Seasonality and immunity to laboratory-confirmed seasonal coronaviruses (HCoV-NL63, HCoV-OC43, and HCoV-229E): results from the Flu Watch cohort study [version 1; peer review: 2 approved with reservations]

Background: There is currently a pandemic caused by the novel coronavirus SARS-CoV-2. The intensity and duration of this first wave in the UK may be dependent on whether SARS-CoV-2 transmits more effectively in the winter than the summer and the UK Government response is partially built upon the assumption that those infected will develop immunity to reinfection in the short term. In this paper we examine evidence for seasonality and immunity to laboratory-confirmed seasonal coronavirus (HCoV) from a prospective cohort study in England. Methods: In this analysis of the Flu Watch cohort, we examine seasonal trends for PCR-confirmed coronavirus infections (HCoV-NL63, HCoV-OC43, and HCoV-229E) in all participants during winter seasons (2006-2007, 2007-2008, 2008-2009) and during the first wave of the 2009 H1N1 influenza pandemic (May-Sep 2009). We also included data from the pandemic and ‘post-pandemic’ winter seasons (2009-2010 and 2010-2011) to identify individuals with two confirmed HCoV infections and examine evidence for immunity against homologous reinfection. Results: We tested 1,104 swabs taken during respiratory illness and detected HCoV in 199 during the first four seasons. The rate of confirmed HCoV infection across all seasons was 390 (95% CI 338-448) per 100,000 person-weeks; highest in the Nov-Mar 2008/9 season at 674 (95%CI 537-835). The highest rate was in February at 759 (95% CI 580-975). Data collected during May-Sep 2009 showed there was small amounts of ongoing transmission, with four cases detected during this period. Eight participants had two confirmed infections, of which none had the same strain twice

Effects of seasonal and pandemic influenza on health-related quality of life, work and school absence in England: results from the Flu Watch cohort study

BACKGROUND: Estimates of health-related quality of life (HRQoL) and work/school absences for influenza are typically based on medically-attended cases or those meeting influenza-like-illness (ILI) case definitions, and thus biased towards severe disease. Although community influenza cases are more common, estimates of their effects on HRQoL and absences are limited. OBJECTIVES: To measure Quality-Adjusted Life Days and Years (QALDs and QALYs) lost and work/school absences among community cases of acute respiratory infections (ARI), ILI and influenza A and B and to estimate community burden of QALY loss and absences from influenza. PATIENTS/ METHODS: Flu Watch was a community cohort in England from 2006-2011. Participants were followed-up weekly. During respiratory illness they prospectively recorded daily symptoms, work/school absences and EQ-5D-3L data and submitted nasal swabs for RT-PCR influenza testing. RESULTS: Average QALD lost was 0.26, 0.93, 1.61 and 1.84 for ARI, ILI, H1N1pdm09 and influenza B cases respectively. 40% of influenza A cases and 24% of influenza B cases took time off work/school with an average duration of 3.6 days and 2.4 days respectively. In England, community influenza cases lost 24,300 QALYs in 2010/11 and had an estimated 2.9 million absences per season based on data from 2006/07 - 2009/10. CONCLUSIONS: Our QALDs and QALYs lost and work and school absence estimates are lower than previous estimates because we focus on community cases, most of which are mild, may not meet ILI definitions and do not result in healthcare consultations. Nevertheless, they contribute a substantial loss of HRQoL on a population level. This article is protected by copyright. All rights reserved

Effects of seasonal and pandemic influenza on health‐related quality of life, work and school absence in England: Results from the Flu Watch cohort study

BACKGROUND: Estimates of health-related quality of life (HRQoL) and work/school absences for influenza are typically based on medically-attended cases or those meeting influenza-like-illness (ILI) case definitions, and thus biased towards severe disease. Although community influenza cases are more common, estimates of their effects on HRQoL and absences are limited. OBJECTIVES: To measure Quality-Adjusted Life Days and Years (QALDs and QALYs) lost and work/school absences among community cases of acute respiratory infections (ARI), ILI and influenza A and B and to estimate community burden of QALY loss and absences from influenza. PATIENTS/ METHODS: Flu Watch was a community cohort in England from 2006-2011. Participants were followed-up weekly. During respiratory illness they prospectively recorded daily symptoms, work/school absences and EQ-5D-3L data and submitted nasal swabs for RT-PCR influenza testing. RESULTS: Average QALD lost was 0.26, 0.93, 1.61 and 1.84 for ARI, ILI, H1N1pdm09 and influenza B cases respectively. 40% of influenza A cases and 24% of influenza B cases took time off work/school with an average duration of 3.6 days and 2.4 days respectively. In England, community influenza cases lost 24,300 QALYs in 2010/11 and had an estimated 2.9 million absences per season based on data from 2006/07 - 2009/10. CONCLUSIONS: Our QALDs and QALYs lost and work and school absence estimates are lower than previous estimates because we focus on community cases, most of which are mild, may not meet ILI definitions and do not result in healthcare consultations. Nevertheless, they contribute a substantial loss of HRQoL on a population level. This article is protected by copyright. All rights reserved

The Human Pancreas as a Source of Protolerogenic Extracellular Matrix Scaffold for a New-generation Bioartificial Endocrine Pancreas

OBJECTIVES: Our study aims at producing acellular extracellular matrix scaffolds from the human pancreas (hpaECMs) as a first critical step toward the production of a new-generation, fully human-derived bioartificial endocrine pancreas. In this bioartificial endocrine pancreas, the hardware will be represented by hpaECMs, whereas the software will consist in the cellular compartment generated from patient's own cells. BACKGROUND: Extracellular matrix (ECM)-based scaffolds obtained through the decellularization of native organs have become the favored platform in the field of complex organ bioengineering. However, the paradigm is now switching from the porcine to the human model. METHODS: To achieve our goal, human pancreata were decellularized with Triton-based solution and thoroughly characterized. Primary endpoints were complete cell and DNA clearance, preservation of ECM components, growth factors and stiffness, ability to induce angiogenesis, conservation of the framework of the innate vasculature, and immunogenicity. Secondary endpoint was hpaECMs’ ability to sustain growth and function of human islet and human primary pancreatic endothelial cells. RESULTS: Results show that hpaECMs can be successfully and consistently produced from human pancreata and maintain their innate molecular and spatial framework and stiffness, and vital growth factors. Importantly, hpaECMs inhibit human naïve CD4+ T-cell expansion in response to polyclonal stimuli by inducing their apoptosis and promoting their conversion into regulatory T cells. hpaECMs are cytocompatible and supportive of representative pancreatic cell types. DISCUSSION: We, therefore, conclude that hpaECMs has the potential to become an ideal platform for investigations aiming at the manufacturing of a regenerative medicine-inspired bioartificial endocrine pancreas

Differential gene expression mediated by 15-hydroxyeicosatetraenoic acid in LPS-stimulated RAW 264.7 cells

<p>Abstract</p> <p>Background</p> <p>Given the immuno-modulatory activity of native haemozoin (Hz), the effects of constitutive Hz components on immune response are of interest. Recently, gene expression changes mediated by HNE and the synthetic analogue of Hz, beta-haematin (BH), were identified and implicated a significant role for lipid peroxidation products in Hz's activity. The study presented herein examines gene expression changes in response to 15(S)-hydroxyeicosatetraenoic acid (HETE) in a model macrophage cell line.</p> <p>Methods</p> <p>LPS-stimulated RAW 264.7 macrophage-like cells were treated with 40 μM 15(S)-HETE for 24 h, and microarray analysis was used to identify global gene expression alterations. Fold changes were calculated relative to LPS-stimulated cells and those genes altered at least 1.8-fold (<it>p </it>value ≤ 0.025) were considered to be differentially expressed. Expression levels of a subset of genes were assessed by qRT-PCR and used to confirm the microarray results.</p> <p>Results</p> <p>Network analysis revealed that altered genes were primarily associated with "lipid metabolism" and "small molecule biochemistry". While several genes associated with PPAR-gamma receptor-mediated signaling were differentially expressed, a number of genes indicated the activation of secondary signaling cascades. Genes related to cytoadherence (cell-cell and cell-matrix), leukocyte extravasation, and inflammatory response were also differentially regulated by treatment, supporting a potential role for 15(S)-HETE in malaria pathogenesis.</p> <p>Conclusion</p> <p>These results add insight and detail to 15-HETE's effects on gene expression in macrophage-like cells. Data indicate that while 15-HETE exerts biological activity and may participate in Hz-mediated immuno-modulation, the gene expression changes are modest relative to those altered by the lipid peroxidation product HNE.</p

Effect of smoking on subgingival microflora of patients with periodontitis in Japan

<p>Abstract</p> <p>Background</p> <p>Smoking is a risk factor for periodontitis. To clarify the contribution of smoking to periodontitis, it is essential to assess the relationship between smoking and the subgingival microflora. The aim of this study was to gain an insight into the influence of smoking on the microflora of Japanese patients with periodontitis.</p> <p>Methods</p> <p>Sixty-seven Japanese patients with chronic periodontitis (19 to 83 years old, 23 women and 44 men) were enrolled in the present study. They consisted of 30 smokers and 37 non-smokers. Periodontal parameters including probing pocket depth (PPD) and bleeding on probing (BOP) and oral hygiene status were recorded. Detection of <it>Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia, Fusobacterium nucleatum/periodonticum, Treponema denticola </it>and <it>Campylobacter rectus </it>in subgingival plaque samples was performed by polymerase chain reaction. Association between the detection of periodontopathic bacteria and smoking status was analyzed by multiple logistic regression analysis and chi-square test.</p> <p>Results</p> <p>A statistically significant association was found between having a PPD ≥ 4 mm and detection of <it>T. denticola, P. intermedia, T. forsythia</it>, or <it>C. rectus</it>, with odds ratios ranging from 2.17 to 3.54. A significant association was noted between BOP and the detection of <it>C. rectus </it>or <it>P. intermedia</it>, and smoking, with odds ratios ranging from 1.99 to 5.62. Prevalence of <it>C. rectus </it>was higher in smokers than non-smokers, whereas that of <it>A. actinomycetemcomitans </it>was lower in smokers.</p> <p>Conclusions</p> <p>Within limits, the analysis of the subgingival microbial flora in smokers and non-smokers with chronic periodontitis suggests a relevant association between smoking and colonization by the specific periodontal pathogens including <it>C. rectus</it>.</p

Novel sialic acid derivatives lock open the 150-loop of an influenza A virus group-1 sialidase

Influenza virus sialidase has an essential role in the virus' life cycle. Two distinct groups of influenza A virus sialidases have been established, that differ in the flexibility of the '150-loop', providing a more open active site in the apo form of the group-1 compared to group-2 enzymes. In this study we show, through a multidisciplinary approach, that novel sialic acid-based derivatives can exploit this structural difference and selectively inhibit the activity of group-1 sialidases. We also demonstrate that group-1 sialidases from drug-resistant mutant influenza viruses are sensitive to these designed compounds. Moreover, we have determined, by protein X-ray crystallography, that these inhibitors lock open the group-1 sialidase flexible 150-loop, in agreement with our molecular modelling prediction. This is the first direct proof that compounds may be developed to selectively target the pandemic A/H1N1, avian A/H5N1 and other group-1 sialidase-containing viruses, based on an open 150-loop conformation of the enzyme

Tannerella forsythia, a periodontal pathogen entering the genomic era

Several questions need to be addressed to evaluate whether Tannerella forsythia is to be considered a periodontal pathogen. T. forsythia has been detected in periodontal health and disease, so could it be a pathogen? The species was not detected in many studies despite finding other putative pathogens, so could it be important in pathogenicity? The challenges of working with T. forsythia include its fastidious and anaerobic growth requirements for cultural detection. Thus, studies associating T. forsythia with periodontal and other oral infections have used noncultural approaches (immunoassays and DNA-based assays) in addition to cultural approaches. We feel the timing of this review represents an interesting transition period in our understanding of the relationships of species with infection. Information from the recently released full genome sequence data of T. forsythia will provide new approaches and tools that can be directed to assess pathogenicity. Furthermore, molecular assessment of gene expression will provide a new understanding of the pathogenical potential of the species, and its effect on the host. T. forsythia, was described in reviews focusing on periodontal pathogens associated with herpesvirus detection (200), species for which genome projects were underway (41), members of polybacterial periodontal pathogenic consortium (91), and participants in periodontal microbial ecology (202). We will describe the history, taxonomy, and characteristics of T. forsythia, and related species or phylotypes in the genus Tannerella. To assess the pathogenic potential of T. forsythia, we first describe species associations with periodontal and other infections, including animal models, as has been the traditional approach arising from Koch’s postulates (203). Criteria for pathogenicity were expanded to incorporate sequence- derived information (58), and again more recently to include molecular signatures of pathogens and disease (170). We used sequence and genome-derived information, in addition to biofilm, pathogenic mediators, and host responses, to further explore the pathogenic potential of T. forsythia

Variation in the Ovine Abomasal Lymph Node Transcriptome between Breeds Known to Differ in Resistance to the Gastrointestinal Nematode

Texel lambs are known to be more resistant to gastrointestinal nematode (GIN) infection than Suffolk lambs, with a greater ability to limit infection. The objectives of this study were to: 1) profile the whole transcriptome of abomasal lymph node tissue of GIN-free Texel and Suffolk lambs; 2) identify differentially expressed genes and characterize the immune-related biological pathways and networks associated with these genes. Abomasal lymph nodes were collected from Texel (n = 6) and Suffolk (n = 4) lambs aged 19 weeks that had been GIN-free since 6 weeks of age. Whole transcriptome profiling was performed using RNA-seq on the Illumina platform. At the time of conducting this study, a well annotated Ovine genome was not available and hence the sequence reads were aligned with the Bovine (UMD3.1) genome. Identification of differentially expressed genes was followed by pathway and network analysis. The Suffolk breed accounted for significantly more of the differentially expressed genes, (276 more highly expressed in Suffolk v 162 in Texel; P < 0.001). The four most significant differentially expressed pathways were all related to immunity and were classified as: Role of Pattern Recognition Receptors in Recognition of Bacteria and Viruses, Activation of IRF by Cytosolic Pattern Recognition Receptors, Role of RIG-I-like Receptors in Antiviral Innate Immunity, and Interferon Signaling. Of significance is the fact that all of these four pathways were more highly expressed in the Suffolk. These data suggest that in a GIN-free environment, Suffolk lambs have a more active immune profile relative to the Texel: this immune profile may contribute to the poorer efficiency of response to a GIN challenge in the Suffolk breed compared to the Texel breed

Skeletal muscle gene expression in response to resistance exercise: sex specific regulation

<p>Abstract</p> <p>Background</p> <p>The molecular mechanisms underlying the sex differences in human muscle morphology and function remain to be elucidated. The sex differences in the skeletal muscle transcriptome in both the resting state and following anabolic stimuli, such as resistance exercise (RE), might provide insight to the contributors of sexual dimorphism of muscle phenotypes. We used microarrays to profile the transcriptome of the biceps brachii of young men and women who underwent an acute unilateral RE session following 12 weeks of progressive training. Bilateral muscle biopsies were obtained either at an early (4 h post-exercise) or late recovery (24 h post-exercise) time point. Muscle transcription profiles were compared in the resting state between men (n = 6) and women (n = 8), and in response to acute RE in trained exercised vs. untrained non-exercised control muscle for each sex and time point separately (4 h post-exercise, n = 3 males, n = 4 females; 24 h post-exercise, n = 3 males, n = 4 females). A logistic regression-based method (LRpath), following Bayesian moderated t-statistic (IMBT), was used to test gene functional groups and biological pathways enriched with differentially expressed genes.</p> <p>Results</p> <p>This investigation identified extensive sex differences present in the muscle transcriptome at baseline and following acute RE. In the resting state, female muscle had a greater transcript abundance of genes involved in fatty acid oxidation and gene transcription/translation processes. After strenuous RE at the same relative intensity, the time course of the transcriptional modulation was sex-dependent. Males experienced prolonged changes while females exhibited a rapid restoration. Most of the biological processes involved in the RE-induced transcriptional regulation were observed in both males and females, but sex specificity was suggested for several signaling pathways including activation of notch signaling and TGF-beta signaling in females. Sex differences in skeletal muscle transcriptional regulation might implicate a mechanism behind disproportional muscle growth in males as compared with female counterparts after RE training at the same relative intensity.</p> <p>Conclusions</p> <p>Sex differences exist in skeletal muscle gene transcription both at rest and following acute RE, suggesting that sex is a significant modifier of the transcriptional regulation in skeletal muscle. The findings from the present study provide insight into the molecular mechanisms for sex differences in muscle phenotypes and for muscle transcriptional regulation associated with training adaptations to resistance exercise.</p