Risikoidentifikation bei Polypharmazie in einer Pflegeheimpopulation

Introduction!#!Multimorbidity in old age is one reason for intensified pharmacotherapy. At the same time, an increase in medications could augment multimorbidity, especially when drug interactions leading to undesired drug effects occur.!##!Methods!#!In this cross-sectional study 918 mentally ill seniors living in nursing homes (mean age 79.3 (±11.6) years; 31.8% male) were included. Two different approaches to assess risks due to pharmacotherapy were applied: first mediQ, an online-based clinical decision support software (CDSS) and the PRISCUS list, which indicates potentially inappropriate medication. PRISCUS is the German equivalent to the American Geriatrics Society Beers criteria.!##!Results!#!Of the patients in the study 76.3% were at clinical risk, 2.2% at potentially high risk for drug interactions regarding the entire medication as tested by mediQ, and about 25% of the studied population received potentially inappropriate medication according to the PRISCUS list.!##!Conclusion!#!This difference clearly underlines the cumbersome complexity of identifying patients at risk by using these exemplary devices. The focus of avoiding undesired drug side effects should be taking medication only after thorough verification of clinical indications and under close monitoring. The CDSS or negative lists may support this process

Response of the thermoacidophilic Archaeon Sulfolobus acidocaldarius to solvent stress exemplified by 1-butanol exposure

Benninghoff JC, Kuschmierz L, Zhou X, et al. Response of the thermoacidophilic Archaeon Sulfolobus acidocaldarius to solvent stress exemplified by 1-butanol exposure. Applied and environmental microbiology. 2021.Sulfolobus acidocaldarius is a thermoacidophilic crenarchaeon with optimal growth at 80 °C and pH 2 - 3. Due to its unique physiological properties allowing life at environmental extremes and recent availability of genetic tools, this extremophile receives increasing interest for biotechnological application. In order to elucidate the potential of tolerating process-related stress conditions, we investigated the response of S. acidocaldarius towards the industrially relevant organic solvent 1-butanol.In response to butanol exposure, biofilm formation of S. acidocaldarius was enhanced and occurred up to 1.5% (v/v) 1-butanol, while planktonic growth was only observed up to 1% (v/v) 1-butanol. Confocal laser scanning microscopy revealed that biofilm architecture changed with the formation of denser and higher tower-like structures. Concomitantly, changes in the extracellular polymeric substances with enhanced carbohydrate and protein content were determined in 1-butanol-exposed biofilms. Using scanning electron microscopy three different cell morphotypes were observed in response to 1-butanol.Transcriptome and proteome analyses were performed comparing the response of planktonic and biofilm cells in absence and presence of 1-butanol. In response to 1% (v/v) 1-butanol transcript levels of genes encoding motility and cell envelope structures as well as membrane proteins were reduced. Cell division and/or vesicle formation was upregulated. Furthermore, changes of immune and defence systems, as well as metabolism and general stress response were observed. Our findings show that the extreme lifestyle of S. acidocaldarius coincided with a high tolerance to organic solvents. This study provides first insights into biofilm formation and membrane/cell stress caused by organic solvents in S. acidocaldarius ImportanceArchaea are unique in terms of metabolic and cellular processes as well as the adaptation to extreme environments. In the past few years, the development of genetic systems and biochemical, genetic and poly-omics studies have provided deep insights into the physiology of some archaeal model organisms. In this study, we used S. acidocaldarius adapted to two extremes, low pH and high temperature, to study its tolerance and robustness as well as its global cellular response towards organic solvents exemplified by 1-butanol. We were able to identify biofilm formation as primary cellular response to 1-butanol. Furthermore, the triggered cell/membrane stress led to significant changes in culture heterogeneity accompanied by changes in central cellular processes such as cell division and cellular defense systems, thus suggesting a global response for the protection at population level. Copyright © 2021 Benninghoff et al

Immunohistochemical localization of glutamate(2a) and 3-nitrotyrosine (2b) in the hippocampal formation.

<p>Representative photomicrographs (scale bar = 200 µM). GrDG granular cell layer of dentate gyrus; MoDG molecular layer of dentate gyrus; PoDG polymorphic layer of dentate gyrus; “CA4” terminal portion of the hippocampal pyramidal cell layer.</p

Effect of haloperidol on MK-801 induced glutamate efflux.

<p>Hippocampal cells were pretreated with 5 µM haloperidol for 4 hours and exposed to ascending concentrations of MK-801 for further 20 hours with haloperidol still being present. Glutamate was determined enzymatically in the culture supernatant. Data represent the mean +/− SD of 6 individual experiments each.</p

Model of the local neuronal circuit disinhibition elicited by MK-801.

<p>The GABAergic interneuron (IN) receives input from the pyramidal cell (PC) thereby exerting an inhibitory control by recurrent projections to the PC. In presence of the NMDA receptor antagonist MK-801, this local feedback inhibition becomes disrupted, whereas the excitatory input is sustained via non-NMDA (AMPA/kainate) receptors, which do not respond to MK-801. Due to this imbalance, the total excitatory output will be enhanced. (GABA, γ-aminobutyric acid; NMDA, N-methyl-D-aspartate).</p

Effect of MK-801 on H₂O₂-induced glutamate efflux.

<p>Hippocampal cells pretreated with 10 µM MK-801 were exposed to ascending concentrations of H₂O₂ for 24 hours under normoxic conditions. Glutamate was determined enzymatically in the culture supernatant. Data represent the mean +/− SD of 6 individual experiments each. * denotes statistical significance vs. untreated cells at p<0.001.</p