694 research outputs found

    Increased risk of pneumonia in residents living near poultry farms: does the upper respiratory tract microbiota play a role?

    Get PDF
    BACKGROUND: Air pollution has been shown to increase the susceptibility to community-acquired pneumonia (CAP). Previously, we observed an increased incidence of CAP in adults living within 1 km from poultry farms, potentially related to particulate matter and endotoxin emissions. We aim to confirm the increased risk of CAP near poultry farms by refined spatial analyses, and we hypothesize that the oropharyngeal microbiota composition in CAP patients may be associated with residential proximity to poultry farms. METHODS: A spatial kernel model was used to analyze the association between proximity to poultry farms and CAP diagnosis, obtained from electronic medical records of 92,548 GP patients. The oropharyngeal microbiota composition was determined in 126 hospitalized CAP patients using 16S-rRNA-based sequencing, and analyzed in relation to residential proximity to poultry farms. RESULTS: Kernel analysis confirmed a significantly increased risk of CAP when living near poultry farms, suggesting an excess risk up to 1.15 km, followed by a sharp decline. Overall, the oropharyngeal microbiota composition differed borderline significantly between patients living <1 km and ≥1 km from poultry farms (PERMANOVA p = 0.075). Results suggested a higher abundance of Streptococcus pneumoniae (mean relative abundance 34.9% vs. 22.5%, p = 0.058) in patients living near poultry farms, which was verified by unsupervised clustering analysis, showing overrepresentation of a S. pneumoniae cluster near poultry farms (p = 0.049). CONCLUSION: Living near poultry farms is associated with an 11% increased risk of CAP, possibly resulting from changes in the upper respiratory tract microbiota composition in susceptible individuals. The abundance of S. pneumoniae near farms needs to be replicated in larger, independent studies

    DNA repair, genome stability and cancer: a historical perspective

    Get PDF
    The multistep process of cancer progresses over many years. The prevention of mutations by DNA repair pathways led to an early appreciation of a role for repair in cancer avoidance. However, the broader role of the DNA damage response (DDR) emerged more slowly. In this Timeline article, we reflect on how our understanding of the steps leading to cancer developed, focusing on the role of the DDR. We also consider how our current knowledge can be exploited for cancer therapy

    How patients understand depression associated with chronic physical disease - A systematic review

    Get PDF
    Background: Clinicians are encouraged to screen people with chronic physical illness for depression. Screening alone may not improve outcomes, especially if the process is incompatible with patient beliefs. The aim of this research is to understand peoples beliefs about depression, particularly in the presence of chronic physical disease. Methods: A mixed method systematic review involving a thematic analysis of qualitative studies and quantitative studies of beliefs held by people with current depressive symptoms. MEDLINE, EMBASE, PSYCHINFO, CINAHL, BIOSIS, Web of Science, The Cochrane Library, UKCRN portfolio, National Research Register Archive, Clinicaltrials.gov and OpenSIGLE were searched from database inception to 31st December 2010. A narrative synthesis of qualitative and quantitative data, based initially upon illness representations and extended to include other themes not compatible with that framework. Results: A range of clinically relevant beliefs was identified from 65 studies including the difficulty in labeling depression, complex causal factors instead of the biological model, the roles of different treatments and negative views about the consequences of depression. We found other important themes less related to ideas about illness: the existence of a self-sustaining depression spiral; depression as an existential state; the ambiguous status of suicidal thinking; and the role of stigma and blame in depression. Conclusions: Approaches to detection of depression in physical illness need to be receptive to the range of beliefs held by patients. Patient beliefs have implications for engagement with depression screening

    Sirt1 carboxyl-domain is an ATP-repressible domain that is transferrable to other proteins

    Get PDF
    Sirt1 is an NAD(+)-dependent protein deacetylase that regulates many physiological functions, including stress resistance, adipogenesis, cell senescence and energy production. Sirt1 can be activated by energy deprivation, but the mechanism is poorly understood. Here, we report that Sirt1 is negatively regulated by ATP, which binds to the C-terminal domain (CTD) of Sirt1. ATP suppresses Sirt1 activity by impairing the CTD&apos;s ability to bind to the deacetylase domain as well as its ability to function as the substrate recruitment site. ATP, but not NAD(+), causes a conformational shift to a less compact structure. Mutations that prevent ATP binding increase Sirt1&apos;s ability to promote stress resistance and inhibit adipogenesis under high-ATP conditions. Interestingly, the CTD can be attached to other proteins, thereby converting them into energy-regulated proteins. These discoveries provide insight into how extreme energy deprivation can impact Sirt1 activity and underscore the complex nature of Sirt1 structure and regulation

    Identification of a novel susceptibility locus at 13q34 and refinement of the 20p12.2 region as a multi-signal locus associated with bladder cancer risk in individuals of European ancestry

    No full text
    Candidate gene and genome-wide association studies (GWAS) have identified 15 independent genomic regions associated with bladder cancer risk. In search for additional susceptibility variants, we followed up on four promising single-nucleotide polymorphisms (SNPs) that had not achieved genome-wide significance in 6911 cases and 11 814 controls (rs6104690, rs4510656, rs5003154 and rs4907479, P < 1 × 10−6), using additional data from existing GWAS datasets and targeted genotyping for studies that did not have GWAS data. In a combined analysis, which included data on up to 15 058 cases and 286 270 controls, two SNPs achieved genome-wide statistical significance: rs6104690 in a gene desert at 20p12.2 (P = 2.19 × 10−11) and rs4907479 within the MCF2L gene at 13q34 (P = 3.3 × 10−10). Imputation and fine-mapping analyses were performed in these two regions for a subset of 5551 bladder cancer cases and 10 242 controls. Analyses at the 13q34 region suggest a single signal marked by rs4907479. In contrast, we detected two signals in the 20p12.2 region—the first signal is marked by rs6104690, and the second signal is marked by two moderately correlated SNPs (r2 = 0.53), rs6108803 and the previously reported rs62185668. The second 20p12.2 signal is more strongly associated with the risk of muscle-invasive (T2-T4 stage) compared with non-muscle-invasive (Ta, T1 stage) bladder cancer (case–case P ≤ 0.02 for both rs62185668 and rs6108803). Functional analyses are needed to explore the biological mechanisms underlying these novel genetic associations with risk for bladder cancer

    Visions of prosperity and conspiracy in Timor-Leste

    Get PDF
    In Timor-Leste, visions of radical societal transformation and future wealth derived from gold and oil are accompanied by concerns that outsiders might be conspiring to rob the country of its riches, as well as conjuring up dystopian scenarios of sinister plots and future mayhem. Examining national narratives and local accounts, this article argues that visions of prosperity and visions of conspiracy are two sides of the same coin; both are embedded in an understanding that power works in invisible ways. In discussing these visions in relation to the literature on “conspiracy theories” and “cargo cults” (terms that have recently been imported to the study of Timor-Leste), it explores the critical potential of these visions. Whereas the labels “conspiracy theory” and “cargo cult” create distinctions between the “rational” perspective of the West and the “irrationality” of non-Western others, as practices these visions end up collapsing such distinctions by appropriating the power of the outside

    Extra-curricular physical activity and socioeconomic status in Italian adolescents

    Get PDF
    BACKGROUND: The relationship between physical activity and health status has been thoroughly investigated in several studies, while the relation between physical activity and socio-economic status (SES) is less investigated. The aim of this study was to measure the extra-curricular physical activity of adolescents related to the socio-economic status (SES) of their families. METHODS: The survey was carried out by submitting an anonymous questionnaire to junior high school students in the following Regions: Lazio, Abruzzo, Molise, Campania, Puglia, during the school year 2002–2003. Extra-curriculum physical activity was evaluated considering whether or not present and hours of activity weekly conducted. 2411 students agreed to participate in the study. RESULTS: Participants were 1121 males (46.5%) and 1290 females (53.5%), aged between 11 and 17 years (median age: 12 years). 71.1% of the students reported to practice extra-curricular physical activity. Parents' educational levels and work activities play an important role in predicting students' physical activity, with the more remunerative activities and higher educational levels being more predictive. CONCLUSION: The results confirm the relationship between adolescents' physical activity and their families' SES. In particular, a positive relationship between participation in extra-curricular physical activity and their families high SES was found. These data will be useful for school administrators and for politicians in order to reduce the gap between adolescents from the least and most disadvantaged families
    corecore