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Holland Whitfield posted an update 6 months ago
Many human viral diseases are a consequence of a zoonotic event. Some of the diseases caused by these zoonotic events have affected millions of people around the world, some of which have resulted in high rates of morbidity/mortality in humans. Changes in the viral proteins that function as ligands of the host receptor may promote the spillover between species. The most recent of these zoonotic events that have caused an ongoing epidemic of high magnitude is the Covid-19 epidemics caused by SARS-CoV-2. The aim of this study was to determine the mutation(s) in the sequence of the spike protein of the SARS-CoV-2 that might be favoring human to human transmission. An in silico approach was performed, and changes were detected in the S1 subunit of the receptor-binding domain of spike. The observed changes have significant effect on SARS-CoV-2 spike/ACE2 interaction and produce a reduction in the binding energy, compared to the one of the Bat-CoV to this receptor. The data presented in this study suggest a higher affinity of the SARS-Cov-2 spike protein to the human ACE2 receptor, compared to the one of Bat-CoV spike and ACE2. This could be the cause of the rapid viral spread of SARS-CoV-2 in humans. Copyright © 2020 Ortega et al.Direct-acting antivirals are effective tools to control viral infections. SARS-CoV-2 is a coronavirus associated with the epidemiological outbreak in late 2019. Previous reports showed that HIV-1 protease inhibitors could block SARS-CoV main protease. Based on that and using an in silico approach, we evaluated SARS-CoV-2 main protease as a target for HIV-1 protease inhibitors to reveal the structural features related to their antiviral effect. Our results showed that several HIV inhibitors such as lopinavir, ritonavir, and saquinavir produce strong interaction with the active site of SARS-CoV-2 main protease. Furthermore, broad library protease inhibitors obtained from PubChem and ZINC (www.zinc.docking.org) were evaluated. Our analysis revealed 20 compounds that could be clustered into three groups based on their chemical features. Then, these structures could serve as leading compounds to develop a series of derivatives optimizing their activity against SARS-CoV-2 and other coronaviruses. Altogether, the results presented in this work contribute to gain a deep understanding of the molecular pharmacology of SARS-CoV-2 treatment and validate the use of protease inhibitors against SARS-CoV-2. Copyright © 2020 Ortega et al.Introduction China has adopted a people-centred integrated care model to reform its severely hospital-centric and fragmented delivery system. As a template of this model in urban China, the Luohu Hospital Group has generated considerable public and academic interest to scale it up. TKI-258 price Methods Guided by a policy triangle framework, this qualitative study explored the context, actors, content, and process of founding the Luohu Hospital Group. Three semi-structured interviews and five focus groups were conducted among 35 key informants. Content analysis was used to analyse the data. Results The reform in Luohu took place in a competitive health care market, based on the comprehensive health reform in Shenzhen. Under the strong leadership of the district government, the reform adopted comprehensive strategies to strengthen primary care and care coordination, improve the quality and efficiency of health care delivery, and promote population health. The reform achieved a high level of organisational integration but was still in the process of fulfilling professional and clinical integration. Conclusions and discussion The establishment of the Luohu Hospital Group transformed the originally fragmented delivery system into a tightly integrated service delivery networks. Though valuable lessons have been generated, the reform and its impacts require ongoing monitoring. Copyright © 2020 The Author(s).Aim A systemic review and analysis of evolution journey of indices, such as conformity index (CI), homogeneity index (HI) and gradient index (GI), described in the literature. Background Modern radiotherapy techniques like VMAT, SRS and SBRT produce highly conformal plans and provide better critical structure and normal tissue sparing. These treatment techniques can generate a number of competitive plans for the same patients with different dose distributions. Therefore, indices like CI, HI and GI serve as complementary tools in addition to visual slice by slice isodose verification while plan evaluation. Reliability and accuracy of these indices have been tested in the past and found shortcomings and benefits when compared to one another. Material and methods Potentially relevant studies published after 1993 were identified through a pubmed and web of science search using words “conformity index”, “Homogeneity index”, “Gradient index”,” Stereotactic radiosurgery”,” stereotactic Body radiotherapy” “complexity metrics” and “plan evaluation index”. Combinations of words “plan evaluation index conformity index” were also searched as were bibliographies of downloaded papers. Results and conclusions Mathematical definitions of plan evaluation indices modified with time. CI definitions presented by various authors tested at their own and could not be generalized. Those mathematical definitions of CI which take into account OAR sparing grant more confidence in plan evaluation. Gradient index emerged as a significant plan evaluation index in addition to CI whereas homogeneity index losing its credibility. Biological index base plan evaluation is becoming popular and may replace or alter the role of dosimetrical indices. © 2020 Greater Poland Cancer Centre. Published by Elsevier B.V. All rights reserved.Background Osteoarthritis (OA) is characterized by inflammation and extracellular matrix (ECM) degradation and is one of the most common chronic degenerative joint diseases that causes pain and disability in adults. Urolithin A (UA) has been widely reported for its anti-inflammatory properties in several chronic diseases. However, the effects of UA on OA remain unclear. The aim of the current study was to investigate the anti-inflammatory effects and mechanism of UA in interleukin-1β (IL-1β)-induced chondrocytes. Results No marked UA cytotoxicity was noted, and UA protected cartilage from damage following IL-1β stimulation in micromasses. Moreover, UA promoted the expression of anabolic factors including Sox-9, Collagen II, and Aggrecan while inhibiting the expression of catabolic factors such as matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4) in rat chondrocytes. Protective effects of UA were also observed in ex vivo organ culture of articular cartilage.