Silica is a promising carrier material for nanoparticle-facilitated drug delivery, gene therapy, and molecular imaging. Understanding of their pharmacokinetics is important to resolve bioapplicability issues. Here we report an extensive study on bare and lipid-coated silica nanoparticles in mice. Results obtained by use of a wide variety of techniques (fluorescence imaging, inductively coupled plasma mass spectrometry, magnetic resonance imaging, confocal laser scanning microscopy, and transmission electron microscopy) showed that the lipid coating, which enables straightforward functionalization and introduction of multiple properties, increases bioapplicability and improves pharmacokinetics.

Background Guidelines recommend exercise as a core treatment for osteoarthritis (OA). However, it is unclear which type of exercise is most effective, leading to inconsistency between different recommendations. Objectives The aim of this systematic review and network meta-analysis was to investigate the relative efficacy of different exercises (aerobic, mind–body, strengthening, flexibility/skill, or mixed) for improving pain, function, performance and quality of life (QoL) for knee and hip OA at, or nearest to, 8 weeks. Methods We searched nine electronic databases up until December 2017 for randomised controlled trials that compared exercise with usual care or with another exercise type. Bayesian network meta-analysis was used to estimate the relative effect size (ES) and corresponding 95% credibility interval (CrI) (PROSPERO registration: CRD42016033865). Findings We identified and analysed 103 trials (9134 participants). Aerobic exercise was most beneficial for pain (ES 1.11; 95% CrI 0.69, 1.54) and performance (1.05; 0.63, 1.48). Mind–body exercise, which had pain benefit equivalent to that of aerobic exercise (1.11; 0.63, 1.59), was the best for function (0.81; 0.27, 1.36). Strengthening and flexibility/skill exercises improved multiple outcomes at a moderate level. Mixed exercise was the least effective for all outcomes and had significantly less pain relief than aerobic and mind–body exercises. The trend was significant for pain ( p = 0.01), but not for function ( p = 0.07), performance ( p = 0.06) or QoL ( p = 0.65). Conclusion The effect of exercise varies according to the type of exercise and target outcome. Aerobic or mind–body exercise may be the best for pain and function improvements. Strengthening and flexibility/skill exercises may be used for multiple outcomes. Mixed exercise is the least effective and the reason for this merits further investigation. Electronic supplementary material The online version of this article (10.1007/s40279-019-01082-0) contains supplementary material, which is available to authorized users.

Bronchial vascular remodeling is an important feature of the pathology of chronic asthma, but the responsible mechanisms and main sources of angiogenic factors are unclear. Here we report that human airway smooth muscle cells express vascular endothelial growth factor (VEGF)121, 165, 189, 206 splice variants and secrete VEGF protein constitutively. VEGF protein secretion was increased by the proinflammatory asthma mediator bradykinin through post-transcriptional mechanisms. Bradykinin-induced VEGF secretion was dependent on the B2 bradykinin receptor, activation of protein kinase C, and generation of endogenous prostanoids. This is the first report that bradykinin can increase VEGF secretion in any biological system and the first to show that airway smooth muscle cells produce VEGF. Our results suggest a novel role for human airway smooth muscle in contributing to bronchial mucosal angiogenesis in chronic asthma by secretion of VEGF and suggest a wider role for mesenchymal cell products in mediating angiogenesis in inflammatory and allergic diseases.

BackgroundExercise is an effective treatment for osteoarthritis. However, the effect may vary from one patient (or study) to another.ObjectiveTo evaluate the efficacy of exercise and its potential determinants for pain, function, performance, and quality of life (QoL) in knee and hip osteoarthritis (OA).MethodsWe searched 9 electronic databases (AMED, CENTRAL, CINAHL, EMBASE, MEDLINE Ovid, PEDro, PubMed, SPORTDiscus and Google Scholar) for reports of randomised controlled trials (RCTs) comparing exercise-only interventions with usual care. The search was performed from inception up to December 2017 with no language restriction. The effect size (ES), with its 95% confidence interval (CI), was calculated on the basis of between-group standardised mean differences. The primary endpoint was at or nearest to 8 weeks. Other outcome time points were grouped into intervals, from < 1 month to ≥ 18 months, for time-dependent effects analysis. Potential determinants were explored by subgroup analyses. Level of significance was set at P ≤ 0.10.ResultsData from 77 RCTs (6472 participants) confirmed statistically significant exercise benefits for pain (ES 0.56, 95% CI 0.44–0.68), function (0.50, 0.38–0.63), performance (0.46, 0.35–0.57), and QoL (0.21, 0.11–0.31) at or nearest to 8 weeks. Across all outcomes, the effects appeared to peak around 2 months and then gradually decreased and became no better than usual care after 9 months. Better pain relief was reported by trials investigating participants who were younger (mean age < 60 years), had knee OA, and were not awaiting joint replacement surgery.ConclusionsExercise significantly reduces pain and improves function, performance and QoL in people with knee and hip OA as compared with usual care at 8 weeks. The effects are maximal around 2 months and thereafter slowly diminish, being no better than usual care at 9 to 18 months. Participants with younger age, knee OA and not awaiting joint replacement may benefit more from exercise therapy. These potential determinants, identified by study-level analyses, may have implied ecological bias and need to be confirmed with individual patient data.

Prostaglandin E 2 (PGE 2 ) can increase vascular endothelial growth factor A (VEGF-A) production but the mechanisms involved are unclear. Here we characterized the transcriptional mechanisms involved in human airway smooth muscle cells (HASMC). PGE 2 increased VEGF-A mRNA and protein but not mRNA stability.

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Proactively identifying smokers who want to quit in primary care populations, and referring them to a cessation service, increased contacts with cessation services and the number of quit attempts. We were unable to detect a significant effect on long-term cessation rates, but the study was not powered to detect the kind of difference that might be expected.

Supplemental Digital Content is Available in the Text.Self-report items measuring 8 pain-related traits represent a unifying construct. This construct, and items, are significant correlates of quantitative sensory testing indices for centrally augmented knee pain.