Introduction
Pollen exposure is known to exacerbate allergic asthma and allergic rhinitis symptoms, yet few studies have investigated if exposure to pollen affects lung function or airway ...inflammation in healthy children.
Methods
We evaluated the extent to which higher pollen exposure was associated with differences in airway inflammation and lung function among 490 early adolescent participants (mean age of 12.9 years) in Project Viva, a prebirth cohort based in Massachusetts. We obtained regional daily total pollen counts, including tree, grass, and weed pollen, from a Rotorod pollen counter. We evaluated associations of 3‐ and 7‐day moving averages of pollen with fractional exhaled nitric oxide (FeNO) and lung function using linear regression models and evaluated the linearity of associations with penalized splines. We tested if associations of pollen with FeNO and lung function were modified by current asthma diagnosis, history of allergic rhinitis, aeroallergen sensitivity, temperature, precipitation, and air pollution.
Results
Three‐ and 7‐day median pollen concentrations were 19.0 grains/m3 (IQR: 73.4) and 20.9 grains/m3 (IQR: 89.7). In main models, higher concentrations of total pollen over the preceding 3 and 7 days were associated with a 4.6% (95% CI: 0.1,9.2) and 7.4% (95% CI: 0.9,14.3) higher FeNO per IQR of pollen, respectively. We did not find associations of pollen with lung function in main models. Asthma, allergic rhinitis, precipitation, and air pollution (nitrogen dioxide and ozone) modified associations of pollen with lung function (Pinteraction < 0.1), while temperature, sex, and aeroallergen sensitization did not.
Conclusion
Short‐term exposure to pollen was associated with higher FeNO in early adolescents, even in the absence of allergic sensitization and asthma.
Cardiomyocyte (CM) replacement is very slow in adult mammalian hearts, preventing regeneration of damaged myocardium. By contrast, fetal hearts display considerable regenerative potential owing to ...the presence of less mature CMs that still have the ability to proliferate. In this study, we demonstrate that heart-specific expression of Oct4, Sox2, Klf4, and c-Myc (OSKM) induces adult CMs to dedifferentiate, conferring regenerative capacity to adult hearts. Transient, CM-specific expression of OSKM extends the regenerative window for postnatal mouse hearts and induces a gene expression program in adult CMs that resembles that of fetal CMs. Extended expression of OSKM in CMs leads to cellular reprogramming and heart tumor formation. Short-term OSKM expression before and during myocardial infarction ameliorates myocardial damage and improves cardiac function, demonstrating that temporally controlled dedifferentiation and reprogramming enable cell cycle reentry of mammalian CMs and facilitate heart regeneration.
Marine Spatial Planning (MSP) has evolved over many years and since its early beginnings there has been a growing urgency to develop transboundary planning. This is because the borders of marine ...ecosystems and the dynamics of some maritime activities, such as navigation, are not restricted to or bound by specific political and administrative borders. Cooperation across borders has been promoted by higher political levels for decades, and the implementation of cross-border consultation procedures is regulated by law. However, literature suggests that transboundary interaction is not an obvious step in the process of MSP and that today's practices have various weaknesses. This paper examines current practices and procedures of transboundary MSP interactions in the Baltic Sea Region to date. It brings together results from MSP process observations and interviews with marine planners in two recent research projects (Baltic SCOPE and BONUS BALTSPACE). Our results confirm the need for transboundary interaction and integration. The research also shows that there are differences in how MSP agencies interact with domestic and foreign stakeholders. Furthermore, formal transboundary consultations often seem to be limited to topics of the environment and health, and to the stakeholders responsible in these realms. The results include a variety of ways to overcome these challenges.
•Various needs for transboundary interaction and integration among authorities were identified.•Currently there are differences in how MSP agencies interact with domestic and foreign stakeholders.•Transboundary consultations often seem to be limited to the topics of environment and health and to their stakeholders.•Nevertheless, many respondents are satisfied with the existing consultation procedures.•More permanent forums for transboundary collaboration are needed.
Background: Diabetes increases the risk of hypertension and orthostatic hypotension and raises the risk of cardiovascular death during heat waves and high pollution episodes. Objective: We examined ...whether short-term exposures to air pollution (fine particles, ozone) and heat resulted in perturbation of arterial blood pressure (BP) in persons with type 2 diabetes mellitus (T2DM). Methods: We conducted a panel study in 70 subjects with T2DM, measuring BP by automated oscillometric sphygmomanometer and pulse wave analysis every 2 weeks on up to five occasions (355 repeated measures). Hourly central site measurements of fine particles, ozone, and meteorology were conducted. We applied linear mixed models with random participant intercepts to investigate the association of fine particles, ozone, and ambient temperature with systolic, diastolic, and mean arterial BP in a multipollutant model, controlling for season, meteorological variables, and subject characteristics. Results: An interquartile increase in ambient fine particle mass paniculate matter (PM) with an aerodynamic diameter of ≤ 2.5 μm (PM2.5) and in the traffic component black carbon in the previous 5 days (3.54 and 0.25 μg/m³, respectively) predicted increases of 1.4 mmHg 95% confidence interval (CI): 0.0, 2.9 mmHg and 2.2 mmHg (95% CI: 0.4, 4.0 mmHg) in systolic BP (SBP) at the population geometric mean, respectively. In contrast, an interquartile increase in the 5-day mean of ozone (13.3 ppb) was associated with a 5.2 mmHg (95% CI: -8.6, -1.8 mmHg) decrease in SBP. Higher temperatures were associated with a marginal decrease in BP. Conclusions: In subjects with T2DM, PM was associated with increased BP, and ozone was associated with decreased BP. These effects may be clinically important in patients with already compromised autoregulatory function.
Abstract Background European regional variation in cancer survival was reported in the EUROCARE-4 study for patients diagnosed in 1995–1999. Relative survival (RS) estimates are here updated for ...patients diagnosed with cancer of the oesophagus, stomach and small intestine from 2000 to 2007. Trends in RS from 1999–2001 to 2005–2007 are presented to monitor and discuss improvements in patient survival in Europe. Materials and methods EUROCARE-5 data from 29 countries (87 cancer registries) were used to investigate 1- and 5-year RS. Using registry-specific life-tables stratified by age, gender and calendar year, age-standardised ‘complete analysis’ RS estimates by country and region were calculated for Northern, Southern, Eastern and Central Europe, and for Ireland and United Kingdom (UK). Survival trends of patients in periods 1999–2001, 2002–2004 and 2005–2007 were investigated using the ‘period’ RS approach. We computed the 5-year RS conditional on surviving the first year (5-year conditional survival), as the ratio of age-standardised 5-year RS to 1-year RS. Results Oesophageal cancer 1- and 5-year RS (40% and 12%, respectively) remained poor in Europe. Patient survival was worst in Eastern (8%), Northern (11%) and Southern Europe (10%). Europe-wide, there was a 3% improvement in oesophageal cancer 5-year survival by 2005–2007, with Ireland and the UK (3%), and Central Europe (4%) showing large improvements. Europe-wide, stomach cancer 5-year RS was 25%. Ireland and UK (17%) and Eastern Europe (19%) had the poorest 5-year patient survival. Southern Europe had the best 5-year survival (30%), though only showing an improvement of 2% by 2005–2007. Small intestine cancer 5-year RS for Europe was 48%, with Central Europe having the best (54%), and Ireland and UK the poorest (37%). Five-year patient survival improvement for Europe was 8% by 2005–2007, with Central, Southern and Eastern Europe showing the greatest increases (⩾9%). Conclusions Survival for these cancer sites, particularly oesophageal cancer, remains poor in Europe with wide variation. Further investigation into the wide variation, including analysis by histology and anatomical sub-site, will yield insights to better monitor and explain the improvements in survival observed over time.
A relatively new field in biotechnology is the cultivation of animal cells in large scale bioreactors. For this, particular requirements for reactor design, process control and careful treatment of ...the cells must be met.
In this paper, modelling and control strategy are presented for a 30 1 and a 70 l-bioreactor with a special bubble-free membrane aeration system. The plants are used for repeated batch and continuous cultivations of modified mouse L 929 Tk-cells.
The cells are growing on micro-carriers and producing glycosilated human interferon-B constitutively. For a mathematical description of the plant, a lumped parameter model of the reactor liquid phase and a distributed parameter model of the bubble-free aeration system was developed. The latter includes mass balances of the gas phase and of gas exchange with the fermentation broth. The control strategy is based on system analysis with this model and the design steps of the control are explained. The control algorithm was implemented on a freely programmable DDC-process-station MICON P-200. (Manufacturer: VDO, Hannover, Germany.
Activation of muscarinic subtype 3 (M3) muscarinic cholinergic receptors (mAChRs) increases airway tone, whereas its blockade improves lung function and quality of life in patients with pulmonary ...diseases. The present study evaluated the pharmacological properties of a novel mAChR antagonist, GSK573719 (4-hydroxy(diphenyl)methyl-1-{2-(phenylmethyl)oxyethyl}-1-azoniabicyclo2.2.2octane; umeclidinium). The affinity (Ki) of GSK573719 for the cloned human M1-M5 mAChRs ranged from 0.05 to 0.16 nM. Dissociation of (3)HGSK573719 from the M3 mAChR was slower than that for the M2 mAChR half-life (t1/2) values: 82 and 9 minutes, respectively. In Chinese hamster ovary cells transfected with recombinant human M3 mAChRs, GSK573719 demonstrated picomolar potency (-log pA2 = 23.9 pM) in an acetylcholine (Ach)-mediated Ca(2+) mobilization assay. Concentration-response curves indicate competitive antagonism with partial reversibility after drug washout. Using isolated human bronchial strips, GSK573719 was also potent and showed competitive antagonism (-log pA2 = 316 pM) versus carbachol, and was slowly reversible in a concentration-dependent manner (1-100 nM). The time to 50% restoration of contraction at 10 nM was about 381 minutes (versus 413 minutes for tiotropium bromide). In mice, the ED50 value was 0.02 μg/mouse intranasally. In conscious guinea pigs, intratracheal administration of GSK573719 dose dependently blocked Ach-induced bronchoconstriction with long duration of action, and was comparable to tiotropium; 2.5 μg elicited 50% bronchoprotection for >24 hours. Thus, GSK573719 is a potent anticholinergic agent that demonstrates slow functional reversibility at the human M3 mAChR and long duration of action in animal models. This pharmacological profile translated into a 24-hour duration of bronchodilation in vivo, which suggested umeclidinium will be a once-daily inhaled treatment of pulmonary diseases.
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