Comments to the predecessor of human SARS coronavirus in 2003-2004 epidemic

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Demonstration of receptor binding properties of VP2 of very virulent strain infectious bursal disease virus on Vero cells

Tissue culture adaptation of infectious bursal disease virus (IBDV) results in alternation of three residues on its major capsid protein VP2 and these residues may engage in receptor binding. Although the key of successful infection of tissue culture adapted IBDV in tissue cultures was defined as the virus entering steps, mechanism of the adaptation is poorly understood. In this study, recombinant VP2s of an attenuated strain (D78) and a very virulent strain (HK46) of IBDV tagged with rabbit immunoglobulin G heavy chain were expressed in mammalian cells, generating RAVP2 and RVVP2, respectively, in high purity. Using flow cytometry, both RAVP2 and RVVP2 were demonstrated to bind with Vero cells while these bindings were blocked by D78 viral particles, implying both very virulent IBDVs (vvIBDVs) and attenuated IBDVs bind to Vero cells through the same receptor(s). Since vvIBDVs cannot be propagated directly in tissue cultures, the specific binding between RVVP2 and Vero cells suggests the barrier for tissue culture adaptation may be beyond the virus attachment process. © 2006 Elsevier B.V. All rights reserved.link_to_subscribed_fulltex

Evidence of the recombinant origin of a bat Severe Acute Respiratory Syndrome (SARS)-like coronavirus and its implications on the direct ancestor of SARS coronavirus

Bats have been identified as the natural reservoir of severe acute respiratory syndrome (SARS)-like and SARS coronaviruses (SLCoV and SCoV). However, previous studies suggested that none of the currently sampled bat SLCoVs is the descendant of the direct ancestor of SCoV, based on their relatively distant phylogenetic relationship. In this study, evidence of the recombinant origin of the genome of a bat SLCoV is demonstrated. We identified a potential recombination breakpoint immediately after the consensus intergenic sequence between open reading frame 1 and the S coding region, suggesting the replication intermediates may participate in the recombination event, as previously speculated for other CoVs. Phylogenetic analysis of its parental regions suggests the presence of an uncharacterized SLCoV lineage that is phylogenetically closer to SCoVs than any of the currently sampled bat SLCoVs. Using various Bayesian molecular-clock models, interspecies transfer of this SLCoV lineage from bats to the amplifying host (e.g., civets) was estimated to have happened a median of 4.08 years before the SARS outbreak. Based on this relatively short window period, we speculate that this uncharacterized SLCoV lineage may contain the direct ancestor of SCoV. This study sheds light on the possible host bat species of the direct ancestor of SCoV, providing valuable information on the scope and focus of surveillance for the origin of SCoV. Copyright © 2008, American Society for Microbiology. All Rights Reserved.link_to_OA_fulltex

Invasive fungal infections in critically ill children: epidemiology, risk factors and antifungal drugs

Background: Invasive fungal infections (IFIs) are important infectious complications amongst critically ill children. The most common fungal infections are due to Candida species. Aspergillus, Zygomycetes and Fusarium are also emerging because of the empirical use of antifungal drugs. This updated review discusses the epidemiology of IFIs as well as antifungal drugs, dosing and potential adverse effects in critically ill children. Methods: A PubMed search was conducted with Clinical Queries using the key terms “antifungal”, “children”, “critical care” AND “paediatric intensive care unit” OR “PICU”. The search strategy included clinical trials, randomized controlled trials, meta-analyses, observational studies and reviews and was limited to the English literature in paediatrics. Results: Candida and Aspergillus spp. are the most prevalent fungi in paediatric IFIs, causing invasive candidiasis infections (ICIs) and invasive aspergillosis infections (IAIs), respectively. These IFIs are associated with high morbidity, mortality and healthcare costs. Candida albicans is the principal Candida spp. associated with paediatric ICIs. The risks and epidemiology for IFIs vary if considering previously healthy children treated in the paediatric intensive care unit or children with leukaemia, malignancy or a severe haematological disease. The mortality rate for IAIs in children is 2.5–3.5-fold higher than for ICIs. Four major classes of antifungals for critically ill children are azoles, polyenes, antifungal antimetabolites and echinocandins. Conclusions: Antifungal agents are highly efficacious. For successful treatment outcomes, it is crucial to determine the optimal dosage, monitor pharmacokinetics parameters and adverse effects, and individualized therapeutic monitoring. Despite potent antifungal medications, ICIs and IAIs continue to be serious infections with high mortality rates. Pre-emptive therapy has been used for IAIs. Most guidelines recommend voriconazole as initial therapy of invasive aspergillosis in most patients, with consideration of combination therapy with voriconazole plus an echinocandin in selected patients with severe disease. The challenge is to identify critically ill patients at high risks of ICIs for targeted prophylaxis. Intravenous/per os fluconazole is first-line pre-emptive treatment for Candida spp. whereas intravenous micafungin or intravenous liposomal amphotericin B is alternative pre-emptive treatment. This article is part of the Challenges and strategies in the management of invasive fungal infections Special Issue: https://www.drugsincontext.com/special_issues/challenges-and-strategies-in-the-management-of-invasive-fungal-infection

The classification of intestinal polyposis

10.1038/ng.2474Nature Genetics4512-NGEN

Feasibility and effects of virtual reality motor-cognitive training in community-dwelling older people with cognitive frailty : pilot randomized controlled trial

202202 bcvcVersion of RecordOthersThe authors wish to thank Ms Claire Chan and Ms Abigail Kam for their assistance with the intervention implementation. This study would not have been possible without the support of the Innovation and Technology Fund for Better Living (application number ITB/FBL/4015/19/P); School of Nursing, The Hong Kong Polytechnic University for providing financial support; and Pok Oi Hospital for providing logistic and administrative support.Publishe

The complete genome sequence of severe acute respiratory syndrome coronavirus strain HKU-39849 (HK-39)

The complete genomic nucleotide sequence (29.7kb) of a Hong Kong severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) strain HK-39 is determined. Phylogenetic analysis of the genomic sequence reveals it to be a distinct member of the Coronaviridae family. 5′ RACE assay confirms the presence of at least six subgenomic transcripts all containing the predicted intergenic sequences. Five open reading frames (ORFs), namely ORF1a, 1b, S, M, and N, are found to be homologues to other CoV members, and three more unknown ORFs (X1, X2, and X3) are unparalleled in all other known CoV species. Optimal alignment and computer analysis of the homologous ORFs has predicted the characteristic structural and functional domains on the putative genes. The overall nucleotides conservation of the homologous ORFs is low (<5%) compared with other known CoVs, implying that HK-39 is a newly emergent SARS-CoV phylogenetically distant from other known members. SimPlot analysis supports this finding, and also suggests that this novel virus is not a product of a recent recombinant from any of the known characterized CoVs. Together, these results confirm that HK-39 is a novel and distinct member of the Coronaviridae family, with unknown origin. The completion of the genomic sequence of the virus will assist in tracing its origin.link_to_subscribed_fulltex