2,670 research outputs found

    Growing Pains or Opportunities? A Customer Survey of Three Farmers\u27 Markets in One Rural Community

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    The continued growth of farmers\u27 markets is presenting new challenges to Extension. As the number of markets expands, how can Extension help those in the same community work together for mutual benefit? The study reported here examined similarities and differences among customers attending three different farmers\u27 markets within a single locality in Gettysburg, Pennsylvania. Based on 370 customer surveys, study results underscore the diversity of markets operating within the same community and provide insights into ways Extension might assist markets to work together to expand their shared customer base, increase revenues, and better serve local residents

    Shape and Compliance of Endothelial Cells after Shear Stress In Vitro or from Different Aortic Regions: Scanning Ion Conductance Microscopy Study

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    Objective: To measure the elongation and compliance of endothelial cells subjected to different patterns of shear stress in vitro, and to compare these parameters with the elongation and compliance of endothelial cells from different regions of the intact aorta. Materials and Methods: Porcine aortic endothelial cells were cultured for 6 days under static conditions or on an orbital shaker. The shaker generated a wave of medium, inducing pulsatile shear stress with a preferred orientation at the edge of the well or steadier shear stress with changing orientation at its centre. The topography and compliance of these cells and cells from the inner and outer curvature of ex vivo porcine aortic arches were measured by scanning ion conductance microscopy (SICM). Results: Cells cultured under oriented shear stress were more elongated and less compliant than cells grown under static conditions or under shear stress with no preferred orientation. Cells from the outer curvature of the aorta were more elongated and less compliant than cells from the inner curvature. Conclusion: The elongation and compliance of cultured endothelial cells vary according to the pattern of applied shear stress, and are inversely correlated. A similar inverse correlation occurs in the aortic arch, with variation between region

    P2X7 Receptor Primes IL-1β and the NLRP3 Inflammasome in Astrocytes Subjected to Mechanical Strain

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    Inflammatory responses play a key role in many neural pathologies, with localized signaling from non-immune cells making critical contributions. The NLRP3 inflammasome is an important component of innate immune signaling and can link neural insult to chronic inflammation. Stimulation of the NLRP3 inflammasome is a two-stage process. The priming stage involves upregulation of the biosynthesis of the structural components while activation results in their assembly into the actual inflammasome complex and subsequent activation. The priming step can be rate limiting and can connect insult to chronic inflammation but our knowledge of the signals that regulate NLRP3 inflammasome priming in sterile inflammatory conditions is limited. This study examined the link between mechanical strain and inflammasome priming in neural systems. Transient non-ischemic elevation of intraocular pressure (IOP) increased mRNA for inflammasome components IL-1β, NLRP3, ASC, CASP1 and IL-6 in rat and mouse retinas. The P2X7 receptor was implicated in the in vivo mechanosensitive priming of IL-1β and IL-6 transcription and translation. In vitro experiments with optic nerve head astrocytes demonstrated enhanced expression of the IL-1β and IL-6 genes following stretching or swelling. The increase in IL-1β expression was inhibited by degradation of extracellular ATP with apyrase, blocking pannexin hemichannels with carbenoxolone, probenecid or 10Panx1 peptide, P2X7 receptor antagonists (BBG, A839977 or A740003) as well inhibition of the NFκB transcription factor with Bay 11-7082. The swelling-dependent fall in expression of the NFκB inhibitor IκB-α was reduced by treatment of cells with A839977 and in P2X7 knockout mice. In summary, our data suggest that mechanical trauma to the retina results in priming of the NLRP3 inflammasome components and upregulated IL-6 expression and release. This was dependent upon ATP release through pannexin hemichannels and autostimulation of the P2X7 receptor. Since the P2X7 receptor can also trigger inflammasome activation it appears to have a central role in linking mechanical strain to neuroinflammation

    COS-Speech: Protocol to develop a core outcome set for dysarthria after stroke for use in clinical practice and research

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    BACKGROUND: Dysarthria after stroke is when speech intelligibility is impaired, and this occurs in half of all stroke survivors. Dysarthria often leads to social isolation, poor psychological well-being and can prevent return to work and social lives. Currently, a variety of outcome measures are used in clinical research and practice when monitoring recovery for people who have dysarthria. When research studies use different measures, it is impossible to compare results from trials and delays our understanding of effective clinical treatments. The aim of this study is to develop a core outcome set (COS) to agree what aspects of speech recovery should be measured for dysarthria after stroke (COS-Speech) in research and clinical practice. METHODS: The COS-Speech study will include five steps: (1) development of a long list of possible outcome domains of speech that should be measured to guide the survey; (2) recruitment to the COS-Speech study of three key stakeholder groups in the UK and Australia: stroke survivors, communication researchers and speech and language therapists/pathologists; (3) two rounds of the Delphi survey process; (4) a consensus meeting to agree the speech outcomes to be measured and a follow-up consensus meeting to match existing instruments/measures (from parallel systematic review) to the agreed COS-Speech; (5) dissemination of COS-Speech. DISCUSSION: There is currently no COS for dysarthria after stroke for research trials or clinical practice. The findings from this research study will be a minimum COS, for use in all dysarthria research studies and clinical practice looking at post-stroke recovery of speech. These findings will be widely disseminated using professional and patient networks, research and clinical forums as well as using a variety of academic papers, videos, accessible writing such as blogs and links on social media. TRIAL REGISTRATION: COS-Speech is registered with the Core Outcome Measures in Effectiveness Trials (COMET) database, October 2021 https://www.comet-initiative.org/Studies/Details/1959. In addition, “A systematic review of the psychometric properties and clinical utility of instruments measuring dysarthria after stroke” will inform the consensus meeting to match measures to COS-Speech. The protocol for the systematic reviews registered with the International Prospective Register of Systematic Reviews. PROSPERO registration number: CRD42022302998. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-022-06958-7

    Farmers Markets and the Local Food System: The Case of Gettysburg, Pennsylvania

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    In order to examine and obtain a better understanding of the local food system within Adams County, Pennsylvania, this study explores the characteristics and perspectives of the customers and vendors at the farmers markets in Gettysburg, Pennsylvania. Survey findings from the Gettysburg Farmers Market and the three Adams County Farmers Markets include customer demographic information, perspectives and shopping behavior as well as vendor product information, farm size and location and preference for market management. Introductory background information on the Farm Bill and the influence of agricultural practices on the environment, human health and nutrition and the relationship between farmers markets and the local economy are offered in order to emphasize the value of a well-managed local food system. Conclusions provide evidence that lower income and lower education levels are not sufficiently represented at all the markets and food stamp programs are being underutilized. This study suggests employing additional marketing to target underrepresented demographic groups, public transportation to potentially inaccessible market locations and increased advertisement and encouragement of food stamp programs at all markets in order to expand the customer base and increase access to healthy, local foods for less advantaged citizens. The results from this study are intended to offer evidence that will promote and facilitate market management, strengthen customer/vendor relationships and encourage better ties between the local community and local food systems at the farmers markets within Gettysburg in Adams County, Pennsylvania

    Stimulation of an α1-adrenergic receptor downregulates ecto-5′ nucleotidase activity on the apical membrane of RPE cells

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    The purines ATP and adenosine play an important role in the communication between the photoreceptors and the retinal pigment epithelium (RPE). While the RPE is known to release ATP into subretinal space, the source of extracellular adenosine is unclear. In other tissues, ecto-nucleotidases mediate the consecutive dephosphorylation of ATP to AMP, and AMP is converted to adenosine by ecto-5′ nucleotidase (CD73). This study identifies ecto-5′ nucleotidase on RPE cells and investigates modulation of enzyme activity. The RPE was the most active site of 5′AMP dephosphorylation in the posterior rat eye. The ecto-5′ nucleotidase inhibitor αβmADP prevented the production adenosine by the apical membrane of the bovine RPE. Cultured human ARPE-19 cells expressed mRNA and protein for ecto-5′ nucleotidase. The production of phosphate from 5′AMP by ARPE-19 cells was inhibited by αβmADP, but the ecto-alkaline phosphatase inhibitor levamisole had no effect. Degradation of 5′AMP was blocked by norepinephrine, epinephrine and phenylephrine, with inhibition by antagonists prazosin and corynanthine implicating the α1 adrenergic receptor. The block of enzyme activity by norepinephrine was rapid, occurring within 1 min, and was similar at both 4 and 37°C, consistent with cleavage of the enzyme from its GPI anchor. HPLC measurements indicated norepinephrine reduced levels of adenosine in the bath. In the apical face of the bovine-RPE eyecup, norepinephrine reduced the production of phosphate from 5′AMP, suggesting that both receptor and enzyme face sub-retinal space. In conclusion, RPE cells express ecto-5′ nucleotidase, with activity on the apical membrane, and stimulation of α-1 adrenergic receptors downregulates activity. As epinephrine is released at light onset, and adenosine can inhibit phagocytosis, the corresponding decrease in subretinal adenosine levels may contribute to the enhanced the phagocytosis of rod outer segments that occurs at this time

    Polarized Cytokine Release Triggered by P2X7 Receptor from Retinal Pigmented Epithelial Cells Dependent on Calcium Influx

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    Cytokine release from non-inflammatory cells is a key step in innate immunity, and agonists triggering cytokine release are central in coordinating responses. P2X7 receptor (P2X7R) stimulation by extracellular ATP is best known to active the NLRP3 inflammasome and release IL-1β, but stimulation also leads to release of other cytokines. As cytokine signaling by retinal pigmented epithelial (RPE) cells is implicated in retinal neurodegeneration, the role of P2X7R in release of cytokine IL-6 from RPE cells was investigated. P2X7R stimulation triggered IL-6 release from primary mouse RPE, human iPS-RPE and human ARPE-19 cells. IL-6 release was polarized, with predominant rise across apical membranes. IL-6 release was inhibited by P2X7R antagonists A438079, A839977, and AZ10606120, but not the NRTI lamivudine (3TC), P2X1R antagonist NF279, or P2Y1R antagonist MRS2179. P2X7R-mediated IL-6 release required extracellular Ca2+ and was blocked by Ca2+ chelator BAPTA. IL-6 release and Ca2+ elevation occurred rapidly, consistent with vesicular IL-6 staining in unstimulated cells. P2X7R stimulation did not trigger IL-1β release in these unprimed cells. P2X7R-mediated IL-6 release was enhanced in RPE cells from the ABCA4-/- mouse model of retinal degeneration. In summary, P2X7R stimulation triggers rapid Ca2+-dependent IL-6 release across the apical membrane of RPE cells

    Emergency ambulance service involvement with residential care homes in the support of older people with dementia : an observational study

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    © 2014 Amador et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.BACKGROUND: Older people resident in care homes have a limited life expectancy and approximately two-thirds have limited mental capacity. Despite initiatives to reduce unplanned hospital admissions for this population, little is known about the involvement of emergency services in supporting residents in these settings.METHODS: This paper reports on a longitudinal study that tracked the involvement of emergency ambulance personnel in the support of older people with dementia, resident in care homes with no on-site nursing providing personal care only. 133 residents with dementia across 6 care homes in the East of England were tracked for a year. The paper examines the frequency and reasons for emergency ambulance call-outs, outcomes and factors associated with emergency ambulance service use. RESULTS: 56% of residents used ambulance services. Less than half (43%) of all call-outs resulted in an unscheduled admission to hospital. In addition to trauma following a following a fall in the home, results suggest that at least a reasonable proportion of ambulance contacts are for ambulatory care sensitive conditions. An emergency ambulance is not likely to be called for older rather than younger residents or for women more than men. Length of residence does not influence use of emergency ambulance services among older people with dementia. Contact with primary care services and admission route into the care home were both significantly associated with emergency ambulance service use. The odds of using emergency ambulance services for residents admitted from a relative's home were 90% lower than the odds of using emergency ambulance services for residents admitted from their own home. CONCLUSIONS: Emergency service involvement with this vulnerable population merits further examination. Future research on emergency ambulance service use by older people with dementia in care homes, should account for important contextual factors, namely, presence or absence of on-site nursing, GP involvement, and access to residents' family, alongside resident health characteristics.Peer reviewedFinal Published versio
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