Parkinson's disease staging based of the non-motor symptoms scale

Objective: The Non-Motor Symptoms Scale (NMSS) is a unified instrument for assessment of non-motor symptoms (NMS) in Parkinson’s disease (PD). Present study is aimed at exploring a PD staging based on NMS severity levels determined through NMSS. Methods: International, multicentre, cross-sectional study. Data on patients’ sex, age, disease duration, and treatment were collected. NMSS, Hoehn and Yahr staging (HY), motor examination and motor complications scales, and the PDQ-8 were applied. NMSS scores were broken down by quartiles to establish severity levels. Chi squared, Mann-Whitney, and Kruskal-Wallis tests were applied to compare NMSS severity levels with other variables in the study. Results: The sample was composed by 750 PD patients (58.5% men; mean age: 65.98±10.33 years; disease duration: 7.37±5.64 years; HY median: 2, limits: 1–5). NMSS total score was 56.82±43.62 (range: 0–243, median: 44). NMSS levels were established as follows: level 0 (no NMS); 1 (slight): 1–7 points; 2 (mild): 8–24; 3 (moderate): 25–44; 4 (severe): 45–80; 5 (very severe): ≥81 points. No differences were detected in NMS severity level distribution by gender (p = 0.14) and age (p = 0.09). Disease duration, motor examination, motor complications, and PDQ-8 scores showed significant differences by NMSS severity levels (p < 0.0001). There was also a significant difference between HY and NMS levels (p < 0.0001). Conclusions: Severity levels, based on quartiles, can be extracted from NMSS scores and may be the basis for a staging system based on NMS. A significant difference was found between HY and NMS classifications, showing that motor and non-motor manifestations have a different patter

Sequences derived from self-RNA containing certain natural modifications act as suppressors of RNA-mediated inflammatory immune responses

The ability of the host to distinguish between self and foreign nucleic acids is one of the critical factors contributing to the recognition of pathogens by Toll-like receptors (TLRs). Under certain circumstances, eukaryotic self-RNA may reach TLR-containing compartments allowing for self-recognition. Specific modifications were previously demonstrated to suppress immune activation when placed at several positions in an immune stimulatory RNA or silencing RNA (siRNA). However, we show that even a simple natural modification such as a single 2′-O-methylation at different nucleotide positions throughout a sequence derived from a self-RNA strongly interferes with TLR-mediated effects. Such a single modification can even have an inhibitory effect in vitro and in vivo when placed in a different than the immune stimulatory RNA strand acting as suppressive RNA. Several safeguard mechanisms appear to have evolved to avoid cellular TLR-mediated activation by self-RNAs that may under other circumstances result in inflammatory or autoimmune responses. This knowledge can be used to include as few as a single 2′-O-methyl modification at a specific position in a siRNA sense or anti-sense strand to avoid TLR immune effects