Single-channel qEEG characteristics distinguish delirium from no delirium, but not postoperative from non-postoperative delirium

OBJECTIVE: This exploratory study examined quantitative electroencephalography (qEEG) changes in delirium and the use of qEEG features to distinguish postoperative from non-postoperative delirium. METHODS: This project was part of the DeltaStudy, a cross-sectional,multicenterstudy in Intensive Care Units (ICUs) and non-ICU wards. Single-channel (Fp2-Pz) four-minutes resting-state EEG was analyzed in 456 patients. After calculating 98 qEEG features per epoch, random forest (RF) classification was used to analyze qEEG changes in delirium and to test whether postoperative and non-postoperative delirium could be distinguished. RESULTS: An area under the receiver operatingcharacteristic curve (AUC) of 0.76 (95% Confidence Interval (CI) 0.71-0.80) was found when classifying delirium with a sensitivity of 0.77 and a specificity of 0.63 at the optimal operating point. The classification of postoperative versus non-postoperative delirium resulted in an AUC of 0.50 (95%CI 0.38-0.61). CONCLUSIONS: RF classification was able to discriminate delirium from no delirium with reasonable accuracy, while also identifying new delirium qEEG markers like autocorrelation and theta peak frequency. RF classification could not distinguish postoperative from non-postoperative delirium. SIGNIFICANCE: Single-channel EEG differentiates between delirium and no delirium with reasonable accuracy. We found no distinct EEG profile for postoperative delirium, which may suggest that delirium is one entity, whether it develops postoperatively or not

The N-end rule pathway promotes seed germination and establishment through removal of ABA sensitivity in Arabidopsis

The N-end rule pathway targets protein degradation through the identity of the amino-terminal residue of specific protein substrates. Two components of this pathway in Arabidopsis thaliana, PROTEOLYSIS6 (PRT6) and arginyl-tRNA:protein arginyltransferase (ATE), were shown to regulate seed after-ripening, seedling sugar sensitivity, seedling lipid breakdown, and abscisic acid (ABA) sensitivity of germination. Sensitivity of prt6 mutant seeds to ABA inhibition of endosperm rupture reduced with after-ripening time, suggesting that seeds display a previously undescribed window of sensitivity to ABA. Reduced root growth of prt6 alleles and the ate1 ate2 double mutant was rescued by exogenous sucrose, and the breakdown of lipid bodies and seed-derived triacylglycerol was impaired in mutant seedlings, implicating the N-end rule pathway in control of seed oil mobilization. Epistasis analysis indicated that PRT6 control of germination and establishment, as exemplified by ABA and sugar sensitivity, as well as storage oil mobilization, occurs at least in part via transcription factors ABI3 and ABI5. The N-end rule pathway of protein turnover is therefore postulated to inactivate as-yet unidentified key component(s) of ABA signaling to influence the seed-to-seedling transition

Symmetry-free cryo-EM structures of the chaperonin TRiC along its ATPase-driven conformational cycle

Chaperonins are multisubunit entities that are composed of two stacked rings enclosing a central chamber for ATP-dependent protein folding. A series of cryo-EM structures of the eukaryotic group II chaperonin TRiC/CCT reveal the conformational changes during the ATPase cycle and provide insight into how the subunits cooperate to close the lid

DeltaScan for the Assessment of Acute Encephalopathy and Delirium in ICU and non-ICU Patients, a Prospective Cross-Sectional Multicenter Validation Study

Objectives: To measure the diagnostic accuracy of DeltaScan: a portable real-time brain state monitor for identifying delirium, a manifestation of acute encephalopathy (AE) detectable by polymorphic delta activity (PDA) in single-channel electroencephalograms (EEGs). Design: Prospective cross-sectional study. Setting: Six Intensive Care Units (ICU's) and 17 non-ICU departments, including a psychiatric department across 10 Dutch hospitals. Participants: 494 patients, median age 75 (IQR:64-87), 53% male, 46% in ICUs, 29% delirious. Measurements: DeltaScan recorded 4-minute EEGs, using an algorithm to select the first 96 seconds of artifact-free data for PDA detection. This algorithm was trained and calibrated on two independent datasets. Methods: Initial validation of the algorithm for AE involved comparing its output with an expert EEG panel's visual inspection. The primary objective was to assess DeltaScan's accuracy in identifying delirium against a delirium expert panel's consensus. Results: DeltaScan had a 99% success rate, rejecting 6 of the 494 EEG's due to artifacts. Performance showed and an Area Under the Receiver Operating Characteristic Curve (AUC) of 0.86 (95% CI: 0.83-0.90) for AE (sensitivity: 0.75, 95%CI=0.68-0.81, specificity: 0.87 95%CI=0.83-0.91. The AUC was 0.71 for delirium (95%CI=0.66-0.75, sensitivity: 0.61 95%CI=0.52-0.69, specificity: 72, 95%CI=0.67-0.77). Our validation aim was an NPV for delirium above 0.80 which proved to be 0.82 (95%CI: 0.77-0.86). Among 84 non-delirious psychiatric patients, DeltaScan differentiated delirium from other disorders with a 94% (95%CI: 87-98%) specificity. Conclusions: DeltaScan can diagnose AE at bedside and shows a clear relationship with clinical delirium. Further research is required to explore its role in predicting delirium-related outcomes.</p

Natural anti-CCR5 antibodies in HIV-infection and -exposure

Natural antibodies constitute a first-line of defence against pathogens; they may also play other roles in immune regulation and homeostasis, through their ability to bind host antigens, surface molecules and receptors. Natural anti-CCR5 antibodies can be decisive in preventing HIV infection in mucosal tissues and offer prompt and effective protection just at major sites of virus entry. Among natural anti-CCR5 antibodies, IgG and IgA to the ECL1 domain have been shown to block HIV effectively and durably without causing harm to the host. Their biological properties and their uncommon generation in subsets of HIV-infected and HIV-exposed individuals (so called ESN) will be introduced and discussed, with the aim at exploiting their potential in therapy and prevention

Railway-induced ground vibrations – a review of vehicle effects

This paper is a review of the effect of vehicle characteristics on ground- and track borne-vibrations from railways. It combines traditional theory with modern thinking and uses a range of numerical analysis and experimental results to provide a broad analysis of the subject area. First, the effect of different train types on vibration propagation is investigated. Then, despite not being the focus of this work, numerical approaches to vibration propagation modelling within the track and soil are briefly touched upon. Next an in-depth discussion is presented related to the evolution of numerical models, with analysis of the suitability of various modelling approaches for analysing vehicle effects. The differences between quasi-static and dynamic characteristics are also discussed with insights into defects such as wheel/rail irregularities. Additionally, as an appendix, a modest database of train types are presented along with detailed information related to their physical attributes. It is hoped that this information may provide assistance to future researchers attempting to simulate railway vehicle vibrations. It is concluded that train type and the contact conditions at the wheel/rail interface can be influential in the generation of vibration. Therefore, where possible, when using numerical approach, the vehicle should be modelled in detail. Additionally, it was found that there are a wide variety of modelling approaches capable of simulating train types effects. If non-linear behaviour needs to be included in the model, then time domain simulations are preferable, however if the system can be assumed linear then frequency domain simulations are suitable due to their reduced computational demand

Drosophila IAP1-Mediated Ubiquitylation Controls Activation of the Initiator Caspase DRONC Independent of Protein Degradation

Ubiquitylation targets proteins for proteasome-mediated degradation and plays important roles in many biological processes including apoptosis. However, non-proteolytic functions of ubiquitylation are also known. In Drosophila, the inhibitor of apoptosis protein 1 (DIAP1) is known to ubiquitylate the initiator caspase DRONC in vitro. Because DRONC protein accumulates in diap1 mutant cells that are kept alive by caspase inhibition (“undead” cells), it is thought that DIAP1-mediated ubiquitylation causes proteasomal degradation of DRONC, protecting cells from apoptosis. However, contrary to this model, we show here that DIAP1-mediated ubiquitylation does not trigger proteasomal degradation of full-length DRONC, but serves a non-proteolytic function. Our data suggest that DIAP1-mediated ubiquitylation blocks processing and activation of DRONC. Interestingly, while full-length DRONC is not subject to DIAP1-induced degradation, once it is processed and activated it has reduced protein stability. Finally, we show that DRONC protein accumulates in “undead” cells due to increased transcription of dronc in these cells. These data refine current models of caspase regulation by IAPs

An updated evaluation of the implementation of the sigmoid take-off landmark 1 year after the official introduction in the Netherlands

PURPOSE: The definition of rectal cancer based on the sigmoid take-off (STO) was incorporated into the Dutch guideline in 2019, and became mandatory in the national audit from December 2020. This study aimed to evaluate the use of the STO in clinical practice and the added value of online training, stratified for the period before (group A, historical cohort) and after (group B, current cohort) incorporation into the national audit.METHODS: Participants, including radiologists, surgeons, surgical and radiological residents, interns, PhD students, and physician assistants, were asked to complete an online training program, consisting of questionnaires, 20 MRI cases, and a training document. Outcomes were agreement with the expert reference, inter-rater variability, and accuracy before and after the training.RESULTS: Group A consisted of 86 participants and group B consisted of 114 participants. Familiarity with the STO was higher in group B (76% vs 88%, p = 0.027). Its use in multidisciplinary meetings was not significantly higher (50% vs 67%, p = 0.237). Agreement with the expert reference was similar for both groups before (79% vs 80%, p = 0.423) and after the training (87% vs 87%, p = 0.848). Training resulted in significant improvement for both groups in classifying tumors located around the STO (group A, 69-79%; group B, 67-79%, p &lt; 0.001).CONCLUSIONS: The results of this study show that after the inclusion of the STO in the mandatory Dutch national audit, the STO was consequently used in only 67% of the represented hospitals. Online training has the potential to improve implementation and unambiguous assessment.</p