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61.
Rho GTPases are small proteins that act as binary molecular switches in a wide range of signalling pathways upon stimulation of cell surface receptors. Three different classes of regulatory proteins control their activity. In the activated state small GTPases are able to bind a variety of effector proteins and initiate downstream signalling. Rho GTPases regulate important cellular processes ranging from cytoskeletal remodelling and gene expression to cell proliferation and membrane trafficking. Therefore it is not surprising that deregulated Rho signalling can contribute to disturbed cellular phenotypes in a wide range of diseases. The main focus of this review will be the diversity of functions of Rho GTPases and the effects of aberrant Rho GTPase signalling in various aspects of cancer. 相似文献
62.
Rutjes SA Lodder WJ Bouwknegt M de Roda Husman AM 《Journal of virological methods》2007,143(1):112-116
Pigs have been suggested to be a potential reservoir for locally acquired human hepatitis E virus (HEV) infections in the Netherlands. To study possible trends in HEV prevalence in the Dutch pig population, 97 pig farms have been screened for the presence of HEV in stools. The prevalence rate of HEV was estimated at 55% (53/97) in 2005, indicating a significant increase as compared to the prevalence rate of 22% (25/115) as was reported in 1999. The current data suggest that this increase is due to the inclusion of appropriate quality assurance controls such as internal amplification controls for RT-PCR. The abundant presence of pigs excreting HEV raises concerns on potential zoonotic transmission of the virus, either by exposure through the environment or by consumption of contaminated pork products. Moreover, one of the detected strains belonged to a European cluster which was not detected in the Netherlands before, suggesting that HEV strains spread through European countries. These data demonstrate the need to include appropriate controls in diagnostic assays, especially in complex matrices such as feces which are known to contain PCR inhibitory substances. 相似文献
63.
Dragonieri S Schot R Mertens BJ Le Cessie S Gauw SA Spanevello A Resta O Willard NP Vink TJ Rabe KF Bel EH Sterk PJ 《The Journal of allergy and clinical immunology》2007,120(4):856-862
BACKGROUND: Exhaled breath contains thousands of volatile organic compounds (VOCs) that could serve as biomarkers of lung disease. Electronic noses can distinguish VOC mixtures by pattern recognition. OBJECTIVE: We hypothesized that an electronic nose can discriminate exhaled air of patients with asthma from healthy controls, and between patients with different disease severities. METHODS: Ten young patients with mild asthma (25.1 +/- 5.9 years; FEV(1), 99.9 +/- 7.7% predicted), 10 young controls (26.8 +/- 6.4 years; FEV(1), 101.9 +/- 10.3), 10 older patients with severe asthma (49.5 +/- 12.0 years; FEV(1), 62.3 +/- 23.6), and 10 older controls (57.3 +/- 7.1 years; FEV(1), 108.3 +/- 14.7) joined a cross-sectional study with duplicate sampling of exhaled breath with an interval of 2 to 5 minutes. Subjects inspired VOC-filtered air by tidal breathing for 5 minutes, and a single expiratory vital capacity was collected into a Tedlar bag that was sampled by electronic nose (Cyranose 320) within 10 minutes. Smellprints were analyzed by linear discriminant analysis on principal component reduction. Cross-validation values (CVVs) were calculated. RESULTS: Smellprints of patients with mild asthma were fully separated from young controls (CVV, 100%; Mahalanobis distance [M-distance], 5.32), and patients with severe asthma could be distinguished from old controls (CVV, 90%; M-distance, 2.77). Patients with mild and severe asthma could be less well discriminated (CVV, 65%; M-distance, 1.23), whereas the 2 control groups were indistinguishable (CVV, 50%; M-distance, 1.56). The duplicate samples replicated these results. CONCLUSION: An electronic nose can discriminate exhaled breath of patients with asthma from controls but is less accurate in distinguishing asthma severities. CLINICAL IMPLICATION: These findings warrant validation of electronic noses in diagnosing newly presented patients with asthma. 相似文献
64.
Abu Sin Muna Nahrgang Saskia Ziegelmann Antina Clarici Alexandra Matz Sibylle Tenhagen Bernd-Alois Eckmanns Tim 《Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz》2018,61(5):507-514
Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Die Ausbreitung von Antibiotikaresistenzen wurde in den letzten Jahren zunehmend als Problem im Bereich globale Gesundheit... 相似文献
65.
Johannes Pollmanns Maria Weyermann Max Geraedts Saskia E. Drösler 《Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz》2018,61(11):1462-1471
Background
Hospitalizations and lower limb amputations related to diabetes mellitus (DM) are considered to be potentially avoidable. Appropriate outpatient care of diabetes prevents complications. Rates on potentially avoidable hospitalizations for diabetes are core indicators of the German diabetes surveillance program. International comparisons showed high hospitalization rates in Germany for both indicators.Objectives
The objective of this analysis is to describe time trends on hospitalizations and inpatient lower limb amputations (major amputations) for DM. Furthermore, we analyze small area variations.Materials and methods
Based on the German diagnosis related groups (DRGs) dataset we calculated age-standardized rates covering 2005–2015. Calculations rely on the Organisation for Economic Co-operation and Development (OECD) indicator definitions. Time trends are obtained by linear regression modelling. We also stratified into age groups and analyzed 2015 small-area variations using age-adjusted rates.Results
Crude hospitalization rates were 310 admissions per 100,000 inhabitants in men (amputation rate: 15.6) and 216 admissions per 100,000 inhabitants in women (amputation rate: 7.1) in 2015. Age-adjusted hospitalizations and amputations rates in women decreased over time (10.3 and 1.2 cases per 100,000 inhabitants and year, respectively). In men, the amputation rate decreased significantly (1.5 cases per 100,000 inhabitants and year). We found higher rates for men than for women in almost all age categories. In eastern Germany and parts of Bavaria and North Rhine-Westphalia rates are particularly high.Conclusions
A decrease in hospitalization rates may indicate improvements in ambulatory diabetes care over time. Future studies should consider age-specific differences and small-area variations.66.
Background
When proven effective, decision making regarding reimbursement of new health technology typically involves ethical, social, legal, and health economic aspects and constraints. Nevertheless, when applying standard value of information (VOI) analysis, the value of collecting additional evidence is typically estimated assuming that only cost-effectiveness outcomes guide such decisions.Objectives
To illustrate how decision makers’ constraints can be incorporated into VOI analyses and how these may influence VOI outcomes.Methods
A simulation study was performed to estimate the cost-effectiveness of a new hypothetical technology compared with usual care. Constraints were defined for the new technology on 1) the maximum acceptable rate of complications and 2) the maximum acceptable additional budget. The expected value of perfect information (EVPI) for the new technology was estimated in various scenarios, both with and without incorporating these constraints.Results
For a willingness-to-pay threshold of €20,000 per quality-adjusted life-year, the probability that the new technology was cost-effective equaled 57%, with an EVPI of €1868 per patient. Applying the complication rate constraint reduced the EVPI to €1137. Similarly, the EVPI reduced to €770 when applying the budget constraint. Applying both constraints simultaneously further reduced the EVPI to €318.Conclusions
When decision makers explicitly apply additional constraints, beyond a willingness-to-pay threshold, to reimbursement decisions, these constraints can and should be incorporated into VOI analysis as well, because they may influence VOI outcomes. This requires continuous interaction between VOI analysts and decision makers and is expected to improve both the relevance and the acceptance of VOI outcomes. 相似文献67.
Variability of voriconazole plasma levels measured by new high-performance liquid chromatography and bioassay methods
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Pascual A Nieth V Calandra T Bille J Bolay S Decosterd LA Buclin T Majcherczyk PA Sanglard D Marchetti O 《Antimicrobial agents and chemotherapy》2007,51(1):137-143
Voriconazole (VRC) is a broad-spectrum antifungal triazole with nonlinear pharmacokinetics. The utility of measurement of voriconazole blood levels for optimizing therapy is a matter of debate. Available high-performance liquid chromatography (HPLC) and bioassay methods are technically complex, time-consuming, or have a narrow analytical range. Objectives of the present study were to develop new, simple analytical methods and to assess variability of voriconazole blood levels in patients with invasive mycoses. Acetonitrile precipitation, reverse-phase separation, and UV detection were used for HPLC. A voriconazole-hypersusceptible Candida albicans mutant lacking multidrug efflux transporters (cdr1Delta/cdr1Delta, cdr2Delta/cdr2Delta, flu1Delta/flu1Delta, and mdr1Delta/mdr1Delta) and calcineurin subunit A (cnaDelta/cnaDelta) was used for bioassay. Mean intra-/interrun accuracies over the VRC concentration range from 0.25 to 16 mg/liter were 93.7% +/- 5.0%/96.5% +/- 2.4% (HPLC) and 94.9% +/- 6.1%/94.7% +/- 3.3% (bioassay). Mean intra-/interrun coefficients of variation were 5.2% +/- 1.5%/5.4% +/- 0.9% and 6.5% +/- 2.5%/4.0% +/- 1.6% for HPLC and bioassay, respectively. The coefficient of concordance between HPLC and bioassay was 0.96. Sequential measurements in 10 patients with invasive mycoses showed important inter- and intraindividual variations of estimated voriconazole area under the concentration-time curve (AUC): median, 43.9 mg x h/liter (range, 12.9 to 71.1) on the first and 27.4 mg x h/liter (range, 2.9 to 93.1) on the last day of therapy. During therapy, AUC decreased in five patients, increased in three, and remained unchanged in two. A toxic encephalopathy probably related to the increase of the VRC AUC (from 71.1 to 93.1 mg x h/liter) was observed. The VRC AUC decreased (from 12.9 to 2.9 mg x h/liter) in a patient with persistent signs of invasive aspergillosis. These preliminary observations suggest that voriconazole over- or underexposure resulting from variability of blood levels might have clinical implications. Simple HPLC and bioassay methods offer new tools for monitoring voriconazole therapy. 相似文献
68.
The transverse aortic constriction heart failure animal model: a systematic review and meta-analysis
Bosch Lena de Haan Judith J. Bastemeijer Marissa van der Burg Jennifer van der Worp Erik Wesseling Marian Viola Margarida Odille Clémene el Azzouzi Hamid Pasterkamp Gerard Sluijter Joost P.G. Wever Kimberley E. de Jager Saskia C.A. 《Heart failure reviews》2021,26(6):1515-1524
Heart Failure Reviews - The transverse aortic constriction (TAC) model is frequently used to study adverse cardiac remodeling upon pressure overload. We set out to define the most important... 相似文献
69.
Hugues Lucron Alban-Elouen Baruteau Caroline Ovaert Ali Houeijeh Mélanie Brard Patrice Guerin François Bourlon Claire Dauphin Saskia Tuttle Maha Tagorti Rishika Banydeen François Godart 《Congenital heart disease》2022,17(4):421-436
Objectives: We aim to describe the efficacy, safety, and characteristics of the Amplatzer Vascular Plug (AVP) II and IV “off-label” use for multiple cardiovascular occlusions in children under 10 years. Methods: Observational retrospective multicenter (2007–2020, 6 centers) review of paediatric procedures using AVP II or IV. Results: A total of 125 children (49.6% aged ≤ 1 year, 147 lesions) underwent 136 successive procedures (success rate: 98.5%) using 169 devices (109 AVP IV, 60 AVP II). The mean device diameter was 7.7 ± 3.2 mm (4–20 mm). The median AVP size to vessel diameter ratio was 1.3 (0–2). The median age and weight at implantation were 1.0 year (0.01–9.98) and 8.4 kg (1–69). Procedures were heterogeneous (55 patent ductus arteriosus (PDA), 28 collaterals, 18 sequestrations, 22 arteriovenous/veinovenous/coronary fistulas, 6 vertical veins, 6 conduits, 5 ventricular septal defects, 7 miscellaneous). Day 1 and 6-month occlusion rates were respectively 94.8% and 98.5%. Major adverse events (MAE) occurred in 5.2% of cases (no procedure-related deaths), and more frequently in weight ≤ 5 kg (p = 0.01), younger patients (p = 0.03) during PDA closure (p = 0.02) of tubular types (p = 0.02) using larger devices (p = 0.03) and AVP II (p = 0.003). Independent predictor of MAE risk was a higher AVP diameter to patient weight ratio (Odds-ratio: 2.33, 95% confidence interval 1.31–4.13, p = 0.004, optimal cut off: 1.45). Conclusions: Both AVPs are safe and effective for percutaneous occlusions in children under 10. Such devices represent an alternative “off label” use for well selected paediatric patients. 相似文献
70.
Charlotte M. Nijskens Saskia R. Veldkamp Dymph J. Van Der Werf Arnold H. Boonstra Marije Ten Wolde 《Journal of clinical hypertension (Greenwich, Conn.)》2021,23(1):166-171
According to international guidelines, patients with a suspected hypertensive emergency (HE) admitted to the emergency department (ED) should undergo comprehensive evaluation including funduscopic examination. However, funduscopy is not always readily available and little is known about the prevalence of retinopathy among these patients in the ED setting. In order to characterize patients who should undergo funduscopy, we studied the prevalence, characteristics and clinical outcome in patients with a suspected HE and retinopathy grade III/IV. We conducted a retrospective cohort study of consecutive patients with severe elevation of blood pressure (BP) admitted to the ED between 2012 and 2015. Patients with a systolic blood pressure (SBP) ≥180 mm Hg or diastolic blood pressure (DBP) ≥120 mm Hg at time of presentation were included. A total of 271 patients were included, of whom 18 (6.6%; 95%CI 3.9‐10.5) had a HE. In 121 patients (44.6%; 95%CI 37.1‐53.3), funduscopy was performed, of whom 17 (14.0%; 95%CI 8.2‐22.5) had retinopathy grade III/IV. Mean SBP and DBP were significantly higher in patients with retinopathy (P < .001). However, retinopathy was also seen in patients with lower BP (SBP < 200 mm Hg and DBP < 120 mm Hg). No differences in other clinical characteristics, including visual disturbances, were found. One patient with retinopathy suffered an ischemic stroke after taking oral medication. The prevalence of retinopathy is high among examined patients. Except for higher BP, no clinical signs or symptoms are associated with the presence of retinopathy grade III/IV. We therefore conclude that funduscopic examination should be performed in every patient with a suspected HE. 相似文献