172 research outputs found

    On Stability of Multivariate Polynomials

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    Redesign of an informed consent form to increase participation in a school-based dental program

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    Objectives The study aimed to determine if modifications to the design of a consent form and consenting process increased participation rates in the Indiana University School of Dentistry's Mobile School-Based Dental Program (Seal Indiana). Methods Kaizen methodology was followed to identify problem areas in the consenting process. Additionally, stakeholders were invited to participate in focus groups and fill out surveys to identify issues preventing participation in the Seal Indiana program (N = 48) and later to evaluate the changes made (N = 48). The redesigned form and process were then used in a pilot study at 14 sites to determine the impact that changes had on levels of participation as measured by the number of consent forms completed and returned. Results There was a statistically significant increase in the number of consent forms returned. The measured change represented a 32 percent increase in program participation (P value = 0.035). A statistically significant increase was observed in how participants viewed the attractiveness of the form and how easy it was to read and comprehend. Conclusions In order to increase consenting rates, our results indicate modifications to the consent form should be focused on the following characteristics: esthetics, ease of reading and comprehending information, and making the Health Insurance Portability and Accountability Act of 1996 (HIPPA) privacy regulations easier to read and comprehend

    Eukaryotic elongation factor 2 controls TNF-alpha translation in LPS-induced hepatitis

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    Bacterial LPS (endotoxin) has been implicated in the pathogenesis of acute liver disease through its induction of the proinflammatory cytokine TNF-alpha. TNF-alpha is a key determinant of the outcome in a well-established mouse model of acute liver failure during septic shock. One possible mechanism for regulating TNF-alpha expression is through the control of protein elongation during translation, which would allow rapid cell adaptation to physiological changes. However, the regulation of translational elongation is poorly understood. We found that expression of p38gamma/delta MAPK proteins is required for the elongation of nascent TNF-alpha protein in macrophages. The MKK3/6-p38gamma/delta pathway mediated an inhibitory phosphorylation of eukaryotic elongation factor 2 (eEF2) kinase, which in turn promoted eEF2 activation (dephosphorylation) and subsequent TNF-alpha elongation. These results identify a new signaling pathway that regulates TNF-alpha production in LPS-induced liver damage and suggest potential cell-specific therapeutic targets for liver diseases in which TNF-alpha production is involved

    The neuronal ischemic tolerance is conditioned by the Tp53 Arg72Pro polymorphism

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    Cerebral preconditioning (PC) confers endogenous brain protection after stroke. Ischemic stroke patients with a prior transient ischemic attack (TIA) may potentially be in a preconditioned state. Although PC has been associated with the activation of prosurvival signals, the mechanism by which preconditioning confers neuroprotection is not yet fully clarified. Recently, we have described that PC-mediated neuroprotection against ischemic insult is promoted by p53 destabilization, which is mediated by its main regulatorMDM2. Moreover, we have previously described that the human Tp53 Arg72Pro single nucleotide polymorphism (SNP) controls susceptibility to ischemia-induced neuronal apoptosis and governs the functional outcome of patients after stroke. Here, we studied the contribution of the human Tp53 Arg72Pro SNP on PC-induced neuroprotection after ischemia. Our results showed that cortical neurons expressing the Pro72-p53 variant exhibited higher PC-mediated neuroprotection as compared with Arg72-p53 neurons. PC prevented ischemia-induced nuclear and cytosolic p53 stabilization in Pro72-p53 neurons. However, PC failed to prevent mitochondrial p53 stabilization, which occurs in Arg72-p53 neurons after ischemia. Furthermore, PC promoted neuroprotection against ischemia by controlling the p53/active caspase-3 pathway in Pro72-p53, but not in Arg72-p53 neurons. Finally, we found that good prognosis associated to TIA within 1 month prior to ischemic stroke was restricted to patients harboring the Pro72 allele. Our findings demonstrate that the Tp53 Arg72Pro SNP controls PC-promoted neuroprotection against a subsequent ischemic insult bymodulatingmitochondrial p53 stabilization and then modulates TIA-induced ischemic tolerance.This work was funded by The Instituto de Salud Carlos III grants CP14/00010 (M.D.-E.); PI15/00473 and RD12/0014/ 0007 (A.A.); CM14/00096 (ME.R.-A.); RD16/0019/0018 (C.R.); and Junta de Castilla y Leon grant BIO/SA35/15 (M.D.-E.), and the European Regional Development Fund (R.V.) was funded by the FPU program (Ministerio de Educación)

    Antioxidant and Biological Activity of <em>Cissus sicyoides</em> and <em>Rosmarinus officinalis</em> Extracts

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    This chapter will describe the antioxidant and biological activity of Cissus sicyoides and Rosmarinus officinalis leaf extracts, which represent an important natural source of antioxidants. These plants contain several bioactive compounds with high antioxidant activity, such as phenolic compounds, which are compounds that prevent or delay oxidative stress, acting as free radical scavengers (FRSs), and thus reduce the onset of cardiovascular disease, cancer, diabetes, epilepsy, stroke, among other diseases. The supercritical fluid extraction (SFE) has been studied to obtain antioxidant compounds from natural sources, without the drawbacks associated with conventional extraction processes, such as the use of organic solvents, which present toxicity and contaminate the extracts, is proposed

    Commercial and Therapeutic Potential of Plant-Based Fatty Acids

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    This chapter reviews plant-based fatty acids as well as their methods of production, applications in the industry, and benefits in treatments of cardiovascular and cerebral diseases, besides being a source of food. The fatty acids obtained from vegetable matrices have been acting as alternatives to the use of lipids of animal origin, due to their limitation in relation to the increase in demand. Thus, plants have been investigated in order to act as sources of fatty acids and assist in the supply of such demands. Vegetable oils represent not only an economical alternative but also a beneficial source of human health

    Potential of Medicinal Use of Essential Oils from Aromatic Plants

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    The use of medicinal plants rich in essential oils can represent a viable source for the control of some diseases, being able to constitute a possible therapeutic alternative due to its effectiveness. Essential oils are natural volatile fractions extracted from aromatic plants and formed by classes of substances such as esters of fatty acids, mono and sesquiterpenes, phenylpropanoids, aldehyde alcohols and, in some cases, aliphatic hydrocarbons, among others. Essential oils have been used by mankind for medicinal purposes for several centuries, with reports coming from Ancient Egypt. In this sense, the present work aims to approach the biological activities of essential oils such as antioxidant, anticancer, antiprotozoal, antifungal, antibacterial and anti-inflammatory activities of different plant matrices rich in essential oils

    Supercritical fluid extraction of murici leaves (Byrsonima crassifolia): Global yield, total phenolic compounds, antioxidant activity, and linear correlations / Extracção de fluido supercrítico de folhas de murici (Byrsonima crassifolia): Rendimento global, compostos fenólicos totais, actividade antioxidante, e correlações lineares

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    The objective of this study was to obtain extracts from Byrsonima crassifolia leaves by supercritical CO2 (CO2-SFE) in order to determine the experimental data, global yield isotherms, total phenolic compounds, antioxidant activity, and linear correlations. Moisture, particle diameter, apparent and true density, bed porosity, and morphological characterization of murici leaves were analyzed. CO2-SFE was conducted at 313.15 K–323.15 K, and at 10 MPa to 30 MPa. The bed parameters agreed with those used in CO2-SFE, and the particles presented irregular flat shape. The isotherms showed an inflection point, and the highest global yield was obtained at 323.15 K and 30 MPa (1.24% d.b.). The highest values of phenolic compounds (68.85 mg GAE/g d.b.) and antioxidant activity (174.35 μM trolox/g d.b.) were obtained at 313.15 K and 30 MPa, in which a strong positive linear relationship was observed between these responses

    Differential Role of Human Choline Kinase α and β Enzymes in Lipid Metabolism: Implications in Cancer Onset and Treatment

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    11 pages, 6 figures, 1 table.Background The Kennedy pathway generates phosphocoline and phosphoethanolamine through its two branches. Choline Kinase (ChoK) is the first enzyme of the Kennedy branch of synthesis of 1phosphocholine, the major component of the plasma membrane. ChoK family of proteins is composed by ChoKα and ChoKβ isoforms, the first one with two different variants of splicing. Recently ChoKα has been implicated in the carcinogenic process, since it is over-expressed in a variety of human cancers. However, no evidence for a role of ChoKβ in carcinogenesis has been reported. Methodology/Principal Findings Here we compare the in vitro and in vivo properties of ChoKα1 and ChoKβ in lipid metabolism, and their potential role in carcinogenesis. Both ChoKα1 and ChoKβ showed choline and ethanolamine kinase activities when assayed in cell extracts, though with different affinity for their substrates. However, they behave differentially when overexpressed in whole cells. Whereas ChoKβ display an ethanolamine kinase role, ChoKα1 present a dual choline/ethanolamine kinase role, suggesting the involvement of each ChoK isoform in distinct biochemical pathways under in vivo conditions. In addition, while overexpression of ChoKα1 is oncogenic when overexpressed in HEK293T or MDCK cells, ChoKβ overexpression is not sufficient to induce in vitro cell transformation nor in vivo tumor growth. Furthermore, a significant upregulation of ChoKα1 mRNA levels in a panel of breast and lung cancer cell lines was found, but no changes in ChoKβ mRNA levels were observed. Finally, MN58b, a previously described potent inhibitor of ChoK with in vivo antitumoral activity, shows more than 20-fold higher efficiency towards ChoKα1 than ChoKβ. Conclusion/Significance This study represents the first evidence of the distinct metabolic role of ChoKα and ChoKβ isoforms, suggesting different physiological roles and implications in human carcinogenesis. These findings constitute a step forward in the design of an antitumoral strategy based on ChoK inhibition.This work has been supported by grants to JCL from Comunidad de Madrid (GR-SAL-0821-2004), Ministerio de Ciencia e Innovación (SAF2008-03750, RD06/0020/0016), Fundación Mutua Madrileña, and by a grant to ARM from Fundación Mutua Madrileña.Peer reviewe

    Clear cell carcinoid tumor of the distal common bile duct

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    BACKGROUND: Carcinoid tumors rarely arise in the extrahepatic bile duct and can be difficult to distinguish from carcinoma. There are no reports of clear cell carcinoid (CCC) tumors in the distal bile duct (DBD) to the best of our knowledge. Herein, we report a CCC tumor in the DBD and review the literature concerning extrahepatic bile duct carcinoid tumors. CASE PRESENTATION: A 73-old man presented with fever and occult obstructive jaundice. Ultrasonography, computed tomography (CT) and magnetic resonance cholangiopancreaticography (MRCP) demonstrated a nodular tumor projection in the DBD without regional lymph node swelling. Under suspicion of carcinoma, we resected the head of the pancreas along with 2(nd )portion duodenectomy and a lymph node dissection. The surgical specimen showed a golden yellow polypoid tumor in the DBD (0.8 × 0.6 × 0.5 cm in size). The lesion was composed of clear polygonal cells arranged in nests and a trabecular pattern. The tumor invaded through the wall into the fibromuscular layer. Immunohistochemical stains showed that neoplastic cells were positive for neuron-specific enolase (NSE), chromogranin A, synaptophysin, and pancreatic polypeptide and negative for inhibin, keratin, CD56, serotonin, gastrin and somatostatin. The postoperative course was uneventful and he is living well without relapse 12 months after surgery. CONCLUSION: Given the preoperative difficulty in differentiating carcinoid from carcinoma, the pancreaticoduodenectomy is an appropriate treatment choice for carcinoid tumors located within the intra-pancreatic bile duct
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