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Introduction: Central sensitization is common in knee osteoarthritis patients (KOAP)1. Exercise therapy is suggested to be beneficial by activating endogenous analgesia2. Therefore, this systematic review aims to summarize the basal and/or acute effects of exercises on endogenous analgesia in KOAP. Methods: PubMed, Web of Science, and Embase were systematically searched. If possible, a meta-analysis was performed. Risk of bias was scored using the Cochrane ROB 2.0 or ROBINS-I and strength of evidence was assessed by the GRADE approach. Results: A total of 19 studies were included: 4 studies investigated pain thresholds after an acute bout of exercise; 15 articles focused on basal levels of endogenous analgesia (as measured by pain thresholds (n = 15), -facilitation (n = 3), and -inhibition (n = 2)). A meta-analysis combining 2 studies demonstrated that KOAP did not become more tolerant for pressure pain than healthy controls immediately after resistance training (p > 0.05). Besides that, one study with moderate quality of evidence showed that exercising KOAP had higher pain thresholds than non-exercising KOAP immediately after exercise (p < 0.05). A meta-analysis combining three studies showed that strength training of 6-12 weeks caused a significant increase in pain thresholds in KOAP compared to non-exercising KOAP (p < 0.05). Discussion: Very low quality of evidence proved that strength training of at least 6 weeks is effective in increasing pain thresholds in KOAP. Moderate quality of evidence demonstrated that an acute bout of exercise effectively increases pain thresholds in KOAP. Process evaluation: Literature about this topic is scarce, especially studies investigating pain facilitation (n = 3) and inhibition (n = 1). [ABSTRACT FROM AUTHOR]

Aim: Paracetamol clearance differs between pregnant and non-pregnant women and between women with or without specific oral contraceptives (OCs). However, an association between female sex hormones and paracetamol clearance has never been explored. Methods: In total, 49 women at delivery, 8 female control subjects without OC use, historical data of 14 women taking OCs, and 15 postpartum observations with and without OCs were pooled to explore covariates of paracetamol clearance. All received a single intravenous 2-gram paracetamol dose, and blood samples were collected up to 6 h after dosing. High-performance liquid chromatography was used to quantify paracetamol. The area under the curve to time infinity (AUC0-∞) was determined and clearance (l/h·m2) was calculated by dose/ AUC0-∞. In addition, estradiol and progesterone were quantified by ELISA with electro-chemiluminescence. Results: Median paracetamol clearance at delivery was significantly higher when compared to postpartum or non-pregnant women (11.9 vs. 6.42 and 8.4 l/h·m2, at least p < 0.05), while an association between paracetamol clearance and estradiol was observed (R = 0.494, p < 0.0001). In non-pregnant subjects, there was no impact of OC exposure on paracetamol clearance. Multiple regression revealed a linear association (Radj = 0.41, p < 0.001) between paracetamol clearance and weight (p = 0.0462) and estradiol (p < 0.0001). Conclusion: Estradiol and weight in part explain the variation in paracetamol clearance in young women. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: During migraine, trigeminal sensory nerve terminals release calcitonin gene-related peptide (CGRP), inducing nociception and vasodilation. Applied on the skin, capsaicin activates the transient receptor potential vanilloid type 1 (TRPV1) channel and releases CGRP from sensory nerve terminals, thus increasing dermal blood flow (DBF). Using capsaicin application and electrical stimulation of the forehead skin, a trigeminal nerve-innervated dermatome, we aimed to develop a model to measure trigeminal nerve-mediated vasodilation in humans.Methods: Using laser Doppler imaging, forehead DBF responses to application of capsaicin (0.06 mg/ml and 6.0 mg/ml) and saline, with and without iontophoresis, were studied in healthy subjects. The within-subject coefficient of variation (WCV) of repeated DBF measurements was calculated to assess reproducibility.Results: Maximal DBF responses to 6.0 mg/ml capsaicin with and without iontophoresis did not differ (Emax 459 ± 32 and 424 ± 32 arbitrary units (a.u.), WCV 6 ± 4%). In contrast, DBF responses to 0.06 mg/ml capsaicin were significantly larger with than without iontophoresis (Emax 307 ± 60 versus 187 ± 21 a.u., WCV 21 ± 13%). Saline with iontophoresis significantly increased DBF (Emax: 245 ± 26 a.u, WCV 11 ± 8%), while saline application without iontophoresis did not affect DBF.Conclusion: Topical application of capsaicin and electrical stimulation induce reproducible forehead DBF increases and therefore are suitable to study trigeminal nerve-mediated vasodilation in humans. [ABSTRACT FROM AUTHOR]

Probiotic bacteria have been shown to have health benefits in various situations (inflammation, allergy, infection). We previously showed that a bacteria-free fermentation product of Bifidobacterium breve C50 (BbC50sn) induced high IL-10 secretion by human dendritic cells. As IL-10 is a regulatory cytokine, the aim of the present study was to examine whether DCs cultured in the presence of BbC50sn could induce regulatory T cells in an allogeneic context. Purified CD4+CD25− human T cells were co-cultured with allogeneic BbC50sn-treated dendritic cells for 4 weeks. The T cell population (BbC50sn-T) was analysed both at phenotypical and functional [ability to inhibit a mixed lymphocyte reaction (MLR)] levels. We showed that T lymphocytes acquired phenotype characteristics of regulatory T cells after 4 weeks of co-culture with BbC50sn-DCs, and inhibited in vitro T lymphocyte proliferation and IFN-γ production in an MLR. Transwell experiments demonstrated that this suppressive activity was not T cell contact-dependent but probably mediated by a soluble factor. Although BbC50sn-T cells secreted significant amounts of IL-10 and TGF-β, their suppressive effect is most likely not mediated through these cytokines. This is, to our knowledge, the first demonstration of in vitro regulatory T cell induction by a bacteria-free fermentation product in an allogeneic context. [ABSTRACT FROM AUTHOR]

Document delivery is challenging and complex, particularly in a high-volume library. This situation is further complicated by technology, with its inherent learning curve, need for technical support, and other limitations. This article focuses on the development and implementation of an in-house application, known as the Celsus Electronic Document Delivery System, in a large academic medical center library system, and offers advice for librarians interested in developing alternatives to commercial document delivery software such as Prospero, Ariel®, ILLiad, and Odyssey. [ABSTRACT FROM AUTHOR]

tThe linear time-varying elastance theory is frequently used to describe the change in ventricular stiffness during the cardiac cycle. The concept assumes that all isochrones (i.e., curves that connect pressure-volume data occurring at the same time) are linear and have a common volume intercept. Of specific interest is the steepest isochrone, the end-systolic pressure-volume relationship (ESPVR), of which the slope serves as an index for cardiac contractile function. Pressure-volume measurements, achieved with a combined pressure-conductance catheter in the left ventricle of 13 open-chest anesthetized mice, showed a marked curvilinearity of the isochrones. We therefore analyzed the shape of the isochrones by using six regression algorithms (two linear, two quadratic, and two logarithmic, each with a fixed or time-varying intercept) and discussed the consequences for the elastance concept. Our main observations were 1) the volume intercept varies considerably with time; 2) isochrones are equally well described by using quadratic or logarithmic regression; 3) linear regression with a fixed intercept shows poor correlation (R² < 0.75) during isovolumic relaxation and early filling; and 4) logarithmic regression is superior in estimating the fixed volume intercept of the ESPVR. In conclusion, the linear time-varying elastance fails to provide a sufficiently robust model to account for changes in pressure and volume during the cardiac cycle in the mouse ventricle. A new framework accounting for the nonlinear shape of the isochrones needs to be developed. [ABSTRACT FROM AUTHOR]

The article reports on results of a study of scaling techniques for deriving carotid artery pressures from diameter distension waveforms. A description of the experimental set-up and measurement method is presented. The study concluded that properly calibrated diameter waveforms offer a viable alternative for local pressure estimation at the carotid artery.

The article investigates the possible differences between men and women in age-related central arterial stiffening. It proposes a pressure-dependent, geometry-independent arterial stiffness index. It reveals that the proposed static distensibility derived from a geometry-normalized Langewouters relationship shows results in good agreement with the stiffness index. Both indices demonstrate that the carotid artery becomes stiffer in women then in men around the age of 45.

The article attempts to quantify the relationship between carotid artery intima-media thickness (IMT) and hemodynamic parameters using magnetic resonance imaging assessment of IMT, and numerical computation of wall shear stress (WSS). The method for imaging the carotid arteries is described. The results are consistent with the commonly accepted notion that WSS derived parameters are associated with IMT in the carotid artery.

Abstract: Introduction: Although of pharmacokinetic and -dynamic relevance, data on ontogeny of UDP-glucuronosyltransferase (UGT) activity in neonates are scant. We therefore wanted to assess the impact of both postnatal and postmenstrual age (PNA/PMA) on the interindividual variability of glucuronidation to overall tramadol urinary elimination in neonates. Methods: O-demethyl tramadol (M1) and M1-glucuronide (M1G) were determined in 24 hour urine collections during continuous intravenous tramadol administration in neonates. Glucuronidation fraction (%) was calculated by the ratio of M1G to the sum of M1G and M1 free (M1total). Fractions (%) in early (