Lifetime effects and cost-effectiveness of statin therapy for older people in the United Kingdom: a modelling study.

BACKGROUND: Cardiovascular disease (CVD) risk increases with age. Statins reduce cardiovascular risk but their effects are less certain at older ages. We assessed the long-term effects and cost-effectiveness of statin therapy for older people in the contemporary UK population using a recent meta-analysis of randomised evidence of statin effects in older people and a new validated CVD model. METHODS: The performance of the CVD microsimulation model, developed using the Cholesterol Treatment Trialists' Collaboration (CTTC) and UK Biobank cohort, was assessed among participants ≥70 years old at (re)surveys in UK Biobank and the Whitehall II studies. The model projected participants' cardiovascular risks, survival, quality-adjusted life years (QALYs) and healthcare costs (2021 UK£) with and without lifetime standard (35%-45% low-density lipoprotein cholesterol reduction) or higher intensity (≥45% reduction) statin therapy. CTTC individual participant data and other meta-analyses informed statins' effects on cardiovascular risks, incident diabetes, myopathy and rhabdomyolysis. Sensitivity of findings to smaller CVD risk reductions and to hypothetical further adverse effects with statins were assessed. RESULTS: In categories of men and women ≥70 years old without (15,019) and with (5,103) prior CVD, lifetime use of a standard statin increased QALYs by 0.24-0.70 and a higher intensity statin by a further 0.04-0.13 QALYs per person. Statin therapies were cost-effective with an incremental cost per QALY gained below £3502/QALY for standard and below £11778/QALY for higher intensity therapy and with high probability of being cost-effective. In sensitivity analyses, statins remained cost-effective although with larger uncertainty in cost-effectiveness among older people without prior CVD. CONCLUSIONS: Based on current evidence for the effects of statin therapy and modelling analysis, statin therapy improved health outcomes cost-effectively for men and women ≥70 years old.

In Silico Screening of Therapeutic Targets as a Tool to Optimize the Development of Drugs and Nutraceuticals in the Treatment of Diabetes mellitus: A Systematic Review.

The Target-Based Virtual Screening approach is widely employed in drug development, with docking or molecular dynamics techniques commonly utilized for this purpose. This systematic review (SR) aimed to identify in silico therapeutic targets for treating Diabetes mellitus (DM) and answer the question: What therapeutic targets have been used in in silico analyses for the treatment of DM? The SR was developed following the guidelines of the Preferred Reporting Items Checklist for Systematic Review and Meta-Analysis, in accordance with the protocol registered in PROSPERO (CRD42022353808). Studies that met the PECo strategy (Problem, Exposure, Context) were included using the following databases: Medline (PubMed), Web of Science, Scopus, Embase, ScienceDirect, and Virtual Health Library. A total of 20 articles were included, which not only identified therapeutic targets in silico but also conducted in vivo analyses to validate the obtained results. The therapeutic targets most frequently indicated in in silico studies were GLUT4, DPP-IV, and PPARγ. In conclusion, a diversity of targets for the treatment of DM was verified through both in silico and in vivo reassessment. This contributes to the discovery of potential new allies for the treatment of DM.

Peptides Evaluated In Silico, In Vitro, and In Vivo as Therapeutic Tools for Obesity: A Systematic Review.

Bioinformatics has emerged as a valuable tool for screening drugs and understanding their effects. This systematic review aimed to evaluate whether in silico studies using anti-obesity peptides targeting therapeutic pathways for obesity, when subsequently evaluated in vitro and in vivo, demonstrated effects consistent with those predicted in the computational analysis. The review was framed by the question: "What peptides or proteins have been used to treat obesity in in silico studies?" and structured according to the acronym PECo. The systematic review protocol was developed and registered in PROSPERO (CRD42022355540) in accordance with the PRISMA-P, and all stages of the review adhered to these guidelines. Studies were sourced from the following databases: PubMed, ScienceDirect, Scopus, Web of Science, Virtual Heath Library, and EMBASE. The search strategies resulted in 1015 articles, of which, based on the exclusion and inclusion criteria, 7 were included in this systematic review. The anti-obesity peptides identified originated from various sources including bovine alpha-lactalbumin from cocoa seed (Theobroma cacao L.), chia seed (Salvia hispanica L.), rice bran (Oryza sativa), sesame (Sesamum indicum L.), sea buckthorn seed flour (Hippophae rhamnoides), and adzuki beans (Vigna angularis). All articles underwent in vitro and in vivo reassessment and used molecular docking methodology in their in silico studies. Among the studies included in the review, 46.15% were classified as having an "uncertain risk of bias" in six of the thirteen criteria evaluated. The primary target investigated was pancreatic lipase (n = 5), with all peptides targeting this enzyme demonstrating inhibition, a finding supported both in vitro and in vivo. Additionally, other peptides were identified as PPARγ and PPARα agonists (n = 2). Notably, all peptides exhibited different mechanisms of action in lipid metabolism and adipogenesis. The findings of this systematic review underscore the effectiveness of computational simulation as a screening tool, providing crucial insights and guiding in vitro and in vivo investigations for the discovery of novel anti-obesity peptides.

Computational modelling of mouse atrio ventricular node action potential and automaticity.

The atrioventricular node (AVN) is a crucial component of the cardiac conduction system. Despite its pivotal role in regulating the transmission of electrical signals between atria and ventricles, a comprehensive understanding of the cellular electrophysiological mechanisms governing AVN function has remained elusive. This paper presents a detailed computational model of mouse AVN cell action potential (AP). Our model builds upon previous work and introduces several key refinements, including accurate representation of membrane currents and exchangers, calcium handling, cellular compartmentalization, dynamic update of intracellular ion concentrations, and calcium buffering. We recalibrated and validated the model against existing and unpublished experimental data. In control conditions, our model reproduces the AVN AP experimental features, (e.g. rate = 175 bpm, experimental range [121, 191] bpm). Notably, our study sheds light on the contribution of L-type calcium currents, through both Cav1.2 and Cav1.3 channels, in AVN cells. The model replicates several experimental observations, including the cessation of firing upon block of Cav1.3 or INa,r current. If block induces a reduction in beating rate of 11%. In summary, this work presents a comprehensive computational model of mouse AVN cell AP, offering a valuable tool for investigating pacemaking mechanisms and simulating the impact of ionic current blockades. By integrating calcium handling and refining formulation of ionic currents, our model advances understanding of this critical component of the cardiac conduction system, providing a platform for future developments in cardiac electrophysiology. KEY POINTS: This paper introduces a comprehensive computational model of mouse atrioventricular node (AVN) cell action potentials (APs). Our model is based on the electrophysiological data from isolated mouse AVN cells and exhibits an action potential and calcium transient that closely match the experimental records. By simulating the effects of blocking specific ionic currents, the model effectively predicts the roles of L-type Cav1.2 and Cav1.3 channels, T-type calcium channels, sodium currents (TTX-sensitive and TTX-resistant), and the funny current (If) in AVN pacemaking. The study also emphasizes the significance of other ionic currents, including IKr, Ito, IKur, in regulating AP characteristics and cycle length in AVN cells. The model faithfully reproduces the rate dependence of action potentials under pacing, opening the possibility of use in impulse propagation models. The population-of-models approach showed the robustness of this new AP model in simulating a wide spectrum of cellular pacemaking in AVN.

Defining biomechanical principles in pre-surgical infant orthopedics in a real cleft finite element model.

Presurgical infant orthopedics (PSIO) is the first step in the treatment of cleft lip and palate (CLP) and is designed to approximate the cleft segments as effectively as possible before surgical reconstruction of the lip and palate. The biomechanical efficacy of different PSIO approaches in transferring molding forces to the CLP is unknown. This study aimed to define the biomechanical principles of competing PSIO techniques in a real cleft finite element (FE) model. Active intraoral (Latham), passive alveolar molding (PAM), and extraoral (DynaCleft) molding forces were virtually applied to a real cleft FE model. In the cleft region, PAM (P < 0.001) and Latham (P < 0.05) exerted significantly less stress than DynaCleft. Intraoral molding forces acted primarily at the site of the force initiation without being accompanied by high loads in the midface. PAM showed a tendency toward a better flow behavior of the molding forces than Latham. Extraoral molding transferred high stresses to the cleft, alveolar ridge, and midface. Intraoral passive molding was ultimately characterized by the highest biomechanical efficacy and showed the most favorable load distribution of all of the PSIO approaches considered in this study. Future research is needed to validate the findings against clinical data.

Systematic review of subjective validation methods for computerized colonoscopy simulators.

Introduction: In recent years, different approaches have been used to conduct a subjective assessment of colonoscopy simulators. The purpose of this paper is to review these different approaches, specifically the ones used for computerized simulators, as the first step for the design of a standard validation procedure for this type of simulators. Methods: A systematic review was conducted by searching papers after 2010 in PubMed, Google Scholar, ScienceDirect, and IEEE Xplore databases. Papers were screened and reviewed for procedures regarding the subjective validation of computerized simulators for traditional colonoscopy with an endoscope. Results: An initial search in the databases identified 2094 papers, of which 7 remained after exhaustive review and application of exclusion criteria. All studies used questionnaires for subjective validation, with "face" being the most common validity type tested, while "content" validity and "usability" were less prominent. Conclusions: A classification of subscales for testing face validity was derived from the studies. The Colonoscopy Simulator Realism Questionnaire (CSRQ) was selected as the guide to follow for the development of future questionnaires related to subjective validation. Mislabeling of the validity tested in the studies due to ambiguous interpretations of the validity types was a common occurrence observed in the reviewed studies.

Computer simulation of low-power and long-duration bipolar radiofrequency ablation under various baseline impedances.

Compared to traditional unipolar radiofrequency ablation (RFA), bipolar RFA offers advantages such as more precise heat transfer and higher ablation efficiency. Clinically, myocardial baseline impedance (BI) is one of the important factors affecting the effectiveness of ablation. We aim at finding suitable ablation protocols and coping strategies by analyzing the ablation effects and myocardial impedance changes of bipolar RFA under different BIs. In this research, a three-dimensional local myocardial computer model was constructed for bipolar RFA simulation, and in vitro experimental data were used to validate accuracy. Four fixed low-power levels (20 W, 25 W, 30 W, and 35 W) and six myocardial BIs (91.02 Ω, 99.83 Ω, 111.03 Ω, 119.77 Ω, 130.03 Ω, and 135.45 Ω) were set as initial conditions, with an ablation duration of 120-s. In the context of low-power and long-duration (LPLD) ablation, the maximum TID (TIDM) decreased by 21-32 Ω, depending on the BI. In cases where steam pop did not occur, TIDM increased with the increase in power. For the same power, there was no significant difference in TIDM for the range of BIs. In cases where steam pop occurred, for every 1 Ω increase in BI, TIDM increased by 0.34-0.41 Ω. The simulation results also showed that using a higher power resulted in a smaller decrease in TIDM. This study provided appropriate ablation times and impedance decrease ranges for bipolar LPLD RFA. The combination of 25 W for 120-s offered optimal performance when considering effectiveness and safety simultaneously.

Modelling patient trajectories in emergency department simulations using retrospective patient cohorts.

Computer simulations of emergency departments (EDs) are tools that can support managing and optimising ED operations. A core component of ED simulation models is patient trajectories, defined as the series of activities patients undergo in the ED from arrival to discharge. The combined duration of these activities, and waiting times between them, determines a patient's length of stay (LOS). Patient trajectories are often calibrated and validated solely based on the estimated acuity of patients assigned upon arrival. However, acuity is a prospective patient indicator that inconsistently reflects patients' actual urgency and resource usage as seen retrospectively upon discharge. Here, we propose a data-driven ED simulation model in which patient trajectories are modelled based on both acuity and retrospective patient indicators. We show that including retrospective patient indicators recovers the observed LOS distributions more accurately than when using acuity alone. We also demonstrate how the use of retrospective patient indicators leads to more plausible estimates of the impact of increased stress in the ED on patients' LOS. Our work exemplifies how we can better utilise ED data to make the development and evaluation of ED simulation models more accurate and robust, enabling them to provide more reliable and useful operational insights.

Computer Modelling Study of Volume Kinetics in Intraocular Segments Following Airbag Impact Using Finite Element Analysis.

Background: We have previously studied the physiological and mechanical responses of the eye to blunt trauma in various situations using finite element analysis (FEA). In this study, we evaluated the volume kinetics of an airbag impact on the eye using FEA to sequentially determine the volume change rates of intraocular segments at various airbag deployment velocities. Methods: The human eye model we created was used in simulations with the FEA program PAM-GENERISTM (Nihon ESI, Tokyo, Japan). Different airbag deployment velocities, 30, 40, 50, 60 and 70 m/s, were applied in the forward direction. The volume of the deformed eye impacted by the airbag was calculated as the integrated value of all meshes in each segment, and the decrease rate was calculated as the ratio of the decreased volume of each segment at particular timepoints to the value before the airbag impact. Results: The minimum volume of the anterior chamber was 63%, 69% and 50% at 50, 60 and 70 m/s airbag impact velocity, respectively, showing a curve with a sharp decline followed by gradual recovery. In contrast to the anterior chamber, the volume of the lens recovered promptly, reaching 80-90% at the end of observation, except for the case of 60 m/s. Following the decrease, the volume increased to more than that of baseline at 60 m/s. The rate of volume change of the vitreous was distributed in a narrow range, 99.2-100.4%. Conclusion: In this study, we found a large, prolonged decrease of volume in the anterior chamber, a similar large decrease followed by prompt recovery of volume in the lens, and a time-lag in the volume decrease between these tissues. These novel findings may provide an important insight into the pathophysiological mechanism of airbag ocular injuries through this further evaluation, employing a refined FEA model representing cuboidal deformation, to develop a more safe airbag system.

Computer simulation help predict the frame deformation following a Venus-A transcatheter aortic valve implantation in patients with pure aortic regurgitation: a retrospective study.

Background: Patient-specific computer simulation of transcatheter aortic valve implantation (TAVI) predicts the interaction between an implanted device and the surrounding anatomy. In this study, we validated the predictive value of computer simulation for the frame deformation following a Venus-A TAVI implant in patients with pure aortic regurgitation (AR). Furthermore, we used the validated computational model to evaluate the anchoring mechanism within the same cohort. Methods: This was a retrospective study. FEops HEARTguide technology was used to simulate the virtual implantation of a Venus-A valve model in a patient-specific geometry. The predicted frame deformation was quantitatively compared to the postoperative device deformation at multiple levels. The outward forces acting on the frame were extracted for each patient and the total outward force acting around the aortic annular (AA) and sinotubular junction (STJ) planes were recorded. Results: Thirty patients were enrolled in the study with 10 in the migration group and 20 in the non-migration group. The dimensions of the simulated and observed frames had good correlations at Dmax (R2=0.88), Dmin (R2=0.91), perimeter (R2=0.92), and area (R2=0.92). The predicted outward force acting on the frame at the AA level was comparable between the migration and no-migration groups. The predicted outward force acting on the frame at the STJ level was always significantly higher in the migration group than the no migration group at different bandwidths: 3 mm (P=0.002), 5 mm (P=0.005), 10 mm (P=0.002). Conclusions: Patient-specific computer simulation of TAVI accurately predicted frame deformation in Chinese patients with pure AR. The forces at the STJ facilitated stabilization of the device within the aortic root, which might be used as a discriminator to identify patients at risk of device migration prior to intervention.

Dynamic VAD simulations: Performing accurate simulations of ventricular assist devices in interaction with the cardiovascular system.

Medical advancements, particularly in ventricular assist devices (VADs), have notably advanced heart failure (HF) treatment, improving patient outcomes. However, challenges such as adverse events (strokes, bleeding and thrombosis) persist. Computational fluid dynamics (CFD) simulations are instrumental in understanding VAD flow dynamics and the associated flow-induced adverse events resulting from non-physiological flow conditions in the VAD.This study aims to validate critical CFD simulation parameters for accurate VAD simulations interacting with the cardiovascular system, building upon the groundwork laid by Hahne et al. A bidirectional coupling technique was used to model dynamic (pulsatile) flow conditions of the VAD CFD interacting with the cardiovascular system. Mesh size, time steps and simulation method (URANS, LES) were systematically varied to evaluate their impact on the dynamic pump performance (dynamic H-Q curve) of the HeartMate 3, aiming to find the optimal simulation configuration for accurately reproduce the dynamic H-Q curve. The new Overlapping Ratio (OR) method was developed and applied to quantify dynamic H-Q curves.In particular, mesh and time step sizes were found to have the greatest influence on the calculated pump performance. Therefore, small time steps and large mesh sizes are recommended to obtain accurate dynamic H-Q curves. On the other hand, the influence of the simulation method was not significant in this study. This study contributes to advancing VAD simulations, ultimately enhancing clinical efficacy and patient outcomes.

Digital twin and artificial intelligence technologies for predictive planning of endovascular procedures.

Current planning of aortic and peripheral endovascular procedures is based largely on manual measurements performed from the 3-dimensional reconstruction of preoperative computed tomography scans. Assessment of device behavior inside patient anatomy is often difficult, and available tools, such as 3-dimensional-printed models, have several limitations. Digital twin (DT) technology has been used successfully in automotive and aerospace industries and applied recently to endovascular aortic aneurysm repair. Artificial intelligence allows the treatment of large amounts of data, and its use in medicine is increasing rapidly. The aim of this review was to present the current status of DTs combined with artificial intelligence for planning endovascular procedures. Patient-specific DTs of the aorta are generated from preoperative computed tomography and integrate aorta mechanical properties using finite element analysis. The same methodology is used to generate 3-dimensional models of aortic stent-grafts and simulate their deployment. Post processing of DT models is then performed to generate multiple parameters related to stent-graft oversizing and apposition. Machine learning algorithms allow parameters to be computed into a synthetic index to predict Type 1A endoleak risk. Other planning and sizing applications include custom-made fenestrated and branched stent-grafts for complex aneurysms. DT technology is also being investigated for planning peripheral endovascular procedures, such as carotid artery stenting. DT provides detailed information on endovascular device behavior. Analysis of DT-derived parameters with machine learning algorithms may improve accuracy in predicting complications, such as Type 1A endoleaks.

Optimizing Medical Care during a Nerve Agent Mass Casualty Incident Using Computer Simulation.

INTRODUCTION: Chemical mass casualty incidents (MCIs) pose a substantial threat to public health and safety, with the capacity to overwhelm healthcare infrastructure and create societal disorder. Computer simulation systems are becoming an established mechanism to validate these plans due to their versatility, cost-effectiveness and lower susceptibility to ethical problems. METHODS: We created a computer simulation model of an urban subway sarin attack analogous to the 1995 Tokyo sarin incident. We created and combined evacuation, dispersion and victim models with the SIMEDIS computer simulator. We analyzed the effect of several possible approaches such as evacuation policy ('Scoop and Run' vs. 'Stay and Play'), three strategies (on-site decontamination and stabilization, off-site decontamination and stabilization, and on-site stabilization with off-site decontamination), preliminary triage, victim distribution methods, transport supervision skill level, and the effect of search and rescue capacity. RESULTS: Only evacuation policy, strategy and preliminary triage show significant effects on mortality. The total average mortality ranges from 14.7 deaths in the combination of off-site decontamination and Scoop and Run policy with pretriage, to 24 in the combination of onsite decontamination with the Stay and Play and no pretriage. CONCLUSION: Our findings suggest that in a simulated urban chemical MCI, a Stay and Play approach with on-site decontamination will lead to worse outcomes than a Scoop and Run approach with hospital-based decontamination. Quick transport of victims in combination with on-site antidote administration has the potential to save the most lives, due to faster hospital arrival for definitive care.

Error in jump height estimation using the flight time method: simulation of the effect of ankle position between takeoff and landing.

During vertical jump evaluations in which jump height is estimated from flight time (FT), the jumper must maintain the same body posture between vertical takeoff and landing. As maintaining identical posture is rare during takeoff and landing between different jump attempts and in different individuals, we simulated the effect of changes in ankle position from takeoff to landing in vertical jumping to determine the range of errors that might occur in real-life scenarios. Our simulations account for changes in center of mass position during takeoff and landing, changes in ankle position, different subject statures (1.44-1.98 m), and poor to above-average jump heights. Our results show that using FT to estimate jump height without controlling for ankle position (allowing dorsiflexion) during the landing phase of the vertical jump can overestimate jump height by 18% in individuals of average stature and performing an average 30 cm jump or may overestimate by ≤60% for tall individuals performing a poor 10 cm jump, which is common for individuals jumping with added load. Nevertheless, as assessing jump heights based on FT is common practice, we offer a correction equation that can be used to reduce error, improving jump height measurement validity using the FT method allowing between-subject fair comparisons.

Modelling insertion behaviour of PVP (Polyvinylpyrrolidone) and PVA (Polyvinyl Alcohol) microneedles.

A comprehensive investigation into the effects of nonlinear material behaviour of polymeric (MN) and skin on the dynamics of the MN insertion in skin was undertaken in this study using experiments and numerical simulations. The nonlinearity of the material behaviour was incorporated by employing the Ramberg-Osgood and neo-Hookean equations for stress-strain relationships for the MN materials and skin, respectively. For this purpose, a characteristic type of dissolving MN array was selected. This type of MN is made by a combination of poly(vinyl alcohol) and poly(vinyl pyrrolidone). The numerical simulations were validated using experimental investigations where the MNs were fabricated using laser-engineered silicone micromould templates technology. Young's modulus, Poisson's ratio, and compression breaking force for the MN polymers were determined using a texture analyser. The alignment between experimental findings and simulation data underscores the accuracy of the parameters determined through mechanical testing and mathematical calculations for both MN materials (PVP/PVA) and skin behaviour during the MN insertion. This study has demonstrated a strong alignment between the experimental findings and computational simulations, confirming the accuracy of the established parameters for MNs and skin interactions for modelling MN insertion behaviour in skin, providing a solid foundation for future research in this area.

Predictive pharmacodynamic performance of the Eleveld pharmacokinetic-pharmacodynamic model for propofol: comparison of predicted and measured bispectral index.

BACKGROUND: The Eleveld pharmacokinetic-pharmacodynamic model for propofol predicts bispectral index (BIS) processed electroencephalogram values from estimated effect-site concentrations. We investigated agreement between measured and predicted BIS values during total intravenous anaesthesia (TIVA). METHODS: Forty participants undergoing lower limb surgery received TIVA using remifentanil target-controlled infusions and propofol by manually controlled, target-guided infusions based upon the Eleveld model and directed by two pharmacokinetic computer simulation applications: PKPD Tools and StelSim. We evaluated the predictive performance of the Eleveld model by calculating median prediction errors (BIS units) and by Bland-Altman analyses. We also performed |Bland-Altman analysis of supplementary data provided by the authors of the Eleveld model. RESULTS: Whereas median prediction errors were small (MDPE -1.9, MDAPE 10), the ranges were wide (-18.5 to 24.3 and 1.7 to 24.3). The proportion of MDAPE >10 BIS units was 47.8%. Bland-Altman analysis showed a small mean bias (-0.52 BIS units) with wide limits of agreement (-27.7 to 26.2). Each participant's limits of agreement did not meet the requirements for declaring interchangeability between the two measurements. The measurement differences depended on the BIS values, as indicated by the positive slopes of the differences vs BIS values. Bland-Altman analysis of the Eleveld model supplementary data revealed similar results. CONCLUSION: BIS predictions by the Eleveld model should be interpreted with caution. In spite of the acceptable MDPE and MDAPE, there are unacceptable degrees of both within-subject and between-subject variation during propofol target-controlled infusions. This limits the use of adjusting targeted concentrations to achieve desired simulated BIS values with confidence.

Parasites and the ecology of fear: Nonconsumptive effects of ectoparasites on larvae reduce growth in simulated Drosophila populations.

Predators negatively affect prey outside of direct attack, and these nonconsumptive effects (NCEs) may cause over half the impacts of predators on prey populations. This "ecology of fear" framework has been extended to host-parasite interactions. The NCEs of parasites are thought to be small relative to those of predators. However, recent research shows ectoparasites exert NCEs on multiple life stages of Drosophila. In this study, we apply recent data to a matrix-based model of fly populations experiencing infection/consumption and NCEs from an ectoparasitic mite. We found the NCEs of parasites on larvae, which are not actively parasitized, decreased the size of simulated host populations. By contrast, the NCEs on adult flies increased population size through compensatory egg production. The negative NCEs on larvae outweighed the positive effects on adults to reduce population size. This study suggests that parasitic NCEs can suppress host populations independent of infection.

In silico attempt to reveal the link between cancer development and combined exposure to the maize herbicides: Glyphosate, nicosulfuron, S-metolachlor and terbuthylazine.

Pesticides are crucial for crop protection and have seen a 50 % increase in use in the last decade. Besides preventing significant crop losses their use has raised health concerns due to consumer exposure through residues in food and water. The toxicity data from individual components is often used to assess overall mixture toxicity, but uncertainty persists in understanding the behaviors of individual chemicals within these mixtures. Assessing the risk of pesticide mixture exposure remains challenging, potentially leading to overestimation or underestimation of toxicity. This study aims to establish a possible link between exposure to a herbicide mixture and genotoxic effects, focusing on cancer development. Our analysis was focused on four herbicides glyphosate, nicosulfuron, S-metolachlor and terbuthylazine. To determine the link between genes associated with cancer development due to exposure to herbicide mixture, a CTD database tools were used. Through the ToppFun tool molecular function and biological process associated with genes common to the disease of interest and selected herbicides were evaluated. And finally, GeneMANIA was used in order to analyze the function and interaction between common genes of herbicide mixture. Among the 7 common genes for herbicide mixture and cancer development coexpression characteristics were dominant at 65.41 %, 22.14 % of annotated genes shared the same pathway and 7.88 % showed co-localization. Among six target genes involved in genetic disease development co-expression was dominant at 87.34 %, colocalization at 8.03 % and shared protein domains at 4.52 %. Comprehensive molecular analyses, encompassing genomics, proteomics, and pathway analysis, are essential to unravel the specific mechanisms involved in the context of the studied mixture and its potential carcinogenic effects.

Haemodynamic study of left nonthrombotic iliac vein lesions: a preliminary report.

Nonthrombotic iliac vein lesions (NIVLs) are significant causes of chronic venous insufficiency (CVI) in the left lower limb and symptom recurrence following left lower limb varicose vein treatment. The goal of this study was to explore the haemodynamic and morphological characteristics of iliac veins in patients with NIVLs. Pressure at the caudal end of the stenotic left common iliac vein (LCIV) segment, local blood flow velocity, and time-averaged wall shear stress in the stenotic segment exhibited positive correlations with the clinical CVI classification (R = 0.92, p < 0.001; R = 0.94, p < 0.001; R = 0.87, p < 0.001), while the relative retention time showed a negative correlation (R = -0.94, p < 0.001). The pressure difference (∆P) between the two ends of the stenotic segment and the velocity difference (∆V) between the stenotic segment and the caudal end were positively correlated with the clinical classification (R = 0.92, p < 0.001; R = 0.9, p < 0.001). The cross-sectional area stenosis rate and length of the stenotic LCIV segment were positively correlated with the clinical classification (R = 0.93, p < 0.001; R = 0.63, p < 0.001). The results suggest that haemodynamic assessment of the iliac vein could effectively portray blood flow disturbances in stenotic segments of the LCIV, potentially reflecting the degree of iliac vein stenosis. Haemodynamic indicators are correlated with the severity of clinical CVI symptoms.

Evaluating hydrogen ion mobilization during hemodialysis using only predialysis and postdialysis blood bicarbonate concentrations.

INTRODUCTION: The hydrogen ion (H+) mobilization model has been previously shown to provide a quantitative description of intradialytic changes in blood bicarbonate (HCO3) concentration during hemodialysis (HD). The current study evaluated the accuracy of different methods for estimating the H+ mobilization parameter (Hm) from this model. METHODS: The study compared estimates of the H+ mobilization parameter using predialysis, hourly during the HD treatment, and postdialysis blood HCO3 concentrations (Hm-full2) with those determined using only predialysis and postdialysis blood HCO3 concentrations assuming steady state conditions (Hm-SS2) during the midweek treatment in 24 chronic HD patients treated thrice weekly. RESULTS: Estimated Hm-full2 values (0.163 ± 0.079 L/min [mean ± standard deviation]) were higher than, but not statistically different (p = 0.067) from, those of Hm-SS2 (0.152 ± 0.065 L/min); the values of Hm-full2 and Hm-SS2 were highly correlated with a correlation coefficient of 0.948 and a mean difference that was small (0.011 L/min). Further, the H+ mobilization parameter values calculated using only predialysis and postdialysis blood HCO3 concentrations during the first and third HD treatments of the week were not different from those calculated during the midweek treatment. CONCLUSIONS: The H+ mobilization model can be used to provide estimates of the H+ mobilization parameter without the need to measure hourly intradialytic blood HCO3 concentrations.