Does Acute Exercise Improve Driving Performance In Patients With Untreated Sleep Apnea?

poster abstractDecreased awareness among drivers with obstructive sleep apnea (OSA), a condition in which the airflow decreases during breathing, has been shown to increase motor vehicular crash risk. Those who suffer from OSA have been found to have between a two and tenfold increase of accident risk due to feelings of fatigue resulting from fragmented sleep (George, C.F.P. 2007). Treatment using continuous positive airway pressure (CPAP) has shown mixed effects in improving driver performance (Vkaulin, et al., 2011). Therefore, our objective is to determine if acute aerobic exercise (i.e. walking) prior to driving for patients with OSA can reduce the amount of accidents. Patients with OSA that are awaiting sleep apnea treatment will first undergo a ten minute moderate-intensity exercise session and then use a high fidelity driving simulator for the next fifteen minutes. A nighttime countryside scenario with two naturalistic obstacles at random times will be used. While the subject is driving, the simulator will record lane deviation, collision events, and braking response time. The same subjects will also test the simulator without doing any exercise in order to determine if there was any benefit from the exercise. The order of the simulator sessions, both with and without exercise, will be randomized to prevent practice effect. We hope to see improved driving behavior when the subjects undergo a ten minute aerobic exercise prior to driving

The development of novel antimicrobial peptides with activity against MRSA

MRSA is a significant pathogen, which can cause a range of minor and major infections both in the hospital and community environments. MRSA is developing resistance to many antibiotics, including vancomycin, which is now the first choice antibiotic to treat MRSA infections in the UK. This together with the dearth of new antibiotics being introduced could see the emergence of untreatable S. aureus strains. This has led to renewed interest in alternative antimicrobial agents. Lysostaphin is an endopeptidase produced by Staphylococcus simulans biovar staphylolyticus, which cleaves the peptidoglycan cross-bridges of other staphylococcal species. Lysostaphin has been investigated as a potential therapeutic agent and has shown promise in in vitro and in vivo studies and in clinical trials. However, resistance to lysostaphin is likely to emerge and there will be a demand for second generation Iysostaphins and/or other similar novel antimicrobials that can counteract this resistance. This study describes the cloning, purification and assaying of an endolysin of the S. aureus P68 bacteriophage. Lys16 lysin has previously been shown to possess staphylolytic activity. This study demonstrates that the purified recombinant protein is poorly soluble and is inactive against live cells. The Atl autolysin of S. aureus was also investigated as a potential antimicrobial. This study confirmed the hydrolytic profiles of the enzymes, and a chimeric peptide incorporating the lysostaphin targeting domain with the Atl glucosaminidase was designed. This did not confer greater activity against S. aureus, although the targeting domains of each enzyme were shown to utilise different cell surface receptors. Finally, this study reports the development of a novel assay to measure the activity of antimicrobial peptides against S. aureus, using a bioluminescence reporter. This was shown to be a sensitive assay, able to distinguish small differences in the activity of antimicrobial peptides

The development of novel antimicrobial peptides with activity against MRSA

MRSA is a significant pathogen, which can cause a range of minor and major infections both in the hospital and community environments. MRSA is developing resistance to many antibiotics, including vancomycin, which is now the first choice antibiotic to treat MRSA infections in the UK. This together with the dearth of new antibiotics being introduced could see the emergence of untreatable S. aureus strains. This has led to renewed interest in alternative antimicrobial agents. Lysostaphin is an endopeptidase produced by Staphylococcus simulans biovar staphylolyticus, which cleaves the peptidoglycan cross-bridges of other staphylococcal species. Lysostaphin has been investigated as a potential therapeutic agent and has shown promise in in vitro and in vivo studies and in clinical trials. However, resistance to lysostaphin is likely to emerge and there will be a demand for second generation Iysostaphins and/or other similar novel antimicrobials that can counteract this resistance. This study describes the cloning, purification and assaying of an endolysin of the S. aureus P68 bacteriophage. Lys16 lysin has previously been shown to possess staphylolytic activity. This study demonstrates that the purified recombinant protein is poorly soluble and is inactive against live cells. The Atl autolysin of S. aureus was also investigated as a potential antimicrobial. This study confirmed the hydrolytic profiles of the enzymes, and a chimeric peptide incorporating the lysostaphin targeting domain with the Atl glucosaminidase was designed. This did not confer greater activity against S. aureus, although the targeting domains of each enzyme were shown to utilise different cell surface receptors. Finally, this study reports the development of a novel assay to measure the activity of antimicrobial peptides against S. aureus, using a bioluminescence reporter. This was shown to be a sensitive assay, able to distinguish small differences in the activity of antimicrobial peptides

Unique Transcriptional Profile of Sustained Ligand-Activated Preconditioning in Pre- and Post-Ischemic Myocardium

BACKGROUND: Opioidergic SLP (sustained ligand-activated preconditioning) induced by 3–5 days of opioid receptor (OR) agonism induces persistent protection against ischemia-reperfusion (I-R) injury in young and aged hearts, and is mechanistically distinct from conventional preconditioning responses. We thus applied unbiased gene-array interrogation to identify molecular effects of SLP in pre- and post-ischemic myocardium. METHODOLOGY/PRINCIPAL FINDINGS: Male C57Bl/6 mice were implanted with 75 mg morphine or placebo pellets for 5 days. Resultant SLP did not modify cardiac function, and markedly reduced dysfunction and injury in perfused hearts subjected to 25 min ischemia/45 min reperfusion. Microarray analysis identified 14 up- and 86 down-regulated genes in normoxic hearts from SLP mice (≥1.3-fold change, FDR≤5%). Induced genes encoded sarcomeric/contractile proteins (Myh7, Mybpc3,Myom2,Des), natriuretic peptides (Nppa,Nppb) and stress-signaling elements (Csda,Ptgds). Highly repressed genes primarily encoded chemokines (Ccl2,Ccl4,Ccl7,Ccl9,Ccl13,Ccl3l3,Cxcl3), cytokines (Il1b,Il6,Tnf) and other proteins involved in inflammation/immunity (C3,Cd74,Cd83, Cd86,Hla-dbq1,Hla-drb1,Saa1,Selp,Serpina3), together with endoplasmic stress proteins (known: Dnajb1,Herpud1,Socs3; putative: Il6, Gadd45g,Rcan1) and transcriptional controllers (Egr2,Egr3, Fos,Hmox1,Nfkbid). Biological themes modified thus related to inflammation/immunity, together with cellular/cardiovascular movement and development. SLP also modified the transcriptional response to I-R (46 genes uniquely altered post-ischemia), which may influence later infarction/remodeling. This included up-regulated determinants of cellular resistance to oxidant (Mgst3,Gstm1,Gstm2) and other forms of stress (Xirp1,Ankrd1,Clu), and repression of stress-response genes (Hspa1a,Hspd1,Hsp90aa,Hsph1,Serpinh1) and Txnip. CONCLUSIONS: Protection via SLP is associated with transcriptional repression of inflammation/immunity, up-regulation of sarcomeric elements and natriuretic peptides, and modulation of cell stress, growth and development, while conventional protective molecules are unaltered

Toward collaborative open data science in metabolomics using Jupyter Notebooks and cloud computing

Background A lack of transparency and reporting standards in the scientific community has led to increasing and widespread concerns relating to reproduction and integrity of results. As an omics science, which generates vast amounts of data and relies heavily on data science for deriving biological meaning, metabolomics is highly vulnerable to irreproducibility. The metabolomics community has made substantial efforts to align with FAIR data standards by promoting open data formats, data repositories, online spectral libraries, and metabolite databases. Open data analysis platforms also exist; however, they tend to be inflexible and rely on the user to adequately report their methods and results. To enable FAIR data science in metabolomics, methods and results need to be transparently disseminated in a manner that is rapid, reusable, and fully integrated with the published work. To ensure broad use within the community such a framework also needs to be inclusive and intuitive for both computational novices and experts alike. Aim of Review To encourage metabolomics researchers from all backgrounds to take control of their own data science, mould it to their personal requirements, and enthusiastically share resources through open science. Key Scientific Concepts of Review This tutorial introduces the concept of interactive web-based computational laboratory notebooks. The reader is guided through a set of experiential tutorials specifically targeted at metabolomics researchers, based around the Jupyter Notebook web application, GitHub data repository, and Binder cloud computing platform

Elasmobranch qPCR reference genes: a case study of hypoxia preconditioned epaulette sharks

<p>Abstract</p> <p>Background</p> <p>Elasmobranch fishes are an ancient group of vertebrates which have high potential as model species for research into evolutionary physiology and genomics. However, no comparative studies have established suitable reference genes for quantitative PCR (qPCR) in elasmobranchs for any physiological conditions. Oxygen availability has been a major force shaping the physiological evolution of vertebrates, especially fishes. Here we examined the suitability of 9 reference candidates from various functional categories after a single hypoxic insult or after hypoxia preconditioning in epaulette shark (<it>Hemiscyllium ocellatum</it>).</p> <p>Results</p> <p>Epaulette sharks were caught and exposed to hypoxia. Tissues were collected from 10 controls, 10 individuals with single hypoxic insult and 10 individuals with hypoxia preconditioning (8 hypoxic insults, 12 hours apart). We produced sequence information for reference gene candidates and monitored mRNA expression levels in four tissues: cerebellum, heart, gill and eye. The stability of the genes was examined with analysis of variance, geNorm and NormFinder. The best ranking genes in our study were <it>eukaryotic translation elongation factor 1 beta </it>(<it>eef1b</it>), <it>ubiquitin </it>(<it>ubq</it>) and <it>polymerase (RNA) II (DNA directed) polypeptide F </it>(<it>polr2f</it>). The performance of the <it>ribosomal protein L6 </it>(<it>rpl6</it>) was tissue-dependent. Notably, in one tissue the analysis of variance indicated statistically significant differences between treatments for genes that were ranked as the most stable candidates by reference gene software.</p> <p>Conclusions</p> <p>Our results indicate that <it>eef1b </it>and <it>ubq </it>are generally the most suitable reference genes for the conditions and tissues in the present epaulette shark studies. These genes could also be potential reference gene candidates for other physiological studies examining stress in elasmobranchs. The results emphasise the importance of inter-group variation in reference gene evaluation.</p

A Mixed-method Analysis of Community-Engaged Theatre Illuminates Black Women’s Experiences of Racism and Addresses Healthcare Inequities by Targeting Provider Bias

Theatre has been a powerful means of eliciting social change. This paper describes methods and outcomes of a theatre project to reduce healthcare inequities experienced by Black women. We conducted narrative interviews with a convenience sample of Black women and conducted thematic analysis of interview transcripts to learn about their experiences of healthcare and to inform development of a professional theatrical production. To assess the impact of the performance on the audience, we used a single post-test concurrent mixed-methods design using a self-created Likert-type survey that included space for open-ended responses. Ten Black women completed narrative interviews. Thematic analysis revealed 5 main themes: being ignored, being accused, being talked-down to, fearing harm, and being hurt. Narratives were used to create a script that centered on these themes, and that was professionally produced and performed. Audience members (n = 113, 25% healthcare providers) produced a mean total post-test score of 19.28 (agree/strongly agree) on a 25-point survey with 2 items scoring in the 2 to 3 range (disagree/not sure). Thematic analysis data revealed the extent to which Black women experienced discrimination in multiple settings. Quantitative survey data suggested audience members conceptually understood and were aware of inequity, but open-ended responses revealed this information was new for some, and prior knowledge for others. The audience reported planning to change personal behaviors that may contribute to inequity. Participants were unsure if they had contributed to inequity in the past. The performance stimulated conversation about implicit bias and discrimination and encouraged audience members to examine their contributions to the problem. Future pre-post studies are needed to better assess the impact of the performance. Theatre has the potential to illuminate the extent and nature of discrimination in healthcare and society, and to foster conversations that allow audience members to consider their own potential contributions to discrimination

Understanding valuing devices in tourism through ‘place-making’

The paper explores how valuing devices and verification mechanisms such as user-generated content (UGC) websites partake in performing placeness. The findings are based upon a corpus of data including a case study at the offices of the largest user-generated travel website, TripAdvisor, a longitudinal netnographic approach and a conceptual review. Originally inspired by theorists of space we treat places as sites of becoming that are performed through everyday practices. In claiming that places become meaningful only in and through practices we stress the importance of treating rating and ranking mechanisms as generative, rather than merely reductive algorithmically produced representations. By juxtaposing traditional enactments of traveling, we are discussing how placeness has been transformed and how this has fueled a series of further revisions to valuing tourism. We conclude the paper by appreciating the multiplicity of performativity as being implicated in the algorithmic configurations on contemporary valuing devices and enacted as we read, interpret, write, imagine. It is suggested that although earlier valuing devices have evoked place-making in various ways, the rise of UGC websites has converted the travel experience into a constant negotiation process whereby both the value of places and the value of valuing devices are contested

Molecular techniques reveal cryptic life history and demographic processes of a critically endangered marine turtle

The concept of ‘effective population size’ (Ne), which quantifies how quickly a population will lose genetic variability, is one of the most important contributions of theoretical evolutionary biology to practical conservation management. Ne is often much lower than actual population size: how much so depends on key life history and demographic parameters, such as mating systems and population connectivity, that often remain unknown for species of conservation concern. Molecular techniques allow the indirect study of these parameters, as well as the estimation of current and historical Ne. Here, we use genotyping to assess the genetic health of an important population of the critically endangered hawksbill turtle (Eretmochelys imbricata), a slow-to-mature, difficult-to-observe species with a long history of severe overhunting. Our results were surprisingly positive: we found that the study population, located in the Republic of Seychelles, Indian Ocean, has a relatively large Ne, estimated to exceed 1000, and showed no evidence of a recent reduction in Ne (i.e. no genetic bottleneck). Furthermore, molecular inferences suggest the species' mating system is conducive to maintaining a large Ne, with a relatively large and widely distributed male population promoting considerable gene flow amongst nesting sites across the Seychelles area. This may also be reinforced by the movement of females between nesting sites. Our study underlines how molecular techniques can help to inform conservation biology. In this case our results suggest that this important hawksbill population is starting from a relatively strong position as it faces new challenges, such as global climate change