A scoping review of remote facilitation during simulation-based healthcare education.

BACKGROUND: Remote facilitation is a synchronous distance education method where instructors facilitate a lesson, in real-time, in physically separate conditions. In this scoping review, we aimed to describe types of remote facilitation used in a healthcare simulation, the influences on learner outcomes, and related factors. METHODS: We accessed PubMed, EMBASE, CINAHL, ERIC, and Web of Science using our search strategies. Five reviewers performed the review using the Preferred Reporting Items for Systematic Reviews and Meta Analysis extension for Scoping Reviews (PRISMA-ScR) framework, and the Johanna Briggs Institute (JBI) guidelines. RESULTS: We included a total of 29 articles presenting 28 simulation studies. The most common tool was videoconferencing (n = 26, 89.7%). Knowledge improvement was the most frequently measured outcome. There was no significant difference in learning outcomes between the two teaching modes. There were differences in learners' preferences and satisfaction with remote facilitators before and after COVID-19. CONCLUSIONS: Our scoping review indicates that remote facilitation has been widely accepted in many healthcare professions using various types of simulation modalities. Remote facilitation can be used to overcome logistical problems of synchronous multi-location education, and to improve learner knowledge, skills, and confidence measured by instructor evaluation or self-assessment.

T3 Intratracheal Therapy Alleviates Pulmonary Pathology in an Elastase-Induced Emphysema-Dominant COPD Mouse Model.

Chronic obstructive pulmonary disease (COPD) is a complex pulmonary condition characterized by bronchitis, emphysema, and mucus stasis. Due to the variability in symptoms among patients, traditional approaches to treating COPD as a singular disease are limited. This led us to focus on phenotype/endotype classifications. In this study, we explore the potential therapeutic role of thyroid hormone (T3) by using mouse models: emphysema-dominant elastase-induced COPD and airway-dominant C57BL/6-ßENaC-Tg to represent different types of the disease. Here, we showed that intratracheal T3 treatment (40, 80 µg/kg, i.t., every other day) resulted in significant improvements regarding emphysema and the enhancement of respiratory function in the elastase-induced COPD model. T3-dependent improvement is likely linked to the up-regulation of Ppargc1a, a master regulator of mitochondrial biogenesis, and Gclm, a factor associated with oxidative stress. Conversely, neither short- nor long-term T3 treatments improved COPD pathology in the C57BL/6-ßENaC-Tg mice. Because the up-regulation of extrathyroidal T3-producing enzyme Dio2, which is also considered a marker of T3 requirement, was specifically observed in elastase-induced COPD lungs, these results demonstrate that exogenous T3 supplementation may have therapeutic potential for acute but not chronic COPD exacerbation. Moreover, this study highlights the relevance of considering not only COPD phenotypes but also COPD endotypes (expression levels of Ppargc1a and/or Dio2) in the research and development of better treatment approaches for COPD.

A case of toxic epidermal necrolysis comorbid with severe burns.

Toxic epidermal necrolysis (TEN) and severe burns both have high mortality rates, but coexistence is extremely rare. The specificity of developing TEN in burn patients is not well understood and its treatment strategy is not established. Case Presentation: A 68-year-old man was carried to our hospital with severe burns covering 35% of his body surface area. He developed bacteremia during treatment of burns and required antimicrobial therapy. However, erythema appeared on the trunk and upper limbs and rapidly spread to the extremities, leading to a diagnosis of TEN. The rash gradually improved after terminating antimicrobial therapy and administrating of 1,000 mg/day methylprednisolone for 3 days. The rash caused by TEN was confined to non-burned areas, suggesting that TEN may less likely occur at burn sites. Conclusion: It is necessary to pay attention because burn patients can develop TEN concomitantly. Corticosteroids therapy may be effective for TEN even in severe burn patients.

Metformin suppresses epithelial sodium channel hyperactivation and its associated phenotypes in a mouse model of obstructive lung diseases.

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death in the world, and has no radical treatment. Inhibition of amiloride-sensitive epithelial sodium ion channel (ENaC) has now been considered as a potential therapeutic target against COPD. One possible modulator of ENaC is AMP-activated protein kinase (AMPK), a key molecule that controls a wide variety of cellular signals; however, little is known about whether metformin, a clinically available AMPK activator, has a protective role against ENaC-associated chronic pulmonary phenotypes, such as emphysema and pulmonary dysfunction. We first used ENaC-overexpressing human bronchial epithelial cells (ß/γENaC-16HBE14o-) and identified that Metformin significantly reduced ENaC activity. Consistently, in vivo treatment of ENaC-overexpressing COPD mouse model (C57BL/6-ßENaC-Tg mice) showed improvement of emphysema and pulmonary dysfunction, without any detrimental effect on non-pulmonary parameters (blood glucose level etc.). Bronchoalveolar lavage fluid (BALF) and lung tissue analyses revealed significant suppression in the infiltration of neutrophils as well as the expression of inflammatory markers (KC), neutrophil gelatinase (MMP9) and macrophage elastase (MMP12) in metformin-treated C57BL/6-ßENaC-Tg mice. Overall, the present study demonstrates that metformin directly inhibits ENaC activity in vitro and provides the first evidence of therapeutical benefit of Metformin for COPD with higher ENaC activity.

Higher Blood Uric Acid in Female Humans and Mice as a Protective Factor against Pathophysiological Decline of Lung Function.

The oxidant/antioxidant imbalance plays a pivotal role in the lung. Uric acid (UA), an endogenous antioxidant, is highly present in lung tissue, however, its impact on lung function under pathophysiological conditions remains unknown. In this work, pharmacological and genetic inhibition of UA metabolism in experimental mouse models of acute and chronic obstructive pulmonary disease (COPD) revealed that increased plasma UA levels improved emphysematous phenotype and lung dysfunction in accordance with reduced oxidative stress specifically in female but not in male mice, despite no impact of plasma UA induction on the pulmonary phenotypes in nondiseased mice. In vitro experiments determined that UA significantly suppressed hydrogen peroxide (H2O2)-induced oxidative stress in female donor-derived primary human bronchial epithelial (NHBE) cells in the absence of estrogen, implying that the benefit of UA is limited to the female airway in postmenopausal conditions. Consistently, our clinical observational analyses confirmed that higher blood UA levels, as well as the SLC2A9/GLUT9 rs11722228 T/T genotype, were associated with higher lung function in elderly human females. Together, our findings provide the first unique evidence that higher blood UA is a protective factor against the pathological decline of lung function in female mice, and possibly against aging-associated physiological decline in human females.

Melinjo seed extract increases adiponectin multimerization in physiological and pathological conditions.

Melinjo seed extract (MSE) contains large amounts of polyphenols, including dimers of trans-resveratrol (e.g. gnetin C, L, gnemonoside A, B and D), and has been shown to potentially improve obesity. However, there is no clinical evidence regarding the anti-obesity effects of MSE, and its mechanisms are also unclear. We investigated the hypothesis that MSE supplementation increases the adiponectin (APN) multimerization via the up-regulation of disulfide bond A oxidoreductase-like protein (DsbA-L) under either or both physiological and obese conditions. To investigate the effect of MSE on the physiological condition, 42 healthy young volunteers were enrolled in a randomized, double-blind placebo-controlled clinical trial for 14 days. The participants were randomly assigned to the MSE 150 mg/day, MSE 300 mg/day or placebo groups. Furthermore, in order to investigate the effect of MSE on APN levels under obese conditions, we administered MSE powder (500 or 1000 mg/kg/day) to control-diet- or high-fat-diet (HFD)-fed C57BL/6 mice for 4 weeks. All participants completed the clinical trial. The administration of MSE 300 mg/day was associated with an increase in the ratio of HMW/total APN in relation to the genes regulating APN multimerization, including DsbA-L. Furthermore, this effect of MSE was more pronounced in carriers of the DsbA-L rs191776 G/T or T/T genotype than in others. In addition, the administration of MSE to HFD mice suppressed their metabolic abnormalities (i.e. weight gain, increased blood glucose level and fat mass accumulation) and increased the levels of total and HMW APN in serum and the mRNA levels of ADIPOQ and DsbA-L in adipose tissue. The present study suggests that MSE may exert beneficial effects via APN multimerization in relation to the induction of DsbA-L under both physiological and obese conditions.

Azithromycin Inhibits Constitutive Airway Epithelial Sodium Channel Activation in Vitro and Modulates Downstream Pathogenesis in Vivo.

Epithelial sodium channel (ENaC) is an amiloride-sensitive sodium ion channel that is expressed in epithelial tissues. ENaC overexpression and/or hyperactivation in airway epithelial cells cause sodium over-absorption and dysregulated ciliary movement for mucus clearance; however, the agents that suppress constitutive airway ENaC activation are yet to be clinically available. Here, we focused on macrolides, which are widely used antibiotics that have many potential immunomodulatory effects. We examined whether macrolides could modulate constitutive ENaC activity and downstream events that typify cystic fibrosis (CF) and chronic obstructive pulmonary diseases (COPD) in in vitro and in vivo models of ENaC overexpression. Treatment of ENaC-overexpressing human bronchial epithelial cells (ß/γENaC-16HBE14o- cells) with three macrolides (erythromycin, clarithromycin, azithromycin) confirmed dose-dependent suppression of ENaC function. For in vivo studies, mice harboring airway specific ßENaC overexpression (C57BL/6J-ßENaC-transgenic mice) were treated orally with azithromycin, a well-established antimicrobial agent that has been widely prescribed. Azithromycin treatment modulated pulmonary mechanics, emphysematous phenotype and pulmonary dysfunction. Notably, a lower dose (3 mg kg-1) of azithromycin significantly increased forced expiratory volume in 0.1 s (FEV0.1), an inverse indicator of bronchoconstriction. Although not statistically significant, improvement of pulmonary obstructive parameters such as emphysema and lung dysfunction (FEV0.1%) was observed. Our results demonstrate that macrolides directly attenuate constitutive ENaC function in vitro and may be promising for the treatment of obstructive lung diseases with defective mucociliary clearance, possibly by targeting ENaC hyperactivation.

Intratracheal GLP-1 receptor agonist treatment up-regulates mucin via p38 and exacerbates emphysematous phenotype in mucus hypersecretory obstructive lung diseases.

Glucagon-like peptide-1 (GLP-1) is a gastrointestinal hormone that stimulates glucose-mediated insulin production by pancreatic beta cells. It is also associated with protective effects in multiple tissues. GLP-1 receptor is highly expressed in pulmonary tissue, hinting possible pulmonary delivery of GLP-1 drugs. However, little is known about the role of GLP-1 signaling in the lung, especially in mucus hypersecretory obstructive lung diseases. Here, we showed that treatment with exendin-4, a clinically available GLP-1 receptor agonist, up-regulates mucin expression in normal airway epithelial cells and in the lung of normal mice, indicating mucus stimulatory effect of GLP-1 under physiological condition. Exendin-4 also increased mucin expression in in vitro cellular and in vivo murine models of obstructive lung diseases via the activation of p38 MAP kinase. Notably, mucin induction in vivo exacerbated key pulmonary abnormalities including emphysematous phenotypes, implying that GLP-1 signaling in the lung is detrimental under pulmonary obstructive condition. Another GLP-1 receptor agonist liraglutide had similar induction of mucin. Together, our studies not only demonstrate novel physiological and pathological roles of GLP-1 in the lung but may also caution against the clinical use of inhaled GLP-1 receptor agonists in the patients with obstructive lung diseases.

Auto-measure emphysematous parameters and pathophysiological gene expression profiles in experimental mouse models of acute and chronic obstructive pulmonary diseases.

Pulmonary emphysema, inflammation and senescence-like phenotype are pathophysiological characteristics of chronic obstructive pulmonary disease (COPD). Recently, a murine model of COPD has been established by inducing airway-specific overexpression of epithelial Na+ channel ß subunit (ßENaC-Tg mice). However, little is known about the histological and biochemical differences between ßENaC-Tg mice and an existing acute emphysematous mouse model (elastase-induced model). Here, we first utilized whole lung image-based quantification method for histological analysis to determine auto-measure parameters, including alveolar area, alveolar perimeter, (major axis + minor axis)/2 and Feret diameter. Even though the extent of emphysema was similar in both models, the coefficient of variation (CV) of all histological parameters was smaller in ßENaC-Tg mice, indicating that ßENaC-Tg mice show homogeneous emphysema as compared with elastase-induced acute model. Expression analysis of lung tissue RNAs further revealed that elastase-induced model exhibits transient changes of inflammation markers (Kc, Il-6, Lcn2) and senescence-related markers (Sirt1, p21) at emphysema-initiation stage (1 day), which does not last until emphysema-manifestation stage (3 weeks); while the up-regulation is stable at emphysema-manifestation stage in ßENaC-Tg mice (14-week old). Thus, these studies demonstrate that ßENaC-Tg mice exhibit diffuse-type emphysema with stable expression of inflammatory and senescence-like markers.

Integrative expression analysis identifies a novel interplay between CFTR and linc-SUMF1-2 that involves CF-associated gene dysregulation.

Cystic fibrosis transmembrane regulator (CFTR) is a cyclic AMP-dependent Cl- channel, and its dysfunction, due to CFTR gene mutations, causes the lethal inherited disorder cystic fibrosis (CF). To date, widespread dysregulation of certain coding genes in CF airway epithelial cells is well studied and considered as the driver of pulmonary abnormality. However, the involvement of non-coding genes, novel classes of functional RNAs with little or no protein-coding capacity, in the regulation of CF-associated gene dysregulation is poorly understood. Here, we utilized integrative analyses of human transcriptome array (HTA) and characterized 99 coding and 91 non-coding RNAs that are dysregulated in CFTR-defective CF bronchial epithelial cell line CFBE41o-. Among these genes, the expression level of linc-SUMF1-2, an intergenic non-coding RNA (lincRNA) whose function is unknown, was inversely correlated with that of WT-CFTR and consistently higher in primary human CF airway epithelial cells (DHBE-CF). Further integrative analyses under linc-SUMF1-knockdown condition determined MXRA5, SEMA5A, CXCL10, AK022877, CTGF, MYC, AREG and LAMB3 as both CFTR- and linc-SUMF1-2-dependent dysregulated gene sets in CF airway epithelial cells. Overall, our analyses reveal linc-SUMF1-2 as a dysregulated non-coding gene in CF as well as CFTR-linc-SUMF1-2 axis as a novel regulatory pathway involved in CF-associated gene dysregulation.