Increased Asymmetric Dimethylarginine in Severe Falciparum Malaria: Association with Impaired Nitric Oxide Bioavailability and Fatal Outcome

Asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), is a predictor of mortality in critical illness. Severe malaria (SM) is associated with decreased NO bioavailability, but the contribution of ADMA to the pathogenesis of impaired NO bioavailability and adverse outcomes in malaria is unknown. In adults with and without falciparum malaria, we tested the hypotheses that plasma ADMA would be: 1) increased in proportion to disease severity, 2) associated with impaired vascular and pulmonary NO bioavailability and 3) independently associated with increased mortality. We assessed plasma dimethylarginines, exhaled NO concentrations and endothelial function in 49 patients with SM, 78 with moderately severe malaria (MSM) and 19 healthy controls (HC). Repeat ADMA and endothelial function measurements were performed in patients with SM. Multivariable regression was used to assess the effect of ADMA on mortality and NO bioavailability. Plasma ADMA was increased in SM patients (0.85 µM; 95% CI 0.74–0.96) compared to those with MSM (0.54 µM; 95%CI 0.5–0.56) and HCs (0.64 µM; 95%CI 0.58–0.70; p<0.001). ADMA was an independent predictor of mortality in SM patients with each micromolar elevation increasing the odds of death 18 fold (95% CI 2.0–181; p = 0.01). ADMA was independently associated with decreased exhaled NO (rs = −0.31) and endothelial function (rs = −0.32) in all malaria patients, and with reduced exhaled NO (rs = −0.72) in those with SM. ADMA is increased in SM and associated with decreased vascular and pulmonary NO bioavailability. Inhibition of NOS by ADMA may contribute to increased mortality in severe malaria

Asymmetric Dimethylarginine, Endothelial Nitric Oxide Bioavailability and Mortality in Sepsis

Background: Plasma concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxidesynthase, are raised in patients with chronic vascular disease, causing increased cardiovascular risk and endothelialdysfunction, but the role of ADMA in acute inflammatory states is less well defined.Methods and Results: In a prospective longitudinal study in 67 patients with acute sepsis and 31 controls, digitalmicrovascular reactivity was measured by peripheral arterial tonometry and blood was collected at baseline and 2&ndash;4 dayslater. Plasma ADMA and L-arginine concentrations were determined by high performance liquid chromatography. Baselineplasma L-arginine: ADMA ratio was significantly lower in sepsis patients (median [IQR] 63 [45&ndash;103]) than in hospital controls(143 [123&ndash;166], p,0.0001) and correlated with microvascular reactivity (r = 0.34, R2 = 0.12, p = 0.02). Baseline plasma ADMAwas independently associated with 28-day mortality (Odds ratio [95% CI] for death in those in the highest quartile($0.66 mmol/L) = 20.8 [2.2&ndash;195.0], p = 0.008), and was independently correlated with severity of organ failure. Increase inADMA over time correlated with increase in organ failure and decrease in microvascular reactivity.Conclusions: Impaired endothelial and microvascular function due to decreased endothelial NO bioavailability is a potentialmechanism linking increased plasma ADMA with organ failure and death in sepsis

Incidence of self-reported brain injury and the relationship with substance abuse: findings from a longitudinal community survey

<p>Abstract</p> <p>Background</p> <p>Traumatic or serious brain injury (BI) has persistent and well documented adverse outcomes, yet 'mild' or 'moderate' BI, which often does not result in hospital treatment, accounts for half the total days of disability attributed to BI. There are currently few data available from community samples on the incidence and correlates of these injuries. Therefore, the study aimed to assess the 1) incidence of self-reported mild (not requiring hospital admission) and moderate (admitted to hospital)) brain injury (BI), 2) causes of injury 3) physical health scores and 4) relationship between BI and problematic alcohol or marijuana use.</p> <p>Methods</p> <p>An Australian community sequential-cohort study (cohorts aged 20-24, 40-44 and 60-64 years at wave one) used a survey methodology to assess BI and substance use at baseline and four years later.</p> <p>Results</p> <p>Of the 7485 wave one participants, 89.7% were re-interviewed at wave two. There were 56 mild (230.8/100000 person-years) and 44 moderate BI (180.5/100000 person-years) reported between waves one and two. Males and those in the 20-24 year cohort had increased risk of BI. Sports injury was the most frequent cause of BI (40/100) with traffic accidents being a greater proportion of moderate (27%) than mild (7%) BI. Neither alcohol nor marijuana problems at wave one were predictors of BI. BI was not a predictor of developing substance use problems by wave two.</p> <p>Conclusions</p> <p>BI were prevalent in this community sample, though the incidence declined with age. Factors associated with BI in community samples differ from those reported in clinical samples (e.g. typically traumatic brain injury with traffic accidents the predominate cause). Further, detailed evaluation of the health consequences of these injuries is warranted.</p

Changes in health risk behaviors of elementary school students in northern Taiwan from 2001 to 2003: results from the child and adolescent behaviors in long-term evolution study

[[abstract]]Background: Previous research has indicated that children's behaviors have long-term effects on later life. Hence it is important to monitor the development of health risk behaviors in childhood. This study examined the changes in health risk behaviors in fourth- to sixth-grade students in northern Taiwan from 2001 to 2003. Methods: The Child and Adolescent Behaviors in Long-Term Evolution (CABLE) study collected data from 1,820 students from 2001 to 2003 (students were 9 or 10 years old in 2001). Exploratory factor analysis was used to determine the aggregation of health risk behaviors. A linear growth curve model was used to determine whether health risk behaviors changed over time. Results: Of the 13 behaviors, staying up late and eating snacks late at night were the most prevalent (82.3% of subjects in 2001, 81.8% in 2002, 88.5% in 2003) and second most prevalent (68.7%, 67.4%, 71.6%) behaviors, respectively, from 2001 to 2003. The three least prevalent health risk behaviors were chewing betel nut (1.0%, 0.4%, 0.2%), smoking (1.4%, 1.0%, 0.8%), and drinking alcohol (8.5%, 6.0%, 5.2%). The frequencies of swearing and staying up late showed the greatest significant increases with time. On the other hand, suppressing urination and drinking alcohol decreased over time. Using exploratory factor analysis, we aggregated the health risk behaviors into three categories: unhealthy habits, aggressive behaviors, and substance use. Although students did not display high levels of aggressive behavior or experimentation with substances, the development of these behaviors in a small proportion of students should not be ignored. The results of the linear growth curve model indicated that unhealthy habits and aggressive behaviors increased over time. However, substance use slightly decreased over time. Conclusion: We found that some health risk behaviors increased with time while others did not. Unhealthy habits and aggressive behaviors increased, whereas substance use slightly decreased during this period. Educational professionals should pay attention to the different patterns of change in these behaviors in elementary school students

Falls and falls efficacy: the role of sustained attention in older adults

<p>Abstract</p> <p>Background</p> <p>Previous evidence indicates that older people allocate more of their attentional resources toward their gait and that the attention-related changes that occur during aging increase the risk of falls. The aim of this study was to investigate whether performance and variability in sustained attention is associated with falls and falls efficacy in older adults.</p> <p>Methods</p> <p>458 community-dwelling adults aged ≥ 60 years underwent a comprehensive geriatric assessment. Mean and variability of reaction time (RT), commission errors and omission errors were recorded during a fixed version of the Sustained Attention to Response Task (SART). RT variability was decomposed using the Fast Fourier Transform (FFT) procedure, to help characterise variability associated with the arousal and vigilance aspects of sustained attention.</p> <p>The number of self-reported falls in the previous twelve months, and falls efficacy (Modified Falls Efficacy Scale) were also recorded.</p> <p>Results</p> <p>Significant increases in the mean and variability of reaction time on the SART were significantly associated with both falls (p < 0.01) and reduced falls efficacy (p < 0.05) in older adults. An increase in omission errors was also associated with falls (p < 0.01) and reduced falls efficacy (p < 0.05). Upon controlling for age and gender affects, logistic regression modelling revealed that increasing variability associated with the vigilance (top-down) aspect of sustained attention was a retrospective predictor of falling (p < 0.01, OR = 1.14, 95% CI: 1.03 - 1.26) in the previous year and was weakly correlated with reduced falls efficacy in non-fallers (p = 0.07).</p> <p>Conclusions</p> <p>Greater variability in sustained attention is strongly correlated with retrospective falls and to a lesser degree with reduced falls efficacy. This cognitive measure may provide a novel and valuable biomarker for falls in older adults, potentially allowing for early detection and the implementation of preventative intervention strategies.</p

Socio-demographic and health-related factors associated with cognitive impairment in the elderly in Taiwan

<p>Abstract</p> <p>Background</p> <p>Cognitive impairment is an age-related condition as the rate of cognitive decline rapidly increases with aging. It is especially important to better understand factors involving in cognitive decline for the countries where the older population is growing rapidly. The aim of this study was to examine the association between socio-demographic and health-related factors and cognitive impairment in the elderly in Taiwan.</p> <p>Methods</p> <p>We analysed data from 2119 persons aged 65 years and over who participated in the 2005 National Health Interview Survey. Cognitive impairment was defined as having the score of the Mini Mental State Examination lower than 24. The χ²test and multiple logistic regression models were used to evaluate the association between cognitive impairment and variables of socio-demography, chronic diseases, geriatric conditions, lifestyle, and dietary factors.</p> <p>Results</p> <p>The prevalence of cognitive impairment was 22.2%. Results of multivariate analysis indicated that low education, being single, low social support, lower lipid level, history of stroke, physical inactivity, non-coffee drinking and poor physical function were associated with a higher risk of cognitive impairment.</p> <p>Conclusion</p> <p>Most of the characteristics in relation to cognitive impairment identified in our analysis are potentially modifiable. These results suggest that improving lifestyle behaviours such as regular exercise and increased social participation could help prevent or decrease the risk of cognitive impairment. Further investigations using longitudinal data are needed to clarify our findings.</p

An Observational Cohort Study of the Kynurenine to Tryptophan Ratio in Sepsis: Association with Impaired Immune and Microvascular Function

Both endothelial and immune dysfunction contribute to the high mortality rate in human sepsis, but the underlying mechanisms are unclear. In response to infection, interferon-γ activates indoleamine 2,3-dioxygenase (IDO) which metabolizes the essential amino acid tryptophan to the toxic metabolite kynurenine. IDO can be expressed in endothelial cells, hepatocytes and mononuclear leukocytes, all of which contribute to sepsis pathophysiology. Increased IDO activity (measured by the kynurenine to tryptophan [KT] ratio in plasma) causes T-cell apoptosis, vasodilation and nitric oxide synthase inhibition. We hypothesized that IDO activity in sepsis would be related to plasma interferon-γ, interleukin-10, T cell lymphopenia and impairment of microvascular reactivity, a measure of endothelial nitric oxide bioavailability. In an observational cohort study of 80 sepsis patients (50 severe and 30 non-severe) and 40 hospital controls, we determined the relationship between IDO activity (plasma KT ratio) and selected plasma cytokines, sepsis severity, nitric oxide-dependent microvascular reactivity and lymphocyte subsets in sepsis. Plasma amino acids were measured by high performance liquid chromatography and microvascular reactivity by peripheral arterial tonometry. The plasma KT ratio was increased in sepsis (median 141 [IQR 64–235]) compared to controls (36 [28–52]); p<0.0001), and correlated with plasma interferon-γ and interleukin-10, and inversely with total lymphocyte count, CD8+ and CD4+ T-lymphocytes, systolic blood pressure and microvascular reactivity. In response to treatment of severe sepsis, the median KT ratio decreased from 162 [IQR 100–286] on day 0 to 89 [65–139] by day 7; p = 0.0006) and this decrease in KT ratio correlated with a decrease in the Sequential Organ Failure Assessment score (p<0.0001). IDO-mediated tryptophan catabolism is associated with dysregulated immune responses and impaired microvascular reactivity in sepsis and may link these two fundamental processes in sepsis pathophysiology

RNA-Seq reveals large quantitative differences between the transcriptomes of outbreak and non-outbreak locusts

Outbreaks of locust populations repeatedly devastate economies and ecosystems in large parts of the world. The consequent behavioural shift from solitarious to gregarious and the concomitant changes in the locusts’ biology are of relevant scientific interest. Yet, research on the main locust species has not benefitted from recent advances in genomics. In this first RNA-Seq study on Schistocerca gregaria, we report two transcriptomes, including many novel genes, as well as differential gene expression results. In line with the large biological differences between solitarious and gregarious locusts, almost half of the transcripts are differentially expressed between their central nervous systems. Most of these transcripts are over-expressed in the gregarious locusts, suggesting positive correlations between the levels of activity at the population, individual, tissue and gene expression levels. We group these differentially expressed transcripts by gene function and highlight those that are most likely to be associated with locusts’ phase change either in a species-specific or general manner. Finally, we discuss our findings in the context of population-level and physiological events leading to gregariousness.M. Bakkali wishes to thank the Spanish Ministerio de Ciencia y Tecnología for the for the Ramón y Cajal fellowship and for the BFU2010-16438 grant that supported both this research and the FPI studentship to Rubén Martín Blázquez. We thank Mrs. Pernille Lavgesen for revision of the English language writing of this manuscript. We also thank the editor for the valuable comments on the manuscript

Falls in the general elderly population: a 3- and 6- year prospective study of risk factors using data from the longitudinal population study 'Good ageing in Skane'.

Accidental falls in the elderly are a major health problem, despite extensive research on risk factors and prevention. Only a limited number of multifactorial, long-term prospective studies have been performed on risk factors for falls in the general elderly population. The aim of this study was to identify risk factors predicting falls in a general elderly population after three and six years, using a prospective design

Protocol for a randomised controlled trial investigating the effectiveness of an online e-health application compared to attention placebo or sertraline in the treatment of generalised anxiety disorder

Background: Generalised anxiety disorder (GAD) is a high prevalence, chronic psychiatric disorder which commonly presents early in the lifespan. Internet e-health applications have been found to be successful in reducing symptoms of anxiety and stress for post traumatic stress disorder (PTSD), panic disorder, social phobia and depression. However, to date, there is little evidence for the effectiveness of e-health applications in adult GAD. There are no studies which have directly compared e-health applications with recognised evidence-based medication. This study aims to determine the effectiveness of a web-based program for treating GAD relative to sertraline and attention placebo.Methods/Design: 120 community-dwelling participants, aged 18-30 years with a clinical diagnosis of GAD will be recruited from the Australian Electoral Roll. They will be randomly allocated to one of three conditions: (i) an online treatment program for GAD, E-couch (ii) pharmacological treatment with a selective serotonin re-uptake inhibitor (SSRI), sertraline (a fixed-flexible dose of 25-100 mg/day) or (iii) an attention control placebo, HealthWatch. The treatment program will be completed over a 10 week period with a 12 month follow-up.Discussion: As of February 2010, there were no registered trials evaluating the effectiveness of an e-health application for GAD for young adults. Similarly to date, this will be the first trial to compare an e-health intervention with a pharmacological treatment.Trial Registration: Current Controlled Trials ISRCTN76298775