Does regular exercise reduce the pain and stiffness of osteoarthritis?

Exercise helps reduce the pain, but it's unclear whether it helps with stiffness. Exercise moderately reduces pain in elderly patients with osteoarthritis (strength of recommendation [SOR]: A, 3 systematic reviews, including high-quality studies) and has a small effect on reducing self-reported disability (SOR: B, 2 systematic reviews, including reviews of smaller studies). No studies have evaluated the effect of exercise on stiffness

Pulmonary arterial pressures, arterial blood-gas tensions, and serum biochemistry of beef calves born and raised at high altitude

Includes bibliographical references (page 8).High-altitude exposure is physiologically challenging. This is particularly true for animals native to low-altitude environments, such as British breeds of cattle. The objective of this study was to document the effect of high altitude on select physiological parameters of healthy beef calves (Bos taurus) born and raised on a high-altitude ranch typical of the Rocky Mountain region. Pulmonary arterial pressures, arterial blood-gas tensions, serum biochemistry, and hematocrit were evaluated. The calves studied were a composite of British (50%-75%) and Continental (25-50%) breeds born on one ranch at an altitude of 2410 m. Calves were sampled at an altitude of 2410 m when 1 month old and again at an altitude of 2730 m when 3 and 6 months old. Between 3 and 6 months of age, calves had access to grazing from 2730 m to approximately 3500 m above sea level. On each occasion, 16 to 50 calves were sampled. Only calves that remained healthy throughout all three testing periods were included in the dataset. Calves with the highest pulmonary arterial pressures at 1 month of age tended to have the highest pressures at 6 months of age (r = 0.43, P = 0.16, n = 12). Respiratory alkalosis was greatest at 6 months of age (pH 7.48 ± 0.06). Mean alveolar-arterial oxygen pressure gradients were 11.7and 11.6 mmHg at 3 and 6 months of age, indicating poor transfer of oxygen from the alveoli into the pulmonary blood. Median values for blood lactate ranged from 1.4 to 3.4 mmol/L indicating substantial anaerobic respiration at all ages. Mean hematocrits were ≤ 35.7%, only slightly higher than values obtained from age-matched calves at sea level. These results suggest that the provision of oxygen to the peripheral tissues of beef calves may be compromised at altitudes over 2410 m. This may have implications for diseases of the cardiopulmonary system.Published with support from the Colorado State University Libraries Open Access Research and Scholarship Fund

Gut inflammation provides a respiratory electron acceptor for Salmonella.

Salmonella enterica serotype Typhimurium (S. Typhimurium) causes acute gut inflammation by using its virulence factors to invade the intestinal epithelium and survive in mucosal macrophages. The inflammatory response enhances the transmission success of S. Typhimurium by promoting its outgrowth in the gut lumen through unknown mechanisms. Here we show that reactive oxygen species generated during inflammation react with endogenous, luminal sulphur compounds (thiosulphate) to form a new respiratory electron acceptor, tetrathionate. The genes conferring the ability to use tetrathionate as an electron acceptor produce a growth advantage for S. Typhimurium over the competing microbiota in the lumen of the inflamed gut. We conclude that S. Typhimurium virulence factors induce host-driven production of a new electron acceptor that allows the pathogen to use respiration to compete with fermenting gut microbes. Thus the ability to trigger intestinal inflammation is crucial for the biology of this diarrhoeal pathogen

Effect of Temperature on Cystic Fibrosis Lung Disease and Infections: A Replicated Cohort Study

Progressive lung disease accounts for the majority of morbidity and mortality observed in cystic fibrosis (CF). Beyond secondhand smoke exposure and socio-economic status, the effect of specific environmental factors on CF lung function is largely unknown.Multivariate regression was used to assess correlation between specific environmental factors, the presence of pulmonary pathogens, and variation in lung function using subjects enrolled in the U.S. CF Twin and Sibling Study (CFTSS: n = 1378). Significant associations were tested for replication in the U.S. CF Foundation Patient Registry (CFF: n = 16439), the Australian CF Data Registry (ACFDR: n = 1801), and prospectively ascertained subjects from Australia/New Zealand (ACFBAL: n = 167).In CFTSS subjects, the presence of Pseudomonas aeruginosa (OR = 1.06 per °F; p<0.001) was associated with warmer annual ambient temperatures. This finding was independently replicated in the CFF (1.02; p<0.001), ACFDR (1.05; p = 0.002), and ACFBAL (1.09; p = 0.003) subjects. Warmer temperatures (-0.34 points per °F; p = 0.005) and public insurance (-6.43 points; p<0.001) were associated with lower lung function in the CFTSS subjects. These findings were replicated in the CFF subjects (temperature: -0.31; p<0.001; insurance: -9.11; p<0.001) and similar in the ACFDR subjects (temperature: -0.23; p = 0.057). The association between temperature and lung function was minimally influenced by P. aeruginosa. Similarly, the association between temperature and P. aeruginosa was largely independent of lung function.Ambient temperature is associated with prevalence of P. aeruginosa and lung function in four independent samples of CF patients from two continents

Chemical combination effects predict connectivity in biological systems

Efforts to construct therapeutically useful models of biological systems require large and diverse sets of data on functional connections between their components. Here we show that cellular responses to combinations of chemicals reveal how their biological targets are connected. Simulations of pathways with pairs of inhibitors at varying doses predict distinct response surface shapes that are reproduced in a yeast experiment, with further support from a larger screen using human tumour cells. The response morphology yields detailed connectivity constraints between nearby targets, and synergy profiles across many combinations show relatedness between targets in the whole network. Constraints from chemical combinations complement genetic studies, because they probe different cellular components and can be applied to disease models that are not amenable to mutagenesis. Chemical probes also offer increased flexibility, as they can be continuously dosed, temporally controlled, and readily combined. After extending this initial study to cover a wider range of combination effects and pathway topologies, chemical combinations may be used to refine network models or to identify novel targets. This response surface methodology may even apply to non-biological systems where responses to targeted perturbations can be measured

Tamoxifen Dose Escalation in Patients With Diminished CYP2D6 Activity Normalizes Endoxifen Concentrations Without Increasing Toxicity

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139937/1/onco0795-sup-0002.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139937/2/onco0795-sup-0001.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139937/3/onco0795.pd

Credibility in Policy Expertise: The Function of Boundaries Between Research and Policy

As science becomes an increasingly crucial resource for addressing complex challenges in society, extensive demands are placed upon the researchers who produce it. Creating valuable expert knowledge that intervenes in policy or practice requires knowledge brokers to facilitate interactions at the boundary between research and policy. Yet, existing research lacks a compelling account of the ways in which brokerage is performed to gain credibility. Drawing on mixed-method analysis of twelve policy research settings, I outline a novel set of strategies for attaining symbolic power, whereby policy experts position themselves and others via conceptual distances drawn between the ‘world of ideas’ and the ‘world of policy and practice’. Disciplinary distance works to situate research as either disciplinary or undisciplinary, epistemic distance creates a boundary between complex specialist research and direct digestible outputs, temporal distance represents the separation of slow rigorous research and agile responsive analysis, and economic distance situates research as either pure and intrinsic or marketable and fundable. I develop a theoretical account that unpacks the boundaries between research communities and shows how these boundaries permit policy research actors to achieve various strategic aims.ESRC Future Research Leaders ES/N016319/1 Commonwealth Scholarship Commissio

Systematic identification of functional modules and cis-regulatory elements in Arabidopsis thaliana

<p>Abstract</p> <p>Background</p> <p>Several large-scale gene co-expression networks have been constructed successfully for predicting gene functional modules and cis-regulatory elements in Arabidopsis (<it>Arabidopsis thaliana</it>)<it>.</it> However, these networks are usually constructed and analyzed in an <it>ad hoc</it> manner. In this study, we propose a completely parameter-free and systematic method for constructing gene co-expression networks and predicting functional modules as well as cis-regulatory elements.</p> <p>Results</p> <p>Our novel method consists of an automated network construction algorithm, a parameter-free procedure to predict functional modules, and a strategy for finding known cis-regulatory elements that is suitable for consensus scanning without prior knowledge of the allowed extent of degeneracy of the motif. We apply the method to study a large collection of gene expression microarray data in Arabidopsis. We estimate that our co-expression network has ~94% of accuracy, and has topological properties similar to other biological networks, such as being scale-free and having a high clustering coefficient. Remarkably, among the ~300 predicted modules whose sizes are at least 20, 88% have at least one significantly enriched functions, including a few extremely significant ones (ribosome, <it>p</it> < 1E-300, photosynthetic membrane, <it>p</it> < 1.3E-137, proteasome complex, <it>p</it> < 5.9E-126). In addition, we are able to predict cis-regulatory elements for 66.7% of the modules, and the association between the enriched cis-regulatory elements and the enriched functional terms can often be confirmed by the literature. Overall, our results are much more significant than those reported by several previous studies on similar data sets. Finally, we utilize the co-expression network to dissect the promoters of 19 Arabidopsis genes involved in the metabolism and signaling of the important plant hormone gibberellin, and achieved promising results that reveal interesting insight into the biosynthesis and signaling of gibberellin.</p> <p>Conclusions</p> <p>The results show that our method is highly effective in finding functional modules from real microarray data. Our application on Arabidopsis leads to the discovery of the largest number of annotated Arabidopsis functional modules in the literature. Given the high statistical significance of functional enrichment and the agreement between cis-regulatory and functional annotations, we believe our Arabidopsis gene modules can be used to predict the functions of unknown genes in Arabidopsis, and to understand the regulatory mechanisms of many genes.</p