miRNome Profiling Detects miR-101-3p and miR-142-5p as Putative Blood Biomarkers of Frailty Syndrome

Frailty is an aging-related pathology, defined as a state of increased vulnerability to stressors, leading to a limited capacity to meet homeostatic demands. Extracellular microRNAs (miRNAs) were proposed as potential biomarkers of various disease conditions, including age-related pathologies. The primary objective of this study was to identify blood miRNAs that could serve as potential biomarkers and candidate mechanisms of frailty. Using the Fried index, we enrolled 22 robust and 19 frail subjects. Blood and urine samples were analysed for several biochemical parameters. We observed that sTNF-R was robustly upregulated in the frail group, indicating the presence of an inflammatory state. Further, by RNA-seq, we profiled 2654 mature miRNAs in the whole blood of the two groups. Expression levels of selected differentially expressed miRNAs were validated by qPCR, and target prediction analyses were performed for the dysregulated miRNAs. We identified 2 miRNAs able to significantly differentiate frail patients from robust subjects. Both miR-101-3p and miR-142-5p were found to be downregulated in the frail vs. robust group. Finally, using bioinformatics targets prediction tools, we explored the potential molecular mechanisms and cellular pathways regulated by the two miRNAs and potentially involved in frailty

Frequency and phenotypes of LRRK2 G2019S mutation in Italian patients with Parkinson's disease

To evaluate the frequency of the LRRK2 G2019S mutation in Italy, we tested 1,072 probands with Parkinson's disease (PD; 822 sporadic and 250 familial): 20 patients (1.9%) carried the G2019S mutation, 11 patients (1.3%) were sporadic, and 9 (4.3%) had a positive family history. Considering only probands with autosomal dominant inheritance, the G2019S frequency raises to 5.2%. All presented a typical phenotype with variable onset and shared the common ancestral haplotype. Mutation frequency raised from 1.2% in early onset PD to 4.0% in late onset PD

Validation of the Italian version of the Movement Disorder Society--Unified Parkinson's Disease Rating Scale.

The Movement Disorder Society-sponsored revision of the Unified Parkinson\u2019s Disease Rating Scale (MDS-UPDRS) has been available in English since 2008. As part of this process, the MDS-UPDRS organizing team developed guidelines for development of official non-English translations. We present here the formal process for completing officially approved non-English versions of the MDS-UPDRS and specifically focus on the first of these versions in Italian. The MDS-UPDRS was translated into Italian and tested in 377 native-Italian speaking PD patients. Confirmatory and exploratory factor analyses determined whether the factor structure for the English-language MDS-UPDRS could be confirmed in data collected using the Italian translation. To be designated an \u2018Official MDS translation,\u2019 the Comparative Fit Index (CFI) had to be 650.90 relative to the English-language version. For all four parts of the Italian MDS-UPDRS, the CFI, in comparison with the English-language data, was 650.94. Exploratory factor analyses revealed some differences between the two datasets, however these differences were considered to be within an acceptable range. The Italian version of the MDS-UPDRS reaches the criterion to be designated as an Official Translation and is now available for use. This protocol will serve as outline for further validation of this in multiple languages