Caratteri fenotipici/genotipici per la produzione di Alginato negli isolati clinici di Pseudomonas aeruginosa presenti negli allevamenti ovini

Introduzione - In ambito sanitario il genere Pseudomonas è temuto per la sua resistenza agli antibiotici e agli antimicrobici, resistenza dovuta alla capacità di formare biofilm protettivo. P. aeruginosa è il patogeno più comune isolato nelle infezioni nosocomiali e in campo veterinario è di notevole importanza in bovini, ovini e caprini, dove può causare mastiti ambientali; è un piccolo bacillo Gram negativo caratterizzato da una capsula spessa ricoperta di alginato. L’alginato è il componente principale della matrice extracellulare del biofilm; ha una funzione protettiva in un ambiente relativamente ostile, in cui i batteri sono continuamente sottoposti a stress ossidativo e attaccati dal sistema immunitario. P. aeruginosa presenta un fenotipo non mucoide sensibile agli antibiotici e un fenotipo mucoide resistente agli antimicrobici. In alcuni casi, la conversione del fenotipo non mucoide nel fenotipo mucoide è causata da mutazioni che si verificano in due distinti loci cromosomici denominati MUC. L’inattivazione in vitro di mucA in P. aeruginosa POA1 (non mucoso) produce i ceppi Alg+; questo sembra indicare, quindi, che mucA agisce come un regolatore negativo della produzione di alginato perché può legare e sequestrare il fattore 22 attraverso il dominio citoplasmatico N-terminale. L’obiettivo del nostro lavoro è un’analisi dell’influenza delle mutazioni del gene mucA nei ceppi mucoidi di P. aeruginosa

Disease survival and progression in TARDBP ALS patients from Sardinia, Italy

BackgroundCommon genes implicated in amyotrophic lateral sclerosis (ALS) development may also influence its progression rate. The C9orf72 mutations featured a faster progression rate while the European SOD1 mutations were associated with a slower progression. In this study, we assessed the relationship between TARDBP and ALS progression/survival.MethodsALS incident patients (2010-2019) were diagnosed by El Escorial revised criteria and staged over the disease course by the King's staging system. Disease progression was analysed by Kaplan-Meier survival curves and Cox regression models, with survival measured from symptom onset to death/tracheostomy or censor date.ResultsThe study population included 76 patients carrying TARDBP mutations (A382T/G295S), 28 patients carrying the C9orf72 GGGGCC expansion, and 158 patients who had no evidence of causative genetic mutations (nmALS group). TARDBP patients reached death/tracheostomy later than C9orf72 and nmALS patients, independently of possible prognostic indicators (sex, age at ALS onset, diagnostic delay, phenotype at onset, and family history of ALS). On King's staging, the time elapsed between disease onset (King's stage 1) and involvement of the second body region (King's stage 2B) was similar in TARDBP and nmALS patients but longer in TARDBP than in C9orf72 patients. TARDBP patients reached King's stages 3 and 4 later than C9orf72 and nmALS patients.ConclusionsTARDBP patients have a better survival/prognosis than C9orf72-positive and nmALS patients. King's staging also suggested that the higher survival rate and the slower progression associated with the TARDBP mutation could mainly be attributed to the longer time elapsed between King's stages 2B to 3

Increasing prevalence 2015–2019 of amyotrophic lateral sclerosis in Sardinia, Italy

BackgroundWhile amyotrophiclateral sclerosis (ALS) incidence has increased during the last decades, structured evidence on increased prevalence is lacking. After reporting a significant yearly increase of ALS incidence over a 10-year period, we checked for increased prevalence in Southern Sardinia over a quinquennium.MethodsALS patients (El Escorial Criteria) recruited from the study area and followed at ALS Centre, University of Cagliari, were included. Prevalence was computed for January 1, 2015 and January 1, 2019 and was calculated for the overall ALS population as well as for tracheostomized and non-tracheostomized patients.ResultsWe observed a non-significant trend for greater ALS prevalence in 2019 than in 2015 (18.31 per 100,000 vs. 15.26 per 100,000; rate ratio: 1.83, p = 0.01). By contrast, a significantly raising 2015 to 2019 ALS prevalence was observed in tracheostomized patients. No significant difference could be detected in non-tracheostomized.ConclusionsWe provided the highest prevalence rate to date reported in the worldwide literature, and also showed a non-significant raising ALS prevalence in the Sardinian population over a quinquennium. The trend in raising ALS prevalence was likely due to extended survival due to invasive interventions

Spatial clustering of amyotrophic lateral sclerosis in Sardinia, Italy: The contribution of age, sex, and genetic factors

Introduction/AimsSeveral microgeographic clusters of higher/lower incidence of amyotrophic lateral sclerosis (ALS) have been identified worldwide. Differences in the distribution of local factors were proposed to explain the excess ALS risk, whereas the contribution of known genetic/epigenetic factors remains unclear. The aim is to identify restricted areas of higher risk in Sardinia and to assess whether age, sex, and the most common causative genetic mutations in Sardinia (C9orf72 and TARDBP mutations) contributed to the variation in the ALS risk. MethodsWe performed an ad hoc analysis of the 10-y population-based incident cohort of ALS cases from a recent study of a large Sardinian area. Cluster analysis was performed by age- and sex-adjusted Kulldorff's spatial scan statistic. ResultsWe identified a statistically significant cluster of higher ALS incidence in a relatively large area including 34 municipalities and >100,000 individuals. The investigated genetic mutations were more frequent in the cluster area than outside. Regardless of the genetic mutations, the excess of ALS risk was significantly associated with either sex or with age & GE; 65 y. Finally, an additive interaction between older age and male sex contributed to the excess of ALS risk in the cluster area but not outside. DiscussionOur analysis demonstrated that known genetic factors, age, and sex may contribute to microgeographic variation in ALS incidence. The significant additive interaction between older age and male sex we found in the high-incidence cluster could suggest the presence of a third factor connecting the analyzed risk factors