Serum methylarginines and spirometry-measured lung function in older adults

Rationale: Methylarginines are endogenous nitric oxide synthase inhibitors that have been implicated in animal models of lung disease but have not previously been examined for their association with spirometric measures of lung function in humans. Objectives: This study measured serum concentrations of asymmetric and symmetric dimethylarginine in a representative sample of older community-dwelling adults and determined their association with spirometric lung function measures. Methods: Data on clinical, lifestyle, and demographic characteristics, methylated arginines, and L-arginine (measured using LC-MS/MS) were collected from a population-based sample of older Australian adults from the Hunter Community Study. The five key lung function measures included as outcomes were Forced Expiratory Volume in 1 second, Forced Vital Capacity, Forced Expiratory Volume in 1 second to Forced Vital Capacity ratio, Percent Predicted Forced Expiratory Volume in 1 second, and Percent Predicted Forced Vital Capacity. Measurements and Main Results: In adjusted analyses there were statistically significant independent associations between a) higher asymmetric dimethylarginine, lower Forced Expiratory Volume in 1 second and lower Forced Vital Capacity; and b) lower L-arginine/asymmetric dimethylarginine ratio, lower Forced Expiratory Volume in 1 second, lower Percent Predicted Forced Expiratory Volume in 1 second and lower Percent Predicted Forced Vital Capacity. By contrast, no significant associations were observed between symmetric dimethylarginine and lung function. Conclusions: After adjusting for clinical, demographic, biochemical, and pharmacological confounders, higher serum asymmetric dimethylarginine was independently associated with a reduction in key measures of lung function. Further research is needed to determine if methylarginines predict the decline in lung function

Greenhouse gas emissions in The Netherlands 1990-2012 : National Inventory Report 2014

In 2012 is de totale uitstoot van broeikasgassen van Nederland, zoals CO2, methaan en lachgas, met ongeveer 1,7 procent gedaald ten opzichte van 2011. Deze daling komt vooral door een lager brandstofgebruik in de energie- en transportsector. Dit lijkt een gevolg van de economische recessie, waardoor emissies door elektriciteitsproductie en het wegtransport in Nederland zijn afgenomen. Cijfers De totale broeikasgasemissie wordt uitgedrukt in CO2-equivalenten en bedraagt in 2012 191,7 teragram (megaton of miljard kilogram) . Ten opzichte van de uitstoot in het Kyoto-basisjaar (213,2 Tg CO2-equivalenten) is dit een afname van ongeveer 10 procent. Het basisjaar, dat afhankelijk van het broeikasgas 1990 of 1995 is, dient voor het Kyoto-protocol als referentie voor de uitstoot van broeikasgassen. De uitstoot van de overige broeikasgassen zoals lachgas en methaan is sinds het basisjaar met 51 procent afgenomen. De CO2-uitstoot daarentegen is in deze periode met 4 procent gestegen. Landen zijn voor het Kyoto-protocol verplicht om de totale uitstoot van broeikasgassen op twee manieren te rapporteren: met en zonder het soort landgebruik en de verandering daarin. Dit is namelijk van invloed op de uitstoot van broeikasgassen. Voorbeelden zijn natuurontwikkeling (dat CO2 bindt) of ontbossing (waardoor CO2 wordt uitgestoten). In bovengenoemde getallen zijn deze zogeheten LULUCF-emissies (Land Use, Land Use Change and Forestry) niet meegenomen. Overige onderdelen inventarisatie Het RIVM stelt jaarlijks op verzoek van het Ministerie van Infrastructuur en Milieu (IenM) de inventarisatie van broeikasgasemissies op. De inventarisatie bevat trendanalyses om ontwikkelingen in de uitstoot van broeikasgassen tussen 1990 en 2012 te verklaren, en een analyse van de onzekerheid in deze getallen. Ook is aangegeven welke bronnen het meest aan deze onzekerheid bijdragen. Daarnaast biedt de inventarisatie documentatie van de gebruikte berekeningsmethoden, databronnen en toegepaste emissiefactoren. Met deze inventarisatie voldoet Nederland aan de nationale rapportageverplichtingen voor 2012 van het Klimaatverdrag van de Verenigde Naties (UNFCCC), van het Kyoto-Protocol en van het Bewakingsmechanisme Broeikasgassen van de Europese Unie.Total greenhouse gas emissions from the Netherlands in 2012 decreased by approximately 1.7 per cent, compared with 2011 emissions. This decrease is mainly the result of decreased fuel combustion in the Energy sector (increased electricity import) and in road transport. In 2012, total direct greenhouse gas emissions (excluding emissions from LULUCF - land use, land use change and forestry) in the Netherlands amounted to 191.7 Tg CO2 eq. This is approximately 10 per cent below the emissions in the base year (213.2 Tg CO2 eq.). The 51% reduction in the non-CO2 emissions in this period is counterbalanced by 4 per cent increase in CO2 emissions since 1990. This report documents the Netherlands' 2014 annual submission of its greenhouse gas emissions inventory in accordance with the guidelines provided by the United Nations Framework Convention on Climate Change (UNFCCC), the Kyoto Protocol and the European Union's Greenhouse Gas Monitoring Mechanism. The report comprises explanations of observed trends in emissions; a description of an assessment of key sources and their uncertainty; documentation of methods, data sources and emission factors applied; and a description of the quality assurance system and the verification activities performed on the data.Ministerie van I&

C1 compounds as auxiliary substrate for engineered Pseudomonas putida S12

The solvent-tolerant bacterium Pseudomonas putida S12 was engineered to efficiently utilize the C1 compounds methanol and formaldehyde as auxiliary substrate. The hps and phi genes of Bacillus brevis, encoding two key steps of the ribulose monophosphate (RuMP) pathway, were introduced to construct a pathway for the metabolism of the toxic methanol oxidation intermediate formaldehyde. This approach resulted in a remarkably increased biomass yield on the primary substrate glucose when cultured in C-limited chemostats fed with a mixture of glucose and formaldehyde. With increasing relative formaldehyde feed concentrations, the biomass yield increased from 35% (C-mol biomass/C-mol glucose) without formaldehyde to 91% at 60% relative formaldehyde concentration. The RuMP-pathway expressing strain was also capable of growing to higher relative formaldehyde concentrations than the control strain. The presence of an endogenous methanol oxidizing enzyme activity in P. putida S12 allowed the replacement of formaldehyde with the less toxic methanol, resulting in an 84% (C-mol/C-mol) biomass yield. Thus, by introducing two enzymes of the RuMP pathway, co-utilization of the cheap and renewable substrate methanol was achieved, making an important contribution to the efficient use of P. putida S12 as a bioconversion platform host

Patients' experiences with quality of hospital care: the Consumer Quality Index Cataract Questionnaire

Background. Patients' feedback is of great importance in health care policy decisions. The Consumer Quality Index Cataract Questionnaire (CQI Cataract) was used to measure patients' experiences with quality of care after a cataract operation. This study aims to evaluate the reliability and the dimensional structure of this questionnaire and assesses its ability to measure differences between hospitals in patients' experiences with quality of care. Methods. Survey data of 4,635 respondents were available. An exploratory factor analysis was performed to evaluate the construct validity of the questionnaire and item-correlations and inter-factor correlations were calculated. Secondly, Cronbach's alpha coefficients were calculated to assess the internal consistency of the scales. Thirdly, to evaluate the ability of the questionnaire to discriminate between hospitals, multilevel analyses were performed with patients hierarchically nested within hospitals. Results. Exploratory factor analysis resulted in 14 quality of care items subdivided over three factors (i.e. communication with ophthalmologist, communication with nurses, and communication about medication). Cronbach's alpha coefficients of 0.89, 0.76 and 0.79 indicated good internal consistency. Multilevel analyses showed that the questionnaire was able to measure differences in patients' experiences with hospital care regarding communication with ophthalmologist and communication about medication. In addition, there was variation between hospitals regarding ophthalmologist ratings, hospital ratings and one dichotomous information item. Conclusion. These findings suggest that the CQI Cataract is a reliable and valid instrument. This instrument can be used to measure patients' experiences with three domains of hospital care after a cataract operation and is able to assess differences in evaluated care between hospitals

The Consumer Quality Index Hip Knee Questionnaire measuring patients' experiences with quality of care after a total hip or knee arthroplasty

<p>Abstract</p> <p>Background</p> <p>The Dutch Consumer Quality Index Hip Knee Questionnaire (CQI Hip Knee) was used to assess patients' experiences with and evaluations of quality of care after a total hip (THA) or total knee arthroplasty (TKA). The aim of this study is to evaluate the construct validity and internal consistency reliability of this new instrument and to assess its ability to measure differences in quality of care between hospitals.</p> <p>Methods</p> <p>Survey data of 1,675 subjects who underwent a THA or TKA were used to evaluate the psychometric properties. Exploratory factor analyses were performed and item-total correlations and inter-factor correlations were calculated to assess the construct validity of the instrument. Reliability analyses included tests of internal consistency (Cronbach's alpha coefficients). Finally, multilevel analyses were performed to assess the ability of the instrument to discriminate between hospitals in quality of care.</p> <p>Results</p> <p>Exploratory factor analyses indicated that the survey consisted of 21 items measuring five aspects of care (i.e. communication with nurses, communication with doctors, communication with general practitioner, communication about new medication, and pain control). Cronbach's alpha coefficients ranged from 0.76 to 0.90 indicating good internal consistency. The survey's ability to discriminate between hospitals was partly supported by multilevel analysis. Two scales (i.e. communication with nurses and communication with doctors) were able to measure differences between hospitals with respect to patients' experiences with quality of care. Logistic multilevel analyses indicated that hospitals explained part of the variation between patients in receiving information.</p> <p>Conclusion</p> <p>These findings suggest that the CQI Hip Knee is reliable and valid for use in Dutch health care. Health care providers or health plans can use this survey to measure patients' experiences with hospital care and to identify variations in care between hospitals.</p

Genome-Scale Reconstruction and Analysis of the Pseudomonas putida KT2440 Metabolic Network Facilitates Applications in Biotechnology

A cornerstone of biotechnology is the use of microorganisms for the efficient production of chemicals and the elimination of harmful waste. Pseudomonas putida is an archetype of such microbes due to its metabolic versatility, stress resistance, amenability to genetic modifications, and vast potential for environmental and industrial applications. To address both the elucidation of the metabolic wiring in P. putida and its uses in biocatalysis, in particular for the production of non-growth-related biochemicals, we developed and present here a genome-scale constraint-based model of the metabolism of P. putida KT2440. Network reconstruction and flux balance analysis (FBA) enabled definition of the structure of the metabolic network, identification of knowledge gaps, and pin-pointing of essential metabolic functions, facilitating thereby the refinement of gene annotations. FBA and flux variability analysis were used to analyze the properties, potential, and limits of the model. These analyses allowed identification, under various conditions, of key features of metabolism such as growth yield, resource distribution, network robustness, and gene essentiality. The model was validated with data from continuous cell cultures, high-throughput phenotyping data, 13C-measurement of internal flux distributions, and specifically generated knock-out mutants. Auxotrophy was correctly predicted in 75% of the cases. These systematic analyses revealed that the metabolic network structure is the main factor determining the accuracy of predictions, whereas biomass composition has negligible influence. Finally, we drew on the model to devise metabolic engineering strategies to improve production of polyhydroxyalkanoates, a class of biotechnologically useful compounds whose synthesis is not coupled to cell survival. The solidly validated model yields valuable insights into genotype–phenotype relationships and provides a sound framework to explore this versatile bacterium and to capitalize on its vast biotechnological potential

Overexpression of endothelial nitric oxide synthase suppresses features of allergic asthma in mice

BACKGROUND: Asthma is associated with airway hyperresponsiveness and enhanced T-cell number/activity on one hand and increased levels of exhaled nitric oxide (NO) with expression of inducible NO synthase (iNOS) on the other hand. These findings are in paradox, as NO also relaxes airway smooth muscle and has immunosuppressive properties. The exact role of the endothelial NOS (eNOS) isoform in asthma is still unknown. We hypothezised that a delicate regulation in the production of NO and its bioactive forms by eNOS might be the key to the pathogenesis of asthma. METHODS: The contribution of eNOS on the development of asthmatic features was examined. We used transgenic mice that overexpress eNOS and measured characteristic features of allergic asthma after sensitisation and challenge of these mice with the allergen ovalbumin. RESULTS: eNOS overexpression resulted in both increased eNOS activity and NO production in the lungs. Isolated thoracic lymph nodes cells from eNOS overexpressing mice that have been sensitized and challenged with ovalbumin produced significantly less of the cytokines IFN-γ, IL-5 and IL-10. No difference in serum IgE levels could be found. Further, there was a 50% reduction in the number of lymphocytes and eosinophils in the lung lavage fluid of these animals. Finally, airway hyperresponsiveness to methacholine was abolished in eNOS overexpressing mice. CONCLUSION: These findings demonstrate that eNOS overexpression attenuates both airway inflammation and airway hyperresponsiveness in a model of allergic asthma. We suggest that a delicate balance in the production of bioactive forms of NO derived from eNOS might be essential in the pathophysiology of asthma

Mechanical characterisation of polymer of intrinsic microporosity PIM-1 for hydrogen storage applications

Polymers of intrinsic microporosity (PIMs) are currently attracting interest due to their unusual combination of high surface areas and capability to be processed into free-standing films. However, there has been little published work with regards to their physical and mechanical properties. In this paper, detailed characterisation of PIM-1 was performed by considering its chemical, gas adsorption and mechanical properties. The polymer was cast into films, and characterised in terms of their hydrogen adsorption at −196 °C up to much higher pressures (17 MPa) than previously reported (2 MPa), demonstrating the maximum excess adsorbed capacity of the material and its uptake behaviour in higher pressure regimes. The measured tensile strength of the polymer film was 31 MPa with a Young’s modulus of 1.26 GPa, whereas the average storage modulus exceeded 960 MPa. The failure strain of the material was 4.4%. It was found that the film is thermally stable at low temperatures, down to −150 °C, and decomposition of the material occurs at 350 °C. These results suggest that PIM-1 has sufficient elasticity to withstand the elastic deformations occurring within state-of-the-art high-pressure hydrogen storage tanks and sufficient thermal stability to be applied at the range of temperatures necessary for gas storage applications