Objective
The primary objective was to investigate the relationship between periodontitis and hypertension in two independent large surveys. The secondary objective was to ascertain whether systemic ...inflammation had a mediation effect in the association.
Methods
This cross‐sectional study analysed representative samples of the US (n = 3460; NHANES 2009/10) and Korean (n = 4539; 2015 KNHANES VI‐3) populations. The association between periodontitis (exposure), hypertension (outcome) and inflammatory markers C‐reactive protein (CRP) and white blood cell counts (WBC) (mediators) was assessed using multivariate linear and logistic regression models and mediation analysis.
Results
Participants with periodontitis were more likely to have hypertension (NHANES: OR = 1.3, 95% CI: 1.0–1.6, P = 0.025; KNHANES: OR = 1.2, 95% CI: 1.0–1.4, P = 0.041) and actual systolic blood pressure ≥ 140 mmHg (NHANES: OR = 1.6, 95% CI: 1.1–2.3, P < 0.001; KNHANES: OR = 1.3, 95% CI :1.0–1.6, P < 0.031) than those without the disease. These associations were independent of age, gender, BMI, education level, smoking, alcohol consumption, creatinine, physical activity, presence of other comorbidities and confirmed in participants not taking antihypertensive medications. Diagnosis of periodontitis was directly associated with WBC (in both surveys: NHANES: β ± SE = 0.3 ± 0.1, P < 0.004; KNHANES: β ± SE = 0.3 ± 0.1, P < 0.001) and with CRP levels (in one survey: NHANES: β ± SE = 0.1 ± 0.03, P < 0.007; KNHANES: β ± SE = 0.1 ± 0.04, P > 0.213). Mediation analyses confirmed that CRP acted as a mediator in the association between periodontitis and hypertension in both populations (mediated effect: NHANES: β ± SE = 0.010 ± 0.003, P < 0.001; KNHANES: β ± SE = 0.003 ± 0.001, P = 0.015). WBC acted as a mediator in the KNHANES (mediated effect: β ± SE = 0.004 ± 0.001, P = 0.004) whilst in the NHANES, its effect was dependent of CRP inclusion in the model (mediated effect WBC + CRP: β ± SE = 0.002 ± 0.001, P = 0.001).
Conclusions
These findings suggest that periodontitis is closely linked to hypertension and systemic inflammation is, in part, a mediator of this association.
Background and Purpose
Inflammation plays a key role in atherosclerosis. The protective role of angiotensin 1–7 (Ang‐(1–7)) in vascular pathologies suggested the therapeutic use of low MW, ...non‐peptide Ang‐(1–7) mimetics, such as AVE0991. The mechanisms underlying the vaso‐protective effects of AVE0991, a Mas receptor agonist, remain to be explored.
Experimental Approach
We investigated the effects of AVE0991 on the spontaneous atherosclerosis in apolipoprotein E (ApoE)−/− mice, in the context of vascular inflammation and plaque stability.
Key Results
AVE0991 has significant anti‐atherosclerotic properties in ApoE−/− mice and increases plaque stability, by reducing plaque macrophage content, without effects on collagen. Using the descending aorta of chow‐fed ApoE−/− mice, before significant atherosclerotic plaque develops, we gained insight to early events in atherosclerosis. Interestingly, perivascular adipose tissue (PVAT) and adventitial infiltration with macrophages and T‐cells precedes atherosclerotic plaque or the impairment of endothelium‐dependent NO bioavailability (a measure of endothelial function). AVE0991 inhibited perivascular inflammation, by reducing chemokine expression in PVAT and through direct actions on monocytes/macrophages inhibiting their activation, characterized by production of IL‐1β, TNF‐α, CCL2 and CXCL10, and differentiation to M1 phenotype. Pretreatment with AVE0991 inhibited migration of THP‐1 monocytes towards supernatants of activated adipocytes (SW872). Mas receptors were expressed in PVAT and in THP‐1 cells in vitro, and the anti‐inflammatory effects of AVE0991 were partly Mas dependent.
Conclusions and Implications
The selective Mas receptor agonist AVE0991 exhibited anti‐atherosclerotic and anti‐inflammatory actions, affecting monocyte/macrophage differentiation and recruitment to the perivascular space during early stages of atherosclerosis in ApoE−/− mice.
Linked Articles
This article is part of a themed section on Targeting Inflammation to Reduce Cardiovascular Disease Risk. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.22/issuetoc and http://onlinelibrary.wiley.com/doi/10.1111/bcp.v82.4/issuetoc
A new adaptive clipping‐and‐redistribution method is presented which provides bounds‐preservation for multidimensional interpolation in the context of high‐order finite‐volume discretizations with ...adaptive mesh refinement (AMR). The underlying finite‐volume method (FVM) for the computational fluid dynamics applications is fourth‐order accurate for smooth solutions and utilizes AMR for computational efficiency in solving multiscale problems involving turbulence and combustion. High‐order interpolation between different AMR levels is required. However, this operation often leads to numerical issues because combustion species must have physical bounds preserved. The present study overcomes two major challenges in the development of the high‐order interpolation method. First, the method needs to be bound‐preserving near extrema or discontinuities to prevent the emergence of unphysical oscillations while maintaining fourth‐order accuracy in smooth flows. Second, the method needs to satisfy the conservation requirement in multiple dimensions, particularly in the context of curvilinear coordinate transformations. Additionally, the method is designed to be localized and computationally inexpensive. The new interpolation scheme is demonstrated by solving reacting flows, which are extremely sensitive to unphysical overshoots in conserved quantities. The test problems are shock‐induced H2$$ {\mathrm{H}}_2 $$‐O2$$ {\mathrm{O}}_2 $$ combustion and a C3H8$$ {\mathrm{C}}_3{\mathrm{H}}_8 $$‐air flame in a practical bluff‐body combustor. Results show the method prevents new extrema near discontinuities while maintaining high‐order accuracy in smooth regions. In particular, the method is extremely beneficial for combustion with stiff chemistry. With the proposed new method, even if flame fronts cross AMR interfaces or new grids are created in the vicinity of the flame, solution stability is retained.
For conservative finite‐volume methods, adaptive mesh refinement requires high‐degree polynomial interpolation, which is prone to oscillations around nonsmooth features. We develop the HO‐ACR method and demonstrate that it successfully prevents oscillations while maintaining conservation, solution‐dependent bounds‐preservation, and higher‐order accuracy in smooth regions. This can be demonstrated with a “top‐hat” profile of mass fraction, shown after it has been refined and then advected for 100 steps. Although all four methods are conservative, the base AMR and coarse grid methods both have large, persistent overshoots while the HO‐ACR method prevents these effects and closely resembles the more expensive fine grid‐only solution.
This paper investigates a highly attractive platform for an optical waveguide system based on silica-titania material. The paper is organized into two parts. In the first part, an experimental study ...on the development of an optical waveguide system is conducted via the sol-gel dip-coating method, and the optical characterization of the waveguide system is performed at a visible wavelength. This system is capable of operating from visible to near-IR wavelength ranges. The experimental results prove the dominance of this waveguide platform due to its low-cost, low loss, and easy to develop integrated optics systems. The numerical analysis of a one-dimensional Photonic crystal waveguide optical filter based on the silica-titania platform is considered in the second part of the paper by utilizing the 2D-finite element method (2D-FEM). A Fabry-Perot structure is also analyzed for refractive index sensing applications. We believe that the results presented in this work will be valuable in the realization of low-cost photonic integrated circuits based on the silica-titania platform.
Studies of sex differences in the timing of human circadian rhythms have reported conflicting results. This may be because the studies conducted to date have not controlled for the masking effects of ...the rest activity cycle on the circadian rhythms being assessed. In the present analysis of data collected under controlled conditions, we examined sex differences in the timing of circadian rhythms while minimizing masking from behavioral and environmental factors using a constant routine (CR) protocol. All participants (28 women and 28 men paired by habitual wake time; age range, 18 30 years) maintained a regular self selected sleep wake schedule at home prior to the study. After 3 baseline days in the laboratory, participants began a CR. Women were found to have a signifi cantly higher melatonin amplitude and lower temperature amplitude than men. While sleep timing was the same between the 2 groups, the timing of the circa dian rhythms of core body temperature and pineal melatonin secretion was ear lier relative to sleep time in women as compared to men. Sleep therefore occurred at a later biological time for women than men, despite being at the same clock time. Given that sleep propensity and structure vary with circadian phase and are impacted by circulating melatonin, these findings may have important impli cations for understanding sex differences in sleep timing and duration, diurnal preference, and the prevalence of sleep disorders such as insomnia.
This work focuses on the development of a high-performance fourth-order finite-volume method to solve the nonlinear partial differential equations governing the compressible Navier–Stokes equations ...on a Cartesian grid with adaptive mesh refinement. The novelty of the present study is to introduce the loop chaining concept to this complex fourth-order fluid dynamics algorithm for significant improvement in code performance on parallel machines. Specific operations involved in the algorithm include the finite-volume formulation of fourth-order spatial discretization stencils and optimal inter-loop parallelization strategies. Numerical fluxes of the Navier–Stokes equations comprise the hyperbolic (inviscid) and elliptic (viscous) components. The hyperbolic flux is evaluated using high-resolution Godunov’s method and the elliptic flux is based on fourth-order centered-difference methods everywhere in the computational domain. The use of centered-difference methods everywhere supports the idea of fusing modular codes to achieve high efficiency on modern computers. Temporal discretization is performed using the standard fourth-order Runge–Kutta method. The fourth-order accuracy of solution in space and time is verified with a transient Couette flow problem. The algorithm is applied to solve the Sod’s shock tube and the transient flat-plate boundary layer flow. The numerical predictions are validated by comparing to the analytical solutions. The performance of the baseline code is compared to that of the fused scheme which fuses modular codes via loop chaining concept and a significant improvement in execution time is observed.
Circadian clocks maintain temporal homeostasis by generating daily output rhythms in molecular, cellular, and physiological functions. Output rhythms, such as sleep wake cycles and hormonal ...fluctuations, tend to deteriorate during aging in humans, rodents, and fruit flies. However, it is not clear whether this decay is caused by defects in the core transcriptional clock, or weakening of the clock-output pathways, or both. The authors monitored age-related changes in behavioral and molecular rhythms in Drosophila melanogaster. Aging was associated with disrupted rest activity patterns and lengthening of the free-running period of the circadian locomotor activity rhythm. The expression of core clock genes was measured in heads and bodies of young, middle-aged, and old flies. Transcriptional oscillations of four clock genes, period, timeless, Par domain protein 1 , and vrille, were significantly reduced in heads, but not in bodies, of aging flies. It was determined that reduced transcription of these genes was not caused by the deficient expression of their activators, encoded by Clock and cycle genes. Interestingly, transcriptional activation by CLOCK-CYCLE complexes was impaired despite reduced levels of the PERIOD repressor protein in old flies. These data suggest that aging alters the properties of the core transcriptional clock in flies such that both the positive and the negative limbs of the clock are attenuated. (Author correspondence: giebultj@science.oregonstate.edu)
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► We investigated the phylogenetic structure of endemic amphipods in Australian desert springs. ► Mitochondrial cytochrome oxidase I and nuclear 28S were sequenced from 500 amphipods. ...► Significant lineage diversity was found with 13 ESUs identified; all with highly restricted distributions. ► A number of ESUs showed very reduced genetic diversity, however diversity was not related to habitat size.
Increasing pressure for water in the Australian arid zone is placing enormous stress on the diverse endemic communities inhabiting desert springs. Detailed information about the evolutionary processes occurring within and between individual endemic species will help to develop effective and biologically relevant management strategies this fragile ecosystem. To help determine conservation priorities, we documented the genetic structure of the endemic freshwater amphipod populations in springs fed by the Great Artesian Basin in central Australia. Phylogenetic and phylogeographic history and genetic diversity measures were examined using nuclear and mitochondrial DNA from approximately 500 chiltoniid amphipods across an entire group of springs. Pronounced genetic diversity was identified, demonstrating that levels of endemism have been grossly underestimated in these amphipods. Using the GMYC model, 13 genetically divergent lineages were recognized as Evolutionarily Significant Units (ESUs), all of which could be considered as separate species. The results show that due to the highly fragmented ecosystem, these taxa have highly restricted distributions. Many of the identified ESUs are endemic to a very small number of already degraded springs, with the rarest existing in single springs. Despite their extraordinarily small ranges, most ESUs showed relative demographic stability and high levels of genetic diversity, and genetic diversity was not directly linked to habitat extent. The relatively robust genetic health of ESUs does not preclude them from endangerment, as their limited distributions ensure they will be highly vulnerable to future water extraction.
► Test of the impact of evening light exposure on subjective alertness, EEG wake activity and sleep in older human subjects. ► Subjective alertness and wake EEG activity in the alpha range were ...higher during light exposures, compared to baseline. ► Light exposures produced circadian phase shifts and significantly prolonged latency to REM sleep. ► The increase in wake EEG alpha activity was negatively correlated with REM sleep duration. ► Evening light exposure could benefit older adults with early evening sleepiness, without negatively impacting sleep.
Evening bright light exposure is reported to ameliorate daytime sleepiness and age-related sleep complaints, and also delays the timing of circadian rhythms. We tested whether evening light exposure given to older adults with sleep–wake complaints would delay the timing of their circadian rhythms with respect to their sleep timing, thereby reducing evening sleepiness and improving subsequent sleep quality. We examined the impact of evening light exposure from two different light sources on subjective alertness, EEG activity during wakefulness, and sleep stages.
Ten healthy older adults with sleep complaints (mean age
=
63.3
years; 6F) participated in a 13-day study. After three baseline days, circadian phase was assessed. On the evening of days 5–8 the subjects were exposed for 2
h to either polychromatic blue-enriched white light or standard white fluorescent light, and on the following day circadian phase was re-assessed. Subjects were allowed to leave the laboratory during all but the two days when the circadian phase assessment took place. Evening assessments of subjective alertness, and wake and sleep EEG data were analyzed.
Subjective alertness and wake EEG activity in the alpha range (9.75–11.25
Hz) were significantly higher during light exposures when compared to the pre-light exposure evening (
p
<
0.05). The light exposures produced circadian phase shifts and significantly prolonged latency to rapid eye-movement (REM) sleep for both light groups (
p
<
0.05). The increase in wake EEG alpha activity during the light exposures was negatively correlated with REM sleep duration (
p
<
0.05).
Evening light exposure could benefit older adults with early evening sleepiness, without negatively impacting the subsequent sleep episode.
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