Acute cocoa flavanol supplementation improves muscle macro- and microvascular but not anabolic responses to amino acids in older men

The anabolic effects of nutrition on skeletal muscle may depend on adequate skeletal muscle perfusion, which is impaired in older people. Cocoa flavanols have been shown to improve flow-mediated dilation, an established measure of endothelial function. However, their effect on muscle microvascular blood flow is currently unknown. Therefore, the objective of this study was to explore links between the consumption of cocoa flavanols, muscle microvascular blood flow and muscle protein synthesis (MPS) in response to nutrition in older men. To achieve this objective leg blood flow (LBF), muscle microvascular blood volume (MBV) and MPS were measured under postabsorptive and postprandial (I.V glamin, dextrose to sustain glucose ~7.5 mmol·l-1) conditions in 20 older men. Ten of these men were studied with no cocoa flavanol intervention and a further 10 were studied with the addition of 350 mg of cocoa flavanols at the same time as nutrition began. Leg [femoral artery] blood flow was measured by Doppler ultrasound, muscle MBV by contrast-enhanced ultrasound (CEUS) using DefinityTM perflutren contrast agent and MPS using [1, 2-13C2] leucine tracer techniques. Our results show that although older individuals do not show an increase in LBF or MBV in response to feeding, these absent responses are apparent when cocoa flavanols are given acutely with nutrition. However this restoration in vascular responsiveness is not associated with improved MPS responses to nutrition. We conclude that acute cocoa flavanol supplementation improves muscle macro- and microvascular responses to nutrition, independently of modifying muscle protein anabolism

Urbanisation affects ecosystem functioning more than structure in tropical streams

Urbanisation poses a clear threat to tropical freshwater streams, yet fundamental knowledge gaps hinder our ability to effectively conserve stream biodiversity and preserve ecosystem functioning. Here, we studied the impact of urbanisation on structural and functional ecosystem responses in low-order streams in Singapore, a tropical city with a mosaic landscape of protected natural forests, managed buffer zones (between forest and open-country habitats), and built-up urban areas. We quantified an urbanisation gradient based on landscape, in-stream, and riparian conditions, and found an association between urbanisation and pollution-tolerant macroinvertebrates (e.g. freshwater snail and worm species) in litter bags. We also found greater macroinvertebrate abundance (mean individuals bag−1; forest: 30.3, buffer: 70.1, urban: 109.0) and richness (mean taxa bag−1; forest: 4.53, buffer: 4.75, urban: 7.50) in urban streams, but similar diversity across habitats. Higher levels of primary productivity (measured from algal accrual on ceramic tiles) and microbial decomposition (measured from litter-mass loss in mesh bags) at urban sites indicate rapid microbial activity at higher light, temperature, and nutrient levels. We found that urbanisation affected function 32% more than structure in the studied tropical streams, likely driven by greater algal growth in urban streams. These changes in ecological processes (i.e. ecosystem functioning) possibly lead to a loss of ecosystem services, which would negatively affect ecology, society, and economy. Our results point to possible management strategies (e.g. increasing vegetation density through buffer park creation) to reduce the impacts of urbanisation, restore vital ecosystem functions in tropical streams, and create habitat niches for native species

Record linkage to obtain birth outcomes for the evaluation of screening biomarkers in pregnancy: a feasibility study

<p>Abstract</p> <p>Background</p> <p>Linking population health data to pathology data is a new approach for the evaluation of predictive tests that is potentially more efficient, feasible and efficacious than current methods. Studies evaluating the use of first trimester maternal serum levels as predictors of complications in pregnancy have mostly relied on resource intensive methods such as prospective data collection or retrospective chart review. The aim of this pilot study is to demonstrate that record-linkage between a pathology database and routinely collected population health data sets provides follow-up on patient outcomes that is as effective as more traditional and resource-intensive methods. As a specific example, we evaluate maternal serum levels of PAPP-A and free <it>β</it>-hCG as predictors of adverse pregnancy outcomes, and compare our results with those of prospective studies.</p> <p>Methods</p> <p>Maternal serum levels of PAPP-A and free <it>β</it>-hCG for 1882 women randomly selected from a pathology database in New South Wales (NSW) were linked to routinely collected birth and hospital databases. Crude relative risks were calculated to investigate the association between low levels (multiples of the median ≤ 5^thpercentile) of PAPP-A or free <it>β</it>-hCG and the outcomes of preterm delivery (<37 weeks), small for gestational age (<10^thpercentile), fetal loss and stillbirth.</p> <p>Results</p> <p>Using only full name, sex and date of birth for record linkage, pregnancy outcomes were available for 1681 (89.3%) of women included in the study. Low levels of PAPP-A had a stronger association with adverse pregnancy outcomes than a low level of free <it>β</it>-hCG which is consistent with results in published studies. The relative risk of having a preterm birth with a low maternal serum PAPP-A level was 3.44 (95% CI 1.96–6.10) and a low free <it>β</it>-hCG level was 1.31 (95% CI 0.55–6.16).</p> <p>Conclusion</p> <p>This study provides data to support the use of record linkage for outcome ascertainment in studies evaluating predictive tests. Linkage proportions are likely to increase if more personal identifiers are available. This method of follow-up is a cost-efficient technique and can now be applied to a larger cohort of women.</p

Near-Membrane Dynamics and Capture of TRPM8 Channels within Transient Confinement Domains

The cold and menthol receptor, TRPM8, is a non-selective cation channel expressed in a subset of peripheral neurons that is responsible for neuronal detection of environmental cold stimuli. It was previously shown that members of the transient receptor potential (TRP) family of ion channels are translocated toward the plasma membrane (PM) in response to agonist stimulation. Because the spatial and temporal dynamics of cold receptor cell-surface residence may determine neuronal activity, we hypothesized that the movement of TRPM8 to and from the PM might be a regulated process. Single particle tracking (SPT) is a useful tool for probing the organization and dynamics of protein constituents in the plasma membrane.We used SPT to study the receptor dynamics and describe membrane/near-membrane behavior of particles containing TRPM8-EGFP in transfected HEK-293T and F-11 cells. Cells were imaged using total internal reflection fluorescence (TIRF) microscopy and the 2D and 3D trajectories of TRPM8 molecules were calculated by analyzing mean-square particle displacement against time. Four characteristic types of motion were observed: stationary mode, simple Brownian diffusion, directed motion, and confined diffusion. In the absence of cold or menthol to activate the channel, most TRPM8 particles move in network covering the PM, periodically lingering for 2–8 s in confined microdomains of about 800 nm radius. Removing cholesterol with methyl-beta-cyclodextrin (MβCD) stabilizes TRPM8 motion in the PM and is correlated with larger TRPM8 current amplitude that results from an increase in the number of available channels without a change in open probability.These results reveal a novel mechanism for regulating TRPM8 channel activity, and suggest that PM dynamics may play an important role in controlling electrical activity in cold-sensitive neurons

Identifying a Window of Vulnerability during Fetal Development in a Maternal Iron Restriction Model

It is well acknowledged from observations in humans that iron deficiency during pregnancy can be associated with a number of developmental problems in the newborn and developing child. Due to the obvious limitations of human studies, the stage during gestation at which maternal iron deficiency causes an apparent impairment in the offspring remains elusive. In order to begin to understand the time window(s) during pregnancy that is/are especially susceptible to suboptimal iron levels, which may result in negative effects on the development of the fetus, we developed a rat model in which we were able to manipulate and monitor the dietary iron intake during specific stages of pregnancy and analyzed the developing fetuses. We established four different dietary-feeding protocols that were designed to render the fetuses iron deficient at different gestational stages. Based on a functional analysis that employed Auditory Brainstem Response measurements, we found that maternal iron restriction initiated prior to conception and during the first trimester were associated with profound changes in the developing fetus compared to iron restriction initiated later in pregnancy. We also showed that the presence of iron deficiency anemia, low body weight, and changes in core body temperature were not defining factors in the establishment of neural impairment in the rodent offspring

Serum screening with Down's syndrome markers to predict pre-eclampsia and small for gestational age: Systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Reliable antenatal identification of pre-eclampsia and small for gestational age is crucial to judicious allocation of monitoring resources and use of preventative treatment with the prospect of improving maternal/perinatal outcome. The purpose of this systematic review was to determine the accuracy of five serum analytes used in Down's serum screening for prediction of pre-eclampsia and/or small for gestational age.</p> <p>Methods</p> <p>The data sources included Medline, Embase, Cochrane library, Medion (inception to February 2007), hand searching of relevant journals, reference list checking of included articles, contact with experts. Two reviewers independently selected the articles in which the accuracy of an analyte used in Downs's serum screening before the 25^thgestational week was associated with the occurrence of pre-eclampsia and/or small for gestational age without language restrictions. Two authors independently extracted data on study characteristics, quality and results.</p> <p>Results</p> <p>Five serum screening markers were evaluated. 44 studies, testing 169,637 pregnant women (4376 pre-eclampsia cases) and 86 studies, testing 382,005 women (20,339 fetal growth restriction cases) met the selection criteria. The results showed low predictive accuracy overall. For pre-eclampsia the best predictor was inhibin A>2.79MoM positive likelihood ratio 19.52 (8.33,45.79) and negative likelihood ratio 0.30 (0.13,0.68) (single study). For small for gestational age it was AFP>2.0MoM to predict birth weight < 10^thcentile with birth < 37 weeks positive likelihood ratio 27.96 (8.02,97.48) and negative likelihood ratio 0.78 (0.55,1.11) (single study). A potential clinical application using aspirin as a treatment is given as an example.</p> <p>There were methodological and reporting limitations in the included studies thus studies were heterogeneous giving pooled results with wide confidence intervals.</p> <p>Conclusion</p> <p>Down's serum screening analytes have low predictive accuracy for pre-eclampsia and small for gestational age. They may be a useful means of risk assessment or of use in prediction when combined with other tests.</p