Parasomnias during trans-meridian and long-distance travel: Critical literature review and clinical practice recommendations.

Parasomnias are undesirable events that occur during sleep. They can be classified into rapid eye movement parasomnias and non-rapid eye movement parasomnias. Those who experience parasomnias may be anxious about travel for many reasons, including the occurrence of unwanted events during the trip, increased exposure to environmental trigger factors, and the propensity for harm to occur due to unfamiliar surroundings while travelling. There is a paucity of literature examining this area. This review summarizes the relevant literature and the clinical experience of the authors to compile clinical practice recommendations. The clinical features of parasomnias and how they relate to trans-meridian and long-distance travel are described. Triggers for non-rapid eye movement parasomnias, particularly the use of sedative hypnotic drugs, alcohol, drug withdrawal, sleep deprivation, emotional stress and environmental stimulations, are described. Management of parasomnias whilst travelling is reviewed, with a particular focus on trigger minimalization. The role for clonazepam and melatonin is outlined. At the pre-travel health consultation, the physician is strongly advised to screen the traveller for co-morbid sleep conditions, which exacerbate parasomnias. Areas for further research are explored, including the extent to which these sleep disorders impact on the travel experience.

Experience-based learning: how a crisis solution informed fundamental change in a clinical education curriculum.

BACKGROUND: Clinical education represents the most important formative period in undergraduate medical education. It is often criticised as haphazard and inefficient. Experience-based learning (ExBL) is a novel clinical education design that utilises practices of support, learner participation and real patient learning to enhance students' development of vital professional capabilities. We introduced ExBL to address the challenges of a 50% reduction in clinical placement time that arose during the COVID-19 pandemic. APPROACH: Final year medical students were assimilated into clinical teams as co-workers to facilitate learning through participation rather than observation. Placement education was supported by an integrated case-based learning and high-fidelity simulation program. Real patient learning in workplace contexts was supported by a network of clinician mentors. EVALUATION: A qualitative evaluation revealed that granting students co-worker status strongly supported participatory learning and professional identity formation. Furthermore, the triangulation of placements with cognitive coaching and high-fidelity simulation greatly enhanced skills development and students' sense of readiness for practice. IMPLICATIONS: Utilisation of ExBL significantly enhanced the quality of informal learning on clinical placements despite the reduced clinical placement time. In addition, the integration of cognitive coaching with simulation opportunities meant students were better prepared for meaningful participation as members of clinical teams. The introduction of ExBL increased the workload of clinical teachers. Moreover, favouring learning through participatory experience reduced exposure to more traditional formal bedside teaching encounters. Despite these challenges, we have adopted an ExBL model created in a crisis as our core educational design for our final year clinical programme.

Practical tips for introducing high-fidelity simulation to undergraduates at a large scale: learning from our experience.

The letter provides practical tips for developing, implementing and scaling an effective simulation­based education programme at a large scale for undergraduate medical students. Using time-lapsed scenarios and the pause-discuss method of debrief are some of the useful tips that are discussed further in the letter.

CXCR3A promotes the secretion of the antifibrotic decoy receptor sIL-13Rα2 by pulmonary fibroblasts.

CXC chemokine receptor 3 (CXCR3) A and its IFN-inducible ligands CXCL9 and CXCL10 regulate vascular remodeling and fibroblast motility. IL-13 is a profibrotic cytokine implicated in the pathogenesis of inflammatory and fibroproliferative conditions. Previous work from our laboratory has shown that CXCR3A is negatively regulated by IL-13 and is necessary for the basal regulation of the IL-13 receptor subunit IL-13Rα2. This study investigates the regulation of fibroblast phenotype, function, and downstream IL-13 signaling by CXCR3A in vitro. CXCR3A was overexpressed via transient transfection. CXCR3A-/- lung fibroblasts were isolated for functional analysis. Additionally, the contribution of CXCR3A to tissue remodeling following acute lung injury was assessed in vivo with wild-type (WT) and CXCR3-/- mice challenged with IL-13. CXCR3 and IL-13Rα2 displayed a reciprocal relationship after stimulation with either IL-13 or CXCR3 ligands. CXCR3A reduced expression of fibroblast activation makers, soluble collagen production, and proliferation. CXCR3A enhanced the basal expression of pERK1/2 while inducing IL-13-mediated downregulation of NF-κB-p65. CXCR3A-/- pulmonary fibroblasts were increasingly proliferative and displayed reduced contractility and α-smooth muscle actin expression. IL-13 challenge regulated expression of the CXCR3 ligands and soluble IL-13Rα2 levels in lungs and bronchoalveolar lavage fluid (BALF) of WT mice; this response was absent in CXCR3-/- mice. Alveolar macrophage accumulation and expression of genes involved in lung remodeling was increased in CXCR3-/- mice. We conclude that CXCR3A is a central antifibrotic factor in pulmonary fibroblasts, limiting fibroblast activation and reducing extracellular matrix (ECM) production. Therefore, targeting of CXCR3A may be a novel approach to regulating fibroblast activity in lung fibrosis and remodeling.

Novel differences in gene expression and functional capabilities of myofibroblast populations in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF), a chronic progressive interstitial pneumonia, is characterized by excessive fibroproliferation. Key effector cells in IPF are myofibroblasts that are recruited from three potential sources: resident fibroblasts, fibrocytes, and epithelial cells. We hypothesized that IPF myofibroblasts from different sources display unique gene expression differences and distinct functional characteristics. Primary human pulmonary fibroblasts (normal and IPF), fibrocytes, and epithelial cells were activated using the profibrotic factors TGF-ß and TNF-α. The resulting myofibroblasts were characterized using cell proliferation, soluble collagen, and contractility assays, ELISA, and human fibrosis PCR arrays. Genes of significance in human whole lung were validated by immunohistochemistry on human lung sections. Fibroblast-derived myofibroblasts exhibited the greatest increase in expression of profibrotic genes and genes involved in extracellular matrix remodeling and signal transduction. Functional studies demonstrated that myofibroblasts derived from fibrocytes expressed mostly soluble collagen and chemokine (C-C) motif ligand (CCL) 18 but were the least proliferative of the myofibroblast progeny. Activated IPF fibroblasts displayed the highest levels of contractility and CCL2 production. This study identified novel differences in gene expression and functional characteristics of different myofibroblast populations. Further investigation into the myofibroblast phenotype may lead to potential therapeutic targets in future IPF research.

Altered Expression of Bone Morphogenetic Protein Accessory Proteins in Murine and Human Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis is a chronic, progressive fibrotic disease with a poor prognosis. The balance between transforming growth factor ß1 and bone morphogenetic protein (BMP) signaling plays an important role in tissue homeostasis, and alterations can result in pulmonary fibrosis. We hypothesized that multiple BMP accessory proteins may be responsible for maintaining this balance in the lung. Using the bleomycin mouse model for fibrosis, we examined an array of BMP accessory proteins for changes in mRNA expression. We report significant increases in mRNA expression of gremlin 1, noggin, follistatin, and follistatin-like 1 (Fstl1), and significant decreases in mRNA expression of chordin, kielin/chordin-like protein, nephroblastoma overexpressed gene, and BMP and activin membrane-bound inhibitor (BAMBI). Protein expression studies demonstrated increased levels of noggin, BAMBI, and FSTL1 in the lungs of bleomycin-treated mice and in the lungs of idiopathic pulmonary fibrosis patients. Furthermore, we demonstrated that transforming growth factor ß stimulation resulted in increased expression of noggin, BAMBI, and FSTL1 in human small airway epithelial cells. These results provide the first evidence that multiple BMP accessory proteins are altered in fibrosis and may play a role in promoting fibrotic injury.

CXCL9 Regulates TGF-ß1-Induced Epithelial to Mesenchymal Transition in Human Alveolar Epithelial Cells.

Epithelial to mesenchymal cell transition (EMT), whereby fully differentiated epithelial cells transition to a mesenchymal phenotype, has been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). CXCR3 and its ligands are recognized to play a protective role in pulmonary fibrosis. In this study, we investigated the presence and extent of EMT and CXCR3 expression in human IPF surgical lung biopsies and assessed whether CXCR3 and its ligand CXCL9 modulate EMT in alveolar epithelial cells. Coexpression of the epithelial marker thyroid transcription factor-1 and the mesenchymal marker α-smooth muscle actin and CXCR3 expression was examined by immunohistochemical staining of IPF surgical lung biopsies. Epithelial and mesenchymal marker expression was examined by quantitative real-time PCR, Western blotting, and immunofluorescence in human alveolar epithelial (A549) cells treated with TGF-ß1 and CXCL9, with Smad2, Smad3, and Smad7 expression and cellular localization examined by Western blotting. We found that significantly more cells were undergoing EMT in fibrotic versus normal areas of lung in IPF surgical lung biopsy samples. CXCR3 was expressed by type II pneumocytes and fibroblasts in fibrotic areas in close proximity to cells undergoing EMT. In vitro, CXCL9 abrogated TGF-ß1-induced EMT. A decrease in TGF-ß1-induced phosphorylation of Smad2 and Smad3 occurred with CXCL9 treatment. This was associated with increased shuttling of Smad7 from the nucleus to the cytoplasm where it inhibits Smad phosphorylation. This suggests a role for EMT in the pathogenesis of IPF and provides a novel mechanism for the inhibitory effects of CXCL9 on TGF-ß1-induced EMT.

Modulation of pulmonary fibrosis by IL-13Rα2.

Pulmonary fibrosis is a progressive and fatal disease that involves the remodeling of the distal airspace and the lung parenchyma, which results in compromised gas exchange. The median survival time once diagnosed is less than three years. Interleukin (IL)-13 has been shown to play a role in a number of inflammatory and fibrotic diseases. IL-13 modulates its effector functions via a complex receptor system that includes the IL-4 receptor (R) α, IL-13Rα1, and the IL-13Rα2. IL-13Rα1 binds IL-13 with low affinity, yet, when it forms a complex with IL-4α, it binds with much higher affinity, inducing the effector functions of IL-13. IL-13Rα2 binds IL-13 with high affinity but has a short cytoplasmic tail and has been shown to act as a nonsignaling decoy receptor. Transfection of fibroblasts and epithelial cells with IL-13Rα2 inhibited the IL-13 induction of soluble collagen, TGF-ß, and CCL17. Adenoviral overexpression of IL-13Rα2 in the lung reduced bleomycin-induced fibrosis. Our work shows that overexpression of IL-13Rα2 inhibits the IL-13 induction of fibrotic markers in vitro and inhibits bleomycin-induced pulmonary fibrosis. In summary our study highlights the antifibrotic nature of IL-13Ra2.

Are respiratory specialist registrars trained to teach?

Respiratory SpRs are interested in medical education but rarely observed when teaching and receive little feedback http://ow.ly/Our0m.

Potential role of Calogen as an oral contrast medium in the evaluation of the gastric wall at MRI.

Evaluation of gastric wall pathology using cross-sectional imaging has proved difficult, particularly in the imaging of early, localized disease. The properties of Calogen as a negative oral contrast agent for the evaluation of the upper gastro-intestinal tract and retroperitoneum in CT has been well described. We assess the suitability of this agent as an oral contrast medium for use in MRI examination of the gastric wall, finding the mean scores for Calogen and water with regard to gastric distension to be 8.46 and 5.49, respectively (P < 0.01). Concerning obliteration of mucosal detail, the respective scores are 8.48 and 3.84 (P < 0.01). Calogen is also statistically superior to water with regard to prevention of peristalsis and homogeneity (mean scores 8.15 vs. 5.74 and 8.69 vs. 6.30, respectively). Oral Calogen, therefore, is superior to water as an oral contrast agent for MRI examination of the gastric wall. Its ingestion allows identification of the gastric wall with fat intensity material on both sides, further aiding characterisation of subtle mural anomalies.