Nordentoftmikkelsen9494

BACKGROUND . Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in young infants. However, it is also a significant pathogen in older adults. Validated biomarkers of RSV disease severity would benefit diagnostics, treatment decisions, and prophylactic interventions. This review summarizes knowledge of biomarkers for RSV disease in adults. METHODS A literature review was performed using Ovid Medline, Embase, Global health, Scopus, and Web of Science for articles published 1946-October 2016. Nine articles were identified plus 9 from other sources. RESULTS From observational studies of natural infection and challenge studies in volunteers, biomarkers of RSV susceptibility or disease severity in adults were (1) lower anti-RSV neutralizing antibodies, where neutralizing antibody (and local IgA) may be a correlate of susceptibility/severity; (2) RSV-specific CD8+ T cells in bronchoalveolar lavage fluid preinfection (subjects with higher levels had less severe illness); and (3) elevated interleukin-6 (IL-6), IL-8, and myeloperoxidase levels in the airway are indicative of severe infection. CONCLUSIONS Factors determining susceptibility to and severity of RSV disease in adults have not been well defined. Respiratory mucosal antibodies and CD8+ T cells appear to contribute to preventing infection and modulation of disease severity. Studies of RSV pathogenesis in at-risk populations are needed. © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.BACKGROUND Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory infection (ALRI) in young children aged less then 5 years. METHODS We aimed to identify the global inpatient and outpatient cost of management of RSV-ALRI in young children to assist health policy makers in making decisions related to resource allocation for interventions to reduce severe morbidity and mortality from RSV in this age group. We searched 3 electronic databases including Global Health, Medline, and EMBASE for studies reporting cost data on RSV management in children under 60 months from 2000 to 2017. Unpublished data on the management cost of RSV episodes were collected through collaboration with an international working group (RSV GEN) and claim databases. RESULTS We identified 41 studies reporting data from year 1987 to 2017, mainly from Europe, North America, and Australia, covering the management of a total of 365 828 RSV disease episodes. The average cost per episode was €3452 (95% confidence interval [sions@oup.com.OBJECTIVES This study investigated linear and non-linear age effects on language use with speech samples that were representative of naturally occurring conversations. METHOD Using a corpus-based approach, we examined couples' conflict conversations in the laboratory. The conversations, from a total of 364 community dwelling German-speaking heterosexual couples (aged 19 to 82), were videotaped and transcribed. We examined usage of lower-frequency words, grammatical complexity, and utterance of filled pauses (e.g., äh ["um"]). RESULTS Multilevel models showed that age effects on the usage of lower-frequency words were non-significant. Grammatical complexity increased until middle age (i.e., 54) and then declined. The utterance of filled pauses increased until old age (i.e., 70) and then decreased. DISCUSSION Results are discussed in relation to cognitive aging research. © The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.Monitoring and deciding how to adjust an active regulatory strategy in order to maximize adaptive outcomes is an integral element of emotion regulation, yet existing evidence remains scarce. Filling this gap, the present study examined core factors that determine behavioral regulatory monitoring decisions and the neuro-affective consequences of these decisions. Using a novel paradigm, the initial implementation of central downregulation strategies (distraction, reappraisal) and the emotional intensity (high, low) were manipulated, prior to making a behavioral decision to maintain the initial implemented strategy or switch from it. Neuro-affective consequences of these behavioral decisions were evaluated using the Late Positive Potential (LPP), an electro-cortical measure of regulatory success. Confirming predictions, initial implementation of reappraisal in high intensity and distraction in low intensity (Strategy × Intensity combinations that were established in prior studies as non-preferred by individuals), resulted in increased behavioral switching frequency. Neurally, we expected and found that in high (but not low) emotional intensity, where distraction was more effective than reappraisal, maintaining distraction (relative to switching to reappraisal) and switching to distraction (relative to maintaining reappraisal) resulted in larger LPP modulation. These findings suggest that monitoring decisions are consistent with previously established regulatory preferences and are associated with adaptive short-term neural consequences. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email journals.permissions@oup.com.BACKGROUND Concentrations of cardiac troponin I (cTnI) and T (cTnT) are associated with clinical cardiac outcomes, but do not correlate closely in subjects recruited from the general population. Accordingly, we hypothesized that cTnI and cTnT concentrations would be influenced by different cardiovascular (CV) and non-CV risk factors and reflect different CV phenotypes. METHODS We measured cTnI and cTnT with last generation assays in 1236 women and 1157 men with no known CV disease participating in the prospective observational Akershus Cardiac Examination 1950 Study. All study participants underwent extensive CV phenotyping at baseline, including detailed echocardiography. RESULTS Concentrations of cTnI were measurable in 60.3% and cTnT in 72.5% of study participants (P  less then  0.001), and correlated moderately (r = 0.53; P  less then  0.001). cTnI was more strongly associated with male sex (P = 0.018), higher education (P  less then  0.001), history of hypertension (P  less then  0.001), and age (P  less then  0.001), whereas cTnT was more strongly associated with eGFR (P = 0.015). Both cTnI and cTnT were inversely associated with global longitudinal strain and positively associated with LV mass index (LVMI) in analyses adjusted for CV risk factors. The association between cTnI and LVMI was stronger than the association between cTnT and LVMI (P = 0.035). selleck inhibitor Concentrations of cTnI improved diagnostic accuracy for LV hypertrophy when added to established CV risk factors, but concentrations of cTnT did not improve these models further. CONCLUSIONS In a large community-based cohort examined with extensive echocardiography, concentrations of cTnI and cTnT are associated with subclinical LV hypertrophy and dysfunction. Concentrations of cTnI appear superior to cTnT in predicting subclinical LV hypertrophy. © American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email journals.permissions@oup.com.STUDY QUESTION Are women with a history of first-onset postpartum psychiatric disorders after their first liveborn delivery less likely to have a subsequent live birth? SUMMARY ANSWER Women with incident postpartum psychiatric disorders are less likely to go on to have further children. WHAT IS KNOWN ALREADY Women are particularly vulnerable to psychiatric disorders in the postpartum period. The potential effects of postpartum psychiatric disorders on the mother's future chances of live birth are so far under-researched. STUDY DESIGN, SIZE, DURATION A population-based cohort study consisted of 414 571 women who had their first live birth during 1997-2015. We followed the women for a maximum of 19.5 years from the date of the first liveborn delivery until the next conception leading to a live birth, emigration, death, their 45th birthday or 30 June 2016, whichever occurred first. PARTICIPANTS/MATERIALS, SETTING, METHODS Postpartum psychiatric disorders were defined as filling a prescription for psychotropic meThe authors do not declare any conflicts of interest. TRIAL REGISTRATION NUMBER N/A. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. link2 All rights reserved. For permissions, please e-mail journals.permission@oup.com.BACKGROUND Glioblastoma  (GBM) has been extensively researched over the last few decades, yet despite aggressive multi-modal treatment, recurrence is inevitable and second-line treatment options are limited. Here, we demonstrate how high throughput screening (HTS) in multicellular spheroids can generate physiologically relevant patient chemosensitivity data using patient-derived cells in a rapid and cost-effective manner. Our HTS system identified ACTD to be highly cytotoxic over a panel of twelve patient-derived glioma stem-like cell lines (GSCs). Actinomycin D (ACTD) is antineoplastic antibiotic used in the treatment of childhood cancers. Here, we validate ACTD as a potential repurposed therapeutic for glioblastoma in three-dimensional GSC cultures and patient-derived xenograft models of recurrent glioblastoma. METHODS Twelve patient-derived GSCs were screened at 10µM, as multicellular spheroids, in a 384-well serum-free assay with 133 FDA-approved compounds. GSCs were then treated in vitro with ACTD at established IC50 concentrations. Downregulation of Sox2, a stem-cell transcription factor, was investigated via western blot and through immunohistological assessment of murine brain tissue. RESULTS Treatment with ACTD was shown to significantly reduce tumor growth in two recurrent GBM (rGBM) patient-derived models and significantly increased survival. ACTD is also shown to specifically downregulate the expression of Sox2 both in vitro and in vivo. CONCLUSION These findings indicate that, as predicted by our HTS, ACTD could deplete the cancer stem cell population within the tumor mass, ultimately leading to a delay in tumor progression. © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.Photoperiodic flowering responses are classified into three major types long day (LD), short day (SD), and day neutral (DN). The inverse responses to day length of LD and SD plants have been partly characterized in Arabidopsis and rice, however, the molecular mechanism underlying DN response is largely unknown. Modern roses are economically important ornamental plants with continuous flowering (CF) features, and generally regarded as DN plants. In this paper, RcCO and RcCOL4 were identified as floral activators up-regulated under LD and SD condition in CF cultivar Rosa chinensis 'Old-Blush' respectively. Diminishing the expressions of RcCO or/and RcCOL4 by virus induced gene silence (VIGS) delayed flowering time under both SD and LD. Interestingly, in contrast to RcCO-silenced plants flowering time of RcCOL4-silenced plants were more delayed under SD than LD condition, indicating perturbed plant responses to DN. link3 Further analyses revealed that physical interaction between RcCOL4 and RcCO facilitated binding of RcCO to CORE motif in the promoter of RcFT and induction of RcFT.