24 research outputs found

    Role of neutrophils in CVB3 infection and viral myocarditis

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    Coxsackievirus B3 (CVB3) is a globally prevalent enterovirus of the Picornaviridae family that is frequently associated with viral myocarditis (VM). Neutrophils, as first responders, may be key cells in determining viral disease outcomes; however, neutrophils have been poorly studied with respect to viral infection. Although neutrophils have been ascribed a relevant role in early cardiac inflammation, their precise role in CVB3 infection has not yet been evaluated. In this study, we aimed to determine if the interaction between human neutrophils and CVB3 could lead to viral replication and/or modulation of neutrophil survival and biological functions, and whether neutrophil depletion in a murine model has a beneficial or harmful effect on CVB3 infection. Our results show that CVB3 interacted with but did not replicate in human neutrophils. Neutrophils recognized CVB3 mainly through endosomal TLR-8, and infection triggered NFκB activation. Virus internalization resulted in increased cell survival, up-regulation of CD11b, enhanced adhesion to fibrinogen and fibronectin, and the secretion of IL-6, IL-1β, TNF-α, and IL-8. Supernatants from infected neutrophils exerted chemotactic activity partly mediated by IL-8. The infected neutrophils released myeloperoxidase and triggered neutrophil extracellular trap formation in the presence of TNF-α. In mice infected with CVB3, viral RNA was detected in neutrophils as well as in mononuclear cells. After neutrophil depletion, mice showed reduced VM reflected by a reduction in viral titers, cell exudates, and CCL-2 mRNA levels, as well as the abrogation of reactive cardiomyocyte hypertrophy. Our results indicate that neutrophils have relevant direct and indirect roles in the pathogenesis of CVB3-induced VM.Fil: Rivadeneyra, Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Charó, Nancy Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Kviatcovsky, Denise. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: de la Barrera, Silvia Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Gomez, Ricardo Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; ArgentinaFil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentin

    Perspective:Dietary Biomarkers of Intake and Exposure - Exploration with Omics Approaches

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    While conventional nutrition research has yielded biomarkers such as doubly labeled water for energy metabolism and 24-h urinary nitrogen for protein intake, a critical need exists for additional, equally robust biomarkers that allow for objective assessment of specific food intake and dietary exposure. Recent advances in high-throughput MS combined with improved metabolomics techniques and bioinformatic tools provide new opportunities for dietary biomarker development. In September 2018, the NIH organized a 2-d workshop to engage nutrition and omics researchers and explore the potential of multiomics approaches in nutritional biomarker research. The current Perspective summarizes key gaps and challenges identified, as well as the recommendations from the workshop that could serve as a guide for scientists interested in dietary biomarkers research. Topics addressed included study designs for biomarker development, analytical and bioinformatic considerations, and integration of dietary biomarkers with other omics techniques. Several clear needs were identified, including larger controlled feeding studies, testing a variety of foods and dietary patterns across diverse populations, improved reporting standards to support study replication, more chemical standards covering a broader range of food constituents and human metabolites, standardized approaches for biomarker validation, comprehensive and accessible food composition databases, a common ontology for dietary biomarker literature, and methodologic work on statistical procedures for intake biomarker discovery. Multidisciplinary research teams with appropriate expertise are critical to moving forward the field of dietary biomarkers and producing robust, reproducible biomarkers that can be used in public health and clinical research

    Cognitive aids for people with early stage dementia versus treatment as usual (Dementia Early Stage Cognitive Aids New Trial (DESCANT)): study protocol for a randomised controlled trial

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    Background: There is a growing need for an evidence-based approach to home support for people with dementia and their carers following diagnosis but research on the effectiveness and cost-effectiveness of different approaches is sparse. The Dementia Early Stage Cognitive Aids New Trial (DESCANT) will evaluate the clinical and costeffectiveness of a range of memory aids, training and support to people with mild to moderate dementia and their carers at home and compares that intervention with treatment as usual.Methods/design: This is a multi-site, pragmatic randomised trial preceded by a feasibility study and internal pilot. We aim to allocate at random 360 pairs comprising a person with mild to moderate dementia and an identified carer between the DESCANT intervention and treatment as usual. We assess participants at baseline, 13 and 26 weeks. The primary outcome measure is the Bristol Activities of Daily Living Scale; other participant outcomes include cognition, quality of life, activities of daily living and social networking; carer outcomes include quality of life, sense of competence and mental health. To enhance this quantitative evaluation we are conducting a qualitative component and a process evaluation to assess the implementation process and identify contextual factors associated with variation.Discussion: The DESCANT intervention reflects current policy to enhance the capabilities of people with dementia after diagnosis and their carers. If it is clinically and cost-effective, its modest nature and cost will enhance the likelihood of it being incorporated into mainstream practice.Trial registration: Current Controlled Trials, ISRCTN12591717. Registered on 29 July 2016.Protocol number: 31288: North West - Haydock Research Ethics Committee, 20/06/2016, ref.: 16/NW/0389

    Pretreatment anxiety and pain acceptance are associated with response to trigger point injection therapy for chronic myofascial pain

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    Background and AimThis study examined the psychosocial profile of patients who responded or did not respond to trigger point injection therapy for chronic myofascial pain. MethodsSeventy one patients with a diagnosis of chronic myofascial pain of the paraspinous muscles completed a pretreatment questionnaire measuring demographic and social factors, and validated scales to assess pain intensity, pain interference (physical and emotional), and defined psychological characteristics (pain catastrophizing, pain acceptance, pain self-efficacy, mood and anxiety). Trigger point injection therapy of the affected areas of myofascial pain was performed and follow-up was conducted by telephone at one week (n=65) and one month (n=63) post intervention to assess treatment outcome (pain intensity and pain-related physical interference). ResultsAt one week follow-up and one-month follow-up, using pain-related physical interference as the outcome measure, we found that those who responded well to treatment were characterized by a lower level of pretreatment anxiety and a higher level of pain acceptance, with anxiety being the strongest predictor. ConclusionThese results suggest that responses to interventional pain management in chronic myofascial paraspinous pain may be influenced by psychological characteristics, especially pretreatment anxiety

    Efficient Monitoring of Treatment Response during Youth Psychotherapy: The Behavior and Feelings Survey

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    An emerging trend in youth psychotherapy is measurement-based care (MBC): treatment guided by frequent measurement of client response, with ongoing feedback to the treating clinician. MBC is especially needed for treatment that addresses internalizing and externalizing problems, which are common among treatment-seeking youths. A very brief measure is needed, for frequent administration, generating both youth- and caregiver-reports, meeting psychometric standards, and available at no cost. We developed such a measure to monitor youth response during psychotherapy for internalizing and externalizing problems. Across 4 studies, we used ethnically diverse, clinically relevant samples of caregivers and youths ages 7-15 to develop and test the Behavior and Feelings Survey (BFS). In Study 1, candidate items identified by outpatient youths and their caregivers were examined via an MTurk survey, with item response theory methods used to eliminate misfitting items. Studies 2-4 used separate clinical samples of youths and their caregivers to finalize the 12-item BFS (6 internalizing and 6 externalizing items), examine its psychometric properties, and assess its performance in monitoring progress during psychotherapy. The BFS showed robust factor structure, internal consistency, test-retest reliability, convergent and discriminant validity in relation to three well-established symptom measures, and slopes of change indicating efficacy in monitoring treatment progress during therapy. The BFS is a brief, free youth- and caregiver-report measure of internalizing and externalizing problems, with psychometric evidence supporting its use for MBC in clinical and research contexts
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