An Adverse Outcomes Approach to Study the Effects of SARS-CoV-2 in 3D Organoid Models.

The novel SARS-CoV-2 virus outbreak is the major cause of a respiratory disease known as COVID-19. It has caused a global pandemic and has resulted in mortality in millions. The primary mode of infection is respiratory ailments, however, due to multi-organ complications, COVID-19 patients displays a greater mortality numbers. Due to the 3Rs Principle (Refine, Reduce, Replacement), the scientific community has shifted its focus to 3D organoid models rather than testing animal models. 3D organoid models provide a better physiological architecture as it mimics the real tissue microenvironment and is the best platform to recapitulate organs in a dish. Hence, the organoid approach provides a more realistic drug response in comparison to the traditional 2D cellular models, which lack key physiological relevance due to the absence of proper surface topography and cellular interactions. Furthermore, an adverse outcome pathway (AOPs) provides a best fit model to identify various molecular and cellular events during the exposure of SARS-CoV-2. Hence, 3D organoid research provides information related to gene expression, cell behavior, antiviral studies and ACE2 expression in various organs. In this review, we discuss state-of-the-art lung, liver and kidney 3D organoid system utilizing the AOPs to study SARS-CoV-2 molecular pathogenesis. Furthermore, current challenges are discussed for future application of 3D organoid systems for various disease states.

Cross-sectional examination of 24-hour movement behaviours among 3- and 4-year-old children in urban and rural settings in low-income, middle-income and high-income countries: the SUNRISE study protocol.

INTRODUCTION: 24-hour movement behaviours (physical activity, sedentary behaviour and sleep) during the early years are associated with health and developmental outcomes, prompting the WHO to develop Global guidelines for physical activity, sedentary behaviour and sleep for children under 5 years of age. Prevalence data on 24-hour movement behaviours is lacking, particularly in low-income and middle-income countries (LMICs). This paper describes the development of the SUNRISE International Study of Movement Behaviours in the Early Years protocol, designed to address this gap. METHODS AND ANALYSIS: SUNRISE is the first international cross-sectional study that aims to determine the proportion of 3- and 4-year-old children who meet the WHO Global guidelines. The study will assess if proportions differ by gender, urban/rural location and/or socioeconomic status. Executive function, motor skills and adiposity will be assessed and potential correlates of 24-hour movement behaviours examined. Pilot research from 24 countries (14 LMICs) informed the study design and protocol. Data are collected locally by research staff from partnering institutions who are trained throughout the research process. Piloting of all measures to determine protocol acceptability and feasibility was interrupted by COVID-19 but is nearing completion. At the time of publication 41 countries are participating in the SUNRISE study. ETHICS AND DISSEMINATION: The SUNRISE protocol has received ethics approved from the University of Wollongong, Australia, and in each country by the applicable ethics committees. Approval is also sought from any relevant government departments or organisations. The results will inform global efforts to prevent childhood obesity and ensure young children reach their health and developmental potential. Findings on the correlates of movement behaviours can guide future interventions to improve the movement behaviours in culturally specific ways. Study findings will be disseminated via publications, conference presentations and may contribute to the development of local guidelines and public health interventions.

Low dose lung radiotherapy for COVID-19 pneumonia: A potential treatment.

The covid-19 pandemic has been affecting many countries across the world and lost precious lives. Most patients suffer from respiratory disease which progresses to the severe acute respiratory syndrome, termed as SARS-CoV-2 pneumonia. A systemic inflammatory response occurs in SARS-CoV-2 pneumonia severely ill patients, The inflammation process if uncontrolled has a detrimental effect, and the release of cytokines play an important role leading to lung fibrosis. Radiation therapy used in low doses has an anti-inflammatory and immunomodulatory effect. Its low cost, wider availability, and decreased risk of acute side effects can reduce the burden on the health care system.