Acquisition of Human-Type Receptor Binding Specificity by New H5N1 Influenza Virus Sublineages during Their Emergence in Birds in Egypt

Highly pathogenic avian influenza A virus subtype H5N1 is currently widespread in Asia, Europe, and Africa, with 60% mortality in humans. In particular, since 2009 Egypt has unexpectedly had the highest number of human cases of H5N1 virus infection, with more than 50% of the cases worldwide, but the basis for this high incidence has not been elucidated. A change in receptor binding affinity of the viral hemagglutinin (HA) from α2,3- to α2,6-linked sialic acid (SA) is thought to be necessary for H5N1 virus to become pandemic. In this study, we conducted a phylogenetic analysis of H5N1 viruses isolated between 2006 and 2009 in Egypt. The phylogenetic results showed that recent human isolates clustered disproportionally into several new H5 sublineages suggesting that their HAs have changed their receptor specificity. Using reverse genetics, we found that these H5 sublineages have acquired an enhanced binding affinity for α2,6 SA in combination with residual affinity for α2,3 SA, and identified the amino acid mutations that produced this new receptor specificity. Recombinant H5N1 viruses with a single mutation at HA residue 192 or a double mutation at HA residues 129 and 151 had increased attachment to and infectivity in the human lower respiratory tract but not in the larynx. These findings correlated with enhanced virulence of the mutant viruses in mice. Interestingly, these H5 viruses, with increased affinity to α2,6 SA, emerged during viral diversification in bird populations and subsequently spread to humans. Our findings suggested that emergence of new H5 sublineages with α2,6 SA specificity caused a subsequent increase in human H5N1 influenza virus infections in Egypt, and provided data for understanding the virus's pandemic potential

State of the art review: the data revolution in critical care

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2015 and co-published as a series in Critical Care. Other articles in the series can be found online at http://ccforum.com/series/annualupdate2015. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901

Is childhood trauma associated with lifetime suicide attempts in women with bulimia nervosa?

PURPOSE: The purpose of this study was to explore the association between specific forms of childhood abuse and neglect with lifetime suicide attempts in women with bulimia nervosa (BN). METHODS: Two hundred and four women aged 18–65 (mean = 25.6 years, SD = 9.13) with full or subclinical BN were recruited in five US Midwestern communities and specialized eating disorder clinics. Participants completed questionnaires including the Childhood Trauma Questionnaire (CTQ) and self-reported whether they had ever had a lifetime suicide attempt. Logistic regression analyses were used to predict lifetime suicide attempts from each subscale of the CTQ. RESULTS: Childhood emotional, physical, and sexual abuse were significantly associated with the presence of a lifetime suicide attempt in women with BN. Childhood emotional and physical neglect were not associated with suicide attempts. CONCLUSIONS: Individuals with BN who have experienced childhood emotional and sexual abuse are at increased risk of a lifetime suicide attempt. Future research is needed to understand the mechanism to address in treatment and prevention efforts. It is important for clinicians to be aware of the potential increased risk of suicide in individuals with BN with a history of childhood abuse