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91.
Loes?AM?Leenen Ben?FM?WijnenEmail author Reina?JA?de Kinderen Marian?HJM?Majoie Caroline?M?van Heugten Silvia?MAA?Evers 《BMC neurology》2014,14(1):255
Background
In patients with epilepsy, poor adherence to anti-epileptic drugs has been shown to be the most important cause of poorly controlled epilepsy. Furthermore, it has been noted that the quality of life among patients with epilepsy can be improved by counseling and treatments aimed at increasing their self-efficacy and concordance, thus stimulating self-management skills. However, there is a need for evidence on the effectiveness of such programs, especially within epilepsy care. Therefore, we have developed a multi-component intervention (MCI) which combines a self-management/education program with e-Health interventions. Accordingly, the overall objective of this study is to assess the (cost)-effectiveness and feasibility of the MCI, aiming to improve self-efficacy and concordance in patients with epilepsy.Methods
A RCT in two parallel groups will be conducted to compare the MCI with a control condition in epilepsy patients. One hundred eligible epilepsy patients will be recruited and allocated to either the intervention or control group. The intervention group will receive the MCI consisting of a self-management/education program of six meetings, including e-Health interventions, and will be followed for 12 months. The control group will receive care as usual and will be followed for 6 months, after which patients will be offered the possibility of participating in the MCI. The study will consist of three parts: 1) a clinical effectiveness study, 2) a cost-effectiveness study, and 3) process evaluation. The primary outcome will be self-efficacy. Secondary outcomes include adherence, side effects, change in seizure severity & frequency, improved quality of life, proactive coping, and societal costs. Outcome assessments will be done using questionnaires at baseline and after 3, 6, 9, and 12 months (last two applicable only for intervention group).Discussion
In times of budget constraints, MCI could be a valuable addition to the current healthcare provision for epilepsy, as it is expected that higher concordance and self-efficacy will result in reduced use of healthcare resources and an increased QOL. Accordingly, this study is aimed helping patients to be their own provider of health care, shifting epilepsy management from professionals to self-care by patients equipped with appropriate skills and tools.Trial registration number
NTR4484.92.
PAWEŁ JAŁOSZYŃSKI 《Systematic Entomology》2014,39(1):159-189
Genera of Eutheiini are reviewed and Eutheimorphus is removed from this tribe of ant‐like stone beetles (Scydmaeninae) and transferred to Cephenniini. A monogeneric Marcepaniini trib.n. is described to accommodate Marcepania gen.n. from Malaysia, with five species: M. semengohensis sp.n. (the type species of Marcepania), M. tuberculata sp.n. , M. seramaensis sp.n. , M. minutissima sp.n. and M. elongata sp.n. A phylogenetic analysis of all genera of Cephenniini, Eutheiini and Marcepaniini based on adult morphological characters resulted in recovering a well‐supported monophyletic clade Eutheiini + (Marcepaniini + Cephenniini) and these tribes are included in Cephenniitae stat.n. (Eutheiini and Cephenniini are therefore removed from Scydmaenitae). Only a weak support for monophyly of Eutheiini was found, but morphological characters allow for maintaining this presumably relic group as a separate tribe. Previously proposed monophyletic groups within Cephenniini were recovered as such, but after inclusion of Eutheimorphus, a sister taxon to the ‘Cephennomicrus group’, the latter lineage gained weak statistical support. The evolutionary history of Cephenniitae is discussed, with focus on known northern hemisphere fossils classified in Scydmaenitae and Hapsomelitae, but possibly closely allied to Cephenniitae. Establishing the supertribe Cephenniitae is the first step toward a profound reclassification of Scydmaeninae on a robust phylogenetic basis. This published work has been registered in ZooBank, http://zoobank.org/urn:lsid:zoobank.org:pub:B0E1B12D-9587-4C4F-A908-A12A0C424A8C . 相似文献
93.
Formation of enlarged mitochondria in a liver cell line in response to a synthetic glucocorticoid 下载免费PDF全文
JA Berliner 《The Journal of cell biology》1975,64(3):711-716
For a number of years it has been recognized that glucocorticoids cause alterations in liver cell morphology (6, 9). Several investigators have shown that in liver in vivo mitochondria can be enlarged to many times their normal volume by treatment with cortisone (13, 15). There is a concomitant decrease in mitochondrial number, and the results of Kimberg and Loeb suggest that this is due to mitochondrial fusion (7). However, the exact mechanism whereby mitochondrial volume is altered and whether in fact cortisone is the direct causal agent are not known due to the complexity of studying these questions in a whole animal system. We have found that dexamethasone sodium phosphate (dex), a synthetic glucocorticoid, causes the formation of enlarged mitochondria in a liver cell line RLC-GAI, which grows in defined medium. In this paper we present our observations on the amount of enlargement that occurs after 5 days of treatment. The formation of enlarged mitochondria is reversible upon removal of the hormone from the medium, and we have attempted to determine whether "mitochondrial" or "nonmitochondrial" inhibitors are more effective in blocking the return of mitochondria to their normal size when the hormone is removed. 相似文献
94.
Nicole Willems Frances C Bach Saskia G M Plomp Mattie HP van Rijen Jeannette Wolfswinkel Guy CM Grinwis Clemens Bos Gustav J Strijkers Wouter JA Dhert Bj?rn P Meij Laura B Creemers Marianna A Tryfonidou 《Arthritis research & therapy》2015,17(1)
IntroductionStrategies for biological repair and regeneration of the intervertebral disc (IVD) by cell and tissue engineering are promising, but few have made it into a clinical setting. Recombinant human bone morphogenetic protein 7 (rhBMP-7) has been shown to stimulate matrix production by IVD cells in vitro and in vivo in animal models of induced IVD degeneration. The aim of this study was to determine the most effective dose of an intradiscal injection of rhBMP-7 in a spontaneous canine IVD degeneration model for translation into clinical application for patients with low back pain.MethodsCanine nucleus pulposus cells (NPCs) were cultured with rhBMP-7 to assess the anabolic effect of rhBMP-7 in vitro, and samples were evaluated for glycosaminoglycan (GAG) and DNA content, histology, and matrix-related gene expression. Three different dosages of rhBMP-7 (2.5 μg, 25 μg, and 250 μg) were injected in vivo into early degenerated IVDs of canines, which were followed up for six months by magnetic resonance imaging (T2-weighted images, T1rho and T2 maps). Post-mortem, the effects of rhBMP-7 were determined by radiography, computed tomography, and macroscopy, and by histological, biochemical (GAG, DNA, and collagen), and biomolecular analyses of IVD tissue.ResultsIn vitro, rhBMP-7 stimulated matrix production of canine NPCs as GAG deposition was enhanced, DNA content was maintained, and gene expression levels of ACAN and COL2A1 were significantly upregulated. Despite the wide dose range of rhBMP-7 (2.5 to 250 μg) administered in vivo, no regenerative effects were observed at the IVD level. Instead, extensive extradiscal bone formation was noticed after intradiscal injection of 25 μg and 250 μg of rhBMP-7.ConclusionsAn intradiscal bolus injection of 2.5 μg, 25 μg, and 250 μg rhBMP-7 showed no regenerative effects in a spontaneous canine IVD degeneration model. In contrast, intradiscal injection of 250 μg rhBMP-7, and to a lesser extent 25 μg rhBMP-7, resulted in extensive extradiscal bone formation, indicating that a bolus injection of rhBMP-7 alone cannot be used for treatment of IVD degeneration in human or canine patients.
Electronic supplementary material
The online version of this article (doi:10.1186/s13075-015-0625-2) contains supplementary material, which is available to authorized users. 相似文献95.
HE Gruber E Marrero JA Ingram GL Hoelscher EN Hanley Jr 《Biotechnic & histochemistry》2017,92(3):222-229
The importance of cytokines in disc degeneration is well recognized. Little is known about IL-22 expression in the human intervertebral disc. We investigated IL-22 immuno-localization in disc tissue, and molecular expression and production of IL-22 by annulus cells cultured in three-dimensional (3D) culture. We examined human disc tissue using immunohistochemistry and we cultured isolated annulus cells in 3D to analyze IL-22 expression and production, and its receptor, IL-22R, in conditioned media. Ingenuity pathway analysis (IPA) also was used to identify significant gene expression networks within the molecular data. IL-22 and IL-22R were immunolocalized in many cells in the human outer and inner annulus; fewer cells exhibited localization in the nucleus. Three-dimensional culture of annulus cells demonstrated production of IL-22 in conditioned media; exposure to IL-1ß or TNF-α significantly reduced IL-22 levels. Significant decreases also were identified in conditioned media assayed for IL-22R in TNF-α treated cells. IPA analysis showed that IL-22 ranked among the top canonical pathways. We found constitutive expression and production of IL-22 and IL-22R in the disc, which expands our understanding of the effect of pro-inflammatory cytokines on IL-22 expression and production. Three-dimensional cultured annulus cells exposed to IL-1ß or TNF produced significantly lower levels of IL-22 into their conditioned media compared to levels produced by control cells. Our findings have clinical relevance because of the elevated pro-inflammatory milieu within the degenerating human disc. 相似文献
96.
Fraser JA Kansagra P Kotecki C Saunders RD McLellan LI 《The Journal of biological chemistry》2003,278(47):46369-46377
Glutamate-cysteine ligase (GCL) has a key influence on glutathione homeostasis. It has been proposed that mammalian GCL is regulated by the redox environment, and we show here that cysteine residues in the Drosophila melanogaster GCL modifier subunit (DmGCLM) can form covalent interactions with the catalytic subunit (DmGCLC) and modify its activity. Candidate components of intersubunit disulfides (Cys213, Cys214, and Cys267) were identified using matrix-assisted laser desorption ionization time-of-flight spectroscopy of iodoacetamide-modified DmGCLM as well as examination of the evolutionary conservation of cysteines. Mutation of the 3 cysteine residues allowed DmGCLM to associate with DmGCLC, but inhibited the formation of intersubunit disulfides. This caused a 2-fold reduction in the catalytic efficiency of Drosophila GCL, although activity remained significantly higher than the catalytic subunit alone. The cysteine mutant was also more sensitive to inhibition by glutathione than the unmodified holoenzyme. Notably, human GCLM could substitute for DmGCLM in modification of DmGCLC activity. The role of DmGCLM in vivo was examined by analysis of a Drosophila mutant (l(3)L0580) containing a P-element insertion in Gclm. We found that the P-element is not responsible for the lethal phenotype and separated the recessive lethal mutation from the P-element by recombination. This yielded two fully viable and fertile recombinants bearing the P-element insertion, which Western and Northern blotting indicated is a severely hypomorphic allele of Gclm. Glutathione levels were approximately 2-fold lower in the GclmL0580 mutants than in control strains, demonstrating the importance of DmGCLM in the regulation of glutathione homeostasis in vivo. 相似文献
97.
98.
A rate-independent technique for analysis of nucleic acid sequences: evolutionary parsimony 总被引:24,自引:1,他引:23
The method of evolutionary parsimony--or operator invariants--is a
technique of nucleic acid sequence analysis related to parsimony analysis
and explicitly designed for determining evolutionary relationships among
four distantly related taxa. The method is independent of substitution
rates because it is derived from consideration of the group properties of
substitution operators rather than from an analysis of the probabilities of
substitution in branches of a tree. In both parsimony and evolutionary
parsimony, three patterns of nucleotide substitution are associated
one-to-one with the three topologically linked trees for four taxa. In
evolutionary parsimony, the three quantities are operator invariants. These
invariants are the remnants of substitutions that have occurred in the
interior branch of the tree and are analogous to the substitutions assigned
to the central branch by parsimony. The two invariants associated with the
incorrect trees must equal zero (statistically), whereas only the correct
tree can have a nonzero invariant. The chi 2-test is used to ascertain the
nonzero invariant and the statistically favored tree. Examples, obtained
using data calculated with evolutionary rates and branchings designed to
camouflage the true tree, show that the method accurately predicts the
tree, even when substitution rates differ greatly in neighboring peripheral
branches (conditions under which parsimony will consistently fail). As the
number of substitutions in peripheral branches becomes fewer, the parsimony
and the evolutionary-parsimony solutions converge. The method is robust and
easy to use.
相似文献
99.
Carbamoylphosphate synthetase (CPS) catalyzes the first committed step in
pyrimidine biosynthesis, arginine biosynthesis, or the urea cycle.
Organisms may contain either one generalized or two specific CPS enzymes,
and these enzymes may be heterodimeric (encoded by linked or unlinked
genes), monomeric, or part of a multifunctional protein. In order to help
elucidate the evolution of CPS, we have performed a comprehensive
phylogenetic analysis using the 21 available complete CPS sequences,
including a sequence from Sulfolobus solfataricus P2 which we report in
this paper. This is the first report of a complete CPS gene sequence from
an archaeon, and sequence analysis suggests that it encodes an enzyme
similar to heterodimeric CPSII. We confirm that internal similarity within
the synthetase domain of CPS is the result of an ancient gene duplication
that preceded the divergence of the Bacteria, Archaea, and Eukarya, and use
this internal duplication in phylogenetic tree construction to root the
tree of life. Our analysis indicates with high confidence that this
archaeal sequence is more closely related to those of Eukarya than to those
of Bacteria. In addition to this ancient duplication which created the
synthetase domain, our phylogenetic analysis reveals a complex history of
further gene duplications, fusions, and other events which have played an
integral part in the evolution of CPS.
相似文献
100.
The segregation of laboratory maintained male and larval Myrmecia gulosa from workers resulted in increased levels of culturable microbiota. After 29 days, microbial levels recovered from segregated males and larvae were 27 and 126 times greater than from males and larvae not segregated from workers. These findings are consistent with the hypothesis that metapleural gland secretions, absent in larvae and males, are transferred from workers to larvae, and males contribute to the inhibition of cuticular microbiota. 相似文献