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221.
Felix Fluri Micheal Bieber Jens Volkmann Christoph Kleinschnitz 《Journal of visualized experiments : JoVE》2015,(104)
Deep brain stimulation (DBS) is a widely used and effective therapy for several neurologic disorders, such as idiopathic Parkinson’s disease, dystonia or tremor. DBS is based on the delivery of electrical stimuli to specific deep anatomic structures of the central nervous system. However, the mechanisms underlying the effect of DBS remain enigmatic. This has led to an interest in investigating the impact of DBS in animal models, especially in rats. As DBS is a long-term therapy, research should be focused on molecular-genetic changes of neural circuits that occur several weeks after DBS. Long-term DBS in rats is challenging because the rats move around in their cage, which causes problems in keeping in place the wire leading from the head of the animal to the stimulator. Furthermore, target structures for stimulation in the rat brain are small and therefore electrodes cannot easily be placed at the required position. Thus, a set-up for long-lasting stimulation of rats using platinum/iridium electrodes with an impedance of about 1 MΩ was developed for this study. An electrode with these specifications allows for not only adequate stimulation but also recording of deep brain structures to identify the target area for DBS. In our set-up, an electrode with a plug for the wire was embedded in dental cement with four anchoring screws secured onto the skull. The wire from the plug to the stimulator was protected by a stainless-steel spring. A swivel was connected to the circuit to prevent the wire from becoming tangled. Overall, this stimulation set-up offers a high degree of free mobility for the rat and enables the head plug, as well as the wire connection between the plug and the stimulator, to retain long-lasting strength. 相似文献
222.
Background
Anesthetic administration is increasingly guided by electroencephalography (EEG)-based monitoring, such as the bispectral index (BIS). However, during cardiopulmonary bypass (CPB), factors other than the administered hypnotic agents may influence EEG signals, and their effects on BIS values are unknown.Methods
This report is a secondary analysis of data from a prospective, controlled interventional study comparing the effect of sevoflurane administration guided by BIS monitoring (group SevoBIS) and constant administration of sevoflurane (group Sevo1.8Vol%) during CPB. Sevoflurane plasma concentration (SPC) was measured using gas chromatography. The relationships of BIS to SPC, CPB pump flow, arterial pressure, hematocrit, temperature, time on CPB, and patient characteristics were analysed.Results
No association was observed between BIS values and SPC in group SevoBIS. In group Sevo1.8Vol%, a 40 μg ml-1 increase in SPC, which encompassed the entire range of observed values of the SPC in this analysis, was associated with a decrease of 3.6 (95% confidence interval (CI): 1.1–6.1) in BIS values (p = 0.005). Each increase in CPB time of 10 minutes was associated with an increase in BIS values of 0.25 (95%CI: 0.11–0.39, p<0.001). Path analysis revealed that the BIS values of SevoBIS patients were 5.3 (95%CI: 3.2–7.5) units higher than those of Sevo1.8Vol% patients (p<0.001), which was the strongest effect on BIS values. Path analysis revealed a slope of 0.5 (95%CI: 0.3–0.7) BIS units per 1°C body temperature (p<0.001).Conclusion
BIS monitoring is insensitive to clinically relevant changes in SPC in individual patients during CPB. 相似文献223.
Kamlesh Khunti Hamidreza Mani Felix Achana Nicola Cooper Laura J. Gray Melanie J. Davies 《PloS one》2015,10(9)
Background
Screening for type 2 diabetes (T2DM) and individuals at risk of diabetes has been advocated, yet information on the response rate and diagnostic yield of different screening strategies are lacking.Methods
Studies (from 1998 to March/2015) were identified through Medline, Embase and the Cochrane library and included if they used oral glucose tolerance test (OGTT) and WHO-1998 diagnostic criteria for screening in a community setting. Studies were one-step strategy if participants were invited directly for OGTT and two, three/four step if participants were screened at one or more levels prior to invitation to OGTT. The response rate and diagnostic yield were pooled using Bayesian random-effect meta-analyses.Findings
47 studies (422754 participants); 29 one-step, 11 two-step and seven three/four-step were identified. Pooled response rate (95% Credible Interval) for invitation to OGTT was 65.5% (53.7, 75.6), 63.1% (44.0, 76.8), and 85.4% (76.4, 93.3) in one, two and three/four-step studies respectively. T2DM yield was 6.6% (5.3, 7.8), 13.1% (4.3, 30.9) and 27.9% (8.6, 66.3) for one, two and three/four-step strategies respectively. The number needed to invite to the OGTT to detect one case of T2DM was 15, 7.6 and 3.6 in one, two, and three/four-step strategies. In two step strategies, there was no difference between the response or yield rates whether the first step was blood test or risk-score. There was evidence of substantial heterogeneity in rates across study populations but this was not explained by the method of invitation, study location (rural versus urban) and developmental index of the country in which the study was performed.Conclusions
Irrespective of the invitation method, developmental status of the countries and or rural/urban location, using a multi-step strategy increases the initial response rate to the invitation to screening for diabetes and reduces the number needed to have the final diagnostic test (OGTT in this study) for a definite diagnosis. 相似文献224.
Felix A. Achana Alex J. Sutton Denise Kendrick Persephone Wynn Ben Young David R. Jones Stephanie J. Hubbard Nicola J. Cooper 《PloS one》2015,10(4)
Background
There is evidence from 2 previous meta-analyses that interventions to promote poison prevention behaviours are effective in increasing a range of poison prevention practices in households with children. The published meta-analyses compared any intervention against a “usual care or no intervention” which potentially limits the usefulness of the analysis to decision makers. We aim to use network meta-analysis to simultaneously evaluate the effectiveness of different interventions to increase prevalence of safe storage of i) Medicines only, ii) Other household products only, iii) Poisons (both medicines and non-medicines), iv) Poisonous plants; and v) Possession of poison control centre (PCC) telephone number in households with children.Methods
Data on the effectiveness of poison prevention interventions was extracted from primary studies identified in 2 newly-undertaken systematic reviews. Effect estimates were pooled across studies using a random effects network meta-analysis model.Results
28 of the 47 primary studies identified were included in the analysis. Compared to usual care intervention, the intervention with education and low cost/free equipment elements was most effective in promoting safe storage of medicines (odds ratio 2.51, 95% credible interval 1.01 to 6.00) while interventions with education, low cost/free equipment, home safety inspection and fitting components were most effective in promoting safe storage of other household products (2.52, 1.12 to 7.13), safe storage of poisons (11.10, 1.60 to 141.50) and possession of PCC number (38.82, 2.19 to 687.10). No one intervention package was more effective than the others in promoting safe storage of poisonous plants.Conclusion
The most effective interventions varied by poison prevention practice, but education alone was not the most effective intervention for any poison prevention practice. Commissioners and providers of poison prevention interventions should tailor the interventions they commission or provide to the poison prevention practices they wish to promote.Highlights
- Network meta-analysis is useful for comparing multiple injury-prevention interventions.
- More intensive poison prevention interventions were more effective than education alone.
- Education and low cost/free equipment was most effective in promoting safe storage of medicines.
- Education, low cost/free equipment, home safety inspection and fitting was most effective in promoting safe storage of household products and poisons.
- Education, low cost/free equipment and home inspection were most effective in promoting possession of a poison control centre number.
- None of the intervention packages was more effective than the others in promoting safe storage of poisonous plants.
225.
Francine P. Favaro Lucas Alvizi Roseli M. Zechi-Ceide Debora Bertola Temis M. Felix Josiane de Souza Salmo Raskin Stephen R.F. Twigg Andrea M.J. Weiner Pablo Armas Ezequiel Margarit Nora B. Calcaterra Gregers R. Andersen Simon J. McGowan Andrew O.M. Wilkie Antonio Richieri-Costa Maria L.G. de Almeida Maria Rita Passos-Bueno 《American journal of human genetics》2014
226.
227.
After Barattolo (Abstracts of the 5th international symposium on fossil algae, 1991) and Barattolo and Romano (Bollettino della Societa Paleontologica Italiana, 44(3): 237–254, 2005) emended the diagnosis of the genus Linoporella Steinmann to include species with three orders of laterals, algae included formerly in this genus but with only two orders
of laterals remained in open nomenclature. Comparisons of these algae with other Jurassic and Cretaceous dasycladaleans with
two orders of laterals resulted in the introduction of the new genus Steinmanniporella. 相似文献
228.
Lau T Schneidt T Heimann F Gundelfinger ED Schloss P 《Neurochemistry international》2010,57(8):969-978
Serotonergic neurotransmission plays an important role during neural development. Serotonergic dysfunction is observed in various psychiatric disorders and many psychoactive drugs target proteins on serotonergic neurons. Serotonergic neurons are located in the raphé nuclei and densely innervate the whole brain. The low number and the intricate accessibility of these neurons do not allow to culture them and therefore to date it was impossible to study drug-target interactions on bona fide serotonergic neurons. In order to circumvent such problems we have developed a protocol that allows the rapid and efficient generation of serotonergic neurons from mouse embryonic stem cells. Neuronal precursors were obtained by neuronal stem sphere formation in floating culture in the presence of various mitogens. Differentiation into neurons was induced by withdrawal of the mitogens. About 90% of the resulting neurons exhibited a serotonergic phenotype as judged by immunostaining against serotonin, its synthesising enzyme tryptophan hydroxylase 2, the serotonin transporter as well as 5-HT1(A) and 5-HT1(B) autoreceptors. In addition, we found expression of the vesicular monoamine transporter vMAT2 and the presynaptic protein Bassoon, which is involved in organizing the assembly of the presynaptic active zone. Depolarisation-induced calcium influx was visualised by Fluo-4, and accompanying exocytotic events by FM dye staining. Proteins involved in 5-HT release and re-uptake as well as depolarisation evoked exocytosis were evenly co-distributed on neurites and cell bodies suggesting that ES cell-derived serotonergic neurons also exhibit somatodendritic release comparable to serotonergic neurons in the raphé nuclei. 相似文献
229.
Hannah M��ller David Schmidt Sandra Steinbrink Ekaterina Mirgorodskaya Verena Lehmann Karin Habermann Felix Dreher Niklas Gustavsson Thomas Kessler Hans Lehrach Ralf Herwig Johan Gobom Aspasia Ploubidou Michael Boutros Bodo M H Lange 《The EMBO journal》2010,29(19):3344-3357
Regulation of centrosome structure, duplication and segregation is integrated into cellular pathways that control cell cycle progression and growth. As part of these pathways, numerous proteins with well‐established non‐centrosomal localization and function associate with the centrosome to fulfill regulatory functions. In turn, classical centrosomal components take up functional and structural roles as part of other cellular organelles and compartments. Thus, although a comprehensive inventory of centrosome components is missing, emerging evidence indicates that its molecular composition reflects the complexity of its functions. We analysed the Drosophila embryonic centrosomal proteome using immunoisolation in combination with mass spectrometry. The 251 identified components were functionally characterized by RNA interference. Among those, a core group of 11 proteins was critical for centrosome structure maintenance. Depletion of any of these proteins in Drosophila SL2 cells resulted in centrosome disintegration, revealing a molecular dependency of centrosome structure on components of the protein translation machinery, actin‐ and RNA‐binding proteins. In total, we assigned novel centrosome‐related functions to 24 proteins and confirmed 13 of these in human cells. 相似文献
230.
Felix Friedberg 《Molecular biology reports》2010,37(4):1707-1716
In this paper, the inventory presented for singlet CH (calponin homology/actin binding) domain containing human multidomain
proteins [1] is extended to several duplex and one quadruplet CH containing forms. Invariably, the duplexes are located at the begin
of the molecules. The regions connecting the two CH units suggest amino acid conservations which allows the placing of 18
duplex containing molecules into six groups wherein the gene for one member in each group created the others more recently
by gene duplication. The ancient multidomain proteins, possibly, were primarily the result of an exon shuffling (transposition)
mechanism that also guided the placing of the CH singlet or duplex domain at the amino end of the newly created proteins.
A mechanism that creates pseudogenes could conceivably produce genes that encode multi-domain proteins. Intragenomic duplications
(slippage) might have facilitated the occurrence of encoding repeats, thus allowing for the creation of multiple identical
domains within one molecule. Gene duplication with subsequent modification and small domain gene recombination which formed
multidomain proteins are important forces driving evolution. 相似文献