Haplotypes of intron 4 of the estrogen receptor alpha gene and hip fractures: a replication study in Caucasians

<p>Abstract</p> <p>Background</p> <p>Despite their great impact, few genetic association studies have used hip fractures as an endpoint. However, the association of two polymorphisms on intron 4 of estrogen receptor alpha (<it>ESR1</it>) with hip fractures was recently reported in a Chinese population. The aim of this study was to investigate whether such association is also present in Caucasians.</p> <p>Methods</p> <p>We analyzed those two SNPs and another neighbour SNP located on the exon 4 of <it>ESR1 </it>in 787 patients with hip fractures and 953 controls from Spain.</p> <p>Results</p> <p>The allelic frequencies differed markedly from those reported in Asian populations. Nevertheless, haplotypes including the rs3020314 and rs1884051 loci in intron 4 showed a significant association with hip fractures (omnibus test p = 0.006 in the whole group and 0.00005 in women). In the sex-stratified analysis, the association was significant in females, but not in males. In women, the CA haplotype appeared to have a protective influence, being present in 6.5% of the controls, but only in 3% of patients with fractures (odds ratio 0.39; 95% confidence interval 0.26-0.59; estimated population preventive fraction 3.5%). The inclusion of the rs1801132 SNP of exon 4 further increased the statistical significance of the association (odds ratio 0.17; 95% CI 0.08-0.37; p = 0.00001). Each SNP appeared to contribute independently to the association. No genotype-related differences in gene expression were found in 42 femoral bone samples.</p> <p>Conclusions</p> <p>This study confirms the association of some polymorphisms in the region of exon 4/intron 4 of <it>ESR1 </it>and hip fractures in women. However, there are marked differences in allele frequencies between Asian and Caucasian populations.</p

The changing form of Antarctic biodiversity

Antarctic biodiversity is much more extensive, ecologically diverse and biogeographically structured than previously thought. Understanding of how this diversity is distributed in marine and terrestrial systems, the mechanisms underlying its spatial variation, and the significance of the microbiota is growing rapidly. Broadly recognizable drivers of diversity variation include energy availability and historical refugia. The impacts of local human activities and global environmental change nonetheless pose challenges to the current and future understanding of Antarctic biodiversity. Life in the Antarctic and the Southern Ocean is surprisingly rich, and as much at risk from environmental change as it is elsewher

Development of a Mesoamerican intra-genepool genetic map for quantitative trait loci detection in a drought tolerant × susceptible common bean (Phaseolus vulgaris L.) cross

Drought is a major constraint to common bean (Phaseolus vulgaris L.) production, especially in developing countries where irrigation for the crop is infrequent. The Mesoamerican genepool is the most widely grown subdivision of common beans that include small red, small cream and black seeded varieties. The objective of this study was to develop a reliable genetic map for a Mesoamerican × Mesoamerican drought tolerant × susceptible cross and to use this map to analyze the inheritance of yield traits under drought and fully irrigated conditions over 3 years of experiments. The source of drought tolerance used in the cross was the cream-seeded advanced line BAT477 crossed with the small red variety DOR364 and the population was made up of recombinant inbred lines in the F5 generation. Quantitative trait loci were detected by composite interval mapping for the traits of overall seed yield, yield per day, 100 seed weight, days to flowering and days to maturity for each field environment consisting of two treatments (irrigated and rainfed) and lattice design experiments with three repetitions for a total of six environments. The genetic map based on amplified fragment length polymorphism and random amplified polymorphic DNA markers was anchored with 60 simple sequence repeat (SSR) markers and had a total map length of 1,087.5 cM across 11 linkage groups covering the whole common bean genome with saturation of one marker every 5.9 cM. Gaps for the genetic map existed on linkage groups b03, b09 and b11 but overall there were only nine gaps larger than 15 cM. All traits were inherited quantitatively, with the greatest number for seed weight followed by yield per day, yield per se, days to flowering and days to maturity. The relevance of these results for breeding common beans is discussed in particular in the light of crop improvement for drought tolerance in the Mesoamerican genepool

A review of current Antarctic limno-terrestrial microfauna

First online: 20 July 2014Antarctic arthropods (mites and springtails) have been the subject of numerous studies. However, by far, the most diverse and numerically dominant fauna in Antarctica are the limno-terrestrial microfauna (tardigrades, rotifers and nematodes). Although they have been the focus of several studies, there remains uncertainty of the actual number of species in Antarctica. Inadequate sampling and conserved morphology are the main cause of misclassification of species and underestimation of this diversity. Most species’ distributional records are dominated by proximity to research stations or limited opportunistic collections, and therefore, an absence of records for a species may also be a consequence of the limitations of sampling. Limitations in fundamental knowledge of how many species are present and how widespread they are prevents any meaningful analyses that have been applied more generally to the arthropods within Antarctica, such as exploring ancient origins (at least pre-last glacial maximum) and tracking colonisation routes from glacial refugia. In this review, we list published species names and where possible the distribution of microfaunal (tardigrade, rotifer and nematode) species reported for Antarctica. Our current state of knowledge of Antarctic records (south of 60°S) includes 28 bdelloid rotifers, 66 monogonont rotifers, 59 tardigrades and 68 nematodes. In the light of the difficulties in working with microfauna across such geographical scales, we emphasise the need for molecular markers to help understand the ‘true levels’ of diversity and suggest future directions for Antarctic biodiversity assessment and species discovery.Alejandro Velasco-Castrillón, John A. E. Gibson, Mark I. Steven

Modificación en el patrón de uso de anfotericina B no convencional tras la puesta en marcha de una intervención formativa en el Hospital Clínico San Carlos de Madrid

Background: Amphotericin B is the treatment of choice for systemic fungal infections. Among the different AB formulations available, the lipid forms appear to have a better profile of reliability, however, their cost is noticeably higher. In 1999 (pre-initiative period) an evaluation of the quality of the prescription of these preparations was made in our hospital, which revealed that they were not being used to best advantage and were responsible for generating a significant unnecessary expenditure. As a result of this, an information initiative was implemented with respect to the prescribing physicians for the purpose of reducing the inappropriate use of AB. Method: The quality of 100 prescriptions was evaluated prospectively, according to the standards of use of Amphotericin B established in the hospital. Following each evaluation, a pharmacologist personally handed over to each prescribing physician a set of rules governing the use of the Amphotericin B, discussing the indication and recommending the best alternative in each case. In order to measure the impact of this initiative, the appropriateness of the prescriptions during this period was compared with the pre-initiative period. Results: The percentage of inappropriate prescriptions dropped from 58% to 21% following the implementation of the initiative. Likewise, a 33-million-peseta reduction in the total expenditure was achieved in 15 months as well as a savings of 24 million in inappropriate prescriptions. Conclusions: The information initiative improved the quality of the prescribing of preparations of Amphotericin B associated with lipids and considerably reduced the unnecessary expense associated with Amphotericin B misuse in our hospital.Fundamento: La anfotericina B es el tratamiento de elección para las infecciones fúngicas sistémicas. Dentro de ellas, las formas lipídicas parecen tener un mejor perfil de seguridad, sin embargo el coste es llamativamente superior. En 1999 (periodo pre-intervención) se realizó en nuestro hospital una evaluación de la calidad de la prescripción de estos preparados que demostró que su uso no era óptimo y ocasionó un gasto innecesario importante. Como consecuencia de ello se puso en marcha una intervención formativa sobre los prescriptores con el objetivo de reducir el uso inapropiado de AB. Método: Se evaluó prospectivamente la calidad de 100 prescripciones, según las normas de uso de Anfotericina B vigentes en el hospital. Tras cada evaluación un farmacólogo entregó personalmente a cada prescriptor unas normas de uso del antibiótico, discutiendo la indicación y recomendando la mejor alternativa en cada caso. Para medir el impacto de esta intervención se comparó la adecuación de las prescripciones en este periodo frente al periodo pre-intervención. Resultados: El porcentaje de prescripciones inadecuadas se redujo del 58 % al 21 % tras la puesta en marcha de la intervención. Así mismo, se produjo una reducción en el gasto total de 33 millones de pesetas en 15 meses y un ahorro de 24 millones en prescripciones inadecuadas. Conclusiones: La intervención formativa mejoró la calidad de la prescripción de preparados de AB asociada a lípidos y redujo considerablemente el gasto innecesario de AB en nuestro hospital

Surprisingly high levels of biodiversity and endemism amongst Antarctic rotifers uncovered with mitochondrial DNA

<div><p>Antarctica is one of the harshest environments on the planet because of its extreme climatic conditions, with prolonged winters, freezing temperatures and lack of liquid water. While almost the entire continent (99.7%) is covered year round by snow and ice, some mountain peaks and coastal areas are ice-free and sustain life. Invertebrates dominate in this environment, but despite their obvious abundance, little is known of one major player, the rotifers. In this study, we examine the distribution and diversity of rotifers from across continental Antarctica using mitochondrial <i>c</i> oxidase subunit I DNA sequences, and compare to sequences extracted from specimens collected in limited locations in the Antarctic Peninsula (AP) and in Tierra del Fuego (TF) in South America. We identified rotifers of the Class Bdelloidea to be the most frequently sampled micro-organisms in soil and limno-terrestrial environments. From the Antarctic samples, 514 sequences were generated and 37 distinct lineages were identified (40 putative species based on the PTP model) within <i>Philodina</i>, <i>Adineta</i> and unidentified bdelloids (all currently considered endemic to Antarctica). Overall, we observed widespread ranges for some rotifers in continental Antarctica, many of them exceeding 2000 km. Only one bdelloid lineage (<i>Adineta</i> cf. <i>gracilis</i>) from continental Antarctica was also present in maritime Antarctica. No close similarities were found with worldwide locations, or amongst AP and TF. Our broad coverage across Antarctica shows unique lineages that may represent potential species surpassing what is presently known from morphology, even when conservative approaches are applied for species delimitation.</p></div

Association between bat vitamin D receptor 30 haplotypes and vitamin D levels at baseline and a lower response after increased vitamin D supplementation and exposure to sunlight

[Objective]: The aim of this study was to evaluate the relationship between vitamin D levels at baseline and after 12 weeks of supplementation/exposure to sunlight and VDR genotypes (BsmI, TaqI and ApaI) and haplotypes in a homogeneous population of postmenopausal women.[Methods]: We made a prospective study in which 151 women were randomized to two groups: One with 1000 mg of calcium and 800 IU vitamin D supplementation (102 women) and a placebo group with neither calcium or vitamin D supplementation (49 women). The follow-up was from May to September 2012.Vitamin D was determined by chemiluminescent immunoassay. Genotypes were determined using the Sequenomi Plexplatform and haplotypes using PHASE software.[Results]: Baseline (25 ± 10 ng/mlvs.23 ± 9 ng/ml, p > 0.05) and 12-week (32 ± 8 ng/mlvs.29 ± 10 ng/ml, p > 0.05) vitamin D levels were similar between the two groups. The genetic study was made in the total population. There were no differences in baseline and final levels of vitamin D in terms of genotypes and haplotypes, except for the Bat haplotype, whose baseline values were lower (25OHD: 21 ± 10 ng/mlvs. 21 ± 10 ng/ml, p = 0.038). The rate of nonresponders in this group was 15 % (p = 0.001), compared with 9 %, 2 % and 3 % in the other groups.[Conclusions]: The Bat haplotype was associated with lower baseline levels of vitamin D and a worse response to supplementation and, therefore, may be a risk factor for vitamin D deficiency.Peer reviewe