Protocol for a systematic literature review and network meta-analysis of the clinical benefit of inhaled maintenance therapies in chronic obstructive pulmonary disease

© Author(s) (or their employer(s)) 2019. Introduction Chronic obstructive pulmonary disease (COPD) exacerbations progress the course of disease and impair lung function. Inhaled maintenance therapy reduces exacerbations. It is not yet established which inhaled therapy combination is best to reduce exacerbations, lung function decline and symptom burden. Methods and analysis MEDLINE, EMBASE and the Cochrane Library will be searched for articles between January 2011 and May 2018 using a pre-specified search strategy. Conference proceedings will be searched. Systematic reviews (with or without meta-analysis), randomised controlled trials (RCTs), cohort studies and case controlled studies comparing six interventions comprising different combinations of long-acting bronchodilators and inhaled corticosteroids in unison or on their own. The primary outcome is the reduction in moderate-to-severe exacerbations. Secondary outcomes include: lung function, quality of life, mortality and other adverse events. Titles and abstracts will screened by the primary researcher. A second reviewer will repeat this on a proportion of records. The Population, Intervention, Comparator, Outcomes and Study framework will be used for data extraction. A network meta-analyses of outcomes from RCTs and real-world evidence will be integrated if feasible. The 95% credible interval will be used to assess the statistical significance of each summary effect. Ranking of interventions will be based on their surface under cumulative ranking area. Ethics and dissemination COPD exacerbations are burdensome to patients. We aim to report results that provide clinicians with a more informed choice of which inhaled therapy combinations are best to reduce exacerbations, improve disease burden and reduce lung function and exercise capacity decline, compared with the potential harms, in certain populations with COPD. PROSPERO registration number CRD42018088013Boehringer Ingelheim Ltd. Bracknell, U

Exclusive generation of rat spermatozoa in sterile mice utilizing blastocyst complementation with pluripotent stem cells

Blastocyst complementation denotes a technique that aims to generate organs, tissues, or cell types in animal chimeras via injection of pluripotent stem cells (PSCs) into genetically compromised blastocyst-stage embryos. Here, we report on successful complementation of the male germline in adult chimeras following injection of mouse or rat PSCs into mouse blastocysts carrying a mutation in Tsc22d3, an essential gene for spermatozoa production. Injection of mouse PSCs into Tsc22d3-Knockout (KO) blastocysts gave rise to intraspecies chimeras exclusively embodying PSC-derived functional spermatozoa. In addition, injection of rat embryonic stem cells (rESCs) into Tsc22d3-KO embryos produced interspecies mouse-rat chimeras solely harboring rat spermatids and spermatozoa capable of fertilizing oocytes. Furthermore, using single-cell RNA sequencing, we deconstructed rat spermatogenesis occurring in a mouse-rat chimera testis. Collectively, this study details a method for exclusive xenogeneic germ cell production in vivo, with implications that may extend to rat transgenesis, or endangered animal species conservation efforts. Keywords: Blastocyst complementation; artificial reproductive technology; germ cell production; interspecies chimerism; pluripotency; sterility

Environmental variables, habitat discontinuity and life history shaping the genetic structure of Pomatoschistus marmoratus

Coastal lagoons are semi-isolated ecosystems exposed to wide fluctuations of environmental conditions and showing habitat fragmentation. These features may play an important role in separating species into different populations, even at small spatial scales. In this study, we evaluate the concordance between mitochondrial (previous published data) and nuclear data analyzing the genetic variability of Pomatoschistus marmoratus in five localities, inside and outside the Mar Menor coastal lagoon (SE Spain) using eight microsatellites. High genetic diversity and similar levels of allele richness were observed across all loci and localities, although significant genic and genotypic differentiation was found between populations inside and outside the lagoon. In contrast to the FST values obtained from previous mitochondrial DNA analyses (control region), the microsatellite data exhibited significant differentiation among samples inside the Mar Menor and between lagoonal and marine samples. This pattern was corroborated using Cavalli-Sforza genetic distances. The habitat fragmentation inside the coastal lagoon and among lagoon and marine localities could be acting as a barrier to gene flow and contributing to the observed genetic structure. Our results from generalized additive models point a significant link between extreme lagoonal environmental conditions (mainly maximum salinity) and P. marmoratus genetic composition. Thereby, these environmental features could be also acting on genetic structure of coastal lagoon populations of P. marmoratus favoring their genetic divergence. The mating strategy of P. marmoratus could be also influencing our results obtained from mitochondrial and nuclear DNA. Therefore, a special consideration must be done in the selection of the DNA markers depending on the reproductive strategy of the species

Artificial coastal lagoons at solar salt-working sites: A network of habitats for specialised, protected and alien biodiversity

There are concerns that novel structures might displace protected species, facilitate the spread of nonindigenous species, or modify native habitats. It is also predicted that ocean warming and the associated effects of climate change will significantly increase biodiversity loss within coastal regions. Resilience is to a large extent influenced by the magnitude of dispersal and level of connectivity within and between populations. Therefore it is important to investigate the distribution and ecological significance of novel and artificial habitats, the presence of protected and alien species and potential vectors of propagule dispersal. The legacy of solar salt-making in tropical and warm temperate regions is regionally extensive areas of artificial hypersaline ponds, canals and ditches. Yet the broad-scale contribution of salt-working to a network of benthic biodiversity has not been fully established. Artisanal, abandoned and historic salt-working sites were investigated along the Atlantic coast of Europe between southern England (50 N) and Andalucía, Spain (36 N). Natural lagoons are scarce along this macrotidal coast and are vulnerable to environmental change; however it is suspected that avian propagule dispersal is important in maintaining population connectivity. During bird migration periods, benthic cores were collected for infauna from 70 waterbodies across 21 salt-working sites in 5 coastal regions. Bird ringing data were used to investigate potential avian connectivity between locations. Lagoonal specialist species, some of international conservation importance, were recorded across all regions in the storage reservoirs and evaporation ponds of continental salinas, yet few non-indigenous species were observed. Potential avian propagule transport and connectivity within and between extant salt-working sites is high and these artificial habitats are likely to contribute significantly to a network of coastal lagoon biodiversity in Europ

Frontally mediated inhibitory processing and white matter microstructure: age and alcoholism effects

RationaleThe NOGO P3 event-related potential is a sensitive marker of alcoholism, relates to EEG oscillation in the δ and θ frequency ranges, and reflects activation of an inhibitory processing network. Degradation of white matter tracts related to age or alcoholism should negatively affect the oscillatory activity within the network.ObjectiveThis study aims to evaluate the effect of alcoholism and age on δ and θ oscillations and the relationship between these oscillations and measures of white matter microstructural integrity.MethodsData from ten long-term alcoholics to 25 nonalcoholic controls were used to derive P3 from Fz, Cz, and Pz using a visual GO/NOGO protocol. Total power and across trial phase synchrony measures were calculated for δ and θ frequencies. DTI, 1.5 T, data formed the basis of quantitative fiber tracking in the left and right cingulate bundles and the genu and splenium of the corpus callosum. Fractional anisotropy and diffusivity (λL and λT) measures were calculated from each tract.ResultsNOGO P3 amplitude and δ power at Cz were smaller in alcoholics than controls. Lower δ total power was related to higher λT in the left and right cingulate bundles. GO P3 amplitude was lower and GO P3 latency was longer with advancing age, but none of the time-frequency analysis measures displayed significant age or diagnosis effects.ConclusionsThe relation of δ total power at CZ with λT in the cingulate bundles provides correlational evidence for a functional role of fronto-parietal white matter tracts in inhibitory processing

A multidisciplinary approach to identify priority areas for the monitoring of a vulnerable family of fishes in Spanish Marine National Parks

Background Syngnathid fishes (Actinopterygii, Syngnathidae) are flagship species strongly associated with seaweed and seagrass habitats. Seahorses and pipefishes are highly vulnerable to anthropogenic and environmental disturbances, but most species are currently Data Deficient according to the IUCN (2019), requiring more biological and ecological research. This study provides the first insights into syngnathid populations in the two marine Spanish National Parks (PNIA—Atlantic- and PNAC—Mediterranean). Fishes were collected periodically, marked, morphologically identified, analysed for size, weight, sex and sexual maturity, and sampled for stable isotope and genetic identification. Due the scarcity of previous information, habitat characteristics were also assessed in PNIA. Results Syngnathid diversity and abundance were low, with two species identified in PNIA (Hippocampus guttulatus and Syngnathus acus) and four in PNAC (S. abaster, S. acus, S. typhle and Nerophis maculatus). Syngnathids from both National Parks (NP) differed isotopically, with much lower δ15N in PNAC than in PNIA. The dominant species were S. abaster in PNAC and S. acus in PNIA. Syngnathids preferred less exposed sites in macroalgal assemblages in PNIA and Cymodocea meadows in PNAC. The occurrence of very large specimens, the absence of small-medium sizes and the isotopic comparison with a nearby population suggest that the population of Syngnathus acus (the dominant syngnathid in PNIA) mainly comprised breeders that migrate seasonally. Mitochondrial cytochrome b sequence variants were detected for H. guttulatus, S. acus, and S. abaster, and a novel 16S rDNA haplotype was obtained in N. maculatus. Our data suggest the presence of a cryptic divergent mitochondrial lineage of Syngnathus abaster species in PNAC. Conclusions This is the first multidisciplinary approach to the study of syngnathids in Spanish marine NPs. Habitat preferences and population characteristics in both NPs differed. Further studies are needed to assess the occurrence of a species complex for S. abaster, discarding potential misidentifications of genus Syngnathus in PNAC, and evaluate migratory events in PNIA. We propose several preferential sites in both NPs for future monitoring of syngnathid populations and some recommendations for their conservation.Postprin

Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry

Aims: This study aimed to assess age- and sex-related differences in management and 1-year risk for all-cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results: Of 16 354 patients included in the European Society of Cardiology Heart Failure Long-Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline-directed medical therapy (GDMT) were high (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P\ua0 64 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1-year follow-up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all-cause mortality were lower in women than in men (7.1% vs. 8.7%; P\ua0=\ua00.015), as were rates of all-cause hospitalization (21.9% vs. 27.3%; P\ua075 years. Conclusions: There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all-cause mortality in patients with LVEF 6445%

Energy intake and energy expenditure of pre-professional female contemporary dancers

Many athletes in aesthetic and weight dependent sports are at risk of energy imbalance. However little is known about the exercise and eating behaviours of highly trained dance populations. This investigation sought to determine the energy intake and energy expenditure of pre-professional female contemporary dancers. Twenty-five female contemporary dance students completed the study. Over a 7-day period, including five week days (with scheduled dance training at a conservatoire) and two weekend days (with no scheduled dance training at the conservatoire), energy intake (self-reported weighed food diary and 24 h dietary recall) and expenditure (tri-axial accelerometry) were recorded. Mean daily energy intake and expenditure were different over the 7-day period (P = 0.014) equating to an energy deficit of -356 ± 668 kcal·day-1 (or -1.5 ± 2.8 MJ·day-1). Energy expenditure was not different when comparing week and weekend days (P = 0.297). However daily energy intake (P = 0.002), energy availability (P = 0.003), and energy balance (P = 0.004) were lower during the week compared to the weekend, where energy balance became positive. The percentage contribution of macronutrients to total energy intake also differed; with higher fat (P = 0.022) and alcohol (P = 0.020), and lower carbohydrate (P = 0.001) and a trend for lower protein (P = 0.051) at the weekend. Energy balance and appropriate macronutrient intake are essential for maintaining the demands of training, performance and recovery. Whilst aesthetics are important, female contemporary dancers may be at risk of the numerous health and performance impairments associated with negative energy balance, particularly during periods of scheduled training

The 42nd Symposium Chromatographic Methods of Investigating Organic Compounds : Book of abstracts

The 42nd Symposium Chromatographic Methods of Investigating Organic Compounds : Book of abstracts. June 4-7, 2019, Szczyrk, Polan

Farmers' incoms in Poland and new member states of the European Union under the conditions of globalization

W rozważaniach na temat znaczenia globalizacji ekonomicznej dla rolnictwa w zjednoczonej Europie zauważono, że jako proces zewnętrzny nie ma ona, jak dotąd, tak silnego wpływu na dochody rolników, jak integracja regionalna w ramach Unii Europejskiej. Charakterystyce poddano nowe kraje członkowskie UE opisując znaczenie rolnictwa dla ich gospodarek oraz wpływ podstawowych czynników produkcji na dochód rolniczy.The significance of economic globalization for agriculture in united Europe was under consideration in this paper. This globalization as an exterior process has not as strong influence on farmers' earnings until now as regional integration in European Union. New Member Countries of UE was profiled to describe the meaning of their agriculturein country’s economy and influence of basis production factors on farmers' earnings