Curing cats with Feline Infectious Peritonitis with an oral multi-component drug containing GS-441524

Feline infectious peritonitis (FIP) caused by feline coronavirus (FCoV) is a common dis-ease in cats, fatal if untreated, and no effective treatment is currently legally available. The aim of this study was to evaluate efficacy and toxicity of the multi-component drug Xraphconn$^{®}$ in vitro and as oral treatment in cats with spontaneous FIP by examining survival rate, development of clinical and laboratory parameters, viral loads, anti-FCoV antibodies, and adverse effects. Mass spectrometry and nuclear magnetic resonance identified GS-441524 as an active component of Xraphconn$^{®}$. Eighteen cats with FIP were prospectively followed up while being treated orally for 84 days. Values of key parameters on each examination day were compared to values before treatment initiation using linear mixed-effect models. Xraphconn$^{®}$ displayed high virucidal activity in cell culture. All cats recovered with dramatic improvement of clinical and laboratory parameters and massive reduction in viral loads within the first few days of treatment without serious adverse effects. Oral treatment with Xraphconn$^{®}$ containing GS-441524 was highly effective for FIP without causing serious adverse effects. This drug is an excellent option for the oral treatment of FIP and should be trialed as potential effective treatment option for other severe coronavirus-associated diseases across species

Human cytomegalovirus immediate-early 1 protein rewires upstream STAT3 to downstream STAT1 signaling switching an IL6-type to an IFNγ-like response

MN and CP were supported by the Wellcome Trust (www.wellcome.ac.uk) Institutional Strategic Support Fund and CP was supported by the Deutsche Forschungsgemeinschaft (PA 815/2-1; www.dfg.de).The human cytomegalovirus (hCMV) major immediate-early 1 protein (IE1) is best known for activating transcription to facilitate viral replication. Here we present transcriptome data indicating that IE1 is as significant a repressor as it is an activator of host gene expression. Human cells induced to express IE1 exhibit global repression of IL6- and oncostatin M-responsive STAT3 target genes. This repression is followed by STAT1 phosphorylation and activation of STAT1 target genes normally induced by IFNγ. The observed repression and subsequent activation are both mediated through the same region (amino acids 410 to 445) in the C-terminal domain of IE1, and this region serves as a binding site for STAT3. Depletion of STAT3 phenocopies the STAT1-dependent IFNγ-like response to IE1. In contrast, depletion of the IL6 receptor (IL6ST) or the STAT kinase JAK1 prevents this response. Accordingly, treatment with IL6 leads to prolonged STAT1 instead of STAT3 activation in wild-type IE1 expressing cells, but not in cells expressing a mutant protein (IE1dl410-420) deficient for STAT3 binding. A very similar STAT1-directed response to IL6 is also present in cells infected with a wild-type or revertant hCMV, but not an IE1dl410-420 mutant virus, and this response results in restricted viral replication. We conclude that IE1 is sufficient and necessary to rewire upstream IL6-type to downstream IFNγ-like signaling, two pathways linked to opposing actions, resulting in repressed STAT3- and activated STAT1-responsive genes. These findings relate transcriptional repressor and activator functions of IE1 and suggest unexpected outcomes relevant to viral pathogenesis in response to cytokines or growth factors that signal through the IL6ST-JAK1-STAT3 axis in hCMV-infected cells. Our results also reveal that IE1, a protein considered to be a key activator of the hCMV productive cycle, has an unanticipated role in tempering viral replication.Publisher PDFPeer reviewe

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

GMF - HO. Gruppenbezogene Menschenfeindlichkeit - Kurzskala Homophobie

Krause D, Zick A. GMF - HO. Gruppenbezogene Menschenfeindlichkeit - Kurzskala Homophobie. In: Kemper CJ, Brähler E, Zenger M, eds. Psychologische und sozialwissenschaftliche Kurzskalen: standardisierte Erhebungsinstrumente für Wissenschaft und Praxis. Berlin: Medizinisch Wissenschaftliche Verlagsgesellschaft; 2013: 119-121

GMF - LZ. Gruppenbezogene Menschenfeindlichkeit - Kurzskala Langzeitarbeitslosenabwertung

Krause D, Zick A. GMF - LZ. Gruppenbezogene Menschenfeindlichkeit - Kurzskala Langzeitarbeitslosenabwertung. In: Kemper CJ, Brähler E, Zenger M, eds. Psychologische und sozialwissenschaftliche Kurzskalen: standardisierte Erhebungsinstrumente für Wissenschaft und Praxis. Berlin: Medizinisch Wissenschaftliche Verlagsgesellschaft; 2013: 122-124

GMF - BE. Gruppenbezogene Menschenfeindlichkeit - Kurzskala Abwertung von Menschen mit Behinderung

Krause D, Zick A. GMF - BE. Gruppenbezogene Menschenfeindlichkeit - Kurzskala Abwertung von Menschen mit Behinderung. In: Kemper CJ, Brähler E, Zenger M, eds. Psychologische und sozialwissenschaftliche Kurzskalen: standardisierte Erhebungsinstrumente für Wissenschaft und Praxis. Berlin: Medizinisch Wissenschaftliche Verlagsgesellschaft; 2013: 109-111

GMF - OB. Gruppenbezogene Menschenfeindlichkeit - Kurzskala Obdachlosenabwertung

Krause D, Zick A. GMF - OB. Gruppenbezogene Menschenfeindlichkeit - Kurzskala Obdachlosenabwertung. In: Kemper CJ, Brähler E, Zenger M, eds. Psychologische und sozialwissenschaftliche Kurzskalen: standardisierte Erhebungsinstrumente für Wissenschaft und Praxis. Berlin: Medizinisch Wissenschaftliche Verlagsgesellschaft; 2013: 128-130

GMF - MI. Gruppenbezogene Menschenfeindlichkeit - Kurzskala Muslim- und Islamfeindlichkeit

Krause D, Zick A. GMF - MI. Gruppenbezogene Menschenfeindlichkeit - Kurzskala Muslim- und Islamfeindlichkeit. In: Kemper CJ, Brähler E, Zenger M, eds. Psychologische und sozialwissenschaftliche Kurzskalen: standardisierte Erhebungsinstrumente für Wissenschaft und Praxis. Berlin: Medizinisch Wissenschaftliche Verlagsgesellschaft; 2013: 125-127

GMF - SX. Gruppenbezogene Menschenfeindlichkeit - Kurzskala Sexismus

Krause D, Zick A. GMF - SX. Gruppenbezogene Menschenfeindlichkeit - Kurzskala Sexismus. In: Kemper CJ, Brähler E, Zenger M, eds. Psychologische und sozialwissenschaftliche Kurzskalen: standardisierte Erhebungsinstrumente für Wissenschaft und Praxis. Berlin: Medizinisch Wissenschaftliche Verlagsgesellschaft; 2013: 134-136

GMF - FF. Gruppenbezogene Menschenfeindlichkeit - Kurzskala Fremdenfeindlichkeit

Krause D, Zick A. GMF - FF. Gruppenbezogene Menschenfeindlichkeit - Kurzskala Fremdenfeindlichkeit. In: Kemper CJ, Brähler E, Zenger M, eds. Psychologische und sozialwissenschaftliche Kurzskalen: standardisierte Erhebungsinstrumente für Wissenschaft und Praxis. Berlin: Medizinisch Wissenschaftliche Verlagsgesellschaft; 2013: 115-118