Prokineticin 1 Induces Inflammatory Response in Human Myometrium: A Potential Role in Initiating Term and Preterm Parturition

The infiltration of human myometrium and cervix with leukocytes and the formation of a pro-inflammatory environment within the uterus have been associated with the initiation of both term and preterm parturition. The mechanism regulating the onset of this pro-inflammatory cascade is not fully elucidated. We demonstrate that prokineticin 1 (PROK1) is up-regulated in human myometrium and placenta during labor. The expression of PROK1 receptor remains unchanged during labor and is abundantly expressed in the myometrium. Gene array analysis identified 65 genes up-regulated by PROK1 in human myometrium, mainly cytokines and chemokines, including IL-1β, chemokine C-C motif ligand 3, and colony-stimulating factor 3. In addition, we demonstrate that PROK1 increases the expression of chemokine C-C motif ligand 20, IL-6, IL-8, prostaglandin synthase 2, and prostaglandin E2 and F2α secretion. The treatment of myometrial explants with 100 ng/mL of lipopolysaccharide up-regulates the expression of PROK1, PROK1 receptor, and inflammatory mediators. The infection of myometrial explants with lentiviral microRNA targeting PROK1, preceding treatment with lipopolysaccharide, reduces the expression of inflammatory genes. We propose that PROK1 is a novel inflammatory mediator that can contribute to the onset of human parturition at term and partially mediate premature onset of inflammatory pathways during bacterial infection

The National Childrens Study: Recruitment Outcomes Using the Provider-Based Recruitment Approach

In 2009, the National Children’s Study (NCS) Vanguard Study tested the feasibility of household-based recruitment and participant enrollment using a birth-rate probability sample. In 2010, the NCS Program Office launched 3 additional recruitment approaches. We tested whether provider-based recruitment could improve recruitment outcomes compared with household-based recruitment

The Absolute of Advaita and the Spirit of Hegel: Situating Vedānta on the Horizons of British Idealisms

$\textit{Purpose}$ A significant volume of philosophical literature produced by Indian academic philosophers in the first half of the twentieth century can be placed under the rubric of ‘Śaṁkara and X’, where X is Hegel, or a German or a British philosopher who had commented on, elaborated or critiqued the Hegelian system. We will explore in this essay the philosophical significance of Hegel-influenced systems as an intellectual conduit for these Indo-European conceptual encounters, and highlight how for some Indian philosophers the British variations on Hegelian systems were both a point of entry into debates over ‘idealism’ and ‘realism’ in contemporary European philosophy and an occasion for defending Advaita against the charge of propounding a doctrine of world illusionism. $\textit{Methodology}$ Our study of the philosophical enquiries of A.C. Mukerji, P.T. Raju, and S.N.L. Shrivastava indicates that they developed distinctive styles of engaging with Hegelian idealisms as they reconfigured certain aspects of the classical Advaita of Śaṁkara through contemporary vocabulary. $\textit{Result and Conclusion}$ These appropriations of Hegelian idioms can be placed under three overlapping styles: (a) Mukerji was partly involved in locating Advaita in an intermediate conceptual space between, on the one hand, Kantian agnosticism and, on the other hand, Hegelian absolutism; (b) Raju and Shrivastava presented Advaitic thought as the fulfilment of certain insights of Hegel and F.H. Bradley; and (c) the interrogations of Hegel’s ‘idealism’ provided several Indian academic philosophers with a hermeneutic opportunity to revisit the vexed question of whether the ‘idealism’ of Śaṁkara reduces the phenomenal world, structured by $\textit{māyā}$, to a bundle of ideas

Spontaneous preterm labor is associated with an increase in the proinflammatory signal transducer TLR4 receptor on maternal blood monocytes

<p>Abstract</p> <p>Background</p> <p>Localized inflammation and increased expression of TLR4 receptors within the uterus has been implicated in the pathogenesis of preterm labor. It remains unclear whether intrauterine inflammatory responses activate the maternal peripheral circulatory system. Therefore we determined whether increased TLR4 expression is present in the peripheral maternal white blood cells of women with spontaneous preterm labor.</p> <p>Methods</p> <p>This is a cross-sectional study of 41 preterm labor cases and 41 non-preterm controls. For each case and control sample, RNA was purified from white blood cells and TLR4 mRNA pool size was evaluated by quantitative PCR. Protein expression levels were determined by flow cytometry. Statistical evaluation using multiple linear regressions was used to determine any significant differences between the cases and controls. The purpose was to determine association prevalence of TLR4 levels and preterm labor.</p> <p>Results</p> <p>Adjusted mean TLR4 mRNA levels of 0.788 ± 0.037 (standard error) for preterm labor and 0.348 ± 0.038 for the corresponding pregnant control women were statistically significantly different <it>(P </it>= 0.002). Using the lower 95% confidence interval of the mean expression level in PTL subjects (0.7) as a cutoff value for elevated TLR4 mRNA levels, 25/41 (60.9%) of PTL patients expressed elevated TLR4 mRNA as compared to 0/41 (0%) in control subjects. The TLR4 receptor levels in the granulocyte fraction of white blood cells from preterm labor and pregnant controls were similar. However, TLR4⁺/CD14⁺monocytes were 2.3 times more frequent (70% vs. 30%) and TLR4 also had a 2.6-fold higher density (750 vs. 280 molecules per cell) in preterm labor women compared with pregnant controls. There was no difference in the levels of TLR4 in patients at term.</p> <p>Conclusions</p> <p>Patients with preterm labor exhibited elevated levels of CD14⁺maternal blood monocytes each bearing enhanced expression of TLR4, indicating that the peripheral circulatory system is activated in patients with preterm labor. Elevated leukocyte TLR4 levels may be a useful biomarker associated with preterm labor.</p

Anaerobic Energy Expenditure and Mechanical Efficiency during Exhaustive Leg Press Exercise

Information about anaerobic energy production and mechanical efficiency that occurs over time during short-lasting maximal exercise is scarce and controversial. Bilateral leg press is an interesting muscle contraction model to estimate anaerobic energy production and mechanical efficiency during maximal exercise because it largely differs from the models used until now. This study examined the changes in muscle metabolite concentration and power output production during the first and the second half of a set of 10 repetitions to failure (10RM) of bilateral leg press exercise. On two separate days, muscle biopsies were obtained from vastus lateralis prior and immediately after a set of 5 or a set of 10 repetitions. During the second set of 5 repetitions, mean power production decreased by 19% and the average ATP utilisation accounted for by phosphagen decreased from 54% to 19%, whereas ATP utilisation from anaerobic glycolysis increased from 46 to 81%. Changes in contraction time and power output were correlated to the changes in muscle Phosphocreatine (PCr; r = −0.76; P<0.01) and lactate (r = −0.91; P<0.01), respectively, and were accompanied by parallel decreases (P<0.01-0.05) in muscle energy charge (0.6%), muscle ATP/ADP (8%) and ATP/AMP (19%) ratios, as well as by increases in ADP content (7%). The estimated average rate of ATP utilisation from anaerobic sources during the final 5 repetitions fell to 83% whereas total anaerobic ATP production increased by 9% due to a 30% longer average duration of exercise (18.4±4.0 vs 14.2±2.1 s). These data indicate that during a set of 10RM of bilateral leg press exercise there is a decrease in power output which is associated with a decrease in the contribution of PCr and/or an increase in muscle lactate. The higher energy cost per repetition during the second 5 repetitions is suggestive of decreased mechanical efficiency

Do personality traits assessed on medical school admission predict exit performance?:A UK-wide longitudinal cohort studyA2

We thank the UKCAT Research Group for funding this independent evaluation and thank Rachel Greatrix and Sandra Nicholson of the UKCAT Consortium for their support throughout this project, and their feedback on the draft paper. We also thank Professor Amanda Lee and Ms Katie Wilde for their input into the application for funding, and ongoing support.Peer reviewedPublisher PD