8,339 research outputs found

    CdSe/TiO2 core-shell nanoparticles produced in AOT reverse micelles: applications in pollutant photodegradation using visible light

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    CdSe quantum dots with a prominent band-edge photoluminescence were obtained by a soft AOT water-in-oil (w/o) microemulsion templating method with an estimated size of 2.7 nm. The CdSe particles were covered with a TiO2 layer using an intermediate SiO2 coupling reagent by a sol-gel process. The resulting CdSe/TiO2 core/shell nanoparticles showed appreciable photocatalytic activity at λ = 405 nm which can only originate because of electron injection from the conduction band of CdSe to that of TiO2

    A microtubule interactome: complexes with roles in cell cycle and mitosis.

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    addresses: Department of Zoology, University of Oxford, Oxford, United Kingdom.notes: PMCID: PMC2323305types: Journal Article; Research Support, Non-U.S. Gov'tCopyright: © 2008 Hughes et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.The microtubule (MT) cytoskeleton is required for many aspects of cell function, including the transport of intracellular materials, the maintenance of cell polarity, and the regulation of mitosis. These functions are coordinated by MT-associated proteins (MAPs), which work in concert with each other, binding MTs and altering their properties. We have used a MT cosedimentation assay, combined with 1D and 2D PAGE and mass spectrometry, to identify over 250 MAPs from early Drosophila embryos. We have taken two complementary approaches to analyse the cellular function of novel MAPs isolated using this approach. First, we have carried out an RNA interference (RNAi) screen, identifying 21 previously uncharacterised genes involved in MT organisation. Second, we have undertaken a bioinformatics analysis based on binary protein interaction data to produce putative interaction networks of MAPs. By combining both approaches, we have identified and validated MAP complexes with potentially important roles in cell cycle regulation and mitosis. This study therefore demonstrates that biologically relevant data can be harvested using such a multidisciplinary approach, and identifies new MAPs, many of which appear to be important in cell division

    How the 'plates' of a health system can shift, change and adjust during economic recessions: A qualitative interview study of public and private health providers in Brazil's Sao Paulo and Maranhao states

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    Background: Economic recessions carry an impact on population health and access to care; less is known on how health systems adapt to the conditions brought by a downturn. This particularly matters now that the COVID-19 epidemic is putting health systems under stress. Brazil is one of the world’s most affected countries, and its health system was already experiencing the aftermath of the 2015 recession. Methods: Between 2018 and 2019 we conducted 46 semi-structured interviews with health practitioners, managers and policy-makers to explore the impact of the 2015 recession on public and private providers in prosperous (São Paulo) and impoverished (Maranhão) states in Brazil. Thematic analysis was employed to identify drivers and consequences of system adaptation and coping strategies. Nvivo software was used to aid data collection and analysis. We followed the Standards for Reporting Qualitative Research to provide an account of the findings. Results: We found the concept of ‘health sector crisis’ to be politically charged among healthcare providers in São Paulo and Maranhão. Contrary to expectations, the public sector was reported to have found ways to compensate for diminishing federal funding, having outsourced services and adopted flexible–if insecure–working arrangements. Following a drop in employment and health plans, private health insurance companies have streamlined their offer, at times at the expenses of coverage. Low-cost walk-in clinics were hit hard by the recession, but were also credited for having moved to cater for higher-income customers in Maranhão. Conclusions: The ‘plates’ of a health system may shift and adjust in unexpected ways in response to recessions, and some of these changes might outlast the crisis. As low-income countries enter post-COVID economic recessions, it will be important to monitor the adjustments taking place in health systems, to ensure that past gains in access to care and job security are not eroded

    Sex Differences in the Association between Serum Levels of Testosterone and Frailty in an Elderly Population: The Toledo Study for Healthy Aging

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    BACKGROUND: Age-associated decline in testosterone levels represent one of the potential mechanisms involved in the development of frailty. Although this association has been widely reported in older men, very few data are available in women. We studied the association between testosterone and frailty in women and assessed sex differences in this relationship. METHODS: We used cross-sectional data from the Toledo Study for Healthy Aging, a population-based cohort study of Spanish elderly. Frailty was defined according to Fried's approach. Multivariate odds-ratios (OR) and 95% confidence intervals (CI) associated with total (TT) and free testosterone (FT) levels were estimated using polytomous logistic regression. RESULTS: In women, there was a U-shaped relationship between FT levels and frailty (p for FT(2) = 0.03). In addition, very low levels of FT were observed in women with ≥ 4 frailty criteria (age-adjusted geometric means = 0.13 versus 0.37 in subjects with <4 components, p = 0.010). The association of FT with frailty appeared confined to obese women (p-value for interaction = 0.05).In men, the risk of frailty levels linearly decreased with testosterone (adjusted OR for frailty = 2.9 (95%CI, 1.6-5.1) and 1.6 (95%CI, 1.0-2.5), for 1 SD decrease in TT and FT, respectively). TT and FT showed association with most of frailty criteria. No interaction was found with BMI. CONCLUSION: There is a relationship between circulating levels of FT and frailty in older women. This relation seems to be modulated by BMI. The relevance and the nature of the association of FT levels and frailty are sex-specific, suggesting that different biological mechanisms may be involved

    Comparison of 8 weeks standard treatment (rifampicin plus clarithromycin) vs. 4 weeks standard plus amoxicillin/clavulanate treatment [RC8 vs. RCA4] to shorten Buruli ulcer disease therapy (the BLMs4BU trial): study protocol for a randomized controlled multi-centre trial in Benin

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    Background Buruli ulcer (BU) is a neglected tropical disease caused by Mycobacterium ulcerans that affects skin, soft tissues, and bones, causing long-term morbidity, stigma, and disability. The recommended treatment for BU requires 8 weeks of daily rifampicin and clarithromycin together with wound care, physiotherapy, and sometimes tissue grafting and surgery. Recovery can take up to 1 year, and it may pose an unbearable financial burden to the household. Recent in vitro studies demonstrated that beta-lactams combined with rifampicin and clarithromycin are synergistic against M. ulcerans. Consequently, inclusion of amoxicillin/clavulanate in a triple oral therapy may potentially improve and shorten the healing process. The BLMs4BU trial aims to assess whether co-administration of amoxicillin/clavulanate with rifampicin and clarithromycin could reduce BU treatment from 8 to 4 weeks. Methods We propose a randomized, controlled, open-label, parallel-group, non-inferiority phase II, multi-centre trial in Benin with participants stratified according to BU category lesions and randomized to two oral regimens: (i) Standard: rifampicin plus clarithromycin therapy for 8 weeks; and (ii) Investigational: standard plus amoxicillin/clavulanate for 4 weeks. The primary efficacy outcome will be lesion healing without recurrence and without excision surgery 12 months after start of treatment (i.e. cure rate). Seventy clinically diagnosed BU patients will be recruited per arm. Patients will be followed up over 12 months and managed according to standard clinical care procedures. Decision for excision surgery will be delayed to 14 weeks after start of treatment. Two sub-studies will also be performed: a pharmacokinetic and a microbiology study. Discussion If successful, this study will create a new paradigm for BU treatment, which could inform World Health Organization policy and practice. A shortened, highly effective, all-oral regimen will improve care of BU patients and will lead to a decrease in hospitalization-related expenses and indirect and social costs and improve treatment adherence. This trial may also provide information on treatment shortening strategies for other mycobacterial infections (tuberculosis, leprosy, or non-tuberculous mycobacteria infections). Trial registration ClinicalTrials.gov NCT05169554. Registered on 27 December 2021

    Contribution of cell blocks obtained through endobronchial ultrasound-guided transbronchial needle aspiration to the diagnosis of lung cancer

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    <p>Abstract</p> <p>Background</p> <p>Conventional smears of samples obtained by endobronchial ultrasound with real-time transbronchial needle aspiration (EBUS-TBNA) have proven useful in lung cancer staging, but the value of additional information from cell-block processing of EBUS-TBNA samples has only been marginally investigated. This study focussed on the contribution of cell block analysis to the diagnostic yield in lung cancer.</p> <p>Methods</p> <p>Patients referred for lung cancer diagnosis and/or staging by means of EBUS-TBNA were enrolled, the adequacy of the obtained samples for preparing cell blocks was assessed, and the additional pathologic or genetic information provided from cell block analysis was examined.</p> <p>Results</p> <p>In 270 lung cancer patients referred for EBUS-TBNA (mean age, 63.3 SD 10.4 years) 697 aspirations were performed. Cell blocks could be obtained from 334 aspirates (47.9%) and contained diagnostic material in 262 (37.6%) aspirates, providing information that was additional to conventional smears in 50 of the 189 samples with smears that were non-diagnostic, corresponding 21 of these blocks to malignant nodes, and allowing lung cancer subtyping of 4 samples. Overall, cell blocks improved the pathologic diagnosis attained with conventional smears in 54 of the 697 samples obtained with EBUS-TBNA (7.7%). Cell blocks obtained during EBUS-TBNA also made epithelial growth factor receptor mutation analysis possible in 39 of the 64 patients with TBNA samples showing metastatic adenocarcinoma (60.1%). Overall, cell blocks provided clinically significant information for 83 of the 270 patients participating in the study (30.7%).</p> <p>Conclusions</p> <p>Cell-block preparation from EBUS-TBNA samples is a simple way to provide additional information in lung cancer diagnosis. Analysis of cell blocks increases the diagnostic yield of the procedure by nearly seven per cent and allows for genetic analysis in a sixty per cent of the patients with metastatic adenocarcinoma.</p

    Vasodilator Phosphostimulated Protein (VASP) Protects Endothelial Barrier Function During Hypoxia

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    The endothelial barrier controls the passage of solutes from the vascular space. This is achieved through active reorganization of the actin cytoskeleton. A central cytoskeletal protein involved into this is vasodilator-stimulated phosphoprotein (VASP). However, the functional role of endothelial VASP during hypoxia has not been thoroughly elucidated. We determined endothelial VASP expression through real-time PCR (Rt-PCR), immunhistochemistry, and Western blot analysis during hypoxia. VASP promoter studies were performed using a PGL3 firefly luciferase containing plasmid. Following approval by the local authorities, VASP−/− mice and littermate controls were subjected to normobaric hypoxia (8% O2, 92% N2) after intravenous injection of Evans blue dye. In in vitro studies, we found significant VASP repression in human microvascular and human umbilical vein endothelial cells through Rt-PCR, immunhistochemistry, and Western blot analysis. The VASP promoter construct demonstrated significant repression in response to hypoxia, which was abolished when the binding of hypoxia-inducible factor 1 alpha was excluded. Exposure of wild-type (WT) and VASP−/− animals to normobaric hypoxia for 4 h resulted in an increase in Evans blue tissue extravasation that was significantly increased in VASP−/− animals compared to WT controls. In summary, we demonstrate here that endothelial VASP holds significant importance for endothelial barrier properties during hypoxia
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