Contact isolation of patients with multi-drug-resistant organisms (MDROs) is an essential element of infection prevention strategies in hospitals worldwide. However, this practice may be associated ...with adverse side effects on patients' health and well-being.
This study was the first to assess mental health and well-being variables among isolated patients compared with non-isolated control patients in a German cohort.
We conducted a matched case–control study among N = 267 patients admitted to a tertiary care teaching hospital in Germany. Their levels of anxiety, depression, loneliness, and dissatisfaction with their hospital experience were assessed using a questionnaire. Additionally, among isolated patients, it was evaluated how well they felt informed about their MDRO status.
In our cohort, patients under contact isolation were significantly more dissatisfied than non-isolated control patients but did not show higher levels of anxiety, depression, and loneliness. A large proportion of patients felt insufficiently informed about their MDRO status. This lack of information was the strongest predictor of dissatisfaction among isolated patients.
These findings underline the importance of adequate patient communication. It is essential for patients' well-being to receive timely, relevant, and understandable information about the background and consequences of their infection or colonisation with MDROs.
Heat shock protein 90 (Hsp90) is a molecular chaperone involved in the maturation of a plethora of substrates ("clients"), including protein kinases, transcription factors, and E3 ubiquitin ligases, ...positioning Hsp90 as a central regulator of cellular proteostasis. Hsp90 undergoes large conformational changes during its ATPase cycle. The processing of clients by cytosolic Hsp90 is assisted by a cohort of cochaperones that affect client recruitment, Hsp90 ATPase function or conformational rearrangements in Hsp90. Because of the importance of Hsp90 in regulating central cellular pathways, strategies for the pharmacological inhibition of the Hsp90 machinery in diseases such as cancer and neurodegeneration are being developed. In this review, we summarize recent structural and mechanistic progress in defining the function of organelle-specific and cytosolic Hsp90, including the impact of individual cochaperones on the maturation of specific clients and complexes with clients as well as ways of exploiting Hsp90 as a drug target.
The HSP90 chaperone machinery Schopf, Florian H; Biebl, Maximilian M; Buchner, Johannes
Nature reviews. Molecular cell biology,
06/2017, Letnik:
18, Številka:
6
Journal Article
Recenzirano
The heat shock protein 90 (HSP90) chaperone machinery is a key regulator of proteostasis under both physiological and stress conditions in eukaryotic cells. As HSP90 has several hundred protein ...substrates (or 'clients'), it is involved in many cellular processes beyond protein folding, which include DNA repair, development, the immune response and neurodegenerative disease. A large number of co-chaperones interact with HSP90 and regulate the ATPase-associated conformational changes of the HSP90 dimer that occur during the processing of clients. Recent progress has allowed the interactions of clients with HSP90 and its co-chaperones to be defined. Owing to the importance of HSP90 in the regulation of many cellular proteins, it has become a promising drug target for the treatment of several diseases, which include cancer and diseases associated with protein misfolding.
The Hsp90 system in the eukaryotic cytosol is characterized by a cohort of co-chaperones that bind to Hsp90 and affect its function. Although progress has been made regarding the underlying ...biochemical mechanisms, how co-chaperones influence Hsp90 client proteins in vivo has remained elusive. By investigating the effect of 12 Hsp90 co-chaperones on the activity of different client proteins in yeast, we find that deletion of co-chaperones can have a neutral or negative effect on client activity but can also lead to more active clients. Only a few co-chaperones are active on all clients studied. Closely related clients and even point mutants can depend on different co-chaperones. These effects are direct because differences in client-co-chaperone interactions can be reconstituted in vitro. Interestingly, some co-chaperones affect client conformation in vivo. Thus, co-chaperones adapt the Hsp90 cycle to the requirements of the client proteins, ensuring optimal activation.
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•Clients dictate the co-chaperone dependence of the Hsp90 system•A core set of generally important co-chaperones is identified•The study reveals the general importance of the co-chaperone Sgt1•Co-chaperones control the conformation of clients
A large cohort of co-chaperones enables Hsp90 to chaperone structurally and functionally diverse client proteins. Sahasrabudhe et al. show that the nature of the client protein dictates the contribution of a co-chaperone to its maturation. Analysis in yeast suggests that only a few co-chaperones are of general importance.
Heat shock protein 90 (Hsp90) is a molecular chaperone regulating the activity of diverse client proteins together with a plethora of different co-chaperones. Whether these functionally cooperate has ...remained enigmatic. We analyze all double mutants of 11 Saccharomyces cerevisiae Hsp90 co-chaperones in vivo concerning effects on cell physiology and the activation of specific client proteins. We find that client activation is supported by a genetic network with weak epistasis between most co-chaperones and a few modules with strong genetic interactions. These include an epistatic module regulating protein translation and dedicated epistatic networks for specific clients. For kinases, the bridging of Hsp70 and Hsp90 by Sti1/Hop is essential for activation, whereas for steroid hormone receptors, an epistatic module regulating their dwell time on Hsp90 is crucial, highlighting the specific needs of different clients. Thus, the Hsp90 system is characterized by plastic co-chaperone networks fine-tuning the conformational processing in a client-specific manner.
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•Genetic interactions between Hsp90 co-chaperones are dynamic and client specific•Sti1, Cpr7, and Cns1 form an epistatic module maintaining eEF2 integrity•Sti1/Hsp70 and Cdc37 act on two parallel pathways for kinase maturation•Aha1 and Hch1 are dwell-time regulators for Hsp90 client complexes
Biebl et al. show that Hsp90 co-chaperones form client-specific genetic networks for client maturation. Tightly interacting core genetic modules of co-chaperones specific for a client are embedded in a network of looser genetic interactions. Distinct epistatic Hsp90 co-chaperone modules regulate kinase activation, steroid hormone receptor maturation, and protein biosynthesis.
The co-chaperone p23 is a central part of the Hsp90 machinery. It stabilizes the closed conformation of Hsp90, inhibits its ATPase and is important for client maturation. Yet, how this is achieved ...has remained enigmatic. Here, we show that a tryptophan residue in the proximal region of the tail decelerates the ATPase by allosterically switching the conformation of the catalytic loop in Hsp90. We further show by NMR spectroscopy that the tail interacts with the Hsp90 client binding site via a conserved helix. This helical motif in the p23 tail also binds to the client protein glucocorticoid receptor (GR) in the free and Hsp90-bound form. In vivo experiments confirm the physiological importance of ATPase modulation and the role of the evolutionary conserved helical motif for GR activation in the cellular context.
A total of 16 analytical methods, spanning from classical solvent extraction over different thermo-analytic and mechanical approaches to acoustic and optical spectroscopy, have been evaluated as to ...their ability to determine the crosslinking state of ethylene vinyl acetate (EVA), the prevailing encapsulant for photovoltaics applications. The key objective of this work was to create a systematic and comprehensive comparison, using a unified set of traceable test samples covering the full range of realistically occurring degrees of EVA crosslinking. A majority number of these tested methods proved fundamentally suitable for detecting changes in the polymer properties during crosslinking based on the effect e.g. its mechanical properties or its crystallinity. Interestingly, when investigated in detail, most of the methods showed mutually different dependencies on the lamination time, indicating a complex range of effects of the chemical crosslinking on the properties and behaviour of the material. Furthermore, Raman spectroscopy could be identified as a potential new method for measuring the degree of crosslinking in-line in the PV module manufacturing process, thus providing an interesting approach for improving process control in PV module processing.
•8 suitable methods for determining the crosslinking state of EVA identified.•physico-chemical basics of analytical procedures highly relevant to information gain.•Soxleth extraction proved a reliable off-line reference method.•Raman spectroscopy is a promising approach for a future inline quality control.
Objective This study examined how chronic experiences of peer victimization throughout childhood relate to mental and physical health outcomes in adolescence. Methods Children were tested in a ...laboratory playroom at the age of 5 years. They completed questionnaires at time 2, between the ages of 10 and 18 years, and a telephone interview at time 3, between the ages of 12 and 20 years. A total of 70 youth participated at all three time periods. Chronic victims were defined as having high levels of peer victimization at all three time points. Results Youth who were chronically victimized reported experiencing significantly more mental and physical health problems than youth categorized as desisters or nonvictims. Also, for girls only, chronic victims reported more specific health problems (headaches, sleep problems) than did nonchronic victims. Conclusions The present findings may assist health professionals in assessing and treating physical and mental health problems that appear to be related to peer victimization.
The objective of this study was to compare the lexical sophistication of personal statements submitted by professional physical therapist education program applicants with those generated by OpenAI's ...Chat Generative Pretrained Transformer (ChatGPT).
Personal statements from 152 applicants and 20 generated by ChatGPT were collected, all in response to a standardized prompt. These statements were coded numerically, then analyzed with recurrence quantification analyses (RQAs). RQA indices including recurrence, determinism, max line, mean line, and entropy were compared with t-tests. A receiver operating characteristic curve analysis was used to examine discriminative validity of RQA indices to distinguish between ChatGPT and human-generated personal statements.
ChatGPT-generated personal statements exhibited higher recurrence, determinism, mean line, and entropy values than did human-generated personal statements. The strongest discriminator was a 13.04% determinism rate, which differentiated ChatGPT from human-generated writing samples with 70% sensitivity and 91.4% specificity (positive likelihood ratio = 8.14). Personal statements with determinism rates exceeding 13% were 8 times more likely to have been ChatGPT than human generated.
Although RQA can distinguish artificial intelligence (AI)-generated text from human-generated text, it is not absolute. Thus, AI introduces additional challenges to the authenticity and utility of personal statements. Admissions committees along with organizations providing guidelines in professional physical therapist education program admissions should reevaluate the role of personal statements in applications.
As AI-driven chatbots like ChatGPT complicate the evaluation of personal statements, RQA emerges as a potential tool for admissions committees to detect AI-generated statements.
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