Cysteine (C)-X-C Receptor 4 Undergoes Transportin 1-Dependent Nuclear Localization and Remains Functional at the Nucleus of Metastatic Prostate Cancer Cells

published_or_final_versio

Populating the swampland: the case of U(1)^496 and E_8 x U(1)^248

For d=10 N=1 SUGRA coupled to d=10 N=1 SYM, anomaly cancellation places severe constraints on the allowed gauge groups. Besides the ones known to appear in string theory, only U(1)^496 and E_8 x U(1)^248 are allowed. There are no known theories of quantum gravity that reduce in some limit to these two last supergravity theories, and in this note I present some evidence that those quantum theories might not exist. The first observation is that, upon compactification, requring that the quantum theory possesses a moduli space with finite volume typically implies the existence of singularities where the 4d gauge group is enhanced, but for these two theories that gauge enhancement is problematic from the 10d point of view. I also point out that while these four supergravity theories present repulson-type singularities, the known mechanism that repairs those singularities for the first two - the non-Abelian enhancon - is not available for the last two theories. In short, these two supergravity theories might be too Abelian for their own good.Comment: 12 page

Dejian mind-body intervention improves the functioning of a patient with chronic epilepsy: a case report

Author name used in this publication: Mei-chun Cheung2009-2010 > Academic research: refereed > Publication in refereed journalpublished_fina

Catheter-based intervention for symptomatic patient with severe mitral regurgitation and very poor left ventricular systolic function - Safe but no room for complacency

Many patients with left ventricular systolic dysfunction have concomitant mitral regurgitation (MR). Their symptoms and prognosis worsen with increasing severity of MR. Percutaneous MitraClip((R)) can be used safely to reduce the severity of MR even in patients with advanced heart failure and is associated with improved symptoms, quality of life and exercise tolerance. However, a few patients with very poor left ventricular systolic function may experience significant haemodynamic disturbance in the peri-procedural period. We present three such patients, highlighting some of the potential problems encountered and discuss their possible pathophysiological mechanisms and safety measures.published_or_final_versio

Individual Predisposition, Household Clustering and Risk Factors for Human Infection with Ascaris lumbricoides: New Epidemiological Insights

Numerous analyses have found that people infected with roundworm (Ascaris lumbricoides) are predisposed to harbor either many or few worms. Members of the same household also tend to harbor similar numbers of worms. These phenomena are called individual predisposition and household clustering respectively. In this article, we use Bayesian methods to fit a statistical model to worm count data collected from a cohort of participants at baseline and after two rounds of re-infection following curative treatment. We show that individual predisposition is extremely weak once the clustering effect of the household has been accounted for. This suggests that predisposition is of limited importance to the epidemiology of roundworm infection. Further, we show that over half of the variability in average worm counts among households is explained by household risk factors. This implies that exposures to infectious roundworm eggs shared by household members are important determinants of household clustering. We argue that these results support the hypothesis proposed in the literature that the household is a key focus of roundworm transmission

Do Interventions Designed to Support Shared Decision-Making Reduce Health Inequalities? : A Systematic Review and Meta-Analysis

Copyright: © 2014 Durand 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.Background: Increasing patient engagement in healthcare has become a health policy priority. However, there has been concern that promoting supported shared decision-making could increase health inequalities. Objective: To evaluate the impact of SDM interventions on disadvantaged groups and health inequalities. Design: Systematic review and meta-analysis of randomised controlled trials and observational studies.Peer reviewe

Non-invasive detection of ischemic vascular damage in a pig model of liver donation after circulatory death

Background and Aims: Liver graft quality is evaluated by visual inspection prior to transplantation, a process highly dependent on the surgeon's experience. We present an objective, noninvasive, quantitative way of assessing liver quality in real time using Raman spectroscopy, a laser-based tool for analyzing biomolecular composition. Approach and Results: A porcine model of donation after circulatory death (DCD) with normothermic regional perfusion (NRP) allowed assessment of liver quality premortem, during warm ischemia (WI) and post-NRP. Ten percent of circulating blood volume was removed in half of experiments to simulate blood recovery for DCD heart removal. Left median lobe biopsies were obtained before circulatory arrest, after 45 minutes of WI, and after 2 hours of NRP and analyzed using spontaneous Raman spectroscopy, stimulated Raman spectroscopy (SRS), and staining. Measurements were also taken in situ from the porcine liver using a handheld Raman spectrometer at these time points from left median and right lateral lobes. Raman microspectroscopy detected congestion during WI by measurement of the intrinsic Raman signal of hemoglobin in red blood cells (RBCs), eliminating the need for exogenous labels. Critically, this microvascular damage was not observed during WI when 10% of circulating blood was removed before cardiac arrest. Two hours of NRP effectively cleared RBCs from congested livers. Intact RBCs were visualized rapidly at high resolution using SRS. Optical properties of ischemic livers were significantly different from preischemic and post-NRP livers as measured using a handheld Raman spectrometer. Conclusions: Raman spectroscopy is an effective tool for detecting microvascular damage which could assist the decision to use marginal livers for transplantation. Reducing the volume of circulating blood before circulatory arrest in DCD may help reduce microvascular damage

Disease progression in Plasmodium knowlesi malaria is linked to variation in invasion gene family members.

Emerging pathogens undermine initiatives to control the global health impact of infectious diseases. Zoonotic malaria is no exception. Plasmodium knowlesi, a malaria parasite of Southeast Asian macaques, has entered the human population. P. knowlesi, like Plasmodium falciparum, can reach high parasitaemia in human infections, and the World Health Organization guidelines for severe malaria list hyperparasitaemia among the measures of severe malaria in both infections. Not all patients with P. knowlesi infections develop hyperparasitaemia, and it is important to determine why. Between isolate variability in erythrocyte invasion, efficiency seems key. Here we investigate the idea that particular alleles of two P. knowlesi erythrocyte invasion genes, P. knowlesi normocyte binding protein Pknbpxa and Pknbpxb, influence parasitaemia and human disease progression. Pknbpxa and Pknbpxb reference DNA sequences were generated from five geographically and temporally distinct P. knowlesi patient isolates. Polymorphic regions of each gene (approximately 800 bp) were identified by haplotyping 147 patient isolates at each locus. Parasitaemia in the study cohort was associated with markers of disease severity including liver and renal dysfunction, haemoglobin, platelets and lactate, (r = ≥ 0.34, p =  <0.0001 for all). Seventy-five and 51 Pknbpxa and Pknbpxb haplotypes were resolved in 138 (94%) and 134 (92%) patient isolates respectively. The haplotypes formed twelve Pknbpxa and two Pknbpxb allelic groups. Patients infected with parasites with particular Pknbpxa and Pknbpxb alleles within the groups had significantly higher parasitaemia and other markers of disease severity. Our study strongly suggests that P. knowlesi invasion gene variants contribute to parasite virulence. We focused on two invasion genes, and we anticipate that additional virulent loci will be identified in pathogen genome-wide studies. The multiple sustained entries of this diverse pathogen into the human population must give cause for concern to malaria elimination strategists in the Southeast Asian region

Patterns of soil-transmitted helminth infection and impact of four-monthly albendazole treatments in preschool children from semi-urban communities in Nigeria: a double-blind placebo-controlled randomised trial

Background Children aged between one and five years are particularly vulnerable to disease caused by soil-transmitted helminths (STH). Periodic deworming has been shown to improve growth, micronutrient status (iron and vitamin A), and motor and language development in preschool children and justifies the inclusion of this age group in deworming programmes. Our objectives were to describe the prevalence and intensity of STH infection and to investigate the effectiveness of repeated four-monthly albendazole treatments on STH infection in children aged one to four years. Methods The study was carried out in four semi-urban villages situated near Ile-Ife, Osun State, Nigeria. The study was a double-blind placebo-controlled randomised trial. Children aged one to four years were randomly assigned to receive either albendazole or placebo every four months for 12 months with a follow-up at 14 months. Results The results presented here revealed that 50% of the preschool children in these semi-urban communities were infected by one or more helminths, the most prevalent STH being Ascaris lumbricoides (47.6%). Our study demonstrated that repeated four-monthly anthelminthic treatments with albendazole were successful in reducing prevalence and intensity of A. lumbricoides infections. At the end of the follow-up period, 12% and 43% of the children were infected with A. lumbricoides and mean epg was 117 (S.E. 50) and 1740 (S.E. 291) in the treatment and placebo groups respectively compared to 45% and 45% of the children being infected with Ascaris and mean epg being 1095 (S.E. 237) and 1126 (S.E. 182) in the treatment and placebo group respectively at baseline. Conclusion Results from this study show that the moderate prevalence and low intensity of STH infection in these preschool children necessitates systematic treatment of the children in child health programmes

ruvA Mutants that resolve Holliday junctions but do not reverse replication forks

RuvAB and RuvABC complexes catalyze branch migration and resolution of Holliday junctions (HJs) respectively. In addition to their action in the last steps of homologous recombination, they process HJs made by replication fork reversal, a reaction which occurs at inactivated replication forks by the annealing of blocked leading and lagging strand ends. RuvAB was recently proposed to bind replication forks and directly catalyze their conversion into HJs. We report here the isolation and characterization of two separation-of-function ruvA mutants that resolve HJs, based on their capacity to promote conjugational recombination and recombinational repair of UV and mitomycin C lesions, but have lost the capacity to reverse forks. In vivo and in vitro evidence indicate that the ruvA mutations affect DNA binding and the stimulation of RuvB helicase activity. This work shows that RuvA's actions at forks and at HJs can be genetically separated, and that RuvA mutants compromised for fork reversal remain fully capable of homologous recombination