Distinct populations of highly potent TAU seed conformers in rapidly progressing Alzheimer's disease

Although genetic factors play a main role in determining the risk of developing Alzheimer’s disease (AD), they do not explain extensive spectrum of clinicopathological phenotypes. Deposits of aggregated TAU proteins are one of the main predictors of cognitive decline in AD. We investigated the hypothesis that variabilities in AD progression could be due to diverse structural assemblies (strains) of TAU protein. Using sensitive biophysical methods in 40 patients with AD and markedly different disease durations, we identified populations of distinct TAU particles that differed in size, structural organization, and replication rate in vitro and in cell assay. The rapidly replicating, distinctly misfolded TAU conformers found in rapidly progressive AD were composed of ~80% misfolded four-repeat (4R) TAU and ~20% of misfolded 3R TAU isoform with the same conformational signatures. These biophysical observations suggest that distinctly misfolded population of 4R TAU conformers drive the rapid decline in AD and imply that effective therapeutic strategies might need to consider not a singular species but a cloud of differently misfolded TAU conformers

Association between concomitant psychiatric drug use, and patients' beliefs about and persistence with chronic cardiovascular medication

Objective: Psychiatric disorders are associated with an increased risk of cardiovascular diseases and may result in additional risk of non-adherence. No data on the influence of concomitant psychiatric drug use on patients' beliefs and persistence related to cardiovascular medication are available. The objective of this study was to assess to what extent the use of concomitant psychiatric drugs is associated with patients' beliefs about and persistence with chronic cardiovascular medication. Methods: An observational study in patients using cardiovascular medication was conducted. A mailed questionnaire containing socio-demographical questions and a measure of beliefs about medication (Beliefs about Medicines Questionnaire - specific) was sent to patients selected from fifteen participating pharmacies. Persistence was evaluated based on pharmacy records. Results: Of the 1547 included patients, 551 responded to key questions in the questionnaire and were included for beliefs about medication analysis. In concomitant users of psychiatric drugs significantly higher necessity (17.0 vs. 16.0) and higher concerns (14.3 vs. 13.3), as well as higher proportion of ambivalent (34.5% vs. 25.6%) and lower proportion of indifferent patients (24.1% vs. 33.0%) were found compared with non-users (p < 0.05). 65.2% (n = 1009) of patients were persistent on all their cardiovascular drugs. There was no significant association between concomitant use of psychiatric drugs and non-persistence (OR = 1.2; 95% CI 0.9-1.5). Conclusion: Concomitant use of psychiatric drugs was found to be associated with increased beliefs about the necessity of and concerns about cardiovascular medication. Clinicians caring for cardiovascular patients should give additional attention to identifying patients' beliefs about medication among those concomitantly using psychiatric drugs

Epoxy/PCL nanocomposites: Effect of layered silicate on structure and behavior

The effect of clay-induced morphological transitions on the structure formed in the course of reactively induced phase separation (RIPS) and its impact on the properties of epoxy/polycaprolactone (PCL) nanocomposites were studied. The effect of organophilized montmorillonite on the behavior of epoxy containing 5–30% PCL was strongly dependent on the epoxy/PCL system composition. With a supercritical 20% PCL content, the increasing amounts of clay led to changes in the morphology that produced phase inversion, causing radical changes in the mechanical behavior. The main effect of the clay, which was located preferentially in the epoxy, was to influence the significant dynamic asymmetry (and thus the phase behavior). The simultaneous pinning effect of the clay on the phase separation changed the composition and parameters of the coexisting phases. The evaluation of the structure-properties relationship indicated the significant potential for nanoclays to control the behavior of thermoplastic- modified epoxy systems