Prehospital delay for acute coronary syndrome in China

Background: Despite the effectiveness of timely reperfusion therapy for acute coronary syndrome, prehospital delay remains a global concern. Objective: This article assesses the state-of-the-science regarding prehospital delay for acute coronary syndrome in China. Method: Electronic databases and hand searching were undertaken using key words such as prehospital delay, care-seeking delay, coronary heart disease, heart disease, acute coronary syndrome, unstable angina pain, acute myocardial infarction, cardiovascular disease, chest pain, and Chin (China/Chinese). The Chinese search was supervised by a Chinese health librarian. Results: Based on the search criteria, 28 studies were identified and reviewed using a standardized data extraction tool. Older age, attribution of symptoms to noncardiac causes, lack of health insurance coverage, poor access to transportation, and female sex were identified as contributing to prehospital delay. Conclusion: Health system reforms in China are necessary, particularly with regard to addressing the needs of older people, women, and other vulnerable populations in the context of the rising number of people with coronary heart disease. Developing targeted strategies, learned from both national and international experience, are required to develop targeted interventions. Copyright © 2010 Wolters Kluwer Health. Lippincott Williams & Wilkins

Statistical modelling of growth using a mixed model with orthogonal polynomials

In statistical modelling, the effects of single-nucleotide polymorphisms (SNPs) are often regarded as time-independent. However, for traits recorded repeatedly, it is very interesting to investigate the behaviour of gene effects over time. In the analysis, simulated data from the 13th QTL-MAS Workshop (Wageningen, The Netherlands, April 2009) was used and the major goal was the modelling of genetic effects as time-dependent. For this purpose, a mixed model which describes each effect using the third-order Legendre orthogonal polynomials, in order to account for the correlation between consecutive measurements, is fitted. In this model, SNPs are modelled as fixed, while the environment is modelled as random effects. The maximum likelihood estimates of model parameters are obtained by the expectation–maximisation (EM) algorithm and the significance of the additive SNP effects is based on the likelihood ratio test, with p-values corrected for multiple testing. For each significant SNP, the percentage of the total variance contributed by this SNP is calculated. Moreover, by using a model which simultaneously incorporates effects of all of the SNPs, the prediction of future yields is conducted. As a result, 179 from the total of 453 SNPs covering 16 out of 18 true quantitative trait loci (QTL) were selected. The correlation between predicted and true breeding values was 0.73 for the data set with all SNPs and 0.84 for the data set with selected SNPs. In conclusion, we showed that a longitudinal approach allows for estimating changes of the variance contributed by each SNP over time and demonstrated that, for prediction, the pre-selection of SNPs plays an important role

Activation of olfactory receptors on mouse pulmonary macrophages promotes monocyte chemotactic protein-1 production

Background: Emerging evidence suggests that non-olfactory tissues and cells can express olfactory receptors (ORs), however, the exact function of ectopic OR expression remains unknown. We have previously shown in mouse models that a unique cooperation between interferon-γ (IFN-γ) and lipopolysaccharide (LPS) drives the activation of pulmonary macrophages and leads to the induction of pathogenic responses in the respiratory tract. Further, through gene array studies, we have shown that activation of macrophages by these molecules results in the selective expression of a number of ORs. In this study, we validated the expression of these ORs in mouse airway and pulmonary macrophages in response to IFN-γ and LPS (γ/LPS) stimulation, and further explored the effect of odorant stimulation on macrophage function. Methodology/Principal Findings: OR expression in airway and pulmonary macrophages in response to IFN-γ, LPS or γ/LPS treatments was assessed by microarray and validated by q-PCR. OR expression (e.g. OR622) on macrophages was confirmed by visualization in immunofluoresence assays. Functional responses to odorants were assessed by quantifying inflammatory cytokine and chemokine expression using q-PCR and cell migration was assessed by a modified Boyden chamber migration assay. Our results demonstrate that eight ORs are expressed at basal levels in both airway and pulmonary macrophages, and that γ/LPS stimulation cooperatively increased this expression. Pulmonary macrophages exposed to the combined treatment of γ/LPS+octanal (an odorant) exhibited a 3-fold increase in MCP-1 protein production, compared to cells treated with γ/LPS alone. Supernatants from γ/LPS+octanal exposed macrophages also increased macrophage migration in vitro. Conclusions/Significance: Eight different ORs are expressed at basal levels in pulmonary macrophages and expression is upregulated by the synergistic action of γ/LPS. Octanal stimulation further increased MCP-1 production and the motility of macrophages. Our results suggest that ORs may mediate macrophage function by regulating MCP-1 production and cell migration. © 2013 Li et al

Collaborative Gaze Channelling for Improved Cooperation During Robotic Assisted Surgery

The use of multiple robots for performing complex tasks is becoming a common practice for many robot applications. When different operators are involved, effective cooperation with anticipated manoeuvres is important for seamless, synergistic control of all the end-effectors. In this paper, the concept of Collaborative Gaze Channelling (CGC) is presented for improved control of surgical robots for a shared task. Through eye tracking, the fixations of each operator are monitored and presented in a shared surgical workspace. CGC permits remote or physically separated collaborators to share their intention by visualising the eye gaze of their counterparts, and thus recovers, to a certain extent, the information of mutual intent that we rely upon in a vis-à-vis working setting. In this study, the efficiency of surgical manipulation with and without CGC for controlling a pair of bimanual surgical robots is evaluated by analysing the level of coordination of two independent operators. Fitts' law is used to compare the quality of movement with or without CGC. A total of 40 subjects have been recruited for this study and the results show that the proposed CGC framework exhibits significant improvement (p<0.05) on all the motion indices used for quality assessment. This study demonstrates that visual guidance is an implicit yet effective way of communication during collaborative tasks for robotic surgery. Detailed experimental validation results demonstrate the potential clinical value of the proposed CGC framework. © 2012 Biomedical Engineering Society.link_to_subscribed_fulltex

Relaxation effect of abacavir on rat basilar arteries

Background The use of abacavir has been linked with increased cardiovascular risk in patients with human immunodeficiency virus infection; however, the mechanism involved remains unclear. We hypothesize that abacavir may impair endothelial function. In addition, based on the structural similarity between abacavir and adenosine, we propose that abacavir may affect vascular contractility through endogenous adenosine release or adenosine receptors in blood vessels. Methods The relaxation effect of abacavir on rat basilar arteries was studied using the myograph technique. Cyclic GMP and AMP levels were measured by immunoassay. The effects of abacavir on nucleoside transporters were studied using radiolabeled nucleoside uptake experiments. Ecto-5′ nucleotidase activity was determined by measuring the generation of inorganic phosphate using adenosine monophosphate as the substrate. Results Abacavir induced the relaxation of rat basilar arteries in a concentration-dependent manner. This relaxation was abolished when endothelium was removed. In addition, the relaxation was diminished by the nitric oxide synthase inhibitor, L-NAME, the guanylyl cyclase inhibitor, ODQ, and the protein kinase G inhibitor, KT5820. Abacavir also increased the cGMP level in rat basilar arteries. Abacavir-induced relaxation was also abolished by adenosine A2 receptor blockers. However, abacavir had no effect on ecto-5’ nucleotidase and nucleoside transporters. Short-term and long-term treatment of abacavir did not affect acetylcholine-induced relaxation in rat basilar arteries. Conclusion Abacavir induces acute endothelium-dependent relaxation of rat basilar arteries, probably through the activation of adenosine A2 receptors in endothelial cells, which subsequently leads to the release of nitric oxide, resulting in activation of the cyclic guanosine monophosphate/protein kinase G-dependent pathway in vascular smooth muscle cells. It is speculated that abacavir-induced cardiovascular risk may not be related to endothelial dysfunction as abacavir does not impair relaxation of blood vessels. The most likely explanation of increased cardiovascular risk may be increased platelet aggregation as suggested by other studies

Effect of the myostatin locus on muscle mass and intramuscular fat content in a cross between mouse lines selected for hypermuscularity

Abstract Background This study is aimed at the analysis of genetic and physiological effects of myostatin on economically relevant meat quality traits in a genetic background of high muscularity. For this purpose, we generated G3 populations of reciprocal crosses between the two hypermuscular mouse lines BMMI866, which carries a myostatin mutation and is lean, and BMMI806, which has high intramuscular and body fat content. To assess the relationship between muscle mass, body composition and muscle quality traits, we also analysed intramuscular fat content (IMF), water holding capacity (WHC), and additional physiological parameters in M. quadriceps and M. longissimus in 308 G3-animals. Results We found that individuals with larger muscles have significantly lower total body fat (r = −0.28) and IMF (r = −0.64), and in females, a lower WHC (r = −0.35). In males, higher muscle mass was also significantly correlated with higher glycogen contents (r = 0.2) and lower carcass pH-values 24 hours after dissection (r = −0.19). Linkage analyses confirmed the influence of the myostatin mutation on higher lean mass (1.35 g), reduced body fat content (−1.15%), and lower IMF in M. longissimus (−0.13%) and M. quadriceps (−0.07%). No effect was found for WHC. A large proportion of variation of intramuscular fat content of the M. longissimus at the myostatin locus could be explained by sex (23%) and direction-of-cross effects (26%). The effects were higher in males (+0.41%). An additional locus with negative over-dominance effects on total fat mass (−0.55 g) was identified on chromosome 16 at 94 Mb (86–94 Mb) which concurs with fat related QTL in syntenic regions on SSC13 in pigs and BTA1 in cattle. Conclusion The data shows QTL effects on mouse muscle that are similar to those previously observed in livestock, supporting the mouse model. New information from the mouse model helps to describe variation in meat quantity and quality, and thus contribute to research in livestock

Using Extended Genealogy to Estimate Components of Heritability for 23 Quantitative and Dichotomous Traits

Important knowledge about the determinants of complex human phenotypes can be obtained from the estimation of heritability, the fraction of phenotypic variation in a population that is determined by genetic factors. Here, we make use of extensive phenotype data in Iceland, long-range phased genotypes, and a population-wide genealogical database to examine the heritability of 11 quantitative and 12 dichotomous phenotypes in a sample of 38,167 individuals. Most previous estimates of heritability are derived from family-based approaches such as twin studies, which may be biased upwards by epistatic interactions or shared environment. Our estimates of heritability, based on both closely and distantly related pairs of individuals, are significantly lower than those from previous studies. We examine phenotypic correlations across a range of relationships, from siblings to first cousins, and find that the excess phenotypic correlation in these related individuals is predominantly due to shared environment as opposed to dominance or epistasis. We also develop a new method to jointly estimate narrow-sense heritability and the heritability explained by genotyped SNPs. Unlike existing methods, this approach permits the use of information from both closely and distantly related pairs of individuals, thereby reducing the variance of estimates of heritability explained by genotyped SNPs while preventing upward bias. Our results show that common SNPs explain a larger proportion of the heritability than previously thought, with SNPs present on Illumina 300K genotyping arrays explaining more than half of the heritability for the 23 phenotypes examined in this study. Much of the remaining heritability is likely to be due to rare alleles that are not captured by standard genotyping arrays

Quantum control of hybrid nuclear-electronic qubits

Pulsed magnetic resonance is a wide-reaching technology allowing the quantum state of electronic and nuclear spins to be controlled on the timescale of nanoseconds and microseconds respectively. The time required to flip either dilute electronic or nuclear spins is orders of magnitude shorter than their decoherence times, leading to several schemes for quantum information processing with spin qubits. We investigate instead the novel regime where the eigenstates approximate 50:50 superpositions of the electronic and nuclear spin states forming "hybrid nuclear-electronic" qubits. Here we demonstrate quantum control of these states for the first time, using bismuth-doped silicon, in just 32 ns: this is orders of magnitude faster than previous experiments where pure nuclear states were used. The coherence times of our states are five orders of magnitude longer, reaching 4 ms, and are limited by the naturally-occurring 29Si nuclear spin impurities. There is quantitative agreement between our experiments and no-free-parameter analytical theory for the resonance positions, as well as their relative intensities and relative Rabi oscillation frequencies. In experiments where the slow manipulation of some of the qubits is the rate limiting step, quantum computations would benefit from faster operation in the hybrid regime.Comment: 20 pages, 8 figures, new data and simulation

Phosphorylation of the androgen receptor is associated with reduced survival in hormonerefractory prostate cancer patients

Cell line studies demonstrate that the PI3K/Akt pathway is upregulated in hormone-refractory prostate cancer (HRPC) and can result in phosphorylation of the androgen receptor (AR). The current study therefore aims to establish if this has relevance to the development of clinical HRPC. Immunohistochemistry was employed to investigate the expression and phosphorylation status of Akt and AR in matched hormone-sensitive and -refractory prostate cancer tumours from 68 patients. In the hormone-refractory tissue, only phosphorylated AR (pAR) was associated with shorter time to death from relapse (&lt;i&gt;P&lt;/i&gt;=0.003). However, when an increase in expression in the transition from hormone-sensitive to -refractory prostate cancer was investigated, an increase in expression of PI3K was associated with decreased time to biochemical relapse (&lt;i&gt;P&lt;/i&gt;=0.014), and an increase in expression of pAkt&lt;sup&gt;473&lt;/sup&gt; and pAR&lt;sup&gt;210&lt;/sup&gt; were associated with decreased disease-specific survival (&lt;i&gt;P&lt;/i&gt;=0.0019 and 0.0015, respectively). Protein expression of pAkt&lt;sup&gt;473&lt;/sup&gt; and pAR&lt;sup&gt;210&lt;/sup&gt; also strongly correlated (&lt;i&gt;P&lt;/i&gt;&#60;0.001, c.c.=0.711) in the hormone-refractory prostate tumours. These results provide evidence using clinical specimens, that upregulation of the PI3K/Akt pathway is associated with phosphorylation of the AR during development of HRPC, suggesting that this pathway could be a potential therapeutic target

Utilization of a deoxynucleoside diphosphate substrate by HIV reverse transcriptase

Background: Deoxynucleoside triphosphates (dNTPs) are the normal substrates for DNA sysnthesis is catalyzed by polymerases such as HIV-1 reverse transcriptase (RT). However, substantial amounts of deoxynucleoside diphosphates (dNDPs) are also present in the cell. Use of dNDPs in HIV-1 DNA sysnthesis could have significant implications for the efficacy of nucleoside RT inhibitors such as AZT which are first line therapeutics fro treatment of HIV infection. Our earlier work on HIV-1 reverse transcriptase (RT) suggested that the interaction between the γ phosphate of the incoming dNTP and RT residue K65 in the active site is not essential for dNTP insertion, implying that this polymerase may be able to insert dNPs in addition to dNTPs. Methodology/Principal Findings: We examined the ability of recombinant wild type (wt) and mutant RTs with substitutions at residue K65 to utilize a dNDP substrate in primer extension reactions. We found that wild type HIV-1 RT indeed catalyzes incorporation of dNDP substrates whereas RT with mutations of residue K645 were unable to catalyze this reaction. Wild type HIV-1 RT also catalyzed the reverse reaction, inorganic phosphate-dependent phosphorolysis. Nucleotide-mediated phosphorolytic removal of chain-terminating 3′-terminal nucleoside inhibitors such as AZT forms the basis of HIV-1 resistance to such drugs, and this removal is enhanced by thymidine analog mutations (TAMs). We found that both wt and TAM-containing RTs were able to catalyze Pi-mediated phosphorolysis of 3′-terminal AZT at physiological levels of Pi with an efficacy similar to that for ATP-dependent AZT-excision. Conclusion: We have identified two new catalytic function of HIV-1 RT, the use of dNDPs as substrates for DNA synthesis, and the use of Pi as substrate for phosphorolytic removal of primer 3′-terminal nucleotides. The ability to insert dNDPs has been documented for only one other DNA polymerase The RB69 DNA polymerase and the reverse reaction employing inorganic phosphate has not been documented for any DNA polymerase. Importantly, our results show that Pi-mediated phosphorolysis can contribute to AZT resistance and indicates that factors that influence HIV resistance to AZT are more complex than previously appreciated. © 2008 Garforth et al