730 research outputs found

    Tachycardia Related Cardiomyopathy: Response to Control of the Arrhythmia

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75609/1/j.1540-8183.1989.tb00780.x.pd

    Organotypic Culture of Neonatal Murine Inner Ear Explants

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    The inner ear is a complex organ containing highly specialised cell types and structures that are critical for sensing sound and movement. In vivo, the inner ear is difficult to study due to the osseous nature of the otic capsule and its encapsulation within an intricate bony labyrinth. As such, mammalian inner ear explants are an invaluable tool for the study and manipulation of the complex intercellular connections, structures, and cell types within this specialised organ. The greatest strength of this technique is that the complete organ of Corti, or peripheral vestibular organs including hair cells, supporting cells and accompanying neurons, is maintained in its in situ form. The greatest weakness of in vitro hair cell preparations is the short time frame in which the explanted tissue remains viable. Yet, cochlear explants have proven to be an excellent experimental model for understanding the fundamental aspects of auditory biology, substantiated by their use for over 40 years. In this protocol, we present a modernised inner ear explant technique that employs organotypic cell culture inserts and serum free media. This approach decreases the likelihood of explant damage by eliminating the need for adhesive substances. Serum free media also restricts excessive cellular outgrowth and inter-experimental variability, both of which are side effects of exogenous serum addition to cell cultures. The protocol described can be applied to culture both cochlear and vestibular explants from various mammals. Example outcomes are demonstrated by immunohistochemistry, hair cell quantification, and electrophysiological recordings to validate the versatility and viability of the protocol

    Antibodies against Merozoite Surface Protein (Msp)-119 Are a Major Component of the Invasion-Inhibitory Response in Individuals Immune to Malaria

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    Antibodies that bind to antigens expressed on the merozoite form of the malaria parasite can inhibit parasite growth by preventing merozoite invasion of red blood cells. Inhibitory antibodies are found in the sera of malaria-immune individuals, however, the specificity of those that are important to this process is not known. In this paper, we have used allelic replacement to construct a Plasmodium falciparum parasite line that expresses the complete COOH-terminal fragment of merozoite surface protein (MSP)-119 from the divergent rodent malaria P. chabaudi. By comparing this transfected line with parental parasites that differ only in MSP-119, we show that antibodies specific for this domain are a major component of the inhibitory response in P. falciparum–immune humans and P. chabaudi–immune mice. In some individual human sera, MSP-119 antibodies dominated the inhibitory activity. The finding that antibodies to a small region of a single protein play a major role in this process has important implications for malaria immunity and is strongly supportive of further understanding and development of MSP-119–based vaccines

    Antibacterial activity of blue light against nosocomial wound pathogens growing planktonically and as mature biofilms

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    The blue wavelengths within the visible light spectrum are intrinisically antimicrobial and can photodynamically inactivate the cells of a wide spectrum of bacteria (Gram positive and negative) and fungi. Furthermore, blue light is equally effective against both drug-sensitive and -resistant members of target species and is less detrimental to mammalian cells than is UV radiation. Blue light is currently used for treating acnes vulgaris and Helicobacter pylori infections; the utility for decontamination and treatment of wound infections is in its infancy. Furthermore, limited studies have been performed on bacterial biofilms, the key growth mode of bacteria involved in clinical infections. Here we report the findings of a multicenter in vitro study performed to assess the antimicrobial activity of 400-nm blue light against bacteria in both planktonic and biofilm growth modes. Blue light was tested against a panel of 34 bacterial isolates (clinical and type strains) comprising Acinetobacter baumannii, Enterobacter cloacae, Stenotrophomonas maltophilia, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Enterococcus faecium, Klebsiella pneumoniae, and Elizabethkingia meningoseptica. All planktonic-phase bacteria were susceptible to blue light treatment, with the majority (71%) demonstrating a ≥ 5-log10 decrease in viability after 15 to 30 min of exposure (54 J/cm2 to 108 J/cm2). Bacterial biofilms were also highly susceptible to blue light, with significant reduction in seeding observed for all isolates at all levels of exposure. These results warrant further investigation of blue light as a novel decontamination strategy for the nosocomial environment, as well as additional wider decontamination applications

    The ethics of diversity, equity, inclusion, and justice in the earth system sciences

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    Institutions’ motivations for pursuing diversity, equity, inclusion and justice (DEIJ) often center on the benefits to the organization, an argument known as the business case for diversity in which diverse teams are more creative, set high bars for research, and produce ideas that are more innovative than those produced by homogeneous groups. As the sole motivation for DEIJ efforts, the business case is flawed and does not address the harmful workplaces many marginalized scholars encounter. Institutions can make more progress towards diversifying the STEM workforce by acknowledging the ethical responsibilities for doing so and transitioning to an equity-centered approach. Emphasizing personal motivations to actively engage in DEIJ work resonates with individuals more, rather than engaging with DEIJ to benefit an institution’s goals. Two recent studies support this argument. The first is an alumni survey and focus groups of postdoctoral fellows in the Advanced Studies Program at the National Center for Atmospheric Research to explore alumni efforts and motivations for engaging in DEIJ work. The second study surveyed attitudes towards DEIJ efforts among STEM graduate students at Colorado State University who took a course on social responsibility in science. Both studies show the motivations for scientists to support and get involved in these efforts and indicate that the business case is misaligned with the motivations of students and professionals in STEM. Understanding the attitudes and motivations that individuals have for DEIJ in STEM presents an opportunity for how institutions can best learn from and support these motivations for systemic change

    Additional Common Polymorphisms in the PON Gene Cluster Predict PON1 Activity but Not Vascular Disease

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    Background. Paraoxonase 1 (PON1) enzymatic activity has been consistently predictive of cardiovascular disease, while the genotypes at the four functional polymorphisms at PON1 have not. The goal of this study was to identify additional variation at the PON gene cluster that improved prediction of PON1 activity and determine if these variants predict carotid artery disease (CAAD). Methods. We considered 1,328 males in a CAAD cohort. 51 tagging single-nucleotide polymorphisms (tag SNPs) across the PON cluster were evaluated to determine their effects on PON1 activity and CAAD status. Results. Six SNPs (four in PON1 and one each in PON2/3) predicted PON1 arylesterase (AREase) activity, in addition to the four previously known functional SNPs. In total, the 10 SNPs explained 30.1% of AREase activity, 5% of which was attributable to the six identified predictive SNPs. We replicate rs854567 prediction of 2.3% of AREase variance, the effects of rs3917510, and a PON3 haplotype that includes rs2375005. While AREase activity strongly predicted CAAD, none of the 10 SNPs predicting AREase predicted CAAD. Conclusions. This study identifies new genetic variants that predict additional PON1 AREase activity. Identification of SNPs associated with PON1 activity is required when evaluating the many phenotypes associated with genetic variation near PON1

    Nature-Based Interventions for Improving Health and Wellbeing : The Purpose, the People and the Outcomes

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    Engagement with nature is an important part of many people's lives, and the health and wellbeing benefits of nature-based activities are becoming increasingly recognised across disciplines from city planning to medicine. Despite this, urbanisation, challenges of modern life and environmental degradation are leading to a reduction in both the quantity and the quality of nature experiences. Nature-based health interventions (NBIs) can facilitate behavioural change through a somewhat structured promotion of nature-based experiences and, in doing so, promote improved physical, mental and social health and wellbeing. We conducted a Delphi expert elicitation process with 19 experts from seven countries (all named authors on this paper) to identify the different forms that such interventions take, the potential health outcomes and the target beneficiaries. In total, 27 NBIs were identified, aiming to prevent illness, promote wellbeing and treat specific physical, mental or social health and wellbeing conditions. These interventions were broadly categorized into those that change the environment in which people live, work, learn, recreate or heal (for example, the provision of gardens in hospitals or parks in cities) and those that change behaviour (for example, engaging people through organized programmes or other activities). We also noted the range of factors (such as socioeconomic variation) that will inevitably influence the extent to which these interventions succeed. We conclude with a call for research to identify the drivers influencing the effectiveness of NBIs in enhancing health and wellbeing.Peer reviewe

    3D Selection of 167 Substellar Companions to Nearby Stars

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    © 2022. The Author(s). Published by the American Astronomical Society. This is an open access article distributed under the Creative Commons Attribution License, to view a copy of the license, see: https://creativecommons.org/licenses/by/4.0/We analyze 5108 AFGKM stars with at least five high-precision radial velocity points, as well as Gaia and Hipparcos astrometric data, utilizing a novel pipeline developed in previous work. We find 914 radial velocity signals with periods longer than 1000 days. Around these signals, 167 cold giants and 68 other types of companions are identified, through combined analyses of radial velocity, astrometry, and imaging data. Without correcting for detection bias, we estimate the minimum occurrence rate of the wide-orbit brown dwarfs to be 1.3%, and find a significant brown-dwarf valley around 40 M Jup. We also find a power-law distribution in the host binary fraction beyond 3 au, similar to that found for single stars, indicating no preference of multiplicity for brown dwarfs. Our work also reveals nine substellar systems (GJ 234 B, GJ 494 B, HD 13724 b, HD 182488 b, HD 39060 b and c, HD 4113 C, HD 42581 d, HD 7449 B, and HD 984 b) that have previously been directly imaged, and many others that are observable at existing facilities. Depending on their ages, we estimate that an additional 10–57 substellar objects within our sample can be detected with current imaging facilities, extending the imaged cold (or old) giants by an order of magnitude.Peer reviewe
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