Angew Chem Int Ed Engl
October 2024
Reported herein is the first total synthesis of the poly-pseudoindoxyl natural product baphicacanthcusine A. The synthesis leverages the oxidative rearrangement of indoles to pseudoindoxyls to install vicinal pseudoindoxyl heterocycles in a diastereoselective manner. Key steps include an acid-mediated cyclization/indole transposition, two diastereoselective oxidative ring contractions, and a site-selective C-H oxygenation.
View Article and Find Full Text PDFWe report the modular preparation of dihydro-1,2,5-thiodiazole dioxide heterocycles starting from methyl ketones and primary amines. This one-pot, three-component coupling employs 2,3-dimethylimidazole-1-sulfonyl azide triflate as a coupling reagent and oxidant. The transformation is scalable and various ketones and amines can be used, yielding thiodiazole dioxide products in up to 89% yield.
View Article and Find Full Text PDFBackground: Access to care for children with kidney disease is limited in less well-resourced regions of the world and paediatric nephrology (PN) workforce development with good practical skills is critical.
Methods: Retrospective review of a PN training program and trainee feedback from 1999 to 2021, based at Red Cross War Memorial Children's Hospital (RCWMCH), University of Cape Town.
Results: A regionally appropriate 1-2-year training program enrolled 38 fellows with an initial 100% return rate to their country of origin.
Leukemia cells re-program their microenvironment to augment blast proliferation and enhance treatment resistance. Means of clinically targeting such niche-driven treatment resistance remain ambiguous. We develop human induced pluripotent stem cell (hiPSC)-engineered niches to reveal druggable cancer-niche dependencies.
View Article and Find Full Text PDFBackground: Refractory reflux-like symptoms have a substantial impact on patients and healthcare providers. The aim of the survey was to qualitatively assess the needs and attitudes of practicing clinicians around the management of refractory reflux symptoms and refractory gastroesophageal reflux disease (rGERD).
Methods: An International Working Group for the Classification of Oesophagitis (IWGCO) steering committee invited clinicians to complete an online survey including 17 questions.
Objectives: We estimated and compared the travel related carbon emissions of the annual meeting of the Canadian Association of Gastroenterology between the two most common geographical locations of the meeting.
Methods: We modelled the car, train and flight travel journey of each registrant to two annual meetings. One was held in Toronto, close to where the majority of Gastroenterogists live, the other in Banff in the west of the country.
Total synthesis has long been depicted as the quest to conquer the structures created by nature, requiring an unflinching, single-minded devotion to the task. The goal is achieved by chemists with grit, strength of will, and a competitive spirit. While there is some truth to this viewpoint, it does not fully capture the rich experiences gained in this research realm.
View Article and Find Full Text PDFBackground And Aim: The value of a multidisciplinary group and patient engagement in guideline groups is uncertain. We compared the recommendations of two guidelines that used the same data during the same time frame but with different participants to obtain a "real world" perspective on influence of the composition of guideline groups.
Methods: The Canadian Association of Gastroenterology (CAG) and the American College of Gastroenterology (ACG) recently updated their clinical practice guidelines for the management of Irritable Bowel Syndrome (IBS).
Objective: Delays in triage processes in the emergency department (ED) can compromise patient safety. The aim of this study was to provide proof-of-concept that a self-check-in kiosk could decrease the time needed to identify ambulatory patients arriving in the ED. We compared the use of a novel automated self-check-in kiosk to identify patients on ED arrival to routine nurse-initiated patient identification.
View Article and Find Full Text PDFIntroduction: Uganda remains seismically vulnerable to earthquakes, which constitute one of the most deadly naturally triggered disasters in the world. This is not surprising given the country's location in the East African Rift Valley System.
Method: This paper draws mainly on the authors' live event experience and some media reports to narratively outline the nature of a sizable earthquake, which measured a magnitude of 5.
Intrachromosomal amplification of chromosome 21 is a heterogeneous chromosomal rearrangement occurring in 2% of cases of childhood precursor B-cell acute lymphoblastic leukemia. These abnormalities are too complex to engineer faithfully in animal models and are unrepresented in leukemia cell lines. As a resource for future functional and preclinical studies, we have created xenografts from the leukemic blasts of patients with intrachromosomal amplification of chromosome 21 and characterized them by and luminescent imaging, flow immunophenotyping, and histological and ultrastructural analyses of bone marrow and the central nervous system.
View Article and Find Full Text PDFThis paper presents the results of a consensus-driven process identifying 50 priority research questions for historical ecology obtained through crowdsourcing, literature reviews, and in-person workshopping. A deliberative approach was designed to maximize discussion and debate with defined outcomes. Two in-person workshops (in Sweden and Canada) over the course of two years and online discussions were peer facilitated to define specific key questions for historical ecology from anthropological and archaeological perspectives.
View Article and Find Full Text PDFRelapsed acute lymphoblastic leukemia is the most common cause of cancer-related mortality in young people and new therapeutic strategies are needed to improve outcome. Recent studies have shown that heterozygous inactivating mutations in the histone acetyl transferase, , are particularly frequent in relapsed childhood acute lymphoblastic leukemia and associated with a hyperdiploid karyotype and mutations. To study the functional impact of haploinsufficiency in acute lymphoblastic leukemia, RNA interference was used to knock down expression of CREBBP in acute lymphoblastic leukemia cell lines and various primagraft acute lymphoblastic leukemia cells.
View Article and Find Full Text PDFBMJ Qual Improv Rep
February 2016
Clinical handovers of patient care among healthcare professionals is vulnerable to the loss of important clinical information. A verbal report is typically provided by paramedics and documented by emergency department (ED) triage nurses. Paramedics subsequently complete a patient care report which is submitted electronically.
View Article and Find Full Text PDFPrevention of central nervous system (CNS) relapse is critical for cure of childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Despite this, mechanisms of CNS infiltration are poorly understood, and the timing, frequency, and properties of BCP-ALL blasts entering the CNS compartment are unknown. We investigated the CNS-engrafting potential of BCP-ALL cells xenotransplanted into immunodeficient NOD.
View Article and Find Full Text PDFAn important mandate of the Canadian Association of Gastroenterology (CAG), as documented in the Association's governance policies, is to optimize the care of patients with digestive disorders. Clinical practice guidelines are one means of achieving this goal. The benefits of timely, high-quality and evidenced-based recommendations include: Enhancing the professional development of clinical members through education and dissemination of synthesized clinical research; Improving patient care provided by members by providing focus on quality and evidence; Creating legislative environments that favour effective clinical practice; Enhancing the clinical care provided to patients with digestive disease by nongastroenterologists; and Identifying areas that require further information or research to improve clinical care.
View Article and Find Full Text PDFChanges in gene dosage are a major driver of cancer, known to be caused by a finite, but increasingly well annotated, repertoire of mutational mechanisms. This can potentially generate correlated copy-number alterations across hundreds of linked genes, as exemplified by the 2% of childhood acute lymphoblastic leukaemia (ALL) with recurrent amplification of megabase regions of chromosome 21 (iAMP21). We used genomic, cytogenetic and transcriptional analysis, coupled with novel bioinformatic approaches, to reconstruct the evolution of iAMP21 ALL.
View Article and Find Full Text PDFBackground: Funders of health research in Canada seek to determine how their funding programs impact research capacity and knowledge creation.
Objective: To evaluate the impact of a focused grants and award program that was cofunded by the Canadian Institutes of Health Research Institute of Nutrition, Metabolism and Diabetes, and the Canadian Association of Gastroenterology; and to measure the impact of the Program on the career paths of funded researchers and assess the outcomes of research supported through the Program.
Methods: A survey of the recipients of grants and awards from 2000 to 2008 was conducted in 2012.