Reduced mechanical efficiency in left-ventricular trabeculae of the spontaneously hypertensive rat.

Long-term systemic arterial hypertension, and its associated compensatory response of left-ventricular hypertrophy, is fatal. This disease leads to cardiac failure and culminates in death. The spontaneously hypertensive rat (SHR) is an excellent animal model for studying this pathology, suffering from ventricular failure beginning at about 18 months of age. In this study, we isolated left-ventricular trabeculae from SHR-F hearts and contrasted their mechanoenergetic performance with those from nonfailing SHR (SHR-NF) and normotensive Wistar rats. Our results show that, whereas the performance of the SHR-F differed little from that of the SHR-NF, both SHR groups performed less stress-length work than that of Wistar trabeculae. Their lower work output arose from reduced ability to produce sufficient force and shortening. Neither their heat production nor their enthalpy output (the sum of work and heat), particularly the energy cost of Ca(2+) cycling, differed from that of the Wistar controls. Consequently, mechanical efficiency (the ratio of work to change of enthalpy) of both SHR groups was lower than that of the Wistar trabeculae. Our data suggest that in hypertension-induced left-ventricular hypertrophy, the mechanical performance of the tissue is compromised such that myocardial efficiency is reduced

How to ... be reflexive when conducting qualitative research

Reflexivity can be a complex concept to grasp when entering the world of qualitative research. In this article, we aim to encourage new qualitative researchers to become reflexive as they develop their critical research skills, differentiating between the familiar concept of reflection and reflective practice and that of reflexivity. Although reflection is, to all intents and purposes, a goal‐oriented action with the aim of improving practice, reflexivity is a continual process of engaging with and articulating the place of the researcher and the context of the research. It also involves challenging and articulating social and cultural influences and dynamics that affect this context. As a hallmark of high‐quality qualitative research, reflexivity is not only an individual process but one that needs to be considered a collective process within a research team, and communicated throughout the research process. In keeping with our previous articles in this series, we have illustrated the theoretical concept of reflexivity using practical examples of published researchPeer reviewe

Design of quadrature rules for Müntz and Müntz-logarithmic polynomials using monomial transformation

A method for constructing the exact quadratures for Müntz and Müntz-logarithmic polynomials is presented. The algorithm does permit to anticipate the precision (machine precision) of the numerical integration of Müntz-logarithmic polynomials in terms of the number of Gauss-Legendre (GL) quadrature samples and monomial transformation order. To investigate in depth the properties of classical GL quadrature, we present new optimal asymptotic estimates for the remainder. In boundary element integrals this quadrature rule can be applied to evaluate singular functions with end-point singularity, singular kernel as well as smooth functions. The method is numerically stable, efficient, easy to be implemented. The rule has been fully tested and several numerical examples are included. The proposed quadrature method is more efficient in run-time evaluation than the existing methods for Müntz polynomial

Nurturing curiosity and creativity in primary school classrooms

Creativity and curiosity are recognised as vital skills to prepare students to engage with the significant challenges and opportunities of the future. To address the research question “What practices do teachers enact with the aim of encouraging creativity and curiosity in primary classrooms?”, 21 teachers were interviewed about their teaching practices; this data was triangulated with self-captured classroom videos from 19 classrooms in nine countries. Results of the analysis demonstrated a variety of promising classroom practices. These findings and implications for practice are discussed in terms of diverse feedback pathways, nurturing inquisitive minds, supporting self-regulatory learning and self-expression

Regulation of pituitary MT1 melatonin receptor expression by gonadotrophin-releasing hormone (GnRH) and early growth response factor-1 (Egr-1) : in vivo and in vitro studies

Copyright: © 2014 Bae et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was funded by the UK Biotechnology and Biological Sciences Research Council (BBSRC; grant BB/F020309/1; http://www.bbsrc.ac.uk/home/home.aspx). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Bedaquiline as Treatment for Disseminated Nontuberculous Mycobacteria Infection in 2 Patients Co-Infected with HIV.

Nontuberculous mycobacteria can cause disseminated infections in immunocompromised patients and are challenging to treat because of antimicrobial resistance and adverse effects of prolonged multidrug treatment. We report successful treatment with bedaquiline, a novel antimycobacterial drug, as part of combination therapy for 2 patients with disseminated nontuberculous mycobacteria co-infected with HIV

Identification of Melatonin-Regulated Genes in the Ovine Pituitary Pars Tuberalis, a Target Site for Seasonal Hormone Control

The pars tuberalis (PT) of the pituitary gland expresses a high density of melatonin (MEL) receptors and is believed to regulate seasonal physiology by decoding changes in nocturnal melatonin secretion. Circadian clock genes are known to be expressed in the PT in response to the decline (Per1) and onset (Cry1) of MEL secretion, but to date little is known of other molecular changes in this key MEL target site. To identify transcriptional pathways that may be involved in the diurnal and photoperiod-transduction mechanism, we performed a whole genome transcriptome analysis using PT RNA isolated from sheep culled at three time points over the 24-h cycle under either long or short photoperiods. Our results reveal 153 transcripts where expression differs between photoperiods at the light-dark transition and 54 transcripts where expression level was more globally altered by photoperiod (all time points combined). Cry1 induction at night was associated with up-regulation of genes coding for NeuroD1 (neurogenic differentiation factor 1), Pbef / Nampt (nicotinamide phosphoribosyltransferase) , Hif1α (hypoxia-inducible factor-1α), and Kcnq5 (K channel) and down-regulation of Rorβ, a key clock gene regulator. Using in situ hybridization, we confirmed day-night differences in expression for Pbef / Nampt, NeuroD1, and Rorβ in the PT. Treatment of sheep with MEL increased PT expression for Cry1, Pbef / Nampt, NeuroD1, and Hif1α, but not Kcnq5. Our data thus reveal a cluster of Cry1-associated genes that are acutely responsive to MEL and novel transcriptional pathways involved in MEL action in the PT