914 research outputs found

    Growth and photosynthetic responses of white spruce seedlings to levels of trembling aspen and red raspberry cover

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    The effect of competitve species upon crop tree regeneration and growth continues to receive attention from researchers due to the importance of the outcomes. This study stakes a new approach, by examining the combined effects of varied levels of trembling aspen (Populus tremuloides Michx.) and red raspberry (Rubus idaeus L.) upon microclimate and 68-83 cm high white spruce (Picea glauca [Moench.] Voss) seedling growth and rates of photosynthesis. Regression, curve estimation and response surface methodology were used to examine the interactions between the two competitive species and the crop species, to ascertain the importance of each competitor and in what aspect it competes

    Early Th2 inflammation in the upper respiratory mucosa as a predictor of severe COVID-19 and modulation by early treatment with inhaled corticosteroids: A mechanistic analysis

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    Background: Community-based clinical trials of the inhaled corticosteroid budesonide in early COVID-19 have shown improved patient outcomes. We aimed to understand the inflammatory mechanism of budesonide in the treatment of early COVID-19. Methods: The STOIC trial was a randomised, open label, parallel group, phase 2 clinical intervention trial where patients were randomly assigned (1:1) to receive usual care (as needed antipyretics were only available treatment) or inhaled budesonide at a dose of 800 μg twice a day plus usual care. For this experimental analysis, we investigated the nasal mucosal inflammatory response in patients recruited to the STOIC trial and in a cohort of SARS-CoV-2-negative healthy controls, recruited from a long-term observational data collection study at the University of Oxford. In patients with SARS-CoV-2 who entered the STOIC study, nasal epithelial lining fluid was sampled at day of randomisation (day 0) and at day 14 following randomisation, blood samples were also collected at day 28 after randomisation. Nasal epithelial lining fluid and blood samples were collected from the SARS-CoV-2 negative control cohort. Inflammatory mediators in the nasal epithelial lining fluid and blood were assessed for a range of viral response proteins, and innate and adaptive response markers using Meso Scale Discovery enzyme linked immunoassay panels. These samples were used to investigate the evolution of inflammation in the early COVID-19 disease course and assess the effect of budesonide on inflammation. Findings: 146 participants were recruited in the STOIC trial (n=73 in the usual care group; n=73 in the budesonide group). 140 nasal mucosal samples were available at day 0 (randomisation) and 122 samples at day 14. At day 28, whole blood was collected from 123 participants (62 in the budesonide group and 61 in the usual care group). 20 blood or nasal samples were collected from healthy controls. In early COVID-19 disease, there was an enhanced inflammatory airway response with the induction of an anti-viral and T-helper 1 and 2 (Th1/2) inflammatory response compared with healthy individuals. Individuals with COVID-19 who clinically deteriorated (ie, who met the primary outcome) showed an early blunted respiratory interferon response and pronounced and persistent Th2 inflammation, mediated by CC chemokine ligand (CCL)-24, compared with those with COVID-19 who did not clinically deteriorate. Over time, the natural course of COVID-19 showed persistently high respiratory interferon concentrations and elevated concentrations of the eosinophil chemokine, CCL-11, despite clinical symptom improvement. There was persistent systemic inflammation after 28 days following COVID-19, including elevated concentrations of interleukin (IL)-6, tumour necrosis factor-α, and CCL-11. Budesonide treatment modulated inflammation in the nose and blood and was shown to decrease IL-33 and increase CCL17. The STOIC trial was registered with ClinicalTrials.gov, NCT04416399. Interpretation: An initial blunted interferon response and heightened T-helper 2 inflammatory response in the respiratory tract following SARS-CoV-2 infection could be a biomarker for predicting the development of severe COVID-19 disease. The clinical benefit of inhaled budesonide in early COVID-19 is likely to be as a consequence of its inflammatory modulatory effect, suggesting efficacy by reducing epithelial damage and an improved T-cell response

    Comparing the effect of CTG+STan with CTG alone on emergency Cesarean section rate : STan Australian Randomized controlled Trial (START)

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    The authors would like to thank the women and their babies for participating. We would like to thank all the staff at the WCH, in particular Priya Umampathysivam, Denise Cheetham and Cecilia Heitmann for their assistance in recruitment of participants for START. We would also like to thank the members of the DSMC, Diogo Ayres-de-Campos, Scott Morris and Katherine Lee, for their oversight of START and the Clinical Information Service (CIS) team at the WCH for the comparative hospital dataPeer reviewedPublisher PD

    Alzheimer's disease-like paired helical filament assembly from truncated tau protein is independent of disulphide cross-linking

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    Abstract Alzheimer's disease is characterised by the self-assembly of tau and amyloid β proteins into oligomers and fibrils. Tau protein assembles into paired helical filaments (PHFs) that constitute the neurofibrillary tangles observed in neuronal cell bodies in individuals with Alzheimer's disease. The mechanism of initiation of tau assembly into {PHFs} is not well understood. Here we report that a truncated 95-amino acid tau fragment (corresponding to residues 297-391 of full-length tau) assembles into PHF-like fibrils in vitro without the need for other additives to initiate or template the process. Using electron microscopy, circular dichroism and X-ray fibre diffraction, we have characterised the structure of the fibrils formed from truncated tau for the first time. To explore the contribution of disulphide formation to fibril formation, we have compared the assembly of tau(297-391) under reduced and non-reducing conditions and for truncated tau carrying a {C322A} substitution. We show that disulphide bond formation inhibits assembly and that the {C322A} variant rapidly forms long and highly ordered PHFs

    The Pattern of AQP4 Expression in the Ageing Human Brain and in Cerebral Amyloid Angiopathy

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    In the absence of lymphatics, fluid and solutes such as amyloid-β (Aβ) are eliminated from the brain along basement membranes in the walls of cerebral capillaries and arteries-the Intramural Peri-Arterial Drainage (IPAD) pathway. IPAD fails with age and insoluble Aβ is deposited as plaques in the brain and in IPAD pathways as cerebral amyloid angiopathy (CAA); fluid accumulates in the white matter as reflected by hyperintensities (WMH) on MRI. Within the brain, fluid uptake by astrocytes is regulated by aquaporin 4 (AQP4). We test the hypothesis that expression of astrocytic AQP4 increases in grey matter and decreases in white matter with onset of CAA. AQP4 expression was quantitated by immunocytochemistry and confocal microscopy in post-mortem occipital grey and white matter from young and old non-demented human brains, in CAA and in WMH. Results: AQP4 expression tended to increase with normal ageing but AQP4 expression in severe CAA was significantly reduced when compared to moderate CAA (p = 0.018). AQP4 expression tended to decline in the white matter with CAA and WMH, both of which are associated with impaired IPAD. Adjusting the level of AQP4 activity may be a valid therapeutic target for restoring homoeostasis in the brain as IPAD fails with age and CAA.</p

    Enrichment of pathogenic alleles in the brittle cornea gene, ZNF469, in keratoconus

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    Keratoconus, a common inherited ocular disorder resulting in progressive corneal thinning, is the leading indication for corneal transplantation in the developed world. Genome-wide association studies have identified common SNPs 100 kb upstream of ZNF469 strongly associated with corneal thickness. Homozygous mutations in ZNF469 and PR domain-containing protein 5 (PRDM5) genes result in brittle cornea syndrome (BCS) Types 1 and 2, respectively. BCS is an autosomal recessive generalized connective tissue disorder associated with extreme corneal thinning and a high risk of corneal rupture. Some individuals with heterozygous PRDM5 mutations demonstrate a carrier ocular phenotype, which includes a mildly reduced corneal thickness, keratoconus and blue sclera. We hypothesized that heterozygous variants in PRDM5 and ZNF469 predispose to the development of isolated keratoconus. We found a significant enrichment of potentially pathologic heterozygous alleles in ZNF469 associated with the development of keratoconus (P = 0.00102) resulting in a relative risk of 12.0. This enrichment of rare potentially pathogenic alleles in ZNF469 in 12.5% of keratoconus patients represents a significant mutational load and highlights ZNF469 as the most significant genetic factor responsible for keratoconus identified to dat

    Leprosy: an educational approach with high school

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    Objetivo: Analisar o conhecimento de escolares do ensino médio sobre hanseníase antes e após a prática da educação em saúde nas salas de aula. Método: Estudo exploratório, descritivo, com população de 358 estudantes do ensino médio e amostra de 200 escolares. Critérios de seleção da amostra: alunos matriculados na escola selecionada para estudo, presentes em sala de aula e que assinaram o TCLE. Para a coleta de dados foi utilizado um questionário contendo questões fechadas sobre a hanseníase. O projeto foi submetido e aprovado pelo CEP da Universidade Federal do Rio Grande do Norte, com número de protocolo 085/08 e CAAE 00780051000-09. Resultados: Em princípio, a hanseníase era pouco conhecida pelos escolares. Entretanto, esta realidade logo se transformou após a realização da palestra como instrumento de educação em saúde. Conclusão: Enfatizou-se a importância de ações de educação em saúde sobre hanseníase realizada pela enfermagem. Descritores: Educação em Saúde, Hanseníase, Enfermagem

    Leprosy: an educational approach with high school

    Get PDF
    Objetivo: Analisar o conhecimento de escolares do ensino médio sobre hanseníase antes e após a prática da educação em saúde nas salas de aula. Método: Estudo exploratório, descritivo, com população de 358 estudantes do ensino médio e amostra de 200 escolares. Critérios de seleção da amostra: alunos matriculados na escola selecionada para estudo, presentes em sala de aula e que assinaram o TCLE. Para a coleta de dados foi utilizado um questionário contendo questões fechadas sobre a hanseníase. O projeto foi submetido e aprovado pelo CEP da Universidade Federal do Rio Grande do Norte, com número de protocolo 085/08 e CAAE 00780051000-09. Resultados: Em princípio, a hanseníase era pouco conhecida pelos escolares. Entretanto, esta realidade logo se transformou após a realização da palestra como instrumento de educação em saúde. Conclusão: Enfatizou-se a importância de ações de educação em saúde sobre hanseníase realizada pela enfermagem. Descritores: Educação em Saúde, Hanseníase, Enfermagem

    Prediction of Small for Gestational Age Infants in Healthy Nulliparous Women Using Clinical and Ultrasound Risk Factors Combined with Early Pregnancy Biomarkers

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    Objective Most small for gestational age pregnancies are unrecognised before birth, resulting in substantial avoidable perinatal mortality and morbidity. Our objective was to develop multivariable prediction models for small for gestational age combining clinical risk factors and biomarkers at 15±1 weeks’ with ultrasound parameters at 20±1 weeks’ gestation. Methods Data from 5606 participants in the Screening for Pregnancy Endpoints (SCOPE) cohort study were divided into Training (n = 3735) and Validation datasets (n = 1871). The primary outcomes were All-SGA (small for gestational age with birthweight <10th customised centile), Normotensive-SGA (small for gestational age with a normotensive mother) and Hypertensive-SGA (small for gestational age with an hypertensive mother). The comparison group comprised women without the respective small for gestational age phenotype. Multivariable analysis was performed using stepwise logistic regression beginning with clinical variables, and subsequent additions of biomarker and then ultrasound (biometry and Doppler) variables. Model performance was assessed in Training and Validation datasets by calculating area under the curve. Results 633 (11.2%) infants were All-SGA, 465(8.2%) Normotensive-SGA and 168 (3%) Hypertensive-SGA. Area under the curve (95% Confidence Intervals) for All-SGA using 15±1 weeks’ clinical variables, 15±1 weeks’ clinical+ biomarker variables and clinical + biomarkers + biometry /Doppler at 20±1 weeks’ were: 0.63 (0.59–0.67), 0.64 (0.60–0.68) and 0.69 (0.66–0.73) respectively in the Validation dataset; Normotensive-SGA results were similar: 0.61 (0.57–0.66), 0.61 (0.56–0.66) and 0.68 (0.64–0.73) with small increases in performance in the Training datasets. Area under the curve (95% Confidence Intervals) for Hypertensive-SGA were: 0.76 (0.70–0.82), 0.80 (0.75–0.86) and 0.84 (0.78–0.89) with minimal change in the Training datasets. Conclusion Models for prediction of small for gestational age, which combine biomarkers, clinical and ultrasound data from a cohort of low-risk nulliparous women achieved modest performance. Incorporation of biomarkers into the models resulted in no improvement in performance of prediction of All-SGA and Normotensive-SGA but a small improvement in prediction of Hypertensive-SGA. Our models currently have insufficient reliability for application in clinical practice however, they have potential utility in two-staged screening tests which include third trimester biomarkers and or fetal biometry

    Presentations from the MIT/Industry Cooperative Research Program : annual meeting, 1990

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    Statement of responsibility reads: Peter P. Belobaba; Catherine H. Bohutinsky; Anthony 0. Lee; Elizabeth L. Williamson; Amedeo R. Odoni, Stephan Kolitz and Mostafa Terrab; John Pararas; Robert W. Simpson; Tom Svrcek and Peter P. BelobabaJune 199
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