30 research outputs found

    Consensus Paper: Neuroimmune Mechanisms of Cerebellar Ataxias

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    Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

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    Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

    Harnessing the properties of dendritic cells in the pursuit of immunological tolerance

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    The acquisition of self-perpetuating, immunological tolerance specific for graft alloantigens has long been described as the “holy grail” of clinical transplantation. By removing the need for life-long immunosuppression following engraftment, the adverse consequences of immunosuppressive regimens, including chronic infections and malignancy, may be avoided. Furthermore, autoimmune diseases and allergy are, by definition, driven by aberrant immunological responses to ordinarily innocuous antigens. The re-establishment of permanent tolerance towards instigating antigens may, therefore, provide a cure to these common diseases. Whilst various cell types exhibiting a tolerogenic phenotype have been proposed for such a task, tolerogenic dendritic cells (tol-DCs) are exquisitely adapted for antigen presentation and interact with many facets of the immune system: as such, they are attractive candidates for use in strategies for immune intervention. We review here our current understanding of tol-DC mediated induction and maintenance of immunological tolerance. Additionally, we discuss recent in vitro findings from animal models and clinical trials of tol-DC immunotherapy in the setting of transplantation, autoimmunity and allergy which highlight their promising therapeutic potential, and speculate how tol-DC therapy may be developed in the future

    Multisectoral Preventive Health Services in Sri Lanka: Lessons for Developing Countries in Providing Public Goods in Health

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    What can other developing countries learn from Sri Lanka on achieving good health at low cost? While its well-organized medical and maternal-child health services have been documented elsewhere, this paper fills a gap in documenting how it organizes services to reduce the population's exposure to disease -- a pure public good. The key factors underlying the effectiveness of these services are (1) strong focal points in the central Health Ministry for supporting preventive services; (2) pro-active outreach by the health line agency to collaborate with other sectors / agents whose work influences public health outcomes; and (3) community-level delivery institutions with well-trained multivalent Public Health Inspectors -- all underpinned by (4) assured tax-based financing. This paper describes this system in some detail such that other countries can learn from Sri Lanka's successful approach to improving population health. It also makes some recommendations for strengthening the system in response to changing conditions

    Harnessing the properties of dendritic cells in the pursuit of immunological tolerance

    No full text
    The acquisition of self-perpetuating, immunological tolerance specific for graft alloantigens has long been described as the “holy grail” of clinical transplantation. By removing the need for life-long immunosuppression following engraftment, the adverse consequences of immunosuppressive regimens, including chronic infections and malignancy, may be avoided. Furthermore, autoimmune diseases and allergy are, by definition, driven by aberrant immunological responses to ordinarily innocuous antigens. The re-establishment of permanent tolerance towards instigating antigens may, therefore, provide a cure to these common diseases. Whilst various cell types exhibiting a tolerogenic phenotype have been proposed for such a task, tolerogenic dendritic cells (tol-DCs) are exquisitely adapted for antigen presentation and interact with many facets of the immune system: as such, they are attractive candidates for use in strategies for immune intervention. We review here our current understanding of tol-DC mediated induction and maintenance of immunological tolerance. Additionally, we discuss recent in vitro findings from animal models and clinical trials of tol-DC immunotherapy in the setting of transplantation, autoimmunity and allergy which highlight their promising therapeutic potential, and speculate how tol-DC therapy may be developed in the future

    Chronic rejection and atherosclerosis in post-transplant cardiovascular mortality: two sides of the same coin

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    Post-transplant cardiovascular disease (CVD) is the single most common cause of death in solid organ transplant recipients. The prevailing school of thought is that post-transplant CVD is driven by the same underlying atherosclerotic processes as the CVD of aging seen in the general population. This is reflected in current management strategies, which focus on the minimisation of traditional cardiovascular risk factors. In this article, we argue that atherosclerosis is not the sole aetiology of post-transplant CVD. Instead, chronic rejection drives post-transplant CVD through an antibody-mediated systemic vasculopathy termed systemic accelerated arteriosclerosis (SAA). SAA is fundamentally distinct from atherosclerosis, associated with unique histology, pathophysiology and risk factors. In order to effectively manage post-transplant CVD, SAA needs to be addressed in current management strategies through revised risk factor minimisation and use of immunomodulatory pharmaceuticals

    Trends in the mortality, incidence and disability-adjusted life-years of appendicitis in EU15+ countries: an observational study of the Global Burden of Disease database, 1990-2019

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    Background: Appendicitis places a substantial burden on healthcare systems, with acute appendicitis alone being the most common abdominal surgical emergency worldwide. Further characterisation of the disease burden in EU15+ countries may help optimise the distribution of healthcare resources. The aim of this observational study was to assess the trends in mortality, incidence and DALYs of appendicitis across European Union (EU) 15+ countries between the years 1990 and 2019, Supplemental Digital Content 3, https://links.lww.com/JS9/A589. Materials and methods: Age standardised mortality rates (ASMRs), age standardised incidence rates (ASIRs) and disability adjusted life years (DALYs) data for appendicitis in males and females were extracted from the 2019 Global Burden of Disease (GBD) study. Temporal trends within the study period were analysed using Joinpoint regression analysis. Results: The median ASMRs across EU15+ countries in 2019 were 0.08/100,000 and 0.13/100,000 for females and males, respectively. Between 1990 and 2019 the median percentage change in ASMR was −52.12% for females and −53.18% in males. The median ASIRs in 2019 for females and males were 251/100,000 and 278/100,000, respectively, with a median percentage change of +7.22% for females and +3.78% for males during the observation period. Decreasing trends in DALYs were observed over the 30-year study period, with median percentage changes of −23.57% and −33.81% for females and males, respectively, Supplemental Digital Content 3, https://links.lww.com/JS9/A589. Conclusion: Overall, a general trend of decreasing appendicitis ASMRs and DALYs was observed across EU15+ countries, despite small overall increases in appendicitis ASIRs, Supplemental Digital Content 3, https://links.lww.com/JS9/A589. Variations in both diagnostic and management strategies over the study period are likely contributory to the changing trends

    Valorization of palm oil agro-waste into cellulose biosorbents for highly effective textile effluent remediation

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    Over the past few decades, enormous interest has been manifested in utilizing biomass or agricultural wastes as a renewable resource for energy and advanced material production. Despite being the utmost abundant polymer on earth, nanocellulose has drawn tremendous attention due to its intrinsic reliability and sustainability. In this study, nanocrystalline cellulose (NCC) was isolated from oil palm biomass waste i.e. oil palm empty fruit bunch (EFB) via a multistep process to testify its high capacity as a biosorbent for textile effluent contaminant remediation. Fourier transform infrared spectroscopy (FTIR) suggested that lignin, hemicellulose and other impurities had been effectively removed at different stages of preparation which was generally in agreement with ASTM chemical composition analysis. Thermogravimetric analysis with derivative thermograms (TGA-DTG) observed the extracted NCC to have the lowest weight loss throughout water evaporation region (25 °C - 100 °C), cellulose thermal degradation region (150 °C - 380 °C) and carbonic residue degradation (up to 600 °C) owing to its compact crystalline structure as evidenced from X-ray diffraction (XRD) analysis. Batch adsorption were conducted to study effect of contact time (up to 200 min), adsorbent dosage (0.005–0.05 g), pH (2–10), agitation (50–250 rpm) and adsorbate concentration (50–300 mg/L) at 30 ± 2 °C. Field emission scanning electron microscope (FESEM) observed a flower-like structure of methylene blue (MB) coating upon adsorption, following a type II adsorption isotherm which suggest an adsorption occurred on mesoporous structure. The kinetic data agreed well with pseudo-second-order model which implied the current study a chemisorption process. As adsorption capacity was highly dependent on adsorbate concentration and adsorbent dosage, 50.91 mg/g was recorded for MB solution (50 mg/L) at adsorbent dosage as low as 0.066 mg/ml; a very encouraging outcome in the recent years of cellulosic research suggesting NCC a highly promising candidate for uprising functional cellulosic soft material fabrication
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