Influence of involvement of anterior leaflet versus posterior leaflet on residual regurgitation as assessed by transesophageal echocardiography in patients undergoing valve repair for mitral regurgitation due to mitral valve prolapse

<p>Abstract</p> <p>Background</p> <p>Repair of anterior leaflet prolapse is technically more challenging and this might influence outcomes as compared to the repair of posterior leaflet prolapse in patients undergoing surgical correction of mitral regurgitation. We investigated the association of anterior leaflet prolapse with minor residual mitral regurgitation (MR) in patients with mitral valve prolapse (MVP) who underwent valve repair.</p> <p>Methods</p> <p>Eligible for this study were consecutive patients with severe MR due to MVP, who underwent mitral valve repair with residual MR by postpump transesophageal echocardiography ≤2+ during a 20-month period at Pasquinucci Hospital, Massa. Patients undergoing other cardiovascular surgical interventions were excluded. Two groups were defined according to the involvement of mitral valve leaflets: group 1, consisting of patients with anterior leaflet prolapse (isolated or not); and group 2, consisting of patients with isolated posterior leaflet prolapse.</p> <p>Results</p> <p>A total of 70 patients (18 in group 1 and 52 in group 2) were analyzed. Patients in group 2 were younger than those in group 1, but the difference was not significant (P = 0.052). There were no significant differences between the 2 study groups with respect to other variables. The proportion of patients with residual MR 1+/2+ was higher in group 1 than in group 2 (61.1% vs. 32.7%, respectively; P = 0.034). In a logistic regression model, anterior leaflet prolapse was an independent predictor of residual MR 1+/2+ (odds ratio, 4.0; 95% confidence interval, 1.14 to 14.04; P = 0.03).</p> <p>Conclusion</p> <p>In our study population, patients with anterior leaflet prolapse had a higher proportion of residual MR 1+/2+ as compared to those with posterior leaflet prolapse after repair of mitral valve.</p

Helical Chirality: a Link between Local Interactions and Global Topology in DNA

DNA supercoiling plays a major role in many cellular functions. The global DNA conformation is however intimately linked to local DNA-DNA interactions influencing both the physical properties and the biological functions of the supercoiled molecule. Juxtaposition of DNA double helices in ubiquitous crossover arrangements participates in multiple functions such as recombination, gene regulation and DNA packaging. However, little is currently known about how the structure and stability of direct DNA-DNA interactions influence the topological state of DNA. Here, a crystallographic analysis shows that due to the intrinsic helical chirality of DNA, crossovers of opposite handedness exhibit markedly different geometries. While right-handed crossovers are self-fitted by sequence-specific groove-backbone interaction and bridging Mg2+ sites, left-handed crossovers are juxtaposed by groove-groove interaction. Our previous calculations have shown that the different geometries result in differential stabilisation in solution, in the presence of divalent cations. The present study reveals that the various topological states of the cell are associated with different inter-segmental interactions. While the unstable left-handed crossovers are exclusively formed in negatively supercoiled DNA, stable right-handed crossovers constitute the local signature of an unusual topological state in the cell, such as the positively supercoiled or relaxed DNA. These findings not only provide a simple mechanism for locally sensing the DNA topology but also lead to the prediction that, due to their different tertiary intra-molecular interactions, supercoiled molecules of opposite signs must display markedly different physical properties. Sticky inter-segmental interactions in positively supercoiled or relaxed DNA are expected to greatly slow down the slithering dynamics of DNA. We therefore suggest that the intrinsic helical chirality of DNA may have oriented the early evolutionary choices for DNA topology

The prognosis of allocentric and egocentric neglect : evidence from clinical scans

We contrasted the neuroanatomical substrates of sub-acute and chronic visuospatial deficits associated with different aspects of unilateral neglect using computed tomography scans acquired as part of routine clinical diagnosis. Voxel-wise statistical analyses were conducted on a group of 160 stroke patients scanned at a sub-acute stage. Lesion-deficit relationships were assessed across the whole brain, separately for grey and white matter. We assessed lesions that were associated with behavioural performance (i) at a sub-acute stage (within 3 months of the stroke) and (ii) at a chronic stage (after 9 months post stroke). Allocentric and egocentric neglect symptoms at the sub-acute stage were associated with lesions to dissociated regions within the frontal lobe, amongst other regions. However the frontal lesions were not associated with neglect at the chronic stage. On the other hand, lesions in the angular gyrus were associated with persistent allocentric neglect. In contrast, lesions within the superior temporal gyrus extending into the supramarginal gyrus, as well as lesions within the basal ganglia and insula, were associated with persistent egocentric neglect. Damage within the temporo-parietal junction was associated with both types of neglect at the sub-acute stage and 9 months later. Furthermore, white matter disconnections resulting from damage along the superior longitudinal fasciculus were associated with both types of neglect and critically related to both sub-acute and chronic deficits. Finally, there was a significant difference in the lesion volume between patients who recovered from neglect and patients with chronic deficits. The findings presented provide evidence that (i) the lesion location and lesion size can be used to successfully predict the outcome of neglect based on clinical CT scans, (ii) lesion location alone can serve as a critical predictor for persistent neglect symptoms, (iii) wide spread lesions are associated with neglect symptoms at the sub-acute stage but only some of these are critical for predicting whether neglect will become a chronic disorder and (iv) the severity of behavioural symptoms can be a useful predictor of recovery in the absence of neuroimaging findings on clinical scans. We discuss the implications for understanding the symptoms of the neglect syndrome, the recovery of function and the use of clinical scans to predict outcome

Modelling the Proportion of Influenza Infections within Households during Pandemic and Non-Pandemic Years

Background: The key epidemiological difference between pandemic and seasonal influenza is that the population is largely susceptible during a pandemic, whereas, during non-pandemic seasons a level of immunity exists. The population-level efficacy of household-based mitigation strategies depends on the proportion of infections that occur within households. In general, mitigation measures such as isolation and quarantine are more effective at the population level if the proportion of household transmission is low. Methods/Results: We calculated the proportion of infections within households during pandemic years compared with non-pandemic years using a deterministic model of household transmission in which all combinations of household size and individual infection states were enumerated explicitly. We found that the proportion of infections that occur within households was only partially influenced by the hazard h of infection within household relative to the hazard of infection outside the household, especially for small basic reproductive numbers. During pandemics, the number of within-household infections was lower than one might expect for a given h because many of the susceptible individuals were infected from the community and the number of susceptible individuals within household was thus depleted rapidly. In addition, we found that for the value of h at which 30% of infections occur within households during non-pandemic years, a similar 31% of infections occur within households during pandemic years. Interpretation: We suggest that a trade off between the community force of infection and the number of susceptible individuals in a household explains an apparent invariance in the proportion of infections that occur in households in our model. During a pandemic, although there are more susceptible individuals in a household, the community force of infection is very high. However, during non-pandemic years, the force of infection is much lower but there are fewer susceptible individuals within the household. © 2011 Kwok et al.published_or_final_versio

Nucleolar Accumulation of RNA Binding Proteins Induced by ActinomycinD Is Functional in Trypanosoma cruzi and Leishmania mexicana but Not in T. brucei

We have recently shown in T. cruzi that a group of RNA Binding Proteins (RBPs), involved in mRNA metabolism, are accumulated into the nucleolus in response to Actinomycin D (ActD) treatment. In this work, we have extended our analysis to other members of the trypanosomatid lineage. In agreement with our previous study, the mechanism seems to be conserved in L. mexicana, since both endogenous RBPs and a transgenic RBP were relocalized to the nucleolus in parasites exposed to ActD. In contrast, in T. brucei, neither endogenous RBPs (TbRRM1 and TbPABP2) nor a transgenic RBP from T. cruzi were accumulated into the nucleolus under such treatment. Interestingly, when a transgenic TbRRM1was expressed in T. cruzi and the parasites exposed to ActD, TbRRM1 relocated to the nucleolus, suggesting that it contains the necessary sequence elements to be targeted to the nucleolus. Together, both experiments demonstrate that the mechanism behind nucleolar localization of RBPs, which is present in T. cruzi and L. mexicana, is not functional in T. brucei, suggesting that it has been lost or retained differentially during the evolution of the trypanosomatid lineage

Female gamers’ experience of online harassment and social support in online gaming: a qualitative study

Female gaming is a relatively under-researched area, and female gamers often report experiencing harassment whilst playing online. The present study explored female experiences of social support while playing online video games, because of the previous research suggesting that females often experience harassment and negative interactions during game play. Data were collected from an online discussion forum, and comprised posts drawn from 271 female gamers. Thematic analysis of the discussions suggested that a lack of social support and harassment frequently led to female gamers playing alone, playing anonymously, and moving groups regularly. The female gamers reported experiencing anxiety and loneliness due to this lack of social support, and for many, this was mirrored in their experiences of social support outside of gaming. The female gamers frequently accepted the incorporation into their gaming of specific coping strategies to mitigate online harassment, including actively hiding their identity and avoiding all forms of verbal communication with other players. These themes are discussed in relation to relevant research in the area, along with recommendations for future research and consideration of possible explanations for the themes observed

Voltage-Gated Ion Channel Dysfunction Precedes Cardiomyopathy Development in the Dystrophic Heart

Duchenne muscular dystrophy (DMD), caused by mutations in the dystrophin gene, is associated with severe cardiac complications including cardiomyopathy and cardiac arrhythmias. Recent research suggests that impaired voltage-gated ion channels in dystrophic cardiomyocytes accompany cardiac pathology. It is, however, unknown if the ion channel defects are primary effects of dystrophic gene mutations, or secondary effects of the developing cardiac pathology.To address this question, we first investigated sodium channel impairments in cardiomyocytes derived from dystrophic neonatal mice prior to cardiomyopahty development, by using the whole cell patch clamp technique. Besides the most common model for DMD, the dystrophin-deficient mdx mouse, we also used mice additionally carrying an utrophin mutation. In neonatal cardiomyocytes, dystrophin-deficiency generated a 25% reduction in sodium current density. In addition, extra utrophin-deficiency significantly altered sodium channel gating parameters. Moreover, also calcium channel inactivation was considerably reduced in dystrophic neonatal cardiomyocytes, suggesting that ion channel abnormalities are universal primary effects of dystrophic gene mutations. To assess developmental changes, we also studied sodium channel impairments in cardiomyocytes derived from dystrophic adult mice, and compared them with the respective abnormalities in dystrophic neonatal cells. Here, we found a much stronger sodium current reduction in adult cardiomyocytes. The described sodium channel impairments slowed the upstroke of the action potential in adult cardiomyocytes, and only in dystrophic adult mice, the QRS interval of the electrocardiogram was prolonged.Ion channel impairments precede pathology development in the dystrophic heart, and may thus be considered potential cardiomyopathy triggers

CpG site degeneration triggered by the loss of functional constraint created a highly polymorphic macaque drug-metabolizing gene, CYP1A2

<p>Abstract</p> <p>Background</p> <p>Elucidating the pattern of evolutionary changes in drug-metabolizing genes is an important subject not only for evolutionary but for biomedical research. We investigated the pattern of divergence and polymorphisms of macaque <it>CYP1A1 </it>and <it>CYP1A2 </it>genes, which are major drug-metabolizing genes in humans. In humans, <it>CYP1A2 </it>is specifically expressed in livers while <it>CYP1A1 </it>has a wider gene expression pattern in extrahepatic tissues. In contrast, macaque <it>CYP1A2 </it>is expressed at a much lower level than <it>CYP1A1 </it>in livers. Interestingly, a previous study has shown that <it>Macaca fascicularis CYP1A2 </it>harbored unusually high genetic diversity within species. Genomic regions showing high genetic diversity within species is occasionally interpreted as a result of balancing selection, where natural selection maintains highly diverged alleles with different functions. Nevertheless many other forces could create such signatures.</p> <p>Results</p> <p>We found that the <it>CYP1A1/2 </it>gene copy number and orientation has been highly conserved among mammalian genomes. The signature of gene conversion between <it>CYP1A1 </it>and <it>CYP1A2 </it>was detected, but the last gene conversion event in the simian primate lineage occurred before the <it>Catarrhini-Platyrrhini </it>divergence. The high genetic diversity of macaque <it>CYP1A2 </it>therefore cannot be explained by gene conversion between <it>CYP1A1 </it>and <it>CYP1A2</it>. By surveying <it>CYP1A2 </it>polymorphisms in total 91 <it>M. fascicularis </it>and <it>M. mulatta</it>, we found several null alleles segregating in these species, indicating functional constraint on <it>CYP1A2 </it>in macaques may have weakened after the divergence between humans and macaques. We propose that the high genetic diversity in macaque <it>CYP1A2 </it>is partly due to the degeneration of CpG sites, which had been maintained at a high level by purifying selection, and the rapid degeneration process was initiated by the loss of functional constraint on macaque <it>CYP1A2</it>.</p> <p>Conclusions</p> <p>Our findings show that the highly polymorphic <it>CYP1A2 </it>gene in macaques has not been created by balancing selection but by the burst of CpG site degeneration after loss of functional constraint. Because the functional importance of <it>CYP1A1/2 </it>genes is different between humans and macaques, we have to be cautious in extrapolating a drug-testing data using substrates metabolized by <it>CYP1A </it>genes from macaques to humans, despite of their somewhat overlapping substrate specificity.</p

Multigrid algorithms for hp-version interior penalty discontinuous Galerkin methods on polygonal and polyhedral meshes

In this paper we analyze the convergence properties of two-level and W-cycle multigrid solvers for the numerical solution of the linear system of equations arising from hp-version symmetric interior penalty discontinuous Galerkin discretizations of second-order elliptic partial differential equations on polygonal/polyhedral meshes. We prove that the two-level method converges uniformly with respect to the granularity of the grid and the polynomial approximation degree p, provided that the number of smoothing steps, which depends on p, is chosen sufficiently large. An analogous result is obtained for the W-cycle multigrid algorithm, which is proved to be uniformly convergent with respect to the mesh size, the polynomial approximation degree, and the number of levels, provided the latter remains bounded and the number of smoothing steps is chosen sufficiently large. Numerical experiments are presented which underpin the theoretical predictions; moreover, the proposed multilevel solvers are shown to be convergent in practice, even when some of the theoretical assumptions are not fully satisfied