163 research outputs found

    Weather Risk and Size Economies of Large Machinery in Wheat Production

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    Major objectives of this study were to determine the existence of economies or diseconomies of size for large farms and to determine the impact of farmers\u27 risk aversion level on the size of farm machinery selected

    "Sometimes, it just stops me from doing anything": A qualitative exploration of epilepsy management in people with intellectual disabilities and their carers

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    Purpose\textit{Purpose}: Epilepsy affects 1 in 5 people with an intellectual disability (ID), but little is known about their experiences of living with epilepsy. A qualitative study was conducted to investigate the impact and management of epilepsy in people with ID. Materials and methods:\textit{Materials and methods:} People with epilepsy and ID and their carers were invited to take part in semi-structured interviews. Eleven participants with ID and their carers were interviewed together, one participant with ID and their carer were interviewed separately, two interviews took place with the participant with ID only, and one interview took place with the carer only. The interviews were transcribed verbatim, coded, and analyzed thematically (dual independent coding for 30% of the transcripts). Results:\textit{Results:} Three themes emerged (participant characteristics, living with epilepsy, epilepsy management and information needs) which indicated the following: 1) diversity regarding health profiles, communication abilities, severity of epilepsy, perceived control of epilepsy, and support needs; 2) a reduction in severity and frequency of seizures for a sizeable proportion of participants through antiepileptic drugs; 3) the lifelong impact of epilepsy and related seizures on participants' activities and quality of life; 4) the perceived burden of epilepsy and difficulty managing the condition for a large proportion of participants; 5) high levels of satisfaction with epilepsy-related services and care; and 6) an overall lack of written accessible information about epilepsy. Conclusions:\textit{Conclusions:} This study has highlighted a significant impact of epilepsy and related seizures on the daily lives and quality of life of people with ID. Although a sizeable proportion of participants and their carers considered their epilepsy to be well controlled, the majority reported difficulties managing epilepsy and minimizing its impact on their wellbeing. Excluding care staff and the support provided by epilepsy clinics, the participants had not accessed any adapted self-management or information resources about epilepsy

    Lithium interactions with non-steroidal anti-inflammatory drugs and diuretics – A review

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    Background: Lithium is often used in bipolar disorder and occasionally in unipolar depression. Non-steroidal anti-inflammatory drugs (NSAIDs) and diuretics are frequently prescribed and their interaction with lithium is based mainly in few small studies. Objectives: Conduct a review, identify different interaction patterns and discuss treatment options. Methods: Three searches were made in PubMed in January 2016: 1) using the keywords “lithium” [and] “non-steroidal anti-inflammatory”; 2) using the keywords “lithium” [and] “diuretics” and the filter “title/abstract”; 3) using the terms “lithium” [and] “toxicity” and the filters “title” [and] “review”. From the 293 remaining articles, 10 were selected. Another search in Scielo.org was made, using the term “lítio” and the filter “Psiquiatria”. Two articles were selected from the initial 53. Six textbooks were added to expand the evidence, achieving a total of 18 references. Results: The majority of NSAIDs and diuretics rises lithium levels, specially thiazides. However, some show great variability or no interaction at all, and others even decrease lithium levels. Discussion: Lower-doses, shorter durations, lithium adjustments and levels' follow-ups are recommended, especially in elderly and multiple co-morbid patients

    Study of cosolvent-induced α-chymotrypsin fibrillogenesis: Does protein surface hydrophobicity trigger early stages of aggregation reaction?

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    The misfolding of specific proteins is often associated with their assembly into fibrillar aggregates, commonly termed amyloid fibrils. Despite the many efforts expended to characterize amyloid formation in vitro, there is no deep knowledge about the environment (in which aggregation occurs) as well as mechanism of this type of protein aggregation. Alpha-chymotrypsin was recently driven toward amyloid aggregation by the addition of intermediate concentrations of trifluoroethanol. In the present study, approaches such as turbidimetric, thermodynamic, intrinsic fluorescence and quenching studies as well as chemical modification have been successfully used to elucidate the underlying role of hydrophobic interactions (involved in early stages of amyloid formation) in α-chymotrypsin-based experimental system. © 2009 Springer Science+Business Media, LLC

    Interaction site prediction by structural similarity to neighboring clusters in protein-protein interaction networks

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    <p>Abstract</p> <p>Background</p> <p>Recently, revealing the function of proteins with protein-protein interaction (PPI) networks is regarded as one of important issues in bioinformatics. With the development of experimental methods such as the yeast two-hybrid method, the data of protein interaction have been increasing extremely. Many databases dealing with these data comprehensively have been constructed and applied to analyzing PPI networks. However, few research on prediction interaction sites using both PPI networks and the 3D protein structures complementarily has explored.</p> <p>Results</p> <p>We propose a method of predicting interaction sites in proteins with unknown function by using both of PPI networks and protein structures. For a protein with unknown function as a target, several clusters are extracted from the neighboring proteins based on their structural similarity. Then, interaction sites are predicted by extracting similar sites from the group of a protein cluster and the target protein. Moreover, the proposed method can improve the prediction accuracy by introducing repetitive prediction process.</p> <p>Conclusions</p> <p>The proposed method has been applied to small scale dataset, then the effectiveness of the method has been confirmed. The challenge will now be to apply the method to large-scale datasets.</p

    Functional characterization of the complement receptor type 1 and its circulating ligands in patients with schizophrenia

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    <p>Abstract</p> <p>Background</p> <p>Whereas the complement system alterations contribute to schizophrenia, complement receptors and regulators are little studied. We investigated complement receptor type 1 (CR1) expression on blood cells, the levels of circulating immune complexes (CIC) containing ligands of CR1, C1q complement protein and fragments of C3 complement protein (C1q-CIC, C3d-CIC), and CR1 C5507G functional polymorphism in schizophrenia patients and controls.</p> <p>Results</p> <p>We found an increased C1q-CIC level and CR1 expression on blood cells, elevated number of CR1 positive erythrocytes and reduced number of CR1 positive lymphocytes and monocytes in patients compared to controls. No difference in the levels of C3d-CIC between groups was observed. Higher CR1 expression on erythrocytes in CC genotype versus CG+GG for both groups was detected, whereas no difference was observed for other cell populations. Our results indicated that schizophrenia is associated with the increased CR1 expression and C1q-CIC level.</p> <p>Conclusions</p> <p>Our study for the first time indicated that schizophrenia is associated with the increased CR1 expression and C1q-CIC level. Further studies in other ethnic groups are needed to replicate these findings.</p

    Morphological features of microglial cells in the hippocampal dentate gyrus of Gunn rat: a possible schizophrenia animal model

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    <p>Abstract</p> <p>Background</p> <p>Schizophrenia is a debilitating and complex mental disorder whose exact etiology remains unknown. There is growing amount of evidence of a relationship between neuroinflammation, as demonstrated by microglial activation, and schizophrenia. Our previous studies have proposed that hyperbilirubinemia plays a role in the pathophysiology of schizophrenia. Furthermore, we suggested the Gunn rat, an animal model of bilirubin encephalopathy, as a possible animal model of schizophrenia. However, the effects of unconjugated bilirubin on microglia, the resident immune cell of the CNS, in Gunn rats have never been investigated. In the present study, we examined how microglial cells respond to bilirubin toxicity in adult Gunn rats.</p> <p>Methods</p> <p>Using immunohistochemical techniques, we compared the distribution, morphology, and ultrastructural features of microglial cells in Gunn rats with Wistar rats as a normal control. We also determined the ratio of activated and resting microglia and observed microglia-neuron interactions. We characterized the microglial cells in the hippocampal dentate gyrus.</p> <p>Results</p> <p>We found that microglial cells showed activated morphology in the hilus, subgranular zone, and granular layer of the Gunn rat hippocampal dentate gyrus. There was no significant difference between cell numbers between in Gunn rats and controls. However, there was significant difference in the area of CD11b expression in the hippocampal dentate gyrus. Ultrastructurally, microglial cells often contained rich enlarged rich organelles in the cytoplasm and showed some phagocytic function.</p> <p>Conclusions</p> <p>We propose that activation of microglia could be an important causal factor of the behavioral abnormalities and neuropathological changes in Gunn rats. These findings may provide basic information for further assessment of the Gunn rat as an animal model of schizophrenia.</p

    Yokukansan Inhibits Neuronal Death during ER Stress by Regulating the Unfolded Protein Response

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    Recently, several studies have reported Yokukansan (Tsumura TJ-54), a traditional Japanese medicine, as a potential new drug for the treatment of Alzheimer's disease (AD). Endoplasmic reticulum (ER) stress is known to play an important role in the pathogenesis of AD, particularly in neuronal death. Therefore, we examined the effect of Yokukansan on ER stress-induced neurotoxicity and on familial AD-linked presenilin-1 mutation-associated cell death.We employed the WST-1 assay and monitored morphological changes to evaluate cell viability following Yokukansan treatment or treatment with its components. Western blotting and PCR were used to observe the expression levels of GRP78/BiP, caspase-4 and C/EBP homologous protein.Yokukansan inhibited neuronal death during ER stress, with Cnidii Rhizoma (Senkyu), a component of Yokukansan, being particularly effective. We also showed that Yokukansan and Senkyu affect the unfolded protein response following ER stress and that these drugs inhibit the activation of caspase-4, resulting in the inhibition of ER stress-induced neuronal death. Furthermore, we found that the protective effect of Yokukansan and Senkyu against ER stress could be attributed to the ferulic acid content of these two drugs.Our results indicate that Yokukansan, Senkyu and ferulic acid are protective against ER stress-induced neuronal cell death and may provide a possible new treatment for AD

    Disruption of arterial perivascular drainage of amyloid-β from the brains of mice expressing the human APOE ε4 allele

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    Failure of elimination of amyloid-β (Aβ) from the brain and vasculature appears to be a key factor in the etiology of sporadic Alzheimer’s disease (AD) and cerebral amyloid angiopathy (CAA). In addition to age, possession of an apolipoprotein E (APOE) ε4 allele is a strong risk factor for the development of sporadic AD. The present study tested the hypothesis that possession of the APOE ε4 allele is associated with disruption of perivascular drainage of Aβ from the brain and with changes in cerebrovascular basement membrane protein levels. Targeted replacement (TR) mice expressing the human APOE3 (TRE3) or APOE4 (TRE4) genes and wildtype mice received intracerebral injections of human Aβ40. Aβ40 aggregated in peri-arterial drainage pathways in TRE4 mice, but not in TRE3 or wildtype mice. The number of Aβ deposits was significantly higher in the hippocampi of TRE4 mice than in the TRE3 mice, at both 3- and 16-months of age, suggesting that clearance of Aβ was disrupted in the brains of TRE4 mice. Immunocytochemical and Western blot analysis of vascular basement membrane proteins demonstrated significantly raised levels of collagen IV in 3-month-old TRE4 mice compared with TRE3 and wild type mice. In 16-month-old mice, collagen IV and laminin levels were unchanged between wild type and TRE3 mice, but were lower in TRE4 mice. The results of this study suggest that APOE4 may increase the risk for AD through disruption and impedance of perivascular drainage of soluble Aβ from the brain. This effect may be mediated, in part, by changes in age-related expression of basement membrane proteins in the cerebral vasculature
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