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Recurrent epithelial erosions develop in the cornea due to prior injury or genetic predisposition. Studies of recurrent erosions in animal models allow us to gain insight into how erosions form and are resolved. While slowing corneal epithelial cell migration and reducing their proliferation following treatment with mitomycin C reduce erosion formation in mice after sterile debridement injury, additional factors have been identified related to cytokine expression and immune cell activation. The relationship between recruitment of immune cells to the region of the cornea where erosions form and their potential roles in erosion formation and/or erosion repair remains unexplored in the C57BL/6 mouse recurrent erosion model. Here, high resolution imaging of mouse corneas was performed at D1, D7, and D28 after dulled-blade debridement injury in C57BL/6 mice. Around 50% of these mice have frank corneal erosions at D28 after wounding. A detailed assessment of corneas revealed the involvement of M2 macrophages in both frank and developing erosions at early stages of their formation.

Objective: This systematic review estimated the pooled R0 for early COVID-19 outbreaks and identified the impact of study-related factors such as methods, study location and study period on the estimated R0., Methods: We searched electronic databases for human studies published in English between 1 December 2019 and 30 September 2020 with no restriction on country/region. Two investigators independently performed the data extraction of the studies selected for inclusion during full-text screening. The primary outcome, R0, was analysed by random-effects meta-analysis using the restricted maximum likelihood method., Results: We identified 26,425 studies through our search and included 151 articles in the systematic review, among which 81 were included in the meta-analysis. The estimates of R0 from studies included in the meta-analysis ranged from 0.4 to 12.58. The pooled R0 for COVID-19 was estimated to be 2.66 (95% CI, 2.41-2.94). The results showed heterogeneity among studies and strong evidence of a small-study effect., Conclusions: The high heterogeneity in studies makes the use of the R0 for basic epidemic planning difficult and presents a huge problem for risk assessment and data synthesis. Consensus on the use of R0 for outbreak assessment is needed, and its use for assessing epidemic risk is not recommended.

The 2020 summer Olympic and Paralympic Games in Tokyo were postponed to July-September 2021 due to the coronavirus disease 2019 (COVID-19) pandemic. While COVID-19 has emerged as a monumental health threat for mass gathering events, heat illness must be acknowledged as a potentially large health threat for maintaining health services. We examined the number of COVID-19 admissions and the Tokyo rule for emergency medical care, in Tokyo, from March to September 2020, and investigated the weekly number of emergency transportations due to heat illness and weekly averages of the daily maximum Wet Bulb Globe Temperature (WBGT) in Tokyo in the summer (2016-2020). The peak of emergency transportations due to heat illness overlapped the resurgence of COVID-19 in 2020, and an increase of heat illness patients and WBGT has been observed. Respect for robust science is critical for the decision-making process of mass gathering events during the pandemic, and science-based countermeasures and implementations for COVID-19 will be warranted. Without urgent reconsiderations and sufficient countermeasures, the double burden of COVID-19 and heat-related illnesses in Tokyo will overwhelm the healthcare provision system, and maintaining essential health services will be challenging during the 2021 summer Olympic and Paralympic Games.

Natural products remain a viable source of novel therapeutics, and as detection and extraction techniques improve, we can identify more molecules from a broader set of plant tissues. The aim of this study was an investigation of the cytotoxic and anti-plasmodial activities of the methanol extract from Stephania dielsiana Y.C. Wu leaves and its isolated compounds. Our study led to the isolation of seven alkaloids, among which oxostephanine ( 1 ) is the most active against several cancer cell lines including HeLa, MDA-MB231, MDA-MB-468, MCF-7, and non-cancer cell lines, such as 184B5 and MCF10A, with IC 50 values ranging from 1.66 to 4.35 μM. Morever, oxostephanine ( 1 ) is on average two-fold more active against cancer cells than stephanine ( 3 ), having a similar chemical structure. Cells treated with oxostephanine ( 1 ) are arrested at G2/M cell cycle, followed by the formation of aneuploidy and apoptotic cell death. The G2/M arrest appears to be due, at least in part, to the inactivation of Aurora kinases, which is implicated in the onset and progression of many forms of human cancer. An in-silico molecular modeling study suggests that oxostephanine ( 1 ) binds to the ATP binding pocket of Aurora kinases to inactivate their activities. Unlike oxostephanine ( 1 ), thailandine ( 2 ) is highly effective against only the triple-negative MDA-MB-468 breast cancer cells. However, it showed excellent selectivity against the cancer cell line when compared to its effects on non-cancer cells. Furthermore, thailandine ( 2 ) showed excellent anti-plasmodial activity against both chloroquine-susceptible 3D7 and chloroquine-resistant W2 Plasmodium falciparum strains. The structure-activity relationship of isolated compound was also discussed in this study. The results of this study support the traditional use of Stephania dielsiana Y.C. Wu and the lead molecules identified can be further optimized for the development of highly effective and safe anti-cancer and anti-plasmodial drugs.