458 research outputs found
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Black Carbon Exposure, Oxidative Stress Genes, and Blood Pressure in a Repeated-measures Study
Background: Particulate matter (PM) air pollution has been associated with cardiovascular morbidity and mortality, and elevated blood pressure (BP) is a known risk factor for cardiovascular disease. A small number of studies have investigated the relationship between PM and BP and found mixed results. Evidence suggests that traffic-related air pollution contributes significantly to PM-related cardiovascular effects. Objectives: We hypothesized that black carbon (BC), a traffic-related combustion by-product, would be more strongly associated with BP than would fine PM [aerodynamic diameter †2.5 ÎŒm (PM)], a heterogeneous PM mixture, and that these effects would be larger among participants with genetic variants associated with impaired antioxidative defense. Methods: We performed a repeated-measures analysis in elderly men to analyze associations between PM and BC exposure and BP using mixed-effects models with random intercepts, adjusting for potential confounders. We also examined statistical interaction between BC and genetic variants related to oxidative stress defense: GSTM1, GSTP1, GSTT1, NQO1, catalase, and HMOX-1. Results: A 1-SD increase in BC concentration was associated with a 1.5-mmHg increase in systolic BP [95% confidence interval (CI), 0.1â2.8] and a 0.9-mmHg increase in diastolic BP (95% CI, 0.2â1.6). We observed no evidence of statistical interaction between BC and any of the genetic variants examined and found no association between PM and BP. Conclusions: We observed positive associations between BP and BC, but not between BP and PM, and found no evidence of effect modification of the association between BC and BP by gene variants related to antioxidative defense
Unguided low intensity cognitive behaviour therapy for anxiety and depression during the COVID-19 pandemic: A randomised trial.
The COVID-19 pandemic has had a severe impact on mental health worldwide, with increased rates of anxiety and depression widely documented. The aim of this study was to examine unguided low intensity cognitive behaviour therapy for anxiety and depression during the pandemic. A sample of 225 individuals in Australia and the United Kingdom (M age 37.79, SD = 14.02, range 18-80 years; 85% female) were randomised into intervention or waitlist control. The intervention group demonstrated significant decreases in anxiety (d = 0.36 [0.18, 0.54]) and depression (d = 0.28 [0.11, 0.45]) compared to controls. The majority of participants (96%) rated the intervention as useful, and most (83%) reported they spent 30 min or less reading the guide, with 83% agreeing the intervention was easy to read. The results indicate that low intensity cognitive behaviour therapy has efficacy in reducing anxiety and depression during the COVID-19 pandemic. There is an urgent need to disseminate low intensity psychological therapies to improve mental health in this challenging time
On the computation of zone and double zone diagrams
Classical objects in computational geometry are defined by explicit
relations. Several years ago the pioneering works of T. Asano, J. Matousek and
T. Tokuyama introduced "implicit computational geometry", in which the
geometric objects are defined by implicit relations involving sets. An
important member in this family is called "a zone diagram". The implicit nature
of zone diagrams implies, as already observed in the original works, that their
computation is a challenging task. In a continuous setting this task has been
addressed (briefly) only by these authors in the Euclidean plane with point
sites. We discuss the possibility to compute zone diagrams in a wide class of
spaces and also shed new light on their computation in the original setting.
The class of spaces, which is introduced here, includes, in particular,
Euclidean spheres and finite dimensional strictly convex normed spaces. Sites
of a general form are allowed and it is shown that a generalization of the
iterative method suggested by Asano, Matousek and Tokuyama converges to a
double zone diagram, another implicit geometric object whose existence is known
in general. Occasionally a zone diagram can be obtained from this procedure.
The actual (approximate) computation of the iterations is based on a simple
algorithm which enables the approximate computation of Voronoi diagrams in a
general setting. Our analysis also yields a few byproducts of independent
interest, such as certain topological properties of Voronoi cells (e.g., that
in the considered setting their boundaries cannot be "fat").Comment: Very slight improvements (mainly correction of a few typos); add DOI;
Ref [51] points to a freely available computer application which implements
the algorithms; to appear in Discrete & Computational Geometry (available
online
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Postural Changes in Blood Pressure Associated with Interactions between Candidate Genes for Chronic Respiratory Diseases and Exposure to Particulate Matter
Background: Fine particulate matter [aerodynamic diameter †2.5 ÎŒm (PM2.5)] has been associated with autonomic dysregulation.Objective We hypothesized that PM2.5 influences postural changes in systolic blood pressure (ÎSBP) and in diastolic blood pressure (ÎDBP) and that this effect is modified by genes thought to be related to chronic lung disease. Methods: We measured blood pressure in participants every 3â5 years. ÎSBP and ÎDBP were calculated as sitting minus standing SBP and DBP. We averaged PM2.5 over 48 hr before study visits and analyzed 202 single nucleotide polymorphisms (SNPs) in 25 genes. To address multiple comparisons, data were stratified into a split sample. In the discovery cohort, the effects of SNP Ă PM2.5 interactions on ÎSBP and ÎDBP were analyzed using mixed models with subject-specific random intercepts. We defined positive outcomes as p < 0.1 for the interaction; we analyzed only these SNPs in the replicate cohort and confirmed them if p < 0.025 with the same sign. Confirmed associations were analyzed within the full cohort in models adjusted for anthropometric and lifestyle factors. Results: Nine hundred forty-five participants were included in our analysis. One interaction with rs9568232 in PHD finger protein 11 (PHF11) was associated with greater ÎDBP. Interactions with rs1144393 in matrix metalloprotease 1 (MMP1) and rs16930692, rs7955200, and rs10771283 in inositol 1,4,5-triphosphate receptor, type 2 (ITPR2) were associated with significantly greater ÎSBP. Because SNPs associated with ÎSBP in our analysis are in genes along the reninâangiotensin pathway, we then examined medications affecting that pathway and observed significant interactions for angiotensin receptor blockers but not angiotensin-converting enzyme inhibitors with PM2.5. Conclusions: PM2.5 influences blood pressure and autonomic function. This effect is modified by genes and drugs that also act along this pathway
Black Carbon Exposure, Oxidative Stress Genes, and Blood Pressure in a Repeated-Measures Study
BACKGROUND. Particulate matter (PM) air pollution has been associated with cardiovascular morbidity and mortality, and elevated blood pressure (BP) is a known risk factor for cardiovascular disease. A small number of studies have investigated the relationship between PM and BP and found mixed results. Evidence suggests that traffic-related air pollution contributes significantly to PM-related cardiovascular effects. OBJECTIVES. We hypothesized that black carbon (BC), a traffic-related combustion by-product, would be more strongly associated with BP than would fine PM [aerodynamic diameter †2.5 Όm (PM2.5)], a heterogeneous PM mixture, and that these effects would be larger among participants with genetic variants associated with impaired antioxidative defense. METHODS. We performed a repeated-measures analysis in elderly men to analyze associations between PM2.5 and BC exposure and BP using mixed-effects models with random intercepts, adjusting for potential confounders. We also examined statistical interaction between BC and genetic variants related to oxidative stress defense: GSTM1, GSTP1, GSTT1, NQO1, catalase, and HMOX-1. RESULTS. A 1-SD increase in BC concentration was associated with a 1.5-mmHg increase in systolic BP [95% confidence interval (CI), 0.1-2.8] and a 0.9-mmHg increase in diastolic BP (95% CI, 0.2-1.6). We observed no evidence of statistical interaction between BC and any of the genetic variants examined and found no association between PM2.5 and BP. CONCLUSIONS. We observed positive associations between BP and BC, but not between BP and PM2.5, and found no evidence of effect modification of the association between BC and BP by gene variants related to antioxidative defense.National Institute of Environmental Health Sciences (ES015172, ES014663); National Cancer Institute (2-T32-CA009330); United States Environmental Protection Agency (R832416); United States Deparment of Veterans Affairs; Massachusetts Veterans Epidemiology Research and Information Cente
Identification and functional characterisation of CRK12:CYC9, a novel cyclin-dependent kinase (CDK)-cyclin complex in Trypanosoma brucei
The protozoan parasite, Trypanosoma brucei, is spread by the tsetse fly and causes trypanosomiasis in humans and animals. Both the life cycle and cell cycle of the parasite are complex. Trypanosomes have eleven cdc2-related kinases (CRKs) and ten cyclins, an unusually large number for a single celled organism. To date, relatively little is known about the function of many of the CRKs and cyclins, and only CRK3 has previously been shown to be cyclin-dependent in vivo. Here we report the identification of a previously uncharacterised CRK:cyclin complex between CRK12 and the putative transcriptional cyclin, CYC9. CRK12:CYC9 interact to form an active protein kinase complex in procyclic and bloodstream T. brucei. Both CRK12 and CYC9 are essential for the proliferation of bloodstream trypanosomes in vitro, and we show that CRK12 is also essential for survival of T. brucei in a mouse model, providing genetic validation of CRK12:CYC9 as a novel drug target for trypanosomiasis. Further, functional characterisation of CRK12 and CYC9 using RNA interference reveals roles for these proteins in endocytosis and cytokinesis, respectively
Association of newborn diseases with weight/length ratio and the adequacy of weight for gestational age
Unusual 1,6-diphenyl-1,3,5-hexatriene (DPH) spectrophotometric behavior in water/ethanol and water/DMSO mixtures
The absorption spectra of DPH at fixed concentration do not change with water content in organic solvents. It exhibits monomer bands, such as those obtained in ethanol. The absorption did not change for solutions up to 54 and 46% of water in ethanol and DMSO, respectively, for [DPH] = 5.0 Ă 10-6 mol L-1 at 30 °C. However, at the same experimental conditions, a gradual sharp decay of the DPH fluorescence is observed. It is proposed that water molecules below these water concentration limits act as quenchers of the excited states of DPH. Stern-Volmer quenching constants by intensities measurements are 7.4 Ă 10-2 (water/ethanol) and 2.6 Ă 10-2 L mol-1 (water/DMSO). DPH lifetime measurements in the absence and presence of water resulted in 7.1 Ă 10-2 L mol-1 in water/ethanol, which pointed out that the process is a dynamic quenching by water molecules. For experiments using DPH as probe, this process can affect data, leading to misunderstanding interpretation.O espectro de absorção de DPH, em concentração fixa, nĂŁo varia com o teor de ĂĄgua em solvente orgĂąnico. Tem-se a banda de monĂŽmeros igual Ă quela em etanol puro. A absorção nĂŁo muda atĂ© o limite de 54 e 46% de ĂĄgua em etanol e DMSO, respectivamente, para [DPH] = 5,0 Ă 10-6 mol L-1 a 30 °C. Entretanto, em misturas com ĂĄgua muito abaixo desses conteĂșdos crĂticos, observou-se um decaimento intenso de fluorescĂȘncia enquanto a absorção manteve-se constante. PropĂ”e-se que molĂ©culas de ĂĄgua atuam como supressores dos estados excitados e a constante de supressĂŁo de Stern-Volmer atravĂ©s de intensidade relativas, resultou em 7,4 Ă 10-2 (ĂĄgua/etanol) e 2,6 Ă 10-2 L mol-1 (ĂĄgua/DMSO). Os tempos de vida do DPH na ausĂȘncia e presença do supressor forneceram constantes de 7,1 Ă 10-2 L mol-1 em ĂĄgua/etanol, indicando supressĂŁo dinĂąmica. Em investigaçÔes de ambientes com esta sonda, este processo deve ser considerado tendo em vista o risco de erros de interpretação
Photoelectrochemical H2 Evolution with a Hydrogenase Immobilized on a TiO2-Protected Silicon Electrode.
The combination of enzymes with semiconductors enables the photoelectrochemical characterization of electron-transfer processes at highly active and well-defined catalytic sites on a light-harvesting electrode surface. Herein, we report the integration of a hydrogenase on a TiO2-coated p-Si photocathode for the photo-reduction of protons to H2. The immobilized hydrogenase exhibits activity on Si attributable to a bifunctional TiO2 layer, which protects the Si electrode from oxidation and acts as a biocompatible support layer for the productive adsorption of the enzyme. The p-Si|TiO2|hydrogenase photocathode displays visible-light driven production of H2 at an energy-storing, positive electrochemical potential and an essentially quantitative faradaic efficiency. We have thus established a widely applicable platform to wire redox enzymes in an active configuration on a p-type semiconductor photocathode through the engineering of the enzyme-materials interface
Inhibition of Acid Sphingomyelinase by Antidepressants Counteracts Stress-Induced Activation of P38-Kinase in Major Depression
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