Наноалмазы как идеальные наноносители для циансодежащих цитостатиков

Цианосодержащие цитостатики - новый класс открытых нами лекарств, которые благодаря цианогруппам хорошо закрепляются на наноалмазах, с увеличением активности

The impact of direct oral anticoagulants on viscoelastic testing – A systematic review

Background: In case of bleeding patients and in acute care, the assessment of residual direct oral anticoagulant (DOAC) activity is essential for evaluating the potential impact on hemostasis, especially when a timely decision on urgent surgery or intervention is required. Viscoelastic tests are crucial in a modern goal-directed coagulation management to assess patients' coagulation status. However, the role of viscoelastic test to detect and quantify residual DOAC plasma levels is controversially discussed. The aim of this review was to systematically summarize the evidence of viscoelastic tests for the assessment of residual DOAC activity. Method: PubMed, Embase, Scopus, and the Cochrane Library were searched for original articles investigating the effect of rivaroxaban, apixaban, edoxaban, or dabigatran plasma levels on different viscoelastic tests of the adult population from database inception to December 31, 2021. Results: We included 53 studies from which 31 assessed rivaroxaban, 22 apixaban, six edoxaban, and 29 dabigatran. The performance of viscoelastic tests varied across DOACs and assays. DOAC specific assays are more sensitive than unspecific assays. The plasma concentration of rivaroxaban and dabigatran correlates strongly with the ROTEM EXTEM, ClotPro RVV-test or ECA-test clotting time (CT) and TEG 6s anti-factor Xa (AFXa) or direct thrombin inhibitor (DTI) channel reaction time (R). Results of clotting time (CT) and reaction time (R) within the normal range do not reliable exclude relevant residual DOAC plasma levels limiting the clinical utility of viscoelastic assays in this context. Conclusion: Viscoelastic test assays can provide fast and essential point-of-care information regarding DOAC activity, especially DOAC specific assays. The identification and quantification of residual DOAC plasma concentration with DOAC unspecific viscoelastic assays are not sensitive enough, compared to recommended anti-Xa activity laboratory measurements. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=320629], identifier [CRD42022320629]. Keywords: ClotPro; DOAC; FII inhibitor; FXa inhibitor; ROTEM; TEG; point-of-car

Relaxation of Vibrational Excitons in Molecular-Ionic Crystal s Measured by Picosecond Time-Resolved CARS

The decay times of the internal vibrations in K2S04, KCl04, NaN03 and CaC03 single crystals have been measured at different temperature s by picosecond time-resolved CARS. The low temperature experimental data and their temperature dependence are interpreted on the basis of an energy relaxation mechanism, involving two-phonon and higher order decay processes

Improved Task Performance, Low Workload, and User-Centered Design in Medical Diagnostic Equipment Enhance Decision Confidence of Anesthesia Providers: A Meta-Analysis and a Multicenter Online Survey

Decision confidence-the subjective belief to have made the right decision-is central in planning actions in a complex environment such as the medical field. It is unclear by which factors it is influenced. We analyzed a pooled data set of eight studies and performed a multicenter online survey assessing anesthesiologists' opinions on decision confidence. By applying mixed models and using multiple imputation to determine the effect of missing values from the dataset on the results, we investigated how task performance, perceived workload, the utilization of user-centered medical diagnostic devices, job, work experience, and gender affected decision confidence. The odds of being confident increased with better task performance (OR: 1.27, 95% CI: 0.94 to 1.7; p = 0.12; after multiple imputation OR: 3.19, 95% CI: 2.29 to 4.45; p < 0.001) and when user-centered medical devices were used (OR: 5.01, 95% CI: 3.67 to 6.85; p < 0.001; after multiple imputation OR: 3.58, 95% CI: 2.65 to 4.85; p < 0.001). The odds of being confident decreased with higher perceived workload (OR: 0.94, 95% CI: 0.93 to 0.95; p < 0.001; after multiple imputation, OR: 0.94, 95% CI: 0.93 to 0.95; p < 0.001). Other factors, such as gender, job, or professional experience, did not affect decision confidence. Most anesthesiologists who participated in the online survey agreed that task performance (25 of 30; 83%), perceived workload (24 of 30; 80%), work experience (28 of 30; 93%), and job (21 of 30; 70%) influence decision confidence. Improved task performance, lower perceived workload, and user-centered design in medical equipment enhanced the decision confidence of anesthesia providers. Keywords: diagnostic; diagnostic confidence; gender; online survey; over-confidence; self-assessment; under-confidence; user-centered design; workloa

Improved Task Performance, Low Workload, and User-Centered Design in Medical Diagnostic Equipment Enhance Decision Confidence of Anesthesia Providers: A Meta-Analysis and a Multicenter Online Survey

Decision confidence-the subjective belief to have made the right decision-is central in planning actions in a complex environment such as the medical field. It is unclear by which factors it is influenced. We analyzed a pooled data set of eight studies and performed a multicenter online survey assessing anesthesiologists' opinions on decision confidence. By applying mixed models and using multiple imputation to determine the effect of missing values from the dataset on the results, we investigated how task performance, perceived workload, the utilization of user-centered medical diagnostic devices, job, work experience, and gender affected decision confidence. The odds of being confident increased with better task performance (OR: 1.27, 95% CI: 0.94 to 1.7; p = 0.12; after multiple imputation OR: 3.19, 95% CI: 2.29 to 4.45; p < 0.001) and when user-centered medical devices were used (OR: 5.01, 95% CI: 3.67 to 6.85; p < 0.001; after multiple imputation OR: 3.58, 95% CI: 2.65 to 4.85; p < 0.001). The odds of being confident decreased with higher perceived workload (OR: 0.94, 95% CI: 0.93 to 0.95; p < 0.001; after multiple imputation, OR: 0.94, 95% CI: 0.93 to 0.95; p < 0.001). Other factors, such as gender, job, or professional experience, did not affect decision confidence. Most anesthesiologists who participated in the online survey agreed that task performance (25 of 30; 83%), perceived workload (24 of 30; 80%), work experience (28 of 30; 93%), and job (21 of 30; 70%) influence decision confidence. Improved task performance, lower perceived workload, and user-centered design in medical equipment enhanced the decision confidence of anesthesia providers. Keywords: diagnostic; diagnostic confidence; gender; online survey; over-confidence; self-assessment; under-confidence; user-centered design; workloa

Faster Time to Treatment Decision of Viscoelastic Coagulation Test Results through Improved Perception with the Animated Visual Clot: A Multicenter Comparative Eye-Tracking Study

As the interpretation of viscoelastic coagulation test results remains challenging, we created Visual Clot, an animated blood clot aiming to facilitate raw rotational thromboelastometry (ROTEM) parameters. This study investigated anesthesia personnel's cognitive processing in managing simulated bleeding scenarios using eye-tracking technology. This multicenter, international, computer-based study across five large, central European hospitals included 35 participants with minimal to no prior experience interpreting viscoelastic test results. Using eye-tracking technology and an iPad tagged with quick response codes, we defined the time to treatment decision and the time on screen surface in seconds of correctly solved scenarios as our outcomes. The median time to treatment decision was 52 s for Visual Clot and 205 s for ROTEM (p < 0.0001). The probability of solving the scenario correctly was more than 8 times higher when using Visual Clot than when using ROTEM (Hazard ratio [HR] 8.54, 95% CI from 6.5 to 11.21; p < 0.0001). Out of 194 correctly answered scenarios of participants with the eye-tracker, 154 (79.4%) were solved with Visual Clot and 40 (20.6%) with ROTEM. Participants spent on average 30 s less looking at the screen surface with Visual Clot compared to ROTEM (Coefficient -30.74 s, 95% CI from -39.27 to -22.27; p < 0.0001). For a comparison of the two modalities in terms of information transfer, we calculated the percentage of time on the screen surface of the overall time to treatment decision, which with Visual Clot was 14 percentage points shorter than with ROTEM (Coefficient -14.55, 95% CI from -20.05 to -9.12; p < 0.0001). Visual Clot seems to improve perception and detection of coagulopathies and leads to earlier initiation of the appropriate treatment. In a high-pressure working environment such as the operating and the resuscitation room, correct and timely decisions regarding bleeding management may have a relevant impact on patients' outcomes. Keywords: Visual Clot; avatar; blood coagulation; eye-tracking; point-of-care; rotational thromboelastometry; viscoelastic test; visual perception

DNA bending facilitates the error-free DNA damage tolerance pathway and upholds genome integrity

Abstract DNA replication is sensitive to damage in the template. To bypass lesions and complete replication, cells activate recombination-mediated (error-free) and translesion synthesis-mediated (error-prone) DNA damage tolerance pathways. Crucial for error-free DNA damage tolerance is template switching, which depends on the formation and resolution of damage-bypass intermediates consisting of sister chromatid junctions. Here we show that a chromatin architectural pathway involving the high mobility group box protein Hmo1 channels replication-associated lesions into the error-free DNA damage tolerance pathway mediated by Rad5 and PCNA polyubiquitylation, while preventing mutagenic bypass and toxic recombination. In the process of template switching, Hmo1 also promotes sister chromatid junction formation predominantly during replication. Its C-terminal tail, implicated in chromatin bending, facilitates the formation of catenations/hemicatenations and mediates the roles of Hmo1 in DNA damage tolerance pathway choice and sister chromatid junction formation. Together, the results suggest that replication-associated topological changes involving the molecular DNA bender, Hmo1, set the stage for dedicated repair reactions that limit errors during replication and impact on genome stability

Physics-informed laboratory estimation of Sargassum windage

A recent Maxey--Riley theory for \sarg raft motion, which models a raft as a network of elastically interacting finite-size, buoyant particles, predicts the carrying flow velocity to be given by the weighted sum of the water and air velocities $(1-\alpha)\mathbf{v} + \alpha \mathbf w$. The theory provides a closed formula for parameter $\alpha$, referred to as \emph{windage}, depending on water-to-particle-density ratio or buoyancy ($\delta$). From a series of laboratory experiments in an air--water stream flume facility under controlled conditions, we estimate $\alpha$ ranging from 0.02 to 0.96\pct. On average, our windage estimates can be up to 9 times smaller than considered in conventional \emph{Sargassum} raft transport modeling, wherein it is customary to add a fraction of $\mathbf w$ to $\mathbf{v}$ chosen in an ad-hoc piecemeal manner. Using the formula provided by the Maxey--Riley theory, we estimate $\delta$ ranging from 1.00 to 1.49. This is consistent with direct $\delta$ measurements, ranging from 0.9 to 1.25, which provide support for our $\alpha$ estimation