Septic shock is correlated with asymmetrical dimethyl arginine levels, which may be influenced by a polymorphism in the dimethylarginine dimethylaminohydrolase II gene: a prospective observational study

INTRODUCTION: Asymmetrical dimethyl arginine (ADMA) is an endogenous non-selective inhibitor of nitric oxide synthase that may influence the severity of organ failure and the occurrence of shock secondary to an infectious insult. Levels may be genetically determined by a promoter polymorphism in a regulatory gene encoding dimethylarginine dimethylaminohydrolase II (DDAH II), which functions by metabolising ADMA to citrulline. The aim of this study was to examine the association between ADMA levels and the severity of organ failure and shock in severe sepsis and also to assess the influence of a promoter polymorphism in DDAH II on ADMA levels. METHODS: A prospective observational study was designed, and 47 intensive care unit (ICU) patients with severe sepsis and 10 healthy controls were enrolled. Serum ADMA and IL-6 were assayed on admission to the ICU and seven days later. Allelic variation for a polymorphism at position -449 in the DDAH II gene was assessed in each patient. Clinical and demographic details were also collected. RESULTS: On day 1 more ADMA was detectable in the ICU group than in the control group (p = 0.005). Levels subsequently increased during the first week in ICU (p = 0.001). ADMA levels were associated with vasopressor requirements on day one (p = 0.001). ADMA levels and Sequential Organ Failure Assessment scores were directly associated on day one (p = 0.0001) and day seven (p = 0.002). The degree of acidaemia and lactaemia was directly correlated with ADMA levels at both time points (p < 0.01). On day seven, IL-6 was directly correlated with ADMA levels (p = 0.006). The variant allele with G at position -449 in the DDAH II gene was associated with increased ADMA concentrations at both time points (p < 0.05). CONCLUSION: Severity of organ failure, inflammation and presence of early shock in severe sepsis are associated with increased ADMA levels. ADMA concentrations may be influenced by a polymorphism in the DDAH II gene

Habitual physical activity and cardiometabolic risk factors in adults with cerebral palsy

2014 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license(http://creativecommons.org/licenses/by/3.0/).This article has been made available through the Brunel Open Access Publishing Fund.Adults with cerebral palsy (CP) are known to participate in reduced levels of total physical activity. There is no information available however, regarding levels of moderate-to-vigorous physical activity (MVPA) in this population. Reduced participation in MVPA is associated with several cardiometabolic risk factors. The purpose of this study was firstly to compare levels of sedentary, light, MVPA and total activity in adults with CP to adults without CP. Secondly, the objective was to investigate the association between physical activity components, sedentary behavior and cardiometabolic risk factors in adults with CP. Adults with CP (n = 41) age 18–62 yr (mean ± SD = 36.5 ± 12.5 yr), classified in Gross Motor Function Classification System level I (n = 13), II (n = 18) and III (n = 10) participated in this study. Physical activity was measured by accelerometry in adults with CP and in age- and sex-matched adults without CP over 7 days. Anthropometric indicators of obesity, blood pressure and several biomarkers of cardiometabolic disease were also measured in adults with CP. Adults with CP spent less time in light, moderate, vigorous and total activity, and more time in sedentary activity than adults without CP (p < 0.01 for all). Moderate physical activity was associated with waist-height ratio when adjusted for age and sex (β = −0.314, p < 0.05). When further adjustment was made for total activity, moderate activity was associated with waist-height ratio (β = −0.538, p < 0.05), waist circumference (β = −0.518, p < 0.05), systolic blood pressure (β = −0.592, p < 0.05) and diastolic blood pressure (β = −0.636, p < 0.05). Sedentary activity was not associated with any risk factor. The findings provide evidence that relatively young adults with CP participate in reduced levels of MVPA and spend increased time in sedentary behavior, potentially increasing their risk of developing cardiometabolic disease

Postprandial effect of dietary fat quantity and quality on arterial stiffness and wave reflection: a randomised controlled trial.

BACKGROUND: Arterial stiffness is a component of vascular function and an established risk factor for cardiovascular disease. There is a lack of conclusive evidence on the effect of a meal rich in monounsaturated fat (MUFA) compared with an isoenergetic meal rich in saturated fat (SFA) on postprandial vascular function and specifically on arterial stiffness. METHODS: Twenty healthy, non-smoking males (BMI 24???2 kg/m2; age 37.7???14.4 y) participated in this single-blind, randomised, cross-over dietary intervention study. Each subject was randomised to receive a high-fat test-meal (3 MJ; 56???2 g fat) at breakfast on 2 separate occasions, one rich in oleic acid (MUFA-meal) and one rich in palmitic acid (SFA-meal), and the meals were isoenergetic. Blood pressure (BP), arterial stiffness (PWV) and arterial wave reflection (augmentation index, AIx) were measured using applanation tonometry at baseline and every 30 minutes up to 4 hours after the ingestion of the test-meals. RESULTS: All subjects completed both arms of the dietary intervention. There was no significant difference in BP parameters, PWV or AIx at baseline between the two treatments (P?>?0.05). There was a significant increase in brachial and aortic BP, mean arterial pressure (MAP), heart rate and PVW (time, P??0.05). There was a significant reduction in AIx (time, P??0.05). There was no difference in AIx between the two treatments (treatment*time, P?>?0.05). However, the reduction in heart rate corrected augmentation index (AIx75) was significant when corrected for the increase in MAP (time, P??0.05). CONCLUSIONS: This study has demonstrated a BP dependent increase in PWV and a decrease in arterial wave reflection in the four hour period in response to a high-fat meal. There was no evidence however that replacement of some of the SFA with MUFA had a differential effect on these parameters. The study highlights the need for further research to understand the effects of the substitution of SFA with MUFA on non-serum, new and emerging risk factors for CVD such as arterial stiffness

Habitual physical activity and cardiometabolic risk factors in adults with cerebral palsy

Adults with cerebral palsy (CP) are known to participate in reduced levels of total physical activity. There is no information available however, regarding levels of moderate-to-vigorous physical activity (MVPA) in this population. Reduced participation in MVPA is associated with several cardiometabolic risk factors. The purpose of this study was firstly to compare levels of sedentary, light, MVPA and total activity in adults with CP to adults without CP. Secondly, the objective was to investigate the association between physical activity components, sedentary behavior and cardiometabolic risk factors in adults with CP. Adults with CP (n = 41) age 18?62 yr (mean ? SD = 36.5 ? 12.5 yr), classified in Gross Motor Function Classification System level I (n = 13), II (n = 18) and III (n = 10) participated in this study. Physical activity was measured by accelerometry in adults with CP and in age- and sex-matched adults without CP over 7 days. Anthropometric indicators of obesity, blood pressure and several biomarkers of cardiometabolic disease were also measured in adults with CP. Adults with CP spent less time in light, moderate, vigorous and total activity, and more time in sedentary activity than adults without CP (p &lt; 0.01 for all). Moderate physical activity was associated with waist-height ratio when adjusted for age and sex (? = ?0.314, p &lt; 0.05). When further adjustment was made for total activity, moderate activity was associated with waist-height ratio (? = ?0.538, p &lt; 0.05), waist circumference (? = ?0.518, p &lt; 0.05), systolic blood pressure (? = ?0.592, p &lt; 0.05) and diastolic blood pressure (? = ?0.636, p &lt; 0.05). Sedentary activity was not associated with any risk factor. The findings provide evidence that relatively young adults with CP participate in reduced levels of MVPA and spend increased time in sedentary behavior, potentially increasing their risk of developing cardiometabolic disease

Septic shock is correlated with asymmetrical dimethyl arginine levels, which may be influenced by a polymorphism in the dimethylarginine dimethylaminohydrolase II gene: a prospective observational study.

peer-reviewedINTRODUCTION: Asymmetrical dimethyl arginine (ADMA) is an endogenous non-selective inhibitor of nitric oxide synthase that may influence the severity of organ failure and the occurrence of shock secondary to an infectious insult. Levels may be genetically determined by a promoter polymorphism in a regulatory gene encoding dimethylarginine dimethylaminohydrolase II (DDAH II), which functions by metabolising ADMA to citrulline. The aim of this study was to examine the association between ADMA levels and the severity of organ failure and shock in severe sepsis and also to assess the influence of a promoter polymorphism in DDAH II on ADMA levels. METHODS: A prospective observational study was designed, and 47 intensive care unit (ICU) patients with severe sepsis and 10 healthy controls were enrolled. Serum ADMA and IL-6 were assayed on admission to the ICU and seven days later. Allelic variation for a polymorphism at position -449 in the DDAH II gene was assessed in each patient. Clinical and demographic details were also collected. RESULTS: On day 1 more ADMA was detectable in the ICU group than in the control group (p = 0.005). Levels subsequently increased during the first week in ICU (p = 0.001). ADMA levels were associated with vasopressor requirements on day one (p = 0.001). ADMA levels and Sequential Organ Failure Assessment scores were directly associated on day one (p = 0.0001) and day seven (p = 0.002). The degree of acidaemia and lactaemia was directly correlated with ADMA levels at both time points (p < 0.01). On day seven, IL-6 was directly correlated with ADMA levels (p = 0.006). The variant allele with G at position -449 in the DDAH II gene was associated with increased ADMA concentrations at both time points (p < 0.05). CONCLUSION: Severity of organ failure, inflammation and presence of early shock in severe sepsis are associated with increased ADMA levels. ADMA concentrations may be influenced by a polymorphism in the DDAH II gene

Verification of Abbott 25-OH-vitamin D assay on the architect system

Objectives: Analytical and clinical verification of both old and new generations of the Abbott total 25-hydroxyvitamin D (25OHD) assays, and an examination of reference Intervals. Methods: Determination of between-run precision, and Deming comparison between patient sample results for 25OHD on the Abbott Architect, DiaSorin Liaison and AB SCIEX API 4000 (LC-MS/MS). Establishment of uncertainty of measurement for 25OHD Architect methods using old and new generations of the reagents, and estimation of reference interval in healthy Irish population. Results: For between-run precision the manufacturer claims 2.8% coefficients of variation (CVs) of 2.8% and 4.6% for their high and low controls, respectively. Our instrument showed CVs between 4% and 6.2% for all levels of the controls on both generations of the Abbott reagents. The between-run uncertainties were 0.28 and 0.36, with expanded uncertainties 0.87 and 0.98 for the old and the new generations of reagent, respectively. The difference between all methods used for patients’ samples was within total allowable error, and the instruments produced clinically equivalent results. The results covered the medical decision points of 30, 40, 50 and 125 nmol/L. The reference interval for total 25OHD in our healthy Irish subjects was lower than recommended levels (24–111 nmol/L). Conclusion: In a clinical laboratory Abbott 25OHD immunoassays are a useful, rapid and accurate method for measuring total 25OHD. The new generation of the assay was confirmed to be reliable, accurate, and a good indicator for 25OHD measurement. More study is needed to establish reference intervals that correctly represent the healthy population in Ireland

Geomapping Vitamin D Status in a Large City and Surrounding Population—Exploring the Impact of Location and Demographics

Vitamin D status was assessed in a large urban area to compare differences in deficiency and to geomap the results. In total, 36,466 participants from 28 geographical areas were identified in this cross-sectional, retrospective analysis of general practitioner (GP)-requested 25(OH)D tests at St James&rsquo;s Hospital, Dublin between 2014 and 2018. The population were community-dwelling adults, median age 50.7 (18&ndash;109 years) with 15% of participants deficient (&lt;30 nmol/L), rising to 23% in the winter. Deficiency was greatest in younger (18&ndash;39 years) and oldest (80+ years) adults, and in males versus females (18% vs. 11%, p &lt; 0.001). Season was the biggest predictor of deficiency (OR 4.44, winter versus summer, p &lt; 0.001), followed by location (west Dublin OR 2.17, north Dublin 1.54, south Dublin 1.42 versus rest of Ireland, p &lt; 0.001) where several urban areas with an increased prevalence of deficiency were identified. There was no improvement in 25(OH)D over the 5-year period despite increased levels of testing. One in four adults were vitamin D deficient in the winter, with significant variations across locations and demographics. Overall this study identifies key groups at risk of 25(OH)D deficiency and insufficiency, thus providing important public health information for the targeting of interventions to optimise 25(OH)D. Mandatory fortification may be necessary to address this widespread inadequacy