The living scar - cardiac fibroblasts and the injured heart

Cardiac scars, often dubbed ‘dead tissue’, are very much alive, with heterocellular activity contributing to the maintenance of structural and mechanical integrity following heart injury. To form a scar, non-myocytes such as fibroblasts are recruited from intra- and extra-cardiac sources. Fibroblasts perform important autocrine and paracrine signaling functions. They also establish mechanical and, as is increasingly evident, electrical junctions with other cells. While fibroblasts were previously thought to act simply as electrical insulators, they may be electrically connected among themselves and, under some circumstances, to other cells including cardiomyocytes. A better understanding of these biophysical interactions will help to target scar structure and function, and will facilitate the development of novel therapies aimed at modifying scar properties for patient benefit

Multiple Stellar Populations in the Globular Cluster omega Centauri as Tracers of a Merger Event

The discovery of the Sagittarius dwarf galaxy, which is being tidally disrupted by and merging with the Milky Way, supports the view that the halo of the Galaxy has been built up at least partially by the accretion of similar dwarf systems. The Sagittarius dwarf contains several distinct populations of stars, and includes M54 as its nucleus, which is the second most massive globular cluster associated with the Milky Way. The most massive globular cluster is omega Centauri, and here we report that omega Centauri also has several distinct stellar populations, as traced by red-giant-branch stars. The most metal-rich red-giant-branch stars are about 2 Gyr younger than the dominant metal-poor component, indicating that omega Centauri was enriched over this timescale. The presence of more than one epoch of star formation in a globular cluster is quite surprising, and suggests that omega Centauri was once part of a more massive system that merged with the Milky Way, as the Sagittarius dwarf galaxy is in the process of doing now. Mergers probably were much more frequent in the early history of the Galaxy and omega Centauri appears to be a relict of this era.Comment: 7 pages, 3 figures, Latex+nature.sty (included), To appear in November 4th issue of Natur

Satisfaction with democracy in Turkey: findings from a national survey

A variety of factors affect citizens' satisfaction with democracy. Based on Turkey's political and economic context, as well as the existing literature, this study investigates the effect of four factors on people's satisfaction with democracy in Turkey: citizens' conceptualizations of democracy, being a political winner, citizens' perceptions of electoral integrity, and ethnic identity. Regression analysis of a nationally representative survey reveals that political losers and those with negative perceptions of electoral integrity are less satisfied with democracy in Turkey, while people's conceptualizations of democracy and ethnic identity do not have an effect on satisfaction with democracy. We conclude that, in Turkey, political polarization and negative perceptions of electoral integrity trigger a decline in citizens' satisfaction with democracy, which requires the attention of policymakers

The many facets of the matricelluar protein periostin during cardiac development, remodeling, and pathophysiology

Periostin is a member of a growing family of matricellular proteins, defined by their ability to interact with components of the extracellular milieu, and with receptors at the cell surface. Through these interactions, periostin has been shown to play a crucial role as a profibrogenic molecule during tissue morphogenesis. Tissues destined to become fibrous structures are dependent on cooperative interactions between periostin and its binding partners, whereas in its absence, these structures either totally or partially fail to become mature fibrous entities. Within the heart, fibrogenic differentiation is required for normal tissue maturation, remodeling and function, as well as in response to a pathological myocardial insult. In this review, aspects related to the function of periostin during cardiac morphogenesis, remodeling and pathology are summarized

An administrative data merging solution for dealing with missing data in a clinical registry: adaptation from ICD-9 to ICD-10

<p>Abstract</p> <p>Background</p> <p>We have previously described a method for dealing with missing data in a prospective cardiac registry initiative. The method involves merging registry data to corresponding ICD-9-CM administrative data to fill in missing data 'holes'. Here, we describe the process of translating our data merging solution to ICD-10, and then validating its performance.</p> <p>Methods</p> <p>A multi-step translation process was undertaken to produce an ICD-10 algorithm, and merging was then implemented to produce complete datasets for 1995–2001 based on the ICD-9-CM coding algorithm, and for 2002–2005 based on the ICD-10 algorithm. We used cardiac registry data for patients undergoing cardiac catheterization in fiscal years 1995–2005. The corresponding administrative data records were coded in ICD-9-CM for 1995–2001 and in ICD-10 for 2002–2005. The resulting datasets were then evaluated for their ability to predict death at one year.</p> <p>Results</p> <p>The prevalence of the individual clinical risk factors increased gradually across years. There was, however, no evidence of either an abrupt drop or rise in prevalence of any of the risk factors. The performance of the new data merging model was comparable to that of our previously reported methodology: c-statistic = 0.788 (95% CI 0.775, 0.802) for the ICD-10 model versus c-statistic = 0.784 (95% CI 0.780, 0.790) for the ICD-9-CM model. The two models also exhibited similar goodness-of-fit.</p> <p>Conclusion</p> <p>The ICD-10 implementation of our data merging method performs as well as the previously-validated ICD-9-CM method. Such methodological research is an essential prerequisite for research with administrative data now that most health systems are transitioning to ICD-10.</p

Using small molecules to facilitate exchange of bicarbonate and chloride anions across liposomal membranes

Bicarbonate is involved in a wide range of biological processes, which include respiration, regulation of intracellular pH and fertilization. In this study we use a combination of NMR spectroscopy and ion-selective electrode techniques to show that the natural product prodigiosin, a tripyrrolic molecule produced by microorganisms such as Streptomyces and Serratia, facilitates chloride/bicarbonate exchange (antiport) across liposomal membranes. Higher concentrations of simple synthetic molecules based on a 4,6-dihydroxyisophthalamide core are also shown to facilitate this antiport process. Although it is well known that proteins regulate Cl-/HCO3- exchange in cells, these results suggest that small molecules may also be able to regulate the concentration of these anions in biological systems

Who should be prioritized for renal transplantation?: Analysis of key stakeholder preferences using discrete choice experiments

Background Policies for allocating deceased donor kidneys have recently shifted from allocation based on Human Leucocyte Antigen (HLA) tissue matching in the UK and USA. Newer allocation algorithms incorporate waiting time as a primary factor, and in the UK, young adults are also favoured. However, there is little contemporary UK research on the views of stakeholders in the transplant process to inform future allocation policy. This research project aimed to address this issue. Methods Discrete Choice Experiment (DCE) questionnaires were used to establish priorities for kidney transplantation among different stakeholder groups in the UK. Questionnaires were targeted at patients, carers, donors / relatives of deceased donors, and healthcare professionals. Attributes considered included: waiting time; donor-recipient HLA match; whether a recipient had dependents; diseases affecting life expectancy; and diseases affecting quality of life. Results Responses were obtained from 908 patients (including 98 ethnic minorities); 41 carers; 48 donors / relatives of deceased donors; and 113 healthcare professionals. The patient group demonstrated statistically different preferences for every attribute (i.e. significantly different from zero) so implying that changes in given attributes affected preferences, except when prioritizing those with no rather than moderate diseases affecting quality of life. The attributes valued highly related to waiting time, tissue match, prioritizing those with dependents, and prioritizing those with moderate rather than severe diseases affecting life expectancy. Some preferences differed between healthcare professionals and patients, and ethnic minority and non-ethnic minority patients. Only non-ethnic minority patients and healthcare professionals clearly prioritized those with better tissue matches. Conclusions Our econometric results are broadly supportive of the 2006 shift in UK transplant policy which emphasized prioritizing the young and long waiters. However, our findings suggest the need for a further review in the light of observed differences in preferences amongst ethnic minorities, and also because those with dependents may be a further priority.</p

Kinematics and Dynamics of the Galactic Stellar Halo

The structure, kinematics and dynamics of the Galactic stellar halo are reviewed including evidence of substructure in the spatial distribution and kinematics of halo stars. Implications for galaxy formation theory are subsequently discussed; in particular it is argued that the observed kinematics of stars in the outer Galactic halo can be used as an important constraint on viable galaxy formation scenarios