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settings Order Article Reprints Open AccessArticle In Silico Analyses of the Role of Codon Usage at the Hemagglutinin Cleavage Site in Highly Pathogenic Avian Influenza Genesis by Mathis Funk 1, Anja C. M. de Bruin 1, Monique I. Spronken 1, Alexander P. Gultyaev 1,2and Mathilde Richard 1,* 1 Department of Viroscience, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands 2 Group Imaging and Bioinformatics, Leiden Institute of Advanced Computer Science (LIACS), Leiden University, 2300 RA Leiden, The Netherlands * Author to whom correspondence should be addressed. Viruses2022,14(7), 1352;https://doi.org/10.3390/v14071352 Received: 22 May 2022/Revised: 10 June 2022/Accepted: 13 June 2022/Published: 21 June 2022 (This article belongs to the Special IssueHighly Pathogenic Avian Influenza Virus Emergence) Download Browse Figures ReviewReportsVersionsNotes Article Views1162 Citations1 Abstract A vast diversity of 16 influenza hemagglutinin (HA) subtypes are found in birds. Interestingly, viruses from only two subtypes, H5 and H7, have so far evolved into highly pathogenic avian influenza viruses (HPAIVs) following insertions or substitutions at the HA cleavage site by the viral polymerase. The mechanisms underlying this striking subtype specificity are still unknown. Here, we compiled a comprehensive dataset of 20,488 avian influenza virus HA sequences to investigate differences in nucleotide and amino acid usage at the HA cleavage site between subtypes and how these might impact the genesis of HPAIVs by polymerase stuttering and realignment. We found that sequences of the H5 and H7 subtypes stand out by their high purine content at the HA cleavage site. In addition, fewer substitutions were necessary in H5 and H7 HAs than in HAs from other subtypes to acquire an insertion-prone HA cleavage site sequence, as defined based on in vitro and in vivo data from the literature. Codon usage was more favorable for HPAIV genesis in sequences of viruses isolated from species or geographical regions in which HPAIV genesis is more frequently observed in nature. The results of the present analyses suggest that the subtype restriction of HPAIV genesis to H5 and H7 influenza viruses might be due to the particular codon usage at the HA cleavage site in these subtypes

Highly Pathogenic Avian Influenza Viruses (HPAIVs) arise from low pathogenic precursors following spillover from wild waterfowl into poultry populations. The main virulence determinant of HPAIVs is the presence of a multi-basic cleavage site (MBCS) in the hemagglutinin (HA) glycoprotein. The MBCS allows for HA cleavage and, consequently, activation by ubiquitous proteases, which results in systemic dissemination in terrestrial poultry. Since 1959, 51 independent MBCS acquisition events have been documented, virtually all in HA from the H5 and H7 subtypes. In the present article, data from natural LPAIV to HPAIV conversions and experimental in vitro and in vivo studies were reviewed in order to compile recent advances in understanding HA cleavage efficiency, protease usage, and MBCS acquisition mechanisms. Finally, recent hypotheses that might explain the unique predisposition of the H5 and H7 HA sequences to obtain an MBCS in nature are discussed.

Border practices at the Italy-Austria border are part of a wider trend of questionable practices used by EU Member States which render irrelevant both the Schengen Agreement and the Dublin Regulation.

BackgroundSyphilitic uveitis is re-emerging alongside the systemic infection. In July 2017, an international group of uveitis-specialised ophthalmologists formed the International Ocular Syphilis Study Group to define current practice patterns.Methods103 Study Group members based in 35 countries completed a 25-item questionnaire focused on case load, clinical presentations, use and interpretation of investigations, treatment and clinical indicators of poor prognosis.ResultsMembers managed a mean of 6.1 patients with syphilitic uveitis in clinics that averaged 707 annual cases of uveitis (0.9%); 53.2% reported increasing numbers over the past decade. Patients presented to more members (40.2%) during secondary syphilis. Uveitis was usually posterior (60.8%) or pan (22.5%); complications included optic neuropathy, macular oedema and posterior synechiae. All members diagnosed syphilitic uveitis using serological tests (simultaneous or sequential testing algorithms), and 97.0% routinely checked for HIV co-infection. Cerebrospinal fluid (CSF) analysis was ordered by 90.2% of members, and 92.7% took uveitis plus Venereal Disease Research Laboratory test (VDRL) or fluorescent treponemal antibody absorption test (FTA-ABS) to indicate neurosyphilis. Patients were commonly co-managed with infectious disease physicians, and treated with penicillin for at least 10–14 days, plus corticosteroid. Features predicting poor outcome included optic neuropathy (86.3%) and initial misdiagnosis (63.7%). Reasons for delayed diagnosis were often practitioner-related. 82.5% of members tested every patient they managed with uveitis for syphilis.ConclusionThis comprehensive report by an international group of uveitis-specialised ophthalmologists provides a current approach for the management of syphilitic uveitis.

Einleitung: Das Kühlen von Verbrennungen ist wichtig, nicht nur um Schmerzen zu lindern, sondern auch um die intradermalen Schäden sowie das Nachbrennen zu verringern. Studien haben gezeigt, dass das Kühlen für etwa 20 bis 30 Minuten mit mäßig warmen Leitungswasser am effizientesten[zum vollständigen Text gelangen Sie über die oben angegebene URL], 38. Jahrestagung der Deutschsprachigen Arbeitsgemeinschaft für Verbrennungsbehandlung (DAV 2020)

Einleitung: Bakterielle Nanocellulose (BNC) ist eine relativ neue Verbandsmatrix, die zu fast 95% aus Wasser besteht. Diese Eigenschaft ermöglicht es dieser Wundauflage, wässrige Substanzen wie Antiseptika zu absorbieren und wieder freizusetzen. Wir untersuchten, wie gut bakterielle Nanocellulose[zum vollständigen Text gelangen Sie über die oben angegebene URL], 38. Jahrestagung der Deutschsprachigen Arbeitsgemeinschaft für Verbrennungsbehandlung (DAV 2020)

Objectives: Subgroup analyses of clinical trial data can be an important tool for understanding when treatment effects differ across populations. That said, even effect estimates from prespecified subgroups in well-conducted trials may not apply to corresponding subgroups in the source population. While this divergence may simply reflect statistical imprecision, there has been less discussion of systematic or structural sources of misleading subgroup estimates. Study Design and Setting: We use directed acyclic graphs to show how selection bias caused by associations between effect measure modifiers and trial selection, whether explicit (e.g., eligibility criteria) or implicit (e.g., self-selection based on race), can result in subgroup estimates that do not correspond to subgroup effects in the source population. To demonstrate this point, we provide a hypothetical example illustrating the sorts of erroneous conclusions that can result, as well as their potential consequences. We also provide a tool for readers to explore additional cases. Conclusion: Treating subgroups within a trial essentially as random samples of the corresponding subgroups in the wider population can be misleading, even when analyses are conducted rigorously and all findings are internally valid. Researchers should carefully examine associations between (and consider adjusting for) variables when attempting to identify heterogeneous treatment effects.

Designing products, spaces, and services for the Everyday has become the focus of designerly research and practice over the last decade. As designers create complex systems that are space-aware, grow and dynamically morph, their tools and methods have to undergo a similar parallel transformation and extension–often towards and borrowing from technical disciplines. Current designers work with complexity and let data shape all facets and modalities of designed artifacts. This article investigates new challenges for design operating at macro, meso, and micro scales. A translational perspective is proposed together with new types of labs and design research infrastructure that address challenges and emerging needs of the design community.