S Berrettini

Università di Pisa, Pisa, Tuscany, Italy

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Publications (156)280.62 Total impact

  • Luca Bruschini · Francesca Forli · Andrea de Vito · Stefano Berrettini
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    ABSTRACT: OBJECTIVE: The direct acoustic cochlear implant (DACI) is among the latest developments in the field of implantable acoustic prostheses. The surgical procedure requires a mastoidectomy and a posteriorinferior tympanotomy, with access to the facial recess at the level of the oval window, in a complex and lengthy surgical approach. Here, we report a new and considerably shorter surgical approach. METHODS: The new approach involves positioning of artificial incus above the oval window through the superioranterior tympanotomy. We performed DACI placement in temporal bone specimens (N = 5) to assess the feasibility of the new approach. RESULTS: The average time for the DACI implant in the temporal bones was only 112 min (range: 94 min142 min) and there was little clinical risk associated with the procedure. Access was easy and drilling was minimal. CONCLUSION: Our approach simplified the surgical procedure and consequently reduced the time required for DACI placement.
    No preview · Article · Dec 2016 · Clinical and Experimental Otorhinolaryngology
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    ABSTRACT: A retrospective chart review was used for 31 patients with sudden, progressive or fluctuating sensorineural hearing loss (SHL) in the only hearing ear who had been consecutively evaluated at the ENT, Audiology and Phoniatrics Unit of the University of Pisa. The group of patients was evaluated with a complete history review, clinical evaluation, imaging exam (MRI, CT), audiologic tests (tone and speech audiometry, tympanometry, study of stapedial reflexes, ABR and otoacoustic emission) evaluation. In order to exclude genetic causes, patients were screened for CX 26 and 30 mutations and for mitochondrial DNA mutation A1555G. Patients with sudden or rapidly progressive SHL in the only hearing ear were treated with osmotic diuretics and corticosteroids. In patients who did not respond to intravenous therapy we performed intratympanic injections of corticosteroid. Hearing aids were fitted when indicated and patients who developed severe to profound SHL were scheduled for cochlear implant surgery. The aim of this study is to report and discuss the epidemiology, aetiopathogenesis, therapy and clinical characteristic of patients affected by SHL in the only hearing hear and to discuss the issues related to the cochlear implant procedure in some of these patients, with regard to indications, choice of the ear to implant and results.
    No preview · Article · Aug 2016 · Acta otorhinolaryngologica Italica: organo ufficiale della Società italiana di otorinolaringologia e chirurgia cervico-facciale
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    ABSTRACT: Purpose: To assess the capability of three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) sequences in detecting signal alterations of the endolabyrinthine fluid in patients with otosclerosis. Materials and methods: 3D-FLAIR before and after (-/+) gadolinium (Gd) administration was added to the standard MR protocol and acquired in 13 patients with a clinical/audiological diagnosis of severe/profound hearing loss in otosclerosis who were candidates for cochlear implantation and in 11 control subjects using 3-T magnetic resonance imaging (MRI) equipment. The MRI signal of the fluid-filled cochlea was assessed both visually and calculating the signal intensity ratio (SIR = signal intensity cochlea/brainstem). Results: We revealed no endocochlear signal abnormalities on T1-weighted -/+ Gd images for either group, while on 3D-FLAIR we found bilateral hyperintensity with enhancement after Gd administration in eight patients and bilateral hyperintensity without enhancement in one patient. No endocochlear signal abnormalities were detected in other patients or the control group. Conclusion: Using 3-T MRI equipment, the 3D-FLAIR -/+ Gd sequence is able to detect the blood-labyrinth barrier (BLB) breakdown responsible for alterations of the endolabyrinthine fluid in patients with cochlear otosclerosis. We believe that 3D-FLAIR +/- Gd is an excellent imaging modality to assess the intra-cochlear damage in otosclerosis patients. Key points: • Gd-enhanced T1-weighted MRI has limited application to detect intra-cochlear damage. • 3D-FLAIR is less sensitive to flux artefacts and allows multiplanar reconstruction. • Post-Gd 3D-FLAIR is advantageous as it may highlight the BLB breakdown. • Using 3D-FLAIR -/+ Gd, we were able to identify intra-cochlear signal hyperintensities. • 3D-FLAIR might be applied for monitoring disease progression and treatment response.
    No preview · Article · Jan 2016 · European Radiology
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    ABSTRACT: AbstractObjective: Tissue engineering has recently been identified as a suitable tool to develop replacements for the tympanic membrane. This study aimed at investigating PEOT/PBT copolymer scaffolds obtained via electrospinning as potential eardrum substitutes using an in vitro approach.Study design: PEOT/PBT copolymer ultrafine fibre meshes were manufactured and characterized for morphology and pore features. The scaffolds were cultured with human mesenchymal stromal cells (MSCs) under a dynamic flow regimen to improve cell infiltration and viability. The expression of basic extracellular matrix molecules was evaluated and compared to that of the human eardrum. Finally, the interaction between human tympanic membrane keratinocytes and the scaffolds was investigated.Results: The electrospun scaffolds had a fibre diameter of 1.9?±?0.9??m, thickness of 220?±?56??m, and porosity of 80%?±?0.8%. The macroporous meshes were suitable for cell infiltration, since 83.3% of relative void volume was from pore
    No preview · Article · Oct 2015
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    ABSTRACT: Here, we report on a patient with a 625 kb duplication in Xp22.12, detected by array comparative genomic hybridization (CGH). The duplicated region contains only one gene, RPS6KA3, that results in partial duplication. The same duplication was present in his mother and his maternal uncle. This partial duplication inhibits the RPS6KA3 expression, mimicking the effect of loss-of-function mutations associated with Coffin-Lowry syndrome (CLS). The phenotype of the patient here presented is not fully evocative of this syndrome because he does not present some of the facial, digital and skeletal abnormalities that are considered the main diagnostic features of CLS. This case is one of the few examples where RPS6KA3 mutations are associated with a non-specific X-linked mental retardation.Journal of Human Genetics advance online publication, 10 September 2015; doi:10.1038/jhg.2015.106.
    No preview · Article · Sep 2015 · Journal of Human Genetics

  • No preview · Conference Paper · Sep 2015
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    ABSTRACT: In this communication, we introduce boron nitride nanotube (BNNT)-functionalised muscle cell/microfibre mesh constructs, obtained via tissue engineering, as a three-dimensional (3D) platform to study a wireless stimulation system for electrically responsive cells and tissues. Our stimulation strategy exploits the piezoelectric behaviour of some classes of ceramic nanoparticles, such as BNNTs, able to polarize under mechanical stress, e.g. using low-frequency ultrasound (US). In the microfibre scaffolds, C2C12 myoblasts were able to differentiate into viable myotubes and to internalize BNNTs, also upon US irradiation, so as to obtain a nanotech-assisted 3D in vitro model. We then tested our stimulatory system on 2D and 3D cellular models by investigating the expression of connexin 43 (Cx43), as a molecule involved in cell crosstalk and mechanotransduction, and myosin, as a myogenic differentiation marker. Cx43 gene expression revealed a marked model dependency. In control samples (without US and/or BNNTs), Cx43 was upregulated under 2D culture conditions (10.78 ± 1.05-fold difference). Interactions with BNNTs increased Cx43 expression in 3D samples. Cx43 mRNA dropped in 2D under the ‘BNNTs + US’ regimen, while it was best enhanced in 3D samples (3.58 ± 1.05 vs 13.74 ± 1.42-fold difference, p = 0.0001). At the protein level, the maximal expressions of Cx43 and myosin were detected in the 3D model. In contrast with the 3D model, in 2D cultures, BNNTs and US exerted a synergistic depletive effect upon myosin synthesis. These findings indicate that model dimensionality and stimulatory regimens can strongly affect the responses of signalling and differentiation molecules, proving the importance of developing proper in vitro platforms for biological modelling. Copyright © 2014 John Wiley & Sons, Ltd.
    Full-text · Article · Jul 2015 · Journal of Tissue Engineering and Regenerative Medicine
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    ABSTRACT: The tympanic membrane (TM) is a thin tissue able to efficiently collect and transmit sound vibrations across the middle ear thanks to the particular orientation of its collagen fibers, radiate on one side and circular on the opposite side. Through the combination of advanced scaffolds and autologous cells, tissue engineering (TE) could offer valuable alternatives to autografting in major TM lesions. In this study, a multiscale approach based on electrospinning (ES) and additive manufacturing (AM) was investigated to fabricate scaffolds, based on FDA approved copolymers, resembling the anatomic features and collagen fiber arrangement of the human TM. A single scale TM scaffold was manufactured using a custom-made collector designed to confer a radial macro-arrangement to poly(lactic-co-glycolic acid) electrospun fibers during their deposition. Dual and triple scale scaffolds were fabricated combining conventional ES with AM to produce poly(ethylene oxide terephthalate)/poly(butylene terephthalate) block copolymer scaffolds with anatomic-like architecture. The processing parameters were optimized for each manufacturing method and copolymer. TM scaffolds were cultured in vitro with human mesenchymal stromal cells, which were viable, metabolically active and organized following the anisotropic character of the scaffolds. The highest viability, cell density and protein content were detected in dual and triple scale scaffolds. Our findings showed that these biomimetic micro-patterned substrates enabled cell disposal along architectural directions, thus appearing as promising substrates for developing functional TM replacements via TE.
    No preview · Article · May 2015 · Biofabrication
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    Jodi M Cutler · Deborah Renda · Giovanni Lenzi · Stefano Berrettini

    Preview · Article · Dec 2014 · Italian Journal of Pediatrics
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    Giovanni Lenzi · Stefano Berrettini · Jodi M Cutler

    Preview · Article · Dec 2014 · Italian Journal of Pediatrics
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    ABSTRACT: Objective: To evaluate the long-term stability of intratympanic steroids and investigate the 'real' impact of sudden sensorineural hearing loss on patients. Method: A total of 14 patients treated with intratympanic steroids were evaluated by audiometric and vestibular examinations. The modified Glasgow Benefit Inventory was used to evaluate quality of life changes after intratympanic steroid treatment. Results: There was no significant difference between pure tone average post-intratympanic steroids and at follow up. The general Glasgow Benefit Inventory score was not significantly associated with the presence of tinnitus or dizziness, or with patient age. The change in pure tone average after intratympanic steroid treatment did not correlate with social or physical scores, but correlated strongly with the general Glasgow Benefit Inventory score (p = 0.0023). Intratympanic steroid administration led to a stable improvement in hearing. Quality of life assessment showed that patients can feel satisfaction regardless of the hearing outcome. Patients who regained a social hearing level expressed greater satisfaction than patients without serviceable hearing. Overall, quality of life improvement was not related to hearing improvement. Conclusion: Sudden sensorineural hearing loss is devastating. Considering the audiological effects alone ignores the 'human' perspective. Audiological success can correlate with poor quality of life outcome.
    No preview · Article · Aug 2014 · The Journal of Laryngology & Otology
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    ABSTRACT: In this study, we performed a complete histologic analysis of constructs based on large diameter ( > 100 μm) poly-L-lactic acid (PLLA) microfibers obtained via dry-wet spinning and rat Mesenchymal Stromal Cells (rMSCs) differentiated towards the osteogenic lineage, using acrylic resin embedding.In many synthetic polymer-based microfiber meshes, ex post processability of fiber/cell constructs for histologic analysis may face deterring difficulties, leading to an incomplete investigation of the potential of these scaffolds. Indeed, while polymeric nanofiber (fiber diameter = tens of nanometers)/cell constructs can usually be embedded in common histologic media and easily sectioned, preserving the material structure and the antigenic reactivity, histologic analysis of large polymeric microfiber/cell constructs in the literature is really scant. This affects microfiber scaffolds based on FDA-approved and widely used polymers such as PLLA and its copolymers. Indeed, for such constructs, especially those with fiber diameter and fiber interspace much larger than cell size, standard histologic processing is usually inefficient due to inhomogeneous hardness and lack of cohesion between the synthetic and the biological phases under sectioning.In this study, the microfiber/MSC constructs were embedded in acrylic resin and the staining/reaction procedures were calibrated to demonstrate the possibility of successfully employing histologic methods in tissue engineering studies even in such difficult cases. We histologically investigated the main osteogenic markers and extracellular matrix molecules, such as alkaline phosphatase, osteopontin, osteocalcin, TGF-β1, Runx2, Collagen type I and the presence of amorphous, fibrillar and mineralized matrix. Biochemical tests were employed to confirm our findings. This protocol permitted efficient sectioning of the treated constructs and good penetration of the histologic reagents, thus allowing distribution and expression of almost all the tested molecules to be revealed. Our results demonstrated that it is possible to perform histologic analyses of large-diameter PLLA-based microfiber scaffold/MSC constructs that face the failure of standard histologic procedures.
    No preview · Article · Jul 2014 · Biomedical Materials
  • Maria Palmieri · Francesca Forli · Stefano Berrettini
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    ABSTRACT: Objective: To investigate the improvement in different skills following cochlear implantation (CI) in deaf children with additional disabilities (AD), and present an overview of the different outcome measures and the corresponding tests used. Methods: The MEDLINE and Embase databases were searched for studies published in English, Italian, French, German, Spanish or Dutch, up to 4 December 2013, including studies published ahead of print. The search was directed toward studies with a clear diagnosis of additional disability. Only studies including a comparison with pre-CI data of the same group or with post-CI performance of a control group were retained. Two reviewers independently assessed methodological quality and extracted data from the studies by means of forms. Because of the heterogeneity of the study groups and the reported outcome measures, meta-analysis was not possible. Data were collected in tables and described by means of a structured review. Results: The initial search yielded 464 unique studies, of which 41 met the inclusion criteria. These studies show that children with AD improve on average in most of the outcome measures, although often to a lesser degree and more slowly than their peers with cochlear implants and no AD. However, in cases of mild AD, they may reach similar skills to normally developing peers. Many receive measurable benefit from CI that adds to their quality of life. Conclusions: There is a need for alternative tools for measuring those outcomes that are difficult to quantify. Early implantation appears to be beneficial and, over the last 13 years, the mean average age of CI in children with AD decreased from 45 to 30 months. There is ample consensus that cognitive and global developmental levels have significant implications for expectation of benefit and are accurate predictors of certain outcomes.
    No preview · Article · Mar 2014
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    H Mostafa · M Saad · A El-Attar · G Ahmed · S Berrettini · F Forli · G Siciliano · M Mancuso
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    ABSTRACT: The aim of this study was to investigate the presence of mitochondrial DNA (mtDNA) alterations and metabolic dysfunctions in patients with presbyacusis, and to discover correlations between presbyacusis and the degree of hearing loss and mitochondrial damage. Seventy patients with presbyacusis were examined, including 40 Egyptian patients and 30 Italian patients. Forty eight normal subjects were included as control group, including 24 Egyptians and 24 Italians. There was no common point mutation, and A1555G, A3243G, A7445G not were detected in any patients or controls. Haplogroup U was significantly common in patients in comparison to controls. Mutation of antioxidant genes (GSTT1, GSTM1) were significantly present in only Italian patients compared to Italian controls.
    Preview · Article · Feb 2014 · Acta otorhinolaryngologica Italica: organo ufficiale della Società italiana di otorinolaringologia e chirurgia cervico-facciale
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    ABSTRACT: Functional Transcranial Doppler ultrasonography (fTCD) was used to investigate the effects of early acoustic deprivation and subsequent reafferentation on cerebral dominance for language in deaf children provided with Cochlear Implantation (CI). Twenty children with CI (13 in right ear and 7 in left ear) and 20 controls matched for age, sex and handedness were administered a fTCD animation description task. Left hemisphere dominance for language with comparable mean Laterality Indexes (LIs) was found in children with CI and controls; right-ear implanted subjects showed cerebral activation controlateral to implanted ear more frequently than left-ear implanted ones. Linguistic proficiency of CI recipients was below age expectation in comparison to controls; language scores did not significantly differ between children with left and right LI, whereas both age and side of implantation were significantly related to language outcome. Theoretical implication and potential clinical application of fTCD in CI management are discussed.
    Full-text · Article · Jan 2014 · Brain and Language
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    ABSTRACT: We have evaluated neuropsychic development in 70 normal schoolchildren in an area of severe endemic goitre and cretinism in the Central Apennines (Montefeltro). In each subject we have studied auxological, psychometric and audiometric parameters, together with tympanograms and stapedial reflexograms. Auxological data were in the normal range, as were the stapedial reflexograms and tympanograms. On the contrary, 54.8% of the sample performed below the 25th percentile in psychometric tests (Raven test PM-47), being also 22.8% below the 5th percentile. Audiometric data showed a neurological hearing impairment in 3.1% of the children tested, as compared with 0.28% in the area of Pisa. These data point out that an impairment of central nervous system function still persists in this area of severe endemic goitre.
    Full-text · Article · Jan 2014 · Minerva endocrinologica
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    ABSTRACT: Abstract Congenital Cytomegalovirus (CMV) infection affects many organs: reticuloendothelial and central nervous system are particularly involved. Congenital CMV infection is the leading cause of nongenetic sensorineural hearing loss. Hearing impairment can be present at birth or it can occur months or even years after birth. It is as well an important risk factor for antenatal stillbirth, preterm birth and SGA (Small for Gestational Age) condition. For these reasons we should early identify congenital CMV infection investigating at least at risk newborns such as preterm or SGA babies given that a simple and standardized method for a large scale screening program is lacking. In our study we found an association between congenital CMV infection and preterm births (3.03 %) and with SGA condition (3.7 %). Consequently routine CMV urine detection should be performed at least in all babies born before 37 weeks of gestational age and in term SGA newborns.
    No preview · Article · Dec 2013 · The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians
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    ABSTRACT: In this paper we investigated a novel and non-invasive approach for an endogenous osteoblast stimulation mediated by boron nitride nanotubes (BNNTs). Specifically, following the cellular uptake of the piezoelectric nanotubes, cultures of primary human osteoblasts (hOBs) were irradiated with low frequency ultrasound (US), as a simple method to apply a mechanical input to the cells loaded with BNNTs. This in vitro study was aimed at investigating the main interactions between hOBs and BNNTs and to study the effects of the 'BNNTs + US' stimulatory method on the osteoblastic function and maturation.A non-cytotoxic BNNT concentration to be used in vitro with hOB cultures was established. Moreover, investigation with transmission electron microscopy/electron energy loss spectroscopy (TEM/EELS) confirmed that BNNTs were internalized in membranal vesicles. The panel of investigated osteoblastic markers disclosed that BNNTs were capable of fostering the expression of late-stage bone proteins in vitro, without using any mineralizing culture supplements. In our samples, the maximal osteopontin expression, with the highest osteocalcin and Ca(2+) production, in the presence of mineral matrix with nodular morphology, was observed in the samples treated with BNNTs + US. In this group was also shown a significantly enhanced synthesis of TGF-β1, a molecule sensitive to electric stimulation in bone. Finally, gene deregulations of the analyzed osteoblastic genes leading to depletive cellular effects were not detected. Due to their piezoelectricity, BNNT-based therapies might disclose advancements in the treatment of bone diseases.
    Full-text · Article · Oct 2013 · Nanotechnology
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    ABSTRACT: Lymphomas represent the second most frequent malignant tumor (incidence 2.5%) in the head and neck region. Non-Hodgkin lymphomas (NHLs) present with cervical lymph node involvement, but in 40% extranodal site could be primary involved: nasopharynx, the lacrimal sac, the temporal bone, or the others areas. NHLs of the ear are rarely reported. In this report, we described a patient with primary NHL of the external ear canal who was successfully treated with surgical excision and chemotherapy.
    Full-text · Article · Aug 2013
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    A Martini · R Bovo · P Trevisi · F Forli · S Berrettini
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    ABSTRACT: A cochlear implant (CI) is a partially implanted electronic device that can help to provide a sense of sound and support speech to severely to profoundly hearing impaired patients. It is constituted by an external portion, that usually sits behind the ear and an internal portion surgically placed under the skin. The external components include a microphone connected to a speech processor that selects and arranges sounds pucked up by the microphone. This is connected to a transmitter coil, worn on the side of the head, which transmits data to an internal receiver coil placed under the skin. The received data are delivered to an array of electrodes that are surgically implanted within the cochlea. The primary neural targets of the electrodes are the spiral ganglion cells which innervate fibers of the auditory nerve. When the electrodes are activated by the signal, they send a current along the auditory nerve and auditory pathways to the auditory cortex. Children and adults who are profoundly or severely hearing impaired can be fitted with cochlear implants. According to the Food and Drug Administration, approximately 188,000 people worldwide have received implants. In Italy it is extimated that there are about 6-7000 implanted patients, with an average of 700 CI surgeries per year. Cochlear implantation, followed by intensive postimplantation speech therapy, can help young children to acquire speech, language, and social skills. Early implantation provides exposure to sounds that can be helpful during the critical period when children learn speech and language skills. In 2000, the Food and Drug Administration lowered the age of eligibility to 12 months for one type of CI. With regard to the results after cochlear implantation in relation to early implantation, better linguistic results are reported in children implanted before 12 months of life, even if no sufficient data exist regarding the relation between this advantage and the duration of implant use and how long this advantage persists in the subsequent years. With regard to cochlear implantation in children older than 12 months the studies show better hearing and linguistic results in children implanted at earlier ages. A sensitive period under 24-36 months has been identified over which cochlear implantation is reported to be less effective in terms of improvement in speech and hearing results. With regard to clinical effectiveness of bilateral cochlear implantation, greater benefits from bilateral implants compared to monolateral ones when assessing hearing in quiet and in noise and in sound localization abilities are reported to be present in both case of simultaneous or sequential bilateral implantation. However, with regard to the delay between the surgeries in sequential bilateral implantation, although benefit is reported to be present even after very long delays, on average long delays between surgeries seems to negatively affect the outcome with the second implant. With regard to benefits after cochlear implantation in children with multiple disabilities, benefits in terms of speech perception and communication as well as in quality of the daily life are reported even if benefits are slower and lower in comparison to those generally attained by implanted children without additional disabilities. Regarding the costs/efficacy ratio, the CI is expensive, in particular because of the cost of the high technological device, long life support, but even if healthcare costs are high, the savings in terms of indirect costs and quality of life are important. The CI, in fact, has a positive impact in terms of quality of life.
    Full-text · Article · Jun 2013 · Minerva pediatrica

Publication Stats

2k Citations
280.62 Total Impact Points

Institutions

  • 1986-2016
    • Università di Pisa
      • • Department of Translational Research on New Technologies in Medicine and Surgery
      • • Department of Clinical and Experimental Medicine
      • • Department of Biology
      Pisa, Tuscany, Italy
  • 2009-2011
    • Azienda Ospedaliero-Universitaria Pisana
      Pisa, Tuscany, Italy
  • 1998
    • Santa Chiara Hospital
      Trient, Trentino-Alto Adige, Italy