Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide

The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied "explainable" machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk

A new era for understanding amyloid structures and disease

The aggregation of proteins into amyloid fibrils and their deposition into plaques and intracellular inclusions is the hallmark of amyloid disease. The accumulation and deposition of amyloid fibrils, collectively known as amyloidosis, is associated with many pathological conditions that can be associated with ageing, such as Alzheimer disease, Parkinson disease, type II diabetes and dialysis-related amyloidosis. However, elucidation of the atomic structure of amyloid fibrils formed from their intact protein precursors and how fibril formation relates to disease has remained elusive. Recent advances in structural biology techniques, including cryo-electron microscopy and solid-state NMR spectroscopy, have finally broken this impasse. The first near-atomic-resolution structures of amyloid fibrils formed in vitro, seeded from plaque material and analysed directly ex vivo are now available. The results reveal cross-β structures that are far more intricate than anticipated. Here, we describe these structures, highlighting their similarities and differences, and the basis for their toxicity. We discuss how amyloid structure may affect the ability of fibrils to spread to different sites in the cell and between organisms in a prion-like manner, along with their roles in disease. These molecular insights will aid in understanding the development and spread of amyloid diseases and are inspiring new strategies for therapeutic intervention

Eltern

Killus D, Paseka A, Schütz P, Walther U, Wischer B, eds. Eltern. Friedrich-Jahresheft. Vol 35. Seelze: Friedrich; 2017

Work-related stress among peer workers in social psychiatry: stressors, resources and their relationship to health-related and motivational outcomes.

People with mental illnesses and with specific training, such as EX-IN training, are increasingly working in social psychiatric institutions. In the following, the collective term "peer workers" (PW) is used for this group of people. Initial findings from field reports and a few studies suggest that PWs can be exposed to many occupational stressors, e.g. experiences of stigmatization, competitive pressure, and role conflicts. Stress at work can promote negative stress consequences in the long term if the stress is not successfully managed. These consequences for PW will be analyzed in this study. Furthermore, this study focuses on factors that can promote work motivation. Research questions of this study are: What is the relationship between stressors/resources, depression, and job satisfaction/fluctuation? What special role do personal resources play, especially in the form of identity as a PW? What are the inter-individual differences regarding stressors/resources and effects