The effect of gender, age, and geographical location on the incidence and prevalence of renal replacement therapy in Wales

BACKGROUND: This study used a cross sectional survey to examine the effect of gender, age, and geographical location on the population prevalence of renal replacement therapy (RRT) provision in Wales. METHODS: Physicians in renal centres in Wales and in adjacent areas of England were asked to undertake a census of patients on renal replacement therapy on 30 June 2004 using an agreed protocol. Data were collated and analysed in anonymous form. RESULTS: 2434 patients were on RRT in Wales at the census date. Median age of patients on RRT was 56 years, peritoneal dialysis 58 years, haemodialysis 66 years and transplantation 50 years. The three treatment modalities had significantly different age-specific peak prevalence rates and distributions. RRT age-specific prevalence rates peaked at around 70 years (1790 pmp), transplantation at around 60 years (924 pmp), haemodialysis at around 80 years (1080 pmp) and peritoneal dialysis did not have a clear peak prevalence rate. Age-specific incidence of RRT peaked at a rate of 488 pmp at 79 years, as did incidence rates for haemodialysis, which peaked at the same age. Age had less effect on the initiation of peritoneal dialysis, which had a broad plateau between the early fifties and late seventies. Kidney transplantation rates were highest in the early fifties but were markedly absent in old age. CONCLUSION: Differences in the provision of RRT are evident, particularly in the very elderly, where the gender difference for haemodialysis is particularly marked. The study illustrates that grouping patients over 75 years into a single age-band may mask significant diversity within this age group. Significant numbers of very elderly patients who are currently not receiving RRT may wish to receive RRT as the elderly population increases, and as technology improves survival and quality of life on RRT. The study suggests that if technologies that are more effective were developed, and which had a lower impact on quality of life, there might be up to a 17% increase in demand for RRT in those aged over 75 years; around 90% of this increased demand would be for haemodialysis

Structure, mechanism, and inhibition of Hedgehog acyltransferase

The Sonic Hedgehog (SHH) morphogen pathway is fundamental for embryonic development and stem cell maintenance and is implicated in various cancers. A key step in signaling is transfer of a palmitate group to the SHH N terminus, catalyzed by the multi-pass transmembrane enzyme Hedgehog acyltransferase (HHAT). We present the high-resolution cryo-EM structure of HHAT bound to substrate analog palmityl-coenzyme A and a SHH-mimetic megabody, revealing a heme group bound to HHAT that is essential for HHAT function. A structure of HHAT bound to potent small-molecule inhibitor IMP-1575 revealed conformational changes in the active site that occlude substrate binding. Our multidisciplinary analysis provides a detailed view of the mechanism by which HHAT adapts the membrane environment to transfer an acyl chain across the endoplasmic reticulum membrane. This structure of a membrane-bound O-acyltransferase (MBOAT) superfamily member provides a blueprint for other protein-substrate MBOATs and a template for future drug discovery

Lipidomics: A Tool for Studies of Atherosclerosis

Lipids, abundant constituents of both the vascular plaque and lipoproteins, play a pivotal role in atherosclerosis. Mass spectrometry-based analysis of lipids, called lipidomics, presents a number of opportunities not only for understanding the cellular processes in health and disease but also in enabling personalized medicine. Lipidomics in its most advanced form is able to quantify hundreds of different molecular lipid species with various structural and functional roles. Unraveling this complexity will improve our understanding of diseases such as atherosclerosis at a level of detail not attainable with classical analytical methods. Improved patient selection, biomarkers for gauging treatment efficacy and safety, and translational models will be facilitated by the lipidomic deliverables. Importantly, lipid-based biomarkers and targets should lead the way as we progress toward more specialized therapeutics

Inclusion of diverse populations in genomic research and health services: Genomix workshop report

Clinical genetic services and genomic research are rapidly developing but, historically, those with the greatest need are the least to benefit from these advances. This encompasses low-income communities, including those from ethnic minority and indigenous backgrounds. The “Genomix” workshop at the European Society of Human Genetics (ESHG) 2016 conference offered the opportunity to consider possible solutions for these disparities from the experiences of researchers and genetic healthcare practitioners working with underserved communities in the USA, UK and Australia. Evident from the workshop and corresponding literature is that a multi-faceted approach to engaging communities is essential. This needs to be complemented by redesigning healthcare systems that improves access and raises awareness of the needs of these communities. At a more strategic level, institutions involved in funding research, commissioning and redesigning genetic health services also need to be adequately represented by underserved populations with intrinsic mechanisms to disseminate good practice and monitor participation. Further, as genomic medicine is mainstreamed, educational programmes developed for clinicians should incorporate approaches to alleviate disparities in accessing genetic services and improving study participation

Mother Knows Best: Dominant Females Determine Offspring Dispersal in Red Foxes (Vulpes vulpes)

Background: Relatedness between group members is central to understanding the causes of animal dispersal. In many group-living mammals this can be complicated as extra-pair copulations result in offspring having varying levels of relatedness to the dominant animals, leading to a potential conflict between male and female dominants over offspring dispersal strategies. To avoid resource competition and inbreeding, dominant males might be expected to evict unrelated males and related females, whereas the reverse strategy would be expected for dominant females. Methodology/Principal Findings: We used microsatellites and long-term data from an urban fox (Vulpes vulpes) population to compare dispersal strategies between offspring with intra- and extra-group fathers and mothers of differing social status in red foxes. Relatedness to the dominant male had no effect on dispersal in offspring of either sex, whereas there was a strong effect of relatedness to resident females on offspring dispersal independent of population density. Males with dominant mothers dispersed significantly more often than males with subordinate mothers, whereas dispersing females were significantly more likely to have subordinate mothers compared to philopatric females. Conclusions/Significance: This is the first study to demonstrate that relatedness to resident females is important in juvenile dispersal in group-living mammals. Male dispersal may be driven by inbreeding avoidance, whereas female dispersal appears to be influenced by the fitness advantages associated with residing with the same-sex dominant parent. Selection pressure for paternal influence on offspring dispersal is low due to the limited costs associated with retaining unrelated males and the need for alternative inbreeding avoidance mechanisms between the dominant male and his female offspring. These findings have important implications for the evolution of dispersal and group living in social mammals, and our understanding of a key biological process.peerReviewe

Supramolecular recognition of estrogens via molecularly imprinted polymers

The isolation and preconcentration of estrogens from new types of biological samples (acellular and protein-free simulated body fluid) by molecularly imprinted solid-phase extraction has been described. In this technique, supramolecular receptors, namely molecularly imprinted polymers (MIPs) are used as a sorbent material. The recognition sites of MIPs were prepared by non-covalent multiple interactions and formed with the target 17β-estradiol as a template molecule. High-performance liquid chromatography with spectroscopic UV, selective, and a sensitive electrochemical CoulArray detector was used for the determination of 17β-estradiol, estrone, and estriol in simulated body fluid which mimicked human plasma

Prevalence Distribution and Risk Factors for Schistosoma hematobium Infection among School Children in Blantyre, Malawi

Schistosoma hematobium infection is a parasitic infection endemic in Malawi. Schistosomiasis usually shows a focal distribution of infection and it is important to identify communities at high risk of infection and assess effectiveness of control programs. We conducted a survey in one district in Malawi to determine prevalence and factors associated with S. hematobium infection among primary school pupils. Using a questionnaire, information on history of passing bloody urine and known risk factors associated with infection was collected. Urine samples were collected and examined for S. hematobium eggs. One thousand one hundred and fifty (1,150) pupils were interviewed, and out of 1,139 pupils who submitted urine samples, 10.4% were infected. Our data showed that male gender, child's knowledge of an existing open water source (includes river, dam, springs, lake, etc.) in the area, history of urinary schistosomiasis in the past month, distance of less than 1 km from school to nearest open water source and age 8–10 years compared to those 14 years and older were independently associated with infection. These findings suggest that children attending schools in close proximity to open water sources are at increased risk of infection

Diversity Arrays Technology (DArT) for Pan-Genomic Evolutionary Studies of Non-Model Organisms

Background: High-throughput tools for pan-genomic study, especially the DNA microarray platform, have sparked a remarkable increase in data production and enabled a shift in the scale at which biological investigation is possible. The use of microarrays to examine evolutionary relationships and processes, however, is predominantly restricted to model or near-model organisms. Methodology/Principal Findings: This study explores the utility of Diversity Arrays Technology (DArT) in evolutionary studies of non-model organisms. DArT is a hybridization-based genotyping method that uses microarray technology to identify and type DNA polymorphism. Theoretically applicable to any organism (even one for which no prior genetic data are available), DArT has not yet been explored in exclusively wild sample sets, nor extensively examined in a phylogenetic framework. DArT recovered 1349 markers of largely low copy-number loci in two lineages of seed-free land plants: the diploid fern Asplenium viride and the haploid moss Garovaglia elegans. Direct sequencing of 148 of these DArT markers identified 30 putative loci including four routinely sequenced for evolutionary studies in plants. Phylogenetic analyses of DArT genotypes reveal phylogeographic and substrate specificity patterns in A. viride, a lack of phylogeographic pattern in Australian G. elegans, and additive variation in hybrid or mixed samples. Conclusions/Significance: These results enable methodological recommendations including procedures for detecting and analysing DArT markers tailored specifically to evolutionary investigations and practical factors informing the decision to use DArT, and raise evolutionary hypotheses concerning substrate specificity and biogeographic patterns. Thus DArT is a demonstrably valuable addition to the set of existing molecular approaches used to infer biological phenomena such as adaptive radiations, population dynamics, hybridization, introgression, ecological differentiation and phylogeography