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1.
Neural Netw ; 176: 106345, 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38733798

ABSTRACT

Local Interpretability Model-agnostic Explanations (LIME) is a well-known post-hoc technique for explaining black-box models. While very useful, recent research highlights challenges around the explanations generated. In particular, there is a potential lack of stability, where the explanations provided vary over repeated runs of the algorithm, casting doubt on their reliability. This paper investigates the stability of LIME when applied to multivariate time series classification. We demonstrate that the traditional methods for generating neighbours used in LIME carry a high risk of creating 'fake' neighbours, which are out-of-distribution in respect to the trained model and far away from the input to be explained. This risk is particularly pronounced for time series data because of their substantial temporal dependencies. We discuss how these out-of-distribution neighbours contribute to unstable explanations. Furthermore, LIME weights neighbours based on user-defined hyperparameters which are problem-dependent and hard to tune. We show how unsuitable hyperparameters can impact the stability of explanations. We propose a two-fold approach to address these issues. First, a generative model is employed to approximate the distribution of the training data set, from which within-distribution samples and thus meaningful neighbours can be created for LIME. Second, an adaptive weighting method is designed in which the hyperparameters are easier to tune than those of the traditional method. Experiments on real-world data sets demonstrate the effectiveness of the proposed method in providing more stable explanations using the LIME framework. In addition, in-depth discussions are provided on the reasons behind these results.

2.
Soft Matter ; 2024 May 22.
Article in English | MEDLINE | ID: mdl-38775063

ABSTRACT

Blood is a highly complex fluid with rheological properties that have a significant impact on various flow phenomena. In particular, it exhibits a non-Newtonian elongational viscosity that is comparable to polymer solutions. In this study, we investigate the effect of three different anticoagulants, namely EDTA (ethylene diamine tetraacetic acid), heparin, and citrate, on the elongational properties of both human and swine blood. We observe a unique two stage thinning process and a strong dependency of the characteristic relaxation time on the chosen anticoagulant, with the longest relaxation time and thus the highest elongational viscosity being found for the case of citrate. Our findings for the latter are consistent with the physiological values obtained from a dripping droplet of human blood without any anticoagulant. Furthermore, our study resolves the discrepancy found in the literature regarding the reported range of characteristic relaxation times, confirming that the elongational viscosity must be taken into account for a full rheological characterization of blood. These results have important implications for understanding blood flow in various physiological, pathological and technological conditions.

3.
Biomicrofluidics ; 18(2): 024104, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38577010

ABSTRACT

The ability to change shape is essential for the proper functioning of red blood cells (RBCs) within the microvasculature. The shape of RBCs significantly influences blood flow and has been employed in microfluidic lab-on-a-chip devices, serving as a diagnostic biomarker for specific pathologies and enabling the assessment of RBC deformability. While external flow conditions, such as the vessel size and the flow velocity, are known to impact microscale RBC flow, our comprehensive understanding of how their shape-adapting ability is influenced by channel confinement in biomedical applications remains incomplete. This study explores the impact of various rectangular and square channels, each with different confinement and aspect ratios, on the in vitro RBC flow behavior and characteristic shapes. We demonstrate that rectangular microchannels, with a height similar to the RBC diameter in combination with a confinement ratio exceeding 0.9, are required to generate distinctive well-defined croissant and slipper-like RBC shapes. These shapes are characterized by their equilibrium positions in the channel cross section, and we observe a strong elongation of both stable shapes in response to the shear rate across the different channels. Less confined channel configurations lead to the emergence of unstable other shape types that display rich shape dynamics. Our work establishes an experimental framework to understand the influence of channel size on the single-cell flow behavior of RBCs, providing valuable insights for the design of biomicrofluidic single-cell analysis applications.

4.
Eur Urol ; 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38644144

ABSTRACT

BACKGROUND AND OBJECTIVE: Different training programs have been developed to improve trainee outcomes in urology. However, evidence on the optimal training methodology is sparse. Our aim was to provide a comprehensive description of the training programs available for urological robotic surgery and endourology, assess their validity, and highlight the fundamental elements of future training pathways. METHODS: We systematically reviewed the literature using PubMed/Medline, Embase, and Web of Science databases. The validity of each training model was assessed. The methodological quality of studies on metrics and curricula was graded using the MERSQI scale. The level of evidence (LoE) and level of recommendation for surgical curricula were awarded using the educational Oxford Centre for Evidence-Based Medicine classification. KEY FINDINGS AND LIMITATIONS: A total of 75 studies were identified. Many simulators have been developed to aid trainees in mastering skills required for both robotic and endourology procedures, but only four demonstrated predictive validity. For assessment of trainee proficiency, we identified 18 in robotics training and six in endourology training; however, the majority are Likert-type scales. Although proficiency-based progression (PBP) curricula demonstrated superior outcomes to traditional training in preclinical settings, only four of six (67%) in robotics and three of nine (33%) in endourology are PBP-based. Among these, the Fundamentals of Robotic Surgery and the SIMULATE curricula have the highest LoE (level 1b). The lack of a quantitative synthesis is the main limitation of our study. CONCLUSIONS AND CLINICAL IMPLICATIONS: Training curricula that integrate simulators and PBP methodology have been introduced to standardize trainee outcomes in robotics and endourology. However, evidence regarding their educational impact remains restricted to preclinical studies. Efforts should be made to expand these training programs to different surgical procedures and assess their clinical impact. PATIENT SUMMARY: Simulation-based training and programs in which progression is based on proficiency represent the new standard of quality for achieving surgical proficiency in urology. Studies have demonstrated the educational impact of these approaches. However, there are still no standardized training pathways for several urology procedures.

5.
J Epidemiol Community Health ; 78(6): 345-353, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38429085

ABSTRACT

BACKGROUND: Cancer burden is higher and cancer screening participation is lower among individuals living in more socioeconomically deprived areas of England, contributing to worse health outcomes and shorter life expectancy. Owing to higher multi-cancer early detection (MCED) test sensitivity for poor-prognosis cancers and greater cancer burden in groups experiencing greater deprivation, MCED screening programmes may have greater relative benefits in these groups. We modelled potential differential benefits of MCED screening between deprivation groups in England at different levels of screening participation. METHODS: We applied the interception multi-cancer screening model to cancer incidence and survival data made available by the National Cancer Registration and Analysis Service in England to estimate reductions in late-stage diagnoses and cancer mortality from an MCED screening programme by deprivation group across 24 cancer types. We assessed the impact of varying the proportion of people who participated in annual screening in each deprivation group on these estimates. RESULTS: The modelled benefits of an MCED screening programme were substantial: reductions in late-stage diagnoses were 160 and 274 per 100 000 persons in the least and most deprived groups, respectively. Reductions in cancer mortality were 60 and 99 per 100 000 persons in the least and most deprived groups, respectively. Benefits were greatest in the most deprived group at every participation level and were attenuated with lower screening participation. CONCLUSIONS: For the greatest possible population benefit and to decrease health inequalities, an MCED implementation strategy should focus on enhancing equitable, informed participation, enabling equal participation across all socioeconomic deprivation groups. TRIAL REGISTRATION NUMBER: NCT05611632.


Subject(s)
Early Detection of Cancer , Neoplasms , Adult , Aged , Female , Humans , Male , Middle Aged , England/epidemiology , Incidence , Mass Screening , Neoplasms/mortality , Neoplasms/diagnosis , Social Class , Socioeconomic Factors
6.
Nat Commun ; 15(1): 2259, 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38480707

ABSTRACT

The discrete and charge-separated nature of matter - electrons and nuclei - results in local electrostatic fields that are ubiquitous in nanoscale structures and relevant in catalysis, nanoelectronics and quantum nanoscience. Surface-averaging techniques provide only limited experimental access to these potentials, which are determined by the shape, material, and environment of the nanostructure. Here, we image the potential over adatoms, chains, and clusters of Ag and Au atoms assembled on Ag(111) and quantify their surface dipole moments. By focusing on the total charge density, these data establish a benchmark for theory. Our density functional theory calculations show a very good agreement with experiment and allow a deeper analysis of the dipole formation mechanisms, their dependence on fundamental atomic properties and on the shape of the nanostructures. We formulate an intuitive picture of the basic mechanisms behind dipole formation, allowing better design choices for future nanoscale systems such as single-atom catalysts.

8.
Microb Cell Fact ; 23(1): 67, 2024 Feb 24.
Article in English | MEDLINE | ID: mdl-38402403

ABSTRACT

BACKGROUND: In recent years, the production of inclusion bodies that retain substantial catalytic activity was demonstrated. These catalytically active inclusion bodies (CatIBs) are formed by genetic fusion of an aggregation-inducing tag to a gene of interest via short linker polypeptides. The resulting CatIBs are known for their easy and cost-efficient production, recyclability as well as their improved stability. Recent studies have outlined the cooperative effects of linker and aggregation-inducing tag on CatIB activities. However, no a priori prediction is possible so far to indicate the best combination thereof. Consequently, extensive screening is required to find the best performing CatIB variant. RESULTS: In this work, a semi-automated cloning workflow was implemented and used for fast generation of 63 CatIB variants with glucose dehydrogenase of Bacillus subtilis (BsGDH). Furthermore, the variant BsGDH-PT-CBDCell was used to develop, optimize and validate an automated CatIB screening workflow, enhancing the analysis of many CatIB candidates in parallel. Compared to previous studies with CatIBs, important optimization steps include the exclusion of plate position effects in the BioLector by changing the cultivation temperature. For the overall workflow including strain construction, the manual workload could be reduced from 59 to 7 h for 48 variants (88%). After demonstration of high reproducibility with 1.9% relative standard deviation across 42 biological replicates, the workflow was performed in combination with a Bayesian process model and Thompson sampling. While the process model is crucial to derive key performance indicators of CatIBs, Thompson sampling serves as a strategy to balance exploitation and exploration in screening procedures. Our methodology allowed analysis of 63 BsGDH-CatIB variants within only three batch experiments. Because of the high likelihood of TDoT-PT-BsGDH being the best CatIB performer, it was selected in 50 biological replicates during the three screening rounds, much more than other, low-performing variants. CONCLUSIONS: At the current state of knowledge, every new enzyme requires screening for different linker/aggregation-inducing tag combinations. For this purpose, the presented CatIB toolbox facilitates fast and simplified construction and screening procedures. The methodology thus assists in finding the best CatIB producer from large libraries in short time, rendering possible automated Design-Build-Test-Learn cycles to generate structure/function learnings.


Subject(s)
Automation, Laboratory , High-Throughput Screening Assays , Reproducibility of Results , Bayes Theorem , Inclusion Bodies , Automation
9.
Int J Mol Sci ; 25(3)2024 Jan 24.
Article in English | MEDLINE | ID: mdl-38338693

ABSTRACT

The Gárdos channel (KCNN4) and Piezo1 are the best-known ion channels in the red blood cell (RBC) membrane. Nevertheless, the quantitative electrophysiological behavior of RBCs and its heterogeneity are still not completely understood. Here, we use state-of-the-art biochemical methods to probe for the abundance of the channels in RBCs. Furthermore, we utilize automated patch clamp, based on planar chips, to compare the activity of the two channels in reticulocytes and mature RBCs. In addition to this characterization, we performed membrane potential measurements to demonstrate the effect of channel activity and interplay on the RBC properties. Both the Gárdos channel and Piezo1, albeit their average copy number of activatable channels per cell is in the single-digit range, can be detected through transcriptome analysis of reticulocytes. Proteomics analysis of reticulocytes and mature RBCs could only detect Piezo1 but not the Gárdos channel. Furthermore, they can be reliably measured in the whole-cell configuration of the patch clamp method. While for the Gárdos channel, the activity in terms of ion currents is higher in reticulocytes compared to mature RBCs, for Piezo1, the tendency is the opposite. While the interplay between Piezo1 and Gárdos channel cannot be followed using the patch clamp measurements, it could be proved based on membrane potential measurements in populations of intact RBCs. We discuss the Gárdos channel and Piezo1 abundance, interdependencies and interactions in the context of their proposed physiological and pathophysiological functions, which are the passing of small constrictions, e.g., in the spleen, and their active participation in blood clot formation and thrombosis.


Subject(s)
Erythrocytes , Intermediate-Conductance Calcium-Activated Potassium Channels , Reticulocytes , Biological Transport , Calcium/metabolism , Erythrocytes/metabolism , Reticulocytes/metabolism , Humans , Intermediate-Conductance Calcium-Activated Potassium Channels/metabolism , Ion Channels/metabolism
10.
PNAS Nexus ; 3(1): pgad416, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38145245

ABSTRACT

Erythrocyte sedimentation rate (ESR) is a clinical parameter used as a nonspecific marker for inflammation, and recent studies have shown that it is linked to the collapse of the gel formed by red blood cells (RBCs) at physiological hematocrits (i.e. RBC volume fraction). Previous research has suggested that the observation of a slower initial dynamics is related to the formation of fractures in the gel. Moreover, RBC gels present specific properties due to the anisotropic shape and flexibility of the RBCs. Namely, the onset of the collapse is reached earlier and the settling velocity of the gel increases with increasing attraction between the RBCs, while the gel of spherical particles shows the opposite trend. Here, we report experimental observations of the gel structure during the onset of the collapse. We suggest an equation modeling this initial process as fracturing of the gel. We demonstrate that this equation provides a model for the motion of the interface between blood plasma and the RBC gel, along the whole time span. We also observe that the increase in the attraction between the RBCs modifies the density of fractures in the gel, which explains why the gel displays an earlier onset when the aggregation energy between the RBCs increases. Our work uncovers the detailed physical mechanism underlying the ESR and provides insights into the fracture dynamics of an RBC gel. These results can improve the accuracy of clinical measurements.

11.
BMJ Open ; 13(11): e075338, 2023 11 27.
Article in English | MEDLINE | ID: mdl-38011978

ABSTRACT

INTRODUCTION: Parkinson's disease (PD) represents the fastest growing neurodegenerative disease with an increasing prevalence worldwide. It is characterised by complex motor and non-motor symptoms that lead to considerable disability. Specialised physiotherapy has been shown to benefit patients with PD. The Parkinson Netzwerk Therapie (PaNTher) was created to improve access to specialised physiotherapy tailored to care priorities of PD patients. This study aims to evaluate the effectiveness, acceptability and needs of the PaNTher network by neurologists and physiotherapists involved in the network in outpatient care. METHODS AND ANALYSIS: This is a mixed-method, prospective, pragmatic non-randomised cohort study of parallel groups, with data collection taking place in Bavaria, Germany, between 2020 and 2024. Patients with PD insured by the Allgemeine Ortskrankenkasse Bayern (AOK Bayern) living in Bavaria will be recruited for study participation by network partners. Patients in the intervention group must reside in Munich or the surrounding area to ensure provision of specialised physiotherapy in close proximity to their place of residence. Controls receive care as usual. Six and 12 months after baseline, all patients receive a follow-up questionnaire. Mixed-effect regression models will be used to examine changes in impairment of activities of daily living and quality of life of patients with PD enrolled in the programme over time compared with usual care. Qualitative interviews will investigate the implementation processes and acceptability of the PaNTher network among neurologists and physiotherapists. The study is expected to show that the PaNTher network with an integrative care approach will improve the quality and effectiveness of the management and treatment of patients with PD. ETHICS AND DISSEMINATION: The study has been approved by the ethics committee at the medical faculty of the Ludwig-Maximilians-University Munich (20-318). Results will be published in scientific, peer-reviewed journals and presented at national and international conferences.


Subject(s)
Neurodegenerative Diseases , Parkinson Disease , Humans , Parkinson Disease/therapy , Parkinson Disease/diagnosis , Quality of Life , Activities of Daily Living , Cohort Studies , Prospective Studies , Ambulatory Care , Observational Studies as Topic
12.
BMJ Open ; 13(9): e071391, 2023 09 21.
Article in English | MEDLINE | ID: mdl-37734900

ABSTRACT

OBJECTIVES: Faecal occult blood testing (FOBT) and faecal immunochemical testing (FIT) are among the most used screening modalities for colorectal cancer (CRC). Colonoscopy is also widely used as a screening and diagnostic test for adults with a positive FOBT/FIT. Patient experience of colonoscopy is an important component for most CRC screening programmes. Individuals with negative experiences are less likely to engage with colonoscopy in the future and can deter others from attending colonoscopy when invited. This review synthesised data on patient experience with colonoscopy, following a positive result, to provide insights into how to improve patient experience within the English Bowel Cancer Screening Programme. METHODS: MEDLINE, EMBASE and PsycINFO were searched for quantitative questionnaire studies evaluating patient-reported experience with colonoscopy, following a positive screening FOB/FIT result. The search was limited to studies published between 2000 and 2021 (ie, when the first FOBT/FIT screening programmes for CRC were introduced). Data-driven and narrative summary techniques were used to summarise the literature. RESULTS: In total, six studies from the UK (n=4), Spain (n=1) and the Netherlands (n=1) were included in the review (total participants: 152 329; response rate: 68.0-79.3%). Patient experiences were categorised into three 'stages': 'pre-colonoscopy', 'during the test' and 'post-colonoscopy'. Overall, patients reported a positive experience in all six studies. Bowel preparation was the most frequently endorsed issue experienced pre-test (experienced by 10.0-41.0% of individuals, across all studies), pain and discomfort for during the test (experienced by 10.0-21.0% of participants) and abdominal pain and discomfort after the test (these were experienced by 14.8-22% of patients). CONCLUSION: This review highlighted that patient-reported experiences associated with colonoscopy were generally positive. To improve the colonoscopy experience, bowel screening centres should investigate means to: make bowel preparation more acceptable, make colonoscopy less painful and reduce post-colonoscopy symptoms.


Subject(s)
Abdominal Pain , Occult Blood , Adult , Humans , Colonoscopy , MEDLINE , Diagnostic Tests, Routine
13.
Transfus Med Hemother ; 50(3): 163-173, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37408647

ABSTRACT

Background: "Artificial intelligence" and "big data" increasingly take the step from just being interesting concepts to being relevant or even part of our lives. This general statement holds also true for transfusion medicine. Besides all advancements in transfusion medicine, there is not yet an established red blood cell quality measure, which is generally applied. Summary: We highlight the usefulness of big data in transfusion medicine. Furthermore, we emphasize in the example of quality control of red blood cell units the application of artificial intelligence. Key Messages: A variety of concepts making use of big data and artificial intelligence are readily available but still await to be implemented into any clinical routine. For the quality control of red blood cell units, clinical validation is still required.

14.
Commun Chem ; 6(1): 136, 2023 Jul 03.
Article in English | MEDLINE | ID: mdl-37400714

ABSTRACT

Studying inorganic/organic hybrid systems is a stepping stone towards the design of increasingly complex interfaces. A predictive understanding requires robust experimental and theoretical tools to foster trust in the obtained results. The adsorption energy is particularly challenging in this respect, since experimental methods are scarce and the results have large uncertainties even for the most widely studied systems. Here we combine temperature-programmed desorption (TPD), single-molecule atomic force microscopy (AFM), and nonlocal density-functional theory (DFT) calculations, to accurately characterize the stability of a widely studied interface consisting of perylene-tetracarboxylic dianhydride (PTCDA) molecules on Au(111). This network of methods lets us firmly establish the adsorption energy of PTCDA/Au(111) via TPD (1.74 ± 0.10 eV) and single-molecule AFM (2.00 ± 0.25 eV) experiments which agree within error bars, exemplifying how implicit replicability in a research design can benefit the investigation of complex materials properties.

15.
Soft Matter ; 19(33): 6255-6266, 2023 Aug 23.
Article in English | MEDLINE | ID: mdl-37522517

ABSTRACT

Bifurcations and branches in the microcirculation dramatically affect blood flow as they determine the spatiotemporal organization of red blood cells (RBCs). Such changes in vessel geometries can further influence the formation of a cell-free layer (CFL) close to the vessel walls. Biophysical cell properties, such as their deformability, which is impaired in various diseases, are often thought to impact blood flow and affect the distribution of flowing RBCs. This study investigates the flow behavior of healthy and artificially hardened RBCs in a bifurcating microfluidic T-junction. We determine the RBC distribution across the channel width at multiple positions before and after the bifurcation. Thus, we reveal distinct focusing profiles in the feeding mother channel for rigid and healthy RBCs that dramatically impact the cell organization in the successive daughter channels. Moreover, we experimentally show how the characteristic asymmetric CFLs in the daughter vessels develop along their flow direction. Complimentary numerical simulations indicate that the buildup of the CFL is faster for healthy than for rigid RBCs. Our results provide fundamental knowledge to understand the partitioning of rigid RBC as a model of cells with pathologically impaired deformability in complex in vitro networks.


Subject(s)
Erythrocytes , Microfluidics , Erythrocytes/physiology , Microcirculation/physiology , Erythrocyte Deformability
16.
J Phys Chem C Nanomater Interfaces ; 127(28): 13817-13836, 2023 Jul 20.
Article in English | MEDLINE | ID: mdl-37492192

ABSTRACT

A bold vision in nanofabrication is the assembly of functional molecular structures using a scanning probe microscope (SPM). This approach requires continuous monitoring of the molecular configuration during manipulation. Until now, this has been impossible because the SPM tip cannot simultaneously act as an actuator and an imaging probe. Here, we implement configuration monitoring using experimental data other than images collected during the manipulation process. We model the manipulation as a partially observable Markov decision process (POMDP) and approximate the actual configuration in real time using a particle filter. To achieve this, the models underlying the POMDP are precomputed and organized in the form of a finite-state automaton, allowing the use of complex atomistic simulations. We exemplify the configuration monitoring process and reveal structural motifs behind measured force gradients. The proposed methodology marks an important step toward the piece-by-piece creation of supramolecular structures in a robotic and possibly automated manner.

17.
Eur Phys J E Soft Matter ; 46(7): 54, 2023 Jul 15.
Article in English | MEDLINE | ID: mdl-37452888

ABSTRACT

We report a study on granular matter with and without small additions of silicon oil, under low-frequency and large amplitude oscillatory shear strain under constant normal pressure, by running experiments with a rotational rheometer with a cup-and-plate geometry. We analysed the expansion with the Chebyshev polynomials of the orthogonal decomposition of stress-strain Lissajous-Bowditch loops. We found the onset of the strain amplitude for the yielding regime indicated a regime change from filament-like structures of grains to grain rearrangements for the dry granulate and from oscillations to the breaking and regeneration of liquid bridges for wet granulates. We have shown that this viscoelastic dynamics can be characterized by a noise temperature following Sollich et al. (Phys Rev Lett https://doi.org/10.1103/PhysRevLett.78.2020 , 1997). The analysis of the first harmonics of the Chebyshev expansion showed that the state of disorder of dry and wet granular matter in pre-yielding and yielding regimes involved ensembles of different inherent states; thus, each of them was governed by a different noise temperature. The higher-order harmonics of the Chebyshev expansion revealed a proportionality between the viscous nonlinearity and the variation in the elastic nonlinearity induced by the deformation, which shows the coupling between the elastic deformation and the viscous flow of mesoscopic-scale structures.


Subject(s)
Powders , Temperature , Viscosity
18.
AAPS J ; 25(4): 60, 2023 06 15.
Article in English | MEDLINE | ID: mdl-37322223

ABSTRACT

Current regulatory guidelines on drug-food interactions recommend an early assessment of food effect to inform clinical dosing instructions, as well as a pivotal food effect study on the to-be-marketed formulation if different from that used in earlier trials. Study waivers are currently only granted for BCS class 1 drugs. Thus, repeated food effect studies are prevalent in clinical development, with the initial evaluation conducted as early as the first-in-human studies. Information on repeated food effect studies is not common in the public domain. The goal of the work presented in this manuscript from the Food Effect PBPK IQ Working Group was to compile a dataset on these studies across pharmaceutical companies and provide recommendations on their conduct. Based on 54 studies collected, we report that most of the repeat food effect studies do not result in meaningful differences in the assessment of the food effect. Seldom changes observed were more than twofold. There was no clear relationship between the change in food effect and the formulation change, indicating that in most cases, once a compound is formulated appropriately within a specific formulation technology, the food effect is primarily driven by inherent compound properties. Representative examples of PBPK models demonstrate that following appropriate validation of the model with the initial food effect study, the models can be applied to future formulations. We recommend that repeat food effect studies should be approached on a case-by-case basis taking into account the totality of the evidence including the use of PBPK modeling.


Subject(s)
Food-Drug Interactions , Models, Biological , Humans , Solubility , Computer Simulation , Food
19.
Cells ; 12(11)2023 06 01.
Article in English | MEDLINE | ID: mdl-37296651

ABSTRACT

Blood flow in the microcirculatory system is crucially affected by intrinsic red blood cell (RBC) properties, such as their deformability. In the smallest vessels of this network, RBCs adapt their shapes to the flow conditions. Although it is known that the age of RBCs modifies their physical properties, such as increased cytosol viscosity and altered viscoelastic membrane properties, the evolution of their shape-adapting abilities during senescence remains unclear. In this study, we investigated the effect of RBC properties on the microcapillary in vitro flow behavior and their characteristic shapes in microfluidic channels. For this, we fractioned RBCs from healthy donors according to their age. Moreover, the membranes of fresh RBCs were chemically rigidified using diamide to study the effect of isolated graded-membrane rigidity. Our results show that a fraction of stable, asymmetric, off-centered slipper-like cells at high velocities decreases with increasing age or diamide concentration. However, while old cells form an enhanced number of stable symmetric croissants at the channel centerline, this shape class is suppressed for purely rigidified cells with diamide. Our study provides further knowledge about the distinct effects of age-related changes of intrinsic cell properties on the single-cell flow behavior of RBCs in confined flows due to inter-cellular age-related cell heterogeneity.


Subject(s)
Diamide , Erythrocyte Deformability , Erythrocyte Deformability/physiology , Microcirculation , Diamide/pharmacology , Erythrocytes , Microfluidics
20.
Cancers (Basel) ; 15(9)2023 May 04.
Article in English | MEDLINE | ID: mdl-37174077

ABSTRACT

Lymphoceles (LC) occur in up to 60% after robot-assisted radical prostatectomy (RARP) and pelvic lymphadenectomy (PLND). In 2-10%, they are symptomatic and may cause complications and require treatment. Data on risk factors for the formation of lymphoceles after RARP and PNLD remain sparse in the urologic literature and are inconclusive to date. The underlying data of this secondary analysis were obtained from the prospective multi-center RCT ProLy. We performed a multivariate analysis to focus on the potential risk factors that may influence lymphocele formation. Patients with LC had a statistically significant higher BMI (27.8 vs. 26.3 kg/m2, p < 0.001; BMI ≥ 30 kg/m2: 31 vs. 17%, p = 0.002) and their surgical time was longer (180 vs. 160 min, p = 0.001) In multivariate analysis, the study group (control vs. peritoneal flap, p = 0.003), BMI (metric, p = 0.028), and surgical time (continuous, p = 0.007) were independent predictors. Patients with symptomatic lymphocele presented with higher BMI (29 vs. 26.6 kg/m2, p = 0.007; BMI ≥ 30 kg/m2: 39 vs. 20%, p = 0.023) and experienced higher intraoperative blood loss (200 vs. 150 mL, p = 0.032). In multivariate analysis, BMI ≥ 30 kg/m2 vs. < 30 kg/m2 was an independent predictor for the formation of a symptomatic lymphocele (p = 0.02). High BMI and prolonged surgical time are general risk factors for the development of LC. Patients with a BMI ≥ 30 kg/m2 had a higher risk for symptomatic lymphoceles.

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