Vandetanib Blocks the Cytokine Storm in SARS-CoV-2-Infected Mice

The portfolio of SARS-CoV-2 small molecule drugs is currently limited to a handful that are either approved (remdesivir), emergency approved (dexamethasone, baricitinib, paxlovid, and molnupiravir), or in advanced clinical trials. Vandetanib is a kinase inhibitor which targets the vascular endothelial growth factor receptor (VEGFR), the epidermal growth factor receptor (EGFR), as well as the RET-tyrosine kinase. In the current study, it was tested in different cell lines and showed promising results on inhibition versus the toxic effect on A549-hACE2 cells (IC500.79 μM) while also showing a reduction of >3 log TCID50/mL for HCoV-229E. The in vivo efficacy of vandetanib was assessed in a mouse model of SARS-CoV-2 infection and statistically significantly reduced the levels of IL-6, IL-10, and TNF-α and mitigated inflammatory cell infiltrates in the lungs of infected animals but did not reduce viral load. Vandetanib also decreased CCL2, CCL3, and CCL4 compared to the infected animals. Vandetanib additionally rescued the decreased IFN-1β caused by SARS-CoV-2 infection in mice to levels similar to that in uninfected animals. Our results indicate that the FDA-approved anticancer drug vandetanib is worthy of further assessment as a potential therapeutic candidate to block the COVID-19 cytokine storm

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time, and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space. While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes, vast areas of the tropics remain understudied. In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity, but it remains among the least known forests in America and is often underrepresented in biodiversity databases. To worsen this situation, human-induced modifications may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge, it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Avaliação dos benefícios da ginástica localizada sobre a postura e a flexibilidade de mulheres na terceira idade Evaluation of the benefits of gymnastic in the posture and flexibility of old women

Desvios posturais e redução na flexibilidade são alterações observadas com o avançar da idade, podendo desencadear dor e dificuldades de movimentação. Este estudo buscou avaliar a influência de um programa de ginástica, de dois meses de duração, sobre a postura e flexibilidade de idosas institucionalizadas (n = 10, 60-75 anos). A postura foi avaliada através do uso de simetrógrafo, fotografias e do teste de equilíbrio sagital pélvico, e a flexibilidade através do teste de sentar e alcançar. Cinco participantes modificaram a postura. Verificamos ainda redução da retroversão pélvica e aumento significativo (p < 0,001) de flexibilidade. Concluímos que um programa de ginástica é capaz de melhorar as alterações posturais de idosas, assim como resgatar a flexibilidade.<br>Ageing is associated with postural alterations and a decrease in flexibility, which results in pain and functional impairment among elders. The objective of this study was to evaluate the effectiveness of an exercise program, conducted during two months, in the posture and flexibility of old women (n = 10, age = 60-75). The posture was evaluated by symetrographic techniques, digital photography and the sagital pelvic balance test, and the flexibility through the sit-and-reach test. Five participants showed alterations in their postures. We verify the reduction of the pelvic retroversion and a significant increase (p < 0.001) in flexibility. We conclude that a gymnastics program is capable of correct some postural alterations of old women due to flexibility improvements

Safety of hospital discharge before return of bowel function after elective colorectal surgery

© 2020 BJS Society Ltd Published by John Wiley & Sons LtdBackground: Ileus is common after colorectal surgery and is associated with an increased risk of postoperative complications. Identifying features of normal bowel recovery and the appropriateness for hospital discharge is challenging. This study explored the safety of hospital discharge before the return of bowel function. Methods: A prospective, multicentre cohort study was undertaken across an international collaborative network. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The main outcome of interest was readmission to hospital within 30 days of surgery. The impact of discharge timing according to the return of bowel function was explored using multivariable regression analysis. Other outcomes were postoperative complications within 30 days of surgery, measured using the Clavien–Dindo classification system. Results: A total of 3288 patients were included in the analysis, of whom 301 (9·2 per cent) were discharged before the return of bowel function. The median duration of hospital stay for patients discharged before and after return of bowel function was 5 (i.q.r. 4–7) and 7 (6–8) days respectively (P < 0·001). There were no significant differences in rates of readmission between these groups (6·6 versus 8·0 per cent; P = 0·499), and this remained the case after multivariable adjustment for baseline differences (odds ratio 0·90, 95 per cent c.i. 0·55 to 1·46; P = 0·659). Rates of postoperative complications were also similar in those discharged before versus after return of bowel function (minor: 34·7 versus 39·5 per cent; major 3·3 versus 3·4 per cent; P = 0·110). Conclusion: Discharge before return of bowel function after elective colorectal surgery appears to be safe in appropriately selected patients