155 research outputs found

    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

    Mammal-Like Organization of the Avian Midbrain Central Gray and a Reappraisal of the Intercollicular Nucleus

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    In mammals, rostrocaudal columns of the midbrain periaqueductal gray (PAG) regulate diverse behavioral and physiological functions, including sexual and fight-or-flight behavior, but homologous columns have not been identified in non-mammalian species. In contrast to mammals, in which the PAG lies ventral to the superior colliculus and surrounds the cerebral aqueduct, birds exhibit a hypertrophied tectum that is displaced laterally, and thus the midbrain central gray (CG) extends mediolaterally rather than dorsoventrally as in mammals. We therefore hypothesized that the avian CG is organized much like a folded open PAG. To address this hypothesis, we conducted immunohistochemical comparisons of the midbrains of mice and finches, as well as Fos studies of aggressive dominance, subordinance, non-social defense and sexual behavior in territorial and gregarious finch species. We obtained excellent support for our predictions based on the folded open model of the PAG and further showed that birds possess functional and anatomical zones that form longitudinal columns similar to those in mammals. However, distinguishing characteristics of the dorsal/dorsolateral PAG, such as a dense peptidergic innervation, a longitudinal column of neuronal nitric oxide synthase neurons, and aggression-induced Fos responses, do not lie within the classical avian CG, but in the laterally adjacent intercollicular nucleus (ICo), suggesting that much of the ICo is homologous to the dorsal PAG

    Regulation of Mycobacterium-Specific Mononuclear Cell Responses by 25-Hydroxyvitamin D3

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    The active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), has been shown to be an important regulator of innate and adaptive immune function. In addition, synthesis of 1,25(OH)2D3 from 25-hydroxyvitamin D3 (25(OH)D3) by the enzyme 1α-hydroxylase in monocytes upon activation by TLR signaling has been found to regulate innate immune responses of monocytes in an intracrine fashion. In this study we wanted to determine what cells expressed 1α-hydroxylase in stimulated peripheral blood mononuclear cell (PBMC) cultures and if conversion of 25(OH)D3 to 1,25(OH)2D3 in PBMC cultures regulated antigen-specific immune responses. Initially, we found that stimulation of PBMCs from animals vaccinated with Mycobacterium bovis (M. bovis) BCG with purified protein derivative of M. bovis (M. bovis PPD) induced 1α-hydroxylase gene expression and that treatment with a physiological concentration of 25(OH)D3 down-regulated IFN-γ and IL-17F gene expression. Next, we stimulated PBMCs from M. bovis BCG-vaccinated and non-vaccinated cattle with M. bovis PPD and sorted them by FACS according to surface markers for monocytes/macrophages (CD14), B cells (IgM), and T cells (CD3). Sorting the PBMCs revealed that 1α-hydroxylase expression was induced in the monocytes and B cells, but not in the T cells. Furthermore, treatment of stimulated PBMCs with 25(OH)D3 down-regulated antigen-specific IFN-γ and IL-17F responses in the T cells, even though 1α-hydroxylase expression was not induced in the T cells. Based on evidence of no T cell 1α-hydroxylase we hypothesize that activated monocytes and B cells synthesize 1,25(OH)2D3 and that 1,25(OH)2D3 down-regulates antigen-specific expression of IFN-γ and IL-17F in T cells in a paracrine fashion
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