Pharmacy student's perceptions, behaviours and attitudes toward virtual reality simulation.

Aims: The definition of virtual reality simulation (VRS) used for study is the recreation of realistic simulation in a fully online situation with an immersive environment for learning an activity. The study aims to evaluate pharmacy students' perspectives, behavioral and attitude characteristics in the process of VRS course requiring practical skills. Materials and methods: This cross-sectional study was based on quantitative questionnaires analysis. A five-point Likert Scale (rating from 1 = Strongly Disagree; 2 = Disagree; 3 = Neutral; 4 = Agree; 5 = Strongly Agree) was utilized to measure the extent to which the students agrees on 30 statements comprised in A-E sections related to VRS. The validity and reliability of the questionnaire were studied by the Cronbach's Alpha calculation. Results: A total of 119 junior and senior pharmacy students, aged 18-25, participated in this study. There is no significant gender difference (P > 0.05) and grade difference (P > 0.05) in mean perception score, mean attitude score, mean behavior score and comparison score respectively. Most pharmacy students had positive perception that VRS could help them in practical ability (61.4 %), autonomous learning (68.9 %) and theoretical knowledge (61.4 %). Nevertheless, less than half the students agreed that VRS courses were indispensable (44.5 %) and needed to be increased (42.9 %). Moreover, the 'disagree' statement (33.6 %) exceeded 'agree' statement (27.7 %) about the question of whether preferring VRS courses to lab teaching. Interestingly, a significant positive correlation that was observed between mean perception score and mean attitude score (r = 0.76, p < 0.001), mean comparison (r = 0.68, p < 0.001) and mean behavior (r = 067, p < 0.001), which revealed that students who thought VRS was beneficial were more likely to accept it. Conclusion: The study highlights the need to establish an interactive, immersive and measurable VRS courses. It is suggested that good interaction between the faculty and student, technology improvement and blended programmatic assessment should be involved in challenges for implementing VRS courses.

A critical review on the fabrication techniques that can enable higher throughput in dielectrophoresis devices.

The sorting of targeted cells in a sample is a cornerstone of healthcare diagnostics and therapeutics. This work focuses on the use of dielectrophoresis for the selective sorting of targeted bioparticles in a sample and how the lack of throughput has been one important practical challenge to its widespread practical implementation. Increasing the cross-sectional area of a channel can lead to higher flow rates and thus the capability to process a larger sample volume per unit of time. However, the required electric field gradient that is generated by polarized electrodes drastically decreases as one moves away from the electrodes. Hence, the scaling up of the channel cross section must be done asymmetrically. One desires a channel aspect ratio AR = height/width that is much smaller or much larger than 1. Since reducing footprint of the DEP device is important to ensure affordability, the use of channels with AR ≫ 1 is desired. This creates the challenge to fabricate electrodes on the sidewalls of multiple channels with AR ≫ 1, or a channel embedding an array of electrodes with a gap in between them with AR ≫ 1. This critical review first details the motivation for using three-dimensional (3D) DEP devices to improve throughput and then describes selected techniques that have been used to fabricate them. Techniques include electrodeposition, deep etching, thick-film photolithography, and co-fabrication. Electrode materials addressed include metals, silicon, carbon, PDMS-based composites as well as conductive polymers and fluids.

Evidence-based Effective Triage Operation During Disaster: Application of Human-trajectory Data to Triage Drill Sessions.

INTRODUCTION: Though many governmental and nongovernmental efforts for disaster prevention have been sought throughout Japan since the Great East Japan Earthquake on March 11, 2011, most of the preparation efforts for disasters have been based more on structural and conventionalized regulations than on scientific and objective grounds. Problem There has been a lack of scientific knowledge for space utilization for triage posts in disaster drill sessions. This report addresses how participants occupy and make use of the space within a triage post in terms of areas of use and occupied time. METHOD: The trajectories of human movement by using Ubiquitous Stereo Vision (USV) cameras during two emergency drill sessions held in 2012 in a large commercial building have been measured. The USV cameras collect each participant's travel distance and the wait time before, during, and after undergoing triage. The correlation between the wait time and the space utilization of patients at a triage post has been analyzed. RESULTS: In the first session, there were some spaces not entirely used. This was caused largely by a patient who arrived earlier than others and lingered in the middle area, which caused the later arrivals to crowd the entrance area. On the other hand, in the second session, the area was used in a more evenly-distributed manner. This is mainly because the earlier arrivals were guided to the back space of the triage post (ie, the opposite side of the entrance), and the late arrivals were also guided to the front half, which was not occupied by anyone. As a result, the entire space was effectively utilized without crowding the entrance. CONCLUSION: This study has shown that this system could measure people's arrival times and the speed of their movements at the triage post, as well as where they are placed until they receive triage. Space utilization can be improved by efficiently planning and controlling the positioning of arriving patients. Based on the results, it has been suggested that for triage operation, it is necessary to efficiently plan and control the placement of patients in order to use strategically limited spatial resources.

Miniaturization of hiPSC-derived 3D neural cultures in stirred-tank bioreactors for parallelized preclinical assessment of rAAV.

Introduction: Engineered 3D models employing human induced pluripotent stem cell (hiPSC) derivatives have the potential to recapitulate the cell diversity and structure found in the human central nervous system (CNS). Therefore, these complex cellular systems offer promising human models to address the safety and potency of advanced therapy medicinal products (ATMPs), such as gene therapies. Specifically, recombinant adeno-associated viruses (rAAVs) are currently considered highly attractive for CNS gene therapy due to their broad tropism, low toxicity, and moderate immunogenicity. To accelerate the clinical translation of rAAVs, in-depth preclinical evaluation of efficacy and safety in a human setting is primordial. The integration of hiPSC-derived CNS models in rAAV development will require, amongst other factors, robust, small-scale, high-throughput culture platforms that can feed the preclinical trials. Methods: Herein, we pioneer the miniaturization and parallelization of a 200 mL stirred-tank bioreactor-based 3D brain cell culture derived from hiPSCs. We demonstrate the applicability of the automated miniaturized Ambr® 15 Cell Culture system for the maintenance of hiPSC-derived neurospheroids (iNSpheroids), composed of neuronal and glial cells. Critical process parameters were optimized, namely, cell density and agitation mode. Results: Under optimized conditions, stable iNSpheroid cultures were attained in the microbioreactors for at least 15 days, with high cell viability and astrocytic and neuronal phenotype maintenance. This culture setup allowed the parallelization of different rAAVs, in different multiplicity of infections (MOIs), to address rAAV-host interactions at a preclinical scale. The iNSpheroids were exposed to rAAV2- and rAAV9-eGFP in the microbioreactors. Transgene expression was detected 14 days post-transduction, revealing different astrocyte/neuron tropism of the two serotypes. Discussion: We advocate that the iNSpheroid cultures in miniaturized bioreactors are reliable and reproducible screening tools for addressing rAAV transduction and tropism, compatible with preclinical demands.

3D assessment of initial fracture displacement of tibial plateau fractures is predictive for risk on conversion to total knee arthroplasty at long-term follow-up.

PURPOSE: Currently used classification systems and measurement methods are insufficient to assess fracture displacement. In this study, a novel 3D measure for fracture displacement is introduced and associated with risk on conversion to total knee arthroplasty (TKA). METHODS: A multicenter cross-sectional study was performed including 997 patients treated for a tibial plateau fracture between 2003 and 2018. All patients were contacted for follow-up and 534 (54%) responded. For all patients, the 3D gap area was determined in order to quantify the degree of initial fracture displacement. A cut-off value was determined using ROC curves. Multivariate analysis was performed to assess the association of 3D gap area with conversion to TKA. Subgroups with increasing levels of 3D gap area were identified, and Kaplan-Meier survival curves were plotted to assess survivorship of the knee free from conversion to TKA. RESULTS: A total of 58 (11%) patients underwent conversation to TKA. An initial 3D gap area ≥ 550 mm2 was independently associated with conversion to TKA (HR 8.4; p = 0.001). Four prognostic groups with different ranges of the 3D gap area were identified: excellent (0-150 mm2), good (151-550 mm2), moderate (551-1000 mm2), and poor (> 1000 mm2). Native knee survival at 10-years follow-up was 96%, 95%, 76%, and 59%, respectively, in the excellent, good, moderate, and poor group. CONCLUSION: A novel 3D measurement method was developed to quantify initial fracture displacement of tibial plateau fractures. 3D fracture assessment adds to current classification methods, identifies patients at risk for conversion to TKA at follow-up, and could be used for patient counselling about prognosis. LEVEL OF EVIDENCE: Prognostic Level III.

Reevaluation of the surgical indications for anterior inferior iliac spine avulsion fractures in an acute setting - A narrative review of the current literature.

Purpose: The anterior inferior iliac spine (AIIS) is a frequent site of avulsion fracture in the pelvis, and these lesions could be observed mainly in teenage athletes. The present study aimed to re-evaluate the appropriate acute surgical treatment of AIIS avulsion fractures considering the three-dimensional anatomy of the supracetabular region. Methods: This study evaluated current evidence of AIIS avulsion fracture treatments and outcomes. A literature search was done in the following databases: PubMed, SCOPUS, Embase, and Cochrane Library. All relevant information was used in this review. Results: Several studies have shown how conservative treatment of these injuries lead to excellent outcomes, even when there is radiological evidence of displacement. However, only some surgeons describe clinical and radiological follow-up beyond six months. On the other side, recent studies have demonstrated the efficacy of arthroscopic or open procedures to solve a frequent cause of extra-articular femur-acetabular impingement (FAI) syndrome associated with previous AIIS avulsion fractures, the so-called sub-spine impingement. The acute surgical indication in AIIS avulsion fractures should be considered according to the three-dimensional anatomy of the supracetabular region, especially in young patients with high functional demands. Conclusions: Three-dimensional assessment allows accurate evaluation of the position and dislocation of the fragment, predicting the risk of complications related to conservative treatment and guiding toward surgical indication only when appropriate.

3D Virtual Reality Rehabilitation Therapy for Patients with Vertigo Due to Peripheral Vestibular Dysfunction.

This study aimed to evaluate 3D virtual reality rehabilitation therapy in patients with vertigo due to peripheral vestibular dysfunction. The subjects were 20 patients with peripheral vestibular dysfunction confirmed by Videonystagmography, Divided into 2 groups: Group 1 (study group) underwent vestibular rehabilitation therapy using 3D virtual reality in a customised VR lab with specific headset (Oculus rift and htc vive) with software application, which allows vestibular rehabilitation treatment using high quality immersive virtual reality console in which environment appears real and in 3D. The exercises are designed for gaze stability, increase postural stability, improve vertigo and daily activities, through sensory stimuli and in addition to conventional Cawthorne-Choksey exercises. Group 2 (control group) are treated by conventional Cawthorne-Choksey exercises alone. A VSS-SF (Vertigo Symptom Scale-short form) questionnaire and VAS (Visual Analog Scale) were used to assess the levels of patient satisfaction compared before and after each treatment session in both groups. A significant higher level of subjective satisfaction was observed in patients who underwent 3D virtual reality rehabilitation therapy with conventional therapy (group 1) compared to patients who underwent conventional cawthorne-Choksey exercises alone (group 2). The study gave a substantial subjective satisfaction in patients using 3D virtual reality rehabilitation therapy with conventional therapy (group1) than conventional Cawthorne-Choksey exercises alone (group 2). Future of VR rehabilitation therapy brings a revolutionary novelty in field of rehabilitation therapy were it involves real time stimulation and interaction between sensory, motor and cognitive channels.

"Slow walk" mimetic tensile loading maintains human meniscus tissue resident progenitor cells homeostasis in photocrosslinked gelatin hydrogel.

Meniscus, the cushion in knee joint, is a load-bearing tissue that transfers mechanical forces to extracellular matrix (ECM) and tissue resident cells. The mechanoresponse of human tissue resident stem/progenitor cells in meniscus (hMeSPCs) is significant to tissue homeostasis and regeneration but is not well understood. This study reports that a mild cyclic tensile loading regimen of ∼1800 loads/day on hMeSPCs seeded in 3-dimensional (3D) photocrosslinked gelatin methacryloyl (GelMA) hydrogel is critical in maintaining cellular homeostasis. Experimentally, a "slow walk" biomimetic cyclic loading regimen (10% tensile strain, 0.5 Hz, 1 h/day, up to 15 days) is applied to hMeSPCs encapsulated in GelMA hydrogel with a magnetic force-controlled loading actuator. The loading significantly increases cell differentiation and fibrocartilage-like ECM deposition without affecting cell viability. Transcriptomic analysis reveals 332 mechanoresponsive genes, clustered into cell senescence, mechanical sensitivity, and ECM dynamics, associated with interleukins, integrins, and collagens/matrix metalloproteinase pathways. The cell-GelMA constructs show active ECM remodeling, traced using a green fluorescence tagged (GFT)-GelMA hydrogel. Loading enhances nascent pericellular matrix production by the encapsulated hMeSPCs, which gradually compensates for the hydrogel loss in the cultures. These findings demonstrate the strong tissue-forming ability of hMeSPCs, and the importance of mechanical factors in maintaining meniscus homeostasis.

Drop-on-powder 3D printing of amorphous high dose oral dosage forms: Process development, opportunities and printing limitations.

Drop-on-powder 3D printing is able to produce highly drug loaded solid oral dosage forms. However, this technique is mainly limited to well soluble drugs. The majority of pipeline compounds is poorly soluble, though, and requires solubility enhancement, e.g., via formation of amorphous solid dispersions. This study presents a detailed and systematic development approach for the production of tablets containing high amounts of a poorly soluble, amorphized drug via drop-on-powder 3D printing (also known as binder jetting). Amorphization of the compound was achieved via hot-melt extrusion using the exemplary system of the model compound ketoconazole and copovidone as matrix polymer at drug loadings of 20% and 40%. The milled extrudate was used as powder for printing and the influence of inks and different ink-to-powder ratios on recrystallization of ketoconazole was investigated in a material-saving small-scale screening. Crystallinity assessment was performed using differential scanning calorimetry and polarized light microscopy to identify even small traces of crystallinity. Printing of tablets showed that the performed small-scale screening was capable to identify printing parameters for the development of amorphous and mechanically stable tablets via drop-on-powder printing. A stability study demonstrated physically stable tablets over twelve weeks at accelerated storage conditions.

Decellularized matrix for repairing intervertebral disc degeneration: Fabrication methods, applications and animal models.

Intervertebral disc degeneration (IDD)-induced low back pain significantly influences the quality of life, placing a burden on public health systems worldwide. Currently available therapeutic strategies, such as conservative or operative treatment, cannot effectively restore intervertebral disc (IVD) function. Decellularized matrix (DCM) is a tissue-engineered biomaterial fabricated using physical, chemical, and enzymatic technologies to eliminate cells and antigens. By contrast, the extracellular matrix (ECM), including collagen and glycosaminoglycans, which are well retained, have been extensively studied in IVD regeneration. DCM inherits the native architecture and specific-differentiation induction ability of IVD and has demonstrated effectiveness in IVD regeneration in vitro and in vivo. Moreover, significant improvements have been achieved in the preparation process, mechanistic insights, and application of DCM for IDD repair. Herein, we comprehensively summarize and provide an overview of the roles and applications of DCM for IDD repair based on the existing evidence to shed a novel light on the clinical treatment of IDD.

The intersegmental pulmonary vein is not always located on the intersegmental plane of the lung: Evaluation with 3-dimensional volume-rendering image reconstruction.

Objective: To clarify whether intersegmental pulmonary veins are always located on the intersegmental plane and determine the division from which blood flows into them. Methods: We analyzed representative intersegmental veins located between the upper/lingular and superior/basal division of the lungs using preoperative chest computed tomography (CT) DICOM data from 22 patients who underwent lobectomy or segmentectomy during 2020. The location and blood flow of V3a+b and V6b+c were assessed using REVORAS (Ziosoft), a novel volume-rendering 3-dimensional (3D) image reconstruction software dedicated to lung segmentectomy. Results: The V3a+b was in the upper division and on the intersegmental plane between the upper and lingular divisions of the left lung in 11 patients (50%) each. A main root of V3a+b was not found in the lingular division, but some peripheral flow in the V3a+b was derived from it in 14 patients (64%). The V6b+c was found in the superior division of the right lower lobe in 13 patients (59%) and the left lower lobe in 10 patients (45%), and on the intersegmental plane between the superior and basal division of the right lower lobe in 6 patients (27%) and the left lower lobe in 10 patients (45%). A main root of V6b+c was imperceptible in the basal division. Some peripheral blood flow was derived from the basal division in 6 patients (27%) with V6b+c veins located in the right lower lobe and in 8 patients (36%) with V6b+c veins located in the left lower lobe. Conclusions: Precise evaluation of intersegmental veins using preoperative volume-rendering 3D reconstructed CT images provides useful anatomic information for separating intersegmental pulmonary parenchyma.

Matritecture: Mapping the extracellular matrix architecture during health and disease.

All cells in multicellular organisms are housed in the extracellular matrix (ECM), an acellular edifice built up by more than a thousand proteins and glycans. Cells engage in a reciprocal relationship with the ECM; they build, inhabit, maintain, and remodel the ECM, while, in turn, the ECM regulates their behavior. The homeostatic balance of cell-ECM interactions can be lost, due to ageing, irritants or diseases, which results in aberrant cell behavior. The ECM can suppress or promote disease progression, depending on the information relayed to cells. Instructions come in the form of biochemical (e.g., composition), biophysical (e.g., stiffness), and topographical (e.g., structure) cues. While advances have been made in many areas, we only have a very limited grasp of ECM topography. A detailed atlas deciphering the spatiotemporal arrangement of all ECM proteins is lacking. We feel that such an extracellular matrix architecture (matritecture) atlas should be a priority goal for ECM research. In this commentary, we will discuss the need to resolve the spatiotemporal matritecture to identify potential disease triggers and therapeutic targets and present strategies to address this goal. Such a detailed matritecture atlas will not only identify disease-specific ECM structures but may also guide future strategies to restructure disease-related ECM patterns reverting to a normal pattern.

Ninjurin1 Deletion in NG2-Positive Pericytes Prevents Microvessel Maturation and Delays Wound Healing.

The formation of mature vasculature through angiogenesis is essential for adequate wound healing, such that blood-borne cells, nutrients, and oxygen can be delivered to the remodeling skin area. Neovessel maturation is highly dependent on the coordinated functions of vascular endothelial cells and perivascular cells, namely pericytes (PCs). However, the underlying mechanism for vascular maturation has not been completely elucidated, and its role in wound healing remains unclear. In this study, we investigated the role of Ninjurin-1 (Ninj1), a new molecule mediating vascular maturation, in wound healing using an inducible PC-specific Ninj1 deletion mouse model. Ninj1 expression increased temporarily in NG2-positive PCs in response to skin injury. When tamoxifen treatment induced a decreased Ninj1 expression in PCs, the neovessels in the regenerating wound margins were structurally and functionally immature, but the total number of microvessels was unaltered. This phenotypic change is associated with a reduction in PC-associated microvessels. Wound healing was significantly delayed in the NG2-specific Ninj1 deletion mouse model. Finally, we showed that Ninj1 is a crucial molecule that mediates vascular maturation in injured skin tissue through the interaction of vascular endothelial cells and PCs, thereby inducing adequate and prompt wound healing.

Age-Related Downregulation of CCN2 Is Regulated by Cell Size in a YAP/TAZ-Dependent Manner in Human Dermal Fibroblasts: Impact on Dermal Aging.

CCN2, a member of the CCN family of matricellular proteins, is a key mediator and biomarker of tissue fibrosis. We previously reported that CCN2 is significantly reduced in aged human dermis, which contributes to dermal aging through the downregulation of collagen production, the major structural protein in the skin. In this study, we investigated the underlying mechanisms of the age-related downregulation of CCN2 in human skin dermal fibroblasts. Dermal fibroblasts isolation and laser-capture microdissection‒coupled RT-PCR from human skin confirmed that age-related reduction of CCN2 expression is regulated by epigenetics. Mechanistic investigation revealed that age-related reduction of CCN2 is regulated by impaired dermal fibroblast spreading/cell size, which is a prominent feature of aged dermal fibroblasts in vivo. Gain-of-function and loss-of-function analysis confirmed that age-related downregulation of CCN2 is regulated by YAP/TAZ in response to reduced cell size. We further confirmed that restoration of dermal fibroblast size rapidly reversed the downregulation of CCN2 in a YAP/TAZ-dependent manner. Finally, we confirmed that reduced YAP/TAZ nuclear staining is accompanied by loss of CCN2 in aged human skin in vivo. Our data reveal a mechanism by which age-related reduction in fibroblast spreading/size drives YAP/TAZ-dependent downregulation of CCN2 expression, which in turn contributes to loss of collagen in aged human skin.

Combining Shape-Sensing Robotic Bronchoscopy With Mobile Three-Dimensional Imaging to Verify Tool-in-Lesion and Overcome Divergence: A Pilot Study.

Objective: To determine whether CT-to-body divergence can be overcome to improve the diagnostic yield of peripheral pulmonary nodules with the combination of shape-sensing robotic-assisted bronchoscopy (SSRAB) and portable 3-dimensional (3D) imaging. Patients and Methods: A single-center, prospective, pilot study was conducted from February 9, 2021, to August 4, 2021, to evaluate the combined use of SSRAB and portable 3D imaging to visualize tool-in-lesion as a correlate to diagnostic yield. Results: Thirty lesions were subjected to biopsy in 17 men (56.7%) and 13 women (43.3%). The median lesion size was 17.5 mm (range, 10-30 mm), with the median airway generation of 7 and the median distance from pleura of 14.9 mm. Most lesions were in the upper lobes (18, 60.0%). Tool-in-lesion was visualized at the time of the procedure in 29 lesions (96.7%). On the basis of histopathologic review, 22 (73.3%) nodules were malignant and 6 (20.0%) were benign. Two (6.7%) specimens were suggestive of inflammation, and the patients elected observation. The mean number of spins was 2.5 (±1.6) with a mean fluoroscopy time of 8.7 min and a mean dose area product of 50.3 Gy cm2 (±32.0 Gy cm2). There were no episodes of bleeding or pneumothorax. The diagnostic yield was 93.3%. Conclusion: This pilot study shows that the combination of mobile 3D imaging and SSRAB of pulmonary nodules appears to be safe and feasible. In conjunction with appropriate anesthetic pathways, nodule motion and divergence can be overcome in most patients. Trial Registration: https://clinicaltrials.gov Identifier NCT04740047.

Accuracy of intraoral digital radiography in assessing maxillary Sinus-Root relationship compared to CBCT.

Background and Objectives: The proper assessment of the relation between the roots of the maxillary posterior teeth and the maxillary sinus floor represents a real concern for dental practitioners when conducting any procedure in the involved region. Many imaging techniques have been employed to assess this relation. This study aimed to (1) compare the accuracy of digital periapical radiographs with that of cone-beam computed tomography images in assessing the relationship between the maxillary molar roots and the maxillary sinus floor and (2) determine periapical radiographic features (if present) that could indicate the actual protrusion of roots into the sinus cavity. Materials and Methods: This observational analytical in vivo study was carried out on 23 Egyptian patients. Cone-beam computed tomography and digital periapical images were obtained for each patient and assessed by three oral radiologists. Results were statistically analyzed in terms of accuracy, specificity, and sensitivity in addition to the McNemar-Bowker and Fleiss's Kappa test. Results: Despite the presence of a significant difference between the results of both techniques, periapical radiography demonstrated 73% accuracy in displaying the sinus-root relation. Moreover, the continuity of the lamina dura suggests (with more than 70% accuracy) that the root is located outside the sinus and vice versa. Conclusion: The digital periapical technique is considered an accurate method of assessing the sinus-root relation especially when the root is located outside the sinus. One of the most indictive periapical features of root intrusion into the maxillary sinus is the discontinuity of the lamina dura.

A double-J stent misguided by zebra guidewire into ileum: A case report and literature review.

The case is a 70-year-old man who underwent a left nephroureterectomy and cutaneous ureterostomy on the contralateral side for invasive bladder cancer had to be accepted replacement of the double-J stent because of stomal stenosis.When replacing the double-J stent, a severe complication that the double-J stent misguided into the ileum occurred. The patient underwent gastrointestinal motility drugs, and the double-J stent was excreted with the feces after 12 hours. Unfortunately，patient suffered a uretero-ileal fistula and died of septic shock finally.The diagnosis and management of Uretero-ileal fistula as an iatrogenic complication of zebra guidewire use is discussed.

Suitability of Human Mesenchymal Stem Cells Derived from Fetal Umbilical Cord (Wharton's Jelly) as an Alternative In Vitro Model for Acute Drug Toxicity Screening.

Preclinical toxicity screening is the first and most crucial test that assesses the safety of new candidate drugs before their consideration for further evaluation in clinical trials. In vitro drug screening using stem cells has lately arisen as a promising alternative to the "gold standard" of animal testing, but their suitability and performance characteristics in toxicological studies have so far not been comprehensively investigated. In this study, we focused on the evaluation of human mesenchymal stem cells isolated from the matrix (Wharton's jelly) of fetal umbilical cord (WJSCs), which bear enhanced in vitro applicability due to their unique biological characteristics. In order to determine their suitability for drug-related cytotoxicity assessment, we adopted a high-throughput methodology that evaluated their sensitivity to a selected panel of chemicals in different culture environments. Cytotoxicity was measured within 48 h by means of MTS and/or NRU viability assays, and was compared directly (in vitro) or indirectly (in silico) to adult human mesenchymal stem cells and to reference cell lines of human and murine origin. Our data clearly suggest that human WJSCs can serve as a robust in vitro alternative for acute drug toxicity screening by uniquely combining rapid and versatile assay setup with high-throughput analysis, good representation of human toxicology, high reproducibility, and low cost.

Mechanical dispersion combined with global longitudinal strain estimated by three dimensional speckle tracking in patients with ST elevation myocardial infarction.

Background: The role of left ventricular (LV) mechanical dispersion estimated after an ST elevation acute myocardial infarction (STEMI) remains unclear. Methods: The study participants were 208 consecutive patients (152 men, age = 72 years) presenting with STEMI for the first time who underwent primary percutaneous coronary intervention (PCI) within 12 h of STEMI onset. Within 48 h of PCI (mean = 24 h), 2D and 3D speckle-tracking echocardiography were performed. The global longitudinal strain (GLS) was calculated using 3D (3D-GLS) and 2D (2D-GLS) speckle tracking. Mechanical dispersion was defined using the standard deviation (SD) of the time to regional peak longitudinal strain (LS) for all 16 segments for both 2D-STE and 3D-STE (2D-LS-SD, 3D-LS-SD). Infarct size was estimated by Tc99m-sestamibi as the total area of < 50% of the uptake area at 2 weeks. The patients were followed up for a longer period of time (median118months) and checked for major adverse cardiac events (MACE: cardiac death, heart failure). Results: During follow-up, 55 patients experienced MACE. The cut-off values were determined using receiver operating characteristic curves. The multivariate analysis revealed that a 3D-LS-SD > 56.7 ms was a significant predictor of MACEs (hazard ratio = 1.991, 95% confidence interval 1.033-3.613, p = 0.03), but 2D-LS-SD > 58.1 ms was not an independent predictor of MACEs (hazard ratio = 1.577, 95% confidence interval 0.815-3.042, p = 0.1). Furthermore, the combination of 3D-GLS and 3D-LS-SD had accurate predictability for MACE, as shown by the Kaplan-Meier curves (log rank, χ2 = 94.1, p < 0.0001). Conclusions: LV mechanical dispersion besides 3D-GLS assessed by 3D-STE immediately after PCI can predict long-term prognosis.

State-of-the-art silicone molded models for simulation of arterial switch operation: Innovation with parting-and-assembly strategy.

Background: Three-dimensional (3D) printed models are widely accepted for use in training of various surgical procedures for congenital heart disease; however, their physical properties have been considered suboptimum for procedures. We created silicone molded models produced using a novel "parting and assembly" strategy and compared their suitability for hands-on training with that of conventional 3D printed models. Methods: Computed tomography imaging data from 2 patients with transposition of the great arteries were used. The heart was divided into multiple parts (atria, ventricles, great arteries, coronary arteries, and valves), and molds of each part were created. The parts reproduced by silicone molding were assembled using an adhesive agent. In an online course, 2 silicone molded models and 1 3D printed model were used for training of 34 surgeons. A questionnaire was distributed to these surgeons aimed at assessing the suitability of the models for the arterial switch operation (ASO). Results: The silicone molded models showed excellent anatomic detail, high elasticity, and high resistance to tearing. The cost per model, based on the production of 50 models, was slightly higher for the silicone molded models compared with the 3D printed models. All 26 surgeons who completed the questionnaire reported that the silicone molded models provided sufficient anatomic information, but only 19% said the same for the 3D printed models. All surgeons also considered the silicone models to be realistic when passing a needle, cutting vessels, suturing, and excision of the coronary buttons, as opposed to <46% for the 3D printed models. Conclusions: Silicone molding of models for the ASO is feasible by applying a "parting and assembly" strategy. Silicone molded models provide excellent physical properties that are far superior to those of 3D printed models for surgical simulation.