570 research outputs found

    Assessing Nepal's national sanitation policy

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    Many researchers and commentators on sanitation have recognised that relevant and effective policies play an important role in ensuring sanitation is addressed at sufficient scale that progress is made towards national sanitation targets in support of the Millennium Development Goals (MDGs). With this in mind, the Environmental Health Programme (EHP) of USAID developed a written ‘Guidelines for the Assessment of National Sanitation Policies’ in 2002, to help countries assess the effectiveness of policy in enabling an environment that encourages effective programmes and strategies. Nepal was selected as one of two countries for field-testing the EHP Guidelines as part of DFID-funded research carried out by WEDC in collaboration with Development Network, a national consulting research firm in Nepal. This paper highlights key findings based on the research process, with implications for challenges facing Nepal in effectively implementing sanitation policy

    Diminished Antioxidant Activity of High-Density Lipoprotein–Associated Proteins in Systolic Heart Failure

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    Background— Diminished serum arylesterase activity, catalyzed by the high-density lipoprotein–associated paraoxonase-1, is associated with heightened systemic oxidative stress and atherosclerosis risk. In the present study, we sought to determine the prognostic role of serum arylesterase activity in subjects with systolic heart failure, particularly in relation to established cardiac biomarkers. Methods and Results— We measured serum arylesterase activity in 760 subjects with impaired left ventricular systolic function (left ventricular ejection fraction \u3c50%), and prospectively followed major adverse cardiac events (including death, nonfatal myocardial infarction, and stroke) for 3 years. In our study cohort (mean age, 64±11 years; 74% men; median left ventricular ejection fraction, 35%; median creatinine clearance, 96 mg/dL), mean serum arylesterase activity (98±25 μmol/L/min/mL) was lower compared with that in healthy control subjects (mean, 115±26 μmol/L/min/mL, P\u3c0.01) but higher compared with advanced decompensated heart failure subjects (mean, 69±22 μmol/L/min/mL, P\u3c0.01). Within our cohort, there was modest correlation between serum arylesterase activity and high-density lipoprotein cholesterol (r=0.33, P\u3c0.01) as well as B-type natriuretic peptide (r=−0.23, P\u3c0.01). Lower serum arylesterase activity was a strong predictor of poorer outcomes (hazard ratio, 2.94; 95% confidence interval, 1.54, 5.62; P\u3c0.001). After adjusting for traditional risk factors, medication use, B-type natriuretic peptide, and creatinine clearance, lower serum arylesterase still conferred an increased risk of major adverse cardiac events at 3 years (hazard ratio, 2.69; 95% confidence interval, 1.37 to 5.28; P=0.004). Conclusions— In patients with systolic heart failure, decreased serum arylesterase activity, a measure of diminished antioxidant properties of high-density lipoprotein, predicts higher risk of incident long-term adverse cardiac event independent of established clinical and biochemical risk factors

    Diminished Antioxidant Activity of High-Density Lipoprotein–Associated Proteins in Systolic Heart Failure

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    Background— Diminished serum arylesterase activity, catalyzed by the high-density lipoprotein–associated paraoxonase-1, is associated with heightened systemic oxidative stress and atherosclerosis risk. In the present study, we sought to determine the prognostic role of serum arylesterase activity in subjects with systolic heart failure, particularly in relation to established cardiac biomarkers. Methods and Results— We measured serum arylesterase activity in 760 subjects with impaired left ventricular systolic function (left ventricular ejection fraction \u3c50%), and prospectively followed major adverse cardiac events (including death, nonfatal myocardial infarction, and stroke) for 3 years. In our study cohort (mean age, 64±11 years; 74% men; median left ventricular ejection fraction, 35%; median creatinine clearance, 96 mg/dL), mean serum arylesterase activity (98±25 μmol/L/min/mL) was lower compared with that in healthy control subjects (mean, 115±26 μmol/L/min/mL, P\u3c0.01) but higher compared with advanced decompensated heart failure subjects (mean, 69±22 μmol/L/min/mL, P\u3c0.01). Within our cohort, there was modest correlation between serum arylesterase activity and high-density lipoprotein cholesterol (r=0.33, P\u3c0.01) as well as B-type natriuretic peptide (r=−0.23, P\u3c0.01). Lower serum arylesterase activity was a strong predictor of poorer outcomes (hazard ratio, 2.94; 95% confidence interval, 1.54, 5.62; P\u3c0.001). After adjusting for traditional risk factors, medication use, B-type natriuretic peptide, and creatinine clearance, lower serum arylesterase still conferred an increased risk of major adverse cardiac events at 3 years (hazard ratio, 2.69; 95% confidence interval, 1.37 to 5.28; P=0.004). Conclusions— In patients with systolic heart failure, decreased serum arylesterase activity, a measure of diminished antioxidant properties of high-density lipoprotein, predicts higher risk of incident long-term adverse cardiac event independent of established clinical and biochemical risk factors

    Low-coverage massively parallel pyrosequencing of cDNAs enables proteomics in non-model species: Comparison of a species-specific database generated by pyrosequencing with databases from related species for proteome analysis of pea chloroplast envelopes

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    Bräutigam A, Shrestha RP, Whitten D, et al. Low-coverage massively parallel pyrosequencing of cDNAs enables proteomics in non-model species: Comparison of a species-specific database generated by pyrosequencing with databases from related species for proteome analysis of pea chloroplast envelopes. Journal of Biotechnology. 2008;136(1-2):44-53.Proteomics is a valuable tool for establishing and comparing the protein content of defined tissues, cell types, or subcellular structures. Its use in non-model species is currently limited because the identification of peptides Critically depends on sequence databases. In this study, we explored the potential of a preliminary cDNA database for the non-model species Pisum sativum created by a small number of massively parallel pyrosequencing (MPSS) runs for its use in proteomics and compared it to comprehensive cDNA databases from Medicago truncatula and Arabidopsis thaliana created by Sanger sequencing. Each database was used to identify Proteins from a pea leaf chloroplast envelope preparation. It is shown that the pea database identified more proteins with higher accuracy, although the sequence quality was low and the sequence contigs were short compared to databases from model species. Although the number of identified proteins in non-species-specific databases could potentially be increased by lowering the threshold for Successful protein identifications, this strategy markedly increases the number of wrongly identified proteins. The identification rate with non-species-specific databases correlated with spectral abundance but not with the predicted membrane helix content, and Strong conservation is necessary but not sufficient for protein identification with a non-species-specific database. It is concluded that massively Parallel sequencing of cDNAs substantially increases the power Of proteomics in non-model species. (C) 2008 Elsevier B.V. All rights reserved

    Intestinal Microbiota-Dependent Phosphatidylcholine Metabolites, Diastolic Dysfunction, and Adverse Clinical Outcomes in Chronic Systolic Heart Failure

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    Background: Trimethylamine-N-oxide (TMAO) has been linked to increased cardiovascular risk. We aimed to determine the prognostic value of TMAO and its dietary precursors, choline and betaine, in heart failure (HF). Methods and Results: In 112 patients with chronic systolic HF with comprehensive echocardiographic evaluation, we measured plasma TMAO, choline, and betaine by mass spectrometry. Median (interquartile range) TMAO levels, choline, and betaine levels were 5.8 (3.6–12.1) μmol/L, 10.9 (8.4–14.0) μmol/L, and 43.8 (37.1–53.0) μmol/L, respectively, and were correlated with each other (all P \u3c .0001 for both). TMAO levels were significantly higher in patients with diabetes mellitus (9.4 [4.9–13.2] vs 4.8 [3.4–9.8] μmol/L; P = .005) and in subjects with New York Heart Association functional class III or greater (7.0 [4.7–14.8] vs 4.7 [3.4–11.3] μmol/L; P = .02). Elevated TMAO, choline, and betaine levels were each associated with higher plasma N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels and more advanced left ventricular diastolic dysfunction, but not systolic dysfunction or inflammatory and endothelial biomarkers. Higher choline (hazard ratio [HR] 1.64, 95% CI 1.22–2.20; P = .001), betaine (HR 1.51, 95% CI 1.10–2.08; P = .01), and TMAO (HR 1.48, 95% CI 1.10–1.96; P = .01) predicted increased risk for 5-year adverse clinical events (death/transplantation). Only higher TMAO levels predicted incident adverse clinical events independently from age, estimated glomerular filtration rate, mitral E/septal Ea, and NT-proBNP levels (HR 1.46, 95% CI 1.03–2.14; P = .03). Conclusion: Elevated plasma TMAO, choline, and betaine levels are each associated with more advanced left ventricular diastolic dysfunction and portend poorer long-term adverse clinical outcomes in chronic systolic HF. However, only higher plasma TMAO was associated with poor prognosis after adjustment for cardiorenal indices
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