Are elevated plasma fibrinogen associated with lung function? An 8-year follow-up of the ELSA study

BACKGROUND: Fibrinogen is an important biomarker of inflammation, but findings from longitudinal studies that correlated fibrinogen with lung function in older adults are inconsistent. AIM: To investigate the relationship between fibrinogen plasma levels and lung function impairment later in life. METHODS: Longitudinal analysis of 2,150 participants of the English Longitudinal Study of Ageing (ELSA) aged 50 years and older. Associations between changes in plasma fibrinogen between waves 2 (2004-05) and 4 (2008-09) and lung function in wave 6 (2012-13) were performed using multiple linear regression adjusted by potential confounders. RESULTS: Regarding the fibrinogen profile, 18.5% of the participants presented higher levels in both waves. In the adjusted models, the maintenance of high fibrinogen levels was associated with a significant reduction of lung function only for men. FEV1 showed a reduction of 0.17L, FVC of 0.22L, and the percentages predicted were 5.16% for FEV1 and 6.21% for FVC compared to those that maintained normal levels of fibrinogen. DISCUSSION: To the best of our knowledge, this was the first study investigating the relationship between changes in fibrinogen levels over a long follow-up period and lung function in older adults without pre-existing chronic diseases. ELSA has information on critical demographic and clinical parameters, which allowed to adjust for potential confounding factors. CONCLUSION: It was found that the persistence of high levels of plasma fibrinogen in older English men, but not women, is associated with lung function decline. Therefore, plasma fibrinogen showed to be an important biomarker of pulmonary dysfunction in this population

Overall survival analyses of female malignancies in Southern Brazil during 2008–2017: A closer look at breast, cervical and ovarian cancer

Background: The aim of this study was to report the overall survival and baseline factors associated with OS for breast, cervical and ovarian cancer in Florianópolis, Southern Brazil, a region with quality-of-life indicators comparable to high-income countries. Methods: Cohort study was performed from probabilistic record linkage of the Mortality Information System and the Population-based cancer registry of Florianópolis. It was included breasts, cervical and ovarian cancer diagnosis during the period of 2008–2012 with a follow up of 60 months. Cox regression and Kaplan-Meier method were used for associations with overall survival and risk factors. Findings: 1857 cases of the three malignancies were included in the analysis. We identified 202 deaths in breast cancer subjects, 53 for cervical cancer and 51 for ovarian cancer. Metastatic disease at diagnosis was present in 31%, 9.6%, and 55% of the cases, respectively. Overall survival was statistically correlated with age, educational level and stage for breast cancer; age and stage for cervical cancer; age and stage for ovarian cancer. Interpretation: Metastatic disease and age are the main prognostic factors for the malignancies studied, as they were associated with both overall survival and risk of death. Better screening and preventive tests for early diagnosis are needed. Funding: Support of Research and Innovation in the State of Santa Catarina, Research Program for the Unified Health System (FAPESC/MS-DECIT/CNPQ/SES-SC-PPSUS); the Brazilian National Research Council (CNPq); and the Coordination for the Improvement of Higher Education Personnel (CAPES)

The fetal mouse is a sensitive genotoxicity model that exposes lentiviral-associated mutagenesis resulting in liver oncogenesis

This article is available open access through the publisher’s website at the link below. Copyright @ 2013 The American Society of Gene & Cell Therapy.Genotoxicity models are extremely important to assess retroviral vector biosafety before gene therapy. We have developed an in utero model that demonstrates that hepatocellular carcinoma (HCC) development is restricted to mice receiving nonprimate (np) lentiviral vectors (LV) and does not occur when a primate (p) LV is used regardless of woodchuck post-translation regulatory element (WPRE) mutations to prevent truncated X gene expression. Analysis of 839 npLV and 244 pLV integrations in the liver genomes of vector-treated mice revealed clear differences between vector insertions in gene dense regions and highly expressed genes, suggestive of vector preference for insertion or clonal outgrowth. In npLV-associated clonal tumors, 56% of insertions occurred in oncogenes or genes associated with oncogenesis or tumor suppression and surprisingly, most genes examined (11/12) had reduced expression as compared with control livers and tumors. Two examples of vector-inserted genes were the Park 7 oncogene and Uvrag tumor suppressor gene. Both these genes and their known interactive partners had differential expression profiles. Interactive partners were assigned to networks specific to liver disease and HCC via ingenuity pathway analysis. The fetal mouse model not only exposes the genotoxic potential of vectors intended for gene therapy but can also reveal genes associated with liver oncogenesis.Imperial College London, the Wellcome Trust, and Brunel University

Star Formation in the Milky Way. The Infrared View

I present a brief review of some of the most recent and active topics of star formation process in the Milky Way using mid and far infrared observations, and motivated by the research being carried out by our science group using data gathered by the Spitzer and Herschel space telescopes. These topics include bringing together the scaling relationships found in extragalactic systems with that of the local nearby molecular clouds, the synthetic modeling of the Milky Way and estimates of its star formation rate.Comment: 12 pages, 9 figures. To apper in "Cosmic-ray induced phenomenology in star-forming environments: Proceedings of the 2nd Session of the Sant Cugat Forum of Astrophysics" (April 16-19, 2012), Olaf Reimer and Diego F. Torres (eds.

Protective effects of exogenous and endogenous hydrogen sulfide in mast cell-mediated pruritus and cutaneous acute inflammation in mice.

Published onlineJournal ArticleThis is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.The recently described 'gasomediator' hydrogen sulfide (H2S) has been involved in pain mechanisms, but its effect on pruritus, a sensory modality that similarly to pain acts as a protective mechanism, is poorly known and controversial. The effects of the slow-releasing (GYY4137) and spontaneous H2S donors (Na2S and Lawesson's reagent, LR) were evaluated in histamine and compound 48/80 (C48/80)-dependent dorsal skin pruritus and inflammation in male BALB/c mice. Animals were intradermally (i.d.) injected with C48/80 (3μg/site) or histamine (1μmol/site) alone or co-injected with Na2S, LR or GYY4137 (within the 0.3-100nmol range). The involvement of endogenous H2S and KATP channel-dependent mechanism were also evaluated. Pruritus was assessed by the number of scratching bouts, whilst skin inflammation was evaluated by the extravascular accumulation of intravenously injected (125)I-albumin (plasma extravasation) and myeloperoxidase (MPO) activity (neutrophil recruitment). Histamine or C48/80 significantly evoked itching behavior paralleled by plasma extravasation and increased MPO activity. Na2S and LR significantly ameliorated histamine or C48/80-induced pruritus and inflammation, although these effects were less pronounced or absent with GYY4137. Inhibition of endogenous H2S synthesis exacerbated C48/80-induced responses, whereas the blockade of KATP channels by glibenclamide did not. High-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) revealed that Na2S and LR, but not GYY4137, significantly attenuated C48/80-induced histamine release from rat peritoneal mast cell in vitro. We provide first evidences that H2S exerted protective effect against acute pruritus mediated via histaminergic pathways in murine skin, thus making of H2S donors a potential alternative/complementary therapy for treatment of acute pruritus.Sao Paulo Research Foundation (Fapesp grant numbers: 2013/04.151-3, 2014/15.576-8, 2014/24.518-1) and CNPq (grant number: 163278/2012-1). GDN, MNM and SKPC are recipients of fellowships from the National Council for Scientific and Technological Development (CNPq). We thank Irene M Gouvea, Flávia B de Lira and Mauro Sucupira for their techinical support

The Atlantic Ocean at the last glacial maximum: 1. Objective mapping of the GLAMAP sea-surface conditions

Recent efforts of the German paleoceanographic community have resulted in a unique data set of reconstructed sea-surface temperature for the Atlantic Ocean during the Last Glacial Maximum, plus estimates for the extents of glacial sea ice. Unlike prior attempts, the contributing research groups based their data on a common definition of the Last Glacial Maximum chronozone and used the same modern reference data for calibrating the different transfer techniques. Furthermore, the number of processed sediment cores was vastly increased. Thus the new data is a significant advance not only with respect to quality, but also to quantity. We integrate these new data and provide monthly data sets of global sea-surface temperature and ice cover, objectively interpolated onto a regular 1°x1° grid, suitable for forcing or validating numerical ocean and atmosphere models. This set is compared to an existing subjective interpolation of the same base data, in part by employing an ocean circulation model. For the latter purpose, we reconstruct sea surface salinity from the new temperature data and the available oxygen isotope measurements

Plant-RRBS, a bisulfite and next-generation sequencing-based methylome profiling method enriching for coverage of cytosine positions

Background: Cytosine methylation in plant genomes is important for the regulation of gene transcription and transposon activity. Genome-wide methylomes are studied upon mutation of the DNA methyltransferases, adaptation to environmental stresses or during development. However, from basic biology to breeding programs, there is a need to monitor multiple samples to determine transgenerational methylation inheritance or differential cytosine methylation. Methylome data obtained by sodium hydrogen sulfite (bisulfite)-conversion and next-generation sequencing (NGS) provide genome- wide information on cytosine methylation. However, a profiling method that detects cytosine methylation state dispersed over the genome would allow high-throughput analysis of multiple plant samples with distinct epigenetic signatures. We use specific restriction endonucleases to enrich for cytosine coverage in a bisulfite and NGS-based profiling method, which was compared to whole-genome bisulfite sequencing of the same plant material. Methods: We established an effective methylome profiling method in plants, termed plant-reduced representation bisulfite sequencing (plant-RRBS), using optimized double restriction endonuclease digestion, fragment end repair, adapter ligation, followed by bisulfite conversion, PCR amplification and NGS. We report a performant laboratory protocol and a straightforward bioinformatics data analysis pipeline for plant-RRBS, applicable for any reference-sequenced plant species. Results: As a proof of concept, methylome profiling was performed using an Oryza sativa ssp. indica pure breeding line and a derived epigenetically altered line (epiline). Plant-RRBS detects methylation levels at tens of millions of cytosine positions deduced from bisulfite conversion in multiple samples. To evaluate the method, the coverage of cytosine positions, the intra-line similarity and the differential cytosine methylation levels between the pure breeding line and the epiline were determined. Plant-RRBS reproducibly covers commonly up to one fourth of the cytosine positions in the rice genome when using MspI-DpnII within a group of five biological replicates of a line. The method predominantly detects cytosine methylation in putative promoter regions and not-annotated regions in rice. Conclusions: Plant-RRBS offers high-throughput and broad, genome- dispersed methylation detection by effective read number generation obtained from reproducibly covered genome fractions using optimized endonuclease combinations, facilitating comparative analyses of multi-sample studies for cytosine methylation and transgenerational stability in experimental material and plant breeding populations

Dispersive charge density wave excitations and temperature dependent commensuration in Bi2Sr2CaCu2O8+{\delta}

Experimental evidence on high-Tc cuprates reveals ubiquitous charge density wave (CDW) modulations, which coexist with superconductivity. Although the CDW had been predicted by theory, important questions remain about the extent to which the CDW influences lattice and charge degrees of freedom and its characteristics as functions of doping and temperature. These questions are intimately connected to the origin of the CDW and its relation to the mysterious cuprate pseudogap. Here, we use ultrahigh resolution resonant inelastic x-ray scattering (RIXS) to reveal new CDW character in underdoped Bi2Sr2CaCu2O8+{\delta} (Bi2212). At low temperature, we observe dispersive excitations from an incommensurate CDW that induces anomalously enhanced phonon intensity, unseen using other techniques. Near the pseudogap temperature T*, the CDW persists, but the associated excitations significantly weaken and the CDW wavevector shifts, becoming nearly commensurate with a periodicity of four lattice constants. The dispersive CDW excitations, phonon anomaly, and temperature dependent commensuration provide a comprehensive momentum space picture of complex CDW behavior and point to a closer relationship with the pseudogap state

The effectiveness of public health interventions to reduce the health impact of climate change:a systematic review of systematic reviews

Climate change is likely to be one of the most important threats to public health in the coming years. Yet despite the large number of papers considering the health impact of climate change, few have considered what public health interventions may be of most value in reducing the disease burden. We aimed to evaluate the effectiveness of public health interventions to reduce the disease burden of high priority climate sensitive diseases