Occurrence of Cryptosporidium Oocysts in Leisure Pools in the UK, 2017, and Modelling of Oocyst Contamination Events

Cryptosporidium is a major cause of diarrhoea outbreaks linked to swimming pools, but little is known about the frequency of contamination. The primary aim was to investigate the occurrence and concentration, through sampling and modelling, of Cryptosporidium oocysts in leisure pools. Secondary aims were to compare detections with operational parameters, provide the evidence-base for guidance, and improve sampling capacity and interpretation for public health investigations. Up to 1000 L pool water was sampled during swim sessions once weekly for 10 weeks from 8 August 2017 at six volunteer pools. Oocysts were detected by microscopy in 12/59 (20%) pool water samples, at least once in each pool; 8/12 (66%) detections were in August when bather loads were highest. At three pools, 1 L filter backwash was sampled weekly and oocysts were detected in 2/29 (7%) samples, following detections in pool water. The probabilities of a bather contaminating the pool ranged from 1 in 1000 to over 1 in 10,000. Monte Carlo analysis showed that when high bather numbers caused contamination on over 70% of days, multiple events per day were more likely than single events. In these generally well-managed leisure pools, Cryptosporidium risk related to high bather loads. We conclude that public awareness campaigns for bather hygiene, and reminding pool operators of current guidance for managing faecal accidents, should be ahead of peak swim season

A rapid intrinsic heart rate resetting response with thermal acclimation in rainbow trout, Oncorhynchus mykiss.

We examined cardiac pacemaker rate resetting in rainbow trout following a reciprocal temperature transfer. In the original experiment, performed in winter, 4°C-acclimated fish transferred to 12°C reset intrinsic heart rate after just 1 h (from 56.8±1.2 to 50.8±1.5 beats min-1); 12°C-acclimated fish transferred to 4°C reset intrinsic heart rate after 8 h (from 33.4±0.7 to 37.7±1.2 beats min-1). However, in a replicate experiment, performed in the summer using a different brood year, intrinsic heart rate was not reset, even after 10 weeks at a new temperature. Using this serendipitous opportunity, we compared mRNA expression changes of a suite of proteins in sinoatrial node (SAN), atrial and ventricular tissues after both 1 h and longer than 3 weeks for both experimental acclimation groups to identify those changes only associated with pacemaker rate resetting. Of the changes in mRNA expression occurring after more than 3 weeks of warm acclimation and associated with pacemaker rate resetting, we observed downregulation of NKA α1c in the atrium and ventricle, and upregulation of HCN1 in the ventricle. However, in the SAN there were no mRNA expression changes unique to the fish with pacemaker rate resetting after either 1 h or 3 weeks of warm acclimation. Thus, despite identifying changes in mRNA expression of contractile cardiac tissues, there was an absence of changes in mRNA expression directly involved with the initial, rapid pacemaker rate resetting with warm acclimation. Importantly, pacemaker rate resetting with thermal acclimation does not always occur in rainbow trout.This work is supported by the Natural Science and Engineering Research Council (NSERC) Discovery Grant 2015-05059 to A.P.F. who holds a Canada Research Chair (Tier I)

Masticatory loading and soft-tissue plasticity in the mammalian circumorbital region

Abstract only availableMasticatory loading is the key to understanding the plasticity or epigenetic responses of many of the soft and hard tissues of the mammalian skull. Diet-induced variation in the magnitude and/or frequency of masticatory loads influences the organization, functional adaptation and postnatal development of craniofacial systems. While experimental work exists concerning masticatory stress as a determinant of maxillomandibular form, similar research concerning the mammalian circumorbital region of soft-tissue structures remains sparse. Indeed, controversy remains over the function of the circumorbital region, specifically whether the postorbital region in primates and other mammals is responsive to biomechanical loading. This hinders our understanding of evolutionary transformations during primate origins, where the earliest primates evolved a bony postorbital bar from an ancestor with a soft-tissue structure along the lateral orbital margin. To fill this gap, we examined the postorbital microanatomy of white rabbits (Oryctolagus cuniculus). Rabbits exhibit a masticatory complex and feeding behaviors like primates, yet retain a primitive circumorbital region similar to their common ancestor. To address the plasticity and function of soft tissues of the lateral orbital wall, three cohorts of 10 rabbits each were raised from weaning (1 month old) to adulthood (6 months old) on diets of different mechanical properties (under-use, control, over-use). Once sacrificed, tissues were collected from the left lateral orbital wall. Dissections revealed that, rather than the anticipated postorbital ligament, rabbits instead exhibit fibrocartilage. Samples were analyzed histologically and immunohistochemically for general anatomy, fibril architecture, collagen expression/organization, and protein abundance using Western Blot analysis. Preliminary data suggests that collagen fibers are aligned differently, with an overexpression of collagen in the over-use dietary cohort versus both the control and under-use groups. In sum, these experimental findings suggest that the postorbital fibrocartilage is mechanically responsive, which contrasts with the non-masticatory nature of bony elements in the circumorbital region.Life Sciences Undergraduate Research Opportunity Progra

The Potential Trajectory of Carbapenem-Resistant Enterobacteriaceae, an Emerging Threat to Health-Care Facilities, and the Impact of the Centers for Disease Control and Prevention Toolkit.

Carbapenem-resistant Enterobacteriaceae (CRE), a group of pathogens resistant to most antibiotics and associated with high mortality, are a rising emerging public health threat. Current approaches to infection control and prevention have not been adequate to prevent spread. An important but unproven approach is to have hospitals in a region coordinate surveillance and infection control measures. Using our Regional Healthcare Ecosystem Analyst (RHEA) simulation model and detailed Orange County, California, patient-level data on adult inpatient hospital and nursing home admissions (2011-2012), we simulated the spread of CRE throughout Orange County health-care facilities under 3 scenarios: no specific control measures, facility-level infection control efforts (uncoordinated control measures), and a coordinated regional effort. Aggressive uncoordinated and coordinated approaches were highly similar, averting 2,976 and 2,789 CRE transmission events, respectively (72.2% and 77.0% of transmission events), by year 5. With moderate control measures, coordinated regional control resulted in 21.3% more averted cases (n = 408) than did uncoordinated control at year 5. Our model suggests that without increased infection control approaches, CRE would become endemic in nearly all Orange County health-care facilities within 10 years. While implementing the interventions in the Centers for Disease Control and Prevention's CRE toolkit would not completely stop the spread of CRE, it would cut its spread substantially, by half

Reducing in-stent restenosis therapeutic manipulation of miRNA in vascular remodeling and inflammation

Background: Drug-eluting stents reduce the incidence of in-stent restenosis, but they result in delayed arterial healing and are associated with a chronic inflammatory response and hypersensitivity reactions. Identifying novel interventions to enhance wound healing and reduce the inflammatory response may improve long-term clinical outcomes. Micro–ribonucleic acids (miRNAs) are noncoding small ribonucleic acids that play a prominent role in the initiation and resolution of inflammation after vascular injury.<p></p> Objectives: This study sought to identify miRNA regulation and function after implantation of bare-metal and drug-eluting stents.<p></p> Methods: Pig, mouse, and in vitro models were used to investigate the role of miRNA in in-stent restenosis.<p></p> Results: We documented a subset of inflammatory miRNAs activated after stenting in pigs, including the miR-21 stem loop miRNAs. Genetic ablation of the miR-21 stem loop attenuated neointimal formation in mice post-stenting. This occurred via enhanced levels of anti-inflammatory M2 macrophages coupled with an impaired sensitivity of smooth muscle cells to respond to vascular activation.<p></p> Conclusions: MiR-21 plays a prominent role in promoting vascular inflammation and remodeling after stent injury. MiRNA-mediated modulation of the inflammatory response post-stenting may have therapeutic potential to accelerate wound healing and enhance the clinical efficacy of stenting

Unlocking biomarker discovery: Large scale application of aptamer proteomic technology for early detection of lung cancer

Lung cancer is the leading cause of cancer deaths, because ~84% of cases are diagnosed at an advanced stage. Worldwide in 2008, ~1.5 million people were diagnosed and ~1.3 million died – a survival rate unchanged since 1960. However, patients diagnosed at an early stage and have surgery experience an 86% overall 5-year survival. New diagnostics are therefore needed to identify lung cancer at this stage. Here we present the first large scale clinical use of aptamers to discover blood protein biomarkers in disease with our breakthrough proteomic technology. This multi-center case-control study was conducted in archived samples from 1,326 subjects from four independent studies of non-small cell lung cancer (NSCLC) in long-term tobacco-exposed populations. We measured >800 proteins in 15uL of serum, identified 44 candidate biomarkers, and developed a 12-protein panel that distinguished NSCLC from controls with 91% sensitivity and 84% specificity in a training set and 89% sensitivity and 83% specificity in a blinded, independent verification set. Performance was similar for early and late stage NSCLC. This is a significant advance in proteomics in an area of high clinical need

Effects of Dexamethasone on Mesenchymal Stromal Cell Chondrogenesis and Aggrecanase Activity: Comparison of Agarose and Self-Assembling Peptide Scaffolds

Objective: Dexamethasone (Dex) is a synthetic glucocorticoid that has pro-anabolic and anticatabolic effects in cartilage tissue engineering systems, though the mechanisms by which these effects are mediated are not well understood. We tested the hypothesis that the addition of Dex to chondrogenic medium would affect matrix production and aggrecanase activity of human and bovine bone marrow stromal cells (BMSCs) cultured in self-assembling peptide and agarose hydrogels. Design: We cultured young bovine and adult human BMSCs in (RADA)[subscript 4] self-assembling peptide and agarose hydrogels in medium containing TGF-β1±Dex and analyzed extracellular matrix composition, aggrecan cleavage products, and the effects of the glucocorticoid receptor antagonist RU-486 on proteoglycan content, synthesis, and catabolic processing. Results: Dex improved proteoglycan synthesis and retention in agarose hydrogels seeded with young bovine cells but decreased proteoglycan accumulation in peptide scaffolds. These effects were mediated by the glucocorticoid receptor. Adult human BMSCs showed minimal matrix accumulation in agarose, but accumulated ~50% as much proteoglycan and collagen as young bovine BMSCs in peptide hydrogels. Dex reduced aggrecanase activity in (RADA)[subscript 4] and agarose hydrogels, as measured by anti-NITEGE Western blotting, for both bovine and human BMSC-seeded gels. Conclusions: The effects of Dex on matrix production are dependent on cell source and hydrogel identity. This is the first report of Dex reducing aggrecanase activity in a tissue engineering culture system.National Science Foundation (U.S.). Graduate Research FellowshipNational Institutes of Health (U.S.) (Grant EB003805

Spectacles of intimacy? Mapping the moral landscape of teenage social media

This paper explores young people's expressed concerns about privacy in the context of a highly mediated cultural environment, mapping social media practices against axes of visibility and participation. Drawing on interdisciplinary conceptual resources from both the humanities and social sciences, we use ‘spectacles of intimacy’ to conceptualise breaches of privacy, mapping an emergent moral landscape for young people that moves beyond concerns with e-safety to engage with the production and circulation of audiences and value. The paper draws on data from a methodological innovation project using multi-media and mixed methods to capture lived temporalities for children and young people. We present a model that captures a moral landscape shaped by emotional concerns about social media, the affordances of those media and affective discourses emerging from young people's use of the media