Digital setup accuracy for moderate crowding correction with fixed orthodontic appliances: a prospective study.

OBJECTIVES: To evaluate the accuracy of a semi-automatic 3D digital setup process in predicting the orthodontic treatment outcome achieved by labial fixed appliances. SUBJECTS AND METHODS: Twenty-five adult patients (18 to 24 years old) with class I malocclusion and moderate crowding were prospectively enrolled and received treatment on both jaws through the straight-wire technique. Prior to treatment commencement, a semi-automatic digital setup simulating the predicted treatment outcome was performed for each patient through Orthoanalyzer software (3Shape®, Copenhagen, Denmark) to obtain the prediction model. This was compared to the final outcome model through 3D superimposition methods. Metric variables and inspection of color-coded distance maps were used to detect how accurately the digital setup predicts the actual treatment outcome. RESULTS: The mean absolute distances (MAD) between the superimposed dental arches of the predicted and the final models were: 0.77 ± 0.13 mm following superimposition on the palate, 0.52 ± 0.06 mm following superimposition on the maxillary dental arch, and 0.55 ± 0.15 mm following superimposition on the mandibular dental arch. The MAD at the palatal reference area was 0.09 ± 0.04 mm. Visualization of color-coded distance maps indicated that the digital setup accurately predicted the final teeth position in a few cases. Almost half of the cases had posteriorly wider upper and lower dental arches and palatally/lingually positioned or inclined anterior teeth, whereas the rest still showed errors within 2-3 mm, distributed over the entire dental arches with no distinct pattern. CONCLUSIONS: The accuracy of semi-automatic prediction of the labial fixed appliance treatment outcome in Class I cases with moderate crowding is not yet sufficient. While average measures showed deviations less than 1 mm, examination of individual color-coded distance maps revealed significant disparities between the simulated and the actual results.

[Comprehensive literature review on the application of the otological-surgical planning software OTOPLAN® for cochlear implantation. German version]. / Umfassender Literaturüberblick über die Anwendung der otologisch-chirurgischen Planungssoftware OTOPLAN® bei der Cochleaimplantation.

BACKGROUND: The size of the human cochlear, measured by the diameter of the basal turn, varies between 7 and 11 mm. For hearing rehabilitation with cochlear implants (CI), the size of the cochlear influences the individual frequency map and the choice of electrode length. OTOPLAN® (CAScination AG [Bern, Switzerland] in cooperation with MED-EL [Innsbruck, Austria]) is a software tool with CE marking for clinical applications in CI treatment which allows for precise pre-planning based on cochlear size. This literature review aims to analyze all published data on the application of OTOPLAN®. MATERIALS AND METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were applied to identify relevant studies published in the PubMed search engine between January 2015 and February 2023 using the search terms "otoplan" [title/abstract] OR "anatomy-based fitting" [title/abstract] OR "otological software tool" [title/abstract] OR "computed tomography-based software AND cochlear" [title/abstract]. RESULTS: The systematic review of the literature identified 32 studies on clinical use of OTOPLAN® in CI treatment. Most studies were reported from Germany (7 out of 32), followed by Italy (5), Saudi Arabia (4), the USA (4), and Belgium (3); 2 studies each were from Austria and China, and 1 study from France, India, Norway, South Korea, and Switzerland. In the majority of studies (22), OTOPLAN® was used to assess cochlear size, followed by visualizing the electrode position using postoperative images (5), three-dimensional segmentation of temporal bone structures (4), planning the electrode insertion trajectory (3), creating a patient-specific frequency map (3), planning of a safe drilling path through the facial recess (3), and measuring of temporal bone structures (1). CONCLUSION: To date, OTOPLAN® is the only DICOM viewer with CE marking in the CI field that can process pre-, intra-, and postoperative images in the abovementioned applications.

Validation of upper thermal thresholds for outdoor sports using thermal physiology modelling.

Thermal safety guidelines with upper thresholds aim to protect athletes' health, yet evidence-based sport-specific thresholds remain unestablished. Experimenting with athletes in severely hot conditions raises ethical concerns, so we used a thermo-physiological model to validate the thresholds of guidelines for outdoor sports. First, the reproducibility of the joint system thermoregulation model (JOS-3) of core temperature has been validated for 18 sports experiments (n = 213) and 11 general exercise experiments (n = 121) using the Bland - Altman analysis. Then, core temperatures were predicted using the JOS-3 in conditions corresponding to the upper thresholds, and if the 90th-99.7th percentile core temperature value (corresponding to 0.3%-10% of the participants) exceeded 40°C, the thresholds were judged as potentially hazardous. Finally, we proposed revisions for sports with potentially hazardous thresholds. As a result, the JOS-3 could simulate core temperature increases in most experiments (27/29) for six sports and general exercises with an accuracy of 0.5°C. The current upper thresholds for marathons, triathlons, and football are potentially hazardous. Suggested revisions, based on specified percentiles, include: Football: revise from wet bulb globe temperature (WBGT) 32°C to 29-31°C or not revise. Marathon: revise from WBGT 28°C to 24-27°C. Triathlon: revise from WBGT 32.2°C to 23-26°C. If conducting sports events under the revised upper thresholds proves difficult, taking measures for a possible high incidence of heat illness becomes crucial, such as placing additional medical resources, assisting heat acclimatization and cooling strategies for participants, and rule changes such as shorter match times and increased breaks.

Numerical study on the three-dimensional temperature distribution according to laser conditions in photothermal therapy of peri-implantitis.

PURPOSE: Dental implants have been successfully implemented as a treatment for tooth loss. However, peri-implantitis, an inflammatory reaction owing to microbial deposition around the implant, can lead to implant failure. So, it is necessary to treat peri-implantitis. Therefore, this numerical study is aimed at investigating conditions for treating peri-implantitis. METHODS: Photothermal therapy, a laser treatment method, utilizes photothermal effect, in which light is converted to heat. This technique has advantage of selectively curing inflamed tissues by increasing their temperature. Accordingly, herein, photothermal effect on peri-implantitis is studied through numerical analysis with using Arrhenius damage integral and Arrhenius thermal damage ratio. RESULTS: Through numerical analysis on peri-implantitis treatment, we explored temperature changes under varied laser settings (laser power, radius, irradiation time). We obtained the temperature distribution on interface of artificial tooth root and inflammation and determined whether temperature exceeds or does not exceed 47℃ to know which laser power affects alveolar bone indirectly. We defined the Arrhenius thermal damage ratio as a variable and determined that the maximum laser power that does not exceed 47℃ at the AA' line is 1.0 W. Additionally, we found that the value of the Arrhenius thermal damage ratio is 0.26 for a laser irradiation time of 100 s and 0.50 for 500 s. CONCLUSION: The result of this numerical study indicates that the Arrhenius thermal damage ratio can be used as a standard for determining the treatment conditions to help assisted laser treatment for peri-implantitis in each numerical analysis scenario.

Preventing Prolonged Times to Awakening While Mitigating the Risk of Patient Awareness: Gas Man Computer Simulations of Sevoflurane Consumption From Brief, High Fresh Gas Flow Before the End of Surgery.

Prolonged times to tracheal extubation are associated with adverse patient and economic outcomes. We simulated awakening patients from sevoflurane after long-duration surgery at 2% end-tidal concentration, 1.0 minimum alveolar concentration (MAC) in a 40-year-old. Our end-of-surgery target was 0.5 MAC, the Michigan Awareness Control Study's threshold for intraoperative alerts. Consider an anesthetist who uses a 1 liter/minute gas flow until surgery ends. During surgical closure, the inspired sevoflurane concentration is reduced from 2.05% to 0.62% (i.e., MAC-awake). The estimated time to reach 0.5 MAC is 28 minutes. From a previous study, 28 minutes exceeded ≥95% of surgical closure times for all 244 distinct surgical procedures (N=23,343 cases). Alternatively, the anesthetist uses 8 liters/minute gas flow with the vaporizer at MAC-awake for 1.8 minutes, which reduces the end-tidal concentration to 0.5 MAC. The anesthetist then increases the vaporizer to keep end-tidal 0.5 MAC until the surgery ends. An additional simulation shows that, compared with simulated end-tidal agent feedback control, this approach consumed 0.45 mL extra agent. Simulation results are the same for an 80-year-old patient. The extra 0.45 mL has a global warming potential comparable to driving 26 seconds at 40 kilometers (25 miles) per hour, comparable to route modification to avoid potential roadway hazards.

Neural network emulation of the human ventricular cardiomyocyte action potential for more efficient computations in pharmacological studies.

Computer models of the human ventricular cardiomyocyte action potential (AP) have reached a level of detail and maturity that has led to an increasing number of applications in the pharmaceutical sector. However, interfacing the models with experimental data can become a significant computational burden. To mitigate the computational burden, the present study introduces a neural network (NN) that emulates the AP for given maximum conductances of selected ion channels, pumps, and exchangers. Its applicability in pharmacological studies was tested on synthetic and experimental data. The NN emulator potentially enables massive speed-ups compared to regular simulations and the forward problem (find drugged AP for pharmacological parameters defined as scaling factors of control maximum conductances) on synthetic data could be solved with average root-mean-square errors (RMSE) of 0.47 mV in normal APs and of 14.5 mV in abnormal APs exhibiting early afterdepolarizations (72.5% of the emulated APs were alining with the abnormality, and the substantial majority of the remaining APs demonstrated pronounced proximity). This demonstrates not only very fast and mostly very accurate AP emulations but also the capability of accounting for discontinuities, a major advantage over existing emulation strategies. Furthermore, the inverse problem (find pharmacological parameters for control and drugged APs through optimization) on synthetic data could be solved with high accuracy shown by a maximum RMSE of 0.22 in the estimated pharmacological parameters. However, notable mismatches were observed between pharmacological parameters estimated from experimental data and distributions obtained from the Comprehensive in vitro Proarrhythmia Assay initiative. This reveals larger inaccuracies which can be attributed particularly to the fact that small tissue preparations were studied while the emulator was trained on single cardiomyocyte data. Overall, our study highlights the potential of NN emulators as powerful tool for an increased efficiency in future quantitative systems pharmacology studies.

Personalized digital simulation­assisted acetabular component implantation in revision hip arthroplasty.

The number of artificial total hip revision arthroplasties is increasing yearly in China, and >50% of these cases have acetabular defects. Accurately locating and quantifying the bone defect is one of the current challenges of this surgery. Thus, the objective of the present study was to simulate acetabular implantation with the aid of Mimics 17.0 software (Materialise NV) in patients with loosened acetabular prosthesis, to evaluate the 'ideal acetabular center' and the 'actual acetabular center' to guide the choice of prosthesis and surgical method. From January 2017 to June 2021, the present study included 10 hips from 10 patients [seven men (seven hips) and three women (three hips)]. In all patients, the Mimics software was applied to simulate the dislocation of the femoral prosthesis and acetabular prosthesis implantation before surgery; calculate the height difference between the 'ideal acetabular center' and the 'actual acetabular center' to assess the bone defect; confirm the size of the acetabular prosthesis, abduction angle, anteversion angle and bone coverage of the acetabular cup; and measure the intraoperative bleeding and postoperative follow-up Harris score of the hip joint. After statistical analysis, the present study revealed that digital simulation assistance could improve the accuracy of hip revision acetabular prosthesis implantation, reduce postoperative shortening of the affected limb, especially for surgeons with relatively little experience in hip revision surgery, and greatly reduce the occurrence of complications such as hip dislocation because of poor postoperative prosthesis position.

Computer-assisted navigation in oral and maxillofacial surgery: A systematic review.

Background: The term "navigation" describes a device that can pinpoint critical anatomical features, the most direct path to the target, and the optimal surgical orientation. This study aimed to conduct a comprehensive literature search on computer-assisted navigation for use in oral and maxillofacial surgery. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, relevant studies were retrieved from five electronic databases: Medline, Web of Science, PubMed, Google Scholar, and Saudi Digital Library (SDL). The central question was, "Does the computer-assisted navigation system improve the outcome of surgical procedures in the oral and maxillofacial region?" The Cochrane Risk of Bias 2 was used to determine the various types of bias. Results: Post-traumatic midfacial reconstruction is one of the many fields that have benefited from the use of computer-assisted navigation because of its reliability. It can also be used to extricate difficult foreign entities from the operative zone. Locating critical anatomical components, communicating the surgical plan to the patient, and verifying surgical success can improve the function and appearance of patients with dentofacial abnormalities. In addition, it decreases the surgical error margin and duration. Conclusion: Computer-assisted navigation is promising in surgical practice. The accuracy of surgery can be significantly enhanced by first planning the process in a virtual environment and then performing it under close supervision in real time. In addition, the time required for preoperative planning and surgery can be reduced by creating and improving software programs.

The influence of aortic stiffness on carotid stiffness: computational simulations using a human aorta carotid model.

Increased aortic and carotid stiffness are independent predictors of adverse cardiovascular events. Arterial stiffness is not uniform across the arterial tree and its accurate assessment is challenging. The complex interactions and influence of aortic stiffness on carotid stiffness have not been investigated. The aim of this study was to evaluate the effect of aortic stiffness on carotid stiffness under physiological pressure conditions. A realistic patient-specific geometry was used based on magnetic resonance images obtained from the OsiriX library. The luminal aortic-carotid model was reconstructed from magnetic resonance images using 3D Slicer. A series of aortic stiffness simulations were performed at different regional aortic areas (levels). By applying variable Young's modulus to the aortic wall under two pulse pressure conditions, one could examine the deformation, compliance and von Mises stress between the aorta and carotid arteries. An increase of Young's modulus in an aortic area resulted in a notable difference in the mechanical properties of the aortic tree. Regional deformation, compliance and von Mises stress changes across the aorta and carotid arteries were noted with an increase of the aortic Young's modulus. Our results indicate that increased carotid stiffness may be associated with increased aortic stiffness. Large-scale clinical validation is warranted to examine the influence of aortic stiffness on carotid stiffness.

Can computer simulation support strategic service planning? Modelling a large integrated mental health system on recovery from COVID-19.

BACKGROUND: COVID-19 has had a significant impact on people's mental health and mental health services. During the first year of the pandemic, existing demand was not fully met while new demand was generated, resulting in large numbers of people requiring support. To support mental health services to recover without being overwhelmed, it was important to know where services will experience increased pressure, and what strategies could be implemented to mitigate this. METHODS: We implemented a computer simulation model of patient flow through an integrated mental health service in Southwest England covering General Practice (GP), community-based 'talking therapies' (IAPT), acute hospital care, and specialist care settings. The model was calibrated on data from 1 April 2019 to 1 April 2021. Model parameters included patient demand, service-level length of stay, and probabilities of transitioning to other care settings. We used the model to compare 'do nothing' (baseline) scenarios to 'what if' (mitigation) scenarios, including increasing capacity and reducing length of stay, for two future demand trajectories from 1 April 2021 onwards. RESULTS: The results from the simulation model suggest that, without mitigation, the impact of COVID-19 will be an increase in pressure on GP and specialist community based services by 50% and 50-100% respectively. Simulating the impact of possible mitigation strategies, results show that increasing capacity in lower-acuity services, such as GP, causes a shift in demand to other parts of the mental health system while decreasing length of stay in higher acuity services is insufficient to mitigate the impact of increased demand. CONCLUSION: In capturing the interrelation of patient flow related dynamics between various mental health care settings, we demonstrate the value of computer simulation for assessing the impact of interventions on system flow.

Optimized signal of calcifications in wide-angle digital breast tomosynthesis: a virtual imaging trial.

OBJECTIVES: Evaluate microcalcification detectability in digital breast tomosynthesis (DBT) and synthetic 2D mammography (SM) for different acquisition setups using a virtual imaging trial (VIT) approach. MATERIALS AND METHODS: Medio-lateral oblique (MLO) DBT acquisitions on eight patients were performed at twice the automatic exposure controlled (AEC) dose. The noise was added to the projections to simulate a given dose trajectory. Virtual microcalcification models were added to a given projection set using an in-house VIT framework. Three setups were evaluated: (1) standard acquisition with 25 projections at AEC dose, (2) 25 projections with a convex dose distribution, and (3) sparse setup with 13 projections, every second one over the angular range. The total scan dose and angular range remained constant. DBT volume reconstruction and synthetic mammography image generation were performed using a Siemens prototype algorithm. Lesion detectability was assessed through a Jackknife-alternative free-response receiver operating characteristic (JAFROC) study with six observers. RESULTS: For DBT, the area under the curve (AUC) was 0.97 ± 0.01 for the standard, 0.95 ± 0.02 for the convex, and 0.89 ± 0.03 for the sparse setup. There was no significant difference between standard and convex dose distributions (p = 0.309). Sparse projections significantly reduced detectability (p = 0.001). Synthetic images had a higher AUC with the convex setup, though not significantly (p = 0.435). DBT required four times more reading time than synthetic mammography. DISCUSSION: A convex setup did not significantly improve detectability in DBT compared to the standard setup. Synthetic images exhibited a non-significant increase in detectability with the convex setup. Sparse setup significantly reduced detectability in both DBT and synthetic mammography. CLINICAL RELEVANCE STATEMENT: This virtual imaging trial study allowed the design and efficient testing of different dose distribution trajectories with real mammography images, using a dose-neutral protocol. KEY POINTS: • In DBT, a convex dose distribution did not increase the detectability of microcalcifications compared to the current standard setup but increased detectability for the SM images. • A sparse setup decreased microcalcification detectability in both DBT and SM images compared to the convex and current clinical setups. • Optimal microcalcification cluster detection in the system studied was achieved using either the standard or convex dose setting, with the default number of projections.

Developing Advanced Patient-Specific In Silico Models: A New Era in Biomechanical Analysis of Tooth Autotransplantation.

INTRODUCTION: As personalized medicine advances, there is an escalating need for sophisticated tools to understand complex biomechanical phenomena in clinical research. Recognizing a significant gap, this study pioneers the development of patient-specific in silico models for tooth autotransplantation (TAT), setting a new standard for predictive accuracy and reliability in evaluating TAT outcomes. METHODS: Development of the models relied on 6 consecutive cases of young patients (mean age 11.66 years ± 0.79), all undergoing TAT procedures. The development process involved creating detailed in silico replicas of patient oral structures, focusing on transplanting upper premolars to central incisors. These models underpinned finite element analysis simulations, testing various masticatory and traumatic scenarios. RESULTS: The models highlighted critical biomechanical insights. The finite element models indicated homogeneous stress distribution in control teeth, contrasted by shape-dependent stress patterns in transplanted teeth. The surface deviation in the postoperative year for the transplanted elements showed a mean deviation of 0.33 mm (±0.28), significantly higher than their contralateral counterparts at 0.05 mm (±0.04). CONCLUSIONS: By developing advanced patient-specific in silico models, we are ushering in a transformative era in TAT research and practice. These models are not just analytical tools; they are predictive instruments capturing patient uniqueness, including anatomical, masticatory, and tissue variables, essential for understanding biomechanical responses in TAT. This foundational work paves the way for future studies, where applying these models to larger cohorts will further validate their predictive capabilities and influence on TAT success parameters.

Computational modeling of dorsal root ganglion stimulation using an Injectrode.

Objective.Minimally invasive neuromodulation therapies like the Injectrode, which is composed of a tightly wound polymer-coated Platinum/Iridium microcoil, offer a low-risk approach for administering electrical stimulation to the dorsal root ganglion (DRG). This flexible electrode is aimed to conform to the DRG. The stimulation occurs through a transcutaneous electrical stimulation (TES) patch, which subsequently transmits the stimulation to the Injectrode via a subcutaneous metal collector. However, it is important to note that the effectiveness of stimulation through TES relies on the specific geometrical configurations of the Injectrode-collector-patch system. Hence, there is a need to investigate which design parameters influence the activation of targeted neural structures.Approach.We employed a hybrid computational modeling approach to analyze the impact of Injectrode system design parameters on charge delivery and neural response to stimulation. We constructed multiple finite element method models of DRG stimulation, followed by the implementation of multi-compartment models of DRG neurons. By calculating potential distribution during monopolar stimulation, we simulated neural responses using various parameters based on prior acute experiments. Additionally, we developed a canonical monopolar stimulation and full-scale model of bipolar bilateral L5 DRG stimulation, allowing us to investigate how design parameters like Injectrode size and orientation influenced neural activation thresholds.Main results.Our findings were in accordance with acute experimental measurements and indicate that the minimally invasive Injectrode system predominantly engages large-diameter afferents (Aß-fibers). These activation thresholds were contingent upon the surface area of the Injectrode. As the charge density decreased due to increasing surface area, there was a corresponding expansion in the stimulation amplitude range before triggering any pain-related mechanoreceptor (Aδ-fibers) activity.Significance.The Injectrode demonstrates potential as a viable technology for minimally invasive stimulation of the DRG. Our findings indicate that utilizing a larger surface area Injectrode enhances the therapeutic margin, effectively distinguishing the desired Aßactivation from the undesired Aδ-fiber activation.

Calibration system correction factor for measuring the reference air kerma rate (RAKR) applied to high dose rate192Ir sources (HDR).

The aim of this study was to use computer simulation to analyze the impact of the aluminum fixing support on the Reference Air Kerma (RAK), a physical quantity obtained in a calibration system that was experimentally developed in the Laboratory of Radiological Sciences of the University of the State of Rio de Janeiro (LCR-UERJ). Correction factors due to scattered radiation and the geometry of the192Ir sources were also sought to be determined. The computational simulation was validated by comparing some parameters of the experimental results with the computational results. These parameters were: verification of the inverse square law of distance, determination of (RAKR), analysis of the source spectrum with and without encapsulation, and the sensitivity curve of the Sourcecheck 4PI ionization chamber response, as a function of the distance from the source along the axial axis, using the microSelectron-v2 (mSv2) and GammaMedplus (GMp) sources. Kerma was determined by activity in the Reference air, with calculated values of 1.725 × 10-3U. Bq-1and 1.710 × 10-3U. Bq-1for the ionization chamber NE 2571 and TN 30001, respectively. The expanded uncertainty for these values was 0.932% and 0.919%, respectively, for a coverage factor (k = 2). The correction factor due to the influence of the aluminum fixing support for measurements at 1 cm and 10 cm from the source was 0.978 and 0.969, respectively. The geometric correction factor of the sources was ksg= 1.005 with an expanded uncertainty of 0.7% for a coverage factor (k = 2). This value has a difference of approximately 0.2% compared to the experimental values.

Finite Element Analysis of Changes in Deformation of Intraocular Segments by Airbag Impact in Eyes of Various Axial Lengths.

Background: We studied the kinetic phenomenon of an airbag impact on eyes with different axial lengths using finite element analysis (FEA) to sequentially determine the physical and mechanical responses 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. The airbag was set to impact eyes with axial lengths of 21.85 mm (hyperopia), 23.85 mm (emmetropia) and 25.85 mm (myopia), at initial velocities of 20, 30, 40, 50 and 60 m/s. The deformation rate was calculated as the ratio of the length of three segments, anterior chamber, lens and vitreous, to that at the baseline from 0.2 ms to 2.0 ms after the airbag impact. Results: Deformation rate of the anterior chamber was greater than that of other segments, especially in the early phase, 0.2-0.4 ms after the impact (P < 0.001), and it reached its peak, 80%, at 0.8 ms. A higher deformation rate in the anterior chamber was found in hyperopia compared with other axial length eyes in the first half period, 0.2-0.8 ms, followed by the rate in emmetropia (P < 0.001). The lens deformation rate was low, its peak ranging from 40% to 75%, and exceeded that of the anterior chamber at 1.4 ms and 1.6 ms after the impact (P < 0.01). The vitreous deformation rate was lower throughout the simulation period than that of the other segments and ranged from a negative value (elongation) in the later phase. Conclusion: Airbag impact on the eyeball causes evident deformation, especially in the anterior chamber. The results obtained in this study, such as the time lag of the peak deformation between the anterior chamber and lens, suggest a clue to the pathophysiological mechanism of airbag ocular injury.

Single-cell ionic current phenotyping explains stem cell-derived cardiomyocyte action potential morphology.

Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) are a promising tool to study arrhythmia-related factors, but the variability of action potential (AP) recordings from these cells limits their use as an in vitro model. In this study, we use recently published brief (10 s), dynamic voltage-clamp (VC) data to provide mechanistic insights into the ionic currents contributing to AP heterogeneity; we call this approach rapid ionic current phenotyping (RICP). Features of this VC data were correlated to AP recordings from the same cells, and we used computational models to generate mechanistic insights into cellular heterogeneity. This analysis uncovered several interesting links between AP morphology and ionic current density: both L-type calcium and sodium currents contribute to upstroke velocity, rapid delayed rectifier K+ current is the main determinant of the maximal diastolic potential, and an outward current in the activation range of slow delayed rectifier K+ is the main determinant of AP duration. Our analysis also identified an outward current in several cells at 6 mV that is not reproduced by iPSC-CM mathematical models but contributes to determining AP duration. RICP can be used to explain how cell-to-cell variability in ionic currents gives rise to AP heterogeneity. Because of its brief duration (10 s) and ease of data interpretation, we recommend the use of RICP for single-cell patch-clamp experiments that include the acquisition of APs.NEW & NOTEWORTHY We present rapid ionic current phenotyping (RICP), a current quantification approach based on an optimized voltage-clamp protocol. The method captures a rich snapshot of the ionic current dynamics, providing quantitative information about multiple currents (e.g., ICa,L, IKr) in the same cell. The protocol helped to identify key ionic determinants of cellular action potential heterogeneity in iPSC-CMs. This included unexpected results, such as the critical role of IKr in establishing the maximum diastolic potential.

An interactive simulator to deepen the understanding of Guyton's venous return curve.

Mean circulatory filling pressure, venous return curve, and Guyton's graphical analysis are basic concepts in cardiovascular physiology. However, some medical students may not know how to view and interpret or understand them adequately. To deepen students' understanding of the graphical analysis, in place of having to perform live animal experiments, we developed an interactive cardiovascular simulator, as a self-learning tool, as a web application. The minimum closed-loop model consisted of a ventricle, an artery, resistance, and a vein, excluding venous resistance. The simulator consists of three modules: setting (parameters and simulation modes), calculation, and presentation. In the setting module, the user can interactively customize model parameters, compliances, resistance, Emax of the ventricular contractility, total blood volume, and unstressed volume. The hemodynamics are calculated in three phases: filling (late diastole), ejection (systole), and flow (early diastole). In response to the user's settings, the simulator graphically presents the hemodynamics: the pressure-volume relations of the artery, vein, and ventricle, the venous return curves, and the stroke volume curves. The mean filling pressure is calculated at approximately 7 mmHg at the initial setting. The venous return curves, linear and concave, are dependent on the venous compliance. The hemodynamic equilibrium point is marked on the crossing point of venous return curve and the stroke volume curve. Users can interactively do discovery learning, and try and confirm their interests and get their questions answered about hemodynamic concepts by using the simulator.

On the feasibility of minimally invasive Le Fort I with patient-specific implants: Proof of concept.

A novel approach to Le Fort I osteotomy is presented, integrating patient-specific implants (PSIs), osteosynthesis and cutting guides within a minimally invasive surgical framework, and the accuracy of the procedure is assessed through 3D voxel-based superimposition. The technique was applied in 5 cases. Differences between the surgical plan and final outcome were evaluated as follows: a 2-mm color scale was established to assess the anterior surfaces of the maxilla, mandible and chin, as well as the condylar surfaces. Measurements were made at 8 specific landmarks, and all of them showed a mean difference of less than 1 mm. In conclusion, the described protocol allows for minimally invasive Le Fort I osteotomy using PSIs. Besides, although the accuracy of the results may be limited by the small sample size, the findings are consistent with those reported in the literature. A prospective comparative study is needed to obtain statistically significant results and draw meaningful conclusions.

Optimizing Patient Care: A Multicentric Study on the Clinical Impact of Sim&Size™ Simulation Software in Intracranial Aneurysm Treatment With Pipeline Embolization Devices.

BACKGROUND: To determine the clinical effects (stent size, and number of stents used) of the Sim&Size™ simulation software on the endovascular treatment of unruptured saccular intracranial aneurysms with Pipeline Embolization Devices (PED). METHODS: This study is a retrospective analytical multicenter study of patients treated with PED (Flex and Flex with SHIELD) for intracranial aneurysm in FOSCAL clinic and CHU de Montpellier. RESULTS: The study included 253 patients, of which 75 were treated in Colombia and 178 were treated in France. The majority of patients were women (83.8%), with a median age of 57.48 years, and had large vessel location (88.1%), with most aneurysms located in the ICA paraclinoid segment (56.8%). Patients in the group with Sim&Size™ simulation had shorter stents than those without simulation (15.62 mm versus 17.36 mm, P-value = 0.001). Also, a lower proportion of these patients required more than one stent (1.4% versus 7.3%, P-value = 0.022). There were 7 complications reported in the group that used the Sim&Size™ simulation software, compared to 9 complications in the group that did not use the software. CONCLUSIONS: Using Sim&Size™ simulation software for endovascular treatment of patients with intracranial aneurysms using PED reduces the stent length and decreasing the number of devices needed per treatment.

On-site rapid detection of perfluorooctanoic acid by visual immunochromatographic strip biosensor in domestic water and real human samples.

The International Agency for Research on Cancer (IARC) classifies PFOA as a Class 1 carcinogen. Here, a new naked-eye PFOA immunochromographic strip was developed to recognize PFOA in domestic water and real human samples within 10 min based on a novel custom designed anti-PFOA monoclonal antibody (mAb) 2A3, which was firstly an immune rapid detection method for PFOA has been proposed. Using computer simulation techniques such as quantum computing to assist in designing the structural formula of PFOA semi antigen, which hapten was firstly proposed. The half maximal inhibitory concentration of PFOA monoclonal antibody (mAb) 2A3 was 2.4 µg/mL. Using mAb 2A3, we developed an immunochromatographic strip (ICS) for detecting PFOA in real samples. The developed method generated results in 10 min, with visual detection limits of 20, 20, and 200 µg/mL and limit of detection of 50, 200, and 500 µg/mL for water, blood and urine samples, respectively. The established ICS and indirect competitive enzyme-linked immunosorbent assay were used to analyze the actual samples, and the results were confirmed by LC-MS/MS. Our study findings showed that the ICS and ic-ELISA can quickly detect PFOA in actual samples.