Research outputs after the Coursework Pathway.

Objectives: The aim of the present study was to quantify research outputs after completing a Coursework Pathway (CP).

Methods: Emergency medicine trainees who completed a CP during 2012-2022 were included. Research outputs were identified using Medline, EMBASE, Pubmed and Google Scholar.

Cyclosporin A toxicity on endothelial cells differentiated from induced pluripotent stem cells: Assembling an adverse outcome pathway.

Cyclosporin A (CSA) is a potent immunosuppressive agent in pharmacologic studies. However, there is evidence for side effects, specifically regarding vascular dysfunction. Its mode of action inducing endothelial cell toxicity is partially unclear, and a connection with an adverse outcome pathway (AOP) is not established yet.

Promoting 21st Century Health and Wellness Skills in Elementary School Children: a Group Randomized Trial.

In a group randomized trial of 45 elementary schools, a whole-child health and wellness curriculum introduced as a regular part of the educational programming was compared to education as usual over 2 years with a 2-year follow-up. The curriculum focused on integrating multiple SEL skills-mindfulness, compassion, and physical awareness-with the intent to advantage developmental patterns for these skills, academic engagement, personal well-being, and student behavior. The program design and trial implementation were launched with end-use delivery and long-term sustainability as integral considerations.

The Effects of a Relationship-Focused Professional Development Intervention on Infant and Toddler Teachers' Mindfulness-Based Strategies for Coping.

Teaching is a demanding profession with teachers of very young children reporting high rates of stress and exhaustion. We tested the effects of a relationship-focused professional development intervention designed to enhance teachers' use of mindfulness-based strategies to support coping on trajectories of teachers' stress, exhaustion (emotional, physical, and mental), and coping. Infant and toddler teachers ( = 81) from Early Head Start (EHS) or EHS childcare partnerships (CCP) were randomized to the intervention or usual care control condition.

Characterization of Organic Anion and Cation Transport in Three Human Renal Proximal Tubular Epithelial Models.

The polarised expression of specific transporters in proximal tubular epithelial cells is important for the renal clearance of many endogenous and exogenous compounds. Thus, ideally, the in vitro tools utilised for predictions would have a similar expression of apical and basolateral xenobiotic transporters as in vivo. Here, we assessed the functionality of organic cation and anion transporters in proximal tubular-like cells (PTL) differentiated from human induced pluripotent stem cells (iPSC), primary human proximal tubular epithelial cells (PTEC), and telomerase-immortalised human renal proximal tubular epithelial cells (RPTEC/TERT1).

Development of a membrane-disruption assay using phospholipid vesicles as a proxy for the detection of cellular membrane degradation.

Snakebite envenoming is a global health issue that affects millions of people worldwide, and that causes morbidity rates surpassing 450,000 individuals annually. Patients suffering from snakebite morbidities may experience permanent disabilities such as pain, blindness and amputations. The (local) tissue damage that causes these life-long morbidities is the result of cell- and tissue-damaging toxins present in the venoms.

Evaluation of the impact of iPSC differentiation protocols on transcriptomic signatures.

Human induced pluripotent stem cells (iPSC) have the potential to produce desired target cell types in vitro and allow for the high-throughput screening of drugs/chemicals at population level thereby minimising the cost of drug discovery and drug withdrawals after clinical trials. There is a substantial need for the characterisation of the iPSC derived models to better understand and utilise them for toxicological relevant applications. In our study, iPSC (SBAD2 or SBAD3 lines obtained from StemBANCC project) were differentiated towards toxicologically relevant cell types: alveolar macrophages, brain capillary endothelial cells, brain cells, endothelial cells, hepatocytes, lung airway epithelium, monocytes, podocytes and renal proximal tubular cells.

Transcriptomic profile of human iPSC-derived podocyte-like cells exposed to a panel of xenobiotics.

Podocytes play a critical role in the formation and maintenance of the glomerular filtration barrier and injury to these cells can lead to a breakdown of the glomerular barrier causing permanent damage leading to progressive chronic kidney disease. Matured podocytes have little proliferative potential, which makes them critical cells from a health perspective, but also challenging cells to maintain in vitro. Differentiating podocyte-like cells from induced pluripotent stem cells (iPSC) provides a novel and continuous source of cells.

Erythropoietin -glycosylation of Therapeutic Formulations Quantified and Characterized: An Interlab Comparability Study of High-Throughput Methods.

Recombinant human erythropoietin (EPO) is a biopharmaceutical frequently used in the treatment of anemia. It is a heavily glycosylated protein with a diverse and complex glycome. EPO -glycosylation influences important pharmacological parameters, prominently serum half-life.

Protectiveness of NAM-based hazard assessment - which testing scope is required?

Hazard assessment requires toxicity tests to allow deriving protective points of departure (PoDs) for risk assessment irrespective of a compound’s mode of action (MoA). The scope of in vitro test batteries (ivTB) needed to assess systemic toxicity is still unclear. We explored the protectiveness regarding systemic toxicity of an ivTB with a scope that was guided by previous findings from rodent studies, where examining six main targets, including liver and kidney, was sufficient to predict the guideline scope-based PoD with high probability.

Stress Intensity and Exhaustion Among Infant and Toddler Teachers: Descriptive Analysis and Associations with Sources of Stress and Coping Strategy Use.

Unlabelled: This study described infant/toddler teachers' (N = 106) perceptions of stress intensity and exhaustion (emotional, physical, mental) intensity. We examined the associations between stress and exhaustion and teachers' reports of stress sources and coping strategy use. Using ecological momentary assessment (EMA), teachers from Early Head Start (EHS), EHS childcare-partnerships, or independent childcare programs (midwestern U.

A pre-hospital mixed methods systematic review protocol.

Introduction: Mixed methods research, a methodology entailing the integration of qualitative and quantitative data within a single study, offers researchers the ability to investigate complex processes and systems in health and healthcare. The collective strength gained through the data combination can provide an enhanced understanding of research problems, providing an ideal solution to understanding complex clinical issues in a range of settings. In pre-hospital practice, where often uncontrollable variables and environmental considerations increase healthcare complexity, mixed methods has emerged as a valuable approach to research.

Differentiation and Subculturing of Renal Proximal Tubular-like Cells Derived from Human iPSC.

Recently, we have developed a protocol to differentiate human induced pluripotent stem cells (iPSC) into proximal tubular-like cells (PTL) (Chandrasekaran et al., 2021). These cells express proximal tubular-specific markers, including megalin, and form a polarized monolayer expressing tight junction proteins, including ZO-3 and occludin.

Development of a high-throughput in vitro screening method for the assessment of cell-damaging activities of snake venoms.

Snakebite envenoming is a globally important public health issue that has devastating consequences on human health and well-being, with annual mortality rates between 81,000 and 138,000. Snake venoms may cause different pathological effects by altering normal physiological processes such as nervous transfer and blood coagulation. In addition, snake venoms can cause severe (local) tissue damage that may result in life-long morbidities, with current estimates pointing towards an additional 450,000 individuals that suffer from permanent disabilities such as amputations, contractions and blindness.

Transforming Empathy-Based Stress to Compassion: Skillful Means to Preventing Teacher Burnout.

Objectives: Teachers play a critical role in preparing our children and adolescents for a successful future. However, despite the large number of students impacted by trauma and adversity, teachers are often not well prepared to provide trauma-sensitive support. Furthermore, while working to support students exposed to trauma and adversity, teachers may experience empathy-based stress exacerbating already high levels of stress among them.

Transcriptional landscape of mitochondrial electron transport chain inhibition in renal cells.

Analysis of the transcriptomic alterations upon chemical challenge, provides in depth mechanistic information on the compound's toxic mode of action, by revealing specific pathway activation and other transcriptional modulations. Mapping changes in cellular behaviour to chemical insult, facilitates the characterisation of chemical hazard. In this study, we assessed the transcriptional landscape of mitochondrial impairment through the inhibition of the electron transport chain (ETC) in a human renal proximal tubular cell line (RPTEC/TERT1).

Exposure to cis- and trans-regioisomers of S-(1,2-dichlorovinyl)-L-cysteine and S-(1,2-dichlorovinyl)-glutathione result in quantitatively and qualitatively different cellular effects in RPTEC/TERT1 cells.

Bioactivation of trichloroethylene (TCE) via glutathione conjugation is associated with several adverse effects in the kidney and other extrahepatic tissues. Of the three regioisomeric conjugates formed, S-(1,2-trans-dichlorovinyl)-glutathione (1,2-trans-DCVG), S-(1,2-cis-dichlorovinyl)-glutathione and S-(2,2-dichlorovinyl)-glutathione, only 1,2-trans-DCVG and its corresponding cysteine-conjugate, 1,2-trans-DCVC, have been subject to extensive mechanistic studies. In the present study, the metabolism and cellular effects of 1,2-cis-DCVG, the major regioisomer formed by rat liver fractions, and 1,2-cis-DCVC were investigated for the first time using RPTEC/TERT1-cells as in vitro renal model.

The Development of Helicopter Emergency Medical Services in the Republic of Ireland.

Helicopter emergency medical services (HEMS) have formed an integral component of the Irish health care system for the past decade; yet, the factors leading their commencement, their evolutions over this time, and the current model of service delivery have not been widely published. Aeromedical service provision may vary significantly from country to country and may also vary regionally within countries. A health system's necessities; capacity and maturity; the level of state, corporate, private, or community investment; and the capacity of the contracted service provider are all factors that influence the service provision.

Capturing time-dependent activation of genes and stress-response pathways using transcriptomics in iPSC-derived renal proximal tubule cells.

Transcriptomic analysis is a powerful method in the utilization of New Approach Methods (NAMs) for identifying mechanisms of toxicity and application to hazard characterization. With this regard, mapping toxicological events to time of exposure would be helpful to characterize early events. Here, we investigated time-dependent changes in gene expression levels in iPSC-derived renal proximal tubular-like cells (PTL) treated with five diverse compounds using TempO-Seq transcriptomics with the aims to evaluate the application of PTL for toxicity prediction and to report on temporal effects for the activation of cellular stress response pathways.

Initial Pain Assessment and Management in Pediatric Burn Patients Presenting to a Major Trauma Center in Saudi Arabia.

Background: Pediatric burn injury is a traumatic experience for affected children and their families. Burn pain is frequently undertreated and may adversely affect patient experience and outcomes. The aim of this study was to investigate the current practice of initial pediatric burn pain assessment and management at a major trauma center in Riyadh, Kingdom of Saudi Arabia.

Transcriptomic-based evaluation of trichloroethylene glutathione and cysteine conjugates demonstrate phenotype-dependent stress responses in a panel of human in vitro models.

Environmental or occupational exposure of humans to trichloroethylene (TCE) has been associated with different extrahepatic toxic effects, including nephrotoxicity and neurotoxicity. Bioactivation of TCE via the glutathione (GSH) conjugation pathway has been proposed as underlying mechanism, although only few mechanistic studies have used cell models of human origin. In this study, six human derived cell models were evaluated as in vitro models representing potential target tissues of TCE-conjugates: RPTEC/TERT1 (kidney), HepaRG (liver), HUVEC/TERT2 (vascular endothelial), LUHMES (neuronal, dopaminergic), human induced pluripotent stem cells (hiPSC) derived peripheral neurons (UKN5) and hiPSC-derived differentiated brain cortical cultures containing all subtypes of neurons and astrocytes (BCC42).

Knotting Optimization and Folding Pathways of a Go-Model with a Deep Knot.

Formation of protein knots is an intriguing offshoot of the protein folding problem. Since experimental resolution on knot formation is limited, theoretical methods currently provide the most detailed insights into the knotting process. While suitable for shallow knots, molecular dynamics simulations have faced challenges capturing the formation of deep knots in proteins such as the minimally tied trefoil α/β methyltransferase from (MTT).

E-cigarette aerosol impairs male mouse skeletal muscle force development and prevents recovery from injury.

To date, there has been a lag between the rise in E-cigarette use and an understanding of the long-term health effects. Inhalation of E-cigarette aerosol delivers high doses of nicotine, raises systemic cytokine levels, and compromises cardiopulmonary function. The consequences for muscle function have not been thoroughly investigated.

Machine learning approach towards explaining water quality dynamics in an urbanised river.

Human activities alter river water quality and quantity, with consequences for the ecosystems of urbanised rivers. Quantifying the role of human-induced drivers in controlling spatio-temporal patterns in water quality is critical to develop successful strategies for improving the ecological health of urban rivers. Here, we analyse high-frequency electrical conductivity and temperature data collected from the River Chess in South-East England during a Citizen Science project.