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 inner centromere is a biomolecular condensate scaffolded by the chromosomal passenger complex.

The inner centromere is a region on every mitotic chromosome that enables specific biochemical reactions that underlie properties, such as the maintenance of cohesion, the regulation of kinetochores and the assembly of specialized chromatin, that can resist microtubule pulling forces. The chromosomal passenger complex (CPC) is abundantly localized to the inner centromeres and it is unclear whether it is involved in non-kinase activities that contribute to the generation of these unique chromatin properties. We find that the borealin subunit of the CPC drives phase separation of the CPC in vitro at concentrations that are below those found on the inner centromere. We also provide strong evidence that the CPC exists in a phase-separated state at the inner centromere. CPC phase separation is required for its inner-centromere localization and function during mitosis. We suggest that the CPC combines phase separation, kinase and histone code-reading activities to enable the formation of a chromatin body with unique biochemical activities at the inner centromere

Microbial regulation of the soil carbon cycle: evidence from gene-enzyme relationships.

A lack of empirical evidence for the microbial regulation of ecosystem processes, including carbon (C) degradation, hinders our ability to develop a framework to directly incorporate the genetic composition of microbial communities in the enzyme-driven Earth system models. Herein we evaluated the linkage between microbial functional genes and extracellular enzyme activity in soil samples collected across three geographical regions of Australia. We found a strong relationship between different functional genes and their corresponding enzyme activities. This relationship was maintained after considering microbial community structure, total C and soil pH using structural equation modelling. Results showed that the variations in the activity of enzymes involved in C degradation were predicted by the functional gene abundance of the soil microbial community (R2>0.90 in all cases). Our findings provide a strong framework for improved predictions on soil C dynamics that could be achieved by adopting a gene-centric approach incorporating the abundance of functional genes into process models

Src Dependent Pancreatic Acinar Injury Can Be Initiated Independent of an Increase in Cytosolic Calcium

Several deleterious intra-acinar phenomena are simultaneously triggered on initiating acute pancreatitis. These culminate in acinar injury or inflammatory mediator generation in vitro and parenchymal damage in vivo. Supraphysiologic caerulein is one such initiator which simultaneously activates numerous signaling pathways including non-receptor tyrosine kinases such as of the Src family. It also causes a sustained increase in cytosolic calcium- a player thought to be crucial in regulating deleterious phenomena. We have shown Src to be involved in caerulein induced actin remodeling, and caerulein induced changes in the Golgi and post-Golgi trafficking to be involved in trypsinogen activation, which initiates acinar cell injury. However, it remains unclear whether an increase in cytosolic calcium is necessary to initiate acinar injury or if injury can be initiated at basal cytosolic calcium levels by an alternate pathway. To study the interplay between tyrosine kinase signaling and calcium, we treated mouse pancreatic acinar cells with the tyrosine phosphatase inhibitor pervanadate. We studied the effect of the clinically used Src inhibitor Dasatinib (BMS-354825) on pervanadate or caerulein induced changes in Src activation, trypsinogen activation, cell injury, upstream cytosolic calcium, actin and Golgi morphology. Pervanadate, like supraphysiologic caerulein, induced Src activation, redistribution of the F-actin from its normal location in the sub-apical area to the basolateral areas, and caused antegrade fragmentation of the Golgi. These changes, like those induced by supraphysiologic caerulein, were associated with trypsinogen activation and acinar injury, all of which were prevented by Dasatinib. Interestingly, however, pervanadate did not cause an increase in cytosolic calcium, and the caerulein induced increase in cytosolic calcium was not affected by Dasatinib. These findings suggest that intra-acinar deleterious phenomena may be initiated independent of an increase in cytosolic calcium. Other players resulting in acinar injury along with the Src family of tyrosine kinases remain to be explored. © 2013 Mishra et al

Nutrient intakes related to osteoporotic fractures in men and women – The Brazilian Osteoporosis Study (BRAZOS)

<p>Abstract</p> <p>Background</p> <p>Adequate nutrition plays an important role in bone mass accrual and maintenance and has been demonstrated as a significant tool for the prevention of fractures in individuals with osteoporosis.</p> <p>Objective</p> <p>The aim of the present study was to evaluate bone health-related nutrients intake and its association with osteoporotic fractures in a representative sample of 2344 individuals aged 40 years or older in Brazil.</p> <p>Methods</p> <p>In a transversal population-based study, a total of 2420 individuals over 40 years old were evaluated from March to April 2006. Participants were men and women from all socio-economic classes and education levels living around the Brazilian territory Individuals responded a questionnaire including self reported fractures as well a 24-hour food recall. Nutrient intakes were evaluated by Nutrition Data System for Research software (NDSR, University of Minnesota, 2007). Low trauma fracture was defined as that resulting of a fall from standing height or less. Nutrient intakes adequacies were performed by using the DRI's proposed values. Statistical analysis comprises Oneway ANCOVA adjusted by age and use of nutritional supplements and multiple logistic regression. SAS software was used for statistical analysis.</p> <p>Results</p> <p>Fractures was reported by 13% of men and 15% of women. Women with fractures presented significantly higher calcium, phosphorus and magnesium intakes. However, in all regions and socio-economical levels mean intakes of bone related nutrients were below the recommended levels. It was demonstrated that for every 100 mg/phosphorus increase the risk of fractures by 9% (OR 1.09; IC95% 1.05–1.13, p < 0.001).</p> <p>Conclusion</p> <p>The results demonstrated inadequacies in bone related nutrients in our population as well that an increase in phosphorus intake is related to bone fractures.</p

Multiplicity Distributions and Charged-neutral Fluctuations

Results from the multiplicity distributions of inclusive photons and charged particles, scaling of particle multiplicities, event-by-event multiplicity fluctuations, and charged-neutral fluctuations in 158$\cdot A$ GeV Pb+Pb collisions are presented and discussed. A scaling of charged particle multiplicity as $N_{part}^{1.07\pm 0.05}$ and photons as $N_{part}^{1.12\pm 0.03}$ have been observed, indicating violation of naive wounded nucleon model. The analysis of localized charged-neutral fluctuation indicates a model-independent demonstration of non-statistical fluctuations in both charged particles and photons in limited azimuthal regions. However, no correlated charged-neutral fluctuations are observed.Comment: Talk given at the International Symposium on Nuclear Physics (ISNP-2000), Mumbai, India, 18-22 Dec 2000, Proceedings to be published in Pramana, Journal of Physic

The Mycobacterium Tuberculosis FAS-II Dehydratases and Methyltransferases Define the Specificity of the Mycolic Acid Elongation Complexes

BACKGROUND: The human pathogen Mycobacterium tuberculosis (Mtb) has the originality of possessing a multifunctional mega-enzyme FAS-I (Fatty Acid Synthase-I), together with a multi-protein FAS-II system, to carry out the biosynthesis of common and of specific long chain fatty acids: the mycolic acids (MA). MA are the main constituents of the external mycomembrane that represents a tight permeability barrier involved in the pathogenicity of Mtb. The MA biosynthesis pathway is essential and contains targets for efficient antibiotics. We have demonstrated previously that proteins of FAS-II interact specifically to form specialized and interconnected complexes. This finding suggested that the organization of FAS-II resemble to the architecture of multifunctional mega-enzyme like the mammalian mFAS-I, which is devoted to the fatty acid biosynthesis. PRINCIPAL FINDINGS: Based on conventional and reliable studies using yeast-two hybrid, yeast-three-hybrid and in vitro Co-immunoprecipitation, we completed here the analysis of the composition and architecture of the interactome between the known components of the Mtb FAS-II complexes. We showed that the recently identified dehydratases HadAB and HadBC are part of the FAS-II elongation complexes and may represent a specific link between the core of FAS-II and the condensing enzymes of the system. By testing four additional methyltransferases involved in the biosynthesis of mycolic acids, we demonstrated that they display specific interactions with each type of complexes suggesting their coordinated action during MA elongation. SIGNIFICANCE: These results provide a global update of the architecture and organization of a FAS-II system. The FAS-II system of Mtb is organized in specialized interconnected complexes and the specificity of each elongation complex is given by preferential interactions between condensing enzymes and dehydratase heterodimers. This study will probably allow defining essential and specific interactions that correspond to promising targets for Mtb FAS-II inhibitors

Laser-directed hierarchical assembly of liquid crystal defects and control of optical phase singularities

Topological defect lines are ubiquitous and important in a wide variety of fascinating phenomena and theories in many fields ranging from materials science to early-universe cosmology, and to engineering of laser beams. However, they are typically hard to control in a reliable manner. Here we describe facile erasable “optical drawing” of self-assembled defect clusters in liquid crystals. These quadrupolar defect clusters, stabilized by the medium's chirality and the tendency to form twisted configurations, are shaped into arbitrary two-dimensional patterns, including reconfigurable phase gratings capable of generating and controlling optical phase singularities in laser beams. Our findings bridge the studies of defects in condensed matter physics and optics and may enable applications in data storage, singular optics, displays, electro-optic devices, diffraction gratings, as well as in both optically- and electrically-addressed pixel-free spatial light modulators

Conducting High-Value Secondary Dataset Analysis: An Introductory Guide and Resources

Secondary analyses of large datasets provide a mechanism for researchers to address high impact questions that would otherwise be prohibitively expensive and time-consuming to study. This paper presents a guide to assist investigators interested in conducting secondary data analysis, including advice on the process of successful secondary data analysis as well as a brief summary of high-value datasets and online resources for researchers, including the SGIM dataset compendium (www.sgim.org/go/datasets). The same basic research principles that apply to primary data analysis apply to secondary data analysis, including the development of a clear and clinically relevant research question, study sample, appropriate measures, and a thoughtful analytic approach. A real-world case description illustrates key steps: (1) define your research topic and question; (2) select a dataset; (3) get to know your dataset; and (4) structure your analysis and presentation of findings in a way that is clinically meaningful. Secondary dataset analysis is a well-established methodology. Secondary analysis is particularly valuable for junior investigators, who have limited time and resources to demonstrate expertise and productivity