Graziella Mangone

Genetics Specialist

Name Graziella
Surname Mangone
Institution Institut du Cerveau et de la Moelle Epinière – Université Pierre et Marie Curie (Paris)
Address Centre d’Investigation Clinique Bâtiment ICM – 1ère étage – Aile A Hôpital Pitié-Salpêtrière 47 – 83 Boulevard de Hôpital 75013 Paris – France
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Graziella Mangone


  • Pneumococcal serotype distribution in adults with invasive disease and in carrier children in Italy: Should we expect herd protection of adults through infants' vaccination?

    Publication Date: 01/01/2016 on Human vaccines & immunotherapeutics
    by Azzari C, Cortimiglia M, Nieddu F, Moriondo M, Indolfi G, Mattei R, Zuliani M, Adriani B, Degl'Innocenti R, Consales G, Aquilini D, Bini G, Di Natale ME, Canessa C, Ricci S, de Vitis E, Mangone G, Bechini A, Bonanni P, Pasinato A, Resti M
    DOI: 10.1080/21645515.2015.1102811

    The 7-valent pneumococcal conjugate vaccine (PCV7) produced a significant herd protection in unvaccinated adult population mostly because of pneumococcus carriage decrease in vaccinated children. It is not known if the 13-valent pneumococcal vaccine can give similar effect on adults. Aims of the work were to evaluate whether the 6 additional serotypes are present in nasopharynx of children and serotype distribution in invasive pneumococcal infections (IPD) in adults. Realtime-PCR was used to evaluate pneumococcal serotypes in adults with confirmed IPD and in nasopharyngeal swabs (NP) from 629 children not vaccinated or vaccinated with PCV7 and resident in the same geographical areas. Two hundred twenty-one patients (116 males, median 67.9 years) with IPD were studied (pneumonia n = 103, meningitis n = 61 sepsis n = 50, other n = 7). Two hundred twelve were serotyped. The most frequent serotypes were 3, (31/212; 14.6%), 19A, (19/212; 9.0%), 12 (17/212; 8.0%), 7F, (14/212; 6.6%). In NP of children, the frequency of those serotypes causing over 50% of IPD in adults was very low, ranging from 0.48% for serotype 7F to 7.9% for serotype 19A. On the other side serotype 5, very frequent in NP (18.7%) caused <1% IPD. In conclusion serotypes causing IPD in adults are very rarely found in children NP. We suggest that herd protection obtainable with the additional 6 serotypes included in PCV13 may be more limited than that demonstrated with PCV7 in the past. In order to reduce the burden of disease in adults, adults should be offered a specific vaccination program with highly immunogenic PCV.

  • Altered natural killer cells subsets distribution in children with hepatitis C following vertical transmission.

    Publication Date: 01/01/2016 on Alimentary pharmacology & therapeutics
    by Indolfi G, Mangone G, Moriondo M, Serranti D, Bartolini E, Azzari C, Resti M
    DOI: 10.1111/apt.13430

    Natural killer (NK) cells number, phenotypes and function have been evaluated in many studies in adults with hepatitis C as compared with healthy controls or dynamically during interferon-based and interferon-free treatments. Overall, in adults with chronic infection number of circulating NK cells has been reported to be lower when compared to spontaneous resolvers and healthy subjects. Different studies yielded inconsistent findings due to patient and virus heterogeneity.

  • The motor inhibition system in Parkinson's disease with levodopa-induced dyskinesias.

    Publication Date: 01/12/2015 on Movement disorders : official journal of the Movement Disorder Society
    by Cerasa A, Donzuso G, Morelli M, Mangone G, Salsone M, Passamonti L, Augimeri A, Arabia G, Quattrone A
    DOI: 10.1002/mds.26378

    Parkinson's disease is primarily a disorder of response initiation characterized by an excessive motor inhibition, whereas levodopa-induced dyskinesias are clearly a clinical expression of disinhibition of movements.

  • Walking indoors, walking outdoors: an fMRI study.

    Publication Date: 01/10/2015 on Frontiers in psychology
    by Dalla Volta R, Fasano F, Cerasa A, Mangone G, Quattrone A, Buccino G
    DOI: 10.3389/fpsyg.2015.01502

    An observation/execution matching system for walking has not been assessed yet. The present fMRI study was aimed at assessing whether, as for object-directed actions, an observation/execution matching system is active for walking and whether the spatial context of walking (open or narrow space) recruits different neural correlates. Two experimental conditions were employed. In the execution condition, while being scanned, participants performed walking on a rolling cylinder located just outside the scanner. The same action was performed also while observing a video presenting either an open space (a country field) or a narrow space (a corridor). In the observation condition, participants observed a video presenting an individual walking on the same cylinder on which the actual action was executed, the open space video and the narrow space video, respectively. Results showed common bilateral activations in the dorsal premotor/supplementary motor areas and in the posterior parietal lobe for both execution and observation of walking, thus supporting a matching system for this action. Moreover, specific sectors of the occipital-temporal cortex and the middle temporal gyrus were consistently active when processing a narrow space versus an open one, thus suggesting their involvement in the visuo-motor transformation required when walking in a narrow space. We forward that the present findings may have implications for rehabilitation of gait and sport training.

  • A network centred on the inferior frontal cortex is critically involved in levodopa-induced dyskinesias.

    Publication Date: 01/02/2015 on Brain : a journal of neurology
    by Cerasa A, Koch G, Donzuso G, Mangone G, Morelli M, Brusa L, Stampanoni Bassi M, Ponzo V, Picazio S, Passamonti L, Salsone M, Augimeri A, Caltagirone C, Quattrone A
    DOI: 10.1093/brain/awu329

    Levodopa-induced dyskinesias are disabling motor complications of long-term dopamine replacement in patients with Parkinson's disease. In recent years, several alternative models have been proposed to explain the pathophysiological mechanisms underlying this hyperkinetic motor disorder. In particular, our group has shed new light on the role of the prefrontal cortex as a key site of interest, demonstrating that, among other areas, the inferior frontal cortex is particularly characterized by altered patterns of anatomical and functional changes. However, how neural activity varies depending on levodopa treatment in patients with dyskinesias and whether the reported prefrontal abnormalities may have a critical role in dyskinesias is debated. To answer these questions we performed independent functional magnetic resonance imaging and repetitive transcranial magnetic stimulation studies. In the first experiment we applied resting state functional magnetic resonance imaging on 12 patients with Parkinson's disease with levodopa-induced dyskinesias and 12 clinically matched patients without dyskinesias, before and after administration of levodopa. Functional connectivity of brain networks in the resting state was assessed in both groups. We chose the right inferior frontal cortex as the seed region given the evidence highlighting the role of this region in motor control. In a second experiment, we applied different forms of repetitive transcranial magnetic stimulation over the right inferior frontal cortex in a new group of dyskinetic patients who were taking a supramaximal dose of levodopa, to verify the clinical relevance of this area in controlling the development of hyperkinetic movements. The resting state functional imaging analysis revealed that in patients with levodopa-induced dyskinesias connectivity of the right inferior frontal cortex was decreased with the left motor cortex and increased with the right putamen when compared to patients without levodopa-induced dyskinesias. This abnormal pattern of connectivity was evident only during the ON phase of levodopa treatment and the degree of such alteration correlated with motor disability. The repetitive TMS experiments showed that a session of continuous but not intermittent or sham theta burst stimulation applied over the inferior frontal cortex was able to reduce the amount of dyskinesias induced by a supramaximal single dose of levodopa, suggesting that this area may play a key role in controlling the development of dyskinesias. Our combined resting state functional magnetic resonance and transcranial magnetic stimulation studies demonstrate that pathophysiological mechanisms underlying levodopa-induced dyskinesias may extend beyond the 'classical' basal ganglia dysfunctions model, including the modulation performed by the neural network centred on the inferior frontal cortex.

  • Interferon-gamma release assay sensitivity in children younger than 5 years is insufficient to replace the use of tuberculin skin test in western countries.

    Publication Date: 01/12/2014 on The Pediatric infectious disease journal
    by Chiappini E, Bonsignori F, Mazzantini R, Sollai S, Venturini E, Mangone G, Cortimiglia M, Olivito B, Azzari C, Galli L, de Martino M
    DOI: 10.1097/INF.0000000000000432

    Tuberculin skin test, QuantiFERON-TB Gold In-Tube and T-SPOT.TB were performed in 338 children at risk for tuberculosis (TB), including 70 active TB cases. In children <5 years of age, QuantiFERON-TB Gold In-Tube sensitivity was 73.3% [95% confidence interval (CI): 57.5-89.1]; and T-SPOT.TB sensitivity was 59.3% (95% CI: 40.1-77.8); both were inferior to tuberculin skin test sensitivity (90.0%; 95% CI: 79.3-100). In children ≥ 5 years QuantiFERON-TB Gold In-Tube sensitivity was 92.5% (95% CI: 84.4-100); T-SPOT.TB sensitivity was 73.0% (95% CI: 58.6-87.3) ; and tuberculin skin test sensitivity was 97.5% (95% CI: 92.6-100).Test specificities were similar in all age groups.

  • 5-HTTLPR, anxiety and gender interaction moderates right amygdala volume in healthy subjects.

    Publication Date: 01/10/2014 on Social cognitive and affective neuroscience
    by Cerasa A, Quattrone A, Piras F, Mangone G, Magariello A, Fagioli S, Girardi P, Muglia M, Caltagirone C, Spalletta G
    DOI: 10.1093/scan/nst144

    Genetic variants within the serotonin transporter gene (5-HTTLPR) impact the neurobiology and risk for anxiety-related behaviours. There are also gender differences in the prevalence of anxiety-related behaviours. Although numerous studies have investigated the influence of 5-HTTLPR genotype on the neural systems involved in emotional regulation, none have investigated how these effects are modulated by gender and anxiety. We investigated this issue using two complementary region of interest-based structural neuroimaging approaches (voxel-based morphometry and Freesurfer) in 138 healthy individuals categorized into 'no anxiety' and 'subclinical anxiety' groups based on the Hamilton Rating Scale for Anxiety (HAM-A). Preliminarily, using anxiety as a continuous variable, we found a significant interaction effect of genotype by gender on anxiety. Females homozygous for the Short allele showed the highest HAM-A scores and males the lowest. In addition, a three-way significant interaction among genotype, gender and anxiety category was found for the right amygdala volume. Post hoc tests revealed that homozygous females carrying the Short variant with a subclinical anxiety condition had larger volume. The reported interaction effects demonstrate that gender strongly modulates the relationship between 5-HTTLPR genotype and subclinical expression of anxiety acting on amygdala, one region of the emotional neural network specifically involved in the anxiety-like behaviours.

  • Pathogenesis and treatment of falls in elderly.

    Publication Date: 01/09/2014 on Clinical cases in mineral and bone metabolism : the official journal of the Italian Society of Osteoporosis, Mineral Metabolism, and Skeletal Diseases
    by Pasquetti P, Apicella L, Mangone G

    Falls in the elderly are a public health problem. Consequences of falls are increased risk of hospitalization, which results in an increase in health care costs. It is estimated that 33% of individuals older than 65 years undergoes falls. Causes of falls can be distinguished in intrinsic and extrinsic predisposing conditions. The intrinsic causes can be divided into age-related physiological changes and pathological predisposing conditions. The age-related physiological changes are sight disorders, hearing disorders, alterations in the Central Nervous System, balance deficits, musculoskeletal alterations. The pathological conditions can be Neurological, Cardiovascular, Endocrine, Psychiatric, Iatrogenic. Extrinsic causes of falling are environmental factors such as obstacles, inadequate footwear. The treatment of falls must be multidimensional and multidisciplinary. The best instrument in evaluating elderly at risk is Comprehensive Geriatric Assessment (CGA). CGA allows better management resulting in reduced costs. The treatment should be primarily preventive acting on extrinsic causes; then treatment of chronic and acute diseases. Rehabilitation is fundamental, in order to improve residual capacity, motor skills, postural control, recovery of strength. There are two main types of exercises: aerobic and muscular strength training. Education of patient is a key-point, in particular through the Back School. In conclusion falls in the elderly are presented as a "geriatric syndrome"; through a multidimensional assessment, an integrated treatment and a rehabilitation program is possible to improve quality of life in elderly.

  • Interleukin 28B rs12979860 single-nucleotide polymorphism predicts spontaneous clearance of hepatitis C virus in children.

    Publication Date: 01/05/2014 on Journal of pediatric gastroenterology and nutrition
    by Indolfi G, Mangone G, Calvo PL, Bartolini E, Regoli M, Serranti D, Calitri C, Tovo PA, de Martino M, Azzari C, Resti M
    DOI: 10.1097/MPG.0000000000000275

    Recent genome-wide association studies performed in adults correlated single-nucleotide polymorphisms (SNPs rs12979860 and rs8099917) located on chromosome 19, upstream of the interleukin 28B gene, with spontaneous clearance of hepatitis C virus and with response to treatment with paginated interferon and ribavirin. The aim of the present collaborative study was to evaluate the rs12979860 SNP in a large cohort of Italian children with perinatal acquisition of hepatitis C.

  • Tractography in amyotrophic lateral sclerosis using a novel probabilistic tool: a study with tract-based reconstruction compared to voxel-based approach.

    Publication Date: 15/03/2014 on Journal of neuroscience methods
    by Sarica A, Cerasa A, Vasta R, Perrotta P, Valentino P, Mangone G, Guzzi PH, Rocca F, Nonnis M, Cannataro M, Quattrone A
    DOI: 10.1016/j.jneumeth.2013.12.014

    Diffusion tensor imaging (DTI) is one of the most sensitive MRI tools for detecting subtle cerebral white matter abnormalities in amyotrophic lateral sclerosis (ALS). Nowadays a plethora of DTI tools have been proposed, but very few methods have been translated into clinical practice.