Simvastatin improves the sexual health-related quality of life in men aged 40 years and over with erectile dysfunction : Additional data from the Erectile Dysfunction and Statin trial

© 2014 Trivedi et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Background: Erectile dysfunction is prevalent in men over 40 years, affecting their quality of life and that of their partners. The aims of this study were:a)To evaluate the internal reliability of the male erectile dysfunction specific quality of life (MED-QoL) scale and explore its factor structure.b)To evaluate the effect of simvastatin on subscales of the MED-QoL in men over forty years with erectile dysfunction. Methods: This is a double blind randomised controlled trial of 40 mg simvastatin or placebo given once daily for six months to men over forty years with untreated erectile dysfunction, who were not at high cardiovascular risk and were not on anti-hypertensive or lipid-lowering medication. 173 eligible men were recruited from 10 general practices in East of England. Data were collected at two points over 30 weeks. We report on the factor structure of MED-QoL, the internal reliability of the scale and the derived subscales, and the effect of simvastatin on MED-QoL subscales. Results: An initial analysis of the MED-QoL items suggested that a number of items should be removed (MED-QoL-R). Exploratory factor analysis identified three subscales within the MED-QoL-R which accounted for 96% of the variance, related to feelings of Control, initiating Intimacy, and Emotional response to erectile dysfunction. The alpha value for the revised scale (MED-Qol-R) was >0.95 and exceeded .82 for each subscale. Regression analysis showed that patients in the placebo group experienced a significantly reduced feeling of Control over erectile dysfunction than those in the statin group. Those in the placebo group had significantly lower Emotional response than those in the statin group at the close of trial, but there was no significant treatment effect on Intimacy. Conclusions: Our revised MED-QoL-R identified three subscales. Secondary analysis showed a significant improvement in sexual health related quality of life, specifically in relation to perception of control and emotional health in men with untreated erectile dysfunction given 40 mg simvastatin for six months. Trial registration: Current Controlled Trials ISRCTN66772971.Peer reviewe

The importance of engaging in physical activity in older adulthood for transitions between cognitive status categories and death: A coordinated analysis of 14 longitudinal studies

Background: Given increasing incidence of cognitive impairment and dementia, further understanding of modifiable factors contributing to increased healthspan is crucial. Extensive literature provides evidence that physical activity (PA) delays the onset of cognitive impairment; however, it is unclear whether engaging in PA in older adulthood is sufficient to influence progression through cognitive status categories. Method: Applying a coordinated analysis approach, this project independently analyzed 14 longitudinal studies (NTotal = 52 039; mean baseline age across studies = 69.9-81.73) from North America and Europe using multistate survival models to estimate the impact of engaging in PA on cognitive status transitions (nonimpaired, mildly impaired, severely impaired) and death. Multinomial regression models were fit to estimate life expectancy (LE) based on American PA recommendations. Meta-analyses provided the pooled effect sizes for the role of PA on each transition and estimated LEs. Results: Controlling for baseline age, sex, education, and chronic conditions, analyses revealed that more PA is significantly associated with decreased risk of transitioning from nonimpaired to mildly impaired cognitive functioning and death, as well as substantially longer LE. Results also provided evidence for a protective effect of PA after onset of cognitive impairment (eg, decreased risk of transitioning from mild-to-severe cognitive impairment; increased likelihood of transitioning backward from severe-to-mild cognitive impairment), though between-study heterogeneity suggests a less robust association. Conclusions: These results yield evidence for the importance of engaging in PA in older adulthood for cognitive health, and a rationale for motivating older adults to engage consistently in PA

Evaluation of coronary blood flow velocity during cardiac arrest with circulation maintained through mechanical chest compressions in a porcine model

<p>Abstract</p> <p>Background</p> <p>Mechanical chest compressions (CCs) have been shown capable of maintaining circulation in humans suffering cardiac arrest for extensive periods of time. Reports have documented a visually normalized coronary blood flow during angiography in such cases (TIMI III flow), but it has never been actually measured. Only indirect measurements of the coronary circulation during cardiac arrest with on-going mechanical CCs have been performed previously through measurement of the coronary perfusion pressure (CPP). In this study our aim was to correlate average peak coronary flow velocity (APV) to CPP during mechanical CCs.</p> <p>Methods</p> <p>In a closed chest porcine model, cardiac arrest was established through electrically induced ventricular fibrillation (VF) in eleven pigs. After one minute, mechanical chest compressions were initiated and then maintained for 10 minutes upon which the pigs were defibrillated. Measurements of coronary blood flow in the left anterior descending artery were made at baseline and during VF with a catheter based Doppler flow fire measuring APV. Furthermore measurements of central (thoracic) venous and arterial pressures were also made in order to calculate the theoretical CPP.</p> <p>Results</p> <p>Average peak coronary flow velocity was significantly higher compared to baseline during mechanical chests compressions and this was observed during the entire period of mechanical chest compressions (12 - 39% above baseline). The APV slowly declined during the 10 min period of mechanical chest compressions, but was still higher than baseline at the end of mechanical chest compressions. CPP was simultaneously maintained at > 20 mmHg during the 10 minute episode of cardiac arrest.</p> <p>Conclusion</p> <p>Our study showed good correlation between CPP and APV which was highly significant, during cardiac arrest with on-going mechanical CCs in a closed chest porcine model. In addition APV was even higher during mechanical CCs compared to baseline. Mechanical CCs can, at minimum, re-establish coronary blood flow in non-diseased coronary arteries during cardiac arrest.</p

Photo-antagonism of the GABAA receptor

Neurotransmitter receptor trafficking is fundamentally important for synaptic transmission and neural network activity. GABAA receptors and inhibitory synapses are vital components of brain function, yet much of our knowledge regarding receptor mobility and function at inhibitory synapses is derived indirectly from using recombinant receptors, antibody-tagged native receptors and pharmacological treatments. Here we describe the use of a set of research tools that can irreversibly bind to and affect the function of recombinant and neuronal GABAA receptors following ultraviolet photoactivation. These compounds are based on the competitive antagonist gabazine and incorporate a variety of photoactive groups. By using site-directed mutagenesis and ligand-docking studies, they reveal new areas of the GABA binding site at the interface between receptor β and α subunits. These compounds enable the selected inactivation of native GABAA receptor populations providing new insight into the function of inhibitory synapses and extrasynaptic receptors in controlling neuronal excitation

Strong Ultraviolet Pulse From a Newborn Type Ia Supernova

Type Ia supernovae are destructive explosions of carbon oxygen white dwarfs. Although they are used empirically to measure cosmological distances, the nature of their progenitors remains mysterious, One of the leading progenitor models, called the single degenerate channel, hypothesizes that a white dwarf accretes matter from a companion star and the resulting increase in its central pressure and temperature ignites thermonuclear explosion. Here we report observations of strong but declining ultraviolet emission from a Type Ia supernova within four days of its explosion. This emission is consistent with theoretical expectations of collision between material ejected by the supernova and a companion star, and therefore provides evidence that some Type Ia supernovae arise from the single degenerate channel.Comment: Accepted for publication on the 21 May 2015 issue of Natur

Extreme genetic fragility of the HIV-1 capsid

Genetic robustness, or fragility, is defined as the ability, or lack thereof, of a biological entity to maintain function in the face of mutations. Viruses that replicate via RNA intermediates exhibit high mutation rates, and robustness should be particularly advantageous to them. The capsid (CA) domain of the HIV-1 Gag protein is under strong pressure to conserve functional roles in viral assembly, maturation, uncoating, and nuclear import. However, CA is also under strong immunological pressure to diversify. Therefore, it would be particularly advantageous for CA to evolve genetic robustness. To measure the genetic robustness of HIV-1 CA, we generated a library of single amino acid substitution mutants, encompassing almost half the residues in CA. Strikingly, we found HIV-1 CA to be the most genetically fragile protein that has been analyzed using such an approach, with 70% of mutations yielding replication-defective viruses. Although CA participates in several steps in HIV-1 replication, analysis of conditionally (temperature sensitive) and constitutively non-viable mutants revealed that the biological basis for its genetic fragility was primarily the need to coordinate the accurate and efficient assembly of mature virions. All mutations that exist in naturally occurring HIV-1 subtype B populations at a frequency &gt;3%, and were also present in the mutant library, had fitness levels that were &gt;40% of WT. However, a substantial fraction of mutations with high fitness did not occur in natural populations, suggesting another form of selection pressure limiting variation in vivo. Additionally, known protective CTL epitopes occurred preferentially in domains of the HIV-1 CA that were even more genetically fragile than HIV-1 CA as a whole. The extreme genetic fragility of HIV-1 CA may be one reason why cell-mediated immune responses to Gag correlate with better prognosis in HIV-1 infection, and suggests that CA is a good target for therapy and vaccination strategies

A search for the decay modes B+/- to h+/- tau l

We present a search for the lepton flavor violating decay modes B+/- to h+/- tau l (h= K,pi; l= e,mu) using the BaBar data sample, which corresponds to 472 million BBbar pairs. The search uses events where one B meson is fully reconstructed in one of several hadronic final states. Using the momenta of the reconstructed B, h, and l candidates, we are able to fully determine the tau four-momentum. The resulting tau candidate mass is our main discriminant against combinatorial background. We see no evidence for B+/- to h+/- tau l decays and set a 90% confidence level upper limit on each branching fraction at the level of a few times 10^-5.Comment: 15 pages, 7 figures, submitted to Phys. Rev.