105 research outputs found

    Reversible and Irreversible Interactions of Poly(3-hexylthiophene) with Oxygen Studied by Spin-Sensitive Methods

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    Understanding of degradation mechanisms in polymer:fullerene bulk-heterojunctions on the microscopic level aimed at improving their intrinsic stability is crucial for the breakthrough of organic photovoltaics. These materials are vulnerable to exposure to light and/or oxygen, hence they involve electronic excitations. To unambiguously probe the excited states of various multiplicities and their reactions with oxygen, we applied combined magneto-optical methods based on multifrequency (9 and 275 GHz) electron paramagnetic resonance (EPR), photoluminescence (PL), and PL-detected magnetic resonance (PLDMR) to the conjugated polymer poly(3-hexylthiophene) (P3HT) and polymer:fullerene bulk heterojunctions (P3HT:PCBM; PCBM = [6,6]-phenyl-C61-butyric acid methyl ester). We identified two distinct photochemical reaction routes, one being fully reversible and related to the formation of polymer:oxygen charge transfer complexes, the other one, irreversible, being related to the formation of singlet oxygen under participation of bound triplet excitons on the polymer chain. With respect to the blends, we discuss the protective effect of the methanofullerenes on the conjugated polymer bypassing the triplet exciton generation

    Natriuretic peptides and integrated risk assessment for cardiovascular disease. an individual-participant-data meta-analysis

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    BACKGROUND: Guidelines for primary prevention of cardiovascular diseases focus on prediction of coronary heart disease and stroke. We assessed whether or not measurement of N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentration could enable a more integrated approach than at present by predicting heart failure and enhancing coronary heart disease and stroke risk assessment. METHODS: In this individual-participant-data meta-analysis, we generated and harmonised individual-participant data from relevant prospective studies via both de-novo NT-proBNP concentration measurement of stored samples and collection of data from studies identified through a systematic search of the literature (PubMed, Scientific Citation Index Expanded, and Embase) for articles published up to Sept 4, 2014, using search terms related to natriuretic peptide family members and the primary outcomes, with no language restrictions. We calculated risk ratios and measures of risk discrimination and reclassification across predicted 10 year risk categories (ie, <5%, 5% to <7·5%, and ≥7·5%), adding assessment of NT-proBNP concentration to that of conventional risk factors (ie, age, sex, smoking status, systolic blood pressure, history of diabetes, and total and HDL cholesterol concentrations). Primary outcomes were the combination of coronary heart disease and stroke, and the combination of coronary heart disease, stroke, and heart failure. FINDINGS: We recorded 5500 coronary heart disease, 4002 stroke, and 2212 heart failure outcomes among 95 617 participants without a history of cardiovascular disease in 40 prospective studies. Risk ratios (for a comparison of the top third vs bottom third of NT-proBNP concentrations, adjusted for conventional risk factors) were 1·76 (95% CI 1·56-1·98) for the combination of coronary heart disease and stroke and 2·00 (1·77-2·26) for the combination of coronary heart disease, stroke, and heart failure. Addition of information about NT-proBNP concentration to a model containing conventional risk factors was associated with a C-index increase of 0·012 (0·010-0·014) and a net reclassification improvement of 0·027 (0·019-0·036) for the combination of coronary heart disease and stroke and a C-index increase of 0·019 (0·016-0·022) and a net reclassification improvement of 0·028 (0·019-0·038) for the combination of coronary heart disease, stroke, and heart failure. INTERPRETATION: In people without baseline cardiovascular disease, NT-proBNP concentration assessment strongly predicted first-onset heart failure and augmented coronary heart disease and stroke prediction, suggesting that NT-proBNP concentration assessment could be used to integrate heart failure into cardiovascular disease primary prevention

    DNA glycosylase Neil3 regulates vascular smooth muscle cell biology during atherosclerosis development.

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    BACKGROUND AND AIMS: Atherogenesis involves a complex interaction between immune cells and lipids, processes greatly influenced by the vascular smooth muscle cell (VSMC) phenotype. The DNA glycosylase NEIL3 has previously been shown to have a role in atherogenesis, though whether this is due to its ability to repair DNA damage or to other non-canonical functions is not yet clear. Hereby, we investigate the role of NEIL3 in atherogenesis, specifically in VSMC phenotypic modulation, which is critical in plaque formation and stability. METHODS: Chow diet-fed atherosclerosis-prone Apoe-/- mice deficient in Neil3, and NEIL3-abrogated human primary aortic VSMCs were characterized by qPCR, and immunohistochemical and enzymatic-based assays; moreover, single-cell RNA sequencing, mRNA sequencing, and proteomics were used to map the molecular effects of Neil3/NEIL3 deficiency in the aortic VSMC phenotype. Furthermore, BrdU-based proliferation assays and Western blot were performed to elucidate the involvement of the Akt signaling pathway in the transdifferentiation of aortic VSMCs lacking Neil3/NEIL3. RESULTS: We show that Neil3 deficiency increases atherosclerotic plaque development without affecting systemic lipids. This observation was associated with a shift in VSMC phenotype towards a proliferating, lipid-accumulating and secretory macrophage-like cell phenotype, without changes in DNA damage. VSMC transdifferentiation in Neil3-deficient mice encompassed increased activity of the Akt signaling pathway, supported by cell experiments showing Akt-dependent proliferation in NEIL3-abrogated human primary aortic VSMCs. CONCLUSIONS: Our findings show that Neil3 deficiency promotes atherosclerosis development through non-canonical mechanisms affecting VSMC phenotype involving activation of the Akt signaling pathway

    Lower-thermosphere–ionosphere (LTI) quantities: current status of measuring techniques and models

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    The lower-thermosphere-ionosphere (LTI) system consists of the upper atmosphere and the lower part of the ionosphere and as such comprises a complex system coupled to both the atmosphere below and space above. The atmospheric part of the LTI is dominated by laws of continuum fluid dynamics and chemistry, while the ionosphere is a plasma system controlled by electromagnetic forces driven by the magnetosphere, the solar wind, as well as the wind dynamo. The LTI is hence a domain controlled by many different physical processes. However, systematic in situ measurements within this region are severely lacking, although the LTI is located only 80 to 200 km above the surface of our planet. This paper reviews the current state of the art in measuring the LTI, either in situ or by several different remote-sensing methods. We begin by outlining the open questions within the LTI requiring high-quality in situ measurements, before reviewing directly observable parameters and their most important derivatives. The motivation for this review has arisen from the recent retention of the Daedalus mission as one among three competing mission candidates within the European Space Agency (ESA) Earth Explorer 10 Programme. However, this paper intends to cover the LTI parameters such that it can be used as a background scientific reference for any mission targeting in situ observations of the LTI.Peer reviewe

    SARS-CoV-2 antibody prevalence among homeless people and shelter workers in Denmark:a nationwide cross-sectional study

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    BACKGROUND: People experiencing homelessness (PEH) and associated shelter workers may be at higher risk of infection with “Severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2). The aim of this study was to determine the prevalence of SARS-CoV-2 among PEH and shelter workers in Denmark. DESIGN AND METHODS: In November 2020, we conducted a nationwide cross-sectional seroprevalence study among PEH and shelter workers at 21 recruitment sites in Denmark. The assessment included a point-of-care test for antibodies against SARS-CoV-2, followed by a questionnaire. The seroprevalence was compared to that of geographically matched blood donors considered as a proxy for the background population, tested using a total Ig ELISA assay. RESULTS: We included 827 participants in the study, of whom 819 provided their SARS-CoV-2 antibody results. Of those, 628 were PEH (median age 50.8 (IQR 40.9–59.1) years, 35.5% female) and 191 were shelter workers (median age 46.6 (IQR 36.1–55.0) years and 74.5% female). The overall seroprevalence was 6.7% and was similar among PEH and shelter workers (6.8% vs 6.3%, p = 0.87); and 12.2% among all participants who engaged in sex work. The overall participant seroprevalence was significantly higher than that of the background population (2.9%, p < 0.001). When combining all participants who reported sex work or were recruited at designated safe havens, we found a significantly increased risk of seropositivity compared to other participants (OR 2.23, 95%CI 1.06–4.43, p = 0.02). Seropositive and seronegative participants reported a similar presence of at least one SARS-CoV-2 associated symptom (49% and 54%, respectively). INTERPRETATIONS: The prevalence of SARS-CoV-2 antibodies was more than twice as high among PEH and associated shelter workers, compared to the background population. These results could be taken into consideration when deciding in which phase PEH are eligible for a vaccine, as part of the Danish national SARS-CoV-2 vaccination program rollout. FUNDING: TrygFonden and HelseFonden. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-022-13642-7

    Psoriasis Carries an Increased Risk of Venous Thromboembolism: A Danish Nationwide Cohort Study

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    Psoriasis is an immunoinflammatory disease associated with cardiovascular risk factors, atherothrombotic events, and hypercoagulability. Venous thromboembolism (VTE) is potentially lethal and shares risk factors with psoriasis, but the risk of VTE associated with psoriasis is unknown. The present study investigated the potential association between psoriasis and VTE.Information from nationwide prospectively recorded registers of hospitalization, drug dispensing from pharmacies, socio-economic data, and causes of death was linked on an individual level. In an unselected nationwide cohort, we used multivariate Poisson regression models controlling for age, gender, comorbidity, concomitant medication, socio-economic data, and calendar year, to assess the risk of VTE associated with psoriasis. A total of 35,138 patients with mild and 3,526 patients with severe psoriasis were identified and compared with 4,126,075 controls. Patients with psoriasis had higher incidence rates per 1000 person-years of VTE than controls (1.29, 1.92, and 3.20 for controls, mild psoriasis, and severe psoriasis, respectively). The rate ratio (RR) of VTE was elevated in all patients with psoriasis with RR 1.35 (95% confidence interval [CI] 1.21–1.49) and RR 2.06 (CI 1.63–2.61) for mild and severe psoriasis, respectively. Exclusion of patients with malignancies, and censoring of patients undergoing surgery did not alter the results.This nationwide cohort study indicates that patients with psoriasis are at increased risk of VTE. The risk was highest in young patients with severe psoriasis. Physicians should be aware that patients with psoriasis may be at increased risk of both venous and arterial thromboembolic events
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