Spotlight Commentary:What's new with the old drug aspirin in older adults?

The benefit‐to‐harm balance of aspirin has been further questioned

Flat fiber: the flexible format for distributed lab-on-a-chip

Integrated optical devices offer dense, multifunctional capability in a single robust package but are rarely considered compatible with the fields of remote or distributed sensing or long-haul 'one-dimensional' fibers. Here we aim to change that by introducing a 'flat-fiber' process that combines the advantages of existing low-cost fiber drawing with the functionality of planar lightwave circuits in a novel hybrid format. By taking this approach, we hope to extend beyond the limitations of traditional planar and fiber substrates - allowing exotic material compositions, device layouts, and local sensing functions to be distributed over extended distances with no coupling or compatibility concerns in highly functional distributed lab-on-a-chip devices

Exercise with prebreathe appears to increase protection from decompression sickness: Preliminary findings

Extravehicular activity (EVA) from the Space Shuttle involves one hour of prebreath with 100% oxygen, decompression of the entire Shuttle to 10.2 psia for at least 12 hours, and another prebreath for 40 minutes before decompression to the 4.3 psia suit pressure. We are investigating the use of a one-hour prebreathe with 100% oxygen beginning with a ten-minute strenuous exercise period as an alternative for the staged decompression schedule described above. The 10-minute exercise consists of dual-cycle ergometry performed at 75% of the subject's peak oxygen uptake to increase denitrogenation efficiency by increasing ventilation and perfusion. The control exposures were preceded by a one-hour prebreathe with 100% oxygen while resting in a supine position. The twenty-two male subjects were exposed to 4.3 psia for 4 hours while performing light to moderate exercise. Preliminary results from 22 of the planned 26 subjects indicate 76% DCS following supine, resting prebreathe and 38% following prebreathe with exercise. The staged decompression schedule has been shown to result in 23% DCS which is not significantly different from the exercise-enhanced prebreathe results. Prebreathe including exercise appears to be comparable to the protection afforded by the more lengthy staged decompression schedule. Completion of the study later this year will enable planned statistical analysis of the results

Heterogeneous models place the root of the placental mammal phylogeny

Heterogeneity among life traits in mammals has resulted in considerable phylogenetic conflict, particularly concerning the position of the placental root. Layered upon this are gene- and lineage-specific variation in amino acid substitution rates and compositional biases. Life trait variations that may impact upon mutational rates are longevity, metabolic rate, body size, and germ line generation time. Over the past 12 years, three main conflicting hypotheses have emerged for the placement of the placental root. These hypotheses place the Atlantogenata (common ancestor of Xenarthra plus Afrotheria), the Afrotheria, or the Xenarthra as the sister group to all other placental mammals. Model adequacy is critical for accurate tree reconstruction and by failing to account for these compositional and character exchange heterogeneities across the tree and data set, previous studies have not provided a strongly supported hypothesis for the placental root. For the first time, models that accommodate both tree and data set heterogeneity have been applied to mammal data. Here, we show the impact of accurate model assignment and the importance of data sets in accommodating model parameters while maintaining the power to reject competing hypotheses. Through these sophisticated methods, we demonstrate the importance of model adequacy, data set power and provide strong support for the Atlantogenata over other competing hypotheses for the position of the placental root

Network analysis of host-virus communities in bats and rodents reveals determinants of cross-species transmission.

Bats are natural reservoirs of several important emerging viruses. Cross-species transmission appears to be quite common among bats, which may contribute to their unique reservoir potential. Therefore, understanding the importance of bats as reservoirs requires examining them in a community context rather than concentrating on individual species. Here, we use a network approach to identify ecological and biological correlates of cross-species virus transmission in bats and rodents, another important host group. We show that given our current knowledge the bat viral sharing network is more connected than the rodent network, suggesting viruses may pass more easily between bat species. We identify host traits associated with important reservoir species: gregarious bats are more likely to share more viruses and bats which migrate regionally are important for spreading viruses through the network. We identify multiple communities of viral sharing within bats and rodents and highlight potential species traits that can help guide studies of novel pathogen emergence.This work was supported by the Research and Policy for Infectious Disease Dynamics (RAPIDD) program of the Science and Technology Directorate (US Department of Homeland Security) and the Fogarty International Center (National Institutes of Health). D.T.S.H. acknowledges funding from a David H. Smith post-doctoral fellowship. A.A.C. is partially funded by a Royal Society Wolfson Research Merit award, and J.L.N.W. is supported by the Alborada Trust. Thanks to Paul Cryan and Michael O'Donnell of the USGS Fort Collins Science Center for help with species distribution analyses.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1111/ele.1249

Cardiac effects of 6 months' dietary nitrate and spironolactone in patients with hypertension and with/at risk of type 2 diabetes, in the factorial design, double-blind, randomized controlled VaSera trial

Aims: The aims of the present study were to explore whether a long-term intervention with dietary nitrate [(NO 3 −), a potential tolerance-free source of beneficial vasoactive nitric oxide] and spironolactone (to oppose aldosterone's potential deleterious cardiovascular effects) improve cardiac structure/function, independently of blood pressure (BP), in patients with/at risk of type 2 diabetes (a population at risk of heart failure).Methods: A subsample of participants in our double-blind, randomized, factorial-design intervention (VaSera) trial of active beetroot juice as a nitrate source (≤11.2 mmol) or placebo (nitrate depleted) beetroot juice, and either ≤50 mg spironolactone or ≤16 mg doxazosin (control), had transthoracic cardiac ultrasounds at baseline (n = 105), and at 3 months and 6 months (n = 87) after the start of the intervention. Analysis was by modified intent-to-treat.Results: Nitrate-containing juice (n = 40) decreased left ventricular (LV) end-diastolic volume {−6.3 [95% confidence interval (CI) –11.1, –1.6] ml} and end-systolic volume [−3.2 (95% CI −5.9, –0.5) ml], and increased end-diastolic mass/volume ratio [+0.04 (95% CI 0.00, 0.07)], relative to placebo juice (n = 47). Spironolactone (n = 44) reduced relative wall thickness compared with doxazosin (n = 43) [−0.01 (95% CI −0.02, –0.00)]. Although spironolactone reduced LV mass index relative to baseline [−1.48 (95% CI −2.08, –0.88) g m –2.7], there was no difference vs. doxazosin [−0.85 (95% CI −1.76, 0.05) g m –2.7]. Spironolactone also decreased the E/A ratio [−0.12 (95% CI −0.19, –0.04)] and increased S′ (a tissue-Doppler systolic function index) by 0.52 (95% CI 0.05, 1.0) cm s –1. BP did not differ between the juices, or between the drugs.Conclusions: Six months' dietary nitrate decreased LV volumes ~5%, representing new, sustained, BP-independent benefits on cardiac structure, extending mechanisms characterized in preclinical models of heart failure. Spironolactone's effects on cardiac remodelling and systolic–diastolic function, although confirmatory, were independent of BP. </p

Network analysis of host–virus communities in bats and rodents reveals determinants of cross-species transmission

Bats are natural reservoirs of several important emerging viruses. Cross-species transmission appears to be quite common among bats, which may contribute to their unique reservoir potential. Therefore, understanding the importance of bats as reservoirs requires examining them in a community context rather than concentrating on individual species. Here, we use a network approach to identify ecological and biological correlates of cross-species virus transmission in bats and rodents, another important host group. We show that given our current knowledge the bat viral sharing network is more connected than the rodent network, suggesting viruses may pass more easily between bat species. We identify host traits associated with important reservoir species: gregarious bats are more likely to share more viruses and bats which migrate regionally are important for spreading viruses through the network. We identify multiple communities of viral sharing within bats and rodents and highlight potential species traits that can help guide studies of novel pathogen emergence

High yield production of a soluble human interleukin-3 variant from E. coli with wild-type bioactivity and improved radiolabeling properties

Human interleukin-3 (hIL-3) is a polypeptide growth factor that regulates the proliferation, differentiation, survival and function of hematopoietic progenitors and many mature blood cell lineages. Although recombinant hIL-3 is a widely used laboratory reagent in hematology, standard methods for its preparation, including those employed by commercial suppliers, remain arduous owing to a reliance on refolding insoluble protein expressed in E. coli. In addition, wild-type hIL-3 is a poor substrate for radio-iodination, which has been a long-standing hindrance to its use in receptor binding assays. To overcome these problems, we developed a method for expression of hIL-3 in E. coli as a soluble protein, with typical yields of >3mg of purified hIL-3 per litre of shaking microbial culture. Additionally, we introduced a non-native tyrosine residue into our hIL-3 analog, which allowed radio-iodination to high specific activities for receptor binding studies whilst not compromising bioactivity. The method presented herein provides a cost-effective and convenient route to milligram quantities of a hIL-3 analog with wild-type bioactivity that, unlike wild-type hIL‑3, can be efficiently radio-iodinated for receptor binding studies

How Can Nutrition Research Better Reflect the Relationship Between Wasting and Stunting in Children? Learnings from the Wasting and Stunting Project

Childhood wasting and stunting affect large numbers of children globally. Both are important risk factors for illness and death yet, despite the fact that these conditions can share common risk factors and are often seen in the same child, they are commonly portrayed as relatively distinct manifestations of undernutrition. In 2014, the Wasting and Stunting project was launched by the Emergency Nutrition Network. Its aim was to better understand the complex relationship and associations between wasting and stunting and examine whether current separations that were apparent in approaches to policy, financing, and programs were justified or useful. Based on the project's work, this article aims to bring a wasting and stunting lens to how research is designed and financed in order for the nutrition community to better understand, prevent, and treat child undernutrition. Discussion of lessons learnt focuses on the synergy and temporal relationships between children's weight loss and linear growth faltering, the proximal and distal factors that drive diverse forms of undernutrition, and identifying and targeting people most at risk. Supporting progress in all these areas requires research collaborations across interest groups that highlight the value of research that moves beyond a focus on single forms of undernutrition, and ensures that there is equal attention given to wasting as to other forms of malnutrition, wherever it is present