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Amyloid diseases are characterized by the formation of insoluble amyloid fibrils from previously soluble polypeptides. In Alzheimer's disease (AD), amyloid fibrils, formed from beta-amyloid peptides, are deposited as extracellular amyloid plaques only inside the brain. As previously shown, Alzheimer's-like plaque formation in human monocyte culture recapitulates the features of in vivo amyloid plaque formation. Here we show that this cell model can be used to screen compounds that potentially influence amyloid formation in a throughput manner. We found that cellular amyloid fibril formation can be enhanced by dextran sulfate as well as heparin and can be impaired by stabilization of a micell-like beta-amyloid conformer by using myoinositol or by inhibition of phagocytosis with cytochalasin D. Altogether, our data demonstrate the utility of this cell model for investigating pathways and molecular interactions critical to amyloidogenesis.

Bone and joint infection (BJI) epidemiology and outcomes in solid organ transplant recipients (SOTr) remain largely unknown. We aim to describe BJI in a multi-center cohort of SOTr (Swiss Transplant Cohort Study). All consecutive SOTr with BJI (01.05.2008BJI (01.05. -31.12.2019 were included. A nested case-control study to identify risk factors for BJI was performed. Among 4482 patients, 61 SOTr with 82 BJI were included, at an incidence of 1.4% (95% CI 1.1-1.7), higher in heart and kidney-pancreas SOTr (Gray's test p < .01). Although BJI were predominately late events (median of 18.5 months post-SOT), most infections occurred during the first year post-transplant in thoracic SOTr. Diabetic foot osteomyelitis was the most frequent infection (38/82, 46.3%), followed by non-vertebral osteomyelitis (26/82, 31.7%). Pathogens included Gram-positive cocci (70/131, 53.4%), Gram-negative bacilli (34/131, 26.0%), and fungi (9/131, 6.9%). BJI predictors included male gender (OR 2.94, 95% CI 1.26-6.89) and diabetes (OR 2.97, 95% CI 1.34-6.56). Treatment failure was observed in 25.9% (21/81) patients and 1-year mortality post-BJI diagnosis was 14.8% (9/61). BJI remain a rare event in SOTr, associated with subtle clinical presentations, high morbidity and relapses, requiring additional studies in the future.