Myxomatous mitral valve disease with mitral valve prolapse and mitral annular disjunction: clinical and functional significance of the coincidence

The morphological changes that occur in myxomatous mitral valve disease (MMVD) involve various components, ultimately leading to the impairment of mitral valve (MV) function. In this context, intrinsic mitral annular abnormalities are increasingly recognized, such as a mitral annular disjunction (MAD), a specific anatomical abnormality whereby there is a distinct separation between the mitral annulus and the left atrial wall and the basal portion of the posterolateral left ventricular myocardium. In recent years, several studies have suggested that MAD contributes to myxomatous degeneration of the mitral leaflets, and there is growing evidence that MAD is associated with ventricular arrhythmias and sudden cardiac death. In this review, the morphological characteristics of MAD and imaging tools for diagnosis will be described, and the clinical and functional aspects of the coincidence of MAD and myxomatous MVP will be discussed

Reduction of mitomycin C is catalysed by human recombinant NRH:quinone oxidoreductase 2 using reduced nicotinamide adenine dinucleotide as an electron donating co-factor

NRH:Quinone Oxidoreductase 2 (NQO2) has been described as having no enzymatic activity with nicotinamide adenine dinucleotide (NADH) or NADPH as electron donating cosubstrates. Mitomycin C (MMC) is both a substrate for and a mechanistic inhibitor of the NQO2 homologue NQO1. NRH:quinone oxidoreductase 2 catalysed the reduction of MMC at pH 5.8 with NADH as a co-factor. This reaction results in species that inhibit the NQO2-mediated metabolism of CB1954. In addition, MMC caused an increase in DNA cross-links in a cell line transfected to overexpress NQO2 to an extent comparable to that observed with an isogenic NQO1-expressing cell line. These data indicate that NQO2 may contribute to the metabolism of MMC to cytotoxic species

Long-term patterns of body mass and stature evolution within the hominin lineage.

Body size is a central determinant of a species' biology and adaptive strategy, but the number of reliable estimates of hominin body mass and stature have been insufficient to determine long-term patterns and subtle interactions in these size components within our lineage. Here, we analyse 254 body mass and 204 stature estimates from a total of 311 hominin specimens dating from 4.4 Ma to the Holocene using multi-level chronological and taxonomic analytical categories. The results demonstrate complex temporal patterns of body size variation with phases of relative stasis intermitted by periods of rapid increases. The observed trajectories could result from punctuated increases at speciation events, but also differential proliferation of large-bodied taxa or the extinction of small-bodied populations. Combined taxonomic and temporal analyses show that in relation to australopithecines, early Homo is characterized by significantly larger average body mass and stature but retains considerable diversity, including small body sizes. Within later Homo, stature and body mass evolution follow different trajectories: average modern stature is maintained from ca 1.6 Ma, while consistently higher body masses are not established until the Middle Pleistocene at ca 0.5-0.4 Ma, likely caused by directional selection related to colonizing higher latitudes. Selection against small-bodied individuals (less than 40 kg; less than 140 cm) after 1.4 Ma is associated with a decrease in relative size variability in later Homo species compared with earlier Homo and australopithecines. The isolated small-bodied individuals of Homo naledi (ca 0.3 Ma) and Homo floresiensis (ca 100-60 ka) constitute important exceptions to these general patterns, adding further layers of complexity to the evolution of body size within the genus Homo. At the end of the Late Pleistocene and Holocene, body size in Homo sapiens declines on average, but also extends to lower limits not seen in comparable frequency since early Homo

Network Physiology reveals relations between network topology and physiological function

The human organism is an integrated network where complex physiologic systems, each with its own regulatory mechanisms, continuously interact, and where failure of one system can trigger a breakdown of the entire network. Identifying and quantifying dynamical networks of diverse systems with different types of interactions is a challenge. Here, we develop a framework to probe interactions among diverse systems, and we identify a physiologic network. We find that each physiologic state is characterized by a specific network structure, demonstrating a robust interplay between network topology and function. Across physiologic states the network undergoes topological transitions associated with fast reorganization of physiologic interactions on time scales of a few minutes, indicating high network flexibility in response to perturbations. The proposed system-wide integrative approach may facilitate the development of a new field, Network Physiology.Comment: 12 pages, 9 figure

Pre-cooling for endurance exercise performance in the heat: a systematic review.

PMCID: PMC3568721The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1741-7015/10/166. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Endurance exercise capacity diminishes under hot environmental conditions. Time to exhaustion can be increased by lowering body temperature prior to exercise (pre-cooling). This systematic literature review synthesizes the current findings of the effects of pre-cooling on endurance exercise performance, providing guidance for clinical practice and further research

Strategically Equivalent Contests

Using a two-player Tullock-type contest, we show that intuitively and structurally different contests can be strategically equivalent. Strategically equivalent contests generate the same best response functions and, as a result, the same equilibrium efforts. However, strategically equivalent contests may yield different equilibrium payoffs. We propose a simple two-step procedure to identify strategically equivalent contests. Using this procedure, we identify contests that are strategically equivalent to the original Tullock contest, and provide new examples of strategically equivalent contests. Finally, we discuss possible contest design applications and avenues for future theoretical and empirical research

Has education lost sight of children?

The reflections presented in this chapter are informed by clinical and personal experiences of school education in the UK. There are many challenges for children and young people in the modern education system and for the professionals who support them. In the UK, there are significant gaps between the highly selective education provided to those who pay privately for it and to the majority of those educated in the state-funded system. Though literacy rates have improved around the world, many children, particularly boys, do not finish their education for reasons such as boredom, behavioural difficulties or because education does not ‘pay’. Violence, bullying, and sexual harassment are issues faced by many children in schools and there are disturbing trends of excluding children who present with behavioural problems at school whose origins are not explored. Excluded children are then educated with other children who may also have multiple problems which often just make the situation worse. The experience of clinicians suggests that school-related mental health problems are increasing in severity. Are mental health services dealing with the consequences of an education system that is not meeting children’s needs? An education system that is testing- and performance-based may not be serving many children well if it is driving important decisions about them at increasingly younger ages. Labelling of children and setting them on educational career paths can occur well before they reach secondary schools, limiting potential very early on in their developmental trajectory. Furthermore, the emphasis at school on testing may come at the expense of creativity and other forms of intelligence, which are also valuable and important. Meanwhile the employment marketplace requires people with widely different skills, with an emphasis on innovation, creativity, and problem solving. Is education losing sight of the children it is educating

Borrelia valaisiana resist complement-mediated killing independently of the recruitment of immune regulators and inactivation of complement components

Spirochetes belonging to the Borrelia (B.) burgdorferi sensu lato complex differ in their resistance to complement-mediated killing, particularly in regard to human serum. In the present study, we elucidate the serum and complement susceptibility of B. valaisiana, a genospecies with the potential to cause Lyme disease in Europe as well as in Asia. Among the investigated isolates, growth of ZWU3 Ny3 was not affected while growth of VS116 and Bv9 was strongly inhibited in the presence of 50% human serum. Analyzing complement activation, complement components C3, C4 and C6 were deposited on the surface of isolates VS116 and Bv9, and similarly the membrane attack complex was formed on their surface. In contrast, no surface-deposited components and no aberrations in cell morphology were detected for serum-resistant ZWU3 Ny3. While further investigating the protective role of bound complement regulators in mediating complement resistance, we discovered that none of the B. valaisiana isolates analyzed bound complement regulators Factor H, Factor H-like protein 1, C4b binding protein or C1 esterase inhibitor. In addition, B. valaisiana also lacked intrinsic proteolytic activity to degrade complement components C3, C3b, C4, C4b, and C5. Taken together, these findings suggest that certain B. valaisiana isolates differ in their capability to resist complement-mediating killing by human serum. The molecular mechanism utilized by B. valaisiana to inhibit bacteriolysis appears not to involve binding of the key host complement regulators of the alternative, classical, and lectin pathways as already known for serum-resistant Lyme disease or relapsing fever borreliae

Breast-Lesion Characterization using Textural Features of Quantitative Ultrasound Parametric Maps

© 2017 The Author(s). This study evaluated, for the first time, the efficacy of quantitative ultrasound (QUS) spectral parametric maps in conjunction with texture-analysis techniques to differentiate non-invasively benign versus malignant breast lesions. Ultrasound B-mode images and radiofrequency data were acquired from 78 patients with suspicious breast lesions. QUS spectral-analysis techniques were performed on radiofrequency data to generate parametric maps of mid-band fit, spectral slope, spectral intercept, spacing among scatterers, average scatterer diameter, and average acoustic concentration. Texture-analysis techniques were applied to determine imaging biomarkers consisting of mean, contrast, correlation, energy and homogeneity features of parametric maps. These biomarkers were utilized to classify benign versus malignant lesions with leave-one-patient-out cross-validation. Results were compared to histopathology findings from biopsy specimens and radiology reports on MR images to evaluate the accuracy of technique. Among the biomarkers investigated, one mean-value parameter and 14 textural features demonstrated statistically significant differences (p < 0.05) between the two lesion types. A hybrid biomarker developed using a stepwise feature selection method could classify the legions with a sensitivity of 96%, a specificity of 84%, and an AUC of 0.97. Findings from this study pave the way towards adapting novel QUS-based frameworks for breast cancer screening and rapid diagnosis in clinic