272 research outputs found

    Active vs. Passive Green Space Use and Measures of Well-Being among University Students

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    Frequent exposure to green space has been linked to positive health and well-being in varying populations. Yet, there is still limited research exploring the restorative benefits associated with differing types of green space use among students living in the university setting. To address this gap, we explored green space use amongst a population of undergraduate students (n = 207) attending a university with abundant opportunities to access the restorative properties of nature. The purpose of this study was to examine the type and frequency of green space interactions that are most strongly associated with indicators of health and well-being, and investigate student characteristics associated with frequent use of green space. Results revealed that students who frequently engage with green spaces in active ways report higher quality of life, better overall mood, and lower perceived stress. Passive green space interactions were not strongly associated with indicators of health and well-being. Having had daily interactions with green space in childhood was associated with frequent green space use as a university student, and identified barriers to green space use included “not enough time,” and “not aware of opportunities” These results could assist in the tailoring of “green exercise” interventions conducted in the university setting

    Estimating Risk from Ambient Concentrations of Acrolein across the United States

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    BACKGROUND: Estimated ambient concentrations of acrolein, a hazardous air pollutant, are greater than the U.S. Environmental Protection Agency (EPA) reference concentration throughout the United States, making it a concern for human health. However, there is no method for assessing the extent of risk under the U.S. EPA noncancer risk assessment framework. OBJECTIVES: We estimated excess risks from ambient concentrations of acrolein based on dose–response modeling of a study in rats with a relationship between acrolein and residual volume/total lung capacity ratio (RV/TLC) and specific compliance (sC(L)), markers for altered lung function. METHODS: Based on existing literature, we defined values above the 90th percentile for controls as “adverse.” We estimated the increase over baseline response that would occur in the human population from estimated ambient concentrations of acrolein, taken from the U.S. EPA’s National-Scale Air Toxics Assessment for 1999, after standard animal-to-human conversions and extrapolating to doses below the experimental data. RESULTS: The estimated median additional number of adverse sC(L) outcomes across the United States was approximately 2.5 cases per 1,000 people. The estimated range of additional outcomes from the 5th to the 95th percentile of acrolein concentration levels across census tracts was 0.28–14 cases per 1,000. For RV/TLC, the median additional outcome was 0.002 per 1,000, and the additional outcome at the 95th percentile was 0.13 per 1,000. CONCLUSIONS: Although there are uncertainties in estimating human risks from animal data, this analysis demonstrates a method for estimating health risks for noncancer effects and suggests that acrolein could be associated with decreased respiratory function in the United States

    Successful Implementation of a Perioperative Glycemic Control Protocol in Cardiac Surgery: Barrier Analysis and Intervention Using Lean Six Sigma

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    Although the evidence strongly supports perioperative glycemic control among cardiac surgical patients, there is scant literature to describe the practical application of such a protocol in the complex ICU environment. This paper describes the use of the Lean Six Sigma methodology to implement a perioperative insulin protocol in a cardiac surgical intensive care unit (CSICU) in a large academic hospital. A preintervention chart audit revealed that fewer than 10% of patients were admitted to the CSICU with glucose <200 mg/dL, prompting the initiation of the quality improvement project. Following protocol implementation, more than 90% of patients were admitted with a glucose <200 mg/dL. Key elements to success include barrier analysis and intervention, provider education, and broadening the project scope to address the intraoperative period

    p-tau Ser356 is associated with Alzheimer's disease pathology and is lowered in brain slice cultures using the NUAK inhibitor WZ4003

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    Tau hyperphosphorylation and aggregation is a common feature of many dementia-causing neurodegenerative diseases. Tau can be phosphorylated at up to 85 different sites, and there is increasing interest in whether tau phosphorylation at specific epitopes, by specific kinases, plays an important role in disease progression. The AMP-activated protein kinase (AMPK)-related enzyme NUAK1 has been identified as a potential mediator of tau pathology, whereby NUAK1-mediated phosphorylation of tau at Ser356 prevents the degradation of tau by the proteasome, further exacerbating tau hyperphosphorylation and accumulation. This study provides a detailed characterisation of the association of p-tau Ser356 with progression of Alzheimer's disease pathology, identifying a Braak stage-dependent increase in p-tau Ser356 protein levels and an almost ubiquitous presence in neurofibrillary tangles. We also demonstrate, using sub-diffraction-limit resolution array tomography imaging, that p-tau Ser356 co-localises with synapses in AD postmortem brain tissue, increasing evidence that this form of tau may play important roles in AD progression. To assess the potential impacts of pharmacological NUAK inhibition in an ex vivo system that retains multiple cell types and brain-relevant neuronal architecture, we treated postnatal mouse organotypic brain slice cultures from wildtype or APP/PS1 littermates with the commercially available NUAK1/2 inhibitor WZ4003. Whilst there were no genotype-specific effects, we found that WZ4003 results in a culture-phase-dependent loss of total tau and p-tau Ser356, which corresponds with a reduction in neuronal and synaptic proteins. By contrast, application of WZ4003 to live human brain slice cultures results in a specific lowering of p-tau Ser356, alongside increased neuronal tubulin protein. This work identifies differential responses of postnatal mouse organotypic brain slice cultures and adult human brain slice cultures to NUAK1 inhibition that will be important to consider in future work developing tau-targeting therapeutics for human disease.</p

    Trials and tribulations of recruiting 2,000 older women onto a clinical trial investigating falls and fractures : vital D study

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    Background Randomised, placebo-controlled trials are needed to provide evidence demonstrating safe, effective interventions that reduce falls and fractures in the elderly. The quality of a clinical trial is dependent on successful recruitment of the target participant group. This paper documents the successes and failures of recruiting over 2,000 women aged at least 70 years and at higher risk of falls or fractures onto a placebo-controlled trial of six years duration. The characteristics of study participants at baseline are also described for this study.Methods The Vital D Study recruited older women identified at high risk of fracture through the use of an eligibility algorithm, adapted from identified risk factors for hip fracture. Participants were randomised to orally receive either 500,000 IU vitamin D3 (cholecalciferol) or placebo every autumn for five consecutive years. A variety of recruitment strategies were employed to attract potential participants.Results Of the 2,317 participants randomised onto the study, 74% (n = 1716/2317) were consented onto the study in the last five months of recruiting. This was largely due to the success of a targeted mail-out. Prior to this only 541 women were consented in the 18 months of recruiting. A total of 70% of all participants were recruited as a result of targeted mail-out. The response rate from the letters increased from 2 to 7% following revision of the material by a public relations company. Participant demographic or risk factor profile did not differ between those recruited by targeted mail-outs compared with other methods.Conclusion The most successful recruitment strategy was the targeted mail-out and the response rate was no higher in the local region where the study had extensive exposure through other recruiting strategies. The strategies that were labour-intensive and did not result in successful recruitment include the activities directed towards the GP medical centres. Comprehensive recruitment programs employ overlapping strategies simultaneously with ongoing assessment of recruitment rates. In our experience, and others direct mail-outs work best although rights to privacy must be respected. <br /

    rAAV-compatible MiniPromoters for restricted expression in the brain and eye

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    Abstract Background Small promoters that recapitulate endogenous gene expression patterns are important for basic, preclinical, and now clinical research. Recently, there has been a promising revival of gene therapy for diseases with unmet therapeutic needs. To date, most gene therapies have used viral-based ubiquitous promoters–however, promoters that restrict expression to target cells will minimize off-target side effects, broaden the palette of deliverable therapeutics, and thereby improve safety and efficacy. Here, we take steps towards filling the need for such promoters by developing a high-throughput pipeline that goes from genome-based bioinformatic design to rapid testing in vivo. Methods For much of this work, therapeutically interesting Pleiades MiniPromoters (MiniPs; ~4 kb human DNA regulatory elements), previously tested in knock-in mice, were “cut down” to ~2.5 kb and tested in recombinant adeno-associated virus (rAAV), the virus of choice for gene therapy of the central nervous system. To evaluate our methods, we generated 29 experimental rAAV2/9 viruses carrying 19 different MiniPs, which were injected intravenously into neonatal mice to allow broad unbiased distribution, and characterized in neural tissues by X-gal immunohistochemistry for icre, or immunofluorescent detection of GFP. Results The data showed that 16 of the 19 (84 %) MiniPs recapitulated the expression pattern of their design source. This included expression of: Ple67 in brain raphe nuclei; Ple155 in Purkinje cells of the cerebellum, and retinal bipolar ON cells; Ple261 in endothelial cells of brain blood vessels; and Ple264 in retinal Müller glia. Conclusions Overall, the methodology and MiniPs presented here represent important advances for basic and preclinical research, and may enable a paradigm shift in gene therapy
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