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Cagliari, Italy

Orru S.,University of Cagliari | Manolakos E.,University of Cagliari | Manolakos E.,Laboratory of Genetics | Orru N.,University of Cagliari | And 5 more authors.
Clinical Genetics | Year: 2012

Recently, rare mutations in the TARDBP gene have been identified in familial and sporadic amyotrophic lateral sclerosis (ALS) patients. The purpose of this study was to characterize the genetic variability of the TARDBP gene in a cohort of Sardinian ALS patients. The coding region of the gene was analyzed in 97 unrelated patients previously tested negative for superoxide dismutase (SOD1) mutations. The p.Ala382Thr (c.1144G>A) mutation was found in 30 patients (30.9%). The mutation was predominant in familial ALS patients (FALS) as it was represented in 24 of 30 FALS cases (80%) (p < 0.0003). Six cases were apparently sporadic (9% of sporadic ALS patients). No further mutation of TARDBP was found in our cohort of ALS patients. Patients carrying the mutation showed spinal site of onset in 24 cases (80%), an average age at onset of 54.7 ± 11.1 years, not significantly different from patients not harboring TARDBP mutations (56.7 ± 9.6) and a female:male gender ratio of 1:1.1. The haplotype analysis carried out using eight microsatellite markers flanking the gene showed a founder effect for this mutation. Finally, we estimated the age-specific penetrance of the TARDBP p.Ala382Thr mutation in an additional sample of 47 carriers (20 affected and 27 unaffected). The average penetrance to 70 years was 60% (95% confidence interval 41-79%). A trend toward a higher penetrance in males was observed. Even in the presence of a causal mutation, most of the ALS clinical heterogeneity, however, draws upon from a multifactorial context. © 2011 John Wiley & Sons A/S.

Ponzin D.,Fondazione Banca Degli Occhi Del Veneto | Fasolo A.,Fondazione Banca Degli Occhi Del Veneto | Vidale E.,Fondazione Banca Degli Occhi Del Veneto | Pozzi A.,Fondazione Banca Degli Occhi Del Veneto | And 3 more authors.
Giornale Italiano di Medicina del Lavoro ed Ergonomia | Year: 2015

The aim of this study was to evaluate the effects of a team-building learning project on job satisfaction, psychological wellbeing, and performance of health care workers involved in the process of organ and tissue donation. The project was conducted between June and September 2011 and consisted of two one-day meetings and a one week sailing, involving 20 staff members. GHQ-12, MBI-HSS, and 25 items taken from the Multidimensional Organizational Health Questionnaire (MOHQ) were used to assess health status, burnout, and job satisfaction. Results of the descriptive analyses were expressed as mean ± SD and as counts and percentages; Chi-square test was used to evaluate statistical significance of differences before and after the initiative. 6 (30,0%) participants showed the likelihood to suffering from anxiety and depression (i.e. recognized as 'cases' by the GHQ-12), 3 (15.0%) of them at baseline and 3 (15.0%), different from the previous ones, in the post-intervention. The presence of stress was revealed in 9 (45.0%) and 12 subjects (60.0%) before and after the experience, respectively (6 subjects showed the presence of stress in both circumstances). We documented 4 burnout cases, 3 (15.0%) at baseline and 1 (5.0%) after the experience. Nevertheless, about 80% of the participants showed a high degree of job satisfaction, in terms of positive influence of job in the professional satisfaction and of clear satisfaction for the organization, during both evaluation. In respect to 2010, the number of organ donors and that of ocular tissue donors improved of about 16% and 10%, respectively, during the year of the project and in the following year (mean value). We recognize that our team-building project for personnel involved in the stressful and demanding setting of organ and tissue donation, worthwhile and recompensing at the same time, possibly influenced the personal commitment and the quality of job provided. The high level of stress showed by participants should be appropriately targeted in order to prevent burnout. © PI-ME, Pavia 2015.

Orru S.,University of Cagliari | Orru N.,University of Cagliari | Manolakos E.,University of Cagliari | Littera R.,Centro Regionale Trapianti | And 12 more authors.
Human Immunology | Year: 2012

Polymorphisms of the cytotoxic T-lymphocyte antigen-4 gene (CTLA-4) have been associated with autoimmune diseases and it has recently been reported that donor genotypes correlate with the outcome of allogeneic hematopoietic stem cell transplantation in leukemia patients. With the aim of confirming this finding in thalassemia patients, we investigated the influence of genotype distribution of 3 CTLA-4 gene polymorphisms in 72 thalassemia patients and their unrelated donors. A significant association was observed for recipient CT60-AA genotype and onset of grade II-IV (63.2% vs 24.5%; p = 0.001) and grade III-IV (36.4% vs 7.6%; p = 0.005) acute graft-versus-host disease (aGVHD). The same association was observed for the 88-base-pair allele of the CTLA-4 (AT)n polymorphism, which was determined to be in complete linkage disequilibrium with the CT60 A allele. Multinomial Cox regression demonstrated that this association was independent of CT60 donor genotypes or other risk factors (p = 0.016; hazard ratio = 2.8). Our data confirm that the genetic variability in CTLA-4 is an important prognostic factor for aGVHD and suggest that some of the risk factors for this complication are generated by recipient cells that persist after the myeloablative conditioning regimen. © 2012 American Society for Histocompatibility and Immunogenetics.

Littera R.,Centro Regionale Trapianti | Orru N.,University of Cagliari | Caocci G.,University of Cagliari | Sanna M.,University of Cagliari | And 12 more authors.
British Journal of Haematology | Year: 2012

In a study conducted on 114 patients undergoing unrelated donor haematopoietic stem cell transplantation (HSCT) for thalassaemia, we observed that the lack of activating killer immunoglobulin-like receptors (KIRs) on donor natural killer (NK) cells significantly increased the risk of graft-versus-host disease (GvHD) [hazard risk (HR) 4·2, 95% confidence interval (CI) 1·7-10·1, P=0·002] and transplantation-related mortality (HR 4·7, 95% CI 1·6-14·2, P=0·01). The risk of GvHD furthermore increased when recipients heterozygous for HLA-C KIR ligand groups (C1/C2) were transplanted from donors completely lacking activating KIRs (HR 6·1, 95% CI 1·9-19·2, P=0·002). We also found that the risk of rejection was highest when the recipient was homozygous for the C2 HLA-KIR ligand group and the donor carried two or more activating KIRs (HR 6·8, 95% CI 1·9-24·4, P=0·005). By interpolating the number of donor activating KIRs with recipient HLA-C KIR ligands, we created an algorithm capable of stratifying patients according to the immunogenetic risk of complications following unrelated HSCT. In clinical practice, this predictive tool could serve as an important supplement to clinical judgement and decision-making. © 2011 Blackwell Publishing Ltd.

Littera R.,Centro Regionale Trapianti | Orr N.,University of Cagliari | Vacca A.,Centro Trapianti Midollo Osseo | Bertaina A.,University of Pavia | And 12 more authors.
Bone Marrow Transplantation | Year: 2010

Recent insight into the pathophysiology of acute GVHD after allogeneic haematopoietic SCT has led to a growing interest in the role of natural killer (NK) cells. NK cell cytotoxicity is mainly regulated by the interaction of activating and inhibitory killer immunoglobulin-like receptors (KIRs) with their respective ligands. To investigate the impact of KIRs and their ligands on haematopoietic SCT outcome, we performed a retrospective study of 78 transfusion-dependent thalassaemia patients (median age 10 years, range 1-29 years) transplanted from an unrelated donor selected using high-resolution molecular typing for both class I and II loci after a myeloablative conditioning regimen. GVHD prophylaxis consisted of CsA, short-term MTX and antithymocyte globulin in all patients. We found that patients transplanted from donors homozygous for KIR haplotype A had a greater risk of developing grade II-IV acute GVHD compared with those transplanted from a donor carrying at least one B haplotype (hazard ratio=4.5, 99% confidence interval=1.2-17.1, P=0.003). Our study suggests that KIR genotyping of donor and recipient pairs could contribute to the identification of patients at high risk for developing severe complications of haematopoietic SCT and thus may help with the choice of intensity of GVHD prophylaxis. © 2010 Macmillan Publishers Limited. All rights reserved.

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