RESUMEN
Background: Non-motor symptoms are common in Parkinson's disease (PD) patients, decreasing quality of life and having no specific treatments. This research investigates dynamic functional connectivity (FC) changes during PD duration and its correlations with non-motor symptoms. Methods: Twenty PD patients and 19 healthy controls (HC) from PPMI dataset were collected and used in this study. Independent component analysis (ICA) was performed to select significant components from the entire brain. Components were grouped into seven resting-state intrinsic networks. Static and dynamic FC changes during resting-state functional magnetic resonance imaging (fMRI) were calculated based on selected components and resting state networks (RSN). Results: Static FC analysis results showed that there was no difference between PD-baseline (PD-BL) and HC group. Network averaged connection between frontoparietal network and sensorimotor network (SMN) of PD-follow up (PD-FU) was lower than PD-BL. Dynamic FC analysis results suggested four distinct states, and each state's temporal characteristics, such as fractional windows and mean dwell time, were calculated. The state 2 of our study showed positive coupling within and between SMN and visual network, while the state 3 showed hypo-coupling through all RSN. The fractional windows and mean dwell time of PD-FU state 2 (positive coupling state) were statistically lower than PD-BL. Fractional windows and mean dwell time of PD-FU state 3 (hypo-coupling state) were statistically higher than PD-BL. Outcome scales in Parkinson's disease-autonomic dysfunction scores of PD-FU positively correlated with mean dwell time of state 3 of PD-FU. Conclusion: Overall, our finding indicated that PD-FU patients spent more time in hypo-coupling state than PD-BL. The increase of hypo-coupling state and decrease of positive coupling state might correlate with the worsening of non-motor symptoms in PD patients. Dynamic FC analysis of resting-state fMRI can be used as monitoring tool for PD progression.
RESUMEN
Despite the various vaccines that have been developed to combat the coronavirus disease 2019 (COVID-19) pandemic, the persistent and unpredictable mutations of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) require innovative and unremitting solutions to cope with the resultant immune evasion and establish a sustainable immune barrier. Here we introduce a vaccine-delivery system with a combination of a needle-free injection (NFI) device and a SARS-CoV-2-Spike-specific mRNA-Lipid Nanoparticle (LNP) vaccine. The benefits are duller pain and a significant increase of immunogenicity compared to the canonical needle injection (NI). From physicochemical and bioactivity analyses, the structure of the mRNA-LNP maintains stability upon NFI, contradictory to the belief that LNPs are inclined towards destruction under the high-pressure conditions of NFI. Moreover, mRNA-LNP vaccine delivered by NFI induces significantly more binding and neutralizing antibodies against SARS-CoV-2 variants than the same vaccine delivered by NI. Heterogeneous vaccination of BA.5-LNP vaccine with NFI enhanced the generation of neutralizing antibodies against Omicron BA.5 variants in rabbits previously vaccinated with non-BA.5-specific mRNA-LNP or other COVID-19 vaccines. NFI parameters can be adjusted to deliver mRNA-LNP subcutaneously or intramuscularly. Taken together, our results suggest that NFI-based mRNA-LNP vaccination is an effective substitute for the traditional NI-based mRNA-LNP vaccination.