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 μm (PM$_{2.5}$)], 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 PM$_{2.5}$ 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 PM$_{2.5}$ and BP. Conclusions: We observed positive associations between BP and BC, but not between BP and PM$_{2.5}$, 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

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 μm (PM2.5)] has been associated with autonomic dysregulation.Objective We hypothesized that PM2.5 influences postural changes in systolic blood pressure (ΔSBP) and in diastolic blood pressure (ΔDBP) and that this effect is modified by genes thought to be related to chronic lung disease. Methods: We measured blood pressure in participants every 3–5 years. ΔSBP and ΔDBP 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 × PM2.5 interactions on ΔSBP and ΔDBP 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 ΔDBP. 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 ΔSBP. Because SNPs associated with ΔSBP in our analysis are in genes along the renin–angiotensin 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 μm (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

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 × 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 × 10-2 (water/ethanol) and 2.6 × 10-2 L mol-1 (water/DMSO). DPH lifetime measurements in the absence and presence of water resulted in 7.1 × 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, não varia com o teor de água em solvente orgânico. Tem-se a banda de monômeros igual àquela em etanol puro. A absorção não muda até o limite de 54 e 46% de água em etanol e DMSO, respectivamente, para [DPH] = 5,0 × 10-6 mol L-1 a 30 °C. Entretanto, em misturas com água muito abaixo desses conteúdos críticos, observou-se um decaimento intenso de fluorescência enquanto a absorção manteve-se constante. Propõe-se que moléculas de água atuam como supressores dos estados excitados e a constante de supressão de Stern-Volmer através de intensidade relativas, resultou em 7,4 × 10-2 (água/etanol) e 2,6 × 10-2 L mol-1 (água/DMSO). Os tempos de vida do DPH na ausência e presença do supressor forneceram constantes de 7,1 × 10-2 L mol-1 em água/etanol, indicando supressão dinâmica. Em investigações 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