119 research outputs found

    Facial Reconstruction: Anthropometric Studies Regarding the Morphology of the Nose for Romanian Adult Population I: Nose Width

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    Craniofacial reconstruction often represents a final step in medico-legal identification and is dependent on facial tissue thickness measurements and feature shape estimation. This study’s aim is to create a reliable and readily reproductible method of predicting the maximum nose width (MNW) based on the maximum nasal aperture width (MAW) for a Romanian adult population. A sample of 55 computer tomography (CT) scans consisting of Romanian adult subjects was selected from the database of a neurosurgery hospital. The craniometrics measured consisted of a first measure of MAW and second one of the MNW using 3D systems Freeform Modelling Plus Software. Correlation analysis indicated a moderate link between the MAW and the MNW. Regression analysis showed that MAW and sex form a statistically significant regression pattern (R2 = 0.340, SEE (Standard Error of Estimate) = 3.801). The preliminary results obtained provide reliable predictions of MNW for facial reconstruction based on MAW measured on the skull

    The von Hippel-Lindau Chuvash mutation in mice alters cardiac substrate and high energy phosphate metabolism

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    Hypoxia-inducible factor (HIF) appears to function as a global master regulator of cellular and systemic responses to hypoxia. HIF-pathway manipulation is of therapeutic interest, however global, systemic upregulation of HIF may have as yet unknown effects on multiple processes. We utilized a mouse model of Chuvash polycythemia (CP), a rare genetic disorder which modestly increases expression of HIF target genes in normoxia, to understand what these effects might be within the heart. An integrated in and ex vivo approach was employed. In comparison to wild-type controls, CP mice had evidence (using in vivo MRI) of pulmonary hypertension, right ventricular hypertrophy, and increased left ventricular ejection fraction. Glycolytic flux (measured using 3H glucose) in the isolated, contracting, perfused CP heart was 1.8-fold higher. Net lactate efflux was 1.5-fold higher. Furthermore, in vivo 13C magnetic resonance spectroscopy (MRS) of hyperpolarized 13C1 pyruvate revealed a 2-fold increase in real-time flux through lactate dehydrogenase in the CP hearts, and a 1.6-fold increase through pyruvate dehydrogenase. 31P MRS of perfused CP hearts under increased workload (isoproterenol infusion) demonstrated increased depletion of phosphocreatine relative to ATP. Intriguingly, no changes in cardiac gene expression were detected. In summary, a modest systemic dysregulation of the HIF pathway resulted in clear alterations in cardiac metabolism and energetics. However, in contrast to studies generating high HIF levels within the heart, the CP mice showed neither the predicted changes in gene expression nor any degree of LV impairment. We conclude that the effects of manipulating HIF on the heart are dose-dependent. New and noteworthy This is the first integrative metabolic and functional study of the effects of modest HIF manipulation within the heart. Of particular note, the combination (and correlation) of perfused heart metabolic flux measurements with the new technique of real-time in vivo MR spectroscopy using hyperpolarized pyruvate is a novel development

    Detecting Awareness in the Vegetative State: Electroencephalographic Evidence for Attempted Movements to Command

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    Patients in the Vegetative State (VS) do not produce overt motor behavior to command and are therefore considered to be unaware of themselves and of their environments. However, we recently showed that high-density electroencephalography (EEG) can be used to detect covert command-following in some VS patients. Due to its portability and inexpensiveness, EEG assessments of awareness have the potential to contribute to a standard clinical protocol, thus improving diagnostic accuracy. However, this technique requires refinement and optimization if it is to be used widely as a clinical tool. We asked a patient who had been repeatedly diagnosed as VS for 12-years to try to move his left and right hands, between periods of rest, while EEG was recorded from four scalp electrodes. We identified appropriate and statistically reliable modulations of sensorimotor beta rhythms following commands to try to move, which could be significantly classified at a single-trial level. These reliable effects indicate that the patient attempted to follow the commands, and was therefore aware, but was unable to execute an overtly discernable action. The cognitive demands of this novel task are lower than those used previously and, crucially, allow for awareness to be determined on the basis of a 20-minute EEG recording made with only four electrodes. This approach makes EEG assessments of awareness clinically viable, and therefore has potential for inclusion in a standard assessment of awareness in the VS

    Swearing, Euphemisms, and Linguistic Relativity

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    Participants read aloud swear words, euphemisms of the swear words, and neutral stimuli while their autonomic activity was measured by electrodermal activity. The key finding was that autonomic responses to swear words were larger than to euphemisms and neutral stimuli. It is argued that the heightened response to swear words reflects a form of verbal conditioning in which the phonological form of the word is directly associated with an affective response. Euphemisms are effective because they replace the trigger (the offending word form) by another word form that expresses a similar idea. That is, word forms exert some control on affect and cognition in turn. We relate these findings to the linguistic relativity hypothesis, and suggest a simple mechanistic account of how language may influence thinking in this context

    Differentiation-Dependent Secretion of Proangiogenic Factors by Mesenchymal Stem Cells

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    Mesenchymal stem cells (MSCs) are a promising cell population for cell-based bone repair due to their proliferative potential, ability to differentiate into bone-forming osteoblasts, and their secretion of potent trophic factors that stimulate angiogenesis and neovascularization. To promote bone healing, autogenous or allogeneic MSCs are transplanted into bone defects after differentiation to varying degrees down the osteogenic lineage. However, the contribution of the stage of osteogenic differentiation upon angiogenic factor secretion is unclear. We hypothesized that the proangiogenic potential of MSCs was dependent upon their stage of osteogenic differentiation. After 7 days of culture, we observed the greatest osteogenic differentiation of MSCs when cells were cultured with dexamethasone (OM+). Conversely, VEGF protein secretion and upregulation of angiogenic genes were greatest in MSCs cultured in growth media (GM). Using conditioned media from MSCs in each culture condition, GM-conditioned media maximized proliferation and enhanced chemotactic migration and tubule formation of endothelial colony forming cells (ECFCs). The addition of a neutralizing VEGF165/121 antibody to conditioned media attenuated ECFC proliferation and chemotactic migration. ECFCs seeded on microcarrier beads and co-cultured with MSCs previously cultured in GM in a fibrin gel exhibited superior sprouting compared to MSCs previously cultured in OM+. These results confirm that MSCs induced farther down the osteogenic lineage possess reduced proangiogenic potential, thereby providing important findings for consideration when using MSCs for bone repair

    Epigenetic silencing of DSC3 is a common event in human breast cancer

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    INTRODUCTION: Desmocollin 3 (DSC3) is a member of the cadherin superfamily of calcium-dependent cell adhesion molecules and a principle component of desmosomes. Desmosomal proteins such as DSC3 are integral to the maintenance of tissue architecture and the loss of these components leads to a lack of adhesion and a gain of cellular mobility. DSC3 expression is down-regulated in breast cancer cell lines and primary breast tumors; however, the loss of DSC3 is not due to gene deletion or gross rearrangement of the gene. In this study, we examined the prevalence of epigenetic silencing of DSC3 gene expression in primary breast tumor specimens. METHODS: We used bisulfite genomic sequencing to analyze the methylation state of the DSC3 promoter region from 32 primary breast tumor specimens. We also used a quantitative real-time RT-PCR approach, and analyzed all breast tumor specimens for DSC3 expression. Finally, in addition to bisulfite sequencing and RT-PCR, we used an in vivo nuclease accessibility assay to determine the chromatin architecture of the CpG island region from DSC3-negative breast cancer cells lines. RESULTS: DSC3 expression was downregulated in 23 of 32 (72%) breast cancer specimens comprising: 22 invasive ductal carcinomas, 7 invasive lobular breast carcinomas, 2 invasive ductal carcinomas that metastasized to the lymph node, and a mucoid ductal carcinoma. Of the 23 specimens showing a loss of DSC3 expression, 13 (56%) were associated with cytosine hypermethylation of the promoter region. Furthermore, DSC3 expression is limited to cells of epithelial origin and its expression of mRNA and protein is lost in a high proportion of breast tumor cell lines (79%). Lastly, DNA hypermethylation of the DSC3 promoter is highly correlated with a closed chromatin structure. CONCLUSION: These results indicate that the loss of DSC3 expression is a common event in primary breast tumor specimens, and that DSC3 gene silencing in breast tumors is frequently linked to aberrant cytosine methylation and concomitant changes in chromatin structure

    Are vaccination programmes delivered by lay health workers cost-effective? A systematic review

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    <p>Abstract</p> <p>Background</p> <p>A recently updated Cochrane systematic review on the effects of lay or community health workers (LHWs) in primary and community health care concluded that LHW interventions could lead to promising benefits in the promotion of childhood vaccination uptake. However, understanding of the costs and cost-effectiveness of involving LHWs in vaccination programmes remains poor. This paper reviews the costs and cost-effectiveness of vaccination programme interventions involving LHWs.</p> <p>Methods</p> <p>Articles were retrieved if the title, keywords or abstract included terms related to 'lay health workers', 'vaccination' and 'economics'. Reference lists of studies assessed for inclusion were also searched and attempts were made to contact authors of all studies included in the Cochrane review. Studies were included after assessing eligibility of the full-text article. The included studies were then reviewed against a set of background and technical characteristics.</p> <p>Results</p> <p>Of the 2616 records identified, only three studies fully met the inclusion criteria, while an additional 11 were retained as they included some cost data. Methodologically, the studies were strong but did not adequately address affordability and sustainability and were also highly heterogeneous in terms of settings and LHW outcomes, limiting their comparability. There were insufficient data to allow any conclusions to be drawn regarding the cost-effectiveness of LHW interventions to promote vaccination uptake. Studies focused largely on health outcomes and did illustrate to some extent how the institutional characteristics of communities, such as governance and sources of financial support, influence sustainability.</p> <p>Conclusion</p> <p>The included studies suggest that conventional economic evaluations, particularly cost-effectiveness analyses, generally focus too narrowly on health outcomes, especially in the context of vaccination promotion and delivery at the primary health care level by LHWs. Further studies on the costs and cost-effectiveness of vaccination programmes involving LHWs should be conducted, and these studies should adopt a broader and more holistic approach.</p
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