Single-cell analysis tools for drug discovery and development

The genetic, functional or compositional heterogeneity of healthy and diseased tissues presents major challenges in drug discovery and development. Such heterogeneity hinders the design of accurate disease models and can confound the interpretation of biomarker levels and of patient responses to specific therapies. The complex nature of virtually all tissues has motivated the development of tools for single-cell genomic, transcriptomic and multiplex proteomic analyses. Here, we review these tools and assess their advantages and limitations. Emerging applications of single cell analysis tools in drug discovery and development, particularly in the field of oncology, are discussed

Computational propaganda in Canada: The use of political bots

Are bots active in Canada? Yes. Are they influential? Maybe. Using a combination of quantitative social media analysis, content analysis of news articles and qualitative interviews, we study the use of political bots in Canada. We identify four kinds of bots. Amplifiers game digital systems to promote a message or channel. Dampeners supress and remove information online. Alongside these problematic bots, we also find a number of benign bots that help journalists, civil society and governments. These bots include transparency bots that disclose information to the public and servant bots that help maintain services and infrastructures. Even though bots might not yet be influential in Canada, improved media literacy and increased public discussion of the pitfalls of social media are required

613 cases of splenic rupture without risk factors or previously diagnosed disease: a systematic review

Background Rupture of the spleen in the absence of trauma or previously diagnosed disease is largely ignored in the emergency literature and is often not documented as such in journals from other fields. We have conducted a systematic review of the literature to highlight the surprisingly frequent occurrence of this phenomenon and to document the diversity of diseases that can present in this fashion. Methods Systematic review of English and French language publications catalogued in Pubmed, Embase and CINAHL between 1950 and 2011. Results We found 613 cases of splenic rupture meeting the criteria above, 327 of which occurred as the presenting complaint of an underlying disease and 112 of which occurred following a medical procedure. Rupture appeared to occur spontaneously in histologically normal (but not necessarily normal size) spleens in 35 cases and after minor trauma in 23 cases. Medications were implicated in 47 cases, a splenic or adjacent anatomical abnormality in 31 cases and pregnancy or its complications in 38 cases. The most common associated diseases were infectious (n = 143), haematologic (n = 84) and non-haematologic neoplasms (n = 48). Amyloidosis (n = 24), internal trauma such as cough or vomiting (n = 17) and rheumatologic diseases (n = 10) are less frequently reported. Colonoscopy (n = 87) was the procedure reported most frequently as a cause of rupture. The anatomic abnormalities associated with rupture include splenic cysts (n = 6), infarction (n = 6) and hamartomata (n = 5). Medications associated with rupture include anticoagulants (n = 21), thrombolytics (n = 13) and recombinant G-CSF (n = 10). Other causes or associations reported very infrequently include other endoscopy, pulmonary, cardiac or abdominal surgery, hysterectomy, peliosis, empyema, remote pancreato-renal transplant, thrombosed splenic vein, hemangiomata, pancreatic pseudocysts, splenic artery aneurysm, cholesterol embolism, splenic granuloma, congenital diaphragmatic hernia, rib exostosis, pancreatitis, Gaucher's disease, Wilson's disease, pheochromocytoma, afibrinogenemia and ruptured ectopic pregnancy. Conclusions Emergency physicians should be attuned to the fact that rupture of the spleen can occur in the absence of major trauma or previously diagnosed splenic disease. The occurrence of such a rupture is likely to be the manifesting complaint of an underlying disease. Furthermore, colonoscopy should be more widely documented as a cause of splenic rupture

Expression of toll-like receptor -7 and -9 in B cell subsets from patients with primary Sjögren's syndrome

Introduction: Sjögren’s syndrome (SS) is a rheumatic autoimmune disease characterized by inflammation of exocrine glands. As autoantibodies are present in a majority of patients, B cells have been suggested to play an important role in onset and development of the disease. Toll-like receptors (TLRs) are pattern recognition receptors triggering innate immune responses. Since an increased expression of TLRs has been detected in other rheumatic diseases the purpose of this study was to explore TLRs in B cells of SS patients. Methods: The expression of TLR-7 and -9 in B cell subsets of 25 patients with primary SS (pSS) and 25 healthy controls was analysed in peripheral blood using flow cytometry and real time quantitative PCR. Results: We detected similar levels of CD19+ B cells in pSS patients and healthy controls. An increased number of naïve B cells, as well as fewer pre-switched memory B cells were found in pSS patients. No significant differences were observed in TLR-7 and -9 expression in B cells between pSS patients and healthy controls. Conclusion: This study shows that pSS patients have an alteration in the B cell subpopulation composition compared to controls, with less pre-switched memory B cells and more naïve B cells. We did not detect any significant disparities in TLR-7 and -9 expression between the two groups