Coronary heart disease in Indian Asians.

The Indian Asian population accounts for a fifth of all global deaths from coronary heart disease (CHD). CHD deaths on the Indian subcontinent have doubled since 1990, and are predicted to rise a further 50% by 2030. Reasons underlying the increased CHD mortality among Indian Asians remain unknown. Although conventional cardiovascular risk factors contribute to CHD in Indian Asians as in other populations, these do not account for their increased risk. Type-2 diabetes, insulin resistance and related metabolic disturbances are more prevalent amongst Indian Asians than Europeans, and have been proposed as major determinants of higher CHD risk among Indian Asians. However, this view is not supported by prospective data. Genome-wide association studies have not identified differences in allele frequencies or effect sizes in known loci to explain the increased CHD risk in Indian Asians. Limited knowledge of mechanisms underlying higher CHD risk amongst Indian Asians presents a major obstacle to reducing the burden of CHD in this population. Systems biology approaches such as genomics, epigenomics, metabolomics and transcriptomics, provide a non-biased approach for discovery of novel biomarkers and disease pathways underlying CHD. Incorporation of these omic approaches in prospective Indian Asian cohorts such as the London Life Sciences Population Study (LOLIPOP) provide an exciting opportunity for the identification of new risk factors underlying CHD in this high risk population

High-precision photometry of WASP-12 b transits

The transiting extrasolar planet WASP-12 b was found to be one of the most intensely irradiated exoplanets. It is unexpectedly bloated and is losing mass that may accrete into the host star. Our aim was to refine the parameters of this intriguing system and search for signs of transit timing variations. We gathered high-precision light curves for two transits of WASP-12 b. Assuming various limb-darkening laws, we generated best-fitting models and redetermined parameters of the system. Error estimates were derived by the prayer bead method and Monte Carlo simulations. System parameters obtained by us are found to agree with previous studies within one sigma. Use of the non-linear limb-darkening laws results in the best-fitting models. With two new mid-transit times, the ephemeris was refined to BJD(TDB)=(2454508.97682 +/- 0.00020) + (1.09142245 +/- 0.00000033) E. Interestingly, indications of transit timing variation are detected at the level of 3.4 sigma. This signal can be induced by an additional planet in the system. Simplified numerical simulations shows that a perturber could be a terrestrial-type planet if both planets are in a low-order orbital resonance. However, we emphasise that further observations are needed to confirm variation and to constrain properties of the perturber.Comment: 5 pages, 3 figures, accepted for publication in A&

Sorting live stem cells based on Sox2 mRNA expression.

PMCID: PMC3507951This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.While cell sorting usually relies on cell-surface protein markers, molecular beacons (MBs) offer the potential to sort cells based on the presence of any expressed mRNA and in principle could be extremely useful to sort rare cell populations from primary isolates. We show here how stem cells can be purified from mixed cell populations by sorting based on MBs. Specifically, we designed molecular beacons targeting Sox2, a well-known stem cell marker for murine embryonic (mES) and neural stem cells (NSC). One of our designed molecular beacons displayed an increase in fluorescence compared to a nonspecific molecular beacon both in vitro and in vivo when tested in mES and NSCs. We sorted Sox2-MB(+)SSEA1(+) cells from a mixed population of 4-day retinoic acid-treated mES cells and effectively isolated live undifferentiated stem cells. Additionally, Sox2-MB(+) cells isolated from primary mouse brains were sorted and generated neurospheres with higher efficiency than Sox2-MB(-) cells. These results demonstrate the utility of MBs for stem cell sorting in an mRNA-specific manner

Ventral and dorsal striatal dopamine efflux and behavior in rats with simple vs. co-morbid histories of cocaine sensitization and neonatal ventral hippocampal lesions

xposing animal models of mental illness to addictive drugs provides an approach to understanding the neural etiology of dual diagnosis disorders. Previous studies have shown that neonatal ventral hippocampal lesions (NVHL) in rats produce features of both schizophrenia and addiction vulnerability. Objective This study investigated ventral and dorsal striatal dopamine (DA) efflux in NVHL rats combined with behavioral sensitization to cocaine. Methods Adult NVHL vs. SHAM-operated rats underwent a 5-day injection series of cocaine (15 mg/kg/day) vs. saline. One week later, rats were cannulated in nucleus accumbens SHELL, CORE, or caudate–putamen. Another week later, in vivo microdialysis sampled DA during locomotor testing in which a single cocaine injection (15 mg/kg) was delivered. Results NVHLs and cocaine history significantly increased behavioral activation approximately 2-fold over SHAM-saline history rats. DA efflux curves corresponded time dependently with the cocaine injection and locomotor curves and varied significantly by striatal region: Baseline DA levels increased 5-fold while cocaine-stimulated DA efflux decreased by half across a ventral to dorsal striatal gradient. However, NVHLs, prior cocaine history, and individual differences in behavior were not underpinned by differential DA efflux overall or within any striatal region.Conclusion Differences in ventral/dorsal striatal DA efflux are not present in and are not required for producing differential levels of acute cocaine-induced behavioral activation in NVHLs with and without a behaviorally sensitizing cocaine history. These findings suggest other neurotransmitter systems, and alterations in striatal network function post-synaptic to DA transmission are more important to understanding the interactive effects of addictive drugs and mental illness

The South Asian genome

Genetics of disease Microarrays Variant genotypes Population genetics Sequence alignment AllelesThe genetic sequence variation of people from the Indian subcontinent who comprise one-quarter of the world's population, is not well described. We carried out whole genome sequencing of 168 South Asians, along with whole-exome sequencing of 147 South Asians to provide deeper characterisation of coding regions. We identify 12,962,155 autosomal sequence variants, including 2,946,861 new SNPs and 312,738 novel indels. This catalogue of SNPs and indels amongst South Asians provides the first comprehensive map of genetic variation in this major human population, and reveals evidence for selective pressures on genes involved in skin biology, metabolism, infection and immunity. Our results will accelerate the search for the genetic variants underlying susceptibility to disorders such as type-2 diabetes and cardiovascular disease which are highly prevalent amongst South Asians.Whole genome sequencing to discover genetic variants underlying type-2 diabetes, coronary heart disease and related phenotypes amongst Indian Asians. Imperial College Healthcare NHS Trust cBRC 2011-13 (JS Kooner [PI], JC Chambers)

Transit timing variation in exoplanet WASP-3b

Photometric follow-ups of transiting exoplanets may lead to discoveries of additional, less massive bodies in extrasolar systems. This is possible by detecting and then analysing variations in transit timing of transiting exoplanets. We present photometric observations gathered in 2009 and 2010 for exoplanet WASP-3b during the dedicated transit-timing-variation campaign. The observed transit timing cannot be explained by a constant period but by a periodic variation in the observations minus calculations diagram. Simplified models assuming the existence of a perturbing planet in the system and reproducing the observed variations of timing residuals were identified by three-body simulations. We found that the configuration with the hypothetical second planet of the mass of about 15 Earth masses, located close to the outer 2:1 mean motion resonance is the most likely scenario reproducing observed transit timing. We emphasize, however, that more observations are required to constrain better the parameters of the hypothetical second planet in WASP-3 system. For final interpretation not only transit timing but also photometric observations of the transit of the predicted second planet and the high precision radial-velocity data are needed.Comment: MNRAS accepte

Transit timing variation and activity in the WASP-10 planetary system

Transit timing analysis may be an effective method of discovering additional bodies in extrasolar systems which harbour transiting exoplanets. The deviations from the Keplerian motion, caused by mutual gravitational interactions between planets, are expected to generate transit timing variations of transiting exoplanets. In 2009 we collected 9 light curves of 8 transits of the exoplanet WASP-10b. Combining these data with published ones, we found that transit timing cannot be explained by a constant period but by a periodic variation. Simplified three-body models which reproduce the observed variations of timing residuals were identified by numerical simulations. We found that the configuration with an additional planet of mass of $\sim$0.1 $M_{\rm{J}}$ and orbital period of $\sim$5.23 d, located close to the outer 5:3 mean motion resonance, is the most likely scenario. If the second planet is a transiter, the estimated flux drop will be $\sim$0.3 per cent and can be observable with a ground-based telescope. Moreover, we present evidence that the spots on the stellar surface and rotation of the star affect the radial velocity curve giving rise to spurious eccentricity of the orbit of the first planet. We argue that the orbit of WASP-10b is essentially circular. Using the gyrochronology method, the host star was found to be $270 \pm 80$ Myr old. This young age can explain the large radius reported for WASP-10b.Comment: MNRAS accepte

The use of rapid review methods in health technology assessments: 3 case studies.

BACKGROUND: Rapid reviews are of increasing importance within health technology assessment due to time and resource constraints. There are many rapid review methods available although there is little guidance as to the most suitable methods. We present three case studies employing differing methods to suit the evidence base for each review and outline some issues to consider when selecting an appropriate method. METHODS: Three recently completed systematic review short reports produced for the UK National Institute for Health Research were examined. Different approaches to rapid review methods were used in the three reports which were undertaken to inform the commissioning of services within the NHS and to inform future trial design. We describe the methods used, the reasoning behind the choice of methods and explore the strengths and weaknesses of each method. RESULTS: Rapid review methods were chosen to meet the needs of the review and each review had distinctly different challenges such as heterogeneity in terms of populations, interventions, comparators and outcome measures (PICO) and/or large numbers of relevant trials. All reviews included at least 10 randomised controlled trials (RCTs), each with numerous included outcomes. For the first case study (sexual health interventions), very diverse studies in terms of PICO were included. P-values and summary information only were presented due to substantial heterogeneity between studies and outcomes measured. For the second case study (premature ejaculation treatments), there were over 100 RCTs but also several existing systematic reviews. Data for meta-analyses were extracted directly from existing systematic reviews with new RCT data added where available. For the final case study (cannabis cessation therapies), studies included a wide range of interventions and considerable variation in study populations and outcomes. A brief summary of the key findings for each study was presented and narrative synthesis used to summarise results for each pair of interventions compared. CONCLUSIONS: Rapid review methods need to be chosen to meet both the nature of the evidence base of a review and the challenges presented by the included studies. Appropriate methods should be chosen after an assessment of the evidence base

Knowledge and behaviour of nurse/midwives in the prevention of vertical transmission of HIV in Owerri, Imo State, Nigeria: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Mother-to-Child Transmission (MTCT) of HIV remains the main mode of acquisition of HIV in children. Transmission of HIV may occur during pregnancy, delivery or breastfeeding. Studies have shown that some specific interventions help to reduce the transmission of the virus to the baby. In order to target safe, rational and effective intervention to reduce MTCT of HIV, it is necessary to ensure that the nurse/midwife has knowledge of the strategies for the prevention of vertical transmission of HIV.</p> <p>Method</p> <p>The cross-sectional design was utilized to determine the knowledge and behaviour of nurse/midwives in the prevention of vertical transmission of HIV in Owerri, Imo State, Nigeria. The study sample consisted of 155 nurse/midwives drawn from three selected hospitals through stratified random sampling method. Official permission was obtained from the institutions and consent from participants. Data was collected through the use of a self administered questionnaire. Information sought included respondents' demographic characteristics, knowledge about and behaviour of prevention of vertical transmission as well as factors influencing behaviour.</p> <p>Results</p> <p>Findings revealed that nurse/midwives had moderate level of knowledge with mean score of 51.4%. The mean score on behaviour was 52.5%, major factors that influence behaviour in these settings were mainly fear of getting infected, irregular supply of resources like gloves, goggles, sharp boxes, and water supply was not regular also. Hypotheses tested revealed that there is a positive relationship between knowledge and behaviour (r = 0.583, p = 0.00). Knowledge level of nurse/midwives who had educational exposure was not different from those who did not (t = 1.439, p = 0.152). There was a significant difference in the knowledge of nurse/midwives who had experience in managing pregnant women living with HIV/AIDS and those who did not (t = 2.142, p = 0.03). Also, there was a significant relationship between behaviour and availability of resources (r = 0.318, p = 0.000).</p> <p>Conclusion</p> <p>The study revealed that the nurse/midwives though moderately knowledgeable still had gaps in certain areas. Their behaviours were fairly appropriate. There is need for improved knowledge through structured educational intervention. Resources needed for practice should always be made available and the environment should be much more conducive for practice.</p

Tuberculous dilated cardiomyopathy: an under-recognized entity?

BACKGROUND: Tuberculosis (TB) is a common public health problem in many parts of the world. TB is generally believed to spare these four organs-heart, skeletal muscle, thyroid and pancreas. We describe a rare case of myocardial TB diagnosed on a post-mortem cardiac biopsy. CASE PRESENTATION: Patient presented with history suggestive of congestive heart failure. We describe the clinical presentation, investigations and outcome of this case, and review the literature on the involvement of myocardium by TB. CONCLUSION: Involvement of myocardium by TB is rare. However it should be suspected as a cause of congestive heart failure in any patient with features suggestive of TB. Increasing recognition of the entity and the use of endomyocardial biopsy may help us detect more cases of this "curable" form of cardiomyopathy