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Looking into Post-translational Adjustments to Neuropsychiatric Illness: Another Frontier throughout Man Post-mortem Mental faculties Analysis.
Copyright ©ERS 2020.Accumulating evidence highlights links between iron regulation and respiratory disease. Here, we assessed the relationship between iron levels and regulatory responses in clinical and experimental asthma.We show that cell-free iron levels are reduced in the bronchoalveolar lavage (BAL) supernatant of severe or mild-moderate asthma patients and correlate with lower forced expiratory volume in 1 s (FEV1). Conversely, iron-loaded cell numbers were increased in BAL in these patients and with lower FEV1/forced vital capacity (FEV1/FVC). The airway tissue expression of the iron sequestration molecules divalent metal transporter 1 (DMT1) and transferrin receptor 1 (TFR1) are increased in asthma with TFR1 expression correlating with reduced lung function and increased type 2 (T2) inflammatory responses in the airways. Furthermore, pulmonary iron levels are increased in a house dust mite (HDM)-induced model of experimental asthma in association with augmented Tfr1 expression in airway tissue, similar to human disease. We show that macrophages are the predominant source of increased Tfr1 and Tfr1+ macrophages have increased Il13 expression. We also show that increased iron levels induce increased pro-inflammatory cytokine and/or extracellular matrix (ECM) responses in human airway smooth muscle (ASM) cells and fibroblasts ex vivo and induce key features of asthma, including airway hyper-responsiveness and fibrosis and T2 inflammatory responses, in vivoTogether these complementary clinical and experimental data highlight the importance of altered pulmonary iron levels and regulation in asthma, and the need for a greater focus on the role and potential therapeutic targeting of iron in the pathogenesis and severity of disease. Copyright ©ERS 2020.INTRODUCTION Pain negatively affects the health-related quality of life (HRQL) of adolescents with cancer. The Pain Squad+ smartphone-based application (app), has been developed to provide adolescents with real-time pain self-management support. click here The app uses a validated pain assessment and personalised pain treatment advice with centralised decision support via a registered nurse to enable real-time pain treatment in all settings. The algorithm informing pain treatment advice is evidence-based and expert-vetted. This trial will longitudinally evaluate the impact of Pain Squad+, with or without the addition of nurse support, on adolescent health and cost outcomes. METHODS AND ANALYSIS This will be a pragmatic, multicentre, waitlist controlled, 3-arm parallel-group superiority randomised trial with 111 allocation enrolling 74 adolescents with cancer per arm from nine cancer centres. Participants will be 12 to 18 years, English-speaking and with ≥3/10 pain. Exclusion criteria are significant comorbidities, end-olinicalTrials.gov). © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVE To compare success rates, associated risks and cost-effectiveness between intrauterine insemination (IUI) and in vitro fertilisation (IVF). DESIGN Retrospective observational study. SETTING The UK from 2012 to 2016. PARTICIPANTS Data from Human Fertilisation and Embryology Authority's freedom of information request for 2012-2016 for IVF/ICSI (intracytoplasmic sperm injection)and IUI as practiced in 319 105 IVF/ICSI and 30 669 IUI cycles. Direct-cost calculations for maternal and neonatal expenditure per live birth (LB) was constructed using the cost of multiple birth model, with inflation-adjusted Bank of England index-linked data. A second direct-cost analysis evaluating the incremental cost-effective ratio (ICER) was modelled using the 2016 national mean (baseline) IVF and IUI success rates. OUTCOME MEASURES LB, risks from IVF and IUI, and costs to gain 1 LB. RESULTS This largest comprehensive analysis integrating success, risks and costs at a national level shows IUI is safer and more cost-effectd neonatal complications. It is prudent to offer IUI before IVF nationally. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.INTRODUCTION Chronic pain is prevalent, and approximately half of patients with chronic pain experience sleep disturbance. Exogenous melatonin is licensed to treat primary insomnia and there is some evidence for analgesic effects of melatonin.The aim of this study is to investigate the effects of oral melatonin (as Circadin) 2 mg at night in adults with severe non-malignant pain of at least 3 months' duration. METHODS AND ANALYSIS We will conduct a randomised double-blind placebo-controlled cross-over study. The primary outcome is sleep disturbance. Secondary outcomes are pain intensity, actigraphy, fatigue, reaction time testing, serum melatonin and endogenous opioid peptide levels along with patient views about study participation.We aim to recruit 60 patients with severe chronic pain (average pain intensity ≥7 on the Brief Pain Inventory (BPI)) from a tertiary referral pain clinic in Northeast Scotland. Participants will be randomised to receive melatonin (as modified release Circadin) 2 mg daily for 6 weees. TRIAL REGISTRATION NUMBER ISRCTN12861060. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.INTRODUCTION Laparoscopic anti-reflux surgery is standard of care in surgical treatment of gastro-oesophageal reflux disease and is not without risks of adverse effects, including disruption of the fundoplication and postfundoplication dysphagia, in some cases leading to reoperation. Non-surgical factors such as pre-existing anxiety or depression influence postoperative satisfaction and symptom relief. Previous studies have focused on a short-term follow-up or only certain aspects of disease, such as reoperation or postoperative quality of life. The aim of this study is to evaluate long-term patient-satisfaction and durability of laparoscopic anti-reflux surgery in a large Danish cohort using a comprehensive multimodal follow-up, and to develop a clinically applicable scoring system usable in selecting patients for anti-reflux surgery. METHODS AND ANALYSIS The study is a retrospective cohort study utilising data from patient records and follow-up with patient-reported quality of life as well as registry-based data.
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