Reducing exposure to obesogens is a strategy for preventing obesity.
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•There is an expanding global obesity pandemic.•Ubiquitous environmental chemicals called obesogens play a vital ...role in the obesity pandemic.•Exposure to obesogens occurs throughout the life course from before conception until death.•Development is the most sensitive time for obesogens to impact future weight gain across the lifespan and generations.•Obesogens can act via epigenetic mechanisms.•There is a need to expand understanding of the obesogen paradigm to clinicians and consumers.
Obesity is a multifactorial disease with both genetic and environmental components. The prevailing view is that obesity results from an imbalance between energy intake and expenditure caused by overeating and insufficient exercise. We describe another environmental element that can alter the balance between energy intake and energy expenditure: obesogens. Obesogens are a subset of environmental chemicals that act as endocrine disruptors affecting metabolic endpoints. The obesogen hypothesis posits that exposure to endocrine disruptors and other chemicals can alter the development and function of the adipose tissue, liver, pancreas, gastrointestinal tract, and brain, thus changing the set point for control of metabolism. Obesogens can determine how much food is needed to maintain homeostasis and thereby increase the susceptibility to obesity. The most sensitive time for obesogen action is in utero and early childhood, in part via epigenetic programming that can be transmitted to future generations. This review explores the evidence supporting the obesogen hypothesis and highlights knowledge gaps that have prevented widespread acceptance as a contributor to the obesity pandemic. Critically, the obesogen hypothesis changes the narrative from curing obesity to preventing obesity.
We used satellite remote sensing data; fraction of photosynthetically active radiation absorbed by vegetation (fPAR) from the Moderate Resolution Imaging Spectroradiometer (MODIS) in combination with ...tower eddy covariance and meteorological measurements to characterise the Light Use Efficiency parameter (ε) variability and the maximum ε (εmax) for two contrasting Canadian peatlands. Eight-day MODIS fPAR data were acquired for the Mer Bleue (2000 to 2003) and Western Peatland (2004). Flux tower eddy covariance and meteorological measurements were integrated to the same eight-day time stamps as the MODIS fPAR data. A light use efficiency model: GPP = ε×APAR (where GPP is Gross Primary Productivity and APAR is absorbed photosynthetically active radiation) was used to calculate ε. The εmax value for each year (2000 to 2003) at the Mer Bleue bog ranged from 0.58 g C MJ−1 to 0.78 g C MJ−1 and was 0.91 g C MJ−1 in 2004, for the Western Peatland. The average growing season ε for the Mer Bleue bog for the four year period was 0.35 g C MJ−1 and for the Western Peatland in 2004 was 0.57 g C MJ−1. The average snow free period for the Mer Bleue bog over the four years was 0.27 g C MJ−1 and for the Western Peatland in 2004 was 0.39 g C MJ−1. Using the light use efficiency method we calculated the εmax and the annual variability in ε for two Canadian peatlands. We determined that temperature was a growth-limiting factor at both sites Vapour Pressure Deficit (VPD) however was not. MODIS fPAR is a useful tool for the characterization of ε at flux tower sites.
Vitamin K antagonists reduce the risk of stroke in patients with atrial fibrillation but are considered unsuitable in many patients, who usually receive aspirin instead. We investigated the ...hypothesis that the addition of clopidogrel to aspirin would reduce the risk of vascular events in patients with atrial fibrillation.
A total of 7554 patients with atrial fibrillation who had an increased risk of stroke and for whom vitamin K-antagonist therapy was unsuitable were randomly assigned to receive clopidogrel (75 mg) or placebo, once daily, in addition to aspirin. The primary outcome was the composite of stroke, myocardial infarction, non-central nervous system systemic embolism, or death from vascular causes.
At a median of 3.6 years of follow-up, major vascular events had occurred in 832 patients receiving clopidogrel (6.8% per year) and in 924 patients receiving placebo (7.6% per year) (relative risk with clopidogrel, 0.89; 95% confidence interval CI, 0.81 to 0.98; P=0.01). The difference was primarily due to a reduction in the rate of stroke with clopidogrel. Stroke occurred in 296 patients receiving clopidogrel (2.4% per year) and 408 patients receiving placebo (3.3% per year) (relative risk, 0.72; 95% CI, 0.62 to 0.83; P<0.001). Myocardial infarction occurred in 90 patients receiving clopidogrel (0.7% per year) and in 115 receiving placebo (0.9% per year) (relative risk, 0.78; 95% CI, 0.59 to 1.03; P=0.08). Major bleeding occurred in 251 patients receiving clopidogrel (2.0% per year) and in 162 patients receiving placebo (1.3% per year) (relative risk, 1.57; 95% CI, 1.29 to 1.92; P<0.001).
In patients with atrial fibrillation for whom vitamin K-antagonist therapy was unsuitable, the addition of clopidogrel to aspirin reduced the risk of major vascular events, especially stroke, and increased the risk of major hemorrhage. (ClinicalTrials.gov number, NCT00249873.)
In this study we investigate the costs and benefits of topical mesalazine combined with oral mesalazine therapy for active ulcerative colitis (UC), and once daily (OD ) mesalazine 2 grams versus ...twice daily (BID ) for maintaining UC remission.
Two decision analytic models were constructed to evaluate treatment costs and quality-adjusted life years (QALYs) associated with mesalazine. The first model explored 4 g oral mesalazine in combination with 1 g topical mesalazine during active UC compared with 4 g oral mesalazine monotherapy for achieving clinical remission. The second model compared remission rates at one year for OD 2 g oral mesalazine compared with BID 1 g adjusted for compliance. All direct costs were obtained from established treatment costs in the Netherlands.
The average cost of treatment to transition an active UC patient into remission using oral plus topical mesalazine or oral mesalazine monotherapy was v2207 (95% CI: v1402 to v3332) and v2945 (95% CI: v1717 to v4592), respectively. The annual average cost-saving of adding topical mesalazine delivered for four weeks during active UC was v738. The average annual costs of maintenance of remission with OD and BID therapy were v1293 (95% CI: v1062 to v1496) and v1502 (95% CI: v1262 to 1708), respectively with an annual average per person savings of v209.
Topical mesalazine during acute UC flares results in lower costs due to reduced healthcare consumption attributed to faster symptom resolution. Furthermore, as a result of lower costs and modest QALY gains, maintenance therapy using OD mesalazine is the dominant treatment option if compared with BID mesalazine.
There is a need for humidity sensors that can operate in harsh chemical environments. In this respect SiC is a very promising material. Membrane humidity sensors using porous SiC as the (membrane) ...sensing element have been fabricated and tested. Earlier work established optimal anodisation conditions to make porous SiC (optimised for humidity sensing) to be: electrochemical etching in 73% HF, using an anodisation current density
J
A
=1
mA/
cm
2
. Due to the very low etch-rate of Al in 73% HF, we are able to use Al electrodes instead of Au, making the fabrication process of our sensors more cleanroom friendly. The response of porous SiC membrane devices, with sensitivities up to ∼200% will be discussed. Also, we will discuss the effects on sensor response of accelerated aging in an environmental test furnace and harsh environments such as the outlet of a car exhaust. SEM images are used to examine the membrane structures and porous SiC surfaces.
Unfamiliar, predominantly eccentric exercise, frequently results in muscle damage. A repeated bout of similar eccentric exercise results in less damage and is referred to as the 'repeated bout ...effect'. Despite numerous studies that have clearly demonstrated the repeated bout effect, there is little consensus as to the actual mechanism. In general, the adaptation has been attributed to neural, connective tissue or cellular adaptations. Other possible mechanisms include, adaptation in excitation-contraction coupling or adaptation in the inflammatory response. The 'neural theory' predicts that the initial damage is a result of high stress on a relatively small number of active fast-twitch fibres. For the repeated bout, an increase in motor unit activation and/or a shift to slow-twitch fibre activation distributes the contractile stress over a larger number of active fibres. Although eccentric training results in marked increases in motor unit activation, specific adaptations to a single bout of eccentric exercise have not been examined. The 'connective tissue theory' predicts that muscle damage occurs when the noncontractile connective tissue elements are disrupted and myofibrillar integrity is lost. Indirect evidence suggests that remodelling of the intermediate filaments and/or increased intramuscular connective tissue are responsible for the repeated bout effect. The 'cellular theory' predicts that muscle damage is the result of irreversible sarcomere strain during eccentric contractions. Sarcomere lengths are thought to be highly non-uniform during eccentric contractions, with some sarcomeres stretched beyond myofilament overlap. Loss of contractile integrity results in sarcomere strain and is seen as the initial stage of damage. Some data suggest that an increase in the number of sarcomeres connected in series, following an initial bout, reduces sarcomere strain during a repeated bout and limits the subsequent damage. It is unlikely that one theory can explain all of the various observations of the repeated bout effect found in the literature. That the phenomenon occurs in electrically stimulated contractions in an animal model precludes an exclusive neural adaptation. Connective tissue and cellular adaptations are unlikely explanations when the repeated bout effect is demonstrated prior to full recovery, and when the fact that the initial bout does not have to cause appreciable damage in order to provide a protective effect is considered. It is possible that the repeated bout effect occurs through the interaction of various neural, connective tissue and cellular factors that are dependent on the particulars of the eccentric exercise bout and the specific muscle groups involved.
The application of palladium complexes of a modular series of axially chiral phosphinamine ligands, the Quinazolinaps, to the enantioselective alkylation of 1,3-diphenyl-2-propenyl acetate with ...dimethyl malonate and methyl dimethyl malonate is described. Complete conversions and enantiomeric excesses of up to 91% were obtained. To elucidate the solution structure of these complexes and their dynamic behaviour, 2D COSY and NOESY NMR experiments were carried out. An X-ray crystal structure of a palladacycle derived from 2-phenylQuinazolinap which possesses two Pd3Cl5 units is shown. Computational studies were also undertaken to allow qualitative predictions of diastereomeric ratios. The observed enantioselectivity was then rationalised in terms of combined spectroscopic and theoretical data. The catalytic results obtained are best interpreted by the reaction proceeding with nucleophilic attack on the allyl trans to the phosphorus donor atom of the major diastereomeric intermediate.
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•Palladium-catalysed asymmetric allylic alkylation using axially chiral quinazolinap ligands.•Mechanistic details including rationale for enantioselectivity using NMR, DFT and computational studies.•Isolation and structural characterisation of a Pd-complex containing two Pd3Cl5 units in one molecule.
The very high energy (VHE; E> 100 GeV) blazar Markarian 501 was observed between April 17 and May 5 (MJD 54 938–54 956), 2009, as part of an extensive multi-wavelength campaign from radio to VHE. ...Strong VHE γ-ray activity was detected on May 1st with Whipple and VERITAS, when the flux (E> 400 GeV) increased to 10 times the pre-flare baseline flux (3.9 × 10-11 ph cm-2 s-1), reaching five times the flux of the Crab Nebula. This coincided with a decrease in the optical polarization and a rotation of the polarization angle by 15°. This VHE flare showed a fast flux variation with an increase of a factor ~4 in 25 min, and a falling time of ~50 min. We present the observations of the quiescent state previous to the flare and of the high state after the flare, focusing on the flux and spectral variability from Whipple, VERITAS, Fermi-LAT, RXTE, and Swift combined with optical and radio data.
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