535 research outputs found

    Twenty-Five-Year Alcohol Consumption Trajectories and Their Association With Arterial Aging: A Prospective Cohort Study.

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    BACKGROUND: Emerging evidence suggests that arterial stiffness, an important marker of cardiovascular health, is associated with alcohol consumption. However, the role of longer-term consumption patterns in the progression of arterial stiffness over time remains unclear. A longitudinal cohort design was used to evaluate the association between alcohol consumption over 25 years and subsequent changes in arterial stiffness. METHODS AND RESULTS: Data (N=3869; 73% male) were drawn from the Whitehall II cohort study of British civil servants, in which participants completed repeat pulse wave velocity assessments of arterial stiffness across a 4- to 5-year interval. Repeated alcohol intake measurements were used to categorize participants into alcohol consumer types, accounting for longitudinal variability in consumption. Sex-stratified linear mixed-effects modeling was used to investigate whether drinker types differed in their relationship to pulse wave velocity and its progression over time. Males with consistent long-term heavy intake >112 g of ethanol/week had significantly higher baseline pulse wave velocity (b=0.26 m/s; P=0.045) than those who drank consistently moderately (1-112 g of ethanol/week). Male former drinkers showed significantly greater increases in arterial stiffness longitudinally compared to consistently moderate drinkers (b=0.11 m/s; P=0.009). All associations were nonsignificant for females after adjustment for body mass index, heart rate, mean arterial pressure, diabetes mellitus, high-density lipoprotein, and triglycerides. CONCLUSIONS: This work demonstrates that consistently heavy alcohol consumption is associated with higher cardiovascular risk, especially among males, and also provides new insights into the potential impact of changes in drinking levels over time. It discusses the additional insights possible when capturing longitudinal consumption patterns in lieu of reliance on recent intake alone. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02663791

    Adrenal steroids modulate the immune response during Brucella abortus infection by a mechanism that depends on the regulation of cytokine production

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    Human brucellosis is a protean disease with a diversity of clinical signs and symptoms resulting from infection with Brucella species. Recent reports suggest a cross-regulation between adrenal steroids (cortisol and dehydroepiandrosterone [DHEA]) and the immune system. Monocytes and macrophages are the main replication niche for Brucella. Therefore, we investigated the role of adrenal hormones on the modulation of the immune response mediated by macrophages in B. abortus infection. Cortisol treatment during B. abortus infection significantly inhibits cytokine, chemokine, and MMP-9 secretion. In contrast, DHEA treatment had no effect. However, DHEA treatment increases the expression of costimulatory molecules (CD40, CD86), the adhesion molecule CD54, and major histocompatibility complex class I (MHC-I) and MHC-II expression on the surface of B. abortus-infected monocytes. It is known that B. abortus infection inhibits MHC-I and MHC-II expression induced by gamma interferon (IFN-γ) treatment. DHEA reverses B. abortus downmodulation of the MHC-I and -II expression induced by IFN-γ. Taken together, our data indicate that DHEA immune intervention may positively affect monocyte activity during B. abortus infection.Fil: Gentilini, Maria Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Velasquez, Lis Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Barrionuevo, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Arriola Benitez, Paula Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Giambartolomei, Guillermo Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Delpino, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentin

    Challenges for standardization of Clostridium difficile typing methods

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    Typing of Clostridium difficile facilitates understanding of the epidemiology of the infection. Some evaluations have shown that certain strain types (for example, ribotype 027) are more virulent than others and are associated with worse clinical outcomes. Although restriction endonuclease analysis (REA) and pulsed-field gel electrophoresis have been widely used in the past, PCR ribotyping is the current method of choice for typing of C. difficile. However, global standardization of ribotyping results is urgently needed. Whole-genome sequencing of C. difficile has the potential to provide even greater epidemiologic information than ribotyping

    Quantitative Trait Loci Associated with the Immune Response to a Bovine Respiratory Syncytial Virus Vaccine

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    Infectious disease is an important problem for animal breeders, farmers and governments worldwide. One approach to reducing disease is to breed for resistance. This linkage study used a Charolais-Holstein F2 cattle cross population (n = 501) which was genotyped for 165 microsatellite markers (covering all autosomes) to search for associations with phenotypes for Bovine Respiratory Syncytial Virus (BRSV) specific total-IgG, IgG1 and IgG2 concentrations at several time-points pre- and post-BRSV vaccination. Regions of the bovine genome which influenced the immune response induced by BRSV vaccination were identified, as well as regions associated with the clearance of maternally derived BRSV specific antibodies. Significant positive correlations were detected within traits across time, with negative correlations between the pre- and post-vaccination time points. The whole genome scan identified 27 Quantitative Trait Loci (QTL) on 13 autosomes. Many QTL were associated with the Thymus Helper 1 linked IgG2 response, especially at week 2 following vaccination. However the most significant QTL, which reached 5% genome-wide significance, was on BTA 17 for IgG1, also 2 weeks following vaccination. All animals had declining maternally derived BRSV specific antibodies prior to vaccination and the levels of BRSV specific antibody prior to vaccination were found to be under polygenic control with several QTL detected

    Impact of exposure of methicillin-resistant Staphylococcus aureus to polyhexanide in vitro and in vivo.

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    Staphylococcus aureus (MRSA) resistant to decolonization agents such as mupirocin and chlorhexidine increase the need to develop alternative decolonization molecules. The absence of reported adverse reactions and bacterial resistance to polyhexanide makes it an excellent choice as topical antiseptic. In the present study we evaluated the in vitro and in vivo capacity to generate strains with reduced polyhexanide susceptibility and cross-resistance with chlorhexidine and/or antibiotics currently used in clinic. Here we report the in vitro emergence of reduced-susceptibility to polyhexanide by prolonged-stepwise exposure to low concentrations in broth culture. Reduced susceptibility to polyhexanide was associated with genomic changes in the mprF and purR genes, and with concomitant decreased susceptibility to daptomycin and other cell-wall active antibiotics. However, the in vitro emergence of reduced-susceptibility to polyhexanide did not result in cross-resistance to chlorhexidine antiseptic. During in vivo polyhexanide clinical decolonization treatment, neither polyhexanide reduced-susceptibility nor chlorhexidine cross-resistance were observed. Together, these observations suggest that polyhexanide could be used safely for decolonisation of carriers of chlorhexidine-resistant S. aureus strains but highlight the need for careful use of polyhexanide at low antiseptic concentrations

    Corrigendum to “Synovial volume vs synovial measurements from dynamic contrast enhanced MRI as measures of response in osteoarthritis” [Osteoarthritis Cartilage 24(8) (2016) 1392–1398](S106345841630005X)(10.1016/j.joca.2016.03.015)

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    © 2017 We have been notified by the authors that there was an error in the second sentence of the paragraph headed ‘Image analysis: segmentation’ on p. 1394 of the above article. The term interobserver should have been intraobserver. The correct sentence is as follows: Manual segmentation of the synovial tissue layer was performed on these sagittal post-contrast knee images by a single observer (intraobserver ICC = 0.94), who assessed baseline and follow-up visit MR images paired, but blinded to order. The authors would like to apologise for any inconvenience caused

    Therapeutic revascularisation of ischaemic tissue: the opportunities and challenges for therapy using vascular stem/progenitor cells.

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    Ischaemia-related diseases such as peripheral artery disease and coronary heart disease constitute a major issue in medicine as they affect millions of individuals each year and represent a considerable economic burden to healthcare systems. If the underlying ischaemia is not sufficiently resolved it can lead to tissue damage, with subsequent cell death. Treating such diseases remains difficult and several strategies have been used to stimulate the growth of blood vessels and promote regeneration of ischaemic tissues, such as the use of recombinant proteins and gene therapy. Although these approaches remain promising, they have limitations and results from clinical trials using these methods have had limited success. Recently, there has been growing interest in the therapeutic potential of using a cell-based approach to treat vasodegenerative disorders. In vascular medicine, various stem cells and adult progenitors have been highlighted as having a vasoreparative role in ischaemic tissues. This review will examine the clinical potential of several stem and progenitor cells that may be utilised to regenerate defunct or damaged vasculature and restore blood flow to the ischaemic tissue. In particular, we focus on the therapeutic potential of endothelial progenitor cells as an exciting new option for the treatment of ischaemic diseases.This work was supported by the Medical Research Council, by Fight for Sight, D.E.L. (NI), by the Juvenile Diabetes Research Foundation, by The Royal Society and by the Sir Jules Thorn Trust

    Time separation as a hidden variable to the Copenhagen school of quantum mechanics

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    The Bohr radius is a space-like separation between the proton and electron in the hydrogen atom. According to the Copenhagen school of quantum mechanics, the proton is sitting in the absolute Lorentz frame. If this hydrogen atom is observed from a different Lorentz frame, there is a time-like separation linearly mixed with the Bohr radius. Indeed, the time-separation is one of the essential variables in high-energy hadronic physics where the hadron is a bound state of the quarks, while thoroughly hidden in the present form of quantum mechanics. It will be concluded that this variable is hidden in Feynman's rest of the universe. It is noted first that Feynman's Lorentz-invariant differential equation for the bound-state quarks has a set of solutions which describe all essential features of hadronic physics. These solutions explicitly depend on the time separation between the quarks. This set also forms the mathematical basis for two-mode squeezed states in quantum optics, where both photons are observable, but one of them can be treated a variable hidden in the rest of the universe. The physics of this two-mode state can then be translated into the time-separation variable in the quark model. As in the case of the un-observed photon, the hidden time-separation variable manifests itself as an increase in entropy and uncertainty.Comment: LaTex 10 pages with 5 figure. Invited paper presented at the Conference on Advances in Quantum Theory (Vaxjo, Sweden, June 2010), to be published in one of the AIP Conference Proceedings serie
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