1,700 research outputs found

    Review of presentations at the 6th European Lupus Meeting 3-5 March 2005.

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    The 6th European Lupus Meeting was held at the Royal College of Physicians of London and was attended by 450 delegates. The conference brought together leading speakers from Europe and North America who reviewed current knowledge and exciting new developments in both clinical and basic science aspects of systemic lupus erythematosus. This review summarizes the major points covered in each session

    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

    Home Parenteral Nutrition in Patients with Advanced Cancer: A Systematic Review and Meta-Analysis

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    The use of home parenteral nutrition (HPN) in patients with incurable cancer remains controversial with significant variation worldwide. We aimed to systematically evaluate the literature from 1960 to 2018 examining the use of HPN in advanced cancer patients for all intestinal failure indications and assess the potential benefits/burdens of HPN in this cohort of patients. The primary end point was survival and secondary end points were quality of life and nutritional/performance status. Meta-analysis was performed with a random effects model, where suitable. Of 493 studies retrieved, 22 met the quality inclusion criteria. Studies were mainly conducted in Western countries (Italy, USA, Canada, Germany), including a total of 3564 patients (mean age 57.8 years). Mean duration for HPN was 5.0 mo. Mean overall survival was 7.3 mo. Patients with improved performance status survived for longer on HPN. Quality of life was sparsely reported though there was no observed negative impact of PN. HPN-related complications were reported in eight studies only and were mainly catheter-related blood stream infections. In conclusion, HPN is used for several indications in advanced cancer, though there is significant heterogeneity of results. Disparities in geographical distribution of the studies may reflect variation in accessing HPN

    The pleiotropic effects of decanoic acid treatment on mitochondrial function in fibroblasts from patients with complex I deficient Leigh syndrome

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    There is growing interest in the use of the ketogenic diet (KD) to treat inherited metabolic diseases including mitochondrial disorders. However, neither the mechanism whereby the diet may be working, nor if it could benefit all patients with mitochondrial disease, is known. This study focusses on decanoic acid (C10), a component of the medium chain triglyceride KD, and a ligand for the nuclear receptor PPAR-γ known to be involved in mitochondrial biogenesis. The effects of C10 were investigated in primary fibroblasts from a cohort of patients with Leigh syndrome (LS) caused by nuclear-encoded defects of respiratory chain complex I, using mitochondrial respiratory chain enzyme assays, gene expression microarray, qPCR and flow cytometry. Treatment with C10 increased citrate synthase activity, a marker of cellular mitochondrial content, in 50 % of fibroblasts obtained from individuals diagnosed with LS in a PPAR-γ-mediated manner. Gene expression analysis and qPCR studies suggested that treating cells with C10 supports fatty acid metabolism, through increasing ACADVL and CPT1 expression, whilst downregulating genes involved in glucose metabolism (PDK3, PDK4). PCK2, involved in blocking glucose metabolism, was upregulated, as was CAT, encoding catalase. Moreover, treatment with C10 also decreased oxidative stress in complex I deficient (rotenone treated) cells. However, since not all cells from subjects with LS appeared to respond to C10, prior cellular testing in vitro could be employed as a means for selecting individuals for subsequent clinical studies involving C10 preparations

    PERTANGGUNGJAWABAN PIDANA BAGI YANG MENYEDIAKAN TEMPAT PENYALAHGUNAAN NARKOTIKA DILIHAT DARI PERSPEKTIF HUKUM PIDANA DAN HUKUM PIDANA ISLAM

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    Mudahnya mengakses narkotika ditandai dari peredaran yang sulit dicegah, banyaknya oknum yang terlibat, teknik distribusi yang semakin bervariasi hingga banyaknya tempat- tempat hiburan yang memudahkan untuk mengakses benda-benda terlarang tersebut. Tujuan dari penelitian ini adalah ingin mengetahui pertanggungjawaban pidana bagi penyedia tempat penyalahgunaan narkotika dilihat dari perspektif Hukum Pidana dan Hukum Pidana Islam. Pendekatan dalam penelitian ini adalah pendekatan kualitatif untuk memahami fenomena apa saja yang dialami oleh subjek penelitian dengan jenis penelitian book survey dan content analysis. Sedangkan teknik dalam pengumpulan data dalam penelitian ini menggunakan library research. Berdasarkna penelitian yang dilakukan diperoleh hasil dari penelitian sebagai berikut, pertama yaitu pertanggungjawaban pidana bagi penyedia tempat penyalahgunaan narkotika dapat dilihat berdasarkan pasal 55 KUHP dan Undang-Undang Nomor 35 tahun 2009 pasal 131. Kedua; di dalam Al-Qur‟an dan Sunnah tidak menjelaskan tentang sanksi hukum bagi produsen, pengedar narkoba ataupun penyedia tempat penyalahgunaan narkotika, oleh karena itu hukum bagi mereka adalah takzi

    Systems of education governance and cultures of justice in Ireland, Scotland and Pakistan

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    This chapter compares the issue of cultures of justice in the systems of education governance in three education systems: Ireland, Scotland and Pakistan. The focus for the comparison are the current policies which shape the regulation of education. These policies were reviewed to identify key issues relating to social justice and equality, decision-making and accountability. From the analysis of each system, three central issues were identified: firstly, the improvement of a state education system; secondly, the degree of decentralisation and centralisation in governance structures and thirdly, the expectations placed on school leaders. The chapter concludes by discussing the tensions between the drive for system improvement and opportunities for school leaders to build strategies to address issues of inequality in schools

    Hypophosphataemia after intravenous iron therapy with ferric carboxymaltose—Real world experience from a tertiary centre in the UK

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    Background: Iron deficiency is the most common global cause of anaemia. Intravenous (IV) iron is used to correct iron deficiency anaemia (IDA) where oral iron cannot be used. Despite being effective, certain IV iron formulations cause significant hypophosphataemia. However, current knowledge on the clinical consequences of IV iron‐induced hypophosphataemia is broadly anecdotal or limited to isolated case reports. / Aims: To retrospectively examine the incidence and potential clinical consequences of hypophosphataemia post‐IV ferric carboxymaltose (FCM) in hospitalised patients with IDA (mixed aetiology). / Methods: Data were collected for 162 patients, who received a total of 169 FCM courses during a 2‐year audit period. Outcomes included incidence of moderate/severe hypophosphataemia (serum phosphate <0.65 mmol/L) ≀90 days post‐FCM, changes in alkaline phosphatase, need for phosphate replacement, and length of hospital stay. / Results: The incidence of moderate/severe hypophosphataemia post‐FCM was 33.7%; within this group the rate of severe hypophosphataemia (serum phosphate ≀0.32 mmol/L) was 8.8%. Moderate/severe hypophosphataemia persisted, with 35% of patients having a serum phosphate of <0.65 mmol/L for ≀90 days at the last measurement after IV FCM. Intervention with IV phosphate—an average of 4.4 infusions per person—was required in 29.8% of cases with moderate/severe hypophosphataemia. FCM‐induced moderate/severe hypophosphataemia was associated with a significantly longer hospital stay (P < 0.0035). / Conclusions: Moderate/severe hypophosphataemia is a frequent adverse drug reaction with FCM. In our study, FCM‐induced moderate/severe hypophosphataemia was also persistent, often required treatment, and was associated with longer hospital stay
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