Short term fat feeding rapidly increases plasma insulin but does not result in dyslipidaemia

Although the association between obesity and hypertension is well known, the underlying mechanism remains elusive. Previously, we have shown that 3 week fat feeding in rabbits produces greater visceral adiposity, hypertension, tachycardia and elevated renal sympathetic nerve activity compared to rabbits on a normal diet. Because hyperinsulinaemia, hyperleptinemia and dyslipidaemia are independent cardiovascular risk factors associated with hypertension we compared plasma insulin, leptin and lipid profiles in male New Zealand White rabbits fed a normal fat diet (NFD 4.3% fat, n = 11) or high fat diet (HFD 13.4% fat, n = 13) at days 1, 2, 3 and weeks 1, 2, 3 of the diet. Plasma concentrations of diacylglyceride (DG), triacylglyceride (TG), ceramide and cholesteryl esters (CE) were obtained after analysis by liquid chromatography mass spectrometry. Plasma insulin and glucose increased within the first 3 days of the diet in HFD rabbits (P <0.05) and remained elevated at week 1 (P <0.05). Blood pressure and heart rate followed a similar pattern. By contrast, in both groups, plasma leptin levels remained unchanged during the first few days (P >0.05), increasing by week 3 in fat fed animals alone (P <0.05). Concentrations of total DG, TG, CE and Ceramide at week 3 did not differ between groups (P >0.05). Our data show plasma insulin increases rapidly following consumption of a HFD and suggests that it may play a role in the rapid rise of blood pressure. Dyslipidaemia does not appear to contribute to the hypertension in this animal model

The Rx for Change database: a first-in-class tool for optimal prescribing and medicines use

<p>Abstract</p> <p>Background</p> <p>Globally, suboptimal prescribing practices and medication errors are common. Guidance to health professionals and consumers alone is not sufficient to optimise behaviours, therefore strategies to promote evidence-based decision making and practice, such as decision support tools or reminders, are important. The literature in this area is growing, but is of variable quality and dispersed across sources, which makes it difficult to identify, access, and assess. To overcome these problems, by synthesizing and evaluating the data from systematic reviews, we have developed <it>Rx for Change </it>to provide a comprehensive, online database of the evidence for strategies to improve drug prescribing and use.</p> <p>Methods</p> <p>We use reliable and valid methods to search and screen the literature, and to appraise and analyse the evidence from relevant systematic reviews. We then present the findings in an online format which allows users to easily access pertinent information related to prescribing and medicines use. The database is a result of the collaboration between the Canadian Agency for Drugs and Technologies in Health (CADTH) and two Cochrane review groups.</p> <p>Results</p> <p>To capture the body of evidence on interventions to improve prescribing and medicines use, we conduct comprehensive and regular searches in multiple databases, and hand-searches of relevant journals. We screen articles to identify relevant systematic reviews, and include them if they are of moderate or high methodological quality. Two researchers screen, assess quality, and extract data on demographic details, intervention characteristics, and outcome data. We report the results of our analysis of each systematic review using a standardised quantitative and qualitative format. <it>Rx for Change </it>currently contains over 200 summarised reviews, structured in a multi-level format. The reviews included in the database are diverse, covering various settings, conditions, or diseases and targeting a range of professional and consumer behaviors.</p> <p>Conclusions</p> <p><it>Rx for Change </it>is a novel database that synthesizes current research evidence about the effects of interventions to improve drug prescribing practices and medicines use.</p

Contribution of genetic effects to genetic variance components with epistasis and linkage disequilibrium

<p>Abstract</p> <p>Background</p> <p>Cockerham genetic models are commonly used in quantitative trait loci (QTL) analysis with a special feature of partitioning genotypic variances into various genetic variance components, while the F_∞genetic models are widely used in genetic association studies. Over years, there have been some confusion about the relationship between these two type of models. A link between the additive, dominance and epistatic effects in an F_∞model and the additive, dominance and epistatic variance components in a Cockerham model has not been well established, especially when there are multiple QTL in presence of epistasis and linkage disequilibrium (LD).</p> <p>Results</p> <p>In this paper, we further explore the differences and links between the F_∞and Cockerham models. First, we show that the Cockerham type models are allelic based models with a special modification to correct a confounding problem. Several important moment functions, which are useful for partition of variance components in Cockerham models, are also derived. Next, we discuss properties of the F_∞models in partition of genotypic variances. Its difference from that of the Cockerham models is addressed. Finally, for a two-locus biallelic QTL model with epistasis and LD between the loci, we present detailed formulas for calculation of the genetic variance components in terms of the additive, dominant and epistatic effects in an F_∞model. A new way of linking the Cockerham and F_∞model parameters through their coding variables of genotypes is also proposed, which is especially useful when reduced F_∞models are applied.</p> <p>Conclusion</p> <p>The Cockerham type models are allele-based models with a focus on partition of genotypic variances into various genetic variance components, which are contributed by allelic effects and their interactions. By contrast, the F_∞regression models are genotype-based models focusing on modeling and testing of within-locus genotypic effects and locus-by-locus genotypic interactions. When there is no need to distinguish the paternal and maternal allelic effects, these two types of models are transferable. Transformation between an F_∞model's parameters and its corresponding Cockerham model's parameters can be established through a relationship between their coding variables of genotypes. Genetic variance components in terms of the additive, dominance and epistatic genetic effects in an F_∞model can then be calculated by translating formulas derived for the Cockerham models.</p

An observational study of patient characteristics associated with the mode of admission to acute stroke services in North East, England

Objective Effective provision of urgent stroke care relies upon admission to hospital by emergency ambulance and may involve pre-hospital redirection. The proportion and characteristics of patients who do not arrive by emergency ambulance and their impact on service efficiency is unclear. To assist in the planning of regional stroke services we examined the volume, characteristics and prognosis of patients according to the mode of presentation to local services. Study design and setting A prospective regional database of consecutive acute stroke admissions was conducted in North East, England between 01/09/10-30/09/11. Case ascertainment and transport mode were checked against hospital coding and ambulance dispatch databases. Results Twelve acute stroke units contributed data for a mean of 10.7 months. 2792/3131 (89%) patients received a diagnosis of stroke within 24 hours of admission: 2002 arrivals by emergency ambulance; 538 by private transport or non-emergency ambulance; 252 unknown mode. Emergency ambulance patients were older (76 vs 69 years), more likely to be from institutional care (10% vs 1%) and experiencing total anterior circulation symptoms (27% vs 6%). Thrombolysis treatment was commoner following emergency admission (11% vs 4%). However patients attending without emergency ambulance had lower inpatient mortality (2% vs 18%), a lower rate of institutionalisation (1% vs 6%) and less need for daily carers (7% vs 16%). 149/155 (96%) of highly dependent patients were admitted by emergency ambulance, but none received thrombolysis. Conclusion Presentations of new stroke without emergency ambulance involvement were not unusual but were associated with a better outcome due to younger age, milder neurological impairment and lower levels of pre-stroke dependency. Most patients with a high level of pre-stroke dependency arrived by emergency ambulance but did not receive thrombolysis. It is important to be aware of easily identifiable demographic groups that differ in their potential to gain from different service configurations

Till death (or an intruder) do us part: intrasexual-competition in a monogamous Primate

Polygynous animals are often highly dimorphic, and show large sex-differences in the degree of intra-sexual competition and aggression, which is associated with biased operational sex ratios (OSR). For socially monogamous, sexually monomorphic species, this relationship is less clear. Among mammals, pair-living has sometimes been assumed to imply equal OSR and low frequency, low intensity intra-sexual competition; even when high rates of intra-sexual competition and selection, in both sexes, have been theoretically predicted and described for various taxa. Owl monkeys are one of a few socially monogamous primates. Using long-term demographic and morphological data from 18 groups, we show that male and female owl monkeys experience intense intra-sexual competition and aggression from solitary floaters. Pair-mates are regularly replaced by intruding floaters (27 female and 23 male replacements in 149 group-years), with negative effects on the reproductive success of both partners. Individuals with only one partner during their life produced 25% more offspring per decade of tenure than those with two or more partners. The termination of the pair-bond is initiated by the floater, and sometimes has fatal consequences for the expelled adult. The existence of floaters and the sporadic, but intense aggression between them and residents suggest that it can be misleading to assume an equal OSR in socially monogamous species based solely on group composition. Instead, we suggest that sexual selection models must assume not equal, but flexible, context-specific, OSR in monogamous species.Wenner-Gren Foundation, L.S.B. Leakey Foundation, the National Geographic Society, National Science Foundation (BCS- 0621020), the University of Pennsylvania Research Foundation and the Zoological Society of San Diego, German Science Foundation (HU 1746-2/1

Inferring introduction routes of invasive species using approximate Bayesian computation on microsatellite data

Determining the routes of introduction provides not only information about the history of an invasion process, but also information about the origin and construction of the genetic composition of the invading population. It remains difficult, however, to infer introduction routes from molecular data because of a lack of appropriate methods. We evaluate here the use of an approximate Bayesian computation (ABC) method for estimating the probabilities of introduction routes of invasive populations based on microsatellite data. We considered the crucial case of a single source population from which two invasive populations originated either serially from a single introduction event or from two independent introduction events. Using simulated datasets, we found that the method gave correct inferences and was robust to many erroneous beliefs. The method was also more efficient than traditional methods based on raw values of statistics such as assignment likelihood or pairwise F(ST). We illustrate some of the features of our ABC method, using real microsatellite datasets obtained for invasive populations of the western corn rootworm, Diabrotica virgifera virgifera. Most computations were performed with the DIYABC program (http://www1.montpellier.inra.fr/CBGP/diyabc/)

Validity of the Polar V800 heart rate monitor to measure RR intervals at rest

Purpose To assess the validity of RR intervals and short-term heart rate variability (HRV) data obtained from the Polar V800 heart rate monitor, in comparison to an electrocardiograph (ECG). Method Twenty participants completed an active orthostatic test using the V800 and ECG. An improved method for the identification and correction of RR intervals was employed prior to HRV analysis. Agreement of the data was assessed using intra-class correlation coefficients (ICC), Bland–Altman limits of agreement (LoA), and effect size (ES). Results A small number of errors were detected between ECG and Polar RR signal, with a combined error rate of 0.086 %. The RR intervals from ECG to V800 were significantly different, but with small ES for both supine corrected and standing corrected data (ES 0.999 for both supine and standing corrected intervals. When analysed with the same HRV software no significant differences were observed in any HRV parameters, for either supine or standing; the data displayed small bias and tight LoA, strong ICC (>0.99) and small ES (≤0.029). Conclusions The V800 improves over previous Polar models, with narrower LoA, stronger ICC and smaller ES for both the RR intervals and HRV parameters. The findings support the validity of the Polar V800 and its ability to produce RR interval recordings consistent with an ECG. In addition, HRV parameters derived from these recordings are also highly comparable

Generation and quality control of lipidomics data for the alzheimers disease neuroimaging initiative cohort.

Alzheimers disease (AD) is a major public health priority with a large socioeconomic burden and complex etiology. The Alzheimer Disease Metabolomics Consortium (ADMC) and the Alzheimer Disease Neuroimaging Initiative (ADNI) aim to gain new biological insights in the disease etiology. We report here an untargeted lipidomics of serum specimens of 806 subjects within the ADNI1 cohort (188 AD, 392 mild cognitive impairment and 226 cognitively normal subjects) along with 83 quality control samples. Lipids were detected and measured using an ultra-high-performance liquid chromatography quadruple/time-of-flight mass spectrometry (UHPLC-QTOF MS) instrument operated in both negative and positive electrospray ionization modes. The dataset includes a total 513 unique lipid species out of which 341 are known lipids. For over 95% of the detected lipids, a relative standard deviation of better than 20% was achieved in the quality control samples, indicating high technical reproducibility. Association modeling of this dataset and available clinical, metabolomics and drug-use data will provide novel insights into the AD etiology. These datasets are available at the ADNI repository at http://adni.loni.usc.edu/

Evidence for Pervasive Adaptive Protein Evolution in Wild Mice

The relative contributions of neutral and adaptive substitutions to molecular evolution has been one of the most controversial issues in evolutionary biology for more than 40 years. The analysis of within-species nucleotide polymorphism and between-species divergence data supports a widespread role for adaptive protein evolution in certain taxa. For example, estimates of the proportion of adaptive amino acid substitutions (alpha) are 50% or more in enteric bacteria and Drosophila. In contrast, recent estimates of alpha for hominids have been at most 13%. Here, we estimate alpha for protein sequences of murid rodents based on nucleotide polymorphism data from multiple genes in a population of the house mouse subspecies Mus musculus castaneus, which inhabits the ancestral range of the Mus species complex and nucleotide divergence between M. m. castaneus and M. famulus or the rat. We estimate that 57% of amino acid substitutions in murids have been driven by positive selection. Hominids, therefore, are exceptional in having low apparent levels of adaptive protein evolution. The high frequency of adaptive amino acid substitutions in wild mice is consistent with their large effective population size, leading to effective natural selection at the molecular level. Effective natural selection also manifests itself as a paucity of effectively neutral nonsynonymous mutations in M. m. castaneus compared to humans

Comparative population structure of <i>Plasmodium malariae</i> and <i>Plasmodium falciparum</i> under different transmission settings in Malawi

&lt;b&gt;Background:&lt;/b&gt; Described here is the first population genetic study of Plasmodium malariae, the causative agent of quartan malaria. Although not as deadly as Plasmodium falciparum, P. malariae is more common than previously thought, and is frequently in sympatry and co-infection with P. falciparum, making its study increasingly important. This study compares the population parameters of the two species in two districts of Malawi with different malaria transmission patterns - one seasonal, one perennial - to explore the effects of transmission on population structures. &lt;BR/&gt; &lt;b&gt;Methods:&lt;/b&gt; Six species-specific microsatellite markers were used to analyse 257 P. malariae samples and 257 P. falciparum samples matched for age, gender and village of residence. Allele sizes were scored to within 2 bp for each locus and haplotypes were constructed from dominant alleles in multiple infections. Analysis of multiplicity of infection (MOI), population differentiation, clustering of haplotypes and linkage disequilibrium was performed for both species. Regression analyses were used to determine association of MOI measurements with clinical malaria parameters. &lt;BR/&gt; &lt;b&gt;Results:&lt;/b&gt; Multiple-genotype infections within each species were common in both districts, accounting for 86.0% of P. falciparum and 73.2% of P. malariae infections and did not differ significantly with transmission setting. Mean MOI of P. falciparum was increased under perennial transmission compared with seasonal (3.14 vs 2.59, p = 0.008) and was greater in children compared with adults. In contrast, P. malariae mean MOI was similar between transmission settings (2.12 vs 2.11) and there was no difference between children and adults. Population differentiation showed no significant differences between villages or districts for either species. There was no evidence of geographical clustering of haplotypes. Linkage disequilibrium amongst loci was found only for P. falciparum samples from the seasonal transmission setting. &lt;BR/&gt; &lt;b&gt;Conclusions:&lt;/b&gt; The extent of similarity between P. falciparum and P. malariae population structure described by the high level of multiple infection, the lack of significant population differentiation or haplotype clustering and lack of linkage disequilibrium is surprising given the differences in the biological features of these species that suggest a reduced potential for out-crossing and transmission in P. malariae. The absence of a rise in P. malariae MOI with increased transmission or a reduction in MOI with age could be explained by differences in the duration of infection or degree of immunity compared to P. falciparum