Understanding the mechanisms causing Parkinsons disease (PD) is vital to the development of much needed early diagnostics and therapeutics for this debilitating condition. Here, we report cellular and molecular alterations in skin fibroblasts of late-onset sporadic PD subjects, that were recapitulated in matched induced pluripotent stem cell (iPSC)-derived midbrain dopamine (DA) neurons, reprogrammed from the same fibroblasts. Specific changes in growth, morphology, reactive oxygen species levels, mitochondrial function, and autophagy, were seen in both the PD fibroblasts and DA neurons, as compared to their respective controls. Additionally, significant alterations in alpha synuclein expression and electrical activity were also noted in the PD DA neurons. Interestingly, although the fibroblast and neuronal phenotypes were similar to each other, they also differed in their nature and scale. Furthermore, statistical analysis revealed novel associations between various clinical measures of the PD subjects and the different fibroblast and neuronal data. In essence, these findings encapsulate spontaneous, in-tandem, disease-related phenotypes in both sporadic PD fibroblasts and iPSC-based DA neurons, from the same patient, and generates an innovative model to investigate PD mechanisms with a view towards rational disease stratification and precision treatments.
Objective: To evaluate the reasons for COVID-19 vaccine hesitancy during
pregnancy from first-person reports. Design: We used regular expressions
to identify publicly available social media posts from pregnant people
expressing at least one reason for their decision not to accept COVID-19
vaccine. Setting: WhatToExpect and Twitter. Sample: 1017 posts from 945
pregnant people in WhatToExpect and 435 tweets from 345 pregnant people
in Twitter Methods: Two annotators manually coded posts according to the
Scientific Advisory Group for Emergencies (SAGE) working group’s 3Cs
model of vaccine hesitancy (confidence, complacency, and convenience
barriers). Within each theme we created subthemes which emerged from the
data. Results: Confidence barriers were the most common (75%) and were
related to safety, waiting until after the 2nd trimester, birth or
breastfeeding, efficacy, misinformation or mistrust. Complacency
barriers were also common (52%) with people stating that they did not
need the vaccine because they were taking other precautions, were not at
risk or had already had COVID-19. Convenience barriers were the least
common (13%) with most of these related to medical advice or
eligibility. Some women gave more than one reason for their hesitancy
and many of the reasons were inter-linked. Conclusion: The reasons for
COVID-19 vaccine hesitancy during pregnancy give a clear picture of the
public health messages required. Concerns around safety should be
addressed in a sensitive manner. The relative effectiveness of the
vaccine as compared with other precautions could be better promoted as
could the high-risk nature of a COVID-19 infection during pregnancy.
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