Alzheimer's disease (AD) is the most common form of dementia, which completely lacks a viable, long-term therapeutic intervention. This is partly due to an incomplete understanding of AD etiology and the possible confounding factors associated with its genotypic and phenotypic heterogeneity. Cerebral amyloid angiopathy (CAA) is a common, yet frequently overlooked, pathology associated with AD. CAA manifests with deposition amyloid-beta (Aβ) within the smooth muscle layer of cerebral arteries and arterioles. The role of Aβ in AD and CAA pathophysiology has long been controversial. Although it has demonstrated toxicity at super-physiological levels in vitro, Aβ load does not necessarily correlate with cognitive demise in humans. In this review, we describe the contributions of CAA to AD pathophysiology and important pathomechanisms that may lead to vascular fragility and hemorrhages. Additionally, we discuss the effect of Aβ on smooth muscle cell phenotype and viability, especially in terms of the complement cascade.
Chitosan polymers (Cs), from which microparticles (CsM) may be precipitated to deliver various intracellular payloads, are generally considered biologically inert. We examined the impact of cell culture conditions on CsM size and the effect of chitosan on CD59 expression in primary human smooth muscle cells. We found that particle concentration and incubation time in biological buffers augmented particle size. Between pH 7.0 and pH 7.5, CsM size increased abruptly. We utilized CsM containing a plasmid with a gene for CD59 (pCsM) to transfect cells. Both CD59 mRNA and the number of CD59-positive cells were increased after pCsM treatment. Unexpectedly, CsM also augmented the number of CD59-positive cells. Cs alone enhanced CD59 expression more potently than either pCSM or CsM. This observation strongly suggests that chitosan is in fact bioactive and that chitosan-only controls should be included to avoid misattributing the activity of the delivery agent with that of the payload.
This article was migrated. The article was marked as recommended. Problem: Wikipedia is a ubiquitous source of information for patients, medical students and junior doctors alike. This is despite medical educators discouraging students from Wikipedia as a source of medical information. Intervention: To address this disconnect, Osmosis' Director of Open Learning Initiatives created a novel Wikipedia-editing course structured to leverage the global network of Osmosis-subscribing students. The course was entirely video-conference based and lasted 4 weeks in July 2019. Students typically worked on an article by themselves though one article was selected by two students. Towards the end of the course, each student peer-reviewed another student's edited article. Outcomes:Twelve medical students, from 11 different medical schools across 3 different continents, enrolled in the course and 11 articles were assigned. A total of 8,775 words and 119 higher quality references were added whilst 35 lower-quality references were removed. An exit survey showed students had increased confidence in their ability to contribute to Wikipedia. Students also enjoyed collaborating with a global diversity of peers. Lessons Learned: Numerous students wished that the course had a longer duration. A couple students recommended more groupwork to be incorporated into the course. The global nature of the course meant that time zones proved a challenge to scheduling. Conclusion:Decentralized courses can leverage the large user bases of medical education companies, such as Osmosis, to teach students analytical approaches to online resources as well as improve the quality of publicly available health information on Wikipedia.
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