Physical Activity Environments in Rural Communities: Exploring the Relationship between Community Perceptions and the Environment

Purpose: To assess the physical activity environment, community perceptions of the physical activity environment, and the relationship between these variables in rural and/or underserved communities with high obesity prevalence.Methods: The Rural Active Living Assessment (RALA) was used to assess the programs and policies (PPA), town-wide amenities (TWA), and street segments (SSA) of the physical activity environment and the Rural Active Living Perceived Environmental Support Scale (RALPESS) was used to assess community perception of the physical activity environment within eleven rural and/or underserved communities. Each section of the RALA and RALPESS are further broken down into additional subsections in order to assess specific aspects of the physical activity environment. Due to different absolute scores possible in each subsection, relative scores were calculated to allow for comparison between subsections. Data was analyzed with STATA and presented as mean ± standard deviation. Pairwise correlations were used to assess the relationship between the physical activity environment (RALA) and community perception of the physical activity environment (RALPESS). Statistical significance was set at p \u3c 0.05.Results: Eleven communities completed the RALA and 170 individuals completed the RALPESS. The RALA score was 53.4 ± 9.28%. The TWA scored 58.4 ± 16.0%, parks and playgrounds (78.2 ± 22.0%) scored highest and trails (35 ± 39.7 %) scored lowest (n=11). The PPA score was 43.82 ± 17.97 %, school policies (63.6 ± 32.3 %) scored highest and town policies (17.3 ± 30.7 %) scored lowest (n=11). The SSA score was 69.1 ± 17.5%, (lack of) barriers (90.0 ± 21.6%) scored highest and safety features (27.6 ± 18.0 %) scored lowest (n=10). The RALPESS score was 50.2 ± 13.8%. Schools (71.0 ± 24.6%) scored highest and churches (32.6 ± 20.7 %) scored lowest (n=11). No significant relationship was found between the total score on the RALA and RALPESS (r=0.48, p=0.16).Conclusion: There is not a relationship between perception of the PA environment and the PA environment in rural and/or underserved communities. The quality of amenities may be a main contributor to the lack of relationship as resources in poor quality may influence the way individuals perceive these PA resources. Lack of relationship may also be due to the possible inability of the assessment tools to capture PA support within extremely rural areas. The present study highlighted that schools are a key hub for physical activity efforts within rural and/or underserved communities. Implementation of programs in schools and bringing awareness to these programs may improve the perceptions and physical activity environments in rural communities and promote more physical activity

The Stanford equivalence principle program

The Stanford Equivalence Principle Program (Worden, Jr. 1983) is intended to test the uniqueness of free fall to the ultimate possible accuracy. The program is being conducted in two phases: first, a ground-based version of the experiment, which should have a sensitivity to differences in rate of fall of one part in 10(exp 12); followed by an orbital experiment with a sensitivity of one part in 10(exp 17) or better. The ground-based experiment, although a sensitive equivalence principle test in its own right, is being used for technology development for the orbital experiment. A secondary goal of the experiment is a search for exotic forces. The instrument is very well suited for this search, which would be conducted mostly with the ground-based apparatus. The short range predicted for these forces means that forces originating in the Earth would not be detectable in orbit. But detection of Yukawa-type exotic forces from a nearby large satellite (such as Space Station) is feasible, and gives a very sensitive and controllable test for little more effort than the orbiting equivalence principle test itself

Ca2+ waves coordinate purinergic receptor–evoked integrin activation and polarization

The integrin GPIIb/IIIa is highly abundant on the surface of platelets and can be activated by intracellular Ca2+ signaling in an “inside-out” manner to bind to the adhesive ligand fibrinogen. Bye et al. imaged intracellular Ca2+ signaling and fibrinogen binding events in primary rat megakaryocytes activated through the ADP-stimulated receptors P2Y1 and P2Y12. The authors found that signaling by both receptors was required for full integrin activation, which depended on P2Y1-stimulated Ca2+ signaling and P2Y12-stimulated activation of the kinase PI3K. In addition, fibrinogen binding became polarized in these cells in a manner dependent on the direction of ADP-stimulated Ca2+ waves

Fluticasone propionate — an update on preclinical and clinical experience

AbstractFluticasone propionate (FP) is a novel androstane glucocorticoid with potent anti-inflammatory activity which has been effectively used, intransasally, as therapy for seasonal and allergic perennial rhinitis. When taken by the inhaled route, FP has shown significant therapeutic efficacy in the management of asthma. Fluticasone propionate is a highly lipophilic molecule with good uptake, binding and retention characteristics in human lung tissue. Fluticasone propionate has high glucocorticoid receptor selectivity and affinity, demonstrating rapid receptor association and slow receptor dissociation. In vitro, FP has been shown to potently inhibit T lymphocyte proliferation, cytokine generation, tumour necrosis factor alpha (TNF-α)-induced adhesion molecule expression, interleukin-5-induced eosinophilia, mucosal oedema and toluene 2,4-diisocyanate-induced mast cell proliferation, while promoting secretory leucocyte protease inhibitor production and eosinophil apoptosis. In human studies, FP has demonstrated marked vasoconstrictor potency in normal subjects and inhibited antigen-induced mucosal platelet activating factor/eicosanoid production, T lymphocytes and CD25+ cells in patients with rhinitis. Biopsy data from mild asthmatics demonstrate FP-associated reduction in CD3, CD4, CD8 and CD25 cells, with an accompanying reduction in eosinophil and mast cell markers. Clinical studies have evaluated lung function, bronchial reactivity, exacerbation rates and oral corticosteroid-sparing effect. Results show that FP has at least twice the clinical potency of beclomethasone dipropionate and budesonide. This appears to be achieved without an accompanying increase in systemic effects, suggesting a therapeutic index which may be higher than other currently available inhaled corticosteroids

Cobimetinib and trametinib inhibit platelet MEK but do not cause platelet dysfunction

The MEK inhibitors cobimetinib and trametinib are used in combination with BRAF inhibitors to treat metastatic melanoma but increase rates of hemorrhage relative to BRAF inhibitors alone. Platelets express several members of the MAPK signalling cascade including MEK1 and MEK2 and ERK1 and ERK2 but their role in platelet function and haemostasis is ambiguous as previous reports have been contradictory. It is therefore unclear if MEK inhibitors might be causing platelet dysfunction and contributing to increased hemorrhage. In the present study we performed pharmacological characterisation of cobimetinib and trametinib in vitro to investigate potential for MEK inhibitors to cause platelet dysfunction. We report that whilst both cobimetinib and trametinib are potent inhibitors of platelet MEK activity, treatment with trametinib did not alter platelet function. Treatment with cobimetinib results in inhibition of platelet aggregation, integrin activation, alpha-granule secretion and adhesion but only at suprapharmacological concentrations. We identified that the inhibitory effects of high concentrations of cobimetinib are associated with off-target inhibition on Akt and PKC. Neither inhibitor caused any alteration in thrombus formation on collagen under flow conditions in vitro. Our findings demonstrate that platelets are able to function normally when MEK activity is fully inhibited, indicating MEK activity is dispensable for normal platelet function. We conclude that the MEK inhibitors cobimetinib and trametinib do not induce platelet dysfunction and are therefore unlikely to contribute to increased incidence of bleeding reported during MEK inhibitor therapy

Platelet signaling: a complex interplay between inhibitory and activatory networks

The role of platelets in hemostasis and thrombosis is dependent on a complex balance of activatory and inhibitory signaling pathways. Inhibitory signals released from the healthy vasculature suppress platelet activation in the absence of platelet receptor agonists. Activatory signals present at a site of injury initiate platelet activation and thrombus formation; subsequently, endogenous negative signaling regulators dampen activatory signals to control thrombus growth. Understanding the complex interplay between activatory and inhibitory signaling networks is an emerging challenge in the study of platelet biology and necessitates a systematic approach to utilize experimental data effectively. In this review, we will explore the key points of platelet regulation and signaling that maintain platelets in a resting state, mediate activation to elicit thrombus formation or provide negative feedback. Platelet signaling will be described in terms of key signaling molecules that are common to the pathways activated by platelet agonists and can be described as regulatory nodes for both positive and negative regulators. This article is protected by copyright. All rights reserved

A Specific Role of Hippocampal NMDA Receptors and Arc Protein in Rapid Encoding of Novel Environmental Representations and a More General Long-Term Consolidation Function

Activation of the NMDA receptor (NMDAR) has been proposed to be a key event responsible for the structural changes that occur in neurons during learning and memory formation. It has been extensively studied yet no consensus has been reached on its mnemonic role as both NMDAR dependent and independent forms of learning have been observed. We investigated the role that hippocampal NMDAR have in rapid spatial learning and memory across training environments. Hippocampal NMDAR was blocked via intra-hippocampal injection of the competitive antagonist CPP. Groups of rats were pre-trained on a spatial version of the Morris water task, and then mass reversal training under NMDAR blockade occurred in the same or different training environments as pre-training. We measured expression of Arc protein throughout the main hippocampal subfields, CA1, CA3, and dentate gyrus, after mass-training. We observed that NMDAR blockade allowed for rapid spatial learning, but not consolidation, when the SUBJECTS used previously acquired environmental information. Interestingly, NMDAR blockade impaired rapid spatial learning when rats were mass-trained in a novel context. Arc protein expression in the dentate gyrus followed this pattern of NMDAR dependent spatial behavior, with high levels of expression observed after being trained in the new environment, and low levels when trained in the same environment. CPP significantly reduced Arc expression in the dentate gyrus. These results implicate dentate NMDAR in the acquisition of novel environmental information