Loss of a single N-linked glycan from the hemagglutinin of influenza virus is associated with resistance to collectins and increased virulence in mice

BACKGROUND: Glycosylation on the globular head of the hemagglutinin (HA) protein of influenza virus acts as an important target for recognition and destruction of virus by innate immune proteins of the collectin family. This, in turn, modulates the virulence of different viruses for mice. The role of particular oligosaccharide attachments on the HA in determining sensitivity to collectins has yet to be fully elucidated. METHODS: When comparing the virulence of H3N2 subtype viruses for mice we found that viruses isolated after 1980 were highly glycosylated and induced mild disease in mice. During these studies, we were surprised to find a small plaque variant of strain A/Beijing/353/89 (Beij/89) emerged following infection of mice and grew to high titres in mouse lung. In the current study we have characterized the properties of this small plaque mutant both in vitro and in vivo. RESULTS: Small plaque mutants were recovered following plaquing of lung homogenates from mice infected with influenza virus seed Beij/89. Compared to wild-type virus, small plaque mutants showed increased virulence in mice yet did not differ in their ability to infect or replicate in airway epithelial cells in vitro. Instead, small plaque variants were markedly resistant to neutralization by murine collectins, a property that correlated with the acquisition of an amino acid substitution at residue 246 on the viral HA. We present evidence that this substitution was associated with the loss of an oligosaccharide glycan from the globular head of HA. CONCLUSION: A point mutation in the gene encoding the HA of Beij/89 was shown to ablate a glycan attachment site. This was associated with resistance to collectins and increased virulence in mice

The Impact of the Pandemic on Mental Health in Ethnically Diverse Mothers : Findings from the Born in Bradford, Tower Hamlets and Newham COVID-19 Research Programmes

YesRestrictions implemented by the UK Government during the COVID-19 pandemic have served to worsen mental health outcomes, particularly amongst younger adults, women, those living with chronic health conditions, and parents of young children. Studies looking at the impact for ethnic minorities have reported inconsistent findings. This paper describes the mental health experiences of mothers from a large and highly ethnically diverse population during the pandemic, using secondary analysis of existing data from three COVID-19 research studies completed in Bradford and London (Tower Hamlets and Newham). A total of 2807 mothers participated in this study with 44% White British, 23% Asian/Asian British Pakistani, 8% Other White and 7% Asian/Asian British Bangladeshi backgrounds. We found that 28% of mothers experienced clinically important depressive symptoms and 21% anxiety symptoms during the pandemic. In unadjusted analyses, mothers from White Other, and Asian/Asian British Bangladeshi backgrounds had higher odds of experiencing symptoms, whilst mothers from Asian/Asian British Indian backgrounds were the least likely to experience symptoms. Once loneliness, social support and financial insecurity were controlled for, there were no statistically significant differences in depression and anxiety by ethnicity. Mental health problems experienced during the pandemic may have longer term consequences for public health. Policy and decision makers must have an understanding of the high risk of financial insecurity, loneliness and a lack of social support on mother’s mental health, and also recognise that some ethnic groups are far more likely to experience these issues and are, therefore, more vulnerable to poor mental health as a consequence.This study was funded by The Health Foundation COVID-19 Award (2301201), with further contributions from a Wellcome Trust infrastructure grant (WT101597MA); a joint grant from the UK Medical Research Council (MRC) and UK Economic and Social Science Research Council (ESRC) (MR/N024391/1); the National Institute for Health Research under its Applied Research Collaboration Yorkshire and Humber (NIHR200166); ActEarly UK Prevention Research Partnership Consortium (MR/S037527/1); Better Start Bradford through The National Lottery Community Fund; and the British Heart Foundation (CS/16/4/32482). The research conducted in London was funded by UKRI-ESRC ES/V004891/1 (Tower Hamlets), and by London Borough of Newham Public Health. Heys was supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre

Assessment of Indoor Air Pollution in Homes with Infants

Infants spend most of their indoor time at home; however, residential air quality is poorly understood. We investigated the air quality of infants’ homes in the New England area of the U.S. Participants (N = 53) were parents of infants (0–6 months) who completed telephone surveys to identify potential pollutant sources in their residence. Carbon monoxide (CO), carbon dioxide (CO2), particulate matter with aerodynamic diameter ≤0.5 µm (PM0.5), and total volatile organic compounds (TVOCs) were measured in 10 homes over 4–7 days, and levels were compared with health-based guidelines. Pollutant levels varied substantially across homes and within homes with overall levels for some homes up to 20 times higher than for other homes. Average levels were 0.85 ppm, 663.2 ppm, 18.7 µg/m3, and 1626 µg/m3 for CO, CO2, PM0.5, and TVOCs, respectively. CO2, TVOCs, and PM0.5 levels exceeded health-based indoor air quality guidelines. Survey results suggest that nursery renovations and related potential pollutant sources may be associated with differences in urbanicity, income, and presence of older children with respiratory ailments, which could potentially confound health studies. While there are no standards for indoor residential air quality, our findings suggest that additional research is needed to assess indoor pollution exposure for infants, which may be a vulnerable population

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

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