63 research outputs found

    Fecal microbiota diversity in survivors of adolescent/young adult Hodgkin lymphoma: A study of twins

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    BACKGROUND: Adolescent/young adult Hodgkin lymphoma (AYAHL) survivors report fewer exposures to infections during childhood compared with controls, and they have functional lymphocyte aberrations. The gut microbiota plays a central role in immunity. METHODS: We investigated whether fecal microbial diversity differed between 13 AYAHL survivors and their unaffected co-twin controls. Pyrosequencing of fecal bacterial 16S rRNA amplicons yielded 252 943 edited reads that were assigned to species-level operational taxonomic units (OTUs) and standardised for sequencing depth by random sampling. Microbial diversity was compared within vs between twin pairs and by case–control status. RESULTS: The number of unique OTUs was more similar within twin pairs compared with randomly paired participants (P=0.0004). The AYAHL cases had fewer unique OTUs compared with their co-twin controls (338 vs 369, P=0.015); this difference was not significant (169 vs 183, P=0.10) when restricted to abundant OTUs. CONCLUSION: In this small study, AYAHL survivors appear to have a deficit of rare gut microbes. Further work is needed to determine if reduced microbial diversity is a consequence of the disease, its treatment, or a particularly hygienic environment

    Muc2 Protects against Lethal Infectious Colitis by Disassociating Pathogenic and Commensal Bacteria from the Colonic Mucosa

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    Despite recent advances in our understanding of the pathogenesis of attaching and effacing (A/E) Escherichia coli infections, the mechanisms by which the host defends against these microbes are unclear. The goal of this study was to determine the role of goblet cell-derived Muc2, the major intestinal secretory mucin and primary component of the mucus layer, in host protection against A/E pathogens. To assess the role of Muc2 during A/E bacterial infections, we inoculated Muc2 deficient (Muc2−/−) mice with Citrobacter rodentium, a murine A/E pathogen related to diarrheagenic A/E E. coli. Unlike wildtype (WT) mice, infected Muc2−/− mice exhibited rapid weight loss and suffered up to 90% mortality. Stool plating demonstrated 10–100 fold greater C. rodentium burdens in Muc2−/− vs. WT mice, most of which were found to be loosely adherent to the colonic mucosa. Histology of Muc2−/− mice revealed ulceration in the colon amid focal bacterial microcolonies. Metabolic labeling of secreted mucins in the large intestine demonstrated that mucin secretion was markedly increased in WT mice during infection compared to uninfected controls, suggesting that the host uses increased mucin release to flush pathogens from the mucosal surface. Muc2 also impacted host-commensal interactions during infection, as FISH analysis revealed C. rodentium microcolonies contained numerous commensal microbes, which was not observed in WT mice. Orally administered FITC-Dextran and FISH staining showed significantly worsened intestinal barrier disruption in Muc2−/− vs. WT mice, with overt pathogen and commensal translocation into the Muc2−/− colonic mucosa. Interestingly, commensal depletion enhanced C. rodentium colonization of Muc2−/− mice, although colonic pathology was not significantly altered. In conclusion, Muc2 production is critical for host protection during A/E bacterial infections, by limiting overall pathogen and commensal numbers associated with the colonic mucosal surface. Such actions limit tissue damage and translocation of pathogenic and commensal bacteria across the epithelium

    Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID-19 pandemic

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    BACKGROUND: During the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study\u27s objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines. METHODS: We conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March-31 May 2020. The prior 1-year control period (1 March-31 May 2019) was obtained to account for seasonal variation. FINDINGS: There was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI -24.3% to -20.7%, p\u3c0.0001). Embolisation of ruptured aneurysms declined with 1170-1035 procedures, respectively, representing an 11.5% (95%CI -13.5% to -9.8%, p=0.002) relative drop. Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations, a 24.9% relative decline (95% CI -28.0% to -22.1%, p\u3c0.0001). A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1% (95% CI 32.3% to 50.6%, p=0.008) despite a decrease in SAH admissions in this tertile. INTERPRETATION: There was a relative decrease in the volume of SAH hospitalisations, aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic. These findings in SAH are consistent with a decrease in other emergencies, such as stroke and myocardial infarction

    BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

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    Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

    TRY plant trait database – enhanced coverage and open access

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    Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

    SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

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    Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

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    Language attitudes of parents in Irish-medium primary schools in County Dublin

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    Cette Ă©tude de recherche s’intĂ©resse aux attitudes envers la langue gaĂ©lique en RĂ©publique d’Irlande. Le gaĂ©lique, tout comme l’anglais, est la langue nationale officielle et est enseignĂ©e comme matiĂšre obligatoire de l’école Ă©lĂ©mentaire au lycĂ©e. Bien que le nombre de personnes utilisant le gaĂ©lique dans la vie quotidienne reste faible, il existe depuis les annĂ©es soixante-dix une rĂ©surgence d’intĂ©rĂȘt dans cette langue. Celle-ci se traduit, entre autres, par une demande croissante du nombre d’écoles d’immersion en gaĂ©lique, tout particuliĂšrement dans les rĂ©gions oĂč le gaĂ©lique n’est pas pratiquĂ© au sein de la communautĂ©. Cette Ă©tude cherche Ă  Ă©claircir ce phĂ©nomĂšne en analysant les attitudes envers le gaĂ©lique des parents d’élĂšves d’écoles primaires d’immersion en zone urbaine, et plus prĂ©cisĂ©ment, dans le comtĂ© de Dublin. En effet, peu de recherches ont Ă©tĂ© effectuĂ©es sur les attitudes envers le gaĂ©lique au sein des familles ayant choisi une Ă©ducation par immersion pour leurs enfants.Les personnes participant Ă  cette Ă©tude se composent de parents d’élĂšves avec une expĂ©rience plus ou moins longue de l’enseignement en immersion, ainsi que d’enseignants des Ă©coles participantes. Les donnĂ©es recueillies pour cette Ă©tude proviennent d’un questionnaire auto-administrĂ© ainsi que d’entretiens suivis.La question sur la motivation des parents Ă  choisir un enseignement en immersion est centrale au thĂšme des attitudes envers le gaĂ©lique, puisque dans ce contexte, l’anglais est la seule langue utilisĂ©e dans la communautĂ© ainsi que dans la plupart des foyers. Les rĂ©sultats d’analyse rĂ©vĂšlent que les parents participant ont choisi ce type d’éducation car ils considĂšrent d’une part que le gaĂ©lique est un marqueur d’identitĂ© culturelle voire ethnique pour certains, et d’autre part qu’il permet d’acquĂ©rir du capital culturel. En effet, les participants s’intĂ©ressent de prĂšs Ă  la qualitĂ© de l’éducation de leurs enfants et valorisent le bilinguisme additif. Ainsi, ils attribuent au gaĂ©lique une valeur culturelle importante. Cette Ă©tude montre Ă©galement que les parents d’élĂšves ont une attitude positive envers la langue gaĂ©lique. Ceci s’explique de par leur enclin naturel mais aussi de par leur contact avec ces Ă©coles d’immersion, environnement dans lequel le gaĂ©lique est mis en valeur. Cependant, malgrĂ© les efforts des parents Ă  intĂ©grer la langue gaĂ©lique Ă  la maison ou dans les activitĂ©s rĂ©crĂ©atives de leurs enfants, ce milieu ne semble pas ĂȘtre dĂ©clencheur de pratiques bilingues au sein de la famille. NĂ©anmoins, cette Ă©tude indique que les Ă©coles d’immersion favorisent la crĂ©ation de liens entre quelques familles communiquant entre elles en gaĂ©lique.This study explores attitudes towards the Irish language in the Republic of Ireland. The Irish language—alongside with English—is the national official language and is taught in school as a compulsory subject from primary school through to the end of secondary level. Despite the low percentage of daily Irish-speakers in the country the demand for Irish-medium education as an alternative means of education has been growing since the 1970s, especially in English-speaking areas. This current study focuses on the language attitudes of parents whose child attends an urban Irish-medium primary school in County Dublin and analyses the reasons for choosing such an education. Although there has been a considerable number of research studies conducted on language attitudes towards Irish in the Republic of Ireland, very few have recently concentrated on families involved with Irish-medium education. Participants included parents with both short term and long term experience with immersion education through Irish. The main research instruments included a self-administered questionnaire and follow-up interviews with a sample of questionnaire respondents as well as teachers from the participating schools. One of the main focuses of this study is parental motivation for sending their child to an Irish-medium school. Results reveal that participants selected such education for their child for two main reasons: identity and cultural capital. Firstly, most participants regarded Irish as a strong cultural identity marker while others also considered the language as a strong marker of ethnic identity. Secondly and most importantly, participants expressed a strong interest in both education and additive bilingualism thus attributing a high cultural value to the Irish language. Findings also show that participants have very positive attitudes towards the Irish language. This is mainly due to their natural favourable disposition to Irish but also to their exposure to the Irish-medium school environment which tends to enhance this positive attitude. But despite participants' efforts to include some Irish in their child's life, either during recreational activities or at home, self-reports did not indicate the emergence of bilingual families. However, there is some evidence that the school facilitates the creation of Irish-speaking social networks between a few families
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