Psychometric properties of the Italian Tinnitus Functional Index (TFI)

Diversi questionari sono utilizzati per valutare l\u2019impatto dell\u2019acufene sulla qualit\ue0 della vita. Il Tinnitus Functional Index (TFI) proposto da Meikle et al, nel 2012, ha dimostrato propriet\ue0 eccellenti per misurare la gravit\ue0 e le modificazioni indotte dal trattamento degli acufeni, sia in ambito clinico che di ricerca. Lo scopo di questo studio \ue8 stato valutare le propriet\ue0 psicometriche della versione italiana del TFI, in particolare, l\u2019analisi fattoriale, la consistenza interna, l\u2019affidabilit\ue0 e la validit\ue0. La versione originale inglese del TFI \ue8 stata tradotta in italiano secondo la procedura translation - back translation; 137 partecipanti con acufeni da almeno 3 mesi (39,4% femmine, et\ue0: 18-80 anni, et\ue0 media: 48,26, SD: 14,08), reclutati presso la Tinnitus Clinic di Milano, hanno completato la versione italiana del TFI, il Tinnitus Handicap Inventory, la Beck Depression Inventory - Versione Primary Care e la scala di valutazione numerica per il fastidio. Una parte del campione, 57 pazienti, ha completato la versione italiana del TFI in una seconda visita, dopo 7-14 giorni, prima di ricevere qualsiasi tipo di trattamen- to, per ricavare i dati per la valutazione della riproducibilit\ue0. Le propriet\ue0 psicometriche sono state studiate attraverso un\u2019analisi fattoriale esplorativa ed il calcolo di misure di consistenza interna e affidabilit\ue0 test-retest. La validit\ue0 convergente \ue8 stata valutata mediante i coefficienti di correlazione con le restanti misure. La versione italiana del TFI ha mostrato una struttura a quattro fattori, parzialmente diversa dalla struttura originale a otto fattori. L\u2019adattamento italiano del TFI ha rivelato buoni livelli di consistenza interna (0,92 64 \u3b1 64 0,96) e affidabilit\ue0 test-retest (0,79 64 \u3b1 64 0,85). In termini di validit\ue0 convergente, ha mostrato buone correlazioni con i punteggi del THI (r = 0,77) e della scala del fastidio (r = 0,70) e correlazioni medie con i punteggi del BDI (r = 0,46). Le difficolt\ue0 nel riprodurre la struttura originale a otto fattori sono coerenti con altri studi di validazione del TFI nelle lingue europee. Nonostante tali discrepanze, la versione italiana del TFI ha mostrato una struttura fattoriale caratterizzata da alti livelli di affidabilit\ue0 e validit\ue0. Nel complesso, l\u2019adattamento italiano di TFI si \ue8 rivelato idoneo a misurare l\u2019impatto degli acufeni sulla vita quotidiana degli individui.Various questionnaires are used to assess the impact of tinnitus on the quality of life. The Tinnitus Functional Index (TFI) has excellent properties for scaling the severity of tinnitus and treatment-related changes in both clinical and research settings. The aim of this study was to evaluate the psychometric properties of the Italian version of the TFI with particular emphasis on factor analysis, internal consistency, reliability and validity. The original English version of the TFI was translated into Italian using the translation/back - translation process; 137 participants who were re- cruited at the Tinnitus Clinic in Milan and had suffered from tinnitus for at least three months (39.4% females, age: 18-80 years, mean age: 48.26, SD: 14.08) completed the Italian version of the TFI, the Tinnitus Handicap Inventory (THI), the Beck Depression Inventory - Primary Care Version (BDI-PC) and the Numeric Rating Scale of annoyance (NRS-A). Of these patients, 57 completed the TFI again at a second visit 7-14 days later, before undergoing any intervention, in order to provide data for reproducibility assessment. The psychometric properties were investigated using exploratory factor analysis and internal consistency and test-retest reliability instruments. The convergent validity of the TFI was evalu- ated using correlation coefficients obtained from the remaining measurements. The Italian TFI has a four-factor structure that was somewhat different from the original. The internal consistency proved to be good (0.92 64 \u3b1 64 0.96) as did the test-retest reliability (0.79 64 \u3b1 64 0.85). In terms of convergent validity, the TFI showed high correlations with the THI (r = 0.77) and the NRS-A (r = 0.70) scores, and moderate correlations with the BDI-PC scores (r = 0.46). The difficulties encountered when attempting to reproduce the original eight-factor structure were consistent with other studies in which the TFI was translated into European languages. In spite of this, the factorial structure of the Italian version of the TFI was characterised by high levels of reliability and validity. Overall, the Italian adaptation of the TFI was shown to be suitable to measure the impact of tinnitus on the daily lives of individuals

The Hypermultiplet with Heisenberg Isometry in N=2 Global and Local Supersymmetry

The string coupling of N=2 supersymmetric compactifications of type II string theory on a Calabi-Yau manifold belongs to the so-called universal dilaton hypermultiplet, that has four real scalars living on a quaternion-Kaehler manifold. Requiring Heisenberg symmetry, which is a maximal subgroup of perturbative isometries, reduces the possible manifolds to a one-parameter family that describes the tree-level effective action deformed by the only possible perturbative correction arising at one-loop level. A similar argument can be made at the level of global supersymmetry where the scalar manifold is hyper-Kaehler. In this work, the connection between global and local supersymmetry is explicitly constructed, providing a non-trivial gravity decoupled limit of type II strings already in perturbation theory.Comment: 24 page

Exacerbations and Pseudomonas aeruginosa colonization are associated with altered lung structure and function in primary ciliary dyskinesia

Background: Recurrent bacterial infections of the respiratory tract are one of the major clinical features of the primary ciliary dyskinesia (PCD), a rare genetic disease due to malfunctioning of motile cilia. Chronic infections and persistent inflammation of the respiratory system result in progressive lung disease. Aim of the study was to highlight the main factors associated with clinical, functional and anatomical deterioration in PCD patients. Methods: We retrospectively analyzed data from 58 patients with PCD, 37 adults and 21 children. The demographic and clinical data, forced expiratory volume at 1 s (FEV1) and forced vital capacity (FVC), sputum microbiology and imaging results (chest CT scores-modified Bhalla) were recorded. Patients were stratified according to the number of exacerbations (< 2/year vs 65 2/year) and chronic Pseudomonas aeruginosa (PA) colonization. The possible correlations between lung function and chest CT scores were assessed; we also evaluated the correlation between these parameters and the severity scores for bronchiectasis (BSI, FACED and e-FACED). Results: Chest CT scores showed a significant correlation with FEV1 (p = 0.0002), age (p < 0.0001), BMI (p = 0.0002) and number of lung lobes involved (p < 0.0001). PA colonization had an overall prevalence of 32.6%: no significant difference in FEV1 between PA colonized and non-colonized patients was found (p = 0.70), while chest CT score was significantly worse in chronic PA colonized patients (p = 0.009). Patients with a high number of exacerbation ( 65 2/year) were older (p = 0.01), had lower FEV1 (p = 0.03), greater number of lobes involved (p < 0.001) and worse CT score than patients with low number of exacerbations (p = 0.001); they also had higher prevalence of PA chronic bronchial infection (33.3% versus 13.6%, p = 0.10). Multivariable linear regression analyses adjusted for gender, age and BMI showed positive associations between PA colonization and number of exacerbations with severity of disease (number of lobes involved, CT score, BSI, FACED, and e-FACED). Conclusions: In our PCD population the number of exacerbations ( 65 2/year) and PA colonization were the two most relevant factors associated with severity of disease

Usher syndrome: An effective sequencing approach to establish a genetic and clinical diagnosis

12noUsher syndrome is an autosomal recessive disorder characterized by retinitis pigmentosa, sensorineural hearing loss and, in some cases, vestibular dysfunction. The disorder is clinically and genetically heterogeneous and, to date, mutations in 11 genes have been described. This finding makes difficult to get a precise molecular diagnosis and offer patients accurate genetic counselling. To overcome this problem and to increase our knowledge of the molecular basis of Usher syndrome, we designed a targeted resequencing custom panel. In a first validation step a series of 16 Italian patients with known molecular diagnosis were analysed and 31 out of 32 alleles were detected (97% of accuracy). After this step, 31 patients without a molecular diagnosis were enrolled in the study. Three out of them with an uncertain Usher diagnosis were excluded. One causative allele was detected in 24 out 28 patients (86%) while the presence of both causative alleles characterized 19 patients out 28 (68%). Sixteen novel and 27 known alleles were found in the following genes: USH2A (50%), MYO7A (7%), CDH23 (11%), PCDH15 (7%) and USH1G (2%). Overall, on the 44 patients the protocol was able to characterize 74 alleles out of 88 (84%). These results suggest that our panel is an effective approach for the genetic diagnosis of Usher syndrome leading to: 1) an accurate molecular diagnosis, 2) better genetic counselling, 3) more precise molecular epidemiology data fundamental for future interventional plans.partially_openembargoed_20160106Lenarduzzi, S.; Vozzi, D; Morgan, A.; Rubinato, E.; D'Eustacchio, A.; Osland, T.M.; Rossi, C.; Graziano, C.; Castorina, P.; Ambrosetti, U.; Morgutti, M.; Girotto, G.Lenarduzzi, Stefania; Vozzi, Diego; Morgan, Anna; Rubinato, Elisa; D'Eustacchio, A.; Osland, TERESA MARIA; Rossi, C.; Graziano, C.; Castorina, P.; Ambrosetti, U.; Morgutti, Marcello; Girotto, Giorgi

Primary mediastinal large B-cell lymphoma (PMLBCL): long-term results from a retrospective multicentre Italian experience in 138 patients treated with CHOP or MACOP-B/VACOP-B

The optimal treatment of primary mediastinal large B-cell lymphoma (PMLBCL) is still undefined. In the absence of randomised studies, we retrospectively analysed: (a) the effectiveness of two chemotherapy regimens (CHOP vs MACOP-B/VACOP-B) in complete remission (CR) achievement and event-free survival (EFS) and (b) the role of mediastinal involved-field radiotherapy (IF-RT) as consolidation. From 1982 to 1999, 138 consecutive patients affected by PMLBCL were treated in 13 Italian institutions with CHOP (43) or MACOP-B/VACOP-B (95). The two groups of patients were similar as regard to age, gender, presence of bulky mediastinal mass, pleural effusion, stage and international prognostic indexes category of risk. Overall, 75.5% of patients in CR received IF-RT as consolidation. Complete remission was 51.1% in the CHOP group and 80% in MACOP-B/VACOP-B (P<0.001). Relapse occurred in 22.7% of CHOP- and in 9.2% of MACOP-B/VACOP-B-treated patients (n.s.). Event-free patients were 39.5% in CHOP and 75.7% in the MACOP-B/VACOP-B group (P<0.001). The addition of IF-RT as consolidation improved the outcome, irrespectively of the type of chemotherapy (P=0.04). At a multivariate analysis, achievement of CR (P<0.0001) and type of CT (MACOP-B/VACOP-B) retained the significance for OS (P=0.008) and EFS (P=0.03). In our experience, MACOP-B/VACOP-B appears to positively influence OS and EFS in patients affected by PMLBCL, as compared to CHOP. Consolidation IF-RT on mediastinum further improves the outcome of CR patients

Tollip Is a Mediator of Protein Sumoylation

Tollip is an interactor of the interleukin-1 receptor involved in its activation. The endosomal turnover of ubiquitylated IL-1RI is also controlled by Tollip. Furthermore, together with Tom1, Tollip has a general role in endosomal protein traffic. This work shows that Tollip is involved in the sumoylation process. Using the yeast two-hybrid technique, we have isolated new Tollip partners including two sumoylation enzymes, SUMO-1 and the transcriptional repressor Daxx. The interactions were confirmed by GST-pull down experiments and immunoprecipitation of the co-expressed recombinants. More specifically, we show that the TIR domain of the cytoplasmic region of IL-1RI is a sumoylation target of Tollip. The sumoylated and unsumoylated RanGAP-1 protein also interacts with Tollip, suggesting a possible role in RanGAP-1 modification and nuclear-cytoplasmic protein translocation. In fact, Tollip is found in the nuclear bodies of SAOS-2/IL-1RI cells where it colocalizes with SUMO-1 and the Daxx repressor. We conclude that Tollip is involved in the control of both nuclear and cytoplasmic protein traffic, through two different and often contrasting processes: ubiquitylation and sumoylation

Sox2 Is Essential for Formation of Trophectoderm in the Preimplantation Embryo

In preimplantation mammalian development the transcription factor Sox2 (SRY-related HMG-box gene 2) forms a complex with Oct4 and functions in maintenance of self-renewal of the pluripotent inner cell mass (ICM). Previously it was shown that Sox2-/- embryos die soon after implantation. However, maternal Sox2 transcripts may mask an earlier phenotype. We investigated whether Sox2 is involved in controlling cell fate decisions at an earlier stage.We addressed the question of an earlier role for Sox2 using RNAi, which removes both maternal and embryonic Sox2 mRNA present during the preimplantation period. By depleting both maternal and embryonic Sox2 mRNA at the 2-cell stage and monitoring embryo development in vitro we show that, in the absence of Sox2, embryos arrest at the morula stage and fail to form trophectoderm (TE) or cavitate. Following knock-down of Sox2 via three different short interfering RNA (siRNA) constructs in 2-cell stage mouse embryos, we have shown that the majority of embryos (76%) arrest at the morula stage or slightly earlier and only 18.7-21% form blastocysts compared to 76.2-83% in control groups. In Sox2 siRNA-treated embryos expression of pluripotency associated markers Oct4 and Nanog remained unaffected, whereas TE associated markers Tead4, Yap, Cdx2, Eomes, Fgfr2, as well as Fgf4, were downregulated in the absence of Sox2. Apoptosis was also increased in Sox2 knock-down embryos. Rescue experiments using cell-permeant Sox2 protein resulted in increased blastocyst formation from 18.7% to 62.6% and restoration of Sox2, Oct4, Cdx2 and Yap protein levels in the rescued Sox2-siRNA blastocysts.We conclude that the first essential function of Sox2 in the preimplantation mouse embryo is to facilitate establishment of the trophectoderm lineage. Our findings provide a novel insight into the first differentiation event within the preimplantation embryo, namely the segregation of the ICM and TE lineages