The impact of Covid-19 restrictions in Ireland on symptom severity in mild to moderate Parkinson's disease.

Introduction: The COVID pandemic and public health restrictions significantly impacted those living with neurological conditions such as Parkinson's Disease due to the curtailment of therapies. Patients attending a single centre movement disorders clinic reported reduced physical activity and quality of life during the pandemic. This study aimed to assess the impact of pandemic restrictions on Parkinson's Disease symptom severity in people with mild to moderate Parkinson's Disease. Method: A cross-sectional study design with a convenience sample of 20 people living with mild to moderate Parkinson's Disease was adopted. A telephone survey questionnaire was completed to measure changes in symptom severity on the 14 most common Parkinson's Disease symptoms. Data were analysed using descriptive statistics. Results: Nineteen participants completed the survey. Participants frequently reported a decline in nine symptoms of Parkinson's Disease; bradykinesia, rigidity, walking, sleep, mood, memory, quality of life and fatigue. Nil changes in freezing were reported. No change was reported in the nonmotor symptoms of constipation, speech and pain in 75, 65 and 95% of participants, respectively. Conclusion: Findings of this study acknowledge the negative impact of restrictions on the motor and nonmotor symptoms of Parkinson's Disease. Flexibility to access and delivery of service should be considered to mitigate any future potential restrictions.

Fibulin-3 promotes glioma growth and resistance through a novel paracrine regulation of Notch signaling.

Malignant gliomas are highly invasive and chemoresistant brain tumors with extremely poor prognosis. Targeting of the soluble factors that trigger invasion and resistance, therefore, could have a significant impact against the infiltrative glioma cells that are a major source of recurrence. Fibulin-3 is a matrix protein that is absent in normal brain but upregulated in gliomas and promotes tumor invasion by unknown mechanisms. Here, we show that fibulin-3 is a novel soluble activator of Notch signaling that antagonizes DLL3, an autocrine inhibitor or Notch, and promotes tumor cell survival and invasion in a Notch-dependent manner. Using a strategy for inducible knockdown, we found that controlled downregulation of fibulin-3 reduced Notch signaling and led to increased apoptosis, reduced self-renewal of glioblastoma-initiating cells, and impaired growth and dispersion of intracranial tumors. In addition, fibulin-3 expression correlated with expression levels of Notch-dependent genes and was a marker of Notch activation in patient-derived glioma samples. These findings underscore a major role for the tumor extracellular matrix in regulating glioma invasion and resistance to apoptosis via activation of the key Notch pathway. More importantly, this work describes a noncanonical, soluble activator of Notch in a cancer model and shows how Notch signaling can be reduced by targeting tumor-specific accessible molecules in the tumor microenvironment.

Anachronisms or failures? Family strategies in the sixteenth century, as drawn from collective biographies of solicitors in Aix-en-Provence.

This article highlights the patterns that can be observed in the matrimonial alliances of solicitors in sixteenth-century Aix-en-Provence and family strategies understood as a corpus of rational decisions bearing on the long term. Defined this way, family strategies applied to sixteenth-century solicitors are an anachronism. The new and unstable context in which the sixteenth-century solicitor found himself prevented families from having a clear view of the objectives to achieve and from devising a rational strategy. The article presents the model that most of the solicitors' alliances followed and suggests the obstacles that appeared before the main actor in family planning, the one who wielded paternal authority, in the creation of these alliances. The example of the Maria family shows women who decided, against the will of their family, whom they would marry. This article highlights the historian's reconstruction of typical family behavior and the limited possibilities that families had to plan over the long term.