Energy drink use, problem drinking and drinking motives in a diverse sample of Alaskan college students

Background. Recent research has identified the use of caffeinated energy drinks as a common, potentially risky behaviour among college students that is linked to alcohol misuse and consequences. Research also suggests that energy drink consumption is related to other risky behaviours such as tobacco use, marijuana use and risky sexual activity. Objective. This research sought to examine the associations between frequency of energy drink consumption and problematic alcohol use, alcohol-related consequences, symptoms of alcohol dependence and drinking motives in an ethnically diverse sample of college students in Alaska. We also sought to examine whether ethnic group moderated these associations in the present sample of White, Alaska Native/American Indian and other ethnic minority college students. Design. A paper-and-pencil self-report questionnaire was completed by a sample of 298 college students. Analysis of covariance (ANCOVA) was used to examine the effects of energy drink use, ethnic group and energy drink by ethnic group interactions on alcohol outcomes after controlling for variance attributed to gender, age and frequency of binge drinking. Results. Greater energy drink consumption was significantly associated with greater hazardous drinking, alcohol consequences, alcohol dependence symptoms, drinking for enhancement motives and drinking to cope. There were no main effects of ethnic group, and there were no significant energy drink by ethnic group interactions. Conclusion. These findings replicate those of other studies examining the associations between energy drink use and alcohol problems, but contrary to previous research we did not find ethnic minority status to be protective. It is possible that energy drink consumption may serve as a marker for other health risk behaviours among students of various ethnic groups

cAMP-Signalling Regulates Gametocyte-Infected Erythrocyte Deformability Required for Malaria Parasite Transmission.

Blocking Plasmodium falciparum transmission to mosquitoes has been designated a strategic objective in the global agenda of malaria elimination. Transmission is ensured by gametocyte-infected erythrocytes (GIE) that sequester in the bone marrow and at maturation are released into peripheral blood from where they are taken up during a mosquito blood meal. Release into the blood circulation is accompanied by an increase in GIE deformability that allows them to pass through the spleen. Here, we used a microsphere matrix to mimic splenic filtration and investigated the role of cAMP-signalling in regulating GIE deformability. We demonstrated that mature GIE deformability is dependent on reduced cAMP-signalling and on increased phosphodiesterase expression in stage V gametocytes, and that parasite cAMP-dependent kinase activity contributes to the stiffness of immature gametocytes. Importantly, pharmacological agents that raise cAMP levels in transmissible stage V gametocytes render them less deformable and hence less likely to circulate through the spleen. Therefore, phosphodiesterase inhibitors that raise cAMP levels in P. falciparum infected erythrocytes, such as sildenafil, represent new candidate drugs to block transmission of malaria parasites

Autoimmune and autoinflammatory mechanisms in uveitis

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders

AXIOM: advanced X-ray imaging of the magnetosphere

Planetary plasma and magnetic field environments can be studied in two complementary ways—by in situ measurements, or by remote sensing. While the former provide precise information about plasma behaviour, instabilities and dynamics on local scales, the latter offers the global view necessary to understand the overall interaction of the magnetospheric plasma with the solar wind. Some parts of the Earth’s magnetosphere have been remotely sensed, but the majority remains unexplored by this type of measurements. Here we propose a novel and more elegant approach employing remote X-ray imaging techniques, which are now possible thanks to the relatively recent discovery of solar wind charge exchange X-ray emissions in the vicinity of the Earth’s magnetosphere. In this article we describe how an appropriately designed and located X-ray telescope, supported by simultaneous in situ measurements of the solar wind, can be used to image the dayside magnetosphere, magnetosheath and bow shock, with a temporal and spatial resolution sufficient to address several key outstanding questions concerning how the solar wind interacts with the Earth’s magnetosphere on a global level. Global images of the dayside magnetospheric boundaries require vantage points well outside the magnetosphere. Our studies have led us to propose ‘AXIOM: Advanced X-ray Imaging of the Magnetosphere’, a concept mission using a Vega launcher with a LISA Pathfinder-type Propulsion Module to place the spacecraft in a Lissajous orbit around the Earth–Moon L1 point. The model payload consists of an X-ray Wide Field Imager, capable of both imaging and spectroscopy, and an in situ plasma and magnetic field measurement package. This package comprises a Proton-Alpha Sensor, designed to measure the bulk properties of the solar wind, an Ion Composition Analyser, to characterise the minor ion populations in the solar wind that cause charge exchange emission, and a Magnetometer, designed to measure the strength and direction of the solar wind magnetic field. We also show simulations that demonstrate how the proposed X-ray telescope design is capable of imaging the predicted emission from the dayside magnetosphere with the sensitivity and cadence required to achieve the science goals of the mission

Healthy Hearts – A community-based primary prevention programme to reduce coronary heart disease

Background The ten year probability of cardiovascular events can be calculated, but many people are unaware of their risk and unclear how to reduce it. The aim of this study was to assess whether a community based intervention, for men and women aged between 45 and 64 years without pre-existing coronary heart disease, would reduce their Framingham scores when reassessed one year later. Methods Individuals in the relevant age group from a defined geographical area were sent an invitation to attend for an assessment of their cardiovascular risk. Individuals with pre-existing cardiovascular disease or terminal illness were excluded. The invitation was in the form of a "Many Happy Returns" card with a number of self-screening questions including the question, "If you put the enclosed string around your waist, is it too short?" The card contained a red 80 cm piece of string in the case of women, or a green 90 cm piece of string in the case of men. At the assessment appointment, Framingham scores were calculated and a printout was given to each individual. Advice was provided for relevant risk factors identified using agreed guidelines. If appropriate, onward referral was also made to a GP, dietician, an exercise referral scheme, or to smoking cessation services, using a set of guidelines. Individuals were sent a second invitation one year later to return for re-assessment. Results and discussion 2031 individuals were asked to self-assess their eligibility to participate, 596 individuals attended for assessment and 313 of these attended for follow-up one year later. The mean reduction in the Framingham risk score, was significantly lower at one year (0.876, 95% CI 0.211 to 1.541, p = 0.01). The mean 10-year risk of CHD at baseline was 13.14% (SD 9.18) and had fallen at follow-up to 12.34% (SD 8.71), a mean reduction of 6.7% of the initial 10-year Framingham risk. If sustained, the estimated NNT to prevent each year of CHD would be 1141 (95% CI 4739 to 649) individual appointments. Conclusion This community intervention for primary prevention of CHD reduces Framingham risk scores at one year in those who engage with the programme

AXIOM: Advanced X-Ray Imaging Of the Magnetosheath

AXIOM (Advanced X-ray Imaging Of the Magnetosphere) is a concept mission which aims to explain how the Earth's magnetosphere responds to the changing impact of the solar wind using a unique method never attempted before; performing wide-field soft X-ray imaging and spectroscopy of the magnetosheath. magnetopause and bow shock at high spatial and temporal resolution. Global imaging of these regions is possible because of the solar wind charge exchange (SWCX) process which produces elevated soft X-ray emission from the interaction of high charge-state solar wind ions with primarily neutral hydrogen in the Earth's exosphere and near-interplanetary space

FAK acts as a suppressor of RTK-MAP kinase signalling in Drosophila melanogaster epithelia and human cancer cells

Receptor Tyrosine Kinases (RTKs) and Focal Adhesion Kinase (FAK) regulate multiple signalling pathways, including mitogen-activated protein (MAP) kinase pathway. FAK interacts with several RTKs but little is known about how FAK regulates their downstream signalling. Here we investigated how FAK regulates signalling resulting from the overexpression of the RTKs RET and EGFR. FAK suppressed RTKs signalling in Drosophila melanogaster epithelia by impairing MAPK pathway. This regulation was also observed in MDA-MB-231 human breast cancer cells, suggesting it is a conserved phenomenon in humans. Mechanistically, FAK reduced receptor recycling into the plasma membrane, which resulted in lower MAPK activation. Conversely, increasing the membrane pool of the receptor increased MAPK pathway signalling. FAK is widely considered as a therapeutic target in cancer biology; however, it also has tumour suppressor properties in some contexts. Therefore, the FAK-mediated negative regulation of RTK/MAPK signalling described here may have potential implications in the designing of therapy strategies for RTK-driven tumours

Sex and Death: The Effects of Innate Immune Factors on the Sexual Reproduction of Malaria Parasites

Malaria parasites must undergo a round of sexual reproduction in the blood meal of a mosquito vector to be transmitted between hosts. Developing a transmission-blocking intervention to prevent parasites from mating is a major goal of biomedicine, but its effectiveness could be compromised if parasites can compensate by simply adjusting their sex allocation strategies. Recently, the application of evolutionary theory for sex allocation has been supported by experiments demonstrating that malaria parasites adjust their sex ratios in response to infection genetic diversity, precisely as predicted. Theory also predicts that parasites should adjust sex allocation in response to host immunity. Whilst data are supportive, the assumptions underlying this prediction – that host immune responses have differential effects on the mating ability of males and females – have not yet been tested. Here, we combine experimental work with theoretical models in order to investigate whether the development and fertility of male and female parasites is affected by innate immune factors and develop new theory to predict how parasites' sex allocation strategies should evolve in response to the observed effects. Specifically, we demonstrate that reactive nitrogen species impair gametogenesis of males only, but reduce the fertility of both male and female gametes. In contrast, tumour necrosis factor-α does not influence gametogenesis in either sex but impairs zygote development. Therefore, our experiments demonstrate that immune factors have complex effects on each sex, ranging from reducing the ability of gametocytes to develop into gametes, to affecting the viability of offspring. We incorporate these results into theory to predict how the evolutionary trajectories of parasite sex ratio strategies are shaped by sex differences in gamete production, fertility and offspring development. We show that medical interventions targeting offspring development are more likely to be ‘evolution-proof’ than interventions directed at killing males or females. Given the drive to develop medical interventions that interfere with parasite mating, our data and theoretical models have important implications

A new approach to in silico SNP detection and some new SNPs in the Bacillus anthracis genome

<p>Abstract</p> <p>Background</p> <p><it>Bacillus anthracis </it>is one of the most monomorphic pathogens known. Identification of polymorphisms in its genome is essential for taxonomic classification, for determination of recent evolutionary changes, and for evaluation of pathogenic potency.</p> <p>Findings</p> <p>In this work three strains of the <it>Bacillus anthracis </it>genome are compared and previously unpublished single nucleotide polymorphisms (SNPs) are revealed. Moreover, it is shown that, despite the highly monomorphic nature of <it>Bacillus anthracis</it>, the SNPs are (1) abundant in the genome and (2) distributed relatively uniformly across the sequence.</p> <p>Conclusions</p> <p>The findings support the proposition that SNPs, together with indels and variable number tandem repeats (VNTRs), can be used effectively not only for the differentiation of perfect strain data, but also for the comparison of moderately incomplete, noisy and, in some cases, unknown <it>Bacillus anthracis </it>strains. In the case when the data is of still lower quality, a new DNA sequence fingerprinting approach based on recently introduced markers, based on combinatorial-analytic concepts and called cyclic difference sets, can be used.</p