Selective deletion of connective tissue growth factor attenuates experimentally-induced pulmonary fibrosis and pulmonary arterial hypertension

Connective tissue growth factor (CTGF, CCN2) is a matricellular protein which plays key roles in normal mammalian development and in tissue homeostasis and repair. In pathological conditions, dysregulated CCN2 has been associated with cancer, cardiovascular disease, and tissue fibrosis. In this study, genetic manipulation of the CCN2 gene was employed to investigate the role of CCN2 expression in vitro and in experimentally-induced models of pulmonary fibrosis and pulmonary arterial hypertension (PAH). Knocking down CCN2 using siRNA, reduced expression of pro-fibrotic markers (fibronectin p < 0.01, collagen type I p < 0.05, α-SMA p < 0.0001, TIMP-1 p < 0.05 and IL-6 p < 0.05) in TGF-β-treated lung fibroblasts derived from systemic sclerosis patients. In vivo studies were performed in mice using a conditional gene deletion strategy targeting CCN2 in a fibroblast-specific and time-dependent manner in two models of lung disease. CCN2 deletion significantly reduced pulmonary interstitial scarring and fibrosis following bleomycin-instillation, as assessed by fibrotic scores (wildtype bleomycin 3.733 ± 0.2667 vs CCN2 knockout (KO) bleomycin 4.917 ± 0.3436, p < 0.05) and micro-CT. In the well-established chronic hypoxia model of pulmonary hypertension, CCN2 gene deletion resulted in a significant decrease in pulmonary vessel remodelling, less right ventricular hypertrophy and a reduction in the haemodynamic measurements characteristic of PAH (RVSP and RV/LV + S were significantly reduced (p < 0.05) in CCN2 KO compared to WT mice in hypoxic/SU5416 conditions). These results support a prominent role for CCN2 in pulmonary fibrosis and in vessel remodelling associated with PAH. Therefore, therapeutics aimed at blocking CCN2 function are likely to benefit several forms of severe lung disease

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

The Biochemical Literacy Framework: Inviting pedagogical innovation in higher education

When developing meaningful curricula, institutions must engage with the desired disciplinary attributes of their graduates. Successfully employed in several areas, including psychology and chemistry, disciplinary literacies provide structure for the development of core competencies‐pursuing progressive education. To this end, we have sought to develop a comprehensive blueprint of a graduate biochemist, providing detailed insight into the development of skills in the context of disciplinary knowledge. The Biochemical Literacy Framework (BCLF) aspires to encourage innovative course design in both the biochemical field and beyond through stimulating discussion among individuals developing undergraduate biochemistry degree courses based on pedagogical best practice. Here, we examine the concept of biochemical literacy aiming to start answering the question: What must individuals do and know to approach and transform ideas in the context of the biochemical sciences? The BCLF began with the guidance published by relevant learned societies – including the Royal Society of Biology, the Biochemical Society, the American Society for Biochemistry and Molecular Biology and the Quality Assurance Agency, before considering relevant pedagogical literature. We propose that biochemical literacy is comprised of seven key skills: critical thinking, self‐management, communication, information literacy, visual literacy, practical skills and content knowledge. Together, these form a dynamic, highly interconnected and interrelated meta‐literacy supporting the use of evidence‐based, robust learning techniques. The BCLF is intended to form the foundation for discussion between colleagues, in addition to forming the groundwork for both pragmatic and exploratory future studies into facilitating and further defining biochemical literacy

Scaffolding a collaborative process through concept mapping: a case study on faculty development

Purpose Concept maps have been described as a valuable tool for exploring curriculum knowledge. However, less attention has been given to the use of them to visualise contested and tacit knowledge, i.e. the values and perceptions of teachers that underpin their practice. This paper aims to explore the use of concept mapping to uncover academics’ views and help them articulate their perspectives within the framework provided by the concepts of pedagogic frailty and resilience in a collaborative environment. Design/methodology/approach Participants were a group of five colleagues within a Biochemical Science Department, working on the development of a new undergraduate curriculum. A qualitative single-case study was conducted to get some insights on how concept mapping might scaffold each step of the collaborative process. They answered the online questionnaire; their answers were “translated” into an initial expert-constructed concept map, which was offered as a starting point to articulate their views during a group session, resulting in a consensus map. Findings Engaging with the questionnaire was useful for providing the participants with an example of an “excellent” map, sensitising them to the core concepts and the possible links between them, without imposing a high level of cognitive load. This fostered dialogue of complex ideas, introducing the potential benefits of consensus maps in team-based projects. Originality/value An online questionnaire may facilitate the application of the pedagogic frailty model for academic development by scaling up the mapping process. The map-mediated facilitation of dialogue within teams of academics may facilitate faculty development by making explicit the underpinning values held by team members

Sleep Quality in Adolescents With Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME)

Study Objectives: Little is known about the type and severity of sleep disturbances in the pediatric chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) population, compared with healthy adolescents. Using a range of objective and subjective measures, the aim of this study was to investigate sleep quality, the relationship between objective and subjective measures of sleep quality, and their associations with anxiety in adolescents with CFS/ME compared with healthy controls. Methods: Twenty-one adolescents with CFS/ME aged 13 to 18 years (mean age 15.57 ± 1.40), and 145 healthy adolescents aged 13 to 18 years (mean age 16.2 ± 1.00) wore actigraphy watches continuously for 2 weeks to collect a number of objective sleep variables. The Pittsburgh Sleep Quality Index was used to obtain a subjective measure of sleep quality. Anxiety was measured by the Spence Children&#039;s Anxiety scale. Results: On average over the 2-week period, adolescents with CFS/ME were found to have (1) significantly longer objective sleep onset latency, time in bed, total sleep time, and a later rise time (all P &amp;lt; .005), and (2) significantly poorer subjective sleep quality (P &amp;lt; .001), compared with healthy adolescents. The CFS/ME patient group displayed higher levels of anxiety (P &amp;lt; .05), and in both groups, higher levels of anxiety were significantly related to poorer subjective sleep quality (P &amp;lt; .001). Conclusions: This study provides objective and subjective evidence of sleep disturbance in adolescents with CFS/ME compared with healthy adolescent controls