705 research outputs found

    Statement by Bishop Henry W. Cleary

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    Holograph statement by Bishop Henry W. Cleary of Auckland, Rome, reviewing the Italian translation of Goblet's L'Irlande dans la crise universelle 1914-1920 'the best of the many books, dealing with that critical period, that have come under my notice'. The author possesses both the historic sense and a dramatic instinct

    The nasopharyngeal microbiome

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    Human microbiomes have received increasing attention over the last 10 years, leading to a pervasiveness of hypotheses relating dysbiosis to health and disease. The respiratory tract has received much less attention in this respect than that of, for example, the human gut. Nevertheless, progress has been made in elucidating the immunological, ecological and environmental drivers that govern these microbial consortia and the potential consequences of aberrant microbiomes. In this review, we consider the microbiome of the nasopharynx, a specific niche of the upper respiratory tract. The nasopharynx is an important site, anatomically with respect to its gateway position between upper and lower airways, and for pathogenic bacterial colonisation. The dynamics of the latter are important for long-term respiratory morbidity, acute infections of both invasive and non-invasive disease and associations with chronic airway disease exacerbations. Here, we review the development of the nasopharyngeal (NP) microbiome over the life course, examining it from the early establishment of resilient profiles in neonates through to perturbations associated with pneumonia risk in the elderly. We focus specifically on the commensal, opportunistically pathogenic members of the NP microbiome that includes Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae and Moraxella catarrhalis. In addition, we consider the role of relatively harmless genera such as Dolosigranulum and Corynebacterium. Understanding that the NP microbiome plays such a key, beneficial role in maintaining equilibrium of commensal species, prevention of pathogen outgrowth and host immunity enables future research to be directed appropriately

    Corrigendum: Pneumococcal vaccine impacts on the population genomics of non-typeable haemophilus influenzae: (Microbial Genomics 2021; 9, 10.1099/mgen.0.000209)

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    There was a change in the author names in the published article. The new list should read: David W. Cleary1,2, Vanessa T. Devine3, Denise E. Morris1, Karen L. Osman1, Rebecca A. Gladstone4, Stephen D. Bentley4, Saul N. Faust1,5, Stuart C. Clarke1,2,6 1Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, UK. 2NIHR Southampton Biomedical Research Centre, University Hospital Southampton Foundation NHS Trust, Southampton, UK. 3Northern Ireland Centre for Stratified Medicine and Clinical Translational Research Innovation Centre, Londonderry, UK. 4Pathogen Genomics, Wellcome Trust Sanger Institute, UK. 5NIHR Southampton Clinical Research Facility, University Hospital Southampton Foundation NHS Trust, Southampton, UK. 6Global Health Research Institute, University of Southampton, Southampton, UK.</p

    Dataset supporting the publication &quot;An in silico reverse vaccinology study of Brachyspira pilosicoli, the causative organism of intestinal spirochaetosis, to identify putative vaccine candidates&quot;

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    Dataset supporting the publication by M Christodoulides, D de Oliveira, D W. Cleary, M V Humbert, R A. Machado-de-&Aacute;vila, R M. La Ragione, &quot;An in silico reverse vaccinology study of Brachyspira pilosicoli, the causative organism of intestinal spirochaetosis, to identify putative vaccine candidates&quot;, Process Biochemistry, Volume 122, Part 1, 2022, Pages 128-148, ISSN 1359-5113, https://doi.org/10.1016/j.procbio.2022.08.014 This dataset contains raw data from in silico analyses for reverse vaccinology. IT has supplemental material for Figure 1 including datasets 1 to 21. The data is presented in word document, PDF and excel files. This study was funded by Houghton Trust, UK </span

    Dr John Cleary and Dr Jack Ryan examine shock waves

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    Research School of Earth Sciences - Dr. Ian MacDougall, Wang Sung Shan, Dr. Bill Compston, Chung Fu Tao, Dr. S. W. J. Clements, W. Sinclair, A. E. Ringwood, Prof. Lew Gustafson, Leigh Schmidt, Dr. John Cleary, Dr. Jack Ryan, Dr. I. D. Ryabchikov, Dr. David Green, Mr. Bill Hibberson, Dr. Mike McElhinny, Mr. Charles Barton, Mr. Kurt Kloska, Mr. Dieter Burmann, Prof. Hales & other

    Airway microbiome driven mechanisms of disease during optimised self management:a lesson learned from mechanistic study of the Colour-COPD trial

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    Introduction: Reduced antibiotic consumption due to better self-management (SM) could change the profile of bacteria present in the airway, which might benefit the health of COPD patients. To test this we planned to use sputum samples already being collected from Colour COPD trial patients for mechanistic work. The trial will test whether a sputum colour chart is non-inferior to usual self-management, and has a primary outcome of COPD specific hospital admission. Secondary outcomes include antibiotic consumption and quality of life (QOL). Since only half of exacerbations of COPD (AECOPD) are bacterial, and sputum colour has a good positive predictive value for bacterial presence, it is likely that our intervention will reduce antibiotic consumption. The main route by which our intervention could improve patient outcomes is that it could alter the airway microbiome, and subsequent pathological processes; this add on study tried to assess that concept.Methods: We used all sputum samples submitted by Colour COPD patients and processed them to store for microbiome and cytokine analyses. Sputum plugs were split with one half being diluted in PBS, dispersed using glass beads and stored for qPCR/16S analysis. The second portion was dispersed using sequential PBS and DTT treatment generating supernatants and cytospins. Analysis of the microbial patterns which would have been obtained of the respiratory micobiome will be compared to antibiotic consumption for AECOPD (days/year) steroid load (days/year and mg/year), AECOPD rate, FEV1 and longitudinally within individuals to determine the impact of frequent courses of antibiotics at group and individual level. This work will now be completed outside the duration of this award. Selected inflammatory markers linked to neutrophilic and eosinophilic inflammation were planned to be measured, but this work was abandoned when the study was terminated early.Results and study limitations: The trial was stopped prematurely due to low recruitment. This was due to a combination of insufficient trial sites, the impact of COVID-19 on research infrastructure and a reduced rate of AECOPD during the COVID-19 pandemic, which affected eligibility in primary care sites in particular. Since analysis of the microbiome was planned to occur only after trial results, this was abandoned within this award at termination of the trial. However since the research questions remained, could be answered in other ways, and patients had consented to use of their samples for the proposed work alternative ways to collect samples and fund microbiome analyses were sought. We are now at a point where we expect to have sufficient samples to have adequate power to answer 2 of our research questions by the time the trial ends, and will conduct their analysis thereafter.Conclusion: Although we are not able to address our objectives of describing the airway microbiome in a primary care COPD population, and describing the relationship between antibiotic consumption and changes in airway microbiome during the term of the award, we were able to learn lessons about matching mechanistic work to trials.Future work: We stored samples for a separately funded study to meet our objectives. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Efficacy Mechanisms Evaluation programme.Trial registration: The parent trial was prospectively registered as ISRCTN14955629<br/

    The characterization of Moraxella catarrhalis carried in the general population

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    Moraxella catarrhalis is a common cause of respiratory tract infection, particularly otitis media in children, whilst it is also associated with the onset of exacerbation in chronic obstructive pulmonary disease in adults. Despite the need for an efficacious vaccine against M. catarrhalis, no candidates have progressed to clinical trial. This study, therefore, aimed to characterize the diversity of M. catarrhalis isolated from the upper respiratory tract of healthy children and adults, to gain a better understanding of the epidemiology of M. catarrhalis and the distribution of genes associated with virulence factors, to aid vaccine efforts. Isolates were sequenced and the presence of target genes reported. Contrary to prevailing data, this study found that lipooligosaccharide (LOS) B serotypes are not exclusively associated with 16S type 1. In addition, a particularly low prevalence of LOS B and high prevalence of LOS C serotypes was observed. M. catarrhalis isolates showed low prevalence of antimicrobial resistance and a high gene prevalence for a number of the target genes investigated: ompB2 (also known as copB), ompCD, ompE, ompG1a, ompG1b, mid (also known as hag), mcaP, m35, tbpA, lbpA, tbpB, lbpB, msp22, msp75 and msp78, afeA, pilA, pilQ, pilT, mod, oppA, sbp2, mcmA and mclS.</p

    Dr ID Ryabchikov from the Academy of Sciences USSR with Dr David Green and Mr Bill Hibberson

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    Research School of Earth Sciences - Dr. Ian MacDougall, Wang Sung Shan, Dr. Bill Compston, Chung Fu Tao, Dr. S. W. J. Clements, W. Sinclair, A. E. Ringwood, Prof. Lew Gustafson, Leigh Schmidt, Dr. John Cleary, Dr. Jack Ryan, Dr. I. D. Ryabchikov, Dr. David Green, Mr. Bill Hibberson, Dr. Mike McElhinny, Mr. Charles Barton, Mr. Kurt Kloska, Mr. Dieter Burmann, Prof. Hales & other

    A brief history of and future prospects for pneumococcal vaccination in Malaysia

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    Pneumococcal pneumonia remains a significant global public health issue. Malaysia has recently added the 10 valent pneumococcal conjugate vaccine to its national immunisation programme. Data on pneumococcal serotype epidemiology is vital for informing national vaccination policy. However, there remains a lack of representative population-based pneumococcal surveillance in Malaysia to help both the assessment of vaccine effectiveness in the country and to shape future vaccine policy. This review explores the history of pneumococcal vaccination, the burden of pneumococcal disease in Malaysia, and offers an insight into the prospects for reducing pneumococcal disease in Malaysia

    The adhesins of non-typeable Haemophilus influenzae

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    Introduction: Nontypeable Haemophilus influenzae (NTHi) is an opportunistic pathogen of the respiratory tract and the greatest contributor to invasive Haemophilus disease. Additionally, in children, NTHi is responsible for the majority of otitis media (OM) which can lead to chronic infection and hearing loss. In adults, NTHi infection in the lungs is responsible for the onset of acute exacerbations in chronic obstructive pulmonary disease (COPD). Unfortunately, there is currently no vaccine available to protect against NTHi infections. Areas covered: NTHi uses an arsenal of adhesins to colonise the respiratory epithelium. The adhesins also have secondary roles that aid in the virulence of NTHi, including mechanisms that avoid immune clearance, adjust pore size to avoid antimicrobial destruction, form micro-colonies and invoke phase variation for protein mediation. Bacterial adhesins can also be ideal antigens for subunit vaccine design due to surface exposure and immunogenic capabilities. Expert commentary: The host-pathogen interactions of the NTHi adhesins are not fully investigated. The relationship between adhesins and the extracellular matrix (ECM) play a part in the success of NTHi colonisation and virulence by immune evasion, migration and biofilm development. Further research into these immunogenic proteins would further our understanding and enable a basis for better combatting NTHi disease.</p
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