To determine factors that predispose or protect healthcare workers from severe acute respiratory syndrome (SARS), we conducted a retrospective cohort study among 43 nurses who worked in two Toronto critical care units with SARS patients. Eight of 32 nurses who entered a SARS patient's room were infected. The probability of SARS infection was 6% per shift worked. Assisting during intubation, suctioning before intubation, and manipulating the oxygen mask were high-risk activities. Consistently wearing a mask (either surgical or particulate respirator type N95) while caring for a SARS patient was protective for the nurses, and consistent use of the N95 mask was more protective than not wearing a mask. Risk was reduced by consistent use of a surgical mask, but not significantly. Risk was lower with consistent use of a N95 mask than with consistent use of a surgical mask. We conclude that activities related to intubation increase SARS risk and use of a mask (particularly a N95 mask) is protective.

Chemically-induced vascular toxicity during embryonic development may cause a wide range of adverse effects. To identify putative vascular disrupting chemicals (pVDCs), a predictive pVDC signature was constructed from 124 U.S. EPA ToxCast high-throughput screening (HTS) assays and used to rank 1060 chemicals for their potential to disrupt vascular development. Thirty-seven compounds were selected for targeted testing in transgenic Tg(kdrl:EGFP) and Tg(fli1:EGFP) zebrafish embryos to identify chemicals that impair developmental angiogenesis. We hypothesized that zebrafish angiogenesis toxicity data would correlate with human cell-based and cell-free in vitro HTS ToxCast data. Univariate statistical associations used to filter HTS data based on correlations with zebrafish angiogenic inhibition in vivo revealed 132 total significant associations, 33 of which were already captured in the pVDC signature, and 689 non-significant assay associations. Correlated assays were enriched in cytokine and extracellular matrix pathways. Taken together, the findings indicate the utility of zebrafish assays to evaluate an HTS-based predictive toxicity signature and also provide an experimental basis for expansion of the pVDC signature with novel HTS assays.

Serogroup B is the only major disease-associated capsular group of Neisseria meningitidis for which no protein-polysaccharide conjugate vaccine is available. This has led to the development of multi-component protein-based vaccines that target serogroup B invasive meningococcal disease (IMD), including Bexsero®, which was implemented for UK infants in 2015, and Trumenba®. Given the diversity of meningococcal protein antigens, post-implementation surveillance of IMD isolates, including characterisation of vaccine antigens, is essential for assessing the effectiveness of such vaccines. Whole genome sequencing (WGS), as realised in the Meningitis Research Foundation Meningococcus Genome Library (MRF-MGL), provides a rapid, comprehensive, and cost-effective approach to this. To facilitate the surveillance of the antigen targets included in Bexsero® (fHbp, PorA, NHBA and NadA) for protective immunity, a Bexsero® Antigen Sequence Type (BAST) scheme, based on deduced peptide sequence variants, was implemented in the PubMLST.org/neisseria database, which includes the MRF-MGL and other isolate collections. This scheme enabled the characterisation of vaccine antigen variants and here the invasive meningococci isolated in Great Britain and Ireland in the epidemiological years 2010/11 to 2013/14 are analysed. Many unique BASTs (647) were present, but nine of these accounted for 39% (775/1966) of isolates, with some temporal and geographic differences in BAST distribution. BASTs were strongly associated with other characteristics, such as serogroup and clonal complex (cc), and a significant increase in BAST-2 was associated with increased prevalence of serogroup W clonal complex 11 meningococci. Potential coverage was assessed by the examination of the antigen peptide sequences present in the vaccine and epidemiological dataset. There were 22.8-30.8% exact peptide matches to Bexsero® components and predicted coverage of 66.1%, based on genotype-phenotype modelling for 63.7% of serogroup B isolates from 2010/14 in UK and Ireland. While there are many caveats to this estimate, it lies within the range of other published estimates.

Morbidity and mortality following cardiac valve surgery is high. Immunity is an important contributor to outcome. This study examines the relationship of staphylococcal and endotoxin antibody levels to outcome following cardiac surgery.

The constant exposure of the liver to food and bacterial antigens through the mesenteric circulation requires it to maintain tolerance while preserving the ability to mount an effective immune response against pathogens. We investigated the contribution of the liver's tolerogenic nature on the establishment of chronic viral infections.

The COVID-19 pandemic has necessitated many novel responses in healthcare including sport and exercise medicine. The cessation of elite sport almost globally has had significant economic implications and resulted in pressure to resume sport in very controlled conditions. This includes protecting pitch-side medical staff and players from infection. The ongoing prevalence of SARS-CoV-2 and the desire to resume professional sport required urgent best practice guidelines to be developed so that sport could be resumed as safely as possible. This set of best practice recommendations assembles early evidence for managing SARS-CoV-2 and integrates expert opinion to provide a uniform and pragmatic approach to enhance on-field and pitch-side safety for the clinician and player. The nature of SARS-CoV-2 transmission creates new hazards during resuscitation and emergency care and procedures. Recommendations for the use and type of personal protective equipment during on-field or pitch-side emergency medical care is provided based on the clinical scenario and projected risk of viral transmission.

The ST-4821 complex (cc4821) is a leading cause of serogroup C and serogroup B invasive meningococcal disease in China where diverse strains in two phylogenetic groups (groups 1 and 2) have acquired fluoroquinolone resistance. cc4821 was recently prevalent among carriage isolates in men who have sex with men in New York City (USA). Genome-level population studies have thus far been limited to Chinese isolates. The aim of the present study was to build upon these with an extended panel of international cc4821 isolates.

A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials.

The EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF) was requested to evaluate the genotoxic potential of flavouring substances from subgroup 2.2 of FGE.19 in the Flavouring Group Evaluation 208 Revision 2 (FGE.208Rev2). In FGE.208Rev1, the CEF Panel evaluated genotoxicity studies on p-mentha-1,8-dien-7-al [FL-no: 05.117], the representative substance for FGE.19 subgroup 2.2. The Comet assay performed in liver showed a positive result, and therefore, the Panel concluded that p-mentha-1,8-dien-7-al [FL-no: 05.117] is genotoxic in vivo and that, accordingly, there is a safety concern for its use as flavouring substance. Since p-mentha-1,8-dien-7-al [FL-no: 05.117] is representative for the nine remaining substances of subgroup 2.2 (p-mentha-1,8-dien-7-ol [FL-no: 02.060], myrtenol [FL-no: 02.091], myrtenal [FL-no: 05.106], 2,6,6-trimethyl-1-cyclohexen-1-carboxaldehyde [FL-no: 05.121], myrtenyl formate [FL-no: 09.272], p-mentha-1,8-dien-7-yl acetate [FL-no: 09.278], myrtenyl acetate [FL-no: 09.302], myrtenyl-2-methylbutyrate [FL-no: 09.899] and myrtenyl-3-methylbutyrate [FL-no: 09.900]), the Panel concluded in the previous revision of FGE.208 (FGE.208Rev1) that there is a potential safety concern for these substances. Subsequently, the industry has submitted genotoxicity studies on five substances of FGE.19 subgroup 2.2: p-mentha-1,8-dien-7-ol [FL-no: 02.060], myrtenol [FL-no: 02.091], myrtenal [FL-no: 05.106], p-mentha-1,8-dien-7-yl acetate [FL-no: 09.278] and myrtenyl acetate [FL-no: 09.302], which are evaluated in the present revision of FGE.208 (FGE.208Rev2). The Panel concluded that the concern for genotoxicity could be ruled out for p-mentha-1,8-dien-7-ol [FL-no: 02.060], myrtenol [FL-no: 02.091], p-mentha-1,8-dien-7-yl acetate [FL-no: 09.278] and myrtenyl acetate [FL-no: 09.302], which will be evaluated through the Procedure. Genotoxicity data on myrtenal [FL-no: 05.106] were considered equivocal, therefore, it cannot be evaluated through the Procedure, presently. p-Mentha-1,8-dien-7-al [FL-no: 05.117] and four substances not supported by industry (2,6,6-trimethyl-1-cyclohexen-1-carboxaldehyde [FL-no: 05.121], myrtenyl formate [FL-no: 09.272], myrtenyl-2-methylbutyrate [FL-no: 09.899] and myrtenyl-3-methylbutyrate [FL-no: 09.900]) have been deleted from the Union List.

No abstract available

Nursing has seen a dominance of women within the profession, and today, the presence of men in the role remains less understood and appreciated. Males considering or entering nursing face challenges concerning role misconception, marginalization, and gender bias. With a looming shortage of nurses on the horizon, it is more important now than ever before to find better ways of engaging males into nursing. The aim of the study was to examine the psychological constructs that influence male perceptions of nursing as they seek to navigate the profession, and what aspects influence men to consider nursing as a career. To achieve this, a systematic review and mixed research synthesis (integrated design) was conducted. English language research published between 1999 and 2019 was eligible. The methodological rigor of qualitative articles followed the Critical Appraisal Skills Program, while the Best Evidence Medical Education guided the quantitative review. Among the 24 publications identified, three sub-themes emerged from the overarching theme of the funambulist or tightrope walker. Sub-themes included societal, inner and collective voices that inform men's place in nursing or their decision making about entering the profession. There is a need to re-visit what it means to be a nurse in order to address the gendered stereotypes that impact men entering the nursing profession.

Aggregation of therapeutic bispecific antibodies negatively affects the yield, shelf-life, efficacy and safety of these products. Pairs of stable Chinese hamster ovary (CHO) cell lines produced two difficult-to-express bispecific antibodies with different levels of aggregated product (10-75% aggregate) in a miniaturised bioreactor system. Here, transcriptome analysis was used to interpret the biological causes for the aggregation and to identify strategies to improve product yield and quality. Differential expression- and gene set analysis revealed upregulated proteasomal degradation, unfolded protein response and autophagy processes to be correlated with reduced protein aggregation. Fourteen candidate genes with the potential to reduce aggregation were co-expressed in the stable clones for validation. Of these, HSP90B1, DDIT3, AKT1S1, and ATG16L1, were found to significantly lower aggregation in the stable producers and two (HSP90B1 and DNAJC3) increased titres of the anti-HER2 monoclonal antibody trastuzumab by 50% during transient expression. It is suggested that this approach could be of general use for defining aggregation bottlenecks in CHO cells.

Features of multisystem inflammatory syndrome in children (MIS-C) overlap with other syndromes, making the diagnosis difficult for clinicians. We aimed to compare clinical differences between patients with and without clinical MIS-C diagnosis and develop a diagnostic prediction model to assist clinicians in identification of patients with MIS-C within the first 24 hours of hospital presentation.

Limited research has examined inspiratory muscle performance (IMP) and functional performance (FP) of patients after valve replacement surgery (VRS). The purpose of this study was to examine IMP as well as several measures of FP in patients post-VRS. The study results of 27 patients revealed that patients undergoing transcatheter VRS were significantly (p = 0.01) older than patients undergoing minimally invasive or median sternotomy VRS with the median sternotomy VRS group performing significantly (p < 0.05) better than the transcatheter VRS group in the 6-min walk test, 5x sit-to-stand test, and sustained maximal inspiratory pressure. The 6-min walk test and IMP measures in all groups were significantly (p < 0.001) lower than predicted values. Significant (p < 0.05) relationships were found between IMP and FP with greater IMP being associated with greater FP. Pre-operative and early post-operative rehabilitation may improve IMP and FP post-VRS.

The interplay between epigenetic modifications and chromatin structure are integral to our understanding of genome function. Methylation of cytosine (5mC) at CG dinucleotides, traditionally associated with transcriptional repression, is the most highly studied chemical modification of DNA, occurring at over 70% of all CG dinucleotides in the genome. Hypomethylated regions (HMRs) often occur in CG islands (CGIs), however, they also occur outside of CGIs and function as cell-type specific enhancers. During the process of differentiation, reorganization of chromatin and nucleosome arrangement at regulatory regions is thought to occur in order for the establishment of cell-type specific transcriptional programs. However, the specifics regarding the organization of nucleosomes at HMRs and the potential mechanisms regulating nucleosome occupancy in these regions are unknown. Here, we have investigated nucleosome organization around hypomethylated regions (HMRs) identified in two mouse primary cells.

Spaceflight is a unique environment with profound effects on biological systems including tissue redistribution and musculoskeletal stresses. However, the more subtle biological effects of spaceflight on cells and organisms are difficult to measure in a systematic, unbiased manner. Here we test the utility of the molecularly barcoded yeast deletion collection to provide a quantitative assessment of the effects of microgravity on a model organism. We developed robust hardware to screen, in parallel, the complete collection of ~4800 homozygous and ~5900 heterozygous (including ~1100 single-copy deletions of essential genes) yeast deletion strains, each carrying unique DNA that acts as strain identifiers. We compared strain fitness for the homozygous and heterozygous yeast deletion collections grown in spaceflight and ground, as well as plus and minus hyperosmolar sodium chloride, providing a second additive stressor. The genome-wide sensitivity profiles obtained from these treatments were then queried for their similarity to a compendium of drugs whose effects on the yeast collection have been previously reported. We found that the effects of spaceflight have high concordance with the effects of DNA-damaging agents and changes in redox state, suggesting mechanisms by which spaceflight may negatively affect cell fitness.

Photoreceptor death is the root cause of vision loss in many retinal disorders, and there is an unmet need for neuroprotective modalities to improve photoreceptor survival. The biosynthetic requirement of photoreceptors is among the highest in the body, and to meet this demand, photoreceptors maintain their ability to perform aerobic glycolysis. This highly regulated form of glycolysis allows cells to efficiently budget their metabolic needs and may be a critical link between photoreceptor function and survival. Pyruvate kinase muscle isozyme 2 (PKM2) is a key regulator of aerobic glycolysis. In the present study, we characterized the effect of PKM2 deletion on baseline functioning and survival of photoreceptors over time by utilizing a photoreceptor-specific, PKM2 knockout mouse model. We found that upon PKM2 deletion, PKM1 is upregulated in the outer retina and there is increased expression of genes involved in glucose metabolism, which led to chronic degenerative changes in the outer retina of these mice. We also discovered that this metabolic reprogramming provided a survival advantage to photoreceptors in an experimental model of retinal detachment. This study strongly supports the hypothesis that reprogramming metabolism may be a novel therapeutic strategy for photoreceptor neuroprotection during acute stress.

Evidence is required to quantify the potential risks of transmission of variant Creutzfeldt Jakob (vCJD) through dental procedures. Studies, using animal models relevant to vCJD, were performed to address two questions. Firstly, whether oral tissues could become infectious following dietary exposure to BSE? Secondly, would a vCJD-contaminated dental instrument be able to transmit disease to another patient?

A direct impediment to the optimal use of online databases is the increasing prevalence, severity, and toll of computer and network security incidents. Funding agencies should set up working groups that can provide essential services such as universal backup, archival storage, and mirroring of community resources, consistent with the key goal of security in academia: to preserve data and results for posterity.

Cells such as fibroblasts and endothelial cells migrate through the coordinated responses of discrete integrin-containing focal adhesions and complexes. In contrast, little is known about the organization of integrins on the highly motile T lymphocyte. We have investigated the distribution, activity, and cytoskeletal linkage of the integrin lymphocyte function associated antigen-1 (LFA-1) on human T lymphocytes migrating on endothelial cells and on ligand intercellular adhesion molecule-1 (ICAM-1). The pattern of total LFA-1 varies from low expression in the lamellipodia to high expression in the uropod. However, high affinity, clustered LFA-1 is restricted to a mid-cell zone that remains stable over time and over a range of ICAM-1 densities. Talin is essential for the stability and formation of the LFA-1 zone. Disruption of the talin-integrin link leads to loss of zone integrity and a substantial decrease in speed of migration on ICAM-1. This adhesive structure, which differs from the previously described integrin-containing attachments displayed by many other cell types, we have termed the "focal zone."