Augmented reality simulation-based training for midwifery students and its impact on perceived knowledge, confidence and skills for managing critical incidents.

PROBLEM: Emergency obstetric management is essential in midwifery training to prevent fetal and maternal morbidity. Repeating this management in practice is often not possible. Sustainable confidence in these procedures is usually achieved in the first few years of practice. BACKGROUND: Simulation training complements hands-on learning and improves practical skills, benefiting both students and patients. Research on obstetric emergency simulation training have demonstrated this, but the use of digital simulation approaches, such as augmented reality (AR), is under-researched. AIM: To investigate whether AR simulation training influences midwifery students' subjective perceptions of knowledge, confidence and practical skills in emergency situations. METHODS: A descriptive exploratory study was conducted using a pre-post design. AR scenarios were developed on the topics of 'preparing emergency tocolysis', 'preparing a pregnant woman for caesarean section' and 'resuscitation of newborns'. The AR simulation was conducted in the fourth to fifth semester of the midwifery programme. A questionnaire was developed for students (N = 133) to self-assess their competence in the categories of knowledge, confidence and practical skills. RESULTS: Students rated their competence significantly better in the post-survey than in the pre-survey (p=<0.05). Simulation has an impact on self-assessment of professional knowledge, confidence and practical skills in emergency situations. It enhances students' procedural knowledge and practical skills in complex contexts, complements subject knowledge and builds confidence. CONCLUSION: The results provide initial evidence that AR simulation is an effective learning strategy for emergency management preparedness. Future studies should validate the effect with control cohorts and measure competence through practical examinations.

Enzymatic degradation of polyethylene terephthalate nanoplastics analyzed in real time by isothermal titration calorimetry.

Plastics are globally used for a variety of benefits. As a consequence of poor recycling or reuse, improperly disposed plastic waste accumulates in terrestrial and aquatic ecosystems to a considerable extent. Large plastic waste items become fragmented to small particles through mechanical and (photo)chemical processes. Particles with sizes ranging from millimeter (microplastics, <5 mm) to nanometer (nanoplastics, NP, <100 nm) are apparently persistent and have adverse effects on ecosystems and human health. Current research therefore focuses on whether and to what extent microorganisms or enzymes can degrade these NP. In this study, we addressed the question of what information isothermal titration calorimetry, which tracks the heat of reaction of the chain scission of a polyester, can provide about the kinetics and completeness of the degradation process. The majority of the heat represents the cleavage energy of the ester bonds in polymer backbones providing real-time kinetic information. Calorimetry operates even in complex matrices. Using the example of the cutinase-catalyzed degradation of polyethylene terephthalate (PET) nanoparticles, we found that calorimetry (isothermal titration calorimetry-ITC) in combination with thermokinetic models is excellently suited for an in-depth analysis of the degradation processes of NP. For instance, we can separately quantify i) the enthalpy of surface adsorption ∆AdsH = 129 ± 2 kJ mol-1, ii) the enthalpy of the cleavage of the ester bonds ∆EBH = -58 ± 1.9 kJ mol-1 and the apparent equilibrium constant of the enzyme substrate complex K = 0.046 ± 0.015 g L-1. It could be determined that the heat production of PET NP degradation depends to 95% on the reaction heat and only to 5% on the adsorption heat. The fact that the percentage of cleaved ester bonds (η = 12.9 ± 2.4%) is quantifiable with the new method is of particular practical importance. The new method promises a quantification of enzymatic and microbial adsorption to NP and their degradation in mimicked real-world aquatic conditions.

New thermodynamic activity-based approach allows predicting the feasibility of glycolysis.

Thermodynamic feasibility analyses help evaluating the feasibility of metabolic pathways. This is an important information used to develop new biotechnological processes and to understand metabolic processes in cells. However, literature standard data are uncertain for most biochemical reactions yielding wrong statements concerning their feasibility. In this article we present activity-based equilibrium constants for all the ten glycolytic reactions, accompanied by the standard reaction data (standard Gibbs energy of reaction and standard enthalpy of reaction). We further developed a thermodynamic activity-based approach that allows to correctly determine the feasibility of glycolysis under different chosen conditions. The results show for the first time that the feasibility of glycolysis can be explained by thermodynamics only if (1) correct standard data are used and if (2) the conditions in the cell at non-equilibrium states are accounted for in the analyses. The results here will help to determine the feasibility of other metabolisms and to understand metabolic processes in cells in the future.

Thermodynamics and Kinetics of Glycolytic Reactions. Part I: Kinetic Modeling Based on Irreversible Thermodynamics and Validation by Calorimetry.

In systems biology, material balances, kinetic models, and thermodynamic boundary conditions are increasingly used for metabolic network analysis. It is remarkable that the reversibility of enzyme-catalyzed reactions and the influence of cytosolic conditions are often neglected in kinetic models. In fact, enzyme-catalyzed reactions in numerous metabolic pathways such as in glycolysis are often reversible, i.e., they only proceed until an equilibrium state is reached and not until the substrate is completely consumed. Here, we propose the use of irreversible thermodynamics to describe the kinetic approximation to the equilibrium state in a consistent way with very few adjustable parameters. Using a flux-force approach allowed describing the influence of cytosolic conditions on the kinetics by only one single parameter. The approach was applied to reaction steps 2 and 9 of glycolysis (i.e., the phosphoglucose isomerase reaction from glucose 6-phosphate to fructose 6-phosphate and the enolase-catalyzed reaction from 2-phosphoglycerate to phosphoenolpyruvate and water). The temperature dependence of the kinetic parameter fulfills the Arrhenius relation and the derived activation energies are plausible. All the data obtained in this work were measured efficiently and accurately by means of isothermal titration calorimetry (ITC). The combination of calorimetric monitoring with simple flux-force relations has the potential for adequate consideration of cytosolic conditions in a simple manner.

Thermodynamics and Kinetics of Glycolytic Reactions. Part II: Influence of Cytosolic Conditions on Thermodynamic State Variables and Kinetic Parameters.

For systems biology, it is important to describe the kinetic and thermodynamic properties of enzyme-catalyzed reactions and reaction cascades quantitatively under conditions prevailing in the cytoplasm. While in part I kinetic models based on irreversible thermodynamics were tested, here in part II, the influence of the presumably most important cytosolic factors was investigated using two glycolytic reactions (i.e., the phosphoglucose isomerase reaction (PGI) with a uni-uni-mechanism and the enolase reaction with an uni-bi-mechanism) as examples. Crowding by macromolecules was simulated using polyethylene glycol (PEG) and bovine serum albumin (BSA). The reactions were monitored calorimetrically and the equilibrium concentrations were evaluated using the equation of state ePC-SAFT. The pH and the crowding agents had the greatest influence on the reaction enthalpy change. Two kinetic models based on irreversible thermodynamics (i.e., single parameter flux-force and two-parameter Noor model) were applied to investigate the influence of cytosolic conditions. The flux-force model describes the influence of cytosolic conditions on reaction kinetics best. Concentrations of magnesium ions and crowding agents had the greatest influence, while temperature and pH-value had a medium influence on the kinetic parameters. With this contribution, we show that the interplay of thermodynamic modeling and calorimetric process monitoring allows a fast and reliable quantification of the influence of cytosolic conditions on kinetic and thermodynamic parameters.

Influence of cytosolic conditions on the reaction equilibrium and the reaction enthalpy of the enolase reaction accessed by calorimetry and van 't HOFF.

BACKGROUND: Thermodynamic methods are finding more and more applications in systems biology, which attempts to understand cell functions mechanistically. Unfortunately, the state variables used (reaction enthalpy and Gibbs energy) do not take sufficient account of the conditions inside of cells, especially the crowding with macromolecules. METHODS: For this reason, the influence of crowding agents and various other parameters such as salt concentrations, pH and temperature on equilibrium position and reaction enthalpy of the glycolytic example reaction 9 (2-Phospoglycerate - > Phosphoenolpyruvate + H2O) was investigated. The conditions were chosen to be as close as possible to the cytosolic conditions. Poly(ethylene glycol) MW = 20,000 g mol-1 (PEG 20,000) was used to analyze the influence of crowding with macromolecules. The equation of state electrolyte Perturbed-Chain Statistical Associating Fluid Theory (ePC-SAFT) was applied to consider the influence of crowding agents on the reaction equilibria. RESULTS AND CONCLUSIONS: For the reaction enthalpies and for the equilibria, it was found that the influence of salts and temperature is not pronounced while that of pH and PEG 20,000 concentration is considerable. Furthermore, it could be shown that under identical measurement conditions there are no differences between the van 't Hoff and the calorimetrically determined reaction enthalpy. GENERAL SIGNIFICANCE: The results show how important it is to consider the special cytosolic conditions when applying thermodynamic data in systems biology.

Standard Gibbs energy of metabolic reactions: V. Enolase reaction.

The glycolytic pathway is one of the most important pathways for living organisms, due to its role in energy production and as supplier of precursors for biosynthesis in living cells. This work focuses on determination of the standard Gibbs energy of reaction ΔRg'0 of the enolase reaction, the ninth reaction in the glycolysis pathway. Exact ΔRg'0 values are required to predict the thermodynamic feasibility of single metabolic reactions or even of metabolic reaction sequences under cytosolic conditions. So-called "apparent" standard data from literature are only valid at specific conditions. Nevertheless, such data are often used in pathway analyses, which might lead to misinterpretation of the results. In this work, equilibrium measurements were combined with activity coefficients in order to obtain new standard values ΔRg'0 for the enolase reaction that are independent of the cytosolic conditions. Reaction equilibria were measured at different initial substrate concentrations and temperatures of 298.15 K, 305.15 K and 310.15 K at pH 7. The activity coefficients were predicted using the equation of state electrolyte Perturbed-Chain Statistical Associating Fluid Theory (ePC-SAFT). The ePC-SAFT parameters were taken from literature or fitted to new experimentally determined osmotic coefficients and densities. At 298.15 K and pH 7, a ΔRg'0(298.15 K, pH 7) value of -2.8 ± 0.2 kJ mol-1 was obtained. This value differs by up to 5 kJ mol-1 from literature data. Reasons are the poorly defined "standard" conditions and partly undefined reaction conditions of literature works. Finally, using temperature-dependent equilibrium constants and the van 't Hoff equation, the standard enthalpy of reaction of ΔRh'0(298.15 K, pH 7) = 27 ± 10 kJ mol-1 was determined, and a similar value was found by quantum-chemistry calculations.

Exploring Canadian women's knowledge of and interest in mifepristone: results from a national qualitative study with abortion patients.

INTRODUCTION: Although Canada decriminalized abortion in 1988, significant disparities in access to services and an uneven geographic distribution of providers persists. Health Canada registered mifepristone, the gold standard of medication abortion, in July 2015. Our study explored Canadian women's knowledge of, interest in, and perspectives on mifepristone prior to registration. METHODS: From November 2012 through July 2015 we conducted in-depth interviews with 174 Anglophone and Francophone women from Alberta, Manitoba, New Brunswick, Ontario, and Quebec about their abortion experiences and their opinions about medication abortion. We purposively recruited participants from different age cohorts and different regions within each study province to explore a range of perspectives. We analyzed these interviews for content and themes related to mifepristone using both deductive and inductive analytic techniques. RESULTS: The overwhelming majority of participants had no knowledge of mifepristone at the time of the interview. However, after providing a brief description of an evidence-based mifepristone/misoprostol regimen, more than half of the participants reported that they would have considered this method had it been available at the time of their abortion and most would have been comfortable receiving medication abortion care from a family physician or nurse practitioner. Most women supported the approval of mifepristone and felt Canadian women would benefit from having more options for early pregnancy termination. CONCLUSION: Although knowledge of mifepristone among recent abortion patients was low, considerable interest in medication abortion exists. Expanding awareness-raising efforts and supporting the approval of evidence-based regimens and provision of mifepristone appears warranted. IMPLICATIONS: The approval and introduction of mifepristone for early abortion in Canada promises to increase options and access. Creating tailored and culturally and contextually resonant messages about mifepristone is of high priority. Promoting evidence-based protocols and the inclusion of a full range of qualified professionals in service provision is also warranted.

Discrepancy in the interpretation of cervical histology by gynecologic pathologists.

OBJECTIVE: To determine if subspecialty review of cervical histology improves diagnostic consensus of cervical intraepithelial neoplasia (CIN). METHODS: After routine histologic assessment within the hospital pathology department, 119 colposcopic cervical biopsies were interpreted by two subspecialty-trained gynecologic pathologists (GYN I and GYN II) blinded to each other's interpretations and to the interpretations of the hospital general pathologists (GEN). Biopsies were classified as normal (including cervicitis), low grade (LG, including CIN I and human papillomavirus changes), and high grade (HG, including CIN II/III). The interobserver agreement rates between GEN and GYN I, between GEN and GYN II, and between GYN I and GYN II were described using the kappa statistic. The proportions of biopsies assigned to each biopsy class were compared using McNemar test. RESULTS: Interobserver agreement rates between GEN and GYN I were moderate for normal (kappa = 0.53) and LG (kappa = 0.46) and excellent for HG (kappa = 0.76). There were no significant differences in the classifications between GEN and GYN I. Interobserver agreement rates between GEN and GYN II were moderate for normal (kappa = 0.50) and LG (kappa = 0.44) and excellent for HG (kappa = 0.84). Also, GYN II was significantly more likely to classify biopsies as normal (P <.001) and less likely to classify biopsies as LG (P <.001). The interobserver agreement rates between GYN I and GYN II were moderate for normal (kappa = 0.61) and LG (kappa = 0.41) and excellent for HG (kappa = 0.84). Also, GYN II was significantly more likely to classify biopsies as normal (P <.001) and less likely to classify biopsies as LG (P =.01). CONCLUSION: Interobserver agreement between two gynecologic pathologists was no better than that observed between general and gynecologic pathologists. Subspecialty review of cervical histology does not enhance diagnostic consensus of CIN.