1,145 research outputs found

    Relative importance of microplastics as a pathway for the transfer of hydrophobic organic chemicals to marine life

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    publisher: Elsevier articletitle: Relative importance of microplastics as a pathway for the transfer of hydrophobic organic chemicals to marine life journaltitle: Environmental Pollution articlelink: http://dx.doi.org/10.1016/j.envpol.2016.09.046 content_type: article copyright: © 2016 Published by Elsevier Ltd

    Mapping the complete glycoproteome of virion-derived HIV-1 gp120 provides insights into broadly neutralizing antibody binding

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    The surface envelope glycoprotein (SU) of Human immunodeficiency virus type 1 (HIV-1), gp120SU plays an essential role in virus binding to target CD4+ T-cells and is a major vaccine target. Gp120 has remarkably high levels of N-linked glycosylation and there is considerable evidence that this “glycan shield” can help protect the virus from antibody-mediated neutralization. In recent years, however, it has become clear that gp120 glycosylation can also be included in the targets of recognition by some of the most potent broadly neutralizing antibodies. Knowing the site-specific glycosylation of gp120 can facilitate the rational design of glycopeptide antigens for HIV vaccine development. While most prior studies have focused on glycan analysis of recombinant forms of gp120, here we report the first systematic glycosylation site analysis of gp120 derived from virions produced by infected T lymphoid cells and show that a single site is exclusively substituted with complex glycans. These results should help guide the design of vaccine immunogens

    Effects of anthropogenic emissions on the molecular composition of urban organic aerosols: An ultrahigh resolution mass spectrometry study

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    Identification of the organic composition of atmospheric aerosols is necessary to develop effective air pollution mitigation strategies. However, the majority of the organic aerosol mass is poorly characterized and its detailed analysis is a major analytical challenge. In this study, we applied state-of-the-art direct infusion nano-electrospray (nanoESI) ultrahigh resolution mass spectrometry (UHRMS) and liquid chromatography ESI Quadrupole Time-of-Flight (Q-TOF) MS for the analysis of the organic fraction of fine particulate matter (PM2.5) collected at an urban location in Cork, Ireland. Comprehensive mass spectral data evaluation methods (e.g., Kendrick Mass Defect and Van Krevelen) were used to identify compound classes and mass distributions of the detected species. Up to 850 elemental formulae were identified in negative mode nanoESI-UHR-MS. Nitrogen and/or sulphur containing organic species contributed up to 40% of the total identified formulae and exhibited strong diurnal variations suggesting the importance of night-time NO3 chemistry at the site. The presence of a large number of oxidised aromatic and nitroaromatic compounds in the samples indicated a strong anthropogenic influence, i.e., from traffic emissions and domestic solid fuel (DSF) burning. Most of the identified biogenic secondary organic aerosol (SOA) compounds are later-generation nitrogen- and sulphur-containing products, indicating that SOA composition is strongly affected by anthropogenic species such as NOx and SO2. Unsaturated and saturated C12–C20 fatty acids were found to be the most abundant homologs with a composition reflecting a primary marine origin. The results of this work demonstrate that the studied site is a very complex environment affected by a variety of anthropogenic activities and natural sources.Research at the University of Cambridge was supported by a Marie Curie Intra-European fellowship (project # 254319) and the European Research Council (ERC starting grant 279405).This is the accepted version. The final version is available from Elsevier at http://www.sciencedirect.com/science/article/pii/S1352231014001472

    Visual short-term memory impairments in presymptomatic familial Alzheimer's disease: A longitudinal observational study

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    Visual short-term memory (VSTM) deficits including VSTM binding have been associated with Alzheimer's disease (AD) from preclinical to dementia stages, cross-sectionally. Yet, longitudinal investigations are lacking. The objective of this study was to evaluate VSTM function longitudinally and in relation to expected symptom onset in a cohort of familial Alzheimer's disease. Ninety-nine individuals (23 presymptomatic; 9 symptomatic and 67 controls) were included in an extension cross-sectional study and a sub-sample of 48 (23 presymptomatic carriers, 6 symptomatic and 19 controls), attending two to five visits with a median interval of 1.3 years, included in the longitudinal study. Participants completed the "What was where?" relational binding task (which measures memory for object identification, localisation and object-location binding under different conditions of memory load and delay), neuropsychology assessments and genetic testing. Compared to controls, presymptomatic carriers within 8.5 years of estimated symptom onset showed a faster rate of decline in localisation performance in long-delay conditions (4 seconds) and in traditional neuropsychology measures of verbal episodic memory. This study represents the first longitudinal VSTM investigation and shows that changes in memory resolution may be sensitive to tracking cognitive decline in preclinical AD at least as early as changes in the more traditional verbal episodic memory tasks

    Platelet rich plasma injection for acute Achilles tendon rupture: PATH-2 randomised, placebo controlled, superiority trial

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    This is the final version. Available on open access from BMJ Publishing via the DOI in this record. Objective To determine whether an injection of platelet rich plasma improves outcomes after acute Achilles tendon rupture. Design Randomised, placebo controlled, two arm, parallel group, participant and assessor masked, superiority trial. Setting Secondary care trauma units across 19 hospitals in the United Kingdom's health service. Participants Recruitment commenced in July 2015 and follow-up was completed in March 2018. 230 adults aged 18 years and over were included, with acute Achilles tendon rupture presenting within 12 days of injury and managed with non-surgical treatment. Exclusions were injury at the insertion or musculotendinous junction, major leg injury or deformity, diabetes mellitus, platelet or haematological disorder, systemic corticosteroids, anticoagulation treatment, and other contraindicating conditions. Interventions Participants were randomised 1:1 to platelet rich plasma (n=114) or placebo (dry needle; n=116) injection. All participants received standard rehabilitation care (ankle immobilisation followed by physiotherapy). Main outcomes and measures Primary outcome was muscle tendon function at 24 weeks, measured objectively with the limb symmetry index (injured/uninjured×100) in maximal work done during the heel rise endurance test (an instrumented measure of repeated single leg heel rises until fatigue). Secondary outcomes included patient reported function (Achilles tendon rupture score), quality of life (short form 12 version 2¼), pain (visual analogue scale), goal attainment (patient specific functional scale), and adverse events. A central laboratory analysed the quality and content of platelet rich plasma. Analyses were by modified intention to treat. Results Participants were 46 years old on average, and 57 (25%) of 230 were female. At 24 weeks, 202 (88%) participants completed the heel rise endurance test and 216 (94%) the patient reported outcomes. The platelet rich plasma was of good quality, with expected growth factor content. No difference was detected in muscle tendon function between participants receiving platelet rich plasma injections and those receiving placebo injections (limb symmetry index, mean 34.7% (standard deviation 17.7%) v 38.5% (22.8%); adjusted mean difference -3.9% (95% confidence interval -10.5% to 2.7%)) or in any secondary outcomes or adverse event rates. Complier average causal effect analyses gave similar findings. Conclusions There is no evidence to indicate that injections of platelet rich plasma can improve objective muscle tendon function, patient reported function, or quality of life after acute Achilles tendon rupture compared with placebo, or that they offer any patient benefit. Trial registration ISRCTN54992179.Efficacy and Mechanism Evaluation programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnershi

    Intakes and sources of dietary sugars and their association with metabolic and inflammatory markers: the Fenland Study, UK.

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    It is widely accepted that dietary sugars promote adverse metabolic outcomes via weight-gain through their contribution to energy intake. Emerging evidence suggests that dietary sugars are associated with adverse metabolic outcomes including increased blood pressure and serum lipids, independently of energy intake and body-weight1. However, dietary sugars are a complex component of the diet and their effects on health outcomes are likely to differ depending on the properties of the consumed sugars. Therefore, associations between dietary sugars and metabolic and inflammatory markers may vary according to whether sugars are from beverage or food sources and, extrinsic or intrinsic. The aim of this study was to examine the association between intakes of dietary sugars from different sources and metabolic and inflammatory markers using a population-based cross-sectional study of adults in the East of England. Sugar intakes from beverages (liquids), foods (solids), extrinsic (free sugars) or intrinsic (non-free sugars) were estimated using food frequency questionnaires. Glycated haemoglobin, glucose, insulin, and C-Reactive Protein (CRP) were measured in fasting blood samples and insulin resistance (HOMA-IR) and a continuous metabolic risk z-score were derived. The contributions to total energy intake (TEI) of sugars from liquids, solids, free sugars and non-free sugars contributed 2.9%, 20.0%, 12.0% and 11.6% respectively. In multiple linear regression analyses adjusted for age, sex, socio-economic status, smoking status, alcohol consumption, physical activity, clinical history, BMI, TEI, dietary quality, fat intake and sugars from other sources, and corrected for multiple testing, sugars from liquids (per 10%TEI) were positively associated with ln-CRP [ÎČ-coefficient(95%CI), 0.14(0.05,0.22)] and the metabolic risk z-score [0.13(0.07,0.18)]. Free sugars were positively associated with ln-HOMA-IR [0.05(0.03,0.08)] and the metabolic risk z-score [0.09(0.06,0.12)]. Sugars from solids were not associated with any outcome. Among major food and beverage contributors to intake, sugars (per 10%TEI) in fruit, vegetables, dairy products/egg dishes, cakes/biscuits/confectionary and fruit squash/juice drinks were not associated, but sugar added to tea, coffee, cereal was significantly positively associated with all outcomes. Sugars in 100% fruit juice [0.16(0.06,0.25)] and other non-alcoholic beverages [0.13(0.03,0.23)] and metabolic risk z-score were positively associated. In conclusion, higher intakes of sugars from non-alcoholic beverages and sugar added to tea, coffee, cereal were associated with glycaemia and inflammatory markers. Sugars from solids were not associated, irrespective of whether they were intrinsic or extrinsic. The positive associations of free sugars were largely explained by the contribution of beverages to intake. Adverse metabolic consequences of sugar intake, independent of contribution to caloric intake, may be attributable to sugar intake from beverages. The Fenland Study is funded by the Wellcome Trust and the Medical Research Council. Support from Medical Research Council programmes MC_UU_12015/1 and MC_UU_12015/5 is acknowledged. 1. Te Morenga L, Mallard S Mann J (2013) BMJ 346, e749

    Postdischarge symptoms and rehabilitation needs in survivors of COVID‐19 infection: A cross‐sectional evaluation

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    Background: There is currently very limited information on the nature and prevalence of post‐COVID‐19 symptoms after hospital discharge. Methods: A purposive sample of 100 survivors discharged from a large University hospital were assessed 4 to 8 weeks after discharge by a multidisciplinary team of rehabilitation professionals using a specialist telephone screening tool designed to capture symptoms and impact on daily life. EQ‐5D‐5L telephone version was also completed. Results: Participants were between 29 and 71 days (mean 48 days) postdischarge from hospital. Thirty‐two participants required treatment in intensive care unit (ICU group) and 68 were managed in hospital wards without needing ICU care (ward group). New illness‐related fatigue was the most common reported symptom by 72% participants in ICU group and 60.3% in ward group. The next most common symptoms were breathlessness (65.6% in ICU group and 42.6% in ward group) and psychological distress (46.9% in ICU group and 23.5% in ward group). There was a clinically significant drop in EQ5D in 68.8% in ICU group and in 45.6% in ward group. Conclusions: This is the first study from the United Kingdom reporting on postdischarge symptoms. We recommend planning rehabilitation services to manage these symptoms appropriately and maximize the functional return of COVID‐19 survivors
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