Cerebral autosomal‐dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a stroke and dementia syndrome with degeneration and loss of vascular smooth muscle cells (VSMCs). The disease is due to mutations in NOTCH3 playing an important role in VSMC differentiation, proliferation and apoptosis. Searching for a possible cause of VSMC dysfunction in CADASIL, we investigated morphology and proliferative activity the affected myocytes. In material from autopsy brains and skin‐muscle biopsies of patients with CADASIL diagnosis, assessment of VSMCs in arterial vessels at the level of light and electron microscopy was performed. Proliferative activity of VSMCs was evaluated in immune reactions to proliferative markers: proliferating cell nuclear antigen, and cyclins B1 and D. In CADASIL, abnormal morphology of VSMC nuclei was observed in 18.1%, 11.5%, and 6.9% of the cerebral, skin, and skeletal muscle vessels, respectively. The affected myocytes showed variability in nuclear size, irregularity in nuclear shape, and abnormal chromatin appearance. Frequently, double nuclei of equal size or micronuclei were observed. Sometimes, even multinuclear myocytes were found. In some of the nuclei immune reactions to the examined proliferative markers were positive. Aberrant structure and number of VSCM nuclei, and their immunoreactivity to proliferative markers suggest mitotic instability of vascular myocytes in CADASIL. We speculate that mutant NOTCH3 which is unable to control properly VSMC proliferation, and may be responsible for their premature or inappropriate entry into mitosis, irreversible arrest of the cell cycle, senescence or degeneration and loss.

A b s t r a c t CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is an inher-

Objective: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a generalized vasculopathy caused by mutations in the NOTCH3 gene, leading to degeneration and loss of vascular smooth muscle cells (VSMC). The relationship between NOTCH 3 mutations and VSMC death is unknown. One possible cause of myocyte deficit may be anoikis, a special type of apoptosis due to loss or inappropriate cell adhesion to extracellular matrix. Method:To verify this hypothesis we examined immune expression of main compounds of vascular extracellular matrix (laminin, fibronectin and collagen IV) and selected metallo proteinases (MMP-2, MMP-3, and MMP-9) in cerebral, skin and skeletal muscle arterial vessels in autopsy material and biopsy specimens of CADASIL patients. Results:The immmune reactions revealed decreased expression of laminin and increased expression of collagen IV and fibronectin in arterial vessels. Moderately intense immune reactivity to MMP-9 and MMP-2 was present while immune reactivity to MMP-3 was absent. Conclusion:Quantitative and qualitative changes in vascular extracellular matrix found in CADASIL vessels may lead to VSMC loss via anoikis pathway.

The purpose of this article is to analyze the changes that occurred in the journalism industry during the COVID-19 pandemic. Design/Methodology/Approach: This analysis was conducted based on the results of quantitative research carried out on a sample of 316 journalists working in Poland. The research was designed and implemented under the scientific direction of the author of the publication with the participation of experts representing the Polish Press Agency and the

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