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951.
Hazel J. Jenkins Mark J. Hancock Simon D. French Chris G. Maher Roger M. Engel John S. Magnussen 《CMAJ》2015,187(6):401-408
Background:Rates of imaging for low-back pain are high and are associated with increased health care costs and radiation exposure as well as potentially poorer patient outcomes. We conducted a systematic review to investigate the effectiveness of interventions aimed at reducing the use of imaging for low-back pain.Methods:We searched MEDLINE, Embase, CINAHL and the Cochrane Central Register of Controlled Trials from the earliest records to June 23, 2014. We included randomized controlled trials, controlled clinical trials and interrupted time series studies that assessed interventions designed to reduce the use of imaging in any clinical setting, including primary, emergency and specialist care. Two independent reviewers extracted data and assessed risk of bias. We used raw data on imaging rates to calculate summary statistics. Study heterogeneity prevented meta-analysis.Results:A total of 8500 records were identified through the literature search. Of the 54 potentially eligible studies reviewed in full, 7 were included in our review. Clinical decision support involving a modified referral form in a hospital setting reduced imaging by 36.8% (95% confidence interval [CI] 33.2% to 40.5%). Targeted reminders to primary care physicians of appropriate indications for imaging reduced referrals for imaging by 22.5% (95% CI 8.4% to 36.8%). Interventions that used practitioner audits and feedback, practitioner education or guideline dissemination did not significantly reduce imaging rates. Lack of power within some of the included studies resulted in lack of statistical significance despite potentially clinically important effects.Interpretation:Clinical decision support in a hospital setting and targeted reminders to primary care doctors were effective interventions in reducing the use of imaging for low-back pain. These are potentially low-cost interventions that would substantially decrease medical expenditures associated with the management of low-back pain.Current evidence-based clinical practice guidelines recommend against the routine use of imaging in patients presenting with low-back pain.1–3 Despite this, imaging rates remain high,4,5 which indicates poor concordance with these guidelines.6,7Unnecessary imaging for low-back pain has been associated with poorer patient outcomes, increased radiation exposure and higher health care costs.8 No short- or long-term clinical benefits have been shown with routine imaging of the low back, and the diagnostic value of incidental imaging findings remains uncertain.9–12 A 2008 systematic review found that imaging accounted for 7% of direct costs associated with low-back pain, which in 1998 translated to more than US$6 billion in the United States and £114 million in the United Kingdom.13 Current costs are likely to be substantially higher, with an estimated 65% increase in spine-related expenditures between 1997 and 2005.14Various interventions have been tried for reducing imaging rates among people with low-back pain. These include strategies targeted at the practitioner such as guideline dissemination,15–17 education workshops,18,19 audit and feedback of imaging use,7,20,21 ongoing reminders7 and clinical decision support.22–24 It is unclear which, if any, of these strategies are effective.25 We conducted a systematic review to investigate the effectiveness of interventions designed to reduce imaging rates for the management of low-back pain. 相似文献
952.
Tulika Sarma Athanasia Koutsouris Jiang Zhu Yu Aleksandar Krbanjevic Thomas J. Hope Mark M. Rasenick 《The Journal of biological chemistry》2015,290(16):10045-10056
Signals that activate the G protein Gαs and promote neuronal differentiation evoke Gαs internalization in rat pheochromocytoma (PC12) cells. These agents also significantly increase Gαs association with microtubules, resulting in an increase in microtubule dynamics because of the activation of tubulin GTPase by Gαs. To determine the function of Gαs/microtubule association in neuronal development, we used real-time trafficking of a GFP-Gαs fusion protein. GFP-Gαs concentrates at the distal end of the neurites in differentiated living PC12 cells as well as in cultured hippocampal neurons. Gαs translocates to specialized membrane compartments at tips of growing neurites. A dominant-negative Gα chimera that interferes with Gαs binding to tubulin and activation of tubulin GTPase attenuates neurite elongation and neurite number both in PC12 cells and primary hippocampal neurons. This effect is greatest on differentiation induced by activated Gαs. Together, these data suggest that activated Gαs translocates from the plasma membrane and, through interaction with tubulin/microtubules in the cytosol, is important for neurite formation, development, and outgrowth. Characterization of neuronal G protein dynamics and their contribution to microtubule dynamics is important for understanding the molecular mechanisms by which G protein-coupled receptor signaling orchestrates neuronal growth and differentiation. 相似文献
953.
Zhu Z Burnett CM Maksymov G Stepniak E Sierra A Subbotina E Anderson ME Coetzee WA Hodgson-Zingman DM Zingman LV 《Biochemical and biophysical research communications》2011,(4):637-641
The cardiovascular system operates under demands ranging from conditions of rest to extreme stress. One mechanism of cardiac stress tolerance is action potential duration shortening driven by ATP-sensitive potassium (KATP) channels. KATP channel expression has a significant physiologic impact on action potential duration shortening and myocardial energy consumption in response to physiologic heart rate acceleration. However, the effect of reduced channel expression on action potential duration shortening in response to severe metabolic stress is yet to be established. Here, transgenic mice with myocardium-specific expression of a dominant negative KATP channel subunit were compared with littermate controls. Evaluation of KATP channel whole cell current and channel number/patch was assessed by patch clamp in isolated ventricular cardiomyocytes. Monophasic action potentials were monitored in retrogradely perfused, isolated hearts during the transition to hypoxic perfusate. An 80–85% reduction in cardiac KATP channel current density results in a similar magnitude, but significantly slower rate, of shortening of the ventricular action potential duration in response to severe hypoxia, despite no significant difference in coronary flow. Therefore, the number of functional cardiac sarcolemmal KATP channels is a critical determinant of the rate of adaptation of myocardial membrane excitability, with implications for optimization of cardiac energy consumption and consequent cardioprotection under conditions of severe metabolic stress. 相似文献
954.
Vivi Andasari Alf Gerisch Georgios Lolas Andrew P. South Mark A. J. Chaplain 《Journal of mathematical biology》2011,63(1):141-171
The ability of cancer cells to break out of tissue compartments and invade locally gives solid tumours a defining deadly characteristic.
One of the first steps of invasion is the remodelling of the surrounding tissue or extracellular matrix (ECM) and a major
part of this process is the over-expression of proteolytic enzymes, such as the urokinase-type plasminogen activator (uPA)
and matrix metalloproteinases (MMPs), by the cancer cells to break down ECM proteins. Degradation of the matrix enables the
cancer cells to migrate through the tissue and subsequently to spread to secondary sites in the body, a process known as metastasis.
In this paper we undertake an analysis of a mathematical model of cancer cell invasion of tissue, or ECM, which focuses on
the role of the urokinase plasminogen activation system. The model consists of a system of five reaction-diffusion-taxis partial
differential equations describing the interactions between cancer cells, uPA, uPA inhibitors, plasmin and the host tissue.
Cancer cells react chemotactically and haptotactically to the spatio-temporal effects of the uPA system. The results obtained
from computational simulations carried out on the model equations produce dynamic heterogeneous spatio-temporal solutions
and using linear stability analysis we show that this is caused by a taxis-driven instability of a spatially homogeneous steady-state.
Finally we consider the biological implications of the model results, draw parallels with clinical samples and laboratory
based models of cancer cell invasion using three-dimensional invasion assay, and go on to discuss future development of the
model. 相似文献
955.
Major locus and other novel additive and epistatic loci involved in modulation of isoflavone concentration in soybean seeds 总被引:4,自引:0,他引:4
Gutierrez-Gonzalez JJ Vuong TD Zhong R Yu O Lee JD Shannon G Ellersieck M Nguyen HT Sleper DA 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2011,123(8):1375-1385
Seeds of soybean [Glycine max (L.) Merr.] accumulate more isoflavones than any tissue of any plant species. In other plant parts, isoflavones are usually
released to counteract the effects of various biotic and abiotic stresses. Because of the benefits to the plant and positive
implications that consumption may have on human health, increasing isoflavones is a goal of many soybean breeding programs.
However, altering isoflavone levels through marker-assisted selection (MAS) has been impractical due to the small and often
environmentally variable contributions that each individual quantitative trait locus (QTL) has on total isoflavones. In this
study, we developed a Magellan × PI 437654 F7-RIL population to construct a highly saturated non-redundant linkage map that encompassed 451 SNP and SSR molecular markers
and used it to locate genomic regions that govern accumulation of isoflavones in the seeds of soybean. Five QTLs were found
that contribute to the concentration of isoflavones, having single or multiple additive effects on isoflavone component traits.
We also validated a major locus which alone accounted for up to 10% of the phenotypic variance for glycitein, and 35–37% for
genistein, daidzein and the sum of all three soybean isoflavones. This QTL was consistently associated with increased concentration
of isoflavones across different locations, years and crosses. It was the most important QTL in terms of net increased amounts
of all isoflavone forms. Our results suggest that this locus would be an excellent candidate to target for MAS. Also, several
minor QTLs were identified that interacted in an additive-by-additive epistatic manner, to increase isoflavone concentration. 相似文献
956.
957.
958.
Over two hundred samples were collected in tropical headwater forested catchments in the lowland Amazon basin near Juruena, Mato Grosso Brazil. These were analyzed for fluorescence characteristics and DOC concentrations, and represented a range of terrestrial hydrologic flowpaths and first-order streams during baseflow and stormflow conditions. The fluorescence index (FI) of McKnight et al. (2001) was found to have a significant relationship with DOC concentrations for stream water at baseflow conditions, but FI values within individual terrestrial flowpaths and stormflow varied little for the range of DOC concentrations observed. FI values were seen to increase for increasing residence time of water within the terrestrial ecosystem, while DOC concentration decreased for increasing hydrologic residence time. The FI of terrestrial flow paths indicated that DOC became increasingly characterized by microbially derived carbon for flow paths with longer residence times, on the order through fall and overland flow < percolating soil water < groundwater. Base flow samples of stream water had a mean FI value of 1.78, compared with 1.51 and 1.44 for through fall and overland flow, respectively, and 1.65 for percolating soil water. The FI values for stream water at base flow were also seen to vary seasonally, and were inversely proportional to DOC concentrations over time. 相似文献
959.
Subramanyam C Duplantier AJ Dombroski MA Chang SP Gabel CA Whitney-Pickett C Perregaux DG Labasi JM Yoon K Shepard RM Fisher M 《Bioorganic & medicinal chemistry letters》2011,21(18):5475-5479
The discovery, of a series of 2-Cl-5-heteroaryl-benzamide antagonists of the P2X(7) receptor via parallel medicinal chemistry is described. Initial analogs suffered from poor metabolic stability and low Vd(ss). Multi parametric optimization led to identification of pyrazole 39 as a viable lead with excellent potency and oral bioavailability. Further attempts to improve the low Vd(ss) of 39 via introduction of amines led to analogs 40 and 41 which maintained the favorable pharmacology profile of 39 and improved Vd(ss) after iv dosing. But these analogs suffered from poor oral absorption, probably driven by poor permeability. 相似文献
960.