658 research outputs found

    Experimental Infection of a North American Raptor, American Kestrel (Falco sparverius), with Highly Pathogenic Avian Influenza Virus (H5N1)

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    Several species of wild raptors have been found in Eurasia infected with highly pathogenic avian influenza virus (HPAIV) subtype H5N1. Should HPAIV (H5N1) reach North America in migratory birds, species of raptors are at risk not only from environmental exposure, but also from consuming infected birds and carcasses. In this study we used American kestrels as a representative species of a North American raptor to examine the effects of HPAIV (H5N1) infection in terms of dose response, viral shedding, pathology, and survival. Our data showed that kestrels are highly susceptible to HPAIV (H5N1). All birds typically died or were euthanized due to severe neurologic disease within 4–5 days of inoculation and shed significant amounts of virus both orally and cloacally, regardless of dose administered. The most consistent microscopic lesions were necrosis in the brain and pancreas. This is the first experimental study of HPAIV infection in a North American raptor and highlights the potential risks to birds of prey if HPAIV (H5N1) is introduced into North America

    1,25-Dihydroxyvitamin D3-Conditioned CD11c+ Dendritic Cells are Effective Initiators of CNS Autoimmune Disease

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    Dendritic cells (DC) play a crucial role in regulating T cell activation. Due to their capacity to shape the immune response, tolerogenic DC have been used to treat autoimmune diseases. In this study, we examined whether 1,25 dihydroxyvitamin D3-conditioned bone marrow-derived DC (VitD-BMDC) were able to limit the development of autoimmune pathology in experimental autoimmune encephalomyelitis (EAE). We found that VitD-BMDC had lower expression of MHC class II and co-stimulatory molecules and were less effective at priming autoreactive T cells in vitro. Using our recently described BMDC-driven model of EAE, we demonstrated that VitD-BMDC had a significantly reduced ability to initiate EAE. We found that the impaired ability of VitD-BMDC to initiate EAE was not due to T cell tolerization. Instead, we discovered that the addition of 1,25(OH)2D3 to BMDC cultures resulted in a significant reduction in the proportion of CD11c+ cells. Purified CD11c+ VitD-BMDC were significantly less effective at priming T cells in vitro yet were similarly capable of initiating EAE as vehicle-treated CD11c+ BMDC. This study demonstrates that in vitro assays of DC function can be a poor predictor of in vivo behavior and that CD11c+ VitD-BMDC are highly effective initiators of an autopathogenic T cell response

    Using vital statistics to estimate the population-level impact of osteoporotic fractures on mortality based on death certificates, with an application to France (2000-2004)

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    Abstract Background We developed a methodology using vital statistics to estimate the impact of osteoporotic fractures on the mortality of an entire population, and applied it to France for the period 2000-2004. Methods Current definitions of osteoporotic fractures were reviewed and their components identified. We used the International Classification of Diseases with national vital statistics data for the French adult population and performed cross-classifications between various components: age, sex, I-code (site) and E-code (mechanism of fracture). This methodology allowed identification of appropriate thresholds and categorization for each pertinent component. Results 2,625,743 death certificates were analyzed, 2.2% of which carried a mention of fracture. Hip fractures represented 55% of all deaths from fracture. Both sexes showed a similar pattern of mortality rates for all fracture sites, the rate increased with age from the age of 70 years. The E-high-energy code (present in 12% of death certificates with fractures) was found to be useful to rule-out non-osteoporotic fractures, and to correct the overestimation of mortality rates. Using this methodology, the crude number of deaths associated with fractures was estimated to be 57,753 and the number associated with osteoporotic fractures 46,849 (1.85% and 1.78% of all deaths, respectively). Conclusion Osteoporotic fractures have a significant impact on overall population mortality.</p

    Clinical implications of a possible role of vitamin D in multiple sclerosis

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    Hypovitaminosis D is currently one of the most studied environmental risk factors for multiple sclerosis (MS) and is potentially the most promising in terms of new clinical implications. These practical consequences, which could be applied to MS patients without further delay, constitute the main purpose of this review. Vitamin D is involved in a number of important general actions, which were not even suspected until quite recently. In particular, this vitamin could play an immunomodulatory role in the central nervous system. Many and varied arguments support a significant role for vitamin D in MS. In animal studies, vitamin D prevents and improves experimental autoimmune encephalomyelitis. Epidemiologically, latitude, past exposure to sun and the serum level of vitamin D influence the risk of MS, with, furthermore, significant links existing between these different factors. Clinically, most MS patients have low serum levels of vitamin D and are in a state of insufficiency or even deficiency compared to the international norm, which has been established on a metabolic basis. Large therapeutic trials using vitamin D are still lacking but the first results of phase I/II studies are promising. In the meantime, while awaiting the results of future therapeutic trials, it can no longer be ignored that many MS patients have a lack of vitamin D, which could be detected by a serum titration and corrected using an appropriate vitamin D supplementation in order to restore their serum level to within the normal range. From a purely medical point of view, vitamin D supplementation appears in this light to be unavoidable in order to improve the general state of these patients. Furthermore, it cannot currently be ruled out that this supplementation could also be neurologically beneficial

    Advances in the role of sacral nerve neuromodulation in lower urinary tract symptoms

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    Sacral neuromodulation has been developed to treat chronic lower urinary tract symptoms, resistant to classical conservative therapy. The suspected mechanisms of action include afferent stimulation of the central nervous system and modulation of activity at the level of the brain. Typical neuromodulation is indicated both in overactivity and in underactivity of the lower urinary tract. In the majority of patients, a unilateral electrode in a sacral foramen and connected to a pulse generator is sufficient to achieve significant clinical results also on long term. In recent years, other urological indications have been explored
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