Modulation of Secreted β-Amyloid Precursor Protein and Amyloid β-Peptide in Brain by Cholesterol

The effects of dietary cholesterol on brain amyloid precursor protein (APP) processing were examined using an APP gene-targeted mouse, genetically humanized in the amyloid beta-peptide (Abeta) domain and expressing the Swedish familial Alzheimer's disease mutations. These mice express endogenous levels of APP holoprotein and abundant human Abeta. Increased dietary cholesterol led to significant reductions in brain levels of secreted APP derivatives, including sAPPalpha, sAPPbeta, Abeta1-40, and Abeta1-42, while having little to no effect on cell-associated species, including full-length APP and the COOH-terminal APP processing derivatives. The changes in levels of sAPP and Abeta in brain all were negatively correlated with serum cholesterol levels and levels of serum and brain apoE. These results demonstrate that secreted APP processing derivatives and Abeta can be modulated in the brain of an animal by diet and provide evidence that cholesterol plays a role in the modulation of APP processing in vivo. APP gene-targeted mice lacking apoE, also have high serum cholesterol levels but do not show alterations in APP processing, suggesting that effects of cholesterol on APP processing require the presence of apoE

The importance of the patient voice in vaccination and vaccine safety—are we listening?

Much has been written about the patient-physician relationship over the years. This relationship is essential in maintaining trust in the complex arena of modern diagnostic techniques, treatment and prevention, including vaccines and vaccine safety. However, a great deal of this material was written from the viewpoint of clinicians and academics. The patient voice may be positive or negative, fragmented or complex. Information sources are weighed and treated differently, according to the value system and risk perceptions of the individual. In post-trust societies, when people have less confidence in health authorities, communication needs to be more than a paternalistic top-down process. Notions of empowerment and individual patient choice are becoming crucial in medical care. The 'voice of the patient', which includes healthy individuals receiving vaccines, needs to be heard, considered and addressed. With respect to childhood immunizations, this will be the voice of the parent or caregiver. The key to addressing any concerns could be to listen more and to develop a communication style that is trust-based and science-informed. Regulatory agencies are encouraging clinical and patient-reported outcomes research under the umbrella of personalized medicine, and this is an important step forward. This paper attempts to reflect the paradigm shift towards increasing attention to the patient voice in vaccination and vaccine safety. (C) 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved

Inter-observer agreement among uveitis experts on uveitic diagnoses: the Standardization of Uveitis Nomenclature (SUN) experience

PURPOSE: To evaluate the interobserver agreement among uveitis experts on the diagnosis of the specific uveitic disease. DESIGN: Inter-observer agreement analysis METHODS: Five committees, each of 9 individuals, working in parallel, reviewed cases from a preliminary database of 25 uveitic diseases, collected by disease, and voted independently online whether the case was the disease in question or not. The agreement statistic, κ, was calculated for the 36 pairwise comparisons for each disease, and a mean κ was calculated for each disease. Following the independent online voting, committee consensus conference calls, using nominal group techniques, reviewed all cases not achieving supermajority agreement (>75%) on the diagnosis in the online voting to attempt to arrive at a supermajority agreement. RESULTS: A total of 5766 cases for the 25 diseases were evaluated. The overall mean κ for the entire project was 0.39 with disease-specific variation from 0.23 to 0.79. After the formalized consensus conference calls to address cases which did not achieve supermajority agreement in the online voting, supermajority agreement overall was reached on ∼99% of cases with disease-specific variation from 96 to 100%. CONCLUSIONS: Agreement among uveitis experts on diagnosis is moderate at best but can be improved by discussion among them. These data suggest the need for validated and widely-used classification criteria in the field of uveitis