162 research outputs found

    The Landscape of Connected Cancer Symptom Management in Rural America: A Narrative Review of Opportunities for Launching Connected Health Interventions

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    Background: The 2016 President’s Cancer Panel called for projects focusing on improving cancer symptom management using connected health technologies (broadband and telecommunications). However, rural communities, like those in Appalachia, may experience a “double burden” of high cancer rates and lower rates of broadband access and adoption necessary for connected health solutions. Purpose: To better understand the current landscape of connected health in the management of cancer symptoms in rural America. Methods: A literature search was conducted using four academic databases (PubMed, CINAHL, MEDLINE, and PsycINFO) to locate articles published from 2010 to 2019 relevant to connected cancer symptom management in rural America. Text screening was conducted to identify relevant publications. Results: Among 17 reviewed studies, four were conducted using a randomized controlled trial; the remainder were formative in design or small pilot projects. Five studies engaged stakeholders from rural communities in designing solutions. Most commonly studied symptoms were psychological/emotional symptoms, followed by physical symptoms, particularly pain. Technologies used were primarily telephone-based; few were Internet-enabled video conferencing or web-based. Advanced mobile and Internet-based approaches were generally in the development phase. Overall, both rural patients and healthcare providers reported high acceptance, usage, and satisfaction of connected health technologies. Ten of the 17 studies reported improved symptom management outcomes. Methodological challenges that limited the interpretation of the findings were summarized. Implications: The review identified a need to engage rural stakeholders to develop and test connected cancer symptom management solutions that are based on advanced mobile and broadband Internet technologies

    Serum metabolomic signatures of fatty acid oxidation defects differentiate host-response subphenotypes of acute respiratory distress syndrome

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    BACKGROUND: Fatty acid oxidation (FAO) defects have been implicated in experimental models of acute lung injury and associated with poor outcomes in critical illness. In this study, we examined acylcarnitine profiles and 3-methylhistidine as markers of FAO defects and skeletal muscle catabolism, respectively, in patients with acute respiratory failure. We determined whether these metabolites were associated with host-response ARDS subphenotypes, inflammatory biomarkers, and clinical outcomes in acute respiratory failure. METHODS: In a nested case-control cohort study, we performed targeted analysis of serum metabolites of patients intubated for airway protection (airway controls), Class 1 (hypoinflammatory), and Class 2 (hyperinflammatory) ARDS patients (N = 50 per group) during early initiation of mechanical ventilation. Relative amounts were quantified by liquid chromatography high resolution mass spectrometry using isotope-labeled standards and analyzed with plasma biomarkers and clinical data. RESULTS: Of the acylcarnitines analyzed, octanoylcarnitine levels were twofold increased in Class 2 ARDS relative to Class 1 ARDS or airway controls (P = 0.0004 and \u3c 0.0001, respectively) and was positively associated with Class 2 by quantile g-computation analysis (P = 0.004). In addition, acetylcarnitine and 3-methylhistidine were increased in Class 2 relative to Class 1 and positively correlated with inflammatory biomarkers. In all patients within the study with acute respiratory failure, increased 3-methylhistidine was observed in non-survivors at 30 days (P = 0.0018), while octanoylcarnitine was increased in patients requiring vasopressor support but not in non-survivors (P = 0.0001 and P = 0.28, respectively). CONCLUSIONS: This study demonstrates that increased levels of acetylcarnitine, octanoylcarnitine, and 3-methylhistidine distinguish Class 2 from Class 1 ARDS patients and airway controls. Octanoylcarnitine and 3-methylhistidine were associated with poor outcomes in patients with acute respiratory failure across the cohort independent of etiology or host-response subphenotype. These findings suggest a role for serum metabolites as biomarkers in ARDS and poor outcomes in critically ill patients early in the clinical course

    The increasing threat to European forests from the invasive foliar pine pathogen, Lecanosticta acicola

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    European forests are threatened by increasing numbers of invasive pests and pathogens. Over the past century, Lecanosticta acicola, a foliar pathogen predominantly of Pinus spp., has expanded its range globally, and is increasing in impact. Lecanosticta acicola causes brown spot needle blight, resulting in premature defoliation, reduced growth, and mortality in some hosts. Originating from southern regions of North American, it devastated forests in the USA's southern states in the early twentieth century, and in 1942 was discovered in Spain.Derived from Euphresco project 'Brownspotrisk,' this study aimed to establish the current distribution of Lecanosticta species, and assess the risks of L. acicola to European forests. Pathogen reports from the literature, and new/ unpublished survey data were combined into an open-access geo-database (http://www.portaloff orestpathology.com), and used to visualise the pathogen's range, infer its climatic tolerance, and update its host range. Lecanosticta species have now been recorded in 44 countries, mostly in the northern hemisphere. The type species, L. acicola, has increased its range in recent years, and is present in 24 out of the 26 European countries where data were available. Other species of Lecanosticta are largely restricted to Mexico and Central America, and recently Colombia.The geo-database records demonstrate that L. acicola tolerates a wide range of climates across the northern hemisphere, and indicate its potential to colonise Pinus spp. forests across large swathes of the Europe. Pre-liminary analyses suggest L. acicola could affect 62% of global Pinus species area by the end of this century, under climate change predictions.Although its host range appears slightly narrower than the similar Dothistroma species, Lecanosticta species were recorded on 70 host taxa, mostly Pinus spp., but including, Cedrus and Picea spp. Twenty-three, including species of critical ecological, environmental and economic significance in Europe, are highly susceptible to L. acicola, suffering heavy defoliation and sometimes mortality. Variation in apparent susceptibility between reports could reflect variation between regions in the hosts' genetic make-up, but could also reflect the signif-icant variation in L. acicola populations and lineages found across Europe. This study served to highlight sig-nificant gaps in our understanding of the pathogen's behaviour.Lecanosticta acicola has recently been downgraded from an A1 quarantine pest to a regulated non quarantine pathogen, and is now widely distributed across Europe. With a need to consider disease management, this study also explored global BSNB strategies, and used Case Studies to summarise the tactics employed to date in Europe

    Transferability of PCR-based diagnostic protocols: An international collaborative case study assessing protocols targeting the quarantine pine pathogen Fusarium circinatum

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    [EN] Fusarium circinatum is a harmful pathogenic fungus mostly attacking Pinus species and also Pseudotsuga menziesii, causing cankers in trees of all ages, damping-off in seedlings, and mortality in cuttings and mother plants for clonal production. This fungus is listed as a quarantine pest in several parts of the world and the trade of potentially contaminated pine material such as cuttings, seedlings or seeds is restricted in order to prevent its spread to disease-free areas. Inspection of plant material often relies on DNA testing and several conventional or real-time PCR based tests targeting F. circinatum are available in the literature. In this work, an international collaborative study joined 23 partners to assess the transferability and the performance of nine molecular protocols, using a wide panel of DNA from 71 representative strains of F. circinatum and related Fusarium species. Diagnostic sensitivity, specificity and accuracy of the nine protocols all reached values >80%, and the diagnostic specificity was the only parameter differing significantly between protocols. The rates of false positives and of false negatives were computed and only the false positive rates differed significantly, ranging from 3.0% to 17.3%. The difference between protocols for some of the performance values were mainly due to cross-reactions with DNA from non-target species, which were either not tested or documented in the original articles. Considering that participating laboratories were free to use their own reagents and equipment, this study demonstrated that the diagnostic protocols for F. circinatum were not easily transferable to end-users. More generally, our results suggest that the use of protocols using conventional or real-time PCR outside their initial development and validation conditions should require careful characterization of the performance data prior to use under modified conditions (i.e. reagents and equipment). Suggestions to improve the transfer are proposed.This work was supported by COST action FP1406 Pinestrength . The work of the Estonian team was supported by the Estonian Science Foundation grants PSG136 and IUT21-04. The work of Portuguese team from INIAV was financed by INIAV I.P. Institute. The work at U. Aveiro (Portugal) was financed by European Funds through COMPETE and National Funds through the Portuguese Foundation for Science and Technology (FCT) to CESAM (UID/AMB/50017/2013 POCI-01- 0145-FEDER-007638). The work of Slovenian team was financed through Slovenian Research Agency (P4-0107) and by the Slovenian Ministry of Agriculture, Forestry and Food (Public Forestry Service). The British work was financially supported by the Forestry Commission, UK. The French work was financially supported by the French Agency for Food, environmental and occupational health safety (ANSES). The work in New Zealand was funded by Operational Research Programmes, Ministry for Primary Industries, New Zealand.Ioos, R.; Aloi, F.; Piskur, B.; Guinet, C.; Mullett, M.; Berbegal Martinez, M.; Bragança, H.... (2019). Transferability of PCR-based diagnostic protocols: An international collaborative case study assessing protocols targeting the quarantine pine pathogen Fusarium circinatum. Scientific Reports. 9:1-17. https://doi.org/10.1038/s41598-019-44672-8S1179Schmale, D. G. III & Gordon, T. R. Variation in susceptibility to pitch canker disease, caused by Fusarium circinatum, in native stands of Pinus muricata. Plant Pathol. 52, 720–725 (2003).Gordon, T. R., Kirkpatrick, S. C., Aegerter, B. J., Wood, D. L. & Storer, A. J. 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    Global Geographic Distribution and Host Range of Fusarium circinatum, the Causal Agent of Pine Pitch Canker

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    Fusarium circinatum, the causal agent of pine pitch canker (PPC), is currently one of the most important threats of Pinus spp. globally. This pathogen is known in many pine-growing regions, including natural and planted forests, and can affect all life stages of trees, from emerging seedlings to mature trees. Despite the importance of PPC, the global distribution of F. circinatum is poorly documented, and this problem is also true of the hosts within countries that are affected. The aim of this study was to review the global distribution of F. circinatum, with a particular focus on Europe. We considered (1) the current and historical pathogen records, both positive and negative, based on confirmed reports from Europe and globally; (2) the genetic diversity and population structure of the pathogen; (3) the current distribution of PPC in Europe, comparing published models of predicted disease distribution; and (4) host susceptibility by reviewing literature and generating a comprehensive list of known hosts for the fungus. These data were collated from 41 countries and used to compile a specially constructed geo-database. A review of 6297 observation records showed that F. circinatum and the symptoms it causes on conifers occurred in 14 countries, including four in Europe, and is absent in 28 countries. Field observations and experimental data from 138 host species revealed 106 susceptible host species including 85 Pinus species, 6 non-pine tree species and 15 grass and herb species. Our data confirm that susceptibility to F. circinatum varies between different host species, tree ages and environmental characteristics. Knowledge on the geographic distribution, host range and the relative susceptibility of different hosts is essential for disease management, mitigation and containment strategies. The findings reported in this review will support countries that are currently free of F. circinatum in implementing effective procedures and restrictions and prevent further spread of the pathogen

    Analysis of the Ex Vivo and In Vivo Antiretroviral Activity of Gemcitabine

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    Replication of retroviral and host genomes requires ribonucleotide reductase to convert rNTPs to dNTPs, which are then used as substrates for DNA synthesis. Inhibition of ribonucleotide reductase by hydroxyurea (HU) has been previously used to treat cancers as well as HIV. However, the use of HU as an antiretroviral is limited by its associated toxicities such as myelosuppression and hepatotoxicity. In this study, we examined the ribonucleotide reductase inhibitor, gemcitabine, both in cell culture and in C57Bl/6 mice infected with LP-BM5 murine leukemia virus (LP-BM5 MuLV, a murine AIDS model). Gemcitabine decreased infectivity of MuLV in cell culture with an EC50 in the low nanomolar range with no detectable cytotoxicity. Similarly, gemcitabine significantly decreased disease progression in mice infected with LP-BM5. Specifically, gemcitabine treatment decreased spleen size, plasma IgM, and provirus levels compared to LP-BM5 MuLV infected, untreated mice. Gemcitabine efficacy was observed at doses as low as 1 mg/kg/day in the absence of toxicity. Higher doses of gemcitabine (3 mg/kg/day and higher) were associated with toxicity as determined by a loss in body mass. In summary, our findings demonstrate that gemcitabine has antiretroviral activity ex vivo and in vivo in the LP-BM5 MuLV model. These observations together with a recent ex vivo study with HIV-1[1], suggest that gemcitabine has broad antiretroviral activity and could be particularly useful in vivo when used in combination drug therapy

    Sampling and Detection Strategies for the Pine Pitch Canker (PPC) Disease Pathogen Fusarium circinatum in Europe

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    Fusarium circinatum Nirenberg & O’Donnel is listed among the species recommended for regulation as quarantine pests in Europe. Over 60 Pinus species are susceptible to the pathogen and it also causes disease on Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) and species in genera such as Picea and Larix. The European Food Safety Authority considers the probability of new introductions—via contaminated seeds, wood material, soil and growing substrates, natural means and human activities—into the EU very likely. Due to early detection, constant surveillance and control measures, F. circinatum outbreaks have officially been eradicated in Italy and France. However, the global spread of F. circinatum suggests that the pathogen will continue to be encountered in new environments in the future. Therefore, continuous surveillance of reproductive material, nurseries and plantations, prompt control measures and realistic contingency plans will be important in Europe and elsewhere to limit disease spread and the “bridgehead effect”, where new introductions of a tree pathogen become increasingly likely as new environments are invaded, must be considered. Therefore, survey programs already implemented to limit the spread in Europe and that could be helpful for other EU countries are summarized in this review. These surveys include not only countries where pitch canker is present, such as Portugal and Spain, but also several other EU countries where F. circinatum is not present. Sampling protocols for seeds, seedlings, twigs, branches, shoots, soil samples, spore traps and insects from different studies are collated and compiled in this review. Likewise, methodology for morphological and molecular identification is herein presented. These include conventional PCR with a target-specific region located in the intergenic spacer region, as well as several real-time PCR protocols, with different levels of specificity and sensitivity. Finally, the global situation and future perspectives are addressed
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