuffrey, Frank Verhulst, and Anna Wilson
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Medicine - Abstract
Objective Young people moving from child and adolescent mental health services (CAMHS) to adult mental health services (AMHS) are faced with significant challenges. To improve this state of affairs, there needs to be a recognition of the problem and initiatives and an urgent requirement for appropriate tools for measuring readiness and outcomes at the transfer boundary (16–18 years of age in Europe). The objective of this study was to develop and validate the Transition Readiness and Appropriateness Measure (TRAM) for assessing a young person’s readiness for transition, and their outcomes at the transfer boundary.Design MILESTONE prospective study.Setting Eight European Union (EU) countries participating in the EU-funded MILESTONE study.Participants The first phase (MILESTONE validation study) involved 100 adolescents (pre-transition), young adults (post-transition), parents/carers and both CAMHS and AMHS clinicians. The second phase (MILESTONE cohort study and nested cluster randomised trial) involved over 1000 young people.Results The development of the TRAM began with a literature review on transitioning and a review of important items regarding transition by a panel of 34 mental health experts. A list of 64 items of potential importance were identified, which together comprised the TRAM. The psychometric properties of the different versions of the TRAM were evaluated and showed that the TRAM had good reliability for all versions and low-to-moderate correlations when compared with other established instruments and a well-defined factor structure. The main results of the cohort study with the nested cluster randomised trial are not reported.Conclusion The TRAM is a reliable instrument for assessing transition readiness and appropriateness. It highlighted the barriers to a successful transition and informed clinicians, identifying areas which clinicians on both sides of the transfer boundary can work on to ease the transition for the young person.Trial registration number ISRCTN83240263 (Registered 23 July 2015), NCT03013595 (Registered 6 January 2017); Pre-results.
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- 2020
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15. A2A adenosine receptors are involved in the reparative response of tendon cells to pulsed electromagnetic fields.
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Alessandra Colombini, Carlotta Perucca Orfei, Fabrizio Vincenzi, Paola De Luca, Enrico Ragni, Marco Viganò, Stefania Setti, Katia Varani, and Laura de Girolamo
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Medicine ,Science - Abstract
Tendinopathy is a degenerative disease in which inflammatory mediators have been found to be sometimes present. The interaction between inflammation and matrix remodeling in human tendon cells (TCs) is supported by the secretion of cytokines such as IL-1β, IL-6 and IL-33. In this context, it has been demonstrated that pulsed electromagnetic fields (PEMFs) were able to reduce inflammation and promote tendon marker synthesis. The aim of this study was to evaluate the anabolic and anti-inflammatory PEMF-mediated response on TCs in an in vitro model of inflammation. Moreover, since PEMFs enhance the anti-inflammatory efficacy of adenosine through the adenosine receptors (ARs), the study also focused on the role of A2AARs. Human TCs were exposed to PEMFs for 48 hours. After stimulation, A2AAR saturation binding experiments were performed. Along with 48 hours PEMF stimulation, TCs were treated with IL-1β and A2AAR agonist CGS-21680. IL-1Ra, IL-6, IL-8, IL-10, IL-33, VEGF, TGF-β1, PGE2 release and SCX, COL1A1, COL3A1, ADORA2A expression were quantified. PEMFs exerted A2AAR modulation on TCs and promoted COL3A1 upregulation and IL-33 secretion. In presence of IL-1β, TCs showed an upregulation of ADORA2A, SCX and COL3A1 expression and an increase of IL-6, IL-8, PGE2 and VEGF secretion. After PEMF and IL-1β exposure, IL-33 was upregulated, whereas IL-6, PGE2 and ADORA2A were downregulated. These findings demonstrated that A2AARs have a role in the promotion of the TC anabolic/reparative response to PEMFs and to IL-1β.
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- 2020
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16. COVID-19 in Elderly Patients Surgically Treated for Lower Limbs Fracture
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Alessandra Colombini, Michele Davide Maria Lombardo, Laura de Girolamo, Elena De Vecchi, Riccardo Giorgino, Giuseppe Maria Peretti, Giuseppe Banfi, and Laura Mangiavini
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fractures ,lower limbs ,surgery ,COVID-19 ,elderly ,clinical biochemistry ,Medicine - Abstract
Background: The coronavirus disease 2019 (COVID-19) pandemic outbreak has posed new problems in the context of patients suffering from other diseases. In particular, musculoskeletal sequelae related to the state of debilitation associated with COVID-19 are important to consider in elderly patients undergoing surgery after lower limbs fracture, especially in the post-operative period. The objective of this study was to evaluate whether COVID-19 influenced biochemical parameter, recovery and mortality of surgically treated patients suffering from lower extremity fractures. Methods: Laboratory and clinical data of 30 patients were extrapolated and analyzed in the pre-operative and post-operative periods. Among these patients, 13 had COVID-19 infection (COVID-19 +), whereas 17 had no signs of COVID-19 infections (COVID-19 −). Long-term clinical and functional outcomes were also analyzed. Results: Lower calcium, slightly higher values of CRP and much higher values of CPK and AST were observed pre-operatively in COVID-19 + patients, who also showed higher prevalence of long-term sequelae than COVID-19 − patients. Conclusions: COVID-19 affects long-term outcome of elderly patients with lower limb fractures in a multifactorial way. First, the virus directly damages the muscle tissue. Secondly, the lung function impairment worsens the overall performance, making rehabilitation more challenging.
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- 2021
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17. The cross-national epidemiology of social anxiety disorder: Data from the World Mental Health Survey Initiative
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Dan J. Stein, Carmen C. W. Lim, Annelieke M. Roest, Peter de Jonge, Sergio Aguilar-Gaxiola, Ali Al-Hamzawi, Jordi Alonso, Corina Benjet, Evelyn J. Bromet, Ronny Bruffaerts, Giovanni de Girolamo, Silvia Florescu, Oye Gureje, Josep Maria Haro, Meredith G. Harris, Yanling He, Hristo Hinkov, Itsuko Horiguchi, Chiyi Hu, Aimee Karam, Elie G. Karam, Sing Lee, Jean-Pierre Lepine, Fernando Navarro-Mateu, Beth-Ellen Pennell, Marina Piazza, Jose Posada-Villa, Margreet ten Have, Yolanda Torres, Maria Carmen Viana, Bogdan Wojtyniak, Miguel Xavier, Ronald C. Kessler, Kate M. Scott, and WHO World Mental Health Survey Collaborators
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Social anxiety disorder ,Social phobia ,Cross-national epidemiology ,World Mental Health Survey Initiative ,Medicine - Abstract
Abstract Background There is evidence that social anxiety disorder (SAD) is a prevalent and disabling disorder. However, most of the available data on the epidemiology of this condition originate from high income countries in the West. The World Mental Health (WMH) Survey Initiative provides an opportunity to investigate the prevalence, course, impairment, socio-demographic correlates, comorbidity, and treatment of this condition across a range of high, middle, and low income countries in different geographic regions of the world, and to address the question of whether differences in SAD merely reflect differences in threshold for diagnosis. Methods Data from 28 community surveys in the WMH Survey Initiative, with 142,405 respondents, were analyzed. We assessed the 30-day, 12-month, and lifetime prevalence of SAD, age of onset, and severity of role impairment associated with SAD, across countries. In addition, we investigated socio-demographic correlates of SAD, comorbidity of SAD with other mental disorders, and treatment of SAD in the combined sample. Cross-tabulations were used to calculate prevalence, impairment, comorbidity, and treatment. Survival analysis was used to estimate age of onset, and logistic regression and survival analyses were used to examine socio-demographic correlates. Results SAD 30-day, 12-month, and lifetime prevalence estimates are 1.3, 2.4, and 4.0% across all countries. SAD prevalence rates are lowest in low/lower-middle income countries and in the African and Eastern Mediterranean regions, and highest in high income countries and in the Americas and the Western Pacific regions. Age of onset is early across the globe, and persistence is highest in upper-middle income countries, Africa, and the Eastern Mediterranean. There are some differences in domains of severe role impairment by country income level and geographic region, but there are no significant differences across different income level and geographic region in the proportion of respondents with any severe role impairment. Also, across countries SAD is associated with specific socio-demographic features (younger age, female gender, unmarried status, lower education, and lower income) and with similar patterns of comorbidity. Treatment rates for those with any impairment are lowest in low/lower-middle income countries and highest in high income countries. Conclusions While differences in SAD prevalence across countries are apparent, we found a number of consistent patterns across the globe, including early age of onset, persistence, impairment in multiple domains, as well as characteristic socio-demographic correlates and associated psychiatric comorbidities. In addition, while there are some differences in the patterns of impairment associated with SAD across the globe, key similarities suggest that the threshold for diagnosis is similar regardless of country income levels or geographic location. Taken together, these cross-national data emphasize the international clinical and public health significance of SAD.
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- 2017
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18. Manic episode, aggressive behavior and poor insight are significantly associated with involuntary admission in patients with bipolar disorders
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Chenyuli Luo, Hui Chen, Shaoling Zhong, Huijuan Guo, Qiguang Li, Weixiong Cai, Giovanni de Girolamo, Jiansong Zhou, and Xiaoping Wang
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Involuntary admission ,Bipolar disorder ,Aggressive behavior ,Medicine ,Biology (General) ,QH301-705.5 - Abstract
Objective(s) Serious mental illnesses, such as bipolar disorders and schizophrenia, are closely associated with involuntary admission. Many studies have focused on involuntary admission in people with schizophrenia, but little is known about the factors associated with involuntary admission in Chinese patients with bipolar disorders. This study aimed to investigate socio-demographic and clinical factors associated with involuntary admission in Chinese patients with bipolar disorders. Methods In this multi-center cross-sectional survey in China, a total of 155 newly admitted patients with bipolar disorders were consecutively recruited from 16 psychiatric institutions from 15 March to 14 April, 2013. Patients’ socio-demographic and clinical data were collected from their medical records. The Modified Overt Aggression Scale and the Insight and Treatment Attitudes Questionnaire were used to measure patients’ level of aggression and insight of current psychiatric illness. Results The prevalence of involuntary admission was 52% in this sample of Chinese inpatients with bipolar disorders. In multiple logistic regression, a high level of aggression (odds ratio (OR) = 2.48), diagnosis of manic episode (OR = 3.65), poor insight (OR = 7.52), and a low level of education (OR = 3.13) were significantly associated with involuntary admission. Conclusion Manic episode, aggressive behavior, and poor insight were the significant contributing factors to involuntary admission in Chinese patients with bipolar disorders.
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- 2019
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19. Violence risk and mental disorders (VIORMED-2): A prospective multicenter study in Italy.
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Stefano Barlati, Alberto Stefana, Francesco Bartoli, Giorgio Bianconi, Viola Bulgari, Valentina Candini, Giuseppe Carrà, Cesare Cavalera, Massimo Clerici, Marta Cricelli, Maria Teresa Ferla, Clarissa Ferrari, Laura Iozzino, Ambra Macis, Antonio Vita, Giovanni de Girolamo, and VIORMED-2 Group
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Medicine ,Science - Abstract
BackgroundThe management of mentally ill offenders in the community is one of the great challenges imposed on community psychiatry.AimThe aim of this study was to analyze the association between sociodemographic, clinical, and psychosocial factors and violent behavior in a sample of outpatients with severe mental disorders.MethodThis was a prospective cohort study with a baseline cross-sectional design used to provide a detailed analysis of patients' profiles, followed by a longitudinal design to measure aggressive and violent behavior during a 1-year follow-up. Patients with severe mental disorders, with or without a history of violence, were enrolled in four Italian Departments of Mental Health and underwent a comprehensive multidimensional assessment.ResultsThe sample included 247 outpatients, for a total of 126 cases and 121 controls. Compared to controls, patients with a history of violence had a greater frequency of lifetime domestic violence, a greater lifetime propensity to misuse substances, and a higher number of compulsory admissions. The forthnightly monitoring during the 1-year follow-up did show statistically significant differences in aggressive and violent behavior rates between the two groups. Verbal aggression was significantly associated with aggression against objects and physical aggression. Moreover, outpatients with an history of violence showed statistically significant higher MOAS scores compared to both residential patients with an history of violence, assessed in the first wave of this project, and all controls.ConclusionsPatients with a history of violence had specific characteristics and showed a greater occurrence of additional community violence during a 1-year observation period. Our results may assist clinicians in implementing standardized methods of patient assessment and violence monitoring in outpatient mental health services and may prompt improved collaboration between different community services.
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- 2019
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20. Epidemiology of Posterior Cruciate Ligament Reconstructions in Italy: A 15-Year Study
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Umile Giuseppe Longo, Marco Viganò, Vincenzo Candela, Laura de Girolamo, Eleonora Cella, Gabriele Thiebat, Giuseppe Salvatore, Massimo Ciccozzi, and Vincenzo Denaro
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PCL ,epidemiology ,sports trauma ,ligament reconstruction ,incidence ,Medicine - Abstract
Background: The posterior cruciate ligament (PCL) is an essential element in knee stability. PCL reconstructions represent an under-investigated topic in the literature due to the rarity of this type of knee injury. This study aims to investigate the incidence of PCL reconstructive surgeries in Italy, following their trend during a 15-year period. Methods: The National Hospital Discharge records (SDO) collected by the Italian Ministry of Health between January 2001 and October 2015 were analyzed. The database reports anonymous data comprising patients’ ages, genders, International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for diagnosis and intervention, census regions, regions of hospitalization, lengths of hospitalization and types of reimbursement. Results: The overall incidence of PCL reconstructions in the Italian population during the study period was 0.46 surgeries per 100,000 inhabitants/year, ranging from 0.32 to 0.54. The median patient’s age was 30 years old, and the male:female ratio was 5.3. PCL lesions were isolated in 39.7% of patients, while anterior cruciate ligament injuries were the most frequently associated lesions (31.1%). Conclusions: The incidence of PCL reconstruction in Italy was low and stable during the study period. Young men are the category at the highest risk for these procedures. Given the paucity of epidemiological data on PCL reconstructions, this data may represent a reference for the current and foreseeable needs in PCL surgeries for countries sharing similar cultural context.
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- 2021
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21. Determination of Zearalenone and Trichothecenes, Including Deoxynivalenol and Its Acetylated Derivatives, Nivalenol, T-2 and HT-2 Toxins, in Wheat and Wheat Products by LC-MS/MS: A Collaborative Study
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Annalisa De Girolamo, Biancamaria Ciasca, Michelangelo Pascale, and Veronica M.T. Lattanzio
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trichothecenes ,zearalenone ,Fusarium toxins ,wheat ,liquid chromatography–mass spectrometry ,official control ,Medicine - Abstract
An analytical method for the simultaneous determination of trichothecenes—namely, nivalenol (NIV), deoxynivalenol (DON) and its acetylated derivatives (3- and 15-acetyl-DON), T-2 and HT-2 toxins—and zearalenone (ZEN) in wheat, wheat flour, and wheat crackers was validated through a collaborative study involving 15 participants from 10 countries. The validation study, performed within the M/520 standardization mandate of the European Commission, was carried out according to the IUPAC (International Union of Pure and Applied Chemistry) International Harmonized Protocol. The method was based on mycotoxin extraction from the homogenized sample material with a mixture of acetonitrile-water followed by purification and concentration on a solid phase extraction column. High-performance liquid chromatography coupled with tandem mass spectrometry was used for mycotoxin detection, using isotopically labelled mycotoxins as internal standards. The tested contamination ranges were from 27.7 to 378 μg/kg for NIV, from 234 to 2420 μg/kg for DON, from 18.5 to 137 μg/kg for 3-acetyl-DON, from 11.4 to 142 μg/kg for 15-acetyl-DON, from 2.1 to 37.6 μg/kg for T-2 toxin, from 6.6 to 134 μg/kg for HT-2 toxin, and from 31.6 to 230 μg/kg for ZEN. Recoveries were in the range 71–97% with the lowest values for NIV, the most polar mycotoxin. The relative standard deviation for repeatability (RSDr) was in the range of 2.2–34%, while the relative standard deviation for reproducibility (RSDR) was between 6.4% and 45%. The HorRat values ranged from 0.4 to 2.0. The results of the collaborative study showed that the candidate method is fit for the purpose of enforcing the legislative limits of the major Fusarium toxins in wheat and wheat-based products.
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- 2020
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22. Aflatoxin Reduction in Maize by Industrial-Scale Cleaning Solutions
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Michelangelo Pascale, Antonio F. Logrieco, Matthias Graeber, Marina Hirschberger, Mareike Reichel, Vincenzo Lippolis, Annalisa De Girolamo, Veronica M.T. Lattanzio, and Katarina Slettengren
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grain cleaning ,maize ,aflatoxins ,remediation ,mechanical cleaning ,optical sorting ,Medicine - Abstract
Different batches of biomass/feed quality maize contaminated by aflatoxins were processed at the industrial scale (a continuous process and separate discontinuous steps) to evaluate the effect of different cleaning solutions on toxin reduction. The investigated cleaning solutions included: (i) mechanical size separation of coarse, small and broken kernels, (ii) removal of dust/fine particles through an aspiration channel, (iii) separation of kernels based on gravity and (iv) optical sorting of spatial and spectral kernel defects. Depending on the sampled fraction, dynamic or static sampling was performed according to the Commission Regulation No. 401/2006 along the entire cleaning process lines. Aflatoxin analyses of the water–slurry aggregate samples were performed according to the AOAC Official Method No. 2005.008 based on high-performance liquid chromatography and immunoaffinity column cleanup of the extracts. A significant reduction in aflatoxin content in the cleaned products, ranging from 65% to 84% with respect to the uncleaned products, was observed when continuous cleaning lines were used. Additionally, an overall aflatoxin reduction from 55% to 94% was obtained by combining results from separate cleaning steps. High levels of aflatoxins (up to 490 µg/kg) were found in the rejected fractions, with the highest levels in dust and in the rejected fractions from the aspirator and optical sorting. This study shows that a cleaning line combining both mechanical and optical sorting technologies provides an efficient solution for reducing aflatoxin contamination in maize.
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- 2020
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23. AMIC—Autologous Matrix-Induced Chondrogenesis Technique in Patellar Cartilage Defects Treatment: A Retrospective Study with a Mid-Term Follow-Up
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Daniele Tradati, Paola De Luca, Alessio Maione, Francesco Mattia Uboldi, Piero Volpi, Laura de Girolamo, and Massimo Berruto
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patellar cartilage defects ,Autologous Matrix Induced Chondrogenesis ,retrospective cohort study ,cartilage repair ,Medicine - Abstract
Background: Knee cartilage defects can be retrieved in 60% of patients undergoing knee arthroscopy, especially in the patellofemoral joint. Different techniques have been proposed to treat patellar defects, although most of them are associated with short-term results. In this study Autologous Matrix Induced Chondrogenesis (AMIC), combining subchondral microfractures with a collagen membrane (type I and III collagen), was used in the treatment of isolated patellar cartilage defects. Methods: Twenty-four patients were enrolled in this retrospective study. Subjective-International Knee Documentation Committee (IKDC), Visual Analog Scale for Pain (VAS), and Kujala score were collected at 1, 3, 6, and 12 months after surgery, whereas the Tegner Activity Level Scale was determined preoperatively and at final follow-up (final-FU). The same postoperative management and rehabilitation protocol was adopted for all the patients. Results: Fourteen patients met the inclusion–exclusion criteria and were evaluated at a mean final-FU of 68.2 months (range 25.4–111.2). At 12 months, Kujala, IKDC, and VAS scores significantly increased in comparison to the preoperative assessment, whereas no statistically significant differences were reported between 12 months and final follow-up. Conclusion: This study demonstrated very good results throughout the follow-up, also in sports patients. The AMIC technique, together with an adequate rehabilitation protocol, can be considered as a reliable one-step alternative for the treatment of large isolated patellar cartilage defects.
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- 2020
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24. Ontogenetic Pattern Changes of Nucleobindin-2/Nesfatin-1 in the Brain and Intestinal Bulb of the Short Lived African Turquoise Killifish
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Alessia Montesano, Elena De Felice, Adele Leggieri, Antonio Palladino, Carla Lucini, Paola Scocco, Paolo de Girolamo, Mario Baumgart, and Livia D’Angelo
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nesf-1 ,vertebrate ,nothobranchius furzeri ,aging ,brain-gut axis ,Medicine - Abstract
Nesfatin-1 (Nesf-1) was identified as an anorexigenic and well conserved molecule in rodents and fish. While tissue distribution of NUCB2 (Nucleobindin 2)/Nesf-1 is discretely known in vertebrates, reports on ontogenetic expression are scarce. Here, we examine the age-related central and peripheral expression of NUCB2/Nesf-1 in the teleost African turquoise killifish Nothobranchius furzeri, a consolidated model organism for aging research. We focused our analysis on brain areas responsible for the regulation of food intake and the rostral intestinal bulb, which is analogous of the mammalian stomach. We hypothesize that in our model, the stomach equivalent structure is the main source of NUCB2 mRNA, displaying higher expression levels than those observed in the brain, mainly during aging. Remarkably, its expression significantly increased in the rostral intestinal bulb compared to the brain, which is likely due to the typical anorexia of aging. When analyzing the pattern of expression, we confirmed the distribution in diencephalic areas involved in food intake regulation at all age stages. Interestingly, in the rostral bulb, NUCB2 mRNA was localized in the lining epithelium of young and old animals, while Nesf-1 immunoreactive cells were distributed in the submucosae. Taken together, our results represent a useful basis for gaining deeper knowledge regarding the mechanisms that regulate food intake during vertebrate aging.
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- 2019
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25. Induced Pluripotent Stem Cells as Vasculature Forming Entities
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Antonio Palladino, Isabella Mavaro, Carmela Pizzoleo, Elena De Felice, Carla Lucini, Paolo de Girolamo, Paolo A. Netti, and Chiara Attanasio
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induced pluripotent stem cells ,tissue engineering ,angiogenesis ,tissue regeneration ,from bench to bedside ,Medicine - Abstract
Tissue engineering (TE) pursues the ambitious goal to heal damaged tissues. One of the most successful TE approaches relies on the use of scaffolds specifically designed and fabricated to promote tissue growth. During regeneration the guidance of biological events may be essential to sustain vasculature neoformation inside the engineered scaffold. In this context, one of the most effective strategies includes the incorporation of vasculature forming cells, namely endothelial cells (EC), into engineered constructs. However, the most common EC sources currently available, intended as primary cells, are affected by several limitations that make them inappropriate to personalized medicine. Human induced Pluripotent Stem Cells (hiPSC), since the time of their discovery, represent an unprecedented opportunity for regenerative medicine applications. Unfortunately, human induced Pluripotent Stem Cells-Endothelial Cells (hiPSC-ECs) still display significant safety issues. In this work, we reviewed the most effective protocols to induce pluripotency, to generate cells displaying the endothelial phenotype and to perform an efficient and safe cell selection. We also provide noteworthy examples of both in vitro and in vivo applications of hiPSC-ECs in order to highlight their ability to form functional blood vessels. In conclusion, we propose hiPSC-ECs as the preferred source of endothelial cells currently available in the field of personalized regenerative medicine.
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- 2019
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26. Rapid Analysis of Deoxynivalenol in Durum Wheat by FT-NIR Spectroscopy
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Annalisa De Girolamo, Salvatore Cervellieri, Angelo Visconti, and Michelangelo Pascale
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deoxynivalenol ,FT-NIR ,rapid method ,wheat ,LDA ,PLS ,Medicine - Abstract
Fourier-transform-near infrared (FT-NIR) spectroscopy has been used to develop quantitative and classification models for the prediction of deoxynivalenol (DON) levels in durum wheat samples. Partial least-squares (PLS) regression analysis was used to determine DON in wheat samples in the range of 2,500 µg/kg) (LDA I). A second approach was used to discriminate highly contaminated wheat samples based on three different cut-off limits, namely 1,000 (LDA II), 1,200 (LDA III) and 1,400 µg/kg DON (LDA IV). The overall classification and false compliant rates for the three models were 75%–90% and 3%–7%, respectively, with model LDA IV using a cut-off of 1,400 µg/kg fulfilling the requirement of the European official guidelines for screening methods. These findings confirmed the suitability of FT-NIR to screen a large number of wheat samples for DON contamination and to verify the compliance with EU regulation.
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- 2014
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27. Intra-Articular Injection of Hydrolyzed Collagen to Treat Symptoms of Knee Osteoarthritis. A Functional In Vitro Investigation and a Pilot Retrospective Clinical Study
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Paola De Luca, Alessandra Colombini, Giulia Carimati, Michelangelo Beggio, Laura de Girolamo, and Piero Volpi
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knee ,osteoarthritis ,hydrolyzed collagen ,intra-articular injection ,non-pharmacological therapy ,Medicine - Abstract
Among all joints affected, knee osteoarthritis has a prevalence of about 10% in men and 13% in women over 60 years old. Knee osteoarthritis has high economic and social costs and may have a devastating impact on patient quality of life. Treatment of symptomatic knee Osteoarthritis may involve oral or topical administration of non-steroidal anti-inflammatory drugs or intra-articular injection of corticosteroids. Recently, a novel injectable collagen formulation (ChondroGrid) consisting of bovine hydrolyzed MMP1/MMP3 and TIMP1/TIMP3 was then assessed through RT-PCR and that of TGFβ1, IGF-I, and VEGF using ELISA assays. Shape and ECM deposition were assessed using the Bern score after a 28-day ChondroGrid exposure, and collagen deposition was assessed using immunostaining. Records of 20 patients affected by Kellgren Lawrence grade 1 to 4 knee osteoarthritis who received three 4 mg/2 mL ChondroGrid injections 2 weeks apart were then retrospectively assessed to compare VAS, Lequesne, and WOMAC scores collected before and 15, 45, and 225 days after the first injection. ChondroGrid had no effects on the markers under consideration, but induced type-II and inhibited type-I collagen deposition; the Bern score was higher when cells were cultured with ChondroGrid. Patients experienced a 44% Lequesne score and a 55% VAS at moving score reduction. All other scores decreased >70%. ChondroGrid may prompt chondrocytes to produce hyaline cartilage, prevent fibrous tissue formation, and be a safe and effective adjuvant to treat symptomatic knee osteoarthritis.
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- 2019
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28. Fluorescence Polarization Immunoassay for the Determination of T-2 and HT-2 Toxins and Their Glucosides in Wheat
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Vincenzo Lippolis, Anna C. R. Porricelli, Erminia Mancini, Biancamaria Ciasca, Veronica M. T. Lattanzio, Annalisa De Girolamo, Chris M. Maragos, Susan McCormick, Peiwu Li, Antonio F. Logrieco, and Michelangelo Pascale
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fluorescence polarization immunoassay ,T-2 toxin ,HT-2 toxin ,T-2 glucoside ,HT-2 glucoside ,wheat ,validation study ,screening method ,Medicine - Abstract
T-2 and HT-2 toxins and their main modified forms (T-2 glucoside and HT-2 glucoside) may co-occur in cereals and cereal-based products. A fluorescence polarization immunoassay (FPIA) was developed for the simultaneous determination of T-2 toxin, HT-2 toxin and relevant glucosides, expressed as sum. The developed FPIA, using a HT-2-specific antibody, showed high sensitivity (IC50 = 2.0 ng/mL) and high cross-reactivity (100% for T-2 toxin and 80% for T-2 and HT-2 glucosides). The FPIA has been used to develop two rapid and easy-to-use methods using two different extraction protocols, based on the use of organic (methanol/water, 90:10, v/v) and non-organic (water) solvents, for the determination of these toxins in wheat. The two proposed methods showed analytical performances in terms of sensitivity (LOD 10 µg/kg) recovery (92−97%) and precision (relative standard deviations ≤13%), fulfilling the criteria for acceptability of an analytical method for the quantitative determination of T-2 and HT-2 toxins established by the European Union. Furthermore, the methods were then validated in accordance with the harmonized guidelines for the validation of screening methods included in the Regulation (EU) No. 519/2014. The satisfactory analytical performances, in terms of intermediate precision (≤25%), cut-off level (80 and 96 µg/kg for the two methods) and rate of false positives (
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- 2019
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29. Identification and Expression of Neurotrophin-6 in the Brain of Nothobranchius furzeri: One More Piece in Neurotrophin Research
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Adele Leggieri, Chiara Attanasio, Antonio Palladino, Alessandro Cellerino, Carla Lucini, Marina Paolucci, Eva Terzibasi Tozzini, Paolo de Girolamo, and Livia D’Angelo
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neurotrophin-6 ,phylogeny ,LNA probe ,riboprobe ,neuroanatomy ,fish ,aging ,Medicine - Abstract
Neurotrophins contribute to the complexity of vertebrate nervous system, being involved in cognition and memory. Abnormalities associated with neurotrophin synthesis may lead to neuropathies, neurodegenerative disorders and age-associated cognitive decline. The genome of teleost fishes contains homologs of some mammalian neurotrophins as well as a gene coding for an additional neurotrophin (NT-6). In this study, we characterized this specific neurotrophin in the short-lived fish Nothobranchius furzeri, a relatively new model for aging studies. Thus, we report herein for the first time the age-related expression of a neurotrophin in a non-mammalian vertebrate. Interestingly, we found comparable expression levels of NT-6 in the brain of both young and old animals. More in detail, we used a locked nucleic acid probe and a riboprobe to investigate the neuroanatomical distribution of NT-6 mRNA revealing a significant expression of the neurotrophin in neurons of the forebrain (olfactory bulbs, dorsal and ventral telencephalon, and several diencephalic nuclei), midbrain (optic tectum, longitudinal tori, and semicircular tori), and hindbrain (valvula and body of cerebellum, reticular formation and octavolateral area of medulla oblongata). By combining in situ hybridization and immunohistochemistry, we showed that NT-6 mRNA is synthesized in mature neurons. These results contribute to better understanding the evolutionary history of neurotrophins in vertebrates, and their role in the adult brain.
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- 2019
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30. Autologous Matrix-Induced Chondrogenesis (AMIC) and AMIC Enhanced by Autologous Concentrated Bone Marrow Aspirate (BMAC) Allow for Stable Clinical and Functional Improvements at up to 9 Years Follow-Up: Results from a Randomized Controlled Study
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Laura de Girolamo, Herbert Schönhuber, Marco Viganò, Corrado Bait, Alessandro Quaglia, Gabriele Thiebat, and Piero Volpi
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autologous matrix-induced chondrogenesis (AMIC) ,bone marrow aspirate concentrate (BMAC) ,cartilage repair ,chondral lesions ,mesenchymal stem cells ,Medicine - Abstract
The aims of the study were to evaluate long-term outcomes after autologous matrix-induced chondrogenesis (AMIC) in the treatment of focal chondral lesions and to assess the possible improvements given by the combination of this technique with bone marrow aspirate concentrate (BMAC). Twenty-four patients (age range 18–55 years) affected by focal knee chondral lesions were treated with standard AMIC or AMIC enhanced by BMAC (AMIC+). Pain (Visual Analogue Scale (VAS)) and functional scores (Lysholm, International Knee Documentation Committee (IKDC), Tegner, Knee injury and Osteoarthritis Outcome Score (KOOS)) were collected pre-operatively and then at 6, 12, 24, 60, and 100 months after treatment. Magnetic resonance imaging (MRI) evaluation was performed pre-operatively and at 6, 12, and 24 months follow-ups. Patients treated with AMIC+ showed higher Lysholm scores (p = 0.015) and lower VAS (p = 0.011) in comparison with patients in the standard AMIC group at the 12 months follow-up. Both treatments allowed for functional and pain improvements with respect to pre-operative levels lasting up to 100 months. MRI revealed consistent cartilage repair at 24 months in both groups. This study shows that AMIC and AMIC+ are effective treatments for focal chondral lesions with beneficial effect lasting up to 9 years. AMIC+ allows for faster recovery from injury, and is thus more indicated for patients requiring a prompt return to activity. Level of evidence: II, randomized controlled trial in an explorative cohort.
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- 2019
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31. Human Diseased Articular Cartilage Contains a Mesenchymal Stem Cell-Like Population of Chondroprogenitors with Strong Immunomodulatory Responses
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Paola De Luca, Dimitrios Kouroupis, Marco Viganò, Carlotta Perucca-Orfei, Lee Kaplan, Luigi Zagra, Laura de Girolamo, Diego Correa, and Alessandra Colombini
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cartilage cells ,cartilage-derived stem/progenitor cells ,mesenchymal stem cells ,stemness ,inflammation ,secretome ,immunomodulation ,Medicine - Abstract
Background: osteoarthritic human articular cartilage (AC)-derived cartilage cells (CCs) with same-donor bone marrow (BMSCs) and adipose tissue (ASCs)-derived mesenchymal stem cells were compared, in terms of stemness features, and secretory and immunomodulatory responses to inflammation. Methods: proteoglycan 4 (PRG4) presence was evaluated in AC and CCs. MSCs and CCs (n = 8) were cultured (P1 to P4) and characterized for clonogenicity, nanog homeobox (NANOG), and POU class 5 homeobox 1 (POU5F1) expression, immunotypification, and tri-lineage differentiation. Their basal and interleukin-1β (IL-1β)-stimulated expression of matrix metalloproteases (MMPs), tissue inhibitors (TIMPs), release of growth factors, and cytokines were analyzed, along with the immunomodulatory ability of CCs. Results: PRG4 was mainly expressed in the intact AC surface, whereas shifted to the intermediate zone in damaged cartilage and increased its expression in CCs upon culture. All cells exhibited a similar phenotype and stemness maintenance over passages. CCs showed highest chondrogenic ability, no adipogenic potential, a superior basal secretion of growth factors and cytokines, the latter further increased after inflammatory stimulation, and an immunomodulatory behavior. All stimulated cells shared an increased MMP expression without a corresponding TIMP production. Conclusion: based on the observed features, CCs obtained from pathological joints may constitute a potential tissue-specific therapeutic target or agent to improve damaged cartilage healing, especially damage caused by inflammatory/immune mediated conditions.
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- 2019
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32. Evaluation of Mycotoxin Screening Tests in a Verification Study Involving First Time Users
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Veronica M. T. Lattanzio, Christoph von Holst, Vincenzo Lippolis, Annalisa De Girolamo, Antonio F. Logrieco, Hans G. J. Mol, and Michelangelo Pascale
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mycotoxins ,screening ,validation ,immunoassay ,mass spectrometry ,cereals ,Medicine - Abstract
Rapid screening methods are currently recognized as a strategic tool for mycotoxin issues management. Specific guidelines for validation and verification of mycotoxin screening methods are set in the Commission Regulation (EU) No 2014/519. This regulation establishes that the “aim of the validation is to demonstrate the fitness-for-purpose of the screening method„ and focuses the entire validation procedure on determining specific cut-off values ensuring a maximum rate of false negative results of 5%. In addition, the assessment of the rate of false suspect results is addressed. With regard to rapid test-kits, ‘fitness-for-purpose’ includes not only the criteria more commonly considered when discussing laboratory-based methods (specificity, accuracy, and precision), but also more “practical„ parameters such as speed and ease of implementation in a new operational environment. The latter means demonstrating under local conditions that performance parameters, as established during the validation, can be achieved by first time users. This goal can be achieved through “method verification„. The aim of the present study was to verify the fitness-for-purpose of mycotoxin screening methods when applied by first time users. This was achieved in one laboratory facility via results of a training course with multiple technicians attending. The verification study was organized similarly to a collaborative exercise and involved two groups comprising of 10 technicians each that used the methods for the first time. Different screening methods were applied for deoxynivalenol (DON) in wheat, which was mainly Enzyme Linked Immunosorbent Assay (ELISA), lateral flow device (LFD), fluorescence polarization immunoassay (FPIA), and liquid chromatography-high resolution mass spectrometry (LC-HRMS). An additional verification was done for aflatoxin B1 (AFB1) in maize and wheat using LFD and LC-HRMS, respectively. The results of analyses were used to calculate intermediate precision (RSDip, covering the inter-analyst variability in preparing the analytical samples and the precision under repeatability conditions) cut-off values and false suspect rates. RSDip ranged from 6.5% to 30% for DON, and from 16% to 33% for AFB1. The highest obtained variances were associated with the AFB1 analyses due to working with much lower mass fractions. The rate of false suspect results were lower than 0.1% for all tested methods. All methods showed a fit-for-purpose method performance profile, which allowed a clear distinction of samples containing the analytes at the screening target concentration (STC) from negative control samples. Moreover, the first time users obtained method performances similar to those obtained for validation studies previously performed on the screening methods included in the training course.
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- 2019
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33. Dose-Related and Time-Dependent Development of Collagenase-Induced Tendinopathy in Rats.
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Carlotta Perucca Orfei, Arianna B Lovati, Marco Viganò, Deborah Stanco, Marta Bottagisio, Alessia Di Giancamillo, Stefania Setti, and Laura de Girolamo
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Medicine ,Science - Abstract
Tendinopathy is a big burden in clinics and it represents 45% of musculoskeletal lesions. Despite the relevant social impact, both pathogenesis and development of the tendinopathy are still under-investigated, thus limiting the therapeutic advancement in this field. The purpose of this study was to evaluate the dose-dependent and time-related tissue-level changes occurring in a collagenase-induced tendinopathy in rat Achilles tendons, in order to establish a standardized model for future pre-clinical studies. With this purpose, 40 Sprague Dawley rats were randomly divided into two groups, treated by injecting collagenase type I within the Achilles tendon at 1 mg/mL (low dose) or 3 mg/mL (high dose). Tendon explants were histologically evaluated at 3, 7, 15, 30 and 45 days. Our results revealed that both the collagenase doses induced a disorganization of collagen fibers and increased the number of rounded resident cells. In particular, the high dose treatment determined a greater neovascularization and fatty degeneration with respect to the lower dose. These changes were found to be time-dependent and to resemble the features of human tendinopathy. Indeed, in our series, the acute phase occurred from day 3 to day 15, and then progressed towards the proliferative phase from day 30 to day 45 displaying a degenerative appearance associated with a very precocious and mild remodeling process. The model represents a good balance between similarity with histological features of human tendinopathy and feasibility, in terms of tendon size to create lesions and costs when compared to other animal models. Moreover, this model could contribute to improve the knowledge in this field, and it could be useful to properly design further pre-clinical studies to test innovative treatments for tendinopathy.
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- 2016
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34. Prevalence and Risk Factors of Violence by Psychiatric Acute Inpatients: A Systematic Review and Meta-Analysis.
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Laura Iozzino, Clarissa Ferrari, Matthew Large, Olav Nielssen, and Giovanni de Girolamo
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Medicine ,Science - Abstract
BackgroundViolence in acute psychiatric wards affects the safety of other patients and the effectiveness of treatment. However, there is a wide variation in reported rates of violence in acute psychiatric wards.ObjectivesTo use meta-analysis to estimate the pooled rate of violence in published studies, and examine the characteristics of the participants, and aspects of the studies themselves that might explain the variation in the reported rates of violence (moderators).MethodSystematic meta-analysis of studies published between January 1995 and December 2014, which reported rates of violence in acute psychiatric wards of general or psychiatric hospitals in high-income countries.ResultsOf the 23,972 inpatients described in 35 studies, the pooled proportion of patients who committed at least one act of violence was 17% (95% confidence interval (CI) 14-20%). Studies with higher proportions of male patients, involuntary patients, patients with schizophrenia and patients with alcohol use disorder reported higher rates of inpatient violence.ConclusionThe findings of this study suggest that almost 1 in 5 patients admitted to acute psychiatric units may commit an act of violence. Factors associated with levels of violence in psychiatric units are similar to factors that are associated with violence among individual patients (male gender, diagnosis of schizophrenia, substance use and lifetime history of violence).
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- 2015
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35. Probiotics Reduce Inflammation in Antiretroviral Treated, HIV-Infected Individuals: Results of the 'Probio-HIV' Clinical Trial.
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Gabriella d'Ettorre, Giancarlo Ceccarelli, Noemi Giustini, Sara Serafino, Nina Calantone, Gabriella De Girolamo, Luigi Bianchi, Valeria Bellelli, Tommaso Ascoli-Bartoli, Sonia Marcellini, Ombretta Turriziani, Jason M Brenchley, and Vincenzo Vullo
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Medicine ,Science - Abstract
HIV infection results in damage to the gastrointestinal (GI) tract, microbial translocation and immune activation. These are not completely normalized with combined antiretroviral therapy (cART). Moreover, increate morbidity and mortality of cART-treated HIV-infected individuals is associated with inflammation.In order to enhance GI tract immunity, we recruited and treated 20 HIV-infected humans with cART supplemented with probiotics and followed inflammation and immunological parameters (clinical trial number NCT02164344). 11 HIV seronegative subjects were included as control group. The enumeration of CD4+, CD8+, CD38+ and HLA-DR+ lymphocytes were evaluated on peripheral blood; HIV-RNA levels, sCD14, d-dimer, C-reactive protein (CRP) high sensitivity C-reactive protein (hsCRP), IL-6 and Lipopolysaccharide Binding Protein (LBP) were assayed on plasma.We observe that cART does not normalize the levels of immune activation in HIV positive patients anyway inflammation and markers of microbial translocation were significantly reduced with probiotic supplementation. Patients show a clear and statistically significant reduction in the levels of immune activation on CD4 T-lymphocytes, for both markers CD38 and HLA-DR and their simultaneous expression, LBP and hsCRP plasma levels after probiotic diet supplementation settling to values comparable to controls.Supplementing cART with probiotics in HIV-infected individuals may improve GI tract immunity and there by mitigate inflammatory sequelae, ultimately improving prognosis.ClinicalTrials.gov NCT02164344.
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- 2015
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36. The orexin system in the enteric nervous system of the bottlenose dolphin (Tursiops truncatus).
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Claudia Gatta, Finizia Russo, Maria Grazia Russolillo, Ettore Varricchio, Marina Paolucci, Luciana Castaldo, Carla Lucini, Paolo de Girolamo, Bruno Cozzi, and Lucianna Maruccio
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Medicine ,Science - Abstract
This study provides a general approach to the presence and possible role of orexins and their receptors in the gut (three gastric chambers and intestine) of confined environment bottlenose dolphin. The expression of prepro-orexin, orexin A and B and orexin 1 and 2 receptors were investigated by single immunostaining and western blot analysis. The co-localization of vasoactive intestinal peptide and orexin 1 receptor in the enteric nervous system was examined by double immunostaining. Also, orexin A concentration were measured in plasma samples to assess the possible diurnal variation of the plasma level of peptide in this species. Our results showed that the orexin system is widely distributed in bottlenose dolphin enteric nervous system of the all gastrointestinal tract examined. They are very peculiar and partially differs from that of terrestrial mammals. Orexin peptides and prepro-orexin were expressed in the main stomach, pyloric stomach and proximal intestine; while orexin receptors were expressed in the all examined tracts, with the exception of main stomach where found no evidence of orexin 2 receptor. Co-localization of vasoactive intestinal peptide and orexin 1 receptor were more evident in the pyloric stomach and proximal intestine. These data could suggest a possible role of orexin system on the contractility of bottlenose dolphin gastrointestinal districts. Finally, in agreement with several reports, bottlenose dolphin orexin A plasma level was higher in the morning during fasting. Our results emphasize some common features between bottlenose dolphin and terrestrial mammals. Certainly, further functional investigations may help to better explain the role of the orexin system in the energy balance of bottlenose dolphin and the complex interaction between feeding and digestive physiology.
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- 2014
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37. Comparison of In-Solution Biorecognition Properties of Aptamers against Ochratoxin A
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Maureen McKeague, Ranganathan Velu, Annalisa De Girolamo, Stefania Valenzano, Michelangelo Pascale, McKenzie Smith, and Maria C. DeRosa
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aptamer ,ochratoxin A ,mycotoxins ,biorecognition ,fluorescent assay ,biosensing ,aptasensor ,microscale thermophoresis ,Medicine - Abstract
Ochratoxin A (OTA) is a mycotoxin produced as a secondary metabolite by several species of Aspergillus and Penicillium and frequently found as a natural contaminant in a wide range of food commodities. Novel and robust biorecognition agents for detecting this molecule are required. Aptamers are artificial nucleic acid ligands able to bind with high affinity and specificity to a given target molecule. In the last few years, three separate research groups have selected aptamers for ochratoxin A. While each of these three families of aptamers have been incorporated into various methods for detecting OTA, it is unclear if each aptamer candidate is better suited for a particular application. Here, we perform the first head-to-head comparison of solution-based binding parameters for these groups of aptamers. Based on our results, we provide recommendations for the appropriate choice of aptamer for incorporation into solution-based biorecognition assays and applications.
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- 2016
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38. Disability mediates the impact of common conditions on perceived health.
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Jordi Alonso, Gemma Vilagut, Núria D Adroher, Somnath Chatterji, Yanling He, Laura Helena Andrade, Evelyn Bromet, Ronny Bruffaerts, John Fayyad, Silvia Florescu, Giovanni de Girolamo, Oye Gureje, Josep Maria Haro, Hristo Hinkov, Chiyi Hu, Noboru Iwata, Sing Lee, Daphna Levinson, Jean Pierre Lépine, Herbert Matschinger, Maria Elena Medina-Mora, Siobhan O'Neill, J Hans Ormel, Jose A Posada-Villa, Nezar Ismet Taib, Miguel Xavier, and Ronald C Kessler
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Medicine ,Science - Abstract
BackgroundWe examined the extent to which disability mediates the observed associations of common mental and physical conditions with perceived health.Methods and findingsWHO World Mental Health (WMH) Surveys carried out in 22 countries worldwide (n = 51,344 respondents, 72.0% response rate). We assessed nine common mental conditions with the WHO Composite International Diagnostic Interview (CIDI), and ten chronic physical with a checklist. A visual analog scale (VAS) score (0, worst to 100, best) measured perceived health in the previous 30 days. Disability was assessed using a modified WHO Disability Assessment Schedule (WHODAS), including: cognition, mobility, self-care, getting along, role functioning (life activities), family burden, stigma, and discrimination. Path analysis was used to estimate total effects of conditions on perceived health VAS and their separate direct and indirect (through the WHODAS dimensions) effects. Twelve-month prevalence was 14.4% for any mental and 51.4% for any physical condition. 31.7% of respondents reported difficulties in role functioning, 11.4% in mobility, 8.3% in stigma, 8.1% in family burden and 6.9% in cognition. Other difficulties were much less common. Mean VAS score was 81.0 (SD = 0.1). Decrements in VAS scores were highest for neurological conditions (9.8), depression (8.2) and bipolar disorder (8.1). Across conditions, 36.8% (IQR: 31.2-51.5%) of the total decrement in perceived health associated with the condition were mediated by WHODAS disabilities (significant for 17 of 19 conditions). Role functioning was the dominant mediator for both mental and physical conditions. Stigma and family burden were also important mediators for mental conditions, and mobility for physical conditions.ConclusionsMore than a third of the decrement in perceived health associated with common conditions is mediated by disability. Although the decrement is similar for physical and mental conditions, the pattern of mediation is different. Research is needed on the benefits for perceived health of targeted interventions aimed at particular disability dimensions.
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- 2013
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39. Associations between lifetime traumatic events and subsequent chronic physical conditions: a cross-national, cross-sectional study.
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Kate M Scott, Karestan C Koenen, Sergio Aguilar-Gaxiola, Jordi Alonso, Matthias C Angermeyer, Corina Benjet, Ronny Bruffaerts, Jose Miguel Caldas-de-Almeida, Giovanni de Girolamo, Silvia Florescu, Noboru Iwata, Daphna Levinson, Carmen C W Lim, Sam Murphy, Johan Ormel, Jose Posada-Villa, and Ronald C Kessler
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Medicine ,Science - Abstract
Associations between lifetime traumatic event (LTE) exposures and subsequent physical ill-health are well established but it has remained unclear whether these are explained by PTSD or other mental disorders. This study examined this question and investigated whether associations varied by type and number of LTEs, across physical condition outcomes, or across countries.Cross-sectional, face-to-face household surveys of adults (18+) were conducted in 14 countries (n = 38, 051). The Composite International Diagnostic Interview assessed lifetime LTEs and DSM-IV mental disorders. Chronic physical conditions were ascertained by self-report of physician's diagnosis and year of diagnosis or onset. Survival analyses estimated associations between the number and type of LTEs with the subsequent onset of 11 physical conditions, with and without adjustment for mental disorders.A dose-response association was found between increasing number of LTEs and odds of any physical condition onset (OR 1.5 [95% CI: 1.4-1.5] for 1 LTE; 2.1 [2.0-2.3] for 5+ LTEs), independent of all mental disorders. Associations did not vary greatly by type of LTE (except for combat and other war experience), nor across countries. A history of 1 LTE was associated with 7/11 of the physical conditions (ORs 1.3 [1.2-1.5] to 1.7 [1.4-2.0]) and a history of 5+ LTEs was associated with 9/11 physical conditions (ORs 1.8 [1.3-2.4] to 3.6 [2.0-6.5]), the exceptions being cancer and stroke.Traumatic events are associated with adverse downstream effects on physical health, independent of PTSD and other mental disorders. Although the associations are modest they have public health implications due to the high prevalence of traumatic events and the range of common physical conditions affected. The effects of traumatic stress are a concern for all medical professionals and researchers, not just mental health specialists.
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- 2013
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40. Correction: Disability Mediates the Impact of Common Conditions on Perceived Health.
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Jordi Alonso, Gemma Vilagut, Núria D. Adroher, Somnath Chatterji, Yanling He, Laura Helena Andrade, Evelyn Bromet, Ronny Bruffaerts, John Fayyad, Silvia Florescu, Giovanni de Girolamo, Oye Gureje, Josep Maria Haro, Hristo Hinkov, Chiyi Hu, Noboru Iwata, Sing Lee, Daphna Levinson, Jean Pierre Lépine, Herbert Matschinger, Maria Elena Medina-Mora, Siobhan O'Neill, J. Hormel, Jose A. Posada-Villa, Nezar Ismet Taib, Miguel Xavier, and Ronald C. Kessler
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Medicine ,Science - Published
- 2013
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41. Cross-national analysis of the associations between traumatic events and suicidal behavior: findings from the WHO World Mental Health Surveys.
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Dan J Stein, Wai Tat Chiu, Irving Hwang, Ronald C Kessler, Nancy Sampson, Jordi Alonso, Guilherme Borges, Evelyn Bromet, Ronny Bruffaerts, Giovanni de Girolamo, Silvia Florescu, Oye Gureje, Yanling He, Viviane Kovess-Masfety, Daphna Levinson, Herbert Matschinger, Zeina Mneimneh, Yosikazu Nakamura, Johan Ormel, Jose Posada-Villa, Rajesh Sagar, Kate M Scott, Toma Tomov, Maria Carmen Viana, David R Williams, and Matthew K Nock
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Medicine ,Science - Abstract
BackgroundCommunity and clinical data have suggested there is an association between trauma exposure and suicidal behavior (i.e., suicide ideation, plans and attempts). However, few studies have assessed which traumas are uniquely predictive of: the first onset of suicidal behavior, the progression from suicide ideation to plans and attempts, or the persistence of each form of suicidal behavior over time. Moreover, few data are available on such associations in developing countries. The current study addresses each of these issues.Methodology/principal findingsData on trauma exposure and subsequent first onset of suicidal behavior were collected via structured interviews conducted in the households of 102,245 (age 18+) respondents from 21 countries participating in the WHO World Mental Health Surveys. Bivariate and multivariate survival models tested the relationship between the type and number of traumatic events and subsequent suicidal behavior. A range of traumatic events are associated with suicidal behavior, with sexual and interpersonal violence consistently showing the strongest effects. There is a dose-response relationship between the number of traumatic events and suicide ideation/attempt; however, there is decay in the strength of the association with more events. Although a range of traumatic events are associated with the onset of suicide ideation, fewer events predict which people with suicide ideation progress to suicide plan and attempt, or the persistence of suicidal behavior over time. Associations generally are consistent across high-, middle-, and low-income countries.Conclusions/significanceThis study provides more detailed information than previously available on the relationship between traumatic events and suicidal behavior and indicates that this association is fairly consistent across developed and developing countries. These data reinforce the importance of psychological trauma as a major public health problem, and highlight the significance of screening for the presence and accumulation of traumatic exposures as a risk factor for suicide ideation and attempt.
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- 2010
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42. Cross-national analysis of the associations among mental disorders and suicidal behavior: findings from the WHO World Mental Health Surveys.
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Matthew K Nock, Irving Hwang, Nancy Sampson, Ronald C Kessler, Matthias Angermeyer, Annette Beautrais, Guilherme Borges, Evelyn Bromet, Ronny Bruffaerts, Giovanni de Girolamo, Ron de Graaf, Silvia Florescu, Oye Gureje, Josep Maria Haro, Chiyi Hu, Yueqin Huang, Elie G Karam, Norito Kawakami, Viviane Kovess, Daphna Levinson, Jose Posada-Villa, Rajesh Sagar, Toma Tomov, Maria Carmen Viana, and David R Williams
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Medicine - Abstract
Suicide is a leading cause of death worldwide. Mental disorders are among the strongest predictors of suicide; however, little is known about which disorders are uniquely predictive of suicidal behavior, the extent to which disorders predict suicide attempts beyond their association with suicidal thoughts, and whether these associations are similar across developed and developing countries. This study was designed to test each of these questions with a focus on nonfatal suicide attempts.Data on the lifetime presence and age-of-onset of Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) mental disorders and nonfatal suicidal behaviors were collected via structured face-to-face interviews with 108,664 respondents from 21 countries participating in the WHO World Mental Health Surveys. The results show that each lifetime disorder examined significantly predicts the subsequent first onset of suicide attempt (odds ratios [ORs] = 2.9-8.9). After controlling for comorbidity, these associations decreased substantially (ORs = 1.5-5.6) but remained significant in most cases. Overall, mental disorders were equally predictive in developed and developing countries, with a key difference being that the strongest predictors of suicide attempts in developed countries were mood disorders, whereas in developing countries impulse-control, substance use, and post-traumatic stress disorders were most predictive. Disaggregation of the associations between mental disorders and nonfatal suicide attempts showed that these associations are largely due to disorders predicting the onset of suicidal thoughts rather than predicting progression from thoughts to attempts. In the few instances where mental disorders predicted the transition from suicidal thoughts to attempts, the significant disorders are characterized by anxiety and poor impulse-control. The limitations of this study include the use of retrospective self-reports of lifetime occurrence and age-of-onset of mental disorders and suicidal behaviors, as well as the narrow focus on mental disorders as predictors of nonfatal suicidal behaviors, each of which must be addressed in future studies.This study found that a wide range of mental disorders increased the odds of experiencing suicide ideation. However, after controlling for psychiatric comorbidity, only disorders characterized by anxiety and poor impulse-control predict which people with suicide ideation act on such thoughts. These findings provide a more fine-grained understanding of the associations between mental disorders and subsequent suicidal behavior than previously available and indicate that mental disorders predict suicidal behaviors similarly in both developed and developing countries. Future research is needed to delineate the mechanisms through which people come to think about suicide and subsequently progress from ideation to attempts.
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- 2009
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43. Toward a global view of alcohol, tobacco, cannabis, and cocaine use: findings from the WHO World Mental Health Surveys.
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Louisa Degenhardt, Wai-Tat Chiu, Nancy Sampson, Ronald C Kessler, James C Anthony, Matthias Angermeyer, Ronny Bruffaerts, Giovanni de Girolamo, Oye Gureje, Yueqin Huang, Aimee Karam, Stanislav Kostyuchenko, Jean Pierre Lepine, Maria Elena Medina Mora, Yehuda Neumark, J Hans Ormel, Alejandra Pinto-Meza, José Posada-Villa, Dan J Stein, Tadashi Takeshima, and J Elisabeth Wells
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Medicine - Abstract
BackgroundAlcohol, tobacco, and illegal drug use cause considerable morbidity and mortality, but good cross-national epidemiological data are limited. This paper describes such data from the first 17 countries participating in the World Health Organization's (WHO's) World Mental Health (WMH) Survey Initiative.Methods and findingsHousehold surveys with a combined sample size of 85,052 were carried out in the Americas (Colombia, Mexico, United States), Europe (Belgium, France, Germany, Italy, Netherlands, Spain, Ukraine), Middle East and Africa (Israel, Lebanon, Nigeria, South Africa), Asia (Japan, People's Republic of China), and Oceania (New Zealand). The WHO Composite International Diagnostic Interview (CIDI) was used to assess the prevalence and correlates of a wide variety of mental and substance disorders. This paper focuses on lifetime use and age of initiation of tobacco, alcohol, cannabis, and cocaine. Alcohol had been used by most in the Americas, Europe, Japan, and New Zealand, with smaller proportions in the Middle East, Africa, and China. Cannabis use in the US and New Zealand (both 42%) was far higher than in any other country. The US was also an outlier in cocaine use (16%). Males were more likely than females to have used drugs; and a sex-cohort interaction was observed, whereby not only were younger cohorts more likely to use all drugs, but the male-female gap was closing in more recent cohorts. The period of risk for drug initiation also appears to be lengthening longer into adulthood among more recent cohorts. Associations with sociodemographic variables were consistent across countries, as were the curves of incidence of lifetime use.ConclusionsGlobally, drug use is not distributed evenly and is not simply related to drug policy, since countries with stringent user-level illegal drug policies did not have lower levels of use than countries with liberal ones. Sex differences were consistently documented, but are decreasing in more recent cohorts, who also have higher levels of illegal drug use and extensions in the period of risk for initiation.
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- 2008
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44. Cross-national epidemiology of DSM-IV major depressive episode
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Matschinger Herbert, Levinson Daphna, Lépine Jean-Pierre, Kaur Jagdish, Kostyuchenko Stanislav, Karam Aimee N, Iwata Noboru, Hu Chiyi, Demyttenaere Koen, de Graaf Ron, de Girolamo Giovanni, Alonso Jordi, Sampson Nancy A, Hwang Irving, Bromet Evelyn, Andrade Laura, Mora Maria, Browne Mark, Posada-Villa Jose, Viana Maria, Williams David R, and Kessler Ronald C
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Medicine - Abstract
Abstract Background Major depression is one of the leading causes of disability worldwide, yet epidemiologic data are not available for many countries, particularly low- to middle-income countries. In this paper, we present data on the prevalence, impairment and demographic correlates of depression from 18 high and low- to middle-income countries in the World Mental Health Survey Initiative. Methods Major depressive episodes (MDE) as defined by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DMS-IV) were evaluated in face-to-face interviews using the World Health Organization Composite International Diagnostic Interview (CIDI). Data from 18 countries were analyzed in this report (n = 89,037). All countries surveyed representative, population-based samples of adults. Results The average lifetime and 12-month prevalence estimates of DSM-IV MDE were 14.6% and 5.5% in the ten high-income and 11.1% and 5.9% in the eight low- to middle-income countries. The average age of onset ascertained retrospectively was 25.7 in the high-income and 24.0 in low- to middle-income countries. Functional impairment was associated with recency of MDE. The female: male ratio was about 2:1. In high-income countries, younger age was associated with higher 12-month prevalence; by contrast, in several low- to middle-income countries, older age was associated with greater likelihood of MDE. The strongest demographic correlate in high-income countries was being separated from a partner, and in low- to middle-income countries, was being divorced or widowed. Conclusions MDE is a significant public-health concern across all regions of the world and is strongly linked to social conditions. Future research is needed to investigate the combination of demographic risk factors that are most strongly associated with MDE in the specific countries included in the WMH.
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- 2011
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45. Free d-aspartate triggers NMDA receptor-dependent cell death in primary cortical neurons and perturbs JNK activation, Tau phosphorylation, and protein SUMOylation in the cerebral cortex of mice lacking d-aspartate oxidase activity
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Ilaria Pagano, Daniela Punzo, Loredano Pollegioni, Marco Feligioni, Luigia Cristino, Massimo Carella, Paolo de Girolamo, Filomena Iannuzzi, Serena Marcelli, Carla Petrella, Francesco Errico, Nadia Canu, Livia D'Angelo, Roberta Imperatore, Alessandro Usiello, Silvia Sacchi, Tommaso Nuzzo, Nuzzo, T, Feligioni, M, Cristino, L, Pagano, I, Marcelli, S, Iannuzzi, F, Imperatore, R, D'Angelo, L, Petrella, C, Carella, M, Pollegioni, L, Sacchi, S, Punzo, D, De Girolamo, P, Errico, F, Canu, N, Usiello, A, Nuzzo, T., Feligioni, M., Cristino, L., Pagano, I., Marcelli, S., Iannuzzi, F., Imperatore, R., D'Angelo, L., Petrella, C., Carella, M., Pollegioni, L., Sacchi, S., Punzo, D., De Girolamo, P., Errico, F., Canu, N., Usiello, A., and Errico, Francesco
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0301 basic medicine ,Aging ,D-Aspartate Oxidase ,MAP Kinase Kinase 4 ,Hippocampus ,Mouse models ,Mice ,0302 clinical medicine ,Alzheimer's disease ,JNK ,NMDA receptor ,SUMOylation ,Tau ,d-aspartate ,d-aspartate oxidase ,?-Amiloyd ,Pregnancy ,Phosphorylation ,Aged, 80 and over ,Cerebral Cortex ,Mice, Knockout ,Neurons ,Neuronal Plasticity ,Cell Death ,Chemistry ,D-Aspartic Acid ,D-aspartate ,Middle Aged ,Cell biology ,medicine.anatomical_structure ,Neurology ,Cerebral cortex ,microscopy ,Female ,β-Amiloyd ,Protein sumoylation ,D-aspartate oxidase ,Developmental Neuroscience ,d-aspartato ,brain ,Primary Cell Culture ,Substantia nigra ,tau Proteins ,Settore BIO/09 ,Receptors, N-Methyl-D-Aspartate ,Mouse model ,03 medical and health sciences ,Alzheimer Disease ,medicine ,Animals ,Humans ,Aged ,Pars compacta ,Sumoylation ,istochemistry ,030104 developmental biology ,Synaptic plasticity ,d-aminoacidi ,Cognition Disorders ,030217 neurology & neurosurgery - Abstract
In mammals, free d-aspartate (D-Asp) is abundant in the embryonic brain, while levels remain very low during adulthood as a result of the postnatal expression and activity of the catabolizing enzyme d-aspartate oxidase (DDO). Previous studies have shown that long-lasting exposure to nonphysiological, higher D-Asp concentrations in Ddo knockout (Ddo-/-) mice elicits a precocious decay of synaptic plasticity and cognitive functions, along with a dramatic age-dependent expression of active caspase 3, associated with increased cell death in different brain regions, including hippocampus, prefrontal cortex, and substantia nigra pars compacta. Here, we investigate the yet unclear molecular and cellular events associated with the exposure of abnormally high D-Asp concentrations in cortical primary neurons and in the brain of Ddo-/- mice. For the first time, our in vitro findings document that D-Asp induces in a time-, dose-, and NMDA receptor-dependent manner alterations in JNK and Tau phosphorylation levels, associated with pronounced cell death in primary cortical neurons. Moreover, observations obtained in Ddo-/- animals confirmed that high in vivo levels of D-Asp altered cortical JNK signaling, Tau phosphorylation and enhanced protein SUMOylation, indicating a robust indirect role of DDO activity in regulating these biochemical NMDA receptor-related processes. Finally, no gross modifications in D-Asp concentrations and DDO mRNA expression were detected in the cortex of patients with Alzheimer's disease when compared to age-matched healthy controls. In mammals, free D-aspartate (D-Asp) is abundant in the embryonic brain, while levels remain very low during adulthood as a result of the postnatal expression and activity of the catabolizing enzyme D-aspartate oxidase (DDO). Previous studies have shown that long-lasting exposure to nonphysiological, higher D-Asp concentrations in Ddo knockout (Ddo(-/-)) mice elicits a precocious decay of synaptic plasticity and cognitive functions, along with a dramatic age-dependent expression of active caspase 3, associated with increased cell death in different brain regions, including hippocampus, prefrontal cortex, and substantia nigra pars compacta. Here, we investigate the yet unclear molecular and cellular events associated with the exposure of abnormally high D-Asp concentrations in cortical primary neurons and in the brain of Ddo(-/-) mice. For the first time, our in vitro findings document that D-Asp induces in a time-, dose-, and NMDA receptor-dependent manner alterations in JNK and Tau phosphorylation levels, associated with pronounced cell death in primary cortical neurons, Moreover, observations obtained in Ddo(-/-) animals confirmed that high in vivo levels of D-Asp altered cortical JNK signaling, Tau phosphorylation and enhanced protein SUMOylation, indicating a robust indirect role of DDO activity in regulating these biochemical NMDA receptor-related processes. Finally, no gross modifications in D-Asp concentrations and DDO mRNA expression were detected in the cortex of patients with Alzheimer's disease when compared to age-matched healthy controls.
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- 2018
46. Distinct Pattern of NPY in Gastro-Entero-Pancreatic System of Goat Kids Fed with a New Standardized Red Orange and Lemon Extract (RLE)
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Elena De Felice, Sara Damiano, Livia D'Angelo, Paola Scocco, Paolo de Girolamo, Simona Fabroni, Angela Salzano, Daniela Giaquinto, Roberto Ciarcia, De Felice, E, Giaquinto, D, Damiano, S, Salzano, A, Fabroni, S, Ciarcia, R, Scocco, P, de Girolamo, P, and D'Angelo, L.
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feed additive ,medicine.medical_specialty ,goats ,Feed additive ,Neuropeptide ,Biology ,Abomasum ,Article ,natural compound ,Orexigenic ,Internal medicine ,lcsh:Zoology ,medicine ,lcsh:QL1-991 ,small ruminants ,gastro-intestinal apparatu ,neuropeptide ,polyphenols ,lcsh:Veterinary medicine ,General Veterinary ,Pancreatic islets ,goat ,neuropeptides ,food and beverages ,gastro-intestinal apparatus ,Neuropeptide Y receptor ,humanities ,polyphenol ,medicine.anatomical_structure ,Endocrinology ,Duodenum ,lcsh:SF600-1100 ,Animal Science and Zoology ,Pancreas ,medicine.drug - Abstract
Simple Summary In the last decades the European ban towards antibiotics resulted in an increase of the number of studies on the effects of natural feed additives, that can enhance the health of farm animals intended for human consumption. Polyphenols such as flavanones and anthocyanins (responsible of the red, purple or blue colors) are bioactive compounds found in fruits and vegetables. Polyphenols possess multiple pharmacological characteristics, like antioxidant, anti-inflammatory and immunostimulant properties. Although many of the biological effects of polyphenols are known, only a limited number of studies has been focused on the effects of their supplementation in ruminant diet. Therefore, we evaluated the effect of a diet supplemented with a standardized powder extract, red (blood) orange and lemon extract (RLE), rich in flavanones, anthocyanins and other polyphenols on the neuropeptide Y (NPY) distribution in the gastro–entero–pancreatic system of goat kids. In mammals, NPY occurs in both the central and peripheral nervous systems and it is involved in the control of different physiological processes, including food intake regulation. For the first time, we document that NPY is widely distributed in the abomasum, duodenum and pancreas of goat kids and that significantly increases in the abomasum and pancreas of RLE supplemented feed animals. Abstract The use of natural compounds as feed additive is also increasing in farm animals, thanks to the beneficial effect on both animals and consumers health. Here, we questioned whether natural extracts, such as red orange and lemon extract (RLE) rich in flavanones, anthocyanins, and other polyphenols, used as feed additives could display an effect on the neuropeptide Y (NPY) in the gastro–entero–pancreatic tract of goat kids. NPY is one of the most abundant neuropeptides in mammals, known for its orexigenic role although it is involved in many central and peripheral functions. We carried out immunohistochemical analyses on samples of abomasum, duodenum and pancreas collected from two experimental groups: one fed with standard diet and one with standard diet + RLE. For the first time we document NPY distribution in the abomasum, duodenum and pancreas of goats and observe the highest number of NPY positive cells in neuroendocrine cells of duodenum. Remarkably, upon RLE feed supplementation, NPY immunoreactive cells increased significantly in abomasal epithelium and pancreatic islets but not in duodenum, likely due to pH variation of abomasum and duodenum. Our observations represent a baseline for future studies on the interaction between neuropeptides and polyphenols, used as feed additive.
- Published
- 2021
47. Orexin-A/Hypocretin-1 Controls the VTA-NAc Mesolimbic Pathway via Endocannabinoid-Mediated Disinhibition of Dopaminergic Neurons in Obese Mice
- Author
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Lea Tunisi, Livia D'Angelo, Alba Clara Fernández-Rilo, Nicola Forte, Fabiana Piscitelli, Roberta Imperatore, Paolo de Girolamo, Vincenzo Di Marzo, Luigia Cristino, Tunisi, L, D'Angelo, L, Fernández-Rilo, Ac, Forte, N, Piscitelli, F, Imperatore, R, de Girolamo, P, Di Marzo, V, and Cristino, L.
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0301 basic medicine ,AM251 ,medicine.medical_specialty ,obesity ,Lateral hypothalamus ,cannabinoid receptor (CB1R) ,Mesolimbic pathway ,leptin ,lcsh:RC321-571 ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Dopamine receptor D2 ,Internal medicine ,medicine ,endocannabinoids ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,reward ,Original Research ,Chemistry ,Dopaminergic ,Cell Biology ,endocannabinoid ,Endocannabinoid system ,Orexin ,Ventral tegmental area ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,nervous system ,orexin ,addiction ,live cell microscopy ,Neuroscience ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Disinhibition of orexin-A/hypocretin-1 (OX-A) release occurs to several output areas of the lateral hypothalamus (LH) in the brain of leptin knockout obese ob/ob mice. In this study, we have investigated whether a similar increase of OX-A release occurs to the ventral tegmental area (VTA), an orexinergic LH output area with functional effects on dopaminergic signaling at the mesolimbic circuit. By confocal and correlative light and electron microscopy (CLEM) morphological studies coupled to molecular, biochemical, and pharmacological approaches, we investigated OX-A-mediated dopaminergic signaling at the LH-VTA-nucleus accumbens (NAc) pathway in obese ob/ob mice compared to wild-type (wt) lean littermates. We found an elevation of OX-A trafficking and release to the VTA of ob/ob mice and consequent orexin receptor-1 (OX1R)-mediated over-activation of dopaminergic (DA) neurons via phospholipase C (PLC)/diacylglycerol lipase (DAGL-α)-induced biosynthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG). In fact, by retrograde signaling to cannabinoid receptor type 1 (CB1R) at inhibitory inputs to DA neurons, 2-AG inhibited GABA release thus inducing an increase in DA concentration in the VTA and NAc of ob/ob mice. This effect was prevented by the OX1R antagonist SB-334867 (30 mg/Kg, i.p.), or the CB1R antagonist AM251 (10 mg/Kg, i.p.) and mimicked by OX-A injection (40 μg/Kg, i.p.) in wt lean mice. Enhanced DA signaling to the NAc in ob/ob mice, or in OX-A-injected wt mice, was accompanied by β-arrestin2-mediated desensitization of dopamine D2 receptor (D2R) in a manner prevented by SB-334867 or the D2R antagonist L741 (1.5 mg/Kg, i.p.). These results further support the role of OX-A signaling in the control of neuroadaptive responses, such as compulsive reward-seeking behavior or binge-like consumption of high palatable food, and suggest that aberrant OX-A trafficking to the DA neurons in the VTA of ob/ob mice influences the D2R response at NAc, a main target area of the mesolimbic pathway, via 2-AG/CB1-mediated retrograde signaling.
- Published
- 2021
48. The Thyroid Hormone-target Gene Rhes a Novel Crossroad for Neurological and Psychiatric Disorders: New Insights from Animal Models
- Author
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Francesco Napolitano, Paolo de Girolamo, Livia D'Angelo, Luigi Avallone, Pieter de Lange, Alessandro Usiello, Napolitano, Francesco, D'Angelo, Livia, DE GIROLAMO, Paolo, Avallone, Luigi, de Lange, Pieter, Usiello, Alessandro., Napolitano, F, D'Angelo, L, de Girolamo, P, Avallone, L, de Lange, P, and Usiello, A
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0301 basic medicine ,medicine.medical_specialty ,Huntingtin ,Parkinson's disease ,striatum ,Striatum ,Biology ,03 medical and health sciences ,0302 clinical medicine ,GTP-Binding Proteins ,Dopamine ,Basal ganglia ,medicine ,Animals ,Psychiatry ,PI3K/AKT/mTOR pathway ,Prepulse inhibition ,Brain Diseases ,Mental Disorders ,General Neuroscience ,Brain ,Heterotrimeric G-protein complex ,schizophrenia ,Disease Models, Animal ,030104 developmental biology ,adenosine ,basal ganglia ,Knockout mouse ,dopamine ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Ras homolog enriched in striatum (Rhes) is predominantly expressed in the corpus striatum. Rhes mRNA is localized in virtually all dopamine D1 and D2 receptor-bearing medium-sized spiny neurons (MSNs), and cholinergic interneurons of striatum. Early studies in rodents showed that Rhes is developmentally regulated by thyroid hormone, as well as by dopamine innervation in adult rat, monkey and human brains. At cellular level, Rhes interferes with adenosine A2A- and dopamine D1 receptor-dependent cAMP/PKA pathway, upstream of the activation of the heterotrimeric G protein complex. Besides its involvement in GPCR-mediated signaling, Rhes modulates Akt pathway activation, acts as E3-ligase of mutant huntingtin, whose sumoylation accounts for neurotoxicity in Huntington's disease, and physically interacts with Beclin-1, suggesting its potential involvement in autophagy-related cellular events. In addition, this protein can also bind to and activate striatal mTORC1, one of the key players in L-DOPA-induced dyskinesia in rodent models of Parkinson's disease. Accordingly, lack of Rhes attenuated such motor disturbances in 6-OHDA-lesioned Rhes knockout mice. In support of its role in MSN-dependent functions, several studies documented that mutant animals displayed alterations in striatum-related phenotypes reminiscent of psychiatric illness in humans, including deficits in prepulse inhibition of startle reflex and, most interestingly, a striking enhancement of behavioral responses elicited by caffeine, phencyclidine or amphetamine. Overall, these data suggest that Rhes modulates molecular and biochemical events underlying striatal functioning, both in physiological and pathological conditions. (C) 2018 IBRO. Published by Elsevier Ltd. All rights reserved.
- Published
- 2018
49. Nerve growth factor is expressed and stored in central neurons of adult zebrafish
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C. Gatta, Elisabeth Pellegrini, Antonio Palladino, Pietro Cacialli, Paolo de Girolamo, Livia D'Angelo, Carla Lucini, Adele Leggieri, Cacialli, P., Gatta, C., D'Angelo, L., Leggieri, A., Palladino, A., de Girolamo, P., Pellegrini, E., Lucini, C., Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Università degli studi di Napoli Federico II, Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), University of Naples Federico II = Università degli studi di Napoli Federico II, and Chard-Hutchinson, Xavier
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0301 basic medicine ,Central Nervous System ,Male ,Histology ,medicine.medical_treatment ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Central nervous system ,neurotrophins ,03 medical and health sciences ,0302 clinical medicine ,Neurotrophic factors ,Nerve Growth Factor ,medicine ,Animals ,Proliferation Marker ,encephalon ,Nerve Growth Factors ,RNA, Messenger ,Aromatase ,Molecular Biology ,Zebrafish ,Ecology, Evolution, Behavior and Systematics ,In Situ Hybridization ,fish ,Neurons ,biology ,Growth factor ,neurotrophin ,[SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Brain ,Cell Biology ,Original Articles ,biology.organism_classification ,Cell biology ,030104 developmental biology ,Nerve growth factor ,medicine.anatomical_structure ,nervous system ,biology.protein ,Female ,Anatomy ,030217 neurology & neurosurgery ,Developmental Biology ,Neurotrophin ,zebrafish neurons - Abstract
International audience; Nerve growth factor (NGF), a member of the neurotrophin family, was initially described as neuronal survival and growth factor, but successively has emerged as an active mediator in many essential functions in the central nervous system of mammals. NGF is synthesized as a precursor pro-NGF and is cleaved intracellularly into mature NGF. However, recent evidence demonstrates that pro-NGF is not a simple inactive precursor, but is also secreted outside the cells and can exert multiple roles. Despite the vast literature present in mammals, studies devoted to NGF in the brain of other vertebrate models are scarce. Zebrafish is a teleost fish widely known for developmental genetic studies and is well established as model for translational neuroscience research. Genomic organization of zebrafish and mouse NGF is highly similar, and zebrafish NGF protein has been reported in mature and two-precursors forms. To add further knowledge on neurotrophic factors in vertebrate brain models, we decided to determine the NGF mRNA and protein distribution in the adult zebrafish brain and to characterize the phenotype of NGF-positive cells. NGF mRNA was visualized by in situ hybridization on whole-mount brains. NGF protein distribution was assessed on microtomic sections by using an antiserum against NGF, able to recognize pro-NGF in adult zebrafish brain as demonstrated also in previous studies. To characterize NGF-positive cells, anti-NGF was employed on microtomic slides of aromatase B transgenic zebrafish (where radial glial cells appeared fluorescent) and by means of double-immunolabeling against NGF/proliferative cell nuclear antigen (PCNA; proliferation marker) and NGF/microtube-associated protein2 (MAP2; neuronal marker). NGF mRNA and protein were widely distributed in the brain of adult zebrafish, and their pattern of distribution of positive perikaryal was overlapping, both in males and females, with few slight differences. Specifically, the immunoreactivity to the protein was observed in fibers over the entire encephalon. MAP2 immunoreactivity was present in the majority of NGF-positive cells, throughout the zebrafish brain. PCNA and aromatase B cells were not positive to NGF, but they were closely intermingled with NGF cells. In conclusion, our study demonstrated that mature neurons in the zebrafish brain express NGF mRNA and store pro-NGF.
- Published
- 2019
50. Neurotrophins and Trk receptors in the developing and adult ovary of Coturnix coturnix japonica
- Author
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L. Maruccio, Luciana Castaldo, Luigi Avallone, Carmen Solcan, P. de Girolamo, L.E. Nechita, Carla Lucini, Maruccio, L, Lucini, C, de Girolamo, P, Avallone, L, Solcan, C, Nechita, Le, and Castaldo, L.
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0301 basic medicine ,animal structures ,Stromal cell ,NT-3 ,Blotting, Western ,Ovary ,Tropomyosin receptor kinase B ,Coturnix ,Tropomyosin receptor kinase A ,Trk receptors ,03 medical and health sciences ,0302 clinical medicine ,Bird ,biology.animal ,Nerve Growth Factor ,medicine ,Animals ,Receptor, trkB ,Receptor, trkC ,Nerve Growth Factors ,Receptor, trkA ,Receptor ,NGF ,biology ,Brain-Derived Neurotrophic Factor ,Receptor Protein-Tyrosine Kinases ,General Medicine ,Gonad ,Immunohistochemistry ,Quail ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,BDNF ,nervous system ,Trk receptor ,embryonic structures ,Models, Animal ,biology.protein ,Female ,Anatomy ,030217 neurology & neurosurgery ,Developmental Biology ,Neurotrophin - Abstract
NGF, BDNF, NT-3 and their specific receptors TrkA, TrkB and TrkC are known to be involved in the development and maintenance of vertebrates’ nervous system. However, these molecules play a role also in non-neuronal tissue, such as in the reproductive system. In this study we investigated the presence and localization of neurotrophins and Trk receptors to unravel their potential role in the developing and adult ovary of Japanese quail, a model species well suited for reproduction studies. Western blotting analysis on ovaries of three month old quails in the period of egg laying showed the presence of pro and mature forms of neurotrophins and splice variants of Trk receptors. Immunohistochemical investigation reported that in embryonic ovaries from the 9th day of incubation to the hatching NGF and NT-3 were observed in the cortical and medullar areas respectively, whereas Trk receptors were observed in both areas. In adult ovary, all NTs were detected in glandular stromal cells, NGF and NT-3 also in the nervous component. Regarding follicle components, NGF and BDNF were observed in oocytes and follicular cells. All TrK receptors were present in nervous components and only TrkA in glandular stromal cells. In follicles, TrkA was present in oocyte cytoplasm and TrkB in theca cells. The results suggest an involvement of the neurotrophin system in the quail ovary physiology, promoting the oocyte development and follicular organization in the embryo, as well as oocyte and follicular maturation in adults.
- Published
- 2018
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