71 research outputs found

    The Healthcare Workers' Hand Microbiome: Community Structure and Dynamics.

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    The complex microbial communities that inhabit our bodies, our microbiota, profoundly influence human health. Alterations in microbiota profiles occur as a result of host and environmental factors, and can lead to increased microorganism transmission, pathogen susceptibility, and disease. This interdisciplinary dissertation investigates hand microbiota dynamics over a 3-week period among 34 surgical intensive care unit healthcare workers (HCWs), while accounting for technical sources of variation. We also assess the role hand microbiota play in specific nosocomial pathogen carriage. An accurate profile of the human microbiota requires assessment of the variation in biological patterns between individuals and within individuals over time, while considering technical variation due to (i) specimen collection method, (ii) DNA extraction technique, and (iii) sequencing. Analysis of the HCWs' hand microbiota showed that only sampling collection method appeared to have a significant impact on the observed microbial community structure. Samples collected using the glove-juice method showed that individuals' hands were slightly more similar to each other in microbial composition over time than between individuals. Using the swab method, however, samples from a single individual were no more similar to each other than to other individuals. After HCW hand microbiota characterization, we assessed its role in nosocomial pathogen carriage. The proportion of pathogens detected using qPCR varied by collection visit: Staphylococcus aureus ranged from 41.2%-52.9%; Enterococcus spp. ranged from 52.9%-61.8%; Candida albicans ranged from 2.9%-8.8%; and, MRSA from 2.9%-5.9%. HCWs with lower microbiota diversity were more likely to carry a pathogen on their hands than those with higher diversity. HCWs took a self-administered questionnaire regarding basic demographics, overall health, hand health, hand hygiene practices, and patient contact levels, to explore possible associations with pathogen carriage. Risk factors for pathogen carriage were pathogen specific. Hand microbiota may have mediated the relationship between hand hygiene and pathogen carriage; and, acted as effect modifiers in the relationships between a) age and Enterococcus spp. carriage, and b) work shift and Staphylococcus aureus carriage. Understanding risk factors for pathogen carriage and its relationship to HCW hand microbiota has significant implications for pathogen transmission and hospital infection control policies.PHDEpidemiological ScienceUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/97994/1/rosenbr_1.pd

    Healthcare Workers’ Hand Microbiome May Mediate Carriage of Hospital Pathogens

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    One function of skin microbiota is to resist colonization and infection by external microorganisms. We sought to detect whether the structure of the hand microbiota of 34 healthcare workers (HCW) in a surgical intensive care unit mediates or modifies the relationship between demographic and behavioral factors and potential pathogen carriage on hands after accounting for pathogen exposure. We used a taxonomic screen (16S rRNA) to characterize the bacterial community, and qPCR to detect presence of Staphylococcus aureus, Enterococcus spp., methicillin-resistant Staphylococcus aureus (MRSA), and Candida albicans on their dominant hands. Hands were sampled weekly over a 3-week period. Age, hand hygiene, and work shift were significantly associated with potential pathogen carriage and the associations were pathogen dependent. Additionally, the overall hand microbiota structure was associated with the carriage of potential pathogens. Hand microbiota community structure may act as a biomarker of pathogen carriage, and modifying that structure may potentially limit pathogen carriage among HCW

    Papel dos tricomas glandulares da folha do tomateiro na oviposição de Tuta absoluta

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    Os tricomas glandulares presentes nas folhas e ramos das plantas do gênero Lycopersicon são responsáveis pela secreção de metabólitos de diferentes naturezas. A presença de alguns desses compostos tem sido associada à resistência do tomate a diferentes insetos. A traça-do-tomateiro, Tuta absoluta (Meyrick), é uma das pragas mais nocivas da América do Sul. O adulto oviposita sobre as folhas do tomate e suas larvas abrem galerias no mesófilo das folhas, ramos, flores e frutos. As espécies silvestres do tomate conservam a capacidade de biossintetizar compostos químicos que lhes conferem resistência a esta praga. No presente trabalho, foi avaliada a preferência para oviposição desse inseto sobre folhas com e sem tricomas glandulares de L. esculentum (Mill.) cv. Uco Plata, suscetível, e de L. hirsutum f. glabratum (Mull.) PI 134417, espécie silvestre afim ao tomate, e resistente à traça. Os resultados sugerem que as fêmeas ovipositam indistintamente sobre as folhas de ambas espécies, independentemente da presença, ou não, dos tricomas glandulares. E a presença destes e de seus exsudatos não têm efeito inibidor na oviposição do inseto

    Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

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    CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology

    Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies.

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    With the use of a mouse model expressing human Fc-gamma receptors (FcγRs), we demonstrated that antibodies with isotypes equivalent to ipilimumab and tremelimumab mediate intra-tumoral regulatory T (Treg) cell depletion in vivo, increasing the CD8+ to Treg cell ratio and promoting tumor rejection. Antibodies with improved FcγR binding profiles drove superior anti-tumor responses and survival. In patients with advanced melanoma, response to ipilimumab was associated with the CD16a-V158F high affinity polymorphism. Such activity only appeared relevant in the context of inflamed tumors, explaining the modest response rates observed in the clinical setting. Our data suggest that the activity of anti-CTLA-4 in inflamed tumors may be improved through enhancement of FcγR binding, whereas poorly infiltrated tumors will likely require combination approaches

    Educomunicação e suas áreas de intervenção: Novos paradigmas para o diálogo intercultural

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    oai:omp.abpeducom.org.br:publicationFormat/1O material aqui divulgado representa, em essência, a contribuição do VII Encontro Brasileiro de Educomunicação ao V Global MIL Week, da UNESCO, ocorrido na ECA/USP, entre 3 e 5 de novembro de 2016. Estamos diante de um conjunto de 104 papers executivos, com uma média de entre 7 e 10 páginas, cada um. Com este rico e abundante material, chegamos ao sétimo e-book publicado pela ABPEducom, em seus seis primeiros anos de existência. A especificidade desta obra é a de trazer as “Áreas de Intervenção” do campo da Educomunicação, colocando-as a serviço de uma meta essencial ao agir educomunicativo: o diálogo intercultural, trabalhado na linha do tema geral do evento internacional: Media and Information Literacy: New Paradigms for Intercultural Dialogue

    <scp>ReSurveyEurope</scp>: A database of resurveyed vegetation plots in Europe

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    AbstractAimsWe introduce ReSurveyEurope — a new data source of resurveyed vegetation plots in Europe, compiled by a collaborative network of vegetation scientists. We describe the scope of this initiative, provide an overview of currently available data, governance, data contribution rules, and accessibility. In addition, we outline further steps, including potential research questions.ResultsReSurveyEurope includes resurveyed vegetation plots from all habitats. Version 1.0 of ReSurveyEurope contains 283,135 observations (i.e., individual surveys of each plot) from 79,190 plots sampled in 449 independent resurvey projects. Of these, 62,139 (78%) are permanent plots, that is, marked in situ, or located with GPS, which allow for high spatial accuracy in resurvey. The remaining 17,051 (22%) plots are from studies in which plots from the initial survey could not be exactly relocated. Four data sets, which together account for 28,470 (36%) plots, provide only presence/absence information on plant species, while the remaining 50,720 (64%) plots contain abundance information (e.g., percentage cover or cover–abundance classes such as variants of the Braun‐Blanquet scale). The oldest plots were sampled in 1911 in the Swiss Alps, while most plots were sampled between 1950 and 2020.ConclusionsReSurveyEurope is a new resource to address a wide range of research questions on fine‐scale changes in European vegetation. The initiative is devoted to an inclusive and transparent governance and data usage approach, based on slightly adapted rules of the well‐established European Vegetation Archive (EVA). ReSurveyEurope data are ready for use, and proposals for analyses of the data set can be submitted at any time to the coordinators. Still, further data contributions are highly welcome.</jats:sec

    The evolution of lung cancer and impact of subclonal selection in TRACERx

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    Lung cancer is the leading cause of cancer-associated mortality worldwide. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET, ROS1, ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource
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