The role of the novel D2/β2-agonist, Viozan™ (sibenadet HCl), in the treatment of symptoms of chronic obstructive pulmonary disease: results of a large-scale clinical investigation

AbstractViozan™ (sibenadet HCl, AR-C68397AA) is a novel dual D2 dopamine receptor, β2-adrenoceptor agonist, developed specifically to treat the key symptoms of chronic obstructive pulmonary disease (COPD), breathlessness, cough and sputum. The dual sensory nerve modulation and bronchodilator effects of sibenadet have been demonstrated in initial dose-ranging studies of patients with COPD and large-scale clinical evaluation has now been completed. Sibenadet efficacy was determined by assessing symptomatic changes, as defined by the novel assessment tool, the Breathlessness, Cough and Sputum Scale (BCSS©). The findings of two placebo-controlled studies are reported.These multicentre, double-blind, placebo-controlled studies recruited over 2000 patients with stable COPD, randomized to receive sibenadet (500 μg) or placebo, pressurized metered-dose inhaler (pMDI) (three times daily) for a period of 12 or 26 weeks. Diary cards were completed daily by patients throughout the study to record BCSS scores, peak expiratory flow (PEF), study drug and rescue bronchodilator usage, changes in concomitant medication and adverse events. The primary endpoints were defined as change from baseline to the final 4 weeks of the treatment period in mean BCSS total score, and forced expiratory volume in one second (FEV1) measured 1 hour after administration of the final dose of study drug and expressed as a percentage of the predicted FEV1. In addition, clinic assessments were made to determine changes in pulmonary function, health-related quality of life, perception of treatment efficacy and adverse events.Despite initial improvements in mean daily BCSS total scores in patients receiving sibenadet, the difference in the change from baseline to the final 4 weeks of the treatment period between the two treatment groups was neither statistically significant, nor considered to be of clinical importance. Although marked bronchodilator activity was seen early on with sibenadet treatment, the duration of effect diminished as the studies progressed. Sibenadet use was not associated with any safety concerns.These studies, utilizing the novel BCSS, have clearly illustrated that, despite initial symptomatic improvement with sibenadet therapy, this clinical benefit was not sustained over the course of the study

Mammalian sphingoid bases: Biophysical, physiological and pathological properties

Sphingoid bases encompass a group of long chain amino alcohols which form the essential structure of sphingolipids. Over the last years, these amphiphilic molecules were moving more and more into the focus of biomedical research due to their role as bioactive molecules. In fact, free sphingoid bases interact with specific receptors and target molecules, and have been associated with numerous biological and physiological processes. In addition, they can modulate the biophysical properties of biological membranes. Several human diseases are related to pathological changes in the structure and metabolism of sphingoid bases. Yet, the mechanisms underlying their biological and pathophysiological actions remain elusive. Within this review, we aimed to summarize the current knowledge on the biochemical and biophysical properties of the most common sphingoid bases and to discuss their importance in health and disease

Surface preparation of powder metallurgical tool steels by means of wire electrical discharge machining

The surface of two types of powder metallurgical (PM) tool steels (i.e., with and without nitrogen) was prepared using wire electrical discharge machining (WEDM). From each grade of tool steel, seven surfaces corresponding to one to seven passes of WEDM were prepared. The WEDM process was carried out using a brass wire as electrode and deionized water as dielectric. After eachWEDM pass the surface of the tool steels was thoroughly examined. Surface residual stresses were measured by the X-ray diffraction (XRD) technique. The measured stresses were found to be of tensile nature. The surface roughness of the WEDM specimens was measured using interference microscopy. The surface roughness as well as the residual stress measurements indicated an insignificant improvement of these parameters after four passes of WEDM. In addition, the formed recast layer was characterized by means of scanning electron microscopy (SEM), XRD, and X-ray photoelectron spectroscopy (XPS). The characterization investigation clearly shows diffusion of copper and zinc from the wire electrode into the work material, even after the final WEDM step. Finally, the importance of eliminating excessive WEDM steps is thoroughly discussed

An Analytic Variational Study of the Mass Spectrum in 2+1 Dimensional SU(3) Hamiltonian Lattice Gauge Theory

We calculate the masses of the lowest lying eigenstates of improved SU(2) and SU(3) lattice gauge theory in 2+1 dimensions using an analytic variational approach. The ground state is approximated by a one plaquette trial state and mass gaps are calculated in the symmetric and antisymmetric sectors by minimising over a suitable basis of rectangular states

Life's Essential 8: Updating and Enhancing the American Heart Association's Construct of Cardiovascular Health: A Presidential Advisory from the American Heart Association

In 2010, the American Heart Association defined a novel construct of cardiovascular health to promote a paradigm shift from a focus solely on disease treatment to one inclusive of positive health promotion and preservation across the life course in populations and individuals. Extensive subsequent evidence has provided insights into strengths and limitations of the original approach to defining and quantifying cardiovascular health. In response, the American Heart Association convened a writing group to recommend enhancements and updates. The definition and quantification of each of the original metrics (Life's Simple 7) were evaluated for responsiveness to interindividual variation and intraindividual change. New metrics were considered, and the age spectrum was expanded to include the entire life course. The foundational contexts of social determinants of health and psychological health were addressed as crucial factors in optimizing and preserving cardiovascular health. This presidential advisory introduces an enhanced approach to assessing cardiovascular health: Life's Essential 8. The components of Life's Essential 8 include diet (updated), physical activity, nicotine exposure (updated), sleep health (new), body mass index, blood lipids (updated), blood glucose (updated), and blood pressure. Each metric has a new scoring algorithm ranging from 0 to 100 points, allowing generation of a new composite cardiovascular health score (the unweighted average of all components) that also varies from 0 to 100 points. Methods for implementing cardiovascular health assessment and longitudinal monitoring are discussed, as are potential data sources and tools to promote widespread adoption in policy, public health, clinical, institutional, and community settings

Epidemic centrality - is there an underestimated epidemic impact of network peripheral nodes?

In the study of disease spreading on empirical complex networks in SIR model, initially infected nodes can be ranked according to some measure of their epidemic impact. The highest ranked nodes, also referred to as "superspreaders", are associated to dominant epidemic risks and therefore deserve special attention. In simulations on studied empirical complex networks, it is shown that the ranking depends on the dynamical regime of the disease spreading. A possible mechanism leading to this dependence is illustrated in an analytically tractable example. In systems where the allocation of resources to counter disease spreading to individual nodes is based on their ranking, the dynamical regime of disease spreading is frequently not known before the outbreak of the disease. Therefore, we introduce a quantity called epidemic centrality as an average over all relevant regimes of disease spreading as a basis of the ranking. A recently introduced concept of phase diagram of epidemic spreading is used as a framework in which several types of averaging are studied. The epidemic centrality is compared to structural properties of nodes such as node degree, k-cores and betweenness. There is a growing trend of epidemic centrality with degree and k-cores values, but the variation of epidemic centrality is much smaller than the variation of degree or k-cores value. It is found that the epidemic centrality of the structurally peripheral nodes is of the same order of magnitude as the epidemic centrality of the structurally central nodes. The implications of these findings for the distributions of resources to counter disease spreading are discussed

Social-ecological, motivational and volitional factors for initiating and maintaining physical activity in the context of HIV

Sport and exercise can have several health benefits for people living with HIV. These benefits can be achieved through different types of physical activity, adapting to disease progression, motivation and social-ecological options. However, physical activity levels and adherence to exercise are generally low in people living with HIV. At the same time, high drop-out rates in intervention studies are prevalent; even though they often entail more favourable conditions than interventions in the natural settings. Thus, in the framework of an intervention study, the present study aims to explore social-ecological, motivational and volitional correlates of South African women living with HIV with regard to physical activity and participation in a sport and exercise health promotion programme. The qualitative data was produced in the framework of a non-randomised pre-post intervention study that evaluated structure, processes and outcomes of a 10-week sport and exercise programme. All 25 participants of the programme were included in this analysis, independent of compliance. Data was produced through questionnaires, participatory group discussions, body image pictures, research diaries and individual semi-structured interviews. All participants lived in a low socioeconomic, disadvantaged setting. Hence, the psychological correlates are contextualised and social-ecological influences on perception and behaviour are discussed. The results show the importance of considering social-cultural and environmental influences on individual motives, perceptions and expectancies, the fear of disclosure and stigmatisation, sport and exercise-specific group dynamics and self-supporting processes. Opportunities and strategies to augment physical activity and participation in sport and exercise programmes in the context of HIV are discussed.Scopu

Evolutionary Heritage Influences Amazon Tree Ecology

Lineages tend to retain ecological characteristics of their ancestors through time. However, for some traits, selection during evolutionary history may have also played a role in determining trait values. To address the relative importance of these processes requires large-scale quantification of traits and evolutionary relationships among species. The Amazonian tree flora comprises a high diversity of angiosperm lineages and species with widely differing life-history characteristics, providing an excellent system to investigate the combined influences of evolutionary heritage and selection in determining trait variation. We used trait data related to the major axes of life-history variation among tropical trees (e.g. growth and mortality rates) from 577 inventory plots in closed-canopy forest, mapped onto a phylogenetic hypothesis spanning more than 300 genera including all major angiosperm clades to test for evolutionary constraints on traits. We found significant phylogenetic signal (PS) for all traits, consistent with evolutionarily related genera having more similar characteristics than expected by chance. Although there is also evidence for repeated evolution of pioneer and shade tolerant life-history strategies within independent lineages, the existence of significant PS allows clearer predictions of the links between evolutionary diversity, ecosystem function and the response of tropical forests to global change

Special Libraries, April 1933

Volume 24, Issue 3https://scholarworks.sjsu.edu/sla_sl_1933/1002/thumbnail.jp